Nanoscale octopus guiding telomere entanglement: An innovative strategy for inducing apoptosis in cancer cells.

Telomere length plays a crucial role in cellular aging and the risk of diseases. Unlike normal cells, cancer cells can extend their own survival by maintaining telomere stability through telomere maintenance mechanism. Therefore, regulating the lengths of telomeres have emerged as a promising approach for anti-cancer treatment. In this study, we introduce a nanoscale octopus-like structure designed to induce physical entangling of telomere, thereby efficiently triggering telomere dysfunction. The nanoscale octopus, composed of eight-armed PEG (8-arm-PEG), are functionalized with cell penetrating peptide (TAT) to facilitate nuclear entry and are covalently bound to N-Methyl Mesoporphyrin IX (NMM) to target G-quadruplexes (G4s) present in telomeres. The multi-armed configuration of the nanoscale octopus enables targeted binding to multiple G4s, physically disrupting and entangling numerous telomeres, thereby triggering telomere dysfunction. Both in vitro and in vivo experiments indicate that the nanoscale octopus significantly inhibits cancer cell proliferation, induces apoptosis through telomere entanglement, and ultimately suppresses tumor growth. This research offers a novel perspective for the development of innovative anti-cancer interventions and provides potential therapeutic options for targeting telomeres.

Visualization of Biomolecular Radiation Damage at the Single-Particle Level Using Lanthanide-Sensitized DNA Origami.

Precise monitoring of biomolecular radiation damage is crucial for understanding X-ray-induced cell injury and improving the accuracy of clinical radiotherapy. We present the design and performance of lanthanide-DNA-origami nanodosimeters for directly visualizing radiation damage at the single-particle level. Lanthanide ions (Tb3+ or Eu3+) coordinated with DNA origami nanosensors enhance the sensitivity of X-ray irradiation. Atomic force microscopy (AFM) revealed morphological changes in Eu3+-sensitized DNA origami upon X-ray irradiation, indicating damage caused by ionization-generated electrons and free radicals. We further demonstrated the practical applicability of Eu3+-DNA-origami integrated chips in precisely monitoring radiation-mediated cancer radiotherapy. Quantitative results showed consistent trends with flow cytometry and histological examination under comparable X-ray irradiation doses, providing an affordable and user-friendly visualization tool for preclinical applications. These findings provide new insights into the impact of heavy metals on radiation-induced biomolecular damage and pave the way for future research in developing nanoscale radiation sensors for precise clinical radiography.

Advancing Chlorophyll Photostability: Dual Physicochemical Protection via Ce-Doped Hydrotalcite Organic-Inorganic Hybrid Pigments.

In pursuit of enhancing the photostability of chlorophyll, a novel organic-inorganic hybrid pigment has been synthesized via a supramolecular intercalation assembly method, incorporating cerium-ion-doped hydrotalcite as the host matrix and chlorophyll as the intercalated guest molecule. This innovative pigment amalgamates the vivid coloration properties of organic dyes with the robust stability characteristic of inorganic substances. Determined from the detailed investigation of the structural evolution of chlorophyll during photodegradation, the dual physicochemical protection mechanism is critical to the advancement of chlorophyll photostability. It leverages the oxygen barrier attributes of the hydrotalcite's laminate structure and the ultraviolet light absorption and scattering capabilities of CeO2 nanoparticles formed in situ. Furthermore, Ce-doping introduces a redox cycle between Ce4+ and Ce3+ ions, which serves as a chemical defense by neutralizing reactive oxygen species that emerge during chlorophyll degradation. This multifaceted approach results in a substantial enhancement of photostability, with the hybrid pigment containing 0.3 Ce doped content, demonstrating a mere 5.90% alteration in reflectance at the 635 nm peak after 250 h of UV-accelerated aging. This breakthrough provides a dual physicochemical protective strategy that not only significantly prolongs the lifespan of chlorophyll pigments but also holds potential for broadening their application scope in various industries, including plastics and coatings, where color fastness and durability are paramount.

New secondary metabolites produced by an engineered strain Streptomyces sp. XZQH13OEΔastC.

Two previously undescribed alkaloids (1-2), five known alkaloids (3-7) and five cyclodipeptides (8-12) were obtained from an ansatrienin-producing mutant strain Streptomyces sp. XZQH13OEΔ astC. Their structures were elucidated by analysis of the 1D, 2D NMR and ESI HRMS data and by comparison with the reported data. The antibacterial activities of compounds 1-12 were evaluated.

Enhanced Hydrogen Production via Photothermal-Coupled Ultrasound Pyrolysis of Waste Bio-Oil.

The creation of hydrogen using the lower-cost feedstock, waste organics (WOs), e.g. kitchen waste bio-oil, is a win-win solution, because it can both solve energy problems and reduce environmental pollution. Ultrasound has received considerable interest in organic decomposition; however, the application of ultrasound alone is not a good choice for the hydrogen production from WOs, because of the energy consumption and efficiency. To boost the hydrogen production based on ultrasonic cavitation cracking of bio-oil, photothermal materials are introduced into the hydrogen production system to form localized hot spots. Materials carbon black (CB), carbon nanotubes (CNT), and silicon dioxide (SiO2) all exhibit significant enhancing effects on the hydrogen production from bio-oil, and the CB exhibits the most significant strengthening effect among these materials. When the dosage of CB is 5 mg, hydrogen production rate is 180.1 µmol · h-1, representing a notable 1.7-fold increase compared to the production rate without CB. In the presence of light and ultrasound, the hydrogen production rate can be increased by 66.7-fold compared to the situation where only light is present without ultrasound.

Surface Reconstruction of La0.5Sr0.5CoO3-δ Ceramic toward High Solar Selectivity for High-Temperature Air-Stable Solar-Thermal Conversion.

As a key device for solar energy conversion, solar absorbers play a critical role in improving the operating temperature of concentrated solar power (CSP) systems. However, solar absorbers with high spectral selectivity and good thermal stability at high temperatures in air are still scarce. This study presents a novel surface reconstruction strategy to improve the spectral selectivity of La0.5Sr0.5CoO3-δ (LSC5) for enhanced CSP application. The strategy could efficiently enhance the solar absorptance due to the existence of a high-absorption thin layer composed of nanoparticles on the LSC5 surface. Meanwhile, the crystal facet with low emittance on the LSC5 surface was exposed. Thus, the LSC5 that underwent surface reconstruction achieved a higher solar absorptance (∼0.75) and lower infrared emittance (∼0.19) compared to the original LSC5 (0.63/0.21), representing an improvement of nearly 32%. Additionally, the surface reconstructed LSC5 demonstrated a lower infrared thermographic temperature and a higher solar-thermal conversion equilibrium temperature compared to those of LSC5 and SiC. Moreover, the reconstructed LSC5 could maintain stable performance up to 800 °C in air, which might simplify the complexity of the CSP systems. The surface reconstruction strategy provided a new method to optimize the spectral selectivity of high-temperature stable ceramics, contributing to advancements in solar energy conversion technologies.

Silibinin Induces Both Apoptosis and Necroptosis with Potential Anti-tumor Efficacy in Lung Cancer.

BACKGROUND: Lung cancer incidence is steadily on the rise, posing a growing threat to human health. The search for therapeutic drugs from natural active substance and elucidating their mechanism have been the focus of anti-tumor research. OBJECTIVE: In our work, Silibinin (SiL) was chosen as a possible substance that could inhibit lung cancer. and its effects on inducing tumor cell death have been studied. METHODS: CCK-8 analysis and morphological observation were used to assess the cytotoxic impacts of SiL on lung cancer cells in vitro. The alterations in mitochondrial membrane potential (MMP) and apoptosis rate of cells were detected by flow cytometry. The level of lactate dehydrogenase (LDH) release out of cells was measured. The expression changes of apoptosis or necroptosis-related proteins were detected using western blotting. Protein interactions among RIPK1, RIPK3 and MLKL were analyzed using the co-immunoprecipitation technique. In vivo, SiL was evaluated for its antitumor effects using LLC tumor-bearing mice with mouse lung cancer. RESULTS: With an increased dose of SiL, the proliferation ability of A549 cells was considerably inhibited, and the accompanying cell morphology changed. The results of flow cytometry showed that after SiL treatment, MMP levels decreased, and the proportion of cells undergoing apoptosis increased. The proteins associated with apoptosis were upregulated and activated. The amount of LDH released from the cells increased following SiL treatment, accompanied by augmented expression and phosphorylation levels of necroptosis-related proteins. The co-IP assay further confirmed necrosome formation induced by SiL. Furthermore, Necrosulfonamide (an MLKL inhibitor) increased the apoptotic rate of SiL-treated cells and aggravated the cytotoxic effect of SiL, indicating that necroptosis blockade could switch cell death to apoptosis and increase the inhibitory effect of SiL on A549 cells. In LLC-bearing mice, gastric administration of SiL significantly inhibited tumor growth. CONCLUSIONS: This study helped clarify the anti-tumor mechanism of SiL against lung cancer, elucidating its role in dual induction of apoptosis and necroptosis. In particular, necroptosis blockade could switch cell death to apoptosis and increase the inhibitory effect of SiL. Our work provided an experimental basis for the research on cell death induced by SiL and revealed its possible applications for improving the management of lung cancer.

Synthesis of 2-phenylnaphthalenoid amide derivatives and their topoisomerase IIα inhibitory and antiproliferative activities.

Topoisomerases are highly associated with cell proliferation, becoming an important target for the development of antitumor drugs. 2-Phenylnaphthalenoids (2PNs) have been identified as human DNA topoisomerase IIα (TopoIIα) inhibitors. In this study, based on the 2PN scaffold, 20 amide derivatives (J1-J10, K1-K10) were synthesized. Among them, K10 showed high TopoIIα inhibitory activity and stronger antiproliferation activity against HepG-2 and MDA-MB-231 cells (IC50 0.33 and 0.63 µM, respectively) than the positive control VP-16 (IC50 9.19 and 10.86 µM) and the lead F2 (IC50 0.64 and 1.51 µM). Meanwhile, K10 could also inhibit migration and promote apoptosis of HepG-2 and MDA-MB-231 cells. Therefore, K10 can be developed into a potent TopoIIα inhibitor as an antitumor agent. The structure-activity relationship was also discussed.

A polysubstituted cyclopentane and two glycerol esters from the engineered strain Streptomyces sp. S35-LAL1.

Activation of silencing gene clusters is an important way to discover structurally novel compounds. In this study, three undescribed compounds were obtained from an engineered strain of Streptomyces sp. S35-LAL1. They include a polysubstituted cyclopentane with an unprecedented 10-carbon skeleton (1) and two glycerol esters (2 and 3). The structures of compounds 1-3 were elucidated through analysis of their spectroscopic data including 1D, 2D NMR, optical rotation, and electronic circular dichroism (ECD).

Construction of an exogenously and endogenously Co-activated DNA logic amplifier for highly reliable intracellular MicroRNA imaging.

DNA-based molecular amplifiers offer significant promise for molecular-level disease diagnosis and treatment, yet tailoring their activation for precise timing and localization remains a challenge. Herein, we've pioneered a dual activation strategy harnessing external light and internal ATP to create a highly controlled DNA logic amplifier (FDLA) for accurate miRNA monitoring in cancer cells. The FDLA was constructed by tethered the two functionalized catalytic hairpin assembly (CHA) hairpin modules (ATP aptamer sealed hairpin aH1 and photocleavable (PC-linker) sites modified hairpin pH2) to DNA tetrahedron (DTN). The FDLA system incorporates ATP aptamers and PC-linkers as logic control units, allowing them to respond to both exogenous UV light and endogenous ATP present within cancer cells. This response triggers the release of CHA hairpin modules, enabling amplified FRET miRNA imaging through an AND-AND gate. The DTN structure could improve the stability of FDLA and accelerate the kinetics of the strand displacement reaction. It is noteworthy that the UV and ATP co-gated DNA circuit can control the DNA bio-computing at specific time and location, offering spatial and temporal capabilities that can be harnessed for miRNA imaging. Furthermore, the miRNA-sensing FDLA amplifier demonstrates reliable imaging of intracellular miRNA with minimal background noise and false-positive signals. This highlights the feasibility of utilizing both exogenous and endogenous regulatory strategies to achieve spatial and temporal control of DNA molecular circuits within living cancer cells. Such advancements hold immense potential for unraveling the correlation between miRNA and associated diseases.

Optimization and Parameter Investigation of the Planar Photocatalytic Microreactor.

The microreactor could break the limitation of mass transfer and photon transmission in photocatalysis. Through a facile assembly method, a planar photocatalytic microreactor was constructed to fit most of the photocatalysts regardless of their strict preparation method. This microreactor exhibits a 2.41-fold efficiency compared to a bulk reactor. Parameters that affect the photocatalytic performance were discussed in detail by experiment and calculation. The diffusion rate is the main bottleneck in a planar microreactor under a laminar flow. The microreactor with lower height shows higher efficiency owing to faster mass transfer, while the length and width affect slightly. Elevating the light power density provides a diminishing benefit. Faster flow speed reduces the apparent degradation percent but increases the chemical reaction rate, in fact. The reaction rate increases to 9.31 times by reducing the height from 500 to 100 µm and grows another 1.76 times by adding the flow speed from 10 to 40 mL/h. This work illustrates the influence of parameters on planar photocatalytic microreactors and offers a promising prospect for large-volume photocatalytic water treatment.

Self-assembled metal-phenolic nanocomplexes comprised of green tea catechin for tumor-specific ferroptosis.

Ferroptosis, a newly discovered form of regulated cell death, has garnered significant attention in the field of tumor therapy. However, the presence of overexpressed glutathione (GSH) and insufficient levels of H2O2 in the tumor microenvironment (TME) hinders the occurrence of ferroptosis. In response to these challenges, here we have constructed the self-assembled nanocomplexes (FeE NPs) utilizing epigallocatechin-3-gallate (EGCG) from green tea polyphenols and metal ions (Fe3+) as components. After grafting PEG, the nanocomplexes (FeE@PEG NPs) exhibit good biocompatibility and synergistically enhanced tumor-inhibitory properties. FeE@PEG NPs can be disassembled by H2O2 in the TME, leading to the rapid release of Fe3+ and EGCG. The released Fe3+ produces large amounts of toxic •OH by the Fenton reactions while having minimal impact on normal cells. The generated •OH effectively induces lipid peroxidation, which leads to ferroptosis in tumor cells. Meanwhile, the released EGCG can autoxidize to produce H2O2, which further promotes the production of •OH radicals and increases lipid peroxide levels. Moreover, EGCG also depletes the high levels of intracellular GSH, leading to an intracellular redox imbalance and triggering ferroptosis. This study provides new insights into advancing anticancer ferroptosis through rational material design, offering promising avenues for future research.

mRNA-responsive two-in-one nanodrug for enhanced anti-tumor chemo-gene therapy.

The combination of chemotherapy and gene therapy holds great promise for the treatment and eradication of tumors. However, due to significant differences in physicochemical properties between chemotherapeutic agents and functional nucleic acid drugs, direct integration into a single nano-agent is hindered, impeding the design and construction of an effective co-delivery nano-platform for synergistic anti-tumor treatments. In this study, we have developed an mRNA-responsive two-in-one nano-drug for effective anti-tumor therapy by the direct self-assembly of 2'-fluoro-substituted antisense DNA against P-glycoprotein (2'F-DNA) and chemo drug paclitaxel (PTX). The 2'-fluoro modification of DNA could significantly increase the interaction between the therapeutic nucleic acid and the chemotherapeutic drug, promoting the successful formation of 2'F-DNA/PTX nanospheres (2'F-DNA/PTX NSs). Due to the one-step self-assembly process without additional carrier materials, the prepared 2'F-DNA/PTX NSs exhibited considerable loading efficiency and bioavailability of PTX. In the presence of endogenous P-glycoprotein mRNA, the 2'F-DNA/PTX NSs were disassembled. The released 2'F-DNA could down-regulate the expression of P-glycoprotein, which decreased the multidrug resistance of tumor cells and enhanced the chemotherapy effect caused by PTX. In this way, the 2'F-DNA/PTX NSs could synergistically induce the apoptosis of tumor cells and realize the combined anti-tumor therapy. This strategy might provide a new tool to explore functional intracellular co-delivery nano-systems with high bioavailability and exhibit potential promising in the applications of accurate diagnosis and treatment of tumors.

Pirin Promotes the Progression of Non-Small-Cell Lung Cancer by Increasing ODC1 to Suppress Autophagy.

Non-small-cell lung cancer (NSCLC), a common malignant tumor, requires deeper pathogenesis investigation. Autophagy is an evolutionarily conserved lysosomal degradation process that is frequently blocked during cancer progression. It is an urgent need to determine the novel autophagy-associated regulators in NSCLC. Here, we found that pirin was upregulated in NSCLC, and its expression was positively correlated with poor prognosis. Overexpression of pirin inhibited autophagy and promoted NSCLC proliferation. We then performed data-independent acquisition-based quantitative proteomics to identify the differentially expressed proteins (DEPs) in pirin-overexpression (OE) or pirin-knockdown (KD) cells. Among the pirin-regulated DEPs, ornithine decarboxylase 1 (ODC1) was downregulated in pirin-KD cells while upregulated along with pirin overexpression. ODC1 depletion reversed the pirin-induced autophagy inhibition and pro-proliferation effect in A549 and H460 cells. Immunohistochemistry showed that ODC1 was highly expressed in NSCLC cancer tissues and positively related with pirin. Notably, NSCLC patients with pirinhigh/ODC1high had a higher risk in terms of overall survival. In summary, we identified pirin and ODC1 as a novel cluster of prognostic biomarkers for NSCLC and highlighted the potential oncogenic role of the pirin/ODC1/autophagy axis in this cancer type. Targeting this pathway represents a possible therapeutic approach to treat NSCLC.

Construction of a Robust Radiative Cooling Emitter for Efficient Food Storage and Transportation.

Nowadays, food safety is still facing great challenges. During storage and transportation, perishable goods have to be kept at a low temperature. However, the current logistics still lack enough preservation ability to maintain a low temperature in the whole. Hence, considering the temperature fluctuation in logistics, in this work, the passive radiative cooling (RC) technology was applied to package to enhance the temperature control capability in food storage and transportation. The RC emitter with selective infrared emission property was fabricated by a facile coating method, and Al2O3 was added to improve the wear resistance. The sunlight reflectance and infrared emittance within atmospheric conditions could reach up to 0.92 and 0.84, respectively. After abrasion, the sunlight reflection only decreased by 0.01, and the infrared emission showed a negligible change, revealing excellent wear resistance. During outdoor measurement, the box assembled by RC emitters (RC box) was proved to achieve temperature drops of ∼9 and ∼4 °C compared with the corrugated box and foam box, respectively. Besides, the fruits stored in the RC box exhibited a lower decay rate. Additionally, after printing with patterns to meet the aesthetic requirements, the RC emitter could also maintain the cooling ability. Given the superior optical properties, wear resistance, and cooling capability, the emitter has great potential for obtaining a better temperature control ability in food storage and transportation.

Efficient liquid phase photothermal catalysis realized by Ag2O/Bi4O5I2via heat-localization in a microreactor.

By constructing a Ag2O/Bi4O5I2 p-n heterojunction and applying a heat-localization microreactor, efficient photocatalysis enhanced by both photoinduced carrier separation and the photothermal effect was realized. This work focuses on the utilization of near-infrared light to broaden the absorption spectrum and accelerate the transportation of carriers. Through the production and localization of heat, it provides a novel thought for full-spectrum photocatalysis.

Synthesis of urolithin derivatives and their anti-inflammatory activity.

Two series of urolithin derivatives, totally 38 compounds, were synthesized. Their anti-inflammatory activity was investigated by detecting the inhibitory effects on the expression of TNF-α in bone marrow-derived macrophages (BMDMs), showing that 24 of 38 ones reduced the expression of TNF-α. Compound B2, the ring C opened derivative of urolithin B with a butoxycarbonyl substitution in ring A, showed the strongest inhibitory activity compared with that of indomethacin. Furthermore, B2 treatment decreased the expression of pro-inflammatory factors IL-1ß, IL-6, iNOS and COX-2. Mechanically, the anti-inflammatory effect of B2 was related to the inhibition of NF-κB signaling pathway. These results clearly illustrated that B2 hold potential for application as an anti-inflammatory agent. The present study provided a viable approach to modify the gut metabolites for anti-inflammatory drug development.

Proansamycin B derivatives from the post-PKS modification gene deletion mutant of Amycolatopsis mediterranei S699.

Ten new proansamycin B congeners (1-10) together with one known (11) were isolated and characterized on the basis of 1D and 2D NMR spectroscopic and HRESIMS data from the Amycolatopsis mediterranei S699 ΔPM::rifR+rif-orf19 mutant. Compounds 8 and 9 featured with six-membered ring and five-membered ring hemiketal, respectively. Compounds 1, 2, and 9 displayed antibacterial activity against MRSA (methicillin-resistant Staphylococcus aureus), with the MIC (minimal inhibitory concentration) values of 64, 8, and 128 µg/mL, respectively. Compound 1 showed significant cytotoxicity against MDA-MB-231, HepG2 and Panc-1 cell lines with IC50 (half maximal inhibitory concentration) values of 2.3 ± 0.2, 2.5 ± 0.3 and 3.8 ± 0.5 µM, respectively.

New bioactive secondary metabolites from the soil-derived Streptomyces sp. S045 and their anti-bacterial and anti-type III secretion system activities.

A total of seven compounds were isolated from the ISP3 agar cultures of a soil-derived Streptomyces sp. S045 strain. Their structures were determined based on 1D, 2D NMR spectroscopic data, HR ESI mass spectroscopy, X-ray diffraction analysis and comparison with the reported data. The new compounds were identified to be (S)-4-(1-hydroxyethyl)quinoline-2-carboxamide (1) and methyl 4-(hydroxymethyl)-2-(4-methylpentyl)-4,5-dihydrofuran-3-carboxylate (3), respectively. Their anti-bacterial and anti-type III secretion system (T3SS) activities were evaluated.

Phytotoxic phenols from the needles of Cedrus deodara.

During the course of screening for anti-seed germination phytochemicals, the methanol fraction of the Cedrus deodara fresh needles showed potent activity. Bioactivity-guided fractionation led to the isolation of thirty-eight phenolic compounds. Four ones were identified as previously undescribed including (7S,8S)-3-methoxy-9'-acetoxy-3',7-epoxy-8,4'-oxyneoligna-4,9-diol (7), (7S,8R)-dihydro-3'-hydroxy-8-acetoxymethyl-7-(4-hydroxy-3-methoxy-phenyl)-1'-benzofuranpropanol (10), (8S)-4,9,9'-trihydroxy-3,3'-dimethoxy-8,4'-oxyneolignan (11) and (7S,8S)-4,7,9'-trihydroxy-3,3'-dimethoxy-9-acetoxy-8,4'-oxyneolignan (16), respectively. The potential phytotoxic effects of these compounds on the seed germination and root elongation of Arabidopsis thaliana were evaluated by the filter paper assay developed in our laboratory. Bioassay results indicated that caffeic acid (36) displayed most significant inhibitory activities against the seed germination and root elongation of A. thaliana, stronger than those of the commercial herbicides acetochlor and glyphosate at the same concentration of 200 µg/mL. Ditetrahydrofuran lignan (1), dihydrochalcone (25), and eight simple phenols (28, 29, 31, 33-35, 37 and 38) completely inhibited the seed germination of A. thaliana at the concentration of 400 µg/mL, which were as active as acetochlor. Dihydroflavone (21) and the simple phenols 32-34 displayed stronger inhibitory effects on the root elongation of A. thaliana than that of glyphosate. The inhibitory effects of these active compounds on the seed germination and root elongation of Amaranthus tricolor and Lactuca sativa were evaluated as well. The phytotoxic activity of 11, 16, 22, 25, 31, 34, 37 and 38 were detected for the first time. In addition, the structure-activity relationships of the same class of these phytochemicals were discussed.