GlycoSS: A DNA Glycosignal Sieve for Deciphering Spatially Resolved EpCAM-Specific Glycoforms.

Malignant transformation of cancer is often accompanied by aberrant glycopatterns. Epithelial-mesenchymal transition (EMT) is a crucial biological process in cancer migration and invasion, accelerating cancer deterioration. High-precision analysis of protein-glycan spatial profiling in the EMT process is essential for elucidating glycosylation functions and cancer progression. However, the diversity of glycans in composition and conformation complicates their spatial analysis. Here, we develop a DNA glycosignal sieve (GlycoSS) visualization platform for screening glycoform expression with a protein spatial dimension. GlycoSS utilizes protein-anchored DNA nanoscanners of distinct lengths to control glycosignal readout, enabling protein-glycan distance modulations, and simultaneously orthogonally amplify glycoform output through signal amplification by an exchange reaction. Using GlycoSS, we screened EpCAM-specific hypoglycosylated glycoform signals in different breast cancer cell subtypes, especially characterizing the spatial distribution of glycans on the MCF-7 cell surface. Considering that the EpCAM-specific N-glycan dysregulation in EMT is pivotal, GlycoSS revealed dynamic glycan fluctuations during IGF-1-induced EMT, revealing that the N-glycans were positively associated with tumor malignancy and metastasis. GlycoSS is anticipated to accelerate the identification of aberrant N-glycosylation in tumor progression, advancing systemic glycobiology insights. Notably, GlycoSS is capable of analyzing diverse glycoprotein profiles, offering additional dimensions into the role of glycoprotein nanoenvironments in regulating membrane protein function.

Trophic Transfer of Metal Oxide Nanoparticles in the Tomato-Helicoverpa armigera Food Chain: Effects on Phyllosphere Microbiota, Insect Oxidative Stress, and Gut Microbiome.

Understanding the trophic transfer and ecological cascade effects of nanofertilizers and nanopesticides in terrestrial food chains is crucial for assessing their nanotoxicity and environmental risks. Herein, the trophic transfer of La2O3 (nLa2O3) and CuO (nCuO) nanoparticles from tomato leaves to Helicoverpa armigera (Lepidoptera: Noctuidae) caterpillars and their subsequent effects on caterpillar growth and intestinal health were investigated. We found that 50 mg/L foliar nLa2O3 and nCuO were transferred from tomato leaves to H. armigera, with particulate trophic transfer factors of 1.47 and 0.99, respectively. While nCuO exposure reduced larval weight gain more (34.7%) than nLa2O3 (11.3%), owing to higher oxidative stress (e.g., MDA and H2O2) and more serious intestinal pathological damage (i.e., crumpled columnar cell and disintegrated goblet cell) by nCuO. Moreover, nCuO exposure led to a more compact antagonism between the phyllosphere and gut microbiomes compared to nLa2O3. Specifically, nCuO exposure resulted in a greater increase in pathogenic bacteria (e.g., Mycobacterium, Bacillus, and Ralstonia) and a more significant decrease in probiotics (e.g., Streptomyces and Arthrobacter) than nLa2O3, ultimately destroying larval intestinal immunity. Altogether, our findings systematically revealed the cascade effect of metal oxide nanomaterials on higher trophic consumers through alteration in the phyllosphere and insect gut microbiome interaction, thus providing insights into nanotoxicity and environmental risk assessment of nanomaterials applied in agroecosystems.

Angelica Sinensis polysaccharide antagonizes 5-Fluorouracil-induced spleen injury and dysfunction by suppressing oxidative stress and apoptosis.

Angelica Sinensis polysaccharide (ASP), the main active component of Angelica sinensis, possesses antioxidative and anti-apoptotic properties. In this study, we have investigated the antagonistic effect of ASP on 5-FU-induced injury of mouse spleen in vivo and splenocytes in vitro, and its possible mechanism. Our results showed that ASP inhibited 5-FU-induced decreases in spleen weight and organ index in mice, restored the number of peripheral blood leukocytes and lymphocytes, repaired spleen structure disorder and functional impairment, rescued serum IL-2, IL-6, and IFN-γ levels, and relieved 5-FU-induced mitochondrial swelling， reduced the oxidant accumulation including MDA and ROS, whereas increasing the activities of GSH, SOD and CAT. The mechanism may be related to ASP downregulation of Keap1 protein expression thus motivating the nuclear translocation of Nrf2. Furthermore, ASP alleviated the apoptosis of spleens in vivo and splenocytes in vitro, and reactivated PI3K / AKT signalling. In conclusion, the protective effect of ASP on spleens and splenocytes may be related to the reduction of oxidative stress and apoptosis via reactivation of Nrf2 and PI3K/AKT pathways. This study has provided a new protective agent for minimizing the spleen injury caused by 5-FU and a new idea for improving the prognosis of chemotherapy patients.

An ER-Horse Detonating Stress Cascade for Hepatocellular Carcinoma Nanotherapy.

Persisting and excessive endoplasmic reticulum stress (ERS) can evoke rapid cell apoptosis. Therapeutic interference of ERS signaling holds enormous potential for cancer nanotherapy. Herein, a hepatocellular carcinoma (HCC) cell-derived ER vesicle (ERV) encapsulating siGRP94, denoted as ER-horse, has been developed for precise HCC nanotherapy. Briefly, ER-horse, like the Trojan horse, was recognized via homotypic camouflage, imitated the physiological function of ER, and exogenously opened the Ca2+ channel. Consequently, the mandatory pouring-in of extracellular Ca2+ triggered the aggravated stress cascade (ERS and oxidative stress) and apoptosis pathway with the inhibition of unfolded protein response by siGRP94. Collectively, our findings provide a paradigm for potent HCC nanotherapy via ERS signaling interference and exploring therapeutic interference of physiological signal transduction pathways for precision cancer therapy.

Silicon Nanodots Increase Plant Resistance against Herbivores by Simultaneously Activating Physical and Chemical Defenses.

Nanosilicon applications have been shown to increase plant defenses against both abiotic and biotic stresses. Silicon quantum nanodots (Si NDs), a form of nanosilicon, possess excellent biological and physiochemical properties (e.g., minimal size, high water solubility, stability, and biocompatibility), potentially making them more efficient in regulating plant responses to stress than other forms of silicon. However, to date, we still lack mechanistic evidence for how soil-applied Si NDs alter the regulation of plant physical and chemical defenses against insect herbivores. To address this gap, we compared the effect of fluorescent amine-functionalized Si NDs (5 nm) and the conventional fertilizer sodium silicate on maize (Zea mays L.) physical and chemical defenses against the oriental armyworm (Mythimna separata, Walker) caterpillars. We found that 50 mg/kg Si NDs and sodium silicate additions inhibited the growth of caterpillars the most (35.7% and 22.8%, respectively) as compared to other application doses (0, 10, and 150 mg/kg). Both Si NDs and silicate addition activated biosynthesis genes responsible for chemical (benzoxazinoids) and physical (lignin) defense production. Moreover, Si NDs upregulated the gene expression of antioxidant enzymes (SOD, CAT, and POD) and promoted the antioxidant metabolism (flavonoids) in maize leaves under M. separata attack. Finally, we show that, under field conditions, Si ND addition increased maize cob weight (28.7%), cob grain weight (40.8%), and 100-grain weight (26.5%) as compared to the control, and more so than the conventional silicon fertilizer. Altogether, our findings highlight the potential for Si NDs to be used as an effective and ecofriendly crop protection strategy in agroecosystems.

A mesoporous silica nanocarrier pesticide delivery system for loading acetamiprid: Effectively manage aphids and reduce plant pesticide residue.

A multifunctional nanomaterials-based agrochemical delivery system could supply a powerful tool for the efficient use of pesticides. Redox-responsive carriers as novel delivery systems of pesticide application in agriculture could promote the pest control and reduce plant pesticide residues due to the controllable release of agrochemicals. Herein, neonicotinoid insecticide acetamiprid (Ace) was encapsulated with decanethiol in a mesoporous silica nanocarrier pesticide delivery system for a nanopesticide Ace@MSN-SS-C10. The Ace@MSN-SS-C10 had redox-responsive sustained release behavior triggered by glutathione (GSH). Moreover, the Ace@MSN-SS-C10 possessed excellent wettability, adhesion performance, stability, and biosafety. Greenhouse experiments showed that foliar spraying 1.5 mg Ace@MSN-SS-C10 per plant reduced the populations of adult and juvenile aphids (Aphis craccivora Koch) on Vicia faba L. after 5 days of aphid infestation by 98.7 % and 99.3 %, respectively. Notably, the leaf final Ace residue (0.32 ± 0.004 mg/kg) of Ace@MSN-SS-C10 application at the dose of 1.5 mg/plant after 5 days of aphid infestation was lower than the international Codex Alimentarius Commission (CAC) maximum residue limits (0.4 mg·kg-1) or much lower (24.87-folds decrease) than those treated with conventional Ace (40 % acetamiprid water dispersible granule). Altogether, this GSH-dependent redox-responsive delivery system for loading acetamiprid can develop as an efficient and environmentally-friendly nanopesticide to control aphids in sustainable agriculture.

Earthworms Drive the Effect of La2O3 Nanoparticles on Radish Taproot Metabolite Profiles and Rhizosphere Microbial Communities.

To promote the sustainable and safe application of nanotechnology employing engineered nanoparticles (NPs) in agroecosystems, it is crucial to pay more attention to the NP-mediated biological response process and environmental impact assessment simultaneously. Herein, 50 mg kg-1 La2O3 NPs were added to soils without and with earthworms for cherry radish growth for 50 days to investigate the response changes of metabolites in radish above- and below-ground organs and rhizosphere bacterial communities. We found that La2O3 NP exposure, especially with earthworms, notably increased the La bioavailability and uptake by taproots and eventually increased radish leaf sucrose content and plant biomass. The La2O3 NP exposure significantly altered metabolite profiles in taproot flesh and peel tissues, and particularly La2O3 NP exposure combined with earthworms was more conducive to La2O3 NPs to promote radish taproot peel to synthesize more secondary antioxidant metabolites. Moreover, compared with the control, the La2O3 NP exposure resulted in weaker and fewer correlations between rhizosphere bacteria and taproot metabolites, but this was recovered somewhat after the inoculation of earthworms. Altogether, our results provide novel insights into the soil-fauna-driven biological and biochemical impact of La2O3 NP exposure on edible root crops and the long-term environmental risks to the rhizosphere microbiota in agroecosystems.

Meta-analysis of chitosan-mediated effects on plant defense against oxidative stress.

Chitosan, as a natural non-toxic biomaterial, has been demonstrated to enhance plant defense against oxidative stress. However, the general pattern and mechanism of how chitosan application modifies the amelioration of oxidative stress in plants have not been elucidated yet. Herein, we performed a meta-analysis of 58 published articles up to January 2022 to fill this knowledge gap, and found that chitosan application significantly increased the antioxidant enzyme activity (by 40.6 %), antioxidant metabolites content (by 24.6 %), defense enzyme activity (by 77.9 %), defense-related genes expression (by 103.2 %), phytohormones (by 26.9 %), and osmotic regulators (by 23.2 %) under stress conditions, which in turn notably reduced oxidative stress (by 32.2 %), and increased plant biomass (by 28.1 %) and yield (by 15.7 %). Moreover, chitosan-mediated effects on the amelioration of oxidative stress depended on the properties and application methods of chitosan. Our findings provide a comprehensive understanding of the mechanism of chitosan-alleviated oxidative stress, which would promote the application of chitosan in plant protection in agriculture.

Hierarchical self-uncloaking CRISPR-Cas13a-customized RNA nanococoons for spatial-controlled genome editing and precise cancer therapy.

CRISPR-Cas13a holds enormous potential for developing precise RNA editing. However, spatial manipulation of CRISPR-Cas13a activity remains a daunting challenge for elaborately regulating localized RNase function. Here, we designed hierarchical self-uncloaking CRISPR-Cas13a-customized RNA nanococoons (RNCOs-D), featuring tumor-specific recognition and spatial-controlled activation of Cas13a, for precise cancer synergistic therapy. RNCOs-D consists of programmable RNA nanosponges (RNSs) capable of targeted delivery and caging chemotherapeutic drug, and nanocapsules (NCs) anchored on RNSs for cloaking Cas13a/crRNA ribonucleoprotein (Cas13a RNP) activity. The acidic endo/lysosomal microenvironment stimulates the outer decomposition of NCs with concomitant Cas13a RNP activity revitalization, while the inner disassembly through trans-cleavage of RNSs initiated by cis-recognition and cleavage of EGFR variant III (EGFRvIII) mRNA. RNCOs-D demonstrates the effective EGFRvIII mRNA silencing for synergistic therapy of glioblastoma cancer cells in vitro and in vivo. The engineering of RNSs, together with efficient Cas13a activity regulation, holds immense prospect for multimodal and synergistic cancer therapy.

CeO2/MXene heterojunction-based ultrasensitive electrochemiluminescence biosensing for BCR-ABL fusion gene detection combined with dual-toehold strand displacement reaction for signal amplification.

An "on-off" nonenzymatic and ultrasensitive electrochemiluminescence (ECL) biosensing platform has been constructed to detect BCR-ABL fusion gene based on CeO2/MXene heterojunction and configuration-entropy driven dual-toehold strand displacement reaction (DT-SDR) for signal amplification. The CeO2/MXene heterojunction were prepared via one-step hydrothermal method through in situ synthesis of CeO2 nanocubes on the surface of Ti3C2-MXene nanosheets. Surprisingly, the prepared CeO2/MXene heterojunction with good dispersion and excellent conductivity not only significantly enhanced ECL emission of S2O82-/O2 system, but also acted as good electrode modification materials to provide massive active sites for three-stranded ST/AS/BK complex immobilization. In the presence of target BCR-ABL fusion gene and Bio-FS, target BCR-ABL fusion gene bound to dual-toehold exposed at the ends of ST, replacing AS and BK and obtaining ST/target with a loop. Subsequently, Bio-FS bound to the loop (as toehold) in ST strand of ST/target to form ST/Bio-FS, replacing the target to further trigger a new SDA cycle. This configuration-entropy driven DT-SDR made three-stranded ST/AS/BK complex transform into dual-stranded ST/Bio-FS in the electrode interface. Ultimately, the quenching labels of streptavidin modified Pt nanoparticles functionalized polydopamine composites (SA-Pt@PDA) were introduced via biotin and streptavidin recognition, realizing ECL emission quenching of S2O82-/O2 system for "on-off" detection of BCR-ABL fusion gene. The developed ECL biosensor for BCR-ABL fusion gene detection achieves the wide concentration variation from 1 fM to 100 pM with low limit of detection down to 0.27 fM, which provides new enlightenment and basis for molecular diagnosis of chronic myelogenous leukemia in clinical practice.

Self-electrochemiluminescence biosensor based on CRISPR/Cas12a and PdCuBP@luminol nanoemitter for highly sensitive detection of cytochrome c oxidase subunit III gene of acute kidney injury.

The cytochrome c oxidase subunit III (COX III) gene is a powerful biomarker for the early diagnosis of acute kidney injury. However, current methods for COX III gene detection are usually laborious and time-consuming, with limited sensitivity. Herein, we report a novel self-electrochemiluminescence (ECL) biosensor for highly sensitive detection of the COX III gene based on CRISPR/Cas12a and nanoemitters of luminol-loaded multicomponent metal-metalloid PdCuBP alloy mesoporous nanoclusters. The nanoemitter with excellent self-ECL in neutral media exhibited a high specific surface area for binding luminol and outstanding oxidase-like catalytic activity toward dissolved O2. Meanwhile, the CRISPR/Cas12a system, as a target-trigger, was employed to specifically recognize the COX III gene and efficiently cleave the interfacial quencher of dopamine-labeled hairpin DNA. As a result, the ECL biosensor showed superior analytical performance for COX III gene detection without exogenous coreactant. Benefiting from the high-efficiency ECL emission of the nanoemitter and Cas12a-mediated interfacial cleavage of the quencher, the developed ECL biosensor exhibited high sensitivity to COX III with a low detection limit of 0.18 pM. The established ECL biosensing method possessed excellent practical performance in urine samples. Meaningfully, the proposed strategy presents promising prospects for nucleic acid detection in the field of clinical diagnostics.

Multifunctional liposome for photoacoustic/ultrasound imaging-guided chemo/photothermal retinoblastoma therapy.

Retinoblastoma (RB) is a malignant intraocular neoplasm that occurs in children. Diagnosis and therapy are frequently delayed, often leading to metastasis, which necessitates effective imaging and treatment. In recent years, the use of nanoplatforms allowing both imaging and targeted treatment has attracted much attention. Herein, we report a novel nanoplatform folate-receptor (FR) targeted laser-activatable liposome termed FA-DOX-ICG-PFP@Lip, which is loaded with doxorubicin (DOX)/indocyanine green (ICG) and liquid perfluoropentane (PFP) for photoacoustic/ultrasound (PA/US) dual-modal imaging-guided chemo/photothermal RB therapy. The dual-modal imaging capability, photothermal conversion under laser irradiation, biocompatibility, and antitumor ability of these liposomes were appraised. The multifunctional liposome showed a good tumor targeting ability and was efficacious as a dual-modality contrast agent both in vivo and in vitro. When laser-irradiated, the liposome converted light energy to heat. This action caused immediate destruction of tumor cells, while simultaneously initiating PFP phase transformation to release DOX, resulting in both photothermal and chemotherapeutic antitumor effects. Notably, the FA-DOX-ICG-PFP@Lip showed good biocompatibility and no systemic toxicity was observed after laser irradiation in RB tumor-bearing mice. Hence, the FA-DOX-ICG-PFP@Lip shows great promise for dual-modal imaging-guided chemo/photothermal therapy, and may have significant value for diagnosing and treating RB.

Self-enhanced luminol-based electrochemiluminescent hydrogels: An ultrasensitive biosensing platform for fusion gene analysis coupled with target-initiated DNAzyme motor.

BCR/ABL fusion gene has been discovered as an important and reliable biomarker for early diagnosis of chronic myeloid leukemia (CML). Herein, a novel and switching electrochemiluminescence (ECL) biosensor was developed for ultrasensitive determination of the fusion gene based on the self-enhanced polyethyleneimine-luminol (PEI-Lum) hydrogels coupled with target-initiated DNAzyme motor. The facilely prepared PEI-Lum hydrogels could not only immobilize enormous luminol but shorten the distance of binary system, thus facilitating the mass and electron transfer efficiency of the sensing interface, so that the enhanced ECL signal was achieved. Moreover, the engineering DNA motor was powered by Mg2+-dependent DNAzyme for isothermal DNA signal amplification. As a result, the fabricated ECL biosensor enabled highly sensitive detection of BCR/ABL fusion gene with a broad linear range from 10.0 fM to 10.0 nM and a low detection limit of 3.75 fM (S/N = 3). Significantly, the developed biosensing method provides a potential tool for nucleic acid analysis in clinical diagnosis and a new avenue to design high-efficient ECL nanomaterials.

Dispersion-to-localization of catalytic hairpin assembly for sensitive sensing and imaging microRNAs in living cells from whole blood.

Localized DNA circuits have shown good performance regarding reaction rate and sensitivity for sensing intracellular microRNAs (miRNAs). However, these methods reported recently require large kinds of DNA strands and suffer from low signal-to-background (S/B) ratio, which hinder their clinical application. To circumvent these issues, we herein developed a novel strategy for sensitive sensing and imaging miRNAs in living cells based on dispersion-to-localization of catalytic hairpin assembly (DL-CHA). This strategy consists of only three classes of DNA strands (two hairpins and a linker strand), which largely reduces sequence design complexity. Additionally, owing to the unique engineering of the substrate transformation from dispersion to localization, the DL-CHA exhibits not only minimal background leakage but also intensive signal amplification, thus significantly improving the S/B ratio. In particular, the simple sensing method is capable of imaging miRNAs in cells from clinical blood samples for the diagnosis of breast cancer. Therefore, this work provides a powerful tool for intracellular molecules detection and gives a much broader design space for constructing high-performance DNA circuits.