The ZMYND8-regulated mevalonate pathway endows YAP-high intestinal cancer with metabolic vulnerability.

Cholesterol metabolism is tightly associated with colorectal cancer (CRC). Nevertheless, the clinical benefit of statins, the inhibitor of cholesterol biogenesis mevalonate (MVA) pathway, is inconclusive, possibly because of a lack of patient stratification criteria. Here, we describe that YAP-mediated zinc finger MYND-type containing 8 (ZMYND8) expression sensitizes intestinal tumors to the inhibition of the MVA pathway. We show that the oncogenic activity of YAP relies largely on ZMYND8 to enhance intracellular de novo cholesterol biogenesis. Disruption of the ZMYND8-dependent MVA pathway greatly restricts the self-renewal capacity of Lgr5+ intestinal stem cells (ISCs) and intestinal tumorigenesis. Mechanistically, ZMYND8 and SREBP2 drive the enhancer-promoter interaction to facilitate the recruitment of Mediator complex, thus upregulating MVA pathway genes. Together, our results establish that the epigenetic reader ZMYND8 endows YAP-high intestinal cancer with metabolic vulnerability.

Kinome and phosphoproteome reprogramming underlies the aberrant immune responses in critically ill COVID-19 patients.

SARS-CoV-2 infection triggers extensive host immune reactions, leading to severe diseases in certain individuals. However, the molecular basis underlying the excessive yet non-productive immune responses in severe COVID-19 remains incompletely understood. In this study, we conducted a comprehensive analysis of the peripheral blood mononuclear cell (PBMC) proteome and phosphoproteome in sepsis patients positive or negative for SARS-CoV-2 infection, as well as healthy subjects, using quantitative mass spectrometry. Our findings demonstrate dynamic changes in the COVID-19 PBMC proteome and phosphoproteome during disease progression, with distinctive protein or phosphoprotein signatures capable of distinguishing longitudinal disease states. Furthermore, SARS-CoV-2 infection induces a global reprogramming of the kinome and phosphoproteome, resulting in defective adaptive immune response mediated by the B and T lymphocytes, compromised innate immune responses involving the SIGLEC and SLAM family of immunoreceptors, and excessive cytokine-JAK-STAT signaling. In addition to uncovering host proteome and phosphoproteome aberrations caused by SARS-CoV-2, our work recapitulates several reported therapeutic targets for COVID-19 and identified numerous new candidates, including the kinases PKG1, CK2, ROCK1/2, GRK2, SYK, JAK2/3, TYK2, DNA-PK, PKCδ, and the cytokine IL-12.

The nitrogen-sulfur ratio of acid rain modulates the leaf- and root-mediated co-allelopathy of Solidago canadensis.

The majority of allelopathic studies on invasive plants have focused primarily on their leaf-mediated allelopathy, with relatively little attention paid to their root-mediated allelopathy, especially co-allelopathy mediated by both leaves and roots. It is conceivable that the diversified composition of acid rain may influence the allelopathy of invasive plants. This study aimed to evaluate the leaf and root-mediated co-allelopathy of the invasive plant Solidago canadensis L. under acid rain with different nitrogen-sulfur ratios (N/S) on Lactuca sativa L. via a hydroponic incubation. The root-mediated allelopathy of S. canadensis was found to be more pronounced than the leaf-mediated allelopathy of S. canadensis with nitric acid at pH 4.5, but the leaf-mediated allelopathy of S. canadensis was observed to be more pronounced than the root-mediated allelopathy of S. canadensis with sulfuric-rich acid at pH 4.5. The leaf and root-mediated co-allelopathy of S. canadensis was more pronounced than that of either part alone with sulfuric acid at pH 5.6 and nitric acid at pH 4.5, but not with nitric-rich acid at pH 4.5 and sulfuric-rich acid at pH 4.5. Sulfuric acid and sulfuric-rich acid with stronger acidity intensified the leaf-mediated allelopathy of S. canadensis. Nitric acid and nitric-rich acid attenuated the leaf-mediated allelopathy of S. canadensis, and most types of acid rain (especially nitric acid and nitric-rich acid) also attenuated the root-mediated allelopathy of S. canadensis and the leaf and root-mediated co-allelopathy of S. canadensis. Sulfuric acid and sulfuric-rich acid produced a more pronounced effect than nitric acid and nitric-rich acid. Hence, the N/S ratio of acid rain influenced the allelopathy of S. canadensis under acid rain with multiple N/S ratios.

What modulates the impacts of acid rain on the allelopathy of the two Asteraceae invasives?

Most of the allelopathic studies have focused on the independent allelopathy of one invasive plant, but have ignored the co-allelopathy of the two invasives. The variations in the type of acid rain can modulate the invasiveness of invasives via the changes in the allelopathy. Thus, it is vital to elucidate the allelopathy of invasives, particularly the co-allelopathy of the two invasives, under acid rain with different types, to illuminate the mechanisms driving the co-invasion of two invasives under diversified acid rain. However, little progress has been finished in this aspect presently. This study aimed to evaluate the co-allelopathy of two Asteraceae invasives Solidago canadensis L. and Erigeron annuus L. treated with acid rain with different nitrogen-to-sulfur ratios on seed germination and seedling growth of the horticultural Asteraceae species Lactuca sativa L. via a hydroponic experiment. Aqueous extracts of the two Asteraceae invasives generated obvious allelopathy on L. sativa. S. canadensis aqueous extracts caused stronger allelopathy. There may be an antagonistic effect for the co-allelopathy of the two Asteraceae invasives. Nitric acid at pH 5.6 weakened the allelopathy of the two Asteraceae invasives, but the other types of acid rain strengthened the allelopathy of the two Asteraceae invasives. The allelopathy of the two Asteraceae invasives increases with the increasing acidity of acid rain, but the allelopathy of the two Asteraceae invasives decreases with the increasing nitrogen-to-sulfur ratio of acid rain. Accordingly, the species number of invasives, and the acidity and type of acid rain modulated the impacts of acid rain on the allelopathy of the two Asteraceae invasives.

The co-phytotoxicity of two Asteraceae invasive plants Solidago canadensis L. and Bidens pilosa L. with different invasion degrees.

The phytotoxicity of invasive plants (IPS) has been identified as one of the main factors influencing their invasion success. The invasion of IPS can occur to varying degrees in the habitats. Two IPS can invade one habitat. This study aimed to evaluate the mono- and co-phytotoxicity of two Asteraceae IPS Solidago canadensis L. and Bidens pilosa L. with different invasion degrees (including light invasion (relative abundance <50%) and heavy invasion (relative abundance ≥50%)) on the horticultural Asteraceae species Lactuca sativa L., through a hydroponic experiment conducted on 9 cm Petri dishes. Leaf extracts of the two IPS can cause significant mono- and co-phytotoxicity. The mono- and co-phytotoxicity of the two IPS were concentration-dependent. The mono-phytotoxicity of S. canadensis was significantly increased with increasing invasion degree, but the opposite was true for the mono-phytotoxicity of B. pilosa. Leaf extracts of B. pilosa with light invasion caused stronger phytotoxicity than those of S. canadensis with light invasion. There may be an antagonistic effect for the co-phytotoxicity caused by mixed leaf extracts of the two IPS compared with those of either S. canadensis or B. pilosa. The phytotoxicity of the two IPS on the growth performance of neighboring plants may play a more important role in their mono-invasion than in their co-invasion. The phytotoxicity appeared to affect the growth performance of S. canadensis individuals more significantly when the invasion was heavy, while the growth performance of B. pilosa individuals seemed to be more influenced by phytotoxicity when the invasion was light. Consequently, the concentration of leaf extracts of IPS, the invasion degree of IPS, the species identity of IPS, and the species number of IPS modulated the mono- and co-phytotoxicity of the two IPS.

Circ_0000291 contributes to hepatocellular carcinoma tumorigenesis by binding to miR-1322 to up-regulate UBE2T.

INTRODUCTION AND OBJECTIVES: Circular RNAs (circRNAs) are identified to show important regulatory functions in cancer biology. We attempted to analyze the role of circ_0000291 in hepatocellular carcinoma (HCC) progression and its related mechanism. METHODS: The circular characteristic of circ_0000291 was tested using exonuclease RNase R. Cell proliferation was analyzed by 5-Ethynyl-2'-deoxyuridine (EdU) incorporation and colony formation assays. Cell apoptosis was measured by flow cytometry and a caspase 3 activity assay kit. Transwell assays were performed to analyze cell migration and invasion abilities. Sphere formation assay was conducted to analyze cell stemness. Dual-luciferase reporter and RNA-pull down assays were conducted to verify the interaction between microRNA-1322 (miR-1322) and circ_0000291 or ubiquitin conjugating enzyme E2 T (UBE2T). RESULTS: Circ_0000291 was markedly up-regulated in HCC tissues and cell lines. HCC patients with high expression of circ_0000291 displayed a low survival rate. Circ_0000291 knockdown restrained the proliferation, migration, invasion, and stemness and induced the apoptosis of HCC cells. Circ_0000291 directly interacted with miR-1322 and negatively regulated miR-1322 expression. Circ_0000291 knockdown-mediated anti-tumor impacts in HCC cells were largely overturned by the interference of miR-1322. miR-1322 directly paired with the 3' untranslated region (3'UTR) of UBE2T, and UBE2T was negatively regulated by miR-1322. UBE2T overexpression largely reversed circ_0000291 silencing-induced effects in HCC cells. Circ_0000291 positively regulated UBE2T expression by absorbing miR-1322 in HCC cells. Circ_0000291 silencing notably reduced the tumorigenic potential in vivo. CONCLUSION: Circ_0000291 facilitated HCC progression by targeting miR-1322/UBE2T axis, which provided novel potential biomarkers and targets for HCC patients.

Acid deposition at higher acidity weakens the antagonistic responses during the co-decomposition of two Asteraceae invasive plants.

Co-invasion by two invasive plant species (IPS) can occur in the same habitat. Diversified acid deposition may change the co-invasion process by altering litter decomposition and plant-soil feedback signalling. This study examined the co-decomposition of two Asteraceae IPS (Solidago canadensis L. and Bidens pilosa L.) on litter decomposition rate, soil enzyme activities, and soil N-fixing bacterial communities under diversified acid deposition (mixed acid deposition at pH 5.6 and at pH 4.5, sulfuric acid at pH 4.5, and nitric acid at pH 4.5). B. pilosa litter degraded faster than S. canadensis litter. Acid deposition at higher acidity accelerated the decomposition rate of both pure S. canadensis litter and the equally mixed litters from the two Asteraceae IPS. Antagonistic responses may occur during the co-decomposition of the two Asteraceae IPS with mixed acid deposition, regardless of the pH, as well as with nitric acid deposition at pH 4.5; in contrast, there may be neutral responses for the co-decomposition process with sulfuric acid at pH 4.5. The type of acid deposited may be one of the key factors affecting the intensity of the mixing effect affecting the co-decomposition. Acid deposition at higher acidity weakened the antagonistic responses for the co-decomposition of the two Asteraceae IPS compared with the response to weak acids. Together, these results indicate that acid deposition at higher acidity could facilitate the co-invasion of the two Asteraceae IPS mainly through accelerated litter decomposition as well as weakened antagonistic responses for co-decomposition.

DLC1 SAM domain-binding peptides inhibit cancer cell growth and migration by inactivating RhoA.

Deleted-in-liver cancer 1 (DLC1) exerts its tumor suppressive function mainly through the Rho-GTPase-activating protein (RhoGAP) domain. When activated, the domain promotes the hydrolysis of RhoA-GTP, leading to reduced cell migration. DLC1 is kept in an inactive state by an intramolecular interaction between its RhoGAP domain and the DLC1 sterile α motif (SAM) domain. We have shown previously that this autoinhibited state of DLC1 may be alleviated by tensin-3 (TNS3) or PTEN. We show here that the TNS3/PTEN-DLC1 interactions are mediated by the C2 domains of the former and the SAM domain of the latter. Intriguingly, the DLC1 SAM domain was capable of binding to specific peptide motifs within the C2 domains. Indeed, peptides containing the binding motifs were highly effective in blocking the C2-SAM domain-domain interaction. Importantly, when fused to the tat protein-transduction sequence and subsequently introduced into cells, the C2 peptides potently promoted the RhoGAP function in DLC1, leading to decreased RhoA activation and reduced tumor cell growth in soft agar and migration in response to growth factor stimulation. To facilitate the development of the C2 peptides as potential therapeutic agents, we created a cyclic version of the TNS3 C2 domain-derived peptide and showed that this peptide readily entered the MDA-MB-231 breast cancer cells and effectively inhibited their migration. Our work shows, for the first time, that the SAM domain is a peptide-binding module and establishes the framework on which to explore DLC1 SAM domain-binding peptides as potential therapeutic agents for cancer treatment.

Ketogenic diet prevents paclitaxel-induced neuropathic nociception through activation of PPARγ signalling pathway and inhibition of neuroinflammation in rat dorsal root ganglion.

Chemotherapy-induced peripheral neuropathy (CIPN) is a common side effect during the course of cancer treatment, which is mainly manifested as a series of sensory abnormalities. At present, there are no recommended prevention or treatment strategies, and the underlying mechanisms are unclear. The ketogenic diet (KD), a special diet that is high in fat and low in carbohydrate intake, shows good therapeutic potential in children with epilepsy. In this study, it was found that KD significantly prevented paclitaxel-induced neuropathic nociception. Using the GSE113941 database, 281 differentially expressed genes (DEGs) were found in an animal model of CIPN and controls. The DEGs were mainly enriched in peroxisome proliferator activated receptor (PPAR) and oxidative phosphorylation signalling pathways. As a main regulatory pathway of lipid metabolism, the PPARγ signalling pathway was significantly upregulated in the KD model. In addition, KD also inhibited the expression of pro-inflammatory cytokines and the TLR4/NF-κB signalling pathway in the dorsal root ganglion (DRG) in paclitaxel-treated rats. In vitro, rat primary DRG neurons were used to investigate the role of PPARγ in paclitaxel-induced neurotoxicity. It was found that PPARγ agonist rosiglitazone significantly protected DRG neurons against cell apoptosis and reactive oxygen species generation induced by paclitaxel administration. Therefore, KD is a prospective treatment option when applied as a dietary intervention in the prevention and treatment of paclitaxel-induced neuropathic nociception, possibly through the activation of PPARγ and its neuroprotective functions.

Diagnostic indicators for adult-onset neuronal intranuclear inclusion disease.

Adult-onset neuronal intranuclear inclusion disease (NIID) is a rare neurodegenerative disorder. Abnormally high signals of diffusion-weighted image (DWI) along the corticomedullary junction are a useful diagnostic indicator for patients with adult-onset NIID. However, the DWI abnormalities usually were observed in the late stage of disease; further study might be helpful to elucidate some clinical indicators regarding the early awareness of NIID. In this study, we summarized 9 patients with NIID from multiple centers. The mean age was 60.0 ± 6.2 years. The mean duration of disease was 4.4 ± 3.2 years. The most common symptoms included cognitive impairment, episodic encephalopathy, and bladder dysfunction. Among the 6 patients with bladder dysfunction, 3 patients had the symptom prior to the development of other neurological symptoms; 5 patients needed permanent cystostomy. Isolated high DWI signals on the splenium of corpus callosum were observed in 2 patients at the early stage. The characteristic intranuclear inclusions in the skin were identified in all patients and confirmed by electron microscopy. Episodic encephalopathy or bladder dysfunction prior to other neurological symptoms were valuable diagnostic indicators for adult-onset NIID. High DWI signals on the splenium of corpus callosum might be an early indicator for the diagnosis of NIID. The immunostain of anti-ubiquitin or anti-p62 antibody was a convenient and sensitive biomarker for NIID with the background of typical phenotype with cognitive impairment and autonomic dysfunctions.

Neuroprotective effects of miR-532-5p against ischemic stroke.

Stroke can cause death and disability and has a high incidence with many complications. So far, effective treatment options for stroke are still limited. MicroRNA-532-5p (miR-532-5p) is significantly downregulated in stroke. However, the role of miR-532-5p in ischemic stroke is still unclear. In this study, we established an in vivo middle cerebral artery occlusion (MCAO) model in mice. The expression level of miR-532-5p, neurological score, infarct area, neuronal apoptosis, and phosphoinositide 3-kinase (PI3K)/Akt signaling pathway-related molecules were examined. Low miR-532-5p levels and high phosphatase and tensin homolog deleted on chromosome 10 (PTEN) levels were detected in the mouse MCAO model. MiR-532-5p overexpression improved neurological dysfunction, reduced the infarct area, attenuated neuronal injury and apoptosis, and promoted the activation of the PI3K/Akt signaling pathway in MCAO mice. In vitro, we treated mouse neuroblastoma cells (N2a) with oxygen-glucose deprivation and reperfusion (OGD/R). The expression level of miR-532-5p, cell viability, cell apoptosis, and the PI3K/Akt signaling pathway-related molecules were detected. Consistent with the in vivo tests, the miR-532-5p level was decreased and the PTEN level was increased in OGD-treated N2a cells in vitro. The miR-532-5p mimic increased cell viability, decreased cell apoptosis, and activated the PI3K/Akt signaling pathway. Furthermore, PTEN was verified as a target gene of miR-532-5p by luciferase reporter assay. PTEN overexpression attenuated the protective effect of miR-532-5p in OGD-treated N2a cells. In summary, these findings reveal that miR-532-5p protects against ischemic stroke by inhibiting PTEN and activating the PI3K/Akt signaling pathway and may serve as a novel therapeutic target for ischemic stroke.

Targeting strategies for chemotherapy-induced peripheral neuropathy: does gut microbiota play a role?

Chemotherapy-induced peripheral neuropathy (CIPN) is a progressive, often irreversible condition that produces severe neurological deficits. Emerging data suggest that chemotherapy also exerts detrimental effects on gut microbiota composition and intestinal permeability, contributing to dysbiosis and inflammation. Compared with other complications associated with chemotherapy, such as diarrhoea and mucositis, CIPN is of particular concern because it is the most common reason for terminating or suspending treatment. However, specific and effective curative treatment strategies are lacking. In this review, we provide an update on current preclinical and clinical understandings about the role of gut microbiota in CIPN. The gut microbiota serves as an intersection between the microbiome-gut-brain and the neuroimmune-endocrine axis, forming a complex network that can directly or indirectly affect key components involved in the manifestations of CIPN. Herein, we discuss several potential mechanisms within the context of the networks and summarize alterations in gut microbiome induced by chemotherapeutic drugs, providing great potential for researchers to target pathways associated with the gut microbiome and overcome CIPN.

The MHC class I-LILRB1 signalling axis as a promising target in cancer therapy.

Immune checkpoint inhibitors are among the newest, cutting-edge methods for the treatment of cancer. Currently, they primarily influence T cell adaptive immunotherapy targeting the PD-1/PD-L1 and CTLA-4/B7 signalling pathways. These inhibitors fight cancer by reactivating the patient's own adaptive immune system, with good results in many cancers. With the discovery of the "Don't Eat Me" molecule, CD47, antibody-based drugs that target the macrophage-related innate immunosuppressive signalling pathway, CD47-SIRPα, have been developed and have achieved stunning results in the laboratory and the clinic, but there remain unexplained instances of tumour immune escape. While investigating the immunological tolerance of cancer to anti-CD47 antibodies, a second "Don't Eat Me" molecule on tumour cells, beta 2 microglobulin (ß2m), a component of MHC class I, was described. Some tumour cells reduce their surface expression of MHC class I to escape T cell recognition. However, other tumour cells highly express ß2m complexed with the MHC class I heavy chain to send a "Don't Eat Me" signal by binding to leucocyte immunoglobulin-like receptor family B, member 1 (LILRB1) on macrophages, leading to a loss of immune surveillance. Investigating the mechanisms underlying this immunosuppressive MHC class I-LILRB1 signalling axis in tumour-associated macrophages will be useful in developing therapies to restore macrophage function and control MHC class I signalling in patient tumours. The goal is to promote adaptive immunity while suppressing the innate immune response to tumours. This work will identify new therapeutic targets for the development of pharmaceutical-based tumour immunotherapy.

Increased Peripheral CD137 Expression in a Mouse Model of Permanent Focal Cerebral Ischemia.

Various studies demonstrate that CD137 (TNFRSF9, 4-1BB) promotes atherosclerosis and vascular inflammation in experimental models via interactions with the CD137 ligand (CD137L). However, the exact role of CD137 in ischemic stroke remains unclear. In this study, we analyzed dynamic changes of peripheral CD137 expression on T cells in a mouse model of cerebral ischemia-middle cerebral artery occlusion (MCAO), as well as alternation of neurological function, infarct size and cerebral inflammatory status after inhibition of the CD137/CD137L pathway using an anti-CD137L monoclonal antibody. MCAO mice showed elevated surface expression of CD137 on T cells in both peripheral blood and lymphoid tissues during early cerebral ischemia. Remarkably, blockade of the CD137/CD137L pathway reduced the post-ischemic brain damage. Our findings indicate that enhanced CD137 costimulation occurs in early cerebral ischemia and promotes T cell activation, which in turn upregulates inflammatory immune response and possibly exerting deleterious effects on cerebral ischemia.

Association of apolipoprotein E genotypes with epilepsy risk: A systematic review and meta-analysis.

OBJECTIVE: The objective of this study was to identify the association between certain genotypes or alleles of the APOE (Apolipoprotein E) gene and the epilepsy risk. METHODS: All studies on human APOE genotypes associated with epilepsy were included. Separate meta-analyses were conducted between the patients with epilepsy and the control group from the following three aspects: ε4 carriers or ε2 carriers vs ε3/ε3 (the ε2/ε4 genotype was excluded), ε4 carriers vs ε2 carriers, and five genotypes vs ε3/ε3. The subgroup analysis was conducted on the ethnicity, the control group was healthy or not, and type of epilepsy. RESULTS: Nine studies with 2210 individuals were included. Compared with ε3/ε3 genotype, ε4 carriers increased the epilepsy risk (odds ratios [ORs]: 1.27; 95% confidence intervals [CI]: 1.01 to 1.59; P = 0.042), while ε2 carriers had no association with epilepsy risk (OR: 0.88; 95% CI: 0.66 to 1.18; P = 0.184). The risk of epilepsy was 1.45 times greater in ε4 carriers compared with ε2 carriers (OR: 1.45; 95% CI: 1.02 to 2.04; P = 0.037). When the number of APOE ε4 allele increased, the ORs increased progressively (no ε4 alleles, OR: 0.88, 95% CI: 0.66 to 1.18; one ε4 allele, OR: 1.25, 95% CI: 0.99 to 1.57; two ε4 alleles, OR: 1.84, 95% CI: 0.83 to 4.10). Apolipoprotein E ε4 carriers had a higher epilepsy risk in the population without primary diseases (OR: 1.43; 95% CI: 1.09 to 1.88), and a higher risk in Asian populations (OR: 1.67; 95% CI: 1.12 to 2.49). CONCLUSIONS: Apolipoprotein E ε4 allele genotype was associated with an increased epilepsy risk, which was more prominent in the Asian and the population without primary diseases. These findings may be used to guide the directions of prevention and treatment on epilepsy. Larger clinical studies are needed.

Transition-metal-free synthesis of 3-sulfenylated chromones via KIO3-catalyzed radical C(sp2)-H sulfenylation.

The reactions between o-hydroxylphenyl-functionalized enaminones and sulfonyl hydrazines providing 3-sulfenylated chromones via domino chromone ring construction and C(sp2)-H bond sulfenylation have been achieved under transition-metal-free conditions by using KIO3 as the only catalyst.

Synthesis of ß,ß-diaryl propiophenones via palladium-catalyzed domino arylboronation, elimination and enone hydroarylation of enaminones.

The syntheses of ß,ß-diaryl aryl propiophenones have been realized via palladium-catalyzed domino reactions of dimethyl amino functionalized enaminones and aryl boronic acids. This is the first example of transition metal-catalyzed enaminone C-N bond conversion for the generation of a new C-C(aryl) structure.

Whole transcriptome analysis identifies differentially expressed mRNA, miRNA and lncRNA associated with male sterility in the silkworm, Bombyx mori.

Insect sterility technology is gradually being applied to the control of lepidoptera pests, and the target gene for male sterility is the core of this technology. JMS is a mutant silkworm that exhibits male sterility, and to elucidate its formation mechanism, this study conducted a full transcriptome analysis of the testes of JMS and its wild-type silkworms 48 h after pupation, identifying 205 DElncRNAs, 913 mRNAs, and 92 DEmiRNAs. The KEGG pathway enrichment analysis of the DEmRNAs revealed that they were involved in the biosynthesis of amino acids and ECM-receptor interactions. Combined with ceRNA regulatory network KEGG analysis suggests that pathways from amino acid biosynthesis to hydrolytic processes of protein synthesis may play a crucial role in the formation of JMS mutant variants. Our study deepens our understanding of the regulatory network of male sterility genes in silkworms; it also provides a new perspective for insect sterility technology.

Tuning quantum dots emission on DNA tetrahedron/silica nanosphere/graphene oxide nanointerface for ratiometric fluorescence assay of Pb2+ in multiplex samples.

BACKGROUND: Assembling framework nucleic acid (FNA) nanoarchitectures and tuning luminescent quantum dots (QDs) for fluorescence assays represent a versatile strategy in analytical territory. Rationally, FNA constructs could offer a preferential orientation to efficiently recognize the target and improve detection sensitivity, meanwhile, regulating size-dependent multicolor emissions of QDs in one analytical setting for ratiometric fluorescence assay would greatly simplify operation procedures. Nonetheless, such FNA/QDs-based ratiometric fluorescence nanoprobes remain rarely explored. RESULTS: We designed a sensitive and signal amplification-free fluorescence aptasensor for lead ions (Pb2+) that potentially cause extensive contamination to environment, cosmetic, food and pharmaceuticals. Red and green emission CdTe quantum dots (rQDs and gQDs) were facilely prepared. Moreover, silica nanosphere encapsulating rQDs served as quantitative internal reference and scaffold to anchor a predesigned FNA and DNA sandwich containing Pb2+ binding aptamer and gQD modified DNA signal reporter. On binding of Pb2+, the gQD-DNA signal reporter was set free, resulting in fluorescence quenching at graphene oxide (GO) interface. Owing to the rigid structure of FNA, the fluorescence signal reporter orderly arranged at the silica nanosphere could sensitively respond to Pb2+ stimulation. The dose-dependent fluorescence signal-off mode enabled ratiometric analysis of Pb2+ without cumbersome signal amplification. Linear relationship was established between fluorescence intensity ratio (I555/I720) and Pb2+ concentration from 10 nM to 2 µM, with detection limit of 1.7 nM (0.43 ppb), well addressing the need for Pb2+ routine monitoring. The designed nanoprobe was applied to detection of Pb2+ in soil, cosmetic, milk, drug, and serum samples, with the sensitivity comparable to conventional ICP-MS technique. SIGNIFICANCE: Given the programmable design of FNA and efficient recognition of target, flexible tuning of QDs emission, and signal amplification-free strategy, the present fluorescence nanoprobe could be a technical criterion for other heavy metal ions detection in a straightforward manner.