Gut microbiota, circulating cytokines and dementia: a Mendelian randomization study.

BACKGROUND: Some studies have shown that gut microbiota may be associated with dementia. However, the causal effects between gut microbiota and different types of dementia and whether cytokines act as a mediator remain unclear. METHODS: Gut microbiota, cytokines, and five dementia types, including Alzheimer's disease (AD), frontotemporal dementia (FTD), dementia with Lewy body (DLB), vascular dementia (VD), and Parkinson's disease dementia (PDD) were identified from large-scale genome-wide association studies (GWAS) summary data. We used Mendelian randomization (MR) to investigate the causal relationships between gut microbiota, cytokines, and five types of dementia. Inverse variance weighting (IVW) was used as the main statistical method. In addition, we explored whether cytokines act as a mediating factor in the pathway from gut microbiota to dementia. RESULTS: There were 20 positive and 16 negative causal effects between genetic liability in the gut microbiota and dementia. Also, there were five positive and four negative causal effects between cytokines and dementias. Cytokines did not act as mediating factors. CONCLUSIONS: Gut microbiota and cytokines were causally associated with five types of dementia, and cytokines seemed not to be the mediating factors in the pathway from gut microbiota to dementia.

Afterglow Performance of Phenylenevinylene-Based Semiconducting Polymer Nanoparticles Doped with Photosensitizers Containing Electron-Withdrawing Groups.

It is usually believed that doping with photosensitizers capable of generating singlet oxygen (1O2) plays a pivotal role in enhancing the afterglow performance of semiconducting polymer nanoparticles (SPNs). However, the effect of doping photosensitizer bearing electron-withdrawing groups has not been reported. Here we report the effect of doping with six photosensitizers possessing different electron-withdrawing groups on the afterglow performance of SPNs using poly[(9,9-di(2-ethylhexyl)-9H-fluo-rene-2,7-vinylene)-co-(1-methoxy-4-(2-ethylhexyloxy)-2,5-phenylenevinylene)] (PF-MEHPPV) as substrate. It was found that the afterglow performance of SPNs was significantly influenced by doping with photosensitizers bearing electron-withdrawing groups. For the doped photosensitizers with strong electron-withdrawing groups, the stronger the electron-withdrawing ability of the group, the worse of the afterglow performance of the SPN regardless of the 1O2 generation ability of the photosensitizer. When the doped photosensitizer exhibited weak or none electron-withdrawing effect, the 1O2 generation ability of the photosensitizer played a dominant role on the afterglow performance of the SPNs. This work deepens the understanding of the design and synthesis of SPNs with different afterglow properties.

Maternal inulin supplementation ameliorates prenatal methamphetamine exposure-induced hepatotoxicity and restores gut microbiota in mouse offspring.

Prenatal exposure to methamphetamine (METH) is an issue of global concern due to its adverse effects on offspring, particularly its impact on liver health, an area still not fully understood. Inulin, a recognized prebiotic, is thought to potentially ameliorate these developmental disorders and toxic injuries in progeny. To investigate the effects of prenatal METH exposure on the liver and the role of gut microbiota, we established a murine model, the subjects of which were exposed to METH prenatally and subsequently treated with inulin. Our findings indicate that prenatal METH exposure causes liver damage in offspring, as evidenced by a decreased liver index, histopathological changes, diminished glycogen synthesis, hepatic dysfunction, and alterations in mRNA profiles. Furthermore, it impairs the antioxidant system and induces oxidative stress, possibly due to changes in cecal microbiota and dysregulation of bile acid homeostasis. However, maternal inulin supplementation appears to restore the gut microbiota in offspring and mitigate the hepatotoxic effects induced by prenatal METH exposure. Our study provides definitive evidence of METH's transgenerational hepatotoxicity and suggests that maternal inulin supplementation could be an effective preventive strategy.

Inhibition of HIF-2α expression in cardiomyocytes attenuates PCB126-induced cardiotoxicity associated with decreased apoptosis through the PI3K/Akt and p53 signaling pathways.

PCB126, a type of polychlorinated biphenyl (PCB), is a persistent pollutant found in both biotic and abiotic environments and poses significant public health risks due to its potential to cause cardiac damage with prolonged exposure. Hypoxia-inducible factor-2α (HIF-2α) is part of the hypoxia-inducible factor (HIF) transcription complex family. Previous studies have shown that knocking out or inhibiting HIF-2α expression can ameliorate pulmonary hypertension and right ventricular dysfunction. This study aimed to investigate whether cardiac-specific knockout of HIF-2α can alleviate the cardiotoxicity caused by PCB126. In this study, cardiac-specific knockout mice and wild-type mice were orally administered PCB126 or corn oil (50 µg/kg/week) for eight weeks. Our findings indicated that PCB126 induces cardiotoxicity and myocardial injury, as evidenced by elevated cardiac enzyme levels and increased cardiac collagen fibers. RNA sequencing revealed that PCB126-induced cardiotoxicity involves the PI3K/Akt and p53 signaling pathways, which was confirmed by western blot analysis. Notably, cardiac-specific knockout of HIF-2α mitigated the damage caused by PCB126, reducing the expression of cardiac enzymes, inflammatory cytokines, and myocardial collagen fibers. Under normal conditions, conditional knockout (CKO) of the HIF-2α gene in cardiomyocytes did not affect the morphology or function of the mouse heart. However, HIF-2α CKO in the heart reduced the cardiotoxic effects of PCB126 by decreasing apoptosis through the PI3K/Akt and p53 signaling pathways. In conclusion, inhibiting HIF-2α expression in cardiomyocytes attenuated PCB126-induced cardiotoxicity by modulating apoptosis through these signaling pathways.

The gut microbiota contributes to methamphetamine-induced reproductive toxicity in male mice.

Methamphetamine (METH) is a psychostimulant drug belonging to the amphetamine-type stimulant class, known to exert male reproductive toxicity. Recent studies suggest that METH can disrupt the gut microbiota. Furthermore, the gut-testis axis concept has gained attention due to the potential link between gut microbiome dysfunction and reproductive health. Nonetheless, the role of the gut microbiota in mediating the impact of METH on male reproductive toxicity remains unclear. In this study, we employed a mouse model exposed to escalating doses of METH to assess sperm quality, testicular pathology, and reproductive hormone levels. The fecal microbiota transplantation method was employed to investigate the effect of gut microbiota on male reproductive toxicity. Transcriptomic, metabolomic, and microbiological analyses were conducted to explore the damage mechanism to the male reproductive system caused by METH. We found that METH exposure led to hormonal disorders, decreased sperm quality, and changes in the gut microbiota and testicular metabolome in mice. Testicular RNA sequencing revealed enrichment of several Gene Ontology terms associated with reproductive processes, as well as PI3K-Akt signaling pathways. FMT conveyed similar reproductive damage from METH-treated mice to healthy recipient mice. The aforementioned findings suggest that the gut microbiota plays a substantial role in facilitating the reproductive toxicity caused by METH, thereby highlighting a prospective avenue for therapeutic intervention in the context of METH-induced infertility.

2-Ethylhexyl diphenyl phosphate aggravates colitis-induced neuroinflammation and behavioral abnormalities by inhibiting the PI3K-AKT-NF-κB and Wnt/GSK3ß signaling pathways.

2-Ethylhexyl diphenyl phosphate (EHDPHP), a widely used organophosphorus flame retardant (OPFR), is ubiquitous in daily life because of its extensive application in plastic production. EHDPHPs, which are only superficially applied and not chemically bonded to products, are released into the environment, posing potential health risks. With increasing environmental concentrations, EHDPHP is a growing threat, particularly to individuals with preexisting health conditions who are more susceptible to environmental pollutants. This study examined the effects of EHDPHP exposure in a colitis model, reflecting a rising chronic health issue, by assessing changes in neuroinflammation and neurobehavioral abnormalities. Healthy and dextran sulfate sodium (DSS)-induced colitis C57BL/6 J mice were treated with either 0.2 % Tween or EHDPHP solution (10 mg/kg body weight/day) for 28 days. The study revealed significant increases in the serum and expression levels of TNFα and IL-1ß, accompanied by depressive and anxiety-like behaviors. Coexposure to EHDPHP and DSS exacerbated these neurobehavioral impairments. RNA sequencing confirmed that EHDPHP triggered inflammation via the PI3K-Akt-NF-κB and Wnt/GSK3ß signaling pathways, as confirmed by Western blot analysis. These findings suggest that EHDPHP aggravates colitis-induced neuroinflammation and neurobehavioral abnormalities, highlighting the harmful impact of EHDPHP, particularly in individuals with preexisting inflammatory conditions.

CircFOXN2 alleviates glucocorticoid- and tacrolimus-induced dyslipidemia by reducing FASN mRNA stability by binding to PTBP1 during liver transplantation.

We aimed to examine impacts and functional mechanism of circular RNA forkhead box N2 (FOXN2) in tacrolimus (TAC)- and dexamethasone (Dex)-induced lipid metabolism disorders. RNA level and protein contents in TAC, Dex, or combined TAC- plus Dex-treated patients and Huh-7 cells were measured utilizing quantitative real-time (qRT)-PCR and western blotting assays measured the formation of lipid droplet. Total cholesterol (TC) and triglyceride (TG) levels were determined using corresponding commercial kits and Oil red O staining. RNA immunoprecipitation and RNA pull-down verified the binding relationship among circFOXN2, polypyrimidine tract binding protein 1 (PTBP1) and fatty acid synthase (FASN). Male C57BL/6 mice were used to establish a dyslipidemia mouse model to validate the discoveries at the cellular level. Dex treatment significantly promoted TAC-mediated increase of TC and TG in serum samples and Huh-7 cells. Moreover, circFOXN2 was reduced but FASN was elevated in TAC-treated Huh-7 cells, and these expression trends were markedly enhanced by Dex cotreatment. Overexpression of circFOXN2 could reverse the accumulation of TC and TG and the upregulation of FASN and sterol regulatory element binding transcription factor 2 (SREBP2) mediated by Dex and TAC cotreatment. Mechanistically, circFOXN2 reduced FASN mRNA stability by recruiting PTBP1. The protective roles of circFOXN2 overexpression on lipid metabolism disorders were weakened by FASN overexpression. In vivo finding also disclosed that circFOXN2 greatly alleviated the dysregulation of lipid metabolism triggered by TAC plus Dex. CircFOXN2 alleviated the dysregulation of lipid metabolism induced by the combination of TAC and Dex by modulating the PTBP1/FASN axis.NEW & NOTEWORTHY Collectively, our experiments revealed for the first time that circFOXN2 alleviated the Dex- and TAC-induced dysregulation of lipid metabolism by regulating the PTBP1/FASN axis. These findings suggested that circFOXN2 and FASN might be candidate targets for the treatment of Dex- and TAC-induced metabolic disorders.

Inulin alleviates neuroinflammation and oxidative stress induced by perinatal 2-ethylhexyl diphenyl phosphate (EHDPHP) exposure in female mice and offspring.

Organophosphorus flame retardants (OPFRs), including 2-ethylhexyl diphenyl phosphate (EHDPHP), are prevalent in everyday life due to their broad usage in fields such as healthcare, electronics, industry, and sports. These compounds, added to polymers through physical mixing, can leach into the environment, posing a risk to humans through direct contact or the food chain. Despite known associations with health issues like endocrine disruption, neurotoxicity, and reproductive toxicity, the implications of perinatal EHDPHP exposure on both mothers and offspring are still unclear. This study aimed to investigate the neuroinflammatory effects of EHDPHP and the potential mitigating role of inulin. Pregnant C57 mice were administered either a corn oil control or an EHDPHP solution (300 µg/kg bw/d) from gestation day 7 (GD7) to postnatal day 21 (PND21). Concurrently, mice were provided either regular drinking water or water supplemented with 1% inulin. We found that EHDPHP significantly increased the serum levels of IL-1ß, IL-6, and MDA, but decreased SOD levels in both mothers and pups. These effects were reversed by inulin supplementation. RNA-sequencing revealed that EHDPHP induced inflammation and oxidative stress through the TLR4/NF-κB pathway, which was mitigated by inulin. In conclusion, inulin ameliorated EHDPHP-induced neuroinflammation and oxidative stress in both mothers and offspring, highlighting its potential therapeutic role.

Ratiometric Luminescence Aptasensor Based on Dual-Emissive Persistent Luminescent Nanoparticles for Autofluorescence- and Exogenous Interference-Free Determination of Trace Aflatoxin B1 in Food Samples.

Sensitive and accurate determination of aflatoxin B1 (AFB1) is of great significance to food safety and human health as it is recognized as the most toxic mycotoxin and carcinogenic. Herein, we report a ratiometric luminescence aptasensor based on dual-emissive persistent luminescent nanoparticles (PLNP) for the accurate determination of trace AFB1 in complex food samples without autofluorescence and exogenous interference. Dual-emissive PLNP ZnGa2O4:Cr0.0001 was prepared first and acted as the donor for energy transfer as well as the signal unit with phosphorescence at 714 and 508 nm (the detection and the reference signal, respectively). AFB1 aptamer was then bonded on the surface of PLNP to offer specific recognition ability. Aptamer complementary DNA modified with Cy5.5 was employed as the acceptor for energy transfer and the quenching group to eventually develop a turn-on ratiometric luminescence aptasensor. The developed ratiometric luminescence aptasensor combined the merits of long-lasting luminescence, in situ excitation and autofluorescence-free of PLNP, exogenous interference-free and self-calibration reading of ratiometric sensor, as well as the high selectivity of aptamer, holding great promise for accurate determination of trace AFB1 in complex matrix. The developed ratiometric aptasensor exhibited excellent linearity (0.05-70 ng mL-1), low limit of detection (0.016 ng mL-1), and good precision (2.3% relative standard deviation for 11 replicate determination of 1 ng mL-1 AFB1). The proposed ratiometric aptasensor was successfully applied for the determination of AFB1 in corn, wheat, peanut, millet, oats, and wheat kernels with recoveries of 95.1-106.5%.

Methamphetamine induces intestinal injury by altering gut microbiota and promoting inflammation in mice.

Methamphetamine (METH) is a psychostimulant abused worldwide. Its abuse induces intestinal toxicity. Moreover, the gut microbiota is altered by drugs, which induces intestinal injury. Whether gut microbiota mediates METH-induced intestinal toxicity remains to be validated. In the present study, wild-type and TLR4-/- mice were treated with METH. Gut microbiota was determined using 16S rRNA gene sequencing. Transcriptomics of the intestinal mucosa was performed by RNA-Sequencing. Blood levels of pro-inflammatory cytokines and lipopolysaccharide (LPS), the intestinal barrier, and inflammation were also assessed. METH treatment weakened the intestinal barrier and increased pro-inflammatory cytokines and LPS levels in the blood. Moreover, METH treatment significantly decreased the diversity of probiotics but increased the abundance of pathogenic gut microbiota, contributing to the over-production of LPS and disruption of intestinal barrier. Inflammatory pathways were enriched in the intestinal mucosa of METH-treated mice by KEGG analysis. Consistently, activation of the TLR4 pathway was determined in METH-treated mice, which confirmed intestinal inflammation. However, pretreatment with antibiotics or Tlr4 silencing significantly alleviated METH-induced gut microbiota dysbiosis, LPS over-production, intestinal inflammation, and disruption of the intestinal barrier. These findings suggested that the gut microbiota and LPS-mediated inflammation took an important role in METH-induced intestinal injury. Taken together, these findings suggest that METH-induced intestinal injury is mediated by gut microbiota dysbiosis and LPS-associated inflammation.

Silencing the Tlr4 Gene Alleviates Methamphetamine-Induced Hepatotoxicity by Inhibiting Lipopolysaccharide-Mediated Inflammation in Mice.

Methamphetamine (METH) is a stimulant drug. METH abuse induces hepatotoxicity, although the mechanisms are not well understood. METH-induced hepatotoxicity was regulated by TLR4-mediated inflammation in BALB/c mice in our previous study. To further investigate the underlying mechanisms, the wild-type (C57BL/6) and Tlr4-/- mice were treated with METH. Transcriptomics of the mouse liver was performed via RNA-sequencing. Histopathological changes, serum levels of metabolic enzymes and lipopolysaccharide (LPS), and expression of TLR4-mediated proinflammatory cytokines were assessed. Compared to the control, METH treatment induced obvious histopathological changes and significantly increased the levels of metabolic enzymes in wild-type mice. Furthermore, inflammatory pathways were enriched in the liver of METH-treated mice, as demonstrated by expression analysis of RNA-sequencing data. Consistently, the expression of TLR4 pathway members was significantly increased by METH treatment. In addition, increased serum LPS levels in METH-treated mice indicated overproduction of LPS and gut microbiota dysbiosis. However, antibiotic pretreatment or silencing Tlr4 significantly decreased METH-induced hepatic injury, serum LPS levels, and inflammation. In addition, the dampening effects of silencing Tlr4 on inflammatory pathways were verified by the enrichment analysis of RNA-sequencing data in METH-treated Tlr4-/- mice compared to METH-treated wild-type mice. Taken together, these findings implied that Tlr4 silencing, comparable to antibiotic pretreatment, effectively alleviated METH-induced hepatotoxicity by inhibiting LPS-TLR4-mediated inflammation in the liver.

mRNA microarray analysis for the identification of potential biomarkers for vital reaction in burned skin: a preliminary pilot study.

The identification of ante- and post-mortem burns is challenging in forensic pathology. In this study, microarray analysis was used to detect the mRNA expression profiles in the skin of an experimental burn mouse model; the results were validated using RT-qPCR. Differentially expressed mRNAs (DE-mRNAs) were assessed using the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases. Our results revealed that mRNA expression of 501 genes was significantly different, of which 273 were upregulated and 228 were downregulated in ante-mortem burned mice skin. The expression levels of eight random mRNAs were consistent when measured using the microarray assay-based method and RT-qPCR. Genes from different functional categories and signalling pathways were enriched, including interleukin-20 binding, type IV hypersensitivity, negative regulation of acute inflammatory response, sensory organ development, endocytosis, neuroactive ligand-receptor interaction, and Jak-STAT signalling pathway. Only five of the eight mRNAs exhibited consistent changes in expression between burned skin samples of mice and human autopsy specimens. Our findings showed that DE-mRNAs revealed using microarray are potential biomarkers of ante-mortem burns. However, DE-mRNAs identified from experimental animal models cannot be directly extended to autopsy specimens without careful validation.

Emerging role of RNF2 in cancer: From bench to bedside.

RNF2 (also known as ding, Ring1B or Ring2) is a member of the Ring finger protein family, which functions as E3 ubiquitin ligase for monoubiquitination of histone H2A at lysine 119 (H2AK119ub). RNF2 gene is located at the 1q25.3 site of human chromosome and the coding region is composed of 9 exons, encoding 336 amino acids in total. Many studies have demonstrated that overexpressed RNF2 was involved in the pathological progression of multiple cancers and has an impact on their clinical features. For instance, the upregulated expression level of RNF2 is positively correlated with the occurrence and progression of hepatocellular carcinoma, melanoma, prostate cancer, breast cancer, pancreatic cancer, gastric cancer, and bladder urothelial carcinoma, as well as with the radioresistance of lung cancer and chemoresistance of ovarian cancer. This review provides an up-to-date perspective on the relationship between RNF2 and several cancers and highlights recent studies on RNF2 regulation. In particular, the relevant cellular signaling pathways and potential clinical value of RNF2 in cancers are also discussed, suggesting its potential as an epigenetic biomarker and therapeutic target for these cancers.

Functionalized Persistent Luminescence Nanoparticle-Based Aptasensor for Autofluorescence-free Determination of Kanamycin in Food Samples.

Selective and sensitive determination of trace kanamycin in complex food samples is of great importance for food safety because of its high toxicity. Here, we report a sensitive and autofluorescence-free persistent luminescence (PL) aptasensor for selective, sensitive, and autofluorescence-free determination of kanamycin in food samples. The aptamer for kanamycin was first conjugated onto the surface of magnetic nanoparticles Fe3O4 to serve as the recognition unit as well as the separation element, while the PL nanoparticles ZnGa2O4:Cr (PLNPs) were functionalized with the aptamer complementary DNA (cDNA) as the PL signal. The PL aptasensor consisted of the aptamer-conjugated MNPs (MNPs-apt) and cDNA-functionalized PLNPs (PLNPs-cDNA) and combined the merits of the long-lasting luminescence of PLNPs, the magnetic separation ability of MNPs as well as the selectivity of the aptamer, offering a promising approach for autofluorescence-free determination of kanamycin in food samples. The proposed aptasensor showed excellent linearity in the range from 1 pg mL-1 to 5 ng mL-1 with a limit of detection of 0.32 pg mL-1. The precision for 11 replicate determinations of 100 pg mL-1 kanamycin was 3.1% (relative standard deviation). The developed aptasensor was applied for the determination of kanamycin in milk and honey samples with the recoveries of 95.4-106.3%. The proposed aptasensor is easily extendable to other analytes by simply replacing the aptamer, showing great potential as a universal aptasensor platform for selective, sensitive, and autofluorescence-free detection of hazardous analytes in food samples.

Dual-Emissive Persistent Luminescence Nanoparticle-Based Charge-Reversible Intelligent Nanoprobe for Persistent Luminescence-Ratio Bioimaging along with Chemo-Photothermal Synergic Therapy.

Persistent luminescence nanoparticles (PLNPs) hold great promise for bioimaging owing to no demand for in situ excitation and negligible tissue autofluorescence interference. Nevertheless, huge challenges remain in the further development of single-emissive PLNPs due to the great variation of luminescence with time after excitation ceases. Herein, we report the controllable fabrication of dual-emissive monodispersed PLNPs (ZnGa2O4:Cr) by a surfactant-assisted hydrothermal method in combination with postcalcination for bioimaging. The prepared PLNPs emit luminescence at 508 and 714 nm with a constant luminescence ratio (I508/I714) for more than 1 h after UV excitation stops. Moreover, the prepared PLNPs give a constant I508/I714 ratio signal after repeated excitation by a LED lamp, allowing luminescence ratio imaging to ensure the long-term accuracy for in vivo imaging. In vivo ratio imaging demonstrates the potential of the prepared PLNPs for precision bioimaging. In addition, the prepared PLNPs have been applied to fabricate a theranostic nanoprobe with intelligent tumor-targeted imaging and chemo-photothermal synergistic therapy to further reveal their unique advantage for imaging guided therapy. We believe that the dual-emissive PLNPs will provide a promising nanoplatform for bioimaging and biomedical applications.

Effect of Topology on Photodynamic Sterilization of Porphyrinic Metal-Organic Frameworks.

Porphyrinic metal-organic frameworks (MOFs) are promising photosensitizers due to the lack of self-aggregation of porphyrin in aqueous solution. However, how the topology of porphyrinic MOFs affects the generation of singlet oxygen (1 O2 ) is unclear. Here, the effect of the topology of porphyrinic MOFs on their photodynamic performance is reported. Four porphyrinic zirconium MOFs (MOF-525, MOF-545, PCN-223 and PCN-224 with different topologies: ftw, csq, shp and she, respectively) were selected to study the influence of topology on the photodynamic antibacterial performance. The 1 O2 generation and the photodynamic antibacterial performance followed an decreasing order of MOF-545>MOF-525>PCN-224>PCN-223. The results reveal that the pore size, the distance between porphyrin, and the number of porphyrin per Zr6 O8 cluster in MOFs greatly affected 1 O2 generation. This work provides guidance for designing new MOFs for efficient photodynamic sterilization.

pH-Responsive Torpedo-Like Persistent Luminescence Nanoparticles for Autofluorescence-Free Biosensing and High-Level Information Encryption.

Persistent luminescent nanoparticles (PLNPs) with intrinsic stimuli-responsive properties are desirable because of no autofluorescence background and natural responsive luminescence. However, the stimuli-responsive features of pure PLNPs have been unexplored. Here we show a facile one-pot hydrothermal synthesis of green-emitting Zn2 GeO4 :Mn2+ ,Pr3+ nanoparticles (ZGMP) with regular shape, uniform size and good afterglow luminescent performance. We also report the pH stimuli-responsive luminescent behavior of ZGMP and its possible mechanism. Taking the intriguing feature of pH responsive persistent luminescence, we explore ZGMP as autofluorescence-free probes to achieve stimuli-activated signal switch for biosensing by integrating enzyme catalysis reaction mediated pH modulation. The pH-responsive persistent luminescence also makes ZGMP promising for high-level information encryption.

pH-Driven Targeting Nanoprobe with Dual-Responsive Drug Release for Persistent Luminescence Imaging and Chemotherapy of Tumor.

Multifunctional nanoprobes with both imaging and drug delivery capabilities represent an emerging approach to the diagnosis and treatment of tumor. However, poor accumulation in tumor cells and low drug availability are the main limitations for their further application. Here we show a pH-driven targeting nanoprobe with dual-responsive drug release for persistent luminescence imaging and chemotherapy of tumor. The nanoprobe is constructed by conjugating the pH-low-insertion-peptide (pHLIP) to the surface of the core-shell structure of mesoporous silica-coated persistent luminescence nanoparticles (MSPLNPs) with the peptide GFLG and disulfide bond as bridges. The pHLIP functionalized nanoprobe exhibits higher cellular uptake for A549 and HepG2 cells in an acidic extracellular microenvironment (pH < 6.5) than in normal physiological condition (pH 7.4). The nanoprobe possesses well-defined NIR persistent luminescence performance and can be effectively accumulated in the tumor site, leading to the visual HepG2 tumor target imaging without autofluorescence interference. Furthermore, the nanoprobe realizes the dual-responsive release of doxorubicin loaded in the mesoporous channels in systems containing cathepsin B and glutathione, and can effectively kill tumor cells and inhibit the growth of tumor. This integrated nanoprobe possesses great potential for the diagnosis and treatment of tumors with high specificity and efficiency.

Long Non-Coding RNA CRNDE Regulates Angiogenesis in Hepatoblastoma by Targeting the MiR-203/VEGFA Axis.

OBJECTIVE: MiR-203 has been shown to participate in multiple malignancies, but the role of miR-203 in hepatoblastoma (HB) remains unclear. The aim of our study was to investigate the effects of miR-203 in HB. METHODS: A total of 15 pairs of HB tissues and para-tumour normal tissues were collected for the experiments. RT-qPCR and Western blotting were performed to detect the expression of CRNDE, miR-203, and VEGFA at the mRNA and/or protein levels, respectively. A dual luciferase assay verified the target relationship between miR-203 and the 3'UTR of VEGFA as well as miR-203 and CRNDE. In addition, MTT, wound healing, and tube formation assays were performed to assess the effects of miR-203, VEGFA, and CRNDE on cell proliferation, migration, and angiogenesis, respectively. RESULTS: Our data revealed that miR-203 expression was decreased in HB tissues, while long non-coding RNA (lncRNA) CRNDE expression was increased. The dysregulation of miR-203 and CRNDE was closely related to tumour size and stage. Moreover, overexpression of miR-203 inhibited angiogenesis. A dual luciferase assay verified that VEGFA is a direct target of miR-203 and that CRNDE binds to miR-203. Furthermore, our results showed that miR-203 suppressed cell viability, migration, and angiogenesis by regulating VEGFA expression. Additionally, it was confirmed that CRNDE promoted angiogenesis by negatively regulating miR-203 expression. CONCLUSION: lncRNA CRNDE targets the miR-203/VEGFA axis and promotes angiogenesis in HB. These results provide insight into the underlying mechanisms of HB and indicate that CRNDE and miR-203 might be potential targets for HB therapy.

p-Bromophenol-Enhanced Bienzymatic Chemiluminescence Competitive Immunoassay for Ultrasensitive Determination of Aflatoxin B1.

Aflatoxin B1 (AFB1) contamination is one of the most critical global issues in food safety. The high carcinogenic nature necessitates rapid and specific methods for the determination of AFB1 in foodstuffs at ultratrace levels. Here, we report an enhanced bienzymatic chemiluminescence competitive immunoassay for ultrasensitive and high-throughput determination of AFB1. In this assay, protein G was first coated on the wells of a microplate for recognizing the Fc fragment of anti-AFB1 mAbs to reduce the antibody dosage and guarantee high immunological reaction efficiency. The target AFB1 competed with glucose oxidase labeled AFB1 for the limited anti-AFB1 mAbs in the wells of the microplate. p-Bromophenol was employed as an enhancer to obtain intense and long-lasting chemiluminescence. The utilization of an enhancer and bienzymatic catalysts effectively improved the detection sensitivity. The developed method offered a good linearity over 5 orders of magnitude, a detection limit of 5 pg L-1, and a relative standard deviation of 1.9% for AFB1. The application of the developed method to the analysis of grain samples gave quantitative recoveries from 94.0% to 97.0%. The developed method provides a universal platform for high-throughput, ultrasensitive, and high specific detection of pollutants or nutrients in foods.