Hydrophobic carbon quantum dots with red fluorescence: An optical dual-mode and smartphone imaging sensor for identifying Chinese Baijiu quality.

Chinese Baijiu (Liquor) is a popular alcoholic beverage, and the ethanol content in Baijiu is closely related to its quality; therefore, it is of great significance to explore a facile, sensitive, and rapid method to detect ethanol content in Baijiu. Hydrophobic carbon quantum dots (H-CQDs) with bright red fluorescence (24.14 %) were fabricated by hydrothermal method using o-phenylenediamine, p-aminobenzoic acid, manganese chloride, and hydrochloric acid as reaction precursors. After the introduction of ultrapure water into the ethanol solution dissolved with H-CQDs, the aggregated H-CQDs resulted in significant changes in fluorescence intensity and absorbance. On this basis, a sensor for detecting ethanol by optical dual-mode and smartphone imaging was constructed. More importantly, the sensor can be used for detecting ethanol content in Chinese Baijiu with satisfactory results. This sensing platform has great potential for quality identification in Chinese Baijiu, broadening the application scope of CQDs in food safety detection.

Novel Association of KLRC4-KLRK1 Gene Polymorphisms with Susceptibility and Progression of Antithyroid Drug-Induced Agranulocytosis.

OBJECTIVE: Antithyroid drug (ATD)-induced agranulocytosis (TIA) is the most serious adverse effect during ATD treatment of Graves' disease (GD). Previously, the MICA gene was reported to be associated with TIA. MICA protein is an important ligand for the NKG2D protein, which is encoded by the KLRK1 gene and KLRC4-KLRK1 read-through transcription. This study further investigated the association between KLRC4-KLRK1 gene polymorphisms and susceptibility to TIA. METHODS: Twenty-eight candidate single nucleotide polymorphisms (SNPs) on KLRC4-KLRK1 read-through transcription were evaluated by the iPLEX MassARRAY system in 209 GD control patients and 38 TIA cases. RESULTS: A significant association of rs2734565 polymorphism with TIA was found (p=0.02, OR=1.80, 95% CI=1.09-2.96). The haplotype C-A-A-C-G, including rs2734565-C, was associated with a significantly higher risk of TIA (p=4.79E-09, OR=8.361, 95% CI=3.737-18.707). In addition, the interval time from hyperthyroidism to agranulocytosis onset was shorter in patients carrying the rs2734565-C allele than in non-carrying groups (45.00 (14.00-6570.00) d vs. 1080.00 (30.00-3600.00) d, p=0.046), and the interval from ATD treatment to agranulocytosis onset was also shorter in patients carrying rs2734565-C allele (29.00 (13.00-75.00) d vs. 57.50 (21.00-240.00) d, p=0.023). CONCLUSIONS: The findings suggest that the KLRC4-KLRK1 gene polymorphism is associated with susceptibility and progression of ATD-induced agranulocytosis. Patients carrying the rs2734565-C allele had a higher susceptibility and faster onset time of TIA.

Sequenced-based Rwanda population provides insights into demographic history.

Rwanda is known as the heart of Africa, reflecting the history of the world. Colonization and genocide have led to Rwanda's existing genetic structure. Herein, we used massively parallel sequencing to analyze 296 loci in 185 Rwandans and constructed a database for Rwandan forensic data for the first time. We found the following results: First, forensic parameters demonstrated that all loci were highly informative and could be used for forensic identification and paternity tests in Rwandans. Second, we found that the differences in genetic background between Rwandans and other African populations were similar but slight, as indicated by the massively parallel sequencing panel. Rwandans belonged to the African population and were inseparable from populations from neighboring countries. Also, Rwandans were closer to the European and American populations because of colonization, war, and other reasons. There was no scientific basis for racial classification established by colonization. Further research still needs to be carried out on more loci and larger Rwandan samples.

Screening of Genes Co-Associated with Sudden Infant Death Syndrome and Infectious Sudden Death in Infancy and Bioinformatics Analysis of Their Regulatory Networks.

OBJECTIVES: The common differentially expressed mRNAs in brain, heart and liver tissues of deceased sudden infant death syndrome (SIDS) and infectious sudden death in infancy (ISDI) confirmed by autopsy was screened by bioinformatics to explore the common molecular markers and pathogenesis of SIDS and ISDI. METHODS: The datasets of GSE70422 and GSE136992 were downloaded, the limma of R software was used to screen differentially expressed mRNA in different tissue samples of SIDS and ISDI decedents for overlapping analysis. The clusterProfiler of R software was used to conduct gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. The protein-protein interaction (PPI) network was constructed by STRING database, while the hub gene was screened by cytoHubba plug-in. RESULTS: Compared with the control group, there were 19 significant differentially expressed genes in the tissue samples of SIDS and ISDI decedents, among which 16 in the heart tissue and 3 in the liver tissue, and the astrotactin 1 (ASTN1) gene expression difference in the heart tissue was most significant. The PPI network identified Ras homolog family member A (RHOA), integrin subunit alpha 1 (ITGA1), and H2B clustered histone 5 (H2BC5) were hub genes. The analysis of GO and KEGG showed that differentially expressed genes were enriched in the molecular pathways of actin cytoskeleton regulation, focal adhesion and response to mycophenolic acid. CONCLUSIONS: ASTN1, RHOA and ITGA1 may participate in the development of SIDS and ISDI. The enrichment of differentially expressed genes in immune and inflammatory pathways suggests a common molecular regulatory mechanism between SIDS and ISDI. These findings are expected to provide new biomarkers for molecular anatomy and forensic identification of SIDS and ISDI.

Drug-Primed Self-Assembly of Platinum-Single-Atom Nanozyme to Regulate Cellular Redox Homeostasis Against Cancer.

Single-atom nanozymes (SAzymes) with high catalytic activity exhibit the potential to disequilibrate the reactive oxygen metabolic balance in the tumor microenvironment (TME), which contains several endogenous reductive substances such as glutathione (GSH). Herein, a novel nano-assembly (CDs@Pt SAs/NCs@DOX) is first constructed using drug-primed platinum (Pt) single-atom or nanocluster nanozymes with a Pt loading of 34.8%, which exhibits prominent dual enzymatic activities to mimic peroxidase (POD) and glutathione oxidase (GSHOx). The unique GSHOx-like activity can efficiently scavenge GSH with a relatively low Km (1.04 mm) and high Vmax (7.46 × 10-6  m s-1 ), thus avoiding single oxygen (1 O2 ) depletion. CDs@Pt SAs/NCs@DOX simultaneously demonstrates low-temperature photothermal therapy and TME- or laser-controlled disassembly and drug release, which can effectively regulate cellular redox homeostasis and achieve high tumor growth inhibition. These outcomes may provide promising strategies for the preparation of Pt SAzymes with multiple activities and variable-sized nano-assemblies, allowing for broader applications of SAzymes and nano-assemblies in the biomedical field.

Paper-based visualization of auramine O in food and drug samples with carbon dots-incorporated fluorescent microspheres as sensing element.

A paper-based assay for visualization of auramine O (AO) was for the first time established by using CFMs as a ratiometric fluorescent probe (RFP). The CFMs were melamine formaldehyde microspheres (MFMs) incorporated with carbon dots (CDs), where the CDs species as sensing units and MFMs as a signal amplification carrier. The proposed RFP can quantitatively measure AO content from 0.0 to 10.0 µM and exhibited an ultralow limit of detection (LOD, 15.7 nM). In particular, obvious luminescence color change of CFMs from blue to green was perceived with naked-eyes and therefore, a solution-based and a paper-based visualization platform were respectively proposed for on-site visual detection of AO with LODs of 1.15 µM and 0.83 µM, separately. Finally, those fluorescence methods were adopted in sensitively quantitative measurement of AO within various food and drug samples, providing new prospects for analysts and technical support in food quality monitoring.

High luminescent N,S,P co-doped carbon dots for the fluorescence sensing of extreme acidity and folic acid.

Carbon dots are popular luminescent materials because of their excellent fluorescence properties, but the low quantum yield limits their application. Heteroatom doping is a more convenient and popular approach to increase the quantum yield of carbon dots. Here, novel N,S,P heteroatom co-doped carbon dots (N,S,P-CDs) were synthesized by a simple one-step hydrothermal method using m-phenylenediamine, L-cysteine and phosphoric acid as raw materials. The as-prepared N,S,P-CDs showed excellent photoluminescence properties with a fluorescence quantum yield of up to 41%, which greatly encourages their application in fluorescence sensing. The N,S,P-CDs exhibited good fluorescence stability under salt solution, xenon lamp irradiation and ultraviolet lamp irradiation except for a high sensitivity to extreme acidity. The fluorescence intensity of the N,S,P-CDs can be decreased by as much as 85% when the pH of the solution changes from 2.50 to 4.75, that is, a small fluctuation in pH can cause an intense response of the fluorescence of the N,S,P-CDs. Therefore, an excellent fluorescence sensing platform for accurately monitoring the pH of extreme acidity has been constructed. In addition, the N,S,P-CDs can be applied for quantitative detection of folic acid based on the strong quenching effect of folic acid on the fluorescence of the N,S,P-CDs. Good linearity was obtained in the concentration range of 4.85-82.45 µM, with a detection limit of 0.148 µM. The constructed sensing platform was used for the determination of folic acid in actual samples of orange juice, oatmeal and tablets with satisfactory results.

Robust solvatochromic carbon quantum dots for selective detection of water and Sn4+ and specific lipid imaging.

Developing carbon quantum dots (CQDs) with the solvatochromic effect and exploring multifunctional applications remains challenging. Herein, robust solvatochromic carbon quantum dots (RS-CQDs) with emission shift up to ∼62 nm from yellow to red was fabricated by the hydrothermal method. The RS-CQDs was used to detect water and Sn4+ in the linear ranges and limits of detection of 2.0-97.6% and 0.14% and 6.24-53.18 µM and 66.3 nM, respectively, and was further applied to determine Sn4+ in practical water samples with satisfactory results. In addition, RS-CQDs exhibited bright red emission in oil media with a 9.7-fold increase in fluorescence relative to aqueous media, making them a wash-free probe for specifically staining lipids. Compared to the commercial lipid marker BODIPY 493/503, the RS-CQDs-based probe has significant advantages, such as longer emission, larger Stokes shift, and better photostability, ensuring that RS-CQDs-based marker can implement real-time and wash-free monitoring and imaging of lipids in living cells, liver tissues, zebrafish embryos, and zebrafish larvae. This study provides a novel research direction for the development of metal-doped CQDs by demonstrating RS-CQDs as the viability of fluorescence probes for water and Sn4+ detection and the efficiency of RS-CQDs as a fluorescent marker for lipid imaging.

Transcriptome-wide association study by different approaches reveals candidate causal genes for cannabis use disorder.

Cannabis is one of the most commonly used psychoactive substances, which could induce moderate-severe cannabis use disorders (CUD). Here, a tissue-specific transcriptome-wide association study (TWAS) of CUD was performed by FUSION and S-PrediXcan, utilizing a genome-wide association study (GWAS) dataset of CUD (including 43,380 cases and 141,385 controls of European ancestry) and gene expression reference data from 17 different brain-related and non-brain related tissues, with totally 26 TWAS-associated genes were identified, including CADM2 (P = 2.13 × 10-17), SRR (P = 8.09 × 10-9) and TUFM (P = 1.24 × 10-8). Fine-mapping of causal gene sets (FOCUS) was used to prioritize genes with strong evidence for causality, and SRR, CADM2-AS1, and SH2B1 were prioritized with a posterior probability of 0.973, 0.951, and 0.788, respectively. Furthermore, gene ontology (GO) and pathway enrichment analysis on CUD-associated genes were performed, including cytosol, protein binding, nucleoplasm, metabolic pathways, and herpes simplex virus 1 infection. These findings could provide new insights for understanding the mechanism of CUD.

An ultrasensitive sensing platform based on fluorescence carbon dots for chlorogenic acid determination in food samples.

In this work, an ultrasensitive and convenient method was established for chlorogenic acid (CGA) determination based on fluorescence quenching of carbon dots (CDs). The CDs were prepared by hydrothermal heating of citric acid and p-phenylenediamine. The proposed CDs-based sensing platform showed high selectivity and sensitivity towards CGA detection. Under optimal working conditions, the fluorescence signals of CDs decreased with increasing of CGA contents and presented linear response to CGA content in two ranges of 0.01-0.1 and 0.1-20.0 µM. The detection limits were as low as 8.87 nM and 0.12 µM. The proposed method was successfully applied to analyze CGA in real food samples. The recoveries were between 98.9 % and 106.7 % and the relative standard deviations (RSDs) were below 3.28 %. This work highlights the construction of a facial, simple, economic and highly sensitive fluorescence sensing system for CGA detection with promising application prospects in food analysis.

A novel carbon-nanodots-based theranostic nano-drug delivery system for mitochondria-targeted imaging and glutathione-activated delivering camptothecin.

Chemotherapy is severely limited by continuously decreased therapeutic efficacy and uncontrolled side effects on normal tissue, which can be improved by constructing a nanoparticle-based drug delivery system (DDS). Nevertheless, no studies have reported on DDS-based on carbon-nanodots (CNDs), combining subcellular organelle-targeted imaging/drug delivery, high drug loading content, and glutathione (GSH)-sensitive drug release into one system. Herein, the as-fabricated CNDs can be covalently conjugated with a mitochondria-targeting ligand (triphenylphosphine, TPP), a smart GSH-responsive disulfide linker (S-S), and the anticancer drug (camptothecin, CPT) to initially prepare a theranostic nano-DDS (TPP-CNDs-S-CPT) with the drug loading efficiency of 64.6 wt%. Owing to excellent water dispersibility, superior fluorescence properties, satisfactory cell permeability, and favorable biocompatibility, TPP-CNDs-S-CPT was successfully used for intracellular mitochondrial-targeted imaging in vitro. High intracellular GSH concentrations in tumor cells caused the cleavage of S-S, resulting in concomitant activation and release of CPT, as well as significant fluorescence enhancement. In vivo, TPP-CNDs-S-CPT exhibited lower biological toxicity and even higher tumor-activatable performance than free CPT, as well as specific cancer therapy with few side effects. The mitochondria-targeted ability and the precise drug-release in tumor make TPP-CNDs-S-CPT a hopeful chemotherapy prodrug, providing significant theoretical basis and data support for in-depth understanding and exploration of chemotherapeutic DDS-based on CNDs.

Nitrogen-doped carbon dots coupled with morin-Al3+: Cleverly design an integrated sensing platform for ratiometric optical dual-mode and smartphone-assisted visual detection of fluoride ion.

Ratiometric fluorescence sensor has high selectivity and good sensitivity; however, its development is limited by intricate design, tedious synthesis, etc. Herein, a facile and effective ratiometric fluorescence sensing platform for fluoride ion (F-) detection was developed by simply combining nitrogen-doped carbon dots (N-CDs) and morin-Al3+ based on inner filter effect (IFE). The competitive binding of F- to Al3+ obviously decreased morin-Al3+ fluorescence and increased N-CDs fluorescence, attributing to the inhibition of IFE between N-CDs and morin-Al3+. The as-constructed ratiometric fluorescence sensing platform can be used for F- detection with a wide linear range (0.5-150 µM) and a low detection limit (55.8 nM). Interestingly, with the introduction of F- into the N-CDs/morin-Al3+ sensing platform, a distinguishable change in fluorescence color from green to blue enabled the N-CDs/morin-Al3+ system to be used as a smartphone-assisted visual sensing platform for F- detection with a detection limit of 2.09 µM. This platform was successfully applied for the onsite monitoring of F- in various water samples with satisfying results. These findings provide a novel guidance for the facile construction of a ratiometric optical dual-mode and smartphone-assisted sensing platform based on CDs, revealing the broad application prospect of CDs in environmental monitoring field.

A facile fluorescence platform for chromium and ascorbic acid detection based on "on-off-on" strategy.

In this paper, a facile and rapid fluorescence "on-off-on" strategy for the detection of chromium (Cr(VI)) and ascorbic acid (AA) was developed, which was based on the water-soluble carbon dots (CDs). The CDs was synthesized by a microwave-assisted treatment of L-tartaric acid, citric acid, and urea. The CDs have many advantages, such as high fluorescence quantum yield (20.5%) and good fluorescence stability. Based on inner filter effect (IFE) and static quenching, the fluorescence of the CDs can be quenched by Cr(VI) quickly; while the reduction of IFE and reducing action can make the fluorescence of the CDs recover by AA efficiently. Moreover, under the optimal experimental conditions, the CDs had a good detection performance for Cr(VI) in the range of 0.8 âˆ¼ 189 µM with the limit of detection (LOD) of 0.16 µM. The linear detection for AA was ranged from 0.43 to 25.7 µM with a LOD of 0.1 µM. More importantly, the as-constructed fluorescence detecting platform was successfully applied for Cr(VI) and AA detection in the environmental samples and fruit samples, respectively. In addition, the application potential of the CDs in fluorescent films and anti-counterfeiting materials was further discussed in detail. This work will provide a novel idea for designing a portable sensor based on the CDs to quickly and sensitively detect Cr(VI) and AA.

Intelligently design primary aromatic amines derived carbon dots for optical dual-mode and smartphone imaging detection of nitrite based on specific diazo coupling.

Primary aromatic amines derived carbon dots (PAA-CDs) with the protonated amino groups and high quantum yield of 46% were favorably obtained by one-step solvothermal treatment of m-phenylenediamine (m-PDA) in acidic environment. The interaction between the PAA-CDs and nitrite (NO2-) was inherited the characteristic reaction of m-PDA (a primary aromatic amine) and NO2-, resulting in strong fluorescence quenching and obvious absorption variation of the PAA-CDs. Meanwhile, a chromogenic reaction of diazo coupling can cause significant color changes. Hence, the PAA-CDs were developed for an optical dual-mode and smartphone imaging sensor for NO2- detection in the range of 3.0 ~ 40.0 µM with high selectivity, good sensitivity, and excellent anti-interference capability. A limit of detection (LOD) of 0.024 µM and 0.16 µM was implemented by fluorometry and colorimetry, respectively. For smartphone imaging colorimetry, the LODs of 0.46 µM (visible color) and 0.99 µM (fluorescence color) were acquired. More importantly, the established sensor has been successfully applied for the dynamic detection of NO2- in various food samples with the satisfying results. A smartphone imaging colorimetry method based on the CDs was firstly proposed to visually and quantitatively detect NO2-, which will broaden the application range of the CDs in food safety inspection.

A fluorometric and colorimetric dual-readout nanoprobe based on Cl and N co-doped carbon quantum dots with large stokes shift for sequential detection of morin and zinc ion.

A novel visual nanoprobe was developed for the sequential detection of morin and zinc ion (Zn2+) based on Cl and N co-doped carbon quantum dots (ClNCQDs) via a fluorometric and colorimetric dual-readout mode. The yellow fluorescence ClNCQDs was synthesized by the one-step hydrothermal treatment of o-chlorobenzoic acid and p-phenylenediamine. The most distinctive property of the ClNCQDs is the large stokes shift (177 nm), which is significantly higher than other reported CQDs. The fluorescence of the ClNCQDs can be effectively quenched by morin based on the synergistic effect of IFE, electrostatic interaction, and dynamic quenching process, and recovered upon the addition of Zn2+ due to strong interaction between morin and Zn2+. The nanoprobe exhibited favorable selectivity and sensitivity toward morin and Zn2+ with detection limits of 0.09 µM and 0.17 µM, respectively. Simultaneously, the color of the ClNCQDs solution was changed (light-pink â†’ faint-yellow â†’ dark-yellow) along with the variation of the fluorescence signal of the ClNCQDs. This proposed nanoprobe was successfully applied for morin and Zn2+ analyses in actual samples and live cells with high accuracy. The results of this study demonstrate the great application prospects of the ClNCQDs for morin and Zn2+ detection in complex actual samples and biosystems.

Nitrogen-doped carbon dots for wash-free imaging of nucleolus orientation.

Carbon dots (CDs) are a rising star in the field of cellular imaging, especially cytoplasmic imaging, attributing to the super-stable optical performance and ultra-low biological toxicity. Nucleolus can accurately reflect the expression state of a cell and is strongly linked to the occurrence and development of many diseases, so exploring bran-new CDs for nucleolus-orientation imaging with no-wash technology has important theoretical value and practical significance. Herein, nitrogen-doped carbon dots (N-CDs) with green fluorescence (the relative fluorescence quantum yield of 24.4%) was fabricated by the hydrothermal treatment of m-phenylenediamine and p-aminobenzoic acid. The N-CDs possess small size, bright green fluorescence, abundant surface functional groups, excellent fluorescence stability and good biocompatibility, facilitating that the N-CDs are an excellent imaging reagent for cellular imaging. N-CDs can particularly bind to RNA in nucleoli to enhance their fluorescence, which ensures that the N-CDs can be used in nucleolus-orientation imaging with high specificity and wash-free technique. This study demonstrates that the N-CDs have a significant feasibility to be used for nucleolus-orientation imaging in biomedical analysis and clinical diagnostic applications.

Development of an ultrasensitive spectrophotometric method for carmine determination based on fluorescent carbon dots.

A high-efficiency spectrophotometric method based on nitrogen-doped fluorescent carbon dots (N-FCDs) was developed for the ultrasensitive determination of carmine (CRM) in foodstuffs. The N-FCDs were fabricated via a one-pot hydrothermal method with m-phenylenediamine as the starting material. The detection principle was based on the fluorescence quenching effect of N-FCDs by CRM, where their interaction was due to the inner filter effect (IFE) and static quenching. A good linear relationship was established for CRM detection in a concentration range of 0.1-10.0 µM with a detection limit as low as 11.2 nM. The proposed method achieved satisfactory results for CRM determination in commercial food products with recoveries better than 98.6% and relative standard deviations (RSDs) less than 4.07%. The method established in this study was simple, ultrasensitive and reliable for rapid detecting CRM in a food matrix, which could be potentially used as a useful sensing agent for the analysis of additive food colourants.

A facile synthesis of long-wavelength emission nitrogen-doped carbon dots for intracellular pH variation and hypochlorite sensing.

Intracellular pH and hypochlorite (ClO-) concentration play an important role in life activities, so there is an urgent need to develop a valid strategy to monitor pH and ClO- in biological systems with high sensitivity and specificity. In this study, we report long-wavelength emission nitrogen-doped carbon dots (N-CDs) and their potential applications in intracellular pH variation, ClO- sensing and cell imaging. The N-CDs were prepared via a facile one-pot hydrothermal method of neutral red (NR) and glutamine (Gln). N-CDs exhibited a pH-sensitive response in the range of 4.0-9.0 and a good linear relationship in the range of 5.6-7.4, which indicated that N-CDs are an ideal agent for monitoring pH fluctuations in living cells. In addition, ClO- was capable of reducing the photoluminescence of N-CDs based on static quenching. The linear range is 1.5-112.5 µM and 112.5-187.5 µM, and the LOD is 0.27 µM. Besides, the as-fabricated N-CDs have been smoothly achieved to monitor pH and ClO- in PC-12 living cells due to their great biocompatibility and lower cytotoxicity, demonstrating their promising applications in the biomedical field. Compared with other CD-based methods, the as-proposed N-CDs have a longer fluorescence emission, which makes them potentially valuable in biological systems. The results pave a way towards the construction of long-wavelength carbon-based nanomaterials for fluorescence sensing and cell imaging.

Azithromycin detection in cells and tablets by N,S co-doped carbon quantum dots.

Azithromycin (AZM)1 is one of the most widely used antibiotics. AZM abuse is easy to cause great harm to human body, so developing a rapid and sensitive method to detect AZM is of great importance. Herein, 3-aminothiophenol as only reaction precursor, nitrogen and sulfur co-doped carbon quantum dots (N,S-CQDs)2 were fabricated by one-step hydrothermal carbonization method. All characteristics demonstrate that N,S-CQDs possess good water solubility, high fluorescence stability and low cytotoxicity. Without being disturbed by amino acids and drugs, the most interesting finding is that AZM can efficiently quench the fluorescence of N,S-CQDs by a synergistic effect of electrostatic interaction and static quenching. A fluorescent probe for the detection of AZM was constructed with high selectivity and good sensitivity, achieving two linear ranges of 2.5-32.3 µM and 37.2-110 µM and a limit of detection of 0.76 µM. The proposed fluorescent method was used for the detection of AZM in cells with fulfilling results. More importantly, the fluorescent probe was successfully used to the detection of AZM in tablets and human urine with recovery rate and relative standard deviations of 98.2-104.8% and 0.04-3.46%, respectively, which was confirmed by the standard method of HPLC-UV. This finding illustrates the usefulness and feasibility of N,S-CQDs as an effective fluorescent probe for the detection of AZM in tablets and human urine, which is helpful for supervising and guiding pharmacy.