Association of the CUN-BAE body adiposity estimator and other obesity indicators with cardiometabolic multimorbidity: a cross-sectional study.

Cardiometabolic multimorbidity (CM), defined as the coexistence of two or three cardiometabolic disorders, is one of the most common and deleterious multimorbidities. This study aimed to investigate the association of Clínica Universidad de Navarra-Body Adiposity Estimator (CUN-BAE), body mass index (BMI), waist circumference (WC), and waist-to-height ratio (WHtR) with the prevalence of CM. The data were obtained from the 2021 health checkup database for residents of the Electronic Health Management Center in Xinzheng, Henan Province, China. 81,532 participants aged ≥ 60 years were included in this study. Logistic regression models were used to estimate the odd ratios (ORs) and 95% confidence intervals (CIs) for CUN-BAE, BMI, WC, and WHtR in CM. The area under the receiver operating characteristic curve (AUC) was used to compare the discriminatory ability of different anthropometric indicators for CM. The multivariable-adjusted ORs (95% CIs) (per 1 SD increase) of CM were 1.799 (1.710-1.893) for CUN-BAE, 1.329 (1.295-1.364) for BMI, 1.343 (1.308-1.378) for WC, and 1.314 (1.280-1.349) for WHtR, respectively. Compared with BMI, WC and WHtR, CUN-BAE had the highest AUC in both males and females (AUC: 0.642; 95% CI 0.630-0.653 for males, AUC: 0.614; 95% CI 0.630-0.653 for females). CUN-BAE may be a better measure of the adverse effect of adiposity on the prevalence of CM than BMI, WC, and WHtR.

Puerarin alleviates atherosclerosis via the inhibition of Prevotella copri and its trimethylamine production.

OBJECTIVE: Puerarin (PU) is a natural compound that exhibits limited oral bioavailability but has shown promise in the treatment of atherosclerosis (AS). However, the precise mechanisms underlying its therapeutic effects remain incompletely understood. This study aimed to investigate the effects of PU and its mechanisms in mitigating AS in both mice and humans. DESIGN: The impact of PU on AS was examined in ApoE -/- mice fed a high-fat diet (HFD) and in human patients with carotid artery plaque. To explore the causal link between PU-associated gut microbiota and AS, faecal microbiota transplantation (FMT) and mono-colonisation of mice with Prevotella copri (P. copri) were employed. RESULTS: PU alleviated AS by modulating the gut microbiota, as evidenced by alterations in gut microbiota composition and the amelioration of AS following FMT from PU-treated mice into ApoE-/- mice fed HFD. Specifically, PU reduced the abundance of P. copri, which exacerbated AS by producing trimethylamine (TMA). Prolonged mono-colonisation of P. copri undermines the beneficial effects of PU on AS. In clinical, the plaque scores of AS patients were positively correlated with the abundance of P. copri and plasma trimethylamine-N-oxide (TMAO) levels. A 1-week oral intervention with PU effectively decreased P. copri levels and reduced TMAO concentrations in patients with carotid artery plaque. CONCLUSION: PU may provide therapeutic benefits in combating AS by targeting P. copri and its production of TMA. TRIAL REGISTRATION NUMBER: ChiCTR1900022488.

Association of longitudinal trajectories of fasting plasma glucose with all-cause and cardiovascular mortality among a Chinese older population: a retrospective cohort study.

The association between fasting plasma glucose (FPG), an important indicator of overall glycemic status, and the risk of cardiovascular mortality has been well investigated. The longitudinal study can repeatedly collect measured results for the variables to be studied and then consider the potential effects of intraindividual changes in measurement. This study aimed to identify long-term FPG trajectories and investigate the association between trajectory groups and cardiovascular and all-cause mortality. A latent class growth mixture modeling (LCGMM) was used to identify FPG trajectories. Cox proportional hazard models were used to estimate associations between FPG trajectories and the risk of all-cause and cardiovascular mortality. A U-shaped relationship between FPG and all-cause and cardiovascular mortality was observed in the restricted cubic spline regression models. Two FPG longitudinal trajectories of low-level (mean FPG = 5.12mmol/L) and high-level (mean FPG = 6.74mmol/L) were identified by LCGMM. After being adjusted for potential confounders, compared with the low-level category, the hazard ratios (HRs) for all-cause and cardiovascular mortality were 1.23(1.16-1.30) and 1.25(1.16-1.35), respectively, for the high-level group. Long-term FPG trajectories are significantly associated with and potentially impact the risk of all-cause and cardiovascular mortality.

Single-cell 'omic profiles of human aortic endothelial cells in vitro and human atherosclerotic lesions ex vivo reveal heterogeneity of endothelial subtype and response to activating perturbations.

Heterogeneity in endothelial cell (EC) sub-phenotypes is becoming increasingly appreciated in atherosclerosis progression. Still, studies quantifying EC heterogeneity across whole transcriptomes and epigenomes in both in vitro and in vivo models are lacking. Multiomic profiling concurrently measuring transcriptomes and accessible chromatin in the same single cells was performed on six distinct primary cultures of human aortic ECs (HAECs) exposed to activating environments characteristic of the atherosclerotic microenvironment in vitro. Meta-analysis of single-cell transcriptomes across 17 human ex vivo arterial specimens was performed and two computational approaches quantitatively evaluated the similarity in molecular profiles between heterogeneous in vitro and ex vivo cell profiles. HAEC cultures were reproducibly populated by four major clusters with distinct pathway enrichment profiles and modest heterogeneous responses: EC1-angiogenic, EC2-proliferative, EC3-activated/mesenchymal-like, and EC4-mesenchymal. Quantitative comparisons between in vitro and ex vivo transcriptomes confirmed EC1 and EC2 as most canonically EC-like, and EC4 as most mesenchymal with minimal effects elicited by siERG and IL1B. Lastly, accessible chromatin regions unique to EC2 and EC4 were most enriched for coronary artery disease (CAD)-associated single-nucleotide polymorphisms from Genome Wide Association Studies (GWAS), suggesting that these cell phenotypes harbor CAD-modulating mechanisms. Primary EC cultures contain markedly heterogeneous cell subtypes defined by their molecular profiles. Surprisingly, the perturbations used here only modestly shifted cells between subpopulations, suggesting relatively stable molecular phenotypes in culture. Identifying consistently heterogeneous EC subpopulations between in vitro and ex vivo models should pave the way for improving in vitro systems while enabling the mechanisms governing heterogeneous cell state decisions.

Fluorophore Label-Free Light-up Near Infrared Deoxyribonucleic Acid Nanosensor for Monitoring Extracellular Potassium Levels.

Fluorescent DNA nanosensors have been widely used due to their unique advantages, among which the near-infrared (NIR) imaging mode can provide deeper penetration depth and lower biological background for the nanosensors. However, efficient NIR quenchers require ingenious design, complex synthesis, and modification, which severely limit the development of NIR DNA nanosensors. Label-free strategies based on G-quadruplex (G4) and NIR G4 dyes were first introduced into in situ extracellular imaging, and a novel NIR sensing strategy for the specific detection of extracellular targets is proposed. The strategy avoids complex synthesis and site-specific modification by controlling the change of the NIR signal through the formation of a G4 nanostructure. A light-up NIR DNA nanosensor based on potassium ion (K+)-sensitive G4 chain PS2.M was constructed to verify the strategy. PS2.M forms a stable G4 nanostructure in the presence of K+ and activates the NIR G4 dye CSTS, thus outputting NIR signals. The nanosensor can rapidly respond to K+ with a linear range of 5-50 mM and has good resistance to interference. The nanosensor with cholesterol can provide feedback on the changes in extracellular K+ concentration in many kinds of cells, serving as a potential tool for the study of diseases such as epilepsy and cancer, as well as the development of related drugs. The strategy can be potentially applied to the NIR detection of a variety of extracellular targets with the help of functional DNAs such as aptamer and DNAzyme.

Effect of hot electron induced charge transfer generated by surface plasmon resonance on Ag@Au/ITO/PNTP systems.

The present study discusses the fabrication of a bimetallic material consisting of silver nanorods and gold nanospheres (designated Ag@Au), and its surface modification with 4-nitrothiophenol (PNTP) after deposition on an indium tin oxide (ITO) glass sheet, followed by laser irradiation at various wavelengths. The results indicate that the reduction of PNTP is more complete under irradiation at 532 nm due to the surface plasmon resonance (SPR) effects of the gold and silver nanomaterials. Moreover, the surface enhanced Raman scattering (SERS) of the PNTP adsorbed on the Ag@Au/ITO is found to be significantly stronger than that of PNTP adsorbed on Ag@Au alone, due to charge transfer (CT) at the interface. In addition, the SERS enhancement effect of the PNTP molecules on the Ag@Au/ITO substrate is optimal under 532 nm laser irradiation due to the hot electron-induced CT generated by the SPR effect. Thus, the system constructed herein combines the effects of SPR and CT, thereby assisting in a further understanding of the enhancement mechanism of SERS and, hence, the further development SERS research in metal-semiconductor-molecular systems.

Single cell 'omic profiles of human aortic endothelial cells in vitro and human atherosclerotic lesions ex vivo reveals heterogeneity of endothelial subtype and response to activating perturbations.

Objective: Endothelial cells (ECs), macrophages, and vascular smooth muscle cells (VSMCs) are major cell types in atherosclerosis progression, and heterogeneity in EC sub-phenotypes are becoming increasingly appreciated. Still, studies quantifying EC heterogeneity across whole transcriptomes and epigenomes in both in vitro and in vivo models are lacking. Approach and Results: To create an in vitro dataset to study human EC heterogeneity, multiomic profiling concurrently measuring transcriptomes and accessible chromatin in the same single cells was performed on six distinct primary cultures of human aortic ECs (HAECs). To model pro-inflammatory and activating environments characteristic of the atherosclerotic microenvironment in vitro, HAECs from at least three donors were exposed to three distinct perturbations with their respective controls: transforming growth factor beta-2 (TGFB2), interleukin-1 beta (IL1B), and siRNA-mediated knock-down of the endothelial transcription factor ERG (siERG). To form a comprehensive in vivo/ex vivo dataset of human atherosclerotic cell types, meta-analysis of single cell transcriptomes across 17 human arterial specimens was performed. Two computational approaches quantitatively evaluated the similarity in molecular profiles between heterogeneous in vitro and in vivo cell profiles. HAEC cultures were reproducibly populated by 4 major clusters with distinct pathway enrichment profiles: EC1-angiogenic, EC2-proliferative, EC3-activated/mesenchymal-like, and EC4-mesenchymal. Exposure to siERG, IL1B or TGFB2 elicited mostly distinct transcriptional and accessible chromatin responses. EC1 and EC2, the most canonically 'healthy' EC populations, were affected predominantly by siERG; the activated cluster EC3 was most responsive to IL1B; and the mesenchymal population EC4 was most affected by TGFB2. Quantitative comparisons between in vitro and in vivo transcriptomes confirmed EC1 and EC2 as most canonically EC-like, and EC4 as most mesenchymal with minimal effects elicited by siERG and IL1B. Lastly, accessible chromatin regions unique to EC2 and EC4 were most enriched for coronary artery disease (CAD)-associated SNPs from GWAS, suggesting these cell phenotypes harbor CAD-modulating mechanisms. Conclusion: Primary EC cultures contain markedly heterogeneous cell subtypes defined by their molecular profiles. Surprisingly, the perturbations used here, which have been reported by others to be involved in the pathogenesis of atherosclerosis as well as induce endothelial-to-mesenchymal transition (EndMT), only modestly shifted cells between subpopulations, suggesting relatively stable molecular phenotypes in culture. Identifying consistently heterogeneous EC subpopulations between in vitro and in vivo models should pave the way for improving in vitro systems while enabling the mechanisms governing heterogeneous cell state decisions.

Double-edged role of mechanical stimuli and underlying mechanisms in cartilage tissue engineering.

Mechanical stimuli regulate the chondrogenic differentiation of mesenchymal stem cells and the homeostasis of chondrocytes, thus affecting implant success in cartilage tissue engineering. The mechanical microenvironment plays fundamental roles in the maturation and maintenance of natural articular cartilage, and the progression of osteoarthritis Hence, cartilage tissue engineering attempts to mimic this environment in vivo to obtain implants that enable a superior regeneration process. However, the specific type of mechanical loading, its optimal regime, and the underlying molecular mechanisms are still under investigation. First, this review delineates the composition and structure of articular cartilage, indicating that the morphology of chondrocytes and components of the extracellular matrix differ from each other to resist forces in three top-to-bottom overlapping zones. Moreover, results from research experiments and clinical trials focusing on the effect of compression, fluid shear stress, hydrostatic pressure, and osmotic pressure are presented and critically evaluated. As a key direction, the latest advances in mechanisms involved in the transduction of external mechanical signals into biological signals are discussed. These mechanical signals are sensed by receptors in the cell membrane, such as primary cilia, integrins, and ion channels, which next activate downstream pathways. Finally, biomaterials with various modifications to mimic the mechanical properties of natural cartilage and the self-designed bioreactors for experiment in vitro are outlined. An improved understanding of biomechanically driven cartilage tissue engineering and the underlying mechanisms is expected to lead to efficient articular cartilage repair for cartilage degeneration and disease.

Relationship between obesity indicators and hypertension-diabetes comorbidity in an elderly population: a retrospective cohort study.

BACKGROUND: The prevalence of obesity, hypertension and diabetes is increasing. Hypertension and diabetes are common complications. Additionally, obesity and hypertension-diabetes comorbidity (HDC) are both closely related to insulin resistance. The aim of this study was to determine the association of obesity indicators with HDC in elderly individuals. METHODS: This retrospective cohort study included 74,955 subjects aged ≥ 60 years living in Xinzheng, Henan Province, from January 2011 to December 2019. The data were collected from the annual health examination dataset. Cox proportional hazard regression models and competing-risk survival regression models were used to examine the relationships between the three indicators and HDC risk. RESULTS: After 346,504 person-years of follow-up, HDC developed in 9,647 subjects. After further adjustments for confounders and death competing risks, compared with a body mass index (BMI) of 18.5-23.9 kg/m2, the fully adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) of BMI < 18.5, 24-27.9 and ≥ 28 kg/m2 for HDC morbidity were 0.651(0.538,0.788),1.00,1.396(1.336,1.459) and 1.769(1.666,1.878), respectively. Moreover, participants with abdominal obesity measured via waist circumference (WC) or waist-to-height ratio (WtHR) had a higher risk of HDC (HR:1.513; 95% CI: 1.45,1.578 and HR:1.412;95% CI: 1.353,1.473), respectively, than participants with low WC or with low WtHR. In the joint analyses, the highest risk was observed in participants who were overweight and who had central obesity (HR: 1.721; 95% CI: 1.635, 1.811) compared with the nonoverweight and noncentral obesity groups. CONCLUSIONS: Increased BMI, WC and WtHR were associated with an increased risk of HDC. There was an additive interaction between general body adiposity (as measured via BMI) and central obesity (as measured via WC and WtHR) for HDC. Therefore, reasonable control of BMI, WC and WtHR may be an effective measure to prevent HDC among elderly individuals.

Association of the Clínica Universidad de Navarra-Body Adiposity Estimator With Type 2 Diabetes: A Retrospective Cohort Study.

Objectives: Clínica Universidad de Navarra-Body Adiposity Estimator (CUN-BAE) is considered to be a more accurate indicator of body fat estimation. We aimed to investigate the association of CUN-BAE with the risk of type 2 diabetes mellitus (T2DM) and to compare the strength of the association between CUN-BAE, body mass index (BMI), waist circumference (WC), waist-to-height ratio (WHtR) and T2DM. Methods: The data were obtained from the annual health checkup database of residents in Xinzheng, China. From January 2011 to December 2021, 80,555 subjects aged ≥45 years met the inclusion criteria. Cox proportional hazard regression models were used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) for CUN-BAE, BMI, WC, and WHtR in T2DM. Results: During a mean follow-up of 6.26 years, T2DM occurred in 12,967 subjects. The multivariable-adjusted HRs (95% CIs) of T2DM (highest vs. reference group) were 1.994 (1.811-2.196) for CUN-BAE, 1.751 (1.665-1.842) for WC, 1.715 (1.631-1.804) for WHtR, and 1.510 (1.436-1.588) for BMI, respectively. In addition, the risk of T2DM increased with baseline CUN-BAE (HR: 1.374; 95% CI: 1.328, 1.421), WC (HR: 1.236; 95% CI: 1.215, 1.256), WHtR (HR: 1.228; 95% CI: 1.208, 1.248), and BMI (HR: 1.175; 95% CI: 1.156, 1.195). Conclusion: Compared to BMI, WC or WHtR, CUN-BAE may more adequately reflect the adverse effects of adiposity on the risk of T2DM.

Hairpin Switches-Based Isothermal Transcription Amplification for Simple, Sensitivity Detection of MicroRNA.

The ability to simply, selectively, and sensitively detect low numbers of miRNAs in clinical samples is highly valuable but remains a challenge. In this work, we present a novel miRNA detection system by using the elaborately designed hairpin switch, where the T7 primer, template, target recognize sequence, and light-up RNA aptamer template are edited and embedded in one single-stranded DNA hairpin structure. In the beginning, the hairpin switch maintained the hairpin structure 1, in which the ds promoter of T7 polymerase was disrupted, thus the transcription reaction of T7 polymerase was inhibited. After binding to the target, the hairpin switch 1 was unfolded and turned to the hairpin structure 2. This switch initiates the in vitro T7 transcription reaction, producing plenty of RNA transcripts containing RNA aptamers. Consequently, transcribed tremendous RNA aptamers lighted up the fluorophore for quantitative analysis. Compared with the existing T7 polymerase-based amplification system, this strategy exhibits several advantages, including simplicity, convenience, and high selectivity and sensitivity. The experimental results demonstrated that we could achieve the quantification of miRNA in buffer and complex biological samples.

CRISPR-Cas12a coupled with cyclic reverse transcription for amplified detection of miRNA.

In this work, we present a highly sensitive, specific, and versatile method to quantify miRNA expression by coupling CRISPR-Cas12a with cyclic reverse transcription (CRT), termed as CRISPR-CRT. Each miRNA target was first converted and amplified into multiple hairpin RT products via CRT. Afterward, the hairpin RT products could serve as activators to initiate the collateral cleavage activity of CRISPR-Cas12a. Due to the above two-stage amplification, this assay could detect miRNA at sub-femtomolar level (LOD, 0.201 fM). Since the sequence of target miRNA is double checked: first in the CRT and then in the CRISPR system, the proposed assay also shows an excellent specificity in detecting miR-21. Finally, with the usage of this assay, the sensitive assessment of miR-21 levels in human serum samples has been achieved and the disease human serum has been detected. Conclusively, CRISPR-CRT holds a great application prospective in the field of clinical molecular diagnosis.

Relationship Between Six Insulin Resistance Surrogates and Nonalcoholic Fatty Liver Disease Among Older Adults: A Cross-Sectional Study.

Background: Non-alcoholic fatty liver disease (NAFLD) represents a large and growing public health problem. Insulin resistance (IR) plays a crucial role in the pathogenesis of NAFLD. The aim of this study was to determine the association of triglyceride-glucose (TyG) index, TyG index with body mass index (TyG-BMI), lipid accumulation product (LAP), visceral adiposity index (VAI), triglycerides/high-density lipoprotein cholesterol ratio (TG/HDL-c) and metabolic score for IR (METS-IR) with NAFLD in older adults and to compare the discriminatory abilities of these six IR surrogates for NAFLD. Methods: This cross-sectional study included 72,225 subjects aged ≥60 years living in Xinzheng, Henan Province, from January 2021 to December 2021. The data were collected from the annual health examination dataset. Logistic regression models were used to examine the relationships between the six indicators and NAFLD risk. The area under the receiver operating characteristic curve (AUC) was used to compare the discriminatory ability of different IR surrogates for NAFLD under the influence of potential risk factors. Results: After adjusting for multiple covariates, compared with the first quintile, the odds ratios (ORs) and 95% confidence intervals (CIs) of the highest quintiles of TyG-BMI were the most obvious (OR:43.02, 95% CI:38.89-47.72), followed by the METS-IR (OR:34.49, 95% CI:31.41-37.95). Restricted cubic spline analysis reported that there were non-linear positive association and dose-response relationship between 6 IR surrogates and NAFLD risk. Compared with other IR-related indicators (LAP, TyG, TG/HDL-c and VAI), TyG-BMI showed the highest AUC (AUC:0.8059;95% CI:0.8025-0.8094). Additionally, METS-IR also had a high predictive performance for NAFLD, and the AUC was greater than 0.75 (AUC:0.7959;95% CI:0.7923-0.7994). Conclusion: TyG-BMI and METS-IR had pronounced discrimination ability to NAFLD, which are recommended as complementary markers for the assessment of NAFLD risk both in clinic and in future epidemiological studies.

Association of body roundness index and its trajectories with all-cause and cardiovascular mortality among a Chinese middle-aged and older population: A retrospective cohort study.

Objectives: The body roundness index (BRI) is a novel anthropometric index that is a better indicator for predicting fat distribution than the body mass index (BMI). The longitudinal study can repeatedly collect measured results for the variables to be studied and then consider the potential effects of intraindividual changes in measurement. However, few population-based, longitudinal studies of BRI have been conducted, especially among the Chinese population. The study aimed to investigate the association of BRI and its longitudinal trajectories with all-cause and cardiovascular mortality. Methods: A total of 71,166 participants with four times BRI measurements between January 2010 and December 2019 were included in this longitudinal study, with a median follow-up was 7.93 years, and 11,538 deaths were recorded, of which 5,892 deaths were due to cardiovascular disease (CVD). A latent class growth mixture modeling (LCGMM) was used to identify BRI trajectories. Cox proportional hazard models were used to estimate associations between BRI trajectories and the risk of all-cause and cardiovascular mortality. Results: In the restricted cubic spline regression models, a U-shaped relationship between BRI and all-cause and cardiovascular mortality was observed. Three BRI longitudinal trajectories of low-stable (mean BRI = 2.59), moderate-stable (mean BRI = 3.30), and high-stable (mean BRI = 3.65) were identified by LCGMM. After being adjusted for potential confounders, the HRs for all-cause mortality were 1.18 (1.13-1.24) for the moderate-stable group and 1.74 (1.66-1.82) for the high-stable group compared to the low-stable group. The HRs for cardiovascular mortality were 1.12 (1.05-1.18) for the moderate-stable group and 1.64 (1.53-1.75) for the high-stable group compared to the low-stable group. Conclusion: A nonlinear association of BRI with all-cause and cardiovascular mortality was observed, and participants in the higher BRI longitudinal trajectory group were significantly associated with an increased risk of all-cause and cardiovascular mortality.

Association of Metabolically Healthy Obesity and Risk of Cardiovascular Disease Among Adults in China: A Retrospective Cohort Study.

Purpose: Previous studies have shown that metabolically healthy obesity (MHO) and changes in its status are connected to an increased incidence of cardiovascular disease (CVD). Yet, fewer studies have been conducted in China, especially for the middle-aged and elderly population, a high-risk group. The purpose of the study was to investigate the association between metabolic health status and CVD events. Patients and Methods: A total of 46,055 participants were categorized into 6 subgroups with different metabolic states according to the existence of metabolic syndrome and body mass index (BMI). The changes in obesity and metabolic health status were defined from baseline to follow-up outcomes with a combination of overweight and obesity. Cox proportional hazards models estimated the association of CVD events and each BMI-metabolic groups. Results: MHO and metabolic abnormality normal weight (MANW) subjects had a higher HR of CVD, 1.62 (95% CI, 1.36-1.92) and 1.24 (95% CI, 1.07-1.44), respectively, than their metabolically healthy normal weight (MHNW) counterparts. Then, more than 50% and 30% of the metabolically healthy overweight or obesity (MHOO) populations maintained their status and converted to a metabolically unhealthy state, respectively. Stable MANW, MHOO and metabolically abnormal obesity (MAO) were associated with a higher risk for CVD, 1.68 (95% CI, 1.37-2.05),1.26 (95% CI, 1.08-1.47) and 1.65 (95% CI, 1.45-1.88), respectively, than stable MHNW. Conclusion: Despite being of normal weight, MANW status is in fact a risk factor for CVD, as well as MHO, especially for the Chinese middle-aged and elderly population. Furthermore, metabolic health is a transient state for partial middle-aged and elderly Chinese individuals, and MAO has the highest risk of CVD, including coronary heart disease (CHD) and stroke.

Designing a CRISPR/Cas12a- and Au-Nanobeacon-Based Diagnostic Biosensor Enabling Direct, Rapid, and Sensitive miRNA Detection.

Direct, rapid, sensitive, and selective detection of nucleic acids in complex biological fluids is crucial for medical early diagnosis. We herein combine the trans-cleavage ability of clustered regularly interspaced short palindromic repeats (CRISPR)/Cas12a with Au-nanobeacon to establish a CRISPR-based biosensor, providing rapid miRNA detection with high speed and attomolar sensitivity. In this strategy, we first report that the trans-cleavage activity of CRISPR/cas12a, which was previously reported to be triggered only by target ssDNA or dsDNA, can be activated by the target miRNA directly. Therefore, this method is direct, i.e., does not need the conversion of miRNA into its complementary DNA (cDNA). Meanwhile, as compared to the traditional ssDNA reporters and molecular beacon (MB) reporters, the Au-nanobeacon reporters exhibit improved reaction kinetics and sensitivity. In this assay, the miRNA-21 could be detected with very high sensitivity in only 5 min. Finally, the proposed strategy enables rapid, sensitive, and selective miRNA determination in complex biological samples, providing a potential tool for medical early diagnosis.

Synthesis of some new acylhydrazone compounds containing the 1,2,4-triazole structure and their neuritogenic activities in Neuro-2a cells.

In the present study, a novel series of acylhydrazone compounds (A0-A10) with the structure of 1,2,4-triazole have been designed and synthesized. In addition, all the synthesized compounds have been evaluated for neuritogenic activity in mouse neuroblastoma (Neuro-2a) cells. Notably, we found that one of these 11 acylhydrazone compounds, compound A5 (2-(4-amino-5-(pyridin-4-yl)-4H-1,2,4-triazol-3-ylthio)-N'-(2-hydroxybenzylidene)-acetohydrazide) displays excellent neuritogenic activity. Moreover, our present study revealed that compound A5 had the ability to induce neurite outgrowth through the PI3K/Akt and MEK-ERK signaling pathway in Neuro-2a cells. These findings suggest that compound A5 might exert neuritogenic effects and thus may be useful for the treatment of neural repair and regeneration.

[A study of photoluminescence properties of Si-based CeO2/Tb4O7 superlattices].

CeO2/Tb4O7 superlattices were deposited on P type Si wafers by e-beam evaporation technology. Four typical photoluminescence peaks of Tb3+ ions which located around 488, 544, 588 and 623 nm were obtained after the superlattices annealing in weak reducing atmosphere at high temperature. It was indicated that CeO2 films transferred to amorphous state as the valence transition of Ce4+ --> Ce3+ which was induced by thermal annealing, the energy transfer occurred between Ce3+ ions and Tb3+ ions, and the Tb3+ ions emition could be detected after obtaining the energy from Ce3+ ions. A study about the effect of Tb4O7 thickness on the superlattices photoluminescence showed that the maximum PL intensity as thickness of Tb4 O7 films were about 0.5 nm, the concentration quenching might occur because of the energy transfer among the Tb3+ ions. The annealing conditions research demonstrated that the maximum PL intensity could be obtained as the superlattices annealed at 1 200 degrees C for 2 hour. Further investigation inferred that the concentration of Ce3+ ions, Oxygen vacancy defects and the distance between Ce3+ ions and Tb3+ ions play an important role in the annealing process.