Molecularly imprinted polymers-coated magnetic covalent organic frameworks for efficient solid-phase extraction of sulfonamides in fish.

In this study, covalent organic frameworks (COFs) were grown in situ on magnetic nitrogen-doped graphene foam (MNGF), and the resulting composite of COFs-modified MNGF (MNC) was wrapped by molecularly imprinted polymers (MNC@MIPs) for specifically capturing SAs. A magnetic solid phase extraction (MSPE) method for SAs was established using MNC@MIPs with good magnetic responsiveness. The adsorption performance of MNC@MIPs was superior to that of non-molecularly imprinted polymers (MNC@NIPs), with shorter adsorption/desorption time and higher imprinting factors. A high-efficiency SAs analytical method was developed by fusing HPLC and MNC@MIPs-based MSPE. This approach provides excellent precision, a low detection limit, and wide linearity. By analyzing fish samples, the feasibility of the approach was confirmed, with SAs recoveries and relative standard deviations in spiked samples in the ranges of 77.2-112.7 % and 2.0-7.2 %, respectively. This study demonstrated the potential use of MNC@MIPs-based MSPE for efficient extraction and quantitation of trace hazards in food.

Progress of machine learning-based biosensors for the monitoring of food safety: A review.

Rapid urbanization and growing food demand caused people to be concerned about food safety. Biosensors have gained considerable attention for assessing food safety due to selectivity, and sensitivity but poor stability inherently limits their application. The emergence of machine learning (ML) has enhanced the efficiency of different sensors for food safety assessment. The ML combined with various noninvasive biosensors has been implemented efficiently to monitor food safety by considering the stability of bio-recognition molecules. This review comprehensively summarizes the application of ML-powered biosensors to investigate food safety. Initially, different detector-based biosensors using biological molecules with their advantages and disadvantages and biosensor-related various ML algorithms for food safety monitoring have been discussed. Next, the application of ML-powered biosensors to detect antibiotics, foodborne microorganisms, mycotoxins, pesticides, heavy metals, anions, and persistent organic pollutants has been highlighted for the last five years. The challenges and prospects have also been deliberated. This review provides a new prospect in developing various biosensors for multi-food contaminants powered by suitable ML algorithms to monitor in-situ food safety.

A Predictive Model of Pressure Injury in Children Undergoing Living Donor Liver Transplantation Based on Machine Learning Algorithm.

AIMS: The aim of our study was to formulate and validate a prediction model using machine learning algorithms to forecast the risk of pressure injuries (PIs) in children undergoing living donor liver transplantation (LDLT). DESIGN: A retrospective cohort study. METHODS: The research was carried out at China's largest paediatric liver transplantation centre. A total of 438 children who underwent LDLT between June 2021 and December 2022 constituted the study cohort. The dataset was partitioned randomly into 70% for training datasets (306 cases) and 30% for testing datasets (132 cases). Utilising four machine learning algorithms-Decision Tree, Random Forest, Gradient Boosting Decision Tree and eXtreme Gradient Boosting-we identified risk factors and constructed predictive models. RESULTS: Out of 438 children, 42 developed PIs, yielding an incidence rate of 9.6%. Notably, 94% of these cases were categorised as Stage 1, and 54% were localised on the occiput. Upon evaluating the four prediction models, the Decision Tree model emerged as the most effective. The primary contributors to pressure injury in the Decision Tree model were identified as operation time, intraoperative corticosteroid administration, preoperative skin protection measures and preoperative skin conditions. A visualisation elucidating the logical inference process for the 10 variables within the Decision Tree model was presented. Ultimately, based on the Decision Tree model, a predictive system was developed. CONCLUSION: Machine learning algorithms facilitate the identification of crucial factors, enabling the creation of an effective Decision Tree model to forecast pressure injury development in children undergoing LDLT. IMPACT: With this predictive model at their disposal, nurses can assess the pressure injury risk level in children more intuitively. Subsequently, they can implement tailored preventive strategies to mitigate the occurrence of PIs. PATIENT OR PUBLIC CONTRIBUTION: Paediatric patients contributed electronic health records datasets.

Development of a hydrophilic-lipophilic-balanced copolymer@zirconium-based metal-organic framework-based solid-phase microextraction probe for the trace determination of organophosphorus pesticides in tea infusions.

Organophosphorus pesticides (OPPs) present in tea infusions pose a serious threat to human health. In this study, a sensitive method for the determination of OPPs was developed based on a direct-immersion solid-phase microextraction (DI-SPME) probe. By fine adjustment of the ratio and one-step polymerization of dihydroxy-functionalized zirconium-based metal-organic framework UiO-66-(OH)2 and divinylbenzene-N-vinyl pyrrolidone (DVB-NVP) microspheres, the DVB-NVP@ UiO-66-(OH)2 (D-N@U) composite with an optimal hydrophilic-lipophilic balance (HLB) was achieved. Furthermore, D-N@U was adhesively bonded to stainless-steel wires to fabricate a DI-SPME probe. OPPs, especially those with nonpolar properties characterized by a high octanol-water partition coefficient (log KOW), were selectively and efficiently enriched on the D-N@U-coated DI-SPME probe from tea infusions. Coupled with a gas chromatography-flame photometric detector, the as-fabricated D-N@U-coated DI-SPME probe achieved good performance for OPPs analysis with a wide linear dynamic range of 0.10-500.00 µg/L and low detection limits of 1.96-6.69 ng/L. Moreover, in spiked samples, the recoveries and relative standard deviations were in the ranges of 73.12%-101.20 % and 1.03%-6.56 %, respectively. Owing to its simple operation, high extraction efficiency, and high sensitivity, this approach has great potential for the rapid determination of multiple pesticide trace-level residues in food.

Efficacy of daratumumab on multiple myeloma patients with renal insufficiency: a systematic review and meta-analysis.

BACKGROUND: Renal insufficiency (RI) is a key factor affecting the prognosis of multiple myeloma (MM) patients. Because the benefit of daratumumab for treating MM patients with RI remains unclear, our objective was to evaluate the efficacy of daratumumab on MM patients with RI. METHODS: We conducted a systematic search of the PubMed, EMBASE, and Cochrane Library databases as of October 24, 2023. Two independent reviewers screened the article titles, abstracts, and full text to identify the randomized controlled trials (RCTs) meeting the inclusion and exclusion criteria. Meta-analyses were performed using RevMan version 5.4. Outcomes of interest were progression-free survival (PFS), overall survival (OS), complete response or better (≥CR), and minimal residual disease (MRD) negativity, all calculated as hazard ratios (HRs) or risk ratios (RRs) with 95% confidence intervals (CIs). RESULTS: A total of 10 RCTs with 5003 patients were included. Add-on daratumumab improved PFS and OS among newly diagnosed MM (NDMM) patients with RI (HR 0.48 [95% CI: 0.36, 0.64, I2 = 65%] and HR 0.63 [95% CI: 0.48, 0.82, I2 = 0%]) as well as relapsed/refractory MM (RRMM)-RI patients, compared with the control group (HR 0.46 [95% CI: 0.37, 0.58, I2 = 0%] and HR 0.68 [95% CI: 0.51, 0.92, I2 = 0%]). In terms of the renal status, the efficacy of add-on daratumumab for MMRI patients was similar to that for MM patients with normal renal function. A prolonged PFS benefit for add-on daratumumab treatment versus the control was evident across all RRMM-RI subgroups, and the benefits tended to increase with the follow-up time. CONCLUSIONS: Our results indicate that MM patients with RI could benefit from a daratumumab-added regimen regardless of MM status. Additional high-quality RCTs are still warranted to confirm our findings.

Multiple DNA cycle amplification for highly efficient detection of mercury pollution in food.

Mercury ion (Hg2+), a highly toxic metal pollutant, is widely found in the environment and can enter the human body through the food chain, causing various health issues. Sensitive and accurate methods for monitoring Hg2+ are highly desirable for ensuring food safety. Herein, we propose a self-sustainable multiple amplification system (MAS) for Hg2+ determination through the reciprocal activation between catalytic hairpin assembly (CHA) and rolling circle amplification (RCA). The thymine-encoded recognition element specifically recognizes Hg2+, triggering the exposure of the initiator. The initiator then motivates the mutual activation of CHA and RCA to accelerate the production of an exponentially amplified signal. The MAS method achieved a low detection limit of 11 pM. Due to its reliable target recognition and robust amplification efficiency, the MAS circuit facilitated the highly efficient and accurate analysis of low-abundance Hg2+ in milk and snakehead samples, thus providing a potentially new tool for food safety control.

Identification of Site in the UTY Gene as Safe Harbor Locus on the Y Chromosome of Pig.

Genomic Safe Harbors (GSH) are loci used for the insertion of exogenous genetic elements, enabling exogenous gene expressing predictably without alterations of the host genome. These sites are becoming increasingly important as the gene editing technologies advance rapidly. Currently, only a few GSHs have been identified in the pig genome. In this study, a novel strategy was demonstrated for the efficient insertion of exogenous genetic material into the third exon of the UTY gene on the Y chromosome using CRISPR/Cas9-mediated homology arm-mediated end joining. The safety of the locus was verified according to the proper expression of the inserted EGFP gene without altering the expression of UTY. This approach enables the integration and expression of the exogenous gene at this locus, indicating that the UTY locus serves as a genomic safe harbor site for gene editing in the pig genome. Located on the Y chromosome, this site can be utilized for sex-biased pig breeding and developing biomedical models.

The impact of cognitive impairment on patient activation and their value in self-management among COPD patients.

OBJECTIVES: To examine the impact of the interaction between cognitive function and patient activation on self-management behaviors among COPD patients. METHODS: We conducted a study of 331 COPD patients. Cognitive function and patient activation were evaluated at baseline, relevant information on social demography and diseases was collected simultaneously. The primary outcome was self-management behaviors. We performed a multiple logistic regression analysis to evaluate the interaction between cognitive function and patient activation. RESULTS: We found the interaction between mild cognitive impairment (MCI) and low patient activation on poor self-management behaviors was multiplicative. The proportion of participants with high patient activation was lower than those with low patient activation among patients with MCI. The incidence of poor self-management behaviors in patients with normal cognition differed significantly between participants with different activation levels (90.2 % vs.31.3 % vs.9.7 %). However, the difference was small in those with MCI (94 % vs. 73.5 % vs. 84.5). Notably, poor self-management behaviors were high among patients with MCI, regardless of their activation level. CONCLUSIONS: Patients with COPD are more likely to have poor self-management behaviors when MCI and low patient activation coexist, and it was difficult to be activated for patients with MCI. PRACTICE IMPLICATIONS: The assessment of cognitive function is crucial for patients with COPD, especially those with low activation.

Phase 1a study of ESG401, a Trop2 antibody-drug conjugate, in patients with locally advanced/metastatic solid tumors.

This phase 1a study assesses ESG401 in patients with heavily pretreated locally advanced or metastatic solid tumors, focusing on metastatic breast cancer. Forty patients are enrolled: three experience dose-limiting toxicities, establishing the maximum tolerated dose at 16 mg/kg on days 1, 8, and 15 of a 28-day cycle. The most common grade ≥3 treatment-related adverse events are neutropenia and leukopenia. Among 38 efficacy-evaluable patients, the objective response rate (ORR) is 34.2%, the disease control rate (DCR) is 65.8%, and the clinical benefit rate (CBR) is 50.0% (including stable disease for at least 6 months). The median progression-free survival is 5.1 months, and the median duration of response is 6.3 months. In patients receiving therapeutically relevant doses, the ORR, DCR, and CBR are 40.6%, 75.0%, and 56.3%, respectively. ESG401 demonstrates a favorable safety profile and promising antitumor activity in this heavily treated population. The trial is registered at ClinicalTrials.gov (NCT04892342).

Effectiveness of Escape Room in Medical Education: A Systematic Review and Meta-Analysis.

The primary goal of this meta-analysis is to explore the five factors of knowledge, teamwork, learning satisfaction, anxiety, and interprofessional ability to determine the value of escape rooms in medical education. Up to January 2023, we searched ScienceDirect, Scopus, PubMed, Embase, Web of Science, CNKI, and the Cochrane Library for pertinent works in either English or Chinese. The Risk of Bias 2 (RoB 2) tool and Newcastle-Ottawa Scale (NOS) were used to assess the quality of studies. Subgroup and sensitivity analyses were used to assess statistical heterogeneity, and I2 was used to measure it. Overall, escape rooms had a more significant positive effect than traditional learning on knowledge (standardized mean difference [SMD]: 0.84; 95% confidence interval [CI]: 0.36-1.33), teamwork (SMD: 4.91; 95% CI: 4.58-5.24), learning satisfaction (MD: 0.36; 95% CI: 0.08-0.64), and interprofessional ability (SMD: 1.04, 95% CI: 0.81-1.27). Moreover, the impact of escape rooms on anxiety also had significant effects (SMD: -8.23, 95% CI: -11.64 to -4.82). Escape rooms affect medical students' knowledge, teamwork, learning satisfaction, interprofessional ability, and anxiety. The findings of this study can be used as evidence that escape rooms is a more effective method than traditional teaching for improving active learning.

Safety and 6-month immune persistence of inactivated poliovirus vaccine (Sabin strains) simultaneously administrated with other vaccines for primary and booster immunization in Jiangxi Province, China.

OBJECTIVES: This study aims to evaluate the safety of a new inactivated poliomyelitis vaccine (Sabin strains) (sIPV) for large-scale use in primary and booster immunizations, whether simultaneously administered with other vaccines or not and to explore the persistence of all vaccines at approximately six months after vaccination. METHOD: A total of 3200 infants were recruited into this study, including 2000 infants aged 2-3 months randomly assigned (1:1) into the "sIPV basic" or the "sIPV+DTaP" group for primary immunization of sIPV. Another 1200 children aged 18 months old and above were randomly assigned (2:2:1:1) into the "sIPV booster," "sIPV+HepA-I," "sIPV+MMR", or "sIPV+HepA-L" group for booster immunization of sIPV. Adverse events within 30 days of each vaccination dose in all participants were self-reported by guardians using a WeChat mini-program. Approximately 200 blood samples were collected at 5-7 months after the final vaccination to test for antibodies against poliovirus and other viruses. RESULTS: 3198 participants in total were included in the safety study, including 1999 infants aged 2-3 months old and 1199 children aged 18-26 months old. For primary immunization, the incidence of adverse reactions in the "sIPV basic" and the "sIPV+DTaP" group were 3.19 and 6.21% (P = 0.001), respectively. For booster immunization, the incidences of adverse reaction for the "sIPV booster" group were 2.25%, while the incidence for the "sIPV +others" group in total was 2.50% (P = 0.788). Most adverse reactions were mild. Fever was the most common symptom in all groups. No vaccine-related serious adverse events (SAEs) were observed in this study. The seropositivity rates of antibodies in the "sIPV basic" and the "sIPV+DTaP" group were 92.31 and 100% against type 1 poliovirus (P = 0.031); 96.15% and 98.57% against type 2 poliovirus (P = 0.575); 98.08% and 91.43% against type 3 poliovirus (P = 0.237), respectively. Regarding booster vaccination with sIPV, whether co-administered with other vaccines or not, the seropositivity rates of antibodies against the three types of polioviruses were all 100%. Seropositivity rates of antibodies against hepatitis A, measles, mumps, and rubella were all no <77%, except for pertussis, which was <30%. CONCLUSION: sIPV demonstrated good safety and immune persistence for primary and booster vaccinations, whether administered singly or simultaneously. Antibodies against hepatitis A, measles, mumps and rubella were not disrupted by the co-vaccination. However, the seropositivity rates and geometric mean concentrations (GMCs) of antibodies against pertussis indicate the necessity for a booster dose.

Efficacy and safety of catheter ablation for atrial fibrillation in patients with heart failure with preserved ejection fraction: a systematic review and meta-analysis.

Background: Catheter ablation (CA) effectively treats atrial fibrillation (AF) in heart failure (HF) with reduced ejection fraction (HFrEF), improving clinical outcomes. However, its benefits for AF patients with heart failure with preserved ejection fraction (HFpEF) are still unclear. Methods: We systematically searched PubMed, Embase, Web of Science, the Cochrane Library, and Scopus for studies investigating outcomes of CA in AF patients with HFpEF. Efficacy indicators included freedom from AF and antiarrhythmic drugs (AAD) free AF elimination. Safety indicators comprised total complications, HF admission, all-cause admission, and all-cause mortality. Sixteen studies with 20,796 patients included in our research. Results: The comprehensive analysis demonstrated that, when comparing CA with medical therapy in HFpEF, no significant differences were observed in terms of HF admissions, all-cause admissions, and all-cause mortality [(OR: 0.42; 95% CI: 0.12-1.51, P = 0.19), (HR: 0.78; 95% CI: 0.48-1.27, P = 0.31), and (OR: 1.10; 95% CI: 0.83-1.44, P = 0.51)], while freedom from AF was significantly higher in CA (OR: 5.88; 95% CI: 2.99-11.54, P < 0.00001). Compared with HFrEF, CA in HFpEF showed similar rates of freedom from AF, AAD-free AF elimination, total complications, and all-cause admission were similar [(OR:0.91; 95% CI: 0.71,1.17, P =0.47), (OR: 0.97; 95% CI: 0.50-1.86, P = 0.93), (OR: 1.27; 95% CI: 0.47-3.41, P = 0.64), (OR: 1.11; 95% CI: 0.72, 1.73; P = 0.63)]. However, CA in HFpEF was associated with lower rates of HF admission and all-cause mortality [(OR: 0.35; 95% CI: 0.20, 0.60; P = 0.0002), (OR: 0.40; 95% CI: 0.18, 0.85; P = 0.02)]. Compared with patients without HF, CA in HFpEF patients exhibited lower rates of AAD-free AF elimination (OR: 0.48; 95% CI: 0.30, 0.75; P = 0.001). However, their rates of freedom from AF and total complications were similar [(OR: 0.70; 95% CI: 0.48, 1.02; P = 0.06), (OR: 0.60; 95% CI: 0.19, 1.90; P = 0.38)]. Conclusion: This meta-analysis conducted provided a comprehensive evaluation of the efficacy and safety of CA in patients with AF and HFpEF. The results suggest that CA may represent a valuable treatment strategy for patients with AF and HFpEF. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/#recordDetails, identifier (CRD42024514169).

Lewis Acid-Driven Multicomponent Reactions Enable 2-Alkyl Chromanones with Anticancer Activities.

2-Alkyl chromanone scaffold has become prominent in pharmaceuticals and natural compounds. Consequently, devising robust strategies for synthesizing 2-alkyl chromanones remains crucial. Here, multicomponent reactions were employed to synthesize 2-alkyl chromanones containing an oxazole moiety using 3-formylchromones, amines, and N-propargylamides as reactants. This method utilizes readily available feedstocks with a catalytic amount of Zn(OTf)2 and exhibits an impressive substrate scope compared to existing methods. Importantly, the synthesized compounds demonstrated highly selective anticancer activity against the DU145 cell line.

Development and comparison of model-integrated evidence approaches for bioequivalence studies with pharmacokinetic end points.

By applying nonlinear mixed-effect (NLME) models, model-integrated evidence (MIE) approaches are able to analyze bioequivalence (BE) data with pharmacokinetic end points that have sparse sampling, which is problematic for non-compartmental analysis (NCA). However, MIE approaches may suffer from inflation of type I error due to underestimation of parameter uncertainty and to the assumption of asymptotic normality. In this study, we developed a MIE BE analysis method that is based on a pre-defined model and consists of several steps including model fitting, uncertainty assessment, simulation, and BE determination. The presented MIE approach has several improvements compared with the previously reported model-integrated methods: (1) treatment, sequence, and period effects are only added to absorption parameters (such as relative bioavailability and rate of absorption) instead of all PK parameters; (2) a simulation step is performed to generate confidence intervals of the pharmacokinetic metrics for BE assessment; and (3) in an effort to maintain type I error, two more advanced parameter uncertainty evaluation approaches are explored, a nonparametric (case resampling) bootstrap, and sampling importance resampling (SIR). To evaluate the developed method and compare the uncertainty assessment methods, simulation experiments were performed for BE studies using a two-way crossover design with different amounts of information (sparse to rich designs) and levels of variability. Based on the simulation results, the method using SIR for parameter uncertainty quantification controls type I error at the nominal level of 0.05 (i.e., the significance level set for BE evaluation) even for studies with small sample size and/or sparse sampling. As expected, our MIE approach for BE assessment exhibited higher power than the NCA-based method, especially as the data becomes sparser and/or more variable.

A fully automatic tool for development of population pharmacokinetic models.

Population pharmacokinetic (PK) models are widely used to inform drug development by pharmaceutical companies and facilitate drug evaluation by regulatory agencies. Developing a population PK model is a multi-step, challenging, and time-consuming process involving iterative manual model fitting and evaluation. A tool for fully automatic model development (AMD) of common population PK models is presented here. The AMD tool is implemented in Pharmpy, a versatile open-source library for pharmacometrics. It consists of different modules responsible for developing the different components of population PK models, including the structural model, the inter-individual variability (IIV) model, the inter-occasional variability (IOV) model, the residual unexplained variability (RUV) model, the covariate model, and the allometry model. The AMD tool was evaluated using 10 real PK datasets involving the structural, IIV, and RUV modules in three sequences. The different sequences yielded generally consistent structural models; however, there were variations in the results of the IIV and RUV models. The final models of the AMD tool showed lower Bayesian Information Criterion (BIC) values and similar visual predictive check plots compared with the available published models, indicating reasonable quality, in addition to reasonable run time. A similar conclusion was also drawn in a simulation study. The developed AMD tool serves as a promising tool for fast and fully automatic population PK model building with the potential to facilitate the use of modeling and simulation in drug development.

Evaluation of model-integrated evidence approaches for pharmacokinetic bioequivalence studies using model averaging methods.

Conventional approaches for establishing bioequivalence (BE) between test and reference formulations using non-compartmental analysis (NCA) may demonstrate low power in pharmacokinetic (PK) studies with sparse sampling. In this case, model-integrated evidence (MIE) approaches for BE assessment have been shown to increase power, but may suffer from selection bias problems if models are built on the same data used for BE assessment. This work presents model averaging methods for BE evaluation and compares the power and type I error of these methods to conventional BE approaches for simulated studies of oral and ophthalmic formulations. Two model averaging methods were examined: bootstrap model selection and weight-based model averaging with parameter uncertainty from three different sources, either from a sandwich covariance matrix, a bootstrap, or from sampling importance resampling (SIR). The proposed approaches increased power compared with conventional NCA-based BE approaches, especially for the ophthalmic formulation scenarios, and were simultaneously able to adequately control type I error. In the rich sampling scenario considered for oral formulation, the weight-based model averaging method with SIR uncertainty provided controlled type I error, that was closest to the target of 5%. In sparse-sampling designs, especially the single sample ophthalmic scenarios, the type I error was best controlled by the bootstrap model selection method.

Epicardial Adipose Tissue and Psoriasis: A Systematic Review and Meta-Analysis.

Background: As a novel biomarker for cardiovascular diseases, epicardial adipose tissue (EAT) has been linked to psoriasis. We conducted an updated systematic review, building upon a previous report on the relationship between EAT and psoriasis. Methods: We searched Medline, Embase, and the Cochrane Central Register of Controlled Trials. The methodological quality of each study was assessed using the Newcastle-Ottawa Scale. The pooled mean difference (MD) or standardized mean difference (SMD) and the corresponding confidence interval (CIs) were calculated. Results: We included 10 studies with 1287 participants. Five of the included studies were of high methodological quality, while the other five were of moderate quality. The pooled data indicated that psoriasis patients had significantly increased EAT compared to individuals in the control group (SMD 1.53, 95% CI 0.61 to 2.45, 9 studies, 1195 participants). The subgroup analysis showed that psoriasis patients had significantly increased EAT thickness compared with the controls (SMD 2.45, 95% CI 0.73 to 4.17, 5 studies, 657 participants). Similarly, EAT area in single-slice CT images was significantly higher in the psoriasis group than in the control group (SMD 0.45, 95% CI 0.14 to 0.76, 2 studies, 195 participants). The EAT volume based on CT images appeared to be higher in the psoriasis group than in the control group, but the difference was not statistically significant (SMD 0.32, 95% CI -0.06 to 0.70, 2 studies, 343 participants). Conclusions: EAT, especially echocardiographic EAT thickness and CT-determined EAT area, was significantly associated with psoriasis, but CT-determined EAT volume was not.

Prenatal EDC exposure, DNA Methylation, and early childhood growth: A prospective birth cohort study.

BACKGROUND: Exposure to endocrine-disrupting chemicals (EDCs) has been found to be associated with growth and developmental abnormalities in children. However, the potential mechanisms by which exposure to EDCs during pregnancy increases the risk of obesity in children remain unclear. OBJECTIVE: We aimed to explore associations between prenatal EDC exposure and the body mass index (BMI) of children at age two, and to further explore the potential impact of DNA methylation (DNAm). METHOD: This study included 285 mother-child pairs from a birth cohort conducted in Wuhan, China. The BMI of each child was assessed at around 24 months of age. The concentrations of sixteen EDCs at the 1st, 2nd, and 3rd trimesters were measured using ultra-high performance liquid chromatography coupled to a triple quadrupole mass spectrometer. The research utilized general linear models, weighted quantile sum regression, and Bayesian Kernel Machine Regression to assess the association between prenatal EDC exposure and childhood BMI z-scores (BMIz). Cord blood DNAm was measured using the Human Methylation EPIC BeadChip array. An epigenome-wide DNAm association study related to BMIz was performed using robust linear models. Mediation analysis was then applied to explore potential mediators of DNAm. RESULTS: Urinary concentrations of seven EDCs were positively associated with BMIz in the 1st trimester, which remained significant in the WQS model. A total of 641 differential DNAm positions were associated with elevated BMIz. Twelve CpG positions (annotated to DUXA, TMEM132C, SEC13, ID4, GRM4, C2CD2, PRAC1&PRAC2, TSPAN6 and DNAH10) mediated the associations between urine BP-3/BPS/MEP/TCS and elevated BMIz (P < 0.05). CONCLUSION: Our results revealed that prenatal exposure to EDCs was associated with a higher risk of childhood obesity, with specific DNAm acting as a partial mediator.

A three-channel biosensor based on stimuli-responsive catalytic activity of the Fe3O4@Cu for on-site detection of tetrodotoxin in fish.

Tetrodotoxin (TTX), a lethal neurotoxin, poses a grave threat to human health. The available spectroscopic methods suffer from limitations such as complex procedures and inadequate on-site capabilities. In this study, we proposed a method using Fe3O4@Cu as a catalytic biosensor combined with SERS, colorimetry and image processing for TTX detection. Integrating the aptamer amplifies the specificity of the system and masks the catalytic activity of Fe3O4@Cu. The catalytic efficiency of Fe3O4@Cu in the H2O2-TMB reaction can quantify the concentration of TTX in the system. Consequently, oxidation of TMB (oxTMB) led to the generation and change of signals for SERS, colorimetry and image processing, enabling a three-channel quantitative detection of TTX. Under the optimal conditions, the detection limit of established SERS, colorimetry and image processing were 0.055, 2.127 and 0.243 ng/mL, respectively. This three-channel biosensor was applied to real samples, providing an accurate, stable and adaptable alternative for on-site TTX detection.

Alcoholic Liver Disease in China: A Disease Influenced by Complex Social Factors That Should Not Be Neglected.

Alcoholic liver disease (ALD) encompasses liver damage caused by chronic, excessive alcohol consumption. It manifests initially as marked hepatocellular steatosis and can progress to steatohepatitis, liver fibrosis, and cirrhosis. With China's rapid economic growth, coupled with a complex social background and the influence of a deleterious wine culture, the number of patients with ALD in China has increased significantly; the disease has become a social and health problem that cannot be ignored. In this review, we briefly described the social factors affecting ALD in China and elaborated on differences between alcoholic and other liver diseases in terms of complications (e.g., cirrhosis, upper gastrointestinal bleeding, hepatic encephalopathy, hepatocellular carcinoma, addiction, and other extrahepatic diseases). We also emphasized that ALD was more dangerous and difficult to treat than other liver diseases due to its complications, and that precise and effective treatment measures were lacking. In addition, we considered new ideas and treatment methods that may be generated in the future.