Dietary intake, antioxidants, minerals and vitamins in relation to childhood asthma: a Mendelian randomization study.

Background: Currently, there is limited and inconsistent evidence regarding the risk association between daily dietary intake, antioxidants, minerals, and vitamins with Childhood Asthma (CA). Therefore, this study employs Mendelian Randomization (MR) methodology to systematically investigate the causal relationships between daily dietary intake, serum antioxidants, serum minerals, and the circulating levels of serum vitamins with CA. Methods: This study selected factors related to daily dietary intake, including carbohydrates, proteins, fats, and sugars, as well as serum antioxidant levels (lycopene, uric acid, and ß-carotene), minerals (calcium, copper, selenium, zinc, iron, phosphorus, and magnesium), and vitamins (vitamin A, vitamin B6, folate, vitamin B12, vitamin C, vitamin D, and vitamin E), using them as Instrumental Variables (IVs). Genetic data related to CA were obtained from the FinnGen and GWAS Catalog databases, with the primary analytical methods being Inverse Variance Weighting (IVW) and sensitivity analysis. Results: Following MR analysis, it is observed that sugar intake (OR: 0.71, 95% CI: 0.55-0.91, P: 0.01) is inversely correlated with the risk of CA, while the intake of serum circulating magnesium levels (OR: 1.63, 95% CI: 1.06-2.53, P: 0.03), fats (OR: 1.44, 95% CI: 1.06-1.95, P: 0.02), and serum vitamin D levels (OR: 1.14, 95% CI: 1.04-1.25, P: 0.02) are positively associated with an increased risk of CA. Conclusion: This study identified a causal relationship between the daily dietary intake of sugars and fats, as well as the magnesium and vitamin D levels in serum, and the occurrence of CA. However, further in-depth research is warranted to elucidate the specific mechanisms underlying these associations.

Nomogram for Predicting Hypoglycemia in Type 2 Diabetes Mellitus Patients Treated with Insulin Pump During Enteral Nutrition.

Purpose: To develop a prediction model for hypoglycemia in type 2 diabetes mellitus (T2DM) patients treated with an insulin pump during enteral nutrition. Methods: This retrospective study included T2DM patients treated with an insulin pump during enteral nutrition at the First Affiliated Hospital of Jinan University, Guangzhou Red Cross Hospital, Foshan First People's Hospital, and Guangdong Provincial Hospital of Traditional Chinese Medicine between January 2016 and December 2023. The patients were randomized 3:1 to the training and validation sets. The risk factors for hypoglycemia were analyzed. A prediction model was developed. Results: This study included 122 patients, and 57 patients had at least one hypoglycemic event during their hospitalization (46.72%). The multivariable logistic regression analysis showed that the time to reach the glycemic targets (odds ratio (OR)=1.408, 95% confidence interval (CI)=1.084-1.825, P=0.006), average glycemia (OR=0.387, 95% CI=0.233-0.643, P=0.010), coronary heart disease (OR=0.089, 95% CI=0.016-0.497, P<0.001), and the administration of hormone therapy (OR=6.807, 95% CI=1.128-41.081, P=0.037) were independently associated with hypoglycemia. A nomogram was built. The receiver operating characteristics analysis showed that the area under the curve of the model was 0.872 (95% CI=0.0.803-0.940) for the training set and 0.839 (95% CI=0.688-0.991) in the validation set. Conclusion: A nomogram was successfully built to predict hypoglycemia in T2DM patients treated with an insulin pump during enteral nutrition, based on the time to reach the glycemic targets, average glycemia, coronary heart disease, and the administration of hormone therapy.

A novel senolytic drug for pulmonary fibrosis: BTSA1 targets apoptosis of senescent myofibroblasts by activating BAX.

Idiopathic pulmonary fibrosis is a progressive and age-related disease that results from impaired lung repair following injury. Targeting senescent myofibroblasts with senolytic drugs attenuates pulmonary fibrosis, revealing a detrimental role of these cells in pulmonary fibrosis. The mechanisms underlying the occurrence and persistence of senescent myofibroblasts in fibrotic lung tissue require further clarification. In this study, we demonstrated that senescent myofibroblasts are resistant to apoptosis by upregulating the proapoptotic protein BAX and antiapoptotic protein BCL-2 and BCL-XL, leading to BAX inactivation. We further showed that high levels of inactive BAX-mediated minority mitochondrial outer membrane permeabilization (minority MOMP) promoted DNA damage and myofibroblasts senescence after insult by a sublethal stimulus. Intervention of minority MOMP via the inhibition of caspase activity by quinolyl-valyl-O-methylaspartyl-[2,6-difluorophenoxy]-methyl ketone (QVD-OPH) or BAX knockdown significantly reduced DNA damage and ultimately delayed the progression of senescence. Moreover, the BAX activator BTSA1 selectively promoted the apoptosis of senescent myofibroblasts, as BTSA1-activated BAX converted minority MOMP to complete MOMP while not injuring other cells with low levels of BAX. Furthermore, therapeutic activation of BAX with BTSA1 effectively reduced the number of senescent myofibroblasts in the lung tissue and alleviated both reversible and irreversible pulmonary fibrosis. These findings advance the understanding of apoptosis resistance and cellular senescence mechanisms in senescent myofibroblasts in pulmonary fibrosis and demonstrate a novel senolytic drug for pulmonary fibrosis treatment.

MiR-483-3p promotes dental pulp stem cells osteogenic differentiation via the MAPK signaling pathway by targeting ARRB2.

Human dental pulp stem cells (DPSCs) have become an important component for bone tissue engineering and regenerative medicine due to their ability to differentiate into osteoblast precursors. Two miRNA chip datasets (GSE138180 and E-MTAB-3077) of DPSCs osteogenic differentiation were analyzed respectively to find the expression of miR-483-3p significantly increased in the differentiated groups. We further confirmed that miR-483-3p continued to overexpress during osteogenic differentiation of DPSCs, especially reaching its peak on the 7th day. Moreover, miR-483-3p could significantly promote the expression of osteogenic markers including RUNX2 and OSX, and activate MAPK signaling pathway by inducing phosphorylation of ERK, p38, and JNK. In addition, as a significant gene within the MAPK signaling pathway, ARRB2 was identified as the target gene of miR-483-3p by bioinformatic prediction and experimental verification. In conclusion, we identified miR-483-3p could promote osteogenic differentiation of DPSCs via the MAPK signaling pathway by targeting ARRB2.

The two-step strategy for enhancing the specific activity and thermostability of alginate lyase AlyG2 with mechanism for improved thermostability.

To overcome the trade-off challenge encountered in the engineering of alginate lyase AlyG2 from Seonamhaeicola algicola Gy8T and to expand its potential industrial applications, we devised a two-step strategy encompassing activity enhancement followed by thermal stability engineering. To enhance the specific activity of efficient AlyG2, we strategically substituted residues with bulky steric hindrance proximal to the active pocket with glycine or alanine. This led to the generation of three promising positive mutants, with particular emphasis on the T91S mutant, exhibiting a 1.91-fold specific activity compared to the wild type. To mitigate the poor thermal stability of T91S, mutants with negative ΔΔG values in the thermal flexibility region were screened out. Notably, the S72Y⁎ mutant not only displayed 17.96 % further increase in specific activity but also exhibited improved stability compared to T91S, manifesting as a remarkable 30.97 % increase in relative activity following a 1-hour incubation at 42 °C. Furthermore, enhanced kinetic stability was observed. To gain deeper insights into the mechanism underlying the enhanced thermostability of the S72Y⁎ mutant, we conducted molecular dynamics simulations, principal component analysis (PCA), dynamic cross-correlation map (DCCM), and free energy landscape (FEL) analysis. The results unveiled a reduction in the flexibility of the surface loop, a stronger correlation dynamic and a narrower motion subspace in S72Y⁎ system, along with the formation of more stable hydrogen bonds. Collectively, our findings suggest amino acids substitutions resulting in smaller side chains proximate to the active site can positively impact enzyme activity, while reducing the flexibility of surface loops emerges as a pivotal factor in conferring thermal stability. These insights offer valuable guidance and a framework for the engineering of other enzyme types.

Differential expression of circRNAs during osteogenic/odontogenic differentiation of stem cells from apical papilla promoted by blue light-emitting diode.

BACKGROUND: Circular RNA (circRNA) is a key player in regulating the multidirectional differentiation of stem cells. Previous research by our group found that the blue light-emitting diode (LED) had a promoting effect on the osteogenic/odontogenic differentiation of human stem cells from apical papilla (SCAPs). This research aimed to investigate the differential expression of circRNAs during the osteogenic/odontogenic differentiation of SCAPs regulated by blue LED. MATERIALS AND METHODS: SCAPs were divided into the irradiation group (4 J/cm2) and the control group (0 J/cm2), and cultivated in an osteogenic/odontogenic environment. The differentially expressed circRNAs during osteogenic/odontogenic differentiation of SCAPs promoted by blue LED were detected by high-throughput sequencing, and preliminarily verified by qRT-PCR. Functional prediction of these circRNAs was performed using Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) and the circRNA-miRNA-mRNA networks were also constructed. RESULTS: It showed 301 circRNAs were differentially expressed. GO and KEGG analyses suggested that these circRNAs were associated with some signaling pathways related to osteogenic/odontogenic differentiation. And the circRNA-miRNA-mRNA networks were also successfully constructed. CONCLUSION: CircRNAs were involved in the osteogenic/odontogenic differentiation of SCAPs promoted by blue LED. In this biological process, circRNA-miRNA-mRNA networks served an important purpose, and circRNAs regulated this process through certain signaling pathways.

Optimizing timing for quantification of intracranial aneurysm enhancement: a multi-phase contrast-enhanced vessel wall MRI study.

OBJECTIVES: Aneurysm wall enhancement (AWE) on high-resolution contrast-enhanced vessel wall MRI (VWMRI) is an emerging biomarker for intracranial aneurysms (IAs) stability. Quantification methods of AWE in the literature, however, are variable. We aimed to determine the optimal post-contrast timing to quantify AWE in both saccular and fusiform IAs. MATERIALS AND METHODS: Consecutive patients with unruptured IAs were prospectively recruited. VWMRI was acquired on 1 pre-contrast and 4 consecutive post-contrast phases (each phase was 9 min). Signal intensity values of cerebrospinal fluid (CSF) and aneurysm wall on pre- and 4 post-contrast phases were measured to determine the aneurysm wall enhancement index (WEI). AWE was also qualitatively analyzed on post-contrast images using previous grading criteria. The dynamic changes of AWE grade and WEI were analyzed for both saccular and fusiform IAs. RESULTS: Thirty-four patients with 42 IAs (27 saccular IAs and 15 fusiform IAs) were included. The changes in AWE grade occurred in 8 (30%) saccular IAs and 6 (40%) in fusiform IAs during the 4 post-contrast phases. The WEI of fusiform IAs decreased 22.0% over time after contrast enhancement (p = 0.009), while the WEI of saccular IAs kept constant during the 4 post-contrast phases (p > 0.05). CONCLUSIONS: When performing quantitative analysis of AWE, acquiring post-contrast VWMRI immediately after contrast injection achieves the strongest AWE for fusiform IAs. While the AWE degree is stable for 36 min after contrast injection for saccular IAs. CLINICAL RELEVANCE STATEMENT: The standardization of imaging protocols and analysis methods for AWE will be helpful for imaging surveillance and further treatment decisions of patients with unruptured IAs. KEY POINTS: Imaging protocols and measurements of intracranial aneurysm wall enhancement are reported heterogeneously. Aneurysm wall enhancement for fusiform intracranial aneurysms (IAs) is strongest immediately post-contrast, and stable for 36 min for saccular IAs. Future multi-center studies should investigate aneurysm wall enhancement as an emerging marker of aneurysm growth and rupture.

Dietary protein load affects the energy and nitrogen balance requiring liver glutamate dehydrogenase to maintain physical activity.

Provision of amino acids to the liver is instrumental for gluconeogenesis while it requires safe disposal of the amino group. The mitochondrial enzyme glutamate dehydrogenase (GDH) is central for hepatic ammonia detoxification by deaminating excessive amino acids towards ureagenesis and preventing hyperammonemia. The present study investigated the early adaptive responses to changes in dietary protein intake in control mice and liver-specific GDH knockout mice (Hep-Glud1-/-). Mice were fed chow diets with a wide coverage of protein contents; i.e. suboptimal 10%, standard 20%, over optimal 30%, and high 45% protein diets; switched every 4 days. Metabolic adaptations of the mice were assessed in calorimetric chambers before tissue collection and analyses. Hep-Glud1-/- mice exhibited impaired alanine induced gluconeogenesis and constitutive hyperammonemia. The expression and activity of GDH in liver lysates were not significantly changed by the different diets. However, applying an in situ redox-sensitive assay on cryopreserved tissue sections revealed higher hepatic GDH activity in mice fed the high-protein diets. On the same section series, immunohistochemistry provided corresponding mapping of the GDH expression. Cosinor analysis from calorimetric chambers showed that the circadian rhythm of food intake and energy expenditure was altered in Hep-Glud1-/- mice. In control mice, energy expenditure shifted from carbohydrate to amino acid oxidation when diet was switched to high protein content. This shift was impaired in Hep-Glud1-/- mice and consequently the spontaneous physical activity was markedly reduced in GDH knockout mice. These data highlight the central role of liver GDH in the energy balance adaptation to dietary proteins.

External ceramic membrane contactor for in-situ H2 assisted biogas upgrading.

Biological H2-assisted biogas upgrading has gained significant attention as an environmentally friendly substitute to common physico-chemical upgrading techniques, but is largely limited by the low solubility of H2. This study evaluated the design of a ceramic membrane contactor module for H2 injection. H2 dissolution was maintained at high efficiency by controlling gas supply and sludge recirculation rate, achieving a biogas quality of average 98.8% CH4 during the stable operation phase with a 108% increase in the CH4 production rate. This also outperforms conventional H2 injection using diffuser sparging which could only achieve a biogas quality of 84% CH4 content. Microbial community analysis found high Methanobacterium spp. abundance within the archaea at 95.2% at the end of the operation, allowing the dominance of the hydrogenotrophic methanogenesis pathway for high upgrading efficiencies. The system is a high-performance external membrane connector module coupled to common anaerobic digestion systems for biogas upgrading.

Augmenting vaccine efficacy: Tailored immune strategy with alum-stabilized Pickering emulsion.

BACKGROUND: The achievement of optimal vaccine efficacy is contingent upon the collaborative interactions between T and B cells in adaptive immunity. Although multiple immunization strategies have been proposed, there is a notable scarcity of comprehensive investigations pertaining to enhance immune effects through immune strategy adjustments for individual vaccine. METHODS: The hierarchically structured aluminum hydroxide microgel-stabilized Pickering emulsion (ASPE) was prepared by ultrasonic method. This study explored the influence of the immune strategy of ASPE to immune responses, including antigen exposure pattern, adjuvants and antigen dosage, and administration interval. RESULTS: The findings revealed that external antigen adsorption facilitated increased exposure of antigen epitopes, leading to elevated IgG titers and secretion of cytokines such as interferon-gamma (IFN-γ) or interleukin-4 (IL-4). Additionally, even a low dose (1 µg/dose) of antigens of ASPE boosted sufficient neutralizing antibody levels and memory T cells compared to high-dose antigens, which consistent with the adjuvant dosage effect. Furthermore, maintaining a 4-week immunization interval yielded optimal levels of antigen-specific IgG titers in both short-term and long-term scenarios, as compared to intervals of 2, 3, and 5 weeks. A consistent trend was observed in the proliferation of memory B cells, reaching a superior level at the 4-week interval, which could enhance protection against viral re-infection. CONCLUSION: Tailoring immunization strategies for specific vaccines has emerged as powerful driver in maximizing vaccine efficacy and eliciting robust immune responses, thereby presenting cutting-edge approaches to enhanced vaccination.

CRISPR/Cas9-induced LEAP2 and GHSR1a knockout mutant zebrafish displayed abnormal growth and impaired lipid metabolism.

Investigating the principles of fish fat deposition and conducting related research are current focal points in fish nutrition. This study explores the endocrine regulation of LEAP2 and GHSR1a in zebrafish by constructing mutantmodels andexamining the effects of the endocrine factors LEAP2 and its receptor GHSR1a on zebrafish growth, feeding, and liver fat deposition. Compared to the wild type (WT), the mutation of LEAP2 results in increased feeding and decreased swimming in zebrafish. The impact is more pronounced in adult female zebrafish, characterized by increased weight, length, width, and accumulation of lipid droplets in the liver.Incontrast, deficiency in GHSR1a significantly reduces the growth of male zebrafish and markedly decreases liver fat deposition.These research findings indicate the crucial roles of LEAP2 and GHSR1a in zebrafish feeding, growth, and intracellular fat metabolism. This study, for the first time, investigated the endocrine metabolic regulation functions of LEAP2 and GHSR1a in the model organism zebrafish, providing initial insights into their effects and potential mechanisms on zebrafish fat metabolism.

Ti3C2T x -AuNP based paper substrates for label-free SERS detection of bacteria and multimodal antibacterials.

Bacterial infections have become a serious global health problem due to the misuse of antibiotics which causes the emergence of antibiotic-resistant strains. Photothermal therapy (PTT) has been widely studied in recent years as a method to combat the development of bacterial resistance. However, PPT may cause damage to the human body due to excessive laser power. Therefore, it is important and urgent to develop a multifunctional platform that can sensitively detect bacteria and effectively inhibit or kill bacteria at low laser power. Herein, a novel multifunctional paper substrate of Ti3C2T x -AuNP was successfully synthesized by a self-assembly and freeze-drying method for bacterial detection and photothermal sterilization at low laser power. The typical Gram-negative Escherichia coli (E. coli) and the Gram-positive Methicillin-resistant Staphylococcus aureus (MRSA) were used as models to perform label-free, rapid and sensitive detection of bacteria based on the surface-enhanced Raman spectroscopy (SERS) method with detection limits as low as 105 CFU mL-1 and 5 × 105 CFU mL-1, respectively, demonstrating the paper substrate's ability to detect bacteria with sensitivity and accuracy. The paper substrate of Ti3C2T x -AuNP exhibits significant antibacterial effects when irradiated with 808 nm light at a low laser power of only 300 mW cm-2 and a short irradiation time of 5 minutes, and the germicidal rates for E. coli and MRSA were 99.94% and 92.71%, respectively. At the same time, the paper substrate of Ti3C2T x -AuNP also produces a variety of reactive oxygen species under 808 nm laser irradiation, resulting in photodynamic therapy (PDT). Accordingly, this paper substrate of Ti3C2T x -AuNP can not only sensitively detect bacteria, but also has photothermal and photodynamic sterilization, providing a promising countermeasure for the clinical treatment of diseases caused by multidrug-resistant bacteria.

High-Performance Graphene Flexible Sensors for Pulse Monitoring and Human-Machine Interaction.

Flexible sensors are of great interest due to their potential applications in human physiological signal monitoring, wearable devices, and healthcare. However, sensor devices employed for cardiovascular testing are normally bulky and expensive, which hamper wearability and point-of-care use. Herein, we report a simple method for preparing multifunctional flexible sensors using hydrazine hydrate (N2H4·H2O) as the reducing agent, graphene as the active material, and polyethylene (PE) tape as the encapsulation material. The flexible sensor produced with this method has a low detection limit of 100 mg, a fast response and recovery time of 40 and 20 ms, and shows no performance degradation even after up to 30,000 motion cycles. The sensors we have developed are capable of monitoring the pulse with relative accuracy, which presents an opportunity to replace bulky devices and normalize cardiovascular testing in the future. In order to further broaden the application field, the sensor is installed as a sensor array to recognize objects of different weights and shapes, showing that the sensor has excellent application potential in wearable artificial intelligence.

Associations Between Multiparametric US-Based Indicators and Pathological Status in Patients with Metabolic Associated Fatty Liver Disease.

OBJECTIVE: Noninvasive evaluation of metabolic dysfunction-associated fatty liver disease (MAFLD) using ultrasonography holds significant clinical value. The associations between ultrasound (US)-based parameters and the pathological spectra remain unclear and controversial. This study aims to investigate the associations thoroughly. METHODS: The participants with MAFLD undergoing liver biopsy and multiparametric ultrasonography were prospectively recruited from December 2020 to September 2022. Three US-based parameters, namely attenuation coefficient (AC), liver stiffness (LS) and dispersion slope (DS) were obtained. The relationship between these parameters and steatosis grades, inflammation grades and fibrosis stages was examined. RESULTS: In this study with 116 participants, AC values significantly differed across distinct steatosis grades (p < 0.001), while DS and LS values varied among inflammation grades (p < 0.001) and fibrosis stages (p < 0.001). The area under the receiver operating characteristic curves (AUCs) of AC ranged from 0.82 to 0.84 for differentiating steatosis grades, while AUCs of LS ranged from 0.62 to 0.76 for distinguishing inflammation grades and 0.83-0.95 for discerning fibrosis stages. AUCs for DS ranged from 0.79 to 0.81 in discriminating inflammation grades and 0.80-0.88 for differentiating fibrosis stages. Subgroup analysis revealed that LS demonstrated different trends in inflammation grade but consistent trends in fibrosis stage across subgroups, whereas DS showed consistent trends for both inflammation grade and fibrosis stage across all subgroups. CONCLUSION: AC values indicate the degree of hepatic steatosis but not inflammation or fibrosis. LS values are determined only by fibrosis stage and are not associated with inflammation grades. DS values are associated with both fibrosis and inflammation grades.

A Wearable Self-Charging Electroceutical Device for Bacteria-Infected Wound Healing.

The prolonged wound-healing process caused by pathogen infection remains a major public health challenge. The developed electrical antibiotic administration typically requires metal electrodes wired to a continuous power supply, restricting their use beyond clinical environments. To obviate the necessity for antibiotics and an external power source, we have developed a wearable synergistic electroceutical device composed of an air self-charging Zn battery. This battery integrates sustained tissue regeneration and antibacterial modalities while maintaining more than half of the initial capacity after ten cycles of chemical charging. In vitro bacterial/cell coculture with the self-charging battery demonstrates inhibited bacterial activity and enhanced cell function by simulating the endogenous electric field and dynamically engineering the microenvironment with released chemicals. This electroceutical device provides accelerated healing of a bacteria-infected wound by stimulating angiogenesis and modulating inflammation, while effectively inhibiting bacterial growth at the wound site. Considering the simple structure and easy operation for long-term treatment, this self-charging electroceutical device offers great potential for personalized wound care.

Chain electrospray ionization mass spectrometry for ultra-low volume sample analysis.

In this work, chain electrospray ionization (chain-ESI) was developed to efficiently ionize trace samples for mass spectrometry analysis. The primary ion source was found to have the ability to induce secondary electrospray ionization with an extraordinarily low sample consumption rate in the picoliters per minute (pLs/min). This allows low volume sample to generate substantial tandem mass spectrum (MS2) data for metabolite annotations. Notably, chain-ESI can effectively prevent the electro-redox reaction in the process of electrospray, so as to reflect the native state of the analytes. Furthermore, from a single Broussonetia papyrifera (B. papyrifera) trichome and a single A549 cancer cell, 1426 and 617 metabolites were detected respectively. All of those observations demonstrated that chain-ESI offers the advantages of direct, rapid analysis with extreme-low volumes and high coverage, enabling the measurement of bio-information in low volume samples.

High-quality integratable microlasers from scalable perovskite heterostructures enabled by solution-phase processing.

High-performance transferable and integratable microlasers hold great promise to construct the integrated photonics and optoelectronics. However, the qualified candidates are still being pursued. Herein, a mass-production of low-threshold and wavelength-tunable microlasers that is readily integratable with the optical fiber platform is realized by a two-step solution-phase approach. The demonstration is enabled by the formation of a novel semiconductor heterostructure from halide perovskites featuring the quasi-free-standing and highly emissive properties. Corroborated by the in-situ optical characterization, we reveal that the lateral perovskite heterostructures are constructed through a sequential reaction driven by the surface energy contrast. These perovskite heterostructures exhibit low-threshold and broadband tunable lasing action thanks to the efficient spatial light conversion nature and the facile composition tunability. Taking the merits together, the heterostructure microlasers can be the competitive applicants for photonic integration as demonstrated by the laser-on-fiber configuration.

Membrane-Anchored Aggregation-Induced Emission Luminogens: Accurate Labeling and Efficient Photodynamic Inactivation of Streptococcus mutans in Anticaries Therapy.

Dental caries is a widespread bacterial infectious disease that imposes a significant public health burden globally. The primary culprits in caries development are cariogenic bacteria, notably Streptococcus mutans (S. mutans), due to their robust biofilm-forming capabilities. To address this issue, a series of cationic pyridinium-substituted photosensitizers with aggregation-induced emission have been designed. All of these aggregation-induced emission luminogens (AIEgens) exhibit outstanding microbial visualization and photodynamic killing of S. mutans, thanks to their luminous fluorescence and efficient singlet oxygen generation ability. Notably, one of the membrane-anchored AIEgens (TDTPY) can inactivate planktic S. mutans and its biofilm without causing significant cytotoxicity. Importantly, application of TDTPY-mediated photodynamic treatment on in vivo rodent models has yielded commendable imaging results and effectively slowed down caries progression with assured biosafety. Unlike traditional single-mode anticaries materials, AIEgens integrate the dual functions of detecting and removing S. mutans and are expected to build a new caries management diagnosis and treatment platform. To the best of our knowledge, this is also the first report on the use of AIEgens for anticaries studies both in vitro and in vivo.

Automated online solid-phase extraction-tandem mass spectrometry detection for simultaneous analysis of acidic and alkaline catecholamines and their metabolites in human urine.

Metabolic dysregulation of catecholamines (CAs) is implicated in various human diseases. Simultaneously analyzing these acidic and alkaline CAs and their metabolites poses a significant challenge for clinical detection. This study introduces an efficient method employing automated online solid-phase extraction coupled with tandem mass spectrometry (aoSPE-MS/MS). The method employs weak cation exchange (WCX) and mixed-mode anion exchange (MAX) adsorbents to fabricate an on-line solid-phase extraction (SPE) column, along with an automated injection and multi-valve switching capabilities. The setup allows for automated extraction and analysis of urine samples in 15 minutes while retaining a wide range of acidic and basic CAs and their metabolites. The applicability of this method was demonstrated by optimising the adsorbent dosage volume, extraction solvent, and extraction rate. The limits of detection (LODs) and limits of quantitation (LOQs) for the 8 CAs and their metabolites were determined using the aoSPE-MS/MS approach, with ranges of 0.0625 ∼ 62.5 ng/mL and 0.125 ∼ 125 ng/mL, respectively. Additionally, assessments were made on the linearity, accuracy, and precision within and between batches, as well as matrix and ionic effects, and spiked recoveries. The study discovered that the aoSPE-MS/MS technique simplifies operation, increases efficiency, saves time, and has low detection and quantification limits when detecting a wide range of acid and alkaline CAs and their metabolites in urine. The study successfully demonstrated the high-throughput and automated detection of the 8 CAs and their metabolites with varying acidity and alkalinity in human urine samples. This method is expected to be a potential powerful tool for clinical detection.