Enzyme encapsulation in metal-organic frameworks using spray drying for enhanced stability and controlled release: A case study of phytase.

Encapsulating enzymes in metal-organic frameworks is a common practice to improve enzyme stability against harsh conditions. However, the synthesis of enzyme@MOFs has been primarily limited to small-scale laboratory settings, hampering their industrial applications. Spray drying is a scalable and cost-effective technology, which has been frequently used in industry for large-scale productions. Despite these advantages, its potential for encapsulating enzymes in MOFs remains largely unexplored, due to challenges such as nozzle clogging from MOF particle formation, utilization of toxic organic solvents, controlled release of encapsulated enzymes, and high temperatures that could compromise enzyme activity. Herein, we present a novel approach for preparing phytase@MIL-88 A using solvent-free spray drying. This involves atomizing two MOF precursor solutions separately using a three-fluid nozzle, with enzyme release controlled by manipulating defects within the MOFs. The physicochemical properties of the spray dried particles are characterized using X-ray diffraction, Fourier-transform infrared spectroscopy, and scanning electron microscopy. Leveraging the efficiency and scalability of spray drying in industrial production, this scalable encapsulation technique holds considerable promise for broad industrial applications.

Actomyosin-II protects axons from degeneration induced by mild mechanical stress.

Whether, to what extent, and how the axons in the central nervous system (CNS) can withstand sudden mechanical impacts remain unclear. By using a microfluidic device to apply controlled transverse mechanical stress to axons, we determined the stress levels that most axons can withstand and explored their instant responses at nanoscale resolution. We found mild stress triggers a highly reversible, rapid axon beading response, driven by actomyosin-II-dependent dynamic diameter modulations. This mechanism contributes to hindering the long-range spread of stress-induced Ca2+ elevations into non-stressed neuronal regions. Through pharmacological and molecular manipulations in vitro, we found that actomyosin-II inactivation diminishes the reversible beading process, fostering progressive Ca2+ spreading and thereby increasing acute axonal degeneration in stressed axons. Conversely, upregulating actomyosin-II activity prevents the progression of initial injury, protecting stressed axons from acute degeneration both in vitro and in vivo. Our study unveils the periodic actomyosin-II in axon shafts cortex as a novel protective mechanism, shielding neurons from detrimental effects caused by mechanical stress.

Fragmentation characteristics-based nontargeted screening method of exogenous chemical residues in animal-derived foods using reversed-phase and hydrophilic interaction liquid chromatography-high-resolution mass spectrometry.

Fragmentation characteristics are crucial for nontargeted screening to discover and identify unknown exogenous chemical residues in animal-derived foods. In this study, first, fragmentation characteristics of 51 classes of exogenous chemical residues were summarized based on experimental mass spectra of standards in reversed-phase and hydrophilic interaction liquid chromatography-high-resolution mass spectrometry (MS) and mass spectra from the MassBank of North America (MoNA) library. According to the proportion of fragmentation characteristics to the total number of chemical residues in each class, four screening levels were defined to classify 51 classes of chemical residues. Then, a nontargeted screening method was developed based on the fragmentation characteristics. The evaluation results of 82 standards indicated that more than 90 % of the chemical residues with MS/MS spectra can be identified at concentrations of 100 and 500 µg/kg, and about 80 % can be identified at 10 µg/kg. Finally, the nontargeted screening method was applied to 16 meat samples and 21 egg samples as examples. As a result, eight chemical residues and transformation products (TPs) of 5 classes in the exemplary samples were found and identified, in which 3 TPs of azithromycin were identified by fragmentation characteristics-assisted structure interpretation. The results demonstrated the practicability of the nontargeted screening method for routine risk screening of food safety.

Boosting Enzyme Activity in Enzyme Metal-Organic Framework Composites.

Enzymes, as highly efficient biocatalysts, excel in catalyzing diverse reactions with exceptional activity and selective properties under mild conditions. Nonetheless, their broad applications are hindered by their inherent fragility, including low thermal stability, limited pH tolerance, and sensitivity to organic solvents and denaturants. Encapsulating enzymes within metal-organic frameworks (MOFs) can protect them from denaturation in these harsh environments. However, this often leads to a compromised enzyme activity. In recent years, extensive research efforts have been dedicated to enhancing enzymatic activity within MOFs, leading to the development of new enzyme-MOF composites that not only preserve their catalytic potential but also outperform their free counterparts. This Review provides a comprehensive review on recent developments in enzyme-MOF composites with a specific emphasis on their enhanced enzymatic activity compared to free enzymes.

Investigation of the formation mechanism of the pepper starch-piperine complex.

In this study, a new carrier for loading piperine was prepared using pepper starch, and its interaction mechanism was investigated. The porous pepper starch-piperine complex (PPS-PIP) showed higher loading efficiency (76.15 %) compared to the porous corn starch-piperine complex (PCS-PIP (52.34 %)). This may be ascribed to the hemispherical shell structure of porous pepper starch (PPS) compared to the porous structure of porous corn starch (PCS) based on the SEM result. PPS-PIP had smaller particle size (10.53 µm), higher relative crystallinity (38.95 %), and better thermal stability (87.45 °C) than PCS-PIP (17.37 µm, 32.17 %, 74.35 °C). Fourier transform infrared spectroscopy (FTIR) results implied that piperine not only forms a complex with amylose but may also be physically present in porous starch. This was demonstrated by the short-range order and X-ray type. Molecular dynamics simulations confirmed that hydrogen bonding is the primary interaction between amylose and piperine. Besides the formation of the amylose-piperine complex, some of the piperine is also present in physical form.

Application of a circular-shaped pulsed field ablation catheter with magnetic sensors for pulmonary vein isolation: a multi-centre clinical study report.

AIMS: A few studies have reported the effect and safety of pulsed field ablation (PFA) catheters for ablating atrial fibrillation (AF), which were mainly based on basket-shaped or flower-shaped designs. However, the clinical application of a circular-shaped multi-electrode catheter with magnetic sensors is very limited. To study the efficacy and safety of a PFA system in patients with paroxysmal AF using a circular-shaped multi-electrode catheter equipped with magnetic sensors for pulmonary vein isolation (PVI). METHODS AND RESULTS: A novel proprietary bipolar PFA system was used for PVI, which utilized a circular-shaped multi-electrode catheter with magnetic sensors and allowed for three-dimensional model reconstruction, mapping, and ablation in one map. To evaluate the efficacy, efficiency, and safety of this PFA system, a prospective, multi-centre, single-armed, pre-market clinical study was performed. From July 2021 to December 2022, 151 patients with paroxysmal AF were included and underwent PVI. The study examined procedure time, immediate success rate, procedural success rate at 12 months, and relevant complications. In all 151 patients, all the pulmonary veins were acutely isolated using the studied system. Pulsed field ablation delivery was 78.4 ± 41.8 times and 31.3 ± 16.7 ms per patient. Skin-to-skin procedure time was 74.2 ± 29.8 min, and fluoroscopy time was 13.1 ± 7.6 min. The initial 11 (7.2%) cases underwent procedures with deep sedation anaesthesia, and the following cases underwent local anaesthesia. In the initial 11 cases, 4 cases (36.4%) presented transient vagal responses, and the rest were all successfully preventatively treated with atropine injection and rapid fluid infusion. No severe complications were found during or after the procedure. During follow-up, 3 cases experienced atrial flutter, and 11 cases had AF recurrence. The estimated 12-month Kaplan-Meier of freedom from arrhythmia was 88.4%. CONCLUSION: The PFA system, comprised of a circular PFA catheter with magnetic sensors, could rapidly achieve PVI under three-dimensional guidance and demonstrated excellent safety with comparable effects.

Depressive symptoms, parenting attitude, and violent discipline among caregivers of left-behind children in rural China: a cross-sectional study.

BACKGROUND: The situation of mental health and discipline behaviors of left-behind children's caregivers were not optimistic in rural China. Caregivers' depression might increase the risk of using violent discipline. However, the specific ways in which depressive symptoms impact violent discipline have rarely been explored in rural areas. This study aims to assess the prevalence of violent discipline among left-behind children under 6 years of age in rural China and explore the potential mechanisms of how caregivers' depressive symptoms affect violent discipline. METHODS: We enrolled a total of 396 pairs of left-behind children and their caregivers in our study, which was conducted in 5 counties of Hebei, Henan, Jiangxi, Guizhou, and Sichuan provinces in China. The depressive symptoms of caregivers were measured by using Zung Self-rating Depression Scale (ZSDS) and violent discipline was assessed by the Child Discipline Module of Multiple Indicator Cluster Surveys (MICS). A self-designed questionnaire was utilized to measure caregiver's parenting attitude. Based on the cross-sectional data, controlling for potential confounders, structural equation modeling (SEM) was used to assess the direct and indirect effects of the mediation models by applying the weighted least squares with mean and variance adjusted (WLSMV) estimate. RESULTS: The prevalence of violent discipline, psychological aggression, and physical punishment was 72.7%, 59.3%, and 60.4% respectively of left-behind children under 6 years of age. According to the results of SEM, parenting attitude acted as a suppressor, suppressing the association between caregivers' depressive symptoms and physical punishment/psychological aggression/violent discipline. The caregivers' depressive symptoms positively influenced all the outcome variables by affecting parenting attitudes (p = 0.002, p = 0.013, p = 0.002). CONCLUSIONS: The presence of depressive symptoms in caregivers increases the use of violent discipline through negative parenting attitudes. The mental health status of primary caregivers of left-behind children in rural China needed emphasis and improvement.

An exposome atlas of serum reveals the risk of chronic diseases in the Chinese population.

Although adverse environmental exposures are considered a major cause of chronic diseases, current studies provide limited information on real-world chemical exposures and related risks. For this study, we collected serum samples from 5696 healthy people and patients, including those with 12 chronic diseases, in China and completed serum biomonitoring including 267 chemicals via gas and liquid chromatography-tandem mass spectrometry. Seventy-four highly frequently detected exposures were used for exposure characterization and risk analysis. The results show that region is the most critical factor influencing human exposure levels, followed by age. Organochlorine pesticides and perfluoroalkyl substances are associated with multiple chronic diseases, and some of them exceed safe ranges. Multi-exposure models reveal significant risk effects of exposure on hyperlipidemia, metabolic syndrome and hyperuricemia. Overall, this study provides a comprehensive human serum exposome atlas and disease risk information, which can guide subsequent in-depth cause-and-effect studies between environmental exposures and human health.

Efficient nitrate and Cr(VI) removal by denitrifier: The mechanism of S. oneidensis MR-1 promoting electron production, transportation and consumption.

When Cr(VI) and nitrate coexist, the efficiency of both bio-denitrification and Cr(VI) bio-reduction is poor because chromate hinders bacterial normal functions (i.e., electron production, transportation and consumption). Moreover, under anaerobic condition, the method about efficient nitrate and Cr(VI) removal remained unclear. In this paper, the addition of Shewanella oneidensis MR-1 to promote the electron production, transportation and consumption of denitrifier and cause an increase in the removal of nitrate and Cr(VI). The efficiency of nitrate and Cr(VI) removal accomplished by P. denitrificans as a used model denitrifier increased respectively from 51.3% to 96.1% and 34.3% to 99.8% after S. oneidensis MR-1 addition. The mechanism investigations revealed that P. denitrificans provided S. oneidensis MR-1 with lactate, which was utilized to secreted riboflavin and phenazine by S. oneidensis MR-1. The riboflavin served as coenzymes of cellular reductants (i.e., thioredoxin and glutathione) in P. denitrificans, which created favorable intracellular microenvironment conditions for electron generation. Meanwhile, phenazine promoted biofilm formation, which increased the adsorption of Cr(VI) on the cell surface and accelerated the Cr(VI) reduction by membrane bound chromate reductases thereby reducing damage to other enzymes respectively. Overall, this strategy reduced the negative effect of chromate, thus improved the generation, transportation, and consumption of electrons. SYNOPSIS: The presence of S. oneidensis MR-1 facilitated nitrate and Cr(VI) removal by P. denitrificans through decreasing the negative effect of chromate due to the metabolites' secretion.

Particle-Based Artificial Antigen-Presenting Cell Systems for T Cell Activation in Adoptive T Cell Therapy.

T cell-based adoptive cell therapy (ACT) has emerged as a promising treatment for various diseases, particularly cancers. Unlike other immunotherapy modalities, ACT involves directly transferring engineered T cells into patients to eradicate diseased cells; hence, it necessitates methods for effectively activating and expanding T cells in vitro. Artificial antigen-presenting cells (aAPCs) have been widely developed based on biomaterials, particularly micro- and nanoparticles, and functionalized with T cell stimulatory antibodies to closely mimic the natural T cell-APC interactions. Due to their vast clinical utility, aAPCs have been employed as an off-the-shelf technology for T cell activation in FDA-approved ACTs, and the development of aAPCs is constantly advancing with the emergence of aAPCs with more sophisticated designs and additional functionalities. Here, we review the recent advancements in particle-based aAPCs for T cell activation in ACTs. Following a brief introduction, we first describe the manufacturing processes of ACT products. Next, the design and synthetic strategies for micro- and nanoparticle-based aAPCs are discussed separately to emphasize their features, advantages, and limitations. Then, the impact of design parameters of aAPCs, such as size, shape, ligand density/mobility, and stiffness, on their functionality and biomedical performance is explored to provide deeper insights into the design concepts and principles for more efficient and safer aAPCs. The review concludes by discussing current challenges and proposing future perspectives for the development of more advanced aAPCs.

Super-Flexible Water-Proof Actuators.

Humidity-responsive materials hold broad application prospects in sensing, energy production, and other fields. Particularly, humidity-sensitive, flexibility, and water resistance are pivotal factors in the development of optimized humidity-responsive materials. In this study, hydrophobic linear polyurethane and hydrophilic 4-vinylphenylboronic acid (4-VPBA) form a semi-intercross cross-linking network. This copolymer of polyurethane exhibits excellent humidity-sensitive, mechanical properties, and water resistance. Its maximum tensile strength and maximum elongation can reach 40.56 MPa and 543.47%, respectively. After being immersed in water at various temperatures for 15 days, it exhibited a swelling ratio of only 3.28% in water at 5 °C and 9.58% in water at 70 °C. While the presence of 4-VPBA network imparts humidity-sensitive, reversible, and multidirectional bending abilities, under the stimulus of water vapor, it can bend 43° within 1.4 s. The demonstrated material surpasses current bidirectional humidity actuators in actuating ability. Based on these characteristics, automatically opening waterproof umbrellas and windows, as well as bionic-arms, crawling robots, and self-propelled boats, are successfully developed.

Multidisciplinary management strategies for atrial fibrillation.

There has been a significant increase in the prevalence of atrial fibrillation (AF) over the past 30 years. Pulmonary vein isolation (PVI) is an effective treatment for AF, but research investigations have shown that AF recurrence still occurs in a significant number of patients after ablation. Heart rhythm outcomes following catheter ablation are correlated with numerous clinical factors, and researchers developed predictive models by integrating risk factors to predict the risk of recurrence of atrial fibrillation. The purpose of this article is to outline the risk scores for predicting cardiac rhythm outcomes after PVI and to discuss the modifiable factors that increase the risk of recurrence of AF, with the hope of further improving catheter ablation efficacy through preoperative identification of high-risk populations and postoperative management of modifiable risk factors.

Leveraging Unidentified Metabolic Features for Key Pathway Discovery: Chemical Classification-driven Network Analysis in Untargeted Metabolomics.

Untargeted metabolomics using liquid chromatography-electrospray ionization-high-resolution tandem mass spectrometry (UPLC-ESI-MS/MS) provides comprehensive insights into the dynamic changes of metabolites in biological systems. However, numerous unidentified metabolic features limit its utilization. In this study, a novel approach, the Chemical Classification-driven Molecular Network (CCMN), was proposed to unveil key metabolic pathways by leveraging hidden information within unidentified metabolic features. The method was demonstrated by using the herbivore-induced metabolic response in corn silk as a case study. Untargeted metabolomics analysis using UPLC-MS/MS was performed on wild corn silk and two genetically modified lines (pre- and postinsect treatment). Global annotation initially identified 256 (ESI-) and 327 (ESI+) metabolites. MS/MS-based classifications predicted 1939 (ESI-) and 1985 (ESI+) metabolic features into the chemical classes. CCMNs were then constructed using metabolic features shared classes, which facilitated the structure- or class annotation for completely unknown metabolic features. Next, 844/713 significantly decreased and 1593/1378 increased metabolites in ESI-/ESI+ modes were defined in response to insect herbivory, respectively. Method validation on a spiked maize sample demonstrated an overall class prediction accuracy rate of 95.7%. Potential key pathways were prescreened by a hypergeometric test using both structure- and class-annotated differential metabolites. Subsequently, CCMN was used to deeply amend and uncover the pathway metabolites deeply. Finally, 8 key pathways were defined, including phenylpropanoid (C6-C3), flavonoid, octadecanoid, diterpenoid, lignan, steroid, amino acid/small peptide, and monoterpenoid. This study highlights the effectiveness of leveraging unidentified metabolic features. CCMN-based key pathway analysis reduced the bias in conventional pathway enrichment analysis. It provides valuable insights into complex biological processes.

Fine-Scale Characterization of Plant Diterpene Glycosides Using Energy-Resolved Untargeted LC-MS/MS Metabolomics Analysis.

Plant diterpene glycosides are essential for diverse physiological processes. Comprehensive structural characterization proved to be a challenge due to variations in glycosylation patterns, diverse aglycone structures, and the absence of comprehensive reference databases. In this study, a method for fine-scale characterization was proposed based on energy-resolved (ER) untargeted LC-MS/MS metabolomics analysis using steviol glycosides as a demonstration. Energy-dependent fragmentation patterns were unveiled by a series of model compounds. Distinct glycosylation sites were discerned by leveraging varying fragmentation energies for the precursor ions. The sugar moiety linkage at C19OOH (R1) exhibited facile and intact cleavage at low collision energies, while the sugar moiety at C13-OH (R2) demonstrated consecutive cleavage with increasing energy. Aglycone ions exhibited a higher relative intensity at NCE 50, with relative intensities ranging from 95% to 100%. Subsequently, aglycone candidates, R1 sugar composition, and R2 sugar sequence were deduced through ER-MS/MS analysis. The developed method was applied to Stevia rebaudiana leaves. A total of 91 diterpene glycosides were unambiguously identified, including 16 steviol glycosides with novel acetylglycosylation patterns. This method offers a rapid alternative for glycan analysis and the structural differentiation of isomers. The developed method enhances the understanding of diterpene glycosides in plants, providing a reliable tool for the in-depth characterization of complex metabolite profiles.

Chinese Society of Cardiology guidelines on the diagnosis and treatment of adult fulminant myocarditis.

Fulminant myocarditis is an acute diffuse inflammatory disease of myocardium. It is characterized by acute onset, rapid progress and high risk of death. Its pathogenesis involves excessive immune activation of the innate immune system and formation of inflammatory storm. According to China's practical experience, the adoption of the "life support-based comprehensive treatment regimen" (with mechanical circulation support and immunomodulation therapy as the core) can significantly improve the survival rate and long-term prognosis. Special emphasis is placed on very early identification,very early diagnosis,very early prediction and very early treatment.

Cancer Metastasis-on-a-Chip for Modeling Metastatic Cascade and Drug Screening.

Microfluidic chips are valuable tools for studying intricate cellular and cell-microenvironment interactions. Traditional in vitro cancer models lack accuracy in mimicking the complexities of in vivo tumor microenvironment. However, cancer-metastasis-on-a-chip (CMoC) models combine the advantages of 3D cultures and microfluidic technology, serving as powerful platforms for exploring cancer mechanisms and facilitating drug screening. These chips are able to compartmentalize the metastatic cascade, deepening the understanding of its underlying mechanisms. This article provides an overview of current CMoC models, focusing on distinctive models that simulate invasion, intravasation, circulation, extravasation, and colonization, and their applications in drug screening. Furthermore, challenges faced by CMoC and microfluidic technologies are discussed, while exploring promising future directions in cancer research. The ongoing development and integration of these models into cancer studies are expected to drive transformative advancements in the field.

Screening and identification of unknown chemical contaminants in food based on liquid chromatography-high-resolution mass spectrometry and machine learning.

Unknown or unexpected chemical contaminants and/or their transformation products in food that may be harmful to humans need to be discovered for comprehensive safety evaluation. Liquid chromatography-high-resolution mass spectrometry (LC-HRMS) is a powerful tool for detecting chemical contaminants in food samples. However, identifying all of peaks in LC-HRMS is not possible, but if class information is known in advance, further identification will become easier. In this work, a novel MS2 spectra classification-driven screening strategy was constructed based on LC-HRMS and machine learning. First, the classification model was developed based on machine learning algorithm using class information and experimental MS2 data of chemical contaminants and other non-contaminants. By using the developed artificial neural network classification model, in total 32 classes of pesticides, veterinary drugs and mycotoxins were classified with good prediction accuracy and low false-positive rate. Based on the classification model, a screening procedure was developed in which the classes of unknown features in LC-HRMS were first predicted through the classification model, and then their structures were identified under the guidance of class information. Finally, the developed strategy was tentatively applied to the analysis of pork and aquatic products, and 8 chemical contaminants and 11 transformation products belonging to 8 classes were found. This strategy enables screening of unknown chemical contaminants and transformation products in complex food matrices.