Single-step precision programming of decoupled multiresponsive soft millirobots.

Stimuli-responsive soft robots offer new capabilities for the fields of medical and rehabilitation robotics, artificial intelligence, and soft electronics. Precisely programming the shape morphing and decoupling the multiresponsiveness of such robots is crucial to enable them with ample degrees of freedom and multifunctionality, while ensuring high fabrication accuracy. However, current designs featuring coupled multiresponsiveness or intricate assembly processes face limitations in executing complex transformations and suffer from a lack of precision. Therefore, we propose a one-stepped strategy to program multistep shape-morphing soft millirobots (MSSMs) in response to decoupled environmental stimuli. Our approach involves employing a multilayered elastomer and laser scanning technology to selectively process the structure of MSSMs, achieving a minimum machining precision of 30 µm. The resulting MSSMs are capable of imitating the shape morphing of plants and hand gestures and resemble kirigami, pop-up, and bistable structures. The decoupled multistimuli responsiveness of the MSSMs allows them to conduct shape morphing during locomotion, perform logic circuit control, and remotely repair circuits in response to humidity, temperature, and magnetic field. This strategy presents a paradigm for the effective design and fabrication of untethered soft miniature robots with physical intelligence, advancing the decoupled multiresponsive materials through modular tailoring of robotic body structures and properties to suit specific applications.

Actuation-enhanced multifunctional sensing and information recognition by magnetic artificial cilia arrays.

Artificial cilia integrating both actuation and sensing functions allow simultaneously sensing environmental properties and manipulating fluids in situ, which are promising for environment monitoring and fluidic applications. However, existing artificial cilia have limited ability to sense environmental cues in fluid flows that have versatile information encoded. This limits their potential to work in complex and dynamic fluid-filled environments. Here, we propose a generic actuation-enhanced sensing mechanism to sense complex environmental cues through the active interaction between artificial cilia and the surrounding fluidic environments. The proposed mechanism is based on fluid-cilia interaction by integrating soft robotic artificial cilia with flexible sensors. With a machine learning-based approach, complex environmental cues such as liquid viscosity, environment boundaries, and distributed fluid flows of a wide range of velocities can be sensed, which is beyond the capability of existing artificial cilia. As a proof of concept, we implement this mechanism on magnetically actuated cilia with integrated laser-induced graphene-based sensors and demonstrate sensing fluid apparent viscosity, environment boundaries, and fluid flow speed with a reconfigurable sensitivity and range. The same principle could be potentially applied to other soft robotic systems integrating other actuation and sensing modalities for diverse environmental and fluidic applications.

The activator protein-1 complex governs a vascular degenerative transcriptional programme in smooth muscle cells to trigger aortic dissection and rupture.

BACKGROUND AND AIMS: Stanford type A aortic dissection (AD) is a degenerative aortic remodelling disease marked by an exceedingly high mortality without effective pharmacologic therapies. Smooth muscle cells (SMCs) lining tunica media adopt a range of states, and their transformation from contractile to synthetic phenotypes fundamentally triggers AD. However, the underlying pathomechanisms governing this population shift and subsequent AD, particularly at distinct disease temporal stages, remain elusive. METHODS: Ascending aortas from nine patients undergoing ascending aorta replacement and five individuals undergoing heart transplantation were subjected to single-cell RNA sequencing. The pathogenic targets governing the phenotypic switch of SMCs were identified by trajectory inference, functional scoring, single-cell regulatory network inference and clustering, regulon, and interactome analyses and confirmed using human ascending aortas, primary SMCs, and a ß-aminopropionitrile monofumarate-induced AD model. RESULTS: The transcriptional profiles of 93 397 cells revealed a dynamic temporal-specific phenotypic transition and marked elevation of the activator protein-1 (AP-1) complex, actively enabling synthetic SMC expansion. Mechanistically, tumour necrosis factor signalling enhanced AP-1 transcriptional activity by dampening mitochondrial oxidative phosphorylation (OXPHOS). Targeting this axis with the OXPHOS enhancer coenzyme Q10 or AP-1-specific inhibitor T-5224 impedes phenotypic transition and aortic degeneration while improving survival by 42.88% (58.3%-83.3% for coenzyme Q10 treatment), 150.15% (33.3%-83.3% for 2-week T-5224), and 175.38% (33.3%-91.7% for 3-week T-5224) in the ß-aminopropionitrile monofumarate-induced AD model. CONCLUSIONS: This cross-sectional compendium of cellular atlas of human ascending aortas during AD progression provides previously unappreciated insights into a transcriptional programme permitting aortic degeneration, highlighting a translational proof of concept for an anti-remodelling intervention as an attractive strategy to manage temporal-specific AD by modulating the tumour necrosis factor-OXPHOS-AP-1 axis.

Polyvinylpyrrolidone-Coated Cubic Hollow Nanocages of PdPt3 and PdIr3 as Highly Efficient Self-Cascade Uricase/Peroxidase Mimics.

Uricase-catalyzed uric acid (UA) degradation has been applied for hyperuricemia therapy, but this medication is limited by H2O2 accumulation, which can cause oxidative stress of cells, resulting in many other health issues. Herein, we report a robust cubic hollow nanocage (HNC) system based on polyvinylpyrrolidone-coated PdPt3 and PdIr3 to serve as highly efficient self-cascade uricase/peroxidase mimics to achieve the desired dual catalysis for both UA degradation and H2O2 elimination. These HNCs have hollow cubic shape with average wall thickness of 1.5 nm, providing desired synergy to enhance catalyst's activity and stability. Density functional theory calculations suggest the PdIr3 HNC surface tend to promote OH*/O* desorption for better peroxidase-like catalysis, while the PdPt3 HNC surface accelerates the UA oxidation by facilitating O2-to-H2O2 conversion. The dual catalysis power demonstrated by these HNCs in cell studies suggests their great potential as a new type of nanozyme for treating hyperuricemia.

Crystal Facet Controlled Metal-Support Interaction in Uricase Mimics for Highly Efficient Hyperuricemia Treatment.

The effect of strong metal-support interaction (SMSI) has never been systematically studied in the field of nanozyme-based catalysis before. Herein, by coupling two different Pd crystal facets with MnO2, i.e., (100) by Pd cube (Pdc) and (111) by Pd icosahedron (Pdi), we observed the reconstruction of Pd atomic structure within the Pd-MnO2 interface, with the reconstructed Pdc (100) facet more disordered than Pdi (111), verifying the existence of SMSI in such coupled system. The rearranged Pd atoms in the interface resulted in enhanced uricase-like catalytic activity, with Pdc@MnO2 demonstrating the best catalytic performance. Theoretical calculations suggested that a more disordered Pd interface led to stronger interactions with intermediates during the uricolytic process. In vitro cell experiments and in vivo therapy results demonstrated excellent biocompatibility, therapeutic effect, and biosafety for their potential hyperuricemia treatment. Our work provides a brand-new perspective for the design of highly efficient uricase-mimic catalysts.

The structural biology of type III CRISPR-Cas systems.

CRISPR-Cas system is an RNA-guided adaptive immune system widespread in bacteria and archaea. Among them, type III CRISPR-Cas systems are the most ancient throughout the CRISPR-Cas family, proving anti-phage defense through a crRNA-guided RNA targeting manner and possessing multiple enzymatic activities. Type III CRISPR-Cas systems comprise four typical members (type III-A to III-D) and two atypical members (type III-E and type III-F), providing immune defense through distinct mechanisms. Here, we delve into structural studies conducted on three well-characterized members: the type III-A, III-B, and III-E systems, provide an overview of the structural insights into the crRNA-guided target RNA cleavage, self/non-self discrimination, and the target RNA-dependent regulation of enzymatic subunits in the effector complex.

Visualization of Acrolein Upregulation during Ferroptosis by a Ratiometric Fluorescent Probe.

Ferroptosis is a pattern of cell death caused by iron-dependent accumulation of lipid peroxides and is closely associated with the occurrence and development of multiple diseases. Acrolein (ACR), one of the final metabolites of lipid peroxidation, is a reactive carbonyl species with strong biotoxicity. Effective detection of ACR is important for understanding its role in the progression of ferroptosis and studying the specific mechanisms of ferroptosis-mediated diseases. However, visualization detection of ACR during ferroptosis has not yet been reported. In this work, the first ratiometric fluorescent probe (HBT-SH) based on 2-(2'-hydroxyphenyl) benzothiazole (HBT) was designed for tracing endogenous ACR with an unprecedented regiospecific ACR-induced intramolecular cyclization strategy, which employs 2-aminoethanethiol as an ACR-selective recognition receptor. The experimental results showed that HBT-SH has excellent selectivity, high sensitivity (LOD = 0.26 µM) and good biocompatibility. More importantly, the upregulation of ACR levels was observed during ferroptosis in HeLa cells and zebrafish, indicating that ACR may be a specific active molecule that plays an essential biological role during ferroptosis or may serve as a potential marker of ferroptosis, which has great significance for studying the pathological process and treatment options of ferroptosis-related diseases.

Removing Conjugated Polymers from Aligned Carbon Nanotube Arrays.

Aligned carbon nanotube (A-CNT) with high semiconducting purity and high-density have been considered as one of the most promising active channels for field-effect transistors (FETs), but conjugated polymer dispersant residues on the surface of A-CNT have become the main obstacle for its further development in electronics applications. In this work, a series of removable conjugated polymers (CPs) are designed and synthesized to achieve favorable purification and alignment for CNT arrays with a high density of ≈360 CNTs/µm. Furthermore, a removal process of CPs on the CNT array film is developed. Raman spectra show that the CNTs in array film are almost not damaged after the removal process, and the G/D ratio is as high as 35. The field-effect transistors (FETs) are fabricated with a saturation current density up to 600 µA µm-1 and a current on-off ratio of ≈105, even with a relatively long channel length of ≈3 µm.

Efficient Carrier Transport in 2D Bi2O2Se/CsBi3I10 Perovskite Heterojunction Enables Highly-Sensitive Broadband Photodetection.

2D Bi2O2Se has recently garnered significant attention in the electronics and optoelectronics fields due to its remarkable photosensitivity, broad spectral absorption, and excellent long-term environmental stability. However, the development of integrated Bi2O2Se photodetector with high performance and low-power consumption is limited by material synthesis method and the inherent high carrier concentration of Bi2O2Se. Here, a type-I heterojunction is presented, comprising 2D Bi2O2Se and lead-free bismuth perovskite CsBi3I10, for fast response and broadband detection. Through effective charge transfer and strong coupling effect at the interfaces of Bi2O2Se and CsBi3I10, the response time is accelerated to 4.1 µs, and the detection range is expanded from ultraviolet to near-infrared spectral regions (365-1500 nm). The as-fabricated photodetector exhibits a responsivity of 48.63 AW-1 and a detectivity of 1.22×1012 Jones at 808 nm. Moreover, efficient modulation of the dominant photocurrent generation mechanism from photoconductive to photogating effect leads to sensitive response exceeding 103 AW-1 for heterojunction-based photo field effect transistor (photo-FETs). Utilizing the large-scale growth of both Bi2O2Se and CsBi3I10, the as-fabricated integrated photodetector array demonstrates outstanding homogeneity and stability of photo-response performance. The proposed 2D Bi2O2Se/CsBi3I10 perovskite heterojunction holds promising prospects for the future-generation photodetector arrays and integrated optoelectronic systems.

Self-Assembled Metal-Coordination Nanohelices as Efficient and Robust Chiral Supramolecular Catalysts for Enantioselective Reactions.

The development of chiral nanostructures-based supramolecular catalysts with satisfied enantioselectivity remains a significantly more challenging task. Herein, the synthesis and self-assembly of various amino acid amphiphiles as chiral supramolecular catalysts after metal ion coordination is reported and systematically investigate their enantioselectivity in asymmetric Diels-Alder reactions. In particular, the self-assembly of l/d-phenylglycine-based amphiphiles (l/d-PhgC16) and Cu(II) into chiral supramolecular catalysts in the methanol/water solution mixture is described, which features the interesting M/P nanohelices (diameter ≈8 nm) and mostly well-aligned M/P nanoribbons (NRs). The M/P supramolecular catalysts show both high but inverse enantioselectivity (>90% ee) in Diels-Alder reactions, while their monomeric counterparts display nearly racemic products. Analysis of the catalytic results suggests the outstanding enantioselectivities are closely related to the specific stereochemical microenvironment provided by the arrangement of the amphiphiles in the supramolecular assembly. Based on the experimental evidence of chirality transfer from supramolecular nanohelices to coordinated Cu(II) and substrate aza-chalcone and the molecular dynamics simulations, the enantioselective catalytic mechanisms are proposed. Moreover, the relationships between molecular structures of amino acid amphiphiles (the hydrophilic head group and hydrophobic alkyl chain length) in supramolecular catalysts and enantioselectivity in Diels-Alder reactions are elaborated.

Dissecting the shared genetic landscape of anxiety, depression, and schizophrenia.

BACKGROUND: Numerous studies highlight the genetic underpinnings of mental disorders comorbidity, particularly in anxiety, depression, and schizophrenia. However, their shared genetic loci are not well understood. Our study employs Mendelian randomization (MR) and colocalization analyses, alongside multi-omics data, to uncover potential genetic targets for these conditions, thereby informing therapeutic and drug development strategies. METHODS: We utilized the Consortium for Linkage Disequilibrium Score Regression (LDSC) and Mendelian Randomization (MR) analysis to investigate genetic correlations among anxiety, depression, and schizophrenia. Utilizing GTEx V8 eQTL and deCODE Genetics pQTL data, we performed a three-step summary-data-based Mendelian randomization (SMR) and protein-protein interaction analysis. This helped assess causal and comorbid loci for these disorders and determine if identified loci share coincidental variations with psychiatric diseases. Additionally, phenome-wide association studies, drug prediction, and molecular docking validated potential drug targets. RESULTS: We found genetic correlations between anxiety, depression, and schizophrenia, and under a meta-analysis of MR from multiple databases, the causal relationships among these disorders are supported. Based on this, three-step SMR and colocalization analyses identified ITIH3 and CCS as being related to the risk of developing depression, while CTSS and DNPH1 are related to the onset of schizophrenia. BTN3A1, PSMB4, and TIMP4 were identified as comorbidity loci for both disorders. Molecules that could not be determined through colocalization analysis were also presented. Drug prediction and molecular docking showed that some drugs and proteins have good binding affinity and available structural data. CONCLUSIONS: Our study indicates genetic correlations and shared risk loci between anxiety, depression, and schizophrenia. These findings offer insights into the underlying mechanisms of their comorbidities and aid in drug development.

Chiral Supramolecular Self-Assembly Catalysts with Enhanced Metal Ion Interaction for Higher Enantioselectivity.

Understanding the interaction between metal ions as catalytic centers and supramolecular scaffolds as chiral substrates plays an important role in developing chiral supramolecular catalysts with high enantioselectivity. Herein, we found that compared with l-norleucine chiral amphiphile (l-NorC16), l-methionine chiral amphiphile (l-MetC16) with the only heteroatom of S site difference in the hydrophilic group can form a similar supramolecular chiral nanoribbon (NR) with the bilayer structure through the self-assembly approach; yet, the interaction between the Cu(II) ion catalytic centers and supramolecular scaffolds is reinforced, favoring the chirality transfer and therefore enhancing their catalytic enantioselectivity of Diels-Alder reaction from 23% [l-NorC16-NR-Cu(II)] to 78% [l-MetC16-NR-Cu(II)]. Our work demonstrates a new strategy from the perspective of strengthening the metal ion-supramolecular scaffold interaction for the preparation of chiral supramolecular catalysts with good catalytic enantioselectivity.

Scoring model based on cardiac CT and clinical factors to predict early good mitral valve repair in rheumatic mitral disease.

OBJECTIVE: We aimed to evaluate the mitral valve calcification and mitral structure detected by cardiac computed tomography (cardiac CT) and establish a scoring model based on cardiac CT and clinical factors to predict early good mitral valve repair (EGMR) and guide surgical strategy in rheumatic mitral disease (RMD). MATERIALS AND METHODS: This is a retrospective bi-center cohort study. Based on cardiac CT, mitral valve calcification and mitral structure in RMD were quantified and evaluated. The primary outcome was EGMR. A logical regression algorithm was applied to the scoring model. RESULTS: A total of 579 patients were enrolled in our study from January 1, 2019, to August 31, 2022. Of these, 443 had baseline cardiac CT scans of adequate quality. The calcification quality score, calcification and thinnest part of the anterior leaflet clean zone, and papillary muscle symmetry were the independent CT factors of EGMR. Coronary artery disease and pulmonary artery pressure were the independent clinical factors of EGMR. Based on the above six factors, a scoring model was established. Sensitivity = 95% and specificity = 95% were presented with a cutoff value of 0.85 and 0.30 respectively. The area under the receiver operating characteristic of external validation set was 0.84 (95% confidence interval [CI] 0.73-0.93). CONCLUSIONS: Mitral valve repair is recommended when the scoring model value > 0.85 and mitral valve replacement is prior when the scoring model value < 0.30. This model could assist in guiding surgical strategies for RMD. CLINICAL RELEVANCE STATEMENT: The model established in this study can serve as a reference indicator for surgical repair in rheumatic mitral valve disease. KEY POINTS: • Cardiac CT can reflect the mitral structure in detail, especially for valve calcification. • A model based on cardiac CT and clinical factors for predicting early good mitral valve repair was established. • The developed model can help cardiac surgeons formulate appropriate surgical strategies.

Hydrolysis of Nerve Agent Simulants Accelerated by Stimuli-Responsive Dinuclear Catalysts.

The ability to control the catalytic activity of enzymes in chemical transformations is essential for the design and development of artificial catalysts. Herein, we report the synthesis and characterization of functional ligands featuring two 1,4,7,10-tetraazacyclododecane units linked by an azobenzene group and their corresponding dinuclear Zn(II) complexes. We show that the configuration switching (E/Z) of the azobenzene spacer in the ligands and their dinuclear Zn(II) complexes is reversibly controlled by irradiation with UV and visible light. The Zn(II)-metal complexes are light-responsive catalysts for the hydrolytic cleavage of nerve agent simulants, i.e., p-nitrophenyl diphenyl phosphate and methyl paraoxon. The catalytic activity of the Z-isomers of the dinuclear Zn(II) complexes outperformed that of the E-counterparts. Moreover, combining the less active E-isomers with gold nanoparticles induced an enhancement in the hydrolysis rate of p-nitrophenyl diphenyl phosphate. Kinetic analysis has shown that the catalytic site appears to involve a single metal ion. We explain our results by considering the different desolvation effects occurring in the catalyst's configurations in the solution and the catalytic systems involving gold nanoparticles.

Predictive value of the serum uric acid to high-density lipoprotein cholesterol ratio for culprit plaques in patients with acute coronary syndrome.

BACKGROUND: Hyperuricemia and low level of high-density lipoprotein cholesterol (HDL-C) are both risk factors for coronary artery disease (CAD). The uric acid to HDL-C ratio (UHR) has recently been identified as a new inflammatory and metabolic biomarker. However, the relationship between the UHR and coronary culprit plaques has not been fully investigated in patients with acute coronary syndrome (ACS). METHODS: A total of 346 patients with ACS were enrolled in this study. Culprit lesion characteristics were assessed by optical coherence tomography (OCT). Logistic regression and linear correlation analyses were performed to assess the association between the UHR and culprit plaques. The predictive value of the UHR was investigated by receiver operating characteristic (ROC) curve analysis. RESULTS: The percentages of typical culprit plaques, including ruptures, erosions and thrombi, were greater in the high-UHR subgroup than those in the low-UHR subgroup. A positive relationship was also found between the UHR and diameter stenosis (r = 0.160, P = 0.003) and between the UHR and area stenosis (r = 0.145, P = 0.007). The UHR was found to be independently associated with plaque rupture, erosion and thrombus. Furthermore, ROC analysis suggested that the UHR had a better predictive value than low-density lipoprotein cholesterol. CONCLUSIONS: An elevated UHR level was independently related to the occurrence rate of culprit plaques. The UHR is a simple and easily acquired parameter for detecting culprit plaques in patients with ACS.

Navigating Love in a Post-Pandemic World: Understanding Young Adults' Views on Short- and Long-Term Romantic Relationships.

The uncertain future due to the COVID-19 pandemic and the technological advancements may have altered young adults' experiences of romantic relationships. It is unclear whether individuals will continue to prefer traditional long-term romantic relationships (LTRR) or opt for short-term ones (STRR). This research describes how young adults in Malaysia perceive LTRR and STRR. Using the structured approach of the theory of social representations, data were collected from 512 participants; 238 (46.48%) male; Mage 21.75; majority were heterosexual and students, and analyzed using prototypical analysis to reveal high consensus elements. Five observations were made: (1) females prioritize "love" in both STRR and LTRR, while males prioritize "love" only in LTRR; (2) females prioritize "marriage" in LTRR, while males prioritize "trust," "comfort," and "stability." Males do not consider "marriage" as part of a LTRR; (3) both males and females view STRR positively, while LTRR are viewed more practically; (4) "sex" is a core element in STRR but is absent in LTRR; (5) males differentiate between STRR and LTRR with no overlapping elements. These findings provide insight into the social representations of romantic relationships among young adults in Malaysia and suggest future directions for research in the field.

Storage of plasma-derived exosomes: evaluation of anticoagulant use and preserving temperatures.

Exosomes carry large cargo of proteins, lipids, and nucleic acids, serving as versatile biomarkers for disease diagnosis and vehicles for drug delivery. However, up to date, no well recognized standard procedures for exosome storage were available for clinical application. This study aimed to determine the optimal storage conditions and the anticoagulants for plasma-derived exosome isolation. Fresh whole blood samples were collected from healthy participants and preserved in four different anticoagulants including sodium citrate (SC1/4), sodium citrate (SC1/9), lithium heparin (LH), or Ethylenediamine tetraacetic acid (EDTA), respectively. Exosomes were extracted from the plasma by differential ultracentrifugation and stored at three different temperatures, 4°C, -20°C or - 80°C for a duration ranging from one week to six months. All plasma samples for storage conditions comparison were pretreated with LH anticoagulant. Exosome features including morphological characteristics, pariticles size diameter, and surface protein profiles (TSG101, CD63, CD81, CD9, CALNEXIN) were assessed by transmission electron microscopy, Nanoparticle Tracking Analysis, and Western Blotting, respectively. Exosomes preserved in LH and SC1/4 group tended to remain intact microstructure with highly abundant protein biomarkers. Exosomes stored at 4°C for short time were prone to be more stable compared to thos at -80°C. Exosomes stored in plasma were superior in terms of ultrastructure, size diameter and surface protein expression to those stored in PBS. In conclusion, plasma-dervied exosome characteristics strictly depend on the anticoagulants and storage temperature and duration.

What is the context? Effective isolation of exosomes is a prerequisite for subsequent investigation into its involvemnt in disease development as well as potentialtherapeutic applications.Anticoagulants, storage temperature and durations might change the microscopical structure, integrity and also the stability of plasma-derived exosomes. However, no internationally recognized standard of exosome storage procedure was available for clinical use.What is new? Our finding evaluated the effect of anticoagulants and storage on plasma exosome characteristics.Exosomes isolated from plasma preserved with Li-heparin and sodium citrate (1/4) showed better physical properties and surface marker protein expression.Isolated exosomes appeared more stable in a short time for 4°C compared to −80°C. Storage of exosomes in plasma showed better physical properties and surface marker protein expression than in PBS.What is the impact? Our findings inform the significance of standardizing procedure of exosome isolation and preservation.

Effect of Body Mass Index on Cecal Intubation Time During Unsedated Colonoscopy: Variation Across the Learning Stages of an Endoscopist.

BACKGROUND Body mass index (BMI) and endoscopists' experiences can be associated with cecal intubation time (CIT), but such associations are controversial. This study aimed to clarify the association between BMI and CIT during unsedated colonoscopy at 3 learning stages of a single endoscopist. MATERIAL AND METHODS A total of 1500 consecutive patients undergoing unsedated colonoscopy by 1 endoscopist at our department from December 11, 2020, to August 21, 2022, were reviewed. They were divided into 3 learning stages according to the number of colonoscopies performed by 1 endoscopist, including intermediate (501-1000 colonoscopies), experienced (1001-1500 colonoscopies), and senior stages (1501-2000 colonoscopies). Variables that significantly correlated with CIT were identified by Spearman rank correlation analyses and then included in multiple linear regression analysis. RESULTS Overall, 1233 patients were included. Among them, 392, 420, and 421 patients were divided into intermediate, experienced, and senior stages, respectively. Median CIT was 7.83, 6.38, and 5.58 min at intermediate, experienced, and senior stages, respectively (P.

High-Throughput-Methyl-Reading (HTMR) assay: a solution based on nucleotide methyl-binding proteins enables large-scale screening for DNA/RNA methyltransferases and demethylases.

Epigenetic therapy has significant potential for cancer treatment. However, few small potent molecules have been identified against DNA or RNA modification regulatory proteins. Current approaches for activity detection of DNA/RNA methyltransferases and demethylases are time-consuming and labor-intensive, making it difficult to subject them to high-throughput screening. Here, we developed a fluorescence polarization-based 'High-Throughput Methyl Reading' (HTMR) assay to implement large-scale compound screening for DNA/RNA methyltransferases and demethylases-DNMTs, TETs, ALKBH5 and METTL3/METTL14. This assay is simple to perform in a mix-and-read manner by adding the methyl-binding proteins MBD1 or YTHDF1. The proteins can be used to distinguish FAM-labelled substrates or product oligonucleotides with different methylation statuses catalyzed by enzymes. Therefore, the extent of the enzymatic reactions can be coupled with the variation of FP binding signals. Furthermore, this assay can be effectively used to conduct a cofactor competition study. Based on the assay, we identified two natural products as candidate compounds for DNMT1 and ALKBH5. In summary, this study outlines a powerful homogeneous approach for high-throughput screening and evaluating enzymatic activity for DNA/RNA methyltransferases and demethylases that is cheap, easy, quick, and highly sensitive.

Myopia information on TikTok: analysis factors that impact video quality and audience engagement.

BACKGROUND: TikTok is emerging as a vital platform for health information dissemination. Despite myopia being a global public health issue, the high-quality myopia information shared by health educators often fails to go viral. It is imperative to analyze the factors influencing video quality and popularity, especially from diverse perspectives of researchers, health educators, and audiences. METHODS: TikTok myopia-related videos were retrieved using TikTok's default comprehensive search (DCS) and most liked search (MLS) strategies. Venn diagrams were employed to illustrate the relationships and commonalities between the two strategies across four sample sizes (top 200, 150, 100, and 50). Video metadata, including details such as creator information, production properties, upload time, video duration, and viewer engagement, were collected. Video quality was assessed using the DISCERN tool. Video content covering six aspects of myopia were evaluated. The impact of search strategies, video sample sizes, production properties, and myopia content on video quality and audience engagement was analyzed through single-factor or multi-factor analysis. RESULTS: DCS and MLS retrieval strategies, as well as varying sample sizes, resulted in differences in audience engagement for myopia videos (P < 0.039), while The DISCERN quality scores remained comparable (P > 0.221). Videos published by healthcare professionals (HCPs) and non-profit organizations (NPOs) were associated with high-quality (P ≤ 0.014) but comparatively lower popularity (P < 0.033). Videos that reported contents of risk factors, management, and outcomes showed high popularity (P < 0.018), while longer video duration (> 60s) exhibited the opposite trend (P < 0.032). Content on myopia evaluation (P ≤ 0.001) and management (P ≤ 0.022) and video duration were positively correlated with higher DISCERN quality. CONCLUSION: Videos created by HCPs and NPOs deserve greater attention. Rather than pursuing entertaining effects, professional educators should emphasize producing concise, and high-quality myopia content that readily resonates with the audience and has the potential to go viral on the platform.