First-principles studies on the process of electron transfer between hydrophobic liquids and water.

Using the density functional theory, we conducted a study on the electrification upon contact between hydrophobic liquid molecules and water molecules, revealing localized characteristics of contact-electrification. These "localized features" refer to the specific microscale characteristics where electron transfer predominantly occurs at the contact regions, influenced by factors such as atomic distances and molecular orientations. Although the electrostatic potential and the highest occupied molecular orbital-lowest unoccupied molecular orbital gap offer substantial predictive insights for electron transfer across polymer interfaces, they fall short in capturing the complexities associated with the interaction between hydrophobic liquids and water molecules. The electronegativity of elements at the interface and the localization of molecular orbitals play a decisive role in electron transfer. Simultaneously, for liquid molecules with irregular structures, there is no correlation between the "contact area" and the amount of electron transfer. The "contact area" refers to the surface region where two different liquid molecules come into close proximity. It is defined by the surface area of atoms with interatomic distances smaller than the van der Waals radius. This study challenges traditional assumptions about contact-electrification, particularly in liquid-liquid interfaces, providing new insights into the localized nature of this phenomenon.

Prevalence and risk factors of depression among patients with perianal fistulizing Crohn's disease.

BACKGROUND: Psychological distress, especially depression, associated with perianal fistulizing Crohn's disease (PFCD) is widespread and refractory. However, there is a surprising paucity of studies to date that have sought to identify the prevalence and risk factors of depression associated with PFCD. AIM: To estimate the prevalence of depressive symptoms and investigate the depression-related risk factors in patients with PFCD. METHODS: The study was conducted in the form of survey and clinical data collection via questionnaire and specialized medical staff. Depressive symptoms, life quality, and fatigue severity of patients with PFCD were assessed by Patient Health Questionnaire-9, Inflammatory Bowel Disease Patient Quality of Life Questionnaire (IBDQ), and Inflammatory Bowel Disease (IBD) Fatigue Patient Self-assessment Scale. The basic demographic information, overall disease features, perianal clinical information, and laboratory inflammation indicators were also gathered. Multivariate regression analysis was ultimately used to ascertain the risk factors of depression associated with PFCD. RESULTS: A total of 123 patients with PFCD were involved, and 56.91% were suffering from depression. According to multivariate logistic regression analysis, Perianal Disease Activity Index (PDAI) score [odds ratio (OR) = 0.69, 95% confidence interval (CI): 0.50 to 0.95], IBDQ score (OR = 0.93, 95%CI: 0.88 to 0.97), modified Van Assche index (OR = 1.24, 95%CI: 1.01 to 1.53), and IBD Fatigue score (OR = 1.72, 95%CI: 1.23 to 2.42) were independent risk factors of depression-related prevalence among patients with PFCD (P < 0.05). Multiple linear regression analysis revealed that the increasing perianal modified Van Assche index (ß value = 0.166, 95%CI: 0.02 to 0.31) and decreasing IBDQ score (ß value = -0.116, 95%CI: -0.14 to -0.09) were independently associated with the severity of depression (P < 0.05). CONCLUSION: Depressive symptoms in PFCD patients have significantly high prevalence. PDAI score, modified Van Assche index, quality of life, and fatigue severity were the main independent risk factors.

Extraction of Pithecellobium clypearia Benth polysaccharides by dual-frequency ultrasound-assisted extraction: Structural characterization, antioxidant, hypoglycemic and anti-hyperlipidemic activities.

In this research, the extraction process of polysaccharides from Pithecellobium clypearia Benth (PCBPs) was optimized using dual-frequency ultrasound-assisted extraction (DUAE). The biological activities of PCBPs were investigated by in vitro antioxidant, hypoglycemic, and anti-hyperlipidemic assay. High-performance anion-exchange chromatography, high-performance gel permeation chromatography, SEM, UV-Vis spectroscopy, and FT-IR spectra were used to analyze the monosaccharide composition, molecular weight, microscopic morphology, and characteristic structure of PCBPs. The results showed that the maximum extraction rate of PCBPs was 9.90 ± 0.16% when the ultrasonic time was 8 min, the liquid-to-material ratio was 32 mL/g, and the ultrasonic power was 510 W. The PCBPs also possessed excellent in vitro antioxidant, hypoglycemic, and anti-hyperlipidemic activities. In addition, the average molecular weight of PCBPs was 15.07 kDa. PCBPs consisted of rhamnose, arabinose, galactose, glucose, xylose, mannose, and glucuronic acid, with the molar ratios of 11.07%, 18.54%, 48.17%, 10.44%, 4.62%, 4.96%, and 2.20%, respectively. Moreover, the results of SEM showed that PCBPs mainly showed a fine spherical mesh structure. The above studies provided a valuable theoretical basis for the subsequent in-depth study of PCBPs.

The dual effects of dexmedetomidine on intestinal barrier and intestinal motility during sepsis.

BACKGROUND: Sepsis, characterized by dysregulated host responses to infection, remains a critical global health concern, with high morbidity and mortality rates. The gastrointestinal tract assumes a pivotal role in sepsis due to its dual functionality as a protective barrier against injurious agents and as a regulator of motility. Dexmedetomidine, an α2-adrenergic agonist commonly employed in critical care settings, exhibits promise in influencing the maintenance of intestinal barrier integrity during sepsis. However, its impact on intestinal motility, a crucial component of intestinal function, remains incompletely understood. METHODS: In this study, we investigated dexmedetomidine's multifaceted effects on intestinal barrier function and motility during sepsis using both in vitro and in vivo models. Sepsis was induced in Sprague-Dawley rats via cecal ligation and puncture. Rats were treated with dexmedetomidine post-cecal ligation and puncture, and various parameters were assessed to elucidate dexmedetomidine's impact. RESULTS: Our findings revealed a dichotomous influence of dexmedetomidine on intestinal physiology. In septic rats, dexmedetomidine administration resulted in improved intestinal barrier integrity, as evidenced by reduced mucosal hyper-permeability and morphological alterations. However, a contrasting effect was observed on intestinal motility, as dexmedetomidine treatment inhibited both the frequency and amplitude of contractions in isolated intestinal strips and decreased the distance of ink migration in vivo. Additionally, dexmedetomidine suppressed the secretion of pro-motility hormones while having no influence on hormones that inhibit intestinal peristalsis. CONCLUSION: The study revealed that during sepsis, dexmedetomidine exhibited protective effects on barrier integrity, although concurrently it hindered intestinal motility, partly attributed to its modulation of pro-motility hormone secretion. These findings underscore the necessity of a comprehensive understanding of dexmedetomidine's impact on multiple facets of gastrointestinal physiology in sepsis management, offering potential implications for therapeutic strategies and patient care.

Spontaneously established reverse electric field to enhance the performance of triboelectric nanogenerators via improving Coulombic efficiency.

Mechanical energy harvesting using triboelectric nanogenerators is a highly desirable and sustainable method for the reliable power supply of widely distributed electronics in the new era; however, its practical viability is seriously challenged by the limited performance because of the inevitable side-discharge and low Coulombic-efficiency issues arising from electrostatic breakdown. Here, we report an important progress on these fundamental problems that the spontaneously established reverse electric field between the electrode and triboelectric layer can restrict the side-discharge problem in triboelectric nanogenerators. The demonstration employed by direct-current triboelectric nanogenerators leads to a high Coulombic efficiency (increased from 28.2% to 94.8%) and substantial enhancement of output power. More importantly, we demonstrate this strategy is universal for other mode triboelectric nanogenerators, and a record-high average power density of 6.15 W m-2 Hz-1 is realized. Furthermore, Coulombic efficiency is verified as a new figure-of-merit to quantitatively evaluate the practical performance of triboelectric nanogenerators.

Cerebral autoregulation: A reliable predictor of prognosis in patients receiving intravenous thrombolysis.

AIMS: To investigate the characteristics of dynamic cerebral autoregulation (dCA) after intravenous thrombolysis (IVT) and assess the relationship between dCA and prognosis. METHODS: Patients with unilateral acute ischemic stroke receiving IVT were prospectively enrolled; those who did not were selected as controls. All patients underwent dCA measurements, by quantifying the phase difference (PD) and gain, at 1-3 and 7-10 days after stroke onset. Simultaneously, two dCA-based nomogram models were established to verify the predictive value of dCA for patients with mild-to-moderate stroke. RESULTS: Finally, 202 patients who received IVT and 238 who did not were included. IVT was positively correlated with higher PD on days 1-3 and 7-10 after stroke onset. PD values in both sides at 1-3 days after stroke onset and in the affected side at 7-10 days after onset were independent predictors of unfavorable outcomes in patients who received IVT. Additionally, in patients with mild-to-moderate stroke who received IVT, the dCA-based nomogram models significantly improved the risk predictive ability for 3-month unfavorable outcomes. CONCLUSION: IVT has a positive effect on dCA in patients with acute stroke; furthermore, dCA may be useful to predict the prognosis of patients with IVT.

Acoustically Enhanced Triboelectric Stethoscope for Ultrasensitive Cardiac Sounds Sensing and Disease Diagnosis.

Electronic stethoscope used to detect cardiac sounds that contain essential clinical information is a primary tool for diagnosis of various cardiac disorders. However, the linear electromechanical constitutive relation makes conventional piezoelectric sensors rather ineffective to detect low-intensity, low-frequency heart acoustic signal without the assistance of complex filtering and amplification circuits. Herein, it is found that triboelectric sensor features superior advantages over piezoelectric one for microquantity sensing originated from the fast saturated constitutive characteristic. As a result, the triboelectric sensor shows ultrahigh sensitivity (1215 mV Pa-1) than the piezoelectric counterpart (21 mV Pa-1) in the sound pressure range of 50-80 dB under the same testing condition. By designing a trumpet-shaped auscultatory cavity with a power function cross-section to achieve acoustic energy converging and impedance matching, triboelectric stethoscope delivers 36 dB signal-to-noise ratio for human test (2.3 times of that for piezoelectric one). Further combining with machine learning, five cardiac states can be diagnosed at 97% accuracy. In general, the triboelectric sensor is distinctly unique in basic mechanism, provides a novel design concept for sensing micromechanical quantities, and presents significant potential for application in cardiac sounds sensing and disease diagnosis.

Loneliness and social isolation among informal carers of individuals with dementia: A systematic review and meta-analysis.

OBJECTIVES: This systematic review and meta-analysis aimed to determine the prevalence of loneliness and social isolation among informal carers of individuals with dementia and to identify potential influencing factors. METHODS: We conducted a comprehensive search across 10 electronic databases, including PubMed, Cochrane, Embase, Web of Science, PsycINFO, CINAHL, Scopus, Chinese Biomedical, China National Knowledge Internet, and WANFANG. Our search strategy covered the inception of the databases up to September 16, 2023, with an updated search conducted on March 8, 2024. Prevalence estimates of loneliness and social isolation, presented with 95% confidence intervals, were synthesized through meta-analysis. Subgroup analyses and meta-regression were employed to explore potential moderating variables and heterogeneity. RESULTS: The study encompassed 27 research papers involving 11,134 informal carers from 17 different countries. The pooled prevalence of loneliness among informal carers of individuals with dementia was 50.8% (95% CI: 41.8%-59.8%), while the pooled prevalence of social isolation was 37.1% (95% CI: 26.7%-47.6%). Subgroup analyses and meta-regression indicated that various factors significantly influenced the prevalence of loneliness and social isolation. These factors included the caregiving setting, study design, the intensity of loneliness, geographical location (continent), data collection time, and the choice of assessment tools. CONCLUSIONS: This study underscores the substantial prevalence of loneliness and social isolation among informal carers of individuals with dementia. It suggests that policymakers and healthcare providers should prioritize the development of targeted interventions and support systems to alleviate loneliness and social isolation within this vulnerable population.

Miniaturized and High Volumetric Energy Density Power Supply Device Based on a Broad-Frequency Vibration Driven Triboelectric Nanogenerator.

The widespread vibration is one of the most promising energy sources for IoT and small sensors, and broad-frequency vibration energy harvesting is important. Triboelectric nanogenerators (TENGs) can convert vibration energy into electrical energy through triboelectricity and electrostatic induction, providing an effective solution to the collection of broad-frequency vibration energy. Also, the power supply in constrained and compact spaces has been a long-standing challenge. Here, a miniaturized power supply (MPS) based on a broad-frequency vibration-driven triboelectric nanogenerator (TENG) is developed. The size of the MPS is 38 mm × 26 mm × 20 mm, which can adapt to most space-limited environments. The TENG device is optimized through theoretical mechanical modeling for the external stimuli, it can efficiently harvest vibrational energy in the frequency range of 1-100 Hz and has a high output power density of 134.11 W/cm3. The developed device demonstrates its practical application potential in powering small electronics like LEDs, watches, and timers.

Antibiotic Cocktail Effects on Intestinal Microbial Community, Barrier Function, and Immune Function in Early Broiler Chickens.

This study investigated the effects of an antibiotic cocktail on intestinal microbial composition, mechanical barrier structure, and immune functions in early broilers. One-day-old healthy male broiler chicks were treated with a broad-spectrum antibiotic cocktail (ABX; neomycin, ampicillin, metronidazole, vancomycin, and kanamycin, 0.5 g/L each) or not in drinking water for 7 and 14 days, respectively. Sequencing of 16S rRNA revealed that ABX treatment significantly reduced relative Firmicutes, unclassified Lachnospiraceae, unclassified Oscillospiraceae, Ruminococcus torques, and unclassified Ruminococcaceae abundance in the cecum and relative Firmicutes, Lactobacillus and Baccillus abundance in the ileum, but significantly increased richness (Chao and ACE indices) and relative Enterococcus abundance in the ileum and cecum along with relatively enriched Bacteroidetes, Proteobacteria, Cyanobacteria, and Enterococcus levels in the ileum following ABX treatment for 14 days. ABX treatment for 14 days also significantly decreased intestinal weight and length, along with villus height (VH) and crypt depth (CD) of the small intestine, and remarkably increased serum LPS, TNF-α, IFN-γ, and IgG levels, as well as intestinal mucosa DAO and MPO activity. Moreover, prolonged use of ABX significantly downregulated occludin, ZO-1, and mucin 2 gene expression, along with goblet cell numbers in the ileum. Additionally, chickens given ABX for 14 days had lower acetic acid, butyric acid, and isobutyric acid content in the cecum than the chickens treated with ABX for 7 days and untreated chickens. Spearman correlation analysis found that those decreased potential beneficial bacteria were positively correlated with gut health-related indices, while those increased potential pathogenic strains were positively correlated with gut inflammation and gut injury-related parameters. Taken together, prolonged ABX application increased antibiotic-resistant species abundance, induced gut microbiota dysbiosis, delayed intestinal morphological development, disrupted intestinal barrier function, and perturbed immune response in early chickens. This study provides a reliable lower-bacteria chicken model for further investigation of the function of certain beneficial bacteria in the gut by fecal microbiota transplantation into germ-free or antibiotic-treated chickens.

Endotype-driven Co-module mechanisms of danhong injection in the Co-treatment of cardiovascular and cerebrovascular diseases: A modular-based drug and disease integrated analysis.

ETHNOPHARMACOLOGICAL RELEVANCE: Cardiovascular and cerebrovascular diseases are the leading causes of death worldwide and interact closely with each other. Danhong Injection (DHI) is a widely used preparation for the co-treatment of brain and heart diseases (CTBH). However, the underlying molecular endotype mechanisms of DHI in the CTBH remain unclear. AIM OF THIS STUDY: To elucidate the underlying endotype mechanisms of DHI in the CTBH. MATERIALS AND METHODS: In this study, we proposed a modular-based disease and drug-integrated analysis (MDDIA) strategy for elucidating the systematic CTBH mechanisms of DHI using high-throughput transcriptome-wide sequencing datasets of DHI in the treatment of patients with stable angina pectoris (SAP) and cerebral infarction (CI). First, we identified drug-targeted modules of DHI and disease modules of SAP and CI based on the gene co-expression networks of DHI therapy and the protein-protein interaction networks of diseases. Moreover, module proximity-based topological analyses were applied to screen CTBH co-module pairs and driver genes of DHI. At the same time, the representative driver genes were validated via in vitro experiments on hypoxia/reoxygenation-related cardiomyocytes and neuronal cell lines of H9C2 and HT22. RESULTS: Seven drug-targeted modules of DHI and three disease modules of SAP and CI were identified by co-expression networks. Five modes of modular relationships between the drug and disease modules were distinguished by module proximity-based topological analyses. Moreover, 13 targeted module pairs and 17 driver genes associated with DHI in the CTBH were also screened. Finally, the representative driver genes AKT1, EDN1, and RHO were validated by in vitro experiments. CONCLUSIONS: This study, based on clinical sequencing data and modular topological analyses, integrated diseases and drug targets. The CTBH mechanism of DHI may involve the altered expression of certain driver genes (SRC, STAT3, EDN1, CYP1A1, RHO, RELA) through various enriched pathways, including the Wnt signaling pathway.

All-Oxide Metasurfaces Formed by Synchronized Local Ionic Gating.

Ionic gating of oxide thin films has emerged as a novel way of manipulating the properties of thin films. Most studies are carried out on single devices with a three-terminal configuration, but, by exploring the electrokinetics during the ionic gating, such a configuration with initially insulating films leads to a highly non-uniform gating response of individual devices within large arrays of the devices. It is shown that such an issue can be circumvented by the formation of a uniform charge potential by the use of a thin conducting underlayer. This synchronized local ionic gating allows for the simultaneous manipulation of the electrical, magnetic, and/or optical properties of large arrays of devices. Designer metasurfaces formed in this way from SrCoO2.5 thin films display an anomalous optical reflection of light that relies on the uniform and coherent response of all the devices. Beyond oxides, almost any material whose properties can be controlled by the addition or removal of ions via gating can form novel metasurfaces using this technique. These findings provide insights into the electrokinetics of ionic gating and a wide range of applications using synchronized local ionic gating.

The application of multi-criteria decision analysis in evaluating the value of drug-oriented intervention: a literature review.

Objectives: Multi-Criteria Decision Analysis (MCDA) has gained increasing attention in supporting drug risk-benefit assessment, pricing and reimbursement, as well as optimization of clinical interventions. The objective of this study was to systematically collect and categorize evaluation criteria and techniques of weighting and scoring of MCDA for drug value assessment. Methods: A systematic review of the literature was conducted across seven databases to identify articles utilizing the MCDA frameworks for the evaluation of drug value. Evaluation criteria mentioned in the included studies were extracted and assigned to 5 dimensions including clinical, economic, innovative, societal and humanistic value. A descriptive statistical analysis was performed on the identified drug value evaluation criteria, as well as the weighting and scoring techniques employed. The more a criterion or technique were mentioned in articles, the more important we consider it. Results: Out of the 82 articles included, 111 unique criteria were identified to evaluate the value of drug. Among the 56 unique criteria (448 times) used to measure clinical value, the most frequently mentioned were "comparative safety/tolerability" (58 times), "comparative effectiveness/efficacy" (56 times), "comparative patient-perceived health/patient reported outcomes" (37 times), "disease severity" (34 times), and "unmet needs" (25 times). Regarding economic value measurement, out of the 20 unique criteria (124 times), the most frequently utilized criteria were "cost of intervention" (17 times), "comparative other medical costs" (16 times), and "comparative non-medical costs" (18 times). Out of the 10 criteria (18 times) for assessing innovative value, "a novel pharmacological mechanism" was the most frequently mentioned criterion (5 times). Among the 22 criteria (73 times) used to measure societal value, "system capacity and appropriate use of intervention" was the most frequently cited criterion (14 times). Out of the 3 criteria (15 times) utilized to measure humanistic value, "political/historical/cultural context" was the most frequently mentioned criterion (9 times). Furthermore, 11 scoring and 11 weighting techniques were found from various MCDA frameworks. "Swing weighting" and "a direct rating scale" were the most frequently used techniques in included articles. Conclusion: This study comprehensively presented the current evaluation dimensions, criteria, and techniques for scoring and weighting in drug-oriented MCDA articles. By highlighting the frequently cited evaluation criteria and techniques for scoring and weighting, this analysis will provide a foundation to reasonably select appropriate evaluation criteria and technique in constructing the MCDA framework that aligns with research objectives.

Preparation of protein-stabilized Litsea cubeba essential oil nano-emulsion by ultrasonication: Bioactivity, stability, in vitro digestion, and safety evaluation.

Litsea cubeba essential oil (LCEO) has garnered widespread attention due to its robust biological activity. However, challenges such as high volatility, limited water solubility, and low bioavailability impede its application. Nano-emulsion encapsulation technology offers an effective solution to these issues. In this study, we prepared litsea cubeba essential oil nano-emulsion (LCEO-NE) for the first time using whey protein (WP) as the emulsifier through an ultrasonic-assisted method, achieving high efficiency with minimal energy consumption. Transmission electron microscopy and dynamic light scattering analyses revealed that the nanoparticles were uniformly spherical, with a particle size of 183.5 ± 1.19 nm and a zeta potential of -35.5 ± 0.95 mV. Stability studies revealed that LCEO-NE exhibited excellent thermal and salt stability, maintaining its integrity for up to four weeks when stored at 4 °C and 25 °C. In vitro digestion assays confirmed the digestibility of LCEO-NE. Furthermore, evaluation of the DPPH, ABTS, and antimicrobial activities revealed that LCEO-NE displayed superior bacteriostatic and antioxidant properties compared to LCEO. Scanning electron microscopy elucidated that its bacteriostatic effect involved the disruption of bacterial microstructure. Hemocompatibility and cytotoxicity assays demonstrated the safety of LCEO-NE within the effective concentration range. This research supports the utilization of nanoparticles for encapsulating LCEO, thereby enhancing its stability and bioactivity, and consequently expanding its applications in the food and pharmaceutical industries.

Preparation and utilization of carbon dots as a nanoprobe for sensitive detection of tartrazine and palladium (II).

We prepared novel green, eco-friendly carbon dots as a dual-channel probe for highly sensitive and selective detection of tartrazine (Trz) and palladium(II) (Pd(II)) involving, respectively, FRET and electron transfer mechanisms. Furthermore, the successful utilization of the carbon dots for detecting Trz and Pd(II) in actual samples implies its potential application prospects in analysis.

Reduction of precious metal ions in aqueous solutions by contact-electro-catalysis.

Precious metals are core assets for the development of modern technologies in various fields. Their scarcity poses the question of their cost, life cycle and reuse. Recently, an emerging catalysis employing contact-electrification (CE) at water-solid interfaces to drive redox reaction, called contact-electro-catalysis (CEC), has been used to develop metal free mechano-catalytic methods to efficiently degrade refractory organic compounds, produce hydrogen peroxide, or leach metals from spent Li-Ion batteries. Here, we show ultrasonic CEC can successfully drive the reduction of Ag(ac), Rh3+, [PtCl4]2-, Ag+, Hg2+, Pd2+, [AuCl4]-, and Ir3+, in both anaerobic and aerobic conditions. The effect of oxygen on the reaction is studied by electron paramagnetic resonance (EPR) spectroscopy and ab-initio simulation. Combining measurements of charge transfers during water-solid CE, EPR spectroscopy and gold extraction experiments help show the link between CE and CEC. What's more, this method based on water-solid CE is capable of extracting gold from synthetic solutions with concentrations ranging from as low as 0.196 ppm up to 196 ppm, reaching in 3 h extraction capacities ranging from 0.756 to 722.5 mg g-1 in 3 h. Finally, we showed CEC is employed to design a metal-free, selective, and recyclable catalytic gold extraction methods from e-waste aqueous leachates.

A Human Friendly Self-Assembled Triboelectric Sensor for Multifunctional Tactile Sensing.

Obtaining bioenergy from human movement is not only a prospective complementation to electrochemical power supply such as batteries in portable electronics but also a decipherable process for developing self-powered sensors that can simultaneously monitor the physiological movement. In this study, a low-cost, robust, and environmentally friendly triboelectric nanogenerator (TENG) was prepared with enhanced mechanical stability and tunneling conductivity on the base of cotton fabric. The as-designed TENG may produce energy sustainably by physical movements, and it can yield an amazing 417 V open-circuit voltage, 11.7 µA short-circuit current, and 237.60 mW/m2 excellent power density, showcasing its potential for efficient energy conversion in the single-electrode mode. Besides, such a design also shows real-time tactile perception ability toward human physiological signal and body motion where intelligent application of these environmental benign TENGs in sports and writing training were demonstrated, thus providing vital instruction for the creation of versatile and sustainable TENGs in the Internet of Things era.

Automatic ultrasensitive lateral flow immunoassay based on a color-enhanced signal amplification strategy.

Lateral flow immunoassays (LFIAs) are an essential and widely used point-of-care test for medical diagnoses. However, commercial LFIAs still have low sensitivity and specificity. Therefore, we developed an automatic ultrasensitive dual-color enhanced LFIA (DCE-LFIA) by applying an enzyme-induced tyramide signal amplification method to a double-antibody sandwich LFIA for antigen detection. The DCE-LFIA first specifically captured horseradish peroxidase (HRP)-labeled colored microspheres at the Test line, and then deposited a large amount of tyramide-modified signals under the catalytic action of HRP to achieve the color superposition. A limit of detection (LOD) of 3.9 pg/mL and a naked-eye cut-off limit of 7.8 pg/mL were achieved for detecting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleoprotein. Additionally, in the inactivated virus detections, LOD equivalent to chemiluminescence (0.018 TCID50/mL) was obtained, and it had excellent specificity under the interference of other respiratory viruses. High sensitivity has also been achieved for detection of influenza A, influenza B, cardiac troponin I, and human chorionic gonadotrophin using this DCE-LFIA, suggesting the assay is universally applicable. To ensure the convenience and stability in practical applications, we created an automatic device. It provides a new practical option for point-of-care test immunoassays, especially ultra trace detection and at-home testing.

14-3-3 binding motif phosphorylation disrupts Hdac4-organized condensates to stimulate cardiac reprogramming.

Cell fate conversion is associated with extensive post-translational modifications (PTMs) and architectural changes of sub-organelles, yet how these events are interconnected remains unknown. We report here the identification of a phosphorylation code in 14-3-3 binding motifs (PC14-3-3) that greatly stimulates induced cardiomyocyte (iCM) formation from fibroblasts. PC14-3-3 is identified in pivotal functional proteins for iCM reprogramming, including transcription factors and chromatin modifiers. Akt1 kinase and protein phosphatase 2A are the key writer and key eraser of the PC14-3-3 code, respectively. PC14-3-3 activation induces iCM formation with the presence of only Tbx5. In contrast, PC14-3-3 inhibition by mutagenesis or inhibitor-mediated code removal abolishes reprogramming. We discover that key PC14-3-3-embedded factors, such as histone deacetylase 4 (Hdac4), Mef2c, and Foxo1, form Hdac4-organized inhibitory nuclear condensates. PC14-3-3 activation disrupts Hdac4 condensates to promote cardiac gene expression. Our study suggests that sub-organelle dynamics regulated by a PTM code could be a general mechanism for stimulating cell reprogramming.