Hybrid Organic-Si C-MOSFET Image Sensor Designed with Blue-, Green-, and Red-Sensitive Organic Photodiodes on Si C-MOSFET-Based Photo Signal Sensor Circuit.

The resolution of Si complementary metal-oxide-semiconductor field-effect transistor (C-MOSFET) image sensors (CISs) has been intensively enhanced to follow the technological revolution of smartphones, AI devices, autonomous cars, robots, and drones, approaching the physical and material limits of a resolution increase in conventional Si CISs because of the low quantum efficiency (i.e., ~40%) and aperture ratio (i.e., ~60%). As a novel solution, a hybrid organic-Si image sensor was developed by implementing B, G, and R organic photodiodes on four n-MOSFETs for photocurrent sensing. Photosensitive organic donor and acceptor materials were designed with cost-effective small molecules, i.e., the B, G, and R donor and acceptor small molecules were Coumarin6 and C_60, DMQA and MePTC, and ZnPc and TiOPc, respectively. The output voltage sensing margins (i.e., photocurrent signal difference) of the hybrid organic-Si B, G, and R image sensor pixels presented results 17, 11, and 37% higher than those of conventional Si CISs. In addition, the hybrid organic-Si B, G, and R image sensor pixels could achieve an ideal aperture ratio (i.e., ~100%) compared with a Si CIS pixel using the backside illumination process (i.e., ~60%). Moreover, they may display a lower fabrication cost than image sensors because of the simple image sensor structure (i.e., hybrid organic-Si photodiode with four n-MOSFETs).

Cross-sensitization between inhalant allergens and food allergens: the extent, intensity, and age-related shifts.

BACKGROUND: Encountering individuals sensitized to both inhalant and food allergens is challenging in clinical practice. Despite its rarity, studies have documented cross-sensitization between these allergens. However, the extent, diversity, and age-related variations of this phenomenon remain unclear. OBJECTIVE: Hence, our objective was to investigate a substantial quantity of allergy sensitivity test results in which both inhalant and food allergens were concurrently examined. The primary goal of our study is to calculate the cross-sensitization ratio, with a secondary objective of analyzing this phenomenon across four age groups. METHODS: A retrospective analysis was conducted on a multiple-antigen simultaneous test (MAST) obtained from a domestic laboratory medicine facility and comprising 55 food allergens and 49 inhalant allergens from 368,156 individuals aged 1 to 89. By calculating the cross-sensitization ratio, the degree of cross-sensitization between each food allergen and inhalant allergen was determined. Further subgroup analysis was conducted to ascertain the cross-sensitization ratio between the four subgroups categorized by age. RESULTS: The median cross-sensitization ratio between food and inhalant allergens was 5.14, indicating a significant level of cross-sensitization. The cross-sensitization ratio was greatest among pollen allergens and plant-derived food allergens, followed by between some animal aeroallergens and meat/fish/dairy/poultry food allergens. The degree of overall cross-sensitization was least prominent in adolescents, greater in adults and children, and most pronounced in the elderly. CONCLUSION: Our findings reveal that various inhalant and dietary allergens have considerable cross-sensitivity, with the elderly having the highest degree of cross-sensitivity and adolescents the lowest.

SUPERFICIAL AND DEEP VASCULAR COMPLEXES DAMAGED TO DIFFERENT EXTENTS IN ADVANCED STAGES OF DIABETIC RETINOPATHY.

PURPOSE: To identify the extent of damage to the superficial vascular complex and deep vascular complex as the stage of diabetic retinopathy (DR) increases. METHODS: Subjects were divided into four groups: patients with type 2 diabetes without DR (Group 1), those with mild-to-moderate nonproliferative DR (Group 2), those with severe-to-very severe nonproliferative DR (Group 3), and those with proliferative DR (Group 4). The vessel densities of the superficial vascular complex (superficial vessel density, SVD) and deep vascular complex (deep vessel density, DVD) and their ratios were compared. Linear regression analyses were used to identify factors associated with the SVD/DVD ratio. RESULTS: The SVDs were 25.5% ± 6.1%, 25.1% ± 7.0%, 24.5% ± 9.0%, and 21.6% ± 6.9% (P = 0.048); the DVDs 25.6% ± 5.3%, 23.0% ± 7.0%, 22.3% ± 8.8%, and 17.5% ± 5.0% (P < 0.001); and the SVD/DVD ratios 1.00 ± 0.16, 1.12 ± 0.20, 1.14 ± 0.33, and 1.24 ± 0.27 (P < 0.001) in Groups 1 to 4, respectively. In multivariate analysis, DR severity (B = 7.16, P < 0.001) and the HbA1c level (B = 1.57, P = 0.042) were significantly associated with the SVD/DVD ratio. CONCLUSION: Both the SVD and DVD tended to decrease in the advanced stages of DR, and the SVD/DVD ratio increased, indicating more severe damage to the deep vascular complex than the superficial vascular complex. The ratio was positively associated with the HbA1c level, indicating a significant relationship between that level and DVD rather than SVD damage.

Risk of Cardiovascular Events Associated with Chronic Obstructive Pulmonary Disease and/or Metabolic Syndrome: A Large-Scale Nationwide Population-Based Cohort Study.

Purpose: Chronic obstructive pulmonary disease (COPD) and metabolic syndrome (MetS) are among the most prevalent conditions that might predispose individuals to life-threatening events. We aimed to examine their associations with cardiovascular (CV) events and mortality using a large-scale population dataset from the National Health Information Database in Korea. Patients and Methods: This population-based cohort study enrolled adults aged ≥40 years who had undergone more than two health examinations between 2009 and 2011. They were divided into four groups based on the presence of COPD and MetS. Analysis of the outcomes and CV events or deaths was performed from 2014 to 2019. We compared CV event incidence and mortality rates using a multivariate Cox proportional hazards model and Kaplan-Meier curves. Results: Totally, 5,101,810 individuals were included, among whom 3,738,458 (73.3%) had neither COPD nor MetS, 1,193,014 (23.4%) had only MetS, 125,976 (2.5%) had only COPD, and 44,362 (0.9%) had both. The risk of CV events was significantly higher in individuals with both COPD and MetS than in those with either COPD or MetS alone (HRs: 2.4 vs 1.6 and 1.8, respectively; all P <0.001). Similarly, among those with both COPD and MetS, all-cause and CV mortality risks were also elevated (HRs, 2.9 and 3.0, respectively) compared to the risks in those with either COPD (HRs, 2.6 and 2.1, respectively) or MetS (HRs, 1.7 and 2.1, respectively; all P <0.001). Conclusion: The comorbidity of MetS in patients with COPD increases the incidence of CV events and all-cause and cardiovascular mortality rates.

Ameliorative effect of vanillic acid against scopolamine-induced learning and memory impairment in rat via attenuation of oxidative stress and dysfunctional synaptic plasticity.

Alzheimer's disease (AD) is characterized by cognitive impairment, loss of learning and memory, and abnormal behaviors. Scopolamine (SCOP) is a non-selective antagonist of muscarinic acetylcholine receptors that exhibits the behavioral and molecular hallmarks of AD. Vanillic acid (VA), a phenolic compound, is obtained from the roots of a traditional plant called Angelica sinensis, and has several pharmacologic effects, including antimicrobial, anti-inflammatory, anti-angiogenic, anti-metastatic, and antioxidant properties. Nevertheless, VA's neuroprotective potential associated with the memory has not been thoroughly investigated. Therefore, this study investigated whether VA treatment has an ameliorative effect on the learning and memory impairment induced by SCOP in rats. Behavioral experiments were utilized to assess the learning and memory performance associated with the hippocampus. Using western blotting analysis and assay kits, the neuronal damage, oxidative stress, and acetylcholinesterase activity responses of hippocampus were evaluated. Additionally, the measurement of long-term potentiation was used to determine the function of synaptic plasticity in organotypic hippocampal slice cultures. In addition, the synaptic vesicles' density and the length and width of the postsynaptic density were evaluated using electron microscopy. Consequently, the behavioral, biochemical, electrophysiological, and ultrastructural analyses revealed that VA treatment prevents learning and memory impairments caused by SCOP in rats. The study's findings suggest that VA has a neuroprotective effect on SCOP-induced learning and memory impairment linked to the hippocampal cholinergic system, oxidative damage, and synaptic plasticity. Therefore, VA may be a prospective therapeutic agent for treating AD.

SMARCD3 Overexpression Promotes Epithelial-Mesenchymal Transition in Gastric Cancer.

This study investigates the role of SMARCD3 in gastric cancer by comparing its expression in signet ring cell (SRC) and well-differentiated (WD) groups within gastric cancer cell lines and tissues. We observed elevated SMARCD3 levels in the SRC group compared to the WD group. Functional analysis was conducted through both SMARCD3 knock-in and knock-out methods. Kaplan-Meier survival analysis indicated that higher SMARCD3 expression correlates with poorer overall survival in gastric cancer patients (HR 2.16, p < 0.001). SMARCD3 knock-out cells showed decreased proliferation, migration, invasion, and expression of epithelial-mesenchymal transition (EMT) markers, contrasting with results from temporary and stable SMARCD3 overexpression experiments, which demonstrated increased cell area and irregularity (p < 0.001). Further analysis revealed that SMARCD3 overexpression in MKN-74 cells significantly enhanced p-AKT-S473 and p-ERK levels (p < 0.05), and in KATO III cells, it increased ß-catenin and PI3Kp85 activities (p < 0.05). Conversely, these activities decreased in SNU 601 cells following SMARCD3 depletion. The study concludes that SMARCD3 overexpression may serve as a negative prognostic marker and a potential therapeutic target in gastric cancer treatment due to its role in promoting EMT.

The efficacy and safety of decompression with interspinous fixation for lumbar spondylolisthesis when compared with posterior lumbar interbody fusion: A pilot study.

Posterior lumbar interbody fusion (PLIF) is widely used to treat degenerative spondylolisthesis because it provides definitive decompression and fixation. Although it has several advantages, it has some disadvantages and risks, such as paraspinal muscle injury, potential intraoperative bleeding, postoperative pain, hardware failure, subsidence, and medical comorbidity. Lumbar decompressive bilateral laminectomy with interspinous fixation (DLISF) is less invasive and can be used on some patients with PLIF, but this has not been reported. To compare the efficacy and safety of DLISF in the treatment of low-grade lumbar spondylolisthesis with that of PLIF. We retrospectively analyzed the medical records of 81 patients with grade I spondylolisthesis, who had undergone PLIF or DLISF and were followed up for more than 1 year. Surgical outcomes, visual analog scale, radiologic outcomes, including Cobb angle and difference in body translation, and postoperative complications were assessed. Forty-one patients underwent PLIF, whereas 40 underwent DLISF. The operative times were 271.0 ±â€…57.2 and 150.6 ±â€…29.3 minutes for the PLIF and DLISF groups, respectively. The estimated blood loss was significantly higher in the PLIF group versus the DLISF group (290.7 ±â€…232.6 vs 122.2 ±â€…82.7 mL, P < .001). Body translation did not differ significantly between the 2 groups. Overall pain improved during the 1-year follow-up when compared with baseline data. Medical complications were significantly lower in the DLISF group, whereas perioperative complications and hardware issues were higher in the PLIF group. The outcomes of DLISF, which is less invasive, were comparable to PLIF outcomes in patients with low-grade spondylolisthesis. As a salvage technique, DLISF may be a good option when compared with PLIF.

Chemical Compositions before and after Lactic Acid Fermentation of Isoflavone-Enriched Soybean Leaves and Their Anti-Obesity and Gut Microbiota Distribution Effects.

In this study, we prepared fermented products of isoflavone-enriched soybean leaves (IESLs) and analyzed their nutrients, isoflavones, anti-obesity efficacy, and effects on gut microbiota. Fermented IESLs (FIESLs) were found to be rich in nutrients, especially lauric acid, oleic acid, and linoleic acid. In addition, the concentrations of most essential free amino acids were increased compared to those of IESLs. The contents of bioactive compounds, such as total phenolic, total flavonoid, daidzein, and genistein, significantly increased as well. In addition, FIESLs administration in a high-fat diet (HFD) animal model improved the final body weight, epididymal fat, total lipid, triglyceride, total cholesterol, blood glucose, and leptin levels, as well as reverting microbiota dysbiosis. In conclusion, these findings indicate that FIESLs have the potential to inhibit obesity caused by HFDs and serve as a modulator of gut microbiota, offering the prevention of diet-induced gut dysbiosis and metabolite diseases associated with obesity.

Ca2+-mediated reactive oxygen species signaling regulates cell repair after mechanical wounding in the red alga Griffithsia monilis.

Mechanical damage to a cell can be fatal, and the cell must reseal its membrane and restore homeostasis to survive. Plant cell repair involves additional steps such as rebuilding vacuoles, rearranging chloroplasts, and remodeling the cell wall. When we pierced a Griffithsia monilis cell with a glass needle, a large amount of intracellular contents was released, but the cell membrane resealed in less than a second. The turgor of the vacuole was quickly restored, and the punctured cell returned to its original shape within an hour. Organelles such as chloroplasts and nuclei migrated to the wound site for 12 h and then dispersed throughout the cell after the wound was covered by a new cell wall. Using fluorescent probes, high levels of reactive oxygen species (ROS) and calcium were detected at the wound site from 3 h after wounding, which disappeared when cell repair was complete. Wounding in a solution containing ROS scavengers inhibited cellular repair, and inhibiting nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity or blocking calcium influx reversibly inhibited cell repair. Oryzalin reversibly inhibited both chloroplast movement and ROS production during cell repair. Our results show that cell repair in G. monilis is regulated by calcium-mediated ROS signaling and that microtubules serve as mechanical effectors.

Cough Response to High-Dose Inhaled Corticosteroids in Patients with Chronic Cough and Fractional Exhaled Nitric Oxide Levels ≥ 25 ppb: A Prospective Study.

This study aimed to investigate the effects of high-dose inhaled corticosteroids (ICS) on chronic cough patients with elevated fractional exhaled nitric oxide (FeNO) levels. In a prospective study, adults with chronic cough and FeNO ≥ 25 ppb, without any other apparent etiology, received fluticasone furoate (200 mcg) for three weeks. Outcomes were evaluated using FeNO levels, cough severity, and Leicester Cough Questionnaire (LCQ) before and after treatment. Of the fifty participants (average age: 58.4 years; 58% female), the treatment responder rate (≥ 1.3-point increase in LCQ) was 68%, with a significant improvement in cough and LCQ scores and FeNO levels post-treatment. However, improvements in cough did not significantly correlate with changes in FeNO levels. These findings support the guideline recommendations for a short-term ICS trial in adults with chronic cough and elevated FeNO levels, but the lack of correlations between FeNO levels and cough raises questions about their direct mechanistic link.

The Association of Serum Uric Acid with Risk of Obstructive Sleep Apnea: The Korean National Health and Nutrition Examination Survey 2019-2021.

Upper airway collapse and apneas in obstructive sleep apnea (OSA) induce intermittent hypercapnia and hypoxia, eventually contributing to excessive uric acid production. This study aimed to evaluate the association between hyperuricemia and OSA in the general population via analysis of the eighth KNHANES dataset (2019-2021). OSA risk was identified via the STOP-Bang questionnaire, with a score ≥3 indicating high risk. Among 11,981 total participants, 4572 (38.2%) had a high OSA risk. Participants with a high OSA risk had higher uric acid levels compared to those with a low risk (5.5 ± 1.4 mg/dL vs. 4.8 ± 1.2 mg/dL, p < 0.001). Serum uric acid levels were positively correlated with STOP-Bang score (r: 0.317, p < 0.001). Multivariate analysis revealed that hyperuricemia was associated with a high OSA risk after adjusting for confounders (odds ratio: 1.30, 95%CI: 1.11-1.53, p = 0.001). Therefore, serum uric acid levels are significantly higher in those with a high OSA risk and correlate with the risk of OSA. Further, hyperuricemia is an independently associated risk factor for high OSA risk. More research is warranted to evaluate the long-term clinical outcomes of hyperuricemia in OSA and to determine whether treatment targeting hyperuricemia is effective in the clinical course of OSA.

Toward microfluidic continuous-flow and intelligent downstream processing of biopharmaceuticals.

Biopharmaceuticals have emerged as powerful therapeutic agents, revolutionizing the treatment landscape for various diseases, including cancer, infectious diseases, autoimmune and genetic disorders. These biotherapeutics pave the way for precision medicine with their unique and targeted capabilities. The production of high-quality biologics entails intricate manufacturing processes, including cell culture, fermentation, purification, and formulation, necessitating specialized facilities and expertise. These complex processes are subject to rigorous regulatory oversight to evaluate the safety, efficacy, and quality of biotherapeutics prior to clinical approval. Consequently, these drugs undergo extensive purification unit operations to achieve high purity by effectively removing impurities and contaminants. The field of personalized precision medicine necessitates the development of novel and highly efficient technologies. Microfluidic technology addresses unmet needs by enabling precise and compact separation, allowing rapid, integrated and continuous purification modules. Moreover, the integration of intelligent biomanufacturing systems with miniaturized devices presents an opportunity to significantly enhance the robustness of complex downstream processing of biopharmaceuticals, with the benefits of automation and advanced control. This allows seamless data exchange, real-time monitoring, and synchronization of purification steps, leading to improved process efficiency, data management, and decision-making. Integrating autonomous systems into biopharmaceutical purification ensures adherence to regulatory standards, such as good manufacturing practice (GMP), positioning the industry to effectively address emerging market demands for personalized precision nano-medicines. This perspective review will emphasize on the significance, challenges, and prospects associated with the adoption of continuous, integrated, and intelligent methodologies in small-scale downstream processing for various types of biologics. By utilizing microfluidic technology and intelligent systems, purification processes can be enhanced for increased efficiency, cost-effectiveness, and regulatory compliance, shaping the future of biopharmaceutical production and enabling the development of personalized and targeted therapies.

Ultrafast Flow Synthesis of o-Functionalized Benzenesulfonyl Fluorides and Subsequent SuFEx Connections via Lithiated Chemistry.

Herein we present a flow-based, rapid, and straightforward approach to synthesize diverse functionalized sulfonyl fluorides by harnessing an aryllithium intermediate. The aryllithium intermediate was fully utilized under optimized conditions (0.016 s, -18 °C) to afford various functionalized sulfonyl fluorides and also intramolecular SuFEx cyclization products in high yields (27-94%). Furthermore, the integrated synthesis incorporating subsequent SuFEx connections with even unstable organolithium nucleophiles facilitated one-flow molecular assembly in high yields (42-72%).

Quality of Life and Nutritional Outcomes of Stomach-Preserving Surgery for Early Gastric Cancer: A Secondary Analysis of the SENORITA Randomized Clinical Trial.

Importance: The Sentinel Node Oriented Tailored Approach (SENORITA) randomized clinical trial evaluated quality of life (QoL) and nutritional outcomes between the laparoscopic sentinel node navigation surgery (LSNNS) and laparoscopic standard gastrectomy (LSG). However, there has been no report on the QoL and nutritional outcomes of patients who underwent stomach-preserving surgery among the LSNNS group. Objective: To compare long-term QoL and nutritional outcomes between patients who underwent stomach-preserving surgery and those who underwent standard gastrectomy and to identify factors associated with poor QoL outcomes in patients who underwent stomach-preserving surgery. Design, Setting, and Participants: This study is a secondary analysis of the SENORITA trial, a randomized clinical trial comparing LSNNS with LSG. Patients from 7 tertiary or general hospitals across the Republic of Korea were enrolled from March 2013 to December 2016, with follow-up through 5 years. Data were analyzed between August and September 2022. Among trial participants, patients who underwent actual laparoscopic standard gastrectomy in the LSG group and those who underwent stomach-preserving surgery in the LSNNS group were included. Patients who did not complete the baseline or any follow-up questionnaire were excluded. Intervention: Stomach-preserving surgery vs standard gastrectomy. Main Outcomes and Measures: Overall European Organization for Research and Treatment of Cancer QoL Questionnaire Core 30 (EORTC QLQ-C30) and stomach module (STO22) scores, body mass index, hemoglobin, protein, and albumin levels. Results: A total of 194 and 257 patients who underwent stomach-preserving surgery and standard gastrectomy, respectively, were included in this study (mean [SD] age, 55.6 [10.6] years; 249 [55.2%] male). The stomach-preserving group had better QoL scores at 3 months postoperatively in terms of physical function (87.2 vs 83.9), dyspnea (5.9 vs 11.2), appetite loss (13.1 vs 19.4), dysphagia (8.0 vs 12.7), eating restriction (10.9 vs 18.2), anxiety (29.0 vs 35.2), taste change (7.4 vs 13.0), and body image (19.5 vs 27.2). At 1 year postoperatively, the stomach-preserving group had significantly higher body mass index (23.9 vs 22.1, calculated as weight in kilograms divided by height in meters squared) and hemoglobin (14.3 vs 13.3 g/dL), albumin (4.3 vs 4.25 g/dL), and protein (7.3 vs 7.1 g/dL) levels compared to the standard group. Multivariable analyses showed that tumor location (greater curvature, lower third) was favorably associated with global health status (ß, 10.5; 95% CI, 3.2 to 17.8), reflux (ß, -8.4; 95% CI, -14.7 to -2.1), and eating restriction (ß, -5.7; 95% CI, -10.3 to -1.0) at 3 months postoperatively in the stomach-preserving group. Segmental resection was associated with risk of diarrhea (ß, 40.6; 95% CI, 3.1 to 78.1) and eating restriction (ß, 15.1; 95% CI, 1.1 to 29.1) at 3 years postoperatively. Conclusions and Relevance: Stomach-preserving surgery after sentinel node evaluation was associated with better long-term QoL and nutritional outcomes than standard gastrectomy. These findings may help facilitate decision-making regarding treatment for patients with early-stage gastric cancer. Trial Registration: ClinicalTrials.gov Identifier: NCT01804998.

Tailoring photobiomodulation to enhance tissue regeneration.

Photobiomodulation (PBM), the use of biocompatible tissue-penetrating light to interact with intracellular chromophores to modulate the fates of cells and tissues, has emerged as a promising non-invasive approach to enhancing tissue regeneration. Unlike photodynamic or photothermal therapies that require the use of photothermal agents or photosensitizers, PBM treatment does not need external agents. With its non-harmful nature, PBM has demonstrated efficacy in enhancing molecular secretions and cellular functions relevant to tissue regeneration. The utilization of low-level light from various sources in PBM targets cytochrome c oxidase, leading to increased synthesis of adenosine triphosphate, induction of growth factor secretion, activation of signaling pathways, and promotion of direct or indirect gene expression. When integrated with stem cell populations, bioactive molecules or nanoparticles, or biomaterial scaffolds, PBM proves effective in significantly improving tissue regeneration. This review consolidates findings from in vitro, in vivo, and human clinical outcomes of both PBM alone and PBM-combined therapies in tissue regeneration applications. It encompasses the background of PBM invention, optimization of PBM parameters (such as wavelength, irradiation, and exposure time), and understanding of the mechanisms for PBM to enhance tissue regeneration. The comprehensive exploration concludes with insights into future directions and perspectives for the tissue regeneration applications of PBM.

Examining the Alterations in Metabolite Constituents and Antioxidant Properties in Mountain-Cultivated Ginseng (Panax ginseng C.A. Meyer) Organs during a Two-Month Maturation Period.

The current research was the first to prove the existence of fluctuations in the metabolite constituents and antioxidant properties in different organs (leaves, stems, and roots) of the mountain-cultivated ginseng (MCG) plant during a two-month maturation period. Four metabolites, including fatty acids, amino acids, ginsenosides, and phenolic phytochemicals, exhibited considerable differences in organs and maturation times with the following order: leaves > stems > roots. The predominant metabolite contents were found in leaves, with fatty acid (1057.9 mg/100 g) on 31 May, amino acid (1989.2 mg/100 g) on 13 July, ginsenosides (88.7 mg/g) on 31 May, and phenolic phytochemical (638.3 µg/g) on 31 May. Interestingly, ginsenoside content in leaves were highest, with 84.8 → 88.7 → 82.2 → 78.3 mg/g. Specifically, ginsenosides Re, Rd, and F2 showed abundant content ranging from 19.1 to 16.9 mg/g, 8.5 to 14.8 mg/g, and 9.5 to 13.1 mg/g, respectively. Phenolic phytochemicals exhibited remarkable differences in organs compared to maturation periods, with the highest total phenolic content and total flavonoid content recorded at 9.48 GAE and 1.30 RE mg/g in leaves on 31 May. The antioxidant capacities on radical, FRAP, and DNA protection differed significantly, with leaves on 31 May exhibiting the highest values: 88.4% (DPPH), 89.5% (ABTS), 0.84 OD593 nm (FRAP) at 500 µg/mL, and 100% DNA protection at 50 µg/mL. Furthermore, principal cluster analysis revealed metabolite variability as follows: ginsenoside (83.3%) > amino acid (71.8%) > phenolic phytochemical (61.1%) > fatty acid (58.8%). A clustering heatmap highlighted significant changes in metabolite components under the maturation times for each organ. Our findings suggest that MCG leaves on 31 May may be a potential source for developing nutraceuticals, offering highly beneficial components and strong antioxidants.

Finely tuned ionizable lipid nanoparticles for CRISPR/Cas9 ribonucleoprotein delivery and gene editing.

Nonviral delivery of the CRISPR/Cas9 system provides great benefits for in vivo gene therapy due to the low risk of side effects. However, in vivo gene editing by delivering the Cas9 ribonucleoprotein (RNP) is challenging due to the poor delivery into target tissues and cells. Here, we introduce an effective delivery method for the CRISPR/Cas9 RNPs by finely tuning the formulation of ionizable lipid nanoparticles. The LNPs delivering CRISPR/Cas9 RNPs (CrLNPs) are demonstrated to induce gene editing with high efficiencies in various cancer cell lines in vitro. Furthermore, we show that CrLNPs can be delivered into tumor tissues with high efficiency, as well as induce significant gene editing in vivo. The current study presents an effective platform for nonviral delivery of the CRISPR/Cas9 system that can be applied as an in vivo gene editing therapeutic for treating various diseases such as cancer and genetic disorders.

Charge-Based Isolation of Extracellular Vesicles from Human Plasma.

Extracellular vesicles (EVs) have garnered significant attention due to their potential applications in disease diagnostics and management. However, the process of isolating EVs, primarily from blood samples, is still suboptimal. This is mainly attributed to the abundant nature of soluble proteins and lipoproteins, which are often separated together with EVs in the end products of conventional isolation methods. As such, we devise a single-step charge-based EV isolation method by utilizing positively charged beads to selectively remove negatively charged major impurities from human plasma via electrostatic interaction. By carefully controlling the buffer pH, we successfully collected EVs from undesired plasma components with superior purity and yield compared to conventional EV collection methods. Moreover, the developed process is rapid, taking only about 20 min for overall EV isolation. The charge-based isolation can ultimately benefit the EV-based liquid biopsy field for the early diagnosis of various diseases.