Targeted drug delivery of engineered mesenchymal stem/stromal-cell-derived exosomes in cardiovascular disease: recent trends and future perspectives.

In recent years, stem cells and their secretomes, notably exosomes, have received considerable attention in biomedical applications. Exosomes are cellular secretomes used for intercellular communication. They perform the function of intercellular messengers by facilitating the transport of proteins, lipids, nucleic acids, and therapeutic substances. Their biocompatibility, minimal immunogenicity, targetability, stability, and engineerable characteristics have additionally led to their application as drug delivery vehicles. The therapeutic efficacy of exosomes can be improved through surface modification employing functional molecules, including aptamers, antibodies, and peptides. Given their potential as targeted delivery vehicles to enhance the efficiency of treatment while minimizing adverse effects, exosomes exhibit considerable promise. Stem cells are considered advantageous sources of exosomes due to their distinctive characteristics, including regenerative and self-renewal capabilities, which make them well-suited for transplantation into injured tissues, hence promoting tissue regeneration. However, there are notable obstacles that need to be addressed, including immune rejection and ethical problems. Exosomes produced from stem cells have been thoroughly studied as a cell-free strategy that avoids many of the difficulties involved with cell-based therapy for tissue regeneration and cancer treatment. This review provides an in-depth summary and analysis of the existing knowledge regarding exosomes, including their engineering and cardiovascular disease (CVD) treatment applications.

Custom-designed, mass silk production in genetically engineered silkworms.

Genetically engineered silkworms have been widely used to obtain silk with modified characteristics especially by introducing spider silk genes. However, these attempts are still challenging due to limitations in transformation strategies and difficulties in integration of the large DNA fragments. Here, we describe three different transformation strategies in genetically engineered silkworms, including transcription-activator-like effector nuclease (TALEN)-mediated fibroin light chain (FibL) fusion (BmFibL-F), TALEN-mediated FibH replacement (BmFibH-R), and transposon-mediated genetic transformation with the silk gland-specific fibroin heavy chain (FibH) promoter (BmFibH-T). As the result, the yields of exogenous silk proteins, a 160 kDa major ampullate spidroin 2 (MaSp2) from the orb-weaving spider Nephila clavipes and a 226 kDa fibroin heavy chain protein (EvFibH) from the bagworm Eumeta variegate, reach 51.02 and 64.13% in BmFibH-R transformed cocoon shells, respectively. Moreover, the presence of MaSp2 or EvFibH significantly enhances the toughness of genetically engineered silk fibers by ∼86% in BmFibH-T and ∼80% in BmFibH-R silkworms, respectively. Structural analysis reveals a substantial ∼40% increase in fiber crystallinity, primarily attributed to the presence of unique polyalanines in the repetitive sequences of MaSp2 or EvFibH. In addition, RNA-seq analysis reveals that BmFibH-R system only causes minor impact on the expression of endogenous genes. Our study thus provides insights into developing custom-designed silk production using the genetically engineered silkworm as the bioreactor.

Enhanced removal of rare earth elements from aqueous media: exploring the potential of AM-3 and AM-4 titanosilicates.

This study investigates the impact of three key variables on the performance of nanoporous AM-3 and layered AM-4 titanosilicates in removing nine REEs (Y, La, Ce, Pr, Nd, Eu, Gd, Tb, and Dy) from natural mineral water and identifies optimal operational conditions using Response Surface Methodology (RSM). The experimental conditions were determined by a Box-Behnken Design of 3 factors-3 levels (pH 4, 6, and 8; sorbent dose 20, 100, and 180 mg/L; and element concentration 1, 3, and 5 µmol/L). Three-dimensional response surfaces were used to assess the linear, quadratic, and interaction influences of each factor on the REEs' removal percentage. The pH was the most significant factor in the removal process using AM-3, while the sorbent dose was more important for AM-4. The results highlighted the sorbents' strong capacity for REE removal. The optimal operating conditions obtained by RSM were applied to aqueous solutions with salinity 10 (common in coastal and transitional systems) and 30 (average seawater salinity). The results showed that AM-3 has a strong potential for removing REEs in solutions with salinity 10 and 30, while AM-4 was less efficient due to competition between REEs and other ions present in the solution.

Electrical stress and acid orange 7 synergistically clear the blockage of electron flow in the methanogenesis of low-strength wastewater.

Energy recovery from low-strength wastewater through anaerobic methanogenesis is constrained by limited substrate availability. The development of efficient methanogenic communities is critical but challenging. Here we develop a strategy to acclimate methanogenic communities using conductive carrier (CC), electrical stress (ES), and Acid Orange 7 (AO7) in a modified biofilter. The synergistic integration of CC, ES, and AO7 precipitated a remarkable 72-fold surge in methane production rate compared to the baseline. This increase was attributed to an altered methanogenic community function, independent of the continuous presence of AO7 and ES. AO7 acted as an external electron acceptor, accelerating acetogenesis from fermentation intermediates, restructuring the bacterial community, and enriching electroactive bacteria (EAB). Meanwhile, CC and ES orchestrated the assembly of the archaeal community and promoted electrotrophic methanogens, enhancing acetotrophic methanogenesis electron flow via a mechanism distinct from direct electrochemical interactions. The collective application of CC, ES, and AO7 effectively mitigated electron flow impediments in low-strength wastewater methanogenesis, achieving an additional 34% electron recovery from the substrate. This study proposes a new method of amending anaerobic digestion systems with conductive materials to advance wastewater treatment, sustainability, and energy self-sufficiency.

KLF5-mediated pyroptosis of airway epithelial cells leads to airway inflammation in asthmatic mice through the miR-182-5p/TLR4 axis.

Asthma is viewed as an airway disease and an inflammatory condition. This study aims to reveal the role of Kruppel-like factor 5 (KLF5)-mediated pyroptosis of airway epithelial cells in airway inflammation in asthma. The asthmatic mouse model was established. The mice were infected with the lentivirus containing sh-KLF5, antagomiR-182-5p, and pc-Toll-like receptor 4 (TLR4). Airway hyperresponsiveness was measured, and the cells in bronchoalveolar lavage fluid (BALF) were sorted and counted. The expression levels of interleukin (IL)-4/IL-13/IL-6/IL-18/IL-1ß/NOD-like receptor family pyrin domain containing 3 (NLRP3)/N-gasdermin D (GSDMD-N)/cleaved caspase-1 were detected. The pathological changes in lung tissue were observed. The enrichment of KLF5 in the miR-182-5p promoter region was measured. The binding relationship among KLF5, miR-182-5p, and TLR4 were analyzed. KLF5 was highly expressed in asthmatic mice. Silencing KLF5 improved airway resistance and lung dynamic compliance, reduced the cells in BALF and the expression of IL-4/IL-13/IL-6/NLRP3/GSDMD-N/cleaved caspase-1/IL-18/IL-1ß, and alleviated the pathological changes. Mechanistically, KLF5 bonded to the miR-182-5p promoter to inhibit miR-182-5p expression, and miR-182-5p inhibited TLR4. Silencing miR-182-5p or TLR4 overexpression reversed the improvement of silencing KLF5 on airway inflammation and pyroptosis in asthmatic mice. In conclusion, KLF5 inhibited miR-182-5p to promote TLR4 expression, thus aggravating pyroptosis and airway inflammation in asthmatic mice.

The association between systemic inflammatory response index and contrast-associated acute kidney injury in patients undergoing elective percutaneous coronary intervention.

BACKGROUND: The systemic inflammatory response index (SIRI), served as a novel inflammatory biomarker, is the synthesis of neutrophils, monocytes and lymphocytes. AIMS: We hypothesized that SIRI has predictive value for contrast-associated acute kidney injury (CA-AKI) and long-term mortality in patients undergoing elective percutaneous coronary intervention (PCI). METHODS: We retrospectively observed 5685 patients undergoing elective PCI from January 2012 to December 2018. Venous blood samples were collected to obtain the experimental data on the day of admission or the morning of the next day. SIRI = neutrophil count × monocyte count/lymphocyte count. CA-AKI was defined as an increase of 50% or 0.3 mg/dl in SCr from baseline within 48 h after contrast exposure. RESULTS: The incidence of CA-AKI was 6.1% (n = 352). The best cutoff value of SIRI for predicting CA-AKI was 1.39, with a sensitivity of 52.3% and a specificity of 67.3%. [AUC: 0.620, 95% confidence interval (CI): 0.590-0.651, p < 0.001]. After adjusting for potential confounders, multivariate analysis showed that the high SIRI group (SIRI > 1.39) was a strong independent predictor of CA-AKI in patients undergoing elective PCI compared with the low SIRI group (SIRI ≤ 1.39) (odds ratio = 1.642, 95% CI: 1.274-2.116, p < 0.001). Additionally, COX regression analysis showed that SIRI > 1.39 was significantly associated with long-term mortality at a median follow-up of 2.8 years. [Hazard ratio (HR)=1.448, 95%CI: 1.188-1.765; p < 0.001]. Besides, Kaplan-Meier survival curve also indicated that the cumulative rate of mortality was considerably higher in the high SIRI group. CONCLUSIONS: High levels of SIRI are independent predictors of CA-AKI and long-term mortality in patients undergoing elective PCI.

Functional and esthetic reconstruction of composite lower lip defects with a motor-innervated chimeric facial artery buccinator myomucosal-submental island flap.

OBJECTIVE: This study aimed to assess the functional and esthetic outcomes of a chimeric innervated buccinator myomucosal-submental island flap (BMM-SIF) for large composite lower lip reconstruction. METHODS: This retrospective study included five patients who underwent lower lip tumor resection and BMM-SIF reconstruction at the Hospital of Stomatology, Sun Yat-sen University, between August 2021 and February 2023. Lip function was evaluated using water leakage, cheek puffing tests, and superficial electromyography. Lip appearance was observed using photographs and evaluated through subjective interviews. Donor-site conditions, including facial symmetry and mouth opening, were monitored. RESULTS: All the BMM-SIFs survived. Drooling was the main complication observed shortly after surgery. The water leakage test showed complete oral competence for liquid holding in the 7th month; however, moderate air leakage was present in two patients. Electromyography revealed myoelectric signals from the innervated buccinator at the recipient site. Facial expression and food intake were typically managed. The shape and projection of the vermilion were harmonious and satisfactory for each patient. Neither microstomia nor mouth opening limitation was observed, with an average inter-incisor distance of 37.25±4.4 mm. CONCLUSION: Chimeric motor-innervated BMM-SIF effectively reconstructed large full-thickness lower-lip defects with satisfactory functional and esthetic outcomes.

Emergence of eravacycline heteroresistance in carbapenem-resistant Acinetobacter baumannii isolates in China.

Carbapenem-resistant Acinetobacter baumannii (CRAB) is resistant to almost all antibiotics. Eravacycline, a newer treatment option, has the potential to treat CRAB infections, however, the mechanism by which CRAB isolates develop resistance to eravacycline has yet to be clarified. This study sought to investigate the features and mechanisms of eravacycline heteroresistance among CRAB clinical isolates. A total of 287 isolates were collected in China from 2020 to 2022. The minimum inhibitory concentration (MIC) of eravacycline and other clinically available agents against A. baumannii were determined using broth microdilution. The frequency of eravacycline heteroresistance was determined by population analysis profiling (PAP). Mutations and expression levels of resistance genes in heteroresistant isolates were determined by polymerase chain reaction (PCR) and quantitative real-time PCR (qRT-PCR), respectively. Antisense RNA silencing was used to validate the function of eravacycline heteroresistant candidate genes. Twenty-five eravacycline heteroresistant isolates (17.36%) were detected among 144 CRAB isolates with eravacycline MIC values ≤4 mg/L while no eravacycline heteroresistant strains were detected in carbapenem-susceptible A. baumannii (CSAB) isolates. All eravacycline heteroresistant strains contained OXA-23 carbapenemase and the predominant multilocus sequence typing (MLST) was ST208 (72%). Cross-resistance was observed between eravacycline, tigecycline, and levofloxacin in the resistant subpopulations. The addition of efflux pump inhibitors significantly reduced the eravacycline MIC in resistant subpopulations and weakened the formation of eravacycline heteroresistance in CRAB isolates. The expression levels of adeABC and adeRS were significantly higher in resistant subpopulations than in eravacycline heteroresistant parental strains (P < 0.05). An ISAba1 insertion in the adeS gene was identified in 40% (10/25) of the resistant subpopulations. Decreasing the expression of adeABC or adeRS by antisense RNA silencing significantly inhibited eravacycline heteroresistance. In conclusion, this study identified the emergence of eravacycline heteroresistance in CRAB isolates in China, which is associated with high expression of AdeABC and AdeRS.

Analyzing and engineering of the biosynthetic pathway of mollemycin A for enhancing its production.

Mollemycin A (MOMA) is a unique glyco-hexadepsipeptide-polyketide that was isolated from a Streptomyces sp. derived from the Australian marine environment. MOMA exhibits remarkable inhibitory activity against both drug-sensitive and multidrug-resistant malaria parasites. Optimizing MOMA through structural modifications or product enhancements is necessary for the development of effective analogues. However, modifying MOMA using chemical approaches is challenging, and the production titer of MOMA in the wild-type strain is low. This study identified and characterized the biosynthetic gene cluster of MOMA for the first time, proposed its complex biosynthetic pathway, and achieved an effective two-pronged enhancement of MOMA production. The fermentation medium was optimized to increase the yield of MOMA from 0.9 mg L-1 to 1.3 mg L-1, a 44% boost. Additionally, a synergistic mutant strain was developed by deleting the momB3 gene and overexpressing momB2, resulting in a 2.6-fold increase from 1.3 mg L-1 to 3.4 mg L-1. These findings pave the way for investigating the biosynthetic mechanism of MOMA, creating opportunities to produce a wide range of MOMA analogues, and developing an efficient strain for the sustainable and economical production of MOMA and its analogues.

Observation of an acoustic topological Euler insulator with meronic waves.

Topological band theory has conventionally been concerned with the topology of bands around a single gap. Only recently non-Abelian topologies that thrive on involving multiple gaps were studied, unveiling a new horizon in topological physics beyond the conventional paradigm. Here, we report on the first experimental realization of a topological Euler insulator phase with unique meronic characterization in an acoustic metamaterial. We demonstrate that this topological phase has several nontrivial features: First, the system cannot be described by conventional topological band theory, but has a nontrivial Euler class that captures the unconventional geometry of the Bloch bands in the Brillouin zone. Second, we uncover in theory and probe in experiments a meronic configuration of the bulk Bloch states for the first time. Third, using a detailed symmetry analysis, we show that the topological Euler insulator evolves from a non-Abelian topological semimetal phase via. the annihilation of Dirac points in pairs in one of the band gaps. With these nontrivial properties, we establish concretely an unconventional bulk-edge correspondence which is confirmed by directly measuring the edge states via. pump-probe techniques. Our work thus unveils a nontrivial topological Euler insulator phase with a unique meronic pattern and paves the way as a platform for non-Abelian topological phenomena.

t/k-Diagnosability of Regular Networks under the Comparison Model.

As multiprocessor systems continue to grow in processor scale, the incidence of faults also increases. As a result, fault diagnosis is becoming a key mechanism for maintaining the normal operation of multiprocessor systems. To explore more effective diagnostic methods, Somani et al. introduced a generalized pessimistic diagnostic strategy, named t/k-diagnosis, in which all faulty nodes are isolated in a set of nodes and at most k fault-free nodes are misdiagnosed, provided that the quantity of faults is limited by t. By imposing certain conditions or restrictions, the t/k-diagnosability of some regular networks under the Preparata, Metze, and Chien (PMC) model has been determined. However, the t/k-diagnosability of many networks under the comparison model remains unidentified. In this paper, we provide new insights into the study of t/k-diagnosability under the comparison model. After introducing some new notions, such as the 0-test unit, 0-test set and 0-test subgraph, under the comparison model, we study the relationship in a system G between the 0-test subgraphs and the components of G-F, where F is the set of faulty nodes, and we obtain some important correlation properties. Based on these results, we study t/k-diagnosability under the comparison model. As a result, the t/k-diagnosability of some regular interconnection networks can be efficiently determined.

Unraveling the Enantiomeric Distribution of Glycosidically Bound Linalool in Teas (Camellia sinensis) and Their Acidolysis Characteristics and Pyrolysis Mechanism.

Glycosidically bound linalool plays important roles in the formation of excellent tea flavor, while their enantiomeric distribution in teas and the actual transformations with free linalool are still unclear. In this study, a novel chiral ultrahigh performance liquid chromatography-mass spectrometry/mass spectrometry approach to directly analyze linalyl-ß-primeveroside and linalyl-ß-d-glucopyranoside enantiomers in teas was established and then applied in 30 tea samples. A close transformation relationship existed between the two states of linalool for their consistent dominant configurations (most S-form) and corresponding distribution trend in most teas (r up to 0.81). The acidolysis characterization indicated that free linalool might be slowly released from linalyl-ß-primeveroside with stable enantiomeric ratios during long-term withering of white tea in a weakly acidic environment, along with other isomerized products, e.g., geraniol, nerol, α-terpineol, etc. Furthermore, a novel online thermal desorption-gas chromatography-mass spectrometry approach was established to simulate the pyrolysis releasing of linalyl-ß-primeveroside during tea processing. Interestingly, free linalool was not the selected pyrolysis product of linalyl-ß-primeveroside but rather trans/cis-2,6-dimethyl-2,6-octadiene during the high-fire roasting or baking step of oolong and green teas. The identification of above high-fire chemical marks presented great potential to scientifically evaluate the proper thermal conditions in the practical production of tea.

Role of prostaglandin E2 and its receptors in chronic liver disease.

Chronic liver disease (CLD) is a major global health burden in terms of growing morbidity and mortality. Although many conditions can cause CLD, leading to cirrhosis and hepatocellular carcinoma (HCC), viral hepatitis, drug-induced liver injury (DILI), alcoholic liver disease (ALD) and non-alcoholic fatty liver disease (NAFLD) are the most common culprits. Prostaglandin E2 (PGE2), produced in the liver, is an important lipid mediator derived from the ω-6 polyunsaturated fatty acid, arachidonic acid, and plays a critical role in hepatic homeostasis. The physiological effects of PGE2 are mediated through four classes of E-type prostaglandin (EP) receptors, namely EP1, EP2, EP3 and EP4. In recent years, an increasing number of studies has been done to clarify the effects of PGE2 and EP receptors in regulating liver function and the pathogenesis of CLD to create a new potential clinical impact. In this review, we overview the biosynthesis and regulation of PGE2 and discuss the role of its synthesizing enzymes and receptors in the maintenance of normal liver function and the development and progress of CLD. We also discuss the potential of the PGE2-EP receptors system in treating CLD with various etiologies.

Investigations of the highly efficient processing technique, chemical constituents, and anti-inflammatory effect of N-ethyl-2-pyrrolidinone-substituted flavan-3-ol (EPSF)-enriched white tea.

N-Ethyl-2-pyrrolidinone-substituted flavan-3-ols (EPSFs) are a newly discovered compound class in tea with various bioactivities. This study aimed to develop a novel processing technique to enhance EPSF contents in white tea efficiently. Using optimal processing parameters of 125 °C and 30 min in a high-temperature sterilizing oven, total EPSF content significantly increased by 1.42-18.80-fold to 1.57-6.22 mg/g without impacting sensory characteristics. Metabolomics analysis revealed elevated levels of nucleosides, nucleotides, bases, theaflavins, flavonol aglycones, EPSFs, and most flavone-C-glycosides, as well as decreased levels of amino acids, procyanidins, theasinensins, several flavanols, and flavonol-O-glycosides after EPSF-enrichment treatment. Furthermore, the EPSF-enriched white tea exhibited notable anti-inflammatory effects, mitigating xylene-induced ear edema in mice and carrageenan-induced paw edema and cotton ball-induced granulomas in rats. This study developed a new processing technique for highly efficient enhancement of EPSFs in white tea and demonstrated that EPSF-enriched white tea has a potential to serve as effective anti-inflammatory dietary supplement.

Differential temporal utility of passively sensed smartphone features for depression and anxiety symptom prediction: a longitudinal cohort study.

While studies show links between smartphone data and affective symptoms, we lack clarity on the temporal scale, specificity (e.g., to depression vs. anxiety), and person-specific (vs. group-level) nature of these associations. We conducted a large-scale (n = 1013) smartphone-based passive sensing study to identify within- and between-person digital markers of depression and anxiety symptoms over time. Participants (74.6% female; M age = 40.9) downloaded the LifeSense app, which facilitated continuous passive data collection (e.g., GPS, app and device use, communication) across 16 weeks. Hierarchical linear regression models tested the within- and between-person associations of 2-week windows of passively sensed data with depression (PHQ-8) or generalized anxiety (GAD-7). We used a shifting window to understand the time scale at which sensed features relate to mental health symptoms, predicting symptoms 2 weeks in the future (distal prediction), 1 week in the future (medial prediction), and 0 weeks in the future (proximal prediction). Spending more time at home relative to one's average was an early signal of PHQ-8 severity (distal ß = 0.219, p = 0.012) and continued to relate to PHQ-8 at medial (ß = 0.198, p = 0.022) and proximal (ß = 0.183, p = 0.045) windows. In contrast, circadian movement was proximally related to (ß = -0.131, p = 0.035) but did not predict (distal ß = 0.034, p = 0.577; medial ß = -0.089, p = 0.138) PHQ-8. Distinct communication features (i.e., call/text or app-based messaging) related to PHQ-8 and GAD-7. Findings have implications for identifying novel treatment targets, personalizing digital mental health interventions, and enhancing traditional patient-provider interactions. Certain features (e.g., circadian movement) may represent correlates but not true prospective indicators of affective symptoms. Conversely, other features like home duration may be such early signals of intra-individual symptom change, indicating the potential utility of prophylactic intervention (e.g., behavioral activation) in response to person-specific increases in these signals.

Household air pollution and attributable burden of disease in rural China: A literature review and a modelling study.

Household air pollution prevails in rural residences across China, yet a comprehensive nationwide comprehending of pollution levels and the attributable disease burdens remains lacking. This study conducted a systematic review focusing on elucidating the indoor concentrations of prevalent household air pollutants-specifically, PM2.5, PAHs, CO, SO2, and formaldehyde-in rural Chinese households. Subsequently, the premature deaths and economic losses attributable to household air pollution among the rural population of China were quantified through dose-response relationships and the value of statistical life. The findings reveal that rural indoor air pollution levels frequently exceed China's national standards, exhibiting notable spatial disparities. The estimated annual premature mortality attributable to household air pollution in rural China amounts to 966 thousand (95% CI: 714-1226) deaths between 2000 and 2022, representing approximately 22.2% (95% CI: 16.4%-28.1%) of total mortality among rural Chinese residents. Furthermore, the economic toll associated with these premature deaths is estimated at 486 billion CNY (95% CI: 358-616) per annum, constituting 0.92% (95% CI: 0.68%-1.16%) of China's GDP. The findings quantitatively demonstrate the substantial disease burden attributable to household air pollution in rural China, which highlights the pressing imperative for targeted, region-specific interventions to ameliorate this pressing public health concern.

Dual-potential ratiometric electrochemiluminescence based on single emitter and single coreactant for the sensitive detection of carcinoembryonic antigen.

Dual-potential ratiometric electrochemiluminescence (ECL) is in favor of resistance to environmental interference. However, two kinds of emitters or coreactants, and a wide scan potential range (>2 V) are mandatory. This work developed a new dual-potential ratiometric ECL sensor for detection of carcinoembryonic antigen (CEA) using single emitter (luminol) and single coreactant (H2O2) with a mild potential range from -0.1 to 0.6 V. Luminol could produce a strong cathodic ECL (Ec) induced by hydroxyl radicals (HO‧) from the reduction of H2O2, and a relatively weak anodic ECL (Ea). After the ferrocene modified CEA aptamer (Apt-Fc) was attached, Fc could promote Ea by catalyzing the oxidation of H2O2, and reduce Ec by consuming HO‧. With the cycling amplification of the exonuclease I, CEA could substantially reduce the amount of Apt-Fc, resulting in the decrease of Ea and the rise of Ec. So, the ratio of Ec to Ea (Ec/Ea) was used as the detection signal, realizing the sensitive determination of CEA from 0.1 pg mL-1 to 10 ng mL-1 with a LOD of 41.85 fg mL-1 (S/N = 3). The developed sensor demonstrated excellent specificity, stability and reproducibility, with satisfactory results in practical detection.

Quality and production enhancement of fish mint, Houttuynia cordata Thunb., cultivated in a hydroponic planting system with designed plant growth-promoting additives.

Fish mint, Houttuynia cordata Thunb. (HCT) is an edible vegetable that has also been used in traditional folk medicines. As both a medicinal herb and a dietary source, HCT has been clinically proven to be a pivotal ingredient in formulas administered to alleviate COVID-19 symptoms. With the increasing market demand for imported materials, ensuring the quality consistency of HCT becomes a significant concern. In this study, the growing time for hydroponically-cultivated HCT with seaweed extract and amino acids added (HCTW) reduced by half compared to conventional soil-cultivated HCT (HCTS). Key quantified components in HCTW, flavonoid glycosides and caffeoylquinic acid derivatives, exhibited a 143% increase over HCTS. These crucial constituents were responsible for possessing antioxidant activity (IC50 < 25 µg/mL) and anti-nitrite oxide production (IC50 < 20 µg/mL). An economically-designed hydroponic system with appropriate additives is proposed to replace HCTS with improvements of growth time, overall production yields, and bioactive qualities.

Gene-gene interaction network analysis indicates CNTN2 is a candidate gene for idiopathic generalized epilepsy.

Twin and family studies have established the genetic contribution to idiopathic generalized epilepsy (IGE). The genetic architecture of IGE is generally complex and heterogeneous, and the majority of the genetic burden in IGE remains unsolved. We hypothesize that gene-gene interactions contribute to the complex inheritance of IGE. CNTN2 (OMIM* 615,400) variants have been identified in cases with familial adult myoclonic epilepsy and other epilepsies. To explore the gene-gene interaction network in IGE, we took the CNTN2 gene as an example and investigated its co-occurrent genetic variants in IGE cases. We performed whole-exome sequencing in 114 unrelated IGE cases and 296 healthy controls. Variants were qualified with sequencing quality, minor allele frequency, in silico prediction, genetic phenotype, and recurrent case numbers. The STRING_TOP25 gene interaction network analysis was introduced with the bait gene CNTN2 (denoted as A). The gene-gene interaction pair mode was presumed to be A + c, A + d, A + e, with a leading gene A, or A + B + f, A + B + g, A + B + h, with a double-gene A + B, or other combinations. We compared the number of gene interaction pairs between the case and control groups. We identified three pairs in the case group, CNTN2 + PTPN18, CNTN2 + CNTN1 + ANK2 + ANK3 + SNTG2, and CNTN2 + PTPRZ1, while we did not discover any pairs in the control group. The number of gene interaction pairs in the case group was much more than in the control group (p = 0.021). Taking together the genetic bioinformatics, reported epilepsy cases, and statistical evidence in the study, we supposed CNTN2 as a candidate pathogenic gene for IGE. The gene interaction network analysis might help screen candidate genes for IGE or other complex genetic disorders.