Sterically Encumbered Aryl Isocyanides Extend Excited-State Lifetimes and Improve the Photocatalytic Performance of Three-Coordinate Copper(I) ß-Diketiminate Charge-Transfer Chromophores.

Copper(I) complexes are prominent candidates to replace noble metal-based photosensitizers. We recently introduced a three-coordinate design for copper(I) charge-transfer chromophores that pair ß-diketiminate ligands with aryl isocyanides. The excited-state lifetime in these compounds can be extended using a bichromophoric "triplet reservoir" strategy, which comes at the expense of a decrease in excited-state energy and reducing power. In this work, we introduce a complementary, sterically driven strategy for increasing the excited-state lifetimes of these photosensitizers, which gives a higher-energy, more strongly reducing charge-transfer triplet state than does the bichromophore approach. The compounds presented (Cu1-Cu4) have the general formula Cu(CyNacNacMe)(CN-Ar), where CyNacNacMe is a cyclohexyl-substituted ß-diketiminate and CN-Ar is an aryl isocyanide with a variable steric profile. Their structural features and electrochemical and photophysical properties are described. The complexes with sterically encumbered 2,6-diisopropylphenyl or m-terphenyl isocyanide ligands (Cu2-Cu4) exhibit prolonged excited-state lifetimes relative to those of the parent 2,6-dimethylphenyl isocyanide compound Cu1. Specifically, one of the m-terphenyl isocyanide compounds, Cu3, displays an excited-state lifetime of 276 ns, approximately 30 times longer than that of Cu1 (9.3 ns). The photoluminescence quantum yield of Cu3 (0.09) also increases by two orders of magnitude compared to that of Cu1 (0.0008). The strong excited-state reducing power (*Eox = -2.4 V vs Fc+/0) and long lifetime of Cu3 lead to higher yields in photoredox and photocatalytic isomerization reactions, which include dehalogenation and/or hydrodgenation of benzophenone substrates, C-O bond activation of a lignin model substrate, and photocatalytic E/Z isomerization of stilbene.

Long Excited-State Lifetimes in Three-Coordinate Copper(I) Complexes via Triplet-Triplet Energy Transfer to Pyrene-Decorated Isocyanides.

There has been much effort to improve excited-state lifetimes in photosensitizers based on earth-abundant first-row transition metals. Copper(I) complexes have gained significant attention in this field, and in most cases, sterically driven approaches are used to optimize their lifetimes. This study presents a series of three-coordinate copper(I) complexes (Cu1-Cu3) where the excited-state lifetime is extended by triplet-triplet energy transfer. The heteroleptic compounds feature a cyclohexyl-substituted ß-diketiminate (CyNacNacMe) paired with aryl isocyanide ligands, giving the general formula Cu(CyNacNacMe)(CN-Ar) (CN-dmp = 2,6-dimethylphenyl isocyanide for Cu1; CN-pyr = 1-pyrenyl isocyanide for Cu2; CN-dmp-pyr = 2,6-dimethyl-4-(1-pyrenyl)phenyl isocyanide for Cu3). The nature, energies, and dynamics of the low-energy triplet excited states are assessed with a combination of photoluminescence measurements at room temperature and 77 K, ultrafast transient absorption (UFTA) spectroscopy, and DFT calculations. The complexes with the pyrene-decorated isocyanides (Cu2 and Cu3) exhibit extended excited-state lifetimes resulting from triplet-triplet energy transfer (TTET) between the short-lived charge-transfer excited state (3CT) and the long-lived pyrene-centered triplet state (3pyr). This TTET process is irreversible in Cu3, producing exclusively the 3pyr state, and in Cu2, the 3CT and 3pyr states are nearly isoenergetic, enabling reversible TTET and long-lived 3CT luminescence. The improved photophysical properties in Cu2 and Cu3 result in improvements in activity for both photocatalytic stilbene E/Z isomerization via triplet energy transfer and photoredox transformations involving hydrodebromination and C-O bond activation. These results illustrate that the extended excited-state lifetimes achieved through TTET result in newly conceived photosynthetically relevant earth-abundant transition metal complexes.

Molecular Mechanisms of Anticarcinogenic Potential of Hydrocotyle umbellata and Its Major Components.

Despite the development of several anticancer treatments, there remains a need for new drugs that can overcome resistance and reduce side effects. While the medicinal herb Hydrocotyle umbellata (H. umbellata) has been used to relieve pain and inflammation, its antitumor properties have not yet been explored. In this study, we investigated the anticarcinogenic potential of H. umbellata extract (HUE) and its major components, as well as the underlying molecular mechanisms. Our results showed that HUE inhibited the growth of various tumor cell lines, including B16F10, without affecting non-cancer cells. Furthermore, HUE was effective in treating and preventing tumor growth in mice. Our mechanistic studies revealed that HUE inhibited cellular respiration, thereby reducing tumor cell proliferation. When combined with 2-deoxy-D-glucose, HUE demonstrated an enhanced anticancer effect by increasing the rate apoptosis. Analysis of the ethyl acetate and n-butanol fractions of HUE identified 1,3,4-trihydroxy-2-butanyl-α-d-glucopyranoside and caffeoylquinic acid derivatives as the major components responsible for the observed anticancer effects. In conclusion, our findings suggest that HUE and its two major components have the potential to be developed as effective therapeutic agents for a wide range of tumors by targeting cancer cell metabolism.

Deep learning-based personalised outcome prediction after acute ischaemic stroke.

BACKGROUND: Whether deep learning models using clinical data and brain imaging can predict the long-term risk of major adverse cerebro/cardiovascular events (MACE) after acute ischaemic stroke (AIS) at the individual level has not yet been studied. METHODS: A total of 8590 patients with AIS admitted within 5 days of symptom onset were enrolled. The primary outcome was the occurrence of MACEs (a composite of stroke, acute myocardial infarction or death) over 12 months. The performance of deep learning models (DeepSurv and Deep-Survival-Machines (DeepSM)) and traditional survival models (Cox proportional hazards (CoxPH) and random survival forest (RSF)) were compared using the time-dependent concordance index ([Formula: see text] index). RESULTS: Given the top 1 to all 60 clinical factors according to feature importance, CoxPH and RSF yielded [Formula: see text] index of 0.7236-0.8222 and 0.7279-0.8335, respectively. Adding image features improved the performance of deep learning models and traditional models assisted by deep learning models. DeepSurv and DeepSM yielded the best [Formula: see text] index of 0.8496 and 0.8531 when images were added to all 39 relevant clinical factors, respectively. In feature importance, brain image was consistently ranked highly. Deep learning models automatically extracted the image features directly from personalised brain images and predicted the risk and date of future MACEs at the individual level. CONCLUSIONS: Deep learning models using clinical data and brain images could improve the prediction of MACEs and provide personalised outcome prediction for patients with AIS. Deep learning models will allow us to develop more accurate and tailored prognostic prediction systems that outperform traditional models.

Sterically Encumbered Heteroleptic Copper(I) ß-Diketiminate Complexes with Extended Excited-State Lifetimes.

One of the main challenges in developing effective copper(I) photosensitizers is their short excited-state lifetimes, usually attributed to structural distortion upon light excitation. We have previously introduced copper(I) charge-transfer chromophores of the general formula Cu(N^N)(ArNacNac), where N^N is a conjugated diimine ligand and ArNacNac is a substituted ß-diketiminate ligand. These chromophores were promising regarding their tunable redox potentials and intense visible absorption but were ineffective as photosensitizers, presumably due to short excited-state lifetimes. Here, we introduce sterically crowded analogues of these heteroleptic chromophores with bulky alkyl substituents on the N^N and/or ArNacNac ligand. Structural analysis was combined with electrochemical and photophysical characterization, including ultrafast transient absorption (UFTA) spectroscopy to investigate the effects of the alkyl groups on the excited-state lifetimes of the complexes. The molecular structures determined by single-crystal X-ray diffraction display more distortion in the ground state as alkyl substituents are introduced into the phenanthroline or the NacNac ligand, showing smaller τ4 values due to the steric hindrance. UFTA measurements were carried out to determine the excited-state dynamics. Sterically encumbered Cu5 and Cu6 display excited-state lifetimes 15-20 times longer than unsubstituted complex Cu1, likely indicating that the incorporation of bulky alkyl substituents inhibits the pseudo-Jahn-Teller (PJT) flattening distortion in the excited state. This work suggests that the steric properties of these heteroleptic copper(I) charge-transfer chromophores can be readily modified and that the excited-state dynamics are strongly responsive to these modifications.

Potent inhibition of human tyrosinase inhibitor by verproside from the whole plant of Pseudolysimachion rotundum var. subintegrum.

Affinity-based ultrafiltration-mass spectrometry coupled with ultraperformance liquid chromatography-quadrupole time-of-flight mass spectrometry was utilised for the structural identification of direct tyrosinase ligands from a crude Pseudolysimachion rotundum var. subintegrum extract. False positives were recognised by introducing time-dependent inhibition in the control for comparison. The P. rotundum extract contained nine main metabolites in the UPLC-QTOF-MS chromatogram. However, four metabolites were reduced after incubation with tyrosinase, indicating that these metabolites were bound to tyrosinase. The IC50 values of verproside (1) were 31.2 µM and 197.3 µM for mTyr and hTyr, respectively. Verproside showed 5.6-fold higher efficacy than that of its positive control (kojic acid in hTyr). The most potent tyrosinase inhibitor, verproside, features a 3,4-dihydroxybenzoic acid moiety on the iridoid glycoside and inhibits tyrosinase in a time-dependent and competitive manner. Among these three compounds, verproside is bound to the active site pocket with a docking energy of -6.9 kcal/mol and four hydrogen bonding interactions with HIS61 and HIS85.

Verproside, the Most Active Ingredient in YPL-001 Isolated from Pseudolysimachion rotundum var. subintegrum, Decreases Inflammatory Response by Inhibiting PKCδ Activation in Human Lung Epithelial Cells.

Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory lung disease which causes breathing problems. YPL-001, consisting of six iridoids, has potent inhibitory efficacy against COPD. Although YPL-001 has completed clinical trial phase 2a as a natural drug for COPD treatment, the most effective iridoid in YPL-001 and its mechanism for reducing airway inflammation remain unclear. To find an iridoid most effectively reducing airway inflammation, we examined the inhibitory effects of the six iridoids in YPL-001 on TNF or PMA-stimulated inflammation (IL-6, IL-8, or MUC5AC) in NCI-H292 cells. Here, we show that verproside among the six iridoids most strongly suppresses inflammation. Both TNF/NF-κB-induced MUC5AC expression and PMA/PKCδ/EGR-1-induced IL-6/-8 expression are successfully reduced by verproside. Verproside also shows anti-inflammatory effects on a broad range of airway stimulants in NCI-H292 cells. The inhibitory effect of verproside on the phosphorylation of PKC enzymes is specific to PKCδ. Finally, in vivo assay using the COPD-mouse model shows that verproside effectively reduces lung inflammation by suppressing PKCδ activation and mucus overproduction. Altogether, we propose YPL-001 and verproside as candidate drugs for treating inflammatory lung diseases that act by inhibiting PKCδ activation and its downstream pathways.

Black Ginseng Extract Exerts Potentially Anti-Asthmatic Activity by Inhibiting the Protein Kinase Cθ-Mediated IL-4/STAT6 Signaling Pathway.

Asthma is a chronic inflammatory lung disease that causes respiratory difficulties. Black ginseng extract (BGE) has preventative effects on respiratory inflammatory diseases such as asthma. However, the pharmacological mechanisms behind the anti-asthmatic activity of BGE remain unknown. To investigate the anti-asthmatic mechanism of BGE, phorbol 12-myristate 13-acetate plus ionomycin (PMA/Iono)-stimulated mouse EL4 cells and ovalbumin (OVA)-induced mice with allergic airway inflammation were used. Immune cells (eosinophils/macrophages), interleukin (IL)-4, -5, -13, and serum immunoglobulin E (IgE) levels were measured using an enzyme-linked immunosorbent assay. Inflammatory cell recruitment and mucus secretion in the lung tissue were estimated. Protein expression was analyzed via Western blotting, including that of inducible nitric oxide synthase (iNOS) and the activation of protein kinase C theta (PKCθ) and its downstream signaling molecules. BGE decreased T helper (Th)2 cytokines, serum IgE, mucus secretion, and iNOS expression in mice with allergic airway inflammation, thereby providing a protective effect. Moreover, BGE and its major ginsenosides inhibited the production of Th2 cytokines in PMA/Iono-stimulated EL4 cells. In EL4 cells, these outcomes were accompanied by the inactivation of PKCθ and its downstream transcription factors, such as nuclear factor of activated T cells (NFAT), nuclear factor kappa B (NF-κB), activator of transcription 6 (STAT6), and GATA binding protein 3 (GATA3), which are involved in allergic airway inflammation. BGE also inhibited the activation of PKCθ and the abovementioned transcriptional factors in the lung tissue of mice with allergic airway inflammation. These results highlight the potential of BGE as a useful therapeutic and preventative agent for allergic airway inflammatory diseases such as allergic asthma.

Diplacone Isolated from Paulownia tomentosa Mature Fruit Induces Ferroptosis-Mediated Cell Death through Mitochondrial Ca2+ Influx and Mitochondrial Permeability Transition.

The recently defined type of cell death ferroptosis has garnered significant attention as a potential new approach to cancer treatment owing to its more immunogenic nature when compared with apoptosis. Ferroptosis is characterized by the depletion of glutathione (GSH)/glutathione peroxidase-4 (GPx4) and iron-dependent lipid peroxidation. Diplacone (DP), a geranylated flavonoid compound found in Paulownia tomentosa fruit, has been identified to have anti-inflammatory and anti-radical activity. In this study, the potential anticancer activity of DP was explored against A549 human lung cancer cells. It was found that DP induced a form of cytotoxicity distinct from apoptosis, which was accompanied by extensive mitochondrial-derived cytoplasmic vacuoles. DP was also shown to increase mitochondrial Ca2+ influx, reactive oxygen species (ROS) production, and mitochondrial permeability transition (MPT) pore-opening. These changes led to decreases in mitochondrial membrane potential and DP-induced cell death. DP also induced lipid peroxidation and ATF3 expression, which are hallmarks of ferroptosis. The ferroptosis inhibitors ferrostatin-1 and liproxstatin-1 were effective in counteracting the DP-mediated ferroptosis-related features. Our results could contribute to the use of DP as a ferroptosis-inducing agent, enabling studies focusing on the relationship between ferroptosis and the immunogenic cell death of cancer cells.

Comprehensive Targeted Metabolomic Study in the Lung, Plasma, and Urine of PPE/LPS-Induced COPD Mice Model.

(1) Background: Progression of chronic obstructive pulmonary disease (COPD) leads to irreversible lung damage and inflammatory responses; however, biomarker discovery for monitoring of COPD progression remains challenging. (2) Methods: This study evaluated the metabolic mechanisms and potential biomarkers of COPD through the integrated analysis and receiver operating characteristic (ROC) analysis of metabolic changes in lung, plasma, and urine, and changes in morphological characteristics and pulmonary function in a model of PPE/LPS-induced COPD exacerbation. (3) Results: Metabolic changes in the lungs were evaluated as metabolic reprogramming to counteract the changes caused by the onset of COPD. In plasma, several combinations of phenylalanine, 3-methylhistidine, and polyunsaturated fatty acids have been proposed as potential biomarkers; the α-aminobutyric acid/histidine ratio has also been reported, which is a novel candidate biomarker for COPD. In urine, a combination of succinic acid, isocitric acid, and pyruvic acid has been proposed as a potential biomarker. (4) Conclusions: This study proposed potential biomarkers in plasma and urine that reflect altered lung metabolism in COPD, concurrently with the evaluation of the COPD exacerbation model induced by PPE plus LPS administration. Therefore, understanding these integrative mechanisms provides new insights into the diagnosis, treatment, and severity assessment of COPD.

Anti-Inflammatory Activity of Cajanin, an Isoflavonoid Derivative Isolated from Canavalia lineata Pods.

The bioactive components of Canavalia lineata (Thunb.) DC pods were investigated using bioactivity-guided isolation, and the chemical structures of flavonoids 1-3, isoflavonoid derivatives 4-11, and phenolic compounds 12 and 13 were identified by comparing NMR, MS, and CD spectral data with previously reported spectroscopic data. Compounds 1-13 were evaluated for their anti-inflammatory effects on LPS-stimulated RAW264.7 macrophages. Among these compounds, the isoflavonoid derivative cajanin (7) exhibited the most potent anti-inflammatory activity (IC50 of NO = 19.38 ± 0.05 µM; IC50 of IL-6 = 7.78 ± 0.04 µM; IC50 of TNF-α = 26.82 ± 0.11 µM), exerting its anti-inflammatory effects by suppressing the activation and nuclear translocation of the transcription factor NF-κB by phosphorylating IκB and p65. These results suggested that cajanin (7) may be a potential candidate for improving the treatment of inflammatory diseases.

8-Epi-xanthatin induces the apoptosis of DU145 prostate carcinoma cells through signal transducer and activator of transcription 3 inhibition and reactive oxygen species generation.

Signal transducer and activator of transcription 3 (STAT3) is aberrantly activated in many human cancers. We tried to find STAT3 inhibitors from natural sources and found that Xanthium fruit extracts decreased phosphorylation of STAT3-Y705. 8-Epi-xanthatin (EXT) was isolated from the extracts. When DU145 cancer cells were treated with EXT, p-STAT3-Y705 was decreased with an IC50 of 3.2 µM. EXT decreased the expression of STAT3 target genes, such as cyclin A, cyclin D1, and BCL-2, and induced PARP cleavage, indicating apoptotic cell death. Downregulation of EXT-induced p-STAT3-Y705 was rescued by pretreating DU145 cells with antioxidants, such as N-acetyl-L-cysteine (NAC), indicating that reactive oxygen species (ROS) were involved in the EXT-induced inhibition of STAT3 activation. Furthermore, we proved the association of EXT with STAT3 protein by using a drug affinity responsive target stability (DARTS) assay and a cellular thermal shift assay (CETSA). EXT inhibited proliferation of DU145 cells with a GI50 of 6 µM and reduced tumor growth in mice xenografted with DU145 cells. Immunoblotting showed that phosphorylation of STAT3-Y705 was lower in EXT-treated tumor tissue than in control tissues. Collectively, we found that EXT binds to, and inhibits, STAT3 activation and could be a lead compound for anticancer therapy.

Tip-To-Middle Anisotropic MOF-On-MOF Growth with a Structural Adjustment.

Well-organized construction of hybrid metal-organic frameworks (MOFs) with complicated structures or components is a great importance because of their potential usefulness. In this regard, the conjugation of more than two MOFs, which have dissimilar components and/or structures, is a smart strategy for the production of hybrid MOFs. MOF-on-MOF growth is fundamental for the conjugation of two MOFs and should be deeply understood for the finely controlled conjugation and for the formation of well-organized hybrid MOFs. Herein, we report an interesting MOF growth process for the construction of hybrid MOF particles containing heterogeneous components and cell lattices. Interestingly, even though a newly grown MOF and an MOF template have mismatched cell lattices, the anisotropic growth results in unexpectedly well-defined core-shell-type hybrid MOFs. Comprehensive monitoring of the growth process revealed a tip-to-middle MOF-on-MOF growth, which elucidates the uncommon formation of a well-defined core-shell hybrid despite the anisotropic growth. A tip-to-middle anisotropic growth process is accompanied by self-adjustment of MOF cell lattices to anchor on the template surface having mismatched cell lattices in the early reaction stage and self-reversion of cell lattices to the original comfortable configuration in the middle stage of the reaction.

Longifolioside A inhibits TLR4-mediated inflammatory responses by blocking PKCδ activation in LPS-stimulated THP-1 macrophages.

Longifolioside A is an iridoid glucoside compound isolated from Pseudolysimachion rotundum var. subintegrum, which has been used in traditional herbal medicines to treat respiratory inflammatory diseases. Logifolioside A is a potent antioxidant; however, its underlying pharmacological mechanisms of action in inflammatory diseases are unknown. Here, we investigated the inhibitory effects of longifolioside A in lipopolysaccharide (LPS)-stimulated toll-like receptor 4 (TLR4) signal transduction systems using human THP-1 macrophages and HEK293 cells stably expressing human TLR4 protein (293/HA-hTLR4). Longifolioside A significantly reduced the release of inflammatory cytokines such as interleukin (IL)-6, -8, and tumor necrosis factor (TNF)-α in LPS-stimulated THP-1 macrophages. Furthermore, longifolioside A inhibited the expression of inflammatory mediator genes such as inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2 that produce nitric oxide (NO) and prostaglandin E2 (PGE2), respectively. Longifolioside A suppressed the phosphorylation of PKCδ, IRAK4, IKKα/ß, IκBα, and mitogen-activated protein (MAP) kinases (ERK 1/2 and JNK, but not p38), thereby inactivating the nuclear localization of NF-κB and AP-1, and thus decreasing the expression of inflammatory response genes. Notably, longifolioside A disrupted the interaction between human TLR4 and the TIR domain-containing adaptor protein (TIRAP), an early step during TLR4 activation, thereby reducing IL-8 secretion in 293/HA-hTLR4 cells. This inhibitory effect was comparable to that of TAK-242 (a TLR4 inhibitor, or resatorvid). Our results indicate that longifolioside A prevents inflammatory response by suppressing TLR4 activation required for NF-κB and AP-1 activation.

Anti-inflammatory flavonoids from root bark of Broussonetia papyrifera in LPS-stimulated RAW264.7 cells.

Broussonetia papyrifera has been used as a diuretic, tonic and suppressor of edema. Bioactivity-guided fractionation and metabolite investigation of root bark extracts of this plant resulted in the isolation and identification of six 1,3-diphenylpropanes (1, 2, 8, 10, 17, 20), flavanone (3), two chalcones (4, 5), five flavans (6, 11, 14-16), dihydroflavonol (7) and five flavonols (9, 12, 13, 18, 19), including five new compounds (5, 7, 8, 19, 20) that inhibit NO production in LPS-induced RAW264.7 cells. The structures of compounds 1-20 were elucidated on the basis of spectroscopic data (1D and 2D NMR, MS, MS/MS, and HRMS). In particular, compounds 3, 5, 7, 12, and 20 exhibited significant inhibitory effects on the NO, iNOS, and pro-inflammatory cytokine (TNF-α and IL-6) production. Therefore, this study suggests that the flavonoid-rich products of B. papyrifera, including the new compounds, could be valuable candidates for the development of pharmaceuticals or functional foods in the prevention and treatment of anti-inflammatory disease.

Morphological and Structural Evolutions of Metal-Organic Framework Particles from Amorphous Spheres to Crystalline Hexagonal Rods.

Compositions as well as morphologies and structures of particles are vital factors that define their properties and applications. However, the morphology and structure changes associated with the composition change of metal-organic frameworks (MOFs) are barely studied. Herein, we report the morphology and structure changes of MOF particles associated with the ratio of two organic linkers incorporated within MOF particles, when they are constructed from the reactions of In(NO3)3 in the presence of isophthalic acid (H2IPA) and/or 1,4-benzenedicarboxylic acid (H2BDC). Two tendencies­the tendency of BDC and In(3+) to form porous crystalline hexagonal rods, and the tendency of IPA and In(3+) to form non-porous amorphous spherical particles­compete during the formation of MOF particles. Eventually, the incorporated ratio of BDC and IPA within the MOF particles, and thus their morphology and porosity, are controlled by altering the relative amounts of H2BDC and H2IPA used during the reactions.

Assessment of exposure to sulfuric acid in workers using cleaning equipment operated with lead-acid batteries.

Sulfuric acid, a constituent of lead-acid batteries, is an extremely hazardous substance, necessitating utmost caution. Unfortunately, many workers that utilize battery-operated equipment remain unaware of the potential exposure. This study aims to evaluate the potential exposure to sulfuric acid among workers employed by small companies associated with the operation of floor cleaning equipment powered by lead-acid batteries. Only cleaning equipment (hand-push and ride-on types) that required supplementation of lead-acid batteries with distilled water were targeted. Exposure measurement and analysis were performed according to the guidelines of NIOSH and including personal sampling and stationary sampling on the equipment. Exposure measurements indicated that workers were exposed to sulfuric acid. Additionally, the concentration level was slightly elevated in the stationary samples compared to personal samples. This study affirms that workers can experience exposure to sulfuric acid, even in the absence of direct handling of the substance. Consequently, there is a need to recognize and mitigate the potential risks.

Effectiveness of an Evidence-Based Practice Education Program for Undergraduate Nursing Students: A Systematic Review and Meta-Analysis.

This systematic review and meta-analysis examined the impact of evidence-based practice (EBP) education programs on undergraduate nursing students, focusing on enhancing EBP competency, critical thinking, and problem-solving ability. METHODS: The search, conducted through PubMed, Cochrane Library, EMBASE, CINAHL, and Web of Science up to December 2023, included studies published in English and Korean and adhered to PRISMA guidelines. Qualitative appraisal of the studies was conducted using the revised ROB II for randomized trials and the ROBINS-I for non-randomized trials. For the meta-analysis, the effect size of the intervention was calculated as a standardized mean difference. RESULTS: In our study, 11 studies met our inclusion criteria, and 8 studies of those were included in the meta-analysis. The effect sizes for EBP competency, critical thinking, and problem-solving ability were 1.55, 1.29, and 0.65, respectively. The meta-regression analysis indicated that tailored education programs of 4-7 weeks and being in the 4th grade significantly enhanced EBP competency. CONCLUSION: These findings support the development of a customizable and applied EBP education actively for students, preparing nursing students to effectively implement EBP in clinical settings after graduation. Despite the significant effect size of the outcome variables, the high heterogeneity suggests the need for further investigation to validate the EBP educational outcomes for nursing students.

The complete mitochondrial genome of a ground beetle Synuchus nitidus (Carabidae: Harpalinae: Sphodrini) from South Korea.

The ground beetle Synuchus nitidus (Motschulsky, 1861) (Carabidae: Harpalinae: Sphodrini) is one of the most common species in the forests of South Korea, which has the potential to be utilized as an environmental indicator. Here, we characterized the complete mitochondrial genome (mitogenome) of S. nitidus, which is the first in the harpaline tribe Sphodrini. Its genome is 16,392 bp in length and composed of 13 protein-coding genes (PCGs), 22 tRNA genes, two rRNA genes, and an A + T rich region. In addition, we reconstructed a maximum likelihood tree to elucidate the phylogenetic position of Sphodrini among the seven harpaline tribes using nucleotide sequences of the 13 PCGs. The ML tree supported a monophyletic clade of the subfamily Harpalinae and showed a close relationship between Sphodrini and Lebinii with a low bootstrap value. The complete mitogenome of S. nitidus could be helpful for molecular species identification and exploring phylogenetic relationships among carabids.

Daphnetin alleviates allergic airway inflammation by inhibiting T-cell activation and subsequent JAK/STAT6 signaling.

Allergic asthma is a major health burden on society as a chronic respiratory disease characterized by inflammation and muscle tightening around the airways in response to inhaled allergens. Daphne kiusiana Miquel is a medicinal plant that can suppress allergic airway inflammation; however, its specific molecular mechanisms of action are unclear. In this study, we aimed to elucidate the mechanisms by which D. kiusiana inhibits allergic airway inflammation. We evaluated the anti-inflammatory effects of the ethyl acetate (EA) fraction of D. kiusiana and its major compound, daphnetin, on murine T lymphocyte EL4 cells stimulated with phorbol 12-myristate 13-acetate and ionomycin in vitro and on asthmatic mice stimulated with ovalbumin in vivo. The EA fraction and daphnetin inhibited T-helper type 2 (Th2) cytokine secretion, serum immunoglobulin E production, mucus secretion, and inflammatory cell recruitment in vivo. In vitro, daphnetin suppressed intracellular Ca2+ mobilization (a critical regulator of nuclear factor of activated T cells) and functions of the activator protein 1 transcription factor to reduce interleukin (IL)-4 and IL-13 expression. Daphnetin effectively suppressed the IL-4/-13-induced activation of Janus kinase (JAK)/signal transducer and activator of transcription 6 (STAT6) signaling in vitro and in vivo, thereby inhibiting the expression of GATA3 and PDEF, two STAT6-target genes responsible for producing Th2 cytokines and mucins. These findings indicate that daphnetin suppresses allergic airway inflammation by stabilizing intracellular Ca2+ levels and subsequently inactivating the JAK/STAT6/GATA3/PDEF pathway, suggesting that daphnetin is a promising alternative to existing asthma treatments.