Impact of Electric Field Magnitude in the Left Dorsolateral Prefrontal Cortex on Changes in Intrinsic Functional Connectivity Using Transcranial Direct Current Stimulation: A Randomized Crossover Study.

This study investigated whether the electric field magnitude (E-field) delivered to the left dorsolateral prefrontal cortex (L-DLPFC) changes resting-state brain activity and the L-DLPFC resting-state functional connectivity (rsFC), given the variability in tDCS response and lack of understanding of how rsFC changes. Twenty-one healthy participants received either 2 mA anodal or sham tDCS targeting the L-DLPFC for 10 min. Brain imaging was conducted before and after stimulation. The fractional amplitude of low-frequency fluctuation (fALFF), reflecting resting brain activity, and the L-DLPFC rsFC were analyzed to investigate the main effect of tDCS, main effect of time, and interaction effects. The E-field was estimated by modeling tDCS-induced individual electric fields and correlated with fALFF and L-DLPFC rsFC. Anodal tDCS increased fALFF in the left rostral middle frontal area and decreased fALFF in the midline frontal area (FWE p < 0.050), whereas sham induced no changes. Overall rsFC decreased after sham (positive and negative connectivity, p = 0.001 and 0.020, respectively), with modest and nonsignificant changes after anodal tDCS (p = 0.063 and 0.069, respectively). No significant differences in local rsFC were observed among the conditions. Correlations were observed between the E-field and rsFC changes in the L-DLPFC (r = 0.385, p = 0.115), left inferior parietal area (r = 0.495, p = 0.037), and right lateral visual area (r = 0.683, p = 0.002). Single-session tDCS induced resting brain activity changes and may help maintain overall rsFC. The E-field in the L-DLPFC is associated with rsFC changes in both proximal and distally connected brain regions to the L-DLPFC.

Efficacy of personalized repetitive transcranial magnetic stimulation based on functional reserve to enhance ambulatory function in patients with Parkinson's disease: study protocol for a randomized controlled trial.

BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) is one of the non-invasive brain stimulations that modulate cortical excitability through magnetic pulses. However, the effects of rTMS on Parkinson's disease (PD) have yielded mixed results, influenced by factors including various rTMS stimulation parameters as well as the clinical characteristics of patients with PD. There is no clear evidence regarding which patients should be applied with which parameters of rTMS. The study aims to investigate the efficacy and safety of personalized rTMS in patients with PD, focusing on individual functional reserves to improve ambulatory function. METHODS: This is a prospective, exploratory, multi-center, single-blind, parallel-group, randomized controlled trial. Sixty patients with PD will be recruited for this study. This study comprises two sub-studies, each structured as a two-arm trial. Participants are classified into sub-studies based on their functional reserves for ambulatory function, into either the motor or cognitive priority group. The Timed-Up and Go (TUG) test is employed under both single and cognitive dual-task conditions (serial 3 subtraction). The motor dual-task effect, using stride length, and the cognitive dual-task effect, using the correct response rate of subtraction, are calculated. In the motor priority group, high-frequency rTMS targets the primary motor cortex of the lower limb, whereas the cognitive priority group receives rTMS over the left dorsolateral prefrontal cortex. The active comparator for each sub-study is bilateral rTMS of the primary motor cortex of the upper limb. Over 4 weeks, the participants will undergo 10 rTMS sessions, with evaluations conducted pre-intervention, mid-intervention, immediately post-intervention, and at 2-month follow-up. The primary outcome is a change in TUG time between the pre- and immediate post-intervention evaluations. The secondary outcome variables are the TUG under cognitive dual-task conditions, Movement Disorder Society-Unified Parkinson's Disease Rating Scale Part III, New Freezing of Gait Questionnaire, Digit Span, trail-making test, transcranial magnetic stimulation-induced motor-evoked potentials, diffusion tensor imaging, and resting state functional magnetic resonance imaging. DISCUSSION: The study will reveal the effect of personalized rTMS based on functional reserve compared to the conventional rTMS approach in PD. Furthermore, the findings of this study may provide empirical evidence for an rTMS protocol tailored to individual functional reserves to enhance ambulatory function in patients with PD. TRIAL REGISTRATION: ClinicalTrials.gov NCT06350617. Registered on 5 April 2024.

Unveiling Direct Electrochemical Oxidation of Methane at the Ceria/Gas Interface.

Solid oxide fuel cells (SOFCs) stand out in sustainable energy systems for their unique ability to efficiently utilize hydrocarbon fuels, particularly those from carbon-neutral sources. CeO2-δ (ceria) based oxides embedded in SOFCs are recognized for their critical role in managing hydrocarbon activation and carbon coking. However, even for the simplest hydrocarbon molecule, CH4, the mechanism of electrochemical oxidation at the ceria/gas interface is not well understood and the capability of ceria to electrochemically oxidize methane remains a topic of debate. This lack of clarity stems from the intricate design of standard metal/oxide composite electrodes and the complex nature of electrode reactions involving multiple chemical and electrochemical steps. This study presents a Sm-doped ceria thin-film model cell that selectively monitors CH4 direct-electro-oxidation on the ceria surface. Using impedance spectroscopy, operando X-ray photoelectron spectroscopy, and density functional theory, it is unveiled that ceria surfaces facilitate C─H bond cleavage and that H2O formation is key in determining the overall reaction rate at the electrode. These insights effectively address the longstanding debate regarding the direct utilization of CH4 in SOFCs. Moreover, these findings pave the way for an optimized electrode design strategy, essential for developing high-performance, environmentally sustainable fuel cells.

Elevated Risk of Stroke in Young Adults After Traumatic Brain Injury: A Nationwide Study of 1 Million Individuals.

BACKGROUND: Although stroke is commonly perceived as occurring in older adults, traumatic brain injury, one of the risk factors for stroke, is a leading cause of death in the younger adults. This study evaluated stroke risk in young-to-middle-aged adults based on traumatic brain injury severity and stroke subtypes. METHODS AND RESULTS: For this retrospective, population-based, cohort study, data of adults aged 18 to 49 years who were diagnosed with traumatic brain injury were obtained from the Korean National Health Insurance Service between 2010 and 2017. Traumatic brain injury history was measured based on the International Classification of Diseases, Tenth Revision (ICD-10), codes. Posttraumatic brain injury stroke risk was analyzed using a time-dependent Cox regression model. At baseline, 518423 patients with traumatic brain injury and 518 423 age- and sex-matched controls were included. The stroke incidence rate per 1000 person-years was 3.82 in patients with traumatic brain injury and 1.61 in controls. Stroke risk was approximately 1.89 times as high in patients with traumatic brain injury (hazard ratio, 1.89 [95% CI, 1.84-1.95]). After excluding stroke cases that occurred within 12 months following traumatic brain injury, these significant associations remained. In the subgroup analysis, patients with brain injury other than concussion had an approximately 9.34-fold risk of intracerebral hemorrhage than did the controls. CONCLUSIONS: Stroke prevention should be a priority even in young-to-middle-aged adult patients with traumatic brain injury. Managing stroke risk factors through regular health checkups and modifying health-related behaviors is necessary to prevent stroke.

Reliability of Surface Electromyography From the Lower-limb Muscles During Maximal and Submaximal Voluntary Isometric Contractions in In-bed Healthy Individuals and Patients With Subacute Stroke.

This study aims to develop maximal voluntary isometric contraction (MVIC) and submaximal voluntary isometric contraction (subMVIC) methods and to assess the reliability of the developed methods for in-bed healthy individuals and patients with subacute stroke. The electromyography (EMG) activities from the lower-limb muscles including the tensor fascia lata (TFL), rectus femoris (RF), tibialis anterior (TA), and gastrocnemius (GC) on both sides were recorded during MVIC and subMVIC using surface EMG sensors in 20 healthy individuals and 20 subacute stroke patients. In inter-trial reliability, both MVIC and subMVIC methods demonstrated excellent reliability for all the measured muscles at baseline and follow-up evaluations in both healthy individuals and stroke patients. In inter-day reliability, MVIC showed good reliability for the TFL and moderate reliability for the RF, TA, and GC, while subMVIC showed good reliability for the TFL, RF, and GC and poor reliability for the TA in healthy individuals. In conclusion, the MVIC and subMVIC methods of EMG activities were feasible in in-bed healthy individuals and patients with subacute stroke. The results can serve as a basis for the clinical evaluation of muscular activities using quantitative EMG signals on the lower-limb muscles in stroke patients with impaired mobility.

Nano-anticoagulant based on carrier-free low molecular weight heparin and octadecylamine with an albumin shuttling effect.

Low-molecular-weight heparin (LMWH), derived from unfractionated heparin (UFH), has enhanced anticoagulant efficacy, long duration of action, and extended half-life. Patients receiving LMWH for preventive therapies would strongly benefit from its long-term effects, however, achieving this is challenging. Here, we design and evaluate a nanoengineered LMWH and octadecylamine conjugate (LMHO) that can act for a long time while maintaining close to 97 ± 3% of LMWH activity via end-specific conjugation of the reducing end of LMWH. LMHO can self-assemble into nanoparticles with an average size of 105 ± 1.7 nm in water without any nanocarrier and can be combined with serum albumin, resulting in a lipid-based albumin shuttling effect. Such molecules can circulate in the bloodstream for 4-5 days. We corroborate the self-assembly capability of LMHO and its interaction with albumin through molecular dynamics (MD) simulations and transmission electron microscopy (TEM) analysis. This innovative approach to carrier-free polysaccharide delivery, enhanced by nanoengineered albumin shuttling, represents a promising platform to address limitations in conventional therapies.

Architecture and function of yeast phosphatidate phosphatase Pah1 domains/regions.

Phosphatidate (PA) phosphatase, which catalyzes the Mg2+-dependent dephosphorylation of PA to produce diacylglycerol, provides a direct precursor for the synthesis of the storage lipid triacylglycerol and the membrane phospholipids phosphatidylcholine and phosphatidylethanolamine. The enzyme controlling the key phospholipid PA also plays a crucial role in diverse aspects of lipid metabolism and cell physiology. PA phosphatase is a peripheral membrane enzyme that is composed of multiple domains/regions required for its catalytic function and subcellular localization. In this review, we discuss the domains/regions of PA phosphatase from the yeast Saccharomyces cerevisiae with reference to the homologous enzyme from mammalian cells.

Physical interpretation of entropy, Boltzmann constant, and temperature.

Through the previously reported the quantum-identity, the light-model, and the T(temperature) · S(entropy) energy, the implied meaning of temperature and entropy, respectively, which it was difficult to intuitively recognize, was clearly defined. In order to minimize possible errors at this time, the interrelationship of the SI base unit, which is the smallest unit, and the T(temperature) · S(entropy) unit integration was used. In the process of converting to Planck units, each unit (criterion) for entropy and temperature was calculated, and their physical and chemical meanings were compared and reinterpreted. Thus, the unit of entropy is related to the Boltzmann constant, and the temperature is the oscillation of pure mass units. Therefore, the intuitive recognition of physical and chemical factors based on the unit of meter(m)-time(s) is considered sufficient as an initiator to move closer to new science beyond the current limited application.

Protein kinase Hsl1 phosphorylates Pah1 to inhibit phosphatidate phosphatase activity and regulate lipid synthesis in Saccharomyces cerevisiae.

In Saccharomyces cerevisiae, Pah1 phosphatidate (PA) phosphatase, which catalyzes the Mg2+-dependent dephosphorylation of PA to produce diacylglycerol, plays a key role in utilizing PA for the synthesis of the neutral lipid triacylglycerol and thereby controlling the PA-derived membrane phospholipids. The enzyme function is controlled by its subcellular location as regulated by phosphorylation and dephosphorylation. Pah1 is initially inactivated in the cytosol through phosphorylation by multiple protein kinases and then activated via its recruitment and dephosphorylation by the protein phosphatase Nem1-Spo7 at the nuclear/endoplasmic reticulum membrane where the PA phosphatase reaction occurs. Many of the protein kinases that phosphorylate Pah1 have yet to be characterized with the identification of the target residues. Here, we established Pah1 as a bona fide substrate of septin-associated Hsl1, a protein kinase involved in mitotic morphogenesis checkpoint signaling. The Hsl1 activity on Pah1 was dependent on reaction time and the amounts of protein kinase, Pah1, and ATP. The Hsl1 phosphorylation of Pah1 occurred on Ser-748 and Ser-773, and the phosphorylated protein exhibited a 5-fold reduction in PA phosphatase catalytic efficiency. Analysis of cells expressing the S748A and S773A mutant forms of Pah1 indicated that Hsl1-mediated phosphorylation of Pah1 promotes membrane phospholipid synthesis at the expense of triacylglycerol, and ensures the dependence of Pah1 function on the Nem1-Spo7 protein phosphatase. This work advances the understanding of how Hsl1 facilitates membrane phospholipid synthesis through the phosphorylation-mediated regulation of Pah1.

Elucidating the mechanisms and mitigation strategies for six-phthalate-induced toxicity in male germ cells.

Phthalate esters (PAEs) are primary plasticizers and endocrine-disrupting chemicals (EDCs) that are extensively used in numerous everyday consumer products. Although the adverse effects of single PAEs have been studied, our understanding of the effect of multiple phthalate exposure on male germ cell vitality remains limited. Therefore, this study aimed to investigate the collective effects of a mixture of PAEs (MP) comprising diethyl-, bis (2-ethylhexyl)-, dibutyl-, diisononyl-, diisobutyl-, and benzyl butyl-phthalates in the proportions of 35, 21, 15, 15, 8, and 5%, respectively, on differentiated male germ cells using GC-1 spermatogonia (spg) cells. As a mixture, MP substantially hindered GC-1 spg cell proliferation at 3.13 µg/mL, with a half-maximal inhibitory concentration of 16.9 µg/mL. Treatment with 25 µg/mL MP significantly induced reactive oxygen species generation and promoted apoptosis. Furthermore, MP activated autophagy and suppressed phosphorylation of phosphoinositide 3-kinase, protein kinase B, and mammalian target of rapamycin (mTOR). The triple inhibitor combination treatment comprising parthenolide, N-acetylcysteine, and 3-methyladenine effectively reversed MP-induced GC-1 spg cell proliferation inhibition, mitigated apoptosis and autophagy, and restored mTOR phosphorylation. This study is the first to elucidate the mechanism underlying MP-induced male germ cell toxicity and the restoration of male germ cell proliferation mediated by chemical inhibitors. Therefore, it provides valuable insights into the existing literature by proposing a combinatorial toxicity mitigation strategy to counteract male germ cell toxicity induced by various EDCs exposure.

Efficacy of personalized rTMS to enhance upper limb function in subacute stroke patients: a protocol for a multi-center, randomized controlled study.

Background: Repetitive transcranial magnetic stimulation (rTMS) is widely used therapy to enhance motor deficit in stroke patients. To date, rTMS protocols used in stroke patients are relatively unified. However, as the pathophysiology of stroke is diverse and individual functional deficits are distinctive, more precise application of rTMS is warranted. Therefore, the objective of this study was to determine the effects of personalized protocols of rTMS therapy based on the functional reserve of each stroke patient in subacute phase. Methods: This study will recruit 120 patients with stroke in subacute phase suffering from the upper extremity motor impairment, from five different hospitals in Korea. The participants will be allocated into three different study conditions based on the functional reserve of each participant, measured by the results of TMS-induced motor evoked potentials (MEPs), and brain MRI with diffusion tensor imaging (DTI) evaluations. The participants of the intervention-group in the three study conditions will receive different protocols of rTMS intervention, a total of 10 sessions for 2 weeks: high-frequency rTMS on ipsilesional primary motor cortex (M1), high-frequency rTMS on ipsilesional ventral premotor cortex, and high-frequency rTMS on contralesional M1. The participants of the control-group in all three study conditions will receive the same rTMS protocol: low-frequency rTMS on contralesional M1. For outcome measures, the following assessments will be performed at baseline (T0), during-intervention (T1), post-intervention (T2), and follow-up (T3) periods: Fugl-Meyer Assessment (FMA), Box-and-block test, Action Research Arm Test, Jebsen-Taylor hand function test, hand grip strength, Functional Ambulatory Category, fractional anisotropy measured by the DTI, and brain network connectivity obtained from MRI. The primary outcome will be the difference of upper limb function, as measured by FMA from T0 to T2. The secondary outcomes will be the differences of other assessments. Discussion: This study will determine the effects of applying different protocols of rTMS therapy based on the functional reserve of each patient. In addition, this methodology may prove to be more efficient than conventional rTMS protocols. Therefore, effective personalized application of rTMS to stroke patients can be achieved based on their severity, predicted mechanism of motor recovery, or functional reserves. Clinical trial registration: https://clinicaltrials.gov/, identifier NCT06270238.

Exploring the comparative genome of rice pathogen Burkholderia plantarii: unveiling virulence, fitness traits, and a potential type III secretion system effector.

This study presents a comprehensive genomic analysis of Burkholderia plantarii, a rice pathogen that causes blight and grain rot in seedlings. The entire genome of B. plantarii KACC 18964 was sequenced, followed by a comparative genomic analysis with other available genomes to gain insights into its virulence, fitness, and interactions with rice. Multiple secondary metabolite gene clusters were identified. Among these, 12 demonstrated varying similarity levels to known clusters linked to bioactive compounds, whereas eight exhibited no similarity, indicating B. plantarii as a source of potentially novel secondary metabolites. Notably, the genes responsible for tropolone and quorum sensing were conserved across the examined genomes. Additionally, B. plantarii was observed to possess three complete CRISPR systems and a range of secretion systems, exhibiting minor variations among the analyzed genomes. Genomic islands were analyzed across the four genomes, and a detailed study of the B. plantarii KACC 18964 genome revealed 59 unique islands. These islands were thoroughly investigated for their gene contents and potential roles in virulence. Particular attention has been devoted to the Type III secretion system (T3SS), a crucial virulence factor. An in silico analysis of potential T3SS effectors identified a conserved gene, aroA. Further mutational studies, in planta and in vitro analyses validated the association between aroA and virulence in rice. Overall, this study enriches our understanding of the genomic basis of B. plantarii pathogenicity and emphasizes the potential role of aroA in virulence. This understanding may guide the development of effective disease management strategies.

Effects of Transcutaneous Auricular Vagus Nerve Stimulation on Cortical Excitability in Healthy Adults.

OBJECTIVE: Vagus nerve stimulation (VNS) has recently been reported to exert additional benefits for functional recovery in patients with brain injury. However, the mechanisms underlying these effects have not yet been elucidated. This study examined the effects of transcutaneous auricular VNS (taVNS) on cortical excitability in healthy adults. MATERIALS AND METHODS: We recorded subthreshold and suprathreshold single- and paired-pulse motor-evoked potentials (MEPs) in the right-hand muscles of 16 healthy adults by stimulating the left primary motor cortex. Interstimulus intervals were set at 2 milliseconds and 3 milliseconds for intracortical inhibition (ICI), and 10 milliseconds and 15 milliseconds for intracortical facilitation (ICF). taVNS was applied to the cymba conchae of both ears for 30 minutes. The intensity of taVNS was set to a maximum tolerable level of 1.95 mA. MEPs were measured before stimulation, 20 minutes after the beginning of the stimulation, and 10 minutes after the cessation of stimulation. RESULTS: The participants' age was 33.25 ± 7.08 years, and nine of 16 were male. No statistically significant changes were observed in the mean values of the single-pulse MEPs before, during, or after stimulation. Although the ICF showed an increasing trend after stimulation, the changes in ICI and ICF were not significant, primarily because of the substantial interindividual variability. CONCLUSIONS: The effect of taVNS on cortical excitability varied in healthy adults. An increase in ICF was observed after taVNS, although the difference was not statistically significant. Our findings contribute to the understanding of the mechanisms by which taVNS is effective in patients with brain disorders.

Mitigation of benzyl butyl phthalate toxicity in male germ cells with combined treatment of parthenolide, N-acetylcysteine, and 3-methyladenine.

Benzyl butyl phthalate (BBP) is a widely used plasticizer that poses various potential health hazards. Although BBP has been extensively studied, the direct mechanism underlying its toxicity in male germ cells remains unclear. Therefore, we investigated BBP-mediated male germ cell toxicity in GC-1 spermatogonia (spg), a differentiated mouse male germ cell line. This study investigated the impact of BBP on reactive oxygen species (ROS) generation, apoptosis, and autophagy regulation, as well as potential protective measures against BBP-induced toxicity. A marked dose-dependent decrease in GC-1 spg cell proliferation was observed following treatment with BBP at 12.5 µM. Exposure to 50 µM BBP, approximating the IC50 of 53.9 µM, markedly increased cellular ROS generation and instigated apoptosis, as evidenced by augmented protein levels of both intrinsic and extrinsic apoptosis-related markers. An amount of 50 µM BBP induced marked upregulation of autophagy regulator proteins, p38 MAPK, and extracellular signal-regulated kinase and substantially downregulated the phosphorylation of key kinases involved in regulating cell proliferation, including phosphoinositide 3-kinase, protein kinase B, mammalian target of rapamycin (mTOR), c-Jun N-terminal kinase. The triple combination of N-acetylcysteine, parthenolide, and 3-methyladenine markedly restored cell proliferation, decreased BBP-induced apoptosis and autophagy, and restored mTOR phosphorylation. This study provides new insights into BBP-induced male germ cell toxicity and highlights the therapeutic potential of the triple inhibitors in mitigating BBP toxicity.

Clinical Characteristics, Patterns of Care, and Treatment Outcomes of Radiation-Associated Sarcomas.

Radiation-associated sarcomas (RASs) are rare tumors with limited contemporary data to inform prognostication and management. We sought to identify the clinical presentation, patterns of care, and prognostic factors of RASs. RAS patients treated at a single institution from 2015 to 2021 were retrospectively reviewed for clinicopathologic variables, treatment strategies, and outcomes. Thirty-eight patients were identified with a median follow-up of 30.5 months. The median age at RAS diagnosis was 68.4 years (27.9-85.4), with a median latency from index radiotherapy (RT) of 9.1 years (3.7-46.3). RAS histologies included angiosarcoma (26%), undifferentiated pleomorphic sarcoma (21%), and osteosarcoma (18%). Most were high-grade (76%). Genomic profiling revealed low tumor mutational burden, frequent inactivating TP53 mutations (44%), CDKN2A deletions (26%), and MYC amplifications (22%), particularly in breast angiosarcomas. Of 38 patients, 33 presented with localized disease, 26 of whom were treated with curative intent. Overall, the median progression-free survival (PFS) was 9.5 months (1.4-34.7), and the overall survival (OS) was 11.1 months (0.6-31.6). Patients with localized vs. metastatic RASs had a longer PFS (HR, 3.0 [1.1-8.5]; p = 0.03) and OS (HR, 3.0 [1.04-8.68]; p = 0.03). Among localized RAS patients, high grade was associated with shorter OS (HR, 4.6 [1.04-20.30]; p = 0.03) and resection with longer OS (mean 58.8 vs. 6.1 months, HR, 0.1 [0.03-0.28]; p < 0.001). Among patients undergoing resection, negative margins were associated with improved OS (mean 71.0 vs. 15.5 months, HR, 5.1 [1.4-18.2]; p = 0.006). Patients with localized disease, particularly those undergoing R0 resection, demonstrated significantly better outcomes. Novel strategies are urgently needed to improve treatment outcomes in this challenging group of diseases.

Transcriptome and functional analyses of phenotypic plasticity in sea grape Caulerpa okamurae.

Caulerpa is a marine green macroalga distinguished by a large single cell with multiple nuclei. It also exhibits remarkable morphological intraspecies variations, in response to diverse environmental types. However, the molecular mechanisms underlying this phenotypic plasticity remain poorly understood. In this work, we compare the transcriptomes of Caulerpa okamurae Weber Bosse, 1897 displaying altered phenotypes of cultivation and natural phenotypes and investigate significantly regulated genes and their biological functions using differential expression analyses. We observe light-harvesting complex upregulation and cellular framework stability downregulation in altered phenotypes compared to the natural phenotypes. Intertidal macrophytes reduce light capture to avoid photodamage and regulate their morphology to protect against wave damage. In contrast, the lower light conditions and the cultivation environment augment light capture and increase a morphology prioritizing light trapping. Moreover, the addition of simulated wave-sweeping stimuli induces a return to the natural morphology under high-light conditions, showing how mechanical stress affects morphological organization in C. okamurae. We provide detailed gene expression patterns in C. okamurae under varying light intensities and water conditions, suggesting a distinct influence on its morphological traits.

Effect of Statin Therapy on Cardiovascular Outcome in Stroke Patients with Low Baseline Low-Density Lipoprotein Cholesterol.

OBJECTIVES: To investigate whether post-stroke statin therapy reduces subsequent major vascular events in statin-naïve patients with pretreatment low-density lipoprotein cholesterol (LDL-C) below the recommended target (≤70 mg/dL for atherosclerotic stroke and ≤100 mg/dL for non-atherosclerotic stroke) at stroke onset. METHODS: Patients from an ongoing stroke registry who had an ischemic stroke between 2011 and 2020 were screened. Statin naïve patients with baseline LDL-C below the target were assessed. The effect of post-stroke statin therapy on major vascular events (composite of recurrent stroke, myocardial infarction, and death) was investigated using weighted Cox regression analyses using stabilized inverse probability treatment weighting. RESULTS: The baseline LDL-C level of the 1,858 patients (mean age 67.9 ± 15.3 years, 61.4% men, 13.2% atherosclerotic stroke) included in the study was 75.7 ± 17.0 mg/dL. Statins were prescribed to 1,256 (67.7%) patients (low-to-moderate intensity, 23.5%; high intensity, 44.1%). Post-stroke statin therapy was associated with a lower risk of major vascular events during 1-year follow-up (weighted hazard ratio 0.55, 95% confidence interval 0.42-0.71). In a subgroup of patients who were at very high risk of atherosclerotic cardiovascular disease with LDL-C <55 mg/dL or patients who were not at very high risk of atherosclerotic cardiovascular disease with LDL-C <70 mg/dL, post-stroke statin therapy was also associated with a reduction in major vascular events (weighted hazard ratio 0.45, 95% confidence interval 0.29-0.70). The intensity of the most beneficial statin varied by subtype of stroke. INTERPRETATION: Statin therapy may improve vascular outcomes after ischemic stroke, even in cases of LDL-C below the target without pre-stroke lipid-lowering therapy. ANN NEUROL 2024;95:876-885.

Transcriptomic Insights into Abies koreana Drought Tolerance Conferred by Aureobasidium pullulans AK10.

The conservation of the endangered Korean fir, Abies koreana, is of critical ecological importance. In our previous study, a yeast-like fungus identified as Aureobasidium pullulans AK10, was isolated and shown to enhance drought tolerance in A. koreana seedlings. In this study, the effectiveness of Au. pullulans AK10 treatment in enhancing drought tolerance in A. koreana was confirmed. Furthermore, using transcriptome analysis, we compared A. koreana seedlings treated with Au. pullulans AK10 to untreated controls under drought conditions to elucidate the molecular responses involved in increased drought tolerance. Our findings revealed a predominance of downregulated genes in the treated seedlings, suggesting a strategic reallocation of resources to enhance stress defense. Further exploration of enriched Kyoto Encyclopedia of Genes and Genomes pathways and protein-protein interaction networks revealed significant alterations in functional systems known to fortify drought tolerance, including the terpenoid backbone biosynthesis, calcium signaling pathway, pyruvate metabolism, brassinosteroid biosynthesis, and, crucially, flavonoid biosynthesis, renowned for enhancing plant drought resistance. These findings deepen our comprehension of how AK10 biostimulation enhances the resilience of A. koreana to drought stress, marking a substantial advancement in the effort to conserve this endangered tree species through environmentally sustainable treatment.

Fabrication of Yolk-Shell Structure with Multifarious Nanoparticles via Double-Layered Encapsulation Strategy.

The post-encapsulation method (such as single-layered encapsulation) is a promising strategy to synthesize yolk-shell structures that protect functional nanoparticles by the molecular sieving effect. However, this method exhibited limited loading capacity and nonuniform encapsulation during the co-encapsulation of various nanoparticles owing to the insufficient surface area for nanoparticle attachment. To address these limitations, we proposed a double-layered encapsulation method comprising an increased number of silica template layers and separate attachment of multifarious nanoparticles to different layers. Compared with conventional methods, this strategy can precisely adjust the ratio of encapsulated nanoparticles and increase the loading amount, which improves the functionality of yolk-shell structures, such as the photothermal properties of gold nanoparticle-encapsulated yolk-shell structures (∼69%). We describe, for the first time, the precise control of the ratio of encapsulated nanoparticles and the loading of numerous nanoparticles. Consequently, this strategy has significant potential for various applications of yolk-shell structures.

Bioactivity-Guided Fraction from Viscera of Abalone, Haliotis discus hannai Suppresses Cellular Basophils Activation and Anaphylaxis in Mice.

Basophils and mast cells are specialized effector cells in allergic reactions. Haliotis discus hannai (abalone), is valuable seafood. Abalone male viscera, which has a brownish color and has not been previously reported to show anti-allergic activities, was extracted with acetone. Six different acetone/hexane fractions (0, 10, 20, 30, 40, and 100%) were obtained using a silica column via ß-hexosaminidase release inhibitory activity-guided selection in phorbol myristate acetate and a calcium ionophore, A23187 (PMACI)-induced human basophils, KU812F cells. The 40% acetone/hexane fraction (A40) exhibited the strongest inhibition of PMACI-induced-ß-hexosaminidase release. This fraction dose-dependently inhibited reactive oxygen species (ROS) production and calcium mobilization without cytotoxicity. Western blot analysis revealed that A40 down-regulated PMACI-induced MAPK (ERK 1/2, p-38, and JNK) phosphorylation, and the NF-κB translocation from the cytosol to membrane. Moreover, A40 inhibited PMACI-induced interleukin (IL)-1ß, IL-6, and IL-8 production. Anti-allergic activities of A40 were confirmed based on inhibitory effects on IL-4 and tumor necrosis factor alpha (TNF-α) production in compound (com) 48/80-induced rat basophilic leukemia (RBL)-2H3 cells. A40 inhibited ß-hexosaminidase release and cytokine production such as IL-4 and TNF-α produced by com 48/80-stimulated RBL-2H3 cells. Furthermore, it's fraction attenuated the IgE/DNP-induced passive cutaneous anaphylaxis (PCA) reaction in the ears of BALB/c mice. Our results suggest that abalone contains the active fraction, A40 is a potent therapeutic and functional material to treat allergic diseases.