Spectrally Resolved Exciton Polarizability for Understanding Charge Generation in Organic Bulk Hetero-Junction Diodes.

Despite decades of research, the dominant charge generation mechanism in organic bulk heterojunction (BHJ) devices is not completely understood. While the local dielectric environments of the photoexcited molecules are important for exciton dissociation, conventional characterizations cannot separately measure the polarizability of electron-donor and electron-acceptor, respectively, in their blends, making it difficult to decipher the spectrally different charge generation efficiencies in organic BHJ devices. Here, by spectrally resolved electroabsorption spectroscopy, we report extraction of the excited state polarizability for individual donors and acceptors in a series of organic blend films. Regardless of the donor and acceptor, we discovered that larger exciton polarizability is linked to larger π-π coherence length and faster charge transfer across the heterojunction, which fundamentally explains the origin of the higher charge generation efficiency near 100% in the BHJ photodiodes. We also show that the molecular packing of the donor and acceptor influence each other, resulting in a synergetic enhancement in the exciton polarizability.

Molecular evidence for multiple origins and high genetic differentiation of non-native winter crane fly, Trichocera maculipennis (Diptera: Trichoceridae), in the maritime Antarctic.

Native biodiversity and ecosystems of Antarctica safeguarded from biological invasion face recent threats from non-native species, accelerated by increasing human activities and climate changes. Over two decades ago, the winter crane fly, Trichocera maculipennis, was first detected on King George Island. It has now successfully colonized several research stations across King George Island. To understand the origin, genetic diversity, and population structure of this Holarctic species, we conducted mitochondrial DNA cytochrome c oxidase subunit I (COI) sequence analysis across both its native and invasive ranges. In parallel, we performed microsatellite loci analysis within the invasive ranges, utilizing 12 polymorphic microsatellite markers. Furthermore, we compared body sizes among adult males and females collected from three different locations of King George Island. Our COI sequence analysis exhibited two different lineages present on King George Island. Lineage I was linked to Arctic Svalbard and Polish cave populations and Lineage II was related to Canadian Terra Nova National Park populations, implying multiple origins. Microsatellite analysis further exhibited high levels of genetic diversity and significant levels of genetic differentiation among invasive populations. Body sizes of adult T. maculipennis were significantly different among invasive populations but were not attributed to genetics. This significant genetic diversity likely facilitated the rapid colonization and establishment of T. maculipennis on King George Island, contributing to their successful invasion. Molecular analysis results revealed a substantial amount of genetic variation within invasive populations, which can serve as management units for invasive species control. Furthermore, the genetic markers we developed in the study will be invaluable tools for tracking impending invasion events and the travel routes of new individuals. Taken together, these findings illustrate the highly invasive and adaptable characteristics of T. maculipennis. Therefore, immediate action is necessary to mitigate their ongoing invasion and facilitate their eradication.

Particulate Matter-Induced Neurotoxicity: Unveiling the Role of NOX4-Mediated ROS Production and Mitochondrial Dysfunction in Neuronal Apoptosis.

Urban air pollution, a significant environmental hazard, is linked to adverse health outcomes and increased mortality across various diseases. This study investigates the neurotoxic effects of particulate matter (PM), specifically PM2.5 and PM10, by examining their role in inducing oxidative stress and subsequent neuronal cell death. We highlight the novel finding that PM increases mitochondrial ROS production via stimulating NOX4 activity, not through its expression level in Neuro-2A cells. Additionally, PMs provoke ROS production via increasing the expression and activity of NOX2 in SH-SY5Y human neuroblastoma cells, implying differential regulation of NOX proteins. This increase in mitochondrial ROS triggers the opening of the mitochondrial permeability transition pore (mPTP), leading to apoptosis through key mediators, including caspase3, BAX, and Bcl2. Notably, the voltage-dependent anion-selective channel 1 (VDAC1) increases at 1 µg/mL of PM2.5, while PM10 triggers an increase from 10 µg/mL. At the same concentration (100 µg/mL), PM2.5 causes 1.4 times higher ROS production and 2.4 times higher NOX4 activity than PM10. The cytotoxic effects induced by PMs were alleviated by NOX inhibitors GKT137831 and Apocynin. In SH-SY5Y cells, both PM types increase ROS and NOX2 levels, leading to cell death, which Apocynin rescues. Variability in NADPH oxidase sources underscores the complexity of PM-induced neurotoxicity. Our findings highlight NOX4-driven ROS and mitochondrial dysfunction, suggesting a potential therapeutic approach for mitigating PM-induced neurotoxicity.

Crocin Attenuates NLRP3 Inflammasome Activation by Inhibiting Mitochondrial Reactive Oxygen Species and Ameliorates Monosodium Urate-Induced Mouse Peritonitis.

Crocin is a hydrophilic carotenoid pigment found in the stigma of Crocus sativus or the fruit of Gardenia jasminoides. In this study, we investigated the effects of Crocin on the activation of the nucleotide-binding oligomerization domain, leucine-rich repeat, and pyrin domain containing 3 (NLRP3) inflammasome in J774A.1 murine macrophage cells and monosodium urate (MSU)-induced peritonitis. Crocin significantly inhibited Nigericin-, adenosine triphosphate (ATP)-, MSU-induced interleukin (IL)-1ß secretion, and caspase-1 cleavage without affecting pro-IL-1ß and pro-caspase-1. Crocin also suppressed gasdermin-D cleavage and lactate dehydrogenase release and enhanced cell viability, indicating that Crocin reduces pyroptosis. Similar effects were observed in primary mouse macrophages. However, Crocin did not affect poly(dA:dT)-induced absent in melanoma 2 (AIM2) and muramyl dipeptide-induced NLRP1 inflammasomes. Crocin decreased Nigericin-induced oligimerization and the speck formation of apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC). Crocin also dramatically alleviated the ATP-induced production of mitochondrial reactive oxygen species (mtROS). Finally, Crocin ameliorated the MSU-induced production of IL-1ß and IL-18 and the recruitment of neutrophils during peritoneal inflammation. These results suggest that Crocin suppresses NLRP3 inflammasome activation by blocking mtROS production and ameliorates MSU-induced mouse peritonitis. Thus, Crocin may have therapeutic potential in various NLRP3 inflammasome-related inflammatory diseases.

Dynamics of surface-plasmon lasing in planar metal gratings on semiconductor.

We investigate the dynamics of surface plasmon (SP) lasing in Au gratings fabricated on InGaAs with a period of around 400 nm, which locates the SP resonance near the semiconductor energy gap and facilitates efficient energy transfer. By optically pumping the InGaAs to reach the population inversion required for the amplification and the lasing, we observe SP lasing at specific wavelengths that satisfy the SPR condition depending on the grating period. The carrier dynamics in semiconductor and the photon density in the SP cavity was investigated from the time-resolved pump-probe measurement and the time resolved photoluminescence spectroscopy, respectively. Our results reveal that the photon dynamics is strongly correlated with the carrier dynamics and the lasing build-up is accelerated as the initial gain proportional to the pumping power increases, and this trend is satisfactorily explained using the rate equation model.

Early Prediction of Radiation-Induced Pulmonary Fibrosis Using Gastrin-Releasing Peptide Receptor-Targeted PET Imaging.

Early diagnosis of radiation-induced pulmonary fibrosis (RIPF) in lung cancer patients after radiation therapy is important. A gastrin-releasing peptide receptor (GRPR) mediates the inflammation and fibrosis after irradiation in mice lungs. Previously, our group synthesized a GRPR-targeted positron emission tomography (PET) imaging probe, [64Cu]Cu-NODAGA-galacto-bombesin (BBN), an analogue peptide of GRP. In this study, we evaluated the usefulness of [64Cu]Cu-NODAGA-galacto-BBN for the early prediction of RIPF. We prepared RIPF mice and acquired PET/CT images of [18F]F-FDG and [64Cu]Cu-NODAGA-galacto-BBN at 0, 2, 5, and 11 weeks after irradiation (n = 3-10). We confirmed that [64Cu]Cu-NODAGA-galacto-BBN targets GRPR in irradiated RAW 264.7 cells. In addition, we examined whether [64Cu]Cu-NODAGA-galacto-BBN monitors the therapeutic efficacy in RIPF mice (n = 4). As a result, the lung uptake ratio (irradiated-to-normal) of [64Cu]Cu-NODAGA-galacto-BBN was the highest at 2 weeks, followed by its decrease at 5 and 11 weeks after irradiation, which matched with the expression of GRPR and was more accurately predicted than [18F]F-FDG. These uptake results were also confirmed by the cell uptake assay. Furthermore, [64Cu]Cu-NODAGA-galacto-BBN could monitor the therapeutic efficacy of pirfenidone in RIPF mice. We conclude that [64Cu]Cu-NODAGA-galacto-BBN is a novel PET imaging probe for the early prediction of RIPF-targeting GRPR expressed during the inflammatory response.

Factors for predicting recurrence after burr hole drainage for chronic subdural hematoma: a retrospective study.

Chronic subdural hematoma (SDH) is a common disease in the neurosurgical field, and hematoma drainage through burr hole trephination has been widely considered the optimal treatment for SDH. Despite numerous investigations aimed at predicting recurrence rates and associated factors, studies have demonstrated inconsistent results. In this study, we aimed to comprehensively determine the predictive factors of chronic SDH recurrence in surgically treated patients. We retrospectively evaluated 578 consecutive patients who underwent single burr hole surgery for chronic SDH at our institute between January 2008 and December 2021. Various clinical and radiological factors in patients with and without recurrence were compared using univariate and multivariate logistic regression analyses. A total of 438 patients (531 hemispheres) were analyzed. Fifty-four (10.17%) of the 531 hemispheres had recurrence of chronic SDH within 6 months. Male sex (adjusted odds ratio (aOR) = 3.48; 95% confidence interval (CI), 1.42-8.49), bilateral hematomas (aOR = 2.14; 95% CI, 1.05-4.35), laminar hematoma type (aOR = 2.87; 95% CI, 1.23-6.71), > 30-cm3 volume of postoperative residual hematoma (aOR = 2.99; 95% CI, 1.01-8.83), and preoperative blood glucose level of ≥ 150 mg/dL (aOR = 2.11; 95% CI, 1.10-4.05) were identified as independent factors associated with recurrence in multivariate logistic regression analysis. The present study revealed that male patients and those who had bilateral hematomas, laminar hematoma type, a large volume of hematoma after surgery, and a high preoperative blood glucose level had a higher probability of experiencing recurrent chronic SDH. We recommend close monitoring of patients 6 months postoperatively to detect subsequent chronic SDH recurrence.

Arctic Sea Ice Microalga Chlamydomonas latifrons KNF0041: Identification and Statistical Optimization of Medium for Enhanced Biomass and Omega-3/Omega-6.

Polar microorganisms produce biologically active compounds that enable them to survive in harsh environments. These compounds have potential biomedical applications. The green microalga Chlamydomonas latifrons KNF0041, isolated from Arctic sea ice, has been found to produce polyunsaturated fatty acids (PUFAs), including omega-3 and omega-6, which have antioxidant properties. To improve the biomass production of strain KNF0041, statistical methods such as the Plackett-Burman design, Box-Behnken design, and response surface methodology (RSM) were utilized for medium optimization. The optimized medium was designed with increased potassium phosphate content and reduced acetic acid (AcOH) content. The use of the optimized medium resulted in an increase in the cell number as biomass of strain KNF0041 by 34.18% and the omega-3 and omega-6 fatty acid (FA) content by 10.04% and 58.29%, respectively, compared to that in normal TAP medium, which is known as the growth medium for Chlamydomonas culture. In this study, Chlamydomonas latifrons was discovered for the first time in the polar region and identified using morphology and molecular phylogenetic analyses, the secondary structures of the internal transcribed spacers, and optimized culture conditions. The results of this study provide an efficient method for the application of polar microalgae for the production of bioactive compounds.

Pinus koraiensis Essential Oil Attenuates the Pathogenicity of Superbacteria by Suppressing Virulence Gene Expression.

In the quest to combat infections attributable to antibiotic-resistant superbacteria, an essential oil derived from the needles of Pinus koraiensis Sieb. et Zucc. (PKEO) has emerged as a promising solution. In this study, we demonstrate that PKEO can be used to inhibit the growth, glucose metabolite acidogenicity, and biofilm formation of methicillin-resistant Staphylococcus aureus (MRSA). Quantitative PCR analysis provided direct evidence that PKEO reduces the mRNA expression of the accessory gene regulator A (agrA) and staphylococcal accessory regulator A (sarA), thereby indicating its inhibitory effect on pathogenic regulatory genes. Chromatographic analyses of PKEO identified terpene hydrocarbons as prominent essential oil constituents. These compounds, notably α-pinene, limonene, and ß-caryophyllene, have been established to have antimicrobial properties. Our findings indicate that an oil derived from P. koraiensis can effectively combat antibiotic-resistant strains by disrupting the pathogenicity regulatory system, thereby establishing PKEO as a promising candidate for the treatment of MRSA infections.

A higher probability of subsequent stroke and ischemic heart disease in migraine patients: a longitudinal follow-up study in Korea.

BACKGROUND: Whether migraine is related to the risk of cardiovascular diseases (CVDs) remains unclear. Therefore, we conducted a longitudinal follow-up study to address the association between migraine and the development of CVDs in Korea. METHODS: Using data from the national health screening cohort, we included 45,246 patients diagnosed with migraine between 2002 and 2019 and age-, sex-, income-, and residential region-matched nonmigraine participants at a ratio of 1:4. Participants with previous CVDs were excluded. Cox proportional hazards regression models were used to estimate the hazard ratios of three CVDs, stroke, ischemic heart disease, and heart failure, in patients with migraine after adjusting for potential cardiovascular risk factors. RESULTS: The incidence rate differences of stroke, ischemic heart disease, and heart failure among patients with migraine were 2.61, 1.69, and 0.11, respectively. The probability of developing stroke and ischemic heart disease in patients with migraine was significantly higher than that in controls after controlling for multiple confounders (adjusted hazard ratio [HR] = 1.35, 95% confidence interval [CI] = 1.31-1.39 and adjusted HR = 1.31, 95% CI = 1.26-1.35, respectively). However, when compared with the patients without migraine, patients with migraine did not have an increased HR of developing heart failure (adjusted HR = 1.01, 95% CI = 0.95-1.08). The overall migraine group, as well as groups stratified by migraine subtypes with and without aura, each showed a significantly higher probability of subsequent stroke and ischemic heart disease than the control group. CONCLUSIONS: Our longitudinal follow-up study demonstrated a significant association between the presence of migraine and the development of stroke and ischemic heart disease in Korea, even after adjusting for cardiovascular risk factors.

A chimeric MERS-CoV virus-like particle vaccine protects mice against MERS-CoV challenge.

BACKGROUND: Middle East respiratory syndrome coronavirus (MERS-CoV) causes severe respiratory disease in humans, with a case fatality rate of approximately 35%, thus posing a considerable threat to public health. The lack of approved vaccines or antivirals currently constitutes a barrier in controlling disease outbreaks and spread. METHODS: In this study, using a mammalian expression system, which is advantageous for maintaining correct protein glycosylation patterns, we constructed chimeric MERS-CoV virus-like particles (VLPs) and determined their immunogenicity and protective efficacy in mice. RESULTS: Western blot and cryo-electron microscopy analyses demonstrated that MERS-CoV VLPs were efficiently produced in cells co-transfected with MERS-CoV spike (S), envelope, membrane and murine hepatitis virus nucleocapsid genes. We examined their ability as a vaccine in a human dipeptidyl peptidase 4 knock-in C57BL/6 congenic mouse model. Mice immunized with MERS VLPs produced S-specific antibodies with virus neutralization activity. Furthermore, MERS-CoV VLP immunization provided complete protection against a lethal challenge with mouse-adapted MERS-CoV and improved virus clearance in the lung. CONCLUSIONS: Overall, these data demonstrate that MERS-CoV VLPs have excellent immunogenicity and represent a promising vaccine candidate.

Ultrafast dynamic contrast-enhanced breast MRI: association with pathologic complete response in neoadjuvant treatment of breast cancer.

OBJECTIVES: The purpose of this study was to investigate whether pretreatment kinetic features from ultrafast DCE-MRI are associated with pathological complete response (pCR) in patients with invasive breast cancer and according to immunohistochemistry (IHC) subtype. METHODS: Between August 2018 and June 2019, 256 consecutive breast cancer patients (mean age, 50.2 years; range, 25-86 years) who underwent both ultrafast and conventional DCE-MRI and surgery following neoadjuvant chemotherapy were included. DCE-MRI kinetic features were obtained from pretreatment MRI data. Time-to-enhancement, maximal slope (MS), and volumes at U1 and U2 (U1, time point at which the lesion starts to enhance; U2, subsequent time point after U1) were derived from ultrafast MRI. Logistic regression analysis was performed to identify factors associated with pCR. RESULTS: Overall, 41.4% of all patients achieved pCR. None of the kinetic features was associated with pCR when including all cancers. Among ultrafast DCE-MRI kinetic features, a lower MS (OR, 0.982; p = 0.040) was associated with pCR at univariable analysis in hormone receptor (HR)-positive cancers. In triple-negative cancers, a higher volume ratio U1/U2 was associated with pCR at univariable (OR, 11.787; p = 0.006) and multivariable analysis (OR, 14.811; p = 0.005). Among conventional DCE-MRI kinetic features, a lower peak enhancement (OR, 0.993; p = 0.031) and a lower percentage of washout (OR, 0.904; p = 0.039) was associated with pCR only in HR-positive cancers at univariable analysis. CONCLUSIONS: A higher volume ratio of U1/U2 derived from ultrafast DCE-MRI was independently associated with pCR in triple-negative invasive breast cancer. KEY POINTS: • The ratio of tumor volumes obtained at the first (U1) and second time points (U2) of enhancement was independently associated with pCR in triple-negative invasive breast cancers. • Ultrafast MRI has the potential to improve accuracy in predicting treatment response and personalizing therapy.

Depressive Symptoms, Subjective Cognitive Decline, and Subjective Sleep Quality Are Associated with Slips and Falls: Data from the Community Health Survey in Korean Adults.

BACKGROUND: Identifying the risk factors for falls among the elderly population is arguably one of the most imperative public health issues in the current aging society. OBJECTIVES: This study aimed to determine the associations between depressive symptoms, subjective cognitive decline (SCD), and poor subjective sleep quality and the risk of slips/falls in a Korean older population. METHODS: This cross-sectional study involved 228,340 elderly individuals living in Korea. Measurements included self-reported depressive symptoms, SCD, and self-reported sleep quality. The risk of slips/falls was dichotomized depending on whether slips/falls had occurred during the past year, and the associations between different risk factors and slips/falls were explored. Multiple logistic regression was used to obtain the odds ratios (ORs) and 95% confidence intervals (CIs). Complex sampling methods were used to estimate the weighted value of each participant. RESULTS: The risk of slips/falls was significantly associated with high levels of depressive symptoms (adjusted OR 1.06, 95% CI: 1.05-1.07) and SCD (adjusted OR 1.33, 95% CI: 1.19-1.50). Regarding each sleep quality component, the adjusted ORs for slips/falls were 1.85 for very poor sleep quality, 1.49 for long sleep latency, 1.04 for <5 h of sleep duration, 1.32 for low sleep efficiency, 2.78 for high sleep disturbance, 1.52 for the use of sleep medication ≥3 times a week, and 1.82 for high daytime dysfunction due to sleep problems compared to the respective good sleep conditions. CONCLUSIONS: Our results demonstrated that depressive symptoms, SCD, and poor subjective sleep quality are independent factors affecting the occurrence of slips/falls. Thus, efforts to manage depressive symptoms and cognitive decline early and to improve sleep quality can be an alternative strategy to decrease the likelihood of falls.

Treatment with Commelina communis Extract Exerts Anti-inflammatory Effects in Murine Macrophages via Modulation of the Nuclear Factor-κB Pathway.

The incidence of severe inflammatory diseases caused by chronic inflammation has increased owing to unprecedented changes brought about by industrialization. In this study, we aimed to assess the effect of treatment of lipopolysaccharide- (LPS-) induced murine macrophages with Commelina communis Linne extract (CCE) on synthesis of nitric oxide (NO), hypersecretion of proinflammatory cytokines, intranuclear transition of the p65 subunit of nuclear factor- (NF-) κB, and degradation of the NF-κB inhibitor IκBα. Notably, CCE treatment did not affect cell viability even at a final concentration of 1.5 mg/mL. At a high concentration of CCE, the LPS-induced high levels of NO, tumor necrosis factor-α, interleukin- (IL-) 1ß, and IL-6 were decreased via downregulation of inducible NO synthase and proinflammatory cytokine mRNA expression. Furthermore, phosphorylation of IκBα was significantly decreased upon CCE treatment, and the intranuclear transition of NF-κB p65 triggered by LPS was inhibited at a high concentration of CCE. Polyphenols and flavonoids, secondary metabolites in CCE that regulate the NF-κB pathway, may be responsible for its anti-inflammatory activity. We suggest that CCE has anti-inflammatory effects related to suppression of the NF-κB pathway and can be used to treat chronic inflammation.

Innate immunity and protective effects of orally administered betaine against viral and bacterial diseases in the olive flounder Paralichthys olivaceus (Temminck & Schlegel).

Sustainable methods that increase farmed fish yield while controlling infections are required to prevent economic losses in aquaculture farms. In this study, we evaluated the effects of betaine-supplemented (0%, 0.1%, 0.5%, and 1.0%) feed on the growth and immunity of the olive flounder Paralichthys olivaceus. Feed conversion ratios, post-infection cumulative mortality rates and innate immune responses were monitored. Weight gain was significantly higher with 0.5% and 1.0% than with 0% and 0.1% betaine-supplemented feed. Lysozyme activity was highest with 1.0% betaine. Respiratory burst activity was highest with 0.5% and 1.0% betaine. Serum bactericidal activity against Edwardsiella tarda was highest with 1.0% betaine (40% increase in survival rates compared with those in the control). Furthermore, serum virucidal activity against the viral haemorrhagic septicaemia virus (VHSV) was higher with 1.0% betaine than with other concentrations. With 0.5% and 1.0% betaine, the survival rates against VHSV were higher than those in the control until day 11, after which they declined. Our study suggests that betaine is a promising agent for promoting the growth of and enhancing immunity against E. tarda in olive flounders. Our findings may further contribute to developing necessary alternatives to conventional antibiotics in fish farming.

Escalated Photocurrent with Excitation Energy in Dual-Gated MoTe2.

Although van der Waals-layered transition metal dichalcogenides from transient absorption spectroscopy have successfully demonstrated an ideal carrier multiplication (CM) performance with an onset of nearly 2Eg, interpretation of the CM effect from the optical approach remains unresolved owing to the complexity of many-body electron-hole pairs. We demonstrate the escalated photocurrent with excitation photon energy by fabricating the dual-gate p-n junction of a MoTe2 film on a transparent substrate. Electrons and holes were efficiently extracted by eliminating the Schottky barriers in the metal contact and minimizing multiple reflections. The photocurrent was elevated proportionately to the excitation photon energy. The boosted quantum efficiency confirms the multiple electron-hole pair generation of >2Eg, consistent with CM results from an optical approach, pushing the solar cell efficiency beyond the Shockley-Queisser limit.

2-Methoxyestradiol Inhibits Radiation-Induced Skin Injuries.

Radiation-induced skin injury (RISI) is a main side effect of radiotherapy for cancer patients, with vascular damage being a common pathogenesis of acute and chronic RISI. Despite the severity of RISI, there are few treatments for it that are in clinical use. 2-Methoxyestradiol (2-ME) has been reported to regulate the radiation-induced vascular endothelial-to-mesenchymal transition. Thus, we investigated 2-ME as a potent anti-cancer and hypoxia-inducible factor 1 alpha (HIF-1α) inhibitor drug that prevents RISI by targeting HIF-1α. 2-ME treatment prior to and post irradiation inhibited RISI on the skin of C57/BL6 mice. 2-ME also reduced radiation-induced inflammation, skin thickness, and vascular fibrosis. In particular, post-treatment with 2-ME after irradiation repaired the damaged vessels on the irradiated dermal skin, inhibiting endothelial HIF-1α expression. In addition to the increase in vascular density, post-treatment with 2-ME showed fibrotic changes in residual vessels with SMA+CD31+ on the irradiated skin. Furthermore, 2-ME significantly inhibited fibrotic changes and accumulated DNA damage in irradiated human dermal microvascular endothelial cells. Therefore, we suggest that 2-ME may be a potent therapeutic agent for RISI.

Robot-Assisted Therapy Combined with Trunk Restraint in Acute Stroke Patients: A Randomized Controlled Study.

BACKGROUND: Reducing the compensatory mechanism by restraining unnecessary trunk movements may help enhance the effectiveness of robot-assisted therapy. OBJECTIVE: This study aimed to investigate the effects of robot-assisted therapy in combination with trunk restraint on upper extremity function and on daily activities in patients with acute stroke (≤ 30days of onset). METHODS: Thirty-six acute stroke patients were randomly assigned to an experimental (n=18) or control (n=18) group. The experimental group performed robot-assisted therapy combined with trunk restraint, while the control group performed only robot-assisted therapy. Both groups were treated for 30 min, 5 days a week, for a total of 3 weeks. The outcome measures included the Fugl-Meyer assessment upper extremity, wolf motor function test, motor activity log, upper extremity muscle strength, and modified Barthel index. RESULTS: After the intervention, both groups showed significant improvements in Fugl-Meyer assessment upper extremity, wolf motor function test, motor activity log, elbow extensor muscle strength, and modified Barthel index (p < 0.05). Post-intervention, the experimental group exhibited greater changes in the Fugl-Meyer assessment upper extremity, motor activity log, and elbow extensor muscle strength (p < 0.05). CONCLUSION: Our study suggests that robot-assisted therapy in combination with trunk restraint is more effective for improving upper extremity function than only robot-assisted therapy in acute stroke patients.

Bioactive Terphenyls Isolated from the Antarctic Lichen Stereocaulon alpinum.

Three p-terphenyls (2-4)-2-hydroxy-3,5-dimethoxy-p-terphenyl (2), 2-hydroxy-3,6-dimethoxy-p-terphenyl (3), and 2,3,5,6-tetramethoxy-p-terphenyl (4)-were isolated for the first time as natural products along with seven known compounds (1, 5-10) from the Antarctic lichen Stereocaulon alpinum. Structures of the new compounds were elucidated by comprehensive analyses of 1D and 2D NMR and HREIMS experiments. Compound 3 exhibited cytotoxicity against HCT116 cells with the IC50 value of 3.76 ± 0.03 µM and also inhibited NO production in LPS-induced RAW264.7 macrophages with the IC50 value of 22.82 ± 0.015 µM.

Soluble αKlotho downregulates Orai1-mediated store-operated Ca2+ entry via PI3K-dependent signaling.

αKlotho is a type 1 transmembrane anti-aging protein. αKlotho-deficient mice have premature aging phenotypes and an imbalance of ion homeostasis including Ca2+ and phosphate. Soluble αKlotho is known to regulate multiple ion channels and growth factor-mediated phosphoinositide-3-kinase (PI3K) signaling. Store-operated Ca2+ entry (SOCE) mediated by pore-forming subunit Orai1 and ER Ca2+ sensor STIM1 is a ubiquitous Ca2+ influx mechanism and has been implicated in multiple diseases. However, it is currently unknown whether soluble αKlotho regulates Orai1-mediated SOCE via PI3K-dependent signaling. Among the Klotho family, αKlotho downregulates SOCE while ßKlotho or γKlotho does not affect SOCE. Soluble αKlotho suppresses serum-stimulated SOCE and Ca2+ release-activated Ca2+ (CRAC) channel currents. Serum increases the cell-surface abundance of Orai1 via stimulating vesicular exocytosis of the channel. The serum-stimulated SOCE and cell-surface abundance of Orai1 are inhibited by the preincubation of αKlotho protein or PI3K inhibitors. Moreover, the inhibition of SOCE and cell-surface abundance of Orai1 by pretreatment of brefeldin A or tetanus toxin or PI3K inhibitors prevents further inhibition by αKlotho. Functionally, we further show that soluble αKlotho ameliorates serum-stimulated SOCE and cell migration in breast and lung cancer cells. These results demonstrate that soluble αKlotho downregulates SOCE by inhibiting PI3K-driven vesicular exocytosis of the Orai1 channel and contributes to the suppression of SOCE-mediated tumor cell migration.