Microcurrent therapy as the nonpharmacological new protocol against Alzheimer's disease.

Introduction: Alzheimer's disease (AD) poses an increasing global health challenge and is marked by gradual cognitive deterioration, memory impairment, and neuroinflammation. Innovative therapeutic approaches as non-pharmacological protocol are urgently needed with side effect risk of drugs. Microcurrent therapy, a non-invasive modality involving low-level electrical currents, has emerged as a potential solution to address AD's complex pathogenesis. This study investigates the optimal application of microcurrent therapy as a clinical protocol for AD, utilizing a comprehensive approach that integrates behavioral assessments and neuroinflammation evaluation in a mouse model of dementia. Methods and results: The results reveal that microcurrent therapy holds promise in ameliorating memory impairment and reducing neuroinflammation in AD. Behavioral assessments, including the Novel Object Recognition Test (NOR) and Radial Arm Maze Test (RAM), demonstrated improved cognitive function following microcurrent therapy. Furthermore, microcurrent therapy inhibited expression of neuroinflammatory proteins, including ionized calcium binding adaptor molecule 1 (Iba1), and glial fibrillary acidic protein (GFAP) in current-treated group. Mechanistic insights suggest that microcurrent therapy may modulate neuroinflammation through the regulation of MAPK signaling pathways. Conclusion: This study emphasizes the prospect of microcurrent therapy as a safe and efficacious non-pharmacological strategy for Alzheimer's disease (AD), providing optimism to the countless individuals impacted by this debilitating ailment. These results contribute to the developments of an innovative clinical protocol for AD and recovery from neurological injury, underscoring the significance of investigating unconventional therapeutic approaches for addressing this complex condition.

Universal selective transfer printing via micro-vacuum force.

Transfer printing of inorganic thin-film semiconductors has attracted considerable attention to realize high-performance soft electronics on unusual substrates. However, conventional transfer technologies including elastomeric transfer printing, laser-assisted transfer, and electrostatic transfer still have challenging issues such as stamp reusability, additional adhesives, and device damage. Here, a micro-vacuum assisted selective transfer is reported to assemble micro-sized inorganic semiconductors onto unconventional substrates. 20 µm-sized micro-hole arrays are formed via laser-induced etching technology on a glass substrate. The vacuum controllable module, consisting of a laser-drilled glass and hard-polydimethylsiloxane micro-channels, enables selective modulation of micro-vacuum suction force on microchip arrays. Ultrahigh adhesion switchability of 3.364 × 106, accomplished by pressure control during the micro-vacuum transfer procedure, facilitates the pick-up and release of thin-film semiconductors without additional adhesives and chip damage. Heterogeneous integration of III-V materials and silicon is demonstrated by assembling microchips with diverse shapes and sizes from different mother wafers on the same plane. Multiple selective transfers are implemented by independent pressure control of two separate vacuum channels with a high transfer yield of 98.06%. Finally, flexible micro light-emitting diodes and transistors with uniform electrical/optical properties are fabricated via micro-vacuum assisted selective transfer.

Apoptotic and antihepatofibrotic effect of honokiol via activation of GSK3ß and suppression of Wnt/ß-catenin pathway in hepatic stellate cells.

Though honokiol, derived from the Magnolia tree, was known to suppress renal fibrosis, pulmonary fibrosis, non-alcoholic steatoheptitis, inflammation and cancers, the underlying antifibrotic mechanisms of honokiol are not fully understood in hepatic stellate cells until now. Thus, in the present study, inhibitory mechanism of honokiol on liver fibrosis was elucidated mainly in hepatic stellate cells (HSCs) by 3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, cell cycle analysis and western-blotting. Honokiol exerted cytotoxicity in LX-2, HSC-T6 and Hep-G2 cells. Honokiol increased sub G1 population and activated caspase 3 and cleaved poly (ADP-ribose) polymerase (PARP) in HSCs. Moreover, honokiol attenuated the expression of alpha smooth muscle actin (α-SMA), transforming growth factor beta 1 (TGF-ß1), phospho-Smad3, phospho-AKT, cyclin D1, c-Myc, Wnt3a, ß-catenin, and activated phosphorylation of glycogen synthase kinase 3 beta (GSK3ß) in HSCs. Conversely, GSK3ß inhibitor SB216763 reversed the effect of honokiol on PARP, α-SMA, phospho-GSK3ß, ß-catenin and sub G1 population in LX-2 cells. Overall, honokiol exerts apoptotic and antifibrotic effects via activation of GSK3ß and inhibition of Wnt3a/ß-catenin signalling pathway.

Epidemiology of Congenital Bleeding Disorders: a Nationwide Population-based Korean Study.

BACKGROUND: Except for data in the Korea Hemophilia Foundation Registry, little is known of the epidemiology of congenital bleeding disorders in Korea. METHODS: Data were obtained from the Korean Health Insurance Review and Assessment Service (HIRA) database. RESULTS: From 2010 to 2015, there were 2,029 patients with congenital bleeding disorders in the Korean HIRA database: 38% (n = 775) of these patients had hemophilia A (HA), 25% (n = 517) had von Willebrand disease (vWD), 7% (n = 132) had hemophilia B (HB), and 25% (n = 513) had less common factor deficiencies. The estimated age-standardized incidence rate (ASR) of HA and HB was 1.78-3.15/100,000 and 0.31-0.51/100,000, respectively. That of vWD was 1.38-1.95/100,000. The estimated ASR of HA showed increase over time though the number of new patients did not increase. Most patients with congenital bleeding disorders were younger than 19 years old (47.8%), and most were registered in Gyeonggi (22.1%) and Seoul (19.2%). CONCLUSION: This is the first nationwide population-based study of congenital bleeding disorders in Korea. This study provides data that will enable more accurate estimations of patients with vWD. This information will help advance the comprehensive care of congenital bleeding disorders. We need to continue to obtain more detailed information on patients to improve the management of these diseases.

Auditory Working Memory Explains Variance in Speech Recognition in Older Listeners Under Adverse Listening Conditions.

INTRODUCTION: Older listeners have difficulty understanding speech in unfavorable listening conditions. To compensate for acoustic degradation, cognitive processing skills, such as working memory, need to be engaged. Despite prior findings on the association between working memory and speech recognition in various listening conditions, it is not yet clear whether the modality of stimuli presentation for working memory tasks should be auditory or visual. Given the modality-specific characteristics of working memory, we hypothesized that auditory working memory capacity could predict speech recognition performance in adverse listening conditions for older listeners and that the contribution of auditory working memory to speech recognition would depend on the task and listening condition. METHODS: Seventy-six older listeners and twenty younger listeners completed four kinds of auditory working memory tasks, including digit and speech span tasks, and sentence recognition tasks in four different listening conditions having multi-talker noise and time-compression. For older listeners, cognitive function was screened using the Mini-Mental Status Examination, and audibility was assured. RESULTS: Auditory working memory, as measured by listening span, significantly predicted speech recognition performance in adverse listening conditions for older listeners. A linear regression model showed speech recognition performance for older listeners could be explained by auditory working memory whilst controlling for the impact of age and hearing sensitivity. DISCUSSION: Measuring working memory in the auditory modality facilitated explaining the variance in speech recognition in adverse listening conditions for older listeners. The linguistic features and the complexity of the auditory stimuli may affect the association between working memory and speech recognition performance. CONCLUSION: We demonstrated the contribution of auditory working memory to speech recognition in unfavorable listening conditions in older populations. Taking the modality-specific characteristics of working memory into account may be a key to better understand the difficulty in speech recognition in daily listening conditions for older listeners.

Apoptotic effect of lambertianic acid through AMPK/FOXM1 signaling in MDA-MB231 breast cancer cells.

Though lambertianic acid (LA) was known to exert antitumor effect in liver and prostate cancers, its underlying anticancer mechanism is never reported in breast cancers so far. Thus, in this study, apoptotic mechanism of LA was elucidated in MDA-MB-231 breast cancer cells. Here, LA increased cytotoxicity in MCF-7 and MDA-MB-231 cells; enhanced sub-G1 population, G2/M arrest, and cleaved poly(ADP-ribose) polymerase; activated phosphorylation of AMP-activated protein kinase (AMPK)/acetyl-CoA carboxylase pathway; and also suppressed phosphorylation of AKT and the expression of forkhead box M1 (FOXM1), X-linked inhibitor of apoptosis protein, B-cell lymphoma 2, and CyclinB1 in MDA-MB-231 cells. Furthermore, AMPK inhibitor compound C reversed the effect of LA on FOXM1, Cyclin B1, and cleaved poly(ADP-ribose) polymerase in MDA-MB-231 cells. Notably, immunoprecipitation revealed that LA disturbed the direct binding of AKT and FOXM1 in MDA-MB-231 cells. Overall, these findings suggest that LA-induced apoptosis is mediated via activation of AMPK and inhibition of AKT/FOXM1 signaling pathway.

Effects of Mindfulness-Based Art Therapy on Psychological Symptoms in Patients with Coronary Artery Disease.

BACKGROUND: Mindfulness-based art therapy (MBAT) induces emotional relaxation in coronary artery disease (CAD) patients, and is a treatment known to improve psychological stability. The objective of this study was to evaluate the treatment effects of MBAT for CAD patients. METHODS: A total of 44 CAD patients were selected as participants, 21 patients belonged to a MBAT group, and 23 patients belonged to the control group. The patients in the MBAT group were given 12 sessions of treatments. To measure depression and anxiety, Beck Depression Inventory (BDI) and Trait Anxiety Inventory (TAI) were used. Anger and anger expression were evaluated using the State Trait Anger Expression Inventory (STAXI). The treatment results were analyzed using two-way repeated measures analysis of variance (ANOVA). RESULTS: The results showed that significant effects for groups, time, and interaction in the depression (interaction effect, [F(1,36) = 23.15, P < 0.001]; between groups, [F(1,36) = 5.73, P = 0.022]), trait anxiety (interaction effect, [F(1,36) = 13.23, P < 0.001]; between groups, [F(1,36) = 4.38, P = 0.043]), state anger (interaction effect, [F(1,36) = 5.60, P = 0.023]), trait anger (interaction effect, [F(1,36) = 6.93, P = 0.012]; within group, [F(1,36) = 4.73, P = 0.036]), anger control (interaction effect, [F(1,36) = 8.41, P = 0.006]; within group, [F(1,36) = 9.41, P = 0.004]), anger out (interaction effect, [F(1,36) = 6.88, P = 0.012]; within group, [F(1,36) = 13.17, P < 0.001]; between groups, [F(1,36) = 5.62, P = 0.023]), and anger in (interaction effect, [F(1,36) = 32.66, P < 0.001]; within group, [F(1,36) = 25.90, P < 0.001]; between groups, [F(1,36) = 12.44, P < 0.001]). CONCLUSION: MBAT can be seen as an effective treatment method that improves CAD patients' psychological stability. Evaluation of treatment effects using program development and large-scale research for future clinical application is needed.

Increase in the production of ß-carotene in recombinant Escherichia coli cultured in a chemically defined medium supplemented with amino acids.

Escherichia coli DH5α strain was selected as the recombinant host, and a chemically defined medium supplemented with amino acids was used instead of a complex medium for the efficient production of ß-carotene. In a fed-batch culture using glycerol with a chemically defined medium supplemented with amino acids, the concentration, specific content, and productivity of ß-carotene were 2,470 mg/l, 72 mg/g cells, and 77 mg/l h after 32 h, respectively. These values were, respectively, 43, 33, and 26 % higher than those obtained using the complex medium. This is the highest ß-carotene production that has been reported among the recombinant cells to date.

Effect of fundamental-frequency and sentence-onset differences on speech-identification performance of young and older adults in a competing-talker background.

This study investigated the benefits of differences between sentences in fundamental frequency (F0) and temporal onset for sentence pairs among listener groups differing in age and hearing sensitivity. Two experiments were completed with the primary difference between experiments being the way in which the stimuli were presented. Experiment 1 used blocked stimulus presentation, which ultimately provided redundant acoustic cues to mark the target sentence in each pair, whereas Experiment 2 sampled a slightly more restricted stimulus space, but in a completely randomized presentation order. For both experiments, listeners were required to detect a cue word ("Baron") for the target sentence in each pair and to then identify the target words (color, number) that appeared later in the target sentence. Results of Experiment 1 showed that F0 or onset separation cues were beneficial to both cue-word detection and color-number identification performance. There were no significant differences across groups in the ability to detect the cue word, but groups differed in their ability to identify the correct color-number words. Elderly adults with impaired hearing had the greatest difficulty with the identification task despite the application of spectral shaping to restore the audibility of the speech stimuli. For the most part, the primary results of Experiment 1 were replicated in Experiment 2, although, in the latter experiment, all older adults, whether they had normal or impaired hearing, performed worse than young adults with normal hearing. From Experiment 2, the benefits received for a difference in F0 between talkers of 6 semitones were equivalent to those received for an onset asynchrony of 300 ms between sentences and, for such conditions, the combination of both sound-segregation cues resulted in an additive benefit.

Enhancement of retinal production by supplementing the surfactant Span 80 using metabolically engineered Escherichia coli.

The optimal temperature and pH for retinal production using metabolically engineered Escherichia coli in a 7-l fermentor were found to be 30°C and 7.0, respectively. The agitation speed was a critical factor for retinal production. The optimal agitation speed was 400 rpm (oxygen transfer coefficient, k(L)a, = 92 1/h) in batch culture and 600 rpm (k(L)a=148 1/h) in a fed-batch culture of glycerol. Span 80 was selected as a surfactant for retinal production in metabolically engineered E. coli because Span 80 had proven the most effective for increased retinal production among the tested surfactants. Under the optimal conditions in the fed-batch culture with 5 g/l Span 80, the cell mass and the concentration, content, and productivity of retinal were 24.7 g/l, 600 mg/l, 24.3mg/g-cells, and 18 mg l(-1)h(-1) after 33 h, respectively. They were 1.2-, 2.7-, 2.3-, and 2.7-fold higher than those in the fed-batch culture without Span 80, respectively. The concentration and productivity of retinal in this study were the highest ever reported. The hydrophilic portion of Span 80 (sorbitan) did not affect cell growth and retinal production, but the hydrophobic portion (oleic acid) stimulated cell growth. However, oleic acid plus sorbitan did not stimulate retinal production. Thus, Span 80, as a linked compound of oleic acid and sorbitan produced by esterification, proved to be an effective surfactant for the enhancement of retinal production.

Increase of lycopene production by supplementing auxiliary carbon sources in metabolically engineered Escherichia coli.

In the fed-batch culture of glycerol using a metabolically engineered strain of Escherichia coli, supplementation with glucose as an auxiliary carbon source increased lycopene production due to a significant increase in cell mass, despite a reduction in specific lycopene content. L-Arabinose supplementation increased lycopene production due to increases in cell mass and specific lycopene content. Supplementation with both glucose and L-arabinose increased lycopene production significantly due to the synergistic effect of the two sugars. Cell growth by the consumption of carbon sources was related to endogenous metabolism in the host E. coli. Supplementation with L-arabinose stimulated only the mevalonate pathway for lycopene biosynthesis and supplementation with both glucose and L-arabinose stimulated synergistically only the mevalonate pathway. In the fed-batch culture of glycerol with 10 gl(-1) glucose and 7.5 gl(-1) L-arabinose, the cell mass, lycopene concentration, specific lycopene content, and lycopene productivity after 34 h were 42 gl(-1), 1,350 mgl(-1), 32 mg g cells(-1), and 40 mgl(-1)h(-1), respectively. These values were 3.9-, 7.1-, 1.9-, and 11.7-fold higher than those without the auxiliary carbon sources, respectively. This is the highest reported concentration and productivity of lycopene.

Auditory measures of selective and divided attention in young and older adults using single-talker competition.

In this study, two experiments were conducted on auditory selective and divided attention in which the listening task involved the identification of words in sentences spoken by one talker while a second talker produced a very similar competing sentence. Ten young normal-hearing (YNH) and 13 elderly hearing-impaired (EHI) listeners participated in each experiment. The type of attention cue used was the main difference between experiments. Across both experiments, several consistent trends were observed. First, in eight of the nine divided-attention tasks across both experiments, the EHI subjects performed significantly worse than the YNH subjects. By comparison, significant differences in performance between age groups were only observed on three of the nine selective-attention tasks. Finally, there were consistent individual differences in performance across both experiments. Correlational analyses performed on the data from the 13 older adults suggested that the individual differences in performance were associated with individual differences in memory (digit span). Among the elderly, differences in age or differences in hearing loss did not contribute to the individual differences observed in either experiment.

Melanogenesis inhibitory activities of diarylheptanoids from Alnus hirsuta Turcz in B16 mouse melanoma cell.

Four diarylheptanoids, (5R-1,7-bis (3,4-dihydroxyphenyl)-heptane-5-O-beta-D-glucoside (1), (5R) 1,7-bis (3,4-dihydroxyphenyl)-heptane-5-ol (2), oregonin (3), hirsutanonol (4), were isolated from the bark of Alnus hirsuta Turcz and its inhibitory effects on melanogenesis by measuring the melanin level and tyrosinase activity in B16 melanoma cell were examined. Melanin level and tyrosinase activity were reduced to 75 to 85% by addition of diarylheptanoids to incubation medium of the melanoma cell. On the other hand, melanin level and tyrosinase activity were reduced to 13 to 43% by the addition of diarylheptanoids to incubation medium of the melanoma cell treated with melanogenesis stimulator, alpha-MSH and forskolin. These melanogenesis inhibitory effects were significantly different compared with control.