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Objectives: The aim of this study was to analyze the latest clinical studies on Korean medicine treatment of idiopathic thrombocytopenic purpura (ITP) in the Chinese National Knowledge Infrastructure (CNKI) database.Methods: We searched the last 6 years of clinical studies discussing Oriental medicine-based treatments for ITP in the CNKI database. A meta-analysis of 13 RCTs was performed by synthesizing the outcomes, including the measured platelet count and total effective rate. The quality of the studies was assessed using Cochrane’s risk of bias (RoB) tool. RevMan 5.4.1 software was used for data analysis.Results: Of the 15 selected studies, 1 was a non-randomized controlled trial (nRCT), 2 were case series, and 12 were randomized controlled trials (RCTs). Treatments in all studies included oral herbal medicine. The most frequently used herbal decoction was the Liangxue Jiedu prescription (凉血解毒方), and the most commonly used herb was Agrimonia pilosa (仙鶴草), Astragali Radix (黃芪), Fossilia Glycyrrhizae Radix et Rhizoma (甘草), and Rehmannia glutinosa Liboschitz ex Steudel (地黃). The meta-analysis showed significantly better improvement in platelet counts and total effective rate for ITP in the treatment group than in the control group.Conclusion: Treatment with herbal medicine was effective in treating ITP. However, the significance of this conclusion is somewhat limited due to the low quality of the available studies. Multifaceted and scientifically designed clinical studies are required to develop treatments for ITP based on Korean medicine. The results of this study could be used as basic data for further ITP studies.

Objectives: This study investigated the latest clinical studies on Korean medicine treatment of idiopathic edema in the Chinese National Knowledge Infrastructure Database (CNKI).Methods: We searched the last 9 years of clinical studies discussing Oriental medicine-based treatments for idiopathic edema in the CNKI database. The search focused on the authors, publication year, type of study, purposes of study, method and duration of treatment, evaluation criteria, and results of the selected articles.Results: The search identified 7 randomized controlled trials (RCTs) and 9 others. All studies used oral herbal medicine for treatment. The most commonly used herbs were Poria Sclerotium (茯苓), Atractylodis Rhizoma Alba (白朮), and Alismatis Rhizoma (澤瀉), which are the constituent herbs of Oryeong-san (五苓散). All 16 studies confirmed the efficacy of Oriental medicine treatments.Conclusion: More varied and scientifically designed clinical studies are required to develop treatments for idiopathic edema. The results of this study could be used as basic data for further studies on idiopathic edema.

Changes in symptoms and dysfunction related to meniscus tears following the use of Korean medicine for ≥ 4 days were studied. The medical charts of 53 cases of diagnosed meniscus tears (magnetic resonance imaging) with an admission Numeric Rating Scale (NRS) score ≥ 4, between 2017 and 2022 were retrospectively reviewed. Treatments included acupuncture, pharmacopuncture, herbal treatment, Chuna therapy, and physiotherapy. The NRS, Western Ontario and McMaster Universities Osteoarthritis Index, and European Quality of Life 5 Dimensions were performed at admission and discharge. There were 42 females and 11 males in this study. Patients were more likely to be in their 60s (38.18%), have an unknown etiology (81.13%), and have complex tears (50.94%). After receiving a combination of alternative Korean medicine during hospitalization, the mean NRS score improved from 6.82 ± 1.19 to 3.66 ± 1.83 (p < 0.001), the Western Ontario and McMaster Universities Osteoarthritis Index score improved from 46.47 ± 20.99 to 37.98 ± 19.23 (p < 0.001), and the mean European Quality of Life Five Dimensions score improved from 0.61 ± 0.18 to 0.68 ± 0.14 (p < 0.001) after treatment. These results suggest that Korean medicine treatment of meniscus tears alleviated pain and improved physical function.

The primary cilium, an antenna-like structure on the cell surface, acts as a mechanical and chemical sensory organelle. Primary cilia play critical roles in sensing the extracellular environment to coordinate various developmental and homeostatic signaling pathways. Here, we showed that the depletion of heat shock protein family A member 9 (HSPA9)/mortalin stimulates primary ciliogenesis in SH-SY5Y cells. The downregulation of HSPA9 enhances mitochondrial stress by increasing mitochondrial fragmentation and mitochondrial reactive oxygen species (mtROS) generation. Notably, the inhibition of either mtROS production or mitochondrial fission significantly suppressed the increase in primary ciliogenesis in HSPA9-depleted cells. In addition, enhanced primary ciliogenesis contributed to cell survival by activating AKT in SH-SY5Y cells. The abrogation of ciliogenesis through the depletion of IFT88 potentiated neurotoxicity in HSPA9-knockdown cells. Furthermore, both caspase-3 activation and cell death were increased by MK-2206, an AKT inhibitor, in HSPA9-depleted cells. Taken together, our results suggest that enhanced primary ciliogenesis plays an important role in preventing neurotoxicity caused by the loss of HSPA9 in SH-SY5Y cells.

The effects of concentration, temperature, and time on infusion of fluorescein into corn and waxy rice starches and their controlled release pattern were investigated. At low fluorescein concentration (1 μM), temperature significantly affected infusion efficiency. At high fluorescein concentration (50–150 μM), temperature showed little effect; fluorescein concentration significantly affected infusion efficiency. Corn starch showed relatively higher infusion efficiency than waxy rice starch at high concentration. During controlled release, 50% and 81% of infused fluorescein were released from corn and waxy rice starches, respectively, after bacterial α-amylase treatment. However, 61% and 68% of infused fluorescein were released from corn and waxy rice starches, respectively, after pancreatic α-amylase treatment. The dextrose equivalent (DE) value revealed similar patterns, suggesting that degradation of starch by different α-amylases is a major factor affecting release of fluorescein from starch granules. Moreover, granule size of starch greatly affected enzymatic hydrolysis and controlled release in this system. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10068-022-01059-2.

The effects of immersion time on the physicochemical properties and resistant starch (RS) formation of malic acid-treated rice were investigated. Malic acid treatment decreased the frequency of cracks within the rice kernel. The color (lightness) was significantly affected by the immersion time, reflecting the browning of rice. The degree of substitution gradually increased with the immersion time and reached a plateau after 12 h, and the intensity of the C=O bond peak detected in the Fourier-transform infrared spectroscopy showed a similar trend. However, the crystallinity of rice decreased as the immersion time increased, which was confirmed by the X-ray diffraction and thermal transition properties. A gradual increase in RS was observed as the immersion time and DS increased, ranging from 44.5% to 73.3%, reaching a maximum after 12 h of immersion. Therefore, 12 h was determined to be the optimal immersion time for maximizing RS content. This information about the structural characteristics and heat-stable properties of malic acid-treated rice in starch digestion can be used to develop a low-digestible food ingredient and lead to further application of the study. PRACTICAL APPLICATION: This study reported the preparation and physicochemical properties of malic acid-treated resistant starch with different immersion times. This information could contribute to the structural characterization of resistant starch and the development of low-calorie processed rice products.

Objective: This study examined a case in which insomnia and pain due to herniated intervertebral disks were improved by treatment with an oriental herbal and the administration of Uhwangchungsim-won.Case Summary: Three patients with insomnia diagnosed with herniated intervertebral disks were treated with a series of Korean medical therapies, including the herbal medication Uhwangchungsim-won, acupuncture, herbal acupuncture, and physical therapy. We used the Numerical Rating Scale (NRS) to measure subjective sleep states and the European Quality of Life Five Dimensions (EQ-5d) Scale to evaluate the therapeutic effect. Following treatment, subjective sleep states and the overall scores for pain had improved.Conclusion: The results indicate that Korean medical therapies with Uhwangchungsim-won have beneficial effects on insomnia for patients with herniated intervertebral disks.

Objectives: The purpose of this study was to investigate the factors related to relapse within six months of cessation of smoking in out-of-school adolescents. Methods: The study included 45 adolescents who applied to the outreaching smoking cessation service provided by Daejeon Tobacco Control Center between July 2015 and March 2017 and maintained the abstinence for four weeks since registering for the service. The data on the participants were collected from the Integrated Information System for Smoking Cessation Services and analyzed using The Kaplan-Meier analysis and the Cox proportional hazard model. Results: Our results indicated that the rate of smoking relapse within six months was 75.6%. The variables related to this relapse were attempts to quit smoking in last one year and frequency of counseling. Adolescents who had previously tried to quit smoking were more likely to relapse than those who had never tried quitting (hazard ratio [HR]=4.24; 95% confidence interval [CI]=1.38-13.02). Additionally, if the number of counseling sessions to quit smoking was nine or more, the likelihood of relapse was reduced as compared to when the sessions were five or less. (HR=0.19; 95% CI=0.06-0.60 for ≥9 vs. ≤5 sessions). Conclusion: Our results indicate that it is necessary to offer continued and consistent counseling, focusing on their confidence in quitting, for out-of-school adolescents to discourage a relapse of smoking.

Primary cilia help to maintain cellular homeostasis by sensing conditions in the extracellular environment, including growth factors, nutrients, and hormones that are involved in various signaling pathways. Recently, we have shown that enhanced primary ciliogenesis in dopamine neurons promotes neuronal survival in a Parkinson’s disease model. Moreover, we performed fecal metabolite screening in order to identify several candidates for improving primary ciliogenesis, including L-carnitine and acetyl-L-carnitine. However, the role of carnitine in primary ciliogenesis has remained unclear. In addition, the relationship between primary cilia and neurodegenerative diseases has remained unclear. In this study, we have evaluated the effects of carnitine on primary ciliogenesis in 1-methyl-4-phenylpyridinium ion (MPP+)-treated cells. We found that both L-carnitine and acetyl-L-carnitine promoted primary ciliogenesis in SH-SY5Y cells. In addition, the enhancement of ciliogenesis by carnitine suppressed MPP+-induced mitochondrial reactive oxygen species overproduction and mitochondrial fragmentation in SH-SY5Y cells. Moreover, carnitine inhibited the production of pro-inflammatory cytokines in MPP+-treated SH-SY5Y cells. Taken together, our findings suggest that enhanced ciliogenesis regulates MPP+-induced neurotoxicity and inflammation.

Several pathogens that spread through the air are highly contagious, and related infectious diseases are more easily transmitted through airborne transmission under indoor conditions, as observed during the COVID-19 pandemic. Indoor air contaminated by microorganisms, including viruses, bacteria, and fungi, or by derived pathogenic substances, can endanger human health. Thus, identifying and analyzing the potential pathogens residing in the air are crucial to preventing disease and maintaining indoor air quality. Here, we applied deep learning technology to analyze and predict the toxicity of bacteria in indoor air. We trained the ProtBert model on toxic bacterial and virulence factor proteins and applied them to predict the potential toxicity of some bacterial species by analyzing their protein sequences. The results reflect the results of the in vitro analysis of their toxicity in human cells. The in silico-based simulation and the obtained results demonstrated that it is plausible to find possible toxic sequences in unknown protein sequences.

Peroxisomes play an essential role in cellular homeostasis by regulating lipid metabolism and the conversion of reactive oxygen species (ROS). Several peroxisomal proteins, known as peroxins (PEXs), control peroxisome biogenesis and degradation. Various mutations in the PEX genes are genetic causes for the development of inheritable peroxisomal-biogenesis disorders, such as Zellweger syndrome. Among the peroxins, PEX1 defects are the most common mutations in Zellweger syndrome. PEX1 is an AAA-ATPase that regulates the recycling of PEX5, which is essential for importing peroxisome matrix proteins. However, the post-transcriptional regulation of PEX1 is largely unknown. Here, we showed that heterogeneous nuclear ribonucleoprotein A1 (HNRNPA1) controls PEX1 expression. In addition, we found that depletion of HNRNPA1 induces autophagic degradation of peroxisome, which is blocked in ATG5-knockout cells. In addition, depletion of HNRNPA1 increased peroxisomal ROS levels. Inhibition of the generation of peroxisomal ROS by treatment with NAC significantly suppressed pexophagy in HNRNPA1-deficient cells. Taken together, our results suggest that depletion of HNRNPA1 increases peroxisomal ROS and pexophagy by downregulating PEX1 expression.

This study investigated the physicochemical characteristics of protease-treated wheat starch (PT-WST) to understand the role of starch granule-associated proteins (SGAPs) and the potential capability of PT-WST to provide a nutrient delivery system (NDS). Protease treatment was conducted at 4 °C and 37 °C (PT04 and PT37), respectively. A model delivery system was assessed with PT37 granules infiltrated by λ-carrageenan (λC) under variations of molecular size (λC hydrolysates produced from 0, 2.5, 100, and 500 mM HCl solution), agitation time, and temperature. Protein-specific (3-(4-carboxybenzyl)quioline-2-carboxaldehyde) or non-reactive (methanolic merbromin) fluorescent dye staining revealed that removal of SGAPs on surfaces and channels were more effective for PT37 than for PT04. Consistent amylose content, swelling, and gelatinization temperature before and after protease treatment suggested minimal impact on the starch structure. PT37 presented higher solubility and pasting viscosity than PT04. This resulted from excessive SGAP removal, which enhanced entrapment capacity. λC molecular size and agitation temperature showed a negative correlation with the content of λC entrapped within PT37, and this content depended on the interplay between the agitation time and λC molecular size. As λC molecular size decreased, the λC distribution became uniform throughout the granules, which confirmed the potential of PT-WST as a carrier for NDS.

Self-assembly (formation and crystallization) kinetics of short-chain glucan aggregates (SCGAs) prepared at isothermal conditions (4, 20, 40, and 60℃) with or without nucleation (4℃, 1 h) were investigated. The fastest formation and crystallization rates of SCGA were observed when short-chain glucan was stored at 4℃ and 20℃, respectively. SCGA was not formed at 60℃. However, nucleation resulted in SCGA forming-ability at 60℃. Moreover, nucleation increased the yield in all temperature conditions. SCGA with nucleation decreased the crystal melting transition temperature range. All SCGAs had nanosized particles (500 nm) with B-type crystal patterns regardless of temperature and nucleation. Consequently, self-assembly temperature and presence of nucleation step could change the physicochemical characteristics of SCGA, and manipulation of the nucleation step is expected to be an effective method to increase the yield of SCGA and produce SCGA at high temperature.

Primary cilia help to maintain cellular homeostasis by sensing conditions in the extracellular environment, including growth factors, nutrients, and hormones that are involved in various signaling pathways. Recently, we have shown that enhanced primary ciliogenesis in dopamine neurons promotes neuronal survival in a Parkinson's disease model. Moreover, we performed fecal metabolite screening in order to identify several candidates for improving primary ciliogenesis, including L-carnitine and acetyl-L-carnitine. However, the role of carnitine in primary ciliogenesis has remained unclear. In addition, the relationship between primary cilia and neurodegenerative diseases has remained unclear. In this study, we have evaluated the effects of carnitine on primary ciliogenesis in 1-methyl-4-phenylpyridinium ion (MPP

Melanosomes are specialized membrane-bound organelles that are involved in melanin synthesis. Unlike melanosome biogenesis, the melanosome degradation pathway is poorly understood. Among the cellular processes, autophagy controls degradation of intracellular components by cooperating with lysosomes. In this study, we showed that ursolic acid inhibits skin pigmentation by promoting melanosomal autophagy, or melanophagy, in melanocytes. We found that B16F1 cells treated with ursolic acid suppressed alpha-melanocyte stimulating hormone (α-MSH) stimulated increase in melanin content and activated autophagy. In addition, we found that treatment with ursolic acid promotes melanosomal degradation, and bafilomycin A1 inhibition of autophagosome-lysosome fusion blocked the removal of melanosomes in α-MSH-stimulated B16F1 cells. Furthermore, depletion of the autophagy-related gene 5 (ATG5) resulted in significant suppression of ursolic acid-mediated anti-pigmentation activity and autophagy in α-MSH-treated B16F1 cells. Taken together, our results suggest that ursolic acid inhibits skin pigmentation by increasing melanosomal degradation in melanocytes.

Background Although high-grade salivary gland cancers (SGCs) often express androgen receptor (AR) and/or HER-2/neu, therapeutically targeting these receptors in SGC remains investigational. We investigated the prevalence of receptor expression and the benefit of adjuvant HER-2 directed therapy in the high-risk postoperative setting and explored the clinical utility of sequentially targeting these receptors in the setting of advanced disease. Materials and Methods We clinically annotated 95 patients with SGC (excluding adenoid cystic carcinoma) treated at our institution from 2002 to 2019 and recorded AR, HER-2/neu status, and tumor genomic profiling results when available. Clinicopathologic information was then integrated with outcomes. Results Of 95 patients, most had high-risk histologies, with salivary duct carcinoma (SDC) as the most frequent diagnosis (43, 45%). Thirty-five (37%) experienced recurrence (51% SDC). HER-2/neu was positive (1–3+) by immunostaining in 34 of 52 (65%) evaluable cases. There was no difference in survival based on HER-2/neu or AR expression. Nine of 17 (53%) patients with HER-2+ SDC received adjuvant chemoradiation with trastuzumab. Median disease-free survival (DFS) and overall survival (OS) were longer among patients with HER-2/neu 3+ staining tumors who received adjuvant trastuzumab versus those who did not (DFS, 117 vs. 9 months; p = .02; OS, 74 vs. 43 months; p = .02), with no difference among other HER-2/neu subgroups (0–2+). Two of nine (22%) patients treated with adjuvant trastuzumab demonstrated recurrence, both with low HER-2/neu staining intensity (1+). Longer time to recurrence (hazard ratio, 0.94; p = .01) predicted improved outcomes. Both androgen deprivation and HER-2-directed therapies had clinical benefit beyond the first-line metastatic setting, with partial response observed beyond second-line use. Conclusion Although prospective data are lacking, the use of adjuvant trastuzumab in high-risk patients with SGC appears beneficial, particularly among patients with tumors exhibiting HER-2/neu 3+ immunostaining. Implications for Practice Results of this study showed an improved disease-free and overall survival in patients treated with adjuvant trastuzumab for high-risk salivary gland cancers with strong HER-2/neu staining intensity. Following recurrence or metastatic spread, sequential HER-2, and androgen-directed therapies may benefit certain patients with salivary gland cancer.

Quality control of peroxisomes is essential for cellular homeostasis. However, the mechanism underlying pexophagy is largely unknown. In this study, we identified HSPA9 as a novel pexophagy regulator. Downregulation of HSPA9 increased macroautophagy/autophagy but decreased the number of peroxisomes in vitro and in vivo. The loss of peroxisomes by HSPA9 depletion was attenuated in SQSTM1-deficient cells. In HSPA9-deficient cells, the level of peroxisomal reactive oxygen species (ROS) increased, while inhibition of ROS blocked pexophagy in HeLa and SH-SY5Y cells. Importantly, reconstitution of HSPA9 mutants found in Parkinson disease failed to rescue the loss of peroxisomes, whereas reconstitution with wild type inhibited pexophagy in HSPA9-depleted cells. Knockdown of Hsc70-5 decreased peroxisomes in Drosophila, and the HSPA9 mutants failed to rescue the loss of peroxisomes in Hsc70-5-depleted flies. Taken together, our findings suggest that the loss of HSPA9 enhances peroxisomal degradation by pexophagy.

Controllable graphene Q-switching in an Yb:YAG fs-laser-written beam-splitter-type waveguide laser is demonstrated by tunable beam-splitting ratio and varying pump power. Desired channels are regulated to generate Q-switched pulses separately or simultaneously with a single pumping.

Long-wave multiphonon-assisted emission of rare-earth ions provides broadband gain which is essential for the generation of few-optical-cycle pulses. A phonon-terminated Kerr-lens mode-locked Tm,Ho:CALGO laser generates 37-fs pulses with an ultrabroadband spectrum (1870 - 2337 nm).

We report on a Kerr-lens mode-locked Tm,Ho:CALGO laser delivering 46-fs pulses at ~2.06 μm with an average power of 110 mW. The maximum average power reached 423 mW for a pulse duration of 53 fs.

International audience; Sub-100 fs pulse generation from a passively mode-locked Tm,Ho-codoped cubic multicomponent disordered garnet laser at ∼2 µm is demonstrated. A single-walled carbon nanotube saturable absorber is implemented to initiate and stabilize the soliton mode-locking. The Tm,Ho:LCLNGG (lanthanum calcium lithium niobium gallium garnet) laser generated pulses as short as 63 fs at a central wavelength of 2072.7 nm with an average output power of 63 mW at a pulse repetition rate of ∼102.5 MHz. Higher average output power of 121 mW was obtained at the expense of longer pulse duration (96 fs) at 2067.6 nm using higher output coupling. To the best of our knowledge, this is the first report on mode-locked operation of the Tm,Ho:LCLNGG crystal.

In this study, the rheological properties of several commercial rice noodle strands were investigated. In the bending test, failure stress decreased as the cooking temperature increased from 80 to 90 °C, and the cooking time increased from 3 to 4 min for higher rice content noodles (>60%). The stress–relaxation test and sensory tests were carried out with bundles of noodles to investigate correlations with the bending test. The modulus of elasticity was higher at 80 than 90 °C. However, no correlation was found between cooking temperature and the rheological properties of lower rice content noodles. In the stress relaxation test, the deviation was larger due to the empty space in the bundle. In the correlation analysis, sensory stickiness was correlated with a modulus of elasticity in the bending test. Comparing the bending and stress–relaxation tests, each instrumental variable showed differences in the rheological properties of rice noodles in strands and bundles. However, the bending test measured with noodle strands seemed to be most suitable as a method of measuring the rheological properties of rice noodles.

Dietary restriction (DR) has been revealed to have health benefits as it induces reduction in oxidative stress. Glutathione (GSH), an important cellular antioxidant, is increased in rodent livers owing to DR; however, the exact mechanism and clinical relevance of DR are yet to be fully understood. In this study, male C57BL/6 mice were administered a 50% restricted diet for 7 d, and the hepatic sulfur-containing amino acid (SAA) metabolism was determined to assess the biosynthesis of GSH. The hepatic methionine level was found to decrease, while the homocysteine, cysteine, and GSH levels were increased owing to decreased betaine-homocysteine methyltransferase (BHMT) and increased CβS, CγL, and glutamate cysteine ligase catalytic subunit (GCLC) proteins in the livers of mice subjected to DR. To determine the effects of DR on drug-induced oxidative liver injury, mice subjected to DR were injected with a toxic dose (300 mg/kg) of acetaminophen (APAP). DR significantly alleviated APAP-induced liver damage and oxidative stress, which might be attributed to the higher levels of GSH and related antioxidant enzyme (GPx, GSTα, and GSTµ) in the livers. The decrease in the levels of hepatic CYP1A, 2E1, and 3A, which imply the inhibition of APAP metabolic activation, could contribute to the lower hepatotoxicity in mice subjected to DR. Overall, our findings revealed that DR stimulated the hepatic transsulfuration pathway and GSH synthesis. The consequent elevation of GSH could thus serve as an important mechanism of DR-mediated liver protection against APAP intoxication.

We report on the first sub-100 fs mode-locked laser operation of a Tm3+-doped disordered calcium lithium tantalum gallium garnet (Tm:CLTGG) crystal. Soliton mode-locking was initiated and stabilized by a transmission-type single-walled carbon nanotube saturable absorber. Pulses as short as 69 fs were achieved at a central wavelength of 2010.4 nm with an average power of 28 mW at a pulse repetition rate of ∼87.7 MHz. In the sub-100 fs regime, the maximum average output power amounted to 103 mW.

Particulate matters (PMs) increase oxidative stress and inflammatory response in different tissues. PMs disrupt the formation of primary cilia in various skin cells, including keratinocytes and melanocytes. In this study, we found that 2-isopropylmalic acid (2-IPMA) promoted primary ciliogenesis and restored the PM2.5-induced dysgenesis of primary cilia in dermal fibroblasts. Moreover, 2-IPMA inhibited the generation of excessive reactive oxygen species and the activation of stress kinase in PM2.5-treated dermal fibroblasts. Further, 2-IPMA inhibited the production of pro-inflammatory cytokines, including IL-6 and TNF-α, which were upregulated by PM2.5. However, the inhibition of primary ciliogenesis by IFT88 depletion reversed the downregulated cytokines by 2-IPMA. Moreover, we found that PM2.5 treatment increased the MMP-1 expression in dermal fibroblasts and a human 3-D-skin model. The reduced MMP-1 expression by 2-IPMA was further reversed by IFT88 depletion in PM2.5-treated dermal fibroblasts. These findings suggest that 2-IPMA ameliorates PM2.5-induced inflammation by promoting primary ciliogenesis in dermal fibroblasts.

Selective autophagy controls cellular homeostasis by degrading unnecessary or damaged cellular components. Melanosomes are specialized organelles that regulate the biogenesis, storage, and transport of melanin in melanocytes. However, the mechanisms underlying melanosomal autophagy, known as the melanophagy pathway, are poorly understood. To better understand the mechanism of melanophagy, we screened an endocrine-hormone chemical library and identified nalfurafine hydrochlorides, a κ-opioid receptor agonist, as a potent inducer of melanophagy. Treatment with nalfurafine hydrochloride increased autophagy and reduced melanin content in alpha-melanocyte-stimulating hormone (α-MSH)-treated cells. Furthermore, inhibition of autophagy blocked melanosomal degradation and reversed the nalfurafine hydrochloride-induced decrease in melanin content in α-MSH-treated cells. Consistently, treatment with other κ-opioid receptor agonists, such as MCOPPB or mianserin, inhibited excessive melanin production but induced autophagy in B16F1 cells. Furthermore, nalfurafine hydrochloride inhibited protein kinase A (PKA) activation, which was notably restored by forskolin, a PKA activator. Additionally, forskolin treatment further suppressed melanosomal degradation as well as the anti-pigmentation activity of nalfurafine hydrochloride in α-MSH-treated cells. Collectively, our data suggest that stimulation of κ-opioid receptors induces melanophagy by inhibiting PKA activation in α-MSH-treated B16F1 cells.

We demonstrate multi-gigahertz continuous-wave mode-locking of a Yb:KLuW waveguide laser. A femtosecond-laser-inscribed Yb:KLuW channel waveguide in an extended laser cavity delivers a fundamentally mode-locked laser near 1030 nm. A tunable few-centimeter-long cavity containing a single-walled carbon nanotube saturable absorber as mode-locker generates self-starting femtosecond pulses with average output powers exceeding 210 mW at repetition rates of 2.27, 2.69, and 3.55 GHz. The laser cavity, which includes a wedged waveguide, is extended by using a lens pair that controls the laser fluence on the saturable absorber for reliable mode-locked operation without instability. The presented laser performance, mode-locked up to 3.55 GHz, highly suggests the potential of crystalline Yb:KLuW waveguides for realizing high-power ultrafast lasers with higher GHz repetition rates in a quasi-monolithic cavity.

Primary cilia mediate the interactions between cells and external stresses. Thus, dysregulation of primary cilia is implicated in various ciliopathies, e.g., degeneration of the retina caused by dysregulation of the photoreceptor primary cilium. Particulate matter (PM) can cause epithelium injury and endothelial dysfunction by increasing oxidative stress and inflammatory responses. Previously, we showed that PM disrupts the formation of primary cilia in retinal pigment epithelium (RPE) cells. In the present study, we identified 2-isopropylmalic acid (2-IPMA) as a novel inducer of primary ciliogenesis from a metabolite library screening. Both ciliated cells and primary cilium length were increased in 2-IPMA-treated RPE cells. Notably, 2-IPMA strongly promoted primary ciliogenesis and restored PM2.5-induced dysgenesis of primary cilia in RPE cells. Both excessive reactive oxygen species (ROS) generation and activation of a stress kinase, JNK, by PM2.5 were reduced by 2-IPMA. Moreover, 2-IPMA inhibited proinflammatory cytokine production, i.e., IL-6 and TNF-α, induced by PM2.5 in RPE cells. Taken together, our data suggest that 2-IPMA ameliorates PM2.5-induced inflammation by promoting primary ciliogenesis in RPE cells.

Fluorescein isothiocyanate-dextrans (FDs) of different molecular weights were infused into corn, waxy rice, tapioca, and potato starches under atmospheric and high hydrostatic pressures (HHP). FD4, FD10, FD20, and FD40 (Mw 4000, 10,000, 20,000, and 40,000, respectively) were used as infusion materials. Confocal laser scanning microscopy confirmed that all FDs except FD40 infused into corn, waxy rice, and tapioca starches. However, no FDs infused into potato starch. Corn starch had the highest amounts of infused FDs. As molar mass increased, the amount of infused FD decreased in all starches. The infused amounts of FDs in corn starch were similar at 200–300 MPa and atmospheric pressure. Infusion of FDs at 400 MPa was reduced due to partial gelatinization. These results confirm that infusion efficiency is inversely proportional to the molecular weight of the infused material and large materials (Mw > 40,000) cannot be infused into starch granules under atmospheric pressure or HHP. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10068-021-00972-2.

Mitochondria are essential for providing the energy necessary for neuronal function. Dysregulation of mitochondrial dynamics has been linked with the pathogenesis of many neurodegenerative diseases. Dynamin related protein 1 (Drp1) participates in fission activity in the mitochondria, and post-translational modifications to Drp1 modulate complex mitochondrial dynamics. However, the regulation of Drp1 at the post-transcriptional level remains poorly understood. In this study, we found that the RNA-binding protein Hu antigen R (HuR) post-transcriptionally regulates Drp1 expression. HuR interacts with Drp1 mRNA at its 3' untranslated region. Depletion of HuR reduces Drp1 expression, which leads to mitochondrial elongation in SH-SY5Y neuroblastoma cells. In contrast, ectopic expression of HuR enhances Drp1 expression, which promotes mitochondrial fragmentation in response to treatment with the mitochondrial complex 1 inhibitor MPP+. In addition, depletion of HuR suppressed the generation of mitochondrial ROS and cytotoxicity in MPP+ treated cells. Taken together, these findings suggest that HuR controls mitochondrial morphology via regulation of Drp1.

Physicochemical properties of acetylated (AC), cross-linked (CL), and hydroxypropylated (HP) chestnut starches were investigated. Modified chestnut starch showed low RS and amylose contents. AC revealed the highest solubility and HP showed the highest swelling power at 60 °C. CL showed the lowest solubility and swelling power at both 60 and 90 °C. AC and HP showed a lower pasting temperature and higher peak viscosity than native chestnut starch (NC). Modified chestnut starch formed gels at higher solid content than NC. CL had the lowest freeze-thaw stability, and AC and HP showed the strongest tolerance to freeze-thaw cycles. Amylopectin melting enthalpy of NC dramatically increased over the first 2 days and continued increasing gradually until day 24. On the other hand, all the modified chestnut starches showed a slight increase in amylopectin melting enthalpy, indicating retarded retrogradation. CL showed the lowest degree of retrogradation, followed by HP, AC, and NC.

Several studies have shown that dysfunction of macroautophagy/autophagy is associated with many human diseases, including neurodegenerative disease and cancer. To explore the molecular mechanisms of autophagy, we performed a cell-based functional screening with SH-SY5Y cells stably expressing GFP-LC3, using an siRNA library and identified TMED10 (transmembrane p24 trafficking protein 10), previously known as the γ-secretase-modulating protein, as a novel regulator of autophagy. Further investigations revealed that depletion of TMED10 induced the activation of autophagy. Interestingly, protein-protein interaction assays showed that TMED10 directly binds to ATG4B (autophagy related gene 4B cysteine peptidase), and the interaction is diminished under autophagy activation conditions such as rapamycin treatment and serum deprivation. In addition, inhibition of TMED10 significantly enhanced the proteolytic activity of ATG4B for LC3 cleavage. Importantly, the expression of TMED10 in AD (Alzheimer disease) patients was considerably decreased, and downregulation of TMED10 increased amyloid-β (Aβ) production. Treatment with Aβ increased ATG4B proteolytic activity as well as dissociation of TMED10 and ATG4B. Taken together, our results suggest that the AD-associated protein TMED10 negatively regulates autophagy by inhibiting ATG4B activity.Abbreviations: Aβ: amyloid-β; AD: Alzheimer disease; ATG: autophagy related; BECN1: beclin 1; BiFC: bimolecular fluorescence complementation; CD: cytosolic domain; GFP: green fluorescent protein; GLUC: Gaussia luciferase; IP: immunoprecipitation; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; LD: luminal domain; PD: Parkinson disease; ROS: reactive oxygen species; siRNA: small interfering RNA; SNP: single-nucleotide polymorphisms; TD: transmembrane domain; TMED10: transmembrane p24 trafficking protein 10; VC: C terminus of Venus fluorescent protein; VN: N terminus of Venus fluorescent protein.

Although autophagy regulates the quality and quantity of cellular compartments, the regulatory mechanisms underlying peroxisomal autophagy (pexophagy) remain largely unknown. In this study, we identified several BRD4 inhibitors, including molibresib, a novel pexophagy inducer, via chemical library screening. Treatment with molibresib promotes loss of peroxisomes selectively, but not mitochondria, ER, or Golgi apparatus in HeLa cells. Consistently, depletion of BRD4 expression also induced pexophagy in RPE cells. In addition, the inhibition of BRD4 by molibresib increased autophagic degradation of peroxisome ATG7-dependency. We further found that molibresib produced reactive oxygen species (ROS), which potentiates ATM activation. Inhibition of ROS or ATM suppressed the loss of peroxisomes in molibresib-treated cells. Taken together, our data suggest that inhibition of BRD4 promotes pexophagy by increasing ROS and ATM activation.

The maintenance of lysosomal integrity is essential for lysosome function and cell fate. Damaged lysosomes are degraded by lysosomal autophagy, lysophagy. The mechanism underlying lysophagy remains largely unknown; this study aimed to contribute to the understanding of this topic. A cell-based screening system was used to identify novel lysophagy modulators. Triamterene (6-phenylpteridine-2,4,7-triamine) was identified as one of the most potent lysophagy inducers from the screening process. We found that triamterene causes lysosomal rupture without affecting other cellular organelles and increases autophagy flux in HepG2 cells. Damaged lysosomes in triamterene-treated cells were removed by autophagy-mediated pathway, which was inhibited by depletion of the autophagy regulator, ATG5 or SQSTM1. In addition, treatment of triamterene decreased the integrity of lysosome and cell viability, which were rescued by removing the triamterene treatment in HepG2 cells. Hence, our data suggest that triamterene is a novel lysophagy inducer through the disruption of lysosomal integrity. Supplementary Information The online version contains supplementary material available at 10.1007/s12272-021-01335-5.

Substrate binding proteins (SBPs) bind to specific ligands in the periplasmic regions of cells and then bind to membrane proteins to participate in transport or signal transduction. Typically, SBPs consist of two α/β domains and recognize the substrate by a flexible hinge region between the two domains. Conversely, the short-length SBPs are often observed in protein databases, which are located around methyl-accepting chemotaxis protein genes. We previously determined the crystal structure of Rhodothermus marinus SBP (named as RmSBP), consisting of a single α/β domain; however, the substrate recognition mechanism is still unclear. To better understand the functions of short length RmSBP, we performed a comprehensive study, involving comparative structure analysis, computational substrate docking, and X-ray crystallographic data. RmSBP shares a high level of similarity in the α/β domain region with other SBPs, but it has a distinct topology in the C-terminal domain. The substrate binding model suggested that conformational changes in the peripheral region of RmSBP was required to recognize the substrate. We determined the crystal structures of RmSBP at pH 5.5, 6.0, and 7.5. RmSBP showed structural flexibility in the β1–α2 loop, β5–β6 loop, and extended C-terminal domains, based on the electron density map and temperature B-factor analysis. These results provide information that will further our understanding on the functions of the short length SBP. Supplementary Information The online version contains supplementary material available at 10.1007/s10930-021-09970-z.

We demonstrate diverse pulsed operation regimes adjustable from Q-switching to sub-GHz continuous-wave mode-locking in a Yb:KLuW channel waveguide laser based on the interplay of dispersion and mode area managements.

We report on a power-scalable sub-100-fs laser in the 2-μm spectral range using a Tm3+-doped ‘mixed’ (Lu,Sc)2O3 sesquioxide ceramic as an active medium. Pulses as short as 58 fs at 2076 nm with an average output power of 114 mW at a pulse repetition rate of approximately 82.9 MHz are generated by employing single-walled carbon nanotubes as a saturable absorber. A higher average power of 350 mW at 2075 nm is obtained at the expense of the pulse duration (65 fs). A maximum average power of 486 mW is achieved for a pulse duration of 98 fs and an optical conversion efficiency of 22.3%, representing the highest value ever reported from sub-100-fs mode-locked Tm lasers.

We report on the first passively mode-locked Tm3+-doped calcium tantalum gallium garnet laser generating 69-fs pulses at 2010.4 nm with an average power of 28 mW at a pulse repetition rate of ~87.7 MHz.

We demonstrate sub-100-fs Kerr-lens mode-locking of a

We present an overview of our recent achievements on fabrication, characterization and CW and passively Q-switched laser operation of Thulium and Holmium depressed-cladding waveguide lasers operating at ~2 μm and inscribed in anisotropic crystals by femtosecond direct laser writing. Variable waveguide geometries (buried and surface guides; circular, rectangular and hexagonal channels; Y-splitters) are described.

A transparent Tm:Lu

Using restructuring technology, A- or B-type crystalline granular potato starch was produced from amorphous granular potato starch (AGPS). AGPS was prepared using ethanol-heat processing, and hydrothermal treatments were performed with different moisture contents (18, 29, 200% d.b.) and temperatures (4, 25, 40, 60, 80 °C) for 3 weeks. AGPS showed no endothermic peak in a DSC thermogram, while hydrothermally treated AGPS (HAGPS) revealed endothermic peaks. In X-ray diffraction, AGPS displayed an amorphous pattern, and HAGPS displayed A- or B-type crystalline patterns depending on treatment temperature and moisture content. Neither AGPS nor HAGPS had typical RVA pasting curves, and their viscosities gradually increased. Raman spectroscopy and FT-IR confirmed that ordered structure and crystalline regions increased in HAGPS. Resistant starch (RS) and slowly digestible starch (SDS) contents of HAGPS increased but rapidly digestible starch (RDS) content decreased compared to AGPS. These results elucidated that hydrothermal treatment could change the physicochemical properties of AGPS and produce an identical material, such as granular potato starch with A-type and B-type crystalline granular potato starch.

We report on the diverse pulsed operation regimes of a femtosecond-laser-written Yb:KLuW channel waveguide laser emitting near 1040 nm. By the precise position tuning of a carbon-nanotube-coated saturable absorber (SA) mirror, the transition of the pulsed operation from Q-switching, Q-switched mode-locking and finally sub-GHz continuous-wave mode-locking are obtained based on the interplay of dispersion and mode area control. The Q-switched pulses exhibit typical fast SA Q-switched pulse characteristics depending on absorbed pump powers. In the Q-switched mode-locking, amplitude modulations of the mode-locked pulses on the Q-switched envelope are observed. The radio-frequency spectrum represents the coexistence of Q-switching and mode-locking signals. In the purely mode-locked operation, the waveguide laser generates 2.05-ps pulses at 0.5 GHz., National Research Foundation of Korea (2018H1A2AA1061480, 2019R1A2C3003504, 2020R1A4A2002828); Spanish Government (FIS2017-87970-R, MAT2016-75716-C2-1-R (AEI/FEDER,UE)); Junta de Castilla y León (SA287P18); Generalitat de Catalunya (2017SGR755).