The kinase Btk negatively regulates the production of reactive oxygen species and stimulation-induced apoptosis in human neutrophils.

The function of the kinase Btk in neutrophil activation is largely unexplored. Here we found that Btk-deficient neutrophils had more production of reactive oxygen species (ROS) after engagement of Toll-like receptors (TLRs) or receptors for tumor-necrosis factor (TNF), which was associated with more apoptosis and was reversed by transduction of recombinant Btk. Btk-deficient neutrophils in the resting state showed hyperphosphorylation and activation of phosphatidylinositol-3-OH kinase (PI(3)K) and protein tyrosine kinases (PTKs) and were in a 'primed' state with plasma membrane-associated GTPase Rac2. In the absence of Btk, the adaptor Mal was associated with PI(3)K and PTKs at the plasma membrane, whereas in control resting neutrophils, Btk interacted with and confined Mal in the cytoplasm. Our data identify Btk as a critical gatekeeper of neutrophil responses.

A Comparative Study on the Carcass and Meat Chemical Composition, and Lipid-Metabolism-Related Gene Expression in Korean Hanwoo and Brindle Chikso Cattle.

The objective of this study was to elucidate the effect of cattle breed on carcass and meat chemical composition, fatty acid profiles, and lipid-metabolism-related genes. For this study, same-age Hanwoo and Chikso steers (n = 6 per breed) reared under identical conditions were used. Immediately after slaughter, muscle tissues were collected for analysis of mRNA expression. At 24 h post-mortem, the carcasses were assessed for carcass traits (marbling score, meat yield, etc.), and meat quality and fatty acid profiles in the longissimus lumborum (LL) and semimembranosus (SM) muscles. The results showed that no differences in the slaughter weight, dressing rate, back-fat thickness, trimmed fat, and total meat yield occurred between the two breeds (p > 0.05). However, Hanwoo cattle had a higher marbling score, intramuscular fat (IMF) content, and expression level of lipid-metabolism-related genes such as lipoprotein lipase, peroxisome proliferator-activated receptor gamma, and fatty acid binding protein 4, compared with Chikso (p < 0.05). Contrastingly, Chikso had a higher total unsaturated fatty acid content and expression level of stearoyl CoA desaturase 1 (p < 0.05). It may be said that the difference in the expression levels of lipid-metabolism-related genes could be the molecular factors underlying IMF deposition and fatty acid profile differences in the beef from the two breeds.

Primary Ciliogenesis by 2-Isopropylmalic Acid Prevents PM2.5-Induced Inflammatory Response and MMP-1 Activation in Human Dermal Fibroblasts and a 3-D-Skin Model.

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.

Probing graphene grain boundaries with optical microscopy.

Grain boundaries in graphene are formed by the joining of islands during the initial growth stage, and these boundaries govern transport properties and related device performance. Although information on the atomic rearrangement at graphene grain boundaries can be obtained using transmission electron microscopy and scanning tunnelling microscopy, large-scale information regarding the distribution of graphene grain boundaries is not easily accessible. Here we use optical microscopy to observe the grain boundaries of large-area graphene (grown on copper foil) directly, without transfer of the graphene. This imaging technique was realized by selectively oxidizing the underlying copper foil through graphene grain boundaries functionalized with O and OH radicals generated by ultraviolet irradiation under moisture-rich ambient conditions: selective diffusion of oxygen radicals through OH-functionalized defect sites was demonstrated by density functional calculations. The sheet resistance of large-area graphene decreased as the graphene grain sizes increased, but no strong correlation with the grain size of the copper was revealed, in contrast to a previous report. Furthermore, the influence of graphene grain boundaries on crack propagation (initialized by bending) and termination was clearly visualized using our technique. Our approach can be used as a simple protocol for evaluating the grain boundaries of other two-dimensional layered structures, such as boron nitride and exfoliated clays.

The sensory power of cameras and noise meters for protest surveillance in South Korea.

This article analyzes sensory aspects of material politics in social movements, focusing on two police tools: evidence-collecting cameras and noise meters for protest surveillance. Through interviews with Korean political activists, this article examines the relationship between power and the senses in the material culture of Korean protests and asks why cameras and noise meters appeared in order to control contemporary peaceful protests in the 2000s. The use of cameras and noise meters in contemporary peaceful protests evidences the exercise of what Michel Foucault calls 'micro-power'. Building on material culture studies, this article also compares the visual power of cameras with the sonic power of noise meters, in terms of a wide variety of issues: the control of things versus words, impacts on protest size, differential effects on organizers and participants, and differences in timing regarding surveillance and punishment.

Haplogroup Classification of Korean Cattle Breeds Based on Sequence Variations of mtDNA Control Region.

Many studies have reported the frequency and distribution of haplogroups among various cattle breeds for verification of their origins and genetic diversity. In this study, 318 complete sequences of the mtDNA control region from four Korean cattle breeds were used for haplogroup classification. 71 polymorphic sites and 66 haplotypes were found in these sequences. Consistent with the genetic patterns in previous reports, four haplogroups (T1, T2, T3, and T4) were identified in Korean cattle breeds. In addition, T1a, T3a, and T3b sub-haplogroups were classified. In the phylogenetic tree, each haplogroup formed an independent cluster. The frequencies of T3, T4, T1 (containing T1a), and T2 were 66%, 16%, 10%, and 8%, respectively. Especially, the T1 haplogroup contained only one haplotype and a sample. All four haplogroups were found in Chikso, Jeju black and Hanwoo. However, only the T3 and T4 haplogroups appeared in Heugu, and most Chikso populations showed a partial of four haplogroups. These results will be useful for stable conservation and efficient management of Korean cattle breeds.

Down-regulation of mortalin exacerbates Aß-mediated mitochondrial fragmentation and dysfunction.

Mitochondrial dynamics greatly influence the biogenesis and morphology of mitochondria. Mitochondria are particularly important in neurons, which have a high demand for energy. Therefore, mitochondrial dysfunction is strongly associated with neurodegenerative diseases. Until now various post-translational modifications for mitochondrial dynamic proteins and several regulatory proteins have explained complex mitochondrial dynamics. However, the precise mechanism that coordinates these complex processes remains unclear. To further understand the regulatory machinery of mitochondrial dynamics, we screened a mitochondrial siRNA library and identified mortalin as a potential regulatory protein. Both genetic and chemical inhibition of mortalin strongly induced mitochondrial fragmentation and synergistically increased Aß-mediated cytotoxicity as well as mitochondrial dysfunction. Importantly we determined that the expression of mortalin in Alzheimer disease (AD) patients and in the triple transgenic-AD mouse model was considerably decreased. In contrast, overexpression of mortalin significantly suppressed Aß-mediated mitochondrial fragmentation and cell death. Taken together, our results suggest that down-regulation of mortalin may potentiate Aß-mediated mitochondrial fragmentation and dysfunction in AD.

BIX-01294-induced autophagy regulates elongation of primary cilia.

Previously, we showed that BIX-01294 treatment strongly activates autophagy. Although, the interplay between autophagy and ciliogenesis has been suggested, the role of autophagy in ciliogenesis is controversial and largely unknown. In this study, we investigated the effects of autophagy induced by BIX-01294 on the formation of primary cilia in human retinal pigmented epithelial (RPE) cells. Treatment of RPE cells with BIX-01294 caused strong elongation of the primary cilium and increased the number of ciliated cells, as well as autophagy activation. The elongated cilia in serum starved cultured cells were gradually decreased by re-feeding the cells with normal growth medium. However, the disassembly of cilia was blocked in the BIX-01294-treated cells. In addition, both genetic and chemical inhibition of autophagy suppressed BIX-01294-mediated ciliogenesis in RPE cells. Taken together, these results suggest that autophagy induced by BIX-01294 positively regulates the elongation of primary cilium.

Chaperone-like activity of high-mobility group box 1 protein and its role in reducing the formation of polyglutamine aggregates.

High-mobility group box 1 protein (HMGB1), which mainly exists in the nucleus, has recently been shown to function as a sentinel molecule for viral nucleic acid sensing and an autophagy regulator in the cytoplasm. In this study, we studied the chaperone-like activity of HMGB1 and found that HMGB1 inhibited the chemically induced aggregation of insulin and lysozyme, as well as the heat-induced aggregation of citrate synthase. HMGB1 also restored the heat-induced suppression of cytoplasmic luciferase activity as a reporter protein in hamster lung fibroblast O23 cells with expression of HMGB1. Next, we demonstrated that HMGB1 inhibited the formation of aggregates and toxicity caused by expanded polyglutamine (polyQ), one of the main causes of Huntington disease. HMGB1 directly interacted with polyQ on immunofluorescence and coimmunoprecipitation assay, whereas the overexpression of HMGB1 or exogenous administration of recombinant HMGB1 protein remarkably reduced polyQ aggregates in SHSY5Y cells and hmgb1(-/-) mouse embryonic fibroblasts upon filter trap and immunofluorescence assay. Finally, overexpressed HMGB1 proteins in mouse embryonic primary striatal neurons also bound to polyQ and decreased the formation of polyQ aggregates. To this end, we have demonstrated that HMGB1 exhibits chaperone-like activity and a possible therapeutic candidate in polyQ disease.

A prospective randomized controlled trial of the laryngeal mask airway versus the endotracheal intubation in the thyroid surgery: evaluation of postoperative voice, and laryngopharyngeal symptom.

BACKGROUND: The present study was performed to determine whether thyroidectomy patients undergoing general anesthesia provided with a laryngeal mask airway (LMA) have a lower risk of voice-related complications and laryngopharyngeal symptoms than those undergoing endotracheal intubation (ETI). MATERIALS AND METHODS: In a prospective, double-blinded, randomized clinical trial, we studied 64 patients undergoing elective thyroid lobectomy between July 2013 and February 2014. Acoustic analyses were performed preoperatively and at 48 h and 2 weeks postoperatively. The voice handicap index (VHI), M.D. Anderson dysphagia index (MDADI), and laryngopharyngeal symptom score (LPS) were determined preoperatively and at 24 h, 48 h, 1 week, and 2 weeks post-thyroidectomy. RESULTS: In acoustic analysis, jitter, shimmer and noise-to-harmonic ratio showed significantly better results in the LMA group than the ETI group 48 h after surgery, but there was no difference at 2 weeks. The incidence of postoperative lower-pitched voice in the LMA group was also significantly lower than that in the ETI group. In the LMA group, the VHI, MDADI, and LPS were better compared to those in the ETI group at 24 h postoperatively, and improved to the preoperative state within 1 week. However, those in the ETI group remained poorer than the preoperative values 1 week after surgery. CONCLUSIONS: Use of the LMA in general anesthesia for thyroid surgery has advantages over the ETI in decreasing patients' subjective and objective voice symptoms, reducing the duration of symptoms, and relieving the laryngopharyngeal symptoms.

The Efficacy of Lumbosacral Spine Phantom to Improve Resident Proficiency in Performing Ultrasound-Guided Spinal Procedure.

OBJECTIVE: To evaluate the efficacy of a lumbosacral spine phantom to improve novices' proficiency in performing ultrasound-guided facet joint injection and medial branch block. DESIGN AND SETTING: Prospective study in a university hospital. SUBJECTS: In total, 30 participants with no experience of spinal ultrasonography were included and were allocated to one of two groups (control group, N = 10 and training group, N = 20). METHODS: A lumbosacral spine phantom was prepared using a lumbosacral spine model embedded in a mixture of gelatin and psyllium husk. All participants were tested (test-1) following a basic education introductory program. Participants in the control group were then tested again after 1 week (test-2). Those in the training group received a further 3-h training, individually, and were tested again after 1 week (test-2). RESULTS: The mean performance scores on test-1 were 57.6 ± 6.0 in the control group and 57.3 ± 6.7 in the training group; and at test-2, 61.0 ± 8.6 and 91.7 ± 4.9 (P < 0.001), respectively. The median time of performance at test-1 was 158.3 ± 41.9 seconds in the control group and 185.3 ± 68.1 seconds in the training group; and at test-2, 146.9 ± 38.9 seconds and 69.9 ± 22.0 seconds (P < 0.001), respectively. In the training group, the mean self-rating level of proficiency scores were 2.2 ± 1.0 at pretraining, and 6.8 ± 0.8 at post-training, respectively (P < 0.001). CONCLUSION: Training using a gelatin-based spine phantom helped novices to acquire the skills necessary to perform ultrasound-guided lumbar facet joint injections and medial branch blocks.

Comparison of the size 3 and size 4 ProSeal™ laryngeal mask airway in anesthetized, non-paralyzed women: a randomized controlled trial.

PURPOSE: Based on experimental results, various authors have advocated a size 4 ProSeal™ laryngeal mask airway (PLMA) in preference to a size 3 PLMA for women given a neuromuscular blocking agent because the larger size provided a better airway seal. However, spontaneously breathing patients may be ventilated adequately with a lower seal pressure than that needed for mechanical ventilation. Therefore, a smaller size might be preferable as its reduced bulk possibly induces less mucosal damage in non-paralyzed patients. METHODS: A total of 152 females undergoing general anesthesia for short outpatient gynecological surgeries were randomly allocated in equal numbers to insertion of a size 3 or 4 PLMA. The insertion time, success rate, seal pressure, hemodynamic variables, and complications, such as blood staining and sore throat, were evaluated. RESULTS: The incidence of blood staining was lower with the size 3 PLMA compared to the size 4 PLMA (18 vs. 36 %; P = 0.028). Compared with the size 3 LMA, the size 4 PLMA resulted in higher fluctuations in both blood pressure (P = 0.003) and heart rate (P = 0.01). The insertion time was shorter with the size 3 PLMA (9 vs. 16 s; P < 0.001). The airway seal pressure with the size 3 PLMA, although lower than that of the size 4 PLMA (23 vs. 28 cmH2O; P = 0.001), was sufficient for spontaneous ventilation. CONCLUSIONS: Due to the reduced incidence of mucosal injury and greater hemodynamic stability, the size 3 PLMA may be preferable to the size 4 PLMA for non-paralyzed females.

Autophagy induced by resveratrol suppresses α-MSH-induced melanogenesis.

Autophagy degrades cellular components and organelles through a cooperative process involving autophagosomes and lysosomes. Although autophagy is known to mainly regulate the turnover of cellular components, the role of autophagy in melanogenesis has not been well addressed. Here, we show that inhibition of autophagy suppresses the antimelanogenesis activity of resveratrol (RSV), a well-known antimelanogenic agent. RSV strongly increased autophagy in melanocytes. However, the depletion of ATG5 significantly suppressed RSV-mediated antimelanogenesis as well as RSV-induced autophagy in melanocytes. Moreover, suppression of ATG5 retrieved the RSV-mediated downregulation of tyrosinase and TRP1 in α-MSH-treated cells. Most importantly, electron microscopy analysis revealed that autophagosomes engulfed melanin or melanosomes after combined treatment of α-MSH and RSV. Taken together, these results suggest that RSV-mediated autophagy regulates melanogenesis.

Cervical subcutaneous emphysema and pneumomediastinum after septorhinoplasty.

Cervical and facial subcutaneous emphysema is mainly caused by maxillofacial trauma or head and neck surgery. There are only 2 cases of subcutaneous emphysema after septorhinoplasty in the English literature. We report a case of subcutaneous emphysema and pneumomediastinum after a septorhinoplasty.A healthy 35-year-old man with nasal obstruction and dissatisfaction with the shape of his nose was referred to our outpatient clinic. The patient had a septorhinoplasty including bilateral medial and lateral osteotomy under general anesthesia. On the fifth day after the surgery, the patient visited the emergency department with swelling and pain in the right submandibular area and cheek. On computed tomographic (CT) scans, air was observed in the right temporal space, masticator space, submandibular space, and superior mediastinal space. He was immediately hospitalized for administration of intravenous antibiotics and bed rest.On the fifth day after the hospitalization, follow-up CT scans were performed. Subcutaneous emphysema and pneumomediastinum were markedly decreased. The patient was discharged on the fifth day.

Hemorrhagic Complications Following Ultrasound-Guided Breast Biopsy: A Prospective Patient-Centered Study.

OBJECTIVE: We aimed to evaluate the clinical and imaging factors associated with hemorrhagic complications and patient discomfort following ultrasound (US)-guided breast biopsy. MATERIALS AND METHODS: We prospectively enrolled 94 patients who were referred to our hospital between June 2022 and December 2022 for US-guided breast biopsy. After obtaining informed consent, two breast radiologists independently performed US-guided breast biopsy and evaluated the imaging findings. A hemorrhagic complication was defined as the presence of bleeding or hematoma on US. The patients rated symptoms of pain, febrile sensation, swelling at the biopsy site, and dyspnea immediately, 20 minutes, and 2 weeks after the procedure on a visual analog scale, with 0 for none and 10 for the most severe symptoms. Additional details recorded included those of nausea, vomiting, bleeding, bruising, and overall satisfaction score. We compared the clinical symptoms, imaging characteristics, and procedural features between patients with and those without hemorrhagic complications. RESULTS: Of 94 patients, 7 (7%) developed hemorrhagic complications, while 87 (93%) did not. The complication resolved with 20 minutes of manual compression, and no further intervention was required. Vascularity on Doppler examination (P = 0.008), needle type (P = 0.043), and lesion location (P < 0.001) were significantly different between the groups. Patients with hemorrhagic complications reported more frequent nausea or vomiting than those without hemorrhagic complications (29% [2/7] vs. 2% [2/87], respectively; P = 0.027). The overall satisfaction scores did not differ between the two groups (P = 0.396). After 2 weeks, all symptoms subsided, except bruising (50% 2/4 in the complication group and 25% [16/65] in the no-complication group). CONCLUSION: US-guided breast biopsy is a safe procedure with a low complication rate. Radiologists should be aware of hemorrhagic complications, patient discomfort, and overall satisfaction related to this procedure.

Autophagy mediates anti-melanogenic activity of 3'-ODI in B16F1 melanoma cells.

Autophagy is a cellular degradation process for cellular aggregates and unneeded cellular compartments including damaged mitochondria, ER, and peroxisomes. Melanosome is cellular organelle that is the cellular site of generation, storage and transports of melanin in melanocytes. Despite potential importance of autophagy, the role of autophagy in melanogenesis and melanosome autophagy are largely unknown. In here, we identified 3'-hydroxydaidzein (3'-ODI) as an autophagy inducer from a phytochemical library screening. Treatment with 3'-ODI significantly reduced α-MSH-mediated melanogenesis but efficiently increased autophagy both in melanoma cells and melanocytes. Furthermore, inhibition of autophagy significantly reduced the anti-melanogenic effects of 3'-ODI in α-MSH-stimulated melanoma cells. Taken together, these results suggest that autophagy mediates anti-melanogenic activity of 3'-ODI.

Intranasal delivery of the cytoplasmic domain of CTLA-4 using a novel protein transduction domain prevents allergic inflammation.

CTLA-4 is a negative regulator of T-cell activation, and its inhibitory effects can be accomplished either by competition with CD28 or by transmitting negative signals through its intracellular domain. To utilize the cytoplasmic domain of CTLA-4 to suppress allergic inflammation, we fused it to a novel protein-transduction domain in the human transcriptional factor Hph-1. Transduction efficiency was verified in vitro and in vivo after ocular, intranasal and intradermal administration. After transduction into T cells, the Hph-1-ctCTLA-4 fusion protein inhibited the production of interleukin (IL)-2, and downregulated CD69 and CD25. Intranasal administration of Hph-1-ctCTLA-4 resulted in markedly reduced infiltration of inflammatory cells, secretion of T helper type 2 (T(H)2) cytokines, serum IgE levels and airway hyper-responsiveness in a mouse model of allergic airway inflammation. These results indicated that Hph-1-ctCTLA-4 constitutes an effective immunosuppressive protein drug for potential use in the treatment of allergic asthma, via nasal administration.

mtDNA Diversity and Phylogenetic State of Korean Cattle Breed, Chikso.

In order to analyze the genetic diversity and phylogenetic status of the Korean Chikso breed, we determined sequences of mtDNA cytochrome b (cyt b) gene and performed phylogenetic analysis using 239 individuals from 5 Chikso populations. Five non-synonymous mutations of a total of 15 polymorphic sites were identified among 239 cyt b coding sequences. Thirteen haplotypes were defined, and haplotype diversity was 0.4709 ranging from 0.2577 to 0.6114. Thirty-five haplotypes (C1-C35) were classified among 9 Asia and 3 European breeds. C2 was a major haplotype that contained 206 sequences (64.6%) from all breeds used. C3-C13 haplotypes were Chikso-specific haplotypes. C1 and C2 haplotypes contained 80.5% of cyt b sequences of Hanwoo, Yanbian, Zaosheng and JB breeds. In phylogenetic analyses, the Chikso breed was contained into B. taurus lineage and was genetically more closely related to two Chinese breeds than to Korean brown cattle, Hanwoo. These results suggest that Chikso and Hanwoo have a genetic difference based on the mtDNA cyt b gene as well as their coat color, sufficient for classification as a separate breed.

A Comparative Study on the Meat Quality, Taste and Aroma Related Compounds between Korean Hanwoo and Chikso Cattle.

The aim of this study was to compare the meat quality and taste-and-aroma-related components of beef between breeds. For this purpose, Hanwoo and Chikso steers (n = 7 per breed) raised under identical conditions until 30 months old were used. After 24 h of slaughter, longissimus lumborum (LL) and semimembranosus (SM) muscles were collected and analyzed for technological quality, free amino acids, metabolites, and volatile compounds. The Chikso meat showed lower values for shear force and color traits (lightness, redness, and yellowness) compared to Hanwoo (p < 0.05). The Chikso presented a higher amount of sweetness-related free amino acids (alanine, proline, and threonine) in the LL muscle, while Hanwoo had a higher amount of methionine and glutamine associated with umami taste (p < 0.05). A total of 36 metabolites were identified and quantified in the meat samples; out of them, 7 compounds were affected by breed (p < 0.05). Regarding aroma compounds, a significantly higher amount of fat-derived aldehydes associated with fatty and sweet notes was found in Hanwoo, whereas a higher amount of pyrazines associated with roasty notes was found in Chikso (p < 0.05). Thus, under identical feeding conditions, breed showed a significant effect on the quality and taste-and-aroma-related components that may influence the eating quality of beef between the two breeds studied.

Transducible form of p47phox and p67phox compensate for defective NADPH oxidase activity in neutrophils of patients with chronic granulomatous disease.

Protein delivery to primary cells by protein transduction domain (PTD) serves as a novel measure for manipulation of the cells for biological study and for the treatment of various human conditions. Although the method has been employed to modulate cellular function in vitro, only limited reports are available on its application in the replacement of deficient signaling molecules into primary cells. We examined the potential of recombinant proteins to compensate for defective cytosolic components of the NADPH oxidase complex in chronic granulomatous disease (CGD) neutrophils in both p47(phox) and p67(phox) deficiency. The p47(phox) or p67(phox) protein linked to Hph-1 PTD was effectively expressed in soluble form and transduced into human neutrophils efficiently without eliciting unwanted signal transduction or apoptosis. The delivered protein was stable for more than 24h, expressed in the cytoplasm, translocated to the membrane fraction upon activation, and, most importantly able to restored reactive oxygen species (ROS) production. Although research on human primary neutrophils using the protein delivery system is still limited, our data show that the protein transduction approach for neutrophils may be applicable to the control of local infections in CGD patients by direct delivery of the protein product.