Very Early Pulsed Dye Laser Intervention for Optimal Cosmetic Outcome in Post-Thyroidectomy Scars.

Purpose: Early intervention of surgical scars with a pulsed dye laser is known to effectively prevent pathologic scars. Despite multiple reports on the effectiveness of the treatment, very few studies have demonstrated its appropriate initiation timing. In this study, our objective was to determine the optimal timing for initiating laser treatment following thyroidectomy. Methods: This study retrospectively analyzed 91 patients undergoing pulsed dye laser treatment post-thyroidectomy, grouping them by treatment initiation timing. The patients underwent treatment at intervals of 3-4 weeks with at least five sessions. Those with a high pliability score were injected with intralesional corticosteroids. The Antera 3D® skin imaging analyzer was used to assess biophysical parameters. Results: The total Vancouver Scar Scale score significantly reduced after treatment in all groups. The Vancouver Scar Scale score reduction rate was significantly higher after treatment in the group for which the treatment was initiated within 3 weeks of surgery. The pigmentation and erythema score analyzed by Antera 3D® was also lower in this group. Conclusion: Early intervention using a pulsed dye laser within 3 weeks of thyroidectomy can substantially inhibit pathological scar development, providing physicians with a guide for optimal treatment commencement.

Polymeric Binder Design for Sustainable Lithium-Ion Battery Chemistry.

The design of binders plays a pivotal role in achieving enduring high power in lithium-ion batteries (LIBs) and extending their overall lifespan. This review underscores the indispensable characteristics that a binder must possess when utilized in LIBs, considering factors such as electrochemical, thermal, and dispersion stability, compatibility with electrolytes, solubility in solvents, mechanical properties, and conductivity. In the case of anode materials, binders with robust mechanical properties and elasticity are imperative to uphold electrode integrity, particularly in materials subjected to substantial volume changes. For cathode materials, the selection of a binder hinges on the crystal structure of the cathode material. Other vital considerations in binder design encompass cost effectiveness, adhesion, processability, and environmental friendliness. Incorporating low-cost, eco-friendly, and biodegradable polymers can significantly contribute to sustainable battery development. This review serves as an invaluable resource for comprehending the prerequisites of binder design in high-performance LIBs and offers insights into binder selection for diverse electrode materials. The findings and principles articulated in this review can be extrapolated to other advanced battery systems, charting a course for developing next-generation batteries characterized by enhanced performance and sustainability.

Comparison of Various Thyroidectomy Approaches: A Retrospective Cross-sectional Study.

BACKGROUND: To avoid anterior neck scarring, numerous remote-access techniques to approach the thyroid gland (Remote access approach) have been described, including the transaxillary approach (TA), bilateral axillo-breast approach (BABA), and transoral robotic thyroidectomy (TORT). Popular worldwide, Remote access approachs have unique characteristics, advantages, and disadvantages. Herein, we investigated the characteristics of these distinct thyroidectomy approaches to aid surgeons in selecting the most appropriate method for patients. PATIENTS AND METHODS: In total, 2351 cases of patients who underwent thyroidectomy between 2019 and 2021 were reviewed, including 1973, 281, 66, and 31 patients who underwent the conventional transcervical approach (TCA), TA, BABA, and TORT, respectively. Demographic characteristics, outcomes, and complications associated with these procedures were compared. The data were analyzed using the Student t test and the χ 2 test. Kruskal-Wallis and Mann-Whitney U tests were used if normality was not found. RESULTS: Central lymph nodes (LNs) were retrieved mostly in patients who underwent lobectomy through TORT (mean: 9.4, P < 0.001). Metastatic central LNs were found more frequently (mean: 1.9 in lobectomy, 3.7 in total thyroidectomy) in patients who underwent lobectomy through TCA and TORT than in those who underwent lobectomy through other approaches (mean: 1.4 and 2.4, respectively, P < 0.05). BABA group patients had significantly fewer central LNs retrieved than those in other groups in lobectomy and total thyroidectomy (mean: 4.8 and 6.2, respectively, P < 0.05). Stimulated thyroglobulin levels did not differ among the 4 groups. The incidence of transient vocal cord palsy was statistically higher in the BABA group (5 cases, 7.5%) than in the other groups; however, all patients recovered. No difference was found in permanent vocal cord palsy (0.4% in TCA) or hypoparathyroidism (1.3% to 3.1%) among the 4 groups. The tumor size was significantly larger in the BABA group than in the other groups, with 10.6% of the patients having tumors larger than 4 cm. Total thyroidectomy was performed more frequently in the BABA group (51.8%) than in the other groups ( P = 0.005). The path of the external branch of the superior laryngeal nerve was more evident in TA, and the Cernea type was confirmed and preserved in 90.6% of TA cases. CONCLUSIONS: Owing to the differences in working space and direction of the surgical field, TA was advantageous for preserving the external branch of the superior laryngeal nerve, whereas BABA was effective for total thyroidectomy and excision of large goiters. TORT was beneficial for central compartment neck dissection. These characteristics should be considered when choosing the best approach to improving cosmesis, function, and recurrence.

Therapeutic role of 2-stearoxyphenethyl phosphocholine targeting microtubule dynamics and Wnt/ß-catenin/EMT signaling in human colorectal cancer cells.

The inhibition of cell death, perturbation of microtubule dynamics, and acceleration of Wnt/ß-catenin/epithelial-mesenchymal transition (EMT) signaling are fundamental processes in the progression and metastasis of colorectal cancer (CRC). To explore the role of 2-stearoxyphenethyl phosphocholine (stPEPC), an alkylphospholipid-based compound, in CRC, we conducted an MTT assay, cell cycle analysis, western blot analysis, immunoprecipitation, immunofluorescence staining, Annexin V/propidium iodide double staining, small interfering RNA gene silencing, a wound-healing assay, an invasion assay, and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay in the human CRC cell lines HT29 and HCT116. stPEPC showed anti-proliferative properties and mitotic cell accumulation via upregulated phosphorylation of BUBR1 and an association between mitotic arrest deficiency 2 (MAD2) and cell division cycle protein 20 homolog (CDC20). These results suggest that activation of the mitotic checkpoint complex and tubulin polymerization occurred, resulting in mitotic catastrophe in HT29 and HCT116 cells. In addition, stPEPC attenuated cell migration and invasion by regulating proteins mediated by EMT, such as E-cadherin and occludin. stPEPC altered the protein expression of Wnt3a and phosphorylation of low-density lipoprotein receptor-related protein 6 (LRP6), glycogen synthase kinase 3ß (GSK3ß), and ß-catenin as well as their target genes, including cMyc and cyclin D1, in CRC cells. Thus, stPEPC may be useful for developing new drugs to treat human CRC.

Solute Stabilization Effects of Nanoparticles Containing Boronic Acids in the Absence of Binding Pairs.

Boronic acids are widely used in materials science because of their ability to reversibly bind with diol and catechol moieties through dynamic covalent interactions in a pH- and oxidative-dependent manner. Considerably fewer studies focus on property modulation of boronic acid-based materials in the absence of a biding pair. Herein, we discuss the effects of the boronic acid-containing polymer block length on solute release kinetics from nanoparticles in a stimuli-responsive manner for on-demand delivery. In this study, ABC-type linear amphiphiles of poly(d,l-lactide) and poly(2-methacryloyloxyethyl phosphorylcholine) containing a middle block functionalized with 3-aminophenylboronic acid were synthesized by a combination of ring-opening and controlled free radical polymerizations. Nile red-loaded nanoparticles were self-assembled using a multi-inlet vortex mixer in a well-controlled manner. Release was evaluated at pH above and below the pKa of the boronic acid and in the presence of hydrogen peroxide. Our results show that release kinetics from nanoparticles incorporating a boronic acid-functionalized interlayer were slower than those without it, and the rate could be modulated according to pH and oxidative conditions. These effects can be attributed to several factors, including the hydrophobicity of the boronic acid block as well as hydrogen bonding interactions existing between locally confined boronic acids. While boronic acids are generally utilized as boronic/boronate esters, their stabilizing effects in the absence of appropriate binding pairs are relevant and should be considered in the design of boronic acid-based technologies.

NQO1 regulates cell cycle progression at the G2/M phase.

Rationale: Overexpression of NAD(P)H:quinone oxidoreductase 1 (NQO1) is associated with tumor cell proliferation and growth in several human cancer types. However, the molecular mechanisms underlying the activity of NQO1 in cell cycle progression are currently unclear. Here, we report a novel function of NQO1 in modulation of the cell cycle regulator, cyclin-dependent kinase subunit-1 (CKS1), at the G2/M phase through effects on the stability of c­Fos. Methods: The roles of the NQO1/c-Fos/CKS1 signaling pathway in cell cycle progression were analyzed in cancer cells using synchronization of the cell cycle and flow cytometry. The mechanisms underlying NQO1/c-Fos/CKS1-mediated regulation of cell cycle progression in cancer cells were studied using siRNA approaches, overexpression systems, reporter assays, co-immunoprecipitation, pull-down assays, microarray analysis, and CDK1 kinase assays. In addition, publicly available data sets and immunohistochemistry were used to investigate the correlation between NQO1 expression levels and clinicopathological features in cancer patients. Results: Our results suggest that NQO1 directly interacts with the unstructured DNA-binding domain of c-Fos, which has been implicated in cancer proliferation, differentiation, and development as well as patient survival, and inhibits its proteasome-mediated degradation, thereby inducing CKS1 expression and regulation of cell cycle progression at the G2/M phase. Notably, a NQO1 deficiency in human cancer cell lines led to suppression of c-Fos-mediated CKS1 expression and cell cycle progression. Consistent with this, high NQO1 expression was correlated with increased CKS1 and poor prognosis in cancer patients. Conclusions: Collectively, our results support a novel regulatory role of NQO1 in the mechanism of cell cycle progression at the G2/M phase in cancer through effects on c­Fos/CKS1 signaling.

Effect of withdrawal of thyroid hormones versus administration of recombinant human thyroid-stimulating hormone on renal function in thyroid cancer patients.

This study was conducted to investigate the effects of thyroid hormone withdrawal (THW) and recombinant human thyroid-stimulating hormone (rhTSH) administration on renal function in patients with thyroid cancer after total thyroidectomy. This study included 202 patients who discontinued thyroid hormone therapy and/or received rhTSH after total thyroidectomy. Creatinine (Cr), blood urea nitrogen (BUN) levels, and estimated glomerular filtration rate (eGFR) were assessed at the following three time points: before thyroidectomy, at least 3 weeks after THW, and 1 day after the second injection of rhTSH. The median serum Cr level was significantly higher following THW compared to that before thyroidectomy (0.95 versus 0.70). In contrast, the median BUN level was significantly lower after THW compared to that before thyroidectomy (9.8 versus 11.3). Over a fifth (22.2%) of patients had abnormal eGFR values after THW, which was significantly greater than that before thyroidectomy. In contrast, renal parameter values after rhTSH administration were not significantly different than those before thyroidectomy. In conclusion, THW affects renal function in patients with thyroid cancer who have undergone total thyroidectomy. However, renal function in such patients is not affected by rhTSH administration.

Grabody B, an IGF1 receptor-based shuttle, mediates efficient delivery of biologics across the blood-brain barrier.

Effective delivery of therapeutics to the brain is challenging. Molecular shuttles use receptors expressed on brain endothelial cells to deliver therapeutics. Antibodies targeting transferrin receptor (TfR) have been widely developed as molecular shuttles. However, the TfR-based approach raises concerns about safety and developmental burden. Here, we report insulin-like growth factor 1 receptor (IGF1R) as an ideal target for the molecular shuttle. We also describe Grabody B, an antibody against IGF1R, as a molecular shuttle. Grabody B has broad cross-species reactivity and does not interfere with IGF1R-mediated signaling. We demonstrate that administration of Grabody B-fused anti-alpha-synuclein (α-Syn) antibody induces better improvement in neuropathology and behavior in a Parkinson's disease animal model than the therapeutic antibody alone due to its superior serum pharmacokinetics and enhanced brain exposure. The results indicate that IGF1R is an ideal shuttle target and Grabody B is a safe and efficient molecular shuttle.

Thyroid-Stimulating Hormone as a Biomarker for Stress After Thyroid Surgery: A Prospective Cohort Study.

BACKGROUND Thyroid-stimulating hormone (TSH), which is regulated by the negative feedback of triiodothyronine (T3) and thyroxine (T4), is affected by cortisol (a stress hormone) and cytokines during allostasis. Thus, we assessed changes in TSH levels under stress and its potential as a stress marker in patients lacking T3 or T4 feedback after thyroid surgery. MATERIAL AND METHODS Three stress questionnaires (Korean version of the Daily Stress Inventory, Social Readjustment Rating Scale, and Stress Overload Scale-Short [SOSS]), an open-ended questionnaire (OQ), and thyroid function tests were administered twice to 106 patients enrolled from January 2019 to October 2020. RESULTS In a multiple generalized linear mixed-effect model (GLMM) involving 106 patients, the T3 and free T4 levels, OQ, body weight, extent of thyroidectomy, and preoperative TSH levels were significantly correlated with log-transformed TSH (lnTSH). The modified SOSS (category) based on recent stressors on OQ interview was significantly associated with lnTSH. In the GLMM with modified SOSS (category), the lnTSH increased by 2.3 and 0.56 in the unconscious high- and high-risk groups, respectively, compared to that in the low-risk group (P<0.05). The calculated power of this study was 0.92 based on alpha=0.05. CONCLUSIONS TSH had a significant relationship with stress and the extent of thyroidectomy. An OQ supported the SOSS to help detect unrecognized stressors. TSH has potential utility as a stress marker combined with the modified SOSS (category) with sufficient power. However, questionnaires on social environments and research on coping strategies for stress are necessary for future studies.

Tuning of Peptide Cytotoxicity with Cell Penetrating Motif Activatable by Matrix Metalloproteinase-2.

Although diverse cell penetrating motifs not only from naturally occurring proteins but also from synthetic peptides have been discovered and developed, the selectivity of cargo delivery connected to these motifs into the desired target cells is generally low. Here, we demonstrate the selective cytotoxicity tuning of an anticancer KLA peptide with a cell penetrating motif activatable by matrix metalloproteinase-2 (MMP2). The anionic masking sequence introduced at the end of the KLA peptide through an MMP2-cleavable linker is selectively cleaved by MMP2 and the cationic cell penetrating motif is activated. Upon treatment of the peptide to H1299 cells (high MMP2 level), it is selectively internalized into the cells by MMP2, which consequently induces membrane disruption and cell death. In contrast, the peptide shows negligible cytotoxicity toward A549 cancer cells with low MMP2 levels. Furthermore, the selective therapeutic efficacy of the peptide induced by MMP2 is also corroborated using in vivo study.

Anti-Colitic Effect of an Exopolysaccharide Fraction from Pediococcus pentosaceus KFT-18 on Dextran Sulfate Sodium-Induced Colitis through Suppression of Inflammatory Mediators.

We previously reported the immunostimulatory effect of an exopolysaccharide fraction from Pediococcus pentosaceus KFT18 (PE-EPS), a lactic acid bacterium, in macrophages and primary splenocytes, as well as in cyclophosphamide-induced immunosuppressed mice. In this study, the anti-colitic activity of PE-EPS was investigated in a dextran sulfate sodium (DSS)-induced colitis animal model. PE-EPS relieved DSS-induced colitis symptoms, such as stool blood, decreased colon length, crypt disruption, and mucus layer edema. Regarding the molecular mechanism, PE-EPS reduced the enhanced expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and pro-inflammatory cytokines (TNF-α, IL-6, and IL-1) in the colon tissue of colitis-induced mice. Additionally, PE-EPS protected against DSS-induced phosphorylation of p65 and signal transducer and activator of transcription 1 (STAT1). These findings suggested that the exopolysaccharide fraction from Ped. pentosaceus KFT18 can be used to treat inflammatory bowel disease by alleviating colonic inflammation.

Complete Genome Sequence of a Novel Monopartite Mastrevirus, Soybean Geminivirus B, Isolated from Soybean (Glycine max (L.) Merrill).

Soybean is one of the most important crops in Korea. To identify the viruses infecting soybean, we conducted RNA sequencing with samples displaying symptoms of viral disease. A contig displaying sequence similarity to the known Geminivirus was identified. A polymerase chain reaction (PCR) using two different pairs of back-to-back primers and rolling circle amplification (RCA) confirmed the complete genome of a novel virus named soybean geminivirus B (SGVB), consisting of a circular monopartite DNA genome measuring 2616 nucleotides (nt) in length. SGVB contains four open reading frames (ORFs) and three intergenic regions (IRs). IR1 includes a nonanucleotide origin of replication in the stem-loop structure. Phylogenetic and BLAST analyses demonstrated that SGVB could be a novel virus belonging to the genus Mastrevirus in the family Geminiviridae. We generated infectious clones for SGVB by adding a copy of the IR1 region of SGVB, comparing the V-ori in addition to the full-length genome of SGVB. Using the infectious clones, we observed chlorosis and leaf curling with a latent infection in the inoculated Nicotiana benthamiana plants, while none of the inoculated soybean plants showed any visible symptoms of disease. This study provides the complete genome sequence and infectious clones of a novel Mastrevirus referred to as SGVB from soybean in Korea.

Rapid-Onset Antidepressant-Like Effect of Nelumbinis semen in Social Hierarchy Stress Model of Depression.

Depression is a disease with increasing prevalence worldwide, and it is necessary to develop a therapeutic agent with better efficacy than existing antidepressant drugs. Antidepressants that act on the glutamatergic nervous system, such as ketamine, have a rapid-onset antidepressant effect and are effective against treatment-resistant depression. However, because of the addictive potential of ketamine, alternative substances without psychological side effects are recommended. In particular, many natural compounds have been tested for their antidepressant effects. The antidepressant effects of Nelumbinis semen (NS) have been tested in many studies, along with the various actions of NS on the glutamatergic system. Thus, it was expected that NS might have a rapid-onset antidepressant effect. To test the antidepressant potential, despair and anhedonic behaviors were measured after administering NS to mice exposed to social hierarchy stress (SHS), and biochemical changes in the prefrontal cortex and hippocampus were analyzed. NS reduced despair-like responses in the forced swim test and tail suspension test. Mice exposed to SHS showed depression-like responses such as increased despair, reduced hedonia, and an anxiety-like response in the novelty suppressed feeding test. NS, but not fluoxetine, improved those depression-like behaviors after acute treatment, and NBQX, an AMPA receptor blocker, inhibited the antidepressant-like effects of NS. The antidepressant-like effect of NS was related to enhanced phosphorylation of mTOR in the prefrontal cortex and dephosphorylation of GluR1 S845 in the hippocampus. Since NS has shown antidepressant-like potential in a preclinical model, it may be considered as a candidate for the development of antidepressants in the future.

The effect of fibrin glue on the quantity of drainage after thyroidectomy: a randomized controlled pilot trial.

Purpose: A seroma is a collection of exudates after surgical trauma in wound healing. Fibrin glue is used to prevent seroma by reducing the generation of exudate. However, the impact of fibrin glue on the prevention of seroma remains debatable. Therefore, we conducted a randomized controlled pilot trial to investigate the effect of the amount of fibrin glue used on the generation of exudate after thyroidectomy and the sample size of future definitive trials. Methods: Between February and December 2020, 41 patients were enrolled; 21 patients in the low fibrin group and 20 in the high fibrin group. Stratified randomization was performed based on sex, body mass index, and thyroiditis. All patients underwent total thyroidectomy and bilateral central compartment dissection. In the low and high fibrin groups, 2 mL and 6 mL of fibrin glue were applied to patients, respectively. Results: Both the total drain volume and flow rate during the first 12 hours were lower in the high fibrin group than in the low fibrin group (65.0 mL vs. 47.6 mL, P = 0.008 and 2.7 mL/hr vs. 1.8 mL/hr, P = 0.002, respectively). The calculated sample size for future randomized controlled trial was 32 patients (α = 0.05, power = 0.8), and the power of this trial was 0.91 with µ1 = 2.7, µ2 = 1.8, σ = 0.9, and α = 0.05 (µ = mean, σ = standard deviation). Conclusion: Six milliliters of fibrin glue could reduce total drain volume and flow rate of exudate after thyroidectomy. Therefore, applying an appropriate amount of fibrin glue after thyroidectomy may reduce postoperative seroma.

Identification of highly selective type II kinase inhibitors with chiral peptidomimetic tails.

Identification of highly selective type II kinase inhibitors is described. Two different chiral peptidomimetic scaffolds were introduced on the tail region of non-selective type II kinase inhibitor GNF-7 to enhance the selectivity. Kinome-wide selectivity profiling analysis showed that type II kinase inhibitor 7a potently inhibited Lck kinase with great selectivity (IC50 of 23.0 nM). It was found that 7a and its derivatives possessed high selectivity for Lck over even structurally conserved all Src family kinases. We also observed that 7a inhibited Lck activation in Jurkat T cells. Moreover, 7a was found to alleviate clinical symptoms in DSS-induced colitis mice. This study provides a novel insight into the design of selective type II kinase inhibitors by adopting chiral peptidomimetic moieties on the tail region.

Assessment of thyroid-specific quality of life in patients with benign symptomatic thyroid nodules treated with radiofrequency or ethanol ablation: a prospective multicenter study.

PURPOSE: Radiofrequency ablation (RFA) and ethanol ablation (EA) are effective and safe for benign symptomatic thyroid nodules (BSTNs). However, relatively little is known about the effects of these procedures on patients' quality of life (QoL). This prospective, multicenter study evaluated the effects of RFA and EA on changes in thyroid-specific QoL in patients with BSTNs and assessed the volume reduction and safety of these procedures. METHODS: Eighty-six consecutive patients with 86 BSTNs were prospectively included from two medical centers. RFA was performed for 55 BSTNs with solidity ≥50% and EA was performed for 31 BSTNs with solidity <50%. QoL was evaluated using an 11-scale, multiple-choice thyroid-specific QoL questionnaire. Nodule characteristics and QoL were evaluated at diagnosis and 1, 6, and 12 months after treatment. Overall QoL was rated from 0 (good) to 4 (poor). RESULTS: The mean longest size and volume of the index nodule were 4.2±1.5 cm and 21.6±22.1 mL, respectively. Patients received 1.1 treatments on average (range, 1 to 2). Significant post-treatment volume reductions were noted; however, the EA group showed a higher volume reduction than the RFA group at 1 (78.7%-16.1% vs. 49.1%-15.8%), 6 (86.3%-21.7% vs. 73.0%-14.5%), and 12 (90.9%-14.9% vs. 80.3%-12.4%) months. The score for each scale of the QoL questionnaire improved significantly during follow-up (all P<0.001). Overall QoL improved significantly, from 1.7±0.9 at diagnosis to 0.6±0.7 at the 12-month follow-up (P<0.001). There were no major complications. CONCLUSION: Both RFA and EA are safe and effective in reducing nodule volume and improving thyroid-specific QoL in patients with BSTNs.

Regulation of ROS-Dependent JNK Pathway by 2'-Hydroxycinnamaldehyde Inducing Apoptosis in Human Promyelocytic HL-60 Leukemia Cells.

The present study demonstrated that 2'-hydroxycinnamaldehyde (2'-HCA) induced apoptosis in human promyelocytic leukemia HL-60 cells through the activation of mitochondrial pathways including (1) translocation of Bim and Bax from the cytosol to mitochondria, (2) downregulation of Bcl-2 protein expression, (3) cytochrome c release into the cytosol, (4) loss of mitochondrial membrane potential (ΔΨm), and (5) caspase activation. 2'-HCA also induced the activation of c-Jun N-terminal kinase (JNK) and extracellular signal-regulated kinase1/2 (ERK1/2) in HL-60 cells. The pharmacological and genetic inhibition of JNK effectively prevented 2'-HCA-induced apoptosis and activator protein-1 (AP-1)-DNA binding. In addition, 2'-HCA resulted in the accumulation of reactive oxygen species (ROS) and depletion of intracellular glutathione (GSH) and protein thiols (PSH) in HL-60 cells. NAC treatment abrogated 2'-HCA-induced JNK phosphorylation, AP-1-DNA binding, and Bim mitochondrial translocation, suggesting that oxidative stress may be required for 2'-HCA-induced intrinsic apoptosis. Xenograft mice inoculated with HL-60 leukemia cells demonstrated that the intraperitoneal administration of 2'-HCA inhibited tumor growth by increasing of TUNEL staining, the expression levels of nitrotyrosine and pro-apoptotic proteins, but reducing of PCNA protein expression. Taken together, our findings suggest that 2'-HCA induces apoptosis via the ROS-dependent JNK pathway and could be considered as a potential therapeutic agent for leukemia.

AKF-D52, a Synthetic Phenoxypyrimidine-Urea Derivative, Triggers Extrinsic/Intrinsic Apoptosis and Cytoprotective Autophagy in Human Non-Small Cell Lung Cancer Cells.

Previously, we discovered that 1-(3,5-dimethoxyphenyl)-3-(4-(3-methoxyphenoxy)-2-((4-morpholinophenyl)amino)pyrimidin-5-yl)urea (AKF-D52), a synthetic phenoxypyrimidine urea derivative, acts as a growth inhibitor of various cancer cell types. In this study, we elucidated the antiproliferative properties of AFK-D52 and underlying mechanisms in non-small cell lung cancer (NSCLC) cells and an A549 xenograft animal model. AKF-D52 was found to induce both caspase-dependent and -independent apoptotic cell death. Furthermore, the mitochondrial component of the AKF-D52-induced apoptosis mechanism involves a reduction in mitochondrial membrane potential and regulation in B cell lymphoma-2 family protein expression. Moreover, AKF-D52 activates the extrinsic pathway through up-regulated expression of death receptor 3 and Fas and then the formation of a death-inducing signaling complex. AKF-D52 also induced autophagy by increasing acidic vesicular organelle formation and microtubule-associated protein 1A/1B-light chain 3-II levels and reducing p62 levels. Notably, pretreatment with autophagy inhibitors enhanced AKF-D52-induced cell death, indicating that the induced autophagy is cytoprotective. AKF-D52 treatment also triggered reactive oxygen species (ROS) production in NSCLC cells, whereas the antioxidant α-tocopherol abolished AKF-D52-induced cell death. In a xenograft lung cancer mouse model, AKF-D52 administration attenuated tumor growth by inducing apoptosis and autophagy in tumor tissues. Collectively, our data indicate that AKF-D52-induced ROS production plays a role in mediating apoptosis and cytoprotective autophagy in NSCLC.

An empyema caused by Streptococcus constellatus in an older immunocompetent patient: Case report.

RATIONALE: Empyema caused by Streptococcus constellatus is rare in patients without underlying diseases. However, the importance of the Streptococcus anginosus group, which consists of S constellatus, S anginosus, and Streptococcus intermedius, as causative organisms of empyema has been increasing. PATIENT CONCERNS: A 78-year-old man initially presented with dyspnea and chills for 4 days. He had no medical history. DIAGNOSIS: Chest X-ray and chest computed tomography showed a large and multiloculated pleural effusion with an air bubble on the right side. Cultivation of the pleural effusion using clone library analysis of the 16S rRNA gene revealed S constellatus positivity. INTERVENTIONS: The patient was treated by drainage of the pleural effusion and intravenous ceftriaxone and clindamycin for the possibility of anaerobes, followed by 10 weeks of oral antibiotics. OUTCOMES: On the 11th day of admission, the thoracic drainage tube was removed. After 1 year of treatment, there were no sequelae of empyema. LESSONS: Although S constellatus can cause serious infections in patients with underlying diseases and immunosuppression, physicians need to consider S constellatus infection in community-acquired empyema in elderly individuals. It should be treated with early pleural drainage and antibiotics to avoid surgical decortication and prolonged hospitalization.

Recurrent neural network FPGA hardware accelerator for delay-tolerant indoor optical wireless communications.

The optical wireless communication (OWC) system has been widely studied as a promising solution for high-speed indoor applications. The transmitter diversity scheme has been proposed to improve the performance of high-speed OWC systems. However, the transmitter diversity is vulnerable to the delay of multiple channels. Recently neural networks have been studied to realize delay-tolerant indoor OWC systems, where long-short term memory (LSTM) and attention-augmented LSTM (ALSTM) recurrent neural networks (RNNs) have shown their capabilities. However, they have high computation complexity and long computation latency. In this paper, we propose a low complexity delay-tolerant RNN scheme for indoor OWC systems. In particular, an RNN with parallelized structure is proposed to reduce the computation cost. The proposed RNN schemes show comparable capability to the more complicated ALSTM, where a bit-error-rate (BER) performance within the forward-error-correction (FEC) limit is achieved for up to 5.5 symbol periods delays. In addition, previously studied LSTM/ALSTM schemes are implemented using high-end GPUs, which have high cost, high power consumption, and long processing latency. To solve these practical limitations, in this paper we further propose and demonstrate the FPGA-based RNN hardware accelerator for delay-tolerant indoor OWC systems. To optimize the processing latency and power consumption, we also propose two optimization methods: the parallel implementation with triple-phase clocking and the stream-in based computation with additive input data insertion. Results show that the FPGA-based RNN hardware accelerator with the proposed optimization methods achieves 96.75% effective latency reduction and 90.7% lower energy consumption per symbol compared with the FPGA-based RNN hardware accelerator without optimization. Compared to the GPU implementation, the latency is reduced by about 61% and the power consumption is reduced by about 58.1%.