IDH2 regulates macrophage polarization and tumorigenesis by modulating mitochondrial metabolism in macrophages.

BACKGROUND: Targeting the tumor microenvironment represents an emerging therapeutic strategy for cancer. Macrophages are an essential part of the tumor microenvironment. Macrophage polarization is modulated by mitochondrial metabolism, including oxidative phosphorylation (OXPHOS), the tricarboxylic acid (TCA) cycle, and reactive oxygen species content. Isocitrate dehydrogenase 2 (IDH2), an enzyme involved in the TCA cycle, reportedly promotes cancer progression. However, the mechanisms through which IDH2 influences macrophage polarization and modulates tumor growth remain unknown. METHODS: In this study, IDH2-deficient knockout (KO) mice and primary cultured bone marrow-derived macrophages (BMDMs) were used. Both in vivo subcutaneous tumor experiments and in vitro co-culture experiments were performed, and samples were collected for analysis. Western blotting, RNA quantitative analysis, immunohistochemistry, and flow cytometry were employed to confirm changes in mitochondrial function and the resulting polarization of macrophages exposed to the tumor microenvironment. To analyze the effect on tumor cells, subcutaneous tumor size was measured, and growth and metastasis markers were identified. RESULTS: IDH2-deficient macrophages co-cultured with cancer cells were found to possess increased mitochondrial dysfunction and fission than wild-type BMDM. Additionally, the levels of M2-associated markers decreased, whereas M1-associated factor levels increased in IDH2-deficient macrophages. IDH2-deficient macrophages were predominantly M1. Tumor sizes in the IDH2-deficient mouse group were significantly smaller than in the wild-type mouse group. IDH2 deficiency in macrophages was associated with inhibited tumor growth and epithelial-mesenchymal transition. CONCLUSIONS: Our findings suggest that IDH2 deficiency inhibits M2 macrophage polarization and suppresses tumorigenesis. This study underlines the potential contribution of IDH2 expression in macrophages and tumor microenvironment remodeling, which could be useful in clinical cancer research.

Mitofusin 1 and 2 overexpression reduces AßO-mediated ER stress and apoptosis in N2a APPswe cells.

Alzheimer's disease (AD) is the most common neurodegenerative disorder, and amyloid beta oligomers (AßO), which are pathological markers of AD, are known to be highly toxic. AßO increase mitochondrial dysfunction, which is accompanied by a decrease in mitochondrial fusion. Although mitofusin (Mfn) 1 and Mfn2 are mitochondrial fusion proteins, Mfn2 is known to regulate endoplasmic reticulum (ER) function, as it is located in the ER. Several studies have shown that AßO exacerbates ER stress, however, the exact mechanism requires further elucidation. In this study, we used mouse neuroblastoma cells stably overexpressing the amyloid precursor protein (APP) with the Swedish mutation (N2a APPswe cells) to investigate the role of Mfn in ER stress. Our results revealed that  amyloid beta (Aß) caused cellular toxicity in N2a APPswe cells, upregulated ER stress-related proteins, and promoted ER expansion. The AßO-mediated ER stress was reduced when Mfn1 and Mfn2 were overexpressed. Moreover, Mfn1 and Mfn2 overexpressed resulted in reduced apoptosis of N2a APPswe cells. In conclusion, our results indicate that both Mfn1 and Mfn2 reduce ER stress and apoptosis. Our data provide a foundation for future studies on the roles of Mfn1 and Mfn2 in the molecular mechanisms underlying AßO-mediated ER stress and the pathogenesis of AD.

Peroxiredoxin 1 inhibits streptozotocin-induced Alzheimer's disease-like pathology in hippocampal neuronal cells via the blocking of Ca2+/Calpain/Cdk5-mediated mitochondrial fragmentation.

Oxidative stress plays an essential role in the progression of Alzheimer's disease (AD), the most common age-related neurodegenerative disorder. Streptozotocin (STZ)-induced abnormal brain insulin signaling and oxidative stress play crucial roles in the progression of Alzheimer's disease (AD)-like pathology. Peroxiredoxins (Prxs) are associated with protection from neuronal death induced by oxidative stress. However, the molecular mechanisms underlying Prxs on STZ-induced progression of AD in the hippocampal neurons are not yet fully understood. Here, we evaluated whether Peroxiredoxin 1 (Prx1) affects STZ-induced AD-like pathology and cellular toxicity. Prx1 expression was increased by STZ treatment in the hippocampus cell line, HT-22 cells. We evaluated whether Prx1 affects STZ-induced HT-22 cells using overexpression. Prx1 successfully protected the forms of STZ-induced AD-like pathology, such as neuronal apoptosis, synaptic loss, and tau phosphorylation. Moreover, Prx1 suppressed the STZ-induced increase of mitochondrial dysfunction and fragmentation by down-regulating Drp1 phosphorylation and mitochondrial location. Prx1 plays a role in an upstream signal pathway of Drp1 phosphorylation, cyclin-dependent kinase 5 (Cdk5) by inhibiting the STZ-induced conversion of p35 to p25. We found that STZ-induced of intracellular Ca2+ accumulation was an important modulator of AD-like pathology progression by regulating Ca2+-mediated Calpain activation, and Prx1 down-regulated STZ-induced intracellular Ca2+ accumulation and Ca2+-mediated Calpain activation. Finally, we identified that Prx1 antioxidant capacity affected Ca2+/Calpain/Cdk5-mediated AD-like pathology progress. Therefore, these findings demonstrated that Prx1 is a key factor in STZ-induced hippocampal neuronal death through inhibition of Ca2+/Calpain/Cdk5-mediated mitochondrial dysfunction by protecting against oxidative stress.

The overexpression of DSP1 in neurons induces neuronal dysfunction and neurodegeneration phenotypes in Drosophila.

Dorsal switch protein 1(DSP1), a mammalian homolog of HMGB1, is firstly identified as a dorsal co-repressor in 1994. DSP1 contains HMG-box domain and functions as a transcriptional regulator in Drosophila melanogaster. It plays a crucial role in embryonic development, particularly in dorsal-ventral patterning during early embryogenesis, through the regulation of gene expression. Moreover, DSP1 is implicated in various cellular processes, including cell fate determination and tissue differentiation, which are essential for embryonic development. While the function of DSP1 in embryonic development has been relatively well-studied, its role in the adult Drosophila brain remains less understood. In this study, we investigated the role of DSP1 in the brain by using neuronal-specific DSP1 overexpression flies. We observed that climbing ability and life span are decreased in DSP1-overexpressed flies. Furthermore, these flies demonstrated neuromuscular junction (NMJ) defect, reduced eye size and a decrease in tyrosine hydroxylase (TH)-positive neurons, indicating neuronal toxicity induced by DSP1 overexpression. Our data suggest that DSP1 overexpression leads to neuronal dysfunction and toxicity, positioning DSP1 as a potential therapeutic target for neurodegenerative diseases.

Amount Estimation Method for Food Intake Based on Color and Depth Images through Deep Learning.

In this paper, we propose an amount estimation method for food intake based on both color and depth images. Two pairs of color and depth images are captured pre- and post-meals. The pre- and post-meal color images are employed to detect food types and food existence regions using Mask R-CNN. The post-meal color image is spatially transformed to match the food region locations between the pre- and post-meal color images. The same transformation is also performed on the post-meal depth image. The pixel values of the post-meal depth image are compensated to reflect 3D position changes caused by the image transformation. In both the pre- and post-meal depth images, a space volume for each food region is calculated by dividing the space between the food surfaces and the camera into multiple tetrahedra. The food intake amounts are estimated as the difference in space volumes calculated from the pre- and post-meal depth images. From the simulation results, we verify that the proposed method estimates the food intake amount with an error of up to 2.2%.

A narrative review of anastomotic leak in the Ivor Lewis esophagectomy: expected, accepted, but preventable.

Background and Objective: Anastomotic leak (AL) remains a common and highly morbid complication after Ivor Lewis Esophagectomy. Leak is associated with increased morbidity, mortality, strictures and even cancer recurrence. Unfortunately, despite advances in surgical technique and perioperative care, the reported frequency of AL has remained largely unchanged. Methods: A PubMed search for all English-language articles that discuss Ivor Lewis esophagectomy, AL, risk factors, and outcomes was conducted from 1901 to 2023 prioritizing research from randomized trials that evaluated outcomes from patients undergoing esophagectomy. Key Content and Findings: This narrative review will discuss the prevailing literature on AL, risk factors and outcomes with a focus on its relationship to the Ivor Lewis esophagectomy (ILE). In particular, we emphasize that the gastric conduit, as commonly created for most esophagectomy procedures, is inherently vulnerable to ischemia. We will show trends in the literature that have contributed to the high rate of postoperative complications, with a focus on the AL. In addition, we propose that the traditional Ivor Lewis procedure itself is a risk factor for AL. We review a surgical alternative that increases blood supply of the conduit, and is associated with reduced leak, no strictures, and improved surgical outcomes. Conclusions: Multiple factors contribute to AL after esophagectomy; including several current surgical practices. We believe that some of them, especially the commonly accepted approach to the gastric conduit, can be modified to optimize tissue perfusion. With further investigation, we may reduce the incidence of short and long-term anastomotic complications and improve surgical outcomes.

Extracellular Prdx1 mediates bacterial infection and inflammatory bone diseases.

AIM: We aimed to determine the role of extracellular peroxiredoxin 1 (Prdx1) in the pathogenesis of bacterial infections and inflammatory bone disease. MATERIALS AND METHODS: We first investigated the role of Prdx1 using knockout mice. Next, we determined the role of extracellular Prdx1 in bacterial infections by using a neutralizing antibody against Prdx1. We finally investigated whether blockade of extracellular Prdx1 affected high- or low-grade inflammatory bone diseases using calvarial osteolysis, collagen-induced arthritis (CIA), and microgravity-induced bone loss in mouse models. KEY FINDINGS: The lack of Prdx1 increased susceptibility to infections by Listeria monocytogenes or Escherichia coli. Prdx1 is released into the serum upon E. coli infection, and blockade of extracellular Prdx1 confers significant protection against bacterial infections. Our data suggested that circulating Prdx1 is increased by the development of osteolytic disease, and that blockade of extracellular Prdx1 exerts therapeutic effects against high- and low-grade inflammatory bone loss. In addition, the release of Prdx1 under inflammatory osteolytic conditions partly depends on non-canonical TIR-domain-containing adapter-inducing interferon-ß (TRIF)-caspase-11-gasdemin D (GSDMD) inflammasome pathways. SIGNIFICANCE: Extracellular Prdx1 is involved in the development of bacterial infections and inflammatory bone disease. Thus, extracellular Prdx1 may represent a novel therapeutic target for bacterial infections or inflammatory osteolytic diseases.

Discovery and Feasibility Study of Medical Fluorophore 33 as a Novel Theranostic Agent.

Fluorescent dyes have garnered significant attention as theranostic platforms owing to their inherent characteristics. In this study, we present the discovery of Medical Fluorophore 33 (MF33), a novel and potent theranostic agent with a phenaleno-isoquinolinium salt structure that can serve as a cancer therapeutic strategy. The synthesis of MF33 is readily achievable through a simple Rh(III)-catalyzed reaction. Moreover, MF33 displayed strong fluorescence signals, excellent microsomal stability, and high biocompatibility in vivo. It induces significant apoptosis in cancer cells via the p53/p21/caspase-3 signaling pathway, leading to selective cytotoxicity in various cancer cells. In vivo fluorescence imaging with MF33 enabled the visualization of sentinel lymph nodes in living mice. Notably, repeated intraperitoneal administration of MF33 resulted in antitumor activity in mice with colorectal cancer. Collectively, our findings suggest that phenaleno-isoquinolinium salt-based MF33 is a viable theranostic agent for biomedical imaging and cancer treatment.

Anti-Cancer Effect of Neural Stem Cells Transfected with Carboxylesterase and sTRAIL Genes in Animals with Brain Lesions of Lung Cancer.

A metastatic brain tumor is the most common type of malignancy in the central nervous system, which is one of the leading causes of death in patients with lung cancer. The purpose of this study is to evaluate the efficacy of a novel treatment for metastatic brain tumors with lung cancer using neural stem cells (NSCs), which encode rabbit carboxylesterase (rCE) and the secretion form of tumor necrosis factor-related apoptosis-inducing ligand (sTRAIL). rCE and/or sTRAIL were transduced in immortalized human fetal NSCs, HB1.F3. The cytotoxic effects of the therapeutic cells on human lung cancer cells were evaluated in vitro with the ligands and decoy receptor expression for sTRAIL in the presence of CPT-11. Human NSCs encoding rCE (F3.CE and F3.CE.sTRAIL) significantly inhibited the growth of lung cancer cells in the presence of CPT-11 in vitro. Lung cancer cells were inoculated in immune-deficient mice, and therapeutic cells were transplanted systematically through intracardiac arterial injection and then treated with CPT-11. In resting state, DR4 expression in lung cancer cells and DcR1 in NSCs increased to 70% and 90% after CPT-11 addition, respectively. The volumes of the tumors in immune-deficient mice were reduced significantly in mice with F3.CE.sTRAIL transplantation and CPT-11 treatment. The survival was also significantly prolonged with treatment with F3.sTRAIL and F3.CE plus CPT-11 as well as F3.CE.sTRAIL plus CPT-11. NSCs transduced with rCE and sTRAIL genes showed a significant anti-cancer effect on brain metastatic lung cancer in vivo and in vitro, and the effect may be synergistic when rCE/CPT-11 and sTRAIL are combined. This stem-cell-based study using two therapeutic genes of different biological effects can be translatable to clinical application.

Negative association between high temperature-humidity index and milk performance and quality in Korean dairy system: big data analysis.

The aim of this study was to investigate the effects of heat stress on milk traits in South Korea using comprehensive data (dairy production and climate). The dataset for this study comprised 1,498,232 test-day records for milk yield, fat- and protein-corrected milk, fat yield, protein yield, milk urea nitrogen (MUN), and somatic cell score (SCS) from 215,276 Holstein cows (primiparous: n = 122,087; multiparous: n = 93,189) in 2,419 South Korean dairy herds. Data were collected from July 2017 to April 2020 through the Dairy Cattle Improvement Program, and merged with meteorological data from 600 automatic weather stations through the Korea Meteorological Administration. The segmented regression model was used to estimate the effects of the temperature-humidity index (THI) on milk traits and elucidate the break point (BP) of the THI. To acquire the least-squares mean of milk traits, the generalized linear model was applied using fixed effects (region, calving year, calving month, parity, days in milk, and THI). For all parameters, the BP of THI was observed; in particular, milk production parameters dramatically decreased after a specific BP of THI (p < 0.05). In contrast, MUN and SCS drastically increased when THI exceeded BP in all cows (p < 0.05) and primiparous cows (p < 0.05), respectively. Dairy cows in South Korea exhibited negative effects on milk traits (decrease in milk performance, increase in MUN, and SCS) when the THI exceeded 70; therefore, detailed feeding management is required to prevent heat stress in dairy cows.

ATF6 is a critical regulator of cadmium-mediated apoptosis in spermatocytes.

In this study, we examined the mechanisms of cadmium exposure-induced endoplasmic reticulum (ER) stress response and apoptosis in spermatocytes. Responses to cadmium toxicity were investigated using spermatocytes overexpressing p50ATF6, ATF4, and spliced XBP1s, belonging to the 3 unfolded protein response pathways. The ER stress and apoptosis response to cadmium were most strongly stimulated through the activating transcription factor 6 (ATF6) pathway; in contrast, siRNA-induced inhibition of protein expression could reduce apoptosis under stressful conditions. An in vivo experiment using mice confirmed that upregulation of p50ATF6 in the testis increased apoptosis in response to cadmium exposure. Further, when confirming the correlation between ER stress and MAPK in cadmium toxicity, p38 MAPK phosphorylation was strongly regulated by p50ATF6; p-p38 also mediated the activity of p50ATF6. Overall, these findings suggest that modulating the activity of p38 MAPK and p50ATF6 in cadmium exposure-induced toxicity can be considered a potential strategy to treat infertility.

Development of a novel endolysin, PanLys.1, for the specific inhibition of Peptostreptococcus anaerobius.

OBJECTIVE: The objective of this study was to develop a novel endolysin (PanLys.1) for the specific killing of the ruminal hyper-ammonia-producing bacterium Peptostreptococcus anaerobius (P. anaerobius). METHODS: Whole genome sequences of P. anaerobius strains and related bacteriophages were collected from the National Center for Biotechnology Information database, and the candidate gene for PanLys.1 was isolated based on amino acid sequences and conserved domain database (CDD) analysis. The gene was overexpressed using a pET system in Escherichia coli BL21 (DE3). The lytic activity of PanLys.1 was evaluated under various conditions (dosage, pH, temperature, NaCl, and metal ions) to determine the optimal lytic activity conditions. Finally, the killing activity of PanLys.1 against P. anaerobius was confirmed using an in vitro rumen fermentation system. RESULTS: CDD analysis showed that PanLys.1 has a modular design with a catalytic domain, amidase-2, at the N-terminal, and a cell wall binding domain, from the CW-7 superfamily, at the C-terminal. The lytic activity of PanLys.1 against P. anaerobius was the highest at pH 8.0 (p<0.05) and was maintained at 37°C to 45°C, and 0 to 250 mM NaCl. The activity of PanLys.1 significantly decreased (p<0.05) after Mn2+ or Zn2+ treatment. The relative abundance of P. anaerobius did not decrease after administration PanLys.1 under in vitro rumen conditions. CONCLUSION: The application of PanLys.1 to modulate P. anaerobius in the rumen might not be feasible because its lytic activity was not observed in in vitro rumen system.

Ondine's curse: clinical presentation with diaphragmatic pacing and spontaneous respiratory recovery. Illustrative case.

BACKGROUND: The complexity of posterior fossa surgery can often lead to rare complications due to the anatomy involved. Vestibular schwannoma resection is a common pathology in the posterior fossa, often requiring surgical intervention. Given the proximity of this space to the brainstem, cranial nerve VII/VIII complex, and posterior inferior cerebellar artery (PICA), neurovascular complications are not infrequent. A rare vascular complication from this surgical approach is a lateral medullary infarction from injury to the lateral medullary segment of the proximal PICA, leading to central hypoventilation syndrome (CHS). OBSERVATIONS: This report presents a unique case of a 51-year-old man who underwent a retrosigmoid craniectomy for resection of a vestibular schwannoma. Following surgery, the patient was unable to be weaned off the ventilator and was noted to become apneic while he slept, a clinical picture consistent with Ondine's curse. LESSONS: This report discusses the anatomical considerations of this surgical corridor leading to this complication and the management of a patient with acquired Ondine's curse and reviews the scarce literature on this uncommon cause of acquired CHS.

A Sensing-Based Visualization Method for Representing Pressure Distribution in a Multi-Zone Building by Floor.

Airflow in a multi-zone building can be a major cause of pollutant transfer, excessive energy consumption, and occupants discomfort. The key to monitoring airflows and mitigating related problems is to obtain a comprehensive understanding of pressure relationships within the buildings. This study proposes a visualization method for representing pressure distribution within a multi-zone building by using a novel pressure-sensing system. The system consists of a Master device and a couple of Slave devices that are connected with each other by a wireless sensor network. A 4-story office building and a 49-story residential building were installed with the system to detect pressure variations. The spatial and numerical mapping relationships of each zone were further determined through grid-forming and coordinate-establishing processes for the building floor plan. Lastly, 2D and 3D visualized pressure mappings of each floor were generated, illustrating the pressure difference and spatial relationship between adjacent zones. It is expected that the pressure mappings derived from this study will allow building operators to intuitively perceive the pressure variations and the spatial layouts of the zones. These mappings also make it possible for operators to diagnose the differences in pressure conditions between adjacent zones and plan a control scheme for the HVAC system more efficiently.

Mitochondrial peroxiredoxin 5 overexpression suppresses insulin-induced adipogenesis by downregulating the phosphorylation of p38.

Obesity is caused by the accumulation of excess lipids due to an energy imbalance. Differentiation of pre-adipocytes induces abnormal lipid accumulation, and reactive oxygen species (ROS) generated in this process promote the differentiation of pre-adipocytes through mitogen-activated protein kinase (MAPK) signaling. Peroxiredoxin (Prx) is a potent antioxidant enzyme, and peroxiredoxin 5 (Prx5), which is mainly expressed in cytosol and mitochondria, inhibits adipogenesis by regulating ROS levels. Based on previous findings, the present study was performed to investigate whether cytosolic Prx5 (CytPrx5) or mitochondrial Prx5 (MtPrx5) has a greater effect on the inhibition of adipogenesis. In this study, MtPrx5 decreased insulin-mediated ROS levels to reduce adipogenic gene expression and lipid accumulation more effectively than CytPrx5. In addition, we found that p38 MAPK mainly participates in adipogenesis. Furthermore, we verified that MtPrx5 overexpression suppressed the phosphorylation of p38 during adipogenesis. Thus, we suggest that MtPrx5 inhibits insulin-induced adipogenesis more effectively than CytPrx5.

Established Immortalized Cavernous Endothelial Cells Improve Erectile Dysfunction in Rats with Cavernous Nerve Injury.

The main cause of erectile dysfunction (ED) is the damage in penile cavernous endothelial cells (EC). Murine primary ECs have a limited growth potential, and the easy availability of murine ECs will facilitate the study of cavernous endothelial dysfunction in rats. This study was performed to establish immortalized rat penile cavernous ECs (rEC) and investigate how they could repair erectile dysfunction in rats with cavernous nerve injury (CNI). rEC was isolated enzymatically by collagenase digestion and were cultured. An amphotropic replication-incompetent retroviral vector encoding v-myc oncogene was used to transfect rEC for immortalization (vREC). Morphological and immunohistochemical properties of vREC were examined. Eight-week-old male Sprague-Dawley rats were divided into three groups of five rats each, including group 1 = sham operation, group 2 = bilateral CN injury, group 3 = vREC (1 × 106 cells) treatment after CNI. Erectile response was assessed at 2, 4 weeks after transplantation of vREC., Penile tissue were harvested at 4 weeks after transplantation and immune−histochemical examination was performed. vREC showed the expression of CD31, vWF, cell type-specific markers for EC by RT-PCR and flowcytometry. At 2, 4 weeks after transplantation, rats with CNI had significantly lower erectile function than control group (p < 0.05). The group transplanted with vREC showed higher erectile function than the group without vRECs (p < 0.05). vREC was established and repaired erectile dysfunction in rats with CNI. This cell line may be useful for studying mechanisms and drug screening of erectile dysfunction of rats.

PCNB exposure during early embryogenic development induces developmental delay and teratogenicity by altering the gene expression in Xenopus laevis.

Pentachloronitrobenzene (PCNB) is an organochlorine fungicide commonly used to treat seeds against seedling infections and controlling snow mold on golf courses. PCNB has been demonstrated to be toxic to living organisms, including fish and several terrestrial organisms. However, only phenotypical deformities have been studied, and the effects of PCNB on early embryogenesis, where primary organogenesis occurs, have not been completely studied. In the current study, the developmental toxicity and teratogenicity of PCNB is evaluated by using frog embryo teratogenesis assay Xenopus (FETAX). Our results confirmed the teratogenic potential of PCNB revealing the teratogenic index of 1.29 during early embryogenesis. Morphological studies revealed tiny head, bent axis, reduced inter ocular distance, hyperpigmentation, and reduced total body lengths. Whole mount in situ hybridization and reverse transcriptase polymerase chain reaction were used to identify PCNB teratogenic effects at the gene level. The gene expression analyses revealed that PCNB was embryotoxic to the liver and heart of developing embryos. Additionally, to determine the most sensitive developmental stages to PCNB, embryos were exposed to the compound at various developmental stages, demonstrating that the most sensitive developmental stage to PCNB is primary organogenesis. Taken together, we infer that PCNB's teratogenic potential affects not just the phenotype of developing embryos but also the associated genes and involving the oxidative stress as a possible mechanism of toxicity, posing a hazard to normal embryonic growth. However, the mechanisms of teratogenesis require additional extensive investigation to be defined completely.

Intra Prediction Method for Depth Video Coding by Block Clustering through Deep Learning.

In this paper, we propose an intra-picture prediction method for depth video by a block clustering through a neural network. The proposed method solves a problem that the block that has two or more clusters drops the prediction performance of the intra prediction for depth video. The proposed neural network consists of both a spatial feature prediction network and a clustering network. The spatial feature prediction network utilizes spatial features in vertical and horizontal directions. The network contains a 1D CNN layer and a fully connected layer. The 1D CNN layer extracts the spatial features for a vertical direction and a horizontal direction from a top block and a left block of the reference pixels, respectively. 1D CNN is designed to handle time-series data, but it can also be applied to find the spatial features by regarding a pixel order in a certain direction as a timestamp. The fully connected layer predicts the spatial features of the block to be coded through the extracted features. The clustering network finds clusters from the spatial features which are the outputs of the spatial feature prediction network. The network consists of 4 CNN layers. The first 3 CNN layers combine two spatial features in the vertical and horizontal directions. The last layer outputs the probabilities that pixels belong to the clusters. The pixels of the block are predicted by the representative values of the clusters that are the average of the reference pixels belonging to the clusters. For the intra prediction for various block sizes, the block is scaled to the size of the network input. The prediction result through the proposed network is scaled back to the original size. In network training, the mean square error is used as a loss function between the original block and the predicted block. A penalty for output values far from both ends is introduced to the loss function for clear network clustering. In the simulation results, the bit rate is saved by up to 12.45% under the same distortion condition compared with the latest video coding standard.

Generation of induced pluripotent stem cells (cmESF-iPS-C5) derived from cynomolgus monkey ear skin fibroblasts (cmESF).

Cynomolgus monkeys, due to their close anatomical, genetic and physiological similarity to humans, have been employed as a popular laboratory non-human primate model over rodents. Primate animal induced pluripotent stem cell (iPSC) have been used to aid on the investigation of autologous regenerative therapies. Here, we reprogrammed cynomolgus monkey ear skin fibroblasts (cmESFs) into iPSCs as a starting material for autologous based study. The resulting cmESF-iPSCs with canonical features of PSCs will advance the development of autologous transplantation.