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RationalePulmonary fibrosis is a devastating lung disease with few therapeutic options. Chitinase 1 (CHIT1), an 18 glycosyl hydrolase family member, contributes to the pathogenesis of pulmonary fibrosis through regulation of Transforming Growth Factor (TGF)-β signaling and effector function. Therefore, CHIT1 is a potential therapeutic target of pulmonary fibrosis.ObjectivesThis study aimed to identify and characterize a druggable CHIT1 inhibitor with strong antifibrotic activity and minimal toxicity for therapeutic application to pulmonary fibrosis.MethodsExtensive screening of small molecule libraries identified the aminoglycoside antibiotic Kasugamycin as a potent CHIT1 inhibitor.Measurements and Main ResultsElevated levels of CHIT1 were detected in the lungs of patients with pulmonary fibrosis. In vivo bleomycin- and TGF-β-stimulated murine models of pulmonary fibrosis, Kasugamycin showed impressive anti-fibrotic effects in both preventive and therapeutic conditions. In vitro studies also demonstrated that Kasugamycin inhibits fibrotic macrophage activation, fibroblast proliferation and myofibroblast transformation. Null mutation of transforming growth factor beta associated protein 1 (TGFBRAP1), a recently identified CHIT1 interacting signaling molecule, phenocopied antifibrotic effects of Kasugamycin in in vivo lungs and in vitro fibroblasts responses. Kasugamycin inhibits physical association between CHIT1 and TGFBRAP1, suggesting that antifibrotic effect of Kasugamycin is mediated through regulation of TGFBRAP1, at least in part.ConclusionsThese studies demonstrate that Kasugamycin is a novel CHIT1 inhibitor with strong antifibrotic effect that can be further developed as an effective and safe therapeutic drug for pulmonary fibrosis.

Background: Bariatric or metabolic surgery is a safe and effective intervention for patients with obesity at higherrisk. In 2019, after the reimbursement in Korea, the number of metabolic surgery cases has rapidly increased. We aimed to introduce the current metabolic surgery concepts.Current Concepts: Patients with a body mass index (BMI) of ≥35 kg/m2 without coexisting medical problems and those with a BMI of ≥30 kg/m2 and ≥1 severe obesity-related complication remediable by weight loss could be considered as the candidates for metabolic surgery. The standardized and effective procedures are adjustable gastric banding, sleeve gastrectomy, Roux-en-Y gastric bypass, and biliopancreatic diversion with duodenal switch. The decision on bariatric procedures should be based on the characteristics of patients considering the effectiveness and anticipated complications.Discussion and Conclusion: Metabolic surgery was shown to induce greater weight loss, better control of comorbidities, such as type 2 diabetes, hypertension, and dyslipidemia, and more significant decrease in death compared to that of the nonsurgical approach. Postoperatively, a comprehensive approach consisting of psychosocial, behavioral, nutritional, and pharmacological aspects should be performed to amplify and maintain the effectiveness of metabolic surgery.

IntroductionPrealbumin (PAB) is a plasma protein synthesized in the hepatic parenchymal cells. PAB has a short half-life (~2 days), and its concentration is affected by changes in transcapillary escape. Measurement of PAB is widely used in hospitalized patients in human medicine due to its decreasing concentration in states of inflammation and malnutrition. However, only a few studies are available in dogs. The aim of this study is to determine whether the plasma PAB concentration decreases in dogs with inflammation and to evaluate the relationship between the plasma PAB concentration and inflammation-related parameters in dogs.MethodsA total of 94 dogs were divided into healthy (n = 33) and diseased (n = 61) groups. These were further divided into group A (n = 24) and group B (n = 37) according to plasma C-reactive protein (CRP) levels. Group A included dogs with a plasma CRP ResultsThe plasma PAB concentration was found to be lower in group B than in the other groups (p p > 0.05). A plasma PAB r = −0.670, p ConclusionIn conclusion, this is the first study to demonstrate the clinical usefulness of the plasma PAB concentration as an inflammatory marker in dogs. These findings suggest that measuring the plasma PAB concentration along with the CRP concentration may be more useful for evaluating inflammation than measuring CRP alone in canine patients.

Rice cultivars with floury endosperm provide a useful raw material for producing dry-milled rice flour, helping to enhance the processed rice food industry. To expand the genetic resources for breeding floury endosperm rice cultivars, we developed Samkwang(SA)-flo3 (SK-flo3), a floury endosperm mutant line derived from the chemical mutagenesis of Samkwang, an elite Korean japonica rice cultivar. Compared with Samkwang, SK-flo3 showed significantly lower grain hardness, which is suitable for producing dry-milled flour without the soaking and drying processes required in regular wet rice milling. The dry-milled flour of SK-flo3 exhibited excellent physicochemical properties with less damaged starch and finer flour particles relative to Samkwang. Genetic analyses revealed a G-to-A point mutation in exon 7 of cyOsPPDKB, substituting glycine with aspartic acid as a causative mutation for the floury endosperm of SK-flo3. We named this allele flo4-6 and developed a molecular marker to efficiently transfer it to commercial rice cultivars. Our results provide useful genetic resources and information for developing specialty rice cultivars for high-quality rice flour production with reduced milling costs.

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Effective activation of dendritic cells (DCs) toward T helper (Th)-1 cell polarization would improve DC-based antitumor immunotherapy, helping promote the development of immunotherapeutic vaccines based on T-cell immunity. To achieve this goal, it is essential to develop effective immune adjuvants that can induce powerful Th1 cell immune responses. The pathogenic organism Mycobacterium tuberculosis includes certain constitutes, such as heparin-binding hemagglutinin (HBHA), that possess a strong immunostimulatory potential. In this study, we report the first clarification of the functions and precise mechanism of HBHA in immune stimulation settings relevant to cancer. HBHA induced DC maturation in a TLR4-dependent manner, elevating expression of the surface molecules CD40, CD80, and CD86, MHC classes I and II and the proinflammatory cytokines IL-6, IL-12, IL-1β, TNF-α, and CCR7, as well as stimulating the migratory capacity of DCs in vitro and in vivo. Mechanistic investigations established that MyD88 and TRIF signaling pathways downstream of TLR4 mediated secretion of HBHA-induced proinflammatory cytokines. HBHA-treated DCs activated naïve T cells, polarized CD4+ and CD8+ T cells to secrete IFN-γ, and induced T-cell–mediated cytotoxicity. Notably, systemic administration of DCs that were HBHA-treated and OVA251–264-pulsed ex vivo greatly strengthened immune priming in vivo, inducing a dramatic regression of tumor growth associated with long-term survival in a murine E.G7 thymoma model. Together, our findings highlight HBHA as an immune adjuvant that favors Th1 polarization and DC function for potential applications in DC-based antitumor immunotherapy. Cancer Res; 71(8); 2858–70. ©2011 AACR.

The prototypic chitinase-like protein Chi3l1 is induced in cancers and portends a poor prognosis, but whether it contributes to cancer progression is unknown. To address this gap in knowledge, we investigated the production of Chi3l1 in melanoma lung metastases. We found that Chi3l1 was induced during pulmonary melanoma metastasis and that this induction was regulated by the semaphorin Sema7a, interacting in stimulatory or inhibitory ways with its β1 integrin or Plexin C1 receptors, respectively. In mouse strains with genetic deletions of Chi3l1 or Sema7a, there was a significant reduction in pulmonary metastasis. Notably, antiserum raised against Chi3l1 or Sema7a phenocopied the reduction produced by genetic deletions. Melanoma lung metastasis was also decreased in the absence of IL13Rα2, a recently identified receptor for Chi3l1, consistent with a key role for Chi3l1 in melanoma spread. We confirmed roles for Sema7a and Chi3l1 in pulmonary metastasis of EMT6 breast cancer cells. Taken together, our studies establish a novel pathway through which Sem7a and its receptors regulate Chi3l1, revealing a host axis involving IL13Rα2 that plays a critical role in generating a pulmonary microenvironment that is critical to license metastasis. Cancer Res; 75(3); 487–96. ©2014 AACR.

Supplementary Figures 1-5. Supplementary Figure 1. Dose and time kinetic evaluation of the production of Chi3l1 by recombinant murine Sema7a (rmSema7a) stimulated macrophages. Supplementary Figure 2. Double label immunohistochemical staining of CD4, Ly-6G, and Chi3l1. Supplementary Figure 3. Growth of melanoma cells 10 weeks of B16-F10 cell subcutaneous (s.c.) inoculation. Supplementary Figure 4. The expression of Chi3l1 and Sema7a in lungs with and without metastatic breast cancer cells. Supplementary Figure 5. Role of integrin β3 in Sema7a-stimualted expression of Chi3l1.

Supplementary Methods, Figures 1-6 from Enhanced Efficacy of Therapeutic Cancer Vaccines Produced by Co-Treatment with Mycobacterium tuberculosis Heparin-Binding Hemagglutinin, a Novel TLR4 Agonist

A new method of dose calculation algorithm, called GPU-accelerated Monte Carlo and collapsed cone Convolution (GMCC) was developed to improve the calculation speed of BNCT treatment planning system. The GPU-accelerated Monte Carlo routine in GMCC is used to simulate the neutron transport over whole energy range and the Collapsed Cone Convolution method is to calculate the gamma dose. Other dose components due to alpha particles and protons, are calculated using the calculated neutron flux and reaction data. The mathematical principle and the algorithm architecture are introduced. The accuracy and performance of the GMCC were verified by comparing with the FLUKA results. A water phantom and a head CT voxel model were simulated. The neutron flux and the absorbed dose obtained by the GMCC were consistent well with the FLUKA results. In the case of head CT voxel model, the mean absolute percentage error for the neutron flux and the absorbed dose were 3.98% and 3.91%, respectively. The calculation speed of the absorbed dose by the GMCC was 56 times faster than the FLUKA code. It was verified that the GMCC could be a good candidate tool instead of the Monte Carlo method in the BNCT dose calculations.

Herein, an unprecedented report is presented on the incorporation of size-dependent gold nanoparticles (AuNPs) with polyvinylpyrrolidone (PVP) capping into a conventional hole transport layer, poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS). The hole transport layer blocks ion-diffusion/migration in methylammonium-lead-bromide (MAPbBr3)-based perovskite light-emitting diodes (PeLEDs) as a modified interlayer. The PVP-capped 90 nm AuNP device exhibited a seven-fold increase in efficiency (1.5%) as compared to the device without AuNPs (0.22%), where the device lifetime was also improved by 17-fold. This advancement is ascribed to the far-field scattering of AuNPs, modified work function and carrier trapping/detrapping. The improvement in device lifetime is attributed to PVP-capping of AuNPs which prevents indium diffusion into the perovskite layer and surface ion migration into PEDOT:PSS through the formation of induced electric dipole. The results also indicate that using large AuNPs (> 90 nm) reduces exciton recombination because of the trapping of excess charge carriers due to the large surface area.

Situs inversus totalis (SIT) is a rare anatomical condition, where all the viscera appear in its reverse position. Although minimally invasive surgery has evolved to achieve totally laparoscopic gastrectomy for gastric cancer patients with SIT, it is difficult to perform lymphadenectomy in such a transposed anatomical condition. Recently, we performed a single-port laparoscopic total gastrectomy (SPTG) for gastric cancer in a patient with SIT. No postoperative complications or dietary problems were observed. Based on this experience, we are to design a safe strategy to perform D2 lymphadenectomy during SPTG in patients with SIT.

Foregut surgery largely involves benign diseases, and not only malignant diseases. However, for foregut surgeons in Asia, this fact has not been extensively utilized in their clinical practice due to the high burden of gastric cancer surgery. Although the prevalence of gastroesophageal reflux disease (GERD) in Eastern Asia, including Korea, is increasing, antireflux surgery (ARS) is still a fairly rare procedure in Korea. ARS is effective as proton pump inhibitors and is cost-effective compared to continuous double-dose proton pump inhibitors in patients with severe GERD. Therefore, we should focus on ARS as a treatment option for GERD also in Asian population. Similarly, although bariatric/metabolic surgery is effective in weight reduction and diabetes mellitus (DM) remission in patients with morbid obesity or DM, bariatric/metabolic surgery is only performed in a limited number of patients. Given that the prevalence of obesity and DM is continuously increasing in Korea, bariatric/metabolic surgery should become an interest among Korean foregut surgeons and should be considered a treatment for obesity and DM. Furthermore, there are new surgical fields that can control both benign and malignant diseases. Oncometabolic surgery is a field under foregut surgery that treats both malignant and benign components of a condition, an example being the control of metabolic syndrome while performing gastric cancer surgery. Therefore, in future gastric cancer treatment, oncometabolic surgery can be applied to patients with gastric cancer accompanied by obesity or metabolic syndrome.

ICOS/ICOSL and CD28/B7-1/B7-2 are T cell co-stimulators and CTLA-4 is an immune checkpoint inhibitor that play critical roles in the pathogenesis of neoplasia. Chitinase 3-like-1 (CHI3L1) is induced in many cancers where it portends a poor prognosis and contributes to tumor metastasis. Here we demonstrate that CHI3L1 inhibits the expression of ICOS, ICOSL and CD28 while stimulating CTLA-4 and the B7 moieties in melanoma lung metastasis. We also demonstrate that RIG-like helicase innate immune activation augments T cell co-stimulation, inhibits CTLA-4 and suppresses pulmonary metastasis. At least additive antitumor responses were seen in melanoma lung metastasis treated with anti-CTLA-4 and anti-CHI3L1 antibodies in combination. Synergistic cytotoxic T cell-induced tumor cell death and the heightened induction of the tumor suppressor PTEN were seen in co-cultures of T and tumor cells treated with bispecific antibodies that target both CHI3L1 and CTLA-4. Thus, CHI3L1 contributes to pulmonary metastasis by inhibiting T cell co-stimulation and stimulating CTLA-4. The simultaneous targeting of CHI3L1 and the CTLA-4 axis with individual and, more powerfully with bispecific antibodies, represent promising therapeutic strategies for pulmonary metastasis.

BACKGROUND Optimal length of biliopancreatic (BP) and Roux limb in Roux-en-Y gastric bypass (RYGB) for improved glycemic control are not known. PURPOSE To investigate how the lengths of the BP and Roux limbs in RYGB differentially affect postoperative glycemic outcomes in patients with type 2 diabetes. DATA SOURCES We conducted a systematic literature search using the PubMed, Embase, and the Cochrane Library databases. STUDY SELECTION We included studies that reported glycemic outcomes after RYGB and lengths of the BP and Roux limbs. DATA EXTRACTION A total of 28 articles were included for data extraction. Glycemic outcomes after RYGB were assessed on the basis of two definitions: remission and improvement. DATA SYNTHESIS We categorized the included studies into four groups according to the BP and Roux limb lengths. The type 2 diabetes remission/improvement rates were as follows: long BP–long Roux group 0.80 (95% CI 0.70–0.90)/0.81 (0.73–0.89), long BP–short Roux group 0.76 (0.66–0.87)/0.82 (0.75–0.89), short BP–long Roux group 0.57 (0.36–0.78)/0.64 (0.53–0.75), and short BP–short Roux group 0.62 (0.43–0.80)/0.53 (0.45–0.61). Meta-regression analysis also showed that a longer BP limb resulted in higher postoperative type 2 diabetes remission and improvement rates, whereas a longer Roux limb did not. There was no significant difference or heterogeneity in baseline characteristics, including diabetes-related variables, among the four groups. LIMITATIONS Not all included studies were randomized controlled trials. CONCLUSIONS Longer BP limb length led to higher rates of type 2 diabetes remission and improvement by 1 year after RYGB in comparisons with the longer Roux limb length.

The objective of this study was to evaluate the efficacy of an imidacloprid 10% and flumethrin 4.5% polymer matrix collar against the developmental stages of Haemaphysalis longicornis infesting dogs using the hair from treated dogs in a semi-in-vitro assay set. When incubated with 0.5 g of the hair collected from the dogs installed with the drug-embedded collar after 10 days, average death rate of the larval, nymphal, and adult H. longicornis was 21.5%, 77.9%, and 100% at 30 min, 1 hr, and 2 hr, respectively. This study showed the larval stages as well as the nymphal and adult stages of H. longicornis ticks are killed upon contact with the hair from dogs treated with the collar within 2 hr.

ICOS/ICOSL and CD28/B7-1/B7-2 are T cell co-stimulators and CTLA-4 is an immune checkpoint inhibitor that play critical roles in the pathogenesis of neoplasia. Chitinase 3-like-1 (CHI3L1) is induced in many cancers where it portends a poor prognosis and contributes to tumor metastasis. Here we demonstrate that CHI3L1 inhibits the expression of ICOS, ICOSL and CD28 while stimulating CTLA-4 and the B7 moieties in melanoma lung metastasis. We also demonstrate that RIG-like helicase innate immune activation augments T cell co-stimulation, inhibits CTLA-4 and suppresses pulmonary metastasis. At least additive antitumor responses were seen in melanoma lung metastasis treated with anti-CTLA-4 and anti-CHI3L1 antibodies in combination. Synergistic cytotoxic T cell-induced tumor cell death and the heightened induction of the tumor suppressor PTEN were seen in co-cultures of T and tumor cells treated with bispecific antibodies that target both CHI3L1 and CTLA-4. Thus, CHI3L1 contributes to pulmonary metastasis by inhibiting T cell co-stimulation and stimulating CTLA-4. The simultaneous targeting of CHI3L1 and the CTLA-4 axis with individual and, more powerfully with bispecific antibodies, represent promising therapeutic strategies for pulmonary metastasis.

Indole-3-carbinol (I3C) is a phytochemical that exhibits growth-inhibitory activity against various cancer cells. However, there are limited studies on the effects of I3C on colon cancer cells. In this study, the growth-inhibitory activity of I3C against the human colorectal carcinoma cell line (LoVo) was examined. The results of the 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyltetrazolium bromide, colony formation, and cell counting assays revealed that I3C suppressed the proliferation of LoVo cells. Microscopy and wound-healing analyses revealed that I3C affected the morphology and inhibited the migration of LoVo cells, respectively. I3C induced apoptosis and DNA fragmentation as evidenced by the results of fluorescein isothiocyanate-conjugated annexin V staining and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling assay, respectively. Additionally, I3C arrested the cell cycle at the G0/G1 phase and enhanced the reactive oxygen species levels. Western blotting analysis revealed that treatment with I3C resulted in the activation of apoptotic proteins, such as poly(ADP-ribose) polymerase, caspase-3, caspase-7, caspase-9, Bax, Bim, and p53 in LoVo cells. These results indicate that I3C induces apoptosis in LoVo cells by upregulating p53, leading to the activation of Bax and caspases. Taken together, I3C exerts cytotoxic effects on LoVo cells by activating apoptosis.

Background The stability of cultivation and production in terms of crop yield has been threatened by climate change due to global warming. Pre-harvest sprouting (PHS) is a threat to crops, especially staple foods, including rice, because of reductions in yield and quality. To address the problem of precocious germination before harvest, we performed quantitative trait loci (QTL) analysis for PHS using F8 RILs populations derived from japonica weedy rice in Korea. Results QTL analysis revealed that two stable QTLs, qPH7 and qPH2, associated with PHS resistance were identified on chromosomes 7 and 2, respectively, explaining approximately 38% of the phenotypic variation. The QTL effect in the tested lines significantly decreased the degree of PHS, based on the number of QTLs included. Through fine mapping for main QTL qPH7, the region for the PHS was found to be anchored within 23.575–23.785 Mbp on chromosome 7 using 13 cleaved amplified sequence (CAPS) markers. Among 15 open reading frames (ORFs) within the detected region, one ORF, Os07g0584366, exhibited upregulated expression in the resistant donor, which was approximately nine times higher than that of susceptible japonica cultivars under PHS-inducing conditions. Conclusion A QTLs introgression japonica line was developed to improve the characteristics of PHS and design practical PCR-based DNA markers for marker-assisted backcrosses of many other PHS-susceptible japonica cultivars.

Eco-friendliness is an important global issue, and the maritime field is no exception. Predicting the composition of exhaust gases emitted by ship engines will be of consequence in this respect. Therefore, in this study, exhaust gas data were collected from the generator engine of a real ship along with engine-related data to predict emission characteristics. This is because installing an emission gas analyzer on a ship has substantial economic burden, and, even if it is installed, the accuracy can be increased by a virtual sensor. Furthermore, data were obtained with and without operating the SCR (often mounted on ships to reduce NOx), which is a crucial facility to satisfy environment regulation. In this study, four types of datasets were created by adding cooling and electrical-related variables to the basic engine dataset to check whether it improves model performance or not; each of these datasets consisted of 15 to 26 variables as inputs. CO2 (%), NOx (ppm), and tEx (°C) were predicted from each dataset using an artificial neural network (ANN) model and a support vector machine (SVM) model with optimal hyperparameters selected by trial and error. The results confirmed that the SVM model performed better on smaller datasets, such as the one used in this study compared to the ANN model. Moreover, the dataset type, DaCE, which had both cooling and electrical-related variables added to the basic engine dataset, yielded the best overall prediction performance. When the performance of the SVM model was measured using the test data of a DaCE on both no-SCR mode and SCR mode, the RMSE (R2) of CO2 was between 0.1137% (0.8119) and 0.0912% (0.8975), the RMSE (R2) of NOx was between 17.1088 ppm (0.9643) and 13.6775 ppm (0.9776), and the RMSE (R2) of tEx was between 4.5839 °C (0.8754) and 1.5688 °C (0.9392).

The desire to enhance the efficiency of organic light-emitting devices (OLEDs) has driven to the investigation of advanced materials with fascinating properties. In this work, the efficiency of top-emission OLEDs (TEOLEDs) is enhanced by introducing ampicillin microstructures (Amp-MSs) with dual phases (α-/β-phase) that induce photoluminescence (PL) and electroluminescence (EL). Moreover, Amp-MSs can adjust the charge balance by Fermi level (E

As the development of autonomous ships is underway in the maritime industry, the automation of ship spare part management has become an important issue. However, there has been little development of dedicated devices or applications for ships. This study aims to develop a Raspberry Pi-based embedded application that identifies the type and quantity of spare parts using a transfer learning model and image processing algorithm suitable for ship spare part recognition. A newly improved image processing algorithm was used to select a transfer learning model that balances accuracy and training speed through training and validation on a real spare parts dataset, achieving a prediction accuracy of 98.2% and a training time of 158 s. The experimental device utilizing this model used a camera to identify the type and quantity of spare parts on an actual ship. It displayed the spare parts list on a remotely connected computer. The ASSM (Automated Ship Spare-Part Management) device utilizing image processing and transfer learning is a new technology that successfully automates spare part management.

Grain shape is one of the key factors deciding the yield product and the market value as appearance quality in rice (Oryza sativa L.). The grain shape of japonica cultivars in Korea is quite monotonous because the selection pressure of rice breeding programs works in consideration of consumer preference. In this study, we identified QTLs associated with grain shape to improve the variety of grain shapes in Korean cultivars. QTL analysis revealed that eight QTLs related to five tested traits were detected on chromosomes 2, 5, and 10. Among them, three QTLs—qGL2 (33.9% of PEV for grain length), qGW5 (64.42% for grain width), and qGT10 (49.2% for grain thickness)—were regarded as the main effect QTLs. Using the three QTLs, an ideal QTL combination (qGL2P + qGW5P + qGT10B) could be constructed on the basis of the accumulated QTL effect without yield loss caused by the change in grain shape in the population. In addition, three promising lines with a slender grain type were selected as a breeding resource with a japonica genetic background based on the QTL combination. The application of QTLs detected in this study could improve the grain shape of japonica cultivars without any linkage drag or yield loss.