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Lulu Wang, Yan Li, Luchun Li, Zhijuan Wu, Dan Yang, Huiwen Ma, Donglin Wang Oncology Department, Chongqing University Cancer Hospital & Chongqing Cancer Institute & Chongqing Cancer Hospital, Shapingba District, Chongqing, China Purpose: This study was conducted to compare the efficacy of a combination of icotinib and chemotherapy with icotinib or chemotherapy alone in untreated non-small cell lung cancer (NSCLC) patients harboring epidermal growth factor receptor (EGFR)-sensitive mutations and to analyze the curative effect of different treatments on different genetic mutations (EGFR 19 exon deletion and L858R mutation) in a real-life setting. Patients and methods: One hundred ninety-one patients were studied in this retrospective analysis from January 2013 to December 2015. The baseline characteristics, curative effects and adverse events of patients were analyzed. The primary endpoint was progression free survival (PFS). Results: Longer PFS and overall survival (OS), and better objective response rate (ORR) were observed in the combination group compared to icotinib or chemotherapy along. For patients with an EGFR 19 exon deletion, the PFS, OS, and ORR in the combination group were superior to those in the icotinib or chemotherapy group. For the patients with the EGFR L858R mutation, better PFS and ORR were observed in the combination group, but OS was not obviously prolonged. Grade 3 or 4 adverse events were most commonly reported with combination therapy or chemotherapy alone. No possible drug-related interstitial lung disease or of drug related deaths occurred. Conclusion: The combination of icotinib and chemotherapy in patients with untreated NSCLC harboring sensitive EGFR mutations resulted in improved PFS and OS,especially in those who harbored the EGFR exon 19 deletion. Keywords: non-small-cell lung cancer, EGFR-TKI, icotinib, chemotherapy, first-line treatment

Background: Numerous studies have assessed the efficacy and safety of fecal microbiota transplantation (FMT) as a therapy for ulcerative colitis (UC). However, the treatment processes and outcomes of these studies vary., Aim: To evaluate the efficacy and safety of FMT for treating UC by conducting a systematic meta-analysis., Methods: The inclusion criteria involved reports of adult patients with UC treated with FMT, while studies that did not report clinical outcomes or that included patients with infection were excluded. Clinical remission (CR) and endoscopic remission (ER) were the primary and secondary outcomes, respectively., Results: We included nine studies retrieved from five electronic databases. The FMT group had better CR than the control group [relative risk (RR) = 1.53; 95% confidence interval (CI): 1.19-1.94; P < 0.0008]. ER was statistically significantly different between the two groups (RR = 2.80; 95%CI: 1.93-4.05; P < 0.00001). Adverse events did not differ significantly between the two groups., Conclusion: FMT demonstrates favorable performance and safety; however, well-designed randomized clinical trials are still needed before the widespread use of FMT can be recommended. Furthermore, standardizing the FMT process is urgently needed for improved safety and efficacy., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

In this study, an active film composed of gallic acid (GA), chitosan (CS), and cellulose nanocrystals (CNC) was prepared using a solution casting method and synergistic photodynamic inactivation (PDI) technology. Characterization of the film showed that the CS-CNC-GA composite film had high transparency and UV-blocking ability. The addition of GA (0.2 %-1.0 %) significantly enhanced the mechanical properties, water resistance, and thermal stability of the film. The tensile strength increased up to 46.30 MPa, and the lowest water vapor permeability was 1.16 × e -12 g/(cm·s·Pa). The PDI-treated CS-CNC-GA1.0 composite film exhibited significantly enhanced antibacterial activity, with inhibition zone diameters of 31.83 mm against Staphylococcus aureus and 21.82 mm against Escherichia coli. The CS-CNC-GA composite film also showed good antioxidant activity. Additionally, the CS-CNC-GA 1.0 composite film generated a large amount of singlet oxygen under UV-C light irradiation. It was found that using the CS-CNC-GA 1.0 composite film for packaging and storage of oysters at 4 °C effectively delayed the increase in pH, total colony count, and lipid oxidation in oysters. In conclusion, the CS-CNC-GA composite film based on PDI technology has great potential for applications in the preservation of aquatic products., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

The gut microbial and metabolic characteristics of intestinal Behçet's disease (BD), a condition sharing many clinical similarities with ulcerative colitis (UC) and Crohn's disease (CD), are largely unexplored. This study investigated the gut microbial and metabolic characteristics of intestinal BD as well as potential biomarkers, comparing them with those in UC, CD, and healthy controls. Colon tissue and stool samples from 100 patients (35 UC, 30 CD, and 35 intestinal BD) and 41 healthy volunteers were analyzed using 16S ribosomal RNA sequencing to assess microbial diversity, taxonomic composition, and functional profiling. Plasma metabolomic analyses were performed using gas chromatography and ultra-performance liquid chromatography-mass spectrometry. Results indicated reduced microbial diversity in CD but not in intestinal BD, with intestinal BD showing fewer changes compared to controls yet distinct taxonomic features from UC, CD, and controls. Common alterations across all diseases included a reduction in beneficial bacteria producing short-chain fatty acids. Intestinal BD-specific changes featured a decreased abundance of Bacteroides fragilis. Metabolomic profiles in intestinal BD were similar to those in CD but distinct from those in UC, displaying significant changes in energy metabolism and genetic information processing. This integrative analysis revealed both shared and unique profiles in intestinal BD compared with UC, CD, and controls, advancing our understanding of the distinctive features of these diseases.

Anaerobic parasitic ciliates are a specialized group of ciliates that are adapted to anoxic and oxygen-depleted habitats. Among them, Balantidium polyvacuolum, which inhabits the hindgut of Xenocyprinae fishes, has received very limited scientific attention, so the molecular mechanism of its adaptation to the digestive tract microenvironment is still unclear. In this study, transmission electron microscopy (TEM) and single-cell transcriptome analysis were used to uncover the metabolism of B. polyvacuolum. Starch granules, endosymbiotic bacteria, and multiple specialized mitochondrion-related organelles (MROs) of various shapes were observed. The MROs may have completely lost the electron transport chain (ETC) complexes I, III, IV, and V and only retained succinate dehydrogenase subunit A (SDHA) of complex II. The tricarboxylic acid (TCA) cycle was also incomplete. It can be inferred that the hypoxic intestinal environment has led to the specialization of the mitochondria in B. polyvacuolum. Moreover, carbohydrate-active enzymes (CAZymes), including carbohydrate esterases, enzymes with a carbohydrate-binding module, glycoside hydrolases, and glycosyltransferases, were identified, which may constitute evidence that B. polyvacuolum is able to digest carbohydrates and starch. These findings can improve our knowledge of the energy metabolism and adaptive mechanisms of B. polyvacuolum., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background/aims: The purpose of the current study was to examine the anti-inflammatory effects of CKD-506, a novel histone deacetylase 6 inhibitor, on human peripheral blood mononuclear cells (PBMCs) and CD4+ T cells and to explore the relationship between CKD-506 and gut epithelial barrier function., Methods: Lipopolysaccharide-stimulated human PBMCs from inflammatory bowel disease (IBD) patients were treated with CKD-506, and tumor necrosis factor (TNF)-α expression was measured using an enzyme-linked immunosorbent assay. The proliferation of CD4+ T cells from IBD patients was evaluated using flow cytometric analysis. The effects of CKD-506 on gut barrier function in a cell line and colon organoids, based on examinations of mRNA production, goblet cell differentiation, and E-cadherin recovery, were investigated using quantitative reverse transcription polymerase chain reaction, immunofluorescence, and a fluorescein isothiocyanate-dextran permeability assay., Results: Secretion of TNF-α, a pivotal pro-inflammatory mediator in IBD, by lipopolysaccharide-triggered PBMCs was markedly decreased by CKD-506 treatment in a dose-dependent manner and to a greater extent than by tofacitinib or tubastatin A treatment. E-cadherin mRNA expression and goblet cell differentiation increased significantly and dose-dependently in HT-29 cells in response to CKD-506, and inhibition of E-cadherin loss after TNF-α stimulation was significantly reduced both in HT-29 cells and gut organoids. Caco-2 cells treated with CKD-506 showed a significant reduction in barrier permeability in a dose-dependent manner., Conclusions: The present study demonstrated that CKD-506 has anti-inflammatory effects on PBMCs and CD4 T cells and improves gut barrier function, suggesting its potential as a small-molecule therapeutic option for IBD.

In recent years, there has been an increase in the scientific production of youth soccer. However, a panoramic map of research on this subject does not exist. The aim of this study was to identify global research trends in youth soccer over time, among the main levels of analysis: sources, authors, documents, and keywords. The bibliometric software Biblioshiny was used to analyze 2606 articles in Web of Science (WoS) published between 2012 and 2021. The main conclusion is that US and UK scholars dominate the research; the topics of research are changing with the real needs, and research on the topic of performance has been of interest to scholars; talent identification and development, performance, injury prevention, and concussion are the studies of interest to scholars in this area. This finding, which offers a global picture of youth soccer research over time, can help future research in this or similar domains., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2023.)

Owing to their structural designability and tuneable properties, supramolecular metal-organic complexes have recently emerged as promising candidates for the sensing and detection of molecules and anions. Herein, we synthesised three tripyrazolate-linked [M 6 L 2 ] metallocages with the formulas [(bpyPd) 6 L 2 ](NO 3 ) 6 (1), [(dmbpyPd) 6 L 2 ](NO 3 ) 6 (2), and [(phenPd) 6 L 2 ](NO 3 ) 6 (3) (H 3 L = tris(4-(5-(trifluoromethyl)-1 H -pyrazol-3-yl)phenyl)amine, bpy = 2,2'-bipyridine, dmbpy = 4,4'-dimethylbipyridine, phen = 1,10-phenanthroline). Crystallography revealed that metal-directed coordination and the bidentate chelate behaviour of the ligand induced the self-assembly of supramolecular metal-organic cages. Notably, these cages were employed as turn-on fluorescence sensors for SO 2 and its derivative (HSO 3 - ) through a disassembly mechanism. Cages 1, 2, and 3 showed a highly selective and sensitive detection of HSO 3 - over other common anions in aqueous solutions and of SO 2 gas over other common gasses, with an excellent anti-interference ability. These metallocages were subsequently applied as sensors in environmental and biological samples. This study not only enriches the ongoing research on metal-organic supramolecular materials but also facilitates the future preparation of stimuli-responsive supramolecular coordination complexes.

Development of colorectal cancer (CRC) is regulated by a series of genetic and microenvironmental alterations. Olfactomedin 4 (OLFM4) is a secreted glycoprotein that is highly expressed in the gastrointestinal tract and modulates inflammation. However, the role of OLFM4 in CRC is uncertain. Here we aimed to explore the function of OLFM4 in CRC in vivo and in vitro. The mRNA expression of OLFM4 was up-regulated in precursor lesions with dysplasia or ulcerative colitis but was reduced in CRC. OLFM4 neutralizing antibody suppressed inflammation-mediated early-stage CRC formation in an AOM/DSS colitis-associated cancer model. OLFM4 knockdown cells exhibited increased cell proliferation and motility in vitro and in vivo. Ablation of OLFM4 increased tumor growth and metastasis in xenograft experiments. In addition, OLFM4 knockdown cells showed elevated expression of colon cancer stem cell markers including CD133, resulting in increased metastasis via epithelial-mesenchymal transition signaling. This study demonstrated that OLFM4 regulates inflammation and cancer progression differently; ablation of OLFM4 promotes cancer metastasis via stemness and epithelial-mesenchymal transition. These results suggest a new route for controlling cancer progression and metastasis., (© 2022. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Osteoporosis is a prevalent bone metabolic disease in menopause, and long-term medication is accompanied by serious side effects. Ginger, a food spice and traditional medicine with ancient history, exhibits the potential to alleviate osteoporosis in preclinical experiments, whereas its complex composition leads to ambiguous pharmacological mechanisms. The purpose of this study was to investigate the effect and mechanism of Ced in estrogen-deficient osteoporosis, a sesquiterpene alcohol recently discovered from Ginger with multiple pharmacological properties. RANKL was stimulated BMM (bone marrow macrophages) differentiation into osteoclasts in vitro. And the osteoclast activity and number were assessed by TRAcP and SEM. We found that Ced mitigated RANKL-induced osteoclastogenesis by descending the ROS content and obstructing NFATc1, NF-κB, and MAPK signaling. Also, Ced-mediated anti-osteolytic property was found in ovariectomized mice by Micro-CT scanning and histological staining. Summarily, our works demonstrated the anti-osteoporotic potential of Cedrol in Ginger for the first time, which also offered more pharmacological evidence for Ginger as food or medicine used for bone metabolic disease., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Recent studies have proposed three lymphatic drainage systems in the brain, that is, the glymphatic system, the intramural periarterial drainage pathway, and meningeal lymphatic vessels, whose roles in various neurological diseases have been widely explored. The glymphatic system is a fluid drainage and waste clearance pathway that utilizes perivascular space and aquaporin-4 protein located in the astrocyte endfeet to provide a space for exchange of cerebrospinal fluid and interstitial fluid. The intramural periarterial drainage pathway drives the flow of interstitial fluid through the capillary basement membrane and the arterial tunica media. Meningeal lymphatic vessels within the dura mater are involved in the removal of cerebral macromolecules and immune responses. After ischemic stroke, impairment of these systems could lead to cerebral edema, accumulation of toxic factors, and activation of neuroinflammation, while restoration of their normal functions can improve neurological outcomes. In this review, we summarize the basic concepts of these drainage systems, including drainage routes, physiological functions, regulatory mechanisms, and detection technologies. We also focus on the roles of lymphatic drainage systems in brain injury after ischemic stroke, as well as recent advances in therapeutic strategies targeting these drainage systems. These findings provide information for potential novel strategies for treatment of stroke., Competing Interests: None

A large number of female goats are needed for the dairy goat industry; therefore, the development of a method to ensure the birth of more females than males in a single pregnancy will lead to economic benefits. Increasing the number of X-sperm would be an effective way to increase the proportion of female offspring. In this study, goat semen was incubated at pH 7.4 in alkaline diluent combined with resiquimod (R848) and the number of X-sperm was enriched by the swim-up method. The percentage of X-sperm was determined using the double TaqMan qPCR method. Sperm total motility, progressive motility, average path velocity, straight-line velocity, and curvilinear velocity were measured using a computer-aided sperm analysis system, and the functional parameters of the sperm plasma membrane, the acrosome, mitochondrial activity, ATP content, and reactive oxygen species levels were also measured. Lastly, the ratio of female embryos was determined by in vitro fertilization, and the number of female kids and the pregnancy rate of does was assessed by artificial insemination. The results showed that dilution of semen in an alkaline buffer containing R848 could enrich the number of X-sperm to 85.57% ± 3.27%. The progressive motility, average path velocity, straight-line velocity, curvilinear velocity, mitochondrial activity, and ATP level of the collected X-sperm-enriched semen were significantly reduced, but its total motility, plasma membrane, and acrosome were not affected. The in vitro fertilization experiments showed that the rate of female embryo production using X-sperm-rich seminal fluid could reach 83.25% (174/209), which was significantly higher than the proportion of female embryos in the control group, 47.71% ± 1.80% (104/218). As determined by artificial insemination, the number of female kids in the test group increased by 62.79% (243/387), which was significantly higher than that in the control group (47.65%, 193/405). There was no significant difference in pregnancy rate between the test group and the control group (71.71% vs. 78.48%). Therefore, this study demonstrated that use of a pH 7.4 diluent containing R848 is a simple and effective method of X-sperm enrichment for dairy goat production. Its application would allow does to produce more female offspring for herd expansion and milk production., (The Authors. Published by Elsevier Inc. and Fass Inc. on behalf of the American Dairy Science Association®. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).)

Background: Glucocorticoids (GCs) overuse is associated with decreased bone mass and osseous vasculature destruction, leading to severe osteoporosis. Platelet lysates (PL) as a pool of growth factors (GFs) were widely used in local bone repair by its potent pro-regeneration and pro-angiogenesis. However, it is still seldom applied for treating systemic osteopathia due to the lack of a suitable delivery strategy. The non-targeted distribution of GFs might cause tumorigenesis in other organs., Results: In this study, PL-derived exosomes (PL-exo) were isolated to enrich the platelet-derived GFs, followed by conjugating with alendronate (ALN) grafted PEGylated phospholipid (DSPE-PEG-ALN) to establish a bone-targeting PL-exo (PL-exo-ALN). The in vitro hydroxyapatite binding affinity and in vivo bone targeting aggregation of PL-exo were significantly enhanced after ALN modification. Besides directly modulating the osteogenic and angiogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) and endothelial progenitor cells (EPCs), respectively, PL-exo-ALN also facilitate their coupling under GCs' stimulation. Additionally, intravenous injection of PL-exo-ALN could successfully rescue GCs induced osteoporosis (GIOP) in vivo., Conclusions: PL-exo-ALN may be utilized as a novel nanoplatform for precise infusion of GFs to bone sites and exerts promising therapeutic potential for GIOP., (© 2022. The Author(s).)

The incidence of tuberculosis remains high in South Korea; the management of latent tuberculosis infection (LTBI) has become the prime target for reducing the infection rate. The management of pediatric LTBI is especially crucial because children can serve as a long-term source of infection upon developing active tuberculosis. Therefore, it is important to assess pediatric LTBI using contact investigation and follow-up. We conducted a retrospective study on children aged between 0 and 18 years who visited our hospital for tuberculosis contact screening from February 2012 to February 2021. Tuberculosis index cases and their clinical characteristics were also reviewed retrospectively. A total of 350 children were investigated, and 68 of 247 (27.5%) were diagnosed with LTBI. The rate of LTBI (r = 7.98, p < 0.001) and the risk of loss to follow-up (r = 27.038, p < 0.001) were higher in cases with close household contact. Sputum (r = 10.992, p < 0.001) and positive acid-fast bacillus (AFB) stain (r = 4.458, p = 0.001) in tuberculosis index cases were related to the diagnosis of LTBI in pediatric contacts. Active management is needed for tuberculosis screening in pediatric contacts, especially when the contacts are older and the index case is within the family, and when the index case has sputum and has tested positive for AFB smear.

Objective: To understand the current situation of emergency department nurses' work engagement, and analyze the relationship between emergency department nurses' organizational climate perception, work-related acceptance actions and work engagement. Methods: In May 2021, 273 emergency department nurses from 6 class Ⅲ class a general hospitals in Tianjin were selected as the research objects by using the convenient sampling method, and the general information questionnaire, work input scale, nurses' organizational climate perception scale and work-related acceptance action questionnaire were used for questionnaire survey. The correlation between job involvement and nurses' organizational climate perception and job-related acceptance action was analyzed by pearson correlation, and the influencing factors of job involvement were analyzed by multiple linear regression. Results: The average score of job involvement was (3.57±0.45) , the average score of nurses' organizational climate perception was (3.29±0.69) , and the score of work-related acceptance action was 35.00 (29.00, 47.00) . The results of correlation analysis showed that there was a positive correlation between nurses' organizational climate perception, job acceptance action and job involvement in emergency department ( r =0.435, 0.518, P <0.05) . Multiple stepwise regression analysis showed that job acceptance, nurses' perception of organizational climate, health status, specialist nurses, education and emergency work years were the influencing factors of emergency department nurses' job involvement ( P <0.05) , accounting for 41.9% of the total variation. Conclusion: We should create a good organizational atmosphere, improve the acceptance of emergency department nurses to nursing work, and improve the level of nurses' work input.

Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide synthase and plays a significant role in the pathogenesis of arteriovenous fistula (AVF) dysfunction. The aim of this study is to evaluate the effect of far-infrared (FIR) therapy on the maturation and patency of newly-created AVFs in patients with advanced diabetic kidney disease (DKD) as well as the concurrent change in plasma ADMA. The study enrolled 144 participants with advanced DKD where 101 patients were randomly allocated to the FIR therapy group (N = 50) and control group (N = 51). Patients receiving FIR therapy had a decreased AVF failure rate within 12 months (16% versus 35.3%; p = 0.027); decreased incremental change of ADMA concentration at the 3rd and 12th month; increased AVF blood flow at the 1st, 3rd, and 12th month; increased 3-month physiologic maturation rate (88% versus 68.6%; p = 0.034); increased 1-year unassisted AVF patency rate (84% versus 64.7%; p = 0.017); and increased clinical AVF maturation rate within 12 months (84% versus 62.7%; p = 0.029) compared to the control group. The study demonstrates that FIR therapy can reduce the incremental changes in plasma ADMA concentration, which may be associated with the improvement of AVF prognosis in patients with advanced DKD.

Inflammatory bowel disease (IBD) is a chronic immune-mediated disorder characterized by prolonged inflammation of the gastrointestinal tract. IBD can result from gut barrier dysfunction, altered gut microbiota, and abnormal intestinal immunity induced by environmental factors in genetically susceptible individuals. Proton pump inhibitors (PPIs) such as rabeprazole are frequently employed for gastric acid inhibition. However, long-term PPI administration can alter the intestinal microbiome composition, possibly worsening IBD severity. The present study revealed that tegoprazan, a potassium-competitive acid blocker, significantly improved colitis in mice and enhanced the intestinal epithelial barrier function. Tegoprazan alleviated gut microbiota dysbiosis and enhanced the growth of Bacteroides vulgatus . In turn, B. vulgatus alleviated intestinal inflammation by inhibiting epithelial adhesion of pathogenic bacteria. Unlike rabeprazole, tegoprazan did not induce gut dysbiosis. Our findings provide novel insights into the potential role of tegoprazan as an intestinal protectant for IBD and as a therapeutic agent for gastric acid-related diseases., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Son, Park, Kim, Ma, Kim, Kim, Kim, Han, Kim and Cheon.)

In modern steelmaking, multiple processes comprise a continuous manufacturing system, but not all phosphorus content data are connected or integrated into a holistic and systematic database. Disconnected data hinder the improvement of material management and resource efficiency in the industry. The objective of this study was to establish a method to evaluate material flows, reduce uncertainty, and perform quality control for waste recycling in the steelmaking industry. The results indicate that 10% of the phosphorus input is present in the final products, 30% accumulates in the slags, and more than 60% of the total mass remains in the processes. Comparing the material flow analysis results obtained using static and probabilistic approaches, the partition ratio of the phosphorus content in slags changes from 24.07% to 40.78%, but that in processes changes from 49.10% to 68.05%. This indicates that the variations in phosphorus content in slags and processes might affect the effectiveness of slag recycling and might increase the resource consumption required to maintain the quality of final products. The probability of forming substandard products in the baseline scenario is 0.43. Adopting a 50% removal rate, the probabilities of forming substandard products are reduced to 0.36 (waste removal scenario), 0.38 (slag reduction scenario), and 0.31 (raw material treatment scenario). The performance of raw material treatment and waste removal is more efficient for quality control. The method used in this study can be applied to evaluate the possible outcomes of waste recycling and reduce the probability of forming substandard products., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Beta-type titanium alloys are excellent candidates for biomedical applications because of their very low elastic modulus, excellent corrosion resistance, and biocompatibility. However, many traditional β-type titanium alloys exhibit low yield strength. In this study, a small amount of Si (3 and 5 at.%) was added to a Ti-35Nb-7Zr-5Ta (wt%, TNZT) biomedical alloy prepared via laser powder bed fusion (LPBF) to increase its yield strength. The Si addition resulted in a significant increase in the compression yield strength of the alloy (from 802 to 1282 MPa). Meanwhile, the elastic moduli of the TNZT alloys (48.7-60.6 GPa) with 3 and 5 at.% Si were much lower than that of the Ti-6Al-4 V alloy (110 GPa), which is used extensively in clinical applications. The microstructural analyses indicated that the ultrahigh-strength of the TNZT alloy containing Si was due to the presence of ultrafine (Ti, Nb, Zr) 5 Si 3 (S1) grains in the β-Ti matrix. In addition, thin shell-shaped S1 and (Ti, Nb, Zr) 2 Si (S2) grains precipitated along the columnar β-Ti grain boundaries in the TNZT alloys containing 3 and 5 at.% Si, respectively. Moreover, the introduction of Si to the TNZT alloy significantly refined the grains, weakened the cubic texture, decreased surface roughness, and improved Vickers hardness. The ultrahigh strength of the Si-containing TNZT alloys was due to grain boundary strengthening and precipitation strengthening. In addition, in vitro studies with MC3T3-E1 cells revealed that the cytocompatibilities of the LPBF-fabricated TNZT and Si-containing TNZT alloys were equivalent and were better than that of the LPBF-fabricated Ti-6Al-4 V alloy. In particular, the TNZT alloy with 3 at.% Si showed the best elastic modulus (48.7 ± 1.0 GPa), yield strength (1151 ± 17 MPa), and cell biological response among all the alloys investigated in this study, and hence was found to be a suitable candidate for application in load-bearing bone implants., Competing Interests: Declaration of competing interest We declare that we have no financial and personal relationships with other people or organizations that can inappropriately influence our work, there is no professional or other personal interest of any nature or kind in any product, service and/or company that could be construed as influencing the position presented in, or the review of, the manuscript entitled., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Depression is a common psychiatric comorbidity in patients with epilepsy, especially those with temporal lobe epilepsy (TLE). The aim of this study was to assess changes in high mobility group box protein 1 (HMGB1) expression in epileptic patients with and without comorbid depression. Sixty patients with drug-resistant TLE who underwent anterior temporal lobectomy were enrolled. Anterior hippocampal samples were collected after surgery and analyzed by immunofluorescence ( n  = 7/group). We also evaluated the expression of HMGB1 in TLE patients with hippocampal sclerosis and measured the level of plasma HMGB1 by enzyme-linked immunosorbent assay. The results showed that 28.3% of the patients (17/60) had comorbid depression. HMGB1 was ubiquitously expressed in all subregions of the anterior hippocampus. The ratio of HMGB1-immunoreactive neurons and astrocytes was significantly increased in both TLE patients with hippocampal sclerosis and TLE patients with comorbid depression compared to patients with TLE only. The ratio of cytoplasmic to nuclear HMGB1-positive neurons in the hippocampus was higher in depressed patients with TLE than in nondepressed patients, which suggested that more HMGB1 translocated from the nucleus to the cytoplasm in the depressed group. There was no significant difference in the plasma level of HMGB1 among patients with TLE alone, TLE with hippocampal sclerosis, and TLE with comorbid depression. The results of the study revealed that the translocation of HMGB1 from the nucleus to the cytoplasm in hippocampal neurons may play a previously unrecognized role in the initiation and amplification of epilepsy and comorbid depression. The direct targeting of neural HMGB1 is a promising approach for anti-inflammatory therapy.

Background: Inflammatory bowel disease (IBD) is a chronic inflammatory disease of the gastrointestinal tract whose occurrence is attributed to various factors, including genetic factors, immune response, microbial changes, and oxidative stress. Microbial-targeted therapy has emerged as an alternative to immunosuppressive therapy for IBD., Methods: The effects of an atypical commensal Escherichia coli strain harboring an additional catalase gene (compared to typical E. coli strain) on dextran sulfate sodium (DSS)-induced colitis were explored in mice., Results: The atypical E. coli (atEc) significantly restored body weight, reduced disease activity score, and improved histological scores in mice with colitis. Hydrogen peroxide levels in colitis mice were noticeably decreased when the mice were administered atEc. The proinflammatory cytokine levels were decreased and regulatory T cell numbers were increased after the administration of atEc. The abundance of Firmicutes was significantly recovered, while that of Proteobacteria decreased in atEc -treated mice compared with that in vehicle-treated wild-type mice. To investigate the role of interleukin (IL)-17A in mediating the anti-inflammatory effects of the atEc, IL-17A‒knockout mice were orally administered atEc. Clinical and immune responses and microbial composition were significantly reduced in IL-17A‒knockout mice compared with those in wild-type mice., Conclusions: atEc ameliorates colonic inflammation by controlling hydrogen peroxide levels, immune responses (including regulatory T cells and IL-17A), and microbial composition. atEc could be a novel candidate of probiotic for IBD treatment., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background/aims: The safety and effectiveness of adalimumab was demonstrated in a phase 3 trial in Japanese patients with intestinal Behçet's disease. The aim of this study was to evaluate the long-term safety and effectiveness of adalimumab in Japanese patients with intestinal Behçet's disease.

Alzheimer's Disease-resemblance atrophy index (AD-RAI) is an MRI-based machine learning derived biomarker that was developed to reflect the characteristic brain atrophy associated with AD. Recent study showed that AD-RAI (≥0.5) had the best performance in predicting conversion from mild cognitive impairment (MCI) to dementia and from cognitively unimpaired (CU) to MCI. We aimed to validate the performance of AD-RAI in detecting preclinical and prodromal AD. We recruited 128 subjects (MCI=50, CU=78) from two cohorts: CU-SEEDS and ADNI. Amyloid (A+) and tau (T+) status were confirmed by PET ( 11 C-PIB, 18 F-T807) or CSF analysis. We investigated the performance of AD-RAI in detecting preclinical and prodromal AD (i.e. A+T+) among MCI and CU subjects and compared its performance with that of hippocampal measures. AD-RAI achieved the best metrics among all subjects (sensitivity 0.74, specificity 0.91, accuracy 85.94%) and among MCI subjects (sensitivity 0.92, specificity 0.81, accuracy 86.00%) in detecting A+T+ subjects over other measures. Among CU subjects, AD-RAI yielded the best specificity (0.95) and accuracy (85.90%) over other measures, while hippocampal volume achieved a higher sensitivity (0.73) than AD-RAI (0.47) in detecting preclinical AD. These results showed the potential of AD-RAI in the detection of early AD, in particular at the prodromal stage.

Background: Post-stroke depression (PSD) is one of the most common stroke complications with high morbidity. Researchers have done much clinical research on Traditional Chinese Medicine (TCM) treatment, but very little research on diagnosis. Based on the thought of combination of disease and syndrome, this study will establish a unified and objective quantitative diagnosis model of TCM syndromes of PSD, so as to improve the clinical diagnosis and treatment of PSD., Objective: First: To establish a unified and objective quantitative diagnosis model of TCM syndromes in PSD under different disease courses, and identify the corresponding main, secondary, and concurrent symptoms, which are based on the weighting factor of each TCM symptom. Second: To find out the relationship between different stages of PSD and TCM syndromes. Clarify the main syndrome types of PSD under different stages of disease. Reveal the evolution and progression mechanism of TCM syndromes of PSD., Methods and Analysis: This is a retrospective study of PSD TCM diagnosis. Three hundred patients who were hospitalized in the First Teaching Hospital of Tianjin University of TCM with complete cases from January 2014 to January 2019 are planned to be recruited. The study will mainly collect the diagnostic information from the cases, find the related indicators of TCM and Western medicine in PSD, and clarify the relationship between different disease stages and TCM syndromes. Finally, the PSD TCM syndrome quantitative diagnosis model will be established based on the operation principle of Back Propagation (BP) artificial neural network., Conclusion: To collect sufficient medical records and establish models to speed up the process of TCM diagnosis., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Triggering receptor expressed on myeloid cell-1 (TREM-1) signaling is expressed on neutrophils and monocytes that is necessary for the successful antimicrobial response and resolution of inflammation in the gut. In this study, we determined the effect of an anti-TREM-1 agonistic antibody (α-TREM-1) on colitis and identify its underlying mechanism of action. Administration of α-TREM-1 alleviated colitis in mice and resolved dysbiosis, which required TLR4/Myd88 signaling. α-TREM-1 increased the production of neutrophil extracellular traps and interleukin-22 by CD177 + neutrophils, which led to pathogen clearance and protection of the intestinal barrier. TREM-1 activation using an α-TREM-1 antibody protects against colitis by rebalancing the microbiota and protecting the epithelium against the immune response as well as modulates the function of neutrophils and macrophages. These results highlight the importance of the TREM-1 pathway in intestinal homeostasis and suggest that α-TREM-1 treatment may be an effective therapeutic strategy for inflammatory bowel disease., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Seo, Che, Kim, Kim, Ma, Kim, Kim, Kim, Kim and Cheon.)

In order to identify the contribution to health risk derived from various emission sources, this study investigated monsoon variations in PM 2.5 mass and concentrations of the associated trace elements in a region with complex pollution sources in central Taiwan. This study applied the Chemical Mass Balance model to analyze the source contribution of PM 2.5 . The source apportionment to obtain the risk contribution of different sources were conducted for different monsoon periods according to the monsoon patterns. In this way, the contributions of individual sources and chemicals to health risk under different monsoon types can be understood to support development of effective control strategies. Among the top contributors of PM 2.5 during the north-east monsoon were Secondary Aerosol 28.93% >Coal Boiler 19.82% >Crustal Dust 15.99%; in south-west monsoon were Coal Boiler 37.29% >Traffic Emission 21.19% >Secondary Aerosol 17.84%. The total risk of cancer was above the acceptable risk (3.07 × 10 -6 ), while the non-carcinogenic risk was within the acceptable range (0.262). The variation in the concentration and composition of PM 2.5 was related to the change of monsoon type. During the north-east monsoon, the air mass had a long transmission distance and the PM 2.5 concentration was relatively high. During the south-west monsoon, the air mass had a short transmission distance and the composition was mainly influenced by nearby emission sources, which resulted in higher risk due to chemical characteristics. To provide sound air quality management, attention should be paid to the composition of PM 2.5 in addition to its concentration., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Infliximab (IFX), a TNF-α blocking chimeric monoclonal antibody, induces clinical response and mucosal healing in patients with inflammatory bowel disease (IBD). However, systemic administration of this agent causes unwanted side effects. Oral delivery of antibody therapeutics might be an effective treatment strategy for IBD compared to intravenous administration., Results: All three carriers had a high encapsulation efficiency, narrow size distribution, and minimal systemic exposure. There was a higher interaction between nanocomposite carriers and monocytes compared to lymphocytes in the PBMC of IBD patients. Orally administered nanocomposite carriers targeted to inflamed colitis minimized systemic exposure. All IFX delivery formulations with nanocomposite carriers had a significantly less colitis-induced body weight loss, colon shortening and histomorphological score, compared to the DSS-treated group. AC-IFX-L and EAC-IFX-L groups showed significantly higher improvement of the disease activity index, compared to the DSS-treated group. In addition, AC-IFX-L and EAC-IFX-L alleviated pro-inflammatory cytokine expressions (Tnfa, Il1b, and Il17)., Conclusion: We present orally administered antibody delivery systems which improved efficacy in murine colitis while reducing systemic exposure. These oral delivery systems suggest a promising therapeutic approach for treating IBD.

Lactobacillus plantarum has been identified as a probiotic bacterium owing to its role in immune regulation and maintenance of intestinal permeability. Here, we investigated the anti-colitic effects and mechanism of L. plantarum CBT LP3 (LP3). This in vivo study was performed using dextran sodium sulfate (DSS) to induce colitis in mice. Mice were randomly divided into three groups: a control supplied with normal drinking water, a DSS-treated group followed by oral administration of vehicle, and a DSS-treated group gavaged with LP3 daily for 7 days following DSS administration. An analysis of macrophages and T cell subsets harvesting from peritonium cavity cells and splenocytes was performed using a flow cytometric assay. Gene expression and cytokine profiles were measured using quantitative reverse transcriptase polymerase chain reaction. The administration of LP3 significantly attenuated disease activity and histolopathology compared to control. LP3 had anti-inflammatory effects, with increased induction of regulatory T cells and type 2 helper T cells in splenocytes and restoration of goblet cells accompanied by suppression of proinflammatory cytokine expressions. These findings suggest that L. plantarum CBT LP3 can be used as a potent immunomodulator, which has significant implications for IBD treatment., Competing Interests: Declarations of Competing Interest None., (Copyright © 2020 The Authors. Published by Elsevier GmbH.. All rights reserved.)

The enzyme glutathione S-transferase theta 1 (GSTT1) is involved in detoxifying chemicals, including reactive oxygen species (ROS). Here, we provide a significant insight into the role of GSTT1 in inflammatory bowel disease (IBD). We identified decreased expression of GSTT1 in inflamed colons from IBD patients compared to controls. We intrarectally or intraperitoneally delivered Gstt1 gene to mice with dextran sodium sulfate (DSS)-induced colitis and noted attenuation of colitis through gene transfer of Gstt1 via an IL-22 dependent pathway. Downregulation of GSTT1 by pathogen-associated molecular patterns (PAMPs) of microbes reduced innate defense responses and goblet cell differentiation. The GSTT1 mutation in intestinal epithelial cells (IECs) and IBD patients decreased its dimerization, which was connected to insufficient phosphorylation of signal transducer and activator of transcription-3 and p38/mitogen-activated protein kinase by their common activator, IL-22. GSTT1 ameliorated colitis and contributed as a modulator of goblet cells through sensing pathogens and host immune responses. Its mutations are linked to chronic intestinal inflammation due to its insufficient dimerization. Our results provide new insights into GSTT1 mutations that are linked to chronic intestinal inflammation due to its insufficient dimerization and their functional consequences in IBDs., (© 2020 Federation of American Societies for Experimental Biology.)

Background: Actin filament-associated protein 1-antisense RNA 1 (AFAP1-AS1) plays an important role in the development and progression of several human cancers. However, its biological function in gastric cancer (GC) progression is still unknown., Methods: We used qRT-PCR to detect the relative expression of AFAP1-AS1 in GC tissues and cell lines. The loss-of-function assays were conducted to detect the effect of AFAP1-AS1 on GC development. Bioinformatics analysis, luciferase reporter gene analysis, and RIP analysis were used to identify and validate target genes of AFAP1-AS1. Finally, rescue tests were performed to confirm the influence of the AFAP1-AS1-miR-155-5p-FGF7 axis on GC development., Results: AFAP1-AS1 was upregulated in GC tissues and cell lines and was closely correlated with poor prognosis of GC patients. AFAP1-AS1 knockdown inhibited proliferation, migration, and invasion of GC cells, indicating that AFAP1-AS1 acts as an oncogene in GC. Bioinformatics analysis, dual-luciferase reporter gene detection, and RIP assays validated that AFAP1-AS1 directly interacts to miR-155-5p and could positively affect cell proliferation, migration, and invasion by regulation of the expression of miR-155-5p and FGF7. Further rescue assays revealed that AFAP1-AS1 promotes cell proliferation and metastasis through the miR-155-5p/FGF7 axis in GC., Conclusions: AFAP1-AS1 might be an oncogenic lncRNA that promoted GC progression by acting as a competing endogenous RNA (ceRNA) that regulates the expression of FGF7 through sponging miR-155-5p, suggesting that AFAP1-AS1 may be a novel potential therapeutic target for GC., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2020 Hong-Wu Ma et al.)

This article reports the clinical features and C12orf65 gene mutations of a girl with autosomal recessive spastic paraplegia-55. The 8-year-old girl experienced disease onset at the age of 5 years and had optic atrophy as the main clinical manifestation, with slow movements in standing up and a slight duck-shaped gait. Peripheral blood DNA samples were collected from this child and her parents and brother to perform high-throughput whole-exome sequencing and high-throughput mitochondrial genome sequencing. Sanger sequencing was performed for verification. The results showed two compound heterozygous mutations, c.394C>T and c.447&#95;449delGGAinsGT, in the C12orf65 gene. The former mutation came from her father and was a known pathogenic mutation, and the latter came from her mother and was a novel mutation which had not been reported in literature. This study expands the mutation spectrum of the C12orf65 gene and thus provides a molecular basis for the etiological diagnosis of the child and the genetic counseling of the family.

Exposure to negative life stress has been associated with difficulty retrieving memories for specific autobiographical events, with important consequences for the emergence of emotional disorders. We examined whether social support can protect against the effects of negative events on memory specificity. University students ( N  = 143) were assigned to groups based on whether or not they experienced a negative stressor, operationalised as whether or not their recent exam performance was in line with their expectations. After receiving their exam results (T1), and one month later (T2), participants completed measures of memory specificity, their attitudes towards themselves and the occurrence of other stress-related events. Participants also completed a general measure of perceived social support from friends, family, and significant others, and an equivalent measure for social support related to performance. For participants who experienced an exam-related stressor, reduced performance-specific social support from friends was associated with reduced memory specificity at T2, even when accounting for T1 memory specificity, individual differences in attitudes towards self, the experience of additional stressors, and gender. No such relation was present for participants who did not experience a stressor. These findings provide new understanding of the influence of social variables on autobiographical memory specificity.

Protection of human health from air pollution has been typically pursued primarily via regulations of air quality standards and emission standards. Although reducing air pollution from the largest sources and placing more stringent emission limits on the industries of focus is a criterion used by decision makers to control air pollution, it is not clear whether this criterion is the most effective and efficient in improving health protection. Pollutants released from sources into the environment are spatially fluctuating rather than uniformly distributed, and hence, health risk is an issue of geographic variability. To address this issue, this study used a representative example of lead (Pb) in Taiwan. This study implemented an IO-RA methodology to redefine the effectiveness of air pollution management and rank the control priorities of target industries using different perspectives, i.e., environmental responsibility, economic benefit and repercussion potential. This study also considered the potential differences in policy effectiveness based on the air pollution control targets and ranked the industries according to their effectiveness in health risk improvement across the three perspectives and pure emission quantities. After determining the cause-effect chain of health risk through IO-RA, authorities can partner with specific industries according to the chosen effectiveness criteria and thus facilitate better policy performance., (Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Flexible land management that allows risk-based remediation approaches can increase local financial assistance in brownfield development investments. The evaluation of brownfields investment has always been mired in uncertainty because of the complexity of contamination and land policy. To clarify the uncertainty in investment costs resulting from a flexible risk-based land management, this research analyzes the uncertainty of remediation costs (I r ) and damaged land value (I p ). Sizable statistical data for 30,000 abandoned factories in Taiwan are used to derive the uncertainty of investment cost. The results show that the range and value of the uncertainty of I p is more than I r because the present land value and the change in flexible land management are the main sensitivity factors. The saved investment costs at the 90% confidence interval ranges five orders of magnitude. Moreover, investors could have saved approximately 5.74E+13 USD resulting from I p and I r . The study's two major findings with regard to investment risk in brownfield redevelopment are: (1) an explanation of the extent to which investment costs are to be reduced for investors by adjusting remediation goals depending on different land types; (2) characterization of the uncertainty of brownfields in the real investment market for brownfield redevelopment., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background and Aim: Nuclear factor kappa B (NF-κB) activation and endoplasmic reticulum (ER) stress signaling play significant roles in the pathogenesis of inflammatory bowel disease (IBD). Thus, we evaluated whether new therapeutic probiotics have anti-colitic effects, and we investigated their mechanisms related to NF-κB and ER-stress pathways., Methods: Luciferase, nitric oxide, and cytokine assays using HT-29 or RAW264.7 cells were conducted. Mouse colitis was induced using dextran sulfate sodium and confirmed by disease activity index and histology. Macrophages and T-cell subsets in isolated peritoneal cavity cells and splenocytes were analyzed by flow cytometry. Gene and cytokine expression profiles were determined using reverse-transcription polymerase chain reaction., Results: Lactobacillus acidophilus (LA1) and Pediococcus pentosaceus inhibited nitric oxide production in RAW264.7 cells, but only LA1 inhibited Tnfa and induced Il10 expression. LA1 increased the lifespan of dextran sulfate sodium-treated mice and attenuated the severity of colitis by inducing M2 macrophages in peritoneal cavity cells and Th2 and Treg cells in splenocytes. The restoration of goblet cells in the colon was accompanied by the induction of Il10 expression and the suppression of pro-inflammatory cytokines. Additionally, we found that LA1 exerts an anti-colitic effect by improving ER stress in HT-29 cells as well as in vivo., Conclusions: We showed that LA1 significantly interferes with ER stress and suppresses NF-κB activation. Our findings suggest that LA1 can be used as a potent immunomodulator in IBD treatment, and the regulation of ER stress may have significant implications in treating IBD., (© 2018 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Three new aristololactam derivatives, aristololactam W-Y (1-3), and three known compounds (4-6) were isolated from the fruits of Aristolochia contorta Bunge. Compounds 1 and 2 represent the first example of an N-CH 2 OCH 3 aristololactam derivative from natural products. Their structures were elucidated by 1D/2D NMR and HRESIMS spectra. All of the isolated compounds were evaluated for their insecticidal activity against 4th instar larvae of Aedes aegypti. Compound 4 displayed insecticidal activity with LC 50 value of 3.54 μg/mL.

The aqueous self-assembly of the flexible ligand L bis(1H-benz[d]imidazole-1-yl)methane and cis-coordinated Pt II precursors [(en)Pt 2+ , (tmeda)Pt 2+ , en=ethylenediamine, tmeda=N,N,N',N'-tetramethylethylenediamine)] led to the formation of the metallacalixarenes with full alternative conformations (e.g., two novel water-soluble metallacalixarenes [M 2 L 2 ] 4+ and [M 3 L 3 ] 6+ with D 2 and D 3 symmetry, respectively). Their molecular structures were determined by single crystal X-ray analyses in solid state. The two metallacalixarenes present different cavity sizes and the [M 3 L 3 ] 6+ cavity encapsulates one NO 3 - . NOESY NMR revealed that the conformational interconversion between 1,3-alternate conformer in methanol and cone conformer in DMSO was tuned via the synergistic effect between solvent and anion. Guest encapsulation is also discussed., (© 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Ultrasonic echo estimation is important in ultrasonic non-destructive evaluation and material characterization. Matching pursuit is one of the most popular methods for the purpose of estimating ultrasonic echoes. In this paper, an artificial bee colony optimization based matching pursuit approach (ABC-MP) is proposed specifically for ultrasonic signal decomposition by integrating the artificial bee colony algorithm into the matching pursuit method. The optimal atoms are searched from a continuous parameter space over a tailored Gabor dictionary in ABC-MP instead of a discrete parameter space in matching pursuit. As a result, echoes characterized by a set of physical parameters can be estimated accurately and efficiently. The performance of ABC-MP is tested using both simulated signals and real ultrasonic signals, and compared with matching pursuit. Results clearly demonstrate the superior performance of the proposed ABC-MP approach over matching pursuit in ultrasonic echo estimation in terms of the shape and amplitude of the recovered echoes and the reconstructed signal, and the residue signal., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Genome-wide association studies and meta-analyses have revealed the genetic background of ulcerative colitis (UC) by identifying common variants. However, these variants do not fully explain the disease variance in UC. To identify novel variants, we performed deep resequencing of UC-associated genes in Korean UC patients and subsequently investigated the functional roles of identified susceptibility genes., Methods: We performed targeted deep resequencing of 108 genes in 24 Korean UC patients and then performed association analysis with data from 126 healthy controls. We validated these variants using 2-stage replication studies including 793 UC patients and 783 controls. We performed in silico and pathway analyses and functional analyses., Results: The combined analysis including 2 replication studies identified 6 novel susceptibility loci and reconfirmed 10 previously reported loci. Among the novel single nucleotide variants (SNVs), rs10035653 in C5orf55 (P = 2.08 × 10-3; OR = 1.50), rs41417449 in BTNL2 (P = 1.27 × 10-2; OR = 1.32), rs3117099 in HCG23 (P = 9.98 × 10-6; OR = 1.40), rs7192 in HLA-DRA (P = 6.95 × 10-9; OR = 1.57), and rs3744246 in ORMDL3 (P = 2.21 × 10-2; OR = 1.21) were identified as causal variants, whereas rs713669 in IL17REL (P = 2.69 × 10-2; OR = 0.84) as a protective variant for UC. When correcting multiple testing, 3 novel SNVs (rs41417449 in BTNL2, rs3744246 in ORMDL3, and rs713669 in IL17REL) and 4 previously reported SNVs did not reach a statistical significance. Functional study suggested that SNVs of BTNL2 and C5orf55 exacerbated the inflammatory response both in vitro and in vivo., Conclusions: This study identified 3 novel susceptibility loci and validated 6 previously reported SNVs for UC through deep resequencing in Koreans and revealed the functional roles of BTNL2 and C5orf55.