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Stem cell transplantation (SCT) from an unrelated donor (URD) is often considered in patients with severe aplastic anemia (SAA) whom immunosuppressive therapy failed and matched sibling donor is not available. To reduce the incidence of graft-versus-host disease (GVHD) in URD SCT, introducting antithymocyte globulin (ATG) into the conditioning regimen has been proposed. Although ATG was shown to play a role in reducing GVHD in a cohort with diverse hematologic diseases, its role in SAA remains uncertain. The aim of this study was to determine the efficacy and toxicity of ATG in URD SCT for adult patients with SAA. We investigated 83 adult patients with SAA who underwent URD SCT between 2003 and 2014. The transplantation strategy consisted of total body irradiation (total 800 cGy) and cyclophosphamide (total 100 mg/kg to 120 mg/kg), followed by tacrolimus and a short-term methotrexate. We divided patients into 2 groups: group 1 (n = 25), which received HLA-matched (8/8) bone marrow (BM) without ATG, and group 2 (n = 58), which received SCT from either an HLA-mismatched donor or peripheral blood (PB). Thereafter, group 2 was subdivided according to ATG use into group 2A (without ATG, n = 26), which served as a historical cohort, and group 2B (with ATG, n = 32). Rabbit ATG (Thymoglobulin; Genzyme-Sanofi, Lyon, France) was used in group 2B at a dose of 2.5 mg/kg. The median age of all patients was 30 years (range, 17 to 59 years). The incidence of GVHD was significantly lower in group 2B than group 2A, as demonstrated by the rate of grade II to IV acute GVHD at day 100 (31.2% versus 61.5%, P = .003) and the rate of chronic GVHD at 3 years (21.9% versus 65.4%, P = .002). The overall survival rates of the 3 groups were similar. However, GVHD-free, failure-free survival (GFFS) was significantly higher in group 2B than group 2A (P = .034). A multivariable model identified use of ATG as an independent factor affecting grades II to IV acute GVHD (hazard ratio [HR], 2.902; 95% confidence interval [CI], 1.417 to 5.942; P = .004), chronic GVHD (HR , 3.005; 95% CI, 1.279 to 7.059; P = .012), and GFFS (HR, 2.363; 95% CI, 1.162 to 4.805; P = .014). Toxicities, including infectious complications, were not different among the 3 groups. In conclusion, low-dose ATG (2.5 mg/kg) can reduce the incidence of acute and chronic GVHD and improve the quality of life in patients with SAA who receive stem cells from either an HLA-mismatched donor or PB; importantly, these benefits are achieved without increased toxicity. Furthermore, ATG can be considered in URD SCT from HLA-matched BM cells.

Probiotics have been known to reduce high-fat diet (HFD)-induced metabolic diseases, such as obesity, insulin resistance, and type 2 diabetes. We recently observed that Lactobacillus acidophilus NS1 (LNS1), distinctly suppresses increase of blood glucose levels and insulin resistance in HFD-fed mice. In the present study, we demonstrated that oral administration of LNS1 with HFD feeding to mice significantly reduces hepatic expression of phosphoenolpyruvate carboxykinase (PEPCK), a key enzyme in gluconeogenesis which is highly increased by HFD feeding. This suppressive effect of LNS1 on hepatic expression of PEPCK was further confirmed in HepG2 cells by treatment of LNS1 conditioned media (LNS1-CM). LNS1-CM strongly and specifically inhibited HNF4α-induced PEPCK promoter activity in HepG2 cells without change of HNF4α mRNA levels. Together, these data demonstrate that LNS1 suppresses PEPCK expression in the liver by regulating HNF4α transcriptional activity, implicating its role as a preventive or therapeutic approach for metabolic diseases.

This retrospective study aimed to compare the clinical features of paramedullary lesions (PLs) and extramedullary lesions (ELs) of plasmacytomas at diagnosis, using positron emission tomography integrated with computed tomography, using glucose labeled with the positron-emitting radionuclide 18F (18F-FDG-PET/CT) in newly diagnosed multiple myeloma (NDMM), and to address their prognostic impact. Sixty-four patients with NDMM presenting ELs (n=22) and/or PLs (n=42) were included. Patients with ELs at initial presentation had unfavorable laboratory parameters of calcium and lactate dehydrogenase, a higher percentage of bone marrow plasma cells, and showed a trend toward advanced international staging system (ISS), compared to patients with PLs. Using X-ray imaging, high bone disease (HBD) was observed in 50% and 71% of patients with ELs and PLs, respectively. After a median follow-up of 29.2 months (range, 3.4-76.5 months) in survivors, patients with ELs had a significantly lower overall survival (OS) (p=0.033) than patients with PLs did, whereas the progression-free survival (PFS) did not differ significantly (p=0.818). However, the PFS after 1st progression was significantly worse in patients with ELs than in those with PLs (p=0.017). In the multivariate analyses, the negative impact of initial ELs on OS (p=0.033) was sustained. Our results demonstrated the different clinical features and outcomes of ELs and PLs in NDMM. Patients with initial ELs showed a shorter PFS after 1st progression, which translated into poor OS, providing insight into the different biological effect of ELs.

We fabricated polycrystalline yttrium-iron-garnet (Y3Fe5O12, YIG) samples using the sol-gel synthesis method to develop an energy harvesting material based on the spin Seebeck effect. We confirmed that crystallization occurred during calcination at 850 °C and that only the polycrystalline YIG structure was formed. We found that a sintering process at 1400 °C not only increased the size of the YIG particles and the densification of their microstructure but also enhanced their saturation magnetization (Ms) and dramatically reduced their coercivity (Hc). A mechanical pressing process was carried out between the calcination and sintering treatments to prepare a free-standing YIG fillet sample. We found that Ms was enhanced by almost three times without an associated reduction in Hc. We found that mechanical pressing assists the oxidation reaction during the subsequent sintering process by increasing the surface energy and densification before the heat treatment.

The microstructure and tensile properties of Mg–6Zn–0.5Zr alloy processed by low-temperature indirect extrusion utilizing artificial cooling were investigated. Remarkable grain refinement was obtained by the application of artificial cooling, resulting in an increase in the yield strength of as much as 53 MPa at room temperature, as compared to the case (245 MPa) of indirect extrusion without artificial cooling. Besides this, the fine-grained alloy was found to have superplastic properties at elevated temperature, revealing tensile elongations of 720–810% at 200 °C at strain rates of 2 × 10 −4 –1 × 10 −3 s −1 . Mechanisms responsible for the high strength and superplastic properties are discussed.

The role of autologous hematopoietic cell transplantation (auto-HCT) for postremission therapy of acute myeloid leukemia is yet to be elucidated. We retrospectively analyzed 240 patients treated with auto-HCT in first remission. All patients were treated with standard induction chemotherapy, and CD34+ stem cells were collected at each cycle of consolidation. Stem cells were infused after total body irradiation (1200 cGy), cytarabine (9 g/m2), and melphalan (100 mg/m2). Estimated 5-year overall survival, disease-free survival (DFS), cumulative incidence of relapse (CIR), and nonrelapse mortality were 58.4%, 55.3%, 38.8%, and 5.9%, respectively. We identified that poor-risk karyotype showed very poor outcome after auto-HCT, and then analyzed 85 patients with good to intermediate-risk molecular cytogenetics with available molecular study results and markers for minimal residual disease (MRD) such as WT1 and core-binding factor (CBF) associated MRD (ie, AML1/ETO and CBFβ/MYH11). Our data identified that old age, pre-HCT markers for MRD, and high post-HCT WT1, high dose of CD34+ stem cell (≥4.5 × 106/kg) infusion, and c-kit or FLT3-ITD mutations were associated with higher relapse rate and poor DFS. Using pre-HCT parameters, except for post-HCT WT1, multivariate analysis revealed that patients with young age (

We report that alloying with Y remarkably enhances the corrosion resistance of extruded Mg–Al–Ca-based alloy. The corrosion rates, measured by immersion tests in 0.6 M NaCl solution at 25 °C, were 0.31 and 1.84 mm y −1 for the Mg–6Al–1Zn–0.5Ca–0.3Mn (wt.%) alloys with and without 0.25 wt.% Y, respectively. The improved corrosion resistance is mainly attributed to a change in the type of Al-containing intermetallic particles toward reducing their electrochemical nobility, resulting in reduced H 2 evolution rate during corrosion.

Introduction Acute myeloid leukemia (AML) has been considered as a hematological emergency. However, debates on how much the time from diagnosis to treatment (TDT) can be justified to choose the optimal treatment in AML have been raised due to the increased possibility of customized treatment with novel targeted agents based on genetic abnormalities tested by newly applicable diagnostic tools. Three recent studies with a large data set from Western countries showed conflicting results about the relationship between TDT and prognosis. Thus, we evaluated the influence of TDT on patients' outcomes from a large data set of Asian patients. Methods We retrospectively evaluated a cohort of AML patients aged 18 and older who visited the Catholic Hematology Hospital in Korea and received anthracycline-based intensive chemotherapy from 2002 to 2016. A total of 1313 patients were included in this analysis, of which 1282 were used for analysis, excluding 26 patients with incomplete documentation and with more than 90 days of TDT. Patients under the age of 60 (Young group, YG) and patients over 60 years of age (Elderly group, EG) were analyzed as an individual cohort. In both cohorts, the effects of TDT on complete remission (CR/CRi), early death (ED), and overall survival (OS) were analyzed. The TDT was analyzed as a continuous variable to minimize the loss of information, while also grouped into four ordinal groups of 1-5, 6-10, 11-15, and 16- to visualize data and find appropriate cutoff. In order to adjust for the influence of established prognostic variables on the outcomes, we used multivariate regression models. In both univariate and multivariate analyses, the transformation of variables or relaxing the linearity such as restricted cubic splining (RCS) were considered to reflect the data properly and not to violate the model assumptions. When TDT was treated as an ordinal variable, the effects of TDT on CR/CRi and ED were evaluated by Cochran-Armitage trend tests, and the effect on OS was checked by the log-rank test. Results Median age of YG (n=1104) and EG (n=178) were 40 years (interquartile range, IQR; 32-49) and 63 years (IQR; 61-64), respectively. Median TDT of both groups was 8 in days (IQR; 6-11 in YG and 6-13 in EG). When TDT was categorized into 4 groups, patients with higher WBC count tended to belong to earlier TDT groups in both YG and EG cohorts, and secondary AML patients were more placed in the later TDT groups especially in YG cohort. Univariate analyses of TDT in YG showed that TDT had significant correlation with CR/CRi rate, ED rate, and OS. Odds ratio (OR) of CR/CRi per one day treatment delay was -0.0206 (95% CI; -0.0412~-0.0000), and OR of ED per one day delay was 0.0439 (95% CI; 0.0126~0.0752) (Table 1 and Figure 1). RCS method was applied on OS model, so a single value of the hazard ratio (HR) per one day treatment delay was not available, but we could say HR of patients of TDT 2 versus (vs.) patients of TDT 16 was 0.6063 (95% CI; 0.4450-0.8259) in our model (Figure 2). Even after TDT was treated as a grouped variable, TDT was still significant on the ED rate and OS in YG. Especially, High ED rate and low 2-year OS of a group of TDT more than 15 days were noticed (Table 1). In EG, there was no significant effect of TDT on all patients' outcomes (Table 1). Multivariate analyses including age, WBC, AML type, MRC risk, and HSCT status showed that, in YG, TDT effect on CR/CRi rate turned to be insignificant, but TDT still acted as a significant variable for ED and OS. In EG, there was no significant effects of TDT on ED and OS, as like univariate analyses. When the treatment course was divided into 'during induction', 'between induction and HSCT', and 'after HSCT' in YG, there was no significant difference in the rate of death between TDT groups except for the deaths during the induction period (Table 3 and Figure 3). Conclusion Our data revealed the effects of TDT on OS and ED in YG, which were significant in multivariate analyses adjusting the effects of other variables. When the timing of death was divided in YG, the only ED was significantly different between TDT groups, especially in the group with more than 15 days of TDT. These results suggest that TDT matters in YG and delayed initiation of treatment over 15 days after diagnosis would increase risk of early mortalities. On the other hand, little effects of TDT on EG provide a rational for sufficient evaluation of comorbidity and functional impairments to select appropriate initial treatment. Disclosures Kim: Takeda: Research Funding; ILYANG: Consultancy, Honoraria, Research Funding; Sun Pharma.: Research Funding; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Novartis: Consultancy, Honoraria, Research Funding, Speakers Bureau. Lee:Alexion Pharmaceuticals Inc.: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Kim:Abbvie: Honoraria; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Sanofi-Genzyme: Honoraria; SL VaxiGen: Consultancy, Honoraria; Yuhan: Consultancy, Honoraria; AML Global Portal: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Astella: Consultancy, Membership on an entity's Board of Directors or advisory committees; BL&H: Research Funding; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Chugai: Consultancy, Honoraria; Daiichi Sankyo: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Hanmi: Consultancy, Honoraria; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees.

Real-world outcomes of daratumumab monotherapy (DM) for relapsed/refractory multiple myeloma (RRMM) have remained unclear. We conducted a multicentre retrospective study of 107 patients receiving DM for RRMM. The cohort included 64 trial-unfit patients whose characteristics could not meet inclusion criteria in two previous clinical trials (GEN501 and SIRIUS). The overall response rate (ORR), and median first and second progression-free survival (PFS1 and PFS2) and overall survival were 42·1%, and 3·6, 8·1 and 11·9 months, respectively. Refractoriness to carfilzomib and/or lenalidomide, and neutropenia (

Some HLA alleles have been shown to be associated with susceptibility to cytomegalovirus (CMV) disease incidence in vitro. The objective of this study was to identify correlations between donor HLA allotypes and CMV disease incidence in patients with acute myeloid leukemia who had undergone allogeneic hematopoietic stem cell transplantation (HSCT). Methods and materials we retrospectively analyzed the medical records of 613 donors and recipients with acute myeloid leukemia who had received an allogeneic HSCT from matched sibling (n = 260), unrelated (n = 168), or haploidentical (n = 186) donors, from 2012 to 2017. The HLA-A, -B, -C, and -DRB1 allotypes in the donors were determined using sequence-based typing. Overall, CMV disease incidence was significantly associated with three genotype alleles, HLA-A*30:04:01G, -B*51:01:01G, and -DRB1*09:01:02G. In the donor CMV IgG seropositive subgroup, CMV disease incidence was significantly associated with HLA-B*51:01:01G and -DRB1*09:01:02G. In the IgG seropositive donors in the unrelated allo-HSCT subgroup CMV disease incidence was also significantly associated with HLA-B*51:01:01G. In the CMV seropositive donors in the haploidentical allo-HSCT subgroup, the incidence of CMV disease was significantly associated with HLA-A*24:02:01G and -DRB1*09:01:02G. HLA-DRB1*13:02:01G was a protective marker among IgG seropositive donors in the unrelated allo-HSCT recipient category. Discussion and conclusions The incidence of CMV disease among HSCT recipients varies according to donor HLA alleles and the donor CMV IgG serostatus. Certain donor HLA alleles can be considered to be risk or protective markers. Donors' HLA types and CMV IgG serostatus should be considered in donor selection.

Accurate prediction of non-small cell lung cancer (NSCLC) prognosis after surgery remains challenging. The Cox proportional hazard (PH) model is widely used, however, there are some limitations associated with it. In this study, we developed novel neural network models called binned time survival analysis (DeepBTS) models using 30 clinico-pathological features of surgically resected NSCLC patients (training cohort, n = 1,022; external validation cohort, n = 298). We employed the root-mean-square error (in the supervised learning model, s- DeepBTS) or negative log-likelihood (in the semi-unsupervised learning model, su-DeepBTS) as the loss function. The su-DeepBTS algorithm achieved better performance (C-index = 0.7306; AUC = 0.7677) than the other models (Cox PH: C-index = 0.7048 and AUC = 0.7390; s-DeepBTS: C-index = 0.7126 and AUC = 0.7420). The top 14 features were selected using su-DeepBTS model as a selector and could distinguish the low- and high-risk groups in the training cohort (p = 1.86 × 10−11) and validation cohort (p = 1.04 × 10−10). When trained with the optimal feature set for each model, the su-DeepBTS model could predict the prognoses of NSCLC better than the traditional model, especially in stage I patients. Follow-up studies using combined radiological, pathological imaging, and genomic data to enhance the performance of our model are ongoing.

The infection of a novel coronavirus found in Wuhan of China (2019-nCoV) is rapidly spreading, and the incidence rate is increasing worldwide. Due to the lack of effective treatment options for 2019-nCoV, various strategies are being tested in China, including drug repurposing. In this study, we used our pretrained deep learning-based drug-target interaction model called Molecule Transformer-Drug Target Interaction (MT-DTI) to identify commercially available drugs that could act on viral proteins of 2019-nCoV. The result showed that atazanavir, an antiretroviral medication used to treat and prevent the human immunodeficiency virus (HIV), is the best chemical compound, showing a inhibitory potency with Kd of 94.94 nM against the 2019-nCoV 3C-like proteinase, followed by efavirenz (199.17 nM), ritonavir (204.05 nM), and dolutegravir (336.91 nM). Interestingly, lopinavir, ritonavir, and darunavir are all designed to target viral proteinases. However, in our prediction, they may also bind to the replication complex components of 2019-nCoV with an inhibitory potency with Kd < 1000 nM. In addition, we also found that several antiviral agents, such as Kaletra, could be used for the treatment of 2019-nCoV, although there is no real-world evidence supporting the prediction. Overall, we suggest that the list of antiviral drugs identified by the MT-DTI model should be considered, when establishing effective treatment strategies for 2019-nCoV.

The infection of a novel coronavirus found in Wuhan of China (SARS-CoV-2) is rapidly spreading, and the incidence rate is increasing worldwide. Due to the lack of effective treatment options for SARS-CoV-2, various strategies are being tested in China, including drug repurposing. In this study, we used our pre-trained deep learning-based drug-target interaction model called Molecule Transformer-Drug Target Interaction (MT-DTI) to identify commercially available drugs that could act on viral proteins of SARS-CoV-2. The result showed that atazanavir, an antiretroviral medication used to treat and prevent the human immunodeficiency virus (HIV), is the best chemical compound, showing an inhibitory potency with Kd of 94.94 nM against the SARS-CoV-2 3C-like proteinase, followed by remdesivir (113.13 nM), efavirenz (199.17 nM), ritonavir (204.05 nM), and dolutegravir (336.91 nM). Interestingly, lopinavir, ritonavir, and darunavir are all designed to target viral proteinases. However, in our prediction, they may also bind to the replication complex components of SARS-CoV-2 with an inhibitory potency with Kd

In this study, the charge transport mechanism of Pd/Si-based FS-GaN Schottky diodes was investigated. A temperature-dependent current&ndash, voltage analysis revealed that the I-V characteristics of the diodes show a good rectifying behavior with a large ratio of 103&ndash, 105 at the forward to reverse current at &plusmn, 1 V. The interface states and non-interacting point defect complex between the Pd metal and FS-GaN crystals induced the inhomogeneity of the barrier height and large ideality factors. Furthermore, we revealed that the electronic conduction of the devices prefers the thermionic field emission (TFE) transport, not the thermionic emission (TE) model, over the entire measurement conditions. The investigation on deep level transient spectroscopy (DLTS) suggests that non-interacting point-defect-driven tunneling influences the charge transport. This investigation about charge transport paves the way to achieving next-generation optoelectronic applications using Si-based FS-GaN Schottky diodes.

OBJECTIVE We investigated the role of anti-thymocyte globulin (ATG; Thymoglobulin) in matched sibling donor hematopoietic stem cell transplantation (MSD-HSCT) after reduced intensity conditioning (RIC) in myelodysplastic syndrome (MDS). METHODS Forty-seven patients with 10 mg/kg ATG (ATG group; median age 53 years) and 33 without ATG (no-ATG group; median age 43, P

The recent improvements in the outcomes of severe aplastic anemia (SAA) patients who received allogeneic stem cell transplantation (SCT) from unrelated donors (URD) suggest the possibility of its alternative first-line treatment. To address this issue, results of adult SAA patients receiving allogeneic SCT were compared between the following three donor-type groups: 8/8–matched sibling (MSD; n = 153), 8/8 well-matched unrelated (WM-URD; n = 72), and 6–7/8 partially matched unrelated (PM-URD; n = 33). Proportion of patients who experienced immunosuppressive treatment failures was significantly higher in the URD groups than in the MSD group (P

We explored prognostic roles of circulating microRNAs (miRs) in multiple myeloma (MM) treated with autologous stem cell transplantation (ASCT) following induction chemotherapy. In part I of the study (n = 40), we identified a decreasing dynamics of circulating miR-193a-5p expression from diagnosis to pre-ASCT. In patients who experienced early relapse within one year post ASCT (n = 9) these patterns were distinctive compared to those without early relapse in a 1:2 matched cohort (n = 18). In part II (n = 90), multivariate analyses showed that the International Staging System score and miR-193a-5p expression before ASCT were independent prognostic factors. Conclusively, expression of circulating miR-193a-5p before ASCT could be a prognostic biomarker for transplant-eligible MM.

In this study, we investigated the safety and efficacy of arsenic trioxide (ATO) and all-trans retinoic acid (ATRA) in patients with acute promyelocytic leukemia (APL). The patients had been classified as unfit to receive anthracycline-based chemotherapy due to high-risk factors for early death. Twenty-five patients with APL receiving ATO/ATRA between 2007 and 2018 were divided into 3 groups as follows: elderly patients (age ≥ 70 years) with poor performance status (32%); patients with severe active infections at diagnosis (56%); and patients with multiple significant comorbidities (24%) who were unfit for conventional chemotherapy, regardless of age. Induction therapy comprised 0.15 mg/kg/day ATO combined with 45 mg/m2/day ATRA until patients attained complete remission (CR). Notably, only one patient (4.0%) died of septic shock 2 days after the ATO treatment had been initiated. The remaining 24 patients attained CR despite their serious and desperate conditions at diagnosis. In total, 44%, 28%, and 32% of the patients experienced neutropenia (grade 3 or 4), thrombocytopenia, and hepatopathy, respectively. Twenty-three of the 24 patients in CR proceeded to consolidation therapy and attained complete molecular remission with favorable overall survival (90.7%). This study demonstrates the safety and efficacy profile of ATO/ATRA first-line therapy for patients with APL and high-risk features for early death.

Browning of white adipose tissue (WAT) is currently considered a potential therapeutic strategy to treat diet-induced obesity. While some probiotics have protective effects against diet-induced obesity, the role of probiotics in adipose browning has not been explored. Here, we show that administration of the probiotic bacterium Lactobacillus amylovorus KU4 (LKU4) to mice fed a high-fat diet (HFD) enhanced mitochondrial levels and function, as well as the thermogenic gene program (increased Ucp1, PPARγ, and PGC-1α expression and decreased RIP140 expression), in subcutaneous inguinal WAT and also increased body temperature. Furthermore, LKU4 administration increased the interaction between PPARγ and PGC-1α through release of RIP140 to stimulate Ucp1 expression, thereby promoting browning of white adipocytes. In addition, lactate, the levels of which are elevated in plasma of HFD-fed mice following LKU4 administration, elicited the same effect on the interaction between PPARγ and PGC-1α in 3T3-L1 adipocytes, leading to a brown-like adipocyte phenotype that included enhanced Ucp1 expression, mitochondrial levels and function, and oxygen consumption rate. Together, these data reveal that LKU4 facilitates browning of white adipocytes through the PPARγ-PGC-1α transcriptional complex, at least in part by increasing lactate levels, leading to inhibition of diet-induced obesity.

Mesoporous silica nanospheres (MSNs-AH) with a Schiff-base ligand were synthesized using a snap-top strategy and post-synthetic grafting strategy for metal ion adsorption. The mesoporous MSNs-AH with the Schiff-base ligand were used for the adsorption of metal ions from artificial wastewater and artificial seawater. The adsorption characteristics of the functionalized adsorbents for various metal ions were tested for different adsorption times (1~48 h) in artificial wastewater and artificial seawater. In the case of artificial wastewater, the functionalized adsorbents had no preferential selectivity for metal ions except for Na+ ions, even though the MSNs-AH adsorbent adsorbed most of the metal ions investigated in this work, including Li+, Co2+, Ca2+, Fe3+, Mn2+, Mg2+, Al3+, Zn2+, and Ni2+. In the case of artificial seawater, however, the MSN absorbent showed high selectivity for Li+ ions.

Graft-versus-host disease (GVHD) is a serious complication of allogeneic stem cell transplantation (SCT). Here, we report a rare case of GVHD involving the central nervous system (CNS). A 35-year-old woman was diagnosed with myelodysplastic syndrome unclassifiable and underwent allogeneic peripheral blood SCT for disease progression to myelodysplastic syndrome with excess blasts-2. One year following SCT, she experienced chronic oral and hepatic GVHD symptoms, which were managed with oral steroids and tacrolimus. Sixteen months after SCT, she developed sudden-onset, generalized, tonic–clonic-type seizures. Magnetic resonance imaging and cerebrospinal fluid evaluation showed multiple discrete white lesions and elevated IgG levels. Brain biopsy revealed periventricular plaques with the destruction of axons, representing a demyelinating disease of the CNS. We diagnosed the case as CNS GVHD. Neurologic symptoms gradually improved with methylprednisolone pulse therapy and total plasma exchange combined with a calcineurin inhibitor; the brain lesions nearly disappeared after decreasing steroid maintenance dosage, and were completely resolved 1 year after the onset of CNS GVHD. The patient is CNS GVHD-symptom-free, 3-year post-transplantation. Thus, CNS GVHD should be considered in cases of newly developed neurologic symptoms in SCT recipients showing evidence of preceding chronic GVHD.

Medulloblastoma is the most common malignant brain tumor of childhood. Therapeutic approaches to medulloblastoma have led to significant improvements but are achieved at a high cost to quality of life. The Notch pathway governs cell proliferation in many biological contexts, including medulloblastoma tumorigenesis. Using our proteomic platform, we discovered an interaction between RBPJ, a key co-factor of Notch for the mediation of Notch signals, and L3MBTL3, a methyllysine reader for which deletions are observed in medulloblastoma. We demonstrated that L3MBTL3 is part of a molecular mechanism linking the KDM1A demethylase to Notch signal modulation. We hypothesize that malfunction of this molecular mechanism may contribute to the previously suggested tumor suppressor role of L3MBTL3 in medulloblastoma. In a survival analysis using our L3mbtl3 KO mouse in combination with a genetically engineered mouse model of medulloblastoma, we validated our hypothesis that L3mbtl3 is a tumor suppressor in this disease context. Our discovery provides insights into the role of the L3MBTL3 in medulloblastoma that could be harnessed in the future for the therapeutic benefit of medulloblastoma patients.

We report that the corrosion resistance of hot-rolled Mg–8Sn–1Al–1Zn alloy was significantly enhanced by Sm microalloying. Corrosion rates, measured after immersion for 72 h in 0.6 M NaCl solution, were found to be 2.7 and 19 mm y−1 for the alloys with and without an addition of 0.02 wt% Sm, respectively. Electrochemical and microstructural analyses revealed that the enhanced corrosion resistance achieved by Sm microalloying is mainly a result of a reduced H2 evolution rate owing to the presence of Al8Fe4Sm particles instead of nobler Al5Fe2 particles, which highly accelerate microgalvanic corrosion in the alloy without Sm microalloying.

The efficient adsorption of pollutants from wastewater is of considerable importance for environmental protection. Herein, a novel polyethyleneimine (PEI)-functionalised polysilsesquioxane hollow sphere (H-PVTMS-PEI) was prepared successfully via a facile grafting approach. The product was characterised using scanning electron microscopy with energy-dispersive spectroscopy, transmission electron microscopy, X-ray diffraction, N2 adsorption–desorption behaviour, Fourier transform infrared spectroscopy, thermogravimetric analysis, small-angle X-ray scattering, and X-ray photoelectron spectroscopy. The adsorption behaviours of H-PVTMS-PEI towards Congo red (CR) and Cr(VI) were evaluated by studying the effects of solution pH, initial pollutant concentration, coexisting metal ions, and contact time in batch adsorption experiments. The hollow adsorbent H-PVTMS-PEI-2, prepared using 2% PEI in tetrahydrofuran solution, exhibited fast adsorption kinetics and superior adsorption capacities for Cr(VI) (391.1 mg/g

We report that twin-roll cast and subsequently heat-treated Mg–6Zn–1Mn–1Al alloy sheets with a thin thickness of 1 mm were successfully joined by surface-friction welding process. The welded sheet revealed several distinct weld zones, which are closely related to plastic flow and frictional heat generation during welding. Although large microstructural differences were found among the welded zones, the presence of thermally stable Al 8 Mn 5 particles pre-existing in the sheet appeared uninfluenced by the welding process. The role of the microstructural changes induced by the welding process in the hardness variation and tensile properties of the welded sheet is discussed.

A redox-responsive delivery system has been formulated for cancer therapy using mesoporous silica nanoparticles (MSNs). The silica surface is modified with carboxylic acid groups prior to loading with 5-fluorouracil (5-FU). Subsequently, the pores of the MSNs are sealed by reacting cystamine-modified carboxymethyl cellulose (CMC), which contains disulfide bonds, with the surface of the MSNs via carbodiimide chemistry. Because these bonds are the sites of cleavage, cells overexpressing reducing agents should be able to cleave Cystamine-modified CMC and release the encapsulated drug. Characterization of the resulting nanoparticles shows a decrease in surface area and pore volume, which suggests that the pores of MSNs has been sealed by the attachment of Cystamine-modified CMC. Transmission electron microscopy confirms these results and shows a coating of Cystamine-modified CMC on the surface of the MSNs. The release of 5-FU can be triggered in the presence of dithiothreitol (DDT), a reducing agent. The breast cancer cells (MCF-7) show the positive uptake of Redox-responsive MSNs Moreover, these nanoparticles exhibit higher cytotoxicity when the breast cancer cells are preincubated with DTT compared to the control nanoparticles or 5-FU loaded MSNs in the absence of DTT. These results show that MSNs crosslinked with Cystamine-modified CMC are redox-responsive and can be developed further for cancer therapy.

A snap-top nanocontainer type of cryptand [211] (C211) encapsulated spherical MCM-41 nanovalve (CP-MCM-41) was synthesized via surfactant assisted sol-gel methodology and post modification process. The spherical MCM-41 has been tailored as a metal carrier system by the insertion of N-3-(trimethoxysilyl)propylaniline (TMSPA) at the pore opening before extracting the surfactant. The surfactant extracted MCM-41 (PA-MCM-41) exhibits excellent textural properties such as high specific surface area (1107 m2 g−1), pore diameter (24.5 A) and pore volume (0.65 cm3 g−1). The transmission electron microscope (TEM) and scanning electron microscope (SEM) images of mesosphere reflect highly uniform and mono-dispersed spherical morphology with an average particle size of 500 nm. C211 has been loaded into the pore channels, while β-cyclodextrin (β-CD) was used as the gatekeeper to keep a metal of interest inside. The presence of C211 in the pore channels and the credibility of β-CD capping were ensured by exposing the CP-MCM-41 to pH 4 aqueous solution. Step wise adsorption studies from various aqueous solutions were carried out to analyze the metal adsorption selectivity of CP-MCM-41. The results of adsorption experiments from 5 different metal solutions including artificial and natural seawater concluded that the CP-MCM-41 was selective for Ni2+ ions (99%). The formation of nickel-cryptate was confirmed by control experiments conducted along with every metal adsorption experiment mentioned in this paper. The serendipitous cryptate formation can be attributed to the complementarity and preorganization between C211 and Ni2+ ions.

Multi-functional magnetite–polysilsesquioxane (PSSQ) hybrid nanoparticles were synthesised in a one-pot approach using ferrous and ferric chlorides and various silane monomers by coprecipitation followed by a surface grafting method. The functional groups, surface properties, and thermal stability of the materials were analyzed using a range of characterisation techniques. Furthermore, the functional magnetic hybrid nanoparticles were used for the adsorption of heavy metal ions. The results suggest that the magnetic PSSQ hybrid nanoparticles have excellent adsorption and selectivity behavior for iron (Fe3+) and some heavy metal ions as individual ions or in mixtures of metal ions. The adsorption kinetics highlighted the excellent adsorption behavior of the functionalised magnetic PSSQ hybrid nanoparticles. On the other hand, the adsorption behavior depends on the type of functional groups present in the materials. These promising and highly desirable magnetic hybrid materials can be used in a wide range of applications.

In order to achieve beam acceleration to the beam energy of 10 GeV at the end of its 716 m-long linear accelerator (Linac), the Pohang Accelerator Laboratory X-ray Free Electron Laser (PAL-XFEL) is going to operate the Stanford Linear Accelerator Energy Doubler (SLED) at the maximum klystron output peak power of 80 MW, with a pulse length of 4 μs, and at a repetition rate of 60 Hz. The original SLED that had been used in Pohang Light Source-II (PLS-II) can no longer sustain such a high-power operation because excessive radiation caused by RF breakdown has been frequently detected even at the lower klystron peak power during the PLS-II operation. Therefore, a new SLED is designed by modifying both the 3-dB power hybrid and the waveguide-cavity coupling structure of the original SLED where the excessive radiation has been mainly detected. The finite-difference time-domain (FDTD) simulation in the CST Microwave Studio shows that the new SLED has a peak electric field and a surface current lower than those of the original SLED at the same level of the RF input peak power, which would secure stable high-power operation. All of the 42 SLEDs in the PAL-XFEL Linac are newly fabricated and installed. During the RF conditioning of the PAL-XFEL Linac, no significant vacuum and radiation issue was found in the new SLEDs. Finally, the accelerated electron beam energy of 10 GeV obtained at the end of the PAL-XFEL Linac verified that the RF performance of the new SLED is stable.

This study reports an inexpensive sol-gel method to synthesize TiO2-CNT hybrid materials. Synthesized TiO2-CNT materials show strong antibacterial activity in the absence of light. Cheap TiO2 source TiOCl2 is used during synthesis in the absence of high temperatures, high pressures and organic solvents. TiO2-CNT materials with 0, 2, 5, 10, 15 and 20wt% of CNT were synthesized and compared for antibacterial activity, surface area, porosity, crystalline structure, chemical state, and HaCaT cell proliferation. The antibacterial strength of hybrid materials increased significantly with the increase in CNT loading amount, and the TiO2-CNT samples with a CNT loading of 10wt% or more nearly removed all of the E.coli bacteria. HaCaT cell proliferation studies of synthesized hybrid materials illustrated that prepared TiO2-CNT systems exhibit minimum cytotoxicity. The characteristics of prepared materials were analyzed by means of XRD, FTIR, Raman spectroscopy, XPS, TEM, and nitrogen gas physisorption studies, compared and discussed.

Microstructure and corrosion properties of extruded AZ61 Mg alloys with varying Ca contents were investigated. Microstructure of the extruded AZ61 alloy consisted of α-Mg grains and Al 8 Mn 5 particles. Alloying with 0.1–0.5 wt% Ca to the AZ61 alloy resulted in the additional presence of (Mg,Al) 2 Ca particles in the extruded microstructure. In 0.6 M NaCl solution at 25 °C, the extruded AZ61 alloys with 0.1–0.5 wt% Ca showed corrosion rates over 2 times faster than that of the AZ61 alloy without Ca addition. Such deteriorated corrosion resistance due to Ca addition is discussed in terms of passivation and microgalvanic corrosion.

In this study, we reported the synthesis and characterizationof two different conductive polymers (PANI and PPy) and their nanocomposites with GO and GN (5 wt%). These polymers were modified via in situ EP using DBSA as both a surfactant and a doping agent. AT-FTIR results showed the successful interaction between the polymer chains and GO/GN. The XRD peaks for PANI and its nanocomposites were very sharp, indicating that they were crystalline in nature, whereas the broadened PPy peak in the case of PPy nanocomposites indicated the interaction between PPy and the GO/GN layers. FESEM results indicated that the resulting nanocomposites of both conductive polymers had sheet-like morphologies due to the presence of GO and GN during polymerization. Additionally, TEM results confirmed that PANI and PPy were well-distributed on the surface of GO and GN. TGA results clearly indicated that the thermal properties were enhanced on the addition of GO and GN in the conductive polymer matrices. All of the nanocomposites demonstrated higher values of electrical conductivity at room temperature with 5 wt% of GO and GN as doping agents. PPy nanocomposites with GO and GN showed the highest electrical conductivities (475.67 and 643.5 S/m, respectively) due to the improved interaction of PPy chains with GO and GN, as compared to PANI. This work provides an effective and reproducible method to fabricate conductive polymers (and their nanocomposites) that possess superior and desirable structural and electrical properties for various semiconductor devices.

The adsorption properties of succinamic acid functionalised MCM-41 (SA-MCM-41) towards dyes aqueous solution, such as rhodamine 6G (R6G), methylene blue (MB) and metanil yellow (MY), were studied. SA-MCM-41 was synthesised using a three step synthesis strategy, starting with the preparation of MCM-41 through a sol–gel methodology. Succinamic acid functionality was introduced through a ring opening reaction of succinic anhydride (SA) over the propyl amine functionality of A-MCM-41 in presence of trimethylamine. The materials at each synthesis step were characterised by X-ray diffraction, transmission electron microscopy, scanning electron microscopy, N 2 adsorption–desorption isotherms, Fourier transform infrared spectroscopy, and 29 Si and 13 C nuclear magnetic resonance spectroscopies. SA-MCM-41 exhibited good adsorption capacity towards R6G and MB but poor adsorption for MY from the individual dye solutions. The competitive adsorption from binary and ternary dye mixtures showed that SA-MCM-41 can remove MY effectively in the presence of R6G. The adsorption behaviour of R6G and MY over SA-MCM-41 from binary and ternary mixtures highlight the possibility of multilayer adsorption. The MY removal efficiency of pristine MCM-41 from R6G-MY binary mixture was also tested.

An inexpensive sol–gel technique to synthesize TiO2-Fe2O3 nanocomposites with improved structural and photochemical properties is introduced. A series of TiO2-Fe2O3 nanocomposites with different Fe2O3 contents were prepared through cheap TiO2 precursor titanium oxychloride (TiOCl2). The physicochemical properties of the samples were examined by XRD, XRF, SEM, EDX, HRTEM, UV–vis DRS, FTIR, TGA and nitrogen gas physisorption studies. The effects of calcination temperatures and Fe2O3 content on the mesostructure and photocatalytic strength of the prepared TiO2-Fe2O3 composites were investigated. Results showed that composites with distinct structural, optical and photochemical properties can be formed by varying Fe2O3 content.

Polyimide (PI)/hollow silica (HS) sphere hybrid films with low dielectric constant values (low-k) were synthesized via thermal imidization process using pyromellitic dianhydride (PMDA)/4,4′-oxydianiline (ODA) as the polymer matrix and HS spheres as inorganic particles with the closed air voids. The monodispersed HS spheres were synthesized via a one-step process, which means that the formation of silica shells and dissolution of the core particles (polystyrene particles) occurs in the same medium. The HS particles have uniform size of ca. 1.5 μm in diameter and ca. 100 nm in shell thickness. PI/HS sphere hybrid films synthesized using mixture of polyamic acid (PAA) and HS spheres prepared via one-pot process, which means that the production of PAA and HS spheres mixture occurs with the polymerization of PMDA and ODA in the same bottle. HS spheres of two different kinds (pristine HS spheres (PHS spheres) and amine-modified HS spheres (AHS spheres)) were used for the preparation of the hybrid films....

Bissilylated urea-bridged periodic mesoporous organosilicas (DUP-PMOs) were synthesized by the co-condensation of N,N′-diureylenepyridine-bis-[(3-propyl)triethoxysilane)] (DUP) and tetraethyl orthosilicate (TEOS) using a triblock copolymer (Pluronic P123) as a structure-directing agent at various DUP to TEOS ratios. Sulphonic acid-functionalized PMOs (SUP-PMOs) were prepared based on a reaction between amine groups of DUP-PMO with chlorosulphonic acid in chloroform under mild reaction conditions. These PMOs were well characterized by small angle X-ray scattering, N 2 adsorption–desorption measurements, Fourier-transform infrared spectroscopy, solid state 29 Si magic angle spinning (MAS) and 13 C cross polarisation-MAS nuclear magnetic resonance spectroscopy, transmission electron microscopy, scanning electron microscopy, X-ray photoelectron spectroscopy, and thermogravimetric analysis. The DUP-PMOs and SUP-PMOs had an ordered mesostructure, high to low surface area (ranging from 637 to 38 m 2 g − 1 ), medium pore volume (0.69–0.05 cm 3 g − 1 ) and uniform pore sizes (4.3–5.2 nm). The functionalized PMOs were used effectively for the adsorption of Co 2+ ions with high selectivity from artificial seawater. Owing to the presence of highly hydrophilic sulphonic acid moieties as pendent functional groups in the 1 and 3 positions of the urea nitrogen atoms, the materials were found to be highly suitable for the adsorption of Co 2+ ions from artificial seawater at pH 8 with 96.1% selectivity, even in the presence of several interfering metal ions, such as Cr 3+ , Cu 2+ , Ni 2+ , and Li + . The adsorption experiments showed that the selectivity towards Co 2+ depended heavily on the sulphonic acid loading on the surface nitrogen of diureylenepyridine-bridged PMO and the time of contact with metal ions in the artificial seawater.

The present study reports the antibacterial disinfection properties of a series of silver nanoparticle (AgNP) immobilized membranes. Initially, polyethersulfone (PES) was functionalized through the introduction of amino groups to form aminated polyethersulfone (NH2-PES, APES). AgNPs were then coordinately immobilized on the surface of the APES composite membrane to form AgNPs-APES. The properties of the obtained membrane were examined by FT-IR, XPS, XRD, TGA, ICP-OES and SEM-EDAX analyses. These structural characterizations revealed that AgNPs ranging from 5 to 40 nm were immobilized on the surface of the polymer membrane. Antibacterial tests of the samples showed that the AgNPs-APES exhibited higher activity than the AgNPs-PES un-functionalized membrane. Generally, the AgNPs-APES 1 cm × 3 cm strip revealed a four times longer life than the un-functionalized AgNPs polymer membranes. The evaluation of the Ag(+) leaching properties of the obtained samples indicated that approximately 30% of the AgNPs could be retained, even after 12 days of operation. Further analysis indicated that silver ion release can be sustained for approximately 25 days. The present study provides a systematic and novel approach to synthesize water treatment membranes with controlled and improved silver (Ag(+)) release to enhance the lifetime of the membranes.

The corrosion resistance of conventional and experimental Mg–3Al–1Zn-based alloys with different Mn and Y content was comparatively investigated. After immersion for 72 h in a 0.6 M NaCl solution at 25 °C, an experimental Mg–3Al–1Zn–0.05Mn–0.03Y alloy exhibited a corrosion rate of 0.91 mm y−1, which is about four times slower than that of a conventional Mg–3Al–1Zn–0.3Mn alloy. Microstructural factors underlying the improved corrosion resistance achieved by the trace additions of Mn and Y are discussed.

Dissolved oxygen (DO) is a key factor affecting pipe corrosion in district heating systems (DHS). This study demonstrated effective deoxygenation of water in a DHS using a hollow fiber membrane contactor (HFMC) via systematic investigation from lab-to pilot-scale. First, deoxygenation efficiency was evaluated in a lab-scale HFMC with varying operating parameters including an effective membrane area, flow rate and feedwater temperature. Based on the results from the lab-scale investigation, a pilot HFMC system was designed with capacity of 1 m3 per day. To achieve a permeate DO concentration below 10 μg L−1 at feedwater temperatures of 20–60 °C, the vacuum degree needed to be lower than the saturated water vapor pressure of 10–120 Torr. In addition, the primary foulant for membrane fouling was organic matter in the make-up and district heating (DH) return water. A significant change in corrosion response was observed for pipe steel in the DHS after deoxygenation. Immersion tests for 14 days indicated that weight loss values had greatly reduced by the deoxygenation process from 39.3 to 1.3 mg cm−2 and from 21.9 to 2.1 mg cm−2 for steel pipe samples immersed in the make-up water and the DH return water of the DHS, respectively. This improved corrosion resistance from deoxygenation was interpreted by electrochemical analysis. As such, this study offers a pilot-scale demonstration of the feasibility of a hollow fiber membrane-based deoxygenation process as an effective tool to prevent the corrosion of steel pipes.