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The effect of prerolling before artificial aging on the mechanical properties of the Al–Zn–Mg–Cu–Sc–Zr–Mn alloy with 12.4 wt% Zn (Zn/Mg ratio >1.3 at.%) is studied. The alloy sheets are prepared via casting, homogenization, hot rolling, and solution treatment. The sheets are further cold rolled to reduce their thicknesses by 0%–50% before being artificially aged. Yield strength, ultimate tensile strength, and elongation are increased from 648 to 697 MPa, from 662 to 712 MPa, and from 2.2% to 4.4% by prerolling up to 30%, and prerolling again by 50% reduces both the strength and elongation. Changes in the microstructural features, such as grain morphology, dislocation density, and defect characteristics, are attributed to the variations in the strength and elongation of the alloy. Work hardening during prerolling is responsible for the increase in strength, while pore closure and shear band formation induced by prerolling either increase or decrease the elongation. Furthermore, precipitation kinetics are accelerated by applying prerolling, which facilitates a faster aging response, lesser processing time to reach the peak hardness, and better mechanical properties.

Commercially pure Ti (CP Ti) exhibits an exceptional corrosion resistance, and it is thus critical in the aerospace, marine, and petrochemical fields. However, pure Ti also displays a modest strength and limited wear resistance. Therefore, several studies have explored the incorporation of reinforcing phases, such as ceramics and carbides, leading to the development of metal matrix composites. This study investigates the fabrication of CP Ti-WC composites using an additive manufacturing process and explores the effect of the WC content on the microstructure, mechanical properties, and corrosion resistance. Regarding the mechanical properties, the tensile strength and hardness progressively increase with increasing WC content owing to microstructural refinement and solid solution strengthening caused by W. The alloy containing 5 wt% WC displays the respective maximum strength and hardness of 1042 MPa and 362.2 HV. Furthermore, WC addition enhances the corrosion resistance of CP Ti in a 70 % H2SO4 solution. Compared to those of the other samples, the alloy with 5 wt% WC exhibits the lowest mass loss (0.00242 mg/cm2) and current density in the passivation region, which are attributed to the microstructural refinement aiding in the formation of a stable oxide layer. Thus, this research highlights the potential of CP Ti-WC composites, which exhibit improved mechanical performances and corrosion resistances for use in demanding applications, with insights into microstructural control and property enhancement.

High-entropy alloys (HEAs), a relatively new class of materials, have attracted significant attention in materials science owing to their unique properties and potential applications. High entropy stabilizes the phase of a solid solution over a wide range of chemical compositions, yielding unique properties superior to those of conventional alloys. Therefore, this study analyzed the microstructure and electrochemical behavior of HEAs (Cantor) to evaluate their corrosion resistance, according to their manufacturing process (casting, cold rolling, and annealing). The microstructural morphologies and sizes were analyzed using electron backscatter diffraction. The electrochemical behavior was examined using open circuit potential measurements, electrochemical impedance spectroscopy, potentiodynamic polarization tests, and critical pitting temperature measurements using a potentiostat. The casting process formed a nonuniform microstructure (average grain size = 19 μm). The cold rolling process caused the formation of fine grains (size = 4 μm). A uniform microstructure (grain size > 151 μm) was formed after heat treatment. The corrosion resistance of the HEAs was determined from the passivation layer formed by Cr oxidation. These microstructural differences resulted in variations in the electrochemical behavior. Microstructural and electrochemical analyses are crucial because HEAs have diverse potential applications. Therefore, this study contributes to future improvements in HEA manufacturing processes.

We present a strategy for fabricating aluminum (Al) matrix composites (AMCs) reinforced with interconnected aluminum nitride (AlN) via arc plasma-induced accelerated volume nitridation. AMCs with 10 vol.% AlN are formed in situ by the reaction between liquid Al alloy and nitrogen gas within 1 min of arc melting, revealing very high formation rate of AlN (3.28 × 10−1 g/min·cm3). The rapid nitridation is attributed to the improved wettability and spontaneous infiltration of the melt, which results in the formation of AlN agglomerates and lamellas. In particular, Al-12Si/AlN composites exhibit over two times higher yield strength (195 MPa) than the Al/AlN composites (70 MPa) when compressed along the longitudinal direction to the lamellas. The coefficient of thermal expansion (CTE) is about 30% lower in the Al-12Si/AlN composites (17.0 × 10−6/K) than pure Al (23.6 × 10−6/K). This is attributed to the interconnected AlN architecture and Al–Si eutectic microstructure, which constrain the thermal expansion of the Al matrix. The present AMCs afford an attractive combination of specific thermal conductivity and CTE. These findings would facilitate the development of novel AMCs reinforced with interconnected AlN as cost-effective heat sink materials.

We investigate the coherence properties of a transmission electron microscope by analyzing nano-diffraction speckles originating from bulk metallic glass. The spatial correlation function of the coherent diffraction patterns, obtained in the transmission geometry, reveals the highly coherent nature of the electron probe beam and its spatial dimension incident on the sample. Quantitative agreement between the measured speckle contrast and an analytical model yields estimates for the transverse and longitudinal coherence lengths of the source. We also demonstrate that the coherence can be controlled by changing the beam convergence angle. Our findings underscore the preservation of electron beam coherence throughout the electron optics, as evidenced by the high-contrast speckles observed in the scattering patterns of the amorphous system. This study paves the way for the application of advanced coherent diffraction methodologies to investigate local structures and dynamics occurring at atomic-length scales across a diverse range of materials.

In this study, a post-weld heat treatment (PWHT) was proposed at high temperatures of 600 °C, 750 °C, and 900 °C for 30 min to significantly improve the impact absorbed energy of high manganese steel weld metal. Electron backscatter diffraction (EBSD), electron probe microanalysis (EPMA), and high-angle annular dark field scanning transmission electron microscopy (HAADF-STEM) were employed to characterize the production and study the deformation mechanisms in the high manganese steel weld metal. The impact absorbed energy is divided into crack initiation energy and crack propagation energy, which are divided by the value of Pmax. The cryogenic impact absorbed energy was 81 J. After PWHT at 600 °C, 750 °C, and 900 °C, it was 75 J, 69 J, and 88 J, respectively. The impact absorbed energies did not follow a proportional relationship with the PWHT temperatures. The increase in impact absorbed energy can be attributed to the narrowing of the dendritic region, which blocks the crack propagation path and efficiently prevents crack propagation. Conversely, the decrease in impact absorbed energy can be attributed to the presence of 100-nm-sized (Cr, Mn)23C6-type carbides at the grain boundaries, which facilitate crack propagation.

Producing nacre-like ceramics with a tough, non-polymeric matrix remains a challenge. Here, the authors use the reactive wetting of a zirconium-based bulk metallic glass to successfully infiltrate a porous alumina and create a composite with improved flexural strength and fracture toughness.

Key points 1. This is one of the very few prospective trials focusing on refractory multiple myeloma with extramdedullary disease (EMD). 2. We successfully laid grounds for implementing immunochemotherapy in EMD treatment.

Preaging (PA) is an important process to enhance the performance of automotive aluminum outer panels through regulating solute clustering. In this work, we investigated the effect of PA temperatures in the range of 60°C-225 °C on the hardness before and after paint baking (PB) with different holding times. Tensile properties of partial alloys were checked to help explore the optimum PA condition. Before PB, the PA hardness of alloys preaged in the low-temperature regime (60°C-100 °C) was relatively stable with increasing PA time, but it increased significantly in the high-temperature regime (120°C-200 °C). After PB, the hardness of alloys preaged at temperatures up to 80 °C was low. Alloys preaged at 100 °C for 4 h could reach the same PB hardness as the solution-treated (ST) alloy. However, after reaching saturation of the hardness of preaged alloys in the low-temperature regime, extending the PA time did not induce a higher PB hardness. By contrast, the hardness decreased after long-term PA. The saturation PB hardness of the alloy further increased when preaged at a higher PA temperature and reached a maximum at 170 °C. The optimum PA condition for this alloy is 150 °C for 10 min as it produced better elongation before PB and the highest BHR after PB. The related mechanisms, including clustering and precipitation behaviors, have been discussed in detail.

We investigated the effect of different Cu additions (0.1 wt.% and 0.3 wt.%) on the precipitation activation energy and mechanical properties of Al–Mg–Si alloys under different prestraining levels (0%, 3%, and 5%). Tensile tests were performed before and after paint baking (PB). Differential scanning calorimetry (DSC) and transmission electron microscopy (TEM) analyses were conducted to explore the clustering and precipitation behavior. Our results show that the precipitation activation energy was reduced by higher Cu addition but increased with prestraining level. Before PB, higher Cu addition significantly improved the elongation and work-hardening behavior, and the improvement was more pronounced in the prestrained alloys than in the nonprestrained alloys. After PB, higher Cu addition slightly increased the bake hardening response (BHR) of the alloy, and this improvement was enhanced in the prestrained alloys. However, only by introducing an appropriate amount of prestraining (3%) could the high-Cu alloy increase the BHR more significantly than the low-Cu alloy. When 5% prestraining was introduced, the high-Cu alloy had no advantage in increasing the BHR. After the introduction of 3% prestraining, a small amount of pre-Q′ phases was additionally formed near the dislocation lines, but the β″ phase was still the main strengthening phase. Higher Cu addition significantly refined the β″ phase and increased its number density, thereby improving the BHR. The formation of pre-Q′ phases was more pronounced in the high-Cu alloy under 5% prestraining, which suppressed the formation of the β″ phase and limited the BHR.

A comparative study of the microstructure and mechanical properties (tensile and high-cycle-fatigue) of Incoloy 901 repair welds produced via direct-energy-deposition (DED) and conventional tungsten-inert-gas (TIG) welding was conducted. The initial microstructure of the cast Incoloy 901 substrate exhibited a γ-matrix (an average grain size of ∼235 μm) and spherical γ′ particles (a size of

Abstract Although several studies have identified a distinct gut microbial composition in Parkinson’s disease (PD), few studies have investigated the oral microbiome or functional alteration of the microbiome in PD. We aimed to investigate the connection between the oral and gut microbiome and the functional changes in the PD-specific gut microbiome using shotgun metagenomic sequencing. The taxonomic composition of the oral and gut microbiome was significantly different between PD patients and healthy controls (P = 0.003 and 0.001, respectively). Oral Lactobacillus was more abundant in PD patients and was associated with opportunistic pathogens in the gut (FDR-adjusted P

Background: Carbapenem resistance in Pseudomonas aeruginosa is a serious global health problem. We investigated the clonal distribution and its association with the carbapenem resistance mechanisms of carbapenem-non-susceptible P. aeruginosa isolates from three Korean hospitals. Methods: A total of 155 carbapenem-non-susceptible P. aeruginosa isolates collected between 2011 and 2019 were analyzed for sequence types (STs), antimicrobial susceptibility, and carbapenem resistance mechanisms, including carbapenemase production, the presence of resistance genes, OprD mutations, and the hyperproduction of AmpC ß-lactamase. Results: Sixty STs were identified in carbapenem-non-susceptible P. aeruginosa isolates. Two high-risk clones, ST235 (N=41) and ST111 (N=20), were predominant; however, sporadic STs were more prevalent than high-risk clones. The resistance rate to amikacin was the lowest (49.7%), whereas that to piperacillin was the highest (92.3%). Of the 155 carbapenem-non-susceptible isolates, 43 (27.7%) produced carbapenemases. Three metallo-β-lactamase (MBL) genes, blaIMP-6 (N=38), blaVIM-2(N=3), and blaNDM-1(N=2), were detected. blaIMP-6 was detected in clonal complex 235 isolates. Two ST773 isolates carried blaNDM-1 and rmtB. Frameshift mutations in oprD were identified in all isolates tested, regardless of the presence of MBL genes. Hyperproduction of AmpC was detected in MBL gene-negative isolates. Conclusions: Frameshift mutations in oprD combined with MBL production or hyperproduction of AmpC are responsible for carbapenem resistance in P. aeruginosa. Further attention is required to curb the emergence and spread of new carbapenem-resistant P. aeruginosa clones. [ABSTRACT FROM AUTHOR]

Acute myeloid leukemia (AML) is an aggressive blood cancer with a high rate of relapse associated with adverse survival outcomes, especially in elderly patients. An aberrant expression of cyclin dependent kinase 7 (CDK7) is associated with poor outcomes and CDK7 inhibition has showed antitumor activities in various cancers. We investigated the efficacy of YPN-005, a CDK7 inhibitor in AML cell lines, xenograft mouse model, and primary AML cells. YPN-005 effectively inhibited the proliferation of AML cells by inducing apoptosis and reducing phosphorylation of RNA polymerase II. The c-MYC expression decreased with treatment of YPN-005, and the effect of YPN-005 was negatively correlated with c-MYC expression. YPN-005 also showed antileukemic activities in primary AML cells, especially those harboring FMS-like tyrosine kinase 3–internal tandem duplication (FLT3-ITD) mutation and in in vivo mouse model. Phosphorylated FLT3/Signal transducer and activator of transcription 5 (STAT5) was decreased and FLT3/STAT5 was downregulated with YPN-005 treatment. Our data suggest that YPN-005 has a role in treating AML by suppressing c-MYC and FLT3.

Background: This study aimed to examine the evidence for the effect of Lepidium meyenii Walp. [Brassicaceae] (L. meyenii W.), known as maca, on improving semen quality.Methods: Nine databases were searched for randomized controlled trials (RCTs) that examined the parameters for improvements in semen quality, regardless of the type of L. meyenii W. The risk of bias (ROB) among the studies was evaluated according to the Cochrane ROB tool.Results: Five RCTs met all of the inclusion criteria. Three RCTs showed mixed efficacy of maca in improving semen quality parameters, including sperm concentration and sperm motility, in men experiencing infertility. The meta-analysis also failed to show the efficacy of maca in increasing the sperm concentration compared to the placebo (weighted mean difference, 2.22, 95% confidence interval −2.94 to 7.37, p = 0.4). Two other RCTs also showed mixed effects of maca on several semen quality parameters in healthy men.Conclusion: The evidence from the included studies suggests unclear effects of maca on semen quality parameters in both men experiencing infertility and healthy men. However, the total number of RCTs and the total sample size were too small to draw firm conclusions.

BackgroundAutologous stem cell transplantation (ASCT) remains the standard of care for patients with newly diagnosed multiple myeloma (MM). Several attempts to improve the efficacy of conditioning regimens have been conducted in MM, but no more effective regimen than conventional high-dose melphalan has been introduced.ObjectiveIn this study, the efficacy and toxicity of busulfan and thiotepa (BuTT) and those of high-dose melphalan (HD-MEL) were compared retrospectively as a conditioning regimen for ASCT in patients with MM.Study designIncluded in the analysis were 114 patients who received BuTT and 114 patients who received HD-MEL treatment between March 2008 and May 2020. The BuTT regimen consisted of intravenous thiotepa 5 mg/kg once a day from days 7 to 6, followed by intravenous busulfan 3.2 mg/kg once a day from days 5 to 3. The HD-MEL conditioning regimen consisted of melphalan 100 mg/m2 once a day from days 3 to 2.ResultsThe overall response rate after ASCT did not differ between BuTT and HD-MEL (94.7% in BuTT vs. 97.4% in HD-MEL, p = 0.333). After a median follow-up of 47.6 months, progression-free survival (PFS) tended to be longer in the BuTT group (median PFS, 41.5 months vs. 30.3 months; hazard ratio (HR), 0.706; 95% confidence interval (CI), 0.497–1.004, p = 0.053). In the subgroup analysis of patients who did not proceed to maintenance or consolidation treatment after ASCT, the difference in PFS became more significant (median PFS, 41.5 months vs. 24.4 months; HR, 0.621; 95% CI, 0.388–0.993; p = 0.047). Additionally, the BuTT group had fewer adverse events, such as grade 3 or 4 stomatitis and diarrhea, than the HD-MEL group (stomatitis, 10.5% vs. 23.7%, p = 0.013; diarrhea, 10.5% vs. 25.4%, p = 0.005). There was no difference in the occurrence of venous-occlusive disease (2.6% in BuTT vs. 0.9% in HD-MEL, p = 0.622).ConclusionOur study results suggest that BuTT is an effective alternative conditioning regimen with reduced toxicity in patients with newly diagnosed MM.

Dendritic cells (DCs) are the most potent antigen-presenting cells, and have thus been used in clinical cancer vaccines. However, the effects of DC vaccines are still limited, leading researchers to explore novel ways to make them effective. In this study, we investigated whether human monocyte-derived DCs generated via the addition of interleukin 15 (IL-15) had a higher capacity to induce antigen-specific T cells compared to conventional DCs. We isolated CD14+ monocytes from peripheral blood from multiple myeloma (MM) patients, and induced immature DCs with granulocyte-macrophage colony-stimulating factor (GM-CSF) and IL-4 in the presence or absence of IL-15 for 4–6 days. Then we generated mature DCs (mDCs) with lipopolysaccharide for another 2 days [IL-15 mDCs (6 days), IL-15 mDCs (8 days), and conventional mDCs (8 days)]. IL-15 mDCs (6 days) showed higher expression of MHC I and II, CD40, CD86, and CCR7, and the secretion of IFN-γ was significantly higher compared to conventional mDCs. IL-15 mDCs (6 days) showed superior polarization of naïve T cells toward Th1 cells and a higher proportion of activated T cells, cytokine-induced killer (CIK) cells, and natural killer (NK) cells for inducing strong cytotoxicity against myeloma cells, and lower proportion of regulatory T cells compared to conventional mDCs. These data imply that novel multipotent mDCs generated by the addition of IL-15, which can be cultivated in 6 days, resulted in outstanding activation of T cells, CIK cells and NK cells, and may facilitate cellular immunotherapy for cancer patients.

Polyethylene glycol (PEG) and polysorbate 80 are ingredient in various medical products including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine. However, little is known about the relationship between these allergy and general anesthesia. We present a case of a 41-year-old woman was scheduled to undergo left partial mastectomy. She had a history of PEG and polysorbate 80 allergy. We administered antihistamine and corticosteroid before surgery as pretreatment considering the possibility of pseudoallergy in addition to avoiding exposure to PEG/polysorbate. Despite the pre-treatment, redness was noted around the patient's face and neck upon injection of Propofol 100 mg. However, after administration of additive antihistamine, the lesion disappeared without any allergic symptoms. Propofol, remifentanil and rocuronium with sevoflurane were used for induction and maintenance of the general anesthesia. Following the completion of surgery, the muscle relaxant was reversed by sugammadex. The patient was discharged without any complications. This case report aims to review the relevant patient population and provide guidance for safe surgical management. [ABSTRACT FROM AUTHOR]

Purpose: The role of allogeneic stem cell transplantation (alloSCT) in multiple myeloma (MM) treatment remains controversial. We conducted a retrospective, multicenter, nationwide study in Korea to evaluate the outcomes of alloSCT in Asian patients with MM. Materials and Methods: Overall, 109 patients with MM who underwent alloSCT between 2003 and 2020 were included in this study. Data were collected from the Korean Multiple Myeloma Working Party Registry. Results: The overall response rate and stringent complete response plus complete response (CR) rates were 67.0 and 46.8%, respectively, after alloSCT. At a median follow-up of 32.5 months, the 3-year probability of progression-free survival (PFS) and overall survival (OS) rates were 69.3% and 71.8%, respectively. The 3-year probabilities of OS rates in the upfront alloSCT, tandem auto-alloSCT, and later alloSCT groups were 75.0%, 88.9%, and 61.1%, respectively. Patients who achieved CR before or after alloSCT had significantly longer OS (89.8 vs. 18 months and 89.8 vs. 15.2 months, respectively). Even though patients who did not achieve CR prior to alloSCT, those who achieve CR after alloSCT had improved PFS and OS compared to those who had no achievement of CR both prior and after alloSCT. Patients who underwent alloSCT with 1-2 prior treatment lines had improved PFS (22.4 vs. 4.5 months) and OS (45.6 vs. 15.3 months) compared to those with three or more prior treatment lines. Conclusion AlloSCT may be a promising therapeutic option especially for younger, chemosensitive patients with earlier implementation from relapse. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the validity and reliability of a home-based, guardian-conducted video voiding test for assessing postoperative voiding function after hypospadias surgery. Materials and Methods: In a single center, patients who had undergone urethroplasty by a single surgeon and postoperative uroflowmetry and video voiding tests conducted between 2008 and 2016 were retrospectively reviewed. Urinary stream was categorized into five grades by three pediatric urologists in a blinded manner. The primary outcome was statistical correlation across raters as measured by Spearman correlation coefficient to validate the interpretation of the video voiding test. The secondary outcome was the reliability of the voiding video test compared with maximum urinary flow rate assessed by uroflowmetry. Results: Thirty-one patients with hypospadias were enrolled. The patients' average ages were 12.3±3.2 months (range, 8–21 months) and 42.8±3.9 months (range, 35–48 months) at the time of surgery and voiding video tests, respectively. Hypospadias was anterior, penile, and proximal in 1 (3.2%), 18 (58.1%), and 12 (38.7%) patients, respectively. The number of patients with each voiding stream grade was as follows: very poor, 4; poor, 4; fair, 13; good, 4; and very good, 6. All intraclass correlation coefficients of the stream grade among the three observers were >0.95. Correlation between the maximum flow rate obtained by use of conventional uroflowmetry and the video voiding stream grade was validated (rho 0.778, p

Background: The cellular senescence of primary cultured cells is an irreversible process characterized by growth arrest. Restoration of senescence by ginsenosides has not been explored so far. Rg3(S) treatment markedly decreased senescence-associated β-galactosidase activity and intracellular reactive oxygen species levels in senescent human dermal fibroblasts (HDFs). However, the underlying mechanism of this effect of Rg3(S) on the senescent HDFs remains unknown. Methods: We performed a label-free quantitative proteomics to identify the altered proteins in Rg3(S)-treated senescent HDFs. Upregulated proteins induced by Rg3(S) were validated by real-time polymerase chain reaction and immunoblot analyses. Results: Finally, 157 human proteins were identified, and variable peroxiredoxin (PRDX) isotypes were highly implicated by network analyses. Among them, the mitochondrial PRDX3 was transcriptionally and translationally increased in response to Rg3(S) treatment in senescent HDFs in a time-dependent manner. Conclusion: Our proteomic approach provides insights into the partial reversing effect of Rg3 on senescent HDFs through induction of antioxidant enzymes, particularly PRDX3. Keywords: Ginsenoside Rg3(S), Human dermal fibroblast, Label-free quantitative proteomics, Restoration, Senescence

This study was conducted to examine the effect of calcium nitrate (CaNO3) on berry shattering in and the fruit characteristics of the ‘Cheongsoo’ grape cultivar. The rate of berry shattering was reduced regardless of CaNO3 concentration when the detachment force of the abscission zone at the stalk-berry junction increased. When 0.8% CaNO3 was treated, the berry shattering rate decreased by approximately 40% compared to the control; this was the lowest value. Furthermore, fruit quality declined and side effects were not observed following the CaNO3 treatment although fruit firmness also increased by 57% compared to the control. These results indicate that treatment with CaNO3 can contribute to stable production of ‘Cheongsoo’ grapes.

Remimazolam's ultrashort-acting properties, including reduced injection discomfort, minimal impact on respiratory and cardiovascular functions and rapid metabolism, have garnered significant attention in the field of anesthesia. However, despite its widespread acclaim, we encountered an unusual case in which a patient without hepatic or renal impairment experienced unexpected delays in regaining consciousness following a single intravenous induction dose of remimazolam. The patient, a 63-yearold undergoing laparoscopic cholecystectomy for gallbladder stones, had preoperative tests revealing atrial fibrillation and a reduced ejection fraction observed in an echocardiogram. Anesthesia induction included the administration of remimazolam (0.3 mg/kg), sufentanil and rocuronium. The surgery proceeded uneventfully and was maintained with desflurane and sufentanil. However, after the surgery, the patient experienced delayed emergence from anesthesia. Opioid overdose was ruled out, and we suspected a metabolic delay associated with remimazolam. In response to this suspicion, we administered flumazenil, which promptly restored consciousness and normal breathing. Subsequent post-anesthetic observation revealed no complications, and the patient was discharged two days after surgery. This case highlights the significant delayed emergence phenomenon linked to remimazolam, even when administered as a bolus. Instances of delayed emergence following remimazolam administration underscore the complexities in anesthesia responses, emphasizing the importance of vigilant clinical monitoring and the need for ongoing research in this area. [ABSTRACT FROM AUTHOR]

Abstract Background The antibody-dependent cellular cytotoxicity (ADCC) is a cell-mediated immune defense mechanism in which effector immune cells actively lyse antibody-coated target cells. The ADCC of tumor cells is employed in the treatment of various cancers overexpressing unique antigens, and only natural killer (NK) cells are known to be major effectors of antibody mediated ADCC activity. Canine NK cells are still defined as non-B, non-T large granular lymphocytes because of the lack of information regarding the NK cell-restricted specific marker in dogs, and it has never been demonstrated that canine NK cells have ADCC ability against tumor cells. In the present study, we investigated whether canine non-B, non-T NK cells have ADCC ability against target antibody-coated tumor cells, using cetuximab and trastuzumab, the only human antibodies reported binding to canine cancer cells. Results Activated canine non-B, non-T NK cells (CD3−CD21−CD5−TCRαβ−TCRγδ−) for 13~17 days ex vivo showed ADCC ability against trastuzumab- or cetuximab-coated target tumor cells expressing various levels of human epidermal growth factor receptor 2 (HER-2) and epidermal growth factor receptor (EGFR). Trastuzumab and cetuximab induced significant ADCC responses of canine NK cells even in CMT-U334 and CF41.Mg cells expressing low levels of HER-2 and/or EGFR, as well as in SKBR3 and DU145 cells overexpressing HER-2 and/or EGFR. The trastuzumab-mediated ADCC activity of NK cells was significantly enhanced by treatment with rcIL-21. Conclusions The results of this study suggest that canine non-B, non-T NK lymphocytes have a potential ADCC function and that combinational strategies of monoclonal antibodies with either cytokines, which activate NK cells in vivo, or adoptive transfer of NK cells may be a feasible method for amplifying the efficacy of immunotherapy against malignant cancers even with very low expression of target molecules in dogs.

Abstract Background Dendritic cells (DCs) are professional antigen presenting cells (APCs), which can activate antigen-specific CD8+ T cell immunity, resulting in tumor clearance. Immature DCs are usually stimulated by various adjuvants through their immune receptors. Among them, Toll-like receptor 4 (TLR4) has an important role in activating DCs to cause their maturation. In fact, TLR4 is well-known to induce innate and adaptive immune responses against various external microbial or internal damage associated molecular patterns (DAMP). LPS is widely regarded as a strong stimulator of TLR4 signaling. However, LPS is inappropriate for use in humans since it is an endotoxin. Unfortunately, other TLR4 ligands such as HMGB1 or heat shock proteins have weak adjuvant effects. Therefore, there is a need to identify novel, biocompatible, strong, TLR4 ligands. Methods 40S ribosomal protein S3 (RPS3) was screened through pull-down assay using TLR4. BMDCs from wild type (WT) and TLR4 knock-out mice were treated by RPS3 to identify the activation and maturation of DCs. T cell generation including memory T cells, tumor prevention, and treatment experiments were performed with BMDCs based vaccination. Also, human DCs originated from patients were treated by RPS3 to confirm the activation and maturation of DCs. Results In this study, we identified 40S ribosomal protein S3 (RPS3) through a pull-down assay using a variety of human cancer cell-derived proteins that could bind to TLR4. RPS3 was released from tumor cells following treatment with an anticancer drug, and it was shown that the released RPS3 binds to TLR4. Recombinant RPS3 induced maturation and activation of DCs, and following pulsing with tumor specific antigens, these DCs could be used as a vaccine to significantly increase tumor specific CD8+IFN-γ+ T cells, and provide both tumor prevention and tumor treatment effects. The effect of RPS3 on DC maturation and its utility as a vaccine were shown to be dependent on TLR4 using TLR4 knockout mice. Conclusions This study therefore proved that human cancer cell-derived RPS3, a novel TLR4 ligand, has great potential as an adjuvant in tumor-specific antigen DC-based vaccines.

Abstract It is well‐known that the alkali doping of polycrystalline Cu2ZnSn(S,Se)4 (CZTSSe) and Cu(In,Ga)(Se,S)2 has a beneficial influence on the device performance and there are various hypotheses about the principles of performance improvement. This work clearly explains the effect of Na doping on the fill factor (FF) rather than on all of the solar cell parameters (open‐circuit voltage, FF, and sometimes short circuit current) for overall performance improvement. When doping is optimized, the fabricated device shows sufficient built‐in potential and selects a better carrier transport path by the high potential difference between the intragrains and the grain boundaries. On the other hand, when doping is excessive, the device shows low contact potential difference and FF and selects a worse carrier transport path even though the built‐in potential becomes stronger. The fabricated CZTSSe solar cell on a flexible metal foil optimized with a 25 nm thick NaF doping layer achieves an FF of 62.63%, thereby clearly showing the enhancing effect of Na doping.