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Hippocampal neurogenesis (HN) is considered an important mechanism underlying lifelong brain plasticity, and alterations in this process have been implicated in early Alzheimer's disease progression. APOE polymorphism is the most common genetic risk factor for late-onset Alzheimer's disease where the ε4 genotype is associated with a significantly earlier disease onset compared to the neutral ε3 allele. Recently, APOE has been shown to play an important role in the regulation of HN. However, the time-dependent impact of its polymorphism in humans remains elusive, partially due to the difficulties of studying human HN in vivo. To bridge this gap of knowledge, we used an in vitro cellular model of human HN and performed a time course characterization on isogenic induced pluripotent stem cells with different genotypes of APOE. We found that APOE itself was more highly expressed in ε4 at the stem cell stage, while the divergence of differential gene expression phenotype between ε4 and ε3 became prominent at the neuronal stage of differentiation. This divergence was not associated with the differential capacity to generate dentate gyrus granule cell-like neurons, as its level was comparable between ε4 and ε3. Transcriptomic profiling across different stages of neurogenesis indicated a clear “maturation of functional neurons” phenotype in ε3 neural progenitors and neurons, while genes differentially expressed only in ε4 neurons suggested potential alterations in “metabolism and mitochondrial function.” Taken together, our in vitro investigation suggests that APOE ε4 allele can exert a transcriptome-wide effect at the later stages of HN, without altering the overall level of neurogenesis per se.

LIM domain kinases 1 and 2 (LIMK1 and LIMK2) regulate actin dynamics and subsequently key cellular functions such as proliferation and migration. LIMK1 and LIMK2 phosphorylate and inactivate cofilin leading to increased actin polymerization. As a result, LIMK inhibitors are emerging as a promising treatment strategy for certain cancers and neurological disorders. High-quality chemical probes are required if the role of these kinases in health and disease is to be understood. To that end, we report the results of a comparative assessment of 17 reported LIMK1/2 inhibitors in a variety of

Adult hippocampal neurogenesis is important for learning and memory and is altered early in Alzheimer's disease. As hippocampal neurogenesis is modulated by the circulatory systemic environment, evaluating a proxy of how hippocampal neurogenesis is affected by the systemic milieu could serve as an early biomarker for Alzheimer's disease progression. Here, we used an in vitro assay to model the impact of systemic environment on hippocampal neurogenesis. A human hippocampal progenitor cell line was treated with longitudinal serum samples from individuals with mild cognitive impairment, who either progressed to Alzheimer's disease or remained cognitively stable. Mild cognitive impairment to Alzheimer's disease progression was characterized most prominently with decreased proliferation, increased cell death and increased neurogenesis. A subset of 'baseline' cellular readouts together with education level were able to predict Alzheimer's disease progression. The assay could provide a powerful platform for early prognosis, monitoring disease progression and further mechanistic studies.Adult hippocampal neurogenesis is altered early in the course of Alzheimer's disease. Maruszak et al. show that serum from patients with MCI who do versus do not progress to Alzheimer's disease differentially affects the fate of hippocampal stem cells in vitro, suggesting that this assay could help predict disease progression.

Oncolytic virotherapy is a promising alternative to conventional treatment, yet systemic delivery of these viruses to tumors remains a major challenge. In this regard, mesenchymal stem cells (MSC) with well-established tumor-homing property could serve as a promising systemic delivery tool. We showed that MSCs could be effectively infected by hepatocellular carcinoma (HCC)-targeted oncolytic adenovirus (HCC-oAd) through modification of the virus' fiber domain and that the virus replicated efficiently in the cell carrier. HCC-targeting oAd loaded in MSCs (HCC-oAd/MSC) effectively lysed HCC cells in vitro under both normoxic and hypoxic conditions as a result of the hypoxia responsiveness of HCC-oAd. Importantly, systemically administered HCC-oAd/MSC, which were initially infected with a low viral dose, homed to HCC tumors and resulted in a high level of virion accumulation in the tumors, ultimately leading to potent tumor growth inhibition. Furthermore, viral dose reduction and tumor localization of HCC-oAd/MSC prevented the induction of hepatotoxicity by attenuating HCC-oAd hepatic accumulation. Taken together, these results demonstrate that MSC-mediated systemic delivery of oAd is a promising strategy for achieving synergistic antitumor efficacy with improved safety profiles.Significance:Mesenchymal stem cells enable delivery of an oncolytic adenovirus specifically to the tumor without posing any risk associated with systemic administration of naked virions to the host.

Fig. S1. Efficiency of transduction of GFP-expressing Ads with different fiber types into MSCs; Fig. S2. Release profiles and intracellular viral production of HCC-oAd-WNTi from MSCs; Fig. S3. MSC killing effect of HCC-oAd-WNTi

Dendritic cell (DC)-based immunotherapies have been shown to be a potential treatment option for various cancers; however, the exact strategies in ovarian cancer remain unknown. Here, we report the effectiveness of mouse CD8α+ DCs derived from bone marrow hematopoietic stem cells (BM-HSCs), equivalent to human CD141+ DCs, which have proven to be a highly superior subset. Mono-DCs from monocytes and stem-DCs from HSCs were characterized by CD11c+ CD80+ CD86+ and CD8α+ Clec9a+ expression, respectively. Despite a lower dose compared with Mono-DCs, mice treated with pulsed Stem-DCs showed a reduced amount of ascitic fluid and lower body weights compared with those of vehicle-treated mice. These mice treated with pulsed stem-DCs appeared to have fewer tumor implants, which were usually confined in the epithelium of tumor-invaded organs. All mice treated with DCs showed longer survival than the vehicle group, especially in the medium/high dose pulsed Stem-DC treatment groups. Moreover, the stem-DC-treated group demonstrated a low proportion of myeloid-derived suppressor cells and regulatory T cells, high interleukin-12 and interferon-γ levels, and accumulation of several tumor-infiltrating lymphocytes. Together, these results indicate that mouse CD8α+ DCs derived from BM-HSCs decrease tumor progression and enhance antitumor immune responses against murine ovarian cancer, suggesting that better DC vaccines can be used as an effective immunotherapy in EOC treatment. Further studies are necessary to develop potent DC vaccines using human CD141+ DCs.

Objectives: Dendritic cell (DC) based immunotherapies have been shown to be a potential treatment option for various cancers; however, the exact strategies in ovarian cancer remain unknown. This study aimed to evaluate the effectiveness of mouse CD8α+ dendritic cells (DCs), corresponding to human CD141+ DCs, derived from bone marrow (BM) hematopoietic stem cells (HSCs) in a syngeneic and orthotopic mouse ovarian cancer model. Methods: Stem-DCs from HSCs and Mono-DCs from monocytes were generated from the bone marrow mononuclear cells (BM-MNCs) of C57BL/6 mice in condition of pulsing with ID8 tumor cell lysates. C57BL/6 mice were intraperitoneally injected with 5 × 106 ID8 cells. They were treated with vehicle, low/medium/high dose pulsed Stem-DCs, Mono-DCs, and unpulsed Stem-DCs. At 8 to 9 weeks, the treated mice were sacrificed, and tumor responses and immune responses, such as lymphocyte proliferation and cytokine secretion, were analyzed. Results: Mono-DCs and Stem-DCs were characterized by CD11c+CD80+CD86+ and CD8α+Clec9a+ expression, respectively. They were confirmed by the secretion of immunostimulatory cytokines, such as interleukin (IL)-12 and interferon (IFN)-γ, and T cell proliferation was observed after maturation. Despite a lower dose compared with Mono-DCs, mice treated with pulsed Stem-DCs showed a reduced amount of ascitic fluid and lower body weights compared with those of vehicle treated mice (P = 0.0021 and P = 0.0092, respectively). These mice treated with pulsed Stem-DCs appeared to have fewer tumor implants which were usually confined in the epithelium of ovaries, diaphragm and peritoneum. All mice injected with DCs demonstrated longer survival than the vehicle group (P = 0.0187), especially the medium/high dose pulsed Stem-DC treatment groups. Moreover, these favorable tumor responses were associated with a low proportion of myeloid-derived suppressor cells (MDSCs) and regulatory T cells, high IL-12 and IFN-γ levels, and accumulation of several tumor-infiltrating lymphocytes. Conclusions: We demonstrated that mouse CD8α+ DCs derived from BM HSCs could decrease tumor progression and enhance antitumor immune responses against murine ovarian cancer. Further studies are necessary to develop potent DC vaccines using human CD141+ DCs. Citation Format: Shin-Wha Lee, Dasol Oh, Hyunah Lee, Kyung-Won Lee, Min-Je Kim, Sung Wan Kang, Young-Jae Lee, HyunSoo Kim, Yong-Man Kim. CD8α+ dendritic cells potentiate the antitumor and immune activities against murine ovarian cancers. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6798.

The double-layer blanket (DLB) reverse offset is a newly designed printing process for patterning electronic circuits on a 3D curved surface. Unlike the existing reverse offset process, the DLB reverse offset utilizes an offset roll composed of two layers comprising polydimethylsiloxane (PDMS) and a thick, soft cushioned rubber to print microelectrode patterns and transparent electrodes on a curved surface. The optimal printing process was determined by adjusting the printing pressure and printing speed for horizontal and vertical micropatterns, based on which transparent electrodes with metal mesh and honeycomb structures with a line width of 30 μm and pitch of 600 μm with micropatterns ranging from 30 μm to 60 μm were printed on a curved surface. Ag ink was used, and the 3D curved surface indicated a print quality similar to that of the flat surface for both the vertical and horizontal patterns and transparent electrodes. The DLB reverse offset technique demonstrated the possibility of printing on a 3D curved surface and is expected to broaden the range of printed electronics to applications such as smart glasses and 3D shape sensors.

본 연구는 서울시 찾동 방문노동자인 복지플래너와 방문간호사의 노동경험 중 감정노동에 초점을 두고 이를 형성하는 조건과 사회적 압력, 부정적 영향과 대처를 탐색하고, 이를 토대로 감정노동의 부정적 영향을 완화하기 위한 방안을 모색하는 것을 목적으로 한다. 이를 위해 서울시 찾동 복지플래너와 방문간호사 18명을 선정하여 개별심층면접을 실시하고 그 결과를 분석하였다. 분석결과 가정으로 서비스공간이 전환됨에 따라 서비스 제공자와 주민의 경계가 모호해지며 이중적 관계가 형성되었으며 애매한 직무요구가 발생하고 있었다. 즉, 찾동 방문노동자들의 감정노동은 “찾아감”으로 인한 공간성 변화, 그리고 그 맥락에서 서비스 대상자들과의 인격화된 관계맺음과 요구받는 직무 모호성을 고려하여 이해될 필요가 있었다. 또한 이들은 직업에 덧씌워진 돌봄윤리의 압력과 찾동 사업에 대한 조직의 압력을 함께 받고 있었다. 이로 인해 방문노동자들은 다양한 부정적 영향을 경험하고 있었으며, 이를 대처하기 위해 표면행위, 심층행위, 공식적 대처 등의 전략을 사용하고 있었다. 연구결과를 토대로 방문노동자의 감정노동으로 인한 부정적 영향을 완화할 수 있는 방안으로 심리정서적 서비스 방안과 장기적인 제도 개선 방안을 함께 제시하였다.

리튬 폴리머 배터리는 파우치 형태로 얇고 가벼우며, 설계의 자유도가 높다는 장점을 갖는다. 이들의 외장재인 알루미늄 파우치는 세 개의 서로 다른 필름으로 이루어져 있다. 각 필름들은 서로 다른 특성을 가지고 있으며, 안정적인 결합은 알루미늄 파우치의 신뢰성에 영향을 미친다. 본 논문에서는 성형 후의 알루미늄 파우치의 변화에 대해 알아보았다. 성형 공정에서 펀치가 가압될 때 펀치 및 다이 어깨에서는 굽힘, 인장, 연신 등 복합적인 변형이 집중되며 이는 알루미늄 파우치의 계면에서 미세 크랙 등을 발생시킨다. 성형 후 알루미늄 파우치의 접착 강도는 다이 어깨 부분에서 급격하게 감소된다. 이는 다이 어깨 부분에서 응력 집중이 매우 높기 때문인 것으로 생각된다. 그러나 내전해액성의 경우, 성형 깊이와의 상관관계는 없었으며 이는 내화학성을 가지는 CPP 필름과 접착제에 의해 내전해액성이 안정적으로 유지되는 것으로 생각된다.

Oncolytic virotherapy is a promising alternative to conventional treatment, yet systemic delivery of these viruses to tumors remains a major challenge. In this regard, mesenchymal stem cells (MSC) with well-established tumor-homing property could serve as a promising systemic delivery tool. We showed that MSCs could be effectively infected by hepatocellular carcinoma (HCC)-targeted oncolytic adenovirus (HCC-oAd) through modification of the virus' fiber domain and that the virus replicated efficiently in the cell carrier. HCC-targeting oAd loaded in MSCs (HCC-oAd/MSC) effectively lysed HCC cells in vitro under both normoxic and hypoxic conditions as a result of the hypoxia responsiveness of HCC-oAd. Importantly, systemically administered HCC-oAd/MSC, which were initially infected with a low viral dose, homed to HCC tumors and resulted in a high level of virion accumulation in the tumors, ultimately leading to potent tumor growth inhibition. Furthermore, viral dose reduction and tumor localization of HCC-oAd/MSC prevented the induction of hepatotoxicity by attenuating HCC-oAd hepatic accumulation. Taken together, these results demonstrate that MSC-mediated systemic delivery of oAd is a promising strategy for achieving synergistic antitumor efficacy with improved safety profiles. Significance: Mesenchymal stem cells enable delivery of an oncolytic adenovirus specifically to the tumor without posing any risk associated with systemic administration of naked virions to the host.

Orally administered antisense therapy has been introduced as an effective approach for treating cancer in the gastrointestinal tract. However, its practical application has been limited by the instability of oligonucleotides and their inefficient delivery. To overcome these problems, we synthesized size-dependent, oligonucleotide nanoparticle-patterned chitosan/phytic acid (ODN/CS/PA) capsules with protective shields via a three-step process of self-assembly, nanoparticle encapsulation, and shell formation. The multicompartmental capsule size and oligonucleotide nanoparticle-loading pattern were controlled by applying different potentials during the electrostatic extrusion process used for nanoparticle encapsulation. Over 95% of encapsulated oligonucleotides were protected from nuclease digestion (DNase I) and, depending on their size, showed 40-75% protection against simulated gastric fluid. Their controlled release from capsules correlated with the cellular delivery of released nanoparticles and the inhibition of protein expression in cancer cells. Specifically, large capsules showed approximately 32-fold greater delivery to cancer cells than nonencapsulated nanoparticles. We also confirmed delivery of oligonucleotide nanoparticles to the small intestine and colon of rats following oral administration. These findings demonstrate that the multicompartmental ODN/CS/PA capsules can facilitate efficient oral delivery of oligonucleotides for cancer treatment.

Korean Pavilion is the last national pavilion at Giardini della Biennale in Venice, completed in 1995. This paper explores the unknown history of the pavilion that appeared in the ‘year of art’ of South Korea and the centennial anniversary of the Venice Biennale under the legitimated idealistic name of “Korean” Pavilion. It investigates the politics of the pavilion’s beginning and argues its significance as a premature, but earliest platform of Korean architecture. Also, it observes developing discourse on architecture exhibition and its archive in contemporary Korean architecture reflected in the Korean Pavilion in the last decade. As a result, this paper discusses the pavilion’s ironic contrast, oscillating between its start made in the politics of the national pavilion at the Venice Biennale, and its transformation into being the oldest and most representative architectural platform for Korean architecture.

Generation of autologous human motor neurons holds great promise for cell replacement therapy to treat spinal cord injury (SCI). Direct conversion allows generation of target cells from somatic cells, however, current protocols are not practicable for therapeutic purposes since converted cells are post-mitotic that are not scalable. Therefore, therapeutic effects of directly converted neurons have not been elucidated yet. Here, we show that human fibroblasts can be converted into induced motor neurons (iMNs) by sequentially inducing POU5F1(OCT4) and LHX3. Our strategy enables scalable production of pure iMNs because of the transient acquisition of proliferative iMN-intermediate cell stage which is distinct from neural progenitors. iMNs exhibited hallmarks of spinal motor neurons including transcriptional profiles, electrophysiological property, synaptic activity, and neuromuscular junction formation. Remarkably, transplantation of iMNs showed therapeutic effects, promoting locomotor functional recovery in rodent SCI model. Together, our advanced strategy will provide tools to acquire sufficient human iMNs that may represent a promising cell source for personalized cell therapy.

The current “Dad Craze” trend has changed the South Korean father figure and has increased the number of fathers participating in children’s education. South Korean parents are known for placing a particularly high value on child education. Despite a significant body of research on fathers’ involvement with their children, no research has investigated the factors affecting fathers’ school involvement in South Korea. This study established an empirical framework for fathers’ school involvement based on the Lamb-Pleck four factor model and explored factors that influence Korean fathers’ school involvement. Using data derived from an internet survey of South Korean fathers with school-aged children (N = 500), descriptive statistics analysis and a regression analysis were conducted to examine the level of fathers’ school involvement and its determinants. Regression analysis showed that fathers’ parent efficacy (B = .367, p = .006) as a skill factor, wife’s support (B = .430, p

Objective: Vascular progenitor cells (VPCs), which are able to differentiate into both endothelial cells and smooth muscle cells, have the potential for treatment of ischemic diseases. Generated by pluripotent stem cells, VPCs carry the risk of tumorigenicity in clinical application. This issue could be resolved by direct lineage conversion, the induction of functional cells from another lineage by using only lineage-restricted transcription factors. Here, we show that induced VPCs (iVPCs) can be generated from fibroblasts by ETS (E-twenty six) transcription factors, Etv2 and Fli1 . Approach and Results: Mouse fibroblasts were infected with lentivirus encoding Etv2 and Fli1 . Cell colonies appeared in Fli1 - and Etv2/Fli1 -infected groups and were mechanically picked. The identity of cell colonies was confirmed by proliferation assay and reverse-transcription polymerase chain reaction with vascular markers . Etv2/Fli1 - infected cell colonies were sorted by CD144 (also known as CDH5, VE-cadherin). We defined that CD144-positive iVPCs maintained its own population and expanded stably at multiple passages. iVPCs could differentiate into functional endothelial cells and smooth muscle cells by a defined medium. The functionalities of iVPC-derived endothelial cells and smooth muscle cells were confirmed by analyzing LDL (low-density lipoprotein) uptake, carbachol-induced contraction, and tube formation in vitro. Transplantation of iVPCs into the ischemic hindlimb model enhanced blood flow without tumor formation in vivo. Human iVPCs were generated by human ETS transcription factors ETV2 and FLI1 . Conclusions: We demonstrate that ischemic disease curable iVPCs, which have self-renewal and bipotency, can be generated from mouse fibroblasts by enforced ETS family transcription factors, Etv2 and Fli1 expression. Our simple strategy opens insights into stem cell–based ischemic disease therapy.

Postmortem studies have previously suggested that adult olfactory neurogenesis occurs in humans. In new research, Durante and colleagues obtained fresh tissue from healthy adult humans via endoscopic nasal surgery and used single-cell RNA sequencing (RNA-seq) to identify the entire neurogenic trajectory in the olfactory epithelium, confirming the existence of human olfactory neurogenesis.

Surface disinfection of fresh blueberries is an important food safety challenge due to the delicate texture and short shelf life of these small fruits. A newly designed water-assisted photocatalytic reactor was developed for disinfection of fruits with a delicate texture and complex surface characteristics. Efficacy of UV-TiO2 photocatalysis was evaluated in comparison with UV alone for inactivation of Escherichia coli K12 (as a surrogate for Escherichia coli O157:H7) inoculated onto the surface of the blueberry skin, calyx, and an experimentally prepared agar matrix that was used as a model matrix. Influence of surface characteristics such as surface hydrophobicity and surface free energy on bacterial adhesion were also investigated. The initial bacterial population on all surfaces was approximately 7.0 log CFU/g. UV-TiO2 photocatalysis (4.5 mW/cm2) for 30 s achieved comparatively higher bacterial reductions of 5.3 log and 4.6 log CFU/g on blueberry skin and agar matrix surfaces, respectively, than 4.5 log and 3.4 log CFU/g reductions for UV alone (6.0 mW/cm2). Total phenolic and total anthocyanin contents of fruits were significantly increased after both UV-TiO2 and UV treatments, compared with water washed control fruits. UV-TiO2 photocatalysis technology is a non-chemical and residue-free method with reduced water usage for surface disinfection of fresh blueberries.

The traditional process of manufacturing red bean powder (RBP) using high temperature and extensive cooking causes quality changes, such as an off-flavor, destruction of colors, and a reduced nutritional value of the product. In this study, RBP was manufactured using a novel process of wet grinding, high hydrostatic pressure (HHP), and freeze-drying. The impact of HHP treatment in this innovative manufacturing process on the microbial count, antioxidant activity, anti-nutritional factors, and physicochemical properties of RBP was evaluated by comparison with the conventional method of thermal treatment. Microbial populations in final RBP were reduced to 1.83, 1.55, and 1.05 log CFU/g when treated using HHP 400, 500, and 600 MPa, respectively. HHP treatment improved the nutritional profile and reduced the effects of anti-nutritional factors in RBP. The most effective reduction of trypsin inhibitor activity and phytic acid content was achieved using HHP at 600 MPa for 5 min. Total phenols, flavonoids, proanthocyanidins and total antioxidant capacity in HHP treated RBP were more effectively preserved than in thermally treated RBP. Preparation of RBP using a novel manufacturing process involving HHP treatment rather than a thermal treatment improved physico-chemical and functional properties and enhanced microbiological safety.