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This study investigates the effect of oxygen and copper impurities on the work function of the Cs/H/Mo (001) surface based on the Density Functional Theory (DFT) method. First, the deposition of 2/16 θ impurities on the Cs0.5/H0.5/Mo (001) surface (the subscript 0.5 represents 8/16 θ coverage) is studied. It is found that the deposition of impurities beneath the cesium layer and oxygen impurities as atoms, and in a high-symmetry configuration, both lower the surface system energy. As the impurity coverage increases, it is observed that impurity deposition with a coverage of less than or equal to 8/16 θ effectively reduces the work function of the Cs0.5/H0.5/Mo (001) surface. However, as the cesium and hydrogen coverage increases, the impurities are no longer effective at reducing the work function. Moreover, when the cesium coverage reaches 16/16 θ, the surface work function approaches that of a cesium metal surface. Another important discovery is that when oxygen impurities are deposited above the cesium layer on the Cs0.5/H0.5/Mo (001) surface, a reduction in the surface work function is observed. This anomalous phenomenon is attributed to significant charge polarization caused by the deposition of oxygen impurities. The migration barriers of impurities traversing the dense cesium layer to the Mo (001) substrate are evaluated using the climbing image nudged elastic band (CI-NEB) method. Oxygen impurities tend to traverse the cesium layer in molecular form, facing a minimum barrier of 0.52 eV, while copper atoms encounter a lower barrier of 0.09 eV when traversing the cesium layer.

This study employs first-principles calculations to investigate the structural, electronic, and mechanical properties of La1-xMxB6 (M = Ba, Sr, Ca), focusing on the surface work function, elastic constants, bulk modulus, shear modulus, Young’s modulus, Debye temperature, and melting point. The results indicate that doping generally leads to a reduction in the surface work function, with La0.375Ba0.625B6 achieving a work function as low as 1.27 eV. The influence of doping concentration on the mechanical properties and anisotropy is analyzed, revealing that La1-xMxB6 and La0.5Sr0.5B6 exhibit oscillatory changes related to the layered structure of the dopants. Brittleness is assessed through the B/G ratio and Poisson’s ratio. Thermodynamic analysis shows that the melting points of these compounds exceed 2000 K. These findings provide useful references for choosing cesium-free electrode materials applied for plasma-facing applications in neutral beam injection.

Based on the DFT method, the effects of copper and tungsten impurities present in the negative ion source of neutral beams on the cesiated surface were studied, including their effects on the adsorption energy of cesium on the surface and the surface work function. The results indicate that copper impurities significantly increase the average adsorption energy of cesium, whereas tungsten has limited enhancement on the average adsorption energy of cesium and may even reduce it. The work function calculations show that, at cesium coverages below 4/16 θ, copper impurities cause a significant increase in the work function. However, at cesium coverages above 6/16 θ, high-coverage copper impurities lead to a further decrease in the work function, causing the cesium coverage corresponding to the lowest work function to shift towards higher cesium coverage. Under any tungsten impurity and cesium coverage, tungsten impurities can significantly increase the surface work function, with the maximum increase reaching 0.50 eV. The dipole moment density analysis shows that in most cases, impurities significantly reduce the dipole moment density of the cesiated surface, except when the coverage of cesium and copper impurities is above 6/16 θ. The charge transfer results show that the copper impurity layer has more positive charge compared to the tungsten impurity layer, which significantly affects the dipole moment density of the surface system. In addition, adsorbed atoms cause electrons in the molybdenum atomic layer to migrate to the surface, resulting in the molybdenum substrate having a pronounced negative dipole moment.

The impact of H atoms and O impurities on the adsorption stability and work function of cesiated Mo (001) surface are investigated in this paper through DFT calculations. The 53 surface structures with different surface coverages are constructed in this work. Two types of co-deposition structures are considered: Cs-O (or Cs-H) bonds (1) leaning towards and (2) perpendicular to the surface. Our results demonstrate that the minimum work function corresponds to a 0.5 ML coverage of Cs for any surface coverage of H (or O) when the bonds are tilted. Compared to pure Cs deposition, the work function of Cs and H (or O) co-deposition surface increases at low or saturated Cs coverage, while decreases at 0.5 ML. Analysis of the surface dipole moment revealed that the work function changed inversely with the surface dipole moment density. Comparing charge transfer and polarization, it is evident that charge polarization has a significant impact on dipole moment changes. The presence of O impurities significantly enhances the adsorption stability of Cs, with higher coverage of O impurities leading to greater adsorption stability. The average adsorption energy of Cs atoms increases by ∼0.36 eV when co-deposits with O (0.5 θ). The effect of the H atoms on the adsorption stability of Cs atoms is limited. We also find that the vertical co-deposition case did not offer an advantage in terms of adsorption stability and low work function.

Abstract “Non-growing” is a dominant life form of microorganisms in nature, where available nutrients and resources are limited. In laboratory culture systems, Escherichia coli can survive for years under starvation, denoted as long-term stationary phase, where a small fraction of cells manages to survive by recycling resources released from nonviable cells. Although the physiology by which viable cells in long-term stationary phase adapt to prolonged starvation is of great interest, their genome-wide response has not been fully understood. In this study, we analyzed transcriptional profiles of cells exposed to the supernatant of 30-day long-term stationary phase culture and found that their transcriptome profiles displayed several similar responses to those of cells in the 16-h short-term stationary phase. Nevertheless, our results revealed that cells in long-term stationary phase supernatant exhibit higher expressions of stress-response genes such as phage shock proteins (psp), and lower expressions of growth-related genes such as ribosomal proteins than those in the short-term stationary phase. We confirmed that the mutant lacking the psp operon showed lower survival and growth rate in the long-term stationary phase culture. This study identified transcriptional responses for stress-resistant physiology in the long-term stationary phase environment.

Glioblastoma is a devastating malignant brain tumor with a poor prognosis despite standard therapy. Podoplanin (PDPN), a type I transmembrane mucin-like glycoprotein that is overexpressed in various cancers, is a potential therapeutic target for the treatment of glioblastoma. We previously reported the efficacy of chimeric antigen receptor (CAR)-T cells using an anti-pan-PDPN monoclonal antibody (mAb; NZ-1)-based third-generation CAR in a xenograft mouse model. However, NZ-1 also reacted with PDPN-expressing normal cells, such as lymphatic endothelial cells, pulmonary alveolar type I cells, and podocytes. To overcome possible on-target-off-tumor effects, we produced a cancer-specific mAb (CasMab, LpMab-2)-based CAR. LpMab-2 (Lp2) reacted with PDPN-expressing cancer cells but not with normal cells. In this study, Lp2-CAR-transduced T cells (Lp2-CAR-T) specifically targeted PDPN-expressing glioma cells while sparing the PDPN-expressing normal cells. Lp2-CAR-T also killed patient-derived glioma stem cells, demonstrating its clinical potential against glioblastoma. Systemic injection of Lp2-CAR-T cells inhibited the growth of a subcutaneous glioma xenograft model in immunodeficient mice. Combination therapy with Lp2-CAR-T and oncolytic virus G47Δ, a third-generation recombinant herpes simplex virus (HSV)-1, further inhibited the tumor growth and improved survival. These findings indicate that the combination therapy of Lp2-CAR-T cells and G47Δ may be a promising approach to treat glioblastoma.

The type 2 Ca2+-dependent activator protein for secretion (CAPS2/CADPS2) regulates dense-core vesicle trafficking and exocytosis and is involved in the regulated release of catecholamines, peptidergic hormones, and neuromodulators. CAPS2 is expressed in the pancreatic exocrine acinar cells that produce and secrete digestive enzymes. However, the functional role of CAPS2 in vesicular trafficking and/or exocytosis of non-regulatory proteins in the exocrine pancreas remains to be determined. Here, we analyzed the morpho-pathological indicators of the pancreatic exocrine pathway in Cadps2-deficient mouse models using histochemistry, biochemistry, and electron microscopy. We used whole exosome sequencing to identify CADPS2 variants in patients with chronic pancreatitis (CP). Caps2/Cadps2-knockout (KO) mice exhibited morphophysiological abnormalities in the exocrine pancreas, including excessive accumulation of secretory granules (zymogen granules) and their amylase content in the cytoplasm, deterioration of the fine intracellular membrane structures (disorganized rough endoplasmic reticulum, dilated Golgi cisternae, and the appearance of empty vesicles and autophagic-like vacuoles), as well as exocrine pancreatic cell injury, including acinar cell atrophy, increased fibrosis, and inflammatory cell infiltration. Pancreas-specific Cadps2 conditional KO mice exhibited pathological abnormalities in the exocrine pancreas similar to the global Cadps2 KO mice, indicating that these phenotypes were caused either directly or indirectly by CAPS2 deficiency in the pancreas. Furthermore, we identified a rare variant in the exon3 coding region of CADPS2 in a non-alcoholic patient with CP and showed that Cadps2-dex3 mice lacking CAPS2 exon3 exhibited symptoms similar to those exhibited by the Cadps2 KO and cKO mice. These results suggest that CAPS2 is critical for the proper functioning of the pancreatic exocrine pathway, and its deficiency is associated with a risk of pancreatic acinar cell pathology.

Abstract Addiction has become a major worldwide medical, public health, and social problem. Because the prevalence of addiction varies widely geographically, due to differences in ethnicity, culture, education, social environment, and regulation, each country or region needs to understand its current state of addiction and to take appropriate measures, in multidisciplinary collaboration. In order to understand the direction of addiction research in Japan, we analyzed 50 research and development topics and their characteristics, based on an expert questionnaire survey. The topics were placed in five categories, as follows. Category 1: Basic science; all 10 topics were of the Long‐term project and International cooperation types. Category 2: Translational and clinical research; 6 out of 10 topics were of the Long‐term project. Category 3: Fact‐finding surveys; 8 out of 10 topics were of the Japan‐specific type. Category 4: Health system and service; 8 out of 10 topics were of the Japan‐specific type and Short‐term project. Category 5: Study on society, culture, environment, education, and regulation; 7 out of 10 topics were of the Short‐term project (similar to Category 4). As far as we know, this is the first systematic questionnaire survey on the direction of addiction research. The results of this study might support developing a strategy for addiction research, not only in Japan, but also in other countries.

Background: The term “addiction” encompasses both substance dependence and behavioral addiction and is associated with major societal problems. Measures to combat addiction are currently insufficient in Japan, and further research on addiction is necessary. Methods: Science Council of Japan (SCJ) has three subcommittees – the Addiction Subcommittee, Brain and Mind Subcommittee, and Neuroscience Subcommittee among others. Those three subcommittees are dealing directly or indirectly with addiction problems in Japan. Thus, all authors of this review, members of those subcommittees, collectively recommended what research activities are required in Japan for continuing effort in overcoming addiction problems in Japan. Results: We proposed the following measures. Proposal 1: Understand diversity in addiction and promote related research and education; Proposal 2: Promote personalized measures for patients with addiction disorders; Proposal 3: Foster addiction research personnel; Proposal 4: Develop new guidelines for the rehabilitation of patients with drug dependence; Proposal 5: Establish an institute specializing in addiction research and comprehensively handling information collection, research, countermeasures, treatment, and public relation related to addiction. Conclusion: The opinions of the review are based on the recommendations that were published in 2020 in Japanese by the Addiction Subcommittee, Brain and Mind Subcommittee, and Neuroscience Subcommittee of the SCJ. The authors here are sharing colleagues of Taiwanese Society of Psychiatry with these proposed research activities required to overcome addiction problems in Japan.

Abstract Purpose This study aimed to analyze whether tripronuclear (3PN) zygotes, with two normal‐sized PNs and an additional smaller PN (2.1PN), can be used for embryo transfer. Method(s) A retrospective embryo cohort study was conducted on 695 patients who underwent intracytoplasmic sperm injection treatment. Blastocyst formation rates were compared between 2.1PN and 2PN zygotes and PGT‐A analysis was performed on 15 blastocysts derived from 2.1PN zygotes. Result(s) Blastocyst formation rates were comparable between 2.1PN (43.8%) and 2PN zygotes (54.8%; p = 0.212). The rates of blastocysts with good morphology derived from 2.1 PN and 2PN zygotes were 18.8% and 25.5%, respectively. No significant differences were detected (p = 0.383). All of the analyzed blastocysts were diploid; however, 13 of these were found to be aneuploid, with a further two being mosaic. Conclusion Our results suggest that 2.1PN embryos can reach blastocyst stage. These blastocysts were diploid, however, predominantly aneuploid, and therefore could not be used for embryo transfer.

Microfold cells (M cells) sit at the gut epithelial surface to sample antigens and maintain local immune homeostasis. Here the authors show that M cells are feedback-regulated by M cell-originated osteoprotegerin (OPG) to suppress RNAKL-induced M cell differentiation, and that OPG deficiency alters both gut colitis and infection phenotypes.

Abstract Purpose This study aimed to analyze whether the presence of refractile bodies (RFs) negatively affects fertilization, embryo development, and/or implantation rates following intracytoplasmic sperm injection (ICSI). Methods This retrospective embryo cohort study involved a total of 272 patients undergoing ICSI treatment of blastocyst cryopreservation. Results In the study, no significant differences were found regarding 2PN formation rates between RF(+) (76.5%) and RF(−) oocytes (77.2%). However, the blastocyst formation rate on Day 5 in RF(+) oocytes was 45.8%, which was significantly lower than that of 52.2% in RF(−) oocytes (aOR 0.74, 95% CI 0.59‐0.93, P = .011). Implantation rates were also significantly lower in RF(+) oocytes (24.2%) as compared to RF(−) oocytes (42.2%) (aOR 0.46, 95% CI 0.26‐0.78, P = .005). Furthermore, the implantation rate of RF(+) oocytes (28.6%), when high‐quality blastocysts were transferred, was significantly lower than that of RF(−) oocytes (46.1%) (aOR 0.50, 95% CI 0.25‐0.96, P = .043). Conclusion Our results suggest that oocytes with the presence of RFs have a lower potential for blastocyst development. Even when they develop into high‐quality blastocysts, the chances of implantation are reduced.

Abstract Purpose This study aimed to analyze whether a regimen of aromatase inhibitor (AI) could reduce the occurrence of smooth endoplasmic reticulum clusters (sERCs) in oocytes. Method(s) The AI and the clomiphene citrate (CC) regimens were compared, regarding the sERC (+) rates and the serum estradiol and progesterone levels on the date of hCG administration, and the duration of AI, CC, and hMG administration. Result(s) The occurrence of sERCs in oocytes from patients treated with AI was significantly higher than that in oocytes from those treated with CC. Both the serum estradiol and progesterone levels were found to be significantly higher in sERC (+) than in sERC (‐) cycles. With regard to the CC cycles, no significant differences were detected. The duration of AI and hMG administration was longer for sERC (+) than for sERC (‐) cycles. Conclusion As AI did not reduce the occurrence of sERCs, the elevation of estradiol may not be the cause of sERC occurrence but a consequence. Considering the higher levels of progesterone and longer duration of hMG in sERC (+) cycles, the negative effects of premature luteinization, which frequently occur with the AI protocol, should be investigated further.

Abstract Background It is widely supposed that there is no benefit, including extended survival and decreased rate of pneumonia, in patients with severe dementia receiving enteral tube feeding (TF). However, there have been few studies comparing the frequency of pneumonia before and after TF in severe dementia. Methods Nine psychiatric hospitals in Okayama Prefecture participated in this retrospective survey. All inpatients fulfilling the entry criteria were evaluated. All subjects suffered from difficulty in oral intake. Attending physicians thought that the patients could not live without long-term artificial nutrition, and they decided whether or not to make use of long-term artificial nutrition from January 1, 2014 to December 31, 2014. Results We evaluated 58 patients including 46 with TF and 12 without. The mean age of all patients was 79.6 ± 9.0 years old. Patients with probable Alzheimer’s disease (n = 38) formed the biggest group, and those with vascular dementia the second (n = 14). Median survival times were 23 months among patients with TF and two months among patients without TF. The start of TF decreased the frequency of pneumonia and the use of intravenous antibiotics. Conclusions TF decreased pneumonia and antibiotic use, even in patients with severe dementia. The results of this study do not necessarily indicate that we should administer TF to patients with severe dementia. We should consider the quality of life of patients carefully before deciding the use or disuse of TF for patients with severe dementia.

RNA analytical platforms gained extensive attention recently for RNA-based molecular analysis. However, the major challenge for analyzing RNAs is their low concentration in blood plasma samples, hindering the use of RNAs for diagnostics. Platforms that can enrich RNAs are essential to enhance molecular detection. Here, we developed the annealed ZnO/Al2O3 core-shell nanowire device as a platform to capture RNAs. We showed that the annealed ZnO/Al2O3 core-shell nanowire could capture RNAs with high efficiency compared to that of other circulating nucleic acids, including genomic DNA (gDNA) and cell-free DNA (cfDNA). Moreover, the nanowire was considered to be biocompatible with blood plasma samples due to the crystalline structure of the Al2O3 shell which serves as a protective layer to prevent nanowire degradation. Our developed device has the potential to be a platform for RNA-based extraction and detection.

Abstract : Japanese working class women’s relationship to work during the 1920s – characterised by the ambivalence of their search for freedom and the anxiety caused by their situation – continues to spark fruitful thinking, particularly given the recent rise of precariousness and even poverty in Japan, particularly for women. Exploring what work represented for Japanese women in the 1920s, the article begins with historical elements relating to gender and labour issues, such as they were first formulated in the early 20th century. It goes on to focus more specifically on Japanese women’s work expectations at the time, based on the writings of Hayashi Fumiko, a pioneer of female emancipation. Fumiko’s accounts – unique at the time – offer clues about the role that women played in that society while casting a new light on the historical dynamics that would ultimately lead to partial emancipation, especially of women from poorer backgrounds.

IRBIT is a molecule that interacts with the inositol 1,4,5-trisphosphate (IP3)-binding pocket of the IP3 receptor (IP3R), whereas the antiapoptotic protein, Bcl2l10, binds to another part of the IP3-binding domain. Here we show that Bcl2l10 and IRBIT interact and exert an additive inhibition of IP3R in the physiological state. Moreover, we found that these proteins associate in a complex in mitochondria-associated membranes (MAMs) and that their interplay is involved in apoptosis regulation. MAMs are a hotspot for Ca2+ transfer between endoplasmic reticulum (ER) and mitochondria, and massive Ca2+ release through IP3R in mitochondria induces cell death. We found that upon apoptotic stress, IRBIT is dephosphorylated, becoming an inhibitor of Bcl2l10. Moreover, IRBIT promotes ER mitochondria contact. Our results suggest that by inhibiting Bcl2l10 activity and promoting contact between ER and mitochondria, IRBIT facilitates massive Ca2+ transfer to mitochondria and promotes apoptosis. This work then describes IRBIT as a new regulator of cell death.

Changing social and environmental factors have been the cause of an increase in the number and variety of animals are being imported into Japan. Moreover, the number of Japanese households are keeping companion animals has also risen. These factors, along with the high density of the Japanese population and the low percentage of registered dogs, have increased the risk of animal-to-human transmission of zoonoses. To control zoonosis outbreaks, the Japanese government has implemented a three-stage approach for the border control of zoonoses and has stipulated the monitoring and reporting of eight companion animal-borne zoonoses under the Rabies Prevention Law and the Infectious Diseases Control Law. The fact that no case of human and animal rabies has been reported over the past 50 years indicates that these measures are highly effective in preventing rabies transmission. Although it is known that the total number of possible companion animal-borne zoonosis outbreaks decreased between 2005 and 2009 when compared with numbers between 2001 and 2004, the number of zoonosis cases that can be attributed to transmission by companion animals remains unclear. Active surveillance should be conducted on a national level to collect the data necessary to determine this number and identify trends in companion-animal transmitted diseases. Using the data collected, regulation systems should be evaluated to determine whether they have met reasonable goals and policy planning conducted for the control of emerging diseases.

Japan is one of the few rabies-free countries. Although 3 imported cases of human rabies were seen in 1970 and 2006, no other cases have been reported for ≈50 years. The elimination of rabies in Japan is attributed to not only its geographic isolation but also to effective prevention and control measures, such as registration and vaccination of domestic dogs, required quarantine of susceptible imported animals, and national plans of action based on scientific research. Countermeasures against rabies have been upgraded; an improved management system for domestic dogs under the amended Enforcement Regulations of the Rabies Prevention Law has been in effect since April 2007. The latest regulatory systems for preventing and controlling rabies provide an effective model for elimination of the disease worldwide.