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Properties such as lifetimes and masses of neutron-rich nuclei are key parameters for elucidating the astrophysical rapid neutron capture process (r-process). Due to the lack of experimental nuclear data in the relevant extremely neutron-rich region, especially near and above N = 126, the predictions of theoretical nuclear models are crucial for simulating r-process nucleosynthesis. Experimental studies of the properties and structures of neutron-rich nuclei from near the β stability line up to the r-process path provide important inputs to these theoretical models, improving the accuracy of predictions for the nuclear properties involved in the rprocess. We are developing the KEK Isotope Separation System (KISS) at the RIKEN RIBF facility to produce and separate these nuclei to perform spectroscopy experiments. The nuclei of interest are produced by multinucleon transfer reactions, which have been recently attracting renewed interest as they provide a way to access neutron-rich nuclei that are difficult to produce by other methods such as complete fusion or fragmentation. We have performed nuclear and laser spectroscopy, lifetime and mass measurements of neutron-rich nuclei of refractory elements near the N = 126 region using 198,natPt, natTa, natW, and natIr targets irradiated with 136Xe beams. We also extend our spectroscopic studies into the neutron-rich actinide region using 238U beams. This paper introduces the KISS facility and provides an overview of the nuclear spectroscopy experiments carried out there. We also introduce the KISS-1.5 project, which was started in FY2024 to further extend the research into the neutron-rich region.

Nuclear parameters such as lifetimes and masses of the waiting point nuclei of r-process nucleosynthesis are significant to investigate its astrophysical environment. However, the difficulty in the production of extremely neutron-rich nuclei at the 126 neutron closed shell makes their experimentalstudies unfeasible. Therefore, the theoretical nuclear models play crucial roles in the simulation of the r-process nucleosynthesis. The systematic nuclear spectroscopy of the neutron-rich nuclei around the 126 neutron closed shell provides significant inputs to those theoretical models to improve their predictability for the waiting point nuclei. We are developing KEK Isotope Separation System (KISS) to perform the systematic nuclear spectroscopy of those neutron-rich nuclei. The nuclei of interest are produced by multi-nucleon transfer reactions between 136Xe and 198Pt. The experimental study demonstrated its promising potential to produce them. We have successfully performed the β­γ spectroscopy and the laser ionization spectroscopy at KISS using the nuclear production by the multi-nucleon transfer reactions.

Previously, we developed an α-TOF detector for correlated measurements of atomic masses and decay properties of radioactive isotopes using a multi-reflection time-of-flight mass spectrograph, and successfully demonstrated α-decay-correlated mass measurements of heavy and superheavy nuclides. In this work, we develop a β-TOF detector, an improvement upon the α-TOF detector, to extend this technology to β-decaying nuclides. Online commissioning with 81Ga yielded a measured half-life of 1.44(31) s, in agreement with the previous literature, and confirmed the efficiency of detecting a decay-correlated event to be consistent with the solid angle limitation. [ABSTRACT FROM AUTHOR]

The aim of this study was to determine the association of the type of social support and proactive coping with depressive symptoms (DS) in Japanese people living with human immunodeficiency virus (PLHIV), in order to select effective psychosocial care or intervention. Questionnaires were anonymously collected from randomly recruited participants. The questionnaire included items on demographic characteristics, HIV treatment-related factors, DS, social support, and coping. Hierarchical binary logistic regression was used to identify factors associated with DS. A total of 564 patients completed the questionnaire and 207 (37%) patients reported DS. Demographic factors, such as drug-use-related disorders [adjusted odds ratio (AOR) 7.21, 95% confidence interval (95%CI) 1.95–26.70], unemployment (AOR 3.06, 95%CI 1.50–6.27) and younger age (AOR 0.96, 95%CI 0.94–0.99) were significantly associated with DS. With regard to coping, higher levels of instrumental support seeking (AOR 1.09, 95%CI 1.01–1.18), lower levels of proactive coping (AOR 0.91, 95%CI 0.87–0.96) and lower levels of emotional support seeking (AOR 0.82, 95%CI 0.72–0.92) were significantly associated with DS. Our results highlight the need for psychosocial care to enhance or compensate proactive coping and emotional support seeking abilities in DS. Healthcare workers should pay attention to the mental health of young unemployed PLHIV with drug-use-related disorders. [ABSTRACT FROM AUTHOR]

The rBC2LCN lectin, known as a stem cell marker probe that binds to an H type 3 fucosylated trisaccharide motif, was recently revealed to also bind to pancreatic ductal adenocarcinoma (PDAC) cells. A lectin‐drug conjugate was generated by fusing rBC2LCN with a cytocidal toxin, and it showed a strong anticancer effect in in vitro and in vivo PDAC models. However, it is unclear which molecules are carrier proteins of rBC2LCN on PDAC cells. In this study, we identified a rBC2LCN‐positive glycoprotein expressed in PDAC. Tumor lysates of PDAC patient‐derived xenografts (PDXs) were coprecipitated with rBC2LCN lectin and analyzed by liquid chromatography–mass spectrometry. A total of 343 proteins were initially identified. We used a web‐based database to select five glycoproteins and independently evaluated their expression in PDAC by immunohistochemistry (IHC). Among them, we focused on carcinoembryonic antigen 5 (CEA) as the most cancer‐specific carrier protein in PDAC, as it showed the most prominent difference in expression rate between PDAC cells (74%) and normal pancreatic duct cells (0%, P >.0001). rBC2LCN lectin and CEA colocalization in PDAC samples was confirmed by double‐staining analysis. Furthermore, rBC2LCN‐precipitated fractions were blotted with an anti‐CEA polyclonal antibody (pAb), and CEA pAb–precipitated fractions were blotted with rBC2LCN lectin. The results demonstrate that CEA is in fact a ligand of rBC2LCN lectin. [ABSTRACT FROM AUTHOR]

Drug resistance represents an obstacle in colorectal cancer (CRC) treatment because of its association with poor prognosis. rBC2LCN is a lectin isolated from Burkholderia that binds cell surface glycans that have fucose moieties. Because fucosylation is enhanced in many types of cancers, this lectin could be an efficient drug carrier if CRC cells specifically present such glycans. Therefore, we examined the therapeutic efficacy and toxicity of lectin drug conjugate therapy in CRC mouse xenograft models. The affinity of rBC2LCN for human CRC cell lines HT‐29, LoVo, LS174T, and DLD‐1 was assessed in vitro. The cytocidal efficacy of a lectin drug conjugate, rBC2LCN‐38 kDa domain of pseudomonas exotoxin A (PE38) was evaluated by MTT assay. The therapeutic effects and toxicity for each CRC cell line‐derived mouse xenograft model were compared between the intervention and control groups. LS174T and DLD‐1 cell lines showed a strong affinity for rBC2LCN. In the xenograft model, the tumor volume in the rBC2LCN‐PE38 group was significantly reduced compared with that using control treatment alone. However, the HT‐29 cell line showed weak affinity and poor therapeutic efficacy. No significant toxicities or adverse responses were observed. In conclusion, we demonstrated that rBC2LCN lectin binds CRC cells and that rBC2LCN‐PE38 significantly suppresses tumor growth in vivo. In addition, the efficacy of the drug conjugate correlated with its binding affinity for each CRC cell line. These results suggest that lectin drug conjugate therapy has potential as a novel targeted therapy for CRC cell surface glycans. [ABSTRACT FROM AUTHOR]

Introduction: Since the outermost layer of cancer cells is covered with various glycans, targeting these groups may serve as an effective strategy in cancer therapy. We previously reported that fucosylated glycans are specifically expressed on pancreatic cancer cells, and that a protein specifically binding to these glycans, namely rBC2LCN lectin, is a potential guiding drug carrier. In the present study, a novel type of glycan-targeting nanoparticle was developed by modifying the surface of doxorubicin-containing liposomes with rBC2LCN lectin. The efficiency and specificity of this formulation, termed Lec-Doxosome, were examined in vitro and in vivo in human pancreatic cancer models. Methods: Lec-Doxosome was prepared by a post-insertion method based on the insertion of rBC2LCN lectin into the liposomal surface via a lipid linker. The in vitro cellular binding, uptake, and cytotoxicity of Lec-Doxosome were compared with the corresponding parameters in the unmodified liposomes by applying to human pancreatic cancer cell line (Capan-1) with affinity for rBC2LCN lectin. For the in vivo assay, Lec-Doxosome was intravenously injected once per week for a total of 3 weeks into mice bearing subcutaneous tumors. Results: The in vitro application of Lec-Doxosome resulted in a 1.2- to 1.6-fold higher intracellular doxorubicin accumulation and a 1.5-fold stronger cytotoxicity compared with the respective rates of accumulation and cytotoxicity in the unmodified liposomes. In vivo, Lec-Doxosome reduced the mean tumor weight (368 mg) compared with that in mice treated with unmodified liposomes (456 mg), without causing any additional adverse events. Conclusion: It was demonstrated from the results obtained herein that rBC2LCN lectin is a potent modifier, as a means for boosting the efficiency of nanoparticles in the targeting of cancer cell surface glycans. [ABSTRACT FROM AUTHOR]

This single-institution cross-sectional study aimed to grasp the prevalence and features of neurocognitive dysfunction in HIV-infected hemophilia patients in Japan. We conducted neuropsychological tests and medical examinations in 56 HIV-infected hemophilia patients who received outpatient treatment at the AIDS Clinical Center, National Center for Global Health and Medicine. A total of 388 HIV-infected non-hemophilia patients who received outpatient treatment at the same institution were included as a control group. To investigate sites responsible for neurocognitive dysfunction in HIV-infected hemophilia patients using brain FDG-PET/CT scans, the accumulation of FDG in each brain region was compared. Approximately 50% of HIV-infected hemophilia patients had neurocognitive dysfunction. The prevalence of asymptomatic neurocognitive impairment was high (34%). Neurocognitive dysfunction was associated with educational level in HIV-infected hemophilia patients. In the symptomatic group, hemophilic arthropathy and history of cerebrovascular disorders were associated with neurocognitive dysfunction. Left temporal lobe function was reduced in the symptomatic group. [ABSTRACT FROM AUTHOR]

People living with human immunodeficiency virus (HIV) are at high risk of mental health problems. However, little is known about this risk in HIV-infected patients with hemophilia (HPH) who contracted the virus through blood products. This cross-sectional, observational study assessed patients' mood states and the factors associated with them among Japanese HPH to evaluate the need for psychosocial support. HPH completed self-administered questionnaires (Profile of Mood States [POMS] and General Health Questionnaire-28), neuropsychological tests, and brain magnetic resonance imaging (MRI) and fluorodeoxyglucose positron emission tomography/computerized tomography scans. HIV-infected patients with no hemophilia (HPnH) completed POMS and neuropsychological tests. Socio-demographic characteristics and HIV- and hemophilia-related data were obtained from participants' medical records and interviews. A Mann-Whitney U test and chi-squared analyses were conducted. Fifty-six HPH and 388 HPnH completed the questionnaires and neuropsychological tests. HPH had a significantly lower prevalence of tension-anxiety (HPH, 7%; HPnH, 18%; p = 0.049) and a significantly higher prevalence of low vigor (HPH, 63%; HPnH, 32%; p < 0.001). Low vigor in HPH was significantly associated with impaired executive function (low vigor, 66%; high vigor, 33%; p = 0.019) and a social dysfunction score ≥ 3 (moderate; low vigor, 26%; high vigor, 5%; p = 0.047). Our results highlight the high prevalence of low vigor among HPH, leading to impairments in executive and social functions. Therefore, healthcare workers need to pay attention to the vigor, executive function, and social function of HPH., Competing Interests: Ei Kinai received research grants from Chugai Pharmaceutical and CSL Behring and honoraria from Gilead Sciences, ViiV Healthcare, MSD, Chugai Pharmaceutical, Sanofi, Bayer, Takeda Pharmaceutical, Novo Nordisk, Fujimoto Pharmaceutical Corporation, and CSL Behring. Shinichi Oka received research grants from ViiV Healthcare and Gilead Sciences and honoraria from Gilead Sciences and ViiV Healthcare. The remaining authors have no conflicts of interest to disclose., (2024, National Center for Global Health and Medicine.)

Behavioral persistency reflects internal brain states, which are the foundations of multiple brain functions. However, experimental paradigms enabling genetic analyses of behavioral persistency and its associated brain functions have been limited. Here, we report novel persistent behavioral responses caused by electric stimuli in the nematode Caenorhabditis elegans. When the animals on bacterial food are stimulated by alternating current, their movement speed suddenly increases 2- to 3-fold, persisting for more than 1 minute even after a 5-second stimulation. Genetic analyses reveal that voltage-gated channels in the neurons are required for the response, possibly as the sensors, and neuropeptide signaling regulates the duration of the persistent response. Additional behavioral analyses implicate that the animal's response to electric shock is scalable and has a negative valence. These properties, along with persistence, have been recently regarded as essential features of emotion, suggesting that C. elegans response to electric shock may reflect a form of emotion, akin to fear., Competing Interests: Conflicts of interest The author(s) declare no conflict of interest., (© The Author(s) 2023. Published by Oxford University Press on behalf of The Genetics Society of America.)

The new binary chromium sulfide CrS 3 has been synthesized by reaction of Cr 3 S 4 and sulfur mixtures at 800 °C and 13 GPa. CrS 3 crystallizes in an orthorhombic unit cell with a = 4.6742(7) Å, b = 5.7315(8) Å, c = 10.603(2) Å, and V = 284.873(4) Å 3 . It has a novel structure composed of Cr 2 S 10 edge-shared octahedral dimers, which share all of their corners to form a three-dimensional structure. All of the sulfur atoms form S 2 2- disulfide ions with a S-S distance of 2.063(5) or 2.068(8) Å. The structure of CrS 3 is a derivative of the crystal structure of marcasite FeS 2 , in which one in three metal sites of the marcasite structure is vacant in the CrS 3 structure.

Various cancers, including pancreatic ductal adenocarcinoma (PDAC), remain intractable even with costly tumor-targeting antibody drugs. Because the outermost coatings of cancer cells are composed of cell-specific glycan layers (glycocalyx), lectins, proteins with glycan-binding potential, were evaluated for possible use as drug carriers in PDAC treatment. A human PDAC cell line with well-to-moderately differentiated properties (Capan-1) was subjected to lectin microarray analysis to identify specific lectin-glycan pairs. The selected lectin was fused with a bacterial exotoxin for the construction of a lectin-drug conjugate (LDC), and its safety and antitumor effects were evaluated. A specific affinity between a recombinant bacterial C-type lectin (rBC2LC-N) and Capan-1 was identified, and its positivity was confirmed in 69 human samples. In contrast to the belief that all lectins mediate harmful hemagglutination, rBC2LC-N did not cause hemagglutination with human erythrocytes and was safely administered to mice. The 50% inhibitory concentration of LDC to Capan-1 (1.04 pg/mL = 0.0195 pmol/L) was 1/1,000 lower than that reported for conventional immunotoxins. The intraperitoneal administration of LDC reduced the tumor weight from 390 to 130.8 mg ( P < 0.01) in an orthotopic model and reduced the number of nodules from 48 to 3 ( P < 0.001) and improved survival from 62 to 105 days in a peritoneal dissemination model ( P < 0.0001). In addition, the effect of LDC was reproduced in nodules from patient-derived PDAC xenografts through intravenous injection. Herein, we show the concept of utilizing lectins as drug carriers to target glycans on the cancer cell surface, highlighting new insights into cancer treatments. Mol Cancer Ther; 17(1); 183-95. ©2017 AACR ., (©2017 American Association for Cancer Research.)