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Background: The potential of carbon ion radiation therapy (CIRT) as a curative treatment for localized prostate cancer (PCa) has garnered attention due to its characteristic dose distribution. We prospectively collected and analyzed over five years to investigate the outcomes of localized PCa treated with CIRT at our institution., Patients and Methods: The study included patients with histologically confirmed prostate adenocarcinoma. CIRT treatment was administered at a total dose of 57.6 Gy (RBE) in 16 fractions over four weeks. Uroflowmetry (UFM) and residual urine measurements were performed at various time points: before CIRT treatment, one month after starting CIRT, three months after treatment, and annually for five years starting from 1 year after the completion of CIRT. Prostate volume was measured using transrectal ultrasonography (TRUS)., Results: A total of 304 prostate cancer patients were analyzed. UFM parameters were significantly worsened immediately after the treatment. However, they recovered to pretreatment levels after three months and remained stable until five years post-treatment. Notably, Average flow rate showed significant improvement after three years of treatment compared to before the treatment. Prostate volume decreased to 80% of baseline in patients treated with CIRT alone and to 60-70% of baseline in those receiving combined CIRT and either short- or long-term ADT. The logistic-binomial analysis identified post-voiding residual urine volume (PVR) as a significant factor for predicting adverse events in the acute phase., Conclusions: Following CIRT treatment, the voiding parameters in PCa patients significantly deteriorated immediately. However, after three months, they returned to their pre-treatment levels and remained stable for five years., Competing Interests: Declarations Ethics approval and consent to participate The present study protocol was designed by the Working Group of Genitourinary Tumors of GHMC. The protocol was approved by the institutional ethical committee” Gunma University Hospital Institutional Review Board”, approval number 693, and was registered with the University Medical Information Network Clinical Trial Registry, number UMIN000003827. All patients signed informed consent forms. Consent for publication Not applicable; Only aggregate data is published, and no patient identifying information is presented. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Competing Interests: The authors declare no conflicts of interest.

Carboxymethyl cellulose nanofiber (CMCF) forms mechanically strong hydrogels via freeze cross-linking. We investigated the vapor swelling and drying processes of the freeze cross-linked CMCF hydrogels using infrared spectroscopy and X-ray diffraction. From the shifts of the O-H and C=O stretching modes, the structural changes of water and carboxymethyl celluloses (CMC) were analyzed. The results show that two types of bound water exist in CMCF hydrogels due to a difference in hydrophilicity between the amorphous and crystalline regions of CMCF. Bound water adsorbed on the amorphous region forms a strong hydrogen bond with dangling O-H or C=O bonds of CMC, whereas that adsorbed on the crystalline region has a weak hydrogen bond with the localized hydrophilic groups on the hydrophobic surface. Due to the difference in the hydrogen bonding strength of the two types of bound water, the vapor swelling process of water in CMCF hydrogels is classified into four stages. For the drying process, the residual water, which formed a strong hydrogen bond with the hydrophilic groups of the CMC, has effects on the CMCF structure. The present result suggests that the adsorption and desorption of water are important factors governing the physical and chemical properties of the CMCF hydrogels., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Purpose: To examine longitudinal changes in exercise-induced hormonal responses in adolescent male basketball players., Methods: Fifteen adolescent males were assigned to prepeak height velocity (pre-PHV) and post-PHV groups according to the predicted age at PHV. Salivary testosterone, cortisol levels, and the testosterone-to-cortisol ratio were evaluated before (PRE), immediately after (POST), and 15 minutes after a bodyweight resistance training session, which was repeated after 1 year to analyze longitudinal changes in testosterone and cortisol levels., Results: Resting testosterone levels and acute testosterone responses after bodyweight resistance training increased in both groups after 1 year at all measurement points. The POST testosterone levels at initial measurement and PRE and 15-minute postexercise levels at 1 year in the post-PHV group were significantly higher than those in the pre-PHV group. Cortisol levels significantly decreased in the post-PHV group at baseline and 1 year later. In the post-PHV, the testosterone-to-cortisol ratio after bodyweight resistance training was significantly increased at baseline and 1 year later., Conclusions: Although testosterone levels increase with age, no acute response to bodyweight resistance training was observed after 1 year. The change in anabolic status indicated by the testosterone-to-cortisol ratio was due to a decrease in cortisol levels.

Aim/purpose: This study aimed to apply a shock wave from the ventral side of a pig and examine its effect to use the results for new body armor production for humans., Methods: Seven male hybrid pigs were used. Each pig was placed under general anesthesia on the experimental table in a blast tube in the left lateral position to expose the front chest area, and shock waves generated by compressed air at 3.0 MPa were applied. We examined changes in vital signs and arterial blood gas in the hyper-acute phase and computed tomography (CT) images, and autopsies were performed for organ damage after 3 h of observation. Pathological examination was performed for lung damage, which is considered a characteristic of shock wave injury., Results: All seven pigs survived. Respiratory arrest occurred in two pigs; however, spontaneous breathing resumed promptly afterward. Hypotension occurred at a frequency of 4. No bradycardia or cardiac arrest was observed in any pig. In the arterial blood gas analysis before and immediately after shock wave exposure and 1 h later, PaO2 decreased immediately but tended to improve thereafter. CT revealed pulmonary contusions and multiple bulla-like lesions on the surface of the lungs. An autopsy showed lung injury in all pigs, particularly in five cases with bulla-like lesions of various sizes on the lung surface across all lobes. Pathological findings showed visceral pleural detachment with elastic fibers from the lung parenchyma, and the cavity lesion on the lung surface comprised bullae. The degree of intra-abdominal hemorrhage varied; however, all but one case showed splenic injury., Conclusion: None of the pigs exposed to shock waves from the ventral side died; however, most showed multiple bullae on the lung surface with lung contusion and splenic injury, which may have been greater than those exposed from the dorsal side. This may be due to the direct impact of the shock wave proceeding from the epigastrium and subcostal region, which are not protected by the skeletal structure of the thorax. These characteristics should be considered when producing new body armor for humans to protect the body from shock waves., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: The two-drug regimen of dolutegravir/lamivudine (DTG/3TC) is currently an optional antiretroviral therapy (ART). Despite its reported advantages on body weight and lipid profile, the same effects have not yet been reported for Asian population., Methods: We conducted a single-center retrospective study involving Japanese people living with HIV (PLWH). They were divided into four groups: those who had received abacavir/lamivudine/dolutegravir (ABC/3TC/DTG) and continued the same (ABC-ON group) or switched to DTG/3TC (ABC-OFF group), those who had received tenofovir alafenamide fumarate/emtricitabine/dolutegravir (TAF/FTC/DTG) and continued the same (TAF-ON group) or switched to DTG/3TC (TAF-OFF group). We compared changes in viral load, CD4⁺ cell count, CD4⁺/CD8⁺ ratio, body weight, BMI, lipid profiles, estimated glomerular filtration rate (eGFR), and fibrosis index based on four factors (FIB4-index) between the pre-switch and post-switch period., Results: Of the 541 PLWH on DTG-based ART, 165, 94, 264 and 18 constituted the ABC-ON, ABC-OFF, TAF-ON, and TAF-OFF groups, respectively. Neither viral rebound nor CD4 + decline was observed in the post-switch period in all groups. Multivariate analysis showed significant reduction in total cholesterol, LDL-C and HDL-C in the ABC-OFF group (-6.280, -6.957 and -2.268, p = 0.040, 0.012 and 0.022, respectively), but not in the TAF-OFF group (-3.000, 6.708 and 0.046, p = 0.607, 0.276 and 0.983, respectively). No significant changes were observed in body weight, eGFR, or FIB4-index at 72 weeks after the discontinuation of ABC or TAF., Conclusions: Switching from ABC/3TC/DTG to DTG/3TC lowered lipids significantly, but not with TAF/FTC/DTG. Neither switch affected body weight or other markers., (Copyright © 2024 Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases, and Japanese Society for Infection Prevention and Control. Published by Elsevier Ltd. All rights reserved.)

Background: We developed a Rare Cell Sorter (RCS) for collecting single cell including circulating tumor cells (CTCs). This single-institution pilot study evaluated the ability of this device to detect tumor-like cells in patients with lung cancer and confirmed their genuineness based on the epidermal growth factor receptor (EGFR) mutation concordance with tissue samples., Methods: This study included patients treated for lung cancer from September 2021 to August 2022 in University of Tsukuba Hospital. Peripheral blood samples were obtained before surgery or during periodic medical checks for patients treated with drugs. We used the RCS to capture cells based on size. The cells were stained, and the Hoechst-positive, CD45-negative, and epithelial celladhesion molecule (EpCAM)- positive cells were defined as CTCs, were collected. The presumptive CTCs were counted and tested using digital droplet polymerase chain reaction for EGFR mutations and compared with the tissue EGFR status to check concordance., Results: Eighteen patients were included in this study and CTCs were detected in 6 patients (33%). The CTCs from three patients showed EGFR mutation, and the EGFR mutation status of CTCs concorded with that of tissue samples in 83% of the cases (5/6). Only one CTC showed a different status from the tissue, and the concordance rate of EGFR status between CTCs and the tissue was 96% (24/25)., Conclusion: The ability of the RCS to detect CTCs in patients with lung cancer was demonstrated based on the concordance of EGFR status in this pilot study. This novel hybrid method of CTC recovery using the RCS has the potential to recover a wide range of CTCs regardless of EpCAM. Further validation through a large-scale study is needed., (© 2024. The Author(s).)

Universal to all life is a reliance on energy carriers such as adenosine triphosphate (ATP) which connect energy-releasing reactions to energy-consuming processes. While ATP is ubiquitously used today, simpler molecules such as thioesters and polyphosphates are hypothesized to be primordial energy carriers. Investigating environmental constraints on the non-enzymatic emergence of metabolism, we find that hydrolysis rates-not hydrolysis energies-differentiate phosphate esters and thioesters. At temperatures consistent with thermophilic microbes, thioesters are favored at acidic pH and phosphate esters at basic pH. Thioacids have a high stability across pH 5-10. The planetary availability of sulfur and phosphate is coincident with these calculations, with phosphate being abundant in alkaline and sulfur in acidic environments. Since both sulfur esters and phosphate esters are uniquely required in metabolism, our results point to a non-thermophilic origin of early metabolism at cool, acidic to neutral environments., Competing Interests: The authors declare no competing interests., (© 2024 The Author(s).)

Purpose: Dialysis patients are at an increased risk of developing renal cell carcinoma (RCC); however, differentiating between RCC and benign cysts can sometimes be difficult using modalities, such as computed tomography (CT) and ultrasonography. 18 F-Fluorodeoxyglucose positron emission tomography (FDG-PET)/CT efficiently detects malignant tumors; however, physiological accumulation of FDG in the kidney limits its efficacy in detecting renal tumors. However, in patients with severely impaired renal function, the renal accumulation of FDG is decreased, possibly improving the detection of renal malignancies in this patient population. This study evaluated the usefulness of FDG-PET/CT as a screening tool for detecting RCC in patients with end-stage renal disease., Materials and Methods: This prospective study recruited 150 participants from 2012 to 2016 who were on dialysis or underwent renal transplantation and were on dialysis until transplantation. FDG-PET/CT was performed to screen for RCC. Three radiologists independently evaluated the images. No protocol was defined for the additional management of positive examinations, leaving decisions to the discretion of each participant. Negative examinations were observed until the end of 2019., Results: In total, 150 participants (mean age, 58 ± 13 years; 105 men) underwent FDG-PET/CT. Twenty patients (13.4%) were diagnosed as positive. Fifteen patients underwent additional examinations and/or procedures, and RCC was found in seven patients. Of the four patients who underwent surgical resection, the pathological results were clear cell RCC in one, papillary RCC in one, and acquired cystic disease-associated RCC in two. Two participants were diagnosed with RCC on bone biopsy, and one was diagnosed on dynamic CT but opted for observation. The sensitivity, specificity, and negative predictive value were 100%, 93.9%, and 100%, respectively., Conclusion: FDG-PET/CT was useful for detecting RCC in patients with end-stage renal disease. Our findings show the potential use of FDG-PET/CT as a screening tool for RCC in this patient population., (© 2024. The Author(s).)

Background: To develop and validate a prognostic risk model for high-risk metastatic hormone-sensitive prostate cancer (mHSPC) patients treated with upfront abiraterone acetate (ABI)., Methods: This retrospective multicenter study involved 233 high-risk mHSPC patients who received upfront ABI, developed by three academic centers. The model was externally validated with an independent cohort of 282 patients. To identify independent prognostic factors for second progression-free survival (PFS2) and develop the best-fitted model, Cox proportional hazards regression, followed by the Akaike information criterion, was used. Patients were categorized into three groups based on their risk scores. PFS2 and overall survival (OS) were evaluated according to the risk groups in the discovery and validation cohorts., Results: The median age was 72 (range 51-89) years, with a median follow-up duration of 27 months. Independent factors linked to PFS2 included an Eastern Cooperative Oncology Group performance status ≥2, a primary Gleason score of 5, an extent of disease score of ≥3 or liver metastasis, and lactate dehydrogenase >220 U/L. Median PFS2 for favorable-, intermediate-, and poor-risk groups were not reached, 43 months, and 16 months, respectively. The median OS was 29 months in the poor-risk group, whereas it was not reached in the favorable- and intermediate-risk groups. The 2-year OS rates in the favorable-, intermediate- and poor-risk groups were 94.5%, 80.1%, and 60.3%, respectively. The validation cohort confirmed the risk model's relationship with PFS2 and OS. The median PFS2 and OS in the high-risk group were 21 months and 32 months, respectively., Conclusions: Our prognostic model, including five clinical factors, is useful for patient care and treatment selection in high-risk mHSPC patients treated with ADT plus ABI. The developed model could provide more accurate information, guide treatment decisions, or classify patients in future clinical trials., (© 2024 Wiley Periodicals LLC.)

Exploring methods for assembling functional materials at the molecular level may yield functional expressions derived from the assembly method. This study developed novel switchable molecular assemblies characterized by abrupt, complete phase transitions promoted via hydrogen bonding with a chiral carboxylic acid. These assemblies were prepared by aggregating discrete molecules that are unresponsive to external stimuli. Furthermore, enantiopure hydrogen-bond donor (HBD) molecules provide switchable compounds with cooperative and abrupt phase transitions, whereas the racemic mixture of the HBD provides a hydrogen-bonded one-dimensional compound with a broad and incomplete phase transition when structural disordering is observed. This study presents a novel strategy for observing metal-to-metal electron-transfer-coupled spin transitions via hydrogen-bond formation.

Ammonia, which can be decomposed on-site to produce CO 2 -free H 2 , is regarded as a promising hydrogen carrier because of its high hydrogen density, wide availability, and ease of transport. Unfortunately, ammonia decomposition requires high temperatures (>773 K) to achieve complete conversion, thereby hindering its practical applicability. Here, we demonstrate that high conversion can be achieved at markedly lower temperatures using an applied electric field along with a highly active and readily producible Ru/CeO 2 catalyst. Applying an electric field lowers the apparent activation energies, promotes low-temperature conversion, and even surpasses equilibrium conversion at 398 K, thereby providing a feasible route to economically attractive hydrogen production. Experimentally obtained results and neural network potential studies revealed that this reaction proceeds via HN-NH intermediate formation by virtue of surface protonics., Competing Interests: The authors have no conflict of interest., (This journal is © The Royal Society of Chemistry.)

Designing a cheap, competent, and durable catalyst for the oxygen evolution reaction (OER) is exceedingly necessary for generating oxygen through a water-splitting reaction. In this project, we have designed a ZIF-67-originated molybdenum-doped cobalt phosphide (CoP) using a simplistic dissolution-regrowth method using Na 2 MoO 4 and a subsequent phosphidation process. This leads to the formation of an exceptional hollow nanocage morphology that is useful for enhanced catalytic activity. Metal-organic frameworks, especially ZIF-67, can be used both as a template and as a metal (cobalt) precursor. Molybdenum-doped CoP was fabricated through a two-step synthesis process, and the fabricated Mo-doped CoP showed excellent catalytic activity during the OER with a lower value of overpotential. Furthermore, the effect of the Mo amount on the catalytic activity has been explored. The best catalyst (CoMoP-2) showed an onset potential of around 1.49 V at 10 mA cm -2 to give rise to a Tafel slope of 62.1 mV dec -1 . The improved catalytic activity can be attributed to the increased porosity and surface area of the resultant catalyst., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Background: Epidemiological research highlights the need to understand sports injuries for effective prevention. Yet, detailed knowledge about lateral ankle sprain (LAS) in soccer, especially related to indirect contact mechanisms and specific sports movements, remains scarce. This study aimed to determine the prevalence of LAS by examining injury mechanisms, focusing on indirect contact, and analyzing sports-related movements., Study Design: Prospective study., Methods: In this prospective study, 304 high-school and college soccer players (age: 19.0 ± 2.2 years, height: 168.3 ± 10.6 cm, weight: 64.2 ± 11.1 kg) were monitored for 18.5 months. Attendance and LAS incidents were recorded daily. Injury details, including movement at the time of injury, contact presence, and direction, were collected through interviews conducted on the injury day. LAS were categorized into direct contact, indirect contact, and non-contact mechanisms. Direct contact injuries were due to external forces on the lower leg or foot. Indirect contact injuries resulted from impacts on areas other than the lower leg or foot, and non-contact injuries involved no interaction with the ball or opponent. Incidence rates per 1,000 athlete exposures and 95 % confidence intervals (CIs) were calculated, along with rate ratios (RR) to assess sex differences., Results: The study recorded 59 LAS injuries. Indirect injuries were predominant, accounting for 47.5 % (n = 28) of the cases. Men experienced a higher incidence of indirect injuries, with an RR of 2.29 (95 % CI: 1.06-4.96). Outward contact was the most common (77.8 %; n = 21), while inward contact occurred in 22.2 % of the cases (n = 6)., Conclusion: High school and college soccer players primarily sustained injuries through indirect contact mechanisms, with a significant number of injuries occurring during lateral contact. Men were more prone to indirect contact injuries. Furthermore, 47.5 % of LAS incidents involved reactive movements, and injuries frequently occurred during specific sports actions, such as ball interception., Competing Interests: Declaration of competing interest The authors report no conflict of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Purpose: To verify the usefulness of a deep learning model for determining the presence or absence of contrast-enhanced myocardium in late gadolinium-enhancement images in cardiac MRI., Methods: We used 174 late gadolinium-enhancement myocardial short-axis images obtained from contrast-enhanced cardiac MRI performed using a 3.0T MRI system at the University of Tokyo Hospital. Of these, 144 images were used for training, extracting a region of interest targeting the heart, scaling signal intensity, and data augmentation were performed to obtain 3312 training images. The interpretation report of two cardiology specialists of our hospital was used as the correct label. A learning model was constructed using a convolutional neural network and applied to 30 test data. In all cases, the acquired mean age was 56.4±12.1 years, and the male-to-female ratio was 1 : 0.82., Results: Before and after data augmentation, sensitivity remained consistent at 93.3%, specificity improved from 0.0% to 100.0%, and accuracy improved from 46.7% to 96.7%., Conclusion: The prediction accuracy of the deep learning model developed in this research is high, suggesting its high usefulness.

The surgical outcomes of aortic root replacement for Stanford type A acute aortic dissection( AAAD) remain unacceptable with a 30-day mortality rate of 20%. Additionally, in young patients requiring aortic root replacement for AAAD, the preservation of native valve is desirable, yet challenging to achieve in emergent surgery with poor preoperative status. Ideally, we aim to avoid aortic root replacement whenever possible, opting instead for partial remodeling even in cases necessitating incision into the aortic root. We present our surgical outcomes in the strategy for aortic root pathology due to AAAD. We conducted an analysis of 517 cases of AAAD surgery from 2002 to 2023, wherein 499 cases( 96%) underwent aortic root preservation, 10 cases( 1.9%) underwent partial remodeling, and 8 cases( 1.5%)necessitated emergent aortic root replacement. Of these, 13 cases underwent aortic root replacement after AAAD repair( 8 David procedures and 5 Bentall procedures), all demonstrating favorable surgical outcomes, including long-term results. We believe that this strategy for aortic root pathology holds significant merit, particularly in AAAD in young patients with enlarged aortic root.

Background: Nivolumab plus ipilimumab (NIVO + IPI) is the first-line treatment for patients with metastatic renal cell carcinoma (mRCC). While approximately 40% of patients treated with NIVO + IPI achieve a durable response, 20% develop primary resistance with severe consequences. Therefore, there is a clinical need for criteria to select patients suitable for NIVO + IPI therapy to optimize its therapeutic efficacy. Accordingly, our aim was to evaluate the association between candidate biomarkers measured before treatment initiation and survival., Methods: This was a multi-institutional, retrospective, cohort study of 183 patients with mRCC treated with systematic therapies between August 2015 and July 2023. Of these, 112 received NIVO + IPI as first-line therapy: mean age, 68 years; men, 83.0% (n = 93), and clear cell histology, 80.4% (n = 90). Univariable and multivariable analyses were used to evaluate associations between biomarkers and survival., Results: On univariate analysis, high C-reactive protein and systemic index, a high neutrophil-to-lymphocyte and platelet-to-lymphocyte ratio, and a low lymphocyte-to-monocyte ratio (LMR) were associated with shorter overall survival (OS). On multivariable analysis, a LMR ≤ 3 was retained as an independent factor associated to shorter OS with the highest accuracy (C-index, 0.656; hazard ratio, 7.042; 95% confidence interval, 2.0-25.0; p = 0.002)., Conclusion: A low LMR may identify patients who would be candidate for NIVO + IPI therapy for mRCC., (© 2024. The Author(s) under exclusive licence to Japan Society of Clinical Oncology.)

Purpose: The lung is a unique organ with a ventilation-perfusion mismatch, which can cause inhomogeneous incidence rates of lung cancer depending on the location in the lung. We aimed to evaluate the incidence of lung adenocarcinoma in each lobe by analyzing the incidence per unit volume, to evaluate the incidence without being affected by differences in the size of each lobe or in the size of the lungs between individuals., Methods: The number of adenocarcinomas in each lobe was counted. Lung volumes were measured using a three-dimensional computer workstation. The tumor incidence per unit volume was analyzed based on the number of tumors in each lobe., Results: The number of tumors per unit volume was 0.467 in the right upper lobe (RUL), 0.182 in the right middle lobe, 0.209 in the right lower lobe, 0.306 in the left upper segment (LUS), 0.083 in the left lingular segment, and 0.169 in the left lower lobe. The tumor incidence rate of RUL + LUS was 2.269 times that of the other lobes, a value that was significantly higher when using the bootstrap method (p < 0.001)., Conclusions: The incidence of adenocarcinoma per unit volume in both upper lobes was higher than that in other lobes., (© 2023. The Author(s) under exclusive licence to Springer Nature Singapore Pte Ltd.)

We report gas-phase reactions of free iron-oxide clusters, Fe n O m + , and their Ar adducts with methane in the context of chemical processes in Mars' atmosphere. Methane activation was observed to produce Fe n O m CH 2 + /Fe n O m CD 2 + and Fe n O m C + , where the reactivity exhibited size and composition dependence. For example, the rate coefficients of methane activation for Fe 3 O + and Fe 4 O + were estimated to be 1 × 10 -13 and 3 × 10 -13 cm 3 s -1 , respectively. Based on these reaction rate coefficients, the presence of iron-oxide clusters/particles with a density as low as 10 7 cm -3 in Mars' atmosphere would explain the rapid loss of methane observed recently by the Curiosity rover.

Atomic substitution is a promising approach for controlling structures and properties for developing clusters with desired responses. Although many possible coordination candidates could be deduced for substitution, not all can be prepared. Therefore, predicting the correlation between structures and physical properties is important prior to synthesis. In this study, regarding Keggin-type polyoxometalates (POMs) as a model cluster, the dominant factors affecting the protonation were investigated by atomic substitutions and geometry changes. The valence of Keggin-type POMs and the constituent elements of the cluster shell structure affect the charge and potential distribution, which change the protonation sites. Furthermore, the valence of Keggin-type POMs and the bond length between the core and shell structure determine the protonation energy. These factors also affect the HOMO-LUMO gap, which governs photochemical and redox reactions. These governing factors derived from actual parameters of the α-isomer of Keggin-type POMs enabled us to deduce the protonation energy of the β-isomer, which is more difficult to prepare and isolate than the α-isomer.

Tough carboxymethylcellulose nanofibers (CMF)/zirconium (Zr) hydrogels were easily obtained by a freeze-crosslinking method, where Zr-containing HCl solution was added to frozen CMF sol and the mixture was allowed to thaw. The Zr content of the hydrogels increased with increasing Zr concentration in the initial HCl solution. Furthermore, the mechanical strength increased with increasing Zr content. The Young's modulus value was improved by approximately 6 times compared to the CMF hydrogel without Zr, i.e. , from 4.5 kPa to 27.2 kPa. The hydrogel had a porous structure with a pore size of 133 ± 37 μm and a CMF-Zr sheet structure around the pores. The obtained CMF-Zr hydrogel exhibited high adsorptivity for fluoride. The maximum adsorption capacity ( Q max ) was estimated to be 24.1 mg g -1 . This simple gelation method provides useful insights for the development of easy-to-handle hydrogel-based adsorbents.

Melanoma, originating from melanocytes, is a highly aggressive tumor. Tyrosinase is involved in melanin production in melanocytes, and its overexpression is noted in malignant melanomas. However, the role of tyrosinase in melanomas remains unclear. Therefore, this study aimed to evaluate the potential functions of tyrosinase in the human melanoma cell line A375. The expression level of tyrosinase in A375 cells was undetectable. However, markedly increased expression level was observed in the mouse melanoma cell line B16F10 and the human melanoma cell line WM266-4. Subsequently, we investigated the effect of ectopic tyrosinase expression on A375 cell motility using wound-healing assay. The overexpression of tyrosinase resulted in enhanced cell migration in both stable and transient tyrosinase expression cells. The levels of filamentous actin were decreased in tyrosinase-expressing A375 cells, suggesting that tyrosinase regulates cell motility by modulating actin polymerization. Histidine residues in tyrosinase are important for its enzymatic activity for synthesizing melanin. Substitution of these histidine residues to alanine residues mitigated the promotion of tyrosinase-induced A375 cell metastasis. Furthermore, melanin treatment enhanced A375 cell metastasis and phosphorylation of Cofilin. Thus, our findings suggest that tyrosinase increases the migration of A375 cells by regulating actin polymerization through its enzymatic activity., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Using an engineered mitochondrial clogger, Krakowczyk et al. (https://doi.org/10.1083/jcb.202306051) identified the OMA1 protease as a critical component that eliminates import failure at the TOM translocase in mammalian cells, providing a novel quality control mechanism that is distinct from those described in yeast., (© 2024 Sekine and Sekine.)

Introduction Blast injuries in modern society often occur owing to terrorist attacks in confined spaces, particularly in urban settings, indoors, and in vehicles, leading to significant damage. Therefore, it is important to focus on blast injuries in confined spaces rather than in conventional open-field experiments. Materials and methods We used an air-driven shock wave generator (blast tube) established indoors in 2017 and conducted basic research to potentially save the lives of patients with blast injuries. Under general anesthesia, pigs were divided into with body armor (BA) and without BA groups. The pigs were fixed in the measurement chamber with their dorsal chest directly exposed to the shock wave. The driving pressure was set at 3.0 MPa to achieve a mortality rate of approximately 50%. A generated shock wave was directly applied to the pigs. Comparisons were made between the groups with respect to cardiac arrest and survival, as well as apnea, bradycardia, and hypotension, which are the triad of blast lung. Autopsies were performed to confirm the extent of the organ damage. Statistical analysis was performed using Fisher's exact test, and statistical significance was set at p <0.05. The animal experimentation was conducted according to the protocol reviewed and approved by the Animal Ethics Committee of the National Defense Medical College Hospital (approval number 19041). Results Eight pigs were assigned to the BA group and seven pigs to the non-BA group. In the non-BA group, apnea was observed in four of seven cases, three of which resulted in death. None of the eight pigs in the BA group had respiratory arrest; notably, all survived. Hypotension was observed in some pigs in each group; however, there were no cases of bradycardia in either group. Statistical analysis showed that wearing BA significantly reduced the occurrence of respiratory and cardiac arrest ( p =0.026) but not survival ( p =0.077). No significant differences were found in other vital signs. Conclusions Wearing BA with adequate neck and chest protection reduced mortality and it was effective to reduce cardiac and respiratory arrest against shock wave exposure. Mortality from shock wave injury appears to be associated with respiratory arrest, and the avoidance of respiratory arrest may lead to survival., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Kiriu et al.)

Coexistence and switching between spin-crossover (SCO) and single molecular magnet (SMM) behaviours in one single complex may lead to materials that exhibit bi-stable and stimuli sensitive properties in a wide temperature range and under multiple conditions; unfortunately, the conflict and dilemma in the principle of approaching SCO and SMM molecules make it particularly difficult; at low temperature, low spin (LS) SCO molecules possess highly symmetrical geometry and isotropic spins, which are not suitable for SMM behaviour. Herein, we overcome this issue by using a rationally designed Co(II) mononuclear complex [Co(MeOphterpy) 2 ] (ClO 4 ) 2 (1; MeOphterpy = 4'-(4-methoxyphenyl)-2,2':6',2''-terpyridine), the magnetic properties of which reversibly respond to desolvation and solvation. The solvated structure reinforced a low distortion of the coordination sphere via hydrogen bonding between ligands and methanol molecules, while in the desolvated structure a methoxy group flipping occurred, increasing the distortion of the coordination sphere and stabilising the HS state at low temperature, which exhibited a field-induced slow magnetic relaxation, resulting in a reversible switching between SCO and SMM properties within one molecule.

Ammonia is an extremely important storage and transport medium for renewable energy, and technology is expected to produce it on demand and onsite using renewable energy. Applying a DC (direct current) to a solid catalyst layer with semiconducting properties makes ammonia synthesis highly efficient, even at low temperatures (approximately 400 K). In this process, oxide supports with semiconducting properties play important roles as metal supports and conduction fields for electrons and protons. The influence of the degree of particle aggregation on the support properties and ammonia synthesis using an electric field was evaluated for CeO 2 , which is the best material for this purpose because of its semiconducting properties. The results showed that controlling the aggregation structure of the crystalline particles could significantly influence the surface conductivity of protons and electrons; thus, the activity could be largely controlled. The Ru-CeO 2 interaction could also be controlled by changing the crystallinity, which suppressed the aggregation of the supported Ru and significantly improved the ammonia synthesis activity using an electric field at low temperatures., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

The chemical reaction between Fe and lacquer has been used to create the black color in lacquer coatings since ancient times. Here, the effects of Fe ion addition, UV irradiation, and heating on the microscopic structures of black lacquer films were investigated by using X-ray absorption near edge structure (XANES), extended X-ray absorption fine structure (EXAFS), Fourier transform-infrared spectroscopy (FT-IR), small-angle X-ray scattering (SAXS), and small angle neutron scattering (SANS). The EXAFS result indicated that heating and UV irradiation made the coordination structure of Fe 3+ in the lacquer nonuniform, and that heating caused the greatest nonuniformity. The FT-IR, SAXS, and SANS results demonstrated that the microscopic structural changes in the black lacquer films were induced by both heating and UV irradiation, but the changes were different. Heating caused a substantial structural change on the nanoscale, and UV irradiation mainly caused changes in the molecular binding mode. The results provide important knowledge for analyzing archeological lacquer samples and for developing lacquer-based materials. This work also demonstrates the utility of the complementary use of XANES, EXAFS, FT-IR, SAXS, and SANS for nondestructive analysis of black lacquer in precious cultural relics.

This study aimed to assess the effects of thienopyridine-class antiplatelet agents (including ticlopidine, clopidogrel, and prasugrel) on bleeding complications in patients who underwent robot-assisted radical prostatectomy. This cohort study used a database for robot-assisted radical prostatectomy at 23 tertiary centers nationwide between 2011 and 2022. Patients who received thienopyridines (thienopyridine group) were compared with those who received aspirin monotherapy (aspirin group). The primary outcome was the incidence of bleeding complications. High-grade complications were defined as Clavien-Dindo grade III or higher. The risks of these outcomes were evaluated using inverse probability of treatment weighted regression models. The study results demonstrated that thienopyridine therapy was associated with a higher risk of overall bleeding complications (OR: 3.62, 95%CI 1.54-8.49). The increased risks of the thienopyridine group were detected for low-grade bleeding complications (OR: 3.20, 95%CI 1.23-8.30) but not for high-grade bleeding complications (OR: 5.23, 95%CI 0.78-34.9). The increased risk of bleeding complications was not observed when thienopyridine was discontinued (OR: 2.52, 95%CI 0.83-7.70); however, it became apparent when it was continued perioperatively (OR: 4.35, 95%CI 1.14-16.61). In conclusion, thienopyridine increased the incidence of bleeding complications, particularly low-grade bleeding complications, following robot-assisted radical prostatectomy. These bleeding effects emerged when thienopyridine was continued perioperatively., (© 2024. The Author(s).)

Signal-transducing adaptor protein-2 (STAP-2) is an adaptor molecule involved in several cellular signaling cascades. Here, we attempted to identify novel STAP-2 interacting molecules, and identified c-Cbl associated protein (CAP) as a binding protein through the C-terminal proline-rich region of STAP-2. Expression of STAP-2 increased the interaction between CAP and c-Cbl, suggesting that STAP-2 bridges these proteins and enhances complex formation. CAP/c-Cbl complex is known to regulate GLUT4 translocation in insulin signaling. STAP-2 overexpressed human hepatocyte Hep3B cells showed enhanced GLUT4 translocation after insulin treatment. Elevated levels of Stap2 mRNA have been observed in 3T3-L1 cells and mouse embryonic fibroblasts (MEFs) during adipocyte differentiation. The differentiation of 3T3-L1 cells into adipocytes was highly promoted by retroviral overexpression of STAP-2. In contrast, STAP-2 knockout (KO) MEFs exhibited suppressed adipogenesis. The increase in body weight with high-fat diet feeding was significantly decreased in STAP-2 KO mice compared to WT animals. These data suggest that the expression of STAP-2 correlates with adipogenesis. Thus, STAP-2 is a novel regulatory molecule that controls insulin signal transduction by forming a c-Cbl/STAP-2/CAP ternary complex., (© 2024. The Author(s).)

Background: The quality of life of patients is an important consideration when selecting treatments for localized prostate cancer (PCa). We retrospectively compared sexual function after robot-assisted radical prostatectomy (RARP) and carbon-ion radiotherapy (CIRT) using propensity score matching., Methods: In total, 127 Japanese PCa patients treated with RARP and 190 treated with CIRT monotherapy were evaluated. We evaluated the Expanded Prostate Cancer Index Composite (EPIC) score before treatment and 12 and 24 months after treatment. After propensity score matching, data from 101 patients from each group were analyzed. The study protocol was approved by the Institutional Review Board of Gunma University Hospital (no. IRB2020-050, 1839)., Results: After propensity score matching, the mean EPIC sexual function summary scores in the RARP and CIRT groups were 46.4 and 48.2, respectively. At 12 and 24 months after treatment, these scores were 27.9 (39.9% decrease) and 28.2 (39.2% decrease) in the RARP group and 41.4 (14.1% decrease) and 41.6 (13.7% decrease) in the CIRT group, respectively. Both groups demonstrated significantly decreased scores after 12 and 24 months of treatment compared to before treatment (all p < 0.05). At 12 and 24 months, the sexual function summary score was significantly higher in the CIRT group than in the RARP group (p < 0.001)., Conclusions: There was a smaller decrease in the EPIC sexual function score in the CIRT group than in the RARP group. These results provide useful information for treatment decision-making of Japanese PCa patients., (© 2024. The Author(s).)

We describe nanocellulose (NC) hydrogels formed from chemically unmodified NC by cellulose crystalline transformation and subsequent freeze cross-linking reaction. The freeze cross-linked NC hydrogel with macropores (~100 μm) was prepared by freezing a mixture of NC and NaOH (0.2 mol L -1 ), adding citric acid to the frozen mixture, and thawing it. Using NaOH and freezing together induced the crystalline transformation of NC from cellulose I to II via freeze concentration. After the crystalline transformation, cross-linking between the NC and CA in the freeze concentration layer provided a strong NC network structure, forming NC hydrogels with high mechanical strength. The structural changes in NC caused by NaOH, freezing, and freeze cross-linking on the angstrom to micrometer scale were investigated with FT-IR, SAXS, PXRD, and SEM. The freeze cross-linked NC hydrogel easily retained powder adsorbents in its inner space by mixing the NC-NaOH sol and the powder, and the hydrogel showed high removal efficiency for heavy metals. The results highlight the versatility of chemically unmodified celluloses in developing functional materials and suggest possible practical applications. This study also provides new insights into the efficient use of chemical reactions of cellulose under freezing conditions., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Ltd.)

The elution of pharmaceutical products such as metformin at higher concentrations than the safe level in aquatic systems is a serious threat to human health and the ecosystem. Photocatalytic technology using TiO 2 semiconductors potentially fixes this problem. This study aims to synthesize triphasic anatase-rutile-brookite TiO 2 using ultrasound assisted sol-gel technique in the presence of acid and its application to photodegradation of metformin under UV light irradiation. Based on X-ray diffraction analysis, a TiO 2 sample consisted of anatase (76%), rutile (7%), and brookite (17%) polymorph (A 76 R 7 B 17 ) that was fully crystallized. Scanning electron microscopy (EM)-energy dispersive X-ray spectra results showed agglomerated triphasic A 76 R 7 B 17 with irregular spherical clusters. Transmission EM results revealed that the crystal size of A 76 R 7 B 17 was 4-14 nm. The Brunauer-Emmett-Teller analysis showed the sample's specific surface area of 149 m 2  g -1 . The degradation test of metformin demonstrated that the A 76 R 7 B 17 exhibited a 75.4% degradation efficiency after 120 min under UV light irradiation, significantly higher than using biphasic and single-phase TiO 2 photocatalysts. This difference could be attributed to the heterojunction effect of triphasic materials that effectively reduced electron-hole recombination rate as well as the combination of effective electron transfer from conduction band of brookite and anatase and the utilization of wider range of UV-visible light using rutile., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interestsDiana Rakhmawaty Eddy reports was provided by Padjadjaran University Faculty of Mathematics and Natural Sciences. Yasuo Izumi reports a relationship with Chiba University that includes: non-financial support., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Lean-burn engines are gaining attention for their lower CO 2 emissions, higher thermal efficiency, and improved fuel economy compared to traditional combustion engines. However, they present some difficulty for reducing nitrogen oxides (NO x ) because of residual oxygen. To address this difficulty, NO x storage reduction (NSR) system, which combines noble metals and NO x adsorbents, is developed as a viable approach. But it requires cyclic operation, which adversely affects fuel efficiency. A novel approach proposed in this work is electric field-assisted lean NO x reduction, which applies an electric field to the NSR catalyst during lean conditions. This innovation uses surplus vehicle electricity for exhaust purification, enhances hydrogen transfer, and improves NO x reduction, even at low temperatures. Tests with a 3 wt% Pt-16 wt% BaO/CeO 2 catalyst demonstrate markedly higher NO x conversion to N 2 (13.1% vs. 2.9% without an electric field). This process is effective with extended electric field exposure, doubling the conversion rate. Electric field-assisted lean NO x reduction, by improving NSR technology, can enhance NO x conversion efficiency, reduce emissions, and optimize fuel efficiency in lean-burn engines.

During the production of orexin A and B from preproorexin, a common precursor protein, in hypothalamic orexin neurons, C-terminal peptide (herein called preproorexin C-peptide) is concomitantly produced via post-translational processing. The predicted three-dimensional structure of preproorexin C-peptide is similar among mammalian species, suggestive of a conserved function in the mammalian brain. However, C-peptide has long been regarded as a non-functional peptide. We herein examined the effects of rat and/or mouse preproorexin C-peptide on gene expression and cell viability in cultured rat cerebrocortical cells and on memory behavior in C57BL/6J mice. Rat and mouse C-peptides both increased brain-derived neurotrophic factor (Bdnf) mRNA levels. Moreover, C-peptide enhanced high K + -, glutamate-, and BDNF-induced increases in Bdnf mRNA levels without affecting forskolin-induced Bdnf expression. H-89, a protein kinase A inhibitor, blocked C-peptide-induced Bdnf expression, whereas rolipram, a phosphodiesterase inhibitor, enhanced this effect. Intracellular cyclic AMP concentrations were elevated by C-peptide. These results demonstrate that preproorexin C-peptide promoted Bdnf mRNA expression by a cyclic AMP-dependent mechanism. Eleven amino acids at the N terminus of rat preproorexin C-peptide exerted similar effects on Bdnf expression as full-length preproorexin C-peptide. Preproorexin C-peptide also exerted protective effects against CoCl 2 -induced neuronal cell death. An intracerebroventricular injection of mouse preproorexin C-peptide induced c-fos and Bdnf expression in the cerebral cortex and hippocampus and enhanced novel object recognition memory in mice. Collectively, the present results show that preproorexin C-peptide is a functional substance, at least in some pharmacological and neuronal settings., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Purpose: To investigate the relationship between changes in pulmonary function (PF) and patient-reported outcomes (PROs) of lung cancer surgery., Methods: We recruited 262 patients who underwent lung resection for lung cancer, to evaluate the PROs, using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ)-C30 and the Lung Cancer 13-question supplement (LC13). The patients underwent PF tests and PRO assessments preoperatively (Pre) and 1 year after surgery (Y1). Changes were calculated by subtracting the value at Pre from the value at Y1. We set two cohorts: patients under the ongoing protocol (Cohort 1) and patients who were eligible for lobectomy with clinical stage I lung cancer (Cohort 2)., Results: Cohorts 1 and 2 comprised 206 and 149 patients, respectively. In addition to dyspnea, changes in PF were also correlated with scores for global health status, physical and role function scores, fatigue, nausea and vomiting, pain, and financial difficulties. Absolute correlation coefficient values ranged from 0.149 to 0.311. Improvement of emotional and social function scores was independent of PF. Sublobar resection preserved PF more than lobectomy did. Wedge resection mitigated dyspnea in both cohorts., Conclusion: The correlation between PF and PROs was found to be weak; therefore, further studies are needed to improve the patient's postoperative experience., (© 2023. The Author(s) under exclusive licence to Springer Nature Singapore Pte Ltd.)

Insertion sequence (IS)-excision enhancer (IEE) promotes the excision of ISs in the genome of enterohemorrhagic Escherichia coli O157. Because IEE-dependent IS excision occurs in the presence of transposase, the process of IS transposition may be involved in IS excision; however, little is understood about the molecular mechanisms of IS excision. Our in vitro analysis revealed that IEE exhibits DNA-dependent ATPase activity, which is activated by branched DNA. IEE also catalyzes the branch migration of fork-structured DNA. These results suggest that IEE remodels branched structures of the IS transposition intermediate. Sequence analysis of recombination sites in IS-excision products suggested that microhomologous sequences near the ends of the IS are involved in IS excision. IEE promoted microhomology-mediated end joining (MMEJ), in which base pairing between 6-nucleotides complementary ends of two 3'-protruding DNAs and subsequent elongation of the paired DNA strand occurred. IS-excision frequencies were significantly decreased in cells producing IEE mutants that had lost either branch migration or MMEJ activity, which suggests that these activities of IEE are required for IS excision. Based on our results, we propose a model for IS excision triggered by IEE and transposase., (© 2023 Molecular Biology Society of Japan and John Wiley & Sons Australia, Ltd.)

The signal transducer and activator of transcription 3 (STAT3) protein is a key regulator of cell differentiation, proliferation, and survival in hematopoiesis, immune responses, and other biological systems. STAT3 transcriptional activity is strictly regulated through various mechanisms, such as phosphorylation and dephosphorylation. In this study, we attempted to identify novel phosphatases which regulate STAT3 activity in response to cytokine stimulations. To this end, leukemia inhibitory factor (LIF)/STAT3 dependent phosphatase induction was evaluated in the mouse hepatoma cell line Hepa1-6. After LIF stimulation, the expression of several atypical dual specific phosphatases (aDUSPs) was upregulated in Hepa1-6 cells. Among the LIF-induced aDUSPs, we focused on DUSP15 and clarified its functions in LIF/STAT3 signaling using RNA interference. DUSP15 knockdown decreased LIF-induced Socs3 mRNA expression and STAT3 translocation. Furthermore, loss of DUSP15 reduced the phosphorylation of STAT3 at Tyr705 and Janus family tyrosine kinase 1 (Jak1) at Tyr1034/1035 in response to LIF. The interaction between Jak1 and DUSP15 was observed in LIF-stimulated Hepa1-6 cells. We also demonstrated the suppression of granulocyte colony-stimulating factor (G-CSF)-mediated gp130/STAT3-dependent cell growth of Ba/F-G133 cells via DUSP15 knockdown. Therefore, DUSP15 functions as a positive feedback regulator in the Jak1/STAT3 signaling cascade.

Neuronal regrowth after traumatic injury is strongly inhibited in the central nervous system (CNS) of adult mammals. Cell-intrinsic and extrinsic factors limit the regulation of axonal growth and regrowth of fibers is minimal despite nearly all neurons surviving. Developing medical drugs to promote neurological recovery is crucial since neuronal injuries have few palliative cares and no pharmacological interventions. Herein, we developed a novel in vitro axonal regeneration assay system to screen the chemical reagents using human-induced pluripotent stem cell (hiPSC)-derived neurons. These neurons were cultured in a 96-well plate to form a monolayer and were scraped using a floating metal pin tool for axotomy. The cell number and plate coating conditions were optimized to score the regenerating axon. Treatment using the Rho-associated kinase (ROCK) inhibitor Y-27632 enhanced axonal regeneration in this regeneration assay system with hiPSC-derived neurons. Therefore, our novel screening method is suitable for drug screening to identify the chemical compounds that promote axonal regeneration after axotomy under in vitro conditions.

We retrospectively study the outcome of left atrial appendage (LAA) preserving maze procedure, focus on thrombus formation in left atrium( LA), postoperative stroke, and LA function., Patients and Methods: We studied 131 patients (mean age, 68.2y;77 men and 54 women) who underwent maze procedure for atrial fibrillation( Af) between 2008 and 2020. Full maze was performed for 116 patients with long-standing persistent Af or persistent Af. Pulmonary vein isolation alone was performed for 15 patients with paroxysmal Af. The mean follow-up period was 2.9( 10.1-0.4) years., Results: In perioperative results, there were no death, cerebral infarction, and reoperation in this series. At discharge, 1 year, 3 years, 5 years, and 10 years after the surgery, sinus rhythm was maintained in 92%, 87%, 83%, 77%. Pacemaker was implanted in 8( early 3, late 5) patients. Despite adequate anticoagulant therapy, one patient developed cerebral infarction a month postoperatively. In other patients, there was no cerebral infarction in short-term nor long-term., Conclusions: The LAA preserving maze procedure was not a risk factor of cerebral infarction under appropriate medication. However, close follow-up is essential.

Background/aim: Statins exert antitumor effects via various mechanisms. Additionally, the recurrence rate of prostate cancer after radiation therapy is lower in patients taking statins. This study investigated the efficacy of combination therapy with statins and irradiation in androgen-independent prostate cancer cells., Materials and Methods: PC-3 and LNCaP human prostate cancer cell lines were used in this study. We developed androgen-independent LNCaP cells (LNCaP-LA) by gradually replacing fetal bovine serum (FBS) with charcoal-stripped FBS. Microarray analysis was performed, followed by Ingenuity Pathway Analysis. Cell viability was determined using the MTS assay., Results: Simvastatin alters gene expressions in PC-3 cells. Microarray data showed that the number of differentially expressed genes was the highest in the pathway of "Role of BRCA1 in DNA Damage Response". In the validation, the expression of RAD51, listed in "Role of BRCA1 in DNA Damage Response", decreased significantly by simvastatin in PC-3 cells. Reduction in RAD51 expression following siRNA transfection increased the cytocidal effects of X-ray therapy in PC-3 and LNCaP-LA cells. The combination of simvastatin and irradiation further inhibited cell proliferation compared with monotherapy with either therapy in PC-3 or LNCaP-LA cells. In addition, compared with X-ray monotherapy, the combination of simvastatin and irradiation further enhanced the expression of γH2AX, which is reported to be one of the accurate markers of DNA damage in PC-3 cells., Conclusion: Simvastatin decreased the expression of RAD51 in androgen-independent prostate cancer cells. The combination of irradiation and drugs that reduce RAD51 expression can potentially affect androgen-independent prostate cancer growth., (Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Overdose has become a global social problem. The Japanese government requires gatekeeper training to detect and prevent indicators of overdose and suicide. However, knowledge of necessary factors for the gatekeeper of overdose (patient intervention) is limited. This study aimed to investigate the characteristics of individuals who experienced intervening persons expected to overdose, and to identify the factors required of gatekeepers. A Google form was used to survey 298 pharmacists and registered sellers in Japan. We searched for factors by logistic analysis. Knowledge of prescription drugs used for overdose was higher among pharmacists than among registered sellers. Conversely, pharmacists and registered sellers had similar knowledge about OTC drugs. Overall multivariate logistic regression analysis revealed countermeasures against overdose at their workplace (odds ratio (OR): 4.01, 95% confidence interval (CI): 2.25-7.15, p < 0.01) and knowledge that overdose is on the rise (OR: 1.93, 95% CI: 1.04-3.69, p < 0.05) to be significantly associated with intervention experience as a gatekeeper. Countermeasures against overdose at their workplace (OR: 2.40, 95% CI: 1.10-5.25, p < 0.05) in pharmacists and years of work experience (OR: 1.13, 95% CI: 1.04-1.24, p < 0.05), countermeasure against overdose at their workplace (OR: 3.43, 95% CI: 1.18-10.0, p < 0.05), and willingness to participate in study sessions and workshops on overdose (OR: 3.50, 95% CI: 1.51-8.10, p < 0.05) in registered seller were significantly associated with intervention experience as a gatekeeper. These results are useful evidences for countermeasures and gatekeeper training for overdose at pharmacies and drugstores in the community.

Background: The presence of mediastinal lymph node metastasis is important because it is related to the treatment and prognosis of lung cancer. Although prevalently used, evaluation of lymph nodes is not always reliable. We introduced sphericity as a criterion for evaluating morphologic differences between metastatic and nonmetastatic nodes., Methods: We reviewed the cases of 66 patients with N2 disease and of 68 patients with N0-1 disease who underwent lobectomy with mediastinal dissection between January 2012 and December 2021. The sphericity of the dissected station lymph nodes, which represents how close the node is to being a true sphere, was evaluated along with the diameter and volume. Each parameter was obtained and evaluated for ability to predict metastasis., Results: Metastatic lymph nodes had a larger short-axis diameter (average: 8.2 mm vs. 5.4 mm, p < 0.001) and sphericity (average: 0.72 vs. 0.60, p < 0.001) than those of nonmetastatic lymph nodes. Short-axis diameter ≥ 6 mm and sphericity ≥ 0.60 identified metastasis with 76.2% sensitivity and 70.2% specificity (AUC = 0.78, p < 0.001) and 92.1% sensitivity and 53.9% specificity (AUC = 0.78, p < 0.001), respectively. For lymph nodes with a short-axis diameter ≥ 5 mm, sphericity ≥ 0.60 identified metastasis with 84.1% sensitivity and 89.3% specificity., Conclusion: By using 3D-CT analysis to examine sphericity, we showed that metastatic lymph nodes became spherical. Our method for predicting lymph node metastasis based on sphericity of lymph nodes with a short-axis diameter ≥ 5 mm could do so with higher sensitivity than the conventional method, and with acceptable specificity., (© 2023. The Author(s).)

Amino acids in carbonaceous chondrites may have seeded the origin of life on Earth and possibly elsewhere. Recently, the return samples from a C-type asteroid Ryugu were found to contain amino acids with a similar distribution to Ivuna-type CI chondrites, suggesting the potential of amino acid abundances as molecular descriptors of parent body geochemistry. However, the chemical mechanisms responsible for the amino acid distributions remain to be elucidated particularly at low temperatures (<50°C). Here, we report that two representative proteinogenic amino acids, aspartic acid and glutamic acid, decompose to β-alanine and γ-aminobutyric acid, respectively, under simulated geoelectrochemical conditions at 25°C. This low-temperature conversion provides a plausible explanation for the enrichment of these two n-ω-amino acids compared to their precursors in heavily aqueously altered CI chondrites and Ryugu's return samples. The results suggest that these heavily aqueously altered samples originated from the water-rich mantle of their water/rock differentiated parent planetesimals where protein α-amino acids were decomposed.

Background/aim: Statin has recently been studied for its effects on inducing cell death and inhibiting metastasis. Nevertheless, the precise mechanism of its anti-tumor effect is not yet fully understood. We conducted research on statin as a novel treatment for castration-resistant prostate cancer (CRPC). This study focused on autophagy in prostate cancer cells and assessed the effects of simvastatin., Materials and Methods: After administering simvastatin to PC-3 cells, we conducted a microarray analysis. Simvastatin was administered to prostate cancer cell lines (PC-3, LNCaP-LA; cultured under androgen-depleted conditions, DU145, 22RV1), and the tumor proliferation inhibition was evaluated using the MTS assay and cell count. Autophagy was measured by observing autophagosome staining under a fluorescence microscope and quantifying LC-3 protein using western blot. We also investigated the effects of rapamycin, an autophagy inducer, and chloroquine as an inhibitor., Results: Simvastatin demonstrated a significant concentration-dependent growth inhibition effect on prostate cell lines. Moreover, a significant increase in autophagy was observed in all cell lines following simvastatin administration. When we administered simvastatin with rapamycin at a concentration that did not show a tumor growth inhibitory effect, it significantly enhanced autophagy induction compared to simvastatin alone, and also significantly enhanced the growth inhibition effect on PC-3 cells., Conclusion: Simvastatin induced autophagy and inhibited the proliferation of prostate cancer cell lines. The combination of simvastatin and rapamycin significantly induced autophagy and enhanced the inhibitory effect of simvastatin on proliferation. This mechanism may serve as a novel therapeutic target., (Copyright © 2023 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: Identifying the likelihood of life-threatening recurrence after radical cystectomy by reliable and user-friendly predictive models remains an unmet need in the clinical management of invasive bladder cancer., Methods: A total of 204 consecutive patients undergoing open radical cystectomy (ORC) for bladder cancer were retrospectively enrolled between May 2005 and August 2020. Clinicopathological and peri-ORC therapeutic data were extracted from clinical records. We explored predictive factors that significantly affected the primary endpoint of overall survival (OS) and secondary endpoints of cancer-specific survival (CSS) and recurrence-free survival (RFS)., Results: During a median follow-up of 3.9 years, 42 (20.6%) and 10 (4.9%) patients died due to bladder cancer and other causes, respectively. Five-year RFS, CSS, and OS were 66.5%, 77.6%, and 75.4%, respectively. Pathological T and N categories and lymphovascular invasion (LVI) significantly affected RFS by Cox regression analysis. Accordingly, clinical T and pathological N categories and LVI significantly affected CSS. Clinical T and pathological N categories, LVI, age, and ORC tumor grade significantly affected OS. Based on the assessment score for each independent risk factor, we developed the Gunma University Oncology Study Group (GUOSG) score, which predicts RFS, CSS, and OS. The GUOSG score classified four groups for RFS, three for CSS, and five for OS, with statistically significant distribution for nearly all comparisons., Conclusions: The GUOSG model is helpful to show individualized prognosis and functions as a risk-stratified historical cohort for assessing the lifelong efficacy of new salvage treatment regimens., (© 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Aim: There are few reports on the safety of endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) in the elderly. In this study, we investigated the safety of EUS-FNA for pancreatic solid masses in patients aged ≥80 years., Methods: This is a single-center retrospective study. A total of 600 patients with pancreatic solid masses who underwent EUS-FNA under midazolam-based sedation at our institution between September 2016 and December 2022 were enrolled in this study. Eligible patients were divided into two groups: an elderly group aged ≥80 (n = 84), as well as a nonelderly group aged ≤79 (n = 516). These two groups were compared., Results: The elderly group required significantly fewer midazolam doses for sedation (P < 0.001). Adverse events occurred in eight patients (1.3%), including one (1.2%) and seven (1.4%) in the elderly and nonelderly groups, respectively (P = 0.90). There were no cases of early adverse events in the elderly group and six cases (1.2%) in the nonelderly group (P = 0.32). There was one case of late adverse events in both the elderly and nonelderly groups (P = 0.14), and both were needle tract seeding. There was no significant difference between the two groups in the proportion of cases in which percutaneous oxygen saturation decreased to ≤90% during the EUS-FNA., Conclusions: Our analysis suggests that EUS-FNA for pancreatic solid masses can be safely performed in patients aged >80 years without increasing the adverse event rate compared to nonelderly patients aged <80 years. Geriatr Gerontol Int 2023; 23: 836-841., (© 2023 Japan Geriatrics Society.)

Background: Although nivolumab plus ipilimumab is the standard treatment for metastatic renal cell carcinoma (RCC), its efficacy and safety in older patients remain unclear. Therefore, this study aimed to assess the clinical outcomes of nivolumab plus ipilimumab for metastatic RCC in patients aged ≥ 75 years., Methods: We enrolled 120 patients with metastatic RCC treated with nivolumab plus ipilimumab from August 2015 to January 2023. Objective response rates (ORRs) were compared between patients aged < 75 and ≥ 75 years. Progression-free survival (PFS), overall survival (OS), and adverse events were compared between the groups. Adverse events were evaluated according to the Response Evaluation Criteria in Solid Tumors 1.1., Results: Among the patients, 57 and 63 were classified as intermediate and poor risk, respectively, and one could not be classified. The median follow-up duration after the initiation of treatment was 16 months. The patient characteristics between the groups, except for age, were not significantly different. Intergroup differences in ORR (42% vs. 40%; p = 0.818), PFS (HR: 0.820, 95% CI 0.455-1.479; p = 0.510), and median OS (HR: 1.492, 95% CI 0.737-3.020; p = 0.267) were not significant. The incidence of adverse events (50% vs. 67%; p = 0.111) and nivolumab plus ipilimumab discontinuation due to adverse events was not significantly different between the groups (14% vs. 13%; p = 0.877)., Conclusions: The effectiveness of nivolumab plus ipilimumab was comparable between patients with metastatic RCC aged < 75 and those ≥ 75 years with respect to their ORRs, PFS, OS, and adverse event rates., (© 2023. The Author(s) under exclusive licence to Japan Society of Clinical Oncology.)