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Nonspecific viral adsorption by polymer nanoparticles is more economical and superior in terms of operating cost and energy efficiency than viral adsorption using virus-specific antibodies and filtration techniques involving size exclusion in the order of tens of nanometres. In this study, we synthesised four types of polycyclic aromatic polymer (ArP) nanoparticles with different structures and evaluated their virus adsorption capability for infectious particles of the newly emerged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). ArP nanoparticles with a diameter of approximately 500 nm were prepared by one-pot precipitation polymerisation using structural isomers of bifunctional dihydroxynaphthalene (1,5-dihydroxynaphthalene and 2,6-dihydroxynaphthalene) as phenol monomers, as well as 3-hydroxybenzoic acid and 3-aminophenol as comonomers to introduce carboxylic acid and amino groups, respectively. This wide range of phenolic monomers offers a powerful molecular design capability, enabling the optimisation of surface properties for the adsorption of various infectious virus particles. The virus adsorption capacity of the ArP nanoparticles exceeded 20 000 plaque-forming units and was found to be correlated with the nitrogen (primary and secondary amines) and quinone contents on the ArP nanoparticle surface. Furthermore, a polyvinylidene difluoride membrane filter uniformly coated with the ArP nanoparticles could remove viruses by filtration in a flow system.

Background: Hypereosinophilic syndrome (HES) is characterized by the overproduction of eosinophils and manifests as valvular disease and thrombogenesis. Herein, we report our experience with a patient with HES requiring multiple reoperations for prosthetic heart valve replacement via median sternotomy., Case Presentation: The patient was a 54-year-old man who had undergone four valve replacement operations via median sternotomy (three mitral valve replacements and one double valve replacement) because of valvular diseases complicated by HES since he was 26 years old. All the artificial valves were bioprosthetic to prevent thrombotic events. At presentation, he had developed structural deterioration of the artificial aortic valve with severe stenosis. His prosthetic mitral valve did not fulfil the criteria for intervention, as it exhibited only mild regurgitation and no stenosis. The explanted mitral prosthetic valve at the previous (fourth) surgery had exhibited eosinophilic infiltration, resulting in the introduction of cyclosporin for poorly controlled HES. We conducted re-aortic valve replacement via a fifth median sternotomy using a bioprosthetic valve, and no eosinophilic infiltration was observed in the explanted valve. The patient was discharged on postoperative day 15 without complications., Conclusions: Controlling eosinophil count during the pre- and postoperative course is vital in treating patients with HES after valve replacement surgery. A holistic management and therapeutic strategy, including prosthetic valve selection and medication for HES is required to improve outcomes of patients with HES and heart valve disease., Competing Interests: Declarations Ethics approval and consent to participate Written informed consent was obtained from the patient for publication of this case report and accompanying images. Competing interests The authors declare that they have no competing interests., (© 2024. The Author(s).)

Background/aim: Enfortumab Vedotin (EV) is a widely used antibody-drug conjugate for patients with advanced urothelial carcinoma (UC) who have previously been treated with platinum-based chemotherapy and immune checkpoint inhibitors. However, limited information is currently available on prognostic factors and risk classification. Therefore, the present study attempted to identify clinical factors that predict outcomes in patients with advanced UC treated with EV and to develop a novel risk classification model., Patients and Methods: We conducted a multicenter retrospective study including patients with advanced UC treated with EV. Oncological outcomes were assessed using progression-free survival (PFS) and overall survival (OS), and prognostic factors for PFS and OS were investigated. We then examined the usefulness of risk classification based on the prognostic factors identified., Results: Median PFS and OS were 7.1 and 16.3 months, respectively. High C-reactive protein levels (CRP level ≥0.5 mg/dl) and hypercalcemia (corrected calcium level >10.2 mg/dl) were identified as prognostic factors for PFS (p=0.012 and p=0.003, respectively) and OS (p=0.035 and p<0.001, respectively). We then divided patients into three risk groups: no prognostic factors group, one prognostic factor group, and two prognostic factors group. Significant differences were observed in PFS and OS among the three groups (p<0.001 and p<0.001, respectively) and c-indices were 0.766 for PFS and 0.800 for OS., Conclusion: The risk classification using CRP and hypercalcemia is useful for predicting the outcomes of patients with advanced UC treated with EV., Competing Interests: The Authors declare no conflicts of interest in relation to this study., (©2024 The Author(s). Published by the International Institute of Anticancer Research.)

Recent studies have demonstrated that ultraviolet B (UVB) irradiation impacts both skin and hepatic functions. In this study, we investigated the effects of UVB irradiation on cholesterol metabolism in the liver. Hairless mice were exposed to UVB (1.6 J/cm 2 ) irradiation. Dorsal skin and liver samples were collected 24 h after exposure. Total RNA was extracted from the skin and liver tissues, and used for DNA microarray analysis and real-time polymerase chain reaction (PCR). Hepatic mRNA expression of Cyp7a1 revealed a 4.4-fold decrease in the UVB (+) group compared to that in the UVB (-) group. No differences were observed in the expression of the other genes related to cholesterol metabolism. Additionally, the level of hepatic total cholesterol in the UVB (+) group was significantly higher than in the UVB (-) group. These findings suggest that acute UVB irradiation increases total cholesterol levels and decreases Cyp7a1 expression in the liver., (© 2024 AOCS.)

Identifying the properties of the rapid eye movement (REM) sleep circuitry and its relation to diseases has been challenging due to the neuronal heterogeneity of the brainstem. Here, we show in mice that neurons in the pontine sublaterodorsal tegmentum (SubLDT) that express corticotropin-releasing hormone-binding protein (Crhbp + neurons) and project to the medulla promote REM sleep. Within the medullary area receiving projections from Crhbp + neurons, neurons expressing nitric oxide synthase 1 (Nos1 + neurons) project to the SubLDT and promote REM sleep, suggesting a positively interacting loop between the pons and the medulla operating as a core REM sleep circuit. Nos1 + neurons also project to areas that control wide forebrain activity. Ablating Crhbp + neurons reduces sleep and impairs REM sleep atonia. In Parkinson's disease patients with REM sleep behavior disorders, CRHBP-immunoreactive neurons are largely reduced and contain pathologic α-synuclein, providing insight into the mechanisms underlying the sleep deficits characterizing this disease., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background/aims: The efficacy and safety of endoscopic submucosal dissection using a clutch cutter (ESD-CC) for subepithelial lesions within the esophagogastric submucosa (SELEGSM) has not been investigated. This study aimed to assess the efficacy and safety of ESD-CC for the treatment of SELEGSM., Methods: This prospective study included 15 consecutive patients with 18 SELEGSMs diagnosed by endoscopic ultrasonography. The primary outcomes were short-term outcomes including en bloc resection rate, R0 resection rate, procedure time, and complication rate. The secondary outcome was final histological diagnosis., Results: Among the participants, 18 lesions were identified: 12 in the stomach (nine patients) and six in the esophagus (six patients). The en bloc resection rate was 94.4% (17/18). The R0 resection rate was 88.9% (16/18). The median operating time was 39 min, and no instances of perforation or bleeding were observed. The final diagnoses of SELEGSM included six neuroendocrine tumors (33.3%), six granular cell tumors (33.3%), two ectopic pancreases (11.1%), one inflammatory fibroid polyp (5.6%), one leiomyoma (5.6%), one lipoma (5.6%), and one leiomyosarcoma (5.6%)., Conclusions: ESD-CC appears to be a technically efficient and safe approach for SELEGSM resection, suggesting its potential as a valuable treatment option.

The developmental activation of the corpus luteum (CL) structurally and functionally is critical for the temporally regulated establishment, maintenance, and termination of pregnancy in rats. In this study, we have investigated the possible involvement of autophagy in the regulation of the CL during pregnancy in rats. The expression ratio of microtubule-associated protein light chain 3 (LC3)-II/-I, a widely used indicator of autophagic activity, in the CL remained relatively stable until day 15 of pregnancy. Subsequently, it progressively increased until day 21, and then declined until day 3 postpartum. This fluctuation was closely associated with the tissue weight of the CL rather than progesterone (P4) production activity. Light and electron microscopy revealed the presence of immunoreactive LC3 aggregates and irregularly shaped autolysosome-like microstructures in the cytoplasm of luteal cells during late pregnancy. Notably, a bolus intrabursal injection of the autophagy inhibitor bafilomycin A1 on day 15 of pregnancy resulted in a significant reduction in luteal cell size and disrupted the normal alteration of circulating P4 levels. Consequently, treatment with this inhibitor increased the likelihood of the varied timing (both advanced and delayed) of delivery and led to reduced body weight in neonates when compared with the vehicle-treated control group. Our findings suggest that autophagy in the rat CL contributes to luteal tissue growth, influences P4 production, and thereby fine-tunes the regulation of gestation length in rats.

Purpose: Chordomas are malignant tumors that destroy bones, compress surrounding nerve tissues and exhibit phenotypes that recapitulate notochordal differentiation in the axial skeleton. Chordomas recur frequently, as they resist radio-chemotherapy and are difficult to completely resect, leading to repeated bone destruction and local expansion via unknown mechanisms. Here, using chordoma specimens and JHC7 chordoma cells, we asked whether chordoma cells possess bone-dissolving activity., Methods: CT imaging and histological analysis were performed to evaluate the structure and mineral density of chordoma-invaded bone and osteolytic marker expression. JHC7 cells were subjected to immunocytochemistry, imaging of cell fusion, calcium dynamics and acidic vacuoles, and bone lysis assays., Results: In patients, we found that the skull base invaded by chordoma was highly porous, showed low mineral density and contained brachyury-positive chordoma cells and conventional osteoclasts both expressing the osteolytic markers tartrate-resistant acid phosphatase (TRAP) and collagenases. JHC7 cells expressed TRAP and cathepsin K, became multinucleated via cell-cell fusion, showed spontaneous calcium oscillation, and were partly responsive to the osteoclastogenic cytokine RANKL. JHC7 cells exhibited large acidic vacuoles, and nonregulatory bone degradation without forming actin rings. Finally, bone-derived factors, calcium ions, TGF-β1, and IGF-1 enhanced JHC7 cell proliferation., Conclusion: In chordoma, we propose that in addition to conventional bone resorption by osteoclasts, chordoma cells possess bone-dissolving activity at the tumor-bone boundary. Furthermore, bone destruction and tumor expansion may occur in a positive feedback loop., (© 2024. The Author(s).)

This study reveals the pH-responsive behavior of collagen hydrogels prepared using ultraviolet (UV) irradiation with riboflavin as a photosensitizer. By varying the UV exposure time, we modulated the crosslinking density, thereby influencing the mechanical properties and pH responsiveness. Rheological analysis confirmed successful network formation, whereas swelling studies revealed significant pH-dependent behavior, with maximum swelling at a pH of four and minimal swelling above a pH of six, demonstrating partial reversibility over multiple pH cycles. Mechanical testing showed a pH-dependent elastic modulus, which increased 10 fold from a pH of 6 to 10. Fibroblast proliferation assays confirmed the biocompatibility of the hydrogels, with cell growth positively correlating with the UV exposure time. This research demonstrates the potential of UV-crosslinked collagen hydrogels in biomedical applications, such as tissue engineering and drug delivery, where pH responsiveness is essential., Competing Interests: The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.

Background: In quantifying left ventricular (LV) diameter, which position for echocardiographic measurements, mitral valve tip level (MV-tip) or LV mid level (LV-mid), more accurately represents the LV volume is unclear. Furthermore, which factor affects the measurement error also has not been elucidated., Methods: We enrolled 150 patients without myocardial infarction and local asynergy who underwent echocardiography and cardiac magnetic resonance imaging (CMRI). Echocardiographic LV diastolic diameter (LVDD) and LV systolic diameter (LVDS) were measured at both MV-tip and LV-mid, and the LV end-diastolic volume (LVEDV) and end-systolic volume (LVESV) were quantified using CMRI. We quantified the degree of aortic wedging as the angle between the anterior wall of the aorta and the ventricular septal surface (ASA)., Results: The average LVDD was smaller and average LVDS larger when measured at the MV-tip than at the LV-mid. In regression analyses, the correlation coefficient between LVDD and LVEDV was larger at LV-mid (R = 0.89) than at MV-tip (R = 0.82), and the correlation coefficient between LVDS and LVESV also larger at LV-mid (R = 0.93) than MV-tip (R = 0.87). ASA, Valsalva diameter, left atrial diameter, patient height, and LV mass significantly affected the echocardiographic measurement error, but no factor affected the measurement error when quantifying LVDD at the LV-mid level., Conclusions: The echocardiographic LV diameter measured at LV-mid has a stronger correlation with LV chamber size derived from CMRI than measurements at MV-tip. The LVDD measured at the LV-mid level is not affected by other factors., (© 2024. Japanese Society of Echocardiography.)

Accurate estimation of cryptogam biomass, encompassing bryophytes and lichens, is crucial for understanding their ecological significance. This estimation is conducted based on the strong correlations between mass and volume of cryptogams. However, mass-volume correlations vary among cryptogams because of their morphological differences. This problem can be solved using models that consider life forms that classify cryptogams based on morphological similarities. In this study, we investigated whether life form models improve cryptogam biomass estimation accuracy. The cryptogam mass-volume correlation of each life form was estimated using Bayesian linear models. The coefficients and intercepts of linear models differed between life forms, which was attributed to the morphological characteristics of each life form. Therefore, life form models can improve the accuracy of estimation models by incorporating morphological differences. However, taxonomic models that consider only the taxonomic difference (bryophytes vs lichens) demonstrated better overall estimation than the life form models, probably because of the ability of taxonomic models to capture systematic differences between bryophytes and lichens. Furthermore, these models may mitigate estimation errors related to morphological variations that cannot be adequately represented by life form types. Based on these results, we propose the appropriate use of estimation models., (© 2024. The Author(s).)

Introduction: Primary squamous cell carcinoma of the kidney is rare, with only a few cases reported to date., Case Presentation: A right renal mass was detected in a 73-year-old asymptomatic man. Dynamic contrast-enhanced computed tomography showed a hypodensity mass extending from the upper pole of the kidney to the right lobe of the liver. Renal biopsy revealed that this tumor was squamous cell carcinoma. One month later, computed tomography showed rapid tumor growth. Radical nephrectomy and partial hepatic resection were performed. Pathological analysis indicated that this tumor originated from the tubular epithelium, and the patient was diagnosed with primary squamous cell carcinoma of the kidney.Following up without adjuvant therapy, he developed retroperitoneal recurrence and multiple lung metastases and expired., Conclusion: In this case, squamous cell carcinoma of the kidney invaded the liver and progressed rapidly. Considering these observations, surgical resection should be promptly performed in suspected cases., Competing Interests: The authors declare no conflict of interest., (© 2024 The Author(s). IJU Case Reports published by John Wiley & Sons Australia, Ltd on behalf of Japanese Urological Association.)

Global warming and increased atmospheric nitrogen (N) deposition can adversely impact Sphagnum moss populations and ecological functions in peatlands. Based on the anticipated increases in temperature and N levels at global scale, we investigated the effects of simultaneous warming and N treatment on growth and ecophysiological activity of Sphagnum papillosum, a predominant moss at mid-latitudes, utilizing a growth chamber experiment. Warming treatments increased the maximum yield of photosystem II (Fv/Fm) of S. papillosum while decreasing the stable carbon isotope ratio. However, warming treatment alone did not cause significant changes in the biomass increase from that of the control. Regarding N treatment, the low N treatment decreased Fv/Fm under the current temperature but did not affect the biomass increase. In contrast to these results, a simultaneous warming and high N treatment significantly enhanced the biomass production compared to that of the control, exhibiting additive effect of warming and high N treatment on Sphagnum biomass production. These responses were attributed to the improved photosynthetic performances by warming and N treatment. The results of this study contribute to the prediction of Sphagnum responses to warming and changes in N deposition., (© 2024. The Author(s).)

Purpose: The humanized antivascular endothelial growth factor (VEGF) antibody bevacizumab (Bev) is efficacious for the treatment of NF2-related schwannomatosis (NF2), previously known as neurofibromatosis type 2. This study evaluated the safety and efficacy of a VEGF receptor (VEGFR) vaccine containing VEGFR1 and VEGFR2 peptides in patients with NF2 with progressive schwannomas (jRCTs031180184)., Materials and Methods: VEGFR1 and VEGFR2 peptides were injected subcutaneously into infra-axillary and inguinal regions, once a week for 4 weeks and then once a month for 4 months. The primary end point was safety. Secondary end points included tolerability, hearing response, imaging response, and immunologic response., Results: Sixteen patients with NF2 with progressive schwannomas completed treatment and were assessed. No severe vaccine-related adverse events occurred. Among the 13 patients with assessable hearing, word recognition score improved in five patients at 6 months and two at 12 months. Progression of average hearing level of pure tone was 0.168 dB/mo during the year of treatment period, whereas long-term progression was 0.364 dB/mo. Among all 16 patients, a partial response was observed in more than one schwannoma in four (including one in which Bev had not been effective), minor response in 5, and stable disease in 4. Both VEGFR1-specific and VEGFR2-specific cytotoxic T lymphocytes (CTLs) were induced in 11 patients. Two years after vaccination, a radiologic response was achieved in nine of 20 assessable schwannomas., Conclusion: This study demonstrated the safety and preliminary efficacy of VEGFR peptide vaccination in patients with NF2. Memory-induced CTLs after VEGFR vaccination may persistently suppress tumor progression.

Background/purpose: Retainer debonding of resin-bonded fixed dental prostheses (RBFDPs) is one of the major reasons for their lower survival rates than fixed dental prostheses (FDPs) with full-coverage crowns. Recent advances in milling technology have enabled the fabrication of RBFDPs with complex retainers (D-shaped designs). This study aimed to assess the marginal fit and retention force of zirconia RBFDPs with inlay-, L-, and D-shaped designs to clarify their clinical applications., Materials and Methods: Three abutment teeth models without maxillary second premolars were created using inlay-, L-, and D-shaped retainer designs. The zirconia RBFDPs were designed and fabricated according to the manufacturer's instructions (n = 10). The marginal gap was measured using the silicone replica technique. Zirconia frameworks were bonded to the abutment teeth using resin cement. Tensile test was conducted after thermal cycling and dynamic loading tests. The loads during debonding or fracture were recorded. The failure pattern was analyzed by observing the fracture surface using a scanning electron microscope., Results: D-shaped RBFDPs showed a significantly larger marginal gap than inlay- and L-shaped RBFDPs ( P  < 0.05). However, the mean marginal values were clinically acceptable (<120 μm). The D-shaped model exhibited the highest tensile strength in the tensile tests. The inlay-shaped and most of the D-shaped RBFDPs experienced debonding with cohesive failure, whereas the L-shaped RBFDPs showed fractures near the connector., Conclusion: The D-shaped retainer design was superior to the inlay- and L-shaped designs with respect to the inhibition of retainer debonding. However, the marginal fitness needs to be improved., Competing Interests: The authors have no conflicts of interest relevant to this article., (© 2024 Association for Dental Sciences of the Republic of China. Publishing services by Elsevier B.V.)

Despite widespread adoption of tissue clearing techniques in recent years, poor access to suitable light-sheet fluorescence microscopes remains a major obstacle for biomedical end-users. Here, we present descSPIM (desktop-equipped SPIM for cleared specimens), a low-cost ($20,000-50,000), low-expertise (one-day installation by a non-expert), yet practical do-it-yourself light-sheet microscope as a solution for this bottleneck. Even the most fundamental configuration of descSPIM enables multi-color imaging of whole mouse brains and a cancer cell line-derived xenograft tumor mass for the visualization of neurocircuitry, assessment of drug distribution, and pathological examination by false-colored hematoxylin and eosin staining in a three-dimensional manner. Academically open-sourced ( https://github.com/dbsb-juntendo/descSPIM ), descSPIM allows routine three-dimensional imaging of cleared samples in minutes. Thus, the dissemination of descSPIM will accelerate biomedical discoveries driven by tissue clearing technologies., (© 2024. The Author(s).)

Background: In endovascular aortic repair (EVAR), preemptive embolization of sac branch vessels is effective in preventing postoperative type II endoleak (T2EL). However, this technique has not been widely adopted especially for lumbar arteries (LAs) because of technical difficulties and time constraints. This study aimed to investigate the efficacy of nonselective sac coil embolization, which is a simpler surgical method, in postoperative sac shrinkage for patients at a high risk of T2EL from LAs., Methods: We retrospectively assessed 76 patients who underwent elective EVAR for abdominal aortic aneurysm with 4 or more patent LAs or at least 1 patent LA of ≥2 mm at our hospital between January 2014 and December 2022. The patients who underwent sac coil embolization were included in Group Ⅰ (n = 20), and the others were divided into 2 groups: those with an inferior mesenteric artery that was originally occluded or embolized by coils or stent graft bodies (Group Ⅱ, n = 21), and those without that (Group Ⅲ, n = 35). In Group Ⅰ, 0.035-inch coils were inserted into the sac after complete stent graft deployment. The cumulative incidence of sac shrinkage (≥5 mm) was compared between the groups. Further, univariable and multivariable Cox regression analyses were used to determine the predictors of sac shrinkage., Results: Sac shrinkage (≥5 mm) was observed more frequently in Group Ⅰ (50%) than in Group Ⅱ (19%) and Group Ⅲ (17%) (P = 0.052 and 0.043, respectively). The cumulative incidence of sac shrinkage was significantly higher in Group Ⅰ than in Group Ⅱ (log-rank P = 0.039) and Group Ⅲ (log-rank P = 0.024). Multivariable Cox regression analyses revealed that sac embolization was a significant predictor of sac shrinkage (hazard ratio, 4.23; 95% confidence interval, 1.66-10.8; P = 0.003)., Conclusions: Nonselective sac coil embolization in EVAR is potentially effective for sac shrinkage in the early postoperative phase in patients at high risk of T2EL from LAs. This simple procedure may improve prognosis after EVAR., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Study Design: A retrospective cohort study using the Kaplan-Meier method with propensity-score matching., Purpose: To evaluate whether the presence of prevalent morphometric vertebral fractures (VFs) poses a risk for subsequent clinical VFs after short-fusion surgery in women aged ≥60 years with degenerative spondylolisthesis., Overview of Literature: VFs are common osteoporotic fractures and are associated with a low quality of life. Subsequent VFs are a complication of instrumented fusion in patients with degenerative lumbar disorders. Thus, risk factors for subsequent VFs after fusion surgery must be analyzed. Population-based studies have suggested that prevalent morphometric VFs led to a higher incidence of subsequent VFs in postmenopausal women; however, no studies have investigated whether prevalent morphometric VFs are a risk factor for subsequent VFs after fusion surgery in patients with degenerative spondylolisthesis., Methods: The study enrolled a total of 237 older female patients: 50 and 187 patients had prevalent morphometric VFs (VF [+] group) and nonprevalent morphometric VFs (VF [-] group), respectively. The time to subsequent clinical VFs after fusion surgery was compared between the two groups using the Kaplan-Meier method. Moreover, 40 and 80 patients in the VF (+) and VF (-) groups, respectively, were analyzed and matched by propensity scores for age, follow-up duration, surgical procedure, number of fused segments, body mass index, and number of patients treated for osteoporosis., Results: Kaplan-Meier analysis indicated that the VF (+) group had a higher incidence of subsequent clinical VFs than the VF (-) group, and Cox regression analysis showed that the presence of prevalent morphometric VFs was an independent risk factor for subsequent clinical VFs before matching. Kaplan-Meier analysis demonstrated comparable results after matching., Conclusions: The presence of prevalent morphometric VFs may be a risk factor for subsequent clinical VFs in older women with degenerative spondylolisthesis who underwent short-fusion surgery.

(-)-Epigallocatechin-3-O-gallate (EGCg), the major catechin responsible for the health-enhancing and disease-preventive effects of green tea, is susceptible to auto-oxidation at physiological pH levels. However, whether the oxidized EGCg resulting from its oral consumption possesses any bioactive functions remains unclear. This study presents a differential analysis of intact and oxidized EGCg regarding their interactions with phosphatidylcholine liposomes, serving as a simple biomembrane model. In the presence of ascorbic acid, pre-oxidized EGCg induced liposomal aggregation in a dose-dependent manner, whereas intact EGCg did not. Toxicity evaluation using calcein-loaded liposomes revealed that liposomal aggregation is associated with minimal membrane damage. Through fractionation of the oxidized EGCg sample, the fraction containing theasinensins showed high liposomal aggregation activity. Overall, these results suggest that oxidatively condensed EGCg dimers may stimulate various cells by altering the plasma membrane in a manner different from that of EGCg monomers., 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 B.V. All rights reserved.)

Study Design: A retrospective case-control propensity score-matching study., Purpose: This study aimed to longitudinally evaluate whether preoperative ligamentous stenosis at the spondylolisthetic segments could affect the incidence of symptomatic adjacent canal stenosis following one-segment fusion surgery., Overview of Literature: Several risk factors for symptomatic adjacent canal stenosis following fusion surgery have been assessed. Patients with lumbar canal stenosis mainly due to ligamentum flavum (LF) hypertrophy (ligamentous stenosis) also have LF hypertrophy in other segments., Methods: In total, 76 patients participated in this case-control study (neurologically symptomatic adjacent canal stenosis, n=33; neurologically asymptomatic cases at follow-up, n=43). Their risk factors during surgery and magnetic resonance (MR) images before the surgery and at follow-up were evaluated. Data from the two groups (n=25 each) were matched using propensity scores for age, sex, time to MR imaging at follow-up, surgical procedure, and LF hypertrophy in adjacent segments before the surgery and analyzed., Results: Compared with the asymptomatic group, the symptomatic adjacent canal stenosis group had a significantly larger LF area/spinal canal area in the spondylolisthetic segments before the surgery. During the follow-up periods (in months), they had a larger LF area/ spinal canal area in the adjacent segments: the two values were significantly correlated. The sensitivity, specificity, and positive and negative predictive values for determining symptomatic adjacent canal stenosis were high compared with on the cutoff value for the LF area/spinal canal area at the spondylolisthetic segments before the surgery. These results were the same after matching., Conclusions: Symptomatic adjacent canal stenosis is mainly caused by LF hypertrophy. Ligamentous stenosis at the spondylolisthetic segments before fusion surgery might be strongly associated with symptomatic adjacent canal stenosis at follow-up.

Dyssegmental dysplasia (DD) is a severe skeletal dysplasia comprised of two subtypes: lethal Silverman-Handmaker type (DDSH) and nonlethal Rolland-Desbuquois type (DDRD). DDSH is caused by biallelic pathogenic variants in HSPG2 encoding perlecan, whereas the genetic cause of DDRD remains undetermined. Schwartz-Jampel syndrome (SJS) is also caused by biallelic pathogenic variants in HSPG2 and is an allelic disorder of DDSH. In SJS and DDSH, 44 and 8 pathogenic variants have been reported in HSPG2, respectively. Here, we report that five patients with DDRD carried four pathogenic variants in HSPG2: c.9970 G > A (p.G3324R), c.559 C > T (p.R187X), c7006 + 1 G > A, and c.11562 + 2 T > G. Two patients were homozygous for p.G3324R, and three patients were heterozygous for p.G3324R. Haplotype analysis revealed a founder haplotype spanning 85,973 bp shared in the five patients. SJS, DDRD, and DDSH are allelic disorders with pathogenic variants in HSPG2., (© 2024. The Author(s).)

Histamine H 1 receptor (H 1 R) in the central nervous system plays an important role in various functions, including learning and memory, aggression, feeding behaviors, and wakefulness, as evidenced by studies utilizing H 1 R knockout mice and pharmacological interventions. Although previous studies have reported the widespread distribution of H 1 R in the brains of rats, guinea pigs, monkeys, and humans, the detailed distribution in the mouse brain remains unclear. This study provides a comprehensive description of the distribution of H 1 R mRNA in the mouse brain using two recently developed techniques: RNAscope and in situ hybridization chain reaction, both of which offer enhanced sensitivity and resolution compared to traditional methodologies such as radioisotope labeling, which were used in previous studies. The H 1 R mRNA expression was observed throughout the entire brain, including key regions implicated in sleep-wake regulatory functions, such as the pedunculopontine tegmental nucleus and dorsal raphe. Additionally, strong H 1 R mRNA signals were identified in the paraventricular hypothalamus and ventromedial hypothalamus, which may explain the potential mechanisms underlying histamine-mediated feeding regulation. Notably, we identified strong H 1 R mRNA expression in previously unreported cerebral regions, such as the dorsal endopiriform nucleus, bed nucleus of the accessory olfactory tract, and postsubiculum. These findings significantly contribute to our understanding of the multifaceted roles of H 1 R in diverse brain functions., (© 2024 Wiley Periodicals LLC.)

Developmental prosopagnosia (DP) is a condition that indicates the inability to recognize individuals by their faces from birth, without any history of brain damage. The assessment of face recognition ability and diagnosis of DP involve the use of face tests such as the Cambridge Face Memory Test (CFMT) and the Cambridge Face Perception Test, along with self-reported measures like the 20-Item Prosopagnosia Index (PI20). Face recognition accuracy is affected by anxiety. However, previous studies on the relationship between face recognition ability and anxiety have not used the PI20 measure. This study aimed to investigate the relationship between self-reported measures of face recognition ability and anxiety tendencies among healthy young individuals for DP diagnosis and its implications. We used a face recognition test, involving the PI20, CFMT, Visual Perception Test for Agnosia-Famous Face Test (VPTA-FFT), and State-Trait Anxiety Inventory (STAI). We assessed the performance of 116 Japanese young adults (75 females, median age of 20.7 years, with a standard deviation of 1.2). Subsequently, we conducted a statistical analysis to examine the relationship between the outcomes of the face recognition tests and STAI scores using Pearson correlation analysis and single correlation coefficients. The results showed a positive correlation between state anxiety and PI20 (r = 0.308, p = 0.007), and a weak positive correlation was also observed between trait anxiety and PI20 (r = 0.268, p = 0.04). In contrast, there was no correlation between CFMT and VPTA-FFT with respect to STAI. The results of the hierarchical multiple regression analysis also suggested that the correlation between the performance on the PI20 (self-report) and objective measures of face recognition performance (the CFMT and the VPTA-FFT) are driven by differences in anxiety. This study is the first to explore the relationship between face recognition abilities and anxiety using the PI20 self-report measure. There are implications for future research on the diagnosis of DP and the relationship between anxiety and face recognition., Competing Interests: Declaration of competing interest None., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Aims: Coronary vasospasm is associated with acute coronary syndrome (ACS) and may persist during primary percutaneous coronary intervention (PCI). We aimed to elucidate the incidence, morphological characteristics, and prognostic impact of residual vasospasm in plaque rupture (PR) and plaque erosion (PE) lesions using optical coherence tomography (OCT)., Methods: We enrolled 142 patients with ACS who underwent OCT-guided primary PCI. All patients received intracoronary vasodilators before OCT examination. Residual vasospasm was identified as intimal gathering and categorised as polygonal- or wavy- patterned depending on the luminal shape. A wavy pattern was defined as a curved intimal surface line. A polygonal pattern was defined as a lumen with multiple angles. The incidence of major cardiovascular events, defined as death, non-fatal myocardial infarction, stroke, and any revascularization, within 1-year of PCI was identified., Results: The prevalence of residual vasospasm in PR and PE was 15.1% (13 of 86) and 21.4% (12 of 56), respectively. Wavy pattern was the major shape of the residual vasospasm. Polygonal-patterned lumen was more frequently observed in PR than in PE (38.5 vs. 8.3 %). The polygonal-patterned lumens had significantly larger lipid arcs (257.9 vs. 78.0 °; P＜0.01), and significantly smaller areas (1.27 vs. 1.88 mm 2 ; P=0.05) than wavy-patterned lumens. Residual vasospasm had a prognostic impact on PR but not PE at 1-year of successful primary PCI., Conclusion: Considerable proportion of ACS including both PR and PE had residual vasospasm with variable morphological feature and different prognostic impact.

Introduction: This study aimed to investigate the relationship between childbirth and lower back pain and determine the health-related quality of life of female patients with lower back pain., Methods: A total of 111 patients were divided into three groups: those who had given birth and developed lower back pain due to pregnancy, childbirth, or child-rearing movements (childbirth group, n=41), those who had given birth and developed lower back pain due to other causes (childbirth and other cause group, n=29), and those who were nulliparous (nulliparous group, n=41). A total of 22 physical therapists evaluated the patients during initial rehabilitation. Basic information and health-related quality of life were compared among the three groups using a one-way analysis of variance for the visual analog scale scores for lower back pain, summary scores (physical health [physical component summary] and mental health [mental component summary]), and subscales (physical functioning, role-physical, bodily pain, general health, vitality, social functioning, role-emotional, and mental health) of the Short Form-8 Health Survey. These values were also compared with the national standard values for health-related quality of life. The chi-square test of independence was used to compare distributions, and Fisher's exact probability test was used for cells with an expected value of <5., Results: Most participants had physical component summary scores below the national standard values. The visual analog scale scores for lower back pain were significantly higher in the birth group than in the nonbirth group. The physical component summary, physical functioning, and general health scores were significantly lower in the birth group than in the nonbirth group. Moreover, bodily pain scores were significantly lower in the birth group than in the other groups., Conclusions: For female patients with lower back pain due to pregnancy, childbirth, or childcare activities, physical conditions unique to postpartum women should be considered, and if necessary, instructions for activities of daily living should be provided., Competing Interests: Conflicts of Interest: The authors declare that there are no relevant conflicts of interest., (Copyright © 2024 The Japanese Society for Spine Surgery and Related Research.)

We theoretically analyze possible multiple conformations of protein molecules immobilized by 1-pyrenebutanoic acid succinimidyl ester (PASE) linkers on graphene. The activation barrier between two bi-stable conformations exhibited by PASE is confirmed to be based on the steric hindrance effect between a hydrogen on the pyrene group and a hydrogen on the alkyl group of this molecule. Even after the protein is supplemented, this steric hindrance effect remains if the local structure of the linker consisting of an alkyl group and a pyrene group is maintained. Therefore, it is likely that the kinetic behavior of a protein immobilized with a single PASE linker exhibits an activation barrier-type energy surface between the bi-stable conformations on graphene. We discuss the expected protein sensors when this type of energy surface appears and provide a guideline for improving the sensitivity, especially as an oscillator-type biosensor., (Copyright © 2024, Oishi et al.)

Background: Although open surgical repair (OSR) is the gold standard for treating arch aneurysms, thoracic endovascular aortic repair (TEVAR) may be a less invasive alternative. However, it remains unclear which of the 2 methods yields better outcomes. In this study, we compared the perioperative outcomes of both procedures for arch aneurysms using a nationwide surgical database., Methods: Data of patients who underwent elective aortic repair for true arch aneurysms were extracted from the National Clinical Database of Japan. Patients who underwent OSR and Zone 0/1 TEVAR were matched in a 1:1 ratio using propensity scores and their mortality and morbidity rates were compared., Results: A total of 2,815 and 1,125 patients underwent OSR and Zone 0/1 TEVAR, respectively. After propensity score matching, 1,058 patients were included in both groups. Compared with OSR, Zone 0/1 TEVAR was associated with a significantly higher incidence of stroke (5.8 vs. 10.0%, P < 0.001) and paraplegia/paraparesis (1.6 vs. 4.4%, P < 0.001). However, there were no significant differences in the 30-day and operative mortality rates between the 2 groups (2.2 vs. 2.7% and 4.5 vs. 5.4%, respectively). In the Zone 0/1 TEVAR group, postoperative computed tomography was performed in 92.4% of patients, and types I and III endoleaks were identified in 6.4% and 1.1% of patients, respectively., Conclusions: Zone 0/1 TEVAR has higher incidences of stroke and paraplegia/paraparesis than OSR, with a risk of postoperative endoleaks. Resolving these problems is the key for expanding the application of Zone 0/1 TEVAR and in the meantime OSR remains the gold standard for surgically fit patients., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: The relationship between the cellular pro-inflammatory response and intracellular lipid accumulation in atherosclerosis is not sufficiently studied. Transcriptomic analysis is one way to establish such a relationship. Previously, we identified 10 potential key genes (IL-15, CXCL8, PERK, IL-7, IL-7R, DUSP1, TIGIT, F2RL1, TSPYL2, and ANXA1) involved in cholesterol accumulation in macrophages. It should be noted that all these genes do not directly participate in cholesterol metabolism, but encode molecules related to inflammation., Methods: In this study, we conducted a knock-down of the 10 identified key genes using siRNA to determine their possible role in cholesterol accumulation in macrophages. To assess cholesterol accumulation, human monocyte-derived macrophages (MDM) were incubated with atherogenic LDL from patients with atherosclerosis. Cholesterol content was assessed by the enzymatic method. Differentially expressed genes were identified with DESeq2 analysis. Master genes were determined by the functional analysis., Results: We found that only 5 out of 10 genes (IL-15, PERK, IL-7, IL-7R, ANXA1) can affect intracellular lipid accumulation. Knock-down of the IL-15, PERK, and ANXA1 genes prevented lipid accumulation, while knock-down of the IL-7 and IL-7R genes led to increased intracellular lipid accumulation during incubation of MDM with atherogenic LDL. Seventeen overexpressed genes and 189 underexpressed genes were obtained in the DGE analysis, which allowed us to discover 20 upregulated and 86 downregulated metabolic pathways, a number of which are associated with chronic inflammation and insulin signaling. We also elucidated 13 master regulators of cholesterol accumulation that are immune response-associated genes., Conclusion: Thus, it was discovered that 5 inflammation-related master regulators may be involved in lipid accumulation in macrophages. Therefore, the pro-inflammatory response of macrophages may trigger foam cell formation rather than the other way around, where intracellular lipid accumulation causes an inflammatory response, as previously assumed., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

We experimentally demonstrated the polarization change of femtosecond laser pulses in air by using electric-field-induced second-harmonic generation (E-FISHG) for the first time to our knowledge. The polarization change from linear to elliptical was observed at the laser intensity over the filamentation threshold. These results suggest that the polarization change can occur by the birefringence caused by filamentation. This phenomenon can be used for new applications such as an ultra-fast and precise three-dimensional electric field measurement by E-FISHG. In addition, E-FISHG can be an excellent tool to investigate the characteristics of femtosecond laser propagation such as filamentation.

Macrophages are essential for the proper inflammatory and reparative processes that lead to regeneration of skeletal muscle after injury. Recent studies have demonstrated close links between the function of activated macrophages and their cellular metabolism. Sterol regulatory element-binding protein 1 (SREBP1) is a key regulator of lipid metabolism and has been shown to affect the activated states of macrophages. However, its role in tissue repair and regeneration is poorly understood. Here we show that systemic deletion of Srebf1 , encoding SREBP1, or macrophage-specific deletion of Srebf1a , encoding SREBP1a, delays resolution of inflammation and impairs skeletal muscle regeneration after injury. Srebf1 deficiency impairs mitochondrial function in macrophages and suppresses the accumulation of macrophages at sites of muscle injury. Lipidomic analyses showed the reduction of major phospholipid species in Srebf1 -/- muscle myeloid cells. Moreover, diet supplementation with eicosapentaenoic acid restored the accumulation of macrophages and their mitochondrial gene expression and improved muscle regeneration. Collectively, our results demonstrate that SREBP1 in macrophages is essential for repair and regeneration of skeletal muscle after injury and suggest that SREBP1-mediated fatty acid metabolism and phospholipid remodeling are critical for proper macrophage function in tissue repair., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Oishi, Koike, Kumagami, Nakagawa, Araki, Taketomi, Miki, Matsuda, Kim, Matsuzaka, Ozawa, Shimano, Murakami and Manabe.)

Light-responsive hydrogels containing light-thermal convertible pigments have received interest for their possible applications in light-responsive shutters, valves, drug delivery systems, etc. However, their utility is limited by the slow response time. In this study, we investigated the use of micro-nano bubble water as a preparation solvent to accelerate the volume phase transition kinetics of poly(N-isopropylacrylamide-co-acrylic acid) (PNIPAM-co-AAc) hydrogels. The hydrogels were characterized by dynamic light scattering (DLS) and dissolved oxygen (DO) measurements. The mechanical properties, surface morphology, and chemical composition of the hydrogels were analyzed by Young's modulus measurements, scanning electron microscopy (SEM), and Fourier transform infrared (FT-IR) spectroscopy, respectively. The results showed that hydrogels prepared with bubble water changed the volume transition rate by more than two orders of magnitude by simply changing the standing time of the bubble water for only a few hours. The cooperative diffusion coefficients obtained from the light-induced volume transition kinetics correlated linearly with Young's modulus and metastable state swelling ratio. Our results suggest that bubbles act as efficient water channels, thereby modulating the response rate and providing a simple, additive-free method for preparing hydrogels with a wide range of response rates.

Aims: Eicosapentaenoic acid (EPA) has shown beneficial effects on coronary plaque stabilization. Based on our previous study, we speculated that EPA might be associated with the development of healed plaques and might limit thrombus size. This study aimed to elucidate the association between EPA and arachidonic acid (AA) ratios and various plaque characteristics in patients with plaque rupture., Methods: A total of 95 patients with acute coronary syndrome (ACS) caused by plaque rupture who did not take lipid-lowering drugs and underwent percutaneous coronary intervention using optical coherence tomography (OCT) were included. Clinical characteristics, lipid profiles, and OCT findings were compared between patients with lower and higher EPA/AA ratios (0.41) according to the levels in the Japanese general population., Results: In the high EPA/AA (n=29, 30.5%) and low EPA/AA (n=66, 69.5 %) groups, the high EPA/AA group was significantly older (76.1 vs. 66.1 years, P＜0.01) and had lower peak creatine kinase (556 vs. 1651 U/L, P=0.03) than those with low EPA/AA. Similarly, patients with high EPA/AA had higher prevalence of layered and calcified plaque (75.9 vs. 39.4 %, P＜0.01; 79.3 vs. 50.0 %, P＜0.01, respectively) than low EPA/AA group. Multivariate logistic regression analysis demonstrated that a high EPA/AA ratio was an independent factor in determining the development of layered and calcified plaques., Conclusion: A high EPA/AA ratio may be associated with the development of layered and calcified plaques in patients with plaque rupture.

A wireless 2-channel layered sensor system that enables electromyography (EMG) and near-infrared spectroscopy (NIRS) measurements at two local positions was developed. The layered sensor consists of a thin silver electrode and a photosensor consisting of a photoemitting diode (LED) or photodiode (PD). The EMG and NIRS signals were simultaneously measured using a pair of electrodes and photosensors for the LED and PD, respectively. Two local muscular activities are presented in detail using layered sensors. In the experiments, EMG and NIRS signals were measured for isometric constant and ramp contractions at each forearm using layered sensors. The results showed that local muscle activity analysis is possible using simultaneous EMG and NIRS signals at each local position.

Background: Delayed-onset paraplegia is a disastrous complication after thoracoabdominal aortic open surgery and thoracic endovascular aortic repair. Studies have revealed that transient spinal cord ischemia caused by temporary occlusion of the aorta induces delayed motor neuron death owing to apoptosis and necroptosis. Recently, necrostatin-1 (Nec-1), a necroptosis inhibitor, has been reported to reduce cerebral and myocardial infarction in rats or pigs. In this study, we investigated the efficacy of Nec-1 in delayed paraplegia after transient spinal cord ischemia in rabbits and assessed the expression of necroptosis- and apoptosis-related proteins in motor neurons., Methods: This study used rabbit transient spinal cord ischemia models using a balloon catheter. They were divided into a vehicle-treated group (n = 24), Nec-1-treated group (n = 24), and sham-controls (n = 6). In the Nec-1-treated group, 1 mg/kg of Nec-1 was intravascularly administered immediately before ischemia induction. Neurological function was assessed using the modified Tarlov score, and the spinal cord was removed 8 hr and 1, 2, and 7 days after reperfusion. Morphological changes were examined using hematoxylin and eosin staining. The expression levels of necroptosis-related proteins (receptor-interacting protein kinase [RIP] 1 and 3) and apoptosis-related proteins (Bax and caspase-8) were assessed using western blotting and histochemical analysis. We also performed double-fluorescence immunohistochemical studies of RIP1, RIP3, Bax, and caspase-8., Results: Neurological function significantly improved in the Nec-1-treated group compared with that in the vehicle-treated group 7 days after reperfusion (median 3 and 0, P = 0.025). Motor neurons observed 7 days after reperfusion were significantly decreased in both groups compared with the sham group (vehicle-treated, P < 0.001; Nec-1-treated, P < 0.001). However, significantly more motor neurons survived in the Nec-1-treated group than in the vehicle-treated group (P < 0.001). Western blot analysis revealed RIP1, RIP3, Bax, and caspase-8 upregulation 8 hr after reperfusion in the vehicle-treated group (RIP1, P = 0.001; RIP3, P = 0.045; Bax, P = 0.042; caspase-8, P = 0.047). In the Nec-1-treated group, the upregulation of RIP1 and RIP3 was not observed at any time point, whereas that of Bax and caspase-8 was observed 8 hr after reperfusion (Bax, P = 0.029; caspase-8, P = 0.021). Immunohistochemical study revealed the immunoreactivity of these proteins in motor neurons. Double-fluorescence immunohistochemistry revealed the induction of RIP1 and RIP3, and that of Bax and caspase-8, in the same motor neurons., Conclusions: These data suggest that Nec-1 reduces delayed motor neuron death and attenuates delayed paraplegia after transient spinal cord ischemia in rabbits by selectively inhibiting necroptosis of motor neurons with minimal effect on their apoptosis., (Copyright © 2023. Published by Elsevier Inc.)

Even after successful revascularization with primary percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI), subsequent adverse events still occur. Previous studies have suggested potential benefits of intravascular imaging, including optical coherence tomography (OCT). However, the feasibility of OCT-guided primary PCI has not been systematically examined in these patients. The ATLAS-OCT (ST-elevation Acute myocardial infarcTion and cLinicAl outcomeS treated by Optical Coherence Tomography-guided percutaneous coronary intervention) trial was designed to investigate the feasibility of OCT guidance during primary PCI for STEMI in experienced centers with expertise on OCT-guided PCI as a prospective, multicenter registry of consecutive patients with STEMI who underwent a primary PCI. The sites' inclusion criteria are as follows: (1) acute care hospitals providing 24/7 emergency care for STEMI, and (2) institutions where OCT-guided PCI is the first choice for primary PCI in STEMI. All patients with STEMI who underwent primary PCI at participating sites will be consecutively enrolled, irrespective of OCT use during PCI. The primary end point will be the rate of successful OCT imaging during the primary PCI. As an ancillary imaging modality to angiography, OCT provides morphologic information during PCI for the assessment of plaque phenotypes, vessel sizing, and PCI optimization. Major adverse cardiac events, defined as a composite of all-cause death, myocardial infarction, and target vessel revascularization at 1 year, will also be recorded. The ATLAS-OCT study will clarify the feasibility of OCT-guided primary PCI for patients with STEMI and further identify a suitable patient group for OCT-guided primary PCI., Competing Interests: Declaration of Competing Interest Dr. Ako received a speaking honorarium from Abbott Medical Japan, LLC. Dr. Minami received speaking honorarium and consultant fees from Abbott Medical Japan, LLC. Dr. Shite has received honoraria from Abbott Medical Japan, Nipro, and Terumo. Dr. Kozuki has received honoraria from Abbott Medical (Japan). Dr. Shishido received remuneration for lectures from Abbott Medical, Japan. Dr. Uemura received remuneration from Abbott Vascular Japan, Daiichi-Sankyo, Novartis Pharma, Bayer, and Amgen and scholarship funds from Abbott Vascular Japan. Dr. Kume received remuneration from Abbott Vascular (Japan). Dr. Nanasato received remuneration for lectures from Boston Scientific (Japan). Dr. Otake received a speaking honorarium and research grant from Abbott Vascular, Japan. Dr. Shinke received personal fees and research grants from Abbott Medical Japan, LLC. The remaining authors have no competing interests to declare., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Benzodiazepine, a classical medication utilized in the treatment of insomnia, operates by augmenting the activity of the GABA A receptor. This underscores the significance of GABAergic neurotransmission in both the initiation and maintenance of sleep. Nevertheless, an increasing body of evidence substantiates the notion that GABA-mediated neurotransmission also assumes a vital role in promoting wakefulness in specific neuronal circuits. Despite the longstanding belief in the pivotal function of GABA in regulating the sleep-wake cycle, there exists a dearth of comprehensive documentation regarding the specific regions within the central nervous system where GABAergic neurons are crucial for these functions. In this review, we delve into the involvement of GABAergic neurons in the regulation of sleep-wake cycles, with particular focus on those located in the preoptic area (POA) and ventral tegmental area (VTA). Recent research, including our own, has further underscored the importance of GABAergic neurotransmission in these areas for the regulation of sleep-wake cycles., 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 Inc.)

Preterm birth (PTB) is the leading cause of neonatal mortality, and reducing the PTB rate is one of the most critical issues in perinatal medicine. Cervical insufficiency (CI), a major cause of PTB, is characterised by premature cervical ripening in the second trimester, followed by recurrent pregnancy loss. Although multiple clinical trials have suggested that progesterone inhibits cervical ripening, no studies have focused on progesterone-induced molecular signalling in CI. Here, we established a primary culture system for human uterine cervical fibroblasts using a sample of patients with refractory innate CI who underwent transabdominal cervical cerclage and patients with low Bishop scores who underwent elective caesarean section as controls. RNA sequencing showed that the progesterone response observed in the control group was impaired in the CI group. This was consistent with the finding that progesterone receptor expression was markedly downregulated in CI. Furthermore, the inhibitory effect of progesterone on lipopolysaccharide-induced inflammatory stimuli was also impaired in CI. These results suggest that abnormal cervical ripening in CI is caused by the downregulation of progesterone signalling at the receptor level, and provide a novel insight into the molecular mechanism of PTB., (© 2023. The Author(s).)

Hollow collagen gels are promising materials for drug/cell delivery systems to promote tissue regeneration because they may be able to function as carriers for these types of loads. Controlling the cavity size and swelling suppression is essential to expand the applications and improve the usability of such gel-like systems. We investigated the effects of UV-treated collagen solutions as a pre-gel aqueous mixture on the formation and properties of the hollow collagen gels in terms of their preparation range limits, morphology, and swelling ratio. The UV treatment thickened the pre-gel solutions, which allowed hollowing at lower collagen concentrations. This treatment also prevents the over-swelling of the hollow collagen rods in PBS buffer solutions. The UV-treated collagen solutions provided a large lumen space in the prepared collagen hollow fiber rods with a limited swelling ratio, allowing vascular endothelial cells and ectodermal cells to be cultured separately in the outer and inner lumen.

Poly(A) tail metabolism contributes to post-transcriptional regulation of gene expression. Here, we present a protocol for analyzing intact mRNA poly(A) tail length using nanopore direct RNA sequencing, which excludes truncated RNAs from the measurement. We describe steps for preparing recombinant eIF4E mutant protein, purifying m7G- capped RNAs, library preparation, and sequencing. Resulting data can be used not only for expression profiling and poly(A) tail length estimation but also for detecting alternative splicing and polyadenylation events and RNA base modification. For complete details on the use and execution of this protocol, please refer to Ogami et al. (2022). 1 ., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Macroscopic spatial patterns were formed in calcium alginate gels when a drop of a calcium nitrate solution was placed on the center of a sodium alginate solution on a petri dish. These patterns have been classified into two groups. One is multi-concentric rings consisting of alternating cloudy and transparent areas observed around the center of petri dishes. The other is streaks extending to the edge of the petri dish, which are formed to surround the concentric bands between the concentric bands and the petri dish edge. We have attempted to understand the origins of the pattern formations using the properties of phase separation and gelation. The distance between two adjacent concentric rings was roughly proportional to the distance from where the calcium nitrate solution was dropped. The proportional factor p increased exponentially for the inverse of the absolute temperature of the preparation. The p also depended on the concentration of alginate. The pattern characteristics in the concentric pattern agreed with those in the Liesegang pattern. The paths of radial streaks were disturbed at high temperatures. The length of these streaks shortened with increasing alginate concentration. The characteristics of the streaks were similar to those of crack patterns resulting from inhomogeneous shrinkage during drying.

Evacuation is a critical life-saving action, especially in devastating natural hazards such as near-field tsunamis. However, the development of effective evacuation measures remains challenging to the extent that a successful example has been referred to as a 'miracle'. Here we show that urban structures have the potential to reinforce attitudes towards evacuation and significantly influence the success of tsunami evacuation. Agent-based evacuation simulations revealed that a distinctive root-like urban structure formed in ria coasts reinforces positive evacuation attitudes by effectively gathering evacuation flows and leads to higher evacuation rates compared to typical grid-like urban structures, which can explain the regional differences in the number of casualties in the 2011 Tohoku tsunami. Although a grid-like structure reinforces negative attitudes under low evacuation tendencies, with leading evacuees, its dense feature helps to propagate positive attitudes and drastically improve evacuation tendencies. These findings pave the way for making successful evacuation inevitable through harmonised urban and evacuation plannings., (© 2023. The Author(s).)

After a muscle injury, a process comprising inflammation, repair, and regeneration must occur in a time-sensitive manner for skeletal muscle to be adequately repaired and regenerated. This complex process is assumed to be controlled by various myeloid cell types, including monocytes and macrophages, though the mechanism is not fully understood. Aryl hydrocarbon receptor nuclear translocator-like (Arntl or Bmal1) is a transcription factor that controls the circadian rhythm and has been implicated in regulating myeloid cell functions. In the present study, we generated myeloid cell-specific Arntl conditional knockout (cKO) mice to assess the role of Arntl expressed in myeloid cell populations during the repair process after muscle injury. Myeloid cell-specific Arntl deletion impaired muscle regeneration after cardiotoxin injection. Flow cytometric analyses revealed that, in cKO mice, the numbers of infiltrating neutrophils and Ly6C hi monocytes within the injured site were reduced on days 1 and 2, respectively, after muscle injury. Moreover, neutrophil migration and the numbers of circulating monocytes were significantly reduced in cKO mice, which suggests these effects may account, at least in part, for the impaired regeneration. These findings suggest that Arntl, expressed in the myeloid lineage regulates neutrophil and monocyte recruitment and is therefore required for skeletal muscle regeneration., (© 2023. The Author(s).)

Background: Insomnia is associated with psychiatric illnesses such as bipolar disorder or schizophrenia. Treating insomnia improves psychotic symptoms severity, quality of life, and functional outcomes. Patients with psychiatric disorders are often dissatisfied with the available therapeutic options for their insomnia. In contrast, positive allosteric modulation of adenosine A 2A receptors (A 2A Rs) leads to slow-wave sleep without cardiovascular side effects in contrast to A 2A R agonists. Methods: We investigated the hypnotic effects of A 2A R positive allosteric modulators (PAMs) in mice with mania-like behavior produced by ablating GABAergic neurons in the ventral medial midbrain/pons area and in a mouse model of schizophrenia by knocking out of microtubule-associated protein 6. We also compared the properties of sleep induced by A 2A R PAMs in mice with mania-like behavior with those induced by DORA-22, a dual orexin receptor antagonist that improves sleep in pre-clinical models, and the benzodiazepine diazepam. Results: A 2A R PAMs suppress insomnia associated with mania- or schizophrenia-like behaviors in mice. A 2A R PAM-mediated suppression of insomnia in mice with mania-like behavior was similar to that mediated by DORA-22, and, unlike diazepam, did not result in abnormal sleep. Conclusion: A 2A R allosteric modulation may represent a new therapeutic avenue for sleep disruption associated with bipolar disorder or psychosis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Lin, Roy, Ioka, Otani, Amezawa, Ishikawa, Cherasse, Kaushik, Klewe-Nebenius, Zhou, Yanagisawa, Oishi, Saitoh and Lazarus.)