The mammalian/mechanistic target of rapamycin complex 1 (mTORC1) is activated by the small G-protein, RHEB-GTPase. On lysosome, RHEB activates mTORC1 by binding the domains of N-heat, M-heat, and FAT, which allosterically regulates ATP binding in the active site for further phosphorylation. The crucial role of RHEB in regulating growth and survival through mTORC1, makes it a targetable site for anti-cancer therapeutics. However, the binding kinetics of RHEB to mTORC1 is still unknown at the molecular level. Therefore, we studied the kinetics by in vitro and in-cell protein-protein interaction (PPI) assays. For this, we used the split-luciferase system (NanoBiT®) for in-cell studies, and prepared proteins for the in vitro measurements. Consequently, it was shown that RHEB binds to the whole mTOR both in the presence or absence of GTPɣS, with five-fold weaker affinity in the presence of GTPɣS. Also, RHEB bound to the truncated mTOR fragments of N-heat domain (60-167) and M-heat domain (967-1023) in a GTP independent manner. Furthermore, RHEB bound to the truncated kinase domain (2148-2300) with higher affinity also in GTP independently. In conclusion, RHEB binds two different binding sites of mTOR, which probably regulates the kinase activity of mTOR through multiple different molecular mechanisms.

3D bioprinting holds great promise in the field of regenerative medicine as it can create complex structures in a layer-by-layer manner using cell-laden bioinks, making it possible to imitate native tissues. Current bioinks lack both the high printability and the biocompatibility required in this respect. Hence, the development of bioinks that are capable of both properties is needed. In our previous study, a furfuryl-gelatin based bioink, crosslinkable by visible light, was used for creating mouse mesenchymal stem cell-laden structures with high fidelity. In this study, lattice mesh geometries were printed in a comparative study to test against the properties of a traditional rectangular-sheet. After 3D printing and crosslinking, both structures were analysed for swelling and rheological properties, and their porosity estimated using scanning electron microscopy. Results showed that the lattice structure was relatively more porous but sturdy and exhibited a lower degradation rate compared to the rectangular-sheet. Further, the lattice allowed encapsulation of a greater number of cells, allowing them to proliferate to a greater extent compared to the rectangular-sheet that retained a lesser number of cells initially. All of these results collectively affirmed that the lattice poses as a superior scaffold design for tissue engineering applications.

The effects of orally administered lactic acid bacteria metabolites on the skin were studied using an atopic dermatitis-like murine model created by feeding mice with HR-AD. The lactic acid bacteria metabolites were obtained by inoculating 35 strains of 16 species of lactic acid bacteria into soy milk and culturing them. The atopic dermatitis-like murine model was created by feeding HR-1 mice HR-AD for 40 days. The skin condition of mice that were fed HR-AD worsened compared with normal mice, i.e., reduced water content in the stratum corneum, increased transepidermal water loss (TEWL), reduced ceramide AP content in the stratum corneum, and increased epidermis thickness. When mice that had been fed the HR-AD diet was administered a raw liquid of lactic acid bacteria metabolites orally, the measured values related to water content in the stratum corneum, TEWL, ceramide AP content in the stratum corneum, and epidermis thickness improved. To find out the active components for these effects, filtrate and residue from the raw liquid of lactic acid bacteria metabolites and lipid components extracted from the raw liquid were examined at the same time. Results showed that the water-soluble components or residue after filtration did not demonstrate effects but the raw liquid and the lipid fraction did. These findings suggest that lactic acid bacteria metabolites improve skin injury in an atopic dermatitis-like murine model.

Surface processes such as coatings, corrosion, photocatalysis, and tribology are greatly diversified by acid-base interaction at the surface overlayer. This study focuses on the action of metallic copper surface as an electron donor/acceptor related to inactivation of viruses; it was found that regarding Cu2O or Cu materials electrostatic interaction plays a major role in virus inactivation. We applied TPPE method to clarify the mechanism of electron transfer (ET) occurring at light irradiated copper surfaces. The TPPE characteristics was strongly influenced by the environments, which correspond to the temperature and environment dependence of the total count of emitted electrons in the incident light wavelength scan (PE total count, NT), the photothreshold, and further the activation energy (E) analyzed from Arrhenius plot of NT values obtained in the temperature-increase and subsequent temperature-decrease processes. In this study we reexamined the dependence of the TPPE data from two types of Cu metal surfaces: Sample A, which was mechanically abraded in alcohols, water, and air, and Sample C, which was only ultrasonically cleaned in these liquids. The NT for both Samples slowly increased with increasing temperature, reached a maximum (NTmax) at 250C (maximum temperature, Tmax), and after that decreased. For Sample A the NTmax value decreased in the order H2O > CH3OH > C2H5OH > (CH3)2CHOH > C3H7OH, although the last alcohol gave Tmax = 100C, while with Sample C the NTmax value decreased in the order: C3H7OH > (CH3)2CHOH > C2H5OH > CH3OH > H2O. Interestingly, both orders of the liquids were completely opposite: this means that Cu surface can possess two-way character. The NT intensity was found to be strongly associated with the change of the hydroxyl group (Cu-OH) to the oxide oxygen (O2) in the O1s spectra in the XPS measurement. The difference between the above orders was explained by the acid-base interaction mode of the Cu-OH group with the adsorbed molecule on the surfaces. The H2O adsorbed on Sample A produces the electric dipole Cu-OH+---:OH2 (--- hydrogen bond), while the C3H7OH and (CH3)2CHOH adsorbed on Sample C produce ROH+---:O(H)-Cu (R = alkyl groups). Gutmann’s acceptor number (AN) representing the basicity of the liquid molecules was found to be related to the TPPE characteristics: (CH3)2CHOH (33.5), C2H5OH (37.1), CH3OH (41.3), H2O (54.8) (the AN of C3H7OH could not be confirmed). With Sample A the values of NTmaxa and EaUp1 both increased with increasing AN (Up1 means the 1st temperature-increase process). On the other hand, with Sample C the values of NTmaxc and EcUp1 both decreased with increasing AN. These findings suggest that Sample A acts as an acid, while Sample C functions as a base. However, in the case of both types of Samples A and C the NTmax values were found to increase with increasing EUp1. It was explained that the EUp1 values depending on the liquids originate from the difference in the energy level of the hydroxyl group radical at the surface denoted. This is able to attract electrons in the neighborhood of the Fermi level of the base metal by tunnelling. After that due to Auger emission electrons are released, leading to the ET in the overlayer. These electrons are considered to have a strong ability of reducibility.

The Ames/quantitative structure-activity relationship (QSAR) International Challenge Projects held during 2014–2017 and 2020–2022, evaluated the performance of various predictive models. Despite the significant insights gained, the rules allowing participants to select prediction targets introduced ambiguity in model performance evaluation. This reanalysis identified the highest-performing prediction model, assuming a 100% coverage rate (COV) for all prediction target compounds and an estimated performance variation due to changes in COV. All models from both projects were evaluated using balance accuracy (BA), Matthews correlation coefficient (MCC), F1 Score (F1), and the first principal component (PC1). After normalizing the COV, a correlation analysis with these indicators was conducted, and the evaluation index for all prediction models in terms of the COV was estimated. In total, 109 models, the highest estimated BA (76.9) at 100% COV was MMI-VOTE1, reported by Meiji Pharmaceutical University (MPU). The best models for MCC, F1, and PC1 were all MMI-STK1, also reported by MPU. All models reported by MPU ranked in the top four. MMI-STK1 was estimated to have F1 scores of 59.2, 61.5, and 63.1 at COV levels of 90%, 60%, and 30%, respectively. These findings highlight the current state and potential of the Ames prediction technology.

To analyze the viral titers of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and respiratory syncytial virus (RSV) at the anterior nasal site (ANS) and nasopharyngeal site (NS), evaluate their virological dynamics, and validate the usefulness of a newly developed two antigen-detecting rapid antigen diagnostic test (Ag-RDT) that simultaneously detects SARS-CoV-2 and RSV using clinical specimens. This study included 195 asymptomatic to severely ill patients. Overall, 668 specimens were collected simultaneously from the ANS and NS. The cycle threshold (Ct) values calculated from real-time polymerase chain reaction were used to analyze temporal changes in viral load and evaluate the sensitivity and specificity of the Ag-RDT. The mean Ct values for SARS-CoV-2-positive, ANS, and NS specimens were 28.8, 28.9, and 28.7, respectively. The mean Ct values for RSV-positive, ANS, and NS specimens were 28.7, 28.8, and 28.6, respectively. SARS-CoV-2 and RSV showed the same trend in viral load, although the viral load of NS was higher than that of ANS. The sensitivity and specificity of the newly developed Ag-RDT were excellent in specimens collected up to 10 days after the onset of SARS-CoV-2 infection and up to 6 days after the onset of RSV infection.

Adult X-linked hypophosphatemia (XLH) patients present with specific symptoms, including enthesopathies (e.g., ossification of the longitudinal ligament (OPLL), osteophytes around the large joint, and enthesopathy in the Achilles tendon), the development of severe secondary and tertiary hyperparathyroidism (SHPT/THPT) and the subsequent progression of chronic kidney disease (CKD). In addition, these patients exhibit the typical phenotypes of osteomalacia, such as pseudofracture and fracture in weight-bearing bones, odontitis, and tooth abscess. The mechanism underlying enthesopathy development is unknown; however, a common underlying mechanism among XLH and autosomal recessive hypophosphatemic rickets, ARHR1.2, due to mutations in PHEX, DMP1, and ENPP1, is assumed. Clarification of the pathogenesis and drug discovery for this complication is an urgent issue to address, as many adult XLH patients suffer subsequent debilitating nervus symptoms or impingement syndrome, and existing treatments are ineffective. Severe SHPT and THPT are associated with conventional therapy, including active vitamin D and phosphate supplementation, and complicated and careful adjustment of the dosage by experienced clinicians is required to avoid SHPT/THPT. Burosumab is a very effective therapy without risk for the development of SHPT/THPT. However, the indication of this drug should be carefully considered along with the cost-effectiveness, guidelines or recommendations and health care system of each country.

Seirogan, a wood creosote, is a nonprescription drug used to treat diarrhea. However, reports of its clinical use are rare. Here, we report on the efficacy of wood creosote (3 capsules daily) for the alleviation of diarrheal symptoms in 148 patients from 10 clinics in Japan. The wood creosote capsules were classified as remarkably effective (44 patients), effective (71 patients), and partially effective (13 patients) based on the degree of alleviation of diarrheal symptoms that were induced by a variety of causes. The antidiarrheal efficacy of the capsules did not differ between males and females, and young patients (21–30 years) showed greater improvement in diarrheal symptoms than did old patients (> 61 years). Although this report is based on the re-evaluation of old data that had been preserved by our company, the effectiveness and range of symptoms that were treatable with wood creosote has likely remained unchanged. To the best of our knowledge, this is the first public report on the clinical effectiveness of wood creosote capsules for the treatment of a wide range of diarrheal symptoms.

The cyclin-dependent kinase (Cdk) 1–cyclin B (CycB) complex plays critical roles in cell cycle regulation. Before Drosophila male meiosis, CycB is exported from the nucleus to the cytoplasm via the nuclear porin 62kD (Nup62) subcomplex in the nuclear pore complex. When this is inhibited, Cdk1 is not activated, and meiosis does not initiate. We investigated the mechanism that controls cellular localization and activation of Cdk1. Cdk1–CycB continuously shuttled into and out of the nucleus in the prolonged G2 phase before meiosis. Overexpression of CycB, but not that with nuclear localization signal sequences, rescued reduced cytoplasmic CycB and inhibition of meiosis in Nup62-silenced cells. Full-scale Cdk1 activation occurred in the nucleus shortly after its rapid nuclear entry. Cdk1-dependent centrosome separation did not occur in Nup62-silenced cells, while Cdk1 interacted with Cdk-activating kinase and Twine/Cdc25C in the nucleus of Nup62-silenced cells, suggesting the involvement of another suppression mechanism. Silencing of roughex rescued Cdk1 inhibition and initiated meiosis. Nuclear exports of Cdk1 ensured its escape from inhibition by cyclin-dependent kinase inhibitor. The complex reentered the nucleus via importin β at the onset of meiosis. We propose a model regarding the dynamics and activation mechanism of Cdk1–CycB to initiate male meiosis.

Research on retinoid-based cancer prevention, spurred by the effects of vitamin A deficiency on gastric cancer and subsequent clinical studies on digestive tract cancer, unveils novel avenues for chemoprevention. Acyclic retinoids like 4,5-didehydrogeranylgeranoic acid (4,5-didehydroGGA) emerged as potent agents against hepatocellular carcinoma (HCC), distinct from natural retinoids such as all-trans retinoic acid (ATRA). Mechanistic studies reveal GGA's unique induction of pyroptosis, a rapid cell death pathway, in HCC cells. GGA triggers mitochondrial superoxide hyperproduction and ER stress responses through Toll-like receptor 4 (TLR4) signaling and modulates autophagy, ultimately activating pyroptotic cell death in HCC cells. Unlike ATRA-induced apoptosis, GGA and palmitic acid (PA) induce pyroptosis, underscoring their distinct mechanisms. While all three fatty acids evoke mitochondrial dysfunction and ER stress responses, GGA and PA inhibit autophagy, leading to incomplete autophagic responses and pyroptosis, whereas ATRA promotes autophagic flux. In vivo experiments demonstrate GGA's potential as an anti-oncometabolite, inducing cell death selectively in tumor cells and thus suppressing liver cancer development. This review provides a comprehensive overview of the molecular mechanisms underlying GGA's anti-HCC effects and underscores its promising role in cancer prevention, highlighting its importance in HCC prevention.

AYUMI EYE is an accelerometer-based gait analysis device that measures the 3D accelerations of the human trunk. This study investigated the measurement accuracy of the AYUMI EYE as hardware as well as the accuracy of the gait cycle extraction program via simultaneous measurements using AYUMI EYE, a ground reaction force (GRF), and an optical motion capture system called VICON. The study was conducted with four healthy individuals as participants. The gait data were obtained by simulating four different patterns for three trials each: normal walking, anterior-tilt walking, hemiplegic walking, and shuffling walking. The AYUMI EYE and VICON showed good agreement for both the acceleration and displacement data. The durations of subsequent stride cycles calculated using the AYUMI EYE and GRF were in good agreement based on the calculated cross-correlation coefficients (CCs) with an r value of 0.896 and p-value less than 0.05, and their accuracies for these results were sufficient.

Parkinson-like events are side effects that may persist for an extended period even after drug administration is discontinued. Although these events can be triggered by various drugs, the mechanisms underlying their diverse symptoms remain largely unclear. To investigate this, we used the Japanese Adverse Drug Event Reporting Database, which is maintained by the Phar-maceuticals and Medical Devices Agency, to analyze the risk factors associated with Parkinson-like events along with associated drug trends and characteristics. Our findings indicate that similar to　Parkinson’s disease, age-related differences affect the onset of these events, with older individuals being more susceptible. Hierarchical clustering and principal component analysis revealed that the mechanisms triggering these Parkinson-like events are consistent across reports, suggesting a common underlying cause. However, even with a consistent mechanism, side effects can vary depending on the site of action. These insights underline the importance of swift identification of the drugs suspected of causing these events and implementation of measures to reduce their side effects.

Adverse events associated with opioid use in palliative care have been extensively studied. However, predicting the occurrence of adverse events based on the specific opioid used remains unclear. This study aimed to comprehensively analyze the adverse events caused by µ receptor stimulation of opioids approved in Japan and investigate the tendencies of adverse event occur-rence among different opioids.We utilized the FDA Adverse Event Reporting System (FAERS) database to extract reported adverse events of opioids approved in Japan. Cluster analysis was performed on reporting odds ratios (RORs) of adverse event names among opioids to visualize relationships between opioids and adverse events, facilitating a comparative study of their clas-sifications.We calculated the RORs of adverse events for the target opioids. Based on these RORs, we performed a cluster analysis, which resulted in the classification of 11 target opioids into five distinct groups. we were able to comprehensively compare and examine the relationships between opioids and adverse events. This analysis helps in understanding and managing the risks and benefits of each drug in palliative care settings. By analyzing relationships between opioids and adverse events, clinicians can make informed decisions about opioid selection, dosage, and monitoring to maximize patient safety and comfort.

: Glaucoma is the most common cause of blindness, which significantly reduces quality of life. Most glaucoma cases are primary glaucoma; nevertheless, many patients suffer from glaucoma caused by drugs, such as corticosteroids. A comprehensive review of the risks associated with corticosteroid-induced glaucoma is limited. Therefore, we used the Japanese Adverse Drug Event Reporting Database (JADER) published by the Pharmaceuticals and Medical Devices Agency (PMDA) to analyze the risk factors associated with glaucoma and the trends and characteristics of corticosteroid-induced glaucoma. We did not find sex or age differences associated with the onset of glaucoma. Hierarchical clustering and principal component analysis revealed that triamcinolone acetonide and betamethasone sodium phosphate, which are used around the eyes in Japan, are more likely to induce intraocular pressure (IOP) elevation compared with other corticosteroids. Increased IOP is a direct cause of glaucoma. Based on these findings, it may be necessary to limit or avoid the use of these corticosteroids.

Background: The seventh novel human infecting Betacoronavirus that causes pneumonia (2019 novel coronavirus, 2019-nCoV) originated in Wuhan, China. The evolutionary relationship between 2019-nCoV and the other human respiratory illness-causing coronaviruses is unclear. We sought to characterize the relationship of the translated proteins of 2019-nCoV with other species of Orthocoronavirinae.Methods: A phylogenetic tree was constructed from the genome sequences. A cluster tree was developed from the profiles retrieved from the presence and absence of homologs of ten 2019-nCoV proteins. The combined data were used to characterize the relationship of the translated proteins of 2019-nCoV to other species of Orthocoronavirinae.Results: Our analysis reliably suggests that 2019-nCoV is most closely related to BatCoV RaTG13 and belongs to subgenus Sarbecovirus of Betacoronavirus, together with SARS coronavirus and Bat-SARS-like coronavirus. The phylogenetic profiling cluster of homolog proteins of one annotated 2019-nCoV protein against other genome sequences revealed two clades of ten 2019-nCoV proteins. Clade 1 consisted of a group of conserved proteins in Orthocoronavirinae comprising Orf1ab polyprotein, Nucleocapsid protein, Spike glycoprotein, and Membrane protein. Clade 2 comprised six proteins exclusive to Sarbecovirus and Hibecovirus. Two of six Clade 2 nonstructural proteins, NS7b and NS8, were exclusively conserved among 2019-nCoV, BetaCoV_RaTG, and BatSARS-like Cov. NS7b and NS8 have previously been shown to affect immune response signaling in the SARS-CoV experimental model. Thus, we speculate that knowledge of the functional changes in the NS7b and NS8 proteins during evolution may provide important information to explore the human infective property of 2019-nCoV.

Background: Overall survival is the most important outcome for treatment response in feline chronic kidney disease (CKD). Beraprost has been shown to reduce the kidney function decline in cats with International Renal Interest Society (IRIS) stage 2 and 3 CKD. However, association with prolonged survival has not yet been examined. Objective: To assess the relationship between beraprost and overall survival in cats with CKD in real clinical practice. Animals: Client-owned cats with IRIS stage 3 CKD (n = 134), evaluated between 2017 and 2020. Methods: Retrospective cohort study based on data from electronic medical records of one hospital. Results: Multivariable Cox regression models on all treatment effects showed that beraprost only was related to better survival (P = 0.028). The cohort was divided into “beraprost therapy” and “no beraprost therapy” groups, and survival analyses revealed that overall survival was significantly longer in the beraprost therapy group, using Kaplan-Meier curves (P = 0.004). However, baseline phosphate is known to be an important prognostic indicator and was not well balanced between the two groups. Therefore, a subcohort of 97 cats was selected (those having baseline phosphate < 6.0 mg/dL) that allowed for this parameter to be balanced between groups. The survival data in this subcohort was consistent with that of the overall study cohort. Conclusions: In feline patients with CKD, beraprost therapy was associated with better overall survival.

Sesame seeds are abundant in sesamin, which exerts health-promoting effects such as extending the lifespan of adult Drosophila and suppression of oxidative stress accumulation by activating the Nrf2 transcription factor. Here, we investigated whether sesamin activated Nrf2 in larval tissues and induced the expression of Nrf2 target genes. In sesamin-fed larvae, Nrf2 was activated in the central nervous system (CNS), gut, and salivary glands. However, ectopic expression of Keap1 (Nrf2 inhibitor) in glial cells inhibited sesamin-induced Nrf2 activation in all tissues except in the neurons, indicating that sesamin activates Nrf2 in glia. We labeled the astrocytes as well as cortex and surface glia with red fluorescence to identify these glial cell types in which Nrf2 was activated; we observed their activation in both cell types. These data suggest that sesamin may stimulate the expression of antioxidative genes in glial cells. Among the 17 candidate Nrf2 targets, the mRNA levels of Cyp6a2 and Cyp6g1 in cytochrome P450 were elevated in the CNS, gut, and salivary glands of sesamin-fed larvae. However, this did not lead to resistance against imidacloprid, which is detoxified by these enzymes. Our results suggest that sesamin may exert similar health-promoting effects on the human CNS and digestive tissues.

We introduce a novel method for fabricating perovskite solar modules using selective spin-coating on various Au/ITO patterned substrates. These patterns were engineered for twofold purposes: (1) to enhance selectivity of monolayers primarily self-assembling on the Au electrode, and (2) to enable seamless interconnection between cells through direct contact of the top electrode and the hydrophobic Au connection electrode. Utilizing SAMs-treated Au/ITO, we achieved sequential selective deposition of the electron transport layer (ETL) and the perovskite layer on the hydrophilic amino-terminated ITO, while the hole transport layer (HTL) was deposited on the hydrophobic CH3-terminated Au connection electrodes. Importantly, our approach had negligible impact on the series resistance of the solar cells, as evidenced by the measured specific contact resistivity of the multilayers. A significant outcome was the production of a 6-cell series-connected solar module with a notable average PCE of 8.32%, providing a viable alternative to the conventional laser scribing technique.

Rhotekin is an effector protein for small GTPase Rho. This protein consists of a Rho binding domain (RBD), a pleckstrin homology (PH) domain, proline-rich regions and a C-terminal PDZ-binding motif. We and other groups have identified various binding partners for Rhotekin and proposed their possible physiological roles. However, functions of Rhotekin per se are largely unknown and information about its physiological roles are fragmentary. In this review, we summarize known features of Rhotekin in neuronal tissues and cancer cells. We also describe characteristics of binding partners for Rhotekin and predicted roles of their interaction.

Outdoor air pollution is a leading cause of death and premature death globally. Motorcycle-taxi drivers were most at risk associated with occupational exposure to ambient air pollution in urban areas. Therefore, a cross-sectional study was conducted to determine the influencing factors and prediction of lung function impairment in 308 motorcycle-taxi drivers living in Bangkok and adjacent provinces between February and June 2022. The study design included: data collection using questionnaires applied from the Thai version of ATS-DLD-78A: American Thoracic Society Division of Lung Diseases and Department of Disease Control, Ministry of Public Health, Thailand; a collection of respirable dust, and ambient air pollution parameters measured by per-sonal air sampling pump and real-time air quality index (AQI) station, and lung function determined by the spirometer. The results showed that 14 factors were significantly associated with lung function impairment (p<0.05). Apparently, seven influencing factors showing the most association were included: gender, the height of the subjects, history of allergies, exposure to respirable dust, mask types, helmet types, and family history of lung disease. The lung function impairment of motorcycle-taxi drivers was significantly predicted in 28.1% by regression analysis of these seven variables (R2=0.281). Therefore, this is the first report on influencing factors and prediction of lung function impairment among motorcycle-taxi drivers. These findings would be very useful for preventing and controlling measure ambient air pollution, setting policies and strategies to mitigate the risks for motorcycle-taxi drivers and the other ex-posed population.

The blue sepal color of hydrangea is due to a metal complex anthocyanin composed of 3-O-glucosyldelphinidin (1) and an aluminum ion with the co-pigments 5-O-caffeoylquinic acid (2) and/or 5-O-p-coumaroylquinic acid (3). The three components, namely, anthocyanin, Al³⁺ and 5-O-acylquinic acids, are essential for blue color development, but the complex is unstable and only exists in aqueous solution. Furthermore, the complex did not give analyzable NMR spectra or crystals. Therefore, many trials to determine the detailed chemical structure of the hydrangea-blue complex have failed to date. Instead, via experiments mixing 1, Al³⁺ and 2 or 3 in a buffered solution at pH 4.0, we obtained the same blue solution derived from the sepals. However, the ratio was not stoichiometric but fluctuated. To determine the composition of the complex, we tried direct observation of the molecular ion of the complex using electrospray-ionization mass spectrometry. In a very low-concentration buffer solution (2.0 mM) at pH 4.0, we reproduced the hydrangea-blue color by mixing 1, 2 and Al³⁺ in ratios of 1:1:1, 1:2:1 and 1:3:1. All solution gave the same molecular ion peak at m/z = 843, indicating that the blue solution has a ratio of 1:1:1 for the complex. By using 3, the observed mass number was m/z = 827 and the ratio of 1, 3 and Al³⁺ was also 1:1:1. A mixture of 1, 3-O-caffeoylquinic acid (4) and Al³⁺ did not give any blue color but instead was purple, and the intensity of the molecular ion peak at m/z = 843 was very low. These results strongly indicate that the hydrangea blue-complex is composed of a ratio of 1:1:1 for 1, Al³⁺ and 2 or 3.

Drug-induced pruritus triggers a desire to scratch, thereby diminishing one’s quality of life. Certain instances of this phenomenon follow complex mechanisms of action that diverge from histamine-mediated pathways, known contributors to pruritus. However, investigations into the relationship between drugs and pruritus are limited. In this study, data mining techniques were employed to comprehensively analyze the characteristics of drugs linked to pruritus, using the FDA Adverse Event Reporting System(FAERS) Data maintained in the United States. Reports linked to pruritus demonstrated noteworthy differences in gender, age, and weight when compared with non-pruritus cases. Among the leading candidates for drugs prompting pruritus were ophthalmic drugs, systemic antibacterials, contrast media, dermatological antifungals, and dermatological preparations. Principal component analysis showed that the second principal component served as an indicator for distinguishing between onsets at mucous membranes or the skin surface. Additionally, the third principal component functioned as an indicator for categorizing administration methods as either invasive or noninvasive. Furthermore, a hierarchical cluster analysis conducted on these obtained principal components revealed the potential for classifying drugs based on the site of pruritus onset and the method of drug administration. These findings contribute to the development of targeted prevention and treatment strategies for avoiding pruritus in clinical practice.

Background: The central channel of the nuclear pore complex (NPC) plays an important role in the selective transport of proteins between the nucleus and cytoplasm. Previous studies have demonstrated that depletion of the Nup62 complex, constructing the nuclear pore channel in premeiotic Drosophila cells, resulted in absence of meiotic cells. We attempted understanding the mechanism underlying the cell cycle arrest before meiosis. Methods: We induced dsRNAs against the nucleoporin mRNAs using the Gal4/UAS system in Drosophila. Results: The cell cycle of the Nup62-depleted cells was arrested before meiosis without CDK1 activation. Ectopic over-expression of CycB, but not constitutively active CDK1, resulted in partial rescue from the arrest. CycB accumulated precociously in the nuclei of Nup62-depleted cells and cells depleted of exportin (encoded by emb). Protein complexes containing CycB, Emb, and Nup62 complex components were observed in premeiotic spermatocytes. CycB, which had precociously migrated into the nucleus, was associated with Emb, and the complex was transported back to the cytoplasm through the central channel, interacting with the Nup62 complex. Conclusion: We proposed that CycB is exported with Emb through the channel interacting with the Nup62 complex before initiation of meiosis. The nuclear export ensures production of active CycB-CDK1 in the cytoplasm.

In this study, we explored terahertz (THz) optical properties of the as-deposited and rapid thermal annealing (RTA) at 400°C, 600°C and 800°C of indium-tin-oxide (ITO) thin-films sputtered on high-resistivity silicon (HR-Si) substrate. We further investigated THz frequency dependence complex refractive indices and conductivity of those as-prepared and annealed ITO thin films. We note the transmittance enhanced from 27 % to 39 % for ITO thin film treated with RTA at 800°C while the real part of conductivity improved from 1019 Ω-1∙cm-1 to 4881 Ω-1∙cm-1 for ITO thin film treated with RTA at 600°C in the frequency range of 0.2 to 1 THz. The mobility, carrier concentration, plasma frequency and relaxation time of those sample were also deduced by fitting the experimental results with the Drude-Smith model. For example, the mobility of 29 cm2/V∙s, 110 cm2/V∙s, 226 cm2/V∙s and 70 cm2/V∙s, respectively is deduced for as-deposited, RTA at 400°C, RTA at 600°C and 800°C of ITO thin-films. In addition, the optical bandgap of those ITO thin films were evaluated with a typical Tauc plot showing extrapolation of photon energy spectrum. The transmittance, absorption coefficient and complex refractive indices of those ITO thin films were extracted by Swanepoel method using experimental transmittance and reflectance spectrum throughout the wavelength range from 400 to 1000 nm. Moreover, as expected, the transmittance of the ITO thin film treated with RTA at 800°C is improved at the wavelength of the visible light spectrum. We also displayed the surface morphology, microscopic structural properties and typical chemical composition of as-deposited and RTA at 400°C, RTA at 600°C and 800°C of ITO thin-films. We strongly believed the present study will lead to further enhancement for THz optoelectronics applications.

Metal plasmonic nanostructures have promising applications in biosensing due to their ability to facilitate light-matter interaction. However, the damping of the metal leads to a wide full width at half maximum (FWHM) spectrum and results which restricts its sensing capabilities. In this research, we present a novel non-full-metal nanostructure, namely indium-tin oxide (ITO)-Au nanodisk arrays consisting of top ITO nanodisk arrays and a bottom gold layer, and compare the coupling mode with the full-metal nanodisk arrays. The FWHM of proposed ITO-Au nanodisk array reduces to one fifth of that all metal nanodisk arrays, which is generated mode-coupling by surface plasmon modes at metal interfaces with magnetic resonance mode. Furthermore, the thickness variation of nanodisks has no impact on the sensing performance of this ITO-based nanostructure, ensuring excellent tolerance during preparation. We fabricated both structures by using template transfer and vacuum deposition techniques and calibrated their sensing performances by detect Immunoglobulin G (IgG) protein molecules. Both theoretical and experimental results demonstrate that ITO-Au nanodisk arrays provide an effective solution for biosensing applications.

Here we report highly efficient, indium tin oxide (ITO)-free polymer solar cells (PSCs) with an ultrathin copper (Cu) film(~10 nm) coated with a thin layer of poly[(9,9-bis(3‘-(N,N-dimethylamino)propyl)-2,7-fluorene)-alt-2,7-(9,9-dioctylfluorene)] (PFN) as transparent electrode. Despite of its lower far-field transmittance of the electrode, the obtained ITO-free device based on the ultrathin Cu film can delivery higher absorption efficiency than that of the device based on ITO substrate in the long wavelength region, which can be attributed to the formation of metal resonant microcavity between the opaque back metal mirror (MoO3/Al electrode) and the transparent Cu film with high reflectance. As a result, polymer solar cells based on poly[[2,6'-4,8-di(5-ethylhexylthienyl)benzo[1,2-b;3,3-b]dithiophene][3-fluoro-2[(2-ethylhexyl)carbonyl]thieno[3,4-b]thiophenediyl]] (PTB7-Th) and [6,6]-phenyl C71-butyric acid methyl ester (PC71BM) blend show a high power conversion efficiency (PCE) of 8.21 %, comparable to that of the control device based on ITO electrode (with a PCE of 9.60% ). The results demonstrate that thermally evaporated Cu thin film electrode can be promising candidate to replace ITO for highly efficient PSCs, thus may open up the possibility for massive production of PSCs with low cost.

We demonstrated an ITO-free, highly transparent organic solar cell with the potential to be integrated into window panes for energy harvesting purposes. A transparent, conductive ZnO/Ag/ZnO multilayer electrode and a Ag:Ca thin film electrode were used in this transparent device as the bottom and top electrode, respectively. To further improve the transmittance of the solar cell, the thickness of the top ZnO layer was investigated by both experiment and simulation. An average visible transmittance of > 60% was reached, with a maximum transmittance of 73% at 556 nm. Both top and bottom illumination of the solar cell generated comparable power conversion efficiencies, which indicates the wide application of this solar cell structure. In addition, we fabricated distributed Bragg reflector mirrors with sputtered SiO2 and TiO2, which efficiently increased the power conversion efficiency over 20% for the solar cells on glass and PET substrates,

Aquaculture is growing ever more important due to the decrease in natural marine resources and increase inworldwide demand. To avoid losses due to aging and abnormalweather, it is important to predict seawater temperature in order to maintain a more stable supply, particularly for high value added products, such as pearls and scallops. The increase in species extinction is a prominent societal issue. Furthermore, in order to maintain a stable quality of farmed fishery, water temperature should be measured daily and farming methods altered according to seasonal stresses. In this paper, we propose an algorithm to estimate seawater temperature in marine aquaculture by combining seawater temperature data and actual weather data.

The purpose of this study was to investigate the changes in anterior knee laxity (AKL), stiffness, general joint laxity (GJL), and genu recurvatum (GR) during the menstrual cycle in female non-athletes and female athletes with normal and irregular menstrual cycles. Participants were 19 female non-athletes (eumenorrhea, n=11; oligomenorrhea, n=8) and 15 female athletes (eumenorrhea, n=8; oligomenorrhea, n=7). AKL was measured as the amount of anterior tibial displacement at 67 N - 133 N. Stiffness was calculated as change in (Δ)force/Δ anterior displacement. The Beighton method was used to evaluate the GJL. The GR was measured as the maximum angle of passive knee joint extension. AKL, stiffness, GJL, and GR were measured twice in four phases during the menstrual cycle. Stiffness was significantly higher in oligomenorrhea groups than in eumenorrhea groups, although no significant differences between menstrual cycle phases were evident in female non-athletes. GR was significantly higher in the late follicular, ovulation, and luteal phases than in the early follicular phase, although no significant differences between groups were seen in female athletes. Estradiol may affect the stiffness of the periarticular muscles in the knee, suggesting that GR in female athletes may change during the menstrual cycle.

In this paper, we synthesized MC(BeA-co-MMA) copolymer microcapsules through suspension polymerization. The pendent n-behenyl group of BeA is highly crystalline, and it acts as the side-chain in the structure of BeA-co-MMA copolymer. The highly crystalline n-behenyl side-chain provides BeA-co-MMA copolymer thermal-energy-storage capacity. In order to investigate the correlation between thermal properties and crystal structure of BeA-co-MMA copolymer, the effects of monomer ratio, temperature changing and changing rate, as well as synthesis method were discussed. The monomer ratio influenced crystal transition behavior and thermal properties greatly. The DSC results proved that when the monomer ratio of BeA and MMA was 3:1, MC(BeA-co-MMA)3 showed the highest average phase change enthalpy ΔH (105.1 J·g–1). It indicated that the n-behenyl side-chain formed relatively perfect crystal region, which ensured a high energy storage capacity of copolymer. All the DSC and SAXS results proved that the amount of BeA had a strong effect on the thermal-energy-storage capacity of copolymer and the long spacing of crystals, but barely on the crystal lamella. It was found that MMA units worked like defects in the n-behenyl side-chain crystal structure of BeA-co-MMA copolymer. Therefore, a lower fraction of MMA, that is, a higher fraction of BeA contributed to a higher crystallinity of BeA-co-MMA copolymer for providing a better energy storage capacity and thermoregulation property. ST(BeA-co-MMA) copolymer sheets with the same ingredients as microcapsules were also prepared through light-induced polymerization aiming at clarifying the effect of synthesis method. The results proved that synthesis method mainly influenced the copolymer chemical component, but lightly on the crystal packing of n-behenyl side-chain.

A major advance of drug discovery and targeted therapy directed to cancer cells may be achieved by exploitation and immunomodulation of their unique biological property. This re-view summarizes our efforts to develop novel chemo-thermo-immuno-therapy (CTI therapy) by conjugating a melanogenesis substrate, N-propionyl cysteaminylphenol (NPrCAP: amine analog of tyrosine), with magnetite nanoparticles (MNP). In our approach, NPrCAP provides a unique drug delivery system (DDS) because of its selective incorporation into melanoma cells. It also functions as a melanoma-targeted therapeutic drug because of its production of highly reactive free radicals (melanoma-targeted chemotherapy). Moreover, utilization of MNP is a platform to develop thermo-immunotherapy because of heat shock protein (HSP) generation upon exposure to an alternating magnetic field (AMF). The feasibility of our approach was successfully shown in experimental in vivo and in vitro mouse melanoma models and in preliminary clinical trials to a limited number of advanced melanoma patients.

This paper examines the tropical cyclone (TC) activity in Solomon Islands (SI) using the best track data from Tropical Cyclone Warning Centre Brisbane and Regional Specialized Meteorological Centre Nadi. The long-term trend analysis showed that the frequency of TCs has been decreasing in this region while average TC intensity becomes strong. Then, the datasets were classified according to the phase of Madden-Julian Oscillation (MJO) and the index of El Nino Southern Oscillation (ENSO) provided by Bureau of Meteorology. The MJO has sufficiently influenced TC activity in the SI region with more genesis occurring in phases 6-8, in which the lower outgoing longwave radiation indicates enhanced convective activity. In contrast, TC genesis occurs less frequently in phases 1, 2, and 5. As for the influence of ENSO, more TCs are generated in El Nino period. The TC genesis locations during El Nino (La Nina) period were significantly displaced to the north (south) over SI region. TCs generated during El Nino condition tended to be strong. This paper also argues the modulation in terms of seasonal climatic variability of large-scale environmental conditions such as sea surface temperature, low level relative vorticity, vertical wind shear, and upper level divergence.

Porphyromonas spp. are oral anaerobic Gram-negative bacteria that form black-pigmented colonies on blood agar and produce volatile sulfur compounds (VSCs), such as hydrogen sulfide (H2S), methyl mercaptan (CH3SH), and dimethyl sulfide ((CH3)2S), which cause halitosis and the destruction of periodontal tissues. P. gulae is considered the main pathogen involved in periodontal disease in dogs. However, the characteristics of the VSCs produced by P. gulae are unknown. In the present study, VSCs were measured in 26 isolates of P. gulae and some isolates of the other Porphyromonas spp. obtained from the oral cavities of dogs with periodontal disease using an in vitro assay with an Oral ChromaTM gas chromatograph. The results demonstrated that P. gulae was able to produce large amounts of H2S and CH3SH, and the dominant one was CH3SH (CH3SH/H2S was approximately 2.2). Other Porphyromonas spp. that were also obtained from the oral cavities of dogs with periodontal disease indicated the similar levels of production of H2S and CH3SH to those of P. gulae. It is strongly suggested that the high levels of H2S and CH3SH in P. gulae and other Porphyromonas spp. contribute to halitosis and the destruction of periodontal tissues during the progression of periodontal disease in dogs.

Superficial discolored spots on Atlantic salmon (Salmo salar) fillets are a serious quality problem for commercial seafood farming. Previous reports proposed that the black spots (called melanized focal changes (MFC)) may be melanin, but no convincing evidence has been reported. In this study, we performed chemical characterization of MFC, and also of red pigment (called red focal changes (RFC)), of salmon fillets using alkaline hydrogen peroxide oxidation and hydroiodic acid hydrolysis. This revealed that the MFC contain 3,4-dihydroxyphenylalanine (DOPA)-derived eumelanin whereas the RFC only contain trace amounts of eumelanin. Therefore, probably, the black color of MFC can be explained by the presence of eumelanin from accumulated melanomacrophages. For the red pigment, we could not find a significant signature of either eumelanin or pheomelanin, and the red color is probably predominantly hemorrhagic in nature. However, we found that in RFC the level of pigmentation did increase together with some melanogenic metabolites. Comparison with a “mimicking experiment,” in which a mixture of a salmon homogenate + DOPA was oxidized with tyrosinase, suggested that the RFC include conjugations of DOPAquinone and/or DOPAchrome with salmon muscle tissue proteins. In short, the results suggest that melanogenic metabolites in MFC and RFC derive from different chemical pathways, which would agree with the two different colorations deriving from distinct cellular origins, namely melanomacrophages and red blood cells, respectively.

INTRODUCTION AND OBJECTIVES: Osteoporosis is a common consequence of androgen deprivation therapy (ADT) for prostate cancer. Up to 20% of men on ADT have suffered from fracture within 5 years. The WHO Fracture Risk Assessment Tool (FRAX) has been utilized to predict the 10-year probability of major osteoporotic and hip fracture. However, no large studies assessing the utility of FRAX with versus without dual-energy X-ray absorptiometry (DEXA) in prostate cancer patients have been performed. We validated the usefulness of FRAX combined with DEXA in men with prostate cancer. METHODS: FRAX was done in a total of 1,220 prostate cancer patients including those who underwent brachytherapy (n=547), radical prostatectomy (n=200), external beam radiation therapy (n=264), hormonal therapy only (n=187), and definitive treatment along with hormonal therapy (n=645) in Yokohama City University Hospital. Of these, 109 patients received DEXA. RESULTS: In men without receiving DEXA, the median (mean ± SD) risks for major osteoporotic and hip fracture were 8.5% (9.3 ± 4.8) and 3.2% (4.2 ± 3.9), respectively. One hundred sixteen (9.5%) and 634 (52.0%) of these patients had the major osteoporotic risk of more than 15% and hip fracture risk of more than 3%, respectively. In contrast, in men with DEXA, the median (mean ± SD) risks for major osteoporotic and hip fracture were 5.3% (5.4 ± 2.1) and 0.85% (1.3 ± 1.2), respectively. Two (0.2%) and 4 (8.0%) of these patients had the major osteoporotic risk of more than 15% and hip fracture risk of more than 3%, respectively [Table1]. In the same cohort who received DEXA, the risks for major osteoporotic (p < 0.001) and hip (p < 0.001) fracture were significantly lower in men with DEXA than in those without DEXA. CONCLUSIONS: Our results suggest that FRAX combined with DEXA might prevent unnecessary osteoporosis medication in prostate cancer patients.

Wafer-scale blue micro-light-emitting diode (micro-LED) arrays are fabricated with a pixel size of 12 μm, a pixel pitch of 15 μm, and a pixel density of 1692 pixels per inch, achieved by optimizing the properties of e-beam-deposited and sputter-deposited indium tin oxide (ITO). Although the sputter-deposited ITO (S-ITO) films exhibit a densely packed morphology and lower resistivity compared to those of the e-beam-deposited ITO (E-ITO) films, the forward voltage (VF) values of a micro-LED with the S-ITO films are higher than those with the E-ITO films. The VF values for a single pixel and for four pixels with E-ITO films are 2.82 V and 2.83 V, respectively, while the corresponding values for S-ITO films are 3.50 V and 3.52 V. This was attributed to ion bombardment damage and nitrogen vacancies in the p-GaN layer. Surprisingly, the VF variations of a single pixel and of four pixels with the optimized E-ITO spreading layer from five different regions are only 0.09 V and 0.10 V, respectively. This extremely uniform VF variation is suitable for realizing micro-LED displays to be used in AR and VR applications, circumventing the bottleneck in the development of long-lifespan and high-brightness organic LED devices for industrial mass production.

In this work, nanocomposite photoelectrodes of the TiO2/ Au composition were manufactured, in which the size of plasmonic Au nanoparticles was varied, and the morphology of the TiO2 layer, depending on the thickness, changed from an island to a continuous layer. The influence of the morphology of plasmonic Au nanoparticles and the TiO2 layer on the optical and photoelectrochemical characteristics of hybrid photoelectrodes was studied. It has been shown that continuous coating of Au nanoparticles with a TiO2 layer (layer thickness 10 and 15 nm) leads to a decrease in the photoelectric response, and the decrease in photocurrent density and photoconversion efficiency decreases in proportion to the thickness of the TiO2 layer. The indicated drop in characteristics when plasmonic particles are located under the TiO2 layer is presumably associated with the scattering and recombination of charge carriers in the semiconductor layer. The best performance was shown by a system in which large Au nanoparticles (10 nm) are coated with a 5 nm thick layer of titanium dioxide; in this geometry, Au nanoparticles are decorated with TiO2 nanoparticles, as a result of which the photoelectrode-electrolyte interface has a more complex structure.

Lymph nodes are secondary lymphoid organs that appear as bean-like nodules usually <1 cm in size, and they are localized throughout the body. Many antigen-presenting cells such as dendritic cells and macrophages reside in lymph nodes, where they mediate host defense responses against pathogens such as viruses and bacteria. In cancers, antigen-presenting cells induce cytotoxic T lymphocytes (CTLs) to react to cancer cell–derived antigens. Macrophages located in the lymph node sinus are of particular interest in relation to anti-cancer immune responses because many studies using both human specimens and animal models have suggested that lymph node macrophages play a key role in activating anti-cancer CTLs. The regulation of lymph node macrophages therefore represents a potentially promising novel approach in anti-cancer therapy.

Background: The aim of this study was to demonstrate involvement of whole-body compensatory alignment in different conditions of spinopelvic sagittal balance (compensated/decompensated). Methods: We enrolled 330 healthy subjects and divided them according to sagittal vertical axis (SVA): the compensated group, < 4 cm, (group C) and the decompensated group, ≥ 4 cm, (group D). The correlation between lack of ideal lumbar lordosis (iLL), which is calculated by using the Schwab formula, and the compensatory radiographic parameters in each group were analyzed. The threshold value of KF angle that indicates a spinopelvic sagittal imbalance (SVA ≥ 4) was determined by ROC curve analysis. Results: Correlation analysis of lack of iLL and each com-pensatory parameter showed a strong correlation for pelvic tilt (PT) (r = -.723), and a weak cor-relation for thoracic kyphosis (TK) (r = 275) in Group C. In Group D, the correlations were strong for PT (r = -.796), moderate for TK (r = .462), and KF (r = -.415). The optimal cutoff value for KF angle was determined to be 8.4 degrees (sensitivity 89%, specificity 46%). Conclusions: The pre-sent study showed differences between compensated/decompensated spinopelvic sagittal balance in the correlation strength between lack of iLL and whole-body compensatory parameters.

Parkinson’s disease (PD) is an aging-related and the second most common neurodegenerative disease after Alzheimer’s disease. The main symptoms of PD are movement disorders accompanied with deficiency of neurotransmitter dopamine (DA) in the striatum due to cell death of the nigro-striatal DA neurons. Two main histopathological hallmarks exist in PD: cytosolic inclusion bodies termed Lewy bodies that mainly consist of α-synuclein protein, the oligomers of which produced by misfolding are regarded to be neurotoxic, causing DA cell death; and black pigments termed neuromelanin (NM) that are contained in DA neurons and markedly decrease in PD. Synthesis of human NM is regarded to be similar to that of melanin in melanocytes; Melanin synthesis in skin is via DOPAquinone (DQ) by tyrosinase, whereas NM synthesis in DA neurons is via DAquinone (DAQ) by tyrosine hydroxylase (TH) and aromatic L-amino acid decarboxylase (AADC). DA in cytoplasm is highly reactive and is assumed to be oxidized spontaneously or by an unidentified tyrosinase to DAQ and then synthesized to NM. Intracellular NM accumulation above a specific threshold was reported to be associated to DA neuron death and PD phenotypes. This review reports recent progress in biosynthesis and pathophysiology of NM in PD.

Background and Aim: Tacrolimus is highly effective in intractable ulcerative colitis, but maintenance may be problematic. This study examined 52-week maintenance and adverse events. Methods: This retrospective study of patients who used tacrolimus from April 2009 to December 2021 (N = 136) examined remission induction rates and background factors in the remission (n = 108) and non-remission groups (n = 28); 52-week maintenance; drug-specific maintenance (azathioprine [n = 58] vs tacrolimus [n = 12] and vs biological product [Bio, n = 8]); and adverse events. Results: The mean observation period was 1230175 days. Remission occurred in 72.7%. Significant differences were observed in sex and endoscopic score (before treatment and 2 weeks after tacrolimus trough levels). Maintenance rate at 52 weeks was 61.6%; significant differences were observed in sex, hospitalization duration, and prednisolone during hospitalization (P < 0.05). Drug-specific 52-week maintenance was 67% with azathioprine, 54% with tacrolimus, and 37% with Bio. No tacrolimus-related serious adverse events occurred that led to discontinuation. Discussion: Remission was more common in women with improved endoscopic scores after tacrolimus trough levels and patients with improved endoscopic scores after tacrolimus therapy. Remission maintenance was more common in women with a long hospitalization at remission and high total steroid dose. Results suggest that treatment with adequate prednisolone use during the period with more inflammation may improve subsequent maintenance. Conclusions: In intractable ulcerative colitis, tacrolimus can induce remission even in patients who cannot use azathioprine for maintenance. Remission can be maintained with azathioprine, tacrolimus, or a Bio.

For the polymer electrolyte fuel cell (PEFC), the separator thickness plays an important role to determine the weight, the volume and the costs of the PEFC. In addition, thermal management, i.e. temperature distribution is also important for the PEFC system to obtain higher performance. However, there were few reports investigating the relationship between the temperature distribution and the power generation performance such as current density distribution of PEFC operated at higher temperature (HT-PEFC). The aim of this study is to clarify the impact of separator thickness on the relationship between the temperature distribution and the current density distribution of HT-PEFC. This study has also investigated the impact of separator thickness on the relationship between the temperature distribution and the gases such as H2, O2 and the current density distribution of HT-PEFC numerically using CFD software COMSOL Multiphysics. The separator thicknesses of 2.0 mm, 1.5 mm and 1.0 mm were studied. In the study, the operation temperature and the relative humidity (RH) of supply gas were also changed. As a result, it was revealed that the optimum separator thickness was 2.0 mm to obtain higher power generation of HT-PEFC. Since the heat capacity in the case of the separator thickness of 2.0 mm was the largest among the separators investigated in this study, the dehydration of PEM and catalyst layer was smaller compared with the thinner separator thicknesses. It was also revealed that the impacts of separator thickness on distribution of gases, e.g. O2, H2O, and current density distribution became larger under higher temperature and lower RH conditions. This study also concluded that the tendency of temperature distribution matched those of O2, H2O and current density distributions.

The surface characterization of indium tin oxide (ITO) films was processed by oxygen (O2) plasma gas using a magnetron sputtering method of varying O2-plasma gas from 20 sccm to 100 sccm for potentially fostering in electronic devices applications on dye-sensitize solar cells (DSSC) in this work. In order to gain an outstanding performance rate with high-quality thin films, the affect of correlation between the electrical, optical, and morphology properties was significantly investigated. Clearly, the content of investigation exhibited that the films properties was changed by variation of the gas composition. These changes have contemporary relevance to the sputtering gas during the deposition process. To conclude, the greatest electrical properties was displayed by O2 -plasma gas flow rate of 20 sccm, which showed the lowest resistivity. In addition to this, the final products were practically fabricated to active layers for dye-sensitize solar cells (DSSC) applications. The highest efficiency of DSSC device was indicated of approximately 0.35% which was located by 40 sccm of the O2-plasma gas. Consequently, the study could be a possibility way of preparing ITO thin films with improved special properties of substantial applications for solar cells devices in the near future.

8-Hydroxydeoxyguanosine (8-OHdG) was the most widely used oxidative stress biomarker of the free radical-induced oxidative damage product of DNA, which may allow a premature assessment of various diseases. This paper designed a label-free, portable biosensor device to direct detect 8-OHdG by plasma coupled electrochemistry on transparent and conductive indium tin oxide (ITO) electrode. We reported a flexible printed ITO electrode made from particle-free silver and carbon inks. After inkjet printing, the working electrode was sequentially assembled by gold nanotriangles (AuNTAs) and platinum nanoparticles (PtNPs). This nanomaterial-modified portable biosensor showed excellent electrochemical performance for 8-OHdG detection from 10 μg/mL to 100 μg/mL by our self-developed constant voltage source integrated circuit system. This work demonstrated a portable biosensor for simultaneously integrating nanostructure, electroconductivity, and biocompatibility to construct advanced biosensors for oxidative damage biomarkers. The proposed nanomaterial modified ITO-based electrochemical portable device was a potential biosensor to approach 8-OHdG point-of-care testing (POCT) in various biological fluid samples, such as saliva and urine samples.

This study focuses on a biogas dry reforming to produce H2. Biogas contains CO2 of 40 vol% approximately, indicating that the efficiency of the power generation is reduced because of the smaller heating value compared with a natural gas. The authors have proposed the combination system consisting of biogas dry reforming reactor and solid oxide fuel cell (SOFC). Since a biogas dry reforming is an endothermic reaction, this study adopts a membrane reactor which can be operated by causing the non-equilibrium state with H2 separation from the reaction space. This study aims to clarify the impact of thickness of Pd/Cu membrane on the characteristics of the biogas dry reforming membrane reactor using Pd/Cu membrane and Ni/Cr catalyst. The impact of the operation temperature, the molar ratio of CH4:CO2 and the differential pressure between the reaction chamber and the sweep chamber on the characteristics of the biogas dry reforming membrane reactor using Pd/Cu membrane and Ni/Cr catalyst is examined changing the thickness of Pd/Cu membrane. As a result, the highest concentration of H2 is 122711 ppmV which is obtained in case of CH4:CO2 =1:1 at the reaction temperature of 600 ℃ and the differential pressure of 0 MPa using the Pd/Cu membrane whose thickness of 40 m.

Cancer-associated fibroblasts (CAFs) in the tumor microenvironment perform glycolysis to produce energy, i.e., ATP. Since the origin of CAFs is unidentified, it is not determined whether the intracellular metabolism transitions from oxidative phosphorylation (OXPHOS) to glycolysis when normal tissue fibroblasts differentiate into CAFs. In this study, we established an experimental system and induced the in vitro differentiation of mesenchymal stem cells (MSCs) to CAFs. Additionally, we performed metabolomic and RNA-sequencing analyses before and after differentiation to investigate changes in the intracellular metabolism. Consequently, we discovered that OXPHOS, which was the primary intracellular metabolism in MSCs, was reprogrammed to glycolysis. In addition, we identified CAF-specific metabolites that were expressed during this reprogramming and determined their presence in the pancreatic tumor tissues of mouse models. Thus, we conclude that normal tissue fibroblasts that differentiate into CAFs undergo a metabolic reprogramming from OXPHOS to glycolysis. Moreover, we identified the CAF-specific metabolites expressed during metabolic reprogramming as potential future biomarkers for pancreatic cancer.

Holographic projection is a simple projection because it enlarges or reduces reconstructed images without using a zoom lens. However, one major problem associated with this projection is the deterioration of image quality as the reconstructed image enlarges. In this paper, we propose a time-division holographic projection, in which the original image is divided into blocks and the holograms of each block are calculated. Using a digital micromirror device (DMD), the holograms were projected at high speed to obtain the entire reconstructed image. However, the holograms on the DMD need to be binarized, thereby causing uneven brightness between the divided blocks. We correct this by controlling the displaying time of each hologram. Additionally, combining both the proposed and noise reduction methods, the image quality of the reconstructed image was improved. Results from the simulation and optical reconstructions show we obtained a full-color reconstruction image with reduced noise and uneven brightness.

Highly sensitive multicomponent materials designed for the recognition of hazardous compounds request control over interfacial chemistry. The latter is key parameter in the construction of the sensing (macro)molecular architectures. In this work, multi-walled carbon nanotubes (in short, CNTs) were deposited on diazonium-modified flexible ITO electrodes prior to electropolymerization of pyrrole. This three step process, including diazonium electroreduction, deposition of CNTs and electropolymerization, provided adhesively bonded polypyrrole-wrapped CNT composite coatings on aminophenyl-modified flexible ITO sheets. The aminophenyl (AP) groups were attached to ITO by electroreduction of the in situ generated aminobenzenediazonium compound in aqueous, acidic medium. For the first time, polypyrrole (PPy) was electrodeposited in the presence of both benzenesulfonic acid (dopant) and ethylene glycol-bis(2-aminoethylether)-tetraacetic acid (EGTA) which acts as a chelator. The flexible electrodes were characterized by XPS, Raman and scanning electron microscopy (SEM) which provided strong supporting evidence for the wrapping of CNTs by the electrodeposited PPy. Indeed, the CNT average diameter increased from 182.6 nm to 274.8, 35.65.9 and 17520.1 after 1, 5 and 10 of electropolymerization of pyrrole. The PPy/CNT/NH2-ITO films generated by this strategy exhibit significantly improved stability and higher conductivity compared to a similar PPy coating without any embedded CNTs as assessed by from electrochemical impedance spectroscopy measurements. The potentiometric response was linear in the 10-83×10-7 mol.L-1 Pb(II) concentration range and the detection limit was 2.9×10-9 mol.L-1 at S/N=3. The EGTA was found to drastically improve selectivity for Pb(II) over Cu(II). To account for this improvement, density functional theory (DFT) was employed to calculate the EGTA-metal ion interaction energy which was found to be -374.6 and -116.4 kJ/mol for Pb(II) and Cu(II), respectively, considering solvation effects. This work demonstrates the power of a subtle combination of diazonium coupling agent, CNTs, chelators and conductive polymers to design high-performance electrochemical sensors for environmental applications.

The Arctic freshwater budget is critical for understanding the climate in the northern regions. However, the hydrology of the Arctic circumpolar tundra region (ACTR) and the largest pan-Arctic rivers are still not well understood. In the present paper, we analyze the spatiotemporal variations in terrestrial water storage (TWS) of the ACTR, including three of its largest pan-Arctic river basins (Lena, Mackenzie, Yukon), using monthly Gravity Recovery and Climate Experiment (GRACE) data from 2002 to 2016. Together with global land reanalysis, river runoff, and inundation extent area (IEA) data, we identify declining TWS trends throughout the ACTR that we attribute largely to increasing evapotranspiration driven by increasing summer air temperatures. In terms of regional changes, large and significant negative trends in TWS are observed mainly over the North American continent. At basin scale, we show that, in the Lena River basin, the autumnal TWS signal persists until the winter of the following year, while in the Mackenzie River basin, the TWS levels in the autumn and winter has no significant impact on the following year. As global warming is expected to be particularly significant in the northern regions, our results are important for understanding future TWS trends, with possible further decline.

Global differences in changes in the numbers of population-adjusted daily test-positive cases (NPDP) and deaths (NPDD) by COVID-19 were analyzed for 49 countries, including developed and developing countries. The changes as a proportion of national population were compared, adjusting by the beginning of test-positive cases increase (BPI) or deaths increase (BDI). Remarkable regional differences of more than 100 fold in NPDP and NPDD were observed. The trajectories of NPDD after BDI increased exponentially within 20 days in most countries. Machine learning analysis suggested that NPDD on 30 days after BDI was the highest in developed Western countries (1180 persons per hundred million), followed by countries in the Middle East (128), Latin America (97), and Asia (7). Furthermore, in Western countries with positive rates of the PCR test of less than 7.0%, the increase in NPDP was slowing-down two weeks after BPI, and subsequent NPDD was only 15% compared with those with higher positive rates, which suggested that the situation of testing might have affected the velocity of COVID-19 spread. The causes behind remarkable differences between regions possibly include genetic factors of inhabitants because distributions of the race and of the observed infection increasing rates were in good agreement globally.

Simple weir irrigation was recently introduced in rural areas of Zambia. This irrigation technique is based on gravity diversion of the river flow using simple weirs. This study was conducted between November 2022 to January 2023 in 3 northern region provinces (Luapula, Copperbelt, and North-western) of Zambia to perform a diagnostic assessment on simple weirs during the dry and the wet seasons. In this study, 15 single-line simple weirs were selected. The objective of the study is to assess the physical status, identify problems and extent, and estimate water diversion potential by each single-line weir. The findings of this study showed that 67% of weirs were in excellent status (recently maintained and repaired), and 26% of the weirs were partially damaged (leakages, decayed thatch grass). The study revealed that single-line weirs were able to raise a flood height of 0.1m at low flow and 0.5m at medium flow. It was found that single-line weirs in excellent condition diverted more than 90% of the river flow while poorly maintained weirs diverted below 45% of the river discharge. Based on the findings, Single-line weirs have the potential to assist small-scale farmers in accessing river water for irrigation purposes through diversion.

Recently, Indium Tin Oxide, a highly transparent, well conductive, and CMOS-compatible material, has been paying strong attention to the thermo-optic controlled silicon photonics industry because it allows a miniature of the gap between the core silicon and the heater, thus enabling reducing the electric power consumption and enhancing the switching speed. In this article, we propose an ultralow loss and small-size ITO microheater for the phase shift tuning. The designated microheater is manipulated in realizing a numerical co-design of compact and high bandwidth three-mode converter and three-mode selective router. Simulation results illustrate the 3-dB bandwidth for the three-mode converter and three-mode selective router as much as 100-nm and 40-nm during crosstalk under -25 dB, respectively. Besides, co-designed devices attain relatively large fabrication tolerances corresponding to width and height tolerances of ±50 nm and ±5 nm. In addition, the proposed devices consumed less than 90 mW total power consumption and took a fast switching time below 8 μs. Moreover, both two co-designs can be integrated into an estimated compact footprint of 8 μm2160 μm. Such excellent performances demonstrate the attractive potential of ITO as low-loss thermo-optic phase shifters and open an alternative way for enabling ultrafast and high-speed mode division multiplexing systems and very large-scale photonic integrated circuits.

Fiber-opening treatment of commingled yarns consisting of thermoplastic nylon fibers and carbon fibers could produce superior CFRTP, but few studies toward that end have been conducted. In this study, we investigated whether an open weave fabric consisting of commingled yarns made of carbon and nylon fibers could shorten the impregnation distance of resin to carbon fibers, and there are few reports on the design of fabrics by opening carbon fiber bundles consisting of commingled yarns. From this study, following are cleared. The impregnation speed of the nylon resin on the carbon fiber was very fast, less than 1 minute. As the molding time increased, the tensile strength and tensile fracture strain slightly decreased and the nylon resin deteriorated. The effects of molding time on flexural strength, flexural modulus, and flexural fracture strain were negligible. From the cross-sectional observation conducted to confirm the impregnation state of the matrix resin, no voids were observed in the molded products regardless of molding time or molding pressure, indicating that resin impregnation into the carbon fiber bundle of the open-fiber mixed yarn fabric was completed at a molding pressure of 5 MPa and a molding time of 5 min.

Bottom-up synthesis of porous NiMo alloy reduced by NiMoO₄ nanofibers was systematically investigated to fabricate non-noble metal porous electrodes for hydrogen production. The different annealing temperatures of NiMoO₄ nanofibers under hydrogen atmosphere reveal that the 950 °C annealing temperature is a key to produce bicontinuous porous NiMo alloy without oxide phases. The porous NiMo alloy as cathodes in electrical water splitting demonstrates not only almost identical catalytic activity with commercial Pt/C in 1.0 M KOH solution, but also superb stability for 12 days at an electrode potential of −200 mV (v.s. RHE).

This study aimed to investigate the impact of incorporating indium tin oxide (ITO) nan particles (NPs) with zinc oxide (ZnO) NPs into flexible dye-sensitized solar cells (FDSSCs). ZnO and ITO NPs were separately prepared using the sol-gel method, followed by hybridization of ZnO NP/ITO NP and characterization using techniques such as TEM, SEM, XRD, UV-Vis spectros-copy, PL spectroscopy and cyclic voltammetry (CV). TEM analysis showed hexagonal struc-tures and small sphere-like nanoparticles with mean diameters of 15.22 ± 11 nm for ZnO NPs and 14.54 ± 16 nm for ZnO NPs/ITO NPs. SEM images revealed uniform dispersion and smooth surface morphology, while XRD confirmed the crystalline nature of both ZnO and hybrid NPs, indicating specific crystallographic planes with consistent sizes. UV-Vis spectroscopy demonstrated a redshift in wavelength upon adding ITO NPs, suggesting an impact on the bandgap of ZnO NPs. PL spectra exhibited a broad visible emission peak at 535 nm. These findings enhance our understanding of the optical behavior and interaction between ITO and ZnO NPs in hybrid nanostructures. The study concluded that the ITO NPs improve FDSSC performance by enhancing charge separation and transport, leading to increased photocurrent production, with the characterization techniques providing valuable insights for future research and applications.

The key to the practical application of organometal–halide–crystals perovskite solar cells (PSCs) is to achieve thermal stability through robust encapsulation. This paper presents a method to significantly extend the thermal stability lifetime of perovskite solar cells to over 5,000 h at 85 °C by demonstrating an optimal combination of encapsulation methods and perovskite composition for carbon–based multiporous–layered–electrode (MPLE)–PSCs. We fabricated the four types of MPLE-PSCs using two encapsulation structures (over– and side–sealing with thermoplastic resin films) and two perovskite compositions ((5–AVA)x(methylammonium (MA))1–xPbI3 and (formamidinium (FA))0.9Cs0.1PbI3), and analyzed the 85 ºC thermal stability followed by ISOS–D–2 protocol. Without encapsulation, FA0.9Cs0.1PbI3 exhibited higher thermal stability than (5–AVA)x(MA)1–xPbI3. However, encapsulation reversed the phenomenon (that of (5–AVA)x(MA)1–xPbI3 became stronger). The combination of (5–AVA)x(MA)1–xPbI3 perovskite absorber and over–sealing encapsulation effectively suppressed the thermal degradation, resulting in the PCE value at 91.2% of the initial value after 5,072 h. On the other hand, another combination (side–sealing on (5–AVA)x(MA)1–xPbI3, over– and side–sealing on FA0.9Cs0.1PbI3) resulted in decreased stability. The FA–based perovskite was decomposed for these degradation mechanisms by the condensation reaction between FA and carbon. For side–sealing, the space between the cell and the encapsulant was estimated to contain approximately 1,260,000 times more H2O than in over–sealing, which catalyzed the degradation of the perovskite crystal. Our results demonstrate that MA–based PSCs, which are generally considered to be thermally sensitive, can significantly extend their thermal stability after the proper encapsulation. Therefore, we emphasize that finding the appropriate combination of encapsulation technique and perovskite composition is quite important to achieve further device stability.

Objective: This study examined the impact of Japan’s state of emergency on trends in diabetes care during the coronavirus disease 2019 (COVID-19) pandemic. Design: A descriptive and retrospective study. Setting: Showa University Hospital, Japan. Participants: Patients with diabetes who received medical treatment from 2018 to 2020. Determinants of interest: Number of patients with diabetes visiting the hospital per week. To examine the impact of the Japan’s state of emergency, the number hospital visiting by patients with diabetes was summarized from 28 weeks of data, from calendar week 8 to week 35, for each year. Results: Compared with the mean of 2018 and 2019, no significant difference was found between the three periods (before, during, and after the state of emergency). However, the numbers of patients from both inside and outside Tokyo increased at 7 weeks after the state of emergency was lifted. Conclusions: A significant increase in the numbers of patients with diabetes was seen compared with the same period in 2018 and 2019, suggesting that the state of emergency may have hindered diabetes care. Therefore, patients with diabetes should be followed up continuous of diabetes care while keeping a close eye on measures.

In recent years, more attention has been paid to behavioral problems in children. However, for the most part, risk factors for these problems have yet to be determined. The current prebirth cohort study investigated the relationship between maternal calcium consumption during pregnancy and behavioral problems in five-year-old Japanese children. Subjects were 1199 mother-child pairs. Dietary intake was assessed using a diet history questionnaire. Emotional problems, conduct problems, hyperactivity problems, and peer problems were assessed using the Strengths and Difficulties Questionnaire. Logistic regression analysis was conducted to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for four behavioral problems under study according to the quartile of calcium intake, with the lowest quartile as the reference. Adjustment was made for maternal age, gestation at baseline, region of residence at baseline, number of children at baseline, maternal and paternal education, household income, maternal depressive symptoms during pregnancy, maternal alcohol intake during pregnancy, maternal smoking during pregnancy, child's age, child's birth weight, postnatal secondhand smoke exposure at home during the first year of life, and breastfeeding duration. Higher maternal calcium intake during pregnancy was independently associated with a decreased risk of childhood emotional and hyperactivity problems; the adjusted ORs between extreme quartiles (95% CIs, P for trend) were 0.46 (0.27–0.79, 0.01) and 0.60 (0.37–0.97, 0.046). No such inverse associations were observed for childhood conduct problems or peer problems. Maternal calcium intake during pregnancy may decrease the risk of childhood emotional and hyperactivity problems.

With demand for the long-term continued use of existing building facilities, structural health monitoring and damage detection are attracting interest from society. Sensors of various types have been practically applied in the industry to satisfy this need. Among the sensors, piezoelectric sensors are an extremely promising technology by virtue of their cost advantages and durability. Although they have been used in aerospace and civil engineering, their application for building engineering remains limited. Remarkably, recent catastrophic seismic events have further rein-forced the necessity of rapid damage detection and quick judgment about the safe use of facilities. Faced with these circumstances, this study was conducted to assess the applicability of piezoelectric sensors to evaluate building components. Specifically, this study emphasizes structural damage caused by earthquakes. After first applying to cyclic loading tests to composite beam component specimens and steel frame subassemblies with a folded roof plate, the prospective damage posi-tions were also found using finite element analysis. Crack propagation and buckling locations were predicted adequately. The piezoelectric sensors provided output when the concrete slab showed tensile cracks, or when the folded roof plate experienced local buckling. Furthermore, damage expansion and progression were detected multiple times during loading tests. Results showed that the piezoelectric sensors can detect structural damage of building components, demonstrating their potential for use in inexpensive and stable monitoring systems.

Applied electrostatic engineering can be used to construct greenhouses that prevent entry of insect pests. Two types of electric field screen were used to exclude pests from the greenhouse: single- and double-charged dipolar electric field screens (S- and D-screen, respectively). The S-screen consisted of iron insulated conductor wires (ICWs) arrayed in parallel (ICW-layer), a grounded metal net on either side of the ICW-layer, and a direct current voltage generator. S-screens were attached to the side windows of the greenhouse to repel whiteflies (Bemisia tabaci) that approached the nets. The D-screen was installed in a small anteroom at the greenhouse entrance to capture whiteflies entering through it. The ICW-layers of the D-screen were oppositely charged with equal voltages and arrayed alternately, and an insulator board or grounded metal net was placed on one side of the ICW-layer. The ICW-layers captured whiteflies entering the electric field of the double-charged dipolar electric field. Three screens equipped with yellow or gray boards or a grounded metal net were installed in the anteroom based on the airflow inside the room, as most whiteflies were brought in by air when the door was opened. Two D-screens with boards were useful for directing the airflow toward the wall with the netted D-screen. This screen eliminated the insects and the pest-free air was circulated inside the greenhouse. The D-screen with the yellow board attracted the whiteflies and was effective for trapping them when there was no wind. Our method kept the greenhouse pest-free throughout the entire period of tomato (Solanum lycopersicum) cultivation.

Repetitive transcranial magnetic stimulation (rTMS) with intensive occupational therapy improves upper limb motor paralysis and activities of daily living after stroke; however, amount of improvement according to paralysis severity remains unverified. Target activities for daily living using patients’ upper limb functions can be established by predicting the amount of change after treatment for each severity level of upper limb motor paralysis and further aid practice planning. This study estimated post-treatment score changes for each severity level of motor paralysis (no, poor, limited, notable, and full) stratified according to Action Research Arm Test (ARAT) scores before combined rTMS and intensive occupational therapy. Severity of motor paralysis was the fixed factor for analysis of covariance, delta (post-pre) of the scores was the dependent variable. Ordinal logistic regression analysis was used to compare changes in ARAT subscores in patients, divided according to paralysis severity before treatment. A multicenter retrospective cohort dataset analyzed 907 patients with stroke hemiplegia. Largest treatment-related changes in scores were observed in the Limited recovery group for upper limb motor paralysis and Full recovery group for quality-of-life activities using paralyzed upper limb. These results will help predict treatment effects and determine exercises and goal movements for occupational therapy after rTMS.

Contrast-enhanced ultrasonography (CEUS) is useful for evaluation of the hemodynamics of hepatic tumors and surrounding he-patic parenchyma in real time. CEUS with intravenous contrast administration is well established for evaluation of hepatocellular carcinoma (HCC). On the other hand, intra-arterial (transcatheter) CEUS (IAUS) is an emerging technique that allows more selective evaluation of the arterial supply to the tumor. IAUS was performed by administration of Sonazoid® through the microcatheter and imaging of the area of the target lesion with a dedicated, contrast-specific technique. Sonazoid® (0.5 ml diluted with 49.5 ml of distilled water) was used as the contrast medium in IAUS. The diluted Sonazoid® was introduced into the feeding artery by in-termittent injection of 0.3-1.0 ml through a microcatheter placed in the artery and flushing with saline at the same flow rate. We report the three cases in which IAUS was useful in transarterial chemoembolization (TACE) for HCC. Two cases were performed TACE for hepatic metastasis. In any cases, plain computed tomography (CT) after TACE showed accumulation of Lipiodol® only in the metastases. One case was suspected having HCC rupture and urgent abdominal angiography was performed. IAUS was performed frequently to reduce the amount of iodinated contrast agent as much as possible because of renal failure. Concomitant use of IAUS enabled reduction of the amount of contrast agent.

Rett syndrome (RTT), a neurodevelopmental disorder, is mainly caused by mutations in methyl CpG-binding protein 2 (MECP2), which alter the functions of domains to either bind to methylated DNA or interact with a transcriptional co-repressor complex. It has been established that alterations in cyclin-dependent kinase-like 5 (CDKL5) or forkhead box protein G1 (FOXG1) correspond to distinct neurodevelopmental disorders, given that a series of studies have indicated that RTT is also caused by alterations in either one of these genes. We tried to elucidate RTT through evolution and structure assessment of MeCP2, CDKL5, and FOXG1, by focusing on their binding partners and disordered structures. Here, we provide insight into the similarities of the FOXG1 and MECP2 binding partners evolution and function. On the other hand, we suggest that CDKL5 could be a potential candidate for a classical RTT treatment, particularly based on its disordered structure that spans after the catalytic domain to the C-terminus, which shows abundant linear motifs that can bind to molecules with divergent structures of similar affinity. Additionally, we provide insight into the relationship between disordered structure and disease.

Glycans are involved in various metabolic processes via the functions of glycosyltransferases and glycoside hydrolases. Analysing the evolution of these enzymes is essential for improving the understanding of glycan metabolism and function. Based on our previous study of glycosyltransferases, we performed a genome-wide analysis of whole human glycoside hydrolases using the UniProt, BRENDA, CAZy, and KEGG databases. Using cluster analysis, 319 human glycoside hydrolases were classified into four clusters based on their similarity to enzymes conserved in chordates or metazoans (Class 1), metazoans (Class 2), metazoans and plants (Class 3), and eukaryotes (Class 4). The eukaryote and metazoan clusters included N- and O-glycoside hydrolases, respectively. The significant abundance of disordered regions within the most conserved cluster indicated a role for disordered regions in the evolution of glycoside hydrolases. These results suggest that the biological diversity of multicellular organisms is related to the acquisition of N- and O-linked glycans.

Radiation therapy is employed in treating various cancer types. However, depending on the type and stage of cancer, its benefits can be limited, and it may cause serious side effects that detrimentally affect the quality of life (QOL) for the patient. Preventing the side effects of radiation therapy can enhance the response to cancer treatment and improve the patient’s QOL. Independently, vitamin C and hydrogen have demonstrated potential in reducing the side effects of anticancer drugs and radiation therapy. Furthermore, both have been postulated to possess direct anticancer properties. However, the effects of their combined therapy remain underexplored. This study investigates the hypothesis that combining vitamin C and hydrogen efficiently prevents radiation-induced injuries. Survival rates were investigated in cancer cell lines (MDA-MB231 and GL261) and normal cells (HUVEC) treated with hydrogen, vitamin C and irradiation. Apoptosis was assessed using the FLICA test, and EMT gene expression was elucidated via the qPCR technique. In the normal cell line, the introduction of vitamin C and hydrogen to the culture medium boosted survival rates, exhibiting a radioprotective effect upon irradiation. In contrast, cancer cells showed a decreased survival rate with the introduction of vitamin C and hydrogen, which was further diminished with irradiation. Treated cancer cells showed signs of apoptosis. Caspase activity in viable cells was reduced by the combination treatment with vitamin C and hydrogen. Additionally, glioblastoma cells treated with this combination showed reduced EMT gene expression. This study reveals that a combined therapy of hydrogen and vitamin C offers radioprotective effects on normal cells and exerts direct anticancer effects on cancer cells, while also amplifying the anticancer effects of radiation. Importantly, this combined therapy attenuated the radiation-induced EMT signature in the GL261 murine glioma cell line, suggesting potential in diminishing treatment resistance and tumor invasion.

Rett syndrome (RTT) is mainly caused by mutations in methyl CpG-binding protein 2, cyclin-dependent kinase-like 5, or forkhead box protein G1. These RTT-causing proteins harbor an intrinsically disordered region (IDR) whose conformation exhibits spatiotemporal heterogeneity, which not only confer versatility to the protein, but also implicates them in diseases. The IDR generally evolves more rapidly than an ordered structure. In this study, we examined the relationship between pathogenic RTT-associated point mutations in RTT-causing proteins and the evolutionary dynamics of sequence features including structural order–disorder, phosphorylation sites, and evolutionary rates. We also analyzed the molecular properties and evolution of proteins that interact with RTT-causing proteins in terms of phylogenetic profiles, tissue specificity, subcellular localization, expression level, and functions. The results indicate that constrained IDRs may function by forming contacts with other regions in the protein sequence causing pathogenic missense mutations likely to arise in the rapidly evolving IDR and affect molecular networks, leading to disease. The results also provide novel insights into the genetic basis for RTT and the evolution of the neocortex in higher vertebrates.

Most of the phase change materials (PCMs) have been limited to use as functional additions or sealed in containers, and extra auxiliary equipment or supporting matrix is needed. The emergence of 3D printing technique has dramatically advanced the developments of materials and simplified production processes. This study focuses on a novel strategy to model thermal energy storage crystalline gels with three-dimensional architecture directly from liquid resin without supporting materials through light-induced polymerization 3D printing technique. A mask-projection stereolithography printer was used to measure the 3D printing test, and the printable characters of crystalline thermal energy storage P(SA-DMAA) gels with different molar ratios were evaluated. For the P(SA-DMMA) gels with small fraction of SA, the 3D fabrication was realized with higher printing precision both on mili- and micro-meter scales. As a comparison of 3D printed samples, P(SA-DMAA) gels made by other two methods, post-UV curing treatment after 3D printing and UV curing using conventional mold, were prepared. The 3D printed P(SA-DMAA) gels shown high crystallinity. Post–UV curing treatment was beneficial to full curing of 3D printed gels, but did not lead to the further improvement of crystal structure to get higher crystallinity. The P(SA-DMAA) crystalline gel having the highest energy storage enthalpy that reached 69.6 J·g⁻¹ was developed. Its good thermoregulation property in the temperature range from 25 to 40 °C was proved. The P(SA-DMAA) gels are feasible for practical applications as one kind of 3D printing material with thermal energy storage and thermoregulation functionality.

The concentration of cerebrospinal fluid total protein (CSF-TP) is important for the diagnosis of neurological emergencies. Recently, some Western studies have shown that the current upper reference limit of CSF-TP is quite low for older patients. However, little is reported about the concentration of CSF-TP in older Asian population. In this study, we retrospectively analyzed the CSF-TP concentrations in Japanese healthy older volunteers. CSF samples in 69 healthy Japanese volunteers (age range: 55–73 years) were collected by lumbar puncture, and the data of CSF were retrospectively analyzed. The mean (standard deviation) CSF-TP was 41.7 (12.3) mg/dL. The older group (≥ 65 years old) had higher CSF-TP concentration than the younger group (55–64 years old). The 2.5th percentile and 97.5th percentile of CSF-TP were estimated as 22.5 and 73.2 mg/dL, respectively, which were higher than the current reference range in Japan (10–40 mg/dL).

Background: Intradialytic hypotension (IDH) is a critical pathological condition associated with all−cause mortality in patients undergoing hemodialysis (HD). However, few studies have investigated IDH-related changes in hepatic and cerebral regional tissue oxygen saturation (rSO2). This study investigated IDH-induced changes in hepatic and cerebral rSO2. Methods: Hepatic and cerebral rSO2 during HD were measured using an INVOS 5100C oxygen saturation monitor, and their percentage (%) changes during IDH development were analyzed. Ninety-one patients undergoing HD were investigated, including 20 with IDH development. Results: In patients with IDH, % changes in hepatic and cerebral rSO2 decreased at IDH onset. Additionally, the % change in hepatic rSO2 was significantly larger than those in cerebral rSO2 (P < 0.001). In patients without IDH, no significant differences were found between the % changes in hepatic and cerebral rSO2 at time of the lowest systolic blood pressure during HD. Multivariable linear regression analysis showed that the difference between the % change in cerebral and hepatic rSO2 was significantly associated with IDH development (P < 0.001) and ultrafiltration rate (P = 0.010). Conclusion: Hepatic and cerebral rSO2 significantly decreased in IDH development and hepatic rSO2 was more largely decreased than cerebral rSO2 at IDH onset.

USP21, a member of the ubiquitin protease family, plays a vital role in various biological functions. However, the effects of USP21 dysfunction have yet to be fully understood. Here, we generated Usp21 knockout (KO) mice and conducted microarray to identify genes that Usp21 regulates. Its results raised several genes based on their biological characteristics, and RT-qPCR confirmed their expression. KO mice exhibited significant elevations in the expression of the genes Fabp7 and Nlrc5, which play a role in lipid metabolisms, compared to wild-type mice. Blood tests showed no impairment of liver function but did reveal elevated levels of total cholesterol and free fatty acids in KO mice compared to wild-type mice. These data suggest that Usp21 may play roles in lipid metabolism associated with Fabp7 and Nlrc5. To clarify the involvement of USP21 in human hypercholesterolemia, we examined single nucleotide polymorphisms (SNPs) around USP21 in non-hypercholesterolemic and hypercholesterolemic outpatients. We found that the rs11421 SNP downstream of USP21 was associated with hypercholesterolemia. These data suggest that USP21 plays a role in mice and human lipid metabolism and that its polymorphism may be a diagnostic marker for human hypercholesterolemia.

It is known that eumelanin (EM) is photoprotective while pheomelanin (PM) is phototoxic. A recent study using a mouse model demonstrated that PM produces reactive oxygen species (ROS) that cause DNA damage and eventually lead to melanomagenesis. A biochemical study showed that PM possesses a pro-oxidant activity. PM consists of benzothiazine (BT) and benzothiazole (BZ) moieties, the former being transformed to the latter by heat or light. In this study, we compared the effects of ultraviolet A (UVA) irradiation using synthetic PMs with different BT to BZ ratios and using various coat color mouse hairs. We found that UVA irradiation of BZ-PM increased glutathione (GSH) consumption and generated more H₂O₂ than UVA irradiation of BT-PM. Non-irradiated controls did not exhibit strong pro-oxidant activities. Upon UVA irradiation, yellow mouse hairs oxidized GSH and produced H₂O₂ faster than black or albino mouse hairs. Next, to examine the mechanism of the pro-oxidant activity of BT-PM and BZ-PM, we examined the pro-oxidant activities of 7-(2-amino-2-carboxyethyl)-dihydro-1,4-benzothiazine-3-carboxylic acid (DHBTCA) and 6-(2-amino-2-carboxyethyl)-4-hydroxybenzothiazole (BZ-AA) as BT and BZ monomers, respectively. Their pro-oxidant activities were similar, but a large difference was seen in the effects of ROS scavengers, which suggests that the redox reactions may proceed via singlet oxygen in BZ-AA and via superoxide anions in DHBTCA. These results show that UVA enhances the pro-oxidant activity of PM, in particular BZ-PM.

The effectiveness of simple weirs and the ability of rural farmers to construct durable weirs are still areas of concern in rural areas in Zambia. The objective of this study is to investigate the factors contributing to the varying levels of durability of the simple weir structures used for the diversion of river flows. This study was conducted in 5 districts where 33 SWs located in similar geographical zones were analyzed for their longevity. The research delved into catchment and climatic variables, and the social and psychological perception of simple weirs. The study conducted interviews with key informants who were familiar with the use of SWs in 5 districts in Muchinga provinces between 26 December 2023 and 15 January 2024 using semi-structured questions. The findings of this study indicated that simple weirs constructed on relatively square-shaped catchments and narrow-shaped catchment areas were less vulnerable to damage and easy to operate and maintain. The study also found that climatic factors such as storm rainfall events had little impact on the operation and maintenance of these weirs in Muchinga province, as most sites are in the rainfall shadow while farmers` views about the structures varied from site to site. Overly, planning is necessary for implementing small or large irrigation structures.

Many agonists for the estrogen receptor are known to disrupt endocrine functioning. We have developed a computational model that predicts agonists for the estrogen receptor ligand-binding domain in an assay system. Our model was entered into the Tox21 Data Challenge 2014, a computational toxicology competition organized by the National Center for Advancing Translational Sciences. This competition aims to find high-performance predictive models for various adverse-outcome pathways, including the estrogen receptor. Our predictive model, which is based on the random forest method, delivered the best performance in its competition category. In the current study, the predictive performance of the random forest models was improved by strictly adjusting the hyperparameters to avoid overfitting. The random forest models were optimized from 4,000 descriptors simultaneously applied to 10,000 activity assay results for the estrogen receptor ligand-binding domain, which have been measured and compiled by Tox21. At this time, our model delivers the highest predictive power on estrogen receptor agonists in the world. Furthermore, analysis of the optimized model revealed some important features of the agonists, such as the number of hydroxyl groups in the molecules.

Background: Primary central nervous system lymphomas (PCNSLs) are sensitive to chemotherapy. Standard treatment is high-dose methotrexate (MTX)-based chemotherapy. There are no reports of successful treatment of acute uric acid nephropathy with rasburicase after MTX administration in PCNSL. Case presentation: A 54-year-old man with a history of gout presented with character change and memory loss. MRI showed a large, enhancing mass spanning the bilateral frontal lobes and right temporal lobe. After endoscopic biopsy, MTX, procarbazine and vincristine (MPV) regimen was initiated for treatment of PCNSL. After initiation of chemotherapy, the patient suffered from a gout attack and blood examination revealed acute renal failure (ARF) and hyperuricemia. The considered causes of ARF included MTX toxicity and acute urid acid nephropathy. Since a good response to chemotherapy was observed, the latter was assumed. After improvement of renal function, MTX was resumed, initiating rasburicase for control of hyperuricemia. A complete response was obtained after induction chemotherapy. Hyperuricemia was controlled with rasburicase and renal function was preserved. Conclusions: Acute uric acid nephropathy should be considered when ARF occurs after initiation of MTX in PCNSL. For newly diagnosed PCNSL patients with large tumors or hyperuricemia, upfront usage of rasburicase should be considered to prevent it.

In this study, Plasma-Activated Water (PAW) was synthesized using a coaxial Dielectric Barrier Discharge (DBD) reactor, benefiting from the elevated capacity of air-flow-assisted DBD discharges to enhance nitrogen-based species concentration. By manipulating operational parameters, including gas flow rate, activation time, and DI water volume, we achieved significant concentrations of Reactive Oxygen and Nitrogen Species (RONS). As a result, the PAW obtained displayed pronounced physicochemical attributes: a pH of 2.06, an ORP of 275mV, conductivity of 3mS/cm, and TDS of 1200 mg/L. A pivotal aspect of this research was the evaluation of the reactor's efficiency, as indicated by metrics like the specific input energy and ozone efficiency yield. The antimicrobial potential of the PAW was also assessed against pathogenic microbes, with remarkable reductions in viability for both Staphylococcus aureus and Escherichia coli (99.99%) and a more moderate decrease for Candida albicans (37%). These findings underscore the capability of the coaxial DBD reactor in crafting high-quality PAW with significant antimicrobial properties, necessitating further studies to validate its broad-spectrum and safe application.

Background; Programmed death-1 (PD-1) and PD-1 ligand 1 (PD-L1) are target molecules for immunotherapy in non-small cell lung cancer. PD-L1 is expressed not only in cancer cells, but also on macrophages, and has been suggested to contribute to macrophage-mediated immune suppression. Methods; Clinical significance of PD-L1 expression on macrophages in human lung adenocarcinoma was examined. The mechanisms of PD-L1 overexpression on macrophages were investigated by means of cell culture studies. Results; High PD-L1 expression on macrophages was correlated with the presence of EGFR mutation, a lower cancer grade, and a shorter cancer-specific overall survival. In an in vitro study using lung cancer cell lines and human monocyte-derived macrophages, the conditioned medium from cancer cells was found to up-regulate PD-L1 expression on macrophages via STAT3 activation, and a cytokine array revealed that granulocyte-macrophage colony-stimulating factor (GM-CSF) was a candidate factor that induced PD-L1 expression. Culture studies using recombinant GM-CSF, neutralizing antibody, and inhibitors indicated that PD-L1 overexpression was induced via STAT3 activation by GM-CSF derived from cancer cells. Conclusions; PD-L1 overexpression on macrophages via the GM-CSF/STAT3 pathway was suggested to promote cancer progression in lung adenocarcinoma. Cancer cell-derived GM-CSF might be a promising target for anti-cancer therapy.

Transposable elements (TEs) are highly abundant in plant genomes. Environmental stress is one of the critical stimuli that activate TEs. We analyzed a heat-activated retrotransposon named ONSEN in cruciferous vegetables. The multiple copies of ONSEN-like elements (OLEs) were found in all the cruciferous vegetables that were analyzed. The copy number of OLE was abundant in Brassica oleracea, which includes cabbage, cauliflower, broccoli, Brussels sprout, and kale. Phylogenic analysis demonstrated that some OLEs transposed after the allopolyploidization of parental Brassica species. Furthermore, we found that the increasing number of OLEs in B. oleracea appeared to be induced transpositional silencing by epigenetic regulation, including DNA methylation. The results of this study would be relevant to the understanding of evolutionary adaptations to thermal environmental stress in different species.

The risk of gastric cancer (GC) declines after Helicobacter pylori (H. pylori) eradication and long-term aspirin use. We evaluated the effects of H. pylori eradication (Cohort 1) and aspirin use (Cohort 2) on the methylation of microRNAs (miRNAs) such as miR-34c, miR-124a-3, miR-129-2, and miR-137 in the gastric mucosa with and without GC, i.e., atrophic mucosa (AM) and intestinal metaplasia (IM). DNA was isolated from AM and IM separately using laser caption microdissection. In Cohort 1, H. pylori eradication was associated with a significant reduction of miR-124a-3 methylation only in AM, but not in IM. miR-129-2 methylation in AM may be a surrogate marker of GC in H. pylori-infected patients. In Cohort 2, aspirin did not reverse miRNA methylation in either AM or IM irrespective of H. pylori infection. miR-129-2 methylation in AM was an independent predictive marker of GC in H. pylori-infected but not -eradicated patients. These results indicate that H. pylori eradication and aspirin use were less effective in improving methylation in IM compared with AM; thus, these interventions are recommended at an early stage prior to the development of IM to prevent GC development.

Many anti-tumor effects of group-specific component-derived macrophage-activating factors (GcMAFs) have been reported; however, the specific mechanisms remain unclear. Controlling tumor-associated macrophages (TAMs) in the tumor microenvironment is essential for cancer treatment. This study assessed the role of GcMAF in macrophage activation, elucidated the mechanisms by which it exerts its anti-tumor effects, and determined its effects on TAMs in the tumor microenvironment. GcMAF-stimulated RAW264.7 macrophages and EMT6 breast tumor cells were co-cultured in a 0.4-µm pore cell culture insert, and gene and protein expression and cell viability were evaluated. DNA microarray analysis of GcMAF-stimulated RAW264.7 cells was conducted. The induction of M2 RAW264.7 cells by interleukin (IL)-4 and IL-13 was analyzed. GcMAF stimulation increased the tumor necrosis factor-α and inducible nitric oxide synthase mRNA and protein levels in RAW264.7 cells but decreased the viability of co-cultured EMT6 cells. These results were confirmed in the M2 RAW264M2.7 cells, suggesting that GcMAF exerts anti-tumor effects by inducing the differentiation of macrophages into the M1 type and reprogramming M2 macrophages to the M1 type. The anti-tumor activity of GcMAF via M2-to-M1 macrophage reprogramming could aid in developing novel cancer immunotherapies.

Small cell lung cancer (SCLC) and large cell neuroendocrine carcinoma (LCNEC) have recently been grouped as lung neuroendocrine carcinomas (NECs). Because these lung NECs are clinically malignant and their treatment strategies differ from those of non-SCLC, the quality of diagnosis has a significant prognostic impact. The diagnosis of LCNEC requires positive immunohistochemical staining with chromogranin A, synaptophysin, and CD56, along with morphological diagnosis, and insulinoma-associated protein 1 (INSM1) has been proposed as an additional marker but sometimes experience difficulty in making the diagnosis. We investigated Musashi-1 as a novel immunohistochemical marker in 42 patients with SCLCs and 44 with LCNECs who underwent lung resection between 1998 and 2020 at our institution. We found Musashi-1 expression in 41 (98%) of 42 SCLCs and 40 (90%) of 44 LCNECs. These findings were similar to CD56 expression and superior to synaptophysin, chromogranin A, and INSM1. Musashi-1 also tended to show more diffuse and intense staining, especially in LCNEC, with more cases staining &gt;10% than any other existing markers (Musashi-1, 77%; INSM1, 45%; chromogranin A, 34%; synaptophysin, 41%; and CD56, 66%). In conclusion, we identified Musashi-1 as a novel immunohistochemical staining marker to aid in the diagnosis of lung NEC.

Inflammatory processes play major roles in carcinogenesis and progression of hepatocellular carcinoma (HCC) derived from non-alcoholic steatohepatitis (NASH). But there are no therapies for NASH related HCC, especially focusing on these critical steps. Previous studies reported that farnesyltransferase inhibitors (FTIs) have anti-inflammatory and anti-tumor effects. However, the influence of FTIs on NASH-related HCC has not been elucidated. In HCC cell lines, HepG2, Hep3B, and Huh-7, we confirmed expression of hypoxia-inducible factor (HIF)-1α, an accelerator of tumor aggressiveness and the inflammatory response. We established NASH-related HCC models under inflammation and free fatty acid burden and confirmed that HIF-1α expression was increased under both conditions. Tipifarnib, which is an FTI, strongly suppressed increased HIF-1α, inhibited cell proliferation, and induced apoptosis. Simultaneously, intracellular interleukin-6 as an inflammation marker was increased under both conditions and significantly suppressed by tipifarnib. Additionally, tipifarnib suppressed expression of phosphorylated nuclear factor-κB and transforming growth factor-β. Finally, in a NASH-related HCC mouse model burdened with diethylnitrosamine and a high fat diet, tipifarnib significantly reduced tumor nodule formation in association with decreased serum interleukin-6. In conclusion, tipifarnib has anti-tumor and anti-inflammatory effects in a NASH-related HCC model and may be a promising new agent to treat this disease.

Soil conditions is a major aspect of interest for farmers due to the knowing of the physicochemical properties of the same can help with any necessary restoration of soil that guarantees the quality and the production of their crop. However, technology and analysis of the soil become of difficult access mainly in developing countries, by which the present paper shows the development of a system thought to estimate physicochemical variables of soils growing sugar cane through studies of spectroscopy. Its characteristic is that it is a portable system, with low cost, easy to use and can estimate physicochemical variables in-situ with the objective of knowing the degree of degradation present in the soil and through this help the farmers define possible strategies to restore it. The device uses the frequency response of the soil determining values of magnitude and phase, which are used by algorithms of artificial intelligence capable of getting an estimation of the physicochemical properties. The obtained results show errors below 8% in the estimation of the variables compared to the analysis results of the soil at laboratories.

The emergence of acquired resistance to EGFR-TKIs is almost inevitable even after a remarkable clinical response. Secondary mutations such as T790M and C797S are responsible for the resistance to 1st/2nd generation (1/2G) TKIs and 3G TKIs, respectively. To overcome both the T790M and C797S mutations, novel 4G EGFR-TKIs are now under early clinical development. In this study, we evaluated the efficacy of a 4G EGFR-TKI in the treatment of lung cancer with EGFR mutation as well as explored resistance mechanisms to a 4G TKI. First, we compared the efficacies of seven TKIs including a 4G TKI, BI4020, against Ba/F3 cell models that simulate resistant tumors after frontline osimertinib treatment failure because of a secondary mutation. We also established acquired re-sistant cells to BI4020 by chronic drug exposure. Ba/F3 cells with an osimertinib-resistant secondary mutation were refractory to all 3G TKIs tested (alflutinib, lazertinib, rezivertinib, almonertinib, and befotertinib). BI4020 inhibited the growth of C797S-positive cells; however it was not effective against L718Q-positive cells. Erlotinib was active against all Ba/F3 cells tested. In the analysis of resistance mechanisms of BI4020 resistant (BIR) cells, none harbored secondary EGFR mutations. HCC827BIR cells had MET gene amplification and were sensitive to a combination of capmatinib (MET-TKI) and BI4020. HCC4006BIR and H1975BIR cells exhibited epithelial to mesenchymal transition. This study suggests that erlotinib may be more suitable than 4G TKIs to overcome sec-ondary mutations after front-line osimertinib. We found that off-target mechanisms that cause re-sistance to earlier generation TKIs will also cause resistance to 4G TKIs.

Study design : Technical note. Objectives: To present a new spinal shortening technique for tethered cord syndrome. Background : Tethered cord syndrome (TCS) is a debilitating condition of progressive neurological decline. Surgical detethering for TCS is a gold standard. However, symptomatic retethering of TCS has been reported in 5%–50% of patients after initial release. To solve this problem, posterior spinal shortening osteotomy has been reported. This technique has risks of massive blood loss and neurological deterioration. The authors hereby report a new safe spinal shortening technique for tethered cord syndrome. Materials and Methods : A 31-year-old man with gait disturbance was referred to our hospital. After the delivery, he underwent surgical untethering of spinal cord in another hospital. He had hyperreflexia of Achilles tendon reflex and muscle weakness of bilateral legs (MMT 3-4). He also had urinary and bowel incontinence, and total sensory loss below L5.Anteroposterior lumbar radiogram indicates partial laminectomy of L3 and L4. Lumbar MRI showed retethering of spinal cord. Results: He underwent new spinal shortening technique for tethered cord syndrome under the guidance of O-arm navigation. First, from anterior approach disectomy from T12 to L3 was performed. Second, from posterior Ponte osteotomy was done from T12 to L3, shorten the spinal column 15 mm. The patient was successfully treated surgically. Postoperative lumbar MRI showed the tension of spinal cord was released. Manual muscle testing results and sensory function of the left leg had recovered almost fully on final follow-up at one year. Conclusions/Level of Evidence: Retethered spinal cord after initial untethering was difficult to treat. This new spinal shortening technique was effective and very safe technique to release the tension of spinal cord. Level V.

Background and Objectives: C-arm free MIS techniques can offer significantly reduced rates of postoperative complications such as blood loss and hospitalization time. Another advantageous long-term aspect is the notably diminished exposure to radiation which is known to cause ma-lignant changes. This study emphasizes that, in some cases of spinal conditions which require a procedural intervention, C-arm free MIS techniques hold stronger indications than open surgeries guided by image intensifier. Materials and Methods: In this research, a retrospective analysis and review of various cervical and thoracic spinal procedures, performed in our hospital, by applying C-arm free techniques. The course of the study explains the basic steps of the procedures and demonstrating postoperative or intra-operative results. For anterior cervical surgery, we performed OPLL resection, while for posterior cervical surgery, we performed posterior fossa decompression for Chiari malformation, minimally invasive cervi-cal pedicle screw fixation (MICEPS) and modified Goel technique with C1 lateral mass screw for atlantoaxial subluxation. Re-garding the thoracic spine, we performed anterior correction for Lenke type 5 scoliosis, and transdiscal screw fixation for DISH fractures. Results: C-arm free techniques are safe procedures that offer precise and high-quality postoperative results by offering sufficient spine alignment and adequate decompression depending on the case. Blood loss, postoperative pain and wound infection are other important aspects of spine surgery that must be always taken into consideration. Conclusions: Navigated C-arm free techniques are safe and precise procedures implemented in the treatment of surgically demanding conditions. They can significantly increase accuracy while decreasing the operative time. They represent the advancement in the field spine surgery and are hailed as the future of the same

Background: The effect of velamentous cord insertion (VCI) on perinatal outcomes in twin pregnancies is unclear due to conflicting findings. This retrospective study aimed to examine VCI prevalence and related risk factors in twin pregnancies and its association with adverse perinatal outcomes. Methods: Women with twin pregnancies who delivered between January 2012 and December 2021 in a single tertiary hospital were included. The participants were divided into dichorionic (DC) and monochorionic diamniotic (MCDA) groups, and their maternal and fetal characteristics and VCI rates were compared. Logistic regression models were used to identify risk factors for VCI and VCI-related perinatal outcomes. Results: Among the 694 twin pregnancies included in this study, the VCI rate was significantly higher in MCDA than in DC twins. Body mass index and MCDA twins were significant risk factors for VCI, whereas assisted reproductive technology pregnancy was a significant protective factor against VCI. In DC twins, VCI did not affect perinatal outcomes. Conclusion: In MCDA twins, VCI was a significant risk factor for fetal growth restriction, twin-to-twin transfusion syndrome, and preterm birth at

The detection and quantification of protein–protein interactions (PPIs) is a crucial technique that often involves the use of recombinant proteins with fusion-protein tags, such as maltose-binding protein (MBP) and glutathione-S-transferase (GST). In this study, we improved the cohesive and sticky properties of gelatinized starch by supplementing it with agarose, resulting in a harder gel that could coat the bottom of a microtiter plate. The resulting gelatinized starch/agarose mixture allowed for the efficient immobilization of MBP-tagged proteins on the coated plates, enabling the use of indirect ELISA-like PPI assays. By using the enzymatic activity of GST as an indicator, we succeeded in determining the dissociation constants between MBP-tagged and GST-tagged proteins on 96-well microtiter plates and a microplate reader without any expensive specialized equipment.

Human RAD51 protein (HsRad51)-promoted DNA strand exchange, a crucial step in homologous recombination, is regulated by proteins and calcium ions. The activator protein Swi5-Sfr1 and Ca2+ ions stimulate different reaction steps and induce a perpendicular orientation of DNA bases in the presynaptic complex. To investigate the importance of base orientation in the strand exchange reaction, we examined the Ca2+ concentration dependence of strand exchange activities and structural changes in the presynaptic complex. Our results show that optimal D-loop formation (strand exchange with closed circular DNA) requires Ca2+ concentrations greater than 5 mM, while 1 mM is sufficient for strand exchange between two oligonucleotides. The structural change, which is evidenced by an increase in fluorescence intensity of poly(dεA) (a poly(dA) analog), reaches a plateau at 1 mM Ca2+. Meanwhile, the linear dichroism signal intensity at 260 nm, which is indicative of rigid perpendicular DNA base orientation, requires >2 mM Ca2+ for saturation and thus correlates with the stimulation of D-loop formation. Therefore, Ca2+ exerts two different effects. Thermal stability measurements suggest that HsRad51 binds two Ca2+ ions with KD values of 0.3 mM and 2.5 mM, implying that one step is stimulated by one Ca2+ bond and the other by two Ca2+ bonds. We further discuss the parallels between Mg2+ activation of RecA and Ca2+ activation of HsRad51.

Infection of hosts by morbilliviruses is facilitated by the interaction between viral hemagglutinin (H-protein) and the signaling lymphocytic activation molecule (SLAM). Recently, the functional importance of the N-terminal region of human SLAM as a measles virus receptor was demonstrated. However, the functional roles of this region in the infection process by other morbilliviruses and host range determination remain unknown partly because this region is highly flexible, which has hampered accurate structure determination of this region by X-ray crystallography. In this study, we analyzed the interaction between the H-protein from canine distemper virus (CDV-H) and SLAMs by a computational chemistry approach. Molecular dynamics simulations and fragment molecular orbital analysis demonstrated that the unique His28 in the N-terminal region of SLAM from Macaca is a key determinant that enables formation of a stable interaction with CDV-H, providing a basis for CDV infection in Macaca. The computational chemistry approach presented should enable determination of molecular interactions involving regions of proteins that are difficult to predict from crystal structures because of their high flexibility.

This paper proposes a contact force controller for a constrained flexible manipulator in three-dimensional motion. This controller used the conversion formula obtained empirically and experimental results showed the effectiveness of the proposed contact force controller. First, the manipulator was operated with the tip of the second link restrained, then, time response of the root strain, joint angles and contact force were used to derive the relational between the three quantities. The effectiveness of the relational expression was verified by conducting a target contact force tracking experiment by inputting the angle from the relational expression. The contact force control using the strain feedback method was proposed with the strain amount estimated from the target contact force as the target value, and its effectiveness was verified by experiments. From the results obtained, controller using the strain feedback method was designed for the purpose of controlling the contact force at the tip of a flexible manipulator with two links and three degrees of freedom that performs three-dimensional spatial motion, and its effectiveness was shown by comparison with the contact force feedback method.

Background: Although lower extremity revascularization is commonly performed in hemodialysis patients, poor prognosis remains a major problem. Protein-energy wasting is reportedly associated with chronic inflammation and advanced atherosclerosis in hemodialysis patients. We investigated the association between the geriatric nutritional risk index (GNRI) as a surrogate marker of protein-energy wasting, C-reactive protein (CRP), and their joint roles in the prediction of amputation and/or mortality. Methods: We enrolled 800 patients successfully underwent lower extremity revascularization. Patients were divided into low, middle and high tertile (T1, T2 and T3) according to GNRI and CRP levels, respectively. Results: Amputation-free survival rates for 8 years were 47.0%, 56.9%, and 69.5% in T1, T2, and T3 of the GNRI, and 65.8%, 58.7%, and 33.2% for T1, T2, and T3 of CRP, respectively (p<0.0001 for both). Declined GNRI [adjusted hazard ratio (aHR) 1.78, 95% confidence interval (CI) 1.24-2.59, p=0.0016 for T1 vs. T3] and elevated CRP (aHR 1.86, 95%CI 1.30-2.70, p=0.0007 for T3 vs. T1) were independent predictors of amputation and/or mortality. In the combined setting of both variables, the risk was 3.77-fold higher (95% CI 1.97-7.69, p<0.0001) in the T1 of GNRI with T3 of CRP than in the T3 of GNRI with T1 of CRP. Conclusions: Patients with pre-procedural decreased GNRI and elevated CRP levels frequently experienced amputation and/or mortality, and a combination of both variables could more accurately stratify the risk.

Nanoparticles have been used as a novel drug delivery system. Drug-incorporated nanoparticles for local delivery might optimize the efficacy and minimize the side effects of drugs. The efficacy and safety of intratracheal administration of prostacyclin analog (beraprost)-incorporated nanoparticles and imatinib, a PDGF-receptor tyrosine kinase inhibitor, -incorporated nanoparticles in Sugen-hypoxia-normoxia or monocrotaline rat models of PAH and in human PAH-pulmonary arterial smooth muscle cells have been reported. The use of inhaled drug-incorporated nanoparticles might be a novel approach for treatment of PAH.

Aim: The aim of this study was to estimate the number of nurses who independently care for pa-tients with severe respiratory failure receiving mechanical ventilation (MV) or veno-venous ex-tracorporeal membrane oxygenation (VV-ECMO). Additionally, the study analyzed the actual role of nurses in the treatment of patients with MV and VV-ECMO. Methods: We conducted a cross-sectional study using postal surveys. The study included 725 Japanese intensive care units (ICUs). Descriptive statistics were conducted. Results: Among the 725 ICUs, we obtained 302 re-sponses (41.7%) and analyzed 282 responses. The median number of nurses per bed was 3.25. The median proportion of nurses who independently cared for patients with MV was 60% [IQR: 42.3-77.3]. The median proportion of nurses who independently cared for patients with VV-ECMO was 46.9 (35.7-63.3%) in the ICU experiencing VV-ECMO use. Concerning task-sharing, 33.8% of ICUs and nurses did not facilitate weaning from MV. Nurses always ti-trated sedatives in 44.5% of ICUs. Conclusion: Nurse staffing might be inadequate in all ICUs, es-pecially for severe respiratory failure. The proportion of competent nurses for caring for severe respiratory failure in ICUs should be considered when determining the work force of nurses.

Stroke constitutes a significant public health concern due to its impact on mortality and morbidity. This study investigates the utility of machine learning algorithms in predicting stroke and identifying key risk factors using data from the Suita study, comprising 7,389 participants and 53 variables. Initially, unsupervised K-prototype clustering categorized participants into risk clusters, while five supervised models including Logistic Regression (LR), Random Forest (RF), Support Vector Machine (SVM), eXtreme Gradient Boosting (XGBoost), and Light Gradient Boosted Machine (Light-GBM) were employed to predict stroke outcomes. Stroke incidence disparities among identified risk clusters using the unsupervised K-prototype clustering method are substantial, according to the findings. Supervised learning, particularly RF was a preferable option because of the higher levels of performance metrics. The Shapley Additive Explanations (SHAP) method identified age, systolic blood pressure, hypertension, estimated glomerular filtration rate, metabolic syndrome, and blood glucose level as key predictors of stroke, aligning with findings from the unsupervised clustering approach in high-risk groups. Additionally, previously unidentified risk factors such as elbow joint thickness, fructosamine, hemoglobin, and calcium level demonstrate potential for stroke prediction. In conclusion, machine learning facilitated accurate stroke risk predictions and highlighted potential biomarkers, offering a data-driven framework for risk assessment and biomarker discovery.

Objectives: To study the differences between malignant hypermetabolic axillary lymphadenopathy (MHL) and COVID-19 vaccine-associated axillary hypermetabolic lymphadenopathy (VAHL) using clinical imaging. Methods: A total of 1,096 patients underwent Positron Emission Tomography-Computed Tomography (PET-CT) between June 1, 2021 and April 30, 2022, at Ehime University Hospital. In total, 188 patients with axillary lymphadenopathy after the COVID-19 vaccination were evaluated. The patients were classified into three groups such as VAHL (n=27), MHL (n=21), and equivocal hypermetabolic axillary lymphadenopathy (EqHL; n=140). Differences in lymph nodes (LNs) swellings were statistically analyzed using clinical imagings (echography, CT, and 18F-FDG PET) statistically. Results: MHL included a higher female population (90.5%) owing to a higher frequency of breast cancer frequency (80.9%). Axillary LNs of MHL did not show any LN fatty hilums (0%); however, those of VAHL and EqHL did (15.8 and 36%, respectively). After the logistic regression analysis of the patients who had axillary lymphadenopathy without any LN fatty hilums, the minor axis length and ellipticity (minor axis/major axis) in the largest axillary LN, SUVmax, and Tissue-to-Background Ratio (TBR) were useful in distinguishing malignant lymphadenopathies. Receiver-operating characteristic (ROC) analysis indicated that a cut-off value of ≥7.3 mm for the axillary LN minor axis (sensitivity: 0.714, specificity: 0.684) and of ≥0.671 for ellipticity (0.667 and 0.773, respectively) in the largest LN with the highest SUVmax and TBR were predictive of MHL. Conclusion: Axillary lymphadenopathy ≥7.3 mm of the minor axis and ≥0.671 of ellipticity in LN without fatty hilum suggests malignancy even in patients who have received COVID-19 vaccination. Further examinations such as 18F-FDG PET are recommended for such patients

Study design :Technical note. Objectives : To present a new unilateral biportal endoscopic technique for lumbar disc herniation without C-arm . Background : Lumbar disc herniation requires surgical intervention when conservative methods fail. Shifts towards minimally invasive percutaneous endoscopic lumbar discectomy, including uniportal and biportal approaches, have been hindered by challenges such as steep learning curves and reliance on radiation-intensive C-arm guidance. Our study introduces the use of standard intraoperative navigation in unilateral biportal endoscopy (UBE) to reduce radiation exposure and increase surgical acuracy. Materials and Methods : A 24-year-old man with low back and bilateral leg pain with gait disturbance was referred to our hospital. He had have conservative treatment for 12 months in another hospital before admission. However, the conservative treatment did not work for him. He had low back pain (VAS 4/10) and bilateral leg pain (VAS 8/10), muscle waekness of bilateral legs (Manual muscle testing ;MMT of extensor hullusis longs 4 4), and numbness of bilateral lower leg. Preoperative lumbar MRI showed L4/5 large central disc herniation. Results: He underwent C-arm free unilateral biportal endoscopic discectomy under the guidance of O-arm navigation. The patient was successfully treated surgically. Postoperative lumbar MRI showed good decompression of dural sac and bilateral L5 nerve roots. MMT and sensory function of both leg had recovered fully on final follow-up at one year. Conclusions/Level of Evidence: The new unilateral biportal endoscopic technique under navigation guidance is useful technique for lumbar disc herniation. This innovative technique proved to be safe, accurate, and minimized radiation exposure for surgeons for the treatment of lumbar intervertebral disc herniation. Level V.

The present study provides new insights into the growth of brown algal cell wall by showing that cell wall polysaccharide plays an important role in the process of growth consider- ing the physicochemical characteristic of young and old Cladosiphon okamuranus. To determine its structural variation in detail, the cell wall was sequentially fractionated into five fractions: hot water (HW), ammonium oxalate, hemicellulose-I (HC–I), HC-II, and cellulose, and analyzed physicochemically. Results showed that almost 80% of the total recovery cell wall from both young and old thalli was HW and HC-I contained mainly fucoidan composed of Fuc, GlcA, and sulfate in molar ratios of 1.0: 0.3: 0.6~0.7 and 1.0: 0.3: 0.2~0.3, respectively. Fucoidan in HW was a highly sulfated matrix polysaccharide abundance in young thalli, while fucoidan in HC-I was rich in old thalli and functions as hemicellulose in land plants, crosslink with cellulose and strengthen the cell wall. We found that HW and HC-I were particularly involved in the growth and strength of old thalli appeared to be due to the deposition of HC-I and reducing of water content during the growth process.

Granulomatous mastitis is a benign disease with a clinical presentation similar to that of breast cancer, and is most commonly observed in women of childbearing age. Although it has been suggested that autoimmune diseases are involved in its pathogenesis, no specific treatments have been established. The occurrence of this disease during pregnancy has rarely been reported. Our patient was a 37-year-old woman. She was pregnant and manifested a dichorionic, diamniotic placenta. At 24 weeks of gestation, the patient experienced a sensation of hardness in her left breast. Mastitis was suspected, and she was treated with cephem antibiotics. Simultaneously, she was diagnosed with erythema nodosum in the extremities. As her symptoms did not improve, an incisional drainage was performed. Bacterial cultures were obtained at 31 weeks of gestation, and Corynebacterium kroppenstedtii was detected. An elective cesarean section was performed at 37 weeks of gestation, and the baby was delivered safely. After delivery, a needle biopsy was performed, and the patient was diagnosed with granulomatous mastitis. She was completely cured with prednisolone after weaning. In this case, the patient's condition was maintained through incision and drainage; and antibiotic, anti-inflammatory, and analgesic drugs during pregnancy. This approach was chosen, taking into consideration the potential side effects of steroids. After delivery, breastfeeding and steroidal therapy proved to be effective in treating the condition.

Most pivotal clinical trials in advanced non-small cell lung cancer (NSCLC) have excluded patients with poor performance status (PS), and data on the efficacy and safety of pharmacotherapy have not been fully accumulated. For NSCLC patients with PS 2 and without druggable genetic alterations, monotherapy with cytotoxic agents or carboplatin-based combination therapy is usually administered based on the results of several randomized trials. However, the evidence of cytotoxic chemotherapy for patients with PS 2 is insufficient, with limited efficacy and toxicity concerns. Immune checkpoint inhibitors (ICIs) are a promising treatment for patients with PS 2 because of lower incidence of severe toxicity compared to cytotoxic chemotherapy. Meanwhile, several reports suggest that anti-PD-1 antibodies monotherapy is less effective for patients with PS 2, especially for those with PS 2 caused by disease burden. Although the combination therapy of nivolumab and ipilimumab is a promising treatment option, there is a divergence in efficacy data between clinical trials. The standard of care for advanced NSCLC with PS 2 has not been established, and future therapeutic strategies should take into account the heterogeneity of the PS 2 population.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) often causes severe viral pneumonia, especially among older individuals and those with underlying health conditions. The C57BL/6 mouse is widely used to develop mouse models of obesity, diabetes, hypertension, and immune disorders, conditions that are associated with increased risk of severe COVID-19. Although many studies using these mouse models have examined the pathogenicity of SARS-CoV-2, COVID-19 pathogenesis remains poorly understood. In vivo imaging analysis using two-photon excitation microscopy is useful for elucidating the pathology of COVID-19, providing pathological insights that are not available from conventional histological analysis. However, there is no reporter SARS-CoV-2 that demonstrates pathogenicity in C57BL/6 mice and emits sufficient light intensity for two-photon in vivo imaging. Here, we generated SARS-CoV-2 expressing the fluorescent protein Venus to facilitate in vivo pathological studies using C57BL/6 mouse models. We generated a mouse-adapted strain of SARS-CoV-2, by performing sequential lung-to-lung passages in BALB/c mice, followed by in C57BL/6 mice. We observed that the C57BL/6-adapted SARS-CoV-2 (named MASCV2-p25) replicated efficiently in the lungs of C57BL/6 mice, causing fatal pneumonia. Histopathologic analysis revealed severe inflammation and infiltration of immune cells in the lungs of MASCV2-p25-infected C57BL/6J mice, not unlike that observed in COVID-19 patients with severe pneumonia. Subsequently, we generated a mouse-adapted reporter SARS-CoV-2 (named MASCV-Venus-p9) by inserting the fluorescent gene Venus into MASCV2-p25, and sequential lung-to-lung passages in C57BL/6 mice. C57BL/6 mice infected with MASCV2-Venus-p9 exhibited severe pneumonia similar to that induced by MASCV2-p25. In addition, two-photon excitation microscopy of the lungs of the infected C57BL/6J mice showed that the infected cells emitted sufficient levels of fluorescence for easy observation. These findings suggest that MASCV2-Venus-p9 will be useful for two photon in vivo imaging studies of the pathogenesis of severe COVID-19 and for the development of therapeutic agents for severe pneumonia.