Retinoid X receptor (RXR) antagonists are not only useful as chemical tools for biological research, but also are candidate drugs for treatment of various diseases, including diabetes and allergy, although no RXR antagonist has yet been approved for clinical use. In this review, we describe currently available RXR antagonists, their structural classification, and their evaluation, focusing on the latest research.

Understanding tumor attachments and management of feeding arteries are very important factors to achieve safe resection of skull base meningioma. We examined the distributions and frequencies of feeding arteries in skull base meningioma by cerebral angiography, and also assessed relationships to tumor attachment for skull base meningioma. We enrolled patients with skull base meningioma who underwent MRI and cerebral digital subtraction angiography (DSA), from September 2015 to October 2022. Subjects comprised 115 patients (32 males, 83 females; mean age, 52.7 years) with 117 meningiomas showing tumor attachments around the “cavernous sinus to upper part of the clivus” (Area 1), “lower part of the clivus to foramen magnum” (Area 2), and “tentorium around the petrous bone” (Area 3). We examined feeding arteries based on cerebral angiography and counted the number of related feeding arteries. Particularly frequent arteries, such as the dorsal meningeal artery (DMA), ascending pharyngeal artery (APA), tentorial artery (TA), and petrosal branch (PB) of the middle meningeal artery (MMA) were analyzed for associations of tumor attachment to Areas 1–3. DMA, APA, TA, and PB are very frequent feeding arteries among skull base meningiomas. In some cases, the artery of the foramen rotundum, posterior ethmoidal artery, recurrent meningeal artery, posterior meningeal artery, etc., supply blood to the skull base meningioma. Meningiomas with DMA as a feeding artery correlated strongly with tumor attachment to Area 1 (p<0.001). Meningiomas with APA correlated strongly with tumor attachment to Area 2 (p<0.001). Meningiomas with TA correlated strongly with tumor attachment to Area 3 (p<0.001). PB correlated with Area 3 (p<0.05). Visualization of these arteries suggests tumor attachments to the correlated areas. An accurate anatomical understanding of tumor attachment and feeding arteries is essential to determine appropriate surgical strategies for skull base meningioma. Pre-operative DSA can provide further understanding of the feeding arteries and attachments of skull base meningioma.

Immunoglobulin G (IgG) adopts a modular multidomain structure that mediates antigen recognition and effector functions, such as complement-dependent cytotoxicity. IgG molecules are self-assembled into a hexameric ring on antigen-containing membranes, recruiting the complement component, C1q. To provide deeper insights into the initial step of the complement pathway, we report a high-speed atomic force microscopy study for quantitative visualization of the interaction between IgG and the C1 complex composed of C1q, C1r, and C1s. Results showed that C1q in the C1 complex is restricted regarding internal motion and has a stronger binding affinity for on-membrane IgG assemblages than C1q alone, presumably because of smaller conformational entropy loss upon binding. Furthermore, we visualized a 1:1 stoichiometric interaction between C1/C1q and an IgG variant that lacks the entire CH1 domain in the absence of antigen. In addition to the canonical C1q-binding site on Fc, their interactions are mediated through a secondary site on the CL domain that is cryptic in the presence of the CH1 domain. Our findings offer clues for novel-modality therapeutic antibodies.

This paper is our attempt on the basis of physical theory to bring more clarification on the question ``What is life?'' formulated in the well-known book of Schr\"odinger in 1944. According to Schr\"odinger, the main distinguishing feature of biosystem's functioning is the ability to preserve its order structure or, in the mathematical terms, to prevent increasing of entropy. Since any biosystem is fundamentally open, it is natural to use open system's theory. However, Schr\"odinger's analysis shows that the classical theory is not able to adequately describe the order-stability in a biosystem. Schr\"odinger should also appeal to the ambiguous notion of negative entropy. We suggest to apply the quantum theory. As is well-known, behaviour of the quantum von Neumann entropy crucially differs from behaviour of the classical entropy. We consider a complex biosystem $S$ composed of many subsystems, say proteins, or cells, or neural networks in the brain, i.e., $S=(S_i).$ We study the following problem: if the composed system $S$ can preserve the ``global order'' in the situation of increase of local disorder and if $S$ can preserve its entropy while some of $S_i$ increase their entropies We show that within quantum information theory the answer is positive. The significant role plays entanglement of the subsystems states. In the absence of entanglement, increasing of local disorder generates disorder increasing in the compound system $S$ (as in the classical regime).

For condensed systems, the incorporation of quantum chemical solvent effects into molecular dynamics simulations has been a major concern. To this end, quantum mechanical/molecular mechanical (QM/MM) techniques are popular and powerful options to treat gigantic systems. However, they cannot be directly applied because of temporal and spatial discontinuity problems. To overcome these problems, in a previous study, we proposed a corrective QM/MM method, size-consistent multipartitioning (SCMP) QM/MM, and successfully demonstrated that, using SCMP, it is possible to perform stable molecular dynamics simulations by effectively taking into account solvent quantum chemical effects. The SCMP method is characterized by two original features: size-consistency of a QM region among all QM/MM partitioning and partitioning update. However, in our previous study, the performance was not fully elicited compared to the theoretical upper bound, and the optimal partitioning update protocol and parameters were not fully verified. To elicit the potential performance, in the present study, we simplified the theoretical framework and modified the partitioning protocol.

Introduction: Atrial fibrillation (AF) is a common cardiac arrhythmia whose prevalence rises with age and is linked to increased morbidity and mortality due to the risk of thromboembolism. Management typically involves anticoagulation and rhythm control, but the treatment of elderly patients with multiple comorbidities requires careful consideration of drug side effects and interactions. Cibenzoline, a Vaughan-Williams class IA antiarrhythmic, is effective against AF but has risks of toxicity, especially in older people and those with renal impairment, due to its renal excretion and prolonged half-life in these populations. Discussion: This paper presents a case of an 80-year-old woman with paroxysmal AF who suffered cardiac arrest due to cibenzoline toxicity despite receiving standard adjusted dosages. The patient's cibenzoline blood concentration was significantly higher than the therapeutic range, leading to cardiotoxicity, which was exacerbated by drug interactions with bisoprolol and edoxaban, both metabolized by the CYP3A4 enzyme. Venoarterial extracorporeal membrane oxygenation (V-A ECMO) and intra-aortic balloon pump (IABP) successfully managed the cardiac arrest. This case emphasizes the unpredictable pharmacokinetics of cibenzoline in elderly patients with renal impairment and the need for vigilant therapeutic drug monitoring to avoid adverse events. Conclusions: Cibenzoline can pose a significant risk of severe toxicity in elderly patients with renal impairment, and drug interactions may potentiate this risk. The paper underscores the importance of careful dose adjustment and monitoring of drug levels in this population. In cases of cibenzoline-induced cardiac arrest, V-A ECMO and IABP are effective treatment modalities. The case study serves as a critical reminder for clinicians to remain vigilant for drug-induced complications and to apply aggressive supportive treatments when necessary.

Ground-level ozone (O3) increases in the northeastern part of Eurasia, where larch species are dominant trees and have been planted intensively. The Japanese larch (Larix kaempferi; hereafter larch) is classified as the tree species most of its sensitive to O3 based on data from long-shoot needles of seedlings. This criterion should be reconsidered based on O3 uptake, which is strongly depended on stomatal conductance (Gs) of adult trees through the difference in relevant needle traits. Because Gs is closely correlated with photosynthetic activity, we measured the in situ seasonal and yearly change in photosynthetic function, needle mass per area (LMA) and nitrogen (N) content of both short- and long-shoot needles of the canopy of larch trees over successive 3 years. No difference was observed in the in light saturated photosynthetic rate at ambient CO2 (Psat) between needles of hetero types of shoot in the latter part of the growing season, but clear differences were found within a specific year, indicating that seasonal changes in climatic factors determine Psat in the long term. The Psat-N relations differed significantly between the needle types. However, Psat at saturated CO2 (Pmax)-N was quite similar, implying that the CO2 diffusion difference between short- and long-shoots is responsible for the differing Psat -N. In conclusion, seasonal and yearly variations in photosynthetic capacity are mainly determined mainly by climatic variations, whereas shoot type determined the traits of photosynthetic N utilization as well as Gs regulation.

Acute coronary syndrome (ACS) is a life-threatening condition that requires a prompt diagnosis and therapeutic intervention. Although serum troponin T and creatinine kinase-MB (CK-MB) are established biomarkers for ACS, it may take several hours to reach diagnostic values for ACS. In this study, we attempted to explore novel biomarkers for ACS with higher sensitivity than that of troponin T and CK-MB. The metabolomic profiles of 18 patients with ACS upon hospital arrival and those of the age-matched control (HC) group consisted of 24 healthy volunteers were analyzed using liquid chromatography-time-of-flight mass spectrometry. Volcano plots showed 24 metabolites whose concentrations differed significantly between the ACS and HC groups. Using these data, we developed a multiple logistic regression model for the ACS diagnosis, in which lysine, isocitrate, and tryptophan were selected as minimum-independent metabolites. The area under the receiver operating characteristic curve value for discriminating ACS from HC was 1.00 (95% confidence interval [CI]: 1.00-1.00). In contrast, those for troponin T and CK-MB were 0.917 (95% confidence interval [CI]: 0.812-1.00) and 0.988 (95% CI: 0.966-1.00), respectively. This study showed the potential of combining three plasma metabolites to discriminate ACS from HC with a higher sensitivity than that of troponin T and CK-MB.

Activation of the EGFR pathway plays an important role in the progression of cancer and is associated with a poor prognosis in patients. The monoclonal antibody cetuximab, which displays EGFR extracellular domain-specific binding, has proven effective in the treatment of locally advanced disease and relapsed/metastatic disease. However, the effects of cetuximab are weaker than those of EGFR tyrosine kinase inhibitors (TKIs). This study investigates differences in the effects on cell growth of cetuximab and EGFR TKI AG1478 at the molecular level using oral squamous cell carcinoma (OSCC) cell lines. First, we found that there were EGFR-inhibitor sensitive (EIS) and EGFR-inhibitor resistant cell lines. The EIS cell lines expressed not only EGFR but also ErbB3, and both were clearly phosphorylated. The levels of phosphorylated ErbB3 were unaffected by cetuximab but were reduced by AG1478. EGFR ligand treatment increased the levels of phosphorylated EGFR but not phosphorylated ErbB3. Moreover, when EIS cell lines that were only capable of anchorage-dependent growth were grown in suspension, cell growth was suppressed and the levels of phosphorylated FAK, Src, and ErbB3 were significantly reduced. The levels of phosphorylated ErbB3 were unaffected by the FAK inhibitor PF573228, but were reduced by Src inhibition. Finally, combining cetuximab and a Src inhibitor produced an additive effect on the inhibition of EIS cell line growth.

SDG target 12.3 calls for halving food waste at retail, food service, and household by 2030. The food waste index for this purpose includes parts attached to food that are usually removed intentionally ("unavoidable food waste") and allows counting the conversion to animal feed and utilisation as biomaterial as means of reduction. In Japan, the "Food Waste Recycling Law" which has been in effect since 2001, promotes the recycling of food waste generated from businesses, designating feed conversion as top priority. On the other hand, based on the more recent "Food Loss Reduction Promotion Act" of 2019, the government is currently promoting the reduction of avoidable food waste, as to meet the SDG target. Based on statistical sources and interviews with Ministry officers, this paper explains the history and achievements of Japan's 23-year policy based on the Food Recycling Law, as well as the tension between the two legislations.

Cardiovascular diseases remain the leading cause of mortality worldwide. Although new therapies are actively being developed and used for cardiovascular pathologies, these attempts have not significantly decreased mortality rates. Regenerative medicine has made enormous progress and set promising approaches over the past half-century. However, since autologous (donor-derived) vascular grafts are lacking, an alternative prosthesis must be constructed for cardiovascular disease patients. In vascular tissue manufacturing and regenerative medicine, scientists seek to improve this significant clinical challenge using bio-fabrication techniques combining additive manufacturing, biomaterials science, and advanced cellular biology. In the last few decades, many improvements and changes in various approaches have helped develop bioengineered concepts that reflect native blood vessels’ structure and function. However, numerous challenges must be overcome to clinically translate the next generation of tissue-engineered vascular transplants. This review provides update on the cell sources, scaffold essential for cardiovascular tissue engineering, and tissue engineering approaches as prospective options for curative therapy for blood vessel disease.

Hemoconcentration membranes used in cardiopulmonary bypass require a pore structure design with high pure water permeability, and which does not allow protein adsorption and useful protein loss. However, studies on hemoconcentration membranes have not been conducted yet. The purpose of this study was to analyze three-dimensional pore structures and protein fouling before and after blood contact with capillary membranes using the tortuous pore diffusion model and a scanning probe microscope system. We examined two commercially available capillary membranes of similar polymer composition that are successfully used in hemoconcentration clinically. Assuming the conditions of actual use in cardiopulmonary bypass, we perfused these membranes with bovine blood. Pure water permeability before and after bovine blood perfusion was measured using the dead-end filtration. The scanning probe microscopy system was used for analysis. High-resolution three-dimensional pore structures on the inner surface of the membranes were observed before blood contact. On the other hand, pore structures after blood contact could not be observed due to protein fouling. The pore diameters calculated by the tortuous pore diffusion model and scanning probe microscopy were mostly similar and could be validated reciprocally. Achievable pure water permeabilities showed no difference despite protein fouling, leading to low values of albumin SC. This is due to the mechanism that protein fouling occurs on the membrane surface, while there is little internal pore blocking. Therefore, controlling the fouling is essential for membranes in medical use. These characteristics of the hemoconcentration membranes examined in this study are suitable for clinical use.

Photovoltaic power generation has high variability and uncertainty because it is affected by uncertain factors such as weather conditions. Therefore, probabilistic forecasting is useful for optimal operation and risk hedging in power systems with large amounts of photovoltaic power generation. However, deterministic forecasting is the mainstay of photovoltaic generation forecasting; there are few studies on probabilistic forecasting and feature selection from weather or time-oriented features in such forecasting. In this study, prediction intervals were generated by the lower upper bound estimation using neural networks with two outputs to make probabilistic predictions. The objective was to improve prediction interval coverage probability (PICP), mean prediction interval width (MPIW), and loss, which is the integration of these two metrics, by removing unnecessary features through feature selection. When features with high gain were selected by random forests (RF), in the forecast of 14.7-kW PV systems, loss improved by 1.57 kW, PICP by 0.057, and MPIW by 0.12 kW on average over two weeks compared to the case where all features were used without feature selection. Therefore, the low gain features from RF act as noise in LUBE and reduce the prediction accuracy.

Postprandial hyperlipidemia showing postprandial increase in serum triglyceride (TG) is atherogenic and associated with the development of coronary artery disease (CAD). To diagnose postprandial hyperlipidemia, the oral fat loading test (OFLT) should be performed, however, this test is very time-consuming and is difficult to perform. Ele-vated serum TG levels reflect an increase in TG-rich lipoproteins (TRL) such chylomi-crons (CM), very low-density lipoproteins (VLDL) and their remnants (CM remnant [CMR] and VLDL remnant [VLDLR]). Understanding of elevation in CMR and/or VLDLR can lead us to understand the existence of postprandial hyperlipidemia. The measurements of apo B48 which is a constituent of CM and CMR, non-fasting TG which includes TG content in all lipoproteins including CM and CMR, non-high-density lipoprotein-cholesterol (non-HDL-C) which includes TRL and low-density lipoprotein, and remnant cholesterol, are useful to suspect the existence of postprandial hyperlipidemia. Postprandial hyperlipidemia is observed in patients with familial type III hyperlipoproteinemia, familial combined hyperlipidemia, chronic kidney disease, metabolic syndrome and type 2 diabetes. Postprandial hyperlipidemia is closely related to postprandial hyperglycemia, and insulin resistance may be an in-ducing and enhancing factor for both postprandial hyperlipidemia and postprandial hyperglycemia. Remnant lipoproteins and metabolic disorders associated with post-prandial hyperlipidemia have various atherogenic properties such as induction of in-flammation and endothelial dysfunction. A healthy diet, calorie restriction, weight loss and exercise, positively impact postprandial hyperlipidemia. Anti-hyperlipidemic drugs such pemafibrate, bezafibrate, ezetimibe and eicosapentaenoic acid have shown to improve postprandial hyperlipidemia. Anti-diabetic drugs including metformin, alpha-glucosidase inhibitors, pioglitazone, dipeptidyl-peptidase-4 inhibitors and glu-cagon like peptide 1 analogues, have shown to ameliorate postprandial hyperlipidemia. Although sodium glucose cotransporter-2 inhibitors have not been proven to reduce postprandial hyperlipidemia, they reduced fasting apo B48 and remnant lipoprotein cholesterol. In conclusion, it is important to appropriately understand the existence of postprandial hyperlipidemia and to connect it to optimal treatments.

Therapeutic efficacy of retroviral replicating vector (RRV)-mediated prodrug activator gene therapy has been demonstrated in a variety of tumor models, but clinical investigation of this approach has so far been restricted to glioma and gastrointestinal malignancies. In the present study, we evaluated replication kinetics, transduction efficiency, and therapeutic efficacy of RRV in experimental models of lung cancer. RRV delivering GFP as a reporter gene showed rapid viral replication in a panel of lung cancer cells in vitro, as well as robust intratumoral replication and high levels of tumor transduction in subcutaneous and orthotopic pleural dissemination models of lung cancer in vivo. Toca 511 (vocimagene amiretrorepvec), a clinical-stage RRV encoding optimized yeast cytosine deaminase (yCD) which converts the prodrug 5-fluorocytosine (5-FC) to the active drug 5-fluorouracil (5-FU), showed potent cytotoxicity in lung cancer cells upon exposure to 5-FC prodrug. In vivo, Toca 511 achieved significant tumor growth inhibition following 5-FC treatment in subcutaneous and orthotopic pleural dissemination models of lung cancer in both immunodeficient and immunocompetent hosts, resulting in significantly increased overall survival. This study demonstrates that RRV can serve as highly efficient vehicles for gene delivery to lung cancer, and indicates the translational potential of RRV-mediated prodrug activator gene therapy with Toca 511/5-FC as a novel therapeutic strategy for pulmonary malignancies.

Solidification microstructure is formed under high cooling rates and temperature gradients in powder-based additive manufacturing. In this study, a non-equilibrium multi-phase field method (MPFM), which was based on a finite interface dissipation model proposed by Steinbach et. al., coupled with a CALPHAD database was developed for a multicomponent Ni alloy. A qua-si-equilibrium MPFM was also developed for comparison. Two-dimensional equiaxed micro-structural evolution for the Ni (Bal.)–Al–Co–Cr–Mo–Ta–Ti–W–C alloy was performed at various cooling rates. The temperature–γ fraction profiles obtained under 10^5 K/s using non- and qua-si-equilibrium MPFMs were in good agreement with each other. Over 10^6 K/s, the differences between non- and quasi-equilibrium methods grew as the cooling rate increased. The non-equilibrium solidification was strengthened over a cooling rate of 10^6 K/s. Colum-nar-solidification microstructural evolution was performed under cooling rates from 5×10^5 K/s to 1×10^7 K/s at various temperature gradient values under the constant interface velocity (0.1 m/s). The results showed that as the cooling rate increased, the cell space decreased in both methods, and the non-equilibrium MPFM agreed well with experimental measurements. Our results show that the non-equilibrium MPFM can simulate solidification microstructure in powder bed fusion additive manufacturing.

The core pathological event in Parkinson’s disease (PD) is the specific dying of dopamine (DA) neurons of the substantia nigra pars compacta (SNc). Why SNc DA neurons are especially vulnerable and why idiopathic PD has only been found in humans is still puzzling. The two main underlying factors of SNc DA neuron vulnerability appear related to high DA production, namely (i) the toxic effects of cytoplasmic DA metabolism and (ii) continuous cytosolic Ca2+ oscillations in the absence of the Ca2+-buffer protein calbindin. Both factors cause oxidative stress by producing highly reactive quinones and increasing intra-mitochondrial Ca2+ concentrations, respectively. High DA expression in human SNc DA neuron cell bodies is suggested by the abundant presence of the DA-derived pigment neuromelanin, which is not found in such abundance in other species and has been associated with toxicity at higher levels. The oxidative stress created by their DA production system, despite that the SN does not use unusually high amounts of energy, explains why SNc DA neurons are sensitive to various genetic and environmental factors that create mitochondrial damage and thereby promote PD. Aging increases multiple of the risk factors for PD, and, to a large extent, PD is accelerated aging. To prevent PD neurodegeneration, possible approaches that are discussed here are (1) reducing cytoplasmic DA accumulation, (2) blocking cytoplasmic Ca2+ oscillations, and (3) providing bioenergetic support.

The pathology of idiopathic intracranial hypertension (IIH), a disease characterized by papillary edema and increased intracranial pressure (IICP), is not yet understood; this disease significantly affects quality of life due to symptoms, including vision loss, headache, and pulsatile tinnitus. By contrast, superficial siderosis (SS), a disorder in which hemosiderin is deposited on the surface of the cerebral cortex and cerebellum, potentially causes cerebellar ataxia or hearing loss. So far, no cases of IIH with infratentorial and supratentorial cortical SS have been reported. Herein, we report a case of a 31-year-old woman with obesity who developed this condition. The patient suddenly developed headache and dizziness, had difficulty walking, and subsequently became aware of diplopia. Fundus examination revealed bilateral optic nerve congestive papillae and right eye abducens disturbance. Head magnetic resonance imaging (MRI) showed prominent SS on the cerebellar surface and cerebral cortex. Lumbar puncture revealed IICP of 32 cmH2O, consistent with the diagnostic criteria for IIH, and treatment with oral acetazolamide was started; subsequently, the intracranial pressure decreased to 20 cmH2O. Her abduction disorder disappeared, and the swelling of the optic papilla improved. She was now able return to her life as a teacher without any sequelae. SS is caused by persistent slight hemorrhage into the subarachnoid space. In this case, both infratentorial and supratentorial cortical superficial SS was observed. Although cases of IIH complicated by SS are rare, it should be kept in mind that a causal relationship between IIH and SS was inferred from our case. Our findings also suggest that cerebrospinal fluid dynamic analysis using MRI is effective in diagnosing IIH and in determining the efficacy of treatment.

Beyond plasma glucose-lowering in patients with type 2 diabetes, sodium- glucose cotransporter 2 inhibitors (SGLT2i) significantly reduced the hospitalization for heart failure (HF) and retarded the progression of chronic kidney disease (CKD). Endothelial dysfunction is not only involved in the development and progression of cardiovascular disease (CVD), and is also associated with the progression of CKD. In patients with type 2 diabetes, hyperglycemia, insulin resistance, hyperinsulinemia and dyslipidemia induce the development of endothelial dysfunction. SGLT2i have shown an improvement in endothelial dysfunction, as assessed by flow-mediated vasodila-tion, in individuals at high risk for CVD. Along with an improvement of endothelial dysfunction, SGLT2i showed improvements in oxidative stress, inflammation, mitochondrial dysfunction, glucotoxicity such as advanced glycation end products signaling and nitric oxide bioavailability. The improvements in endothelial dysfunc-tion and such endothelium-derived factors may play an important role in preventing the development of coronary artery disease, coronary microvascular dysfunction and diabetic cardiomyopathy which cause HF and in retarding CKD. The suppression of the development of HF and the progression of CKD achieved by SGLT2i might have been largely induced by the improvement of vascular endothelial function by SGLT2i.

Background The purpose of this study was to clarify the relationship structure of quality of life (QOL) in survivors of breast cancer, including difficulty in daily life and negative experience as health-related indicators. Methods Participants were survivors of breast cancer for more than 2 years after primary breast cancer surgery and belonged to self-help groups. The assessment used FACT-B (QOL), HADS (anxiety and depression), SOC (sense of coherence), WHODAS 2.0 (difficulties in daily life), and CAOD (negative experiences). Bayesian structural equation modeling (BSEM) was performed to analyze the hypothesized model. If the causal model was significant, multiplication of the path coefficient from anxiety and depression to QOL, and from SOC to anxiety and depression, was considered a direct effect on QOL, and from SOC to difficulty in daily life, from difficulty in daily life to negative experiences, and from negative experiences to anxiety and depression were considered indirect effects on QOL. Results Goodness of fit of the model in the BSEM was satisfactory. The direct effect was 0.274, and indirect effect was 0.163. Conclusions These direct and indirect approaches to difficulties in daily life are very significant because they can provide a basis for development of support strategies to increase QOL.

Target 12.3 of the United Nations Sustainable Development Goals (SDGs) calls for halving per capita global food waste at the retail and consumer levels, by 2030. The Food Waste Index is suggested as a methodology for grasping the situation. This paper focuses on the consumer level (household food waste). We argue that in order for generating useful information for devising and implementing effective measures for reducing food waste, it should be measured at Level 3 of the Food Waste Index, based on sorting analysis of generated waste, making a distinction between avoidable and non-avoidable food waste. Furthermore, a breakdown by sub-categories that reflect the flow of food in the household could help identify target behaviours. We have developed a categorisation scheme that is internationally agreeable and adoptable, and 1) generates useful information for policy-making and for tackling with reduction of food waste, 2) makes clear the concept of avoidable food waste, and 3) is practical and does not overcomplicate the work of grasping the situation of food wastage. Results of workshops regarding this scheme suggest that the scheme satisfies the criteria. This scheme has been applied to a few sorting analyses of household food waste in Japan, and their results are compared.

Metabolic-dysfunction associated steatotic liver disease (MASLD) is a chronic liver disease that affects more than a quarter of the global population, and is increasing worldwide, due to the pandemic of obesity. Insulin resistance is closely associated with the development and progression of MASLD. Hepatic entry of increased fatty acids (FA) released from adipose tissue, increase in FA synthesis and reduced FA oxidation in the liver, and hepatic overproduction of triglyceride (TG)-rich lipoproteins may induce the development of MASLD. Since insulin resistance also induces atherosclerosis, the leading cause for death in MASLD patients is cardiovascular disease (CVD). Considering that the development of CVD determines the prognosis of MASLD patients, the ideal therapeutic interventions for MASLD should reduce body weight, improve coronary risk factors, in addition to an improvement in liver functiom. Lifestyle modification such as diet and exercise and surgical interventions such as bariatric surgery and intragastric balloons have shown to improve MASLD by reducing body weight. Sodium glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1RA) have been shown to improve coronary risk factors and to suppress the occurrence of CVD. Both SGLT2i and GLP-1 have been reported to improve liver enzymes, hepatic steatosis and fibrosis. We recently reported that the selective peroxisome proliferator-activated receptor-alpha (PPARα) modulator, pemafibrate, improved liver function. PPARα agonists have multiple anti-atherogenic properties. Here, we consider the pathophysiology of MASLD and the mechanisms of action of such drugs, and consider whether such drugs and the combination therapy of such drugs could be the ideal treatments for MASLD.

Long read sequencers, known for their effectiveness in detecting genomic structural variations (SV), are becoming a standard in comprehensive genetic analysis. In preimplantation genetic testing (PGT) for SV carriers, information on breakpoint junctions is required for the determination of carrier status in embryo selection. These sequencers are employed for challenging cases involving SVs that are difficult to analyze with conventional cytogenetical methods or detailed junctions of chromosomal translocations, providing valuable insights. They also play a crucial role in acquiring simultaneous information on surrounding single-nucleotide polymorphisms (SNPs) around causative variants in PGT. Despite their advantages, challenges related to sequencing accuracy and testing costs exist. Thus, understanding long read sequencers’ characteristics is essential for their effective utilization. This review summarizes the advanced applications of long read sequencers in preclinical workups and their integration into PGT. It also highlights in-house clinical cases, showing the implementation of long-read sequencing and discussing prospects in the field.

The fluctuation of the conditions on Lake Limboto affects people's activities around the lake. They try to survive by facing the problem of the lake, which is shallowing and narrowing. Yet the lake is predicted will be disappeared in 2030. This means that the productivity of the lake also diminishes. This article aims to analyze how the communities around the lake respond to the evolution and shocking prediction toward the lake into their daily activities. This study uses an interdisciplinary approach by integrating some fields of study to understand and solve the problems. One of the approaches involves interviewing people around the lake. Nevertheless, the base of the study is socio-cultural studies, which uses also old texts and oral literature as the support of the study. The research needs the theory of cultural studies to look at the survival and resilience of the people of lake so that they form their special daily activity. The results of the study show that some people know that there is a prediction of disappearing of the lake, but they have not anticipated it, as if this problem is only a government affair. They still live at the lake bank, try to survive and to be resilience even in poor conditions.

Renal uric acid (UA) reabsorption is mainly mediated by urate transporter 1 (URAT1) and glucose transporter 9 (GLUT9). Dotinurad selectively inhibits URAT1 and do not inhibit other UA transporters such as GLUT9, ATP-binding cassette transporter G2 (ABCG2) and organic anion transporter1/3 (OAT1/3). We discovered that dotinurad improved metabolic parameters and renal function in hyperuricemic patients. We consider a significance of high selectivity in inhibiting URAT1 by dotinurad for metabolic syndrome, chronic kidney disease (CKD), and cardiovascular disease (CVD). Dotinurad inhibits selectively URAT1 and increases UA in the proximal tubules, and UA may compete with glucose for GLUT9, reducing glucose reabsorption. The inhibition of UA entry via URAT1 to liver and adipose tissues by dotinurad increased energy expenditure and decrease lipid synthesis and inflammation in rats. The inhibition of URAT1 in kidney, liver and adipose tissues improve metabolic parameters. CKD patients accumulate uremic toxins such as indoxyl sulfate (IS) in the body. ABCG2 regulates renal and intestinal excretion of IS which strongly affects CKD. OAT1/3 inhibitors suppress IS uptake into kidney, increasing plasma IS, which produces oxidative stress, inducing vascular endothelial dysfunction in CKD patients. The high-selective inhibition of URAT1 by dotinurad may be beneficial for metabolic syndrome, CKD and CVD.

Ophthalmological services face global inadequacies, especially in low- and middle-income countries, which are marked by a shortage of both practitioners and equipment. This study employed a portable slit-lamp microscope with video capabilities and cloud storage for a more equitable global diagnostic resource distribution. To enhance accessibility and quality of care, this study targeted corneal opacity, a global cause of blindness. To boost the online diagnosis efficiency, an AI pipeline was developed using anterior segment videos to detect corneal opacity. First, we extracted image frames from videos and learned them using a Convolutional Neural Network(CNN) model. Second, we manually annotated to extract only the corneal margins, adjusted the contrast with CLAHE, and learned using the CNN model. Finally, we performed semantic segmentation of the cornea using the annotated data. The results showed an accuracy of 0.8 for image frames, and 0.96 for corneal margins. Dice and IoU were 0.94 for semantic segmentation of corneal margins. While corneal opacity detection from video frames seemed challenging in the early stages of this study, manual annotation, corneal extraction, and CLAHE contrast adjustment significantly improved accuracy. Integrating manual annotation into the AI pipeline through semantic segmentation achieved a high accuracy in detecting corneal opacity.

Kaposi’s sarcoma-associated herpesvirus (KSHV), also known as human herpesvirus-8, is the causative agent of Kaposi’s sarcoma, Castleman’s disease, and primary effusion lymphoma. Although the functions of the viral thymidine kinases (vTK) of herpes simplex virus-1/2 and varicella zoster virus are well understood, that of KSHV ORF21 (an ortholog of vTK) is largely unknown. Here, we investigated the role of ORF21 in lytic replication and infection by generating two ORF21-mutated KSHV BAC clones: ORF21-kinase activity deficient-KSHV (21KD) and stop codon-induced ORF21-deleted-KSHV (21del). The results showed that both ORF21-mutations did not affect viral genome replication, lytic genes transcription, or the production of viral genome-encapsidated particles. ORF21 molecule-dependent function, other than the kinase function of ORF21, was involved in the infectivity of progeny virus. ORF21 was expressed at 36 h after induction of lytic replication, and endogenously expressed ORF21 was localized in the whole cytoplasm and decreased on the cell surface area. Moreover, the effects of ORF21 expression on signaling pathways and proliferation were analyzed. The results showed that ORF21 upregulated the MEK phosphorylation and anchorage-independent cell growth. These findings indicate that ORF21 plays key roles in both infection and oncogenesis of KSHV through the manipulation of cellular function.

Nanostructured transition metal nitrides (TMNs) have been considered a promising substitute for precious metal catalysts toward ORR due to their multi-electron orbitals, metallic properties, and low cost. To design TMNs catalysts with high catalytic activity toward ORR, the intrinsic features of the influencing factor on the catalytic activity toward ORR of nanostructured TMNs need to be investigated. In the paper, titanium nitride (TiN), zirconium nitride (ZrN), and hafnium nitride (HfN) nanoparticles (NPs) are high-efficiency and one-step synthesized by the direct current arc plasma. TiN, ZrN, and HfN NPs with an oxidation layer are applied as the catalysts of hybrid sodium-air batteries (HSABs). The effect of composition and structure attributes of TMNs on ORR catalysis is defined as follows. (ⅰ) Composition effect. With the increase of the oxygen content, the catalytic ORR capability of TMNs decreases progressively due to the reduction of oxygen adsorption capacity; (ⅱ) Structure effect. The redistribution of the density of states (DOS) of ZrN indicates higher ORR activity than TiN and HfN. HSABs with ZrN exhibit an excellent cyclic stability up to 137 cycles (about 140 h), an outstanding rate performance, and a specific capacity of 2817 mAh·g−1 at 1.0 mA·cm−2.

Membranes based on sulfonated synditoactic polystyrene were thoroughly characterized by contrast variation SANS over a wide Q-range in dry and hydrated states. The film samples were prepared by solid-state sulfonation that allowed a uniform sulfonation of only the amorphous phase while preserving the crystallinity of the membrane. The samples were loaded with different guest molecules in either the amorphous (fullerenes) or the crystalline (toluene) regions, in order to vary the neutron contrast or to reproduce the conditions enabling an increased resistance of the membranes to chemical decomposition. The use of uni-axially deformed film samples and contrast variation with different H2O/D2O mixtures allowed for the identification and characterization of different structural levels with sizes between nm and μm, which form and evolve in the membrane morphology in dry and hydrated states and produce scattering features on different detection sectors and at different detection distances after the sample, depending on their size and orientation.

The contactless coalescence of a droplet is of paramount importance for physical and industrial applications. This paper describes a coalescence method in mid-air via acoustic levitation using an ultrasonic phased array system. Acoustic levitation using ultrasonic phased arrays provides promising lab-on-a-drop applications, such as transportation, coalescence, mixing, separation, evaporation, and extraction in a continuous operation. The mechanism of droplet coalescence in mid-air may be better understood by experimentally and numerically exploring the droplet dynamics immediately before the coalescence. In this study, water droplets were experimentally levitated, transported, and coalesced by controlling acoustic fields. We observed that the edge of droplets deformed and attracted each other immediately before the coalescence. Through image processing, the radii of curvature of the droplets were quantified and the pressure difference between the inside and outside the droplet was simulated to obtain the pressure and velocity information on the droplet surface. The results revealed that the sound pressure acting on the droplet clearly decreased before the impact of the droplets. This pressure on the droplets was quantitatively analyzed from the experimental data. Our experimental and numerical results provide deeper physical insights into contactless droplet manipulation for futuristic lab-on-a-drop applications.

A tabletop system can facilitate multi-user collaboration in a variety of settings including small meetings, group work, and education and training exercises. The ability of identifying the users touching the table and their positions can promote collaborative work among participants, so methods have been studied that involve the attaching of sensors to the table or chairs or to the users themselves. An effective method of recognizing user actions without placing a burden on the user would be some type of visual process, so the development of a method that processes multi-touch gestures by visual means is desired. This paper describes the development of a multi-touch tabletop system using infrared image recognition for user position identification and presents the results of touch-gesture recognition experiments and a system usability evaluation. Using an FTIR touch panel and infrared light, this system picks up the shadow area of the user’s hand by infrared camera in relation to user touch operations and estimates user position by image recognition. The multi-touch gestures prepared for this system include an operation to change the direction of an object to face the user and a copy operation in which two users generate duplicates of an object. The average recognition rate of the change-direction gesture and copy gesture were found to be 96% and 85%, respectively. In addition, the system usability evaluation revealed that prior learning was easy and that system operations could be easily performed.

Insufficient oral ridge tissue presents a challenge in the treatment of dental implants. One method to enhance alveolar crest dimensions is guided bone regeneration (GBR); however, existing membranes have certain limitations. To address this issue, we aimed to compare the effectiveness of a resorbable bilayer membrane composed of poly(l-lactic acid) and poly(-caprolactone) （PLACL）with that of a collagen membrane（COL） in a rat GBR model. The rat calvaria was used as an experimental model by placing a plastic cylinder. Forty male Fisher rats underwent surgery, and micro-computed tomography and histomorphometric analyses were performed to assess bone regeneration. The results showed that bone regeneration was similar across all the groups. However, after 24 weeks, the PLACL membrane demonstrated significant resilience, occasional partial degradation, and intermittent air bubble formation. This extended preservation of the barrier effect has great potential to facilitate optimal bone regeneration. In conclusion, this study shows that the PLACL membrane is a promising alternative to GBR. By providing a durable barrier and supporting bone regeneration over an extended period, this resorbable bilayer membrane may address the limitations of the current membranes. Further studies and clinical trials are warranted to validate the efficacy and safety of this drug in humans.

The Seven Country study showed that traditional Japanese diet and Mediterranean diets are protective against cardiovascular diseases (CVDs). Japanese diet is considered the healthiest because it provides highest longevity and health to Japanese. DASH diet and Mediterranean style diets are also considered the healthy diets, although, it is possible that Indo-Mediterranean style diet may provide better protective effects among patients with CVDs, compared to other diets. The concept of Indo-Mediterranean type of diets was developed, after examining its role in the prevention of CVDs in India, the value of which was confirmed by a landmark study from France; The Lyon Heart Study. These workers found that eating alpha-linolenic acid rich Mediterranean style diet can cause significant decline in CVDs and all-cause mortality. Later on in 2018, PREDIMED Study from Spain also reported that a modified Mediterranean style diet can cause significant decline in CVDs, type 2 diabetes mellitus (T2DM) and cancer. The Indo-Mediterranean diet may be superior to DASH diet and Mediterranean diet because it contains millets, porridge, beans and spices; turmeric, cumin, fenugreek and coriander which may have better anti-inflammatory and cardio-protective effects. These foods are rich sources of nutrients; flavonoids, calcium and iron as well as proteins which are useful in the prevention of under as well as over-nutrition and related diseases. It is known that DASH diet and Mediterranean style diets have similar influence on CVDs. However, Indo-Mediterranean style diet, may be as good as Japanese diet, due to improved food diversity and high content of antioxidants in the diets.

Aedes aegypti is inherently susceptible to arboviruses. The geographical expansion of this vector host species has led to the persistence of Dengue, Zika and Chikungunya human infections. These viruses take advantage of the mosquito’s cell to create an environment conducive for their growth. Arboviral infection triggers transcriptomic and protein dysregulation in Ae. aegypti and in effect, host antiviral mechanisms are compromised. Currently, there are no existing vaccines able to protect human hosts from these infections and thus, vector control strategies such as Wolbachia mass release program is regarded as a viable option. Considerable evidence demonstrates how the presence of Wolbachia interferes with arboviruses by decreasing cellular components vital for the pathogen and strengthening antiviral host responses. However, variation in the magnitude of Wolbachia’s viral inhibition that is neither due to strain nor density has been observed. Furthermore, the cellular mechanisms involved in the endosymbiont’s pathogen-blocking differs among hosts. This prompts the need to explore the cellular interactions between Ae. aegypti-arboviruses-Wolbachia and how these interactions overall affect the mosquito’s cell. Understanding what happens at the cellular and molecular level will provide evidence on the sustainability of Wolbachia vector control.

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.

Multichannel EEGs were obtained from healthy participants in the eyes-closed no-task condition (where the alpha component is typically abolished). EEG dynamics in the two conditions were quantified with two related binary Lempel-Ziv measures of the first principal component and with three measures of integrated information including the more recently proposed integrated synergy. Both integrated information and integrated synergy with model order p=1 had greater values in the eyes closed condition. If the model order of integrated synergy was determined with the Bayesian Information Criterion, this pattern was reversed, and in common with other measures, integrated synergy was greater in the eyes open condition. Eyes open versus eyes closed separation was quantified by calculation of the between-condition effect size. Lempel-Ziv complexity of the first principal component showed greater separation than the measures of integrated information. The performance of the integrated information measures investigated here when distinguishing between indisputably different physiological states encourages caution when advocating for their use as measures of consciousness.

In this paper, a novel pendulum-type accelerometer based on hetero-core fiber optics has been proposed for structural health monitoring targeting large-scale civil infrastructures. Vibration measurement is a non-destructive method for diagnosing the failure of structures by assessing natural frequencies and other vibration patterns. The hetero-core fiber optic sensor utilized in the proposed accelerometer can serve as a displacement sensor with robustness to temperature changes in addition to immunity to electromagnetic interference and chemical corrosions. Thus the hetero-core sensor inside the accelerometer measures applied acceleration by detecting the rotation of an internal pendulum. A series of experiments showed that the hetero-core fiber sensor linearly responded to the rotation angle of the pendulum ranging within ±5°, and furthermore the proposed accelerometer could reproduce the waveform of input vibration in a frequency band of several Hz order.

Various types of electroconductive additives were evaluated for high C-rate capability in an attempt to extend practical application of high-areal-capacity lithium–sulfur batteries that employ an aluminum-foam current collector. Carbon nanofibers (CNFs) were found to be the most effective additive, with the ability to attain a high-sulfur-loading of 40 mg cm−2. A CNF-containing cell exhibited gravimetric capacities of 1094 and 758 mAh gsulfur−1 (46.8 and 32.4 mAh cm−2) at 0.05 and 0.1 C-rate, respectively, in an ether-based electrolyte. Because a CNF-containing slurry exhibits low viscosity even at a high solid ratio, it could be filled into the aluminum foam. Additionally, a lithium–sulfur battery with high-sulfur-loading had an energy density of ~120 Wh kg−1, a value that was calculated from the weight of the components of the cathode, anode, current collectors, electrolyte, and separator. Assuming that the amount of electrolyte decreases and that the energy density of cells accumulate, a theoretical energy density of 522 Wh kg−1 was estimated. Moreover, it was found that even if a high-areal-capacity was achieved, the discharge capacity converged at a high C-rate, unless there was an improvement in ion diffusion in the bulk electrolyte. This is considered a limitation of sulfur cathodes with high-sulfur-loading.

AIM Non-alcoholic　fatty liver disease (NAFLD) is the most common cause of chronic liver disease. Pemafibrate, a selective peroxisome proliferator-activated receptor α modulator (SPPARMα), has been reported to ameliorate liver function among patients with dyslipidemia. However, there are not many reports of the clinical effects of the pemafibrate. This study aims to summarize the experience of using pemafibrate and analyze the effects on liver function in patients with dyslipidemia. METHODS One hundred twelve cases of hyperlipidemia receiving pemafibrate 0.2 mg/day were retrospectively enrolled in this study. Age, gender, BMI, complications, concomitant medications, serum parameters (TG, HDL-C, LDL-C, AST, ALT, γGTP, ALP, platelets, M2BPGi, Cre, eGFR, HbA1c, blood glucose level at any time) were investigated and evaluated. RESULTS Pemafibrate administration significantly improved serum TG and HDL-C, but not in LDL-C. Serum AST, ALT, γGTP, and ALP were also significantly improved. The fib-4 index, a liver fibrosis score, did not change significantly, but M2-BPGi, an index of fibrosis, decreased significantly. No correlation was observed between each lipid parameter and ALT, and ALT decreased independently of the lipid parameters. Conclusions As we expected, pemafibrate demonstrated a lipid-improving effect without adversely affecting hepatic and renal functions. An unexpected finding was the decrease in ALT that was independent of lipid parameters.

Coronavirus disease 2019 (COVID-19) affected not only individuals but also families. The purpose of this study was to clarify the temporal changes in the impact of the COVID-19 pandemic on entire families with older adults susceptible to infection living on small islands in Japan over the duration of the pandemic. Family ethnographic research was conducted from 2021 to 2023, using the Concentric Sphere Family Environment Theory as the theoretical framework. Formal interviews were conducted with 20 families. In addition, data from informal interviews, participant observation and other sources were compiled into field notes. All data on the impact on the entire family were extracted and content analysis was conducted. Five categories and a total of 85 subcategories were extracted. The results show that COVID-19 exerted not only negative but also positive impacts on the entire family, and their temporal changes are clarified. The impact on families is believed to have been influenced by the family external environment, such as increases and decreases of infection cases or events that occurred outside the family. The knowledge acquired from these studies will help healthcare professionals in providing appropriate family support.

Impact load was applied to hardened cement paste (HCP) specimens using a gas gun to investigate microscopic changes in the specimens and develop a better response model of concrete subjected to impact load. Plasma emission was observed at the moment of impact at 420 m/s and the colour of the portion near the impact point turned brighter. This brighter portion was analysed, and it was observed that the pore structure was coarser compared to the other portion; however, the results of thermogravimetry and X-ray diffraction analysis were similar. A possible reason is that the generated heat was instantaneous and the rate of the temperature increase in the HCP decreased due to evaporation of water in the HCP. These results indicate that during impact at a few hundred m/s, porosity increase due to heat effect is more dominant than porosity decrease due to mechanical compaction.

Background: This longitudinal study aimed to investigate the relationship between self-reported chewing status and increases in waist circumference (WC) after 1 year in 10,870 Japanese adults who had received health checkups. Subsequently, 8,068 participants were included in the final analysis at follow-up. Methods: Chewing status was evaluated using a self-reported questionnaire at baseline; 1,080 (13%) respondents were diagnosed as having poor chewing status. We defined an increase in WC of ≥ 5 cm after 1 year as an unhealthy increase; in total, 613 (7.5%) respondents met this criterion. Results: After adjusting for age, gender, WC, body mass index (BMI), and chewing status, an increase in WC ≥ 5 cm was found to be positively associated with gender (females: odds ratios [ORs]: 1.206; 95% confidence intervals [CIs]: 1.008–1.443), WC (ORs: 0.967; 95% CIs: 0.954–0.981), BMI (≥ 25 kg/m2; ORs: 2.194; 95% CIs: 1.715–2.808), and chewing status (poor; ORs: 1.356; 95% CIs: 1.084–1.697). Conclusions: These findings suggest that self-reported poor chewing status is associated with increases in WC after 1 year in Japanese adults.

High-grade gliomas present a significant challenge in neuro-oncology because of their aggressive nature and resistance to current therapies. Boron neutron capture therapy (BNCT) is a potential treatment method; however, the boron carrier compounds used — such as 4-borono-L-phenylalanine (L-BPA) — have limitations. This study evaluated the use of boron-conjugated 4-iodophenylbutanamide (BC-IP), a novel boron compound in BNCT, for the treatment of glioma. Using in vitro drug exposure experiments and in vivo studies, we compared BC-IP and BPA, with a focus on boron uptake and retention characteristics. The results showed that although BC-IP had a lower boron uptake than BPA, it exhibited superior retention. Furthermore, despite lower boron accumulation in tumors, BC-IP showed significant survival improvement in glioma-bearing rats compared to controls. These results suggest that BC-IP, with its unique properties, may be an alternative boron carrier for BNCT. Further research is required to optimize this potential treatment modality, which could significantly contribute to advancing the treatment of high-grade gliomas.

Quality-of-life (QOL) is important for cancer patients with poor prognosis. However, QOL survey is difficult using patients. We created cancer scenarios and investigated QOL utility values among the general public using vignette-based methods. On the other hand, some scenarios may have been difficult for the general public to image and understand. Therefore, we conducted a QOL survey among physicians. This survey was conducted by interviewing physicians adminis-tering chemotherapy to patients for recurrent/metastatic pancreatic cancer. Responses were eval-uated using Composite Time Trade-Off (cTTO) and Visual Analog Scale (VAS) for 11 pancreatic cancer status scenarios to be evaluated (survey scenarios). Survey scenarios consisted of health state, type and Grade of adverse events. Health status was classified into two categories: Stable disease (SD) and Progressive disease (PD). Twenty responders answered in this survey, however two responses were excluded because of inconsistent responses. The stable disease had the highest QOL value for both assessment method. Whereas progression disease (PD) had the lowest QOL value. The physicians scored higher QOL values on VAS and cTTO than the general public in all survey scenarios. The QOL values obtained by physicians were consistent with the degree of sta-tus in any assessment scenarios.

The outdoor field test of the 4-terminal on Si tandem photovoltaic module (specifically, InGaP/GaAs on Si) was investigated and performance model, considering spectrum change affected by fluctuation of atmospheric parameters, was developed and validated. The 4-terminal on Si tandem photovoltaic module had about 40 % advantage in seasonal performance loss compared with standard InGaP/GaAs/InGaAs 2-terminal tandem photovoltaic module. This advantage is expanded in (subarctic zone) < (temperate zone) < (subtropical zone). The developed and validated model used all-climate spectrum model and considered fluctuation of atmospheric parameters, and can be applied every type of on-Si tandem solar cells.

Objectives: This study validated the Japanese version of O’Donovan et al.’s (2020) composite measure of psychological safety scale and examined the associations of psychological safety with mental health and job-related outcomes. Methods: Online surveys were administered twice to Japanese employees with teams of more than three members. Internal consistency and test-retest reliability was tested using Cronbach’s α and intra-class correlation coefficient (ICC). Structural validity was examined using confirmatory factor analysis (CFA) and exploratory factor analysis (EFA). Convergent validity was tested. Multiple linear regression analyses were conducted to examine the relationship between psychological safety and psychological distress, work engagement, job performance, and job satisfaction. Results: Two hundred healthcare workers and 200 non-healthcare workers were analyzed. The Cronbach’s alpha of the total score was 0.92 - 0.96 and ICC was 0.88 - 0.92. CFA demonstrated poor fit, and EFA yielded a two-factor structure, suggesting one factor combined with peers and team. The scale showed good convergent validity. The total score of the scale showed significant associations with all outcomes in adjusted model in all workers. Conclusions: The Japanese version of the measure of the psychological safety scale presented good reliability and validity. Psychological safety is important for employees’ mental health and performance.

Kaposi’s sarcoma-associated herpesvirus (KSHV) is the etiologic agent of Kaposi’s sarcoma, primary effusion lymphoma (PEL) and multicentric Castleman’s disease. During KSHV lytic infection, lytic-related genes, categorized as immediate-early, early, and late genes, are expressed in a temporal manner. The transcription of late genes requires the virus-specific pre-initiation complex (vPIC), which consists of viral transcription factors. However, the characterization of the protein-protein interactions of the vPIC factors has not been completely elucidated. KSHV ORF18 is one of the vPIC factors, and its interaction with other viral factors has not been sufficiently revealed. Here, we analyzed the interaction between ORF18 and another vPIC factor, ORF30, in living cells using the bimolecular fluorescence complementation (BiFC) assay. We identified four amino-acid residues (Leu29, Gln36, His41 and Trp170) on ORF18 that were responsible for its interaction with ORF30. The artificial intelligence (AI) system AlphaFold2 predicted that identified four residues are exposed to the surface of ORF18 and located in proximity to each other in the surface of ORF18. Thus, AI-predicted model supports the importance of four residues for binding of ORF18 to ORF30. Our results indicated that wet experiments in combination with AI may enhance the structural characterization of vPIC protein-protein interactions.

Utilization of wasted heat instead of fuel combustion is effective to reduce primary energy consumption for mitigating global warming problem. Because wasted heat sources are not necessarily located close to areas of heat demand, one of the difficulties is that wasted heat has to be transferred from heat source side to heat demand side, which may require heat transportation over long distance. From this point we proposed and have examined new idea of heat transportation using ammonia-water as the working fluid which system is named Solution Transportation Absorption chiller, in short STA. Our previous studies of STA were mainly the experimental investigation with STA facility which cooling power was 25RT (90kW). As a result, the COP of STA was found almost same value 0.65 with the conventional absorption chiller without depending on the transportation distances. The simulation using AspenHYSYS also examined with same experimental condition. The experimental data showed good agreement with the simulation calculation. In this study, we examined the large-scale cooling power STA on simulation. The examination cooling powers were from 90 kW(25RT) to 3517 kW(1000RT). All cooling power achieved around COP 0.64 including pump power consumptions. In addition, we performed the dynamic simulation. As the results, there was no effect of pipeline size on the cooling capacities and mass flow rates. Furthermore, the stability time of the cooling capacities and mass flow rates were almost same regardless of the pipeline size and cooling capacity. In other words, STA may be achieved the same COP even though having various complex conditions compared with the conventional absorption chiller.

In the process of transcription initiation by RNA polymerase, promoter DNA sequences affect multiple reaction pathways determining the productivity of transcription. However, the question of how the molecular mechanism of transcription initiation depends on sequence properties of promoter DNA remains poorly understood. Here, combining the statistical mechanical approach with high-throughput sequencing results, we characterize abortive transcription and pausing during transcription initiation by Escherichia coli RNA polymerase at a genome-wide level. Our results suggest that initially transcribed sequences enriched with thymine bases represent the signal inducing abortive transcription. On the other hand, certain repetitive sequence elements broadly embedded in promoter regions constitute the signal inducing pausing. Both signals decrease the productivity of transcription initiation. Based on solution NMR and in vitro transcription measurements, we also suggest that repetitive sequence elements of promoter DNA modulate the rigidity of its double-stranded form, which profoundly influences the reaction coordinates of the productive initiation via pausing.

Background: We investigated ion channels at the skin, including peripheral nerve endings, which serve as output machines and molecular integrators of many pruritic inputs mainly received by multiple G protein-coupled receptors (GPCRs). Methods: Based on the level of chronic kidney disease–associated pruritus (CKD-aP), subjects were divided into two groups: non-CKD-aP (no or slight pruritus; n=12) and CKD-aP (mild, moderate, or severe pruritus; n=11). Skin samples were obtained from the forearm or elbow during operations on arteriovenous fistulas. We measured ion channels expressed at the skin, including peripheral nerve endings by RT-PCR: Nav1.8, Kv1.4, Cav2.2, Cav3.2, BKCa, Anoctamin1, TRPV1, TRPA1, and ASIC. Results: Expression of Cav3.2, BKCa, and anoctamin1 was significantly elevated in patients with CKD-aP. On the other hand, expression of TRPV1 was significantly reduced in these patients. We observed no significant difference in the levels of Cav2.2 or ASIC between subjects with and without CKD-aP. TRPA1, Nav1.8，and Kv1.4 were not expressed. Conclusions: It was concluded that this greater difference in expression of ion channels at the skin tissue including specific for cutaneous peripheral nerve endings in CKD patients with CKD-aP may increase generator potential related to itching.

The relationship between city size, coastal land use and air temperature rise with distance from coast during summer day is analyzed using the meso-scale Weather Research & Forecasting (WRF) model in five coastal cities in Japan with different sizes and coastal land use (Tokyo, Osaka, Nagoya, Hiroshima and Sendai) and inland cities in Germany (Berlin, Essen and Karlsruhe). Air temperature increased as distance from the coast increased, reached its maximum, and then decreased slightly. In Nagoya and Sendai, the number of urban land use in coastal areas is less than the other three cities, where air temperature is a little lower. As a result, air temperature difference between coastal and inland urban area is small and the curve of air temperature rise is smaller than those in Tokyo and Osaka. In Sendai, air temperature in the inland urban area is the same as in the other cities, but air temperature in the coastal urban area is a little lower than the other cities, due to about one degree lower sea surface temperature influenced by the latitude. In three German cities, the urban boundary layer may not develop sufficiently because the fetch distance is not enough.

Epithelial-mesenchymal transition (EMT) networks are essential in acquiring the drug resistance and cancer malignant features in cancer stem cells (CSCs). In this regard, gene expression profiles in diffuse- and intestinal-type gastric cancer (GC) have been analyzed to reveal the network pathways in EMT and CSCs, since the diffuse-type GC has much more mesenchymal features than intestinal-type GC that has the intestinal features. The study results revealed that the activation state of several canonical pathways related to cell cycle regulation was altered. The canonical pathway on Cell cycle: G1/S checkpoint regulation was activated in diffuse-type GC, and canonical pathways on Cell cycle control of chromosomal replication and Cyclins and cell cycle regulation were activated in intestinal-type GC. Canonical pathway related to Role of BRCA1 in DNA damage response was activated in intestinal-type GC, where BRCA1, which is related to G1/S phase transition was up-regulated in intestinal-type GC. Several microRNAs (miRNAs), including mir-10, mir-17, mir-19, mir-194, mir-224, mir-25, mir-34, mir-451, and mir-605, were identified to have direct relationships of RNA-RNA interaction in Cell cycle: G1/S checkpoint regulation pathway. Additionally, cell cycle regulation may be altered in EMT conditions. The alterations in activation states of the pathways related to cell cycle regulation in diffuse- and intestinal-type GC would indicate the significance of cell cycle regulation in EMT.

Expression levels of Cav3.2, BKCa, and anoctamin 1 were previously found to be significantly elevated in patients with chronic kidney disease–associated pruritus (CKD-aP). On the other hand, the expression of TRPV1 was significantly reduced. We further compared CKD patients with and without CKD-aP in terms of the expression levels of several ion channels in the skin, including in peripheral nerve endings。Based on CKD-aP severity, subjects were divided into two groups: non-CKD-aP (no or slight pruritus; n = 16) and CKD-aP (mild, moderate, or severe pruritus; n = 16). Skin samples were obtained from the forearm or elbow during arteriovenous fistula surgery. We used quantitative real-time polymerase chain reaction to measure the skin expression levels of the following ion channels in the skin: Nav1.7, Kv7.2, TREK1, HCN2, TrkA, and Piezo2.　RT-PCR analyses showed that CKD-aP patients had significantly higher levels of TREK1 and Piezo2 transcripts and significantly lower levels of HCN2 transcripts than non–CKD-aP patients. No significant differences were noted between groups in the expression of Nav1.7 or TrkA. Moreover, Kv7.2 transcripts were not detected in either group. In skin samples collected from CKD-aP patients, ion channel expression patterns were altered to enhance hyperpolarization of pruriceptive neurons.

Oncostatin M (OSM), an inflammatory cytokine belonging to interleukin-6 superfamily, is recognized as an essential factor secreted by osteal macrophages to orchestrate bone remodelling. Osteoprotegerin (OPG) produced by osteoblasts regulates osteoclastogenesis. We previously demonstrated that bone morphogenetic protein-4 (BMP-4) stimulates OPG synthesis in osteoblast-like MC3T3-E1 cells, and that SMAD1/5/8(9), p38 mitogen-activated protein kinase (MAPK), and p70 S6 kinase positively regulates the OPG synthesis. The present study is aimed to investigate the effect of OSM on BMP-4-stimulated OPG synthesis in osteoblasts. OSM suppressed the release and the mRNA expression of OPG upregulated by BMP-4 in MC3T3-E1 cells.  Neither the BMP-4-induced phosphorylation of SMAD1/5/9 nor that of p38 MAPK affected by OSM. On the other hand, the BMP-4-stimulated phosphorylation of p70 S6 kinase was considerably suppressed by OSM. These results strongly suggest that OSM suppresses the BMP-4-stimulated OPG synthesis via inhibition of the p70 S6 kinase-mediated pathway in osteoblasts.

The digital era has significantly amplified the volume of online reviews, presenting both opportunities and challenges in harnessing insights from consumer feedback. Aspect-Based Sentiment Analysis (ABSA) has emerged as a crucial tool for distilling sentiments from these reviews, providing valuable data for enhancing product and service quality. This study introduces an advanced hybrid model, AdvSentiNet, which integrates adversarial training into the state-of-the-art framework to elevate the precision of sentiment detection at the aspect level. By employing an adversarial network, where a generative model competes against a classifier by crafting highly realistic synthetic samples, we aim to bolster the model's resilience against varied data samples. This innovative approach, unexplored in its entirety within the realm of ABSA, demonstrated remarkable performance improvements on benchmark datasets. For instance, accuracy on the SemEval 2015 dataset escalated from 81.7% to 82.5%, and for the SemEval 2016 dataset, it surged from 84.4% to 87.3%.

Epithelial-mesenchymal transition (EMT) plays an important role in the acquisition of cancer stem cell (CSC) feature and drug resistance, which are the main hallmarks of cancer malignancy. Although previous findings have shown that several signaling pathways are activated in cancer progression, the precise mechanism of signaling pathways in EMT and CSCs are not fully understood. In this study, we focused on the intestinal and diffuse-type gastric cancer (GC), and analyzed the gene expression of public RNAseq data to understand the molecular pathway regulation in different subtypes of gastric cancer. Network pathway analysis was performed by Ingenuity Pathway Analysis (IPA). Total 2815 probe set IDs were significantly different between intestinal- and diffuse-type GC data in cBioPortal Cancer Genomics. The 10 genes including male-specific lethal 3 homolog (Drosophila) pseudogene 1 (MSL3P1), CDC28 protein kinase regulatory subunit 1B (CKS1B), DEAD-box helicase 27 (DDX27), golgi to ER traffic protein 4 (GET4), chromosome segregation 1 like (CSE1L), translocase of outer mitochondrial membrane 34 (TOMM34), YTH N6-methyladenosine RNA binding protein 1 (YTHDF1), ribonucleic acid export 1 (RAE1), par-6 family cell polarity regulator beta (PARD6B), and MRG domain binding protein (MRGBP) were found to have difference in gene expression in intestinal- and diffuse-type GC. Total 463 direct relationships with 3 molecules (MYC, NTRK1, UBE2M) were found in the biomarker-filtered network generated by network pathway analysis. The networks and features in intestinal- and diffuse-type GC have been investigated and profiled in bioinformatics. Our results revealed the signaling pathways networks in intestinal- and diffuse-type GC, bringing new light for the elucidation of drug resistance mechanisms in CSCs.

Digital Microfluidic Biochips (DMFBs), used in various kinds of fields like DNA analysis, clinical diagnosis, and PCR testing, have made biochemical experiments more compact, efficient, and user-friendly than previous ways. However, their reliability is often compromised by their inability to adapt to all kinds of errors. All errors in biochips can be categorized into two types: known errors and unknown errors. Known errors are detectable before the start of the routing process through sensors or cameras. Unknown errors, in contrast, become apparent only during the routing process and remain undetected by sensors or cameras, which is the biggest issue to unexpectedly stop the routing process and diminishes the reliability of biochips. This paper introduces a deep reinforcement learning-based routing algorithm designed to manage not only known errors but also unknown errors. Our experiments demonstrate that our algorithm outperforms previous ones in terms of the success rate of the routing in the scenario including both known errors and unknown errors. Additionally, our algorithm contributes to detecting unknown errors during the routing process and identifying the most efficient routing path with high probability.

Background Community infections of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have increased rapidly since the emergence of the Omicron strain. During the eighth and ninth pandemic waves—when movement restrictions in the community were eased—the all-case registration system was changed, and the actual status of infection became uncertain. Methods We conducted regular rapid antigen tests (R-RAT) once or twice a week to examine the actual state of coronavirus disease (COVID-19) diagnosis among healthcare employees. Results Overall, 320 (1.42/day) and 299 (1.76/day) employees were infected in the eighth and ninth pandemic waves. During both periods, 59/263 doctors (22.4%), 335/806 nurses (41.6%), 92/194 administrative employees (47.4%), and 129/218 clinical laboratory technicians (59.2%) were infected. In the eighth wave, 56 of 195 employees were infected through close contact; in the ninth wave, 26 of 62 employees were infected. No significant difference was observed in the number of vaccinations between infected and non-infected employees. The positivity rate of R-RAT was 0.41% and 0.45% in the eighth and ninth waves. R-RAT detected infection in 212 and 229 employees during the eighth and ninth waves, respectively; the ratio of R-RAT-detected positive employees to those who reported infection was significantly higher during the ninth wave (odds ratio: 1.67, 95% confidence interval: 1.17–2.37, p

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.

Exercise can be hypothesized to play an important role in NAFLD treatment by changing the oral bacterial flora and in the mechanism underlying periodontal disease. We performed salivary component analysis before and after an exercise regimen, and genome analysis of the oral bacterial flora to elucidate the underlying mechanism. Obese middle-aged men with NAFLD and periodontal disease were allocated to 12-week exercise (n=49) or dietary restriction (n=21) groups. We collected saliva to compare the oral microflora; performed predictive analysis of metagenomic functions; and measured the salivary immunoglobulin A, cytokine, bacterial lipopolysaccharide (LPS), and lactoferrin concentrations. The exercise group showed improvements in clinical indices of oral environment. Salivary component analysis revealed significant reductions in LPS, and lactoferrin during the exercise regimen. Diversity analysis of oral bacterial flora revealed higher alpha- and beta-diversity after the exercise regimen. Analysis of the microbial composition revealed that the numbers of Campylobacter (+83.9%), Corynebacterium (+142.3%), Actinomyces (+75.9%), and Lautropia (+172.9%) were significantly higher and that of Prevotella (−28.3%) was significantly lower. The findings suggest that an exercise regimen improves the oral environment of NAFLD patients by increasing the diversity of the oral microflora and reducing the number of periodontal bacteria that produce LPS and its capability.

The highest efficiency solar cell won in the efficiency race does not always give the most excellent annual energy yield in the real world solar condition that the spectrum is ever-changing. The study of the radiative coupling of the concentrator solar cells implied that the efficiency could increase by the recycle of the radiative recombination generated by the surplus current in upper junction. Such configuration is called by a super-multi-junction cell. We expanded the model in the concentrator solar cell to non-concentrating installation. It was shown that this super-multi-junction cell configuration was found robust and can keep the maximum potential efficiency (50 % in realistic spectrum fluctuation) up to 10 junctions. The super-multi-junction cell is also robust in the bandgap engineering of each junction. Therefore, the future multi-junction may not be needed to tune the bandgap for matching the standard solar spectrum, as well as relying upon artificial technologies like ELO (Epitaxial lift-off), wafer-bonding, mechanical-stacking, and reverse-growth, but merely uses up-right and lattice-matching growth technologies. We have two challenging techniques; one is the optical cap layer that may be the directional photon coupling layer in the application of the photonics technologies, and another is the high-quality epitaxial growth with almost 100 % of the radiative efficiency.

To reveal the relationship between metallodrugs and cancer malignancy, molecular networks of anti-cancer drugs were analyzed. Molecular networks in several types of cancers were analyzed in Ingenuity Pathway Analysis (IPA). Analysis of carboplatin revealed the causal network in diffuse large B-cell lymphoma. Analysis of 12 analyses of cisplatin treatment identified causal networks including camptothecin and NUPR1. The causal network of camptothecin, which includes PTEN, FAS, and IRF1, was inactivated in diffuse-type GC and activated in intestinal-type GC. Upstream regulator analysis of cisplatin revealed an increase in FAS, BTG2, SESN1 and CDKN1A, and the involvement of the tumor microenvironment pathway. Upstream regulators of cisplatin-treated lung adenocarcinoma included a histone deacetylase inhibitor, trichostatin A (TSA). Causal network of arsenic was inactivated in diffuse-type GC and activated in intestinal-type GC, and included ERK, EGFR, SRC, IKK and TP53. Prediction of RNA-RNA interactions with the causal network of arsenic identified 10 microRNAs including mir-101, mir-103, and mir-22. The results revealed the involvement of EMT in arsenic treatment. Analysis of oxaliplatin, a platinum drug, revealed that the SPINK1 pancreatic cancer pathway is inactivated in ischemic cardiomyopathy. The study showed the importance of the relationship between platinum drugs or arsenic trioxide and the tumor microenvironment in the treatment of resistant cancer in humans.

Food allergies are common worldwide and have become a major public health concern; more than 220 million people are estimated to suffer from food allergies worldwide. On the other hand, polyphenols, phenolic substances found in plants, have attracted attention for their health-promoting functions, including their anti-allergic effects. In this study, we examined the potential inhibitory effects of 80% ethanol extracts from 22 different vegetables on the degranulation process in RBL-2H3 cells. Our aim was to identify vegetables that could prevent and treat type I allergic diseases. We found strong inhibition of degranulation by the extracts of perilla and chives. Furthermore, we verified the respective efficacy via animal experiments, which revealed that the anaphylactic symptoms caused by ovalbumin (OVA) load were alleviated in OVA allergy model mice that ingested vegetable extracts of perilla and chives. These phenomena were suggested to be caused by induction of suppression in the expression of subunits that constitute the high-affinity IgE receptor, particularly the α-chain of FcεR I. Notably, the anti-allergic effects of vegetables that can be consumed daily are expected to result in the discovery of new anti-immediate allergenic drugs based on the components of these vegetables.

We investigated humoral immune responses in 222 unvaccinated Japanese people after recovery from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in 2021. Anti-spike protein IgG antibody levels and neutralizing antibody titers were measured in serum samples obtained within 20–180 days after diagnosis. The geometric mean of antibody titers was 1555 ELU/mL (95% confidence interval [CI] = 1257-1923), and the neutralizing activities (50% inhibitory dilution) was 253 (95% CI = 204-313). The antibody titer and neutralizing activity both increased with increasing disease severity, and both values were approximately 4-fold higher for hospitalized patients than for non-hospitalized patients. However, these differences were smaller in older patients. The humoral immune response, which increased with increasing disease severity, gradually decreased over time after SARS-CoV-2 infection. Most patients with mild or moderate symptoms sustained neutralizing activity for up to 180 days after the infection, the decay of the neutralizing activity in the patients with asymptomatic was rather faster than other groups. 11.7% (26/222) of patients had very low neutralizing activity, and half of these were in the age of 20s. Our study results show the importance of measuring the neutralizing activity to confirm the immune status and also estimate the timing of vaccine.

We evaluated the change in water dispersibility of lactic acid bacteria (LAB, Enterococcus faecalis KH2) upon powderization and its influence on their efficacy. When cultured LAB are washed, heat-killed, and powdered, adhesion between LAB occurs and they form aggregation (non-treated LAB, n-LAB). However, a dispersed LAB (d-LAB) powder with less aggregates can be prepared by treating them with a high-pressure homogenizer and adding an excipient during powdering. n-LAB or d-LAB was administered to mice and the Peyer's patches in the small intestine were observed. n-LAB administration showed a high amount of aggregated LAB drifting in the intestinal mucosa, whereas d-LAB reached the Peyer's patches and was taken up into the Peyer's patches. Evaluation in a mouse influenza virus infection model showed that d-LAB was more effective than n-LAB in influenza yield of bronchoalveolar lavage fluids (BALFs) on day 3 post-infection, neutralizing antibody titers of sera and influenza virus-specific IgA in the feces on day 14 post-infection. Thus, the physical properties of LAB affect their efficacy; controlling their water dispersibility can improve their effectiveness.

This paper deals with the possibility for construction of the database on friction coefficient on the actual roads from the viewpoint of traffic safety. A measurement algorithm is determined in order to construct road friction measuring device. Next, the tires used for measurement are selected and the characteristics are measured using bench tire characteristic tester, and the measuring device is designed and constructed based on the characteristics. Finally, using this device, the measurement results of the road friction characteristics for two types of road surfaces are shown.

The aim of this study is to describe a research protocol of a multi-country randomized controlled trial to investigate the effect of a smartphone CBT stress management program on improving depression and other health- and work-related outcomes among hospital nurses in Vietnam and Thailand during the COVID-19 epidemic as a part of the COCONATS project. The study is a two-arm, parallel randomized control trial. Hospital nurses (N = 1,500) will be recruited in Vietnam and Thailand, and those who meet the criteria will be randomly allocated to the intervention or control (treatment as usual) group. A seven-week, seven-module smartphone-based stress management program will be developed to teach CBT skills. The intervention group will participate in the program for 10 weeks. Depression as the primary outcome will be measured using the DASS21 at baseline and in 3- and 6-month follow-up surveys. A mixed model repeated measures analysis will be used to test the intervention effect in the total combined sample, on an intention-to-treat basis. This is the first study to investigate the effectiveness of a self-guided smartphone CBT program on improving depression among hospital nurses using a RCT design in South-East Asian middle-income countries during the COVID-19 pandemic.

The thermal properties of novel nanomaterials play a significant role in determining the performance of the material in technological applications. Herein, direct measurement of the temperature diffusivity of cellulose nanocomposite films was carried out by the micro-contact method. Polymer films containing up to 2%wt. of nanocellulose were synthesised by a simple chemical process. Films of a high optical transmittance T ≈ 80 % (for a 200- μ m-thick film), which were up to 44% crystalline, were characterised. Two different modalities of temperature diffusivity based on: 1) a resistance change and 2) micro-thermocouple detected modulation of a heat wave, were used for the polymer films with cross-sections of ∼ 100 μ m thickness. Twice different in-plane α ‖ and out-of-plane α ⊥ temperature diffusivities were directly determined with high fidelity: α ‖ = 2 . 12 × 10 − 7 m 2 /s and α ⊥ = 1 . 13 × 10 − 7 m 2 /s. An amorphous polyethylene terephthalate (PET) fiber was measured for comparison α ‖ = 1 . 15 × 10 − 7 m 2 /s. This work provides an example of a direct contact measurement of thermal properties of nanocellulose composite films. The thermal diffusivity, which is usually high in strongly interconnected networks and crystals, was investigated for the first time in this composite.

Ethyl loflazepate (EL) is a benzodiazepine derivative that has been reported to activate the gustatory cortex. Our department routinely uses EL as a first-line treatment for idiopathic and psychogenic taste disorders, although little has been reported in the literature with respect to patient outcomes, so we conducted a retrospective study examining its safety and efficacy. Between 2008 and 2020, 49 patients (14 males and 35 females; mean age, 62.1 years) were diagnosed with taste disorders and received EL as their only treatment for &gt;14 days. Severity of taste disorder was evaluated using the paper disc method by Sakai et al [7], and treatment efficacy was evaluated using the Visual Analogue Scale, wherein patients gave subjective ratings for their symptoms (reductions by &gt;50% after administration of EL for 4 weeks were defined as mprovements). Results showed that the improvement rates for patients with idiopathic and psychogenic taste disorders were 55% and 70%, respectively. Additionally, the majority (78%) improved within 2 weeks, and side effects were mild (seven cases of sleepiness and one case of dizziness). We conclude that EL is an appropriate first-line medication for patients with idiopathic and psychogenic taste disorders.

Purinergic receptors (P2X) are ATP-gated ion channels with an elusive role in the CNS. While the P2X2 and P2X4 subtypes are widely expressed in most neurons (i.e. at the edge of the postsynaptic densities of excitatory synapses), the direct contribution of P2X to synaptic transmission is uncertain. Several P2X have been shown to participate in receptor cross-talk: an interaction where one receptor (e.g. P2X2) influences the activity of another (e.g. GABA or AMPA receptors.) In this study, we tested for interactions between P2X2 or P2X4 and N-methyl-D-aspartate receptors (NMDARs). Using two-electrode voltage-clamp electrophysiology experiments in X. laevis oocytes, we demonstrate that both P2X2 and P2X4 interact with NMDARs in an inhibitory manner. When investigating the molecular domains responsible for this phenomenon, we found that the P2X2 c-terminus (CT) could interfere with P2X2 and P2X4 interactions with NMDARs. We also report that 11 distal CT residues on the P2X4 facilitate the P2X4-NMDAR interaction, and that a peptide consisting of these P2X4 CT residues (11C) can disrupt the interaction between NMDARs and P2X2 or P2X4. Collectively, these results provide new evidence for the modulatory nature of P2X2 and P2X4, suggesting they might play a more nuanced role in the CNS.

This research program investigated the effects of layer thickness (50 and 100 microns) on the microstructure and mechanical properties of electron beam powder bed fusion (EBPBF) additive manufacturing of Inconel 625 alloy. The as-built 50 and 100 micron layer thickness components were also heat treated at temperatures above 1100 oC, which produced a recrystallized grain structure containing annealing twins in the 50 micron layer thickness components, and a duplex grain structure consisting of islands of very small equiaxed grains dispersed in a recrystallized, large-grain structure containing annealing twins. The heat treated component microstructures and mechanical properties were compared with the as-built components in both the build direction (vertical) and perpendicular (horizontal) to the build direction. Vickers microindentation hardness (HV) values for the vertical and horizontal geometries averaged 227 and 220 for the as-built 50 and 100 micron layer components, and 185 and 282 for the corresponding heat treated components. The yield stress values were 387 MPa and 365 MPa for the as-built layer horizontal and vertical 50 micron layer geometries, and 330 MPa and 340 MPa for the as-built 100 micron layer components. For the heat treated 50 micron components, the yield stress values were 340 and 321 MPa for the horizontal and vertical geometries, and 581 and 489 MPa for the 100 micron layer components, respectively. The elongation for the 100 micron layer as-built horizontal components was 28% in contrast to 65% for the corresponding 100 micron heat treated layer components, an increase of 132% for the duplex grain structure. However, the coarse grains containing annealing twins and the equiaxed small grain islands in the duplex structure for the heat treated components contained continuous carbides in the grain boundaries, and this may indicate sensitization and a reduction in corrosion resistance. These findings point to the potential mechanical property advantage for heat treatment of Inconel 625 alloy 100 micron layer thickness components fabricated by EBPBF.

Abstract: Congenital cytomegalovirus (cCMV) infection poses significant risks to fetal development, particularly affecting the nervous system. This study reports a fetal autopsy case, examining cCMV infection and focusing on CMV DNA measurements in various fetal organs before formalin fixation, a novel approach for comprehensive CMV DNA evaluations in fetal organs affected by cCMV. A 20-week-old male fetus was diagnosed with cCMV following the detection of CMV DNA in ascites obtained via abdominocentesis in utero. After termination of pregnancy, multiple organs of the fetus, including the cerebrum, thyroid gland, heart, lungs, liver, spleen, kidneys, and adrenal glands, were extracted and examined for CMV DNA loads using real-time polymerase chain reaction. Histopathological examination involved hematoxylin-eosin and CMV-specific immunostaining. A correlation was found between CMV DNA loads and pathology, with higher CMV-infected cell numbers observed in organs positively identified with both staining methods, exhibiting CMV DNA levels of ≥1.0 × 104 copies/mL, compared to those detected solely by CMV-specific immunostaining, where CMV DNA levels ranged from 1.0 x 103 to 1.0 x 104 copies/mL. These results highlight a quantifiable relationship between organ infection extent and CMV DNA concentration, providing insights into cCMV pathogenesis and potentially informing future diagnostic and therapeutic strategies for cCMV infection.

To examine the hydrophobicity of torrefied wood fuel, the water resistances of torrefied pellets prepared by two different methods were evaluated using exposure tests under indoor and outdoor conditions. Torrefied pellets from the xylem of Japanese cedar (Sugi, Cryptomeria japonica) and oak (Konara, Quercus serrata) were prepared by two methods: the torrefaction of wood chips followed by pelletization and the pelletization of wood chips followed by torrefaction. It was found that the pellets prepared by pelletization followed by torrefaction had much lower moisture levels than those prepared by the other method and they showed almost no change in diameter after an outdoor weathering test. These characteristics are unique and indicate that the pellets can be applied not only for industrial use but also for residential and commercial purposes.

In this study, the friction factor of turbulent pipe flow for dried rice malt extract solutions is reduced experimentally to that of a Newtonian fluid. The friction factor is measured for four types of solutions at different culture times and concentrations. The results indicate that the experimental data points of the test solutions diverge from the maximum drag reduction asymptote at and above Re√f ≅ 200 and align parallel to those of Newtonian fluids. This drag reduction phenomenon differs from that of artificial high molecular polymer solutions. It is classified as a Type B drag reduction phenomenon of biopolymer solutions and fine solid particle suspensions. The order of drag reduction corresponds approximately to that of 5–50 ppm xanthan-gum solutions reported previously. Furthermore, the velocity profile in a turbulent pipe flow was predicted using a semi-theoretical equation, in which the friction factors were determined using the difference between the experimental results of the tested solutions and Newtonian fluids. The results indicate a more considerable thickening of the viscous sublayer in the turbulent pipe flow of the test solutions than that of Newtonian fluids.

The Kanchenjunga Conservation Area (KCA) is a high mountain protected area in eastern Nepal undergoing socio-economic and environmental changes that are unprecedented in the region’s history. In the following paper, we discuss recent changes involving new road construction, climate change, adventure tourism, and the wildlife/forest cover/medicinal plant sectors. Our assessments are based on the collective results of past and recent field research, remote sensing analysis, oral histories, and literature reviews. While similar changes are occurring in mountain protected areas (MPA) throughout Nepal, it is suggested that the KCA differs from other regions in that it still retains the option of conducting detailed feasibility, environmental, and impact assessments prior to the implementation of major change-associated projects, particularly the construction of roads. In turn, the KCA might avoid many of the environmental, social, and economic problems experienced elsewhere in Nepal, while enhancing its status, income-generating capacities, and sustainability as a global destination for adventure, nature, and cultural tourism.

Recent advancements in semiconductor photonic and electronic devices such as Uni-travelling-carrier photodiodes (UTC-PDs), have played a significant role in the development of Terahertz communication technology. However, a major challenge that still persists is the limited output power from a single UTC-PD required for practical transmission distances. To enhance the output power, we propose and demonstrate a novel Terahertz wave power combining technique using a photomixer device that comprises of two arrayed UTC-PDs monolithically integrated with a microstrip line-based 2 × 1 Wilkinson power combiner and a rectangular patch antenna on a Silicon Carbide (SiC) substrate at 300 GHz. At photocurrents of 8 mA and 10 mA from the two UTC-PDs, the device experimentally exhibited a 7.3 dB increase in power relative to the power obtained with 8 mA UTC-PD and a 4.4 dB increase in power relative to the power obtained with 10 mA UTC-PD, when both UTC-PDs were irradiated. This implies that power can be enhanced by a factor of N2 if the photocurrent is multiplied by a factor of N. This technology presents a holistic and cutting edge platform for further power multiplication by further increasing the number of arrayed UTC-PDs.

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.

Chemotherapy for lung cancer has made remarkable progress, and its selection has been subdivided by genetic analysis. Although response evaluation criteria in solid tumors (RECIST) is a simple and highly objective evaluation method, it has been pointed out that it has the disadvantage of not being able to accurately evaluate the therapeutic effect of molecularly targeted drugs and immune checkpoint inhibitors. The purpose of this study is to determine whether quantitative evaluation of DWIBS is useful in determining the effectiveness of treatment for lung cancer. There were 31 patients with lung cancer and 56 patterns were obtained. First, the determination of treatment effect (PD, SD, PR) based on RECIST was performed on CT. Second, tDV and ADC (median) were measured using BD score from DWI images taken at the same time, and the rate of change was calculated. Then, we compared and examined the correlation between RECIST and the rate of change in tDV. There were correlations between RECIST and the rate of change in tDV in PD and PR cases respectively. Compared RECIST on CT, DWIBS using BD score would be more accurate for response evaluation of treatment. There was a tendency that tDV decreased with increasing ADC values, but some of the cases had a dissociated response with increasing ADC values and increasing tDV. Thus, since the color display of ADC values allows us to infer their contents, it would be useful for the evaluation of cases such as dissociated response and pseudoprogression, which are suspected to be atypical responses that are difficult to evaluate with RECIST and other methods.

Background Enfortumab vedotin shows promise as a targeted therapy for advanced urothelial carcinoma, particularly in patients who previously received platinum-based chemotherapy and immune checkpoint inhibitors. The EV-301 phase III trial demonstrated a significantly improved overall survival and response rates compared with standard chemotherapy. However, more data, especially from larger real-world studies, are needed to assess its effectiveness in Japanese patients. Methods A total of 6,007 urothelial cancer patients treated with pembrolizumab as second-line treatment were analyzed. Among them, 619 patients received enfortumab vedotin after pembrolizumab, while 394 received docetaxel or paclitaxel after pembrolizumab. Results The enfortumab vedotin group showed a longer overall survival than the paclitaxel/docetaxel group (p=0.013, hazard ratio: 0.71). In the multivariate analysis, enfortumab vedotin induction was an independent risk factor for the overall survival (p=0.013, hazard ratio: 0.70). There were no significant differences in the cancer-specific survival. Conclusions Enfortumab vedotin prolonged the overall survival in Japanese patients with advanced or metastatic urothelial carcinoma compared with paclitaxel or docetaxel after pembrolizumab treatment.

Ustekinumab, a new anti-interleukin-12/23 antibody, is an effective treatment for ulcerative colitis; however, data regarding predictive factors of its efficacy are limited. This study aimed to identify biomarkers that can predict the long-term outcome of ustekinumab treatment. We retrospectively reviewed the records of patients with active ulcerative colitis treated with ustekinumab at our hospital from June 2020 to January 2023. We divided patients into non-remission and remission groups, and examined whether baseline biomarkers, including C-reactive protein-to-lymphocyte ratio, and early treatment response could predict clinical remission at week 48 of ustekinumab treatment. Of the 33 patients included in the study, 21 (63.6%) were in clinical remission at week 48 of ustekinumab treatment. The baseline C-reactive protein-to-lymphocyte ratio value was identified as an independent prognostic factor for clinical remission at week 48 (odds ratio: 10, 95% confidence interval: 1.6–62.4, p=0.014), with the cutoff value of 3.353 showing excellent prognostic performance (sensitivity: 71.4%, specificity: 83.3%). Furthermore, the clinical response at week 4 (p=0.009) and that at week 8 (p=0.005) were significantly associated with clinical remission at week 48. The baseline C-reactive protein-to-lymphocyte ratio value and early treatment response are useful biomarkers to predict the long-term efficacy of ustekinumab treatment.

Background. Many anticancer drugs used in clinical practice cause adverse events such as oral mucositis, neurotoxicity, and extravascular leakage. We have reported that two 3-styrylchromone derivatives, 7-methoxy-3-[(1E)-2-phenylethenyl]-4H-1-benzopyran-4-one (compound A) and 3-[(1E)-2-(4-hydroxyphenyl)ethenyl]-7-methoxy-4H-1-benzopyran-4-one (compound B) showed the highest tumor-specificity against human oral squamous cell carcinoma (OSCC) cell lines among 291 related compounds. After confirming their superiority by comparing their tumor specificity with newly synthesized 65 derivatives, we investigated the neurotoxicity of these compounds, in comparison with 4 popular anticancer drugs. Methods: Tumor-specificity (TSM, TSE, TSN) was evaluated as the ratio of mean CC50 for human normal oral mesenchymal (gingival fibroblast, pulp cell), oral epithelial cells (gingival epithelial progenitor), and neuronal cells (PC-12, SH-SY5Y, LY-PPB6, differentiated PC-12) to OSCC cells (Ca9-22, HSC-2), respectively. Results: Compounds A and B showed one-order of magnitude higher TSM as compared with newly synthesized derivatives, confirming its prominent tumor-specificity. Docetaxel showed one order of magnitude higher TSM, but two order of magnitude lower TSE than compounds A and B. Compounds A and B showed higher TSM, TSE and TSN values than doxorubicin, 5-FU and cisplatin, damaging OSCC cells at concentrations that do not affect the viability of normal epithelial and neuronal cells. QSAR prediction based on the Tox21 database suggested that compounds A and B may inhibit the signaling pathway of estrogen-related receptors.

The paper focuses on the application of a multilevel, integrative and territorial approach to the protection of cultural heritage through planning instruments in Serbia. It points out the problems of the sectoral approach and discusses international recommendations that can be integrated into the planning methodology. The case study is the area of Djerdap National Park, which has an already established international and national importance. The research suggests that the cultural heritage in the area, with the exception of the Roman limes, is still recognized at the level of individual localities. The study emphasizes the importance of aligning all levels of governance to safeguard the whole spatial entity rather than focusing solely on its particular areas. The interna-tional and national importance of the planning area contributes to the strengthening of awareness of heritage and its institutional protection. However, the vitality of the area, which is key to its sustainable development, comes from the local level. Planning documents contribute to the inte-gration of local values and local communities into development programs and projects.

Background Late-onset hypogonadism (LOH) is a condition caused by the decline of testosterone with aging, and is associated with various symptoms, including lower urinary tract symptoms (LUTS). Although some reports have shown that testosterone replacement treatment for LOH improved LUTS, no large study has revealed a correlation between LUTS and LOH. This study investigated the correlation between the severity of LOH and LUTS in Asian Japanese males of >40 years of age using a web-based questionnaire. Methods We asked a total of 2,000 Japanese male individuals to answer both the AMS and IPSS/QOL questionnaires using a web-based survey. Among these 2,000 individuals, 500 individuals were assigned to each of the following age groups: 40-49, 50-59, 60-69, and ≥70 years. LOH symptoms were assessed by AMS score as no/little (17-26 points), mild (27-36 points), moderate (37-49 points), and severe (≥50 points). To compare the risk of voiding and storage dysfunction according to the severity of AMS, voiding dysfunction was assessed by the sum of IPSS Q1, Q3, Q5, and Q6, while storage dysfunction was assessed by the sum of IPSS Q2, Q4, and Q7. Results The IPSS total score was positively correlated with the severity of AMS (shown as median [mean±SD]): no/little group, 2 (3.67±5.36); mild group, 6 (7.98±6.91); moderate group, 11 (12.49±8.63); and severe group, 16 (14.83±9.24) (p<0.0001). The prevalence of an IPSS total score of ≥8 in the AMS severity groups was as follows: no/little group, 13.3% (111 of 834); mild group, 38.3% (225 of 587); moderate group, 64.2% (244 of 380); severe group, 72.4% (144/199). The prevalence of nocturia in the AMS severity groups was as follows: no/little group, 19.8% (165 of 834); mild group, 31.5% (185 of 587); moderate group, 43.9% (167 of 380); and severe group, 50.8% (101 of 199). Conclusions Individuals with higher AMS values, which represents severe LOH symptoms, showed a higher risk of nocturia and LUTS.

Glycosidic linkage analysis was conducted on the unfractionated polysaccharides in the alcohol-insoluble residues (AIRs) prepared from six red seaweeds (Gracilariopsis sp., Prionitis sp., Mastocarpus papillatus, Callophyllis sp., Mazzaella splendens, and Palmaria palmata) using GC-MS/FID analysis of partially methylated alditol acetates (PMAAs). The cell walls of P. palmata primarily contained mixed-linkage xylans and small amounts of sulfated galactans and cellulose. In contrast, the unfractionated polysaccharides of the other five species were rich in galactans displaying diverse 3,6-anhydro-galactose and galactose linkages with varied sulfation patterns. Different levels of cellulose were also observed. This glycosidic linkage method offers advantages for cellulose analysis over traditional monosaccharide analysis that is known for underrepresenting glucose in crystalline cellulose. Relative linkage compositions calculated from GC-MS and GC-FID measurements showed that anhydro sugar linkages generated more response in the latter detection method. This improved linkage workflow presents a useful tool for studying polysaccharide structural variations across red seaweed species. Furthermore, for the first time, relative linkage compositions from GC-MS and GC-FID measurements, along with normalized FID and total ion current (TIC) chromatograms without peak assignments, were analyzed using principal component analysis (PCA) as a proof-of-concept demonstration of the technique's potential to differentiate various red seaweed species.

Background: Educating college students about the importance of good sleep habits could lead to the adoption of healthier sleep routines, including sufficient sleep duration and sleep quality. The current pre-post study examines the impact of completing a sleep education program called “Sleep 101” on (1) sleep hygiene practices, (2) sleep quality, and (3) weekday and weekend sleep behaviors among college students. “Sleep 101” is an interactive online course developed to educate college students about the importance of sleep by addressing basic sleep physiology, the impact of sleep on mood, academic and physical performance, the interactions between sleep and various substances, and common sleep disorders. Methods: 338 college students were recruited from a midsized public university in the US and invited to participate in “Sleep 101”, of which 25 participants completed the baseline and post-intervention questionnaire. The Sleep Hygiene Index (SHI) was utilized to evaluate sleep hygiene practices, while standard questions were employed to assess weekday and weekend sleep behaviors and overall sleep quality. Results: Those who completed the study demonstrated a significant increase in weekday sleep duration and were less likely to engage in negative prior bedtime activities. In addition, 40% of those who completed baseline and post-intervention assessments noticed improvements in their sleep quality. Conclusion: These findings suggest that a brief online program is beneficial in improving sleep behaviors among college and could be a scalable approach to addressing current sleep issues and preventing future sleep problems in college students.

Copper (Cu) is a critical element for cancer cell proliferation and considerably accumulates in the nucleus. 64Cu2+ is an anticancer radiopharmaceuticals targeting the copper requirement of cancer cells. However, intravenously injected 64Cu2+ ions primarily accumulate in the liver. Ligand complexation of 64Cu2+ would be a promising method for increasing tumor delivery by reducing liver uptake. Herein, we used three tripodal amine ligands [tris(2-aminoethyl)amine (Tren), diethylenetriamine (Dien), and tris(2-pyridylmethyl)amine (TPMA)] to enclose 64Cu2+ ions and compared their in vivo tumor and liver uptake using a tumor-bearing xenograft mouse model of the extrahepatic bile duct carcinoma cell line TFK-1. We examined intracellular Cu distribution using microparticle-induced X-ray emission (micro-PIXE) analysis for these compounds. 64Cu2+-Tren and 64Cu2+-Dien showed higher tumor uptake than 64Cu2+-TPMA and 64Cu2+ ions in TFK-1 tumors. Among the three 64Cu2+ complexes and 64Cu2+ ions, liver uptake was inversely correlated with tumor uptake. Micro-PIXE analysis showed that in vitro cellular uptake was similar to in vivo tumor uptake and nuclear delivery was the highest for 64Cu2+-Tren. Conclusively, an inverse correlation between tumor and liver uptake was observed using three 64Cu2+ complexes of tripodal amine ligands and 64Cu2+ ions. These results provide useful information for the future development of anticancer 64Cu radiopharmaceuticals.

The profile of secondary metabolites occurring in apple cuticular layer is not only characteristic for particular apple cultivar, but also dynamically reflects various external factors in growing environment. In this study, the possibility to authenticate apple samples based on analysis of their cuticular layer extracts was investigated. Ultra-high-performance liquid chromatography coupled to high resolution tandem mass spectrometry (UHPLC-HRMS/MS) was employed for obtaining metabolomic fingerprints. In total, 274 authentic apple samples, four cultivars harvested within the seasons 2020 to 2022 in the Czech Republic and Poland were analysed. The generated complex data processed by univariate and multivariate statistical methods enabled to build classification models for discrimination of apple cultivars as well as their geographical origin. The models showed very good performance in differentiation of Czech and Polish samples for three of four cultivars: ‘Gala’, ‘Golden Delicious’ and ‘Idared’, moreover, the validity of the models was verified over harvest seasons. The diagnostic markers, besides metabolites of triterpene biosynthetic pathway, mainly represented wax esters. ‘Jonagold’, which is known to be susceptible to mutations, was the only cultivar for which the unambiguous classification of geographical origin was not possible.

Nitroxyl radical catalysts oxidize alcohols under an applied electric potential. It is possible to quantify the alcohol concentration from the resulting oxidation current. In this work, we evaluated the catalytic activity of nitroxyl radicals (or their corresponding hydroxylamines), including 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) as representative nitroxyl radicals, acetoamido-TEMPO, which shows higher oxidation potential than TEMPO owing to the acetoamido group, AZADO, Nor-AZADO, and NNO as less-hindered bicyclic nitroxyl radicals, and NHPI as an N,N-diacyl-type hydroxylamine, in acetonitrile solution. TEMPO, AZADO and NNO were also evaluated for their ability to oxidize alcohols in organic solvents, and their reactivity was compared with the electrochemical response. The most active NNO was used for electrochemical detection of cyclosporin A, a drug with a hydroxyl group.

Strawberry root rot caused by Neopestalotiopsis clavispora is one of the main diseases of strawberry and significantly impacts the yield and quality of strawberry fruit. There are now no effective control techniques available except for fungicide sprays, which may directly impact consumers. Biological control is becoming an alternative method for the control of plant diseases to replace or decrease the application of traditional synthetic chemical fungicides. Trichoderma is widely used as a biological agent for controlling strawberry root rot. In order to provide resources for screening the highly effective biocontrol fungus for controlling strawberry root rot caused by Neopestalotiopsis clavispora, the biocontrol mechanism,the control effects of Trichoderma asperellum CMT10 against strawberry root rot and growth-promoting effects on strawberry seedlings were investigated by plate culture, microscopy observation and root drenching methods.The results showed that CMT10 had obvious competitive, antibiotic and hyperparasitism effects on Neopestalotiopsis clavispora CMGF3. The CMT10 could quickly occupy nutritional space, and the inhibition rates of CMT10 against CMGF3 in confrontation culture on 7 d was 65.49%. The inhibition rates of volatile metabolite and fermentation metabolite produced by CMT10 against CMGF3 were 79.67% and 69.84%, respectively. The mycelium of strain CMT10 can act as hyperparasites by making contacting, winding and penetrating hyphae of CMGF3. Pot experiment showed that the biocontrol efficacy of CMT10 on strawberry root rot caused by Neopestalotiopsis clavispora was 63.00%. CMT10 had obvious promotion effect on strawberry growth, the plant height, root length, total fresh weight, root fresh weight, stem fresh weight and root dry weight, with the promotion rates were 20.09%, 22.39%, 87.11%, 101.58%, 79.82% and 72.33%, respectively. Overall, this study showed the ability of Trichoderma asperellum CMT10 to control strawberry root rot and their potential to develop as novel biocontrol agents to replace chemical fungicides for eco-friendly, sustainable agriculture.

Apis mellifera, especially weak ones, are highly vulnerable to Carpoglyphus lactis mites, which can rapidly infest and consume stored pollen, leading to weakened colonies and potentially colony collapse. This study aimed to ascertain and investigate the prevalence of this mite in honeybee colonies across 9 provinces in the Republic of Korea (ROK). A total of 615 honeybee colonies were collected, from 66 apiaries during the spring and 58 apiaries during the summer of 2023. A 1,242 bp segment of the the Cytochrome c oxidase subunit 1 (COI) gene was amplified using the polymerase chain reaction method. The detection levels of C. lactis in the honeybees were compared between winter and summer. Based on the COI sequence analysis, the nucleotide sequence similarity of C. lactis mites isolated in the ROK with those from China (NC048990.1) was found to be 99.5%, and with those from the United Kingdom (KY922482.1) was 99.3%. This study is the first report of C. lactis in Korean apiaries. The findings in this study demonstrate a significantly higher detection rate in winter, which is 4.1 times greater than that in summer (p &lt; 0.001). Furthermore, the results underscore the usefulness of molecular diagnostic techniques for detecting C. lactis mites.

COX II containing a dual core CuA active site is one of the three core subunits of mitochondrial Cco, which plays a significant role in the physiological process. In this report, the full-length cDNA of COXⅡ gene was cloned from Sitophilus zeamais, which had an ORF of 684 bp encoding 227 amino acids residues. The predicted COXⅡ protein had a molecular mass of 26.2 kDa with pI value of 6.37, and multiple sequence alignment and phylogenetic analysis indicated that Sitophilus zeamais COXⅡ had high sequence identity 78.51% with the COXⅡ of other insect species, especially similarity to sitophilus oryzae. This gene was subcloned into the prokaryotic expression vector pET-32a, and induced by IPTG in E.coli Transetta (DE3) expression system. Finally the COXⅡ with 6-His tag was purified using affinity chromatography with Ni²⁺-NTA agarose. WB showed the recombinant COXⅡ was about 44 kD, and the concentration of fusion protein was 50μg/mL. UV-spectrophotometer and infrared spectrometer analysis showed that recombinant COXⅡ could catalyze the oxidation of substrate Cytc, and influenced by AITC. It was found that AITC could form a hydrophobic region with COXⅡ protein via molecular docking, besides, a sulfur atom of AITC structure could form a length of 2.9 Å hydrogen bond with Leu-31. These results will provide valuable information for elucidating the role of COXⅡ in Sitophilus zeamais responses to AITC, meanwhile, it will helpful to carry out a point mutation in AITC binding sites for the future research.

The properties of the annual, semiannual and triennial oscillations (AO, SAO and TO) in the middle atmosphere have been investigated using the TIMED/SABER temperature data. The Lomb-Scargle and wavelet spectra were used to determine the dominant oscillations in the background temperature field. The AO is prominent at the mid-latitudes. The AO amplitudes present an asymmetry between the two Hemispheres, being larger in the mesosphere than in the stratosphere. The SAO dominates the tropical regions, with three amplitude maxima at altitudes of 45, 75, and 85 km. The SAOs in the upper mesosphere (75 km) are out of phase with those in the mesopause (85 km) in the tropical regions, which can generate an enhancement of 11 K at each equinox, contributing to the lower mesospheric inversion layer. The TO is significant in the tropical region, with amplitude being maximum at 35, 45 and 85 km. Result shows that there may be potential interaction by the TO with SAO at 85km at the equator. The relation between ENSO and TO has also been discussed. The ENSO signal may modulate the amplitude of the TO, mainly in the lower stratosphere. The real origin of the TO may lie in the wave-mean-flow interaction.

This paper is focused on typical rural settlements in the Stara Planina Mountain area in Serbia. They are distinguished by their authenticity, identity and character, and they have still not been destroyed by inappropriate development as is the case in some other mountain areas in Serbia, where the effects of urbanization, globalization and homogenization are obvious. Consequently, there is a need to prevent these effects in mountain areas where there is a threat of disbalance between development and the inherited natural and cultural values. The paper starts from several important concepts that relate contemporary approaches to cultural heritage preservation, place morphology and planning future development. The concept definitions from recent documents from related fields are used. These concepts are then applied to the area of Stara Planina Mountain and its rural settlements. The necessity for an integrative approach to planning this area with significant natural and anthropogenic potential is pointed out, including its integration into international programs of sustainable development.

The research reported on this paper was aimed at improving the overall efficiency of a PDO certified artisanal cheese production process. Being a PDO certified foodstuff by the EU, it is considered to have properties and qualities determined by the geographical environment in which is made, with its production taking place in a specific and determined geographical location, in this case the Serra da Estrela region. In that sense, the authors conducted a mapping according to a systemic perspective of the processes involved in the context of manufacturing and distribution of certified Serra da Estrela cheese. Numerous methods were used throughout the process, such as a systemic design analysis, and techniques derived from ethnographic methods, which led to the collection of data in the field and consequently provided the immersion of the researcher in genuine work situations. Critical points were identified and emphasized in the systemic map with the purpose of encouraging initiatives to address and overcome the gaps and inefficiencies detected. The systemic design analysis triggered the development of design work. Observations following an ethnographic approach identified ergonomic risks in cheese making during the process of cutting excess chips, fostering the emergence of musculoskeletal disorders at the wrist. A tool that fits best to the task at hand was developed. A prototype of the new tool enabled collecting feedback from use in the work context, in order to inform product development. The domains of agricultural production and microbiology, considering the specific microorganisms developed trough the ripening process of the cheese, turned out to be aspects of high importance for the issue under focus, contributing to a broader understanding of the ripening process and its risks, simultaneously improving the efficiency and success of cheese production. If it were not for the systemic analysis, which served as a link between the boundaries of distinct domains such as the risk of microorganism contamination, ergonomics, energy efficiency, legislation and regulation policies, transportation challenges and economic viability, approached throughout the research. Simultaneously creating bridges between them, the various problems might not have been detected in the first place, as they are usually addressed in specialized disciplines, predetermined by the restrictions of each specific area of knowledge. As a consequence of the development of this research, which was based on an analysis that sought to establish possible connections between various disciplines and tried to constantly maintain a holistic perspective, making new connections and observing the issues from a new angle, apart from the already established methodologies. All this allowed to lay out the seeds for the development of a plan to tackle the critical points identified by the systemic analysis reported in this paper.

Promoting green development has become an important way to optimize the ecological and economic structure and promote sustainable development. The Yangtze River Economic Belt is an important economic corridor in China, and it remains to be examined whether the implementation of environmental regulations has enhanced the green total factor productivity (GTFP) of cities. This paper calculates the green total factor productivity of 107 cities within the Yangtze River Economic Belt by using the super-efficient SBM model and the GML index with Chinese city panel data from 2007-2019 and measures the intensity of environmental regulations through textual analysis. The bidirectional fixed-effects model constructed in this paper suggests an inverted U-shaped relationship between environmental regulation and GTFP, which is confirmed by a series of robustness tests. Green technology innovation and advanced industrial structure play a mechanism role in this. In regions with lower levels of green technology and industrial structure, the inverted U-shaped relationship between environmental regulation and green total factor productivity is more significant. In addition, the phenomenon of GTFP rising and then falling because of environmental regulation is more obvious in cities in the middle and upper reaches of the Yangtze River and outside the urban agglomerations. Therefore, when formulating environmental regulation policies, it is necessary to balance the relationship between economic development and environmental protection and harmonize the environment and economic development of the entire Yangtze River Basin.

The wetlands in northeastern Bangladesh are home to some of the most prolific and valuable ecosystems on the planet, offering a wide range of benefits to both the local and wider communities. A limited number of research on this topic have been carried out in various wetlands in coastal hilsa, but none have been located in the northeastern region of Bangladesh. Thus, the goal of this study was to better understand the most commercially relevant species (anadromous hilsa) in northeastern Bangladesh as well as to assess the wetland ecosystem services more thoroughly with the contribution of their fish genetic resources. In addition to laboratory studies, fieldwork was done in the fishing settlements along the Surma River, Hakaluki Haor, and Tanguar Haor. The study classified 77 fish species into 21 subcategories of ecosystem services, of which 56% were not threatened, 17% were vulnerable, and 10% were highly endangered. The species Hilsa was found to be the most economically significant, accounting for 1% of the GDP overall. The study determined if the hilsa stock of the examined wetlands maintains a single or several subpopulations in comparison to other parts of the country when they migrate from saline water to northeastern Bangladesh (freshwater). But when compared to other groups, the FST score was between 0.000 to 0.017, indicating that the populations are identical and that there is genetic material sharing between them. Additionally, these statistics imply that the Sylhet haor and adjacent river systems contain a single stock of Hilsa fish. Nevertheless, a number of stresses and risks, including overexploitation, illicit and destructive fishing, siltation, and natural disasters like flash floods, have been linked to changes in the supply of hilsa and other ecosystem services. This study also emphasizes the necessity of policy attention and research to address the concerns.

Although sarcopenia is characterized by a loss of muscle strength and skeletal muscle mass, few studies have evaluated the effect of muscle strength on hepatocellular carcinoma (HCC) patients. We separately evaluated the impact of sarcopenia-related factors (grip strength [GS] and the skeletal muscle index [SMI]) on the survival among lenvatinib-treated unresectable HCC (u-HCC) patients. This single-center cohort study was conducted at a university hospital. The study population included 63 lenvatinib-treated u-HCC patients managed between April 2018 and April 2020. A decreased GS and decreased SMI were found in 21 (33.3%) and 22 (34.9%) patients, respectively. The overall survival (OS) of the normal GS group was significantly higher than that of the decreased GS group, while that of the normal and decreased SMI groups did not differ markedly. There were no significant differences in the progression-free survival between the normal GS and decreased GS groups or the normal SMI and decreased SMI groups. A multivariate Cox proportional hazards model showed that ALBI2b (hazard ratio [HR] 4.39) and a decreased GS (HR 3.55) were independently associated with an increased risk of poor prognosis. In addition to the hepatic functional reserve, a decreased GS was a poor prognostic factor in lenvatinib-treated u-HCC patients.

With the rapid development of gene therapy technology in recent years, its abuse as a method of sports doping in athletic has become a concern. However, there is still room for improvement in gene doping testing methods, and a robust animal model needs to be developed. Therefore, the purposes of this study were to establish a model of gene doping using recombinant adeno-associated virus vector-9 including the human erythropoietin gene (rAAV9-hEPO), and to establish a relevant testing method. First, it was attempted to establish the model using rAAV9-hEPO on mice. The results showed a significant increase in erythrocyte volume accompanied by an increase in spleen weight, confirming the validity of the model. Next, we attempted to detect proof of gene doping by targeting DNA and RNA. Direct proof of gene doping was detected using a TaqMan-qPCR assay with certain primers/probes. In addition, some indirect proof was identified in RNAs through the combination of a TB Green qPCR assay with RNA sequencing. Taken together, these results could provide the foundation for an effective test for gene doping in human athletes in the future.

In this paper, we introduce a specialized, fully automated experimental arrangement designed for assessing the effectiveness of augmented and virtual reality technologies in healthcare setting and explore its design principles focusing on depth sensor characterization. The main goal of this project is to establish a robust benchtop platform for the quantitative evaluation of extended reality technologies in a controlled environment, emphasizing the practical assessment of augmented reality head-mounted devices. We outline a design concept and considerations for an experimental configuration aimed at creating a realistic testing environment. This apparatus comprises an observation platform mounted on a three-degree-of-freedom motorized system and a test phantom stage. Focusing on real-case scenarios, we utilized a range of sensors, including readily available range-sensing cameras and commercial augmented reality headsets, such as the Intel RealSense L515 LiDAR camera, mounted on the motion control system. The setup enabled automated data collection and facilitates controlled assessments and validation of various facets of augmented reality technologies, including object, hand, and head tracking, as well as static and dynamic image registration. This paper describes the system architecture, the process of automated data collection, and presents several evaluation studies conducted with this setup, providing insights into the quality and temporal noise associated with static or moving objects or observers in augmented reality applications.

Two novel members of the subfamily Betarhabdovirinae, family Rhabdoviridae, were identified in Brazil. Overall, their genomes have the typical organization 3’-N-P-P3-M-G-L-5’ observed in mono-segmented plant-infecting rhabdoviruses. In aristolochia-associated cytorhabdovirus (AaCV), found in the liana aristolochia (Aristolochia gibertii Hook), an additional short orphan ORF encoding a transmembrane helix was detected between P3 and M. AaCV genome and deduced encoded proteins share the highest identity values, consistently < 60%, with their counterparts of yerba mate chlorosis-associated virus (Cytorhabdovirus flaviyerbamate). The second virus, false jalap virus (FaJV), was detected in the herbaceous plant false jalap (Mirabilis jalapa L.) and represents together with tomato betanucleorhabdovirus 2, originally found in tomato plants in Slovenia, a tentative new species of the genus Betanucleorhabdovirus. FaJV particles accumulate in the peri-nuclear space, and electron-lucent viroplasms were observed in the nuclei of the infected cells. Notably, distinct from typical rhabdoviruses, most virions of AaCV were observed to be non-enclosed within membrane-bounded cavities. Instead, they were frequently seen in close association with surfaces of mitochondria or peroxisomes. Unlike FaJV, AaCV was successfully graft-transmitted to healthy plants of three species of the genus Aristolochia, while mechanical and seed transmission proved unsuccessful for both viruses. Data suggest that these viruses belong to two new tentative species within the subfamily Betarhabdovirinae.