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Electrodeposited amorphous hydrated iridium oxide (IrOx) is a promising material for pH sensing due to its high sensitivity and the ease of fabrication. However, durability and variability continue to restrict the sensor’s effectiveness. Variation in probe films can be seen in both performance and fabrication, but it has been found that performance variation can be controlled with potentiostatic conditioning (PC). To make proper use of this technique, the morphological and chemical changes affecting the conditioning process must be understood. Here, a thorough study of this material, after undergoing PC in a pH-sensing-relevant potential regime, was conducted by voltammetry, scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDS), X-ray diffraction (XRD), and X-ray photoelectron spectroscopy (XPS). Fitting of XPS data was performed, guided by raw trends in survey scans, core orbitals, and valence spectra, both XPS and UPS. The findings indicate that the PC process can repeatably control and conform performance and surface bonding to desired calibrations and distributions, respectively; PC was able to reduce sensitivity and offset ranges to as low as ±0.7 mV/pH and ±0.008 V, respectively, and repeat bonding distributions over ~2 months of sample preparation. Both Ir/O atomic ratios (shifting from 4:1 to over 4.5:1) and fitted components assigned hydroxide or oxide states based on the literature (low-voltage spectra being almost entirely with suggested hydroxide components, and high-voltage spectra almost entirely with suggested oxide components) trend across the polarization range. Self-consistent valence, core orbital, and survey quantitative trends point to a likely mechanism of ligand conversion from hydroxide to oxide, suggesting that the conditioning process enforces specific state mixtures that include both theoretical Ir(III) and Ir(IV) species, and raising the conditioning potential alters the surface species from an assumed mixture of Ir species to more oxidized Ir species.

Catalytic substrate, which is devoid of expensive noble metals and enzymes for hydrogen peroxide (H2O2), reduction reactions can be obtained via nitrogen doping of graphite. Here, we report a facile fabrication method for obtaining such nitrogen doped graphitized carbon using polyacrylonitrile (PAN) mats and its use in H2O2 sensing. A high degree of graphitization was obtained with a mechanical treatment of the PAN fibers embedded with carbon nanotubes (CNT) prior to the pyrolysis step. The electrochemical testing showed a limit of detection (LOD) 0.609 µM and sensitivity of 2.54 µA cm−2 mM−1. The promising sensing performance of the developed carbon electrodes can be attributed to the presence of high content of pyridinic and graphitic nitrogens in the pyrolytic carbons, as confirmed by X-ray photoelectron spectroscopy. The reported results suggest that, despite their simple fabrication, the hydrogen peroxide sensors developed from pyrolytic carbon nanofibers are comparable with their sophisticated nitrogen-doped graphene counterparts.

Few studies have reported nationwide changes in dental visit patterns during the COVID-19 pandemic. This study aimed to clarify the impact of the COVID-19 pandemic on the type of dental treatment in Japan based on trends in the frequency of dental clinic visits per month and dental expenses per month or day. An interrupted time-series analysis was performed to examine changes in data from the national database before and after the first declaration of a state of emergency. Between March and April 2020, the monthly dental expenses per patient (MDEPP) increased by approximately JPY 950 (JPY) (p < 0.001) in patients aged ≤64 years and ≥65 years. Dental expenses per treatment (DEPT) increased by approximately JPY 300–400 (p < 0.001) in both age groups. After April 2020, the slope of the regression line for DEPT significantly increased in those aged ≤64 years (p < 0.001) and in those ≥65 years (p = 0.024). The number of treatments per month (NTPM) increased after the declaration of a state of emergency. However, the decreasing trend in the regression line for NTPM was stronger in those aged ≤64 years (p < 0.001). The MDEPP, DEPT, and NTPM showed an increasing trend during the first state of emergency compared to those observed in the previous year. The proportion of patients with relatively severe disease may have increased because patients with mild disease refrained from undergoing dental examinations. These results suggest changes in the type of dental treatment during the COVID-19 pandemic.

The adsorption behavior of recombinant cage-shaped proteins with carbon nanotube (CNT)-binding peptides on carbon surfaces was quantitatively and dynamically analyzed using a highly stable quartz crystal microbalance (QCM). Two types of CNT-binding peptide aptamers obtained by the phage display method were attached to the N- and C-termini of the Dps (DNA-binding protein derived from starved cells) to produce carbonaceous material-binding Dps. The carbon adsorption ability of the mutant Dps was studied by QCM measurement using a carbon-coated QCM sensor. The produced peptide aptamer-modified Dps showed higher affinity than a wild Dps and also showed higher adsorption capacity than a previously used Dps with carbon nanohorn-binding peptides. The newly obtained peptide aptamers were proven to provide Dps with high adsorption affinity on carbon surfaces. Furthermore, the aptamer modified to the N-terminus of the Dps subunit showed more efficient adsorption than the aptamers attached to the C-terminus of the Dp, and the linker was found to improve the adsorption ability.

Intrusion detection systems (IDS) are crucial in safeguarding network security by identifying unauthorized access attempts through various techniques. Statistical Process Control (SPC), particularly Hotelling’s T2 control charts, is noted for monitoring network traffic against known attack patterns or anomaly detection. This research advances the domain by incorporating robust statistical estimators—namely, the Fast-MCD and MRCD (Minimum Regularized Covariance Determinant) estimators—into bootstrap-enhanced Hotelling’s T2 control charts. These enhanced charts aim to strengthen detection accuracy by offering improved resistance to outlier contamination, a prevalent challenge in intrusion detection. The methodology emphasizes the MRCD estimator’s robustness in overcoming the limitations of traditional T2 charts, especially in environments with a high incidence of outliers. Applying the proposed bootstrap-based robust T2 charts to the UNSW-NB15 dataset illustrates a marked enhancement in intrusion detection performance. Results indicate superior performance of the proposed method over conventional T2 and Fast-MCD-based T2 charts in detection accuracy, even in varied levels of outlier contamination. Despite increasing execution time, the precision and reliability in detecting intrusions present a justified trade-off. The findings underscore the significant potential of integrating robust statistical methods to enhance IDS effectiveness.

Juvenile idiopathic inflammatory myopathy (JIIM) is a rare systemic autoimmune disease characterized by skeletal muscle weakness with or without a skin rash. Juvenile dermatomyositis (JDM) is the most common subtype of JIIM, accounting for 80% of JIIM. Recent studies identified several myositis-specific autoantibodies (MSAs) and myositis-associated autoantibodies (MAAs). Each MSA or MAA is associated with distinct clinical features and outcomes, although there are several differences in the prevalence of MSA/MAA and autoantibody–phenotype relationships between age and ethnic groups. Histopathological studies have revealed critical roles of type I interferons and vasculopathy in the development of JDM. Serological classification mostly corresponds to clinicopathological classification. Novel therapeutic agents, such as biologics and Janus kinase inhibitors (JAKi), have been developed; however, to date, there is a lack of high-level evidence. As advances in treatment have reduced the mortality rate of JIIM, recent studies have focused on medium- and long-term outcomes. However, rapidly progressive interstitial lung disease (RP-ILD) remains a major cause of death in anti-melanoma differentiation gene 5 autoantibody-positive JDM. Early diagnosis and intervention using a multi-drug regimen is critical for the treatment of RP-ILD. Rituximab and JAKi may reduce mortality in patients with JDM-associated RP-ILD refractory to conventional therapy.

We aimed to determine the effects of maternal nutrient restriction (MNR) on the DNA methylation and gene expression patterns associated with metabolism and immunopoiesis in the thymuses of fetal Wagyu cattle. Pregnant cows were allocated to two groups: a low-nutrition (LN; 60% nutritional requirement; n = 5) and a high-nutrition (HN; 120% nutritional requirement, n = 6) group, until 8.5 months of gestation. Whole-genome bisulfite sequencing (WGBS) and RNA sequencing were used to analyze DNA methylation and gene expression, while capillary electrophoresis–Fourier transform mass spectrometry assessed the metabolome. WGBS identified 4566 hypomethylated and 4303 hypermethylated genes in the LN group, with the intergenic regions most frequently being methylated. Pathway analysis linked hypoDMGs to Ras signaling, while hyperDMGs were associated with Hippo signaling. RNA sequencing found 94 differentially expressed genes (66 upregulated, 28 downregulated) in the LN group. The upregulated genes were tied to metabolic pathways and oxidative phosphorylation; the downregulated genes were linked to natural killer cell cytotoxicity. Key overlapping genes (GRIA1, CACNA1D, SCL25A4) were involved in cAMP signaling. The metabolomic analysis indicated an altered amino acid metabolism in the MNR fetuses. These findings suggest that MNR affects DNA methylation, gene expression, and the amino acid metabolism, impacting immune system regulation during fetal thymus development in Wagyu cattle.

Background and Objectives: The measurement of hepatitis B surface antigen (HBsAg) is essential for managing chronic hepatitis B virus infection (CHB). HBsAg consists of three different surface envelope proteins: large, middle, and small HB surface proteins. However, in clinical practice, it is not common to evaluate each of these HB surface proteins separately. Materials and Methods: In this study, we investigated preS1 expression using seven monoclonal antibodies (mAbs) in 68 CHB patients, as well as examining their antigenicity. Results: Although the seven mAbs had been derived from genotype (Gt) C, they could recognize preS1 with Gts A to D. The epitopes were concentrated within the aa33-47 region of preS1, and their antigenicity was significantly reduced by an aa45F substitution. We found that preS1 expression remained consistent regardless of HBsAg levels and different Gts in CHB patients, in contrast to what was observed in SHBs. Conclusions: These results suggest that the antigenic epitope is preserved among different Gts and that the expression pattern of preS1 is altered during CHB, highlighting its vital role in the HBV infection cycle. Our present results suggest preS1 is a promising therapeutic target in CHB.

This study investigated the correlation between oxidative stress and blood amino acids associated with nitric oxide metabolism in adult patients with coronavirus disease (COVID-19) pneumonia. Clinical data and serum samples were prospectively collected from 100 adult patients hospitalized for COVID-19 between July 2020 and August 2021. Patients with COVID-19 were categorized into three groups for analysis based on lung infiltrates, oxygen inhalation upon admission, and the initiation of oxygen therapy after admission. Blood data, oxidative stress-related biomarkers, and serum amino acid levels upon admission were compared in these groups. Patients with lung infiltrations requiring oxygen therapy upon admission or starting oxygen post-admission exhibited higher serum levels of hydroperoxides and lower levels of citrulline compared to the control group. No remarkable differences were observed in nitrite/nitrate, asymmetric dimethylarginine, and arginine levels. Serum citrulline levels correlated significantly with serum lactate dehydrogenase and C-reactive protein levels. A significant negative correlation was found between serum levels of citrulline and hydroperoxides. Levels of hydroperoxides decreased, and citrulline levels increased during the recovery period compared to admission. Patients with COVID-19 with extensive pneumonia or poor oxygenation showed increased oxidative stress and reduced citrulline levels in the blood compared to those with fewer pulmonary complications. These findings suggest that combined oxidative stress and abnormal citrulline metabolism may play a role in the pathogenesis of COVID-19 pneumonia.

Background and Objectives: Preeclampsia has been linked to an inflammatory response that may be brought on by endothelial cell dysfunction. This paper investigates the pathomechanism of syncytiotrophoblast basement membrane (STBM) damage and Placental Protein 13 (PP13) release, which may have a role in systemic endothelial dysfunction in preeclampsia. Materials and Methods: This comparative cross-sectional study involves 54 preeclampsia patients (27 early-onset preeclampsia and 27 late-onset preeclampsia) and 27 pregnant women with normal blood pressure. An enzyme-linked immunosorbent assay was performed to evaluate maternal blood levels of PP13. Following birth, a portion of the placenta was collected for transmission electron microscope (TEM) and immunohistochemical (IHC) analysis. The data were analyzed using STATA version 15. Results: PP13 expression in the placental syncytiotrophoblast was significantly lower in the early-onset preeclampsia, compared to late-onset preeclampsia and normotensive pregnancy, group (p < 0.001). In contrast, serum PP13 levels were found to be the highest in the early-onset preeclampsia group, although no significant difference were found in mean maternal serum levels of PP13 between the three groups. The decreased PP13 expression in placental syncytiotrophoblast can be attributed to the greater extent of damage in the STBM in early-onset preeclampsia that leads to the release of a larger amount of PP13 into maternal circulation. The hypothesis aligns with the TEM analysis results. Preeclamptic pregnancies showed placental syncytiotrophoblast aponeurosis, whereas normotensive pregnancies did not. Placental lesions and STBM shedding were found to be more pronounced in early-onset preeclampsia compared to late-onset preeclampsia. Conclusions: PP13 and STBM damage may play a role in systemic endothelial dysfunction in preeclampsia.

Understandings of how visual hallucinations appear have been highly influenced by generative approaches, in particular Friston’s Active Inference conceptualization. Their core proposition is that these phenomena occur when hallucinatory expectations outweigh actual sensory data. This imbalance occurs as the brain seeks to minimize informational free energy, a measure of the distance between predicted and actual sensory data in a stationary open system. We review this approach in the light of old and new information on the role of environmental factors in episodic hallucinations. In particular, we highlight the possible relationship of specific visual triggers to the onset and offset of some episodes. We use an analogy from phase transitions in physics to explore factors which might account for intermittent shifts between veridical and hallucinatory vision. In these triggered forms of hallucinations, we suggest that there is a transient disturbance in the normal one-to-one correspondence between a real object and the counterpart perception such that this correspondence becomes between the real object and a hallucination. Generative models propose that a lack of information transfer from the environment to the brain is one of the key features of hallucinations. In contrast, we submit that specific information transfer is required at onset and offset in these cases. We propose that this transient one-to-one correspondence between environment and hallucination is mediated more by aberrant discriminative than by generative inference. Discriminative inference can be conceptualized as a process for maximizing shared information between the environment and perception within a self-organizing nonstationary system. We suggest that generative inference plays the greater role in established hallucinations and in the persistence of individual hallucinatory episodes. We further explore whether thermodynamic free energy may be an additional factor in why hallucinations are temporary. Future empirical research could productively concentrate on three areas. Firstly, subjective perceptual changes and parallel variations in brain function during specific transitions between veridical and hallucinatory vision to inform models of how episodes occur. Secondly, systematic investigation of the links between environment and hallucination episodes to probe the role of information transfer in triggering transitions between veridical and hallucinatory vision. Finally, changes in hallucinatory episodes over time to elucidate the role of learning on phenomenology. These empirical data will allow the potential roles of different forms of inference in the stages of hallucinatory episodes to be elucidated.

Esotropia and exotropia in the entity of comitant strabismus are multifactorial diseases with both genetic and environmental backgrounds. Idiopathic superior oblique muscle palsy, as the predominant entity of non-comitant (paralytic) strabismus, also has a genetic background, as evidenced by varying degrees of muscle hypoplasia. A genome-wide association study (GWAS) was conducted of 711 Japanese patients with esotropia (n= 253), exotropia (n = 356), and idiopathic superior oblique muscle palsy (n = 102). The genotypes of single nucleotide polymorphisms (SNPs) were determined by Infinium Asian Screening Array. Three control cohorts from the Japanese population were used: two cohorts from BioBank Japan (BBJ) and the Nagahama Cohort. BBJ (180K) was genotyped by a different array, Illumina Infinium OmniExpressExome or HumanOmniExpress, while BBJ (ASA) and the Nagahama Cohort were genotyped by the same Asian array. After quality control of SNPs and individuals, common SNPs between the case cohort and the control cohort were chosen in the condition of genotyping by different arrays, while all SNPs genotyped by the same array were used for SNP imputation. The SNPs imputed with R-square values ≥ 0.3 were used to compare the case cohort of each entity or the combined entity with the control cohort. In comparison with BBJ (180K), the esotropia group and the exotropia group showed CDCA7 and HLA-F, respectively, as candidate genes at a significant level of p < 5 × 10−8, while the idiopathic superior oblique muscle palsy group showed DAB1 as a candidate gene which is involved in neuronal migration. DAB1 was also detected as a candidate in comparison with BBJ (ASA) and the Nagahama Cohort at a weak level of significance of p < 1 × 10−6. In comparison with BBJ (180K), RARB (retinoic acid receptor-β) was detected as a candidate at a significant level of p < 5 × 10−8 in the combined group of esotropia, exotropia, and idiopathic superior oblique muscle palsy. In conclusion, a series of GWASs with three different control cohorts would be an effective method with which to search for candidate genes for multifactorial diseases such as strabismus.

Vitamin D hydroxylation in the liver/kidney results in conversion to its physiologically active form of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3]. 1,25(OH)2D3 controls gene expression through the nuclear vitamin D receptor (VDR) mainly expressed in intestinal epithelial cells. Cytochrome P450 (CYP) 24A1 is a catabolic enzyme expressed in the kidneys. Interestingly, a recently identified mutation in another CYP enzyme, CYP3A4 (gain-of-function), caused type III vitamin D-dependent rickets. CYP3A are also expressed in the intestine, but their hydroxylation activities towards vitamin D substrates are unknown. We evaluated CYP3A or CYP24A1 activities on vitamin D action in cultured cells. In addition, we examined the expression level and regulation of CYP enzymes in intestines from mice. The expression of CYP3A or CYP24A1 significantly reduced 1,25(OH)2D3-VDRE activity. Moreover, in mice, Cyp24a1 mRNA was significantly induced by 1,25(OH)2D3 in the intestine, but a mature form (approximately 55 kDa protein) was also expressed in mitochondria and induced by 1,25(OH)2D3, and this mitochondrial enzyme appears to hydroxylate 25OHD3 to 24,25(OH)2D3. Thus, CYP3A or CYP24A1 could locally attenuate 25OHD3 or 1,25(OH)2D3 action, and we suggest the small intestine is both a vitamin D target tissue, as well as a newly recognized vitamin D-metabolizing tissue.

The necessity of understanding and simulating hydrological phenomena as well as their interactions and the effect of anthropogenic and climate conditions on the ecosystem have encouraged researchers for years to investigate the moisture transfer in soil. Considering the moisture transfer as an isothermal phenomenon might cause a wrong estimation due to the non-isothermal nature of the moisture movement in porous media. Hygrothermal (coupled heat and moisture transfer) models are quite diverse and are the engine of the various hygrothermal software tools used to analyze the heat and moisture in building envelopes, drying technologies, and many other applications. This paper is a literature survey conducted to provide an overview on the classical hygrothermal models to address the historical perspectives on these models. First, it investigated, from a historical point of view, the challenges behind the development of hygrothermal models as unsaturated flow theories, beginning with Buckingham theory. The non-isothermal nature of moisture was the starting point for researchers to deal with new challenges during mathematical modeling and experimental analysis. In general, the theory of coupled heat and moisture transfer first developed by J.R. Philip and De Vries and the authors in the mid-1950s inspired the novel hygrothermal models, including Sophocleous and Milly’s model, Rode’s model, Künzel’s model, and Grunewal’s model. In a parallel of hygrothermal model developments, the models of Whitaker and Luikov can also be classified as hygrothermal models; they were mostly applied in modeling the phenomenon of drying. The study highlights the application of hygrothermal models in building physics and gathered a summary of international efforts such as Annex 24, Annex 41, and the HAMSTAD project and advancements performed from the classical dew point or steady-state Glaser method. Moreover, this study emphasizes the advantages of the standard of EN 15026 and limitations of the Glaser method. To sum up, hygrothermal models are still under development based on various assumptions of moisture driving potentials and transfer coefficients.

The diagnosis of hereditary skin tumors is difficult for “old” diagnostic tools such as immunohistochemistry. Whole-exome sequencing analysis as a “new” diagnostic tool enables us to make a final diagnosis in spite of unknown hereditary diseases in the past. Hereditary leiomyomatosis and renal cell cancer are autosomal dominant hereditary cancer syndromes characterized by uterine myomas, cutaneous leiomyomas, and aggressive renal cell cancer. The syndrome is associated with pathogenic germline variants in the fumarate hydratase gene. Herein, we demonstrate a pathogenic germline variant of the fumarate hydratase gene in a 60-year-old woman with multiple cutaneous leiomyomas, leading to the diagnosis of hereditary leiomyomatosis and renal cell cancer. Whole-exome sequencing analysis using genomic DNA extracted from peripheral blood leukocytes revealed one germline variant in the FH gene on chromosome 1 (c.290G>A, p.Gly97Asp). She received total hysterectomy due to uterine myoma, which strongly supported the diagnosis. No tumor was detected in her kidney by computed tomography and ultrasound examination. Genetic examination for the mutation of the fumarate hydratase gene is important in order to reach the correct diagnosis and to detect renal cancer at its early stage.

We examined whether the administration of growth hormone (GH) improves insulin resistance in females of a non-obese hyperglycemic mouse model after birth with low birth weight (LBW), given that GH is known to increase muscle mass. The intrauterine Ischemia group underwent uterine artery occlusion for 15 min on day 16.5 of gestation. At 4 weeks of age, female mice in the Ischemia group were divided into the GH-treated (Ischemia-GH) and non-GH-treated (Ischemia) groups. At 8 weeks of age, the glucose metabolism, muscle pathology, and metabolome of liver were assessed. The insulin resistance index improved in the Ischemia-GH group compared with the Ischemia group (p = 0.034). The percentage of type 1 muscle fibers was higher in the Ischemia-GH group than the Ischemia group (p < 0.001); the muscle fiber type was altered by GH. In the liver, oxidative stress factors were reduced, and ATP production was increased in the Ischemia-GH group compared to the Ischemia group (p = 0.014), indicating the improved mitochondrial function of liver. GH administration is effective in improving insulin resistance by increasing the content of type 1 muscle fibers and improving mitochondrial function of liver in our non-obese hyperglycemic mouse model after birth with LBW.

Currently available numerical models that describe the fecal contamination of aquatic environments using Escherichia coli as an indicator bacterium did not consider its survival in sediments. We conducted a series of comparative experiments to reveal the independent and interactive effects of sediment factors, including temperature, pH, water-extractable total dissolved solids (TDSs), coexisting microbes, and sampling sites, in lake environments on E. coli survival. In experiments, E. coli survival was observed by controlling any two factors at a time. Consequently, the decrease in pH and presence of coexisting microbes enhanced E. coli die-off, whereas the addition of water-extractable TDSs promoted its growth. To select factors to be considered for modelling E. coli survival in sediments, the independent effects of each factor and the interaction effect of the two factors were statistically compared based on their effect sizes (η2). As a result, pH (η2 = 59.5–89.0%) affected E. coli survival most significantly, followed by coexisting microbes (1.7–48.4%). Among the interactions affecting E. coli survival, including pH or coexisting microbes—which had larger independent effects—relatively larger statistically significant interactions were observed between pH and coexisting microbes (31.1%), coexisting microbes and water-extractable TDSs (85.4%), and coexisting microbes and temperature (26.4%).

The utilization of CO2 mineralization fly ash (F) and coal gangue (G) technology is proposed in this research work to prepare underground backfilling materials. The test process can be divided into pre-treatment and post-treatment stages. In the pre-treatment stage, a sealed stirring vessel is used to conduct CO2 wet mineralization. The ratios of F and G were selected as follows: 20%:60% (F2G6), 30%:50% (F3G5), 40%:40% (F4G4), 50%:30% (F5G3), and 60%:20% (F6G2). The ratios were prepared into Φ50 mm × 100 mm cylindrical samples, with curing durations of 3 d, 7 d, 14 d, and 28 d. In the post-processing stage, the SANS microcomputer-controlled electronic universal testing machine and FLIR A615 infrared thermal imager were used to carry out uniaxial loading and temperature detection, respectively. The unconfined compressive strength (UCS), X-ray diffraction (XRD), average infrared radiation temperature (AIRT), variance of original infrared image temperature (VOIIT), and variance of successive minus infrared image temperature (VSMIT) of the samples were compared and analyzed. The results indicated that when curing reaches 14 d, the strength approaches its peak, with minimal changes in strength over a delayed period; furthermore, as the ratio of F to G continues to increase, the mineralization effect gradually strengthens, reaching its optimum level at a ratio of 5:3. However, when the ratio exceeds 5:3, signs of deteriorating mineralization effect start to appear. During the loading process, the AIRT of the mineralized samples showed a continuous increase, but the VOIIT and VSMIT of the mineralized sample both exhibited significant fluctuations or rapid increases during damage rupture. Moreover, the rise in the AIRT value was found to be linked to the increase in the ratio of F to G. This indicates that F has a higher thermal–mechanical conversion efficiency compared to G, so the temperature change will be greater during the loading process. The drastic changes in the VOIIT and VSMIT indicate that they can be used as sensitive response indicators for sample rupture, and can predict and warn of damage rupture in mineralized samples. Research work can provide practical guidance and reference for underground backfilling of CO2 mineralization industrial waste.

To address the issues of corrosion weakening of solid-waste-based backfill material caused by mine water, a novel hydrophobic solid waste backfill (HSBF) material was developed using polydimethylsiloxane (PDMS) and a silane coupling agent (SCA) as hydrophobic modification additives, and NaOH (SH) and sodium silicate (SS) as alkali activators. Fly ash and slag were chosen as the primary raw solid waste materials. The rheological properties of the hydrophobic-treated backfill slurries were measured, and the resulting physicochemical properties were compared with the unmodified reference group. This study reveals that the fresh HSBF slurry follows a Modified Bingham (M-B) model with shear-thinning characteristics. The addition of PDMS causes an increase in the water contact angle of the hardened HSBF material with F8S2 to up to 134.9°, indicating high hydrophobicity. Morphological observations indicated that PDMS mainly attaches to the inorganic particles’ surface through the bridging action of SCA for the hydrophobic modification of the backfill material. The overall strength of the HSBF materials was further ensured via fly ash–slag ratio optimization, and was found to be enhanced up to 98% by increasing slag content from 20% to 50%. This is mainly attributed to the hydration of slag, forming C-S(A)-H gel, which contributes to the increased strength. The novel HSBF material enables the elimination of cement in mine backfilling applications, demonstrating good economic benefits. Its excellent mechanical and hydrophobic properties can not only prevent overburden displacement in goaf areas, but can also mitigate water resource loss from overlying strata and simultaneously reduce the safety risks associated with long-term mine water deterioration.

Cardiovascular disease (CVD) frequently occurs in patients with chronic kidney disease (CKD), particularly those undergoing dialysis. The mechanisms behind this may be related to traditional risk factors and CKD-specific factors that accelerate atherosclerosis and vascular calcification in CKD patients. The accumulation of uremic toxins is a significant factor in CKD-related systemic disorders. Basic research suggests that indoxyl sulfate (IS), a small protein-bound uremic toxin, is associated with macrophage dysfunctions, including increased oxidative stress, exacerbation of chronic inflammation, and abnormalities in lipid metabolism. Strategies to mitigate the toxicity of IS include optimizing gut microbiota, intervening against the abnormality of intracellular signal transduction, and using blood purification therapy with higher efficiency. Further research is needed to examine whether lowering protein-bound uremic toxins through intervention leads to a reduction in CVD in patients with CKD.

Enhancing immune cell functions in tumors remains a major challenge in cancer immunotherapy. Natural killer cells (NK) are major innate effector cells with broad cytotoxicity against tumors. Accordingly, NK cells are ideal candidates for cancer immunotherapy, including glioblastoma (GBM). Hypoxia is a common feature of solid tumors, and tumor cells and normal cells adapt to the tumor microenvironment by upregulating the transcription factor hypoxia-inducible factor (HIF)-1α, which can be detrimental to anti-tumor effector immune cell function, including that of NK cells. We knocked out HIF-1α in human primary NK cells using clustered regularly interspaced short palindromic repeat (CRISPR)-associated protein 9 (Cas9). Then, cellular characterizations were conducted in normoxic and hypoxic conditions. Electroporating two HIF-1α-targeting guide RNA–Cas9 protein complexes inhibited HIF-1α expression in expanded NK cells. HIF-1α knockout human NK cells, including populations in hypoxic conditions, enhanced the growth inhibition of allogeneic GBM cells and induced apoptosis in GBM-cell-derived spheroids. RNA-sequencing revealed that the cytotoxicity of HIF-1α knockout NK cells could be related to increased perforin and TNF expression. The results demonstrated that HIF-1α knockout human NK cells, including populations, enhanced cytotoxicity in an environment mimicking the hypoxic conditions of GBM. CRISPR–Cas9-mediated HIF-1α knockout NK cells, including populations, could be a promising immunotherapeutic alternative in patients with GBM.

Bladder cancer (BC) is a common genitourinary malignancy that exhibits silent morbidity and high mortality rates because of a lack of diagnostic markers and limited effective treatments. Here, we evaluated the role of the lncRNA brain cytoplasmic RNA 1 (BCYRN1) in BC. We performed loss-of-function assays to examine the effects of BCYRN1 downregulation in T24 and BOY BC cells. We found that BCYRN1 downregulation significantly inhibited the proliferation, migration, invasion, and three-dimensional spheroid formation ability and induced apoptosis in BC cells. Additionally, gene set enrichment analysis (GSEA) using RNA sequences from tumor fractions showed that BCYRN1 downregulation decreased the expression of mRNAs associated with the cell cycle. These findings were supported by observations of G2/M arrest in flow cytometry assays. Finally, we examined the expression of serum exosomal BCYRN1 as a biomarker. Clinically, BCYRN1 expression in serum exosomes from patients with BC (n = 31) was significantly higher than that in healthy donors (n = 19; mean difference: 4.1-fold higher, p < 0.01). Moreover, in patients who had undergone complete resection of BC, serum exosomal BCYRN1 levels were significantly decreased (n = 8). Thus, serum exosomal BCYRN1 may be a promising diagnostic marker and therapeutic target in patients with BC.

This study examined whey protein’s impact on insulin resistance in a high-fat diet-induced pediatric obesity mouse model. Pregnant mice were fed high-fat diets, and male pups continued this diet until 8 weeks old, then were split into high-fat, whey, and casein diet groups. At 12 weeks old, their body weight, fasting blood glucose (FBG), blood insulin level (IRI), homeostatic model assessment for insulin resistance (HOMA-IR), liver lipid metabolism gene expression, and liver metabolites were compared. The whey group showed significantly lower body weight than the casein group at 12 weeks old (p = 0.034). FBG was lower in the whey group compared to the high-fat diet group (p < 0.01) and casein group (p = 0.058); IRI and HOMA-IR were reduced in the whey group compared to the casein group (p = 0.02, p < 0.01, p < 0.01, respectively). The levels of peroxisome proliferator-activated receptor α and hormone-sensitive lipase were upregulated in the whey group compared to the casein group (p < 0.01, p = 0.03). Metabolomic analysis revealed that the levels of taurine and glycine, both known for their anti-inflammatory and antioxidant properties, were upregulated in the whey group in the liver tissue (p < 0.01, p < 0.01). The intake of whey protein was found to improve insulin resistance in a high-fat diet-induced pediatric obesity mouse model.

Thermoelectric gas sensor (THGS) devices with catalysts and Si0.8Ge0.2 thin films of different boron doping levels of 1018, 1019, and 1020 cm−3 were fabricated, and their transport properties are investigated. SiGe films were deposited on Si3N4/SiO2 multilayers on Si substrates using low-pressure chemical vapor deposition (LPCVD) and thermally annealed at 1050 °C. The Seebeck coefficients of the SiGe films were increased after thermal annealing, ranging from 191 to 275 μV/K at temperatures of 74 to 468 °C in air, and reaching the highest power factor of 6.78 × 10−4 W/mK2 at 468 °C. The thermal conductivity of the SiGe films varied from 2.4 to 3.0 W/mK at 25 °C. The THGS detection performance was tested for the H2 gas in air from 0.01 to 1.0%, and compared to the thermoelectric properties of the SiGe films. The high-temperature annealing treatment process was successful in enhancing the thermoelectric performance of both the SiGe films and sensor devices, achieving the best THGS performance with the sensor device fabricated from the annealed SiGe film with 1018 cm−3 boron-doped Si0.8Ge0.2.

Background: Effects of anti-citrullinated polypeptide antibodies (ACPA) on the bone mineral density (BMD) reduction and incidence of major osteoporotic fractures (MOF) in patients with rheumatoid arthritis (RA) were evaluated using a retrospective longitudinal case-control study. Methods: Patients with RA who were examined using dual-energy X-ray absorptiometry and simultaneously treated for more than 5 years were recruited. BMD absolute value and Z-scores at initial measurements (baseline) and changes of these values from baseline were assessed, and associations between BMD and candidate risk factors including ACPA positivity and serum titer levels were statistically evaluated. Additional statistical evaluations of ACPA positivity in regard to the incidence of MOF were tested. Results: A total of 222 patients were included. Higher ACPA titers correlated significantly with lower BMD and Z-scores at baseline using a multivariate model (p < 0.05). ACPA positivity correlated significantly with lower values and an annual decrease in the Z-score in total hip at follow-up using a univariate model (p < 0.05), whereas no significant correlation was found using a multivariate model. Z-scores in the ACPA-positive group were significantly lower than those of the ACPA-negative group (p < 0.05). However, ACPA-positivity demonstrated no higher risk for incident MOF. Conclusions: The presence of ACPA is a potential risk of BMD loss however weak.

Pulmonary arterial hypertension (PAH) remains a significant challenge in cardiology, necessitating advancements in treatment strategies. This study explores the safety and efficacy of transitioning patients from beraprost to selexipag, a novel selective prostacyclin receptor agonist, within a Japanese cohort. Employing a multicenter, open-label, prospective design, 25 PAH patients inadequately managed on beraprost were switched to selexipag. Key inclusion criteria included ongoing beraprost therapy for ≥3 months, a diagnosis of PAH confirmed by mean pulmonary artery pressure (mPAP) ≥ 25 mmHg, and current treatment with endothelin receptor antagonists and/or phosphodiesterase type 5 inhibitors. Outcomes assessed were changes in hemodynamic parameters (mPAP, cardiac index, pulmonary vascular resistance) and the 6 min walk distance (6-MWD) over 3–6 months. The study found no statistically significant changes in these parameters post-switch. However, a subset of patients, defined as responders, demonstrated improvements in all measured hemodynamic parameters, suggesting a potential benefit in carefully selected patients. The transition was generally well-tolerated with no serious adverse events reported. This investigation underscores the importance of personalized treatment strategies in PAH, highlighting that certain patients may benefit from switching to selexipag, particularly those previously on higher doses of beraprost. Further research is needed to elucidate the predictors of positive response to selexipag and optimize treatment regimens for this complex condition.

Background: Extracorporeal shock wave lithotripsy (ESWL) is a common treatment for pancreatic stones in chronic pancreatitis. In contrast, peroral pancreatoscopy-guided lithotripsy (POPS-L) remains underexplored, with limited comparative studies to ESWL. This study compared the treatment outcomes of disposable POPS-L tools and ESWL for pancreatic stones. Methods: A retrospective analysis was conducted on 66 patients who had undergone pancreatic stone treatment at three institutions between 2006 and 2022. The treatment outcomes of POPS-L and ESWL were compared. Results: This study included 19 and 47 patients who had undergone POPS-L and ESWL, respectively. In a comparison between POPS-L and ESWL, the stone clearance rates were 78.9% vs. 70.2% (p = 0.55), while the procedure-related complication rates were 21% vs. 6.3% (p = 0.09). The median total session counts were 1 vs. 5 (p < 0.01). The cumulative stone recurrence rates were comparable in both groups. Multivariate analysis revealed no significant factors influencing the stone clearance rates, and the choice between POPS-L and ESWL did not affect the stone clearance rates. Conclusions: POPS-L and ESWL exhibited comparable treatment outcomes in terms of stone clearance, complications, and recurrence rates. Furthermore, POPS-L is advantageous due to the need for fewer sessions to achieve pancreatic stone clearance.

Spodopotera frugiperda is a worldwide invasive pest that has caused significant economic damage. According to the classical biological control approach, natural enemies that can control invasive pests come from the same area of origin as the pests that have experienced coadaptation processes. However, the new association’s approach suggests that local natural enemies are equally capable of controlling invasive pests. Due to the lack of data on the association of S. frugiperda and local natural enemies, research was conducted through a rapid survey to study the diversity of parasitoids associated with S. frugiperda. The results showed 15 parasitoid species associated with S. frugiperda. Four egg parasitoids, eight larval parasitoids, and three larval–pupal parasitoids were found to be associated with S. frugiperda for three years after it was first discovered in Indonesia. Eleven of them are new reports of parasitoids associated with S. frugiperda in Indonesia. A new association was found between S. frugiperda and twelve parasitoid species, consisting of three egg parasitoids (Platygasteridaesp.01, Platygasteridaesp.02, and Telenomus remus), six larval parasitoids (Apanteles sp., Microplitis sp., Campoletis sp., Coccygidium sp., Eupelmus sp., and Stenobracon sp.), and three larval–pupal parasitoids (Brachymeria lasus, B. femorata, and Charops sp.). Telenomus remus is the most dominant parasitoid, with a higher abundance and parasitism rate. The result suggests another method for selecting biological control using the new association approach since local natural enemies can foster quick adaptation to invasive pests.

Mesenteric phlebosclerosis is a rare ischemic colonic disorder caused by impaired venous drainage. Its prevalence is higher in East Asia, where herbal medicine is widely used. Treatment remains controversial. A 76-year-old woman who had taken Hangeshashinto, an herbal medicine, for 11 years was admitted for endoscopic treatment of high-grade dysplasia in the ascending colon. She had diarrhea and mesenteric phlebosclerosis diagnosed by abdominal computed tomography at age 71. At age 75, small polyps were detected in the ascending colon. A subsequent study revealed an increase in polyp size to 15 mm. Endoscopic mucosal resection failed to remove the lesion. A biopsy showed high-grade dysplasia with possible colon cancer risk. Conservative therapy did not improve mesenteric phlebosclerosis-related diarrhea; therefore, a laparoscopic right hemicolectomy was performed. Intraoperatively, the cecum was adherent to the abdominal wall and the right ovary. The specimen showed high-grade dysplasia in the mucosa and severe submucosal fibrosis. No metastasis was observed. This case shows the link between mesenteric phlebosclerosis and high-grade dysplasia in the ascending colon. Endoscopic mucosal resection was unsuccessful in removing the tumor. Endoscopic submucosal dissection was an alternative, but its safety in mesenteric phlebosclerosis-affected colonic segments remains uncertain. A laparoscopic right hemicolectomy was performed.

Frailty is a major geriatric syndrome with a multifactorial etiology that induces a decline in multiple physiological and psychological functions. In traditional East Asian medicine (TEAM), qi and blood deficiency clinically represent as fatigue, anemia, anorexia, decreased strength after illness, and weakness, commonly interpretated as frailty. An herbal prescription of Insamyangyeongtang (IYT, Ninjin’yoeito in Japanese, Ren-Shen-Yang-Rong-Tang in Chinese) tonifies qi and blood and has the potential to treat multiple targets caused by qi and blood deficiency. As the population ages and frailty increases, there is an increase in the potential effectiveness of IYT in frailty. This study reviewed relevant clinical trials to provide an updated view on the effect of IYT on frailty. IYT has therapeutic effects on frailty associated with chronic respiratory diseases (e.g., chronic obstructive pulmonary disease) and cognitive impairments (e.g., Alzheimer’s disease) and improves respiratory symptoms and cognition. IYT also has therapeutic effects on weight gain, muscle mass, and strength, and improves nutritional status in frail elderly individuals who have decreased muscle mass and strength, loss of appetite, and weight loss. The same effect has been shown in frailty in elderly individuals with rehabilitation treatment and chronic diseases. IYT also improves frailty associated with symptoms such as intractable dizziness and genitourinary symptoms. The beneficial effects of IYT in several diseases could be important for medication replacement, reduction, and prevention of polypharmacy. Based on the results of this review, we suggest that IYT has the potential to be a therapeutic agent against frailty.

Two field trials were conducted in Northern Thailand from 2018 to 2020 to determine the best manual harvesting method for maximizing seed yield and seed quality of two Urochloa ruziziensis cultivars, cv. OKI-1 and cv. Br-203. Four manual seed harvesting methods were implicated in a randomized complete block design with four replicates. The four methods were as follows: knocking seeds from seedheads into a nylon net receptacle and collecting them once every day (T1); knocking seeds from seedheads into a nylon net receptacle and collecting them once every three days (T2); allowing ripe seeds to fall into a nylon net sheet that was stretched as a receptacle beneath the seedheads and collecting seeds once every five days (T3); and covering the tied seedheads with a nylon net bag and collecting seeds once every five days (T4). The highest pure seed yield was obtained from T3 in cv. Br-203 (333.11 kg/ha), as well as the highest trend in cv. OKI-1 (534.67 kg/ha). T3 produced 22–46% and 11–27% more pure germinated seed yields than the other methods in cv. Br-203 and cv. OKI-1, respectively. As a result, T3 was recommended for higher seed yield, convenient seed harvest, and reduced manual seed harvest time.

Cockayne syndrome (CS) is a rare autosomal recessive disorder that affects the DNA repair process. It is a progeroid syndrome predisposing patients to accelerated aging and to increased susceptibility to respiratory infections. Here, we studied the immune status of CS patients to determine potential biomarkers associated with pathological aging. CS patients, as well as elderly and young, healthy donors, were enrolled in this study. Complete blood counts for patients and donors were assessed, immune cell subsets were analyzed using flow cytometry, and candidate cytokines were analyzed via multi-analyte ELISArray kits. In CS patients, we noticed a high percentage of lymphocytes, an increased rate of intermediate and non-classical monocytes, and a high level of pro-inflammatory cytokine IL-8. In addition, we identified an increased rate of particular subtypes of T Lymphocyte CD8+ CD28− CD27−, which are senescent T cells. Thus, an inflammatory state was found in CS patients that is similar to that observed in the elderly donors and is associated with an immunosenescence status in both groups. This could explain the CS patients’ increased susceptibility to infections, which is partly due to an aging-associated inflammation process.

Early enteral nutrition using reliable biomarkers of intestinal function must be established to improve neurodevelopmental outcomes in very low birth weight infants (VLBWIs). Serum citrulline levels reflect the intestinal function in adults. To elucidate the relationship among antenatal growth, postnatal enteral nutrition, and blood citrulline levels, a retrospective single-center observational study was conducted on 248 VLBWIs born between April 2014 and March 2021. A mixed effect model and post hoc simple slope analysis were used to estimate the correlations between clinical variables and citrulline levels at Early (day 5.1) and Late (day 24.3) postnatal ages. Greater gestational age, birth weight, and amount of enteral nutrition at the time of blood sampling were associated with lower citrulline levels at the Early postnatal age and higher citrulline levels at the Late postnatal age. Provided that Early citrulline levels predominantly reflect the consequence of antenatal citrulline metabolism, it is suggested that fetal growth and maturation are likely to promote citrulline catabolism in utero and its synthesis after birth. With additional insights into the temporal transition point wherein the maturation-dependent balance of citrulline metabolism shifts from catabolism-dominant to synthesis-dominant, citrulline emerges as a potential biomarker for assessing intestinal function and gastrointestinal disorders.

The forest products industries play a vital role in the economic, social, and environmental well-being of the Lake States in the United States. While various economic contribution analyses of forest products industries have been conducted to highlight the importance of such industries to regional economies, little effort has yet been made to parse out the contribution of activities in the value chain. The value chain is a series of steps involved in producing goods or services. This study used a matrix decomposition approach to estimate the economic contribution along the value chain through multiple pathways of four forest resource-based industries using wood as inputs: biomass power generation, sawmills, paper mills, and the construction of new single-family residential structures in the Lake States. The direct and indirect economic output values in 2017 resulting from the construction of new single-family residential structures were $19.1 billion, sawmills were $2.5 billion, paper mills were $17.6 billion, and the biomass power generation industry was $759 million. Of the direct and indirect economic output contributed by each industry, the highest percentage of output attributable to the logging industry was observed from the sawmills industry (12%), followed by biomass power generation (9%), paper mills (1.4%), and the construction of new single-family residential structures (

Early-stage lung adenocarcinoma (LUAD) patients remain at substantial risk for recurrence and disease-related death, highlighting the unmet need of biomarkers for the assessment and identification of those in an early stage who would likely benefit from adjuvant chemotherapy. To identify circulating miRNAs useful for predicting recurrence in early-stage LUAD, we performed miRNA microarray analysis with pools of pretreatment plasma samples from patients with stage I LUAD who developed recurrence or remained recurrence-free during the follow-up period. Subsequent validation in 85 patients with stage I LUAD resulted in the development of a circulating miRNA panel comprising miR-23a-3p, miR-320c, and miR-125b-5p and yielding an area under the curve (AUC) of 0.776 in predicting recurrence. Furthermore, the three-miRNA panel yielded an AUC of 0.804, with a sensitivity of 45.8% at 95% specificity in the independent test set of 57 stage I and II LUAD patients. The miRNA panel score was a significant and independent factor for predicting disease-free survival (p < 0.001, hazard ratio [HR] = 1.64, 95% confidence interval [CI] = 1.51–4.22) and overall survival (p = 0.001, HR = 1.51, 95% CI = 1.17–1.94). This circulating miRNA panel is a useful noninvasive tool to stratify early-stage LUAD patients and determine an appropriate treatment plan with maximal efficacy.

Despite standard multimodality treatment, containing maximum safety resection, temozolomide, radiotherapy, and a tumor-treating field, patients with glioblastoma (GBM) present with a dismal prognosis. Natural killer cell (NKC)-based immunotherapy would play a critical role in GBM treatment. We have previously reported highly activated and ex vivo expanded NK cells derived from human peripheral blood, which exhibited anti-tumor effect against GBM cells. Here, we performed preclinical evaluation of the NK cells using an in vivo orthotopic xenograft model, the U87MG cell-derived brain tumor in NOD/Shi-scid, IL-2RɤKO (NOG) mouse. In the orthotopic xenograft model, the retro-orbital venous injection of NK cells prolonged overall survival of the NOG mouse, indirectly indicating the growth-inhibition effect of NK cells. In addition, we comprehensively summarized the differentially expressed genes, especially focusing on the expression of the NKC-activating receptors’ ligands, inhibitory receptors’ ligands, chemokines, and chemokine receptors, between murine brain tumor treated with NKCs and with no agents, by using microarray. Furthermore, we also performed differentially expressed gene analysis between an internal and external brain tumor in the orthotopic xenograft model. Our findings could provide pivotal information for the NK-cell-based immunotherapy for patients with GBM.

Background: this study aimed to evaluate the prognostic factors associated with long-term survival after linear accelerator (linac)-based stereotactic radiosurgery (SRS) and fractionated stereotactic radiotherapy (fSRT) with a micro-multileaf collimator for brain metastasis (BM). Methods: This single-center retrospective study included 226 consecutive patients with BM who were treated with linac-based SRS or fSRT with a micro-multileaf collimator between January 2011 and December 2018. Long-term survival (LTS) was defined as survival for more than 2 years after SRS/fSRT. Results: The tumors originated from the lung (n = 189, 83.6%), breast (n = 11, 4.9%), colon (n = 9, 4.0%), stomach (n = 4, 1.8%), kidney (n = 3, 1.3%), esophagus (n = 3, 1.3%), and other regions (n = 7, 3.1%). The median pretreatment Karnofsky performance scale (KPS) score was 90 (range: 40–100). The median follow-up time was 13 (range: 0–120) months. Out of the 226 patients, 72 (31.8%) were categorized in the LTS group. The median survival time was 43 months and 13 months in the LTS group and in the entire cohort, respectively. The 3-year, 4-year, and 5-year survival rate in the LTS group was 59.1%, 49.6%, and 40.7%, respectively. Multivariate regression logistic analysis showed that female sex, a pre-treatment KPS score ≥ 80, and the absence of extracranial metastasis were associated with long-term survival. Conclusions: female sex, a favorable pre-treatment KPS score, and the absence of extracranial metastasis were associated with long-term survival in the current cohort of patients with BM.

Impacts of subclinical reactive hypoglycemia on food ingestion are not well studied. In the present study, in obese/overweight males without diabetes (n = 34), continuous glucose monitoring and eating behavior were recorded for 6 days after the 75 g glucose challenge. In 50% of subjects, the minimal sensor glucose levels within 24 h post-challenge (CGMmin) were 3 times/day, CGMmin was significantly lower than CGMmin in those without. The receiver operating characteristic curve of CGMmin for detecting eating frequency > 3 times/day showed the area under the curve of 0.74 with the cutoff point of 65 mg/dL (p = 0.027). Eating frequency of subjects with CGMmin < 65 mg/dL was significantly higher than that of subjects with CGMmin ≥ 65 mg/dL (3.68 vs. 3.3 times/day, p = 0.047). When it was defined as reactive hypoglycemia that either the 2 h post-load blood glucose level, the minimal self-monitored blood glucose level within the 1st day, or CGMmin, was below their respective cutoff for detecting eating frequency > 3 times/day, eating frequency of subjects with the reactive hypoglycemia was significantly higher than that of the subjects without the reactive hypoglycemia (3.75 times/day vs. 3.15 times/day, p = 0.001). In addition, the median snacking frequency was 6 times higher in subjects with reactive hypoglycemia compared to those without it (0.9 times/day vs. 0.15 times/day, p < 0.001). In conclusion, in obese/overweight males without diabetes, subclinical reactive hypoglycemia is significantly associated with higher eating/snacking frequencies.