Metabolism and effects of acetoaceto--toluidine in the urinary bladder of humanized-liver mice.

Occupational exposure to aromatic amines is a major risk factor for urinary bladder cancer. Our previous studies showed that acetoaceto--toluidine, which is produced using -toluidine as a raw material, promotes urinary bladder carcinogenesis in rats. We also found high concentrations of -toluidine, a human bladder carcinogen, in the urine of acetoaceto--toluidine-treated rats, indicating that urinary -toluidine derived from acetoaceto--toluidine may play an important role in bladder carcinogenesis.

Sensory processing associated with subcategories of restricted and repetitive behaviors in Japanese children and adolescents with autism spectrum disorder.

Background: Restricted and repetitive behavior (RRB) is a core symptom of autism spectrum disorder (ASD). The structure of RRB subcategories and their relationship with atypical sensory processing in Japan are not well understood. This study examined subcategories of the RRB in Japanese children with ASD and explored their relationship with sensory processing.

Super delayed phase imaging in gadoxetic acid-enhanced MRI: investigating factors contributing to improved liver contrast.

Objectives: To assess whether extended delayed phase imaging, performed after gadoxetic acid administration for 60-120 min (termed as super delayed phase [SDP]), improves liver contrast and nodule visibility in patients with chronic liver disease and to identify predictors for contrast enhancement.

Methods: In this retrospective study, 116 patients with chronic liver disease were selected from 6933 gadoxetic acid-enhanced MRI examinations, which included SDP images. The liver-to-spleen contrast (LSC) was quantitatively evaluated, and factors influencing the improvement of LSC were analyzed.

Photon-counting three-dimensional fluorescence imaging based on the transport of intensity equation.

A transport of intensity equation (TIE) based three-dimensional (3D) fluorescence imaging using photon-counting detection was proposed for low light-level bioimaging applications. The number of photons required to achieve the quantitative phase measurement using the proposed system was investigated experimentally and numerically. Results show that the feasibility of reconstructing phase information with an average number of photons is greater than about 9 per pixel in our plant cells.

3D fluorescence imaging through a scattering medium using the transport of intensity equation and Fresnel ping-pong algorithm.

A three-dimensional (3D) fluorescent imaging method through a scattering medium has been presented. The proposed method combines digital phase conjugate reconstruction of the scattered light wave by the transport of intensity equation-based 3D fluorescent imaging to the position of scattering medium and followed phase retrieval method by Fresnel ping-pong algorithm. The effectiveness of the proposed method is experimentally verified by measuring the 3D distribution of fluorescent beads and tobacco-cultured cells through a thin diffuser.

Transport-of-intensity phase imaging using commercially available confocal microscope.

Significance: Confocal microscopy is an indispensable tool for biologists to observe samples and is useful for fluorescence imaging of living cells with high spatial resolution. Recently, phase information induced by the sample has been attracting attention because of its applicability such as the measurability of physical parameters and wavefront compensation. However, commercially available confocal microscopy has no phase imaging function.

Systemic identification of functionally conserved lncRNA metabolic regulators in human and mouse livers.

Background & Aims: Unlike protein-coding genes, the majority of human long non-coding RNAs (lncRNAs) lack conservation based on their sequences, posing a challenge for investigating their role in a pathophysiological context for clinical translation. This study explores the hypothesis that non-conserved lncRNAs in human and mouse livers may share similar metabolic functions, giving rise to functionally conserved lncRNA metabolic regulators (fcLMRs).

Methods: We developed a sequence-independent strategy to select putative fcLMRs, and performed extensive analysis to determine the functional similarities of putative human and mouse LMR pairs (h/mLMRs).

Induction of drug metabolizing enzyme and drug transporter expression by antifungal triazole pesticides in human HepaSH hepatocytes.

Triazole pesticides are widely used fungicides, to which humans are rather highly exposed. They are known to activate drug-sensing receptors regulating expression of hepatic drug metabolizing enzymes and drug transporters, thus suggesting that the hepatic drug detoxification system is modified by these agrochemicals. To investigate this hypothesis, the effects of 9 triazole fungicides towards expression of drug metabolizing enzymes and transporters were characterized in cultured human HepaSH cells, that are human hepatocytes deriving from chimeric humanized liver TK-NOG mice.

Urinary bladder carcinogenic potential of 4,4'-methylenebis(2-chloroaniline) in humanized-liver mice.

Occupational exposure to 4,4'-methylenebis(2-chloroaniline) (MOCA) has been linked to an increased risk of bladder cancer among employees in Japanese plants, indicating its significance as a risk factor for urinary bladder cancer. To investigate the role of MOCA metabolism in bladder carcinogenesis, we administered MOCA to non-humanized (F1-TKm30 mice) and humanized-liver mice for 4 and 28 wk. We compared MOCA-induced changes in metabolic enzyme expression, metabolite formation, and effects on the urinary bladder epithelium in the 2 models.

Dissociation of LAG-3 inhibitory cluster from TCR microcluster by immune checkpoint blockade.

Lymphocyte activation gene (Lag)-3 is an inhibitory co-receptor and target of immune checkpoint inhibitor (ICI) therapy for cancer. The dynamic behavior of Lag-3 was analyzed at the immune synapse upon T-cell activation to elucidate the Lag-3 inhibitory mechanism. Lag-3 formed clusters and co-localized with T-cell receptor microcluster (TCR-MC) upon T-cell activation similar to PD-1.

Decrease in the Internal Cerebral Vein Pulsation With Improvement of Patent Ductus Arteriosus in Premature Infants at the Risk of Intraventricular Hemorrhage: Two Interesting Case Reports.

Recently, augmenting the pulsation of the internal cerebral vein (ICV) has been reported to be a predictor of premature intraventricular hemorrhage (IVH); however, prophylaxis for IVH has not yet been established. Venous pulsation is a marker of central venous pressure elevation and may be improved after heart failure treatment. Herein, we report two cases of low-birth-weight infants (29 weeks and 31 weeks of gestational age), who exhibited improvements in ICV pulsation with relief of hemodynamically significant patent ductus arteriosus (hs-PDA) following indomethacin administration.

Impact of miR-222-3p-mediated downregulation of arylacetamide deacetylase on drug hydrolysis and lipid accumulation.

Arylacetamide deacetylase (AADAC) is involved in drug hydrolysis and lipid metabolism. In 23 human liver samples, no significant correlation was observed between AADAC mRNA (19.7-fold variation) and protein levels (137.

3D fluorescence imaging through scattering medium using transport of intensity equation and iterative phase retrieval.

In this paper, we have proposed a method of three-dimensional (3D) fluorescence imaging through a scattering medium. The proposed method combines the numerical digital phase conjugation propagation after measurement of the complex amplitude distribution of scattered light waves by the transport of intensity equation (TIE) with followed iterative phase retrieval to achieve 3D fluorescence imaging through a scattering medium. In the experiment, we present the quantitative evaluation of the depth position of fluorescent beads.

Reactive lymphoid hyperplasia of the liver: A case report featuring characteristic nodular and perinodular enhancement.

A 53-year-old female with primary biliary cholangitis was referred for the evaluation of a hepatic nodule identified during routine imaging. Ultrasonography revealed a homogeneous, hypoechoic, 18 mm nodule in segment 3 of the liver. On dynamic CT and MRI, the nodule showed mild enhancement at the hepatic artery-dominant phase.

Imaged periductal infiltration: Diagnostic and prognostic role in intrahepatic mass-forming cholangiocarcinoma.

Purpose: This study examines periductal infiltration in intrahepatic mass-forming cholangiocarcinoma (IMCC), focusing on its importance for differentiating hepatic tumors and its influence on post-surgical survival in IMCC patients.

Methods: Eighty-three consecutive patients with IMCC (n = 43) and liver cancer whose preoperative images showed intrahepatic bile duct dilatation adjacent to the tumor for differential diagnosis from hepatocellular carcinoma (HCC) [n = 21], metastatic liver cancer (MLC) [n = 16] and combined hepatocellular-cholangiocarcinoma (cHCC-CC) [n = 3] were enrolled. CT and MRI findings of simple bile duct compression, imaged periductal infiltration, and imaged intrabiliary growth adjacent to the main tumor were reviewed.

Fluoride Ion in Alcohols: Isopropanol vs Hexafluoroisopropanol.

The utility of alcohol as a hydrogen bonding donor is considered a providential avenue for moderating the high basicity and reactivity of the fluoride ion, typically used with large cations. However, the practicality of alcohol-fluoride systems in reactions is hampered by the limited understanding of the pertinent interactions between the OH group and F. Therefore, this study comparatively investigates the thermal, structural, and physical properties of the CsF-2-propanol and CsF-1,1,1,3,3,3-hexafluoro-2-propanol systems to explicate the effects of the fluoroalkyl group on the interaction of alcohols and F.

Ten-Gram-Scale Total Synthesis of the Anticancer Drug Candidate E7130 to Supply Clinical Trials.

E7130 is a novel drug candidate with an exceedingly complex chemical structure of the halichondrin class, discovered by a total synthesis approach through joint research between the Kishi group at Harvard University and Eisai. Only 18 months after completion of the initial milligram-scale synthesis, ten-gram-scale synthesis of E7130 was achieved, providing the first good manufacturing practice (GMP) batch to supply clinical trials. This paper highlights the challenges in developing ten-gram-scale synthesis from the milligram-scale synthesis.

Comprehensive gene profiling of the metabolic landscape of humanized livers in mice.

Background & Aims: The human liver transcriptome is complex and highly dynamic, e.g. one gene may produce multiple distinct transcripts, each with distinct posttranscriptional modifications.

Empirical scaling factor for predicting human pharmacokinetic profiles of disproportionate metabolites using the Css-MRTpo method and chimeric mice with humanised livers.

Predicting plasma concentration-time profiles of disproportionate metabolites in humans is crucial for evaluating metabolites according to the Safety Testing guidelines. We evaluated Css-MRTpo, an empirical method, using chimeric mice with humanised livers capable of generating human-disproportionate metabolites. Azilsartan and AZ-M2 were administered to humanised chimeric mice, and pharmacokinetic parameters were obtained.

Quantitative phase imaging based on motionless optical scanning holography.

Optical scanning holography (OSH) can be applied to 3D fluorescent imaging. However, the optical setup for OSH is complicated due to the requirement of a phase shifter, a 2D mechanical scanner, and an interferometer. Although motionless optical scanning holography (MOSH) can overcome the problem, quantitative phase imaging (QPI) has not yet been realized because MOSH can only obtain incoherent holograms.

SGX523 causes renal toxicity through aldehyde oxidase-mediated less-soluble metabolite formation in chimeric mice with humanized livers.

SGX523 is a c-Met tyrosine kinase inhibitor that failed in clinical trials because of renal toxicity caused by crystal deposits in renal tubules. SGX523 is metabolized by aldehyde oxidase (AOX) in a species-dependent manner to the considerably less soluble 2-quinolinone-SGX523, which is likely involved in the clinically observed obstructive nephropathy. This study investigated the metabolism and renal toxicity of SGX523 in chimeric mice with humanized livers (humanized-liver mice).

A case of focal nodular hyperplasia-like lesion presenting unusual signal intensity on the hepatobiliary phase of gadoxetic acid-enhanced magnetic resonance image.

Focal nodular hyperplasia (FNH) or FNH-like lesions of the liver are benign lesions that can be mostly diagnosed by hepatobiliary phase gadoxetic acid-enhanced magnetic resonance imaging (MRI). Accurate imaging diagnosis is based on the fact that most FNHs or FNH-like lesions show characteristic hyper- or isointensity on hepatobiliary phase images. We report a case of an FNH-like lesion in a 73-year-old woman that mimicked a malignant tumor.