Triethanolamine-based esterquat in sediments: New analytical method, environmental occurrence, and homologue composition.

The cationic surfactant triethanolamine-based esterquat (TEAQ) is a main ingredient in commercial fabric softeners and is produced and used in large quantities. However, little information is available for its occurrence in the environment, particularly in sediments. Here, we developed an analytical method for quantifying TEAQ in sediment and investigated TEAQ contamination in Japanese river and lake sediments. In our analytical method, TEAQ concentrations were measured by liquid chromatography-tandem mass spectrometry using a polymer-based size-exclusion column, which resulted in excellent peak shapes. TEAQ was detected at significant levels in procedural blanks, resulting in a method limit of detection in the sediment of 8.9-97 µg/kg-dry for TEAQ monoesters and 0.6-24 µg/kg-dry for TEAQ diesters. TEAQ was detected in 22 out of 26 sediment samples, with the sum of all homologue concentrations being up to 1340 µg/kg-dry. The concentration of TEAQ in sediments was high at locations where the concentrations of benzalkoniums and the organic carbon content were also high. TEAQ was detected in 8 out of 14 commercial fabric softeners at concentrations of 1.7-7.4 wt%. TEAQ homologues containing only saturated fatty acids accounted for 83 ± 5% of the total TEAQ in the sediments, whereas those with unsaturated fatty acids accounted for 71 ± 14% of the total TEAQ in a commercial technical mixture and the softener products. The results of this study will be useful for the environmental risk assessment of esterquats.

Expert-Novice Level Classification Using Graph Convolutional Network Introducing Confidence-Aware Node-Level Attention Mechanism.

In this study, we propose a classification method of expert-novice levels using a graph convolutional network (GCN) with a confidence-aware node-level attention mechanism. In classification using an attention mechanism, highlighted features may not be significant for accurate classification, thereby degrading classification performance. To address this issue, the proposed method introduces a confidence-aware node-level attention mechanism into a spatiotemporal attention GCN (STA-GCN) for the classification of expert-novice levels. Consequently, our method can contrast the attention value of each node on the basis of the confidence measure of the classification, which solves the problem of classification approaches using attention mechanisms and realizes accurate classification. Furthermore, because the expert-novice levels have ordinalities, using a classification model that considers ordinalities improves the classification performance. The proposed method involves a model that minimizes a loss function that considers the ordinalities of classes to be classified. By implementing the above approaches, the expert-novice level classification performance is improved.

Gray-white matter contrast reversal on T1-weighted spin-echo in postmortem brain.

PURPOSE: The image contrast of postmortem magnetic resonance imaging (MRI) may differ from that of antemortem MRI because of circulator arrest, changes in postmortem tissue, and low-body-temperature scanning conditions. In fact, we have found that the signal intensity of white matter (WM) on T1-weighted spin-echo (T1WSE) images of the postmortem brain was lower than that of gray matter (GM), which resulted in image contrast reversal between GM and WM relative to the living brain. However, the reason for this phenomenon is unclear. Therefore, the aim of this study is to clarify the reason why image contrast reversal occurs between GM and WM of the postmortem brain. MATERIALS AND METHODS: Twenty-three corpses were included in the study (mean age, 60.6 years; range: 19-60 years; mean rectal temperature at scan, 6.9℃; range: 4-11℃). On a 1.5 T MRI system, postmortem T1W-SE MRI of the brain was conducted in the 23 corpses prior to medico-legal autopsy. Next, T1 and T2 of the GM and WM at the level of the basal ganglia were determined in the same participants using inversion recovery and multiple SE sequences, respectively. The proton density (PD) was also calculated from the T1 and T2 images (in the same slice). RESULTS: T1W-SE image contrast between the GM and WM of all postmortem brains was inverted relative to the living brain. T1 (579 ms in GM and 307 ms in WM) and PD (64 in GM and 44 in WM) of the postmortem brain decreased compared with the living brain. While T1 of WM/GM remained below 1 even postmortem, the PD of WM/GM decreased. T2 (110 ms in GM and 98 ms in WM) of the postmortem brain did not differ from the living brain. CONCLUSION: The decrease in PD of WM/GM in the postmortem brain may be the major driver of contrast reversal between the GM and WM relative to the living brain.

Asymmetric genetic population structures at the range edges of a mangrove whelk.

Many marine species are distributed across incredibly wide geographical ranges spanning thousands of kilometers often due to movement along prevailing ocean currents. However, data are lacking on genetic connectivity among populations of such widespread species within or among ecoregions, possibly due to the lack of appropriate datasets. In this study, we investigated the genetic structure of populations of the mangrove whelk, Terebralia palustris, using mitochondrial cytochrome oxidase subunit I (COI) sequences. Sequences generated for this study from Okinawa, Japan, were compared to samples from the coast of East Africa analyzed in a previous study. Interestingly, despite considerable distance separating them, the African and Japanese populations share major haplotypes and do not show clear genetic differentiation. At lower latitudes, core African populations exhibited higher genetic diversity than either the more southerly African and Japanese populations. Genetic ß-diversity revealed that the northern edge population in Japan has a greater proportion of ßSNE (the nestedness-resultant component), indicating contemporary migration, whereas the southern edge population in Africa is characterized by a predominant ßSIM (the turnover component), suggesting historical demography. A potential cause of this dissimilarity could be due to the strong Kuroshio Current along the Ryukyu Islands, which may promote larval dispersal. These differing patterns suggest that there may be divergent responses to future climate change at the population level at the periphery of the range of T. palustris.

Development of 3ß,4α-dihydroxy-5α-androstan-17-one standard solution for doping analyses.

Doping analyses are essential for sporting events because some athletes might use prohibited substances to win games. To obtain reliable results from doping analyses, it is important to use both reliable standard solutions and validated analytical methods at accredited laboratories. Among the focused compounds related to prohibited substances listed by the World Anti-Doping Agency, we developed a certified reference material (CRM) for 3ß,4α-dihydroxy-5α-androstan-17-one (DHAS), a metabolite of formestane that is used to conceal prohibited anabolic steroids, in methanol solution (NMIJ CRM 6212-a). To develop a CRM traceable to the International System of Units (SI), we newly applied different analytical methods with an SI-traceable internal standard for quantitative NMR (qNMR) instead of mass balance approach because this CRM solution was required to develop rapidly using a limited amount of high-purity DHAS. One method was gravimetric blending using the purity of DHAS powder evaluated by both qNMR and a combination of qNMR and high-performance liquid chromatography (HPLC), and the other was direct quantification of the DHAS mass fraction in the candidate solution CRM by both qNMR and qNMR/HPLC. Because the values obtained by gravimetric blending and direct quantification of the mass fraction were comparable, the arithmetic mean was applied to obtain the certified value. Considering homogeneity and stability according to ISO Guide 35: 2017, the certified values with expanded uncertainties (coverage factor k = 2, approximate 95% confidence interval) were (135.2 ± 9.5) µg/g for the mass fraction and (107.0 ± 7.5) µg/ml for the mass concentration.

[Right Atrial Blood Cyst with Patent Foramen Ovale:Report of a Case].

A woman in 70s was diagnosed with lung cancer, and a right atrial mass was discovered incidentally during preoperative examination by contrast-enhanced computed tomography (CT). Transesophageal echocardiography revealed a 20-mm, stemmed, spherical mass with low internal echogenicity and partially high echogenicity extending from the junction of the inferior vena cava to the posterior wall of the right atrium. Patent foramen ovale( PFO) was also confirmed. To avoid embolization and obtain diagnosis, the patient was referred for right atrial tumor resection. Cardiopulmonary bypass was established; the right atrial tumor was removed while the patient was in cardiac arrest. The tumor membrane was thin and easily ruptured, revealing jelly-like blood content and calcified mass. The patient recovered well after surgery and was discharged on day 15. According to the pathological examination, the tumor was a blood cyst. This is an extremely rare case of a blood cyst with PFO.

Semisynthesis of 5-O-ester derivatives of renieramycin T and their cytotoxicity against non-small-cell lung cancer cell lines.

The semisynthesis of 5-O-ester derivatives of renieramycin T was accomplished through the photoredox reaction of renieramycin M (1), a bistetrahydroisoquinolinequinone alkaloid isolated from the Thai blue sponge Xestospongia sp. This process led to the conversion of compound 1 to renieramycin T (2), which was subsequently subjected to Steglich esterification with appropriate acylating agents containing linear alkyl, N-tert-butoxycarbonyl-L-amino, and heterocyclic aromatic substituent. Notably, the one-pot transformation, combining the photoredox reaction and esterification led to the formation of 7-O-ester derivatives of renieramycin S due to hydrolysis. Subsequently, the in vitro cytotoxicity of the 17 semisynthesized derivatives against human non-small-cell lung cancer (NSCLC) cells in parallel with normal cell lines was evaluated. Among the tested compounds, 5-O-(3-propanoyl) ester of renieramycin T (3b) exhibited potent cytotoxic activity with half-maximal inhibitory concentration (IC50) values at 33.44 and 33.88 nM against H292 and H460 cell lines, respectively. These values were within the same range as compound 1 (IC50 = 34.43 and 35.63 nM) and displayed twofold higher cytotoxicity compared to compound 2 (IC50 = 72.85 and 83.95 nM). The steric characteristics and aromatic orientation of the 5-O-ester substituents played significant roles in their cytotoxicity. Notably, derivative 3b induced apoptosis with minimal necrosis, in contrast to the parental compound 1. Hence, the relationship between the structure and cytotoxicity of renieramycin-ecteinascidin hybrid alkaloids was investigated. This study emphasizes the potential of the series of 5-O-ester derivatives of renieramycin T as promising leads for the further development of potential anti-NSCLC agents.

Macrolide and Ketolide Antibiotics Inhibit the Cytotoxic Effect of Trastuzumab Emtansine in HER2-Positive Breast Cancer Cells: Implication of a Potential Drug-ADC Interaction in Cancer Chemotherapy.

Macrolides are widely used for the long-term treatment of infections and chronic inflammatory diseases. The pharmacokinetic features of macrolides include extensive tissue distribution because of favorable membrane permeability and accumulation within lysosomes. Trastuzumab emtansine (T-DM1), a HER2-targeting antibody-drug conjugate (ADC), is catabolized in the lysosomes, where Lys-SMCC-DM1, a potent cytotoxic agent, is processed by proteinase degradation and subsequently released from the lysosomes to the cytoplasm through the lysosomal membrane transporter SLC46A3, resulting in an antitumor effect. We recently demonstrated that erythromycin and clarithromycin inhibit SLC46A3 and attenuate the cytotoxicity of T-DM1; however, the effect of other macrolides and ketolides has not been determined. In this study, we evaluated the effect of macrolide and ketolide antibiotics on T-DM1 cytotoxicity in a human breast cancer cell line, KPL-4. Macrolides used in the clinic, such as roxithromycin, azithromycin, and josamycin, as well as solithromycin, a ketolide under clinical development, significantly attenuated T-DM1 cytotoxicity in addition to erythromycin and clarithromycin. Of these, azithromycin was the most potent inhibitor of T-DM1 efficacy. These antibiotics significantly inhibited the transport function of SLC46A3 in a concentration-dependent manner. Moreover, these compounds extensively accumulated in the lysosomes at the levels estimated to be 0.41-13.6 mM when cells were incubated with them at a 2 µM concentration. The immunofluorescence staining of trastuzumab revealed that azithromycin and solithromycin inhibit the degradation of T-DM1 in the lysosomes. These results suggest that the attenuation of T-DM1 cytotoxicity by macrolide and ketolide antibiotics involves their lysosomal accumulation and results in their greater lysosomal concentrations to inhibit the SLC46A3 function and T-DM1 degradation. This suggests a potential drug-ADC interaction during cancer chemotherapy.

Skin quality sensor to evaluate vibration and friction generated when sliding over skins.

OBJECTIVE: The mechanical condition and tactile evaluation of skin are essential for the development of skin care products. Most of the existing commercial instruments and studies aim to evaluate the skin surface by pressing it for hardness or by using imaging sensors, but there have been few instrumental measurements employing rubbing motion. Here, we have developed a sensor specialized for tactile sensation and the contact phenomenon during skin rubbing. METHODS: The developed sensor has three features: It can measure body parts including cheeks and arms, automate the rubbing motion of the probe and measure vibration and friction simultaneously. It is hand-held, with metal probes that rub the skin surface while rotating under a motor drive; it has an accelerometer and a force sensor beneath the probe measuring vibration and friction forces. To evaluate the validity of the sensor's measurements, artificial skin models were measured using the developed sensor and commercially available sensors and the results were compared. The relationship between the sensor output, surface roughness measurement and sensory evaluation was also investigated. Additionally, we evaluated the inter-rater reliability when measuring actual skin. RESULTS: The measurements of five artificial skin models with different surface shapes showed a high correlation (r = 0.99) between the vibration intensity values evaluated by the developed sensor and those measured by a tri-axial acceleration sensor attached to a fingernail. The correlation coefficient between the vibration intensity values and surface roughness was r = 0.91, and the correlation with the sensory evaluation score of roughness was r = 0.99. The friction coefficients measured by the developed sensor and the force plate had r = 0.93, based on measurements of five artificial skin models with different friction conditions. The inter-rater correlation coefficients between the three participants of the developed sensor were as high as 0.92 and 0.94 for the vibration and friction measurements respectively. CONCLUSION: The vibration intensities and friction coefficients from the sensor were highly correlated with those of the conventional sensor. The inter-rater reliability was also high. The developed sensor can be useful for tactile evaluation in skin-care product development.

OBJECTIF: l'état mécanique et l'évaluation tactile de la peau sont essentiels au développement de produits de soins de la peau. La plupart des instruments disponibles sur le marché et des études publiées à ce jour évaluent la surface de la peau en la comprimant pour déterminer sa dureté ou en utilisant des capteurs d'imagerie, mais il n'y a eu que peu de mesures instrumentales utilisant le mouvement de frottement. Ici, nous avons développé un capteur spécialisé pour la sensation tactile et le phénomène de contact lors du frottement de la peau. MÉTHODES: le capteur développé possède trois caractéristiques : il permet d'exercer des mesures sur plusieurs parties du corps, y compris les joues et les bras ; il automatise le mouvement de frottement de la sonde et il mesure simultanément les vibrations et les frottements. Tenu à la main, doté de sondes en métal qui frottent la surface de la peau tout en tournant sous l'action d'un moteur, il est équipé d'un accéléromètre et d'un capteur de force situé sous la sonde qui mesure les forces de vibration et de frottement. Pour déterminer la validité des mesures du capteur, des modèles de peau artificielles ont été évalués à l'aide du capteur développé et de capteurs déjà disponibles sur le marché, et les résultats ont été comparés. Le lien entre les mesures réalisées à l'aide du capteur, la mesure de la rugosité de la surface de la peau et l'évaluation sensorielle a également été étudié. En outre, nous avons évalué la fiabilité inter-évaluateurs lors de la mesure réelle de la peau. RÉSULTATS: les mesures de cinq modèles de peau artificielle avec des formes de surface différentes ont montré une forte corrélation (r = 0,99) entre les valeurs d'intensité des vibrations évaluées par le capteur développé et celles mesurées par un capteur d'accélération triaxial fixé à un ongle. Le coefficient de corrélation entre les valeurs d'intensité des vibrations et la rugosité de la surface était r = 0,91, et la corrélation avec le score d'évaluation sensorielle de la rugosité était r = 0,99. Les coefficients de frottement mesurés par le capteur développé et la plaque de force étaient r = 0,93, sur la base des mesures de cinq modèles de peau artificielle avec des conditions de frottement différentes. Les coefficients de corrélation inter-évaluateurs entre les trois participants utilisant le capteur développé ont atteint 0,92 et 0,94 pour les mesures de vibrations et de frottement, respectivement. CONCLUSION: les intensités des vibrations et les coefficients de frottement du capteur se sont avérés fortement corrélés avec ceux du capteur conventionnel. La fiabilité inter-évaluateurs était également élevée. Le capteur développé peut être utile pour l'évaluation tactile lors du développement de produits de soins de la peau.

Light-Mediated Transformation of Renieramycins and Semisynthesis of 4'-Pyridinecarbonyl-Substituted Renieramycin-Type Derivatives as Potential Cytotoxic Agents against Non-Small-Cell Lung Cancer Cells.

The semisynthesis of renieramycin-type derivatives was achieved under mild and facile conditions by attaching a 1,3-dioxole-bridged phenolic moiety onto ring A of the renieramycin structure and adding a 4'-pyridinecarbonyl ester substituent at its C-5 or C-22 position. These were accomplished through a light-induced intramolecular photoredox reaction using blue light (4 W) and Steglich esterification, respectively. Renieramycin M (4), a bis-tetrahydroisoquinolinequinone compound isolated from the Thai blue sponge (Xestospongia sp.), served as the starting material. The cytotoxicity of the 10 natural and semisynthesized renieramycins against non-small-cell lung cancer (NSCLC) cell lines was evaluated. The 5-O-(4'-pyridinecarbonyl) renieramycin T (11) compound exhibited high cytotoxicity with half-maximal inhibitory concentration (IC50) values of 35.27 ± 1.09 and 34.77 ± 2.19 nM against H290 and H460 cells, respectively. Notably, the potency of compound 11 was 2-fold more than that of renieramycin T (7) and equal to those of 4 and doxorubicin. Interestingly, the renieramycin-type derivatives with a hydroxyl group at C-5 and C-22 exhibited weak cytotoxicity. In silico molecular docking and dynamics studies confirmed that the mitogen-activated proteins, kinase 1 and 3 (MAPK1 and MAPK3), are suitable targets for 11. Thus, the structure-cytotoxicity study of renieramycins was extended to facilitate the development of potential anticancer agents for NSCLC cells.

Simple Strategy for Benzo[g]chromene Synthesis via a Photochemical Intramolecular Cyclization Reaction.

Photochemical reactions are often a desirable strategy for organic synthesis because they do not require toxic and expensive reagents and produce less waste than thermal reactions. Herein, a facile photochemical strategy is described to synthesize benzo[g]chromene derivatives. This strategy utilizes the photoredox reaction of quinones, which allows C-H bond oxidation in the vicinity of the photoexcited quinone carbonyl group. The reaction mechanism was investigated using 1H NMR analysis. The intramolecular cyclization reaction proceeded via the formation of 1,3-dioxole compounds as intermediates by the photoredox reaction of p-quinone, followed by re-cyclization. The synthesized benzo[g]chromene derivatives are important heterocyclic skeletons with useful biological and pharmacological properties.

Fresh Dual Presaturation Method for Analyzing H2O-Rich Samples Using Quantitative 1H NMR.

A fresh dual presaturation (pre-SAT) method was developed to quantify analytes accurately near the suppressed water signal in 1H NMR spectra obtained from H2O-rich samples. The method includes an extra dummy pre-SAT with a suitable offset for each analyte signal in addition to the water pre-SAT. The residual HOD signal at 4.66 ppm was observed using D2O solutions containing l-phenylalanine (Phe) or l-valine (Val) and an internal standard of 3-(trimethylsilyl)-1-propanesulfonic acid-d6 sodium salt (DSS-d6). When the HOD signal was suppressed using the conventional single pre-SAT method, the measured concentration of Phe from the NCH signal at 3.89 ppm decreased by a maximum of 48%, whereas the dual pre-SAT method gave a reduction in the Phe concentration measured from the NCH signal of less than 3%. The proposed dual pre-SAT method achieved accurate quantification of glycine (Gly) and maleic acid (MA) in a 10 vol % D2O/H2O solution. The measured concentrations of Gly of 513.5 ± 8.9 mg kg-1 and MA of 512.2 ± 10.3 mg kg-1 corresponded to sample preparation values of Gly of 502.9 ± 1.7 mg kg-1 and MA of 506.7 ± 2.9 mg kg-1 (the number after "±" indicates the expanded uncertainty (k = 2)).

On the Analysis of Tactile Sensation Based on Time Measurement: An Experimental Case Study on the Interaction Between Skin and Lotion.

This paper presents a novel experimental case study in which tactile sensation is analyzed as 4-dimensional subjective data consisting of stimulus, participant, evaluation term, and temporal components, using a temporal measurement approach. Specifically, the skin and lotion interaction was evaluated using the Temporal Check-All-That-Apply (TCATA) method. Two practical analysis examples were conducted to experimentally demonstrate the potential use cases of time-series subjective tactile data. In the first example, stimulus classification accuracy was compared between different sampling periods, including the whole and late periods, with the latter being akin to the conventional Semantic Differential (SD) method condition. The results indicate that the whole and early periods exhibit higher accuracy compared to the latest period, implying that temporal measurements may capture more stimulus characteristics than the conventional approach. In the second example, cluster analysis based on the time-series subjective data was conducted. The results revealed that the participants were classified into two distinct clusters, with the trends of time-series changes being significantly different between the clusters.

Transformation of Renieramycin M into Renieramycins T and S by Intramolecular Photoredox Reaction of 7-Methoxy-6-methyl-1,2,3,4-tetrahydroisoquinoline-5,8-dione Derivatives.

In connection with our studies of biologically active 1,2,3,4-tetrahydroisoquinoline marine natural products, we describe herein a useful intramolecular photoredox transformation of 7-methoxy-6-methyl-1,2,3,4-tetrahydroisoquinoline-5,8-dione tricyclic models into 5-hydroxy-tetrahydroisoquinol[1,3]dioxoles in excellent yields. We applied this methodology to the transformation of renieramycin M into renieramycins T and S and the transformation of saframycin A. The results of cytotoxicity studies are also presented.

Methamphetamine-related forensic autopsy cases in a Japanese prefecture over a 7-year period: Characteristics of deaths and blood concentrations.

Understanding the actual conditions of methamphetamine (MA)-related death is important from the perspectives of criminal justice and public health. In this report, we review 104 cases of MA-related death handled by our departments between January 2014 and December 2020. Based on information from police and autopsy examinations, we classified the cases into the following categories: "accidental intoxication" ("MA only" and "multiple drugs or alcohol"), "fatal disease" ("definitively MA-related," "possibly MA-related," and "unlikely MA-related"), "accident," "suicide," "homicide," and "undetermined." The total number and annual trends for each category and their respective femoral blood concentrations were investigated. "Fatal disease" was the most common category (48 cases), followed by "suicide" (25 cases), "accidental intoxication" (14 cases), and "accident" (11 cases). "Definitively MA-related" in which MA may have played a role in their onset or exacerbation accounted for the majority of "fatal disease": 12 cases of heart disease, 4 cases of aortic dissection, 12 cases of cerebral hemorrhage, and 4 cases of subarachnoid hemorrhage. Cases classified as "definitively MA-related" died with lower femoral blood concentrations of MA compared with "MA only." Cases with "fatal disease" might have been misdiagnosed as "death by natural causes" if a proper autopsy and toxicology examinations were not performed. In death investigations, it is necessary to keep in mind that there are some MA-related deaths, and efforts should be made to increase awareness about the risk of death in using this drug.

[Racemose Hemangioma of the Bronchial Artery with Pulmonary Artery Fistula].

A 55-year-old woman was suspected of having hilar lymph node enlargement on a routine examination of the chest computed tomography( CT) scan at our hospital. On further examination, thoracic contrast CT and bronchial arteriography showed prominent dilation and meandering of the right bronchial artery with an aneurysm which formed a fistula to the pulmonary artery A7 at its distal end. Diagnosed as racemose hemangioma of bronchial artery with pulmonary artery fistula, we performed a surgical resection by open thoracotomy on the second day following bronchial artery embolization( BAE). No recurrence was observed in the five years of follow-up period after surgery. Therefore, surgical resection for asymptomatic racemose hemangioma of bronchial artery with bronchial artery-pulmonary artery fistula can be considered an effective method for the long-term prevention of bleeding.

Smart Pneumatic Artificial Muscle Using a Bend Sensor like a Human Muscle with a Muscle Spindle.

Shortage of labor and increased work of young people are causing problems in terms of care and welfare of a growing proportion of elderly people. This is a looming social problem because people of advanced ages are increasing. Necessary in the fields of care and welfare, pneumatic artificial muscles in actuators of robots are being examined. Pneumatic artificial muscles have a high output per unit of weight, and they are soft, similarly to human muscles. However, in previous research of robots using pneumatic artificial muscles, rigid sensors were often installed at joints and other locations due to the robots' structures. Therefore, we developed a smart actuator that integrates a bending sensor that functions as a human muscle spindle; it can be externally attached to the pneumatic artificial muscle. This paper reports a smart artificial muscle actuator that can sense contraction, which can be applied to developed self-monitoring and robot posture control.

Prevalence of blood-borne infections in forensic samples: Epidemiology in areas of Chiba, Japan.

OBJECTIVES: To statistically clarify the prevalence and risk factors of infections in forensic autopsy cases in Chiba Prefecture, Japan. The aim was to improve preventive measures against infection in forensic autopsies. METHODS: We retrospectively investigated the positive detection rates of five infections (hepatitis B, HBV; hepatitis C, HCV; human immunodeficiency virus, HIV; human T-lymphotropic virus, HTLV; Treponema pallidum, TP) using 1491 samples obtained in forensic autopsy at our facility from 2014 to 2018. In addition, risk factors related to infection such as methamphetamine and tattoos were analyzed. Pearson's chi-square test was used for statistical analysis, and the difference was judged to be significant at p < 0.05. RESULTS: Among our samples, 9.0% of cadavers tested positive for infection, and the prevalence rates for HBV, HCV, HIV, HTLV, and TP were 1.0%, 6.7%, 0.3%, 0.7%, and 1.1% respectively. Statistically, cadavers linked to information about methamphetamine use had a 7.2 times higher rate of infection, and those with tattoos had a 5.6 times higher rate of infection, with HCV being the predominant cause. CONCLUSIONS: To limit the risk of infection among autopsy workers, cadavers and samples should be handled on the presupposition that the bodies are at risk of infections. It is also important to obtain as much information as possible about the medical history and potential illegal drug use to help assess the risk of infection in a patient during forensic autopsy. We propose that all autopsy cases should be screened for infections whenever possible.

Synthesis of γ-Aminobutyric Acid (GABA) Analogues Conformationally Restricted by Bicyclo[3.1.0]hexane/hexene or [4.1.0]Heptane/heptene Backbones as Potent Betaine/GABA Transporter Inhibitors.

Novel γ-aminobutyric acid (GABA) analogues 3-5, having a bicyclo[3.1.0]hexene, [4.1.0]heptane, or [4.1.0]heptene backbone, respectively, were designed from the bioactive form analysis of the previous inhibitor 2 with a bicyclo[3.1.0]hexane backbone. Compounds 3-5 and 2 were synthesized from a common 1,7-diene intermediate 6 using ring-closing metathesis (RCM) to construct the key bicyclo backbones. Compounds 3-5 strongly inhibit betaine/GABA transporter 1 (BGT1) uptake, but compound 4 stands out with its selective low micromolar potency.

Characterization of the nucleotide excision repair pathway and evaluation of compounds for overcoming the cisplatin resistance of non­small cell lung cancer cell lines.

Lung cancer has been reported to be the leading cause of cancer­related mortality worldwide. Cisplatin combination chemotherapy is a standard therapeutic strategy for patients with non­small cell lung cancer (NSCLC) lacking driver mutations. However, the development of cisplatin resistance is a major obstacle to effective cancer treatment. The cellular mechanisms underlying cisplatin resistance have been previously revealed to be multifunctional. Accordingly, mechanistic analysis and the development of novel therapeutic strategies for cisplatin­resistant NSCLC are urgently required. The present study mainly focused on the DNA repair mechanisms in cisplatin­resistant NSCLC cells. Additionally, the effects of an Ecteinascidin (Et) derivative on cisplatin­resistant cell lines were examined, by using a cisplatin­resistant NSCLC cell line subjected to nucleotide excision repair (NER) pathway alterations. The results revealed that xeroderma pigmentosum group F­complementing protein (XPF) mRNA expression was strongly associated with cisplatin resistance in cisplatin­resistant NSCLC cell lines. XPF silencing significantly restored the sensitivity of cisplatin­resistant PC­14/CDDP cells to the drug. A potent anticancer effect of Et was observed in the cisplatin­resistant cell line (PC­14/CDDP), in which the NER pathway was altered. On the whole, these findings revealed that the expression levels of NER pathway­related genes, including XPF, may have potential as biomarkers of cisplatin resistance. It was also suggested that Et may be a very promising compound for the development of novel anticancer drugs for the treatment of cisplatin­resistant lung cancer.