Antiplasmodial triterpenoids from Ekebergia capensis

From the stem bark of Ekebergia capensis, 10 new triterpenoid compounds, ekeberins A (1), B (2), C1 (3), C2 (4), C3 (5), D1 (6), D2 (7), D3 (8), D4 (9), and D5 (10), were isolated together with 17 known compounds. The structures of these new compounds were elucidated on the basis of the results of spectroscopic analysis, and the absolute configuration of compounds 6-10 were determined by partial synthesis from known compounds and using the Mosher ester method. Several of these compounds were screened in vitro against both chloroquine (CQ)-sensitive and -resistant Plasmodium falciparum isolates and were found to exhibit moderate antiplasmodial activity, with compounds 20 (7-deacetoxy-7-oxogedunin) and 27 (2-hydroxymethyl-2,3,22,23-tetrahydroxy-2,6,10,15,19,23-hexamethyl-6,10,14,18-tetracosatetraene) showing IC50 values of 6 and 7 microM, respectively. Compound 27 at a dose of 500 mg/kg showed moderate parasitemia suppression of 52.9% against P. berghei NK 65 in a mouse model.     

Constituents of the root wood of Zanthoxylum wutaiense with antitubercular activity

Bioassay-guided fractionation of the root wood of Zanthoxylum wutaiense led to the isolation of 11 new compounds, wutaiensol methyl ether (1), demethoxywutaiensol methyl ether (2), methyl wutaiensate (3), methyl 7-hydroxyanodendroate (4), methyl 7-methoxyanodendroate (5), wutaifuranol (6), 7-methoxywutaifuranol (7), 7-methoxywutaifuranal (8), methyl wutaifuranate (9), methyl 7-methoxybenzofuran-5-carboxylate (10), and wutaipyranol (12), together with another 37 known compounds, of which one, 7-methoxybenzofuran-5-carboxaldehyde (11), was not previously known as a plant constituent. The structures of these isolates were identified by means of spectroscopic analysis. Five of these isolates were found to be antitubercular constituents, namely, methyl 7-methoxyanodendroate (5), 7-methoxywutaifuranal (8), wutaiensal (13), dictamnine (14), and gamma-fagarine (15), which exhibited antitubercular activity against Mycobacterium tuberculosis H37Rv, showing MIC values of 35, 35, 30, 30, and 30 microg/mL, respectively.     

Torsion of the normal ovary and oviduct in a pre-pubertal girl

We encountered a 10-year-old prepubertal girl with a normal ovary and oviduct torsion. Hemorrhagic infarction of the ovary and oviduct occurred, and these structures were laparoscopically removed. Torsion of the normal ovary and oviduct in a prepubertal girl is discussed.     

Juvenile Hepatocellular Carcinoma in a Healthy Liver

Primary hepatocellular carcinoma (HCC) in patients ＜30 years old is extremely rare. In younger patients, HCC develops against a background of persistent hepatitis B virus infection. We herein report a 23-year-old woman with HCC with all-negative hepatitis virus markers developing in an apparently healthy liver. Imaging studies showed a 50-mm hypervascular mass in segment 4 of the left liver lobe, compatible with HCC. The patient underwent surgical resection. A histological examination showed the presence of poorly differentiated HCC. The patient was diagnosed with HCC developing in a healthy liver. This is an extremely rare case of non-B non-C HCC.     

Genetically Diverse Highly Pathogenic Avian Influenza A(H5N1/H5N8) Viruses among Wild Waterfowl and Domestic Poultry,Japan, 2021

Genetic analyses of highly pathogenic avian influenza H5 subtype viruses isolated from the Izumi Plain, Japan, revealed cocirculation of 2 genetic groups of clade 2.3.4.4b viruses among migratory waterfowl. Our findings demonstrate that both continuous surveillance and timely information sharing of avian influenza viruses are valuable for rapid risk assessment.     

Accumulation System: Distributed Neural Substrates of Perceptual Decision Making Revealed by fMRI Deconvolution

Neural substrates of evidence accumulation have been a central issue in decision-making studies because of the prominent success of the accumulation model in explaining a wide range of perceptual decision making. Since accumulation-shaped activities have been found in multiple brain regions, which are called accumulators, questions regarding functional relations among these accumulators are emerging. This study employed the deconvolution method of functional magnetic resonance imaging (fMRI) signals from human male and female participants during object-category decision tasks, taking advantage of the whole-brain coverage of fMRI with improved availability of temporal information of the deconvolved activity. We detected the accumulation activity in many non-category-selective regions (NCSRs) over the frontal, parietal, and temporal lobes as well as category-selective regions (CSRs) of the categorization task. Importantly, the frontal regions mostly showed activity peaks matching the decision timing (classified as “type-A accumulator”), while activity peaks of the parietal and temporal regions were behind the decision (classified as “type-B accumulator”). The CSRs showed activity peaks whose timing depended on both region and stimulus preference, plausibly reflecting the competition among the alternative choices (classified as “type-C accumulator”). The results suggest that these functionally heterogeneous accumulators form a system for evidence accumulation in which the type-A accumulator regions make decisions in a general manner while the type-B and type-C accumulator regions are employed depending on the modality and content of decision tasks. The concept of the accumulation system may provide a key to understanding the universality of the accumulation model over various kinds of decision tasks.SIGNIFICANCE STATEMENT Perceptual decision making, such as deciding to walk or stop on seeing the signal colors, has been explained theoretically by the accumulation model, in which sensory information is accumulated to reach a certain threshold for making decisions. Neural substrates of this model, however, are still under elucidation among candidate regions found over the brain. We show here that, taking advantage of the whole-brain coverage of functional magnetic resonance imaging (fMRI) with improving availability of temporal information by deconvolution method, the accumulation is conducted by a system comprising many regions in different abstraction levels and only a part of these regions in the frontal cortex make decisions. The system concept may provide a key to explaining the universality of the accumulation model.     

Growth fractions of breast cancer in relation to epidermal growth factor receptor and estrogen receptor

Growth fractions detected by a monoclonal antibody, Ki-67, were examined in 40 human breast cancer tissues and the results compared with the immunocytochemical reactivities of epidermal growth factor receptor (EGFR) and estrogen receptor (ER). The proportion of proliferating cells displaying Ki-67 positive staining was significantly higher in the EGFR positive tumors than in the EGFR negative tumors (p<0.01). The average percentage of Ki-67 positive cells in the EGFR positive tumors was 19.9 per cent, whereas that in the EGFR negative tumors was 8.0 per cent. By contrast, an inverse relationship between the proportion of proliferating cells and ER positive cells detected by anti-ER monoclonal antibody was observed. This data indicated the difference in growth fractions with relation to the EGFR and ER status of breast cancer.     

Effect of long‐term depletion of plasma methionine on the growth and survival of human brain tumor xenografts in athymic mice

Depletion of plasma methionine is expected to inhibit or reverse growth of methionine‐dependent tumors; however, modulation of methionine and other sulfur amino acids is not a trivial task in experimental animals. l‐Methioninase from Pseudomonas putida at 1,000 U/kg causes acute reduction of plasma methionine by 80% in mice, but recovery occurs within 14 hours. Restriction of dietary choline and replacement of dietary methionine with homocystine results in 50% chronic reduction of plasma methionine. A >70% reduction can be accomplished with a diet deficient in methionine, homocystine, and choline, but ultimately this diet is lethal. Plasma methionine can be lowered to a steady state of <5 μM in mice with a combination of dietary restriction of methionine, homocysteine, and choline and synchronous treatments with intraperitoneal injections of 1,000 U/kg L‐methioninase and 25–50 mg/kg homocystine, each administered at 12‐hour intervals. Modulation of plasma methionine by this means causes no weight loss or pathologies in liver or pancreas, and it does not markedly alter levels of cysteine, homocysteine, or glutathione in plasma or in hepatic tissue. When this procedure is applied to athymic mice bearing human medulloblastoma (Daoy) tumors subcutaneously, tumor growth is inhibited. Methionine deprivation arrests mitosis by blocking the cell cycle in G2 and induces apoptosis. Tumor stasis was achieved in 100% of treated animals within 4 days of treatment, and regression was seen in one‐third of animals after a 10‐day period. These data strongly support the use of methionine‐depleting regimens for tumor treatments.