Discovery and biological characterization of a novel mesoionic insecticide fenmezoditiaz.

BACKGROUND: Many piercing-sucking insects have developed resistance or cross-resistance to many insecticides targeting insect neural nicotinic acetylcholine receptor (nAChR). Here we are aiming to present the discovery of a novel mesoionic insecticide, fenmezoditiaz, by BASF through structure-based drug design (SBDD) approaches. It has recently been added to the Insecticide Resistance Action Committee mode of classification (IRAC 4E). It is being developed for plant protection against piercing-sucking pests, especially rice hopper complex. RESULTS: The soluble acetylcholine binding protein (AChBP) from the sea slug Aplysia californica was modified using site-directed mutagenesis and based on putative aphid nAChR subunit sequences to create soluble insect-like AChBPs. Among them, insect-like ß1 AChBP and native aphid membrane preparation showed the highest correlated biochemical affinity toward structurally diverse ligands. This mutant AChBP was used to understand how insect nAChRs structurally interact with mesoionics, which was then utilized to design novel mesoionics including fenmezoditiaz. It is an excellent systemic insecticide with diverse application methods and has a broad insecticidal spectrum, especially against piercing/sucking insects. It lacks cross-resistance for neonicotinoid resistant plant hoppers. Field-collected brown plant hopper populations from Asian countries showed high susceptibility. CONCLUSIONS: Fenmezoditiaz is a systemic insecticide with a broad spectrum, lack of cross-resistance and it could be an additional tool for integrated pest management and insecticide resistance management, especially for the rice hopper complex. © 2024 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

A bioinformatic investigation of proteasome and autophagy expression in the central nervous system.

The ubiquitin proteasome system (UPS) and autophagy lysosome pathway (ALP) are crucial in the control of protein quality. However, data regarding the relative significance of UPS and ALP in the central nervous system (CNS) are limited. In the present study, using publicly available data, we computed the quantitative expression status of UPS- and ALP-related genes and their products in the CNS as compared with that in other tissues and cells. We obtained human and mouse gene expression datasets from the reference expression dataset (RefEx) and Genevestigator (a tool for handling curated transcriptomic data from public repositories) as well as human proteomics data from the proteomics database (ProteomicsDB). The expression levels of genes and proteins in four categories-ubiquitin, proteasome, autophagy, and lysosome--in the cells and tissues were assessed. Perturbation of the gene expression by drugs was also analyzed for the four categories. Compared with that for ubiquitin, autophagy, and lysosome, gene expression for proteasome was consistently lower in the CNS of mice but was more pronounced in humans. Neural stem cells and neurons showed low proteasome gene expression as compared with embryonic stem cells. Proteomic analyses, however, did not show trends similar to those observed in the gene expression analyses. Perturbation analyses revealed that azithromycin and vitamin D3 upregulated the expression of both UPS and ALP. Gene and proteomic expression data could offer a fresh perspective on CNS pathophysiology. Our results indicate that disproportional expression of UPS and ALP might affect CNS disorders and that this imbalance might be redressed by several therapeutic candidates.

Clinical availability of eye movement during reading.

Eyes provide valuable information for neurological diagnosis. So far, the use of diagnostic devices to analyze eye movement is limited. We explored whether the analysis of eye movements can be efficacious. Patients with Parkinson's disease (PD) (n = 29), spinocerebellar degeneration (SCD) (21), progressive supranuclear palsy (PSP) (19), and control individuals (19) participated in this study. The patients read aloud two sets of sentences displayed on a monitor: one was displayed horizontally, and the other vertically. Parameters such as eye movement speed, travel distance, and fixation/saccade ratio were extracted, and comparisons between groups were performed. Maneuvers of eye movements were also subjected to image classification using deep learning. Reading velocity and fixation/saccade ratio were altered in the PD group, and the SCD group exhibited ineffective eye movements due to dysmetria and nystagmus. Vertical gaze parameters showed aberrant values in the PSP group. Vertical written sentences were more sensitive than horizontal ones in detecting these abnormalities. In the regression analysis, vertical reading indicated a high accuracy in identifying each group. The machine learning analysis showed more than 90 % accuracy in distinguishing between the control and SCD groups and between the SCD and PSP groups. Analyzing eye movements is useful and easily applicable.

Phosphorylation of rice sucrose synthase isoforms promotes the activity of sucrose degradation.

Sucrose is utilized as an initial material for production of the storage substances. Sucrose synthase reversibly catalyzes reactions of the sucrose degradation and its synthesis between sucrose with UDP and UDP-glucose with fructose. They also had the activity of the reactions for sucrose degradation of sucrose with ADP, and sucrose synthesis from ADP-glucose and fructose. Rice has three representative isoforms of sucrose synthase, Rsus1, Rsus2, and Rsus3, in which Rsus1 and Rsus3 are highly expressed in developing seeds. These three isoforms were phosphorylated by SPK, a calcium-dependent protein kinase. By phosphorylation, they showed increase of their reactivity for sucrose degradation on both reactions using UDP and ADP. In contrast, the synthetic activity of these isoforms was not altered by phosphorylation in any cases of the reactions with UDP-glucose and ADP-glucose. These results indicated that phosphorylation of sucrose synthase isoforms selectively led to enhance the reactivity for sucrose degradation.

Gastrointestinal stromal tumors of the small intestine in pediatric populations: a case report and literature review.

An 18-year-old girl presented with abdominal pain and a tumor was subsequently detected in the jejunum. We therefore carried out a wedge resection of the jejunum. The diagnosis of GIST was confirmed histologically, and a mutation in exon 9 of the c-kit gene was observed. GISTs are rare in pediatric populations and pediatric GISTs occur predominantly in females and are characterized by a multifocal gastric location and a wild-type phenotype for the c-kit genes. The features of pediatric GISTs of the small intestine have not yet been categorized, and to date, only 11 cases in patients younger than 18 years have been reported. These cases did not occur primarily in females and tended to present as single tumors with mutations in the c-kit gene. This suggests that these cases do not have the same features as pediatric gastric GISTs, but instead are similar to adult GISTs. In pediatric populations, GISTs of the small intestine were expected to show a better response to imatinib treatment than gastric GISTs because of the alterations in the c-kit gene.

Scientific assessment of endoscopic surgical skills.

Recently, significant attention has been focused on training and education for safe endoscopic surgery. A new assessment method, the Hiroshima University Endoscopic Surgical Assessment Device (HUESAD), has been designed at Hiroshima University to evaluate the smoothness of the movement of endoscopic instruments from velocity. Experts (with experience in performing more than 100 laparoscopic surgeries) and novices (with no experience in performing laparoscopic surgery) were recruited for this study. The aim of task 1 was to move the tip of the endoscopic instrument on the tops of poles from A to C, and task 2 was to move it from the right pole B to the left pole D. The peak velocity (Vp) and the time when peak velocity appears (Tp) were analyzed. Both the peak velocity (Vp) and the time when peak velocity appears (Tp) to perform task 1 and task 2 were significantly faster in the expert group than in the novice group. The peak velocity (Vp) and the time when peak velocity appears (Tp) in HUESAD, which indicate the smoothnes of the endoscopic procedure, are among the most important factors for assessing endoscopic surgical skills.

Retroperitoneal abscess complicated with necrotizing fasciitis of the thigh in a patient with sigmoid colon cancer.

BACKGROUND: Necrotizing fasciitis of the thigh due to the colon cancer, especially during chemotherepy, has not been previously reported. CASE PRESENTATION: A 67-year-old man admitted to the hospital was diagnosed with sigmoid colon cancer that had spread to the left psoas muscle. Multiple hepatic metastases were also found, and combination chemotherapy with irinotecan and S-1 was administered. Four months after the initiation of chemotherapy, the patient developed gait disturbance and high fever and was therefore admitted to the emergency department of our hospital. Blood examination revealed generalized inflammation with a high C-reactive protein level. Computed tomography of the abdomen and pelvis showed gas and fluid collection in the retroperitoneum adjacent to the sigmoid colon cancer. The abscess was locally drained under computed tomographic guidance; however, the infection continued to spread and necrotizing fasciitis developed. Consequently, emergent debridement was performed. The patient recovered well, and the primary tumor was resected after remission of the local inflammation. CONCLUSION: Necrotizing fasciitis of the thigh due to the spread of sigmoid colon cancer is unusual, but this fatal complication should be considered during chemotherapy for patients with unresectable colorectal cancer.

Abscess in the inguinal hernial sac after peritonitis surgery: a case report.

In this paper, we report an extremely rare case of an abscess that developed in the inguinal hernial sac after surgery for peritonitis. A 60-year-old man underwent laparoscopic low anterior resection for rectal cancer. One day after this operation, peritoneal drainage and ileostomy were performed for rectal anastomotic leakage. Five days after the second operation, computed tomography revealed an abscess in the left inguinal hernial sac. Subsequently, hernioplasty and resection of the inflamed sac were performed.

[Comparison of Tosoh TRCRapid M.TB assay by transcription-reverse transcription concerted reaction (TRC) with Roche COBAS AMPLICOR assay by PCR and with culture for detection of Mycobacterium tuberculosis complex].

The aim of this study was to test the performance of a new reagent kit Tosoh TRCRapid M.TB using by transcription-reverse transcription concerted reaction(TRC) for detection of Mycobacterium tuberculosis complex (MTC) by comparing both its sensitivity and specificity for detecting MTC with those of Roche COBAS AMPLICOR Mycobacterium assay using polymerase chain reaction (PCR) and comparing with culture. TRC is a novel method, that is rapid and provides real-time monitoring of the isothermal sequence of RNA amplification without any post-amplification procedure, and the resulting detection time was about 30 min. A total of 157 clinical samples from patients were tested. Of the 74 MTC culture-positive samples, TRC was positive in 59(sensitivity, 80%), whereas PCR was positive in 47(sensitivity, 63%). The 26 samples that were positive for Mycobacteria other than tuberculosis (MOTT) were negative by TRCRapid M.TB assay, and the 50 samples that were negative for smear, culture and Roche PCR were also negative by TRCRapid M.TB. The percent agreement between Tosoh TRCRapid M.TB and Roche COBAS AMPLICOR was 90% (142 of 157 samples). These results indicate that Tosoh TRCRapid M.TB may be more useful than Roche COBAS AMPLICOR for detecting MTC because of its higher sensitivity and shorter detection time.

[Clinical significance of Cobas Amplicor HCV Monitor test v 2.0 for quantifying a wide range of serum HCV-RNA in patients with chronic hepatitis C].

Recently, we evaluated the clinical significance of a new assay, the semi-automated Cobas Amplicor HCV Monitor test v 2.0 (Roche, Cobas-HIGH-RANGE assay), for quantifying serum hepatitis C virus RNA throughout a wider range than the traditional assay, Amplicor GT HCV Monitor test v 2.0 (GT-ORIGINAL assay). We compared the results of the Cobas-HIGH-RANGE assay with results of the GT-ORIGINAL assay. This study was conducted on serum from 91 patients with chronic hepatitis C at the Gastroenterological Center, Yokohama City University Medical Center. The percent coefficient of variation (CV) for the within-run and between-run reproducibility of the Cobas-HIGH-RANGE assay ranged from 0.7 to 2.3% and from 1.3 to 2.0%, respectively. The Cobas-HIGH-RANGE assay exhibited a linear range extending from 5 to 5000 KIU/ml. The values for all 17 samples determined as less than 0.5 KIU/ml by the GT-ORIGINAL assay were also determined as less than 5 KIU/ml by the Cobas-HIGH-RANGE assay. For the 48 samples with values of 0.5 to 850 KIU/ml determined by the GT-ORIGINAL assay, the values obtained by these two assay methods were significantly correlated (r2 = 0.9117, y = 1.0667x-0.0801, p < 0.001), but the values of HCV-RNA determined by the Cobas-HIGH-RANGE assay were significantly (p < 0.05) higher than those determined by the GT-ORIGINAL assay. Consequently, these data indicate that the HIGH-RANGE assay is a useful alternative assay method for measurement of HCV-RNA instead of the ORIGINAL assay, and that the HIGH-RANGE assay could be a useful tool for monitoring the efficacy of antiviral treatment.