Protein engineering of conger eel galectins by tracing of molecular evolution using probable ancestral mutants

<p>Abstract</p> <p>Background</p> <p>Conger eel galectins, congerin I (ConI) and congerin II (ConII), show the different molecular characteristics resulting from accelerating evolution. We recently reconstructed a probable ancestral form of congerins, Con-anc. It showed properties similar to those of ConII in terms of thermostability and carbohydrate recognition specificity, although it shares a higher sequence similarity with ConI than ConII.</p> <p>Results</p> <p>In this study, we have focused on the different amino acid residues between Con-anc and ConI, and have performed the protein engineering of Con-anc through site-directed mutagenesis, followed by the molecular evolution analysis of the mutants. This approach revealed the functional importance of loop structures of congerins: (1) N- and C-terminal and loop 5 regions that are involved in conferring a high thermostability to ConI; (2) loops 3, 5, and 6 that are responsible for stronger binding of ConI to most sugars; and (3) loops 5 and 6, and Thr38 residue in loop 3 contribute the specificity of ConI toward lacto-<it>N</it>-fucopentaose-containing sugars.</p> <p>Conclusions</p> <p>Thus, this methodology, with tracing of the molecular evolution using ancestral mutants, is a powerful tool for the analysis of not only the molecular evolutionary process, but also the structural elements of a protein responsible for its various functions.</p

Convolutional neural network can recognize drug resistance of single cancer cells

It is known that single or isolated tumor cells enter cancer patients' circulatory systems. These circulating tumor cells (CTCs) are thought to be an effective tool for diagnosing cancer malignancy. However, handling CTC samples and evaluating CTC sequence analysis results are challenging. Recently, the convolutional neural network (CNN) model, a type of deep learning model, has been increasingly adopted for medical image analyses. However, it is controversial whether cell characteristics can be identified at the single-cell level by using machine learning methods. This study intends to verify whether an AI system could classify the sensitivity of anticancer drugs, based on cell morphology during culture. We constructed a CNN based on the VGG16 model that could predict the efficiency of antitumor drugs at the single-cell level. The machine learning revealed that our model could identify the effects of antitumor drugs with ~0.80 accuracies. Our results show that, in the future, realizing precision medicine to identify effective antitumor drugs for individual patients may be possible by extracting CTCs from blood and performing classification by using an AI system

Irinotecan Plus Mitomycin C as Second-Line Chemotherapy for Advanced Gastric Cancer Resistant to Fluoropyrimidine and Cisplatin: A Retrospective Study

Background. S-1 plus cisplatin has been established to be standard first-line chemotherapy for advanced gastric cancer in Japan. The optimal second-line treatment refractory to S-1 plus cisplatin remains unclear. Methods. We retrospectively studied the efficacy, toxicity, and survival of irinotecan plus mitomycin C in patients with advanced gastric cancer refractory to a fluoropyrimidine plus cisplatin. Results. Twenty-four patients were studied. Prior chemotherapy was S-1 plus cisplatin in 15 patients, S-1 plus cisplatin and docetaxel in 8, and 5-fluorouracil plus cisplatin with radiotherapy in 1. The overall response rate was 17.4%. The median overall survival was 8.6 months, and the median progression-free survival was 3.6 months. Grade 3 or 4 toxicities included leukopenia (33%), neutropenia (50%), anemia (33%), thrombocytopenia (4%), anorexia (13%), diarrhea (4%), and febrile neutropenia (13%). Conclusion. A combination of irinotecan and mitomycin C is potentially effective in patients with advanced gastric cancer refractory to a fluoropyrimidine plus cisplatin

Light triggers molecular shuttling in rotaxanes: control over proximity and charge recombination

We present the synthesis of novel rotaxanes based on mechanically interlocked porphyrins and fullerene and their advanced investigations by means of photophysical measurements. To this end, a fullerene-capped dumbbell-type axle containing a central triazole was threaded through strapped (metallo)porphyrins—either a free-base or a zinc porphyrin. Femtosecond-resolved transient absorption measurements revealed charge-separation between the porphyrin and fullerene upon light excitation. Solvent polarity and solvent coordination effects induced molecular motion of the rotaxanes upon charge separation and enabled, for the first time, subtle control over the charge recombination by enabling and controlling the directionality of shuttling

Catalytic Decomposition of Pyridine with Goethite-Rich Limonite in the Coexistence of Fuel Gas or Coke Oven Gas Components

Catalytic performance of limonite in the decomposition of 100 ppmv pyridine (C5H5N) in the coexistence of fuel gas or coke oven gas (COG) components has been studied mainly with a cylindrical quartz reactor at 750–850°C under a high space velocity of 51000 h−1 to develop a novel hot gas cleanup method of removing the nitrogen in tar as N2. The limonite catalyst achieves the almost complete decomposition of C5H5N in He at 500–850°C and gives a high N2 yield of more than 85 N% at 500°C. When the decomposition run is performed in the presence of fuel gas or COG components, the coexistence of 20% CO/10% H2 at 750°C or 50% H2/30% CH4/5% CO at 850°C deactivates the limonite with remarkable formation of deposited carbon. On the other hand, the addition of a small amount of H2O or CO2 to these atmospheres can improve the catalytic activity without carbon deposition. When 3% H2O or 10% CO2 is added to 20% CO/10% H2, C5H5N conversion and N2 yield at 750°C become 80–95% and 65–80 N%, respectively, and the extent of the improvement is larger with the CO2 than with the H2O. The addition of 5% CO2 to 50% H2/30% CH4/5% CO also restores the conversion or the yield at 850°C to the high level of about 90% or 60–70 N%, respectively, and both values at 950°C are comparable to those at 500°C in inert ga

Removal of Hydrogen Sulfide and Ammonia by Goethite-Rich Limonite in the Coexistence of Coke Oven Gas Components

Hydrogen sulfide (H2S) removal and catalytic ammonia (NH3) decomposition performance of limonite in the presence of coke oven gas (COG) components has been studied in a cylindrical quartz reactor at 300–850°C under a high space velocity of 51000 h−1 to develop a novel hot gas cleanup method. The H2S removal behavior in 50% H2/He depends on the temperature, with high performance observed at lower temperature. An investigation of the removal behavior of H2S in the presence of COG components (CH4, CO, CO2 and H2O) at 400°C reveals that CH4 does not affect the removal performance. On the other hand, the coexistence of CO drastically decreases the H2S removal performance. However, the addition of 5% H2O to 50% H2/30% CH4/5% CO/He dramatically improves the H2S removal performance, whereas the performance is low at 5% CO2 with 50% H2/30% CH4/5% CO/He. In addition, the H2S breakthrough curve strongly depends on the space velocity. The limonite catalyst achieves almost complete decomposition of NH3 in He at 850°C until 240 min. When the decomposition run is performed in the presence of COG components, the coexistence of 30% CH4 deactivates limonite with significant formation of deposited carbon. On the other hand, the addition of 5% CO2, 5% H2O or 5% CO2/5% H2O to 50% H2/30% CH4/5% CO improves the catalytic activity without carbon deposition, and >99% conversion of NH3 to N2 is maintained until 240 min

Japan’s contribution to an ongoing global pediatric cancer clinical trial: The experience of the National Cancer Center Hospital (NCCH) in Tokyo

Compared to Europe and the United States, where the development of pediatric oncology drugs is mandated by law, Japan hosts fewer clinical trials. This can lead to a significant drug lag, especially in the case of treatments for pediatric solid tumors. Notably, regulatory authorities and the government have initiated discussions on strategies to mitigate Japan’s drug lag problem in pediatric oncology. Over the past decade, we have actively sought opportunities to participate in international collaborative clinical trials through Japan’s involvement in ACCELERATE and its predecessor organizations. This approach has aimed to address the issue above, coinciding with the ongoing centralization of medical care and advancements in genomic medicine, among other systems that support pediatric cancer care in Japan. Inspired by the ACCELERATE initiatives and in response to patient advocacy groups’ requests for new pediatric oncology drugs, Japan established its inaugural pediatric oncology support platform in 2021, the National Childhood Cancer Consortium (N3C). N3C comprises patient advocacy groups, industries, and academia. This work outlines the current status of pediatric drug development in Japan and highlights the initial successful experience of NCCH’s participation in a global clinical trial through ACCELERATE resulting in rapid preparation and patient recruitment. Participation of Asian countries including Japan in global collaborative clinical trials may benefit both pharmaceutical companies and the participating countries partnering to advance the development of pediatric oncology drugs