Anthropogenic Mercury Release Flow in China

China is the largest emitter of anthropogenic mercury worldwide. Implementation of the Minamata Convention on Mercury will significantly impact the development, use, and management of mercury resources. Chinese mercury management policies require significant adjustment. There is an urgent need to develop a current national mercury inventory to estimate mercury inputs and outputs by source category, and to clarify the distributions to various environmental scenarios. Here, the mercury releases are quantitatively analysed to facilitate the implementation of strategic mercury management policies in China. First, the mercury inputs and outputs by source categories in 2016 are quantified and then the mercury distributions to various environmental and intermediate sinks are estimated. The total mercury input was 5,116 t in 2016, of which 77% was attributable to mineral production. In total, 3,083 t were released into various environmental and intermediate reservoirs. Of this total, 53.8 % was intentional uses, followed by extraction and combustion (26.5%), and mineral production (19.6 %); 1,501 t were released into air, water, and land, of which extraction and combustion accounted for 48.6 % followed by mineral production (25.7 %) and intentional uses (25.6 %)

Developing a dataset for the expected anthropogenic mercury release in China in response to the Minamata convention on mercury

This paper contains supplementary data in support of a research paper published [1] regarding the expected anthropogenic mercury release in China in response to the Minamata Convention on Mercury (MCM). The dataset provided within this article contains a set of excel spreadsheets. Each spreadsheet contains filtered (collected) and analysed data, i.e., parameters, collected data, calculated and summarized results for mercury distribution by the category of mineral production, intentional uses, secondary metal production, extraction and combustion, and waste treatment in a specific year. The collected (filtered) data in this article consist of the input factor (IF), activity rate data (ARD), output scenario (OS), initial distribution factor (iDF), and redistribution factor (rDF). IF was from the default IF in the United Nations Environment Programme (UNEP) Toolkit Level 2 and published scientific papers. ARD was obtained from the U.S. Geological Survey database, China Statistical Yearbooks, and published scientific papers. The OS content was from the default OS in the UNEP Toolkit Level 2 and published scientific papers. iDF was from the default distribution factor (DF) in the UNEP Toolkit Level 2 and published scientific papers. rDF was from published scientific paper. The mercury input was calculated using IF and ARD. The mercury release to different media in the initial distribution step was calculated using the mercury input and iDF. The release of mercury to the final sinks in the redistribution step was calculated using the amount of sector-specific treatment/disposal, product or by-product, and rDF. The dataset with combination of the collected (filtered) and analyzed data can contribute to an understanding of differences in anthropogenic mercury release before and after implementation of the MCM, especially considering technology transformation in China. Government policymakers involved in hazardous waste management, especially those working on MCM, and engineers and scientists interested in hazardous waste management may benefit from these data. The data can be used for identifying the environmental impact of anthropogenic mercury release before and after the MCM in China. The data can facilitate the creation of strategic management policies for mercury as the MCM is implemented in China

Application of Adoptive T-Cell Therapy Using Tumor Antigen-Specific T-Cell Receptor Gene Transfer for the Treatment of Human Leukemia

The last decade has seen great strides in the field of cancer immunotherapy, especially the treatment of melanoma. Beginning with the identification of cancer antigens, followed by the clinical application of anti-cancer peptide vaccination, it has now been proven that adoptive T-cell therapy (ACT) using cancer antigen-specific T cells is the most effective option. Despite the apparent clinical efficacy of ACT, the timely preparation of a sufficient number of cancer antigen-specific T cells for each patient has been recognized as its biggest limitation. Currently, therefore, attention is being focused on ACT with engineered T cells produced using cancer antigen-specific T-cell receptor (TCR) gene transfer. With regard to human leukemia, ACT using engineered T cells bearing the leukemia antigen-specific TCR gene still remains in its infancy. However, several reports have provided preclinical data on TCR gene transfer using Wilms' tumor gene product 1 (WT1), and also preclinical and clinical data on TCR gene transfer involving minor histocompatibility antigen, both of which have been suggested to provide additional clinical benefit. In this review, we examine the current status of anti-leukemia ACT with engineered T cells carrying the leukemia antigen-specific TCR gene, and discuss the existing barriers to progress in this area

Evaluation of Blood Supply with Indocyanine Green Fluorescence in Resection for Concurrent Gastric and Pancreatic Cancer: A Case Report

We present a rare case of concurrent resection of pancreatic and gastric cancer in which indocyanine green (ICG) fluorescence was used to evaluate the remnant stomach. An 80-year-old man was referred with a tumor in the distal pancreas. Computed tomography showed a 25-mm mass in the pancreatic tail; endoscopic ultrasound-guided fine-needle aspiration revealed adenocarcinoma. Upper gastrointestinal endoscopy and subsequent upper gastrointestinal series revealed advanced gastric cancer in the mid-stomach. Concurrent resection of the pancreatic and gastric tumors was performed. After distal pancreatectomy and distal gastrectomy, ICG evaluation of the stomach showed fluorescence extending only 3 cm distal from the cardia. To avoid ischemic change at the remnant stomach, total gastrectomy was performed. Since remnant gastric necrosis and anastomotic leak following ischemia can lead to fatal outcomes, the use of ICG to evaluate blood supply at anastomotic sites can help determine the extent of safe resection in such cases

Gain-of-function oncogenic mutations in TP53 enhance defined factor-mediated cellular reprogramming

Cancer is a disorder with various genetic and epigenetic alterations. Genetic alterations such as mutations, i.e., substitutions, amplifications, and deletions of nucleotide sequences, are largely irreversible, whereas epigenetic alterations can be modified by pharmacological agents that target components of the epigenetic machinery. Recent studies have showed that introduction of defined factors such as those encoded by c-MYC, SOX2, OCT3/4, and KLF4 in normal somatic cells results in their dedifferentiation into induced pluripotent stem (iPS) cells. In addition, we have reported that these iPS factors induce the development of induced multipotent cancer (iPC) cells from gastrointestinal cancer cells by reducing tumor aggressiveness. The efficiency of iPS reprogramming increased when p53 was inhibited. The study of cancer cells suggests that the p53 pathways might be involved in the aggressive phenotypes of iPC cells in a long-term culture. However, the roles of gain-of-function oncogenic mutations in TP53, which is a key tumor suppressor gene, remain to be elucidated. We investigated reprogramming efficiency of iPS generation in human diploid fibroblasts that were co-transfected with TP53 mutants and defined factors. The results suggest that mutations in those TP53 regions that are involved in DNA contact might play a critical role in the efficiency of iPS generation. Taken together, our studies suggest 2 roles of TP53 mutations in reprogramming: (1) the structural mutations might contribute to, or collaborate with, other mutations to regulate the maintenance of genomic stability; (2) the DNA-contact mutations could affect the downstream target genes, which may be distinct from those involved in wild-type p53 function. These molecular manipulations of tumorigenicity and enhancement of cellular reprogramming efficiency by the p53 pathway will open an attractive and useful avenue for future medicine

Creation of NV centers over a millimeter-sized region by intense single-shot ultrashort laser irradiation

一つの超短レーザーパルスでダイヤモンド量子センサ源を広領域で作製 --超短時間でダイヤモンドを超高感度量子センサに--. 京都大学プレスリリース. 2023-03-15.Recently, ultrashort laser processing has attracted attention for creating nitrogen-vacancy (NV) centers because this method can create single NV centers in spatially-controlled positions, which is an advantage for quantum information devices. On the other hand, creating high-density NV centers in a wide region is also important for quantum sensing because the sensitivity is directly enhanced by increasing the number of NV centers. A recent study demonstrated the creation of high-density NV centers by irradiating femtosecond laser pulses, but the created region was limited to micrometer size, and this technique required many laser pulses to avoid graphitization of diamond. Here, we demonstrate the creation of NV centers in a wide region using only an intense single femtosecond laser pulse irradiation. We irradiated a diamond sample with a femtosecond laser with a focal spot size of 41 µm and a laser fluence of up to 54 J/cm², which is much higher than the typical graphitization threshold in multi-pulse processing. We found that single-pulse irradiation created NV centers without post-annealing for a laser fluence higher than 1.8 J/cm², and the region containing NV centers expanded with increasing laser fluence. The diameter of the area was larger than the focal spot size and reached over 100 µm at a fluence of 54 J/cm². Furthermore, we demonstrated the NV centers' creation in a millimeter-sized region by a single-shot defocused laser pulse over 1100 µm with a fluence of 33 J/cm². The demonstrated technique will bring interest in the fundamentals and applications of fabricating ultrahigh-sensitivity quantum sensors

Understanding and exploiting hTERT promoter regulation for diagnosis and treatment of human cancers

がん進展制御研究所　Telomerase activation is a critical step for human carcinogenesis through the maintenance of telomeres, but the activation mechanism during carcinogenesis remains unclear. Transcriptional regulation of the human telomerase reverse transcriptase (hTERT) gene is the major mechanism for cancer-specific activation of telomerase, and a number of factors have been identified to directly or indirectly regulate the hTERT promoter, including cellular transcriptional activators (c-Myc, Sp1, HIF-1, AP2, ER, Ets, etc.) as well as the repressors, most of which comprise tumor suppressor gene products, such as p53, WT1, and Menin. Nevertheless, none of them can clearly account for the cancer specificity of hTERT expression. The chromatin structure via the DNA methylation or modulation of nucleosome histones has recently been suggested to be important for regulation of the hTERT promoter. DNA unmethylation or histone methylation around the transcription start site of the hTERT promoter triggers the recruitment of histone acetyltransferase (HAT) activity, allowing hTERT transcription. These facts prompted us to apply these regulatory mechanisms to cancer diagnostics and therapeutics. Telomerase-specific replicative adenovirus (Telomelysin, OBP-301), in which E1A and E1B genes are driven by the hTERT promoter, has been developed as an oncolytic virus that replicates specifically in cancer cells and causes cell death via viral toxicity. Direct administration of Telomelysin was proved to effectively eradicate solid tumors in vivo, without apparent adverse effects. Clinical trials using Telomelysin for cancer patients with progressive stages are currently ongoing. Furthermore, we incorporated green fluorescent protein gene (GFP) into Telomelysin (TelomeScan, OBP-401). Administration of TelomeScan into the primary tumor enabled the visualization of cancer cells under the cooled charged-coupled device (CCD) camera, not only in primary tumors but also the metastatic foci. This technology can be applied to intraoperative imaging of metastatic lymphnodes. Thus, we found novel tools for cancer diagnostics and therapeutics by utilizing the hTERT promoter. © 2008 Japanese Cancer Association

Modulating effect of the PI3-kinase inhibitor LY294002 on cisplatin in human pancreatic cancer cells

<p>Abstract</p> <p>Background</p> <p>Chemoresistance is a serious problem in pancreatic cancer, but the mechanism of resistance and strategies against the resistance have not been elucidated. We examined the potential of the phosphatidylinositol 3-kinase (PI3K)/Akt inhibitor LY294002 to enhance the anti-tumor effect of cisplatin and investigated the mechanism of chemoresistance in pancreatic cancer cells using a combination therapy of cisplatin and LY294002, both <it>in vitro </it>and <it>in vivo</it>.</p> <p>Methods</p> <p>Cisplatin and LY294002, individually or in combination, were given to AsPC-1 and PANC-1 cell lines. Tumor growth, DNA fragments, and Akt phosphorylation were examined <it>in vitro</it>. To examine the therapeutic effect of cisplatin and LY294002, individually or combination an AsPC-1 tumor xenograft model was prepared for <it>in vivo </it>study.</p> <p>Results</p> <p>Cisplatin induced growth inhibition and Akt phosphorylation in pancreatic cancer cells. LY294002 also inhibited cell proliferation but without showing Akt phosphorylation. However, the combination therapy markedly increased cleavage of caspase-3 and cytoplasmic histone-associated DNA fragments compared to the results with cisplatin alone. In the <it>in vivo </it>study, blocking the PI3K/Akt cascade with LY294002 increased the efficacy of cisplatin-induced inhibition of tumor growth in nude mice, suppressing half the tumor growth with cisplatin alone. There were no detectable side effects in mice treated with combination therapy.</p> <p>Conclusion</p> <p>Our studies suggest that the PI3K/Akt pathway plays an important role in cisplatin resistance of pancreatic cancer cells. The augmentation of cisplatin with PI3K/Akt inhibitor may resolve the chemoresistance problem of cisplatin, and this might be a plausible strategy for achieving tolerance for chemotherapeutic agents in pancreatic cancer therapy.</p