Background: Unlike many North American and European countries, Japan has observed a continuous increase in cancer incidence over the last few decades. We examined the most recent trends in ...population-based cancer incidence and mortality in Japan. Methods: National cancer mortality data between 1958 and 2018 were obtained from published vital statistics. Cancer incidence data between 1985 and 2015 were obtained from high-quality population-based cancer registries maintained by three prefectures (Yamagata, Fukui, and Nagasaki). Trends in age-standardized rates (ASR) were examined using Joinpoint regression analysis. Results: For males, all-cancer incidence increased between 1985 and 1996 (annual percent change APC +1.1%; 95% confidence interval CI, 0.7–1.5%), increased again in 2000–2010 (+1.3%; 95% CI, 0.9–1.8%), and then decreased until 2015 (−1.4%; 95% CI, −2.5 to −0.3%). For females, all-cancer incidence increased until 2010 (+0.8%; 95% CI, 0.6–0.9% in 1985–2004 and +2.4%; 95% CI, 1.3–3.4% in 2004–2010), and stabilized thereafter until 2015. The post-2000 increase was mainly attributable to prostate in males and breast in females, which slowed or levelled during the first decade of the 2000s. After a sustained increase, all-cancer mortality for males decreased in 1996–2013 (−1.6%; 95% CI, −1.6 to −1.5%) and accelerated thereafter until 2018 (−2.5%; 95% CI, −2.9 to −2.0%). All-cancer mortality for females decreased intermittently throughout the observation period, with the most recent APC of −1.0% (95% CI, −1.1 to −0.9%) in 2003–2018. The recent decreases in mortality in both sexes, and in incidence in males, were mainly attributable to stomach, liver, and male lung cancers. Conclusion: The ASR of all-cancer incidence began decreasing significantly in males and levelled off in females in 2010.
Oxazosulfyl is the first representative of a novel sulfyl class of insecticides with a potent and cross-spectrum insecticidal activity, albeit with an unclear mechanism of action. As a potential ...agent of pest control in rice fields, we investigated the action of oxazosulfyl on the nervous system and voltage-gated sodium channels in insects. After the injection of 10 μg of oxazosulfyl, American cockroaches (Periplaneta americana) were quickly paralyzed, which persisted for more than 7 days. Extracellular recordings revealed a depressed spontaneous nerve activity in the cockroaches injected with oxazosulfyl, which specifically affected the voltage-gated sodium channels (in German cockroaches (Blattella germanica) expressed in Xenopus oocytes) in the slow-inactivated state resulting in the inhibition of sodium currents. The potency of oxazosulfyl and other sodium channel blockers to block sodium channels was consistent with their insecticidal activity. Thus, we conclude that the action mode of oxazosulfyl involves the state-dependent blockage of voltage-gated sodium channels.
Technetium-99m(99mTc) is used worldwide in 85% of nuclear medicine diagnostic imaging procedures. We developed porous MoO2 pellets as an alternative to reactor-based targets in an (n,γ) reaction for ...producing Technetium-99m (99mTc) in nuclear medicine. The pellets, formed through a manufacturing process involving mixing, sintering, eluting, and drying, offer advantages such as selective dissolution and improved yield. This research offers a potential solution for stable 99mTc production, focusing on porous molybdenum dioxide (MoO2) as a target material due to its insolubility in water. Using potassium molybdate (K2MoO4) as a pore former, we developed porous MoO2 pellets that facilitate efficient technetium extraction and target recycling. This approach offers control over pore formation and shows promise in addressing supply challenges and enhancing 99mTc production.
Understanding the spatial structure of a city is essential for formulating a spatial strategy for that city. In this study, we propose a method for analyzing the functional spatial structure of ...cities based on satellite remote sensing data. In this method, we first assume that urban functions consist of residential and central functions, and that these functions are measured by trip attraction by purpose. Next, we develop a model to explain trip attraction using remote sensing data, and estimate trip attraction on a grid basis. Using the estimated trip attraction, we created a contour tree to identify the spatial extent of the city and the hierarchical structure of the central functions of the city. As a result of applying this method to the Tokyo metropolitan area, we found that (1) our method reproduced 84% of urban areas and 94% of non-urban areas defined by the government, (2) our method extracted 848 urban centers, and their size distribution followed a Pareto distribution, and (3) the top-ranking urban centers were consistent with the districts defined in the master plans for the metropolitan area. Based on the results, we discussed the applicability of our method to urban structure analysis.
Make intergrowth, not war! Hierarchically organized MFI zeolites with micro‐, meso‐, and macroporosity (see scheme) in one structure were made by sequential intergrowth by using a simple organic ...structure‐directing agent (OSDA) without meso‐ or macroporogens. The use of an OSDA that imperfectly fits the zeolite framework generated very thin zeolite plates with 90° rotational intergrowth.
Antibodies against the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein prevent SARS-CoV-2 infection. However, the effects of antibodies against other spike protein domains are largely ...unknown. Here, we screened a series of anti-spike monoclonal antibodies from coronavirus disease 2019 (COVID-19) patients and found that some of antibodies against the N-terminal domain (NTD) induced the open conformation of RBD and thus enhanced the binding capacity of the spike protein to ACE2 and infectivity of SARS-CoV-2. Mutational analysis revealed that all of the infectivity-enhancing antibodies recognized a specific site on the NTD. Structural analysis demonstrated that all infectivity-enhancing antibodies bound to NTD in a similar manner. The antibodies against this infectivity-enhancing site were detected at high levels in severe patients. Moreover, we identified antibodies against the infectivity-enhancing site in uninfected donors, albeit at a lower frequency. These findings demonstrate that not only neutralizing antibodies but also enhancing antibodies are produced during SARS-CoV-2 infection.
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•SARS-CoV-2 infectivity is enhanced by specific antibodies independent of the Fc receptor•The open RBD state is induced upon antibody binding to a specific site on the NTD•Divalent bridging of spikes is required to induce the RBD-up state•Infectivity-enhancing antibodies are detected in severe COVID-19 patients
A subset of antibodies detected in patients with severe COVID-19 target a specific region of the N-terminal domain of the spike protein and enhance binding of the virus to the ACE2 receptor.
SARS-CoV-2 has mutated during the global pandemic leading to viral adaptation to medications and vaccinations. Here we describe an engineered human virus receptor, ACE2, by mutagenesis and screening ...for binding to the receptor binding domain (RBD). Three cycles of random mutagenesis and cell sorting achieved sub-nanomolar affinity to RBD. Our structural data show that the enhanced affinity comes from better hydrophobic packing and hydrogen-bonding geometry at the interface. Additional disulfide mutations caused the fixing of a closed ACE2 conformation to avoid off-target effects of protease activity, and also improved structural stability. Our engineered ACE2 neutralized SARS-CoV-2 at a 100-fold lower concentration than wild type; we also report that no escape mutants emerged in the co-incubation after 15 passages. Therapeutic administration of engineered ACE2 protected hamsters from SARS-CoV-2 infection, decreased lung virus titers and pathology. Our results provide evidence of a therapeutic potential of engineered ACE2.
We investigated the relationship between the dispersibility and optical properties of silicon carbide nanotubes (SiCNTs). By dissolving the aggregation of SiCNTs using sodium cholate as an anionic ...surfactant, the cluster size decreased and the dispersibility improved with the increasing surfactant concentration. The macroscopic and microscopic photoluminescence properties were evaluated using excitation lights with variable spot size. The emission intensity of SiCNTs increased with the decreasing cluster size, owing to the improvement of the dispersibility, and the emission intensity of the well-dispersed SiCNTs increased superlinearly with the excitation density. These results indicate the presence of SiCNTs that recombine non-radiatively in the cluster, and the effect of their NTs is suppressed as the cluster size is reduced.
•Dissolution of aggregated SiCNTs was succeeded using anionic surfactant.•Luminescence efficiency increased with the decreasing cluster size of SiCNTs.•PL spectra of each SiCNT were obtained via microscopic measurement.•Surface states and quantum size effect impact luminescence photon energy in SiCNTs.
Many patients with severe COVID-19 suffer from pneumonia and the elucidation of the mechanisms underlying the development of this severe condition is important. The in vivo function of the ORF8 ...protein secreted by SARS-CoV-2 is not well understood. Here, we analyzed the function of ORF8 protein by generating ORF8-knockout SARS-CoV-2 and found that the lung inflammation observed in wild-type SARS-CoV-2-infected hamsters was decreased in ORF8-knockout SARS-CoV-2-infected hamsters. Administration of recombinant ORF8 protein to hamsters also induced lymphocyte infiltration into the lungs. Similar pro-inflammatory cytokine production was observed in primary human monocytes treated with recombinant ORF8 protein. Furthermore, we demonstrated that the serum ORF8 protein levels are well-correlated with clinical markers of inflammation. These results demonstrated that the ORF8 protein is a SARS-CoV-2 viral cytokine involved in the immune dysregulation observed in COVID-19 patients, and that the ORF8 protein could be a novel therapeutic target in severe COVID-19 patients.
Since June 2019, under the umbrella of the national health insurance system, Japan has started cancer genomic medicine (CGM) with comprehensive genomic profiling (CGP) tests. The Ministry of Health, ...Labour and Welfare (MHLW) of Japan constructed a network of CGM hospitals (a total of 233 institutes as of July 1, 2022) and established the Center for Cancer Genomics and Advanced Therapeutics (C-CAT), the national datacenter for CGM. Clinical information and genomic data from the CGP tests are securely transferred to C-CAT, which then generates "C-CAT Findings" reports containing information of clinical annotation and matched clinical trials based on the CGP data. As of June 30, 2022, a total of 36,340 datapoints of clinical/genomic information are aggregated in C-CAT, and the number is expected to increase swiftly. The data are now open for sharing with not only the CGM hospitals but also other academic institutions and industries.
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