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Cells are often exposed to exogenous and endogenous redox disturbances and exert their protective mechanisms in response to stimuli. The KEAP1-NRF2 system plays pivotal roles in counteracting oxidative damage. Due to the transient nature of NRF2 activation, the identification of cells in which NRF2 is activated in response to systemic stimuli is sometimes not easy. To examine the electrophilic stress response at a single-cell resolution, we aimed to develop a new reporter mouse in this study. A cell-tracing strategy exploiting Cre recombinase-mediated activation of a reporter gene was chosen for stable detection of reporter expression instead of real-time monitoring of the cellular response. We established a transgenic mouse line expressing the Neh2-Cre recombinase fusion protein. As Neh2 is an amino-terminal domain of NRF2 that serves as a degron and mediates KEAP1-dependent degradation and electrophile-inducible stabilization, Neh2-Cre was expected to be activated in response to electrophiles. The Neh2-Cre transgenic mouse was crossed with the ROSA26-loxP-stop-loxP-tdTomato reporter mouse (ROSA-LSL-tdTomato mouse). The compound mutant reporter mice exhibited accumulation of tdTomato-positive cells in various organs after repeated administration of CDDO-Im, one of the NRF2-inducing electrophiles. The mice were also successfully used for the detection of cells that experienced a cisplatin-induced electrophilic stress response.

Wetland ecosystems with proper functioning provide various ecosystem services. Therefore, their conservation and restoration are of fundamental importance for sustainable development. This study used a deep learning model for groundwater level prediction to evaluate a wetland restoration project implemented in the Kushiro Wetland in Japan. The Kushiro Wetland had been degraded due to river improvement work. However, in 2010, a wetland restoration project was carried out to restore the meandering river channel, and a decade has passed since its completion. In this study, the wetland restoration project was evaluated by comparing the response of the groundwater level using a model that reproduced physical conditions with different characteristics before and after the restoration. At first, a deep learning model was created to predict groundwater levels pre- and post-restoration of a meandering river channel using observation data. Long short-term memory (LSTM) was used as the deep learning model. The most important aspect of this study was that LSTM was trained for each of the pre- and post-restoration periods when the hydrological and geological characteristics changed due to the river channel’s restoration. The trained LSTM model achieved high performance with a prediction error of the groundwater levels within 0.162 m at all observation points. Next, the LSTM models trained with the observation data of the post-restoration period were applied to evaluate the effectiveness of the meandering channel restoration. The results indicated that the meandering channel restoration improved hydrological processes in groundwater levels, i.e., their rainfall response and average groundwater water levels. Furthermore, the variable importance analysis of the explanatory variables in the LSTM model showed that river discharge and precipitation significantly contributed to groundwater level recovery in the Kushiro Wetland. These results indicated that the LSTM model could learn the differences in hydrological and geological characteristics’ changes due to channel restoration to groundwater levels. Furthermore, LSTM is a data-driven deep learning model, and by learning hydrological and geological conditions to identify factors that may affect groundwater levels, LSTM has the potential to become a powerful analysis method that can be used for environmental management and conservation issues.

Space flight produces an extreme environment with unique stressors, but little is known about how our body responds to these stresses. While there are many intractable limitations for in-flight space research, some can be overcome by utilizing gene knockout-disease model mice. Here, we report how deletion of Nrf2, a master regulator of stress defense pathways, affects the health of mice transported for a stay in the International Space Station (ISS). After 31 days in the ISS, all flight mice returned safely to Earth. Transcriptome and metabolome analyses revealed that the stresses of space travel evoked ageing-like changes of plasma metabolites and activated the Nrf2 signaling pathway. Especially, Nrf2 was found to be important for maintaining homeostasis of white adipose tissues. This study opens approaches for future space research utilizing murine gene knockout-disease models, and provides insights into mitigating space-induced stresses that limit the further exploration of space by humans., Using Nrf2 knockout mice, Suzuki, Uruno, Yumoto et al. show that space travel activates Nrf2 signaling, which contributes to the weight gain of mice by regulating fat metabolism of white adipose tissues. This study provides insights into potential interventions to mitigate stresses that accompany space travels.

Primary ovarian lymphomas are rare, but can potentially evoke diagnostic problems. We present a case of ovarian lymphoma, in which an ambiguous intraoperative pathologic report led to overtreatment (unnecessary surgery). A 73-yr-old woman with fatigue and low-grade fever was diagnosed as having a left ovarian tumor by imaging modalities. Exploratory laparotomy was carried out to confirm the diagnosis. The frozen tissue sections of the ovarian tumor showed condensed proliferation of atypical round cells accompanied with a few small lymphocytes. The pathologists could not determine whether this tumor was a lymphoma or another malignancy (eg, dysgerminoma). Hence, they reported it to gynecologists who operated as simply a malignant tumor in order to evade misdiagnosis. On the basis of the inconclusive pathologic report, the gynecologists decided to change the planned laparotomy to total hysterectomy with bilateral salpingo-oophorectomy and pelvic lymph node dissection. A postoperative paraffin section-based pathologic diagnosis was diffuse large B-cell lymphoma of the ovary, which basically does not require surgical treatments. Subsequently, chemotherapy for B-cell lymphoma was initiated, and no lymphoma recurrence has been reported to date. A more robust preoperative discussion between the gynecologists and the pathologists might have avoided the overtreatment.

In this study, we developed a groundwater level prediction model using deep learning to evaluate a nature restoration project in Kushiro wetland. The accuracy of the model was verified and a method for analyzing the importance of model variables was proposed.In the Kushiro wetland, the marshland was degraded by the straightening of the river channel in the past, and alder trees grew in abundance. In 2010, the river was re-meandered to its original meandering channel in order to restore the natural environment. The observation data of groundwater level time series were collected from this restoration area. In this study, we developed a deep learning model for the two periods before and after the restoration.Long short-term memory (LSTM) was used as a deep learning model. In LSTM, the input layer contained six components as explanatory variables and groundwater level as an objective variable in three days, and the output layer predicted the groundwater level one day later. The six explanatory variables in the input layer were precipitation, air temperature, sunshine duration, snow depth, normalized difference vegetation index (NDVI) and river discharge. The accuracy of the models produced in the pre- and post- restoration periods was evaluated by the root mean squared error (RMSE) of the measured and predicted values. The results showed that the RMSE is 0.055m~0.162m, which indicated that the LSTM model can predict the groundwater level fluctuation characteristics accurately.The importance analysis method proposed in this study was based on the Wrapper Method used in machine learning. This method (Applied Wrapper Method) was able to extract the most important variables from the explanatory variables if the its truncation caused a significant decrease in model accuracy. The results showed that the river flow discharge and precipitation had a significant effect on the groundwater level time series regardless of whether it was before or after the restoration.The groundwater level prediction model based on the deep learning proposed in this study was confirmed to predict the groundwater level fluctuation characteristics in Kushiro wetland with good accuracy by providing important natural factors. In the future, we plan to incorporate the topography and soil properties of the wetland into the analysis to evaluate the effect of the nature restoration project more accurately.

Differentiation of endocervical adenocarcinomas involving the uterine corpus from primary endometrial (EM) carcinomas involving the cervix is, not only clinically but also pathologically, often difficult. We report a case of gastric-type endocervical adenocarcinoma involving the corpus that could be correctly diagnosed because it was a unique endocervical adenocarcinoma subtype. A 69-year-old woman who presented with abnormal genital bleeding was diagnosed as having a uterine adenocarcinoma on pathological examination of EM biopsy. Preoperative imaging findings and a surgical specimen showed that the tumor was mainly located in the corpus and involved the cervix. We considered at first that the tumor was an EM adenocarcinoma invading into the cervix. However, results of an immunohistochemical examination indicated that it was a gastric-type mucinous adenocarcinoma derived from the endocervix. Our final pathological diagnosis was a gastric-type endocervical adenocarcinoma spreading to the uterine corpus.

Remediation of water quality by stimulating algal photosynthesis using light-emitting diodes (LEDs) has attracted attention, but few studies have examined this in outdoor freshwater environments. To understand the effects of LED illumination on water quality, the dissolved oxygen (DO), temperature, pH, and electric conductivity were monitored over 5 months in three depressions with or without a red/blue LED light at the bottom of an experimental pond. The effects of the blue LED on water quality were evident in the period with less rainfall after the change of water quality to an equilibrium state; DO and pH were higher, and EC was lower for the blue LED than for the control. The diel changes of these variables were also lower for the blue LED. The effects of the red LED on DO and pH were also evident, but to a lesser extent compared to those of the blue LED. A vertical mixing of water associated with a nighttime cooling of the surface water was suggested by a rapid DO increase after a temperature decrease in the control. Such internal water circulation and an inflow of water after rainfall might have obscured the LED effects in the rainy period. The bottom water of the blue LED had a higher density and species richness of phytoplankton than that of the control at the end of the experiment. A lower density of phytoplankton and higher nutrient concentrations in the red LED might have been due to a higher density and feeding activity by zooplankton. Our results confirmed the applicability of LED illumination in stimulating algal photosynthesis, and in improving the oxygen condition of the bottom water in freshwater ponds.

Age-related hearing loss (AHL) is a progressive sensorineural hearing loss in elderly people. Although no prevention or treatments have been established for AHL, recent studies have demonstrated that oxidative stress is closely related to pathogenesis of AHL, suggesting that suppression of oxidative stress leads to inhibition of AHL progression. NRF2 is a master transcription factor that regulates various antioxidant proteins and cytoprotection factors. To examine whether NRF2 pathway activation prevents AHL, we used Keap1-knockdown (Keap1FA/FA) mice, in which KEAP1, a negative regulator of NRF2, is decreased, resulting in the elevation of NRF2 activity. We compared 12-month-old Keap1FA/FA mice with age-matched wild-type (WT) mice in the same breeding colony. In the Keap1FA/FA mice, the expression levels of multiple NRF2 target genes were verified to be significantly higher than the expression levels of these genes in the WT mice. Histological analysis showed that cochlear degeneration at the apical and middle turns was ameliorated in the Keap1FA/FA mice. Auditory brainstem response (ABR) thresholds in the Keap1FA/FA mice were significantly lower than those in the WT mice, in particular at low–mid frequencies. Immunohistochemical detection of oxidative stress markers suggested that oxidative stress accumulation was attenuated in the Keap1FA/FA cochlea. Thus, we concluded that NRF2 pathway activation protects the cochlea from oxidative damage during aging, in particular at the apical and middle turns. KEAP1-inhibiting drugs and phytochemicals are expected to be effective in the prevention of AHL.

Highlights • A case of paraneoplastic cerebellar degeneration developed with progressive ovarian cancer during postoperative chemotherapy. • Intravenous immunoglobulin should be attempted when paraneoplastic cerebellar degeneration is diagnosed. • Severe neurological symptoms were dramatically improved without sequelae by intravenous immunoglobulin. • Intravenous immunoglobulin can be effective in improving neuropathy, whether it is severe neuropathy or advanced cancer. • Intravenous immunoglobulin could have beneficial effects on not only neuropathy but also on the tumor itself., We report the effect of intravenous immunoglobulin (IVIG) against paraneoplastic cerebellar degeneration (PCD) in a case of progressive ovarian cancer. Our patient developed PCD soon after postoperative chemotherapy and became bedridden. After undergoing IVIG, however, symptoms dramatically improved, and unexpectedly the remaining tumors were confirmed to have completely disappeared. When PCD is diagnosed, IVIG treatment should be attempted to reduce neuropathy regardless of its degree and the state of the cancer. It may also have further potential benefits that should be considered.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Purpose This paper aims to present a preliminary experimental result on a large-scale experiment on a cyber-physical hybrid discussion support environment in a panel discussion session in an international conference. Design/methodology/approach In this paper, the authors propose a hybrid (cyber-physical) environment in which people can discuss online and also offline simultaneously. The authors conducted a large-scale experiment in a panel discussion session in an international conference where participants can discuss by using their online discussion support system and by physical communications as usual. Findings The authors analyzed the obtained date from the following three viewpoints: participants’ cyber-physical attention, keywords cyber-physical linkage and cyber-physical discussion flow. These three viewpoints indicate that the methodology of the authors can be effective to support hybrid large-scale discussions. Originality/value Online large-scale discussion has been focused as a new methodology that enable people to discuss, argue and make consensus in terms of political issues, social complex problems (like climate change), city planning and so on. In several cases, the authors found that online discussions are very effective to gather people opinions and discussions so far. Moreover, this paper proposes a hybrid (cyber-physical) environment in which people can discuss online and also offline simultaneously.

Uterine perforation, a complication of dilation and curettage, is typically recognized immediately after the procedure by clinical symptoms of peritoneal irritation resulting from intraperitoneal bleeding. Our patient complained of having an uncomfortable feeling, slight dizziness, palpitation in the sitting position and abdominal discomfort but did not show signs of peritoneal irritation 24 h after dilation and curettage. However, she suddenly complained of abdominal pain. Tenderness and rebound tenderness were detected at the lower abdominal wall. Ultrasonography and magnetic resonance imaging suggested uterine perforation. When the abdominal cavity was opened, a hematoma under the broad ligament of the uterus, laceration of the side wall of the uterine cervix and a small amount of bloody ascites and small clots in the abdominal cavity were observed. The uterine cervical wall was sutured. Physicians should postpone discharge and observe the clinical course carefully when a patient complains of inexplicable discomfort after dilation and curettage.