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\"The city of Kyoto has undergone radical shifts in its significance as a political and cultural centre, as a hub of the national bureaucracy, as a symbolic and religious centre, and as a site for the production and display of art. However, the field of Japanese history and culture lacks a book which considers Kyoto on its own terms as a historic city with a changing identity. Examining cultural production in the city of Kyoto in two periods of political transition, this book promises to be a major step forward in advancing our knowledge of Kyoto's history and culture. Its chapters focus on two centuries in Kyoto's history in which the old capital was politically marginalised: the seventeenth century, when the centre of power shifted from the old imperial capital to the new warriors' capital of Edo; and the nineteenth century, when the imperial court itself was moved to the new modern centre of Tokyo. The contributors argue that in both periods the response of Kyoto elites--emperors, courtiers, tea masters, municipal leaders, monks, and merchants--was artistic production and cultural revival. As an artistic, cultural and historical study of Japan's most important historic city, this book will be invaluable to students and scholars of Japanese history, Asian history, the Meiji and Edo periods, art history, visual culture and cultural history\"--Provided by publisher.

Objectives Burnout among health care workers is highly prevalent and has profound impact on quality of care. Hospital on‐duty schedules lead to long working hours and short sleeping hours; both are common factors associated with burnout. We examined the dose‐response relationship and the potential mediating role of sleeping hours on the association between working hours and burnout among health care workers. Methods We collected data on the burnout status, using the Mandarin version of the Copenhagen Burnout Inventory (subscales measure work‐related and personal burnouts), working hours, sleeping hours, and relevant measures for 2081 health care personnel who underwent a routine health examination in a medical center in Taiwan during 2016‐2017. Four subgroups were compared: physicians (n = 369), nurses (n = 973), technicians (n = 391), and administrators (n = 348). Results Average weekly working hours are associated with burnout scores in a non‐linear dose‐response manner. Compared with a work week of 40 hours, the odds ratio of work‐related burnout doubled when hours exceeded 60, tripled when hours exceeded 74, and quadrupled when hours exceeded 84. Physicians’ burnout is less susceptible to incremental increases in working hours, compared to the situations in other health care workers. The proportions eliminated by reducing sleeping hours were 25%‐73% for physicians and 7%‐29% for nurses respectively. Conclusions Our findings suggest that working hours are associated with burnout, and the association was partially mediated by sleeping hours.

Studies on the association between adiponectin and leptin and anxiety and depression among postmenopausal women are limited. Therefore, the present study specifically evaluates the mutual relationships between adiponectin and leptin and anxiety and depression in postmenopausal women. In this cross-sectional study, a total of 190 women aged 40-65 years were enrolled. Depression symptoms were assessed using the Center for Epidemiologic Studies Depression Scale (CES-D), and anxiety symptoms were evaluated using the Hamilton Anxiety Rating Scale (HAM-A). Fasting specimens were collected to measure sex hormone, glucose, insulin, and adipokine levels. Multiple linear regression analysis was performed to evaluate the associations between depression and anxiety and adipocyte-derived hormones. The study was performed in a hospital medical center. Among 190 enrolled postmenopausal women, Spearman's rank correlation analysis revealed significant correlations between CES-D and HAM-A (r = 0.715, P < 0.0001), between CES-D and adiponectin (p = 0.009) and leptin (p = 0.015), and between HAM-A and adiponectin (p = 0.01) and leptin (p = 0.001). The subjects with CES-D ≥ 16 and with HAM-A ≥ 18 had higher adiponectin levels than those with CES-D < 16 and HAM-A < 18, respectively. After adjusting for age, body mass index, exercise, alanine amino transferase and parameters of lipid profiles, Log adiponectin levels were found to be significantly associated with both CES-D and HAM-A, and Log leptin levels were only significantly associated with HAM-A. The data show that adiponectin and leptin levels are significantly associated with depression and anxiety symptoms. These results suggest that higher adiponectin and lower leptin levels may serve as potential markers related to anxiety and mood in postmenopausal women. More future research that is designed to deal with the important confounders (e.g., population heterogeneity) is needed to investigate comprehensively on these associations.

With the climate constantly changing, plants suffer more frequently from various abiotic and biotic stresses. However, they have evolved biosynthetic machinery to survive in stressful environmental conditions. Flavonoids are involved in a variety of biological activities in plants, which can protect plants from different biotic (plant-parasitic nematodes, fungi and bacteria) and abiotic stresses (salt stress, drought stress, UV, higher and lower temperatures). Flavonoids contain several subgroups, including anthocyanidins, flavonols, flavones, flavanols, flavanones, chalcones, dihydrochalcones and dihydroflavonols, which are widely distributed in various plants. As the pathway of flavonoid biosynthesis has been well studied, many researchers have applied transgenic technologies in order to explore the molecular mechanism of genes associated with flavonoid biosynthesis; as such, many transgenic plants have shown a higher stress tolerance through the regulation of flavonoid content. In the present review, the classification, molecular structure and biological biosynthesis of flavonoids were summarized, and the roles of flavonoids under various forms of biotic and abiotic stress in plants were also included. In addition, the effect of applying genes associated with flavonoid biosynthesis on the enhancement of plant tolerance under various biotic and abiotic stresses was also discussed.

Laser speckle contrast imaging (LSCI) is a powerful tool to monitor blood flow distribution and has been widely used in studies of microcirculation, both for animal and clinical applications. Conventionally, LSCI usually works on reflective-detected mode. However, it could provide promising temporal and spatial resolution for in vivo applications only with the assistance of various tissue windows, otherwise, the overlarge superficial static speckle would extremely limit its contrast and resolution. Here, we systematically investigated the capability of transmissive-detected LSCI (TR-LSCI) for blood flow monitoring in thick tissue. Using Monte Carlo simulation, we theoretically compared the performance of transmissive and reflective detection. It was found that the reflective-detected mode was better when the target layer was at the very surface, but the imaging quality would rapidly decrease with imaging depth, while the transmissive-detected mode could obtain a much stronger signal-to-background ratio (SBR) for thick tissue. We further proved by tissue phantom, animal, and human experiments that in a certain thickness of tissue, TR-LSCI showed remarkably better performance for thick-tissue imaging, and the imaging quality would be further improved if the use of longer wavelengths of near-infrared light. Therefore, both theoretical and experimental results demonstrate that TR-LSCI is capable of obtaining thick-tissue blood flow information and holds great potential in the field of microcirculation research.The performance of novel transmissive-detected LSCI was systematically demonstrated through simulation and experiments. With such a simple system, individual vessel-resolution blood flow mapping and monitoring were realized on human hand.

Positive fluid balance is a prognostic factor for mortality in patients with sepsis; however, the association between cumulated fluid balance (CFB) and sepsis-induced multi-organ dysfunction syndrome (MODS) has yet to be elucidated. In this study, we sought to determine whether CFB is correlated with MODS and mortality in cases of septic shock. The study retrospectively recruited patients with septic shock from the intensive care unit of a tertiary care hospital. Multiple organ dysfunction syndrome (MODS) was identified as sequential organ failure assessment (SOFA) score ≥ 2 in more than one organ system. The CFB is the sum of all daily intake and output. An independent t-test, single and multivariate logistic regression, the receiver operating characteristic (ROC) curves, and the Pearson correlation coefficient were used to determine whether a relationship exists between CFB and the development of MODS and mortality. Among the 104 patients enrolled in the study, 58 (55.8%) survived more than 28 days, and 73 (70.2%) developed MODS on day 3. The values of CFB in the first 24 hours and 72 hours after diagnosis of septic shock in patients with MODS were higher than these in patients without MODS (1086.6 ± 176.3 vs. 325.5 ± 205.7 ml, p = 0.013 and 2408 ± 361 vs. 873.1 ± 489 ml, p < 0.0001). In a multivariate logistic regression, the independent factors associated with the development of MODS on day 3 were APACHE II score at ICU admission (27.6 ± 7.6 in patients with MODS vs. 20.5 ± 6.4 in those without; O.R. 1.18; 95% C.1 I. 1.08-1.30; p < 0.001), disseminated intravascular coagulopathy (DIC) (n = 28; 38.4% vs. n = 2; 6.5%; O.R. 23.67; 95% C.I. 3.58-156.5; p = 0.001), and CFB in the first 72 hours (72-hr CFB) > median (1767.50ml) (n = 41; 56.2% vs. n = 11; 35.5%; O.R. 3.67; 95% C.I., 1.18-11.40; p = 0.024). Moreover, a multivariate logistic regression also identified neoplasm (n = 25; 54.3% vs. n = 17; 29.3%; O.R. 3.45; 95% C.I. 1.23-10.0; p = 0.019) and 72-hr CFB > median (n = 30; 65.2% vs. n = 21; 36.2%; O.R. 4.13; 95% C.I. 1.34-12.66; p = 0.013) as independent factors associated with 28-day mortality. 72-hr CFB values were strongly correlated with the SOFA score (r = 0.445, p < 0.0001). The area under the ROC curve revealed that 72-hr CFB has good discriminative power in associating the development of MODS (0.644, p = 0.002) and predicting subsequent 28-day mortality (0.704, p < 0.0001). 72-hr CFB appears to be correlated with the likelihood of developing MODS and mortality in patients with septic shock. Thus, it appears that 72-hr CFB could perhaps be used as an indicator for MODS and a predictor for mortality in those patients.

Mineral mapping from satellite images provides valuable insights into subsurface mineral alteration for geothermal exploration. In previous studies, eight fundamental algorithms were used for mineral mapping utilizing USGS spectra, a collection of reflectance spectra containing samples of minerals, rocks, and soils created by the USGS. We used an ASD FieldSpec 4 Hi-RES NG portable spectrometer to collect spectra for analyzing ASTER images of the Coso Geothermal Field. Then, we established the ground-truth information and the spectral library by analyzing 97 samples. Samples collected from the field were analyzed using the CSIRO TSG (The Spectral Geologist of the Commonwealth Scientific and Industrial Research Organization). Based on the mineralogy study, multiple high-purity spectra of geothermal alteration minerals were selected from collected data, including alunite, chalcedony, hematite, kaolinite, and opal. Eight mineral spectral target detection algorithms were applied to the preprocessed satellite data with a proposed local spectral library. We measured the highest overall accuracy of 87% for alunite, 95% for opal, 83% for chalcedony, 60% for hematite, and 96% for kaolinite out of these eight algorithms. Three, four, five, and eight algorithms were fused to extract mineral alteration with the obtained target detection results. The results prove that the fusion of algorithms gives better results than using individual ones. In conclusion, this paper discusses the significance of evaluating different mapping algorithms. It proposes a robust fusion approach to extract mineral maps as an indicator for geothermal exploration.

HLA‐G is considered as an immune checkpoint protein and a tumor‐associated antigen. In the previous work, it is reported that CAR‐NK targeting of HLA‐G can be used to treat certain solid tumors. However, the frequent co‐expression of PD‐L1 and HLA‐G) and up‐regulation of PD‐L1 after adoptive immunotherapy may decrease the effectiveness of HLA‐G‐CAR. Therefore, simultaneous targeting of HLA‐G and PD‐L1 by multi‐specific CAR could represent an appropriate solution. Furthermore, gamma‐delta T (γδT) cells exhibit MHC‐independent cytotoxicity against tumor cells and possess allogeneic potential. The utilization of nanobodies offers flexibility for CAR engineering and the ability to recognize novel epitopes. In this study, Vδ2 γδT cells are used as effector cells and electroporated with an mRNA‐driven, nanobody‐based HLA‐G‐CAR with a secreted PD‐L1/CD3ε Bispecific T‐cell engager (BiTE) construct (Nb‐CAR.BiTE). Both in vivo and in vitro experiments reveal that the Nb‐CAR.BiTE‐γδT cells could effectively eliminate PD‐L1 and/or HLA‐G‐positive solid tumors. The secreted PD‐L1/CD3ε Nb‐BiTE can not only redirect Nb‐CAR‐γδT but also recruit un‐transduced bystander T cells against tumor cells expressing PD‐L1, thereby enhancing the activity of Nb‐CAR‐γδT therapy. Furthermore, evidence is provided that Nb‐CAR.BiTE redirectes γδT into tumor‐implanted tissues and that the secreted Nb‐BiTE is restricted to the tumor site without apparent toxicity. Elevated PD‐L1 in solid tumors increases the risk of immune escape from HLA‐G‐CAR cell therapy. The bicistronic mRNA construct that drives PD‐L1 Nb‐BiTE and HLA‐G Nb‐CAR in γδT cells via electroporation is designed to address this issue. This Nb‐CAR.BiTE‐γδT therapy can overcome HLA‐G and PD‐L1 dilemma and even kill tumor cells with inadequate antigen expression, resulting in potent anti‐tumor activity without apparent toxicity.

ObjectiveSolid tumours respond poorly to immune checkpoint inhibitor (ICI) therapies. One major therapeutic obstacle is the immunosuppressive tumour microenvironment (TME). Cancer-associated fibroblasts (CAFs) are a key component of the TME and negatively regulate antitumour T-cell response. Here, we aimed to uncover the mechanism underlying CAFs-mediated tumour immune evasion and to develop novel therapeutic strategies targeting CAFs for enhancing ICI efficacy in oesophageal squamous cell carcinoma (OSCC) and colorectal cancer (CRC).DesignAnti-WNT2 monoclonal antibody (mAb) was used to treat immunocompetent C57BL/6 mice bearing subcutaneously grafted mEC25 or CMT93 alone or combined with anti-programmed cell death protein 1 (PD-1), and the antitumour efficiency and immune response were assessed. CAFs-induced suppression of dendritic cell (DC)-differentiation and DC-mediated antitumour immunity were analysed by interfering with CAFs-derived WNT2, either by anti-WNT2 mAb or with short hairpin RNA-mediated knockdown. The molecular mechanism underlying CAFs-induced DC suppression was further explored by RNA-sequencing and western blot analyses.ResultsA negative correlation between WNT2+ CAFs and active CD8+ T cells was detected in primary OSCC tumours. Anti-WNT2 mAb significantly restored antitumour T-cell responses within tumours and enhanced the efficacy of anti-PD-1 by increasing active DC in both mouse OSCC and CRC syngeneic tumour models. Directly interfering with CAFs-derived WNT2 restored DC differentiation and DC-mediated antitumour T-cell responses. Mechanistic analyses further demonstrated that CAFs-secreted WNT2 suppresses the DC-mediated antitumour T-cell response via the SOCS3/p-JAK2/p-STAT3 signalling cascades.ConclusionsCAFs could suppress antitumour immunity through WNT2 secretion. Targeting WNT2 might enhance the ICI efficacy and represent a new anticancer immunotherapy.