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Colorectal cancer (CRC) is the fourth most common cancer in the world, with the second highest incidence rate after lung cancer. Oxaliplatin (OXA) is a broad-spectrum anti-tumor agent with significant therapeutic efficacy in colorectal cancer, and as a divalent platinum analog, it is not selective in its distribution in the body and has systemic toxicity with continued use. Interleukin-12 (IL12) is an immunostimulatory cytokine with cytokine monotherapy that has made advances in the fight against cancer, limiting the clinical use of cytokines due to severe toxicity. Here, we introduced a long alkyl chain and N-methyl-2,2-diaminodiethylamine to the ligand of OXA to obtain OXA-LIP, which effectively reduces its toxicity and improves the uptake of the drug by tumor cells. We successfully constructed IL12 mRNA and used LNPs to deliver IL12 mRNA, and in vivo pharmacodynamic studies demonstrated that OXA-LIP combined with IL12 mRNA had better tumor inhibition and higher biosafety. In addition, it was investigated by pharmacokinetic experiments that the OXA-LIP drug could accumulate in nude mice at the tumor site, which prolonged the half-life and enhanced the anti-tumor efficiency of OXA. It is hoped that these results will provide an important reference for the subsequent research and development of OXA-LIP with IL12 mRNA, as well as provide new therapeutic approaches for the treatment of colon cancer. [ABSTRACT FROM AUTHOR]

Human-object interaction detection can be mainly categorized into two core problems, namely human-object association detection and interaction understanding. Firstly, for association detection, previous methods tend to directly detect obvious human-object interaction pairs, while ignoring some interaction pairs that may have potential interaction relationships, which is contrary to the actual situation. Secondly, for the interaction understanding problem, traditional methods face the challenges of long-tailed distribution and zero-shot detection, which cannot flexibly deal with complex and changing real-world scenarios. To this end, adaptive Query Learning for HOI Detection via vision-language knowledge Transfer(QLDT) is proposed. Specifically, a two-stage dynamic matching scoring algorithm based on dynamically changing thresholds and scores is designed to explore obscure H-O pairs and labeling to enlarge the sample size. Secondly, a visual-language pre-trained model GLIP (Grounded Language-Image Pre-training), is introduced to enhance the model's interactive comprehension ability, extract the visual and linguistic features of the images through GLIP, minimize the gap with the predicted values using cross-entropy loss, and take the maximum value of the score with the obscure H-O pairs as the final prediction, which ensures the model's positivity. The proposed method shows excellent performance on both HICO-DET and V-COCO datasets, for HICO-DET, QLDT achieved 35.37% mAP on the full category, 30.15% mAP on the rare category, and also improved on all five zero-shot metrics. For V-COCO, 62.74% mAP and 67.71% mAP were achieved under Scenario 1 and 2, respectively. [ABSTRACT FROM AUTHOR]

Motivated by applications in DNA storage, we study a setting in which strings are affected by tandem-duplication errors. In particular, we look at two settings: disjoint tandem-duplication errors, and equal-length tandem-duplication errors. We construct codes, with positive asymptotic rate, for the two settings, as well as for their combination. Our constructions are duplication-free codes, comprising codewords that do not contain tandem duplications of specific lengths. Additionally, our codes generalize previous constructions, containing them as special cases. [ABSTRACT FROM AUTHOR]

Human-object interaction (HOI) detection is an important computer vision task for recognizing the interaction between humans and surrounding objects in an image or video. The HOI datasets have a serious long-tailed data distribution problem because it is challenging to have a dataset that contains all potential interactions. Many HOI detectors have addressed this issue by utilizing visual-language models. However, due to the calculation mechanism of the Transformer, the visual-language model is not good at extracting the local features of input samples. Therefore, we propose a novel local feature enhanced Transformer to motivate encoders to extract multi-modal features that contain more information. Moreover, it is worth noting that the application of prompt learning in HOI detection is still in preliminary stages. Consequently, we propose a multi-modal adaptive prompt module, which uses an adaptive learning strategy to facilitate the interaction of language and visual prompts. In the HICO-DET and SWIG-HOI datasets, the proposed model achieves full interaction with 24.21% mAP and 14.29% mAP, respectively. Our code is available at https://github.com/small-code-cat/AMP-HOI. [ABSTRACT FROM AUTHOR]

Multiple myeloma (MM) is the second most common hematological tumor in adults. Immunomodulatory drugs (IMiDs), such as thalidomide and lenalidomide (Len), are effective drugs for the treatment of multiple myeloma. Len can recruit IKZF1 and IKZF3 to cereblon (CRBN), a substrate receptor of the cullin 4-RING E3 ligase (CRL4), promote their ubiquitination and degradation, and finally inhibit the proliferation of myeloma cells. However, MM patients develop resistance to IMiDs over time, leading to disease recurrence and deterioration. To explore the possible approaches that may enhance the sensitivity of IMiDs to MM, in this study, we used the proximity labeling technique TurboID and quantitative proteomics to identify Lys-63-specific deubiquitinase BRCC36 as a CRBN-interacting protein. Biochemical experiments demonstrated that BRCC36 in the BRISC complex protects CRBN from lysosomal degradation by specifically cleaving the K63-linked polyubiquitin chain on CRBN. Further studies found that a small-molecule compound SHIN1, which binds to BRISC complex subunit SHMT2, can upregulate CRBN by elevating BRCC36. The combination of SHIN1 and Len can further increase the sensitivity of MM cells to IMiDs. Therefore, this study provides the basis for the exploration of a possible strategy for the SHIN1 and Len combination treatment for MM. [ABSTRACT FROM AUTHOR]

Objectives: To establish a radiomics-based automatic grading model for knee osteoarthritis (OA) and evaluate the influence of different body positions on the model's effectiveness. Materials and methods: Plain radiographs of a total of 473 pairs of knee joints from 473 patients (May 2020 to July 2021) were retrospectively analyzed. Each knee joint included anteroposterior (AP) and lateral (LAT) images which were randomly assigned to the training cohort and the testing cohort at a ratio of 7:3. First, an assessment of knee OA severity was done by two independent radiologists with Kallgren–Lawrence grading scale. Then, another two radiologists independently delineated the region of interest for radiomic feature extraction and selection. The radiomic classification features were dimensionally reduced and a machine model was conducted using logistic regression (LR). Finally, the classification efficiency of the model was evaluated using receiver operating characteristic curves and the area under the curve (AUC). Results: The AUC (macro/micro) of the model using a combination of AP and LAT (AP&LAT) images were 0.772/0.778, 0.818/0.799, and 0.864/0.879, respectively. The radiomic features from the combined images achieved better classification performance than the individual position image (p < 0.05). The overall accuracy of the radiomic model with AP&LAT images was 0.727 compared to 0.712 and 0.417 for radiologists with 4 years and 2 years of musculoskeletal diagnostic experience. Conclusions: A radiomic model constructed by combining the AP&LAT images of the knee joint can better grade knee OA and assist clinicians in accurate diagnosis and treatment. Critical relevance statement: A radiomic model based on plain radiographs accurately grades knee OA severity. By utilizing the LR classifier and combining AP&LAT images, it improves accuracy and consistency in grading, aiding clinical decision-making, and treatment planning. Key Points: Radiomic model performed more accurately in K/L grading of knee OA than junior radiologists. Radiomic features from the combined images achieved better classification performance than the individual position image. A radiomic model can improve the grading of knee OA and assist in diagnosis and treatment. [ABSTRACT FROM AUTHOR]

Objective: To investigate the diagnostic value of early dynamic 18F-FDG PET/CT(ED 18F-FDG PET/CT) combined with conventional whole-body 18F-FDG PET/CT(WB 18F-FDG PET/CT) in hepatocellular carcinoma (HCC), as well as the difference of early dynamic blood flow parameters and maximum standardized uptake value (SUVmax) in HCC patients with/without liver cirrhosis or microvascular invasion (MVI). Methods: Twenty-two consecutive patients (mean age 57.8 years) with 28 established HCC lesions (mean size 4.5 cm) underwent a blood flow study with an 18F-FDG dynamic scan divided into 24 sequences of 5 s each and a standard PET/CT scan. On the ED PET/CT study, an experienced PET/CT physician obtained volumes of interest (VOIs) where three blood flow estimates (time to peak [TTP], blood flow [BF], and hepatic perfusion index [HPI]) were calculated. On the WB PET/CT study, a VOI was placed on the fused scan for each HCC and maximum standardized uptake value (SUVmax) was obtained. Comparison of blood flow estimates, SUVmax, and tumor/background ratio (TNR) was performed among HCCs with and without angioinvasion, as well as HCCs in cirrhotic and non-cirrhotic liver. Results: Compared with WB 18F-FDG PET/CT alone, ED combined with WB 18F-FDG PET/CT can significantly increase the detection rate of moderately differentiated and poorly differentiated HCCs (both P < 0.05). HPI was higher in HCCs in patients with liver cirrhosis than those without liver cirrhosis (P = 0.044). There was no significant difference in TTP, BF, SUVmax, or TNR between HCCs in patients with liver cirrhosis and those without liver cirrhosis. There was no significant difference in blood flow estimates or SUVmax in background liver parenchyma between patients with and those without cirrhosis. TTP was shorter in HCCs with MVI than without MVI (P = 0.046). There was no significant difference in BF, HPI, SUVmax, or TNR between HCCs with MVI and without MVI. There was no significant difference in blood flow estimates or SUVmax in background liver parenchyma between patients with and those without MVI. Conclusion: ED combined with WB 18F-FDG PET/CT can significantly increase the detection rate of moderately differentiated and poorly differentiated HCCs. HPI was significantly higher in HCCs in patients with liver cirrhosis than those without liver cirrhosis. TTP was significantly shorter in HCCs with MVI than without MVI. [ABSTRACT FROM AUTHOR]

Objective: To assess the detection of changes in knee cartilage and meniscus of amateur marathon runners before and after long-distance running using a 3D ultrashort echo time MRI sequence with magnetization transfer preparation (UTE-MT). Methods: We recruited 23 amateur marathon runners (46 knees) in this prospective cohort study. MRI scans using UTE-MT and UTE-T2* sequences were performed pre-race, 2 days post-race, and 4 weeks post-race. UTE-MT ratio (UTE-MTR) and UTE-T2* were measured for knee cartilage (eight subregions) and meniscus (four subregions). The sequence reproducibility and inter-rater reliability were also investigated. Results: Both the UTE-MTR and UTE-T2* measurements showed good reproducibility and inter-rater reliability. For most subregions of cartilage and meniscus, the UTE-MTR values decreased 2 days post-race and increased after 4 weeks of rest. Conversely, the UTE-T2* values increased 2 days post-race and decreased after 4 weeks. The UTE-MTR values in lateral tibial plateau, central medial femoral condyle, and medial tibial plateau showed a significant decrease at 2 days post-race compared to the other two time points (p < 0.05). By comparison, no significant UTE-T2* changes were found for any cartilage subregions. For meniscus, the UTE-MTR values in medial posterior horn and lateral posterior horn regions at 2 days post-race were significantly lower than those at pre-race and 4 weeks post-race (p < 0.05). By comparison, only the UTE-T2* values in medial posterior horn showed a significant difference. Conclusions: UTE-MTR is a promising method for the detection of dynamic changes in knee cartilage and meniscus after long-distance running. Key Points: • Long-distance running causes changes in the knee cartilage and meniscus. • UTE-MT monitors dynamic changes of knee cartilage and meniscal non-invasively. • UTE-MT is superior to UTE-T2* in monitoring dynamic changes in knee cartilage and meniscus. [ABSTRACT FROM AUTHOR]

Understanding a visual scene requires not only identifying single objects in isolation but also inferring the relationships and interactions between object pairs. In this study, we propose a novel scene graph generation framework based on Transformer to convert image data into linguistic descriptions characterized as nodes and edges of a graph describing the information of the given image. The proposed model consists of three components. First, we propose an enhanced object detection module with bidirectional long short-term memory (Bi-LSTM) for object-to-object information exchange to generate the classification probabilities for object bounding boxes and classes. Second, we introduce a novel context information capture module containing Transformer layers that outputs object categories containing object context as well as edge information for specific object pairs with context. Finally, since the relationship frequencies follow a long-tailed distribution, an adaptive inference module with a special feature fusion strategy is designed to soften the distribution and perform adaptive reasoning about relationship classification based on the visual appearance of object pairs. We have conducted detailed experiments on three popular open-source datasets, namely, Visual Genome, OpenImages, and Visual Relationship Detection, and have performed ablation experiments on each module, demonstrating significant improvements under different settings and in terms of various metrics. [ABSTRACT FROM AUTHOR]

Given the importance of waterway depths in river development, the effects of the evolution of bars and troughs on waterway expansion play an important role in river management and water depth conservation. This study aims to expand the waterway dimensions of the Jingjiang Reach of the Yangtze River. To achieve this objective, determining the relationship between river evolution processes and the potential for waterway depth improvement and navigation hindrances is vital. Therefore, the sedimentation, hydrological, and terrain data of the Jingjiang Reach from 1955 to 2020 are analysed to elucidate the above-mentioned relationship. Since the commissioning of the Three Gorges Dam, the scouring of the low-flow channel has accounted for 90%–95% of all scouring in the Jingjiang Reach. Furthermore, the central bars and beaches have shrunk by 9.4% and 24.9%, respectively, and 18.3% overall. Considering the bed scouring and waterway regulation projects in the Jingjiang Reach, we investigated the continuity of a 4.5 m × 200 m × 1050 m (depth × width × bend radius) waterway along the Jingjiang Reach, and find that navigation-hindering channels account for over 5.3% of the waterway length. Furthermore, part of the Jingjiang Reach is an important nature reserve and shelters numerous water-related facilities, which inhibits the implementation of waterway deepening projects. The findings of this study demonstrate that numerous challenges are associated with increasing the waterway depths of the Jingjiang Reach. [ABSTRACT FROM AUTHOR]

Summary: Melanoma has a high degree of malignancy and mortality. While there are some hopeful clinical trials for melanoma treatment in progress, they have not yet to yield significant long-term cure rates. Cancer vaccines including mRNA are currently one of the most promising strategy for tumor immunotherapy. The aim of this study was to analyze the potential tumor antigens in melanoma that could be used to develop mRNA vaccines and identify suitable vaccine populations. The gene expression data and complete clinical information of 471 melanoma samples and 1 normal tissue were retrieved from TCGA. Then, 812 samples of normal skin and their corresponding gene expression data were obtained from GTEx. Overexpressed genes, mutated genes and IRDEGs are used to identify potential tumor antigens. The relationship between the expression level of potential antigen and prognosis was analyzed in GEPIA, and then the immune cell infiltration was estimated based on TIMER algorithm. The expression profiles of IRDEGs were used to identify consensus clusters and immune subtypes of melanoma. Finally, mutational status and immune microenvironment characterization in immune subtypes were analyzed. Five tumor antigens (PTPRC, SIGLEC10, CARD11, LILRB1, ADAMDEC1) were identified as potential tumor antigens according to overexpressed genes, mutated genes and immune-related genes. They were all associated with OS, DFS and APCs. We identified two immune subtypes of melanoma, named IS1 and IS2, which exhibit different clinical features and immune landscapes. Based on the different immune landscape, we may conclude that IS1 is immunophenotypically "cold", while IS2 is "hot". The present research implicates that PTPRC, SIGLEC10, CARD11, LILRB1 and ADAMDEC1 may be the antigenic targets for melanoma mRNA vaccines and IS2 patients may be more effective to these vaccines. [ABSTRACT FROM AUTHOR]

In recent years, there has been a surge of interest in perception, evaluation, and memory for social interactions from a third-person perspective. One intriguing finding is a spatial distance compression effect when target dyads are facing each other. Specifically, face-to-face dyads are remembered as being spatially closer than back-to-back dyads. There is a vibrant debate about the mechanism behind this effect, and two hypotheses have been proposed. According to the social interaction hypothesis, face-to-face dyads engage a binding process that represents them as a social unit, which compresses the perceived distance between them. In contrast, the configuration hypothesis holds that the effect is produced by the front-to-front configuration of the two visual targets. In the present research we sought to test these accounts. In Experiment 1 we successfully replicated the distance compression effect with two upright faces that were facing each other, but not with inverted faces. In contrast, we found no distance compression effect with three types of nonsocial stimuli: arrows (Experiment 2a), fans (Experiment 2b), and cars (Experiment 3). In Experiment 4, we replicated this effect with another social stimuli: upright bodies. Taken together, these results provide strong support for the social interaction hypothesis. [ABSTRACT FROM AUTHOR]

Key summary points: Aim: The aim of this study was to compare and analyze the clinical and CT features of coronavirus disease 2019 (COVID-19) in four different age groups (children, young adults, middle age, and senior). Findings: Seniors were found to have a higher incidence of the highest clinical classification (severe or critical), large/multiple ground-glass opacity, and involvement of four or five lung lobes in these four groups. Message: Older patients of COVID-19 are more likely to be infected with a larger number of lung lobes and more severe manifestations as visualized by CT. Purpose: To compare and analyze the clinical and CT features of coronavirus disease 2019 (COVID-19) among four different age groups. Methods: 97 patients (45 males, 52 females, mean age, 66.2 ± 5.0) with chest CT examination and positive reverse transcriptase-polymerase chain reaction test (RT-PCR) from January 17, 2020 to February 21, 2020 were retrospectively studied. The patients were divided into four age groups (children [0–17 years], young adults [18–44 years], middle age [45–59 years], and senior [≥ 60 years]) according to their age after the diagnosis was made based on PCR test and clinical symptoms. Results: Comorbidities such as hypertension, diabetes mellitus, and heart disease are more common in the senior group. Cluster onset (two or more confirmed cases in a small area) is more common in the children group and senior group. Older patients were found to have a higher incidence of the highest clinical classification (severe or critical) in these four groups. Senior patients have a higher incidence of large/multiple ground-glass opacity (GGO). Child patients are mostly negative for chest CT or with involvement of only one lobe of the lung; while in older patients, there was a higher incidence of involvement of four or five lung lobes. The frequency of lobe involvement was also found to have significant differences in the four age groups. Conclusion: The clinical and imaging features of patients in different age groups were found to be significantly different. A better understanding of the age differences in comorbidities, cluster onset, highest clinical classification, large/multiple GGO, numbers of lobes affected, and frequency of lobe involvement can be useful in the diagnosis of COVID-19 patients of different ages. [ABSTRACT FROM AUTHOR]

Human gaze is a subtle cue to deliver information and helps impression formation in social interactions. People automatically follow the gaze direction of others and shift their attention accordingly, as well as determine the trustworthiness of others based on the predictable validity of their gaze behavior, yet it remains unclear how this works at the collective level. Therefore, the current study is the first to explore the incidental learning of trust from a group's gaze behavior. To simulate different patterns of perceiving collective information in real life, two ways of presenting group member gazes were used in the object categorization task, the simultaneous way in Experiment 1 and the sequential way in Experiment 3, and a sampling strategy was ruled out in Experiment 2. Converging findings in experiments demonstrated a typical gaze-cueing effect, and more importantly, the Predictive-valid group obtained more trust compared to the Predictive-invalid group. To enrich and expand the applicability of the incidental trust learning effect from gazes, the current study provides supportive evidence at the collective level, confirming that humans have an efficient capability to process gaze information of groups. [ABSTRACT FROM AUTHOR]

Channel evolution and depo-center migrations in braided reaches are significantly influenced by variations in runoff. This study examines the effect of runoff variations on the erosion-deposition patterns and depocenter movements within branching channels of the near-estuary reach of the Yangtze River. We assume that variations in annual mean duration days of runoff discharges, ebb partition ratios in branching channels, and the erosional/depositional rates of entire channels and sub-reaches are representative of variations in runoff intensity, flow dynamics in branching channels, and morphological features in the channels. Our results show that the north region of Fujiangsha Waterway, the Liuhaisha branch of Rugaosha Waterway, the west branch of Tongzhousha Waterway, and the west branch of Langshansha Waterway experience deposition or reduced erosion under low runoff intensity, and erosion or reduced deposition under high runoff intensity, with the depocenters moving upstream and downstream, respectively. Other waterway branches undergo opposite trends in erosion-deposition patterns and depo-center movements as the runoff changes. These morphological changes may be associated with trends in ebb partition ratio as the runoff discharge rises and falls. By flattening the intra-annual distribution of runoff discharge, dam construction in the Yangtze Basin has altered the ebb partition ratios in waterway branches, affecting their erosion-deposition patterns and depo-center movements. Present trends are likely to continue into the future due to the succession of large cascade dams under construction along the upper Yangtze and ongoing climate change. [ABSTRACT FROM AUTHOR]

Vascular calcification is associated with cardiovascular disease as a complication of hypertension, hyperlipidemia, diabetes mellitus, and chronic kidney disease. Vitamin K2 (VK2) delays vascular calcification by an unclear mechanism. Moreover, apoptosis modulates vascular smooth muscle cell (VSMC) calcification. This paper aimed to study VK2-modified VSMC calcification and survival cell signaling mediated by growth arrest-specific gene 6 (Gas6) and its tyrosine kinase receptor Axl. Primary-cultured VSMCs were dose-dependently treated with VK2 in the presence of calcification medium for 8 days, or pre-treated for 1 h with/without the Axl inhibitor R428 (2 μmol/L) or the caspase inhibitor Z-VAD-fmk (20 μmol/L) followed by treatment with VK2 (10 μmol/L) or rmGas6 (200 nmol/L) in calcification medium for 8 days. Calcium deposition was determined by the o-cresolphthalein complexone assay and Alizarin Red S staining. Apoptosis was determined by TUNEL and flow cytometry using Annexin V-FITC and propidium iodide staining. Western blotting detected the expressions of Axl, Gas6, p-Akt, Akt, and Bcl2. VK2 significantly inhibited CaCl- and β-sodium glycerophosphate (β-GP)-induced VSMC calcification and apoptosis, which was dependent on restored Gas6 expression and activated downstream signaling by Axl, p-Akt, and Bcl2. Z-VAD-fmk significantly inhibited CaCl- and β-GP-induced VSMC calcification and apoptosis. Augmented recombinant mouse Gas6 protein (rmGas6) expression significantly reduced VSMC calcification and apoptosis. Furthermore, the Gas6/Axl interaction was inhibited by R428, which abolished the preventive effect of VK2 on CaCl- and β-GP-induced apoptosis and calcification. These results suggest that Gas6 is critical in VK2-mediated functions that attenuate CaCl- and β-GP-induced VSMC calcification by blocking apoptosis. [ABSTRACT FROM AUTHOR]

Quadrature spatial modulation (QSM), where the real and imaginary parts of the transmitted symbol are transmitted separately, was recently proposed to increase the spectral efficiency of spatial modulation. An optimum maximum likelihood (ML) detection was introduced in QSM systems, which leads to high complexity as the exhausting search of all possible transmit antennas. In this paper, a low complexity detection, called signal vector based minimum mean square error (SVMMSE), is proposed for QSM systems. In the proposed SVMMSE detection, we estimate the transmit antenna indices and the transmitted symbol by considering the active transmit antennas in two different scenarios. Simulation results show that the performance of our SVMMSE detection is very close to the ML detection and complexity analysis shows that the computational complexity of the proposed SVMMSE detection is significantly reduced compared with that of the ML detection. [ABSTRACT FROM AUTHOR]

People automatically redirect their visual attention by following others' gaze orientation, a phenomenon called 'gaze following.' This is an evolutionarily generated socio-cognitive process that provides people with information about their environments. Often, however, people in crowds can have rather different gaze orientations. This study investigated how gaze following occurs in situations with many conflicting gazes. In two experiments, we modified the gaze cueing paradigm to use a crowd rather than a single individual. Specifically, participants were presented with a group of human avatars with differing gaze orientations, and the target appeared randomly on the left or right side of a display. We found that (a) when a marked difference existed in the number of avatars with divergent gaze orientations, participants automatically followed the majority's gaze orientation, and (b) the strongest gaze cue effect occurred when all gazes shared the same orientation, with the response superiority of the majority's oriented location monotonically diminishing with the number of gazes with divergent orientations. These findings suggested that the majority rule plays a role in gaze following behavior when individuals are confronted with conflicting multigaze scenes, and that an increasing subgroup size appears to enlarge the strength of the gaze cueing effect. [ABSTRACT FROM AUTHOR]

Paraquat (1,1'-dim ethyl-4-4'-bipyridinium dichloride), a highly toxic quaternary ammonium herbicide widely used in agriculture, exerts potent toxic prooxidant effects resulting in multi-organ failure including the lung and heart although the underlying mechanism remains elusive. Recent evidence suggests possible involvement of endothelin system in paraquat-induced acute lung injury. This study was designed to examine the role of endothelin receptor A (ET) in paraquat-induced cardiac contractile and mitochondrial injury. Wild-type (WT) and cardiac-specific ET receptor knockout mice were challenged to paraquat (45 mg/kg, i.p.) for 48 h prior to the assessment of echocardiographic, cardiomyocyte contractile and intracellular Ca properties, as well as apoptosis and mitochondrial damage. Levels of the mitochondrial proteins for biogenesis and oxidative phosphorylation including UCP2, HSP90 and PGC1α were evaluated. Our results revealed that paraquat elicited cardiac enlargement, mechanical anomalies including compromised echocardiographic parameters (elevated left ventricular end-systolic and end-diastolic diameters as well as reduced factional shortening), suppressed cardiomyocyte contractile function, intracellular Ca handling, overt apoptosis and mitochondrial damage. ET receptor knockout itself failed to affect myocardial function, apoptosis, mitochondrial integrity and mitochondrial protein expression. However, ET receptor knockout ablated or significantly attenuated paraquat-induced cardiac contractile and intracellular Ca defect, apoptosis and mitochondrial damage. Taken together, these findings revealed that endothelin system in particular the ET receptor may be involved in paraquat-induced toxic myocardial contractile anomalies possibly related to apoptosis and mitochondrial damage. [ABSTRACT FROM AUTHOR]

It is important to assess the freezing and thawing condition of ground surface for understanding the impacts of frozen ground on surface and subsurface hydrology, the surface energy and moisture balance, ecosystem conservation, and engineering construction on the Qinghai–Tibet Plateau (QTP). However, assessing the changes of ground surface freezing and thawing condition on the QTP still remains a challenge owing to data sparseness and discontinuous observations. The annual ground surface freezing index (GFI) and ground surface thawing index (GTI) could be used to predict changes of the thermal regime of permafrost and can be good indicators of climate change on the QTP, which has important engineering applications. In this study, we first calibrated the reanalysis ground surface temperature (GST) data using the methods of elevation correction on the QTP. After calibration, the quality of reanalysis data has been improved significantly. For the annual time series, the root mean square error decreased from 7.7 to 1.6 °C, the absolute value of mean bias error decreased from 7.5 to 0.0 °C, and the correlation coefficient increased from 0.62 to 0.86. Second, we estimated the annual and seasonal spatial distributions of GST. The spatial distribution of spring and autumn GST closely resembled the annual mean pattern. The long-term mean GFI and GTI from the calibrated reanalysis dataset were 1322.3 and 2027.9 °C/day, respectively. The GFI and GTI were presented as latitude and elevation zonation; it can also be seen that permafrost mostly occurred in the high GFI and low GTI regions. Estimating the GFI and GTI precisely will be utilized to model the permafrost distribution and estimate active layer thickness in the future. [ABSTRACT FROM AUTHOR]

This study quantified the hydrological responses to land-use change scenarios in the upper and middle Heihe River basin (HRB), northwest China, under constant and changed climatic conditions by combining a land-use/cover change model (dynamic conversion of land use and its effects, Dyna-CLUE) and a hydrological model (soil and water assessment tool, SWAT). Five land-use change scenarios, i.e., historical trend (HT), ecological protection (EP), strict ecological protection (SEP), economic development (ED), and rapid economic development (RED) scenarios, were established. Under constant climatic condition, hydrological variations are only induced by land-use changes in different scenarios. The changes in mean streamflow at the outlets of the upper and the middle HRB are not pronounced, although the different scenarios produce different outcomes. However, more pronounced changes are observed on a subbasin level. The frequency of extreme flood is projected to decrease under the SEP scenario, while under the other scenarios, no changes can be found. Two emission scenarios (A1B and B1) of three general circulation models (HadCM3, CGCM3, and CCSM3) were employed to generate future possible climatic conditions. Under changed climatic condition, hydrological variations are induced by the combination of land-use and climatic changes. The results indicate that the impacts of land-use changes become secondary when the changed climatic conditions have been considered. The frequencies of extreme flood and drought are projected to decrease and increase, respectively, under all climate scenarios. Although some agreements can be reached, pronounced difference of hydrological responses can be observed for different climate scenarios of different GCMs. [ABSTRACT FROM AUTHOR]

This study investigated land-use and land-cover change (LUCC) and hydrological responses under consistent climate change scenarios (A1B and B1) in the Heihe River Basin (HRB), a typical arid inland river basin in northwest China. LUCC was first projected using the Dynamic Conversion of Land-Use and its Effects (Dyna-CLUE) model. Two cases (Case 1 and Case 2) were then established to quantify the hydrological responses to single climate change and the combined responses to climate change and LUCC with the Soil and Water Assessment Tool (SWAT). The results of LUCC modeling under the A1B and B1 scenarios present distinct regional characteristics and also indicate that the projected future land-use patterns are not appreciably different than the actual map for the year 2000. In Case 1, which only considers the impacts of single climate change, overall, the streamflow at the outlet of the upper HRB is projected to decline, whereas at the outlet of the middle HRB to increase, under both climate change scenarios. Meanwhile, the frequency of occurrence of hydrological extremes is expect to increase under both scenarios. In Case 2, which considers the combined impacts of climate change and LUCC, the changes in streamflow and frequency of hydrological extremes are found to be remarkably consistent with those in Case 1. The results imply that climate change rather than LUCC are primarily responsible for the hydrological variations. The role of LUCC varies with regions in the context of climate change dominated hydrological responses. [ABSTRACT FROM AUTHOR]

Berberine (BBR) confers cardioprotective effect against myocardial ischemia reperfusion injury (MI/RI). Activation of Notch1/Hairy and enhancer of split 1 (Hes1) signaling also reduces MI/RI. We hypothesize that BBR may protect against MI/RI by modulating Notch1/Hes1-Phosphatase and tensin homolog deleted on chromosome ten (PTEN)/Akt signaling. In this study, male Sprague-Dawley rats were exposed to BBR treatment (200 mg/kg/d) for 2 weeks and then subjected to MI/RI. BBR significantly improved cardiac function recovery and decreased myocardial apoptosis, infarct size, serum creatine kinase and lactate dehydrogenase levels. Furthermore, in cultured H9c2 cardiomyocytes, BBR (50 μmol/L) attenuated simulated ischemia/reperfusion-induced myocardial apoptosis. Both in vivo and in vitro study showed that BBR treatment up-regulates Notch1 intracellular domain, Hes1, Bcl-2 expression and p-Akt/Akt ratio, down-regulates Bax Caspase-3 and cleaved Caspase-3 expression. However, the anti-apoptotic effect conferred by BBR was blocked by Notch1 siRNA, Hes1 siRNA or LY294002 (the specific inhibitor of Akt signaling) in the cultured cardiomyocytes. In summary, our results demonstrate that BBR treatment attenuates MI/RI by modulating Notch1/Hes1-PTEN/Akt signaling. [ABSTRACT FROM AUTHOR]

Dysregulation of miRNA expression plays an important role in cancer development, and circulating miRNAs are biomarkers of several cancers. We explored whether the miRNAs in plasma could be useful clinical biomarkers for multiple myeloma. miRNA microarray was conducted to identify elevation of four miRNAs and reduced levels of eight miRNAs in the plasma of nine multiple myeloma patients and seven healthy controls. Increased miR-483-5p levels and decreased miR-20a were further validated in the plasma of 40 myeloma patients and 20 healthy controls using TaqMan quantitative real-time PCR. Receiver operating characteristic (ROC) analysis revealed that miR-483-5p and miR-20a had considerable diagnostic accuracy, yielding the areas under the ROC curve of 0.745 (sensitivity 58 %, specificity 90 %) and 0.74 (sensitivity 63 %, specificity 85 %), respectively. Plasma levels of miR-483-5p were associated with ISS staging. Within 14 months of diagnosis, the median progression-free survival of patients with high levels of plasma miR-483-5p was 15 months, in comparison with 21 months for patients with low levels of plasma miR-483-5p ( p = 0.025). However, miR-20a levels were not correlated with progression-free survival ( p > 0.05). miR-483-5p has the potential to be a predictor of myeloma survival. [ABSTRACT FROM AUTHOR]

In this study, we collected radiation and active layer temperature data observed in the northern Qinghai-Xizang Plateau during the period 2006-2008 in order to analyze the impact of surface energy balance on the thawing process of the active layer. Results show that surface energy exhibits an obvious seasonal variation. The largest values of energy variables including global radiation, net radiation, soil heat flux and surface heat source intensity occur during June and July, while the smallest values occur in November and December. The active layer is generally dominated by an endothermic process. During the freeze-thaw period, the variation process of the active layer temperature is similar to that of surface energy. The seasonal thawing depth is closely related to the process of surface energy exchange. During the thawing period, seasonal thawing depth gradually increases as more solar energy enters the surface. When the surface energy accumulation is 0.0 MJ m d, the seasonal thawing depth is the smallest. The seasonal thawing depth gradually increases with further accumulation of surface energy. Thus, the variation processes between the surface energy and seasonal thawing depth can be expressed by a power relation. The values of seasonal thawing depth calculated with the empirical relationship provided in this study agree well with the observed values. The relative error between calculated and observed values is less than 12 %. These results show that this empirical relationship can be successfully used to describe the behavior of active layers. [ABSTRACT FROM AUTHOR]

Interferon regulatory factor 4 (IRF4) is a member of the interferon regulatory family, which plays an important role in many lymphoid and myeloid malignancies. In the current study, using immunohistochemical staining, we found that IRF4 only expressed in plasma cells in bone marrow biopsy samples of multiple myeloma. IRF4-positive patients displayed increased disease stage (Durie-Salmon stage, p = 0.026; and International Staging System, p = 0.005). Silencing IRF4 in myeloma cell lines could inhibit myeloma cells proliferation and induce myeloma cell apoptosis, partly by JNK/Jun pathway. These results demonstrate that IRF4 plays important roles in myelomagenesis and disease progression. [ABSTRACT FROM AUTHOR]

Size matters considerably for victory and defeat during competitive situations. Drawing on the embodied theory of cognition, we examined the reciprocal association between size and competition outcomes. To do so, we used the 'rock-paper-scissors game', whose outcome is not contingent on apparent physical size. In Experiment 1, participants were asked to judge whether the target gesture was a winning or a losing one. Compared to responses in the incompatible condition (small-winner and large-loser), those in the compatible condition (large-winner and small-loser) were quicker. In Experiment 2, we asked participants to adjust the size of gestures to correspond to gestures previously presented, and found that the winning gesture was estimated as much larger than the losing one. In line with our main hypothesis, size information can interfere with judgments about competition outcomes, and vice versa, even when the outcome is unrelated to body size. [ABSTRACT FROM AUTHOR]