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Internal fixation with steel plates is a common method for the therapy of lower limb fractures. Due to the disadvantages of traditional surgical methods such as high trauma and complications, the application of robots for minimally invasive surgery has become a popular research direction. In this article, we have designed and simulated the overall structure of a steel plate internal fixation device used in conjunction with a robotic arm. Firstly, a finite element model of cortical bone drilling was established based on ABAQUS to obtain the torque and axial force when drilling the cortical bone. Then a virtual prototype of the robot-assisted lower limb bone fracture plate internal fixation device was designed, and the outer shell, drilling mechanism, nail placement mechanism, nail supply mechanism, drive mechanism, and guide sleeve were refined based on the overall mechanical structure of the device, so that the device could continuously perform drilling and nail placement. Afterward, the device was simulated based on ADAMS, and the motion curves of each component were obtained to verify the feasibility of the device’s working principle and to validate the performance of the servo. Finally, the modal analysis of the device was carried out with the finite element software ABAQUS, and the modal parameters of the first six orders were obtained, which were compared with the operating frequencies of the motor and the servo to verify that the device is not easy to resonate during normal operation, and the static strength checks of the key components were carried out, and the stress and deformation clouds and upper limits of flexural values of the components were obtained, which proved that the structure has stability.

Weak correlation between gamma passing rates and dose differences in target volumes and organs at risk (OARs) has been reported in several studies. Evaluation on the differences between planned dose-volume histogram (DVH) and reconstructed DVH from measurement was adopted and incorporated into patient-specific quality assurance (PSQA). However, it is difficult to develop a methodology allowing the evaluation of errors on DVHs accurately and quickly.To develop a DVH-based pretreatment PSQA for volumetric modulated arc therapy (VMAT) with combined deep learning (DL) and machine learning models to overcome the limitation of conventional gamma index (GI) and improve the efficiency of DVH-based PSQA.A DL model with a three-dimensional squeeze-and-excitation residual blocks incorporated into a modified U-net was developed to predict the measured PSQA DVHs of 208 head-and-neck (HN) cancer patients underwent VMAT between 2018 and 2021 from two hospitals, in which 162 cases was randomly selected for training, 18 for validation, and 28 for testing. After evaluating the differences between treatment planning system (TPS) and PSQA DVHs predicted by DL model with multiple metrics, a pass or fail (PoF) classification model was developed using XGBoost algorithm. Evaluation of domain experts on dose errors between TPS and reconstructed PSQA DVHs was taken as ground truth for PoF classification model training.The prediction model was able to achieve a good agreement between predicted, measured, and TPS doses. Quantitative evaluation demonstrated no significant difference between predicted PSQA dose and measured dose for target and OARs, except for DThe successful prediction of PSQA doses and classification of PoF for HN VMAT PSQA indicating that this DVH-based PSQA method is promising to overcome the limitations of GI and to improve the efficiency and accuracy of VMAT delivery.

Accumulating pieces of evidence suggested that immunotypes may indicate the overall immune landscape in the tumor microenvironment, which were closely related to therapeutic response. The purpose of this study was to classify and define the immune subtypes of clear cell renal cell carcinoma (ccRCC), so as to authenticate the potential immune subtypes that respond to immunotherapy. Transcriptome expression profile and mutation profile data of ccRCC, as well as clinical characteristics used in this study were obtained from TCGA database. There were significant differences in the infiltration of immune cells, immune checkpoints, and antigens between ccRCC and para-cancerous tissues. According to immune components, patients with ccRCC were divided into three immune subtypes, with different clinical and molecular characteristics. Compared with other subtypes, IS2 showed cold immune phenotype, and was associated with better survival. IS1 represented complex immune populations and was associated with poor overall survival (OS) and progression free survival (PFS). Further analysis indicated that expression of immune checkpoints also differed among the three subtypes, and was abnormally up-regulated in IS3. Pathway enrichment analysis indicated that the mTOR signaling pathway was abnormally enriched in IS3, while the TGF_BETA, ANGIOGENESIS and receptor tyrosine kinase signaling pathways were abnormally enriched in IS2. Furthermore, there was an abnormal enrichment of the epithelial-to-mesenchymal transition (EMT) signaling pathway in IS1, which may be associated with a higher rate of metastasis. Finally, SCG2 was screened as a specific antigen of ccRCC, which was not only related to poor prognosis, but also significantly associated with immune cells and immune checkpoints. In conclusion, the immune subtypes of ccRCC may provide new insights into the tumor biology and the precise clinical management of this disease.

Secchi disk depth (SDD) is a simple but particularly important indicator for characterizing the overall water quality status and assessing the long-term dynamics of water quality for diverse global waters. For this reason, countless efforts have been made to collect SDD data from the field and through remote sensing systems. Many empirical and semianalytical algorithms have been proposed to estimate SDD from different satellite images for a specific or regional water. However, the construction of a robust global SDD estimation model is still challenging due to the nonlinear response of SDD to optical properties and the complex physical and biogeochemical processes of different waters. Therefore, machine learning methods to better interpret nonlinear processes were used to improve remote sensing estimations of SDD for global lakes and reservoirs based on a global matchup dataset from Landsat TM (N = 4099), ETM+ (N = 2420), and OLI (N = 1249) covering in situ SDD from 0.01 m to over 18 m. Overall, extreme gradient boosting (XGBoost) and random forest (RF) had better SDD retrievals than back propagation neural network, support vector regression, empirical and quasi-analytical models showing high precision with mean relative error of approximately 30% and good agreements with the long-term in situ SDD in different waters with various optical properties. Our results can support long-term global-level water quality evaluation and thus making informed decisions about development policy.

Background Tumor cell density is a basic pathological feature of solid tumors. Chemotherapy, radiotherapy, and targeted therapy reduce tumor cell density, whereas unrestricted tumor cell proliferation promotes this feature. The impact of tumor cells on the microenvironment following changes in tumor cell density is still unclear. In this study, we focused on the response of key immune cell subsets to tumor cell density in hepatocellular carcinoma (HCC). Methods We determined the density of tumor and immune cells in the same area by section staining. We then identified potential mediators using polymerase chain reaction (PCR), enzyme-linked immunofluorescence assay (ELISA), 3D and co-culture, flow cytometry, and lentivirus intervention. The mechanism of lactate promotion was verified using lactate tests, bioinformatics, western blotting, and the above methods. The IL-8/DAPK1/lactate/regulatory T cell (Treg) axis was verified using a mouse liver cancer model. Tumor mutation burden was calculated using maftools in R. Results We found that the Treg/CD8 + T cell ratio is not consistent with tumor cell density in HCC, and a decreased Treg/CD8 + T cell ratio in the range of 5000–6000 cells/mm2 may elicit the possibility for immunotherapy in an immunosuppressive microenvironment. We showed that IL-8 mediates this immune fluctuation and promotes the infiltration of Tregs through the DAPK1/pyruvate kinase activity/lactate axis in HCC. Based on tumor ploidy and mutation burden data, we discussed the potential significance of immune fluctuation in the homeostasis of HCC mutation burden and proposed a “density checkpoint” and “entropy model” to describe this phenomenon. Conclusions In summary, we report the mode of infiltration of Tregs/CD8 + T cells in response to tumor cell density and provide a new theoretical basis for IL-8 as a therapeutic target and the selection of an immunotherapy window in HCC.

The cutting hills to back ditches (CHBD) project has been widely implemented since urbanization in hilly areas is steadily rising. The stability of the high-filled slope and the problem of foundation settlement deformation has become one of the vital issues for safe construction. This paper focused on the deformation evolution law and stability assessment of the high-filled deposit slope composed of the soil-rock mixture (S-RM) in the CHBD project, in Shiyan City, Hubei Province as examples. First, large-scale direct shear tests of S-RM with different rock block proportions (RBPs) under different various normal stresses were carried out, and its mechanical properties were analyzed. Next, the finite element method was used to simulate the processes of the step-by-step filling, and the deformation evolution law was analyzed. Then, the limited equilibrium method (LEM) was used to obtain the potential sliding surfaces and the corresponding safety factors of the high-filled slope, and the safety of the construction was assessed. Finally, automated monitoring of the step-by-step settlement and deep soil deformation was computerized for the typical locations, and the long-term stability of the high-filled slope was studied. The results demonstrate that the first layer of backfill in the F area contains the largest incremental settlement displacement in the y-direction, whereas the value in the G area occurs at the site of the fill layer close to the slope surface at each filling timestep. The displacement response value steadily declines with the increasing filling depth and horizontal displacement, presenting a clear spatial influence range, with the site of maximum incremental displacement as the center. After filling, the safety factors of the potential sliding surface in the F and G areas are 2.531 and 1.118, respectively, and the slope is in a stable state. The monitoring data show that the deformation mostly takes place within 10 m of the surface. The study’s findings are thought to offer technical and practical knowledge for the slope risks.

To prolong the lifetime of energy-constrained cooperative networks, radio frequency energy harvesting (RFEH) technology can effectively solve the energy constraints of nodes batteries, and we consider the maximum ratio combining (MRC) method at the destination node to improve the reliability of the link transmission. Thus, we propose the power splitting-based double-relay cooperative transmission (PSDRCT) protocol with RFEH in the decode-and-forward (DF) mode in this study. According to the transmission process of the proposed protocol, the analytical expressions of outage probability, throughput, and energy efficiency are obtained. Numerical simulation results demonstrate that the location of the relay nodes, power allocation ratio, energy conversion efficiency, and transmission power are the key factors affecting the performance of the protocol. In addition, the proposed protocol has lower outage probability than the time switching-based double-relay cooperative transmission (TSDRCT) protocol under the same power allocation ratio and energy conversion efficiency.

Lakes receive and actively process terrestrial dissolved organic matter (DOM) and play an important role in the global carbon cycle. Urbanization results in elevated inputs of nonpoint-source DOM to headwater streams. Retention of water in lakes allows time for alteration and transformation of the chemical composition of DOM by microbes and UV radiation. Yet, it remains unclear how anthropogenic and natural drivers impact the composition and biolability of DOM in non-pristine lakes. We used optical spectroscopy, Fourier transform ion cyclotron mass spectrometry, stable isotopic measurements, and laboratory bioincubations to investigate the chemical composition and biolability of DOM across two large data sets of lakes associated with a large gradient of urbanization in lowland Eastern China, encompassing a total of 99 lakes. We found that increased urban land use, gross domestic products, and population density in the catchment were associated with an elevated trophic level index, higher chlorophyll-a, higher bacterial abundance, and a higher amount of organic carbon with proportionally higher contribution of aliphatic and peptide-like DOM fractions, which can be highly biolabile. Catchment areas, water depth, lake area: catchment area, gross primary productivity, δ18O-H2O, and bacterial abundance, however, had comparatively little linkage with DOM composition and biolability. Urban land use is currently intensifying in many developing countries, and our results anticipate an increase in the level of biolabile aliphatic DOM from nonpoint sources and accelerated carbon cycling in lake ecosystems in such regions.

Long-term geological storage of carbon dioxide in underground engineering is the most economically viable option for reducing emissions of this greenhouse gas to the atmosphere. Underground engineering projects are often subjected to earthquakes during their lives, thus it is essential to investigate the deformation characteristics of surrounding rock of those underground engineering works subjected to seismic load under different confining pressures. To date, however, there have been notably few studies on the characteristics of rock materials under seismic load and the influences of seismic load on dynamic deformation properties of rock material under different confining pressures remain unclear. Therefore, a numerical study of the dynamic mechanical properties of a rock material (T2y6 marble) under Kobe seismic load with four different maximum stresses and four different confining pressures was conducted. The results show cyclic behavior, strain rate effect and damage are found in the stress-strain curves of the rock under simulated Kobe seismic load. Confining pressure can significantly limit the increases in lateral strain and volumetric strain, thus dilation can occur in the rock when the maximum stress of seismic load is large, and the confining pressure is small. Seismic load with small maximum stress cannot cause severe damage to the rock, but the influence is larger than that of static load. The maximum stress can be treated as a main factor affecting the damage to rock under seismic loads, while the effect of confining pressure thereon is smaller than that of the maximum stress. Furthermore, the relationships between deformation characteristics of the rock under these seismic loads, such as maximum strain, residual strain, plastic internal variable, deformation modulus, and maximum stress are different from that between the deformation characteristics and confining pressure.

Landslide-induced surges, as a complex type of fluid-solid coupling problem, are widespread in mountain regions and cause disastrous consequences. In order to reproduce the entire process of landslide-induced surge, by taking full advantage of material point method (MPM) in simulating large deformation of soil and gravity-driven flow of water, the two-phase double-point material point method (TPDP-MPM) was extended: a new algorithm handling the boundary without setting boundary particles was proposed. The classical submarine block-induced surge test and sand column collapse experiment were numerically simulated by the MPM and verified the effectiveness of the program. After that, the multiphase coupling process of Lituya Bay landslide-induced surge was simulated and verified the reliability of the TPDP-MPM code, which have achieved parallel computing by making use of OpenMP model. By comparing the results of numerical simulation with the model experiment, the two-phase double-point material point method can well simulate the starting, propagation, run-up and reflux stage of landslide-induced surge. Moreover, the extension mechanism of landslide-surge disaster chain in both time and space is revealed from the perspective of energy. This study provides a reliable tool for the analysis and assessment of landslide-induced surge disasters.

Background Tumor cell density is a basic pathological feature of solid tumors. Chemotherapy, radiotherapy and targeted therapy reduce tumor cell density, while unrestricted tumor cell proliferation promotes this feature. The impact of tumor cells on the microenvironment during the process of tumor cell density from low to high is still unclear. In this study, we focused on the response mode of key immune cell subsets to tumor cell density in hepatocellular carcinoma (HCC). Methods We determined the density of tumor cells and immune cells in the same area by section staining. We identified mediator through PCR, Elisa, 3D culture, co culture, flow cytometry and lentivirus intervention. The mechanism of lactate promotion was verified by lactate test kit, bioinformatic methods, western blot and the above methods. The IL-8/DAPK1/lactate/Tregs axis was verified by the mouse liver cancer model. Tumor mutation burden was calculated from maftools in R. Results We found that tumor cell density induced fluctuation in Tregs/CD8+ T cells ratio by secreting IL-8, and IL-8 promoted Tregs infiltration through DAPK1/PK activity/lactate axis. Based on tumor ploidy and mutation burden data, we discussed the potential significance of immune fluctuation in the homeostasis of HCC mutation burden and proposed “density checkpoint” and “entropy model” to describe this phenomenon. Conclusion In summary, we report the infiltration mode of Tregs/CD8+ T cells in response to tumor cell density, and the mechanism and significance of this infiltrating mode in HCC. In addition, we provide new theoretical basis for IL-8 as a therapeutic target and the selection of immunotherapy window period in HCC.

The reasonable prediction of mechanical parameters of the soil-rock mixture (S-RM) is crucial to build an engineering structure on the deposit slope. As a typical multiphase geomaterial, the emergence of rock blocks of various sizes destroys the integrity of the soil matrix and results in the complex and varied mechanical properties because of its interaction with the soil matrix. Because of the size effect, which is caused by the size restriction of traditional test apparatus, it is more challenging to measure the precise mechanical parameters of S-RM. This study proposed an approach to predicting the uniaxial compressive strength (UCS) of S-RM taking the particle size effect into account. The impact of the particle size on the mechanical behaviors of S-RM under various volumetric rock block proportion (VBP) conditions was discussed using the particle flow discrete element method from both a macroscopic and mesoscopic view. The parameter “Am” was used to describe the decreasing rate of UCS with various VBPs, and a quantitative description to predict the parameter “Am” of S-RM with various maximum particle sizes was proposed. A method to predict the UCS value of S-RM with various VBPs was conducted while taking the influence of size effect into account using the parameter “Am” and the UCS of the soil matrix.

Urbanization and agricultural land use can increase the transport of nutrients to fluvial ecosystems; yet, the overall impact of urban and nonpoint agricultural inputs on the composition, bio-lability, and the fate of fluvial dissolved organic matter (DOM) remains poorly understood. We investigated the optical and molecular composition and bio-lability of DOM in 76 streams and rivers with varying sizes of catchment area (1 ~ 4850 km2) along large gradients of urban and agricultural land use. Optical spectroscopy and Fourier transform ion cyclotron mass spectrometry (FT-ICR MS) were used to determine the chemical composition of DOM, and laboratory bio-incubations were used to assess DOM bio-lability. We found that urban and agricultural land use intensification was associated with the reduced relative contribution of DOM from pristine soils, enriched dissolved organic carbon (DOC), and higher contributions of aliphatic and peptide-like DOM, as well as enrichment of N- and S-containing molecular formulae. Specifically, FT-ICR MS revealed that the relative abundance of CHO-containing formulae decreased while that of CHOS-containing formulae increased with increasing urban land use. DOM bio-availability was higher in rivers draining urbanized and agricultural landscapes and was related to decreased DOM aromaticity and increased proportions of energy-rich aliphatic formulae. Our results suggested that DOM from urbanized and agricultural catchments significantly altered the chemical composition and bio-availability of DOM with potential effects on ecosystem metabolism and the fate of organic carbon in the downstream-linked streams and rivers. Anthropogenic disturbances may thus boost the microbial processing of organic carbon, including uptake, retention, and outgassing in the impacted ecosystems. Graphical Abstract

We compiled a nationwide dataset of carbon dioxide (CO

Reliable and efficient real-time transmission is an important and challenging issue for wireless sensor networks (WSNs). Truncated retransmission times and relay selection can effectively reduce transmission delay and improve system throughput. A new direct multisource multirelay cooperative automatic repeat request (D-MSMR-CARQ) protocol based on truncation with two relay selection methods in WSNs is analytically analyzed in this paper. Firstly, based on two different relay selection methods under the maximum ratio combining (MRC), the discrete time Markov chain (DTMC) model of D-MSMR-CARQ protocol and state space is established. Secondly, for each D-MSMR-CARQ protocol based on different relay selection method, we obtain the closed-form expressions of the system average transmission delay and the expressions of the system throughput through state transition probabilities. Finally, numerical results reveal that the first relay selection method outperforms the second relay selection method on the average transmission delay performance for the proposed protocol. More specifically, the delay performance of the proposed protocol can be improved by 13% compared with the nondirect-link protocol when the channel environment is the same; the proposed protocol improves the throughput performance by 47% compared with the nondirect protocol when the channel environment is harsh under the same simulation parameters. Furthermore, the optimal number of source nodes and relay nodes is determined.

Two new lactones, named Ardisicreolides A-B (

Calcium oxalate (CaOx) is a major contributor to urolithiasis, one of the most common urological diseases. Our previous study has shown that Klotho rs3752472 polymorphism correlates with an increased risk of CaOx-related urolithiasis in human cohorts. This study aims to identify the effect of Klotho rs3752472 polymorphism on the renal epithelium injury caused by CaOx. A rat urolithiasis model was established and validated. Renal function was assessed, and histological examination was performed. The distribution and expression of Klotho in the rat model were detected by immunohistochemical staining and western blotting analysis. A renal epithelial cell line (HK2) was used and intervened by COM crystals with several concentrations and time points. Expression of Klotho and key mediators in Wnt/β-catenin pathway were assessed by Western blotting analysis. Wide-type and mutated plasmids of Klotho rs3752472 were added in the cell culture, and the activation of Wnt/β-catenin signaling was tested. Finally, Wide-type and mutated plasmids of Klotho rs3752472 were adoptively transferred to the rat model, and the expression of Klotho was verified. In the rat model, Klotho was mainly distributed in the renal tubular area, which significantly declined in the urolithiasis group. In vitro, COM crystals significantly inhibited the expression of Klotho and induced remarkable renal epithelial cell injury. The mutation of Klotho rs3752472 can notably enhance the expression of Klotho, as well as the protection from renal epithelial cell injury and the inhibition of Wnt/β-catenin signaling pathway. After adoptively transferred to the rat urolithiasis model, similar results were observed for the mutation of Klotho rs3752472. Klotho was significantly correlated with the renal epithelial cell injury induced by CaOx crystals. Furthermore, the mutation of Klotho rs3752472 can remarkably enhance the expression of Klotho in renal tissues and cells, and subsequently protect the renal epithelial cell from the formation of CaOx crystals through the inhibition of Wnt/β-catenin signaling pathway.

Eutrophication affects bacterial communities by fueling them with nutrients and carbon sources. While the influence of physicochemical conditions on bacterial communities is well studied, little is known about how dissolved organic matter (DOM) quality affects bacterial interspecific interactions and community composition with increasing eutrophication. Here, we examined the relative importance of physicochemical conditions and chromophoric DOM (CDOM) composition for bacterial community variation across trophic gradients using 109 samples data collected in 33 lakes of the Yangtze-Huaihe River basin. We found a notable increase of bacterial abundance, elevated modularity of co-occurrence networks, and decreased habitat niche breadths from mesotrophic sites to hyper-eutrophic sites, suggesting changes in co-occurrence patterns with eutrophication. Variation partitioning revealed that the proportion purely explained by CDOM composition was higher at the moderate- and hyper-eutrophic sites than at the mesotrophic sites. Moreover, the module structures of the networks correlated significantly with CDOM composition at the eutrophic sites but not at the mesotrophic sites. The significant negative correlation between community-level habitat niche breadths and the intensities of the protein-like components at the moderate- and hyper-eutrophic sites indicates a strong association between biolabile protein-like compounds and habitat specialists in nutrient and substrate enriched lake systems. Our results suggest that consideration of DOM composition can strengthen the identification of links between environmental factors and bacterial community composition and interspecific interactions, especially under resource-rich conditions.

The Eastern Route of the South-to-North Water Diversion Project (SNWDP-ER) is a large scale multi-decade infrastructure project aiming to divert substantial amounts of water (≈45 billion m3 yr−1) to alleviate water shortage in comparatively arid regions of northern China. The project has ramifications for hydrological connectivity and biogeochemical cycling of dissolved organic matter (DOM) in regional lakes affected by the project. We carried out an extensive field sampling campaign along the SNWDP-ER in different hydrological seasons of 2018 and monthly observations in Lake Hongze and Lake Luoma from April 2018 to June 2021. We found the lakes connecting to the SNWDP-ER had higher mean DOC, specific UV absorbance, higher ratio of humic-like to protein-like fluorophores (Humic : Protein), and shallower spectral slope (S275–295) in the wet season compared to the wet-to-dry transition, and dry seasons. The southern lakes and Yangtze River had lower DOC concentration, bioavailable DOC (BDOC), and higher DOM aromaticity compared to the northern two downstream lakes. Ultrahigh-resolution mass spectrometry (FT-ICR MS) revealed higher relative abundance of CHO-containing and aromatic compounds in the Yangtze River and the southern three upstream lakes compared to the northern two lakes. The data from Lake Hongze and Lake Luoma, studied in different hydrological seasons, suggest that water delivery had high consistency in DOM composition and BDOC over the season. We conclude that positioning along the watercourse and seasonally variable hydrological conditions play an important role in influencing the DOM composition and bioavailability of key lakes connecting to the SNWDP-ER. Our results indicated that the water diversion project delivers water with low DOC concentration and higher aromaticity and thus is of higher quality since it has higher DOM removal potential during drinking water treatment.

Red bed slopes in the southwest of China are associated with a grant number of geological hazards, such as landslides, mud-rock flows, and rock blocks falling, which are vital problems in geotechnical engineering. The damage can be induced or triggered due to a series of human and environmental activities, such as excavation, concentrated or long-term rainfall, earthquake, and fluctuation of groundwater level. According to the field observations and geological exploration results, a small-scale landslide was observed on January 10, 2016, after excavation along XiaoMo highway in Yunnan Province. A numerical model in actual size using GeoStudio software based on this typical red bed engineering slope was established in this study. Back analyses and laboratory tests were used to obtain the mechanical parameters of the geomaterial inside the slope. The historic rainfall data of Mengla County from July to September in 2016 was utilized as the flux boundary in analyzing the seepage variation features and the stability of the engineering slope in the rainy season. One major tension crack was set in the shallow region of the silty clay according to the geology survey to perform the disturbance of excavation on the geomorphology of the slope. Attempts were made to establish the anisotropic permeability of the crack induced by the complex fillings, and differences in the hydraulic response between the cracking and completed slope during the rainfall process were discussed. The result shows that the factor of safety of the slope without crack before the rainfall is 1.076, and the slope is considered in the state of the critical limit equilibrium, which is in accordance with the previous state of the slope under real conditions. The pore water pressure variations of the monitor points in the shallow region of the completed slope present close compliance with the rainfall intensity subjected to different rainfall patterns, which also controls the distribution of the plastic zone in the slope after rainfall. The comparisons in the seepage field and plastic zone between the cracking and completed slope reveal that the crack can shorten the infiltration path effectively, and the higher the permeability coefficient in the vertical direction is, the larger the pore water pressure increasing zone is and the higher the underground water level is, which should be paid more attention in highway constructions.

The miR-17-92 cluster (miR-17, miR-18a, miR-19a, miR-20a, miR-19b-1 and miR-92a) contributes to the occurrence and development of various diseases by inhibiting multiple target genes. Here, we explored the effects of miR-18a on insulin sensitivity. Quantitative real-time PCR indicated that serum miR-18a levels were lower in type 2 diabetes mellitus patients than in healthy controls, suggesting that miR-18a may influence blood glucose levels. Global overexpression of miR-18a in transgenic mice increased their glucose tolerance and insulin sensitivity, while it reduced expression of the phosphatase and tensin homolog deleted on chromosome ten (PTEN) in their skeletal muscle and adipose tissue. Western blotting indicated that overexpressing miR-18a in 3T3-L1 and C2C12 cells enhanced insulin-stimulated AKT phosphorylation and suppressed PTEN expression, while inhibiting miR-18a had the opposite effects. These results suggest that miR-18a improves insulin sensitivity by downregulating PTEN. This makes miR-18a a potentially useful target for the treatment of diabetes mellitus in the future.

An accurate and reliable target volume delineation is critical for the safe and successful radiotherapy. The purpose of this study is to develop new 2D and 3D automatic segmentation models based on RefineNet for clinical target volume (CTV) and organs at risk (OARs) for postoperative cervical cancer based on computed tomography (CT) images.A 2D RefineNet and 3D RefineNetPlus3D were adapted and built to automatically segment CTVs and OARs on a total of 44 222 CT slices of 313 patients with stage I-III cervical cancer. Fully convolutional networks (FCNs), U-Net, context encoder network (CE-Net), UNet3D, and ResUNet3D were also trained and tested with randomly divided training and validation sets, respectively. The performances of these automatic segmentation models were evaluated by Dice similarity coefficient (DSC), Jaccard similarity coefficient, and average symmetric surface distance when comparing them with manual segmentations with the test data.The DSC for RefineNet, FCN, U-Net, CE-Net, UNet3D, ResUNet3D, and RefineNet3D were 0.82, 0.80, 0.82, 0.81, 0.80, 0.81, and 0.82 with a mean contouring time of 3.2, 3.4, 8.2, 3.9, 9.8, 11.4, and 6.4 s, respectively. The generated RefineNetPlus3D demonstrated a good performance in the automatic segmentation of bladder, small intestine, rectum, right and left femoral heads with a DSC of 0.97, 0.95, 091, 0.98, and 0.98, respectively, with a mean computation time of 6.6 s.The newly adapted RefineNet and developed RefineNetPlus3D were promising automatic segmentation models with accurate and clinically acceptable CTV and OARs for cervical cancer patients in postoperative radiotherapy.

Cyanobacterial blooms caused by phytoplankton Microcystis have occurred successively since 1980 in Lake Taihu, China, which has led to difficulty collecting clean drinking water. The effects of cyanobacterial scum-derived dissolved organic matter (DOM) on microbial population variations and of algal-derived filtrate and algal residual exudative organic matter caused by the fraction procedure on nutrient mineralization are unclear. This study revealed the microbial-regulated transformation of DOM from a high-molecular-weight labile to a low-molecular-weight recalcitrant, which was characterized by three obvious stages. The bioavailability of DOM derived from cyanobacterial scum by lake microbes was investigated during 80-d dark degradation. Carbon substrates provided distinct growth strategy links to the free-living bacteria abundance variation, and this process was coupled with the regeneration of different forms of inorganic nutrients. The carryover effects of Microcystis cyanobacteria blooms can exist for a long time. We also found the transformation of different biological availability of DOM derived from two different cyanobacterial DOM fractions, which all coupled with the regeneration of different forms of inorganic nutrients. Our study provides new insights into the microbial degradation of cyanobacterial organic matter using a fractionation procedure, which suggests that the exudate and lysate from degradation products of cyanobacteria biomass have heterogeneous impacts on DOM cycling in aquatic environments.

Background: PCGF4 as a cancer stem cells (CSC) marker displays stem cell-like properties, and drug resistance in hepatocellular carcinoma (HCC). PCGF2, a homologue of PCGF4, the effect of PCGF2 on liver CSCs (LCSCs) and drug resistance and the molecular mechanism of this effect have not been documented.Methods: To measure the cell viability, CSCs properties of the cells, the Cell Counting Kit-8, spheroid assay, and flow cytometry assays were applied in the HCC cell lines, respectively. The self-renewal was determined by limiting dilution assay. Also, IHC and western blotting were used to detect protein expression of PCGF2 and PCGF4 in human HCC tissues, cell lines and the effects of PCGF2 overexpression on the p38 MAPK genes expression. Kaplan-Meier curves were generated for overall survival (OS) and disease-free survival (DFS). We performed KEGG analysis on target genes through the R language cluster profiler package.Results: IHC showed that expression of PCGF4 and PCGF2 correlate inversely in HCC cell lines and HCC tumors. Overexpression of PCGF2 inhibited the stemness of HCC cells refected by decreasing sphere-forming and self-renewal capacities as well as the expression of CSCs markers. Interestingly, down-regulating PCGF4 led to similar results as up-regulating PCGF2. We also found that PCGF2 and PCGF4 oppositely regulated the stem-like properties driven by the p38 MAPK signalling pathway.Conclusion: Our results suggest that PCGF2 inhibits the stem cell population, reduces the sphere formation ability in HCC cell lines, and increases sensitivity to sorafenib by targeting p38 MAPK signalling.

Cyanobacterial bloom accumulation and dissipation frequently occur in Lake Taihu, a typically shallow, eutrophic lake due to wind wave disturbance. However, knowledge of the driving mechanisms of cyanobacterial blooms on underwater light attenuation is still limited. In this study, we collected a high-frequency in situ monitoring of the wind field, underwater light environment, and surface water quality to elucidate how cyanobacterial bloom accumulation and dissipation affect the variations in underwater light attenuation in the littoral zone of Lake Taihu. Results showed that cyanobacterial blooms significantly increased the diffuse attenuation coefficient of ultraviolet-B (K

Multi‐isocenter volumetric modulated arc therapy (VMAT) is recommended for craniospinal irradiation (CSI) to smooth the dose distribution in the junction regions relying solely on inverse optimization. However, few studies have measured the dosimetric impact of setup errors on this multi‐isocenter VMAT in the junction areas. The purpose of this study is to evaluate the impact of positional errors during VMAT CSI with two‐dimension (2D) and three‐dimension (3D) dosimetric measurements. A total of 20 patients treated by three‐isocenter VMAT CSI were retrospectively reviewed and analyzed. A 3D diode array ArcCHECK and radiochromic film EBT3 were applied to measure the percentage gamma passing rates (%GPs) and dose distributions in the junction areas between the cranial/upper‐spinal and the upper/lower‐spinal fields with intentionally introduced setup errors of ± 1 mm, ±2 mm, ±3 mm, ±5 mm, and ± 8 mm, respectively. The length and volume of planning target volume (PTV) for these CSI patients ranged from 50.14 to 80.8 cm, and 1572.3 to 2114.5 cm3, respectively. The %GPs for ±3 mm, ±5 mm, and ±8 mm positional errors were around 95%, 90%, and 85%, respectively, in the junction areas. The dosimetric verification results with EBT3 films indicated that cold and hot areas were observed with the increase of introduced setup errors. In conclusion, the dosimetric verification with intentionally introduced setup errors demonstrated that positional errors within 3 mm have a little impact for VMAT CSI, although setup errors should be minimized. Relying on the inverse optimization of VMAT to smooth the dose distribution in the junction areas is feasible for CSI.

Long-term decreases in the incident total radiation and water clarity might substantially affect the underwater light environment in aquatic ecosystems. However, the underlying mechanism and relative contributions of radiation dimming and decreasing water clarity to the underwater light environment on a national or global scale remains largely unknown. Here, we present a comprehensive dataset of unprecedented scale in China’s lakes to address the combined effects of radiation dimming and decreasing water clarity on underwater darkening. Long-term total radiation and sunshine duration showed 5.8% and 7.9% decreases, respectively, after 2000 compared to 1961–1970, resulting in net radiation dimming. An in situ Secchi disk depth (SDD) dataset in 170 lakes showed that the mean SDD significantly decreased from 1.80 ± 2.19 m before 1995 to 1.28 ± 1.82 m after 2005. SDD remote sensing estimations for 641 lakes with areas ≥ 10 km2 showed that SDD markedly decreased from 1.26 ± 0.62 m during 1985–1990 to 1.14 ± 0.66 m during 2005–2010. Radiation dimming and decreasing water clarity jointly caused an approximately 10% decrease in the average available photosynthetically active radiation (PAR) in the euphotic layer. Our results revealed a more important role of decreasing water clarity in underwater darkening than radiation dimming. A meta-analysis of long-term SDD observation data from 61 various waters further elucidated a global extensive underwater darkening. Underwater darkening implies a decrease in water quality for potable water supplies, recession in macrophytes and benthic algae, and decreases in benthic primary production, fishery production, and biodiversity.

Objective To research and assess automatic volumetric modulated arc therapy (VMAT) planning methods for patients with intraocular cancer. Methods The mdaccAutoPlan system was added to the Pinnacle3 treatment planning system as a plug‐in. Automatic VMAT plans were generated for 10 patients diagnosed with intraocular cancer, and evaluated according to standard dose‐volume histogram parameters. Results The planning target volume of enrolled patients ranges from 14.24 to 50.69 cm3. Both planning methods lead to acceptable planning target volume target coverage with a V95 of 97.9 ± 1.4% and 96.4 ± 1.5% for manual and automatic plans (P = 0.03), respectively. Automatic planning lowered the dose delivered to the ipsilateral lens and optical nerves, but increased the dose to the brainstem compared with manual planning. Automatic planning significantly prolonged VMAT planning time (3.25 ± 0.53 h vs. 1.02 ± 0.69 h, P

In a strong earthquake, not only a large number of coseismic landslides are triggered, but relaxation and cracks in the rocks and soils are induced, which make these rocks and soils vulnerable to instability during subsequent rainfall; thus, strong earthquakes always have long-term effects on landslides. The geo-hazards along the Zhaotong-Qiaojia road in the 2014 Ludian earthquake (Ms 6.5) of Yunnan Province, China, were investigated, and the Ganjiazhai giant landslide was chosen as a case study. First, using the limit equilibrium analysis and Newmark method, the critical seismic intensity of the landslide before the earthquake was evaluated. Secondly, the dynamic failure process of the landslide under the measured ground motion was simulated with the discontinuous deformation analysis method. Lastly, based on stress–seepage coupling analysis and precipitation data from Ludian meteorological station, the stability of the landslide during subsequent rainfall after the earthquake was predicted. The results show that the critical seismic intensity was within degrees VIII–IX, which is consistent with the results of the earthquake damage investigation. The dynamic failure process can be divided into four stages, and four scarps formed; the potential sliding zones during the subsequent rainfall were at the first scarp and the fourth scarp, and their critical rainfall amounts were 35–40 mm and 55–60 mm, respectively. In this paper, failure process simulation and stability prediction of the landslide before, during, and after the strong earthquake are presented, which provide analysis methods for the dynamic stability of landslides in the meizoseismal area.

Rainfall events could reduce the thermal stability of water column, deepen the mixing layer depth, and shape the thermocline in the Lake Qiandaohu. Hypoxia and anoxia initial depth increased during rainfall events, which covaried with the mixing layer depth. The impacts of rainfalls on the thermal stratification and dissolved oxygen in riverine zone were more impressive than that in transitional and lacustrine zones.

As an important traditional medicine of Buyi and Miao ethnic groups in Guizhou

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Rock materials are often subjected to medium- and low-strain-rate dynamic cyclic loading such as earthquake action; however, few dynamic constitutive models for rock materials under dynamic...