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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.

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

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.

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.

Soil-rock mixture (SRM) shows complicated mechanical behaviors due to their complex compositions and structures, leading to challenging instability problems during the construction process. Typical SRM are composed of rocks with high strength and fine grained soils, and the mechanical characteristic is largely controlled by the rock block proportion (RBP) and component properties. It is noted that the rock sizes of natural SRM make it difficult for laboratory or in situ tests. There are few studies on empirical formulas to predict the mechanical characteristics of SRM. In this study, the nonlinear relationship between SRM shear strength and RBP was investigated, and an empirical formula predicting the shear strength of mixtures consisted of strong rocks and a weak soil matrix was proposed. For this purpose, a database of shear strength and uniaxial compressive strength (UCS) of SRM with different RBPs was built firstly on the basis of the laboratory test results from previous literatures. In order to focus on the interactions of rock blocks and soil matrix in SRM, a RBP range of 30–90% was set as the applicable range of the empirical formula and both of the compositions are held to provide shear resistance in the applicable range. Subsequently, a nonlinear equation to calculate the shear strength of SRM with RBP range of 30–90% was proposed using regression analysis considering the strengths of components and soil-rock contact faces. Several representative properties of rocks and soil matrix, such as RBP, UCS of the matrix (UCSm), and the friction angle of the blocks (φblock), were chosen as the input parameters based on the mechanical properties of SRM. An additional parameter “A” was used to describe the connect strengths of the soil-rock contact faces. In addition, uniaxial compression tests and large-scale direct shear tests were performed on the Taoyuan SRM samples. The test results and other measured data from the database were used to compare with the corresponding estimated values. The results demonstrated that the empirical approach could predict the shear strength with R2 = 0.75 and can be considered a practical tool in engineering designs when mechanical tests are not available.

Background Accumulating evidence demonstrates that tRFs (tRNA-derived small RNA fragments) and tiRNAs (tRNA-derived stress-induced RNA), an emerging category of regulatory RNA molecules derived from transfer RNAs (tRNAs), are dysregulated in in various human cancer types and play crucial roles. However, their roles and mechanisms in hepatocellular carcinoma (HCC) and liver cancer stem cells (LCSCs) are still unknown. Methods The expression of glycine tRNA-derived fragment (Gly-tRF) was measured by qRT-PCR. Flow cytometric analysis and sphere formation assays were used to determine the properties of LCSCs. Transwell assays and scratch wound assays were performed to detect HCC cell migration. Western blotting was conducted to evaluate the abundance change of Epithelial-mesenchymal transition (EMT)-related proteins. Dual luciferase reporter assays and signalling pathway analysis were performed to explore the underlying mechanism of Gly-tRF functions. Results Gly-tRF was highly expressed in HCC cell lines and tumour tissues. Gly-tRF mimic increased the LCSC subpopulation proportion and LCSC-like cell properties. Gly-tRF mimic promoted HCC cell migration and EMT. Loss of Gly-tRF inhibited HCC cell migration and EMT. Mechanistically, Gly-tRF decreased the level of NDFIP2 mRNA by binding to the NDFIP2 mRNA 3′ UTR. Importantly, overexpression of NDFIP2 weakened the promotive effects of Gly-tRF on LCSC-like cell sphere formation and HCC cell migration. Signalling pathway analysis showed that Gly-tRF increased the abundance of phosphorylated AKT. Conclusions Gly-tRF enhances LCSC-like cell properties and promotes EMT by targeting NDFIP2 and activating the AKT signalling pathway. Gly-tRF plays tumor-promoting role in HCC and may lead to a potential therapeutic target for HCC.

Induced and natural earthquakes will put the rock underground engineering in a state of dangerous destruction during the mining of resources, such as oil and gas. The form of seismic load is regarded as a dynamic cyclic load in general. Generally, the strain rate has a significant influence on the mechanical properties of rock materials, such as strength, subjected to dynamic load and rock materials will suffer damage under cyclic loading; however, the relationship between dynamic strength and a damage variable and strain rate remains unclear when establishing the expression of strength of rock materials under action of dynamic cyclic loading. Therefore, four rock materials were chosen to study whether strain rate affects damage of rock materials subjected to damage-controlled dynamic cyclic loading. Based on the principle of energy dissipation, a modified definition of a damage variable for rock materials subjected to damage-controlled dynamic cyclic loading was proposed by considering the strength of rock materials. Using the proposed damage variable, the relationship between the damage variable at different proportions of peak strength of post-peak stage and strain rate was analyzed in detail. It can be found that the peak strength of these rock materials and the logarithm of the strain rate follow a linear relationship, however, damage variables at different proportions of peak strength of post-peak stage, such as peak strength, 80%, 60%, and 40% of peak strength, vary with different strain rates or loading frequencies. Further, the relation between strain rate/loading frequency and the damage variable of these rock materials differs from each other. Therefore, a hypothesis that no consistent relationship exists between damage variable and loading rate for rock materials when subjected to dynamic cyclic loading was proposed. On this basis, the functional expression of dynamic compressive strength of rock materials under dynamic cyclic loading with independent variables of damage and strain rate was established.

Induced seismicity might occur during underground energy and resource exploitation. Seismic waves usually attenuate during propagation across rock joints. Joint surface configuration parameters such as the joint roughness coefficient (JRC) and joint matching coefficient (JMC) play an important role in affecting stress wave propagation and dynamic property. An experimental study was conducted by using the modified Split Hopkinson Pressure Bar (SHPB) apparatus to reveal the influence of surface characteristics (i.e., JRC and JMC) on wave propagation quantitatively. The two bars of the SHPB apparatus were fabricated from high-strength gypsum. Each specimen has an artificial joint and consists of two parts produced by 3D printing. The effect of JRC and the combined effect of JRC and JMC on wave propagation and the dynamic mechanical property of joints were analyzed. The incident, transmitted and reflected waves were recorded from the strain gauges. Based on the basic theory of SHPB tests, the transmission coefficients, the stress–strain relationships and the specific stiffness of joints were obtained. According to the test results, both JRC and JMC affect stress wave propagation across joints and the joint specific stiffness to a significant extent. The results show that the transmission coefficient and specific stiffness decrease with increasing JRC (e.g., JMC = 1). In addition, for specimens with a given JRC, the transmission coefficient and specific stiffness decrease with the decrease of JMC.

This paper firstly analyzes the transmission mechanism of the wireless broadband multi-media services in the MSW-ARQ(Multi-channel Stop-and-Wait ARQ) system. Considering the real-time multimedia service's four features (high requirement for delay but allows some loss rate, the constraints of the delay and jitter), in order to meet with professional standard, we model the real-time multimedia service packet transmission as an M[X]/G/1 queuing model for MSW-ARQ. The packet transition probability is derived by constructing steady state Markov Chain based on the method of selecting the reference packet. On the basis of equivalent service delay, we also solve the packet mean service delay. Then under the given condition, we analyze the influence of the channel number and channel environments on the mean delay through numerical simulating. The characteristics and superiorities of multi-channel transmission mechanism in wireless communication are checked enough by solving the M[X]/G/1 queuing model. So this paper provides useful thought and approach for optimizing system delay and throughput by checking the change of channel environments and the used number of parallel channels.

Based on field-survey hydrological series in the Dongting Lake watershed from 1951 to 2011, the variations of lakebed sediment siltation/erosion (S/E) regimes of the Dongting Lake after the operation of the Three Gorges Reservoir (TGR) were analyzed. Significantly positive correlations were found between the flow rate from Zhicheng and the Three Outlets (r2=0.859, p

The dual-hop truncated ARQ (DHT-ARQ) and multiple relays cooperative truncated ARQ (MRCT-ARQ) with relay selection in wireless sensor networks are analytically analyzed in this paper. A three-state discrete time Markov chain method is proposed, which is then used to derive the steady state distribution and throughput expressions. Furthermore, the number of retransmission of the two protocols is truncated, and the average packet transmission delay is solved. Finally, considering the power consumptions of source node, relay node and destination node, the energy efficiency expressions are obtained. Numerical simulation results show that the throughput and delay performance of the latter is better than the former. When the channel environment becomes poor, using the DHT-ARQ protocol is more advantageous to reduce system overhead.

Objective The purpose of this study is to investigate the dosimetric advantages of volumetric modulated arc therapy (VMAT) in the treatment of intraocular cancer by comparing it directly with three-dimensional conformal radiotherapy (CRT) and intensity-modulated radiotherapy (IMRT). Methods CRT plan, 7f-IMRT plan, and one-arc VMAT plan were generated for 14 intraocular cancer patients. Dosimetric and biological quality indices for target volume and organs at risks (OARs) were evaluated and compared. Results The target coverage presented by V95 for CRT, IMRT and VMAT were 95.02% ± 0.67%, 95.51% ± 2.25%, and 95.92% ± 3.05%, respectively. The homogeneity index (HI) for CRT, IMRT and VMAT were 0.15 ± 0.05, 0.23 ± 0.05, and 0.23 ± 0.06, respectively. IMRT and VMAT greatly decreased the dose to ipsilateral lens compared with CRT with a D1 of 2972.66 ± 1407.12 cGy, 3317.82 ± 915.28 cGy and 4809.54 ± 524.60 cGy for IMRT, VMAT and CRT, respectively. Similar results were observed for ipsilateral eyeballs. IMRT and VMAT also spared better on brainstem, optical nerves and optical chiasm compared CRT. However, CRT achieved lower dose to the eyeballs compared with IMRT and VMAT. VMAT and IMRT showed mixed results on target coverage and OAR sparing. The average MUs and delivery time of IMRT and VMAT were 531.25 ± 81.21 vs. 400.99 ± 61.49 and 5.05 ± 0.53 vs.1.71 ± 0.69 min, respectively. Conclusions Although no clear distinction on PTV coverage among CRT, IMRT and VMAT plans was observed in the treatment of intraocular cancer, VMAT and IMRT achieved better homogeneity and conformity for target volume, and delivered fewer doses to ipsilateral lens and eyeballs compared with CRT. However, VMAT and IMRT increased the low dose volume to the contralateral OARs. Although VMAT and IMRT showed mixed results on target coverage and OAR sparing, VMAT decreased MU and delivery time significantly compared with IMRT. VMAT is a promising and feasible external beam radiotherapy technique in the treatment of intraocular cancer patients.

This paper presents a new Amplify-and-Forward Cooperative Automatic Repeat reQuest protocol with channel state information-assisted relay which is more suitable for the only-read access networks. The channels of any pair of terminations are quasi static flat Nakagami- $$m$$ m fading channels, which are mutually independent and non-identically distributed. Assuming that the coherent equal gain combining is adopted to combine the retransmitted signals from the same link at the destination and selective combining is adopted to the signals from different links. Based on the approximation of product of Nakagami- $$m$$ m variables, we obtain the end-to-end signal-to-noise rate of any link. The closed-form expression of the average bit error rate for several modulation schemes is obtained by analyzing cumulative distribution function (CDF) and Gaussian Q-function. Then we analyze the amount of fading of the fading channels by the $$n$$ n order moment which is obtained by CDF. Numerical simulation results show that the relay node can resist the fading of system effectively comparing with the system without relay node. And with the increasing of the number of transmission, the performance advantage of relay link is more and more obviously. It is better to let the maximum transmission time $$F=6$$ F = 6 , which is very useful for improving the transmission efficiency of the truncated ARQ system. The maximum reduction of amount of fading can be reached when $$t=3$$ t = 3 , if the total number of transmission is $$f=6$$ f = 6 . The number of bits in the frame should not have too big.

Glutathione-S-transferases mu 2 (GSTM2), a kind of important Phase II antioxidant enzyme of eukaryotes, is degraded by nonsense mediated mRNA decay due to a C27T substitution in the fifth exon of pigs. As a reproductive performance-related gene, GSTM2 is involved in embryo implantation, whereas, functional deficiency of GSTM2 induces pre- or post-natal death in piglets potentially. To have some insight into the role of GSTM2 in embryo development, high throughput RNA sequencing is performed using the swine testis cells (ST) with the deletion of GSTM2. Some embryo development-related genes are observed from a total of 242 differentially expressed genes, including STAT1, SRC, IL-8, DUSP family, CCL family and integrin family. GSTM2 affects expression of SRC, OPN, and SLCs. GSTM2 suppresses phosphorylation of STAT1 by binding to STAT1. In addition, as an important transcription factor, STAT1 regulates expression of uterus receptive-related genes including CCLs, IRF9, IFITs, MXs, and OAS. The present study provides evidence to molecular mechanism of GSTM2 modulating embryo development.

In order to determine the effect of wind-induced waves (influenced by wind velocity and direction) on the dynamics of optical properties in shallow lakes, we determined the short-term variability of the inherent optical properties (IOPs) in Meiliang Bay, Lake Taihu, China, by examining high-frequency data collected between 8 and 21 September 2010 from meteorology and optical sensors. The absorption and beam attenuation coefficients under strong winds were significantly higher than those under weak and moderate winds (t test, P

Terrestrial and aquatic ecosystem degradation is widely recognized as a major global environmental and development problem. Although great efforts have been made to prevent aquatic ecosystem degradation, the degree, extent and impacts of this phenomenon remain controversial and unclear, such as its driving mechanisms. Here, we present results from a 17-year field investigation (1998–2014) of water quality and a 12-year remote sensing mapping (2003–2014) of the aquatic vegetation presence frequency (VPF) in Eastern Lake Taihu, a macrophyte-dominated bay of Lake Taihu in China. In the past 17 years, nutrient concentrations and water level (WL) have significantly increased, but the Secchi disk depth (SDD) has significantly decreased. These changes were associated with increased lake eutrophication and a degraded underwater light climate that further inhibited the growth of aquatic vegetation. In Eastern Lake Taihu, increased nutrients, chlorophyll a and WL, and a decreased SDD were all significantly correlated with a decreased VPF. NH4+-N concentration and SDD/WL were the most important controlling factors for VPF. Therefore, increased anthropogenic nutrient inputs and a degraded underwater light climate surely result in a decreased VPF. These results elucidate the driving mechanism of aquatic vegetation degradation and will facilitate Lake Taihu ecological restoration.

Purpose To investigate the feasibility of constant dose rate volumetric modulated arc therapy (CDR-VMAT) in the treatment of nasopharyngeal cancer (NPC) patients and to introduce rotational arc radiotherapy for linacs incapable of dose rate variation. Materials and methods Twelve NPC patients with various stages treated previously using variable dose rate (VDR) VMAT were enrolled in this study. CDR-VMAT, VDR-VMAT and mutlicriteria optimization (MCO) VMAT plans were generated for each patient on RayStation treatment planning system with identical objective functions and the dosimetric differences among these three planning schemes were evaluated and compared. Non dosimetric parameters of optimization time, delivery time and delivery accuracy were also evaluated. Results The planning target volume of clinical target volume (PTV-CTV) coverage of CDR-VMAT was a bit inferior to those of VDR- and MCO-VMAT. The V93 (p = 0.01) and V95 (percent volume covered by isodose line) (p = 0.04) for CDR-VMAT, VDR-VMAT and MCO-VMAT were 98.74% ± 0.31%, 99.76% ± 0.16%, 99.38% ± 0.43%, and 98.40% ± 0.48%, 99.53% ± 0.28%, 99.07% ± 0.52%, respectively. However, the CDR-VMAT showed a better dose homogeneity index (HI) (p = 0.01) in PTV-CTV. No significant difference in other target coverage parameters was observed. There was no significant difference in OAR sparing among these three planning schemes except for a higher maximum dose (Dmax) on the brainstem for CDR-VMAT. The brainstem Dmax of CDR-VMAT, VDR-VMAT and MCO-VMAT were 54.26 ± 3.21 Gy, 52.19 ± 1.65 Gy, and 52.79 ± 4.77 Gy, respectively. The average delivery time (p

Objective To investigate the anatomic and dosimetric variations of volumetric modulated arc therapy (VMAT) in the treatment of nasopharyngeal cancer (NPC) patients based on weekly cone beam CT (CBCT). Materials and methods Ten NPC patients treated by VMAT with weekly CBCT for setup corrections were reviewed retrospectively. Deformed volumes of targets and organs at risk (OARs) in the CBCT were compared with those in the planning CT. Delivered doses were recalculated based on weekly CBCT and compared with the planned doses. Results No significant volumetric changes on targets, brainstem, and spinal cord were observed. The average volumes of right and left parotid measured from the fifth CBCT were about 4.4 and 4.5 cm3 less than those from the first CBCT, respectively. There were no significant dose differences between average planned and delivered doses for targets, brainstem and spinal cord. For right parotid, the delivered mean dose was 10.5 cGy higher (p = 0.004) than the planned value per fraction, and the V26 and V32 increased by 7.5% (p = 0.002) and 7.4% (p = 0.01), respectively. For the left parotid, the D50 (dose to the 50% volume) was 8.8 cGy higher (p = 0.03) than the planned values per fraction, and the V26 increased by 8.8% (p = 0.002). Conclusion Weekly CBCTs were applied directly to study the continuous volume changes and resulting dosimetric variations of targets and OARs for NPC patients undergoing VMAT. Significant volumetric and dosimetric variations were observed for parotids. Replanning after 30 Gy will benefit the protection on parotids.

Detailed transmission electron microscopic study has been carried out on heteroepitaxial YBa2Cu3O7/SrTiO3/YBa2Cu3O7 trilayer thin films grown on (100)SrTiO3 substrates prepared by DC and RF magnetron sputtering. The microstructural results showed the existence of somea-axis-oriented YBCO grains 20–90 nm wide in thec-axis-oriented YBCO matrix. Some of thea-axis grains in the lower YBCO thin film layer have protruded into the above SrTiO3 layer, which may cause short circuit between the two YBCO superconducting layers. This is unsuitable for the application of trilayer thin films for microelectronic devices. The defects on the surface of the substrates would also influence the growth quality of the YBCO thin films.