The N-Myc-responsive lncRNA MILIP promotes DNA double-strand break repair through non-homologous end joining.

The protooncoprotein N-Myc, which is overexpressed in approximately 25% of neuroblastomas as the consequence of MYCN gene amplification, has long been postulated to regulate DNA double-strand break (DSB) repair in neuroblastoma cells, but experimental evidence of this function is presently scant. Here, we show that N-Myc transcriptionally activates the long noncoding RNA MILIP to promote nonhomologous end-joining (NHEJ) DNA repair through facilitating Ku70-Ku80 heterodimerization in neuroblastoma cells. High MILIP expression was associated with poor outcome and appeared as an independent prognostic factor in neuroblastoma patients. Knockdown of MILIP reduced neuroblastoma cell viability through the induction of apoptosis and inhibition of proliferation, retarded neuroblastoma xenograft growth, and sensitized neuroblastoma cells to DNA-damaging therapeutics. The effect of MILIP knockdown was associated with the accumulation of DNA DSBs in neuroblastoma cells largely due to decreased activity of the NHEJ DNA repair pathway. Mechanistical investigations revealed that binding of MILIP to Ku70 and Ku80 increased their heterodimerization, and this was required for MILIP-mediated promotion of NHEJ DNA repair. Disrupting the interaction between MILIP and Ku70 or Ku80 increased DNA DSBs and reduced cell viability with therapeutic potential revealed where targeting MILIP using Gapmers cooperated with the DNA-damaging drug cisplatin to inhibit neuroblastoma growth in vivo. Collectively, our findings identify MILIP as an N-Myc downstream effector critical for activation of the NHEJ DNA repair pathway in neuroblastoma cells, with practical implications of MILIP targeting, alone and in combination with DNA-damaging therapeutics, for neuroblastoma treatment.

Clusterin Is a Prognostic Biomarker of Lower-Grade Gliomas and Is Associated with Immune Cell Infiltration.

Dysregulation of clusterin (CLU) has been demonstrated in many cancers and has been proposed as a regulator of carcinogenesis. However, the roles of CLU in gliomas remain unclear. The expression of CLU was assessed using TIMER2.0, GEPIA2, and R package 4.2.1 software, leveraging data from TCGA and/or GTEx databases. Survival analysis and Cox regression were employed to investigate the prognostic significance of CLU. Immune infiltration was evaluated utilizing TIMER2.0, ESTIMATE, and CIBERSORT. The findings reveal the dysregulated expression of CLU in many cancers, with a marked increase observed in glioblastoma and lower-grade glioma (LGG). High CLU expression indicated worse survival outcomes and was an independent risk factor for the prognosis in LGG patients. CLU was involved in immune status as evidenced by its strong correlations with immune and stromal scores and the infiltration levels of multiple immune cells. Additionally, CLU was co-expressed with multiple immune-related genes, and high CLU expression was associated with the activation of immune-related pathways, such as binding to the antigen/immunoglobulin receptor and aiding the cytokine and cytokine receptor interaction. In conclusion, CLU appears to play crucial roles in tumor immunity within gliomas, highlighting its potential as a biomarker or target in glioma immunotherapy.

Prediction and control of elevated temperatures within landfills under aeration and recirculation based on the thermal non-equilibrium model.

Aeration is an effective approach to sustainable landfilling but may lead to elevated temperatures within landfills, resulting in landfill fires or explosions. Therefore, aeration is usually combined with leachate recirculation to control the elevated temperatures within landfills. To predict landfill temperatures during aeration and recirculation, a local thermal non-equilibrium model is developed considering the heat generation of biodegradation, the heat removal due to evaporation and leachate-gas flow, and the effects of the capillary. The solver is implemented in OpenFOAM based on the finite volume method and validated against a waste-column experiment and an in-situ aeration test. The simulation results demonstrate that the assumption of local thermal equilibrium will distinctly overestimate the temperature, maximally by 15 °C in the studied case. The model is then used to simulate a typical aerobic landfill unit to investigate the formation of explosive gas mixtures and elevated temperatures under different operating conditions. The simulation results of gas composition suggest that aeration will not result in explosive gas within landfills. A reasonable recirculation method for temperature control with corresponding operating parameters under a group of values of aeration pressure (2000-4000 Pa) and recirculation rate (0.0001-0.0008 m/s) are proposed, which can provide some guides for the design of an aeration and recirculation combined system. For a given total volume of added leachate, a higher recirculation rate does not always mean better cooling, and the cooling effect of continuous recirculation is better than that of intermittent recirculation.

Influence of arginine on the biocontrol efficiency of Metschnikowia citriensis against Geotrichum citri-aurantii causing sour rot of postharvest citrus fruit.

This study investigated the effect of arginine (Arg) on the antagonistic activity of Metschnikowia citriensis against sour rot caused by Geotrichum citri-aurantii in postharvest citrus, and evaluated the possible mechanism therein. Arg treatment up-regulated the PUL genes expression, and significantly induced the pulcherriminic acid (PA) production of M. citriensis, which related to the capability of iron depletion of M. citriensis. By comparing the biocontrol effects of Arg-treated and untreated yeast cells, it was found that Arg treatment significantly enhanced the biocontrol efficacy of M. citriensis, and 5 mmol L-1 Arg exerted the best effect. Additionally, the biofilm formation ability of M. citriensis was greatly enhanced by Arg, and the higher population density of yeast cells in citrus wounds was also observed in Arg treatment groups stored both at 25 °C and 4 °C. Moreover, Arg was shown to function as a cell protectant to elevate antioxidant enzyme activity [including catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPX)] and intracellular trehalose content to resist oxidative stress damage, that directly helped to enhance colonization ability of yeasts in fruit wounds. These results suggest the application of Arg is a useful approach to improve the biocontrol performance of M. citriensis.

Distribution and Characteristics of Human Plague Cases and Yersinia pestis Isolates from 4 Marmota Plague Foci, China, 1950-2019.

We analyzed epidemiologic characteristics and distribution of 1,067 human plague cases and 5,958 Yersinia pestis isolates collected from humans, host animals, and insect vectors during 1950-2019 in 4 Marmota plague foci in China. The case-fatality rate for plague in humans was 68.88%; the overall trend slowly decreased over time but fluctuated greatly. Most human cases (98.31%) and isolates (82.06%) identified from any source were from the Marmota himalayana plague focus. The tendency among human cases could be divided into 3 stages: 1950-1969, 1970-2003, and 2004-2019. The Marmota sibirica plague focus has not had identified human cases nor isolates since 1926. However, in the other 3 foci, Y. pestis continues to circulate among animal hosts; ecologic factors might affect local Y. pestis activity. Marmota plague foci are active in China, and the epidemic boundary is constantly expanding, posing a potential threat to domestic and global public health.

Cofilin-2 Acts as a Marker for Predicting Radiotherapy Response and Is a Potential Therapeutic Target in Nasopharyngeal Carcinoma.

BACKGROUND The purpose of this study was to determine whether cofilin-2 could serve as a protein marker for predicting radiotherapy response and as a potential therapeutic target in nasopharyngeal carcinoma (NPC). MATERIAL AND METHODS Cofilin-2 protein levels in serum and tissue samples from patients with NPC were assessed by sandwich ELISA and IHC. In vitro, cofilin-2 levels in CNE-2R cells were significantly higher than those of CNE-2 cells. Meanwhile, CNE-2R cells were silenced for cofilin-2 to obtain a stable cofilin-2-RNAi-LV3 cell line. Then, cell proliferation, radiosensitivity, invasion and migration abilities, cell cycle, and apoptosis were evaluated by Cell Counting Kit 8 assay (CCK-8), flow cytometry (FCM), clone formation assay, and in vitro. RESULTS The secreted levels of the cofilin-2 protein in radioresistant NPC patients were significantly higher than those of radiosensitive cases. After cofilin-2 knockdown in nasopharyngeal carcinoma CNE-2R cells, proliferation was decreased, while apoptosis and radiosensitivity were enhanced; cell cycle distribution was altered, and the transplanted tumors in nude mice grew significantly less. CONCLUSIONS Overall, our findings suggest that cofilin-2 acts as a marker for predicting radiotherapy response and is a potential therapeutic target in nasopharyngeal carcinoma.

Controlling soft rot of green pepper by bacteriocin paracin wx3 and its effect on storage quality of green pepper.

A bacteriocin paracin wx3 was investigated as a candidate of natural preservative to control green pepper soft rot. Firstly, paracin wx3 was heterologously expressed in Pichia pastoris X33 with an improved yield of 0.537 g/L. Its size and amino acid sequence were confirmed by Tricine-SDS-PAGE and LC-MS/MS. Then, result of antibacterial activity showed that its MIC value against Pectobacterium carotovorum was 16 µg/mL. In vitro, paracin wx3 completely killed the pathogen at high concentrations ≥8 × MIC. In vivo, disease incidence of green pepper soft rot was decreased from 90% (control) to <2% (8 × MIC). Subsequently, results of action mode showed that paracin wx3 inhibited the growth of pathogen by pore-formation on cell membrane. Last, paracin wx3 treatment reduced losses of weight, firmness, total soluble solid, Vc of green pepper during storage. It also inhibited the production of soft rot volatile p-xylene, 1-butanol, 2-methyl-2-propanol, 3-hydroxybutan-2-one-D, 2-pentyl furan, butanal, etc.

Study of LFG bubble accumulation and discontinuous flow in the highly saturated region of landfill below the leachate level.

Landfills in developing countries are typically characterized by high waste water content and elevated leachate levels. Despite the ongoing biodegradation of waste in the highly saturated regions of these landfills, which leads to gas accumulation and bubble formation, the associated gas pressure that poses a risk to landfill stability is often overlooked. This paper introduces a landfill gas (LFG) bubble generation model and a two-fluid model that considers bubble buoyancy and porous medium resistance. The entire process can be divided into two stages based on the force balance and velocity of bubbles: Bubble Development Stage and the Two-Fluid Flow Stage. The models were validated using a one-dimensional analytical solution of hydraulic distribution that considers bubble generation, as well as an experiment involving air injection into a saturated medium. The mechanisms of LFG accumulation and ascent, leachate level rise, and discontinuous leachate-gas flow were then investigated in conjunction with continuous flow in the unsaturated region. The results indicate that the generation of LFG bubbles below the leachate level can cause a rise in the level height of more than 20%. During the Bubble Development Stage, there is a critical height for bubble ascent, above which the buoyancy exceeds the combined forces of gravity and resistance, resulting in less than 10% of bubbles continuously flowing into the unsaturated zone for recovery. The developed model effectively captures the accumulation and flow of LFG bubbles below the leachate level and could be further utilized to study leachate-gas pumping in the future.

Analytical model for the mitigation of VOC vapor with horizontal permeable reactive barrier in the contaminated site considering non-uniform source.

Volatile organic compounds (VOCs) contamination at the groundwater may cause vapor intrusion and pose significant threats to human health. As a novel low-carbon mitigation technology, a horizontal permeable reactive barrier (HPRB) is proposed to remove the VOC vapor in the vadose zone and mitigate the vapor intrusion risk. To estimate the performance of HPRB in the contaminated site with a non-uniform source, a transient two-dimensional analytical model is developed in this study to simulate the VOC vapor migration and oxidation processes in the layered soil. The analytical model is verified against the experimental results and numerical simulation first and the parameter study is then conducted. The HPRB has good performance for the contaminated sites involving factors including deep source and local soil with low effective diffusivity. To consider the vertical heterogeneity of the local soil, the traditional equivalent homogeneity method has limitations in considering the horizontal migration of VOC vapor and is not suitable for the two-dimensional model. On the contrary, the artificial layered method based on the proposed analytical model has better accuracy and is recommended to be adopted in practice. Leading to the exponential decrease in the VOC vapor concentration at the ground surface, increasing the thickness of HPRB is an effective measure to enhance the performance of HPRB. The fitting exponential function can be applied to determine the minimum design value of the thickness of HPRB in practice.

MILIP Binding to tRNAs Promotes Protein Synthesis to Drive Triple-Negative Breast Cancer.

Patients with triple-negative breast cancer (TNBC) have a poor prognosis due to the lack of effective molecular targets for therapeutic intervention. Here we found that the long noncoding RNA (lncRNA) MILIP supports TNBC cell survival, proliferation, and tumorigenicity by complexing with transfer RNAs (tRNA) to promote protein production, thus representing a potential therapeutic target in TNBC. MILIP was expressed at high levels in TNBC cells that commonly harbor loss-of-function mutations of the tumor suppressor p53, and MILIP silencing suppressed TNBC cell viability and xenograft growth, indicating that MILIP functions distinctively in TNBC beyond its established role in repressing p53 in other types of cancers. Mechanistic investigations revealed that MILIP interacted with eukaryotic translation elongation factor 1 alpha 1 (eEF1α1) and formed an RNA-RNA duplex with the type II tRNAs tRNALeu and tRNASer through their variable loops, which facilitated the binding of eEF1α1 to these tRNAs. Disrupting the interaction between MILIP and eEF1α1 or tRNAs diminished protein synthesis and cell viability. Targeting MILIP inhibited TNBC growth and cooperated with the clinically available protein synthesis inhibitor omacetaxine mepesuccinate in vivo. Collectively, these results identify MILIP as an RNA translation elongation factor that promotes protein production in TNBC cells and reveal the therapeutic potential of targeting MILIP, alone and in combination with other types of protein synthesis inhibitors, for TNBC treatment. SIGNIFICANCE: LncRNA MILIP plays a key role in supporting protein production in TNBC by forming complexes with tRNAs and eEF1α1, which confers sensitivity to combined MILIP targeting and protein synthesis inhibitors.

Influence mechanism of thermally enhanced phase change on heat transfer and soil vapour extraction.

Thermal enhanced soil vapour extraction (T-SVE) is a remedial technique involving gas, aqueous, solid and nonaqueous phases along with mass and heat transfer. Interphase mass transfer of contaminants and water evaporation/condensation will cause the redistribution of phase saturation, eventually affecting the performance of T-SVE. In this study, a multiphase, multicompositional and nonisothermal model was developed to simulate the T-SVE treatment of contaminated soil. The model was calibrated using published data from the SVE laboratory and T-SVE field experiments. The temporal and spatial distributions of the contaminant concentrations in the four different phases, the mass transfer rates and the temperatures are presented to reveal the coupling interactions that occur between multiple fields during T-SVE. A series of parametric studies were carried out to investigate the effect of water evaporation and adsorbed/dissolved contaminants on the T-SVE performance. It was found that endothermic evaporation, exothermic condensation and the interaction between different removal paths of a contaminant played critical roles in the thermal enhancement of SVE. Ignoring them can result in significant differences in the removal efficiency values.

Modeling the spreading and remediation efficiency of slow-release oxidants in a fractured and contaminated low-permeability stratum.

Traditional remediation technologies cannot well remediate the low permeability contaminated stratums due to the limitation in the transport capacity of solute. The technology that integrates the fracturing and/or slow-released oxidants can be a new alternative, and its remediation efficiency remains unknown. In this study, an explicit dissolution-diffusion solution for the oxidants in control release beads (CRBs) was developed to describe the time-varying release of oxidants. Together with advection, diffusion, dispersion and the reactions with oxidants and natural oxidants, a two-dimensional axisymmetric model of solute transport in a fracture-soil matrix system was established to compare the removal efficiencies of CRB oxidants and liquid oxidants and to identify the main factors that can significantly affect the remediation of fractured low-permeability matrix. The results show that CRB oxidants can achieve a more effective remediation than liquid oxidants under the same condition due to the more uniform distribution of oxidants in the fracture and hence a higher utilization rate. Increasing the dose of the embedded oxidants can benefit the remediation to some extent, while at small doses the release time over 20 d has little impact. For extremely low-permeability contaminated stratums, the remediation effect can be significantly improved if the average permeability of the fractured soil can be enhanced to more than 10-7 m/s. Increasing the injection pressure at a single fracture during the treatment can enlarge the influence distance of the slow-released oxidants above the fracture (e.g., 0.3-0.9 m in this study) rather than below the fracture (e.g., 0.3 m in this study). In general, this work is expected to provide some meaningful guidance for the design of fracturing and remediating low permeability contaminated stratums.

[Study on mechanism of traditional Chinese medicines reducing phlegm and resolving masses in treatment of goiter].

OBJECTIVE: To discuss the mechanism of traditional Chinese medicines reducing phlegm and resolving masses in treatment of iodine deficiency-induced goiter by observing the expression of growth factors and the balance-regulating mechanism of proliferation and apoptosis. METHOD: 180 four-week-old Wistar rats were selected to establish the iodine deficiency model. After the modeling, the rats were randomly divided into six groups: the normal control group, the model control group, the iodine group, the phlegm compound group, the L-T4 group and the phlegm compound and L-T4 group. At the 21st day and 77th day after administration, 15 rats in each group were killed to collect specimens. Doses were calculated and adjusted according to body surface area and body weight. TT3, TT4 radioimmunoassay, TSH, immunoradiometric method were adopted. Fas, FasL and PCNA protein expressions are detected using immunohistochemical methods. RESULT: Compared with the normal group and the model group, the expressions of fas and FasL in the phlegm Group significantly increased, the expressions of fas and FasL in the phlegm and L-T4 group were also increased significantly. The expression of fas in the L-T4 Group was significantly lower than that of the L-T4 group and the phlegm compound and L-T4 group. Compared with the normal group, the expression of PCNA of the phlegm group and the phlegm and L-T4 group was significantly lower. Compared with the model group, the expression of PCNA of the iodine group, the phlegm groups and the phlegm and L-T4 group were significantly lower. Compared with the normal group, the expression of VEGF in the iodine group significantly decreased after treatment. Compared with the iodine group, the expression of VEGF in the phlegm group and the L-T4 group significantly reduced. Compared with the normal group, the expression of TGF-beta1 in the model group and the phlegm group significantly increased. Compared with model group, the expression of TGF-beta1 in the iodine group significantly reduced. Compared with the phlegm group, the expression of TGF-beta1 in the phlegm compound and L-T4 group was significantly reduced. CONCLUSION: Traditional Chinese medicines reducing phlegm and resolving masses can completely recover goiter by promoting apoptosis of thyroid cells, inhibiting their proliferation and the expression of growth factors and enhancing the expression of TGF-beta, without causing injury on thyroid cells.

Forward and back diffusion of reactive contaminants through multi-layer low permeability sediments.

Contaminants stored in the low permeability sediments will continue to threaten the adjacent shallow groundwater system after the aquifer is remediated. Understanding the storage and discharge behavior of contaminants in the aquitards is essential for the efficient remediation of contaminated sites, but most of the previous analytical studies focused on nonreactive solutes in a single homogenous aquitard. This study presents novel analytical solutions for the forward and back diffusion of contaminants through multi-layer low permeability sediments considering abiotic and biotic environmental degradation. Three representative source depletion patterns (i.e., instantaneous, linear, and exponential patterns) were selected to describe the dissolution of dense non-aqueous phase liquids (DNAPL) in the aquifer more realistically. At the forward diffusion stage, the mass storage of contaminants in the aquitards with the instantaneous pattern is the largest, nearly twice that with the exponential pattern. A simple equivalent homogeneous model is generally adopted in the risk assessment. However, relative to the proposed multi-layer model, it will significantly underestimate the onset of the back-diffusion of heterogeneous aquitards and overestimate the persistence of aquifer plumes. The previously-reported semi-infinite boundary assumption is also not applicable, with a maximum error of over 200% in the long-term prediction of back diffusion behavior of a thin aquitard. Moreover, when the degradation half-life is less than 16 years, less than 10% of the contaminants stored in the aquitards will diffuse into the overlying aquifer, suggesting that biostimulation or bioaugmentation can effectively mitigate back-diffusion risk. Overall, the proposed diffusion-reaction coupled model with multi-layer media is of great value and high demand in predicting the back-diffusion behavior of heterogeneous aquitards and guiding the soil bioremediation.

Enhanced delivery of amendments in fractured clay sites based on multi-point injection: An analytical study.

Fracturing technology that can enhance the delivery of amendments has attracted attention in the remediation of low-permeability contaminated sites. However, there are few works on the enhanced delivery of amendments based on multi-point injection in a fracture-matrix system. This study develops a two-dimensional analytical model for enhanced delivery of amendments in a finite-domain low-permeability matrix through multi-point injection in a natural, hydraulic or pneumatic fracture. The mechanisms of advection, diffusion, dispersion, sorption and degradation are considered in the model and any injection form (e.g., pulse injection, periodic injection or slow-release injection) can be embedded to obtain a specified solution. Then, a new linear factor R*, which is the ratio of the peak concentration to the trough concentration on the same plane, is introduced to evaluate the concentration fluctuation in the fracture and matrix. Results show that with a stronger line source formed in the fracture right after injection (corresponding to a small R*), the concentration distribution of amendments in the matrix is more uniform at each depth resulting in a smaller residual rate, i.e., (R*-1) × 100%. If the injection wells have been installed unreasonably (e.g., a too large spacing), the continuous injection time is an effective controllable parameter to compensate for this defect. Moreover, a controlled slow-release system can maintain a more stable concentration distribution in the fracture than continuous injection and periodic injection systems, giving a longer residence time. Overall, this work is expected to provide some interesting guidelines for the design of multi-point injection in the fracturing low-permeability sites to enhance the remediation of contaminated soil.

Transient migration behavior of VOC vapor in layered unsaturated soils subjected to multiple time-dependent point pollution sources: Analytical study.

Predicting the migration behavior of volatile organic compounds (VOCs) vapor is essential for the remediation of subsurface contamination such as soil vapor extraction. Previous analytical prediction models of VOCs migration are mostly limited to constant-concentration nonpoint sources in homogeneous soil. Thus, this study presents a novel analytical model for two-dimensional transport of VOCs vapor subjected to multiple time-dependent point sources involving transient diffusion, sorption and degradation in layered unsaturated soils. Two representative time-dependent sources, i.e., an instantaneous source and a finite pulse source, are used to describe the short-term and long-term leakage. Results reveal that soil heterogeneity can cause pollution accumulation, especially in low-diffusivity capillary fringe. The assumption of an equivalent plane source from multiple point sources would significantly overestimate the vapor concentration and the contaminated range. The previous single point source model is no longer inapplicable when the relative distance and/or the release interval between sources is small, giving a strong interaction between multiple sources. Moreover, a faster vapor degradation rate or a higher groundwater level will reduce the area of vapor plume linearly. Hence, close attention should be paid to the time-variation characteristics of multiple sources, the vapor degradation and the groundwater level fluctuation in practice to facilitate soil remediation. The proposed model is a promising tool for addressing the above issue.

[Intraoperative IPC combined with 3M warming instrument to prevent lower extremity deep venous thrombosis in patients undergoing proximal femoral anti rotation intramedullary nailing].

OBJECTIVE: To explore the effect of intermittent pneumatic compression(IPC) combined with 3M thermometer on the prevention of deep venous thrombosis(DVT) in patients with femoral intertrochanteric fracture. METHODS: From March 2016 to August 2019, 127 patients with femoral intertrochanteric fractures who underwent proximal femoral nail antirotation(PFNA) were retrospectively analyzed. They were divided into two groups according to different methods of thrombus prevention and treatment. Among them, 63 patients in group A did not use IPC and 3M thermometer;64 cases in group B were treated with IPC combined with 3M thermometer. Color Doppler ultrasound was used to dynamically monitor the DVT and changes of lower limbs during perioperative period. The venous thrombosis of lower limbs was monitored at 0, 24, 72 h and > 72 h after operation(recheck every 3 days until discharge). RESULTS: Occurrence of DVT of lower limbs after PFNA operation in two groups:there were 5 cases (7.8%) in group B and 20 cases (31.7%) in group A, there was significant difference between two groups (P=0.001). There was no significant difference in lower limb DVT between two groups at 0, 72 and > 72 h after operation(P>0.05), but the formation rate of group A was significantly higher than that of group B at 24 h after operation (P=0.049). There was no significant difference in DVT formation between group A and group B(P>0.05). However, the formation of DVT in group A was significantly higher than that in group B(P=0.012). CONCLUSION: Intraoperative IPC combined with 3M thermostat can effectively prevent DVT of lower limbs in patients undergoing PFNA surgery.

Design method of a modified layered aerobic waste landfill divided by coarse material.

To overcome the weaknesses of traditional landfills, a modified aerobic landfill concept with intermediate covers of coarse material between waste layers functioning as facilities of drainage and aeration has been proposed recently. In this study, a one-dimensional coupled model, including aerobic biodegradation, oxygen diffusion, and advection, is proposed to describe oxygen distribution in this new type of landfill. Homotopy analysis method and perturbation method are applied to solve this model at passive aeration and active aeration, respectively. The model has six input variables, that is, oxygen diffusion coefficient, gas permeability, maximum oxygen consumption rate, layer thickness of waste, and injection pressure and extraction pressure. A combination of their typical values gives rise to over 700,000 scenarios which can be calculated by the proposed solution. The coupled effect of the above variables on oxygen migration is quantitatively investigated, followed by an estimation formula of the minimum oxygen concentration in waste layer. The maximum waste layer thickness is defined as a function of other variables for a given aeration target of oxygen volume concentration larger than 5%. A generalized design method of waste layer thickness, injection pressure, and extraction pressure is then developed for the newly proposed modified layered aerobic landfill, which can promote its popularization and application.

The pan-cancer lncRNA PLANE regulates an alternative splicing program to promote cancer pathogenesis.

Genomic amplification of the distal portion of chromosome 3q, which encodes a number of oncogenic proteins, is one of the most frequent chromosomal abnormalities in malignancy. Here we functionally characterise a non-protein product of the 3q region, the long noncoding RNA (lncRNA) PLANE, which is upregulated in diverse cancer types through copy number gain as well as E2F1-mediated transcriptional activation. PLANE forms an RNA-RNA duplex with the nuclear receptor co-repressor 2 (NCOR2) pre-mRNA at intron 45, binds to heterogeneous ribonucleoprotein M (hnRNPM) and facilitates the association of hnRNPM with the intron, thus leading to repression of the alternative splicing (AS) event generating NCOR2-202, a major protein-coding NCOR2 AS variant. This is, at least in part, responsible for PLANE-mediated promotion of cancer cell proliferation and tumorigenicity. These results uncover the function and regulation of PLANE and suggest that PLANE may constitute a therapeutic target in the pan-cancer context.

Effect of LCRS clogging on leachate recirculation and landfill slope stability.

Vertical wells are commonly used for recirculating leachate into a landfill which can offer significant environmental and economic benefits. However, in some cases, the leachate collection and removal system (LCRS) at the bottom is overloaded and clogged due to biological and chemical processes. This results in a relatively high leachate level which could pose a threat to landfill slope stability. This study develops a three-dimensional landfill slope model with vertical recirculation wells and then investigates the effect of LCRS clogging on leachate recirculation and slope stability in terms of leachate saturation, pore water pressure, and factor of safety (FS) of a landfill slope. The results show that with an increase in clogging level that is characterized by an increased leachate level, the pore water pressure below the well injection screen is significantly increased by leachate recirculation, giving rise to a decreased slope FS value. In such conditions, the landfill slope formed by highly anisotropic waste is more likely to suffer instability. To prevent this kind of slope failure, a safe injection pressure of vertical recirculation wells is proposed for a wide range of parameter combinations involving waste anisotropy, clogging level, and the setback distance from the slope surface. This design guideline can be used to control the injection pressure in leachate recirculation applications and contributes to a better understanding of the slope stability of a bioreactor landfill.