•A general framework is developed in regional heterogeneous reservoirs.•Arbitrary boundary shape is considered in the model.•New solutions for fractured horizontal well with finite conductivity are ...obtained.
The focus of this paper is to establish a new general model framework considering both hydraulic fractures with finite conductivity and heterogeneous characteristics of multiple connected regions by using boundary element method. With this framework, we can calculate the pressure performance of any heterogeneous reservoir. The innovation is that the complex fracture flow, boundary shape and heterogeneous characteristics can be flexibly considered in the model. Transient pressure of fractured horizontal wells in heterogeneous reservoir is obtained by using Stehfest numerical inversion method. Subsequently, this proposed regional heterogeneity model was validated by using numerical simulation methods. The results show that the proposed heterogeneous model can be divided into five flow segments, which are bilinear flow, linear flow, radial flow, first boundary dominated flow and second boundary dominated flow. However, the research results show that the presence or absence of some flow sections is closely related to the regional permeability ratio and the regional storage capacity ratio. As the two most important parameters of heterogeneous reservoir, the permeability ratio and regional storage capacity of heterogeneous reservoir will have a huge impact on the pressure response and pressure field. The sensitivity analysis shows that these two factors will lead to the deformation of the pressure field distribution and affect the flow characteristics, and cause some flow segments to fail to appear. The smaller the regional storage capacity ratio, the deeper the V-shape, and the more fluid supplied from the outer zone to the inner zone. This study also suggests that the fracture conductivity mainly affects the early flow characteristics, and the smaller the conductivity, the greater the pressure loss. In addition, irregular boundary will also cause important deformation of pressure field, and the area size will affect the late flow characteristics, and the smaller the area, the greater the pressure loss. The new semi-analytical solutions can form a series of typical curves and be applied to the well test analysis of multi-stage fracturing horizontal wells in heterogeneous and unconventional oil and gas reservoirs. The findings of this study can help for better understanding of the influence of reservoir heterogeneity on pressure response and find some applications in well testing for inverse problems in heterogeneous reservoirs.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
A DNA-based stimulus-responsive drug delivery system for synergetic cancer therapy has been developed. The system is built on a triplex-DNA nanoswitch capable of precisely responding to pH variations ...in the range of ∼5.0–7.0. In extracellular neutral pH space, the DNA nanoswitch keeps a linear conformation, immobilizing multiple therapeutics such as small molecules and antisense compounds simultaneously. Following targeted cancer cell uptake via endocytosis, the nanoswitch inside acidic intracellular compartments goes through a conformational change from linear to triplex, leading to smart release of the therapeutic combination. This stimuli-responsive drug delivery system does not rely on artificial responsive materials, making it biocompatible. Furthermore, it enables simultaneous delivery of multiple therapeutics for enhanced efficacy. Using tumor-bearing mouse models, we show efficient gene silencing and significant inhibition of tumor growth upon intravenous administration of the smart nanoswitch, providing opportunities for combinatorial cancer therapy.
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•A general model in discretely fractured rectangular reservoir is developed.•Flow characteristics of the complex fracture networks is analyzed in detail.•The pressure field will change significantly ...in discretely fractured reservoirs.•The effect of discharge area and eccentric position on type curves is critical.
The focus of this paper is to establish a general model, which is capable of dynamic simulation of discrete fractures at any position and arbitrary distribution in rectangular closed reservoir. In this article, a semi-analytical model for fractured horizontal wells with random distributed fracture networks is proposed to facilitate pressure transient response using a double node method. A rectangular closed reservoir model and fracture network flow model are established respectively, and then coupled at the fracture wall. In order to deal with the flow distribution at the fracture intersection, a simple adaptive material balance method is proposed in this paper, which successfully solves the flow distribution at the intersection. Using advanced mathematical means, the model is successfully solved in Laplace space, and then the pressure response solution in real space is obtained by Stehfest numerical inversion method. The obtained solutions are verified and compared with the numerical simulation results. The calculation results show that the flow characteristics of the orthogonal fracture network can be roughly divided into six stages, namely, bi-linear flow, first linear flow, first radial flow, second linear flow, second radial flow and boundary dominated flow. However, these flow characteristics will deviate or even be missing, depending on the complexity of the fracture network. Finally, the effects of some important parameters (such as dimensionless fracture network conductivity, main fracture length, fracture network density, reservoir area and eccentric position) on pressure response and pressure field distribution are discussed in detail.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Laborious and costly detection of miRNAs has brought challenges to its practical applications, especially for home health care, rigorous military medicine, and the third world. In this work, we ...present a pH-responsive miRNA amplification method, which allows the detection of miRNA just using a pH test paper. The operation is easy and no other costly instrument is involved, making the method very friendly. In our strategy, a highly efficient isothermal amplification of miRNA is achieved using an improved netlike rolling circle amplification (NRCA) technique. Large amounts of H+ can be produced as a byproduct during the amplification to induce significant changes of pH, which can be monitored directly using a pH test paper or pH-sensitive indicators. The degree of color changes depends on the amount of miRNA, making it possible for quantitative analysis. As an example, the method is successfully applied to quantify a miRNA (miR-21) in cancer cells. The results agree well with that from the prevalent qRT-PCR analysis. It is the first time that a paper-based point-of-care testing (POCT) is developed for the detection of miRNAs, which might promote the popularization of miRNAs working as biomarkers for diagnostic purposes.
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Tin phosphide (Sn4P3) nanoparticles with different sizes are synthesized via a facile solvothermal method at 180 °C for 10 h. The as-prepared Sn4P3 nanoparticles have an average size of about 15 nm. ...Meanwhile, their size could be easily controlled by the solvent ratio. The long cycle stability and rate performance of the as-obtained Sn4P3 nanoparticles have been tested as an anode material for lithium ion batteries for the first time. Electrochemical measurements show that the Sn4P3 nanoparticles with a smallest size give the best cycling and rate performances. They deliver a discharge capacity of 612 mAh g−1 after 10 cycles and could still maintain 442 mAh g−1 after 320 cycles at the current density of 100 mA g−1 within voltage limit of 0.01–3.0 V. Even after 200 cycles at a current density of 200 mA g−1, the specific capacity still could be remained at 315 mAh g−1. The improved electrochemical performances of Sn4P3 electrode might be largely attributed to their small-size. Furthermore, the as-prepared Sn4P3 nanoparticles have also been tested as an anode material for Na-ion batteries, this Sn4P3 anode can deliver a reversible capacity of 305 mAh g−1 after 10 cycles at the current density of 50 mA g−1.
The long cycle stability and TEM image of as-obtained Sn4P3 nanoparticles. Display omitted
•Sn4P3 nanoparticles were synthesized via a simple solvothermal route at 180 °C for 10 h.•The solvent ratio play crucial roles on the size modulation of Sn4P3 nanoparticles.•The long cycle stability of Sn4P3 nanoparticles is firstly reported in this study.•It is the first time to report the rate performance of Sn4P3 nanoparticles.•The Sn4P3 nanoparticles have also been applied as an anode material for Na-ion batteries.
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Lung cancer is a highly heterogeneous disease. Cancer cells and cells within the tumor microenvironment together determine disease progression, as well as response to or escape from treatment. To map ...the cell type-specific transcriptome landscape of cancer cells and their tumor microenvironment in advanced non-small cell lung cancer (NSCLC), we analyze 42 tissue biopsy samples from stage III/IV NSCLC patients by single cell RNA sequencing and present the large scale, single cell resolution profiles of advanced NSCLCs. In addition to cell types described in previous single cell studies of early stage lung cancer, we are able to identify rare cell types in tumors such as follicular dendritic cells and T helper 17 cells. Tumors from different patients display large heterogeneity in cellular composition, chromosomal structure, developmental trajectory, intercellular signaling network and phenotype dominance. Our study also reveals a correlation of tumor heterogeneity with tumor associated neutrophils, which might help to shed light on their function in NSCLC.
In electrochemical devices, such as batteries, traditional electric double layer (EDL) theory holds that cations in the cathode/electrolyte interface will be repelled during charging, leaving a large ...amount of free solvents. This promotes the continuous anodic decomposition of the electrolyte, leading to a limited operation voltage and cycle life of the devices. In this work, we design a new EDL structure with adaptive and passivating properties. It is enabled by adding functional anionic additives in the electrolyte, which can selectively bind with cations and free solvents, forming unique cation-rich and branch-chain like supramolecular polymer structures with high electrochemical stability in the EDL inner layer. Due to this design, the anodic decomposition of ether-based electrolytes is significantly suppressed in the high voltage cathodes and the battery shows outstanding performances such as super-fast charging/discharging and ultra-low temperature applications, which is extremely hard in conventional electrolyte design principle. This unconventional EDL structure breaks the inherent perception of the classical EDL rearrangement mechanism and greatly improve electrochemical performances of the device.
The proof-of-principle of an unusual fused γ-Mo
O
chain as an inorganic ligand is presented for the first time. By sharing two Mo-O edges, the γ-Mo
O
subunits are propagated into a one-dimensional ...(1D) zig-zag chain, which acts as a purely inorganic ligand binding octahedral Co(ii) centers into a two-dimensional (2D) CoMo
O
sheet. This material exhibits high initial reversible specific capacity and stable reversible capacity when applied as an anode for lithium-ion batteries (LIBs).
alterations would compromise mismatch repair pathway and increase the number of tumor-infiltrating lymphocytes and PD-L1 expression in some cancers, which would cooperate with immune checkpoint ...inhibitors (ICIs) treatment. However, a comprehensive analysis of
alteration frequency and its predictive value for ICI treatment outcome in cancers has not yet been investigated. Hence, we performed this pan-cancer analysis to evaluate the prevalence and predictive value of
alterations across >40,000 cases in multiple cancer types. We found a high frequency (6.2%) of
, which were associated with significantly higher tumor mutation burden level across various cancers. Importantly, patients with
alterations and advanced cancers had the substantially prolonged overall survival in ICI treatment cohort, suggesting it might be used to predict a survival benefit from ICI therapy across multiple cancer types. Notably,
alterations were correlated with markedly high immune infiltrates in endometrial, stomach and colon cancer. However, patients with
-mutant renal clear cell carcinoma had dramatically lower CD8
T cell infiltrations than those without, indicating the association between
alterations and immune infiltrates was cancer-dependent. Collectively, our findings highlight the important value of
alterations as pan-cancer predictive biomarkers for ICI treatment.
Although immune checkpoint inhibitors (ICIs) that target programmed cell death protein-1/programmed cell death ligand-1 axis have significantly shifted the treatment paradigm in advanced NSCLC, ...clinical benefits of these agents are limited in patients with EGFR-mutated NSCLC. Several predictive biomarkers (e.g., programmed cell death ligand-1 expression, tumor mutation burden), which have been validated in EGFR-wild type NSCLC, however, are not efficacious in EGFR-mutated tumors, suggesting the unique characteristics of tumor microenvironment of EGFR-mutated NSCLC. Here, we first summarized the clinical evidence on the efficacy of ICIs in patients with EGFR-mutated NSCLC. Then, the cancer immunogram features of EGFR-mutated NSCLC was depicted to visualize the state of cancer-immune system interactions, including tumor foreignness, tumor sensitivity to immune effectors, metabolism, general immune status, immune cell infiltration, cytokines, and soluble molecules. We further discussed the potential subpopulations with EGFR mutations that could benefit from ICI treatment. Lastly, we put forward future strategies to adequately maximize the efficacy of ICI treatment in patients with EGFR-mutated NSCLC in the upcoming era of combination immunotherapies.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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