Triblock polyadenine-based electrochemical aptasensor for ultra-sensitive detection of carcinoembryonic antigen via exonuclease III-assisted target recycling and hybridization chain reaction.

Carcinoembryonic antigen (CEA), a key colon biomarker, demands a precise detection method for cancer diagnosis and prognosis. This study introduces a novel electrochemical aptasensor using a triblock polyadenine probe for ultra-sensitive detection of CEA. The method leverages Exonuclease III (Exo III)-assisted target recycling and hybridization chain reaction. The triblock polyadenine probe self-assembles on the bare gold electrode through the strong affinity between adenine and gold electrode, blocking CEA diffusion and providing a large immobilization surface. CEA binding to hairpin probe 1 (HP1), followed by the hybridization between HP1 and hairpin probe 2 (HP2), triggers DNA cleavage by Exo III, amplifying the signal via a hybridization chain reaction and producing numerous dsDNA walkers that generates a dramatic electrochemical impedance signal. Under optimized conditions, the aptasensor achieved two ultra-low detection limits: 0.39 ag∙mL-1 within the concentration range of 5 ag∙mL-1 to 5 × 106 ag∙mL-1, and 1.5 ag∙mL-1 within the concentration range of 5 × 106 ag∙mL-1 to 1 × 1010 ag∙mL-1. Its performance in human serum samples meets the practical standards, offering a promising new tool for ultrasensitive tumor marker detection, potentially revolutionizing early cancer diagnosis.

Molecular mechanism of elemental sulfur dissolution in H2S under stratal conditions.

Resulting from the solubility reduction of elemental sulfur during the development of high sulfur gas formations, sulfur deposition often occurs to reduce the gas production and threaten the safety of gas wells. Understanding the dissolution mechanism of elemental sulfur in natural gas is essential to reduce the risk caused by sulfur deposition. Because of the harsh conditions in the high-sulfur formations, it remains challenging to in situ characterize the dissolution-precipitation processes, making deficient the knowledge of sulfur dissolution mechanism. The dissolution of sulfur allotropes (SN, N = 2, 4, 6 and 8) in H2S, the main solvent of sulfur in natural gas, is studied in this work by means of first-principles calculations and molecular dynamics simulations. While S6 and S8 undergo physical interaction with H2S under the conditions corresponding to those at 1-6 km stratigraphic depths, S2 and S4 react with H2S and form stable polysulfides. Unravelling the mechanism would be helpful for understanding and controlling the sulfur deposition in high-sulfur gas development.

Solubility evolution of elemental sulfur in natural gas with a varying H2S content.

CONTEXT: The solubility variations of elemental sulfur are of great importance in the prevention of sulfur deposition during the development of high-sulfur gas formations. It has been observed that the solubility varies with H2S content, which is the main solvent of elemental sulfur in natural gas. Moreover, the addition of small amounts of CH4 and/or CO2 in H2S leads to a dramatic solubility reduction of which the mechanism remains unclear. Using a modified direct coexistence method, molecular dynamics simulations are conducted to uncover the molecular mechanism of the solubility reduction. The observed solubility variations with H2S content are reproduced, and the solubility reduction is interpreted by the antisolvent effect of CH4 and CO2. While the H2S content varies in a wide range in the known high-sulfur gas formation, our simulations provide useful information for controlling the sulfur deposition in gas development. METHODS: Molecular dynamics simulations are carried out using the LAMMPS package. The initial models are constructed with the Packmol software. The Ballone and Jones' potential is used for S8, the Galliero's potential for H2S and CO2, and the transferable potentials for phase equilibria-united atom (TraPPE-UA) force field for CH4. The time step is set to 1 fs, and the molecular trajectories of additional 2 ns after equilibrium are collected for analysis.

Effects of void defects on the mechanical properties of biphasic calcium phosphate nanoparticles: A molecular dynamics investigation.

Porous biphasic calcium phosphate (BCP) ceramics are widely used in bone tissue engineering, and the mechanical properties of BCP implants must be reliable. However, the effects of pore structure (e.g., shape and size) on the mechanical properties are not well understood. In this study, we used molecular dynamics simulations to investigate the influence of pore shape and size on the mechanical behavior of BCP nanoparticles. BCP void models with cylindrical and cuboid pores ranging from 2 to 16 nm in diameter were constructed, and the elastic moduli were calculated. In addition, uniaxial tensile and compressive tests were performed on the models. We found that the pore size had a more significant impact on the mechanical properties of BCP than pore shape. Further, the elastic moduli decreased nonlinearly with increasing pore size. In addition, the tensile and compressive strength also decreased with the increase in pore size, but the ductility improved. Furthermore, deformation and fracture were more likely to occur near the pores and at the phase interfaces as a result of high atomic local strain in the calcium-deficient hydroxyapatite area. The results of this work reveal the effects of pore parameters on the mechanical properties of porous BCP at the nanometer level, which may aid the design of improved porous and multiphase CaP-based biomaterials for bone regeneration.

Shell effects on the dielectric properties of core-shell quantum dots.

The dielectric properties in semiconductor quantum dots are crucial for exciton formation, migration, and recombination. Different from 3D bulk materials, the dielectric response is, however, ambiguous for the small-sized 0D dots in which the effect of outer atoms on the inner atoms is usually described qualitatively. Based on the first-principles calculated electron density, the polarizability of the core-shell CdSe@ZnS wurtzite quantum dots is decomposed into the distributional contributions among which the dipole polarizability of the core is proposed to measure the shell effect on the dielectric properties of core-shell quantum dots. The shell thickness dependence on the shell effect is then studied, which is significant for the outermost shell but decays rapidly in the additional shells. Moreover, this model gives explicit physical origins of the core dipole polarizability in the core-shell QDs, which is determined by the intra-shell polarization and inter-core-shell charge transfer. Our study proposes a new approach for studying the dielectric properties of core-shell quantum dots, which is effective and extendable for other low-dimensional structures.

Adult Bone Marrow-Derived Mesenchymal Stem Cells Seeded on Tissue-Engineered Cardiac Patch Contribute to Myocardial Scar Remodeling and Enhance Revascularization in a Rabbit Model of Chronic Myocardial Infarction.

BACKGROUND: Although the transplantation of tissue-engineered cardiac patches with adult bone marrow-derived mesenchymal stem cells (MSCs) can enhance cardiac function after acute or chronic myocardial infarction (MI), the recovery mechanism remains controversial. This experiment aimed to investigate the outcome measurements of MSCs within a tissue-engineered cardiac patch in a rabbit chronic MI model. METHODS: This experiment was divided into four groups: left anterior descending artery (LAD) sham-operation group (N = 7), sham-transplantation (control, N = 7), non-seeded patch group (N = 7), and MSCs-seeded patch group (N = 6). PKH26 and 5-Bromo-2'-deoxyuridine (BrdU) labeled MSCs-seeded or non-seeded patches were transplanted onto chronically infarct rabbit hearts. Cardiac function was evaluated by cardiac hemodynamics. H&E staining was performed to count the number of vessels in the infarcted area. Masson staining was used to observe cardiac fiber formation and to measure scar thickness. RESULTS: Four weeks after transplantation, a remarkable improvement in cardiac functionality could be distinctly observed, which was most significant in the MSCs-seeded patch group. Moreover, labeled cells were detected in the myocardial scar, with most of them differentiated into myofibroblasts, some into smooth muscle cells, and only a few into cardiomyocytes in the MSCs-seeded patch group. We also observed significant revascularization in the infarct area implanted in either MSCs-seeded or non-seeded patches. In addition, there were significantly greater numbers of microvessels in the MSCs-seeded patch group than in the non-seeded patch group.

Synthesis and biological evaluation of novel aromatic amide derivatives as potential BCR-ABL inhibitors.

BCR-ABL1 kinase is a key driver of the pathophysiology of chronic myeloid leukemia (CML). Current treatments need to broaden the chemical diversity of BCR-ABL1 kinase inhibitors to overcome drug resistance. We designed and synthesized a series of aromatic amide derivatives based on several generations of BCR-ABL1 kinase inhibitors. Biological studies showed that compared with Imatinib, these compounds showed significant proliferation inhibitory activities of HL-60 and K562 in cell activity assay. Compounds 4g and 4j exhibited significant anti-tumor activity against the K562 cells with IC50 values of 6.03 ± 0.49 µM and 5.66 ± 2.06 µM respectively. Compounds 4g and 4j, as potential BCR-ABL1 inhibitors, inhibit the phosphorylation of ABL1 and CRKL in a dose-dependent manner. Therefore, compounds 4g and 4j can be used as a starting point for further optimization.

Photoexcited wireless electrical stimulation elevates nerve cell growth.

Electrical stimulation was restrained by an external power supply and wires, despite its ability to promote nerve cell growth. Bismuth sulfide (Bi2S3) offered a novel prospect for achieving wireless electrical stimulation due to its photoelectric effect. Herein, silver nanoparticles (Ag NPs) were in-situ grown on Bi2S3 surface (Ag/Bi2S3) and then mixed with poly-L-lactic acid (PLLA) powders to fabricate PLLA-Ag/Bi2S3 conduits. On the one hand, Bi2S3 would generate photocurrent under light excitation, forming a wireless electrical stimulation. On the other hand, Ag NPs would form localized electrical fields under light excitation to inhibit rapid electron-hole recombination of Bi2S3. Moreover, Ag NPs would act as electron mediators to accelerate electron transfer, further elevating photocurrent. Electrochemical tests and FDTD simulations revealed the localized electrical fields generated by Ag NPs acted on Bi2S3, resulting in a boosted electron-hole separation evidenced by a reduction in photoluminescence intensity. EIS measurements demonstrated a faster electron transfer occurred on Ag/Bi2S3. As a result, the photocurrent of PLLA-Ag/Bi2S3 increased from 0.26 to 1.03 µA as compared with PLLA-Bi2S3. The enhanced photocurrent effectively promoted cell differentiation by up-regulating Ca2+ influx and nerve growth-related protein SYN1 expression. This work suggested a promising countermeasure in the design of photocurrent stimulation conduits for nerve repair.

Selective Laser Melted Rare Earth Magnesium Alloy with High Corrosion Resistance.

Magnesium (Mg) degrades too fast in human body, which limits its orthopedic application. Single-phase Mg-based supersaturated solid solution is expected to possess high corrosion resistance. In this work, rare earth scandium (Sc) was used as alloying element to prepare Mg(Sc) solid solution powder by mechanical alloying (MA) and then shaped into implant using selective laser melting (SLM). MA utilizes powerful mechanical force to introduce numerous lattice defects, which promotes the dissolution of Sc in Mg matrix and forms supersaturated solid solution particles. Subsequently, SLM with fast heating and cooling rate maintains the original supersaturated solid solution structure. Immersion tests revealed that high Sc content significantly enhanced the corrosion resistance of Mg matrix because of the formation of protective corrosion product film, which was also proved by the electrochemical impedance spectroscopy measurements. Thereby, Mg(Sc) alloy showed a relatively low degradation rate of 0.61 mm/year. In addition, cell tests showed that the Mg(Sc) exhibited favorable biocompatibility and was suitable for medical application.

Long non-coding RNA tumor protein 73 antisense RNA 1 influences an interaction between lysine demethylase 5A and promoter of tumor protein 73 to enhance the malignancy of colorectal cancer.

Colorectal cancer (CRC) is one of the leading causes of cancer-related death worldwide. The aim of the present study was to explore the expression level of tumor protein 73 (TP73) in highly malignant CRC tumors and how the long non-coding RNA tumor protein 73 antisense RNA 1 (TP73-AS1) influences that transcription. We found that TP73-AS1 was highly expressed in malignant CRC samples in The Cancer Genome Atlas (TCGA) database. We also demonstrated TP73-AS1 was expressed in thirty samples of CRC tissues collected from China Medical University patients as well as in HCT116, RKO and SW480 CRC cell lines but not in HCoEpiC or CCD-18Co normal colon cells. Only wild-type TP73-AS1, but not any of its alternate splicing isoforms, was positively correlated with tumor malignancy. TP73-AS1 transcripts were shown to be located in cell nuclei especially in close proximity to the TP73 promoter in CRC cells, but not in normal colon cells. In addition, an interaction between lysine demethylase 5A (KDM5A) and TP73-AS1 in CRC cells, but not normal colon cells, and KDM5A localization on the TP73 promoter were influenced by TP73-AS1. Interestingly, the H3K4me3 level on the TP73 promoter was reduced, but was elevated by TP73-AS1 knockdown in CRC cells. In conclusion, these results suggest a novel epigenetic role of TP73-AS1 on histone demethylation that influences TP73 transcription, and shed light on malignancy in CRC.

Molecular Network of Colorectal Cancer and Current Therapeutic Options.

Colorectal cancer (CRC), a leading cause of cancer-related mortalities globally, results from the accumulation of multiple genetic and epigenetic alterations in the normal colonic and rectum epithelium, leading to the progression from colorectal adenomas to invasive carcinomas. Almost half of CRC patients will develop metastases in the course of the disease and most patients with metastatic CRC are incurable. Particularly, the 5-year survival rate of patients with stage 4 CRC at diagnosis is less than 10%. Although genetic understanding of these CRC tumors and paired metastases has led to major advances in elucidating early driver genes responsible for carcinogenesis and metastasis, the pathophysiological contribution of transcriptional and epigenetic aberrations in this malignancy which influence many central signaling pathways have attracted attention recently. Therefore, treatments that could affect several different molecular pathways may have pivotal implications for their efficacy. In this review, we summarize our current knowledge on the molecular network of CRC, including cellular signaling pathways, CRC microenvironment modulation, epigenetic changes, and CRC biomarkers for diagnosis and predictive/prognostic use. We also provide an overview of opportunities for the treatment and prevention strategies in this field.

An integrative gene expression signature analysis identifies CMS4 KRAS-mutated colorectal cancers sensitive to combined MEK and SRC targeted therapy.

BACKGROUND: Over half of colorectal cancers (CRCs) are hard-wired to RAS/RAF/MEK/ERK pathway oncogenic signaling. However, the promise of targeted therapeutic inhibitors, has been tempered by disappointing clinical activity, likely due to complex resistance mechanisms that are not well understood. This study aims to investigate MEK inhibitor-associated resistance signaling and identify subpopulation(s) of CRC patients who may be sensitive to biomarker-driven drug combination(s). METHODS: We classified 2250 primary and metastatic human CRC tumors by consensus molecular subtypes (CMS). For each tumor, we generated multiple gene expression signature scores measuring MEK pathway activation, MEKi "bypass" resistance, SRC activation, dasatinib sensitivity, EMT, PC1, Hu-Lgr5-ISC, Hu-EphB2-ISC, Hu-Late TA, Hu-Proliferation, and WNT activity. We carried out correlation, survival and other bioinformatic analyses. Validation analyses were performed in two independent publicly available CRC tumor datasets (n = 585 and n = 677) and a CRC cell line dataset (n = 154). RESULTS: Here we report a central role of SRC in mediating "bypass"-resistance to MEK inhibition (MEKi), primarily in cancer stem cells (CSCs). Our integrated and comprehensive gene expression signature analyses in 2250 CRC tumors reveal that MEKi-resistance is strikingly-correlated with SRC activation (Spearman P < 10-320), which is similarly associated with EMT (epithelial to mesenchymal transition), regional metastasis and disease recurrence with poor prognosis. Deeper analysis shows that both MEKi-resistance and SRC activation are preferentially associated with a mesenchymal CSC phenotype. This association is validated in additional independent CRC tumor and cell lines datasets. The CMS classification analysis demonstrates the strikingly-distinct associations of CMS1-4 subtypes with the MEKi-resistance and SRC activation. Importantly, MEKi + SRCi sensitivities are predicted to occur predominantly in the KRAS mutant, mesenchymal CSC-like CMS4 CRCs. CONCLUSIONS: Large human tumor gene expression datasets representing CRC heterogeneity can provide deep biological insights heretofore not possible with cell line models, suggesting novel repurposed drug combinations. We identified SRC as a common targetable node--an Achilles' heel--in MEKi-targeted therapy-associated resistance in mesenchymal stem-like CRCs, which may help development of a biomarker-driven drug combination (MEKi + SRCi) to treat problematic subpopulations of CRC.

Ras Pathway Activation and MEKi Resistance Scores Predict the Efficiency of MEKi and SRCi Combination to Induce Apoptosis in Colorectal Cancer.

Colorectal cancer (CRC) is the second leading cause of cancer death in the United States. The RAS pathway is activated in more than 55% of CRC and has been targeted for therapeutic intervention with MEK inhibitors. Unfortunately, many patients have de novo resistance, or can develop resistance to this new class of drugs. We have hypothesized that much of this resistance may pass through SRC as a common signal transduction node, and that inhibition of SRC may suppress MEK inhibition resistance mechanisms. CRC tumors of the Consensus Molecular Subtype (CMS) 4, enriched in stem cells, are difficult to successfully treat and have been suggested to evade traditional chemotherapy agents through resistance mechanisms. Here, we evaluate targeting two pathways simultaneously to produce an effective treatment by overcoming resistance. We show that combining Trametinib (MEKi) with Dasatinib (SRCi) provides enhanced cell death in 8 of the 16 tested CRC cell lines compared to treatment with either agent alone. To be able to select sensitive cells, we simultaneously evaluated a validated 18-gene RAS pathway activation signature score along with a 13-gene MEKi resistance signature score, which we hypothesize predict tumor sensitivity to this dual targeted therapy. We found the cell lines that were sensitive to the dual treatment were predominantly CMS4 and had both a high 18-gene and a high 13-gene score, suggesting these cell lines had potential for de novo MEKi sensitivity but were subject to the rapid development of MEKi resistance. The 13-gene score is highly correlated to a score for SRC activation, suggesting resistance is dependent on SRC. Our data show that gene expression signature scores for RAS pathway activation and for MEKi resistance may be useful in determining which CRC tumors will respond to the novel drug combination of MEKi and SRCi.

Understanding zinc-doped hydroxyapatite structures using first-principles calculations and convolutional neural network algorithm.

Element doping is widely used to improve the performance of materials by changing their intrinsic properties. However, the lack of direct crystallographic structures for dopants has restricted the effective high-throughput design or refinement of materials using the doping strategy. Herein, Zn-doped hydroxyapatite (HAP) was selected as the template material. The first-principles optimization and machine learning algorithm were combined to understand the mechanism of HAP doped with Zn2+. Our method could effectively locate the structures in the lowest-energy region. Specifically, our results indicate that the first Zn atom showed a tendency to occupy the Ca(II) site first, and the subsequent Zn atoms entering the Ca(II) sites in a symmetrical manner. The symmetrical entrance of Zn atoms to HAP would minimize the interaction energy between the Zn atoms and the degree of crystal deformation. Finally, we performed uniaxial stretching simulations to evaluate the influence of Zn2+ ions on the mechanical behavior of HAP based on the optimally-doped structure obtained by machine learning (ML). The calculation results were consistent with the experimental conclusion that the doping of Zn2+ ions could improve the fracture toughness of HAP. Our work would provide an effective way to locate possible optimized structures in the doping system and subsequently improve the design of materials.

Laser Additive Manufacturing of Zinc Targeting for Biomedical Application.

Biodegradable zinc (Zn) is expected to be used in clinical application like bone tissue engineering scaffolds, since it possesses favorable biocompatibility and suitable degradation rate. Laser powder bed fusion (LPBF), which is a typical additive manufacturing technique, offers tremendous advantages in fabricating medical devices with personalized geometric shape and complex porous structure. Therefore, the combination of LPBF and biodegradable Zn has gained intensive attention and also achieved rapid development in recent years. However, it severely challenges the formation quality and resultant performance of LPBF-processed Zn-based materials, due to the evaporation and element loss during laser processing. In this study, the current research status and future research trends for LPBF of Zn-based implants are reviewed from comprehensive viewpoints including formation quality, microstructure feature, and performance. The influences of powder characteristics and process parameters on formation quality are described systematically. The microstructure evolution, mechanical properties, as well as the degradation behavior are also discussed. Finally, the research perspectives for LPBF of Zn are summarized, aiming to provide guideline for future study.

Interlayer electron flow and field shielding in twisted trilayer graphene quantum dots.

While multilayer graphene (MLG) possesses excellent intralayer electron mobility, its interlayer electrical conductance exhibits great diversity that results in exotic phenomena and various applications in electronic devices. Driven by a vertical electric field, electron flow occurs across the layers, and its current is tunable by controlling the interlayer stacking and distance, disc size and field strength. The electron rearrangement induced by the external field is appropriately described by the polarizability that measures the electronic response against the applied field. Based on the field-induced electron density variations computed with a first-principles approach, a polarizability decomposition scheme is developed in this work to isolate the inter- and intra-layer contributions from the total polarizability of twisted trilayer graphene (TTG) quantum dots. The inter- and intra-layer counterparts reflect the charge transfer (CT) and field shielding effects among the layers, respectively. Shielded by the top and bottom layers, the middle layer is particularly effective in bridging, switching and promoting the interlayer electron flow. Large CT and shielding effects occur not only in the strongly coupled Bernal stacking, but also in the structures misorientating from the full-AAA stacking by a small twist angle. Moreover, both effects vary with the twist angle and disc size, indicating a controllable conductive/dielectric conversion in the vertical direction. In light of inter- and intralayer polarizability, our study addresses the precise modulation of interlayer conductance for TTG quantum dots, which is required in the microstructure design and performance manipulation of MLG-based electronic devices.

Laser Additively Manufactured Iron-Based Biocomposite: Microstructure, Degradation, and In Vitro Cell Behavior.

A too slow degradation of iron (Fe) limits its orthopedic application. In this study, calcium chloride (CaCl2) was incorporated into a Fe-based biocomposite fabricated by laser additive manufacturing, with an aim to accelerate the degradation. It was found that CaCl2 with strong water absorptivity improved the hydrophilicity of the Fe matrix and thereby promoted the invasion of corrosive solution. On the other hand, CaCl2 could rapidly dissolve once contacting the solution and release massive chloride ion. Interestingly, the local high concentration of chloride ion effectively destroyed the corrosion product layer due to its strong erosion ability. As a result, the corrosion product layer covered on the Fe/CaCl2 matrix exhibited an extremely porous structure, thus exhibiting a significantly reduced corrosion resistance. Besides, in vivo cell testing proved that the Fe/CaCl2 biocomposite also showed favorable cytocompatibility.

APC and TP53 Mutations Predict Cetuximab Sensitivity across Consensus Molecular Subtypes.

Recently, it was suggested that consensus molecular subtyping (CMS) may aide in predicting response to EGFR inhibitor (cetuximab) therapies. We recently identified that APC and TP53 as two tumor suppressor genes, when mutated, may enhance cetuximab sensitivity and may represent easily measured biomarkers in tumors or blood. Our study aimed to use APC and TP53 mutations (AP) to refine the CMS classification to better predict responses to cetuximab. In total, 433 CRC tumors were classified into CMS1-4 subtypes. The cetuximab sensitivity (CTX-S) signature scores of AP vs. non-AP tumors were determined across each of the CMS classes. Tumors harboring combined AP mutations were predominantly enriched in the CMS2 class, and to a lesser degree, in the CMS4 class. On the other hand, AP mutated CRCs had significantly higher CTX-S scores compared to non-AP CRCs across all CMS classes. Similar results were also obtained in independent TCGA tumor collections (n = 531) and in PDMR PDX/PDO/PDC models (n = 477). In addition, the in vitro cetuximab growth inhibition was preferentially associated with the CMS2 cell lines harboring A/P genotypes. In conclusion, the AP mutation signature represents a convenient biomarker that refines the CMS classification to identify CRC subpopulations predicted to be sensitive to EGFR targeted therapies.

Laser-Sintered Mg-Zn Supersaturated Solid Solution with High Corrosion Resistance.

Solid solutions of Zn as an alloy element in Mg matrixes are expected to show improved corrosion resistance due to the electrode potential being positively shifted. In this study, a supersaturated solid solution of Mg-Zn alloy was achieved using mechanical alloying (MA) combined with laser sintering. In detail, supersaturated solid solution Mg-Zn powders were firstly prepared using MA, as it was able to break through the limit of phase diagram under the action of forced mechanical impact. Then, the alloyed Mg-Zn powders were shaped into parts using laser sintering, during which the limited liquid phase and short cooling time maintained the supersaturated solid solution. The Mg-Zn alloy derived from the as-milled powders for 30 h presented enhanced corrosion potential and consequently a reduced corrosion rate of 0.54 mm/year. Cell toxicity tests confirmed that the Mg-Zn solid solution possessed good cytocompatibility for potential clinical applications. This study offers a new strategy for fabricating Mg-Zn solid solutions using laser sintering with MA.

Molecular modeling on the pressure-driven methane desorption in illite nanoslits.

Understanding to the pressure-driven desorption of methane in shale formations is crucial for the establishment of predictive models used in shale gas development. Based on the grand canonical Monte-Carlo simulations of methane adsorption in illite slits of 1-5-nm wide, the pressure-driven desorption processes of methane in the nanoslits are studied with non-equilibrium molecular dynamics simulations. External forces are applied to the methane molecules to mimic a pressure drop that releases the adsorbed molecules and pushes them flowing directionally. Effect of pressure drop and slit aperture on the interchange between adsorbed and free phases of methane is investigated by a statistic analysis on the velocity and density distributions of methane molecules in the nanoslits under various conditions. A minimum pressure drop that initiates the methane desorption in the illite slit exists and varies with slit aperture. Our simulations reveal the microscopic mechanism of pressure-driven methane desorption, which would be useful for subsequent studies on the prediction of mineable yields for shale formations. Under pressure drop, adsorbed methane molecules are desorbed to free phase and then transported to wellbore. The criterion of pressure drop for desorption increases with decreasing slit aperture.