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Abstract Solid tumors are complex ecosystems with heterogeneous 3D structures, but the spatial intra-tumor heterogeneity (sITH) at the macroscopic (i.e., whole tumor) level is under-explored. Using a phylogeographic approach, we sequence genomes and transcriptomes from 235 spatially informed sectors across 13 hepatocellular carcinomas (HCC), generating one of the largest datasets for studying sITH. We find that tumor heterogeneity in HCC segregates into spatially variegated blocks with large genotypic and phenotypic differences. By dissecting the transcriptomic heterogeneity, we discover that 30% of patients had a “spatially competing distribution” (SCD), where different spatial blocks have distinct transcriptomic subtypes co-existing within a tumor, capturing the critical transition period in disease progression. Interestingly, the tumor regions with more advanced transcriptomic subtypes (e.g., higher cell cycle) often take clonal dominance with a wider geographic range, rejecting neutral evolution for SCD patients. Extending the statistical tests for detecting natural selection to many non-SCD patients reveal varying levels of selective signal across different tumors, implying that many evolutionary forces including natural selection and geographic isolation can influence the overall pattern of sITH. Taken together, tumor phylogeography unravels a dynamic landscape of sITH, pinpointing important evolutionary and clinical consequences of spatial heterogeneity in cancer.

Background: Peripheral artery disease (PAD) is a high-risk vascular condition, and vascular remodeling has become a promising therapeutic approach. Paeoniflorin (PF) is the main bioactive compound in the roots of Paeonia lactiflora Pall, which is commonly used to treat a range of cardiovascular disorders. However, the mechanisms underlying the ameliorating effects of PF on PAD remain unclear. Therefore, the purpose of this study was to explore the therapeutic efficiency of PF on PAD and determine its mechanisms. Methods: The blood flow of mice was detected with a laser Doppler dot scanning imaging system. HE staining was used to observe the morphological changes of ischemic muscle. The changes in the serologic indexes were detected with an automatic biochemical assay, and the capillary density of ischemic gastrocnemius was detected with a Lectin immunofluorescence assay. The expression of angiogenesis-related proteins in ischemic gastrocnemius was detected with Western blotting, and the proportion of macrophages and neutrophils in total cells was detected with flow cytometry. Results: PF significantly increased blood flow, capillary density and protein expressions of vascular endothelial growth factor A (VEGFA), matrix metalloproteinase 2 (MMP2), matrix metalloproteinase 2 (MMP9), and estrogen receptor α (ERα) in mouse ischemic tissue in a PAD model. PF enhances the migration of endothelial cells and promotes the formation of tubular structures, involving the ERα/ROCK2 signaling pathway. Furthermore, PF was found to promote the phenotypic transformation of macrophages and alleviated grave inflammatory responses during vascular remodeling. Conclusions: We determined that PF as a potent compound in promoting angiogenesis and mitigating inflammatory responses during revascularization.

In deep brine oil and gas injection–production operations, the combined long-term effects of brine and carbon dioxide on rock mechanical properties are not clear. In order to solve this problem, the influence of long-term salt–CO2 environment on the mechanical properties of sandstone is discussed. The mechanism of interaction evolution and fracture propagation was studied in detail by NMR, the triaxial compression test and a CT scan. The results show that the triaxial compressive strength and mass of sandstone decrease first and then increase with the prolonging of soaking time. The proportion of micropores first decreased and then increased, while the proportion of medium and large pores first increased and then decreased. The pores obtained by Avizo’s segmentation of the threshold value of CT sections first increased and then decreased, and the fractal dimensions obtained first increased and then decreased. In particular, the calcium ions in the immersion solution increased first and then decreased. The reaction rate was obtained and verified according to the changes in calcium carbonate mass and calcium ion mineralization at different times. The failure mode of the sample gradually changed from /-shaped failure to V-shaped composite failure, then to local /-shaped failure, and finally to X-shaped composite failure. On this basis, the process of sandstone was divided into the dissolution stage, precipitation stage and secondary dissolution stage, and the rock microstructure change model under a salt–CO2 environment was established. The mechanics, temperature, chemical interaction mechanism and fracture propagation mechanism of sandstone under a salt–CO2 environment are discussed.

Evaluating underground gas storage (UGS) sealing capacity is essential for its safe construction and operational efficiency. This involves evaluating both the static sealing capacity of traps during hydrocarbon accumulation and the dynamic sealing capacity of UGS under intensive gas injection and withdrawal, and alternating loads. This study detailed the methodology developed by Sinopec. The approach merges disciplines like geology, geomechanics, and hydrodynamics, employing both dynamic-static and qualitative-quantitative analyses. Sinopec's evaluation methods, grounded in the in situ stress analysis, include mechanistic studies, laboratory tests, geological surveys, stress analysis, and fluid-solid interactions. Through tests on the static and dynamic sealing capacity of UGS, alongside investigations into sealing mechanisms and the geological and geomechanical properties of cap rocks and faults, A geomechanics - rock damage - seepage mechanics dynamic coupling analysis method has been developed to predict in situ stress variations relative to pore pressure changes during UGS operations and evaluate fault sealing capacity and cap rock integrity, thereby setting the maximum operational pressures. Utilizing this evaluation technique, Sinopec has defined performance metrics and criteria for evaluating the sealing capacity of depleted gas reservoirs, enabling preliminary sealing capacity evaluations at UGS sites. These evaluations have significantly informed the design of UGS construction schemes and the evaluation of fault sealing capacity and cap rock integrity during UGS operations.

The temperature change under alternating injection-production conditions of underground gas reservoir storage is a key factor for permeability and even deliverability. To explore the temperature-sensitivity of sandstone reservoir permeability and its effect on the deliverability of gas well, experimental studies at multiple rounds were carried out within the realistic temperature range of underground gas storage to simulate more accurately. Results show that: (1) Reservoir permeability negatively correlates with temperature. Permeability exhibits a hysteresis effect under cyclic alternating temperature, and the hysteresis effect gradually weakens with the variation of temperature. (2) Permeability and temperature are linearly correlated, and the hysteresis effect does not change with temperature, which is different from stress-sensitivity. (3) Based on the experimental results, a deliverability equation modified with temperature-sensitivity was established. Calculation shows that, ignoring the temperature-sensitivity of permeability will underestimate the performance of gas well, and its effect will aggravate with the increasing elevation and injection flowrate.