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Abstract Breast cancer (BC) is a multifaceted disease characterized by distinct molecular subtypes and varying responses to treatment. In BC, the phosphatidylinositol 3-kinase (PI3K) pathway has emerged as a crucial contributor to the development, advancement, and resistance to treatment. This review article explores the implications of the PI3K pathway in predictive, preventive, and personalized medicine for BC. It emphasizes the identification of predictive biomarkers, such as PIK3CA mutations, and the utility of molecular profiling in guiding treatment decisions. The review also discusses the potential of targeting the PI3K pathway for preventive strategies and the customization of therapy based on tumor stage, molecular subtypes, and genetic alterations. Overcoming resistance to PI3K inhibitors and exploring combination therapies are addressed as important considerations. While this field holds promise in improving patient outcomes, further research and clinical trials are needed to validate these approaches and translate them into clinical practice. Graphical Abstract

Summary: This review explores the hallmarks of cancer resistance, including drug efflux mediated by ATP-binding cassette (ABC) transporters, metabolic reprogramming characterized by the Warburg effect, and the dynamic interplay between cancer cells and mitochondria. The role of cancer stem cells (CSCs) in treatment resistance and the regulatory influence of non-coding RNAs, such as long non-coding RNAs (lncRNAs), microRNAs (miRNAs), and circular RNAs (circRNAs), are studied. The chapter emphasizes future directions, encompassing advancements in immunotherapy, strategies to counter adaptive resistance, integration of artificial intelligence for predictive modeling, and the identification of biomarkers for personalized treatment. The comprehensive exploration of these hallmarks provides a foundation for innovative therapeutic approaches, aiming to navigate the complex landscape of cancer resistance and enhance patient outcomes.

Abstract Background The purpose of this study was to introduce a modified lateral approach for combined radical resection of buccal squamous cell carcinoma (BSCC) and evaluate its surgical, oncological, functional, and aesthetic outcomes in comparison with the conventional lower-lip splitting approach. Methods This single-center study retrospectively reviewed 80 patients with BSCC, of which 37 underwent the lateral approach and 43 underwent the conventional approach. Surgical, functional, oncological, and aesthetic evaluations, as well as follow-ups, were recorded and compared. Results Compared to the conventional approach group, the lateral approach group had a longer surgical time (P = 0.000), but there was no significant difference in other surgical and oncological parameters. Moreover, the scar in the head and neck had a significantly discreet appearance in the lateral approach group, whose satisfaction was better than those in the conventional approach group (P = 0.000). Other oral function parameters, postoperative mouth-opening, and 3-year survival rate were not significantly different between the two groups. Conclusion The lateral approach could provide superior aesthetic results while maintaining equal surgical, functional, and oncological outcomes compared to the conventional approach for radical resection of BSCC.

Abstract Different from the conventional gas reservoirs, gas transport in nanoporous shales is complicated due to multiple transport mechanisms and reservoir characteristics. In this work, we presented a unified apparent gas permeability model for real gas transport in organic and inorganic nanopores, considering real gas effect, organic matter (OM) porosity, Knudsen diffusion, surface diffusion, and stress dependence. Meanwhile, the effects of monolayer and multilayer adsorption on gas transport are included. Then, we validated the model by experimental results. The influences of pore radius, pore pressure, OM porosity, temperature, and stress dependence on gas transport behavior and their contributions to the total apparent gas permeability (AGP) were analyzed. The results show that the adsorption effect causes Kn(OM) > Kn(IM) when the pore pressure is larger than 1 MPa and the pore radius is less than 100 nm. The ratio of the AGP over the intrinsic permeability decreases with an increase in pore radius or pore pressure. For nanopores with a radius of less than 10 nm, the effects of the OM porosity, surface diffusion coefficient, and temperature on gas transport cannot be negligible. Moreover, the surface diffusion almost dominates in nanopores with a radius less than 2 nm under high OM porosity conditions. For the small-radius and low-pressure conditions, gas transport is governed by the Knudsen diffusion in nanopores. This study focuses on revealing gas transport behavior in nanoporous shales.

Abstract The paper presents a novel hydraulic fracturing model for the characterization and simulation of the complex fracture network in shale gas reservoirs. We go beyond the existing method that uses planar or orthogonal conjugate fractures for representing the “complexity” of the network. Bifurcation of fractures is performed utilizing the Lindenmayer system based on fractal geometry to describe the fracture propagation pattern, density and network connectivity. Four controlling parameters are proposed to describe the details of complex fractures and stimulated reservoir volume (SRV). The results show that due to the multilevel feature of fractal fractures, the model could provide a simple method for contributing reservoir volume calibration. The primary- and second-stage fracture networks across the overall SRV are the main contributions to the production, while the induced fracture network just contributes another 20% in the late producing period. We also conduct simulation with respect to different refracturing cases and find that increasing the complexity of the fracture network provides better performance than only enhancing the fracture conductivity.