Search

Simple Summary: NSCLC accounts for approximately 84% of lung malignancies and the clinical application of ICIs provides a novel and promising strategy. However, approximately 80% of NSCLC patients do not benefit from ICIs due to drug resistance complicated by disciplines and diverse mechanisms. Through this review, we provide a whole map of current understanding of primary and acquired resistance mechanisms in NSCLC. In the first part, resistance mechanisms of 6 FDA-approved ICIs-related primary resistance are collected and arranged into 7 steps of the well-known cancer-immunity cycle. Acquired resistance induced by ICIs are summarized in the second part. In the third part, we discuss the future direction, including the deeper understanding of tumor microenvironment and the combinational treatment. Through this review, clinicians can get clear and direct clues to find the underlying mechanisms in patients and translational researchers can acquire several directions to overcome resistance and apply new combinational treatment. Immune checkpoint inhibitors have emerged as the treatment landscape of advanced non-small cell lung cancer (NSCLC) in recent years. However, approximately 80% of NSCLC patients do not benefit from ICIs due to primary resistance (no initial response) or acquired resistance (tumor relapse after an initial response). In this review, we highlight the mechanisms of primary and secondary resistance. Furthermore, we provide a future direction of the potential predictive biomarkers and the tumor microenvironmental landscape and suggest treatment strategies to overcome these mechanisms. [ABSTRACT FROM AUTHOR]

With the large-scale development of urbanization in the world, phenomena such as the unbalanced allocation of various elements of the rural regional system, as well as the decline of the economic and social structure and functions in the process of urban and rural economic and social transformation and development in China, have endangered the healthy development of rural areas. The "hollowing" of rural areas is becoming more and more intense, and the governance of hollow villages has become a key link to stimulating the vitality of rural development and realizing the coordinated development of urban and rural areas. Taking a typical hollow village in Fangsi Town, Yucheng City, Shandong Province, China as an example, through the recognition method of hollow villages mode, the study adopted the in-depth interviews and questionnaires to obtain governance of hollow villages. Moreover, this study uses the actor–network theory to discuss the governance model mechanism and policy response of hollow villages, extract the applicable conditions of different hollow village governance modes, and provide the promotion of the hollow village governance mechanism. Our findings show that: (1) the governance modes of hollow villages are diverse. Under certain geographical conditions, the governance of hollow villages shows the relocation and merger–urban–rural integration mode, village integration-scale operation mode, village intensive-idle land revitalization mode, and original site optimization–sightseeing tourism development mode, along with other types. In the process of promotion and use, appropriate adjustments should be made in combination with differences and changes in system conditions, and the accurate governance of villages should be carried out. (2) The governance process of hollow villages is dynamic. The governance of hollow villages represents a heterogeneous network of actors led by key actors, which mainly realizes changes in the rural material space. With the change of development goals of the hollow village, the network of actors has been readjusted around the new OPP, and the role of the actors has changed, correspondingly showing a transition from the governance of the hollow village to the optimized development, thus further realizing the transformation of the hollow village. [ABSTRACT FROM AUTHOR]

In accordance with the ecological civilization strategy, it is necessary to conduct in-depth analyses and provide a systematic elaboration of the characteristics of territorial-space structure (TSS). In the present paper, we examine Shandong Province and construct a framework for the evolution and optimization of TSS based on regional functions. The evolutionary process, pattern, and driving mechanisms of TSS are clarified using a geo-information atlas, the gravity center shift model, spatial autocorrelation analyses, and a geographic detector model. Furthermore, multi-scenario territorial-space simulations are carried out using the CA–Markov model, based on which an optimal pattern of territorial space is constructed. The results show that the comprehensive dynamic degree of territorial space in Shandong Province was valued at 0.56% from 2000 to 2020. Furthermore, six geo-information Tupu of TSS evolution changed, with a total area of 35,485 km2, distributed mainly in the Yellow River Delta, the central and southern Shandong Mountain area, and the Jiaodong Peninsula. The migration route of the TSS gravity center curved over time. Territorial spaces are characterized by the exchange of ecological and agricultural space, while urban spaces occupy agricultural ones. The level of economic development, policy, and the institutional environment are driving forces in the transformation of ecological into agricultural spaces, as well as in transforming agricultural space into ecological and urban spaces. The trade-off connection of TSSs is made evident after a multi-scenario simulation of territorial space considering the 2020–2025 timeframe. Based on the goal of regional function co-ordination, Shandong Province is divided into three and four types of single and complex TSS, respectively. The obtained results may provide scientific reference for the co-ordination between human–land relationships and the sustainable use of territorial space, and serve to guide territorial spatial planning. [ABSTRACT FROM AUTHOR]