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Abstract Dual inhibition of vascular endothelial growth factor and epidermal growth factor receptor (EGFR) signaling pathways offers the prospect of improving the effectiveness of EFGR-targeted therapy. In this phase 3 study (ClinicalTrial.gov: NCT04028778), 315 patients with treatment-naïve, EGFR-mutated, advanced non-small cell lung cancer (NSCLC) were randomized (1:1) to receive anlotinib or placebo plus gefitinib once daily on days 1–14 per a 3-week cycle. At the prespecified final analysis of progression-free survival (PFS), a significant improvement in PFS was observed for the anlotinib arm over the placebo arm (hazards ratio [HR] = 0.64, 95% CI, 0.48–0.80, P = 0.003). Particularly, patients with brain metastasis and those harboring EGFR amplification or high tumor mutation load gained significant more benefits in PFS from gefitinib plus anlotinib. The incidence of grade 3 or higher treatment-emergent adverse events was 49.7% of the patients receiving gefitinib plus anlotinib versus 31.0% of the patients receiving gefitinib plus placebo. Anlotinib plus gefitinib significantly improves PFS in patients with treatment-naïve, EGFR-mutated, advanced NSCLC, with a manageable safety profile.

Abstract In today’s world, creating safe, comfortable, and beautiful slow communities has become an urgent research topic for addressing energy crises, environmental pollution, and traffic congestion. This study explored the relationship between the built environment and residents’ leisure-time physical activities in slow communities in Shanghai. This study uses the analytic hierarchy process and entropy weight method to construct a new evaluation model to explore the sustainability mechanism. The results of the study are as follows. First, women participated in walking, jogging, and bicycling activities at a higher rate than men. Second, various leisure-time physical activities have different requirements for the built environment. Third, the built environment of slow communities in Shanghai shows a “pyramid” type of spatial stratification phenomenon. This study contributes to a new evaluation system and optimization model for promoting leisure-time physical activities, providing theoretical and methodological guidance for constructing livable slow communities in developing countries and promoting slow living.

BackgroundGreen and blue spaces, as crucial components of urban ecosystems, significantly impact the physical and mental health of residents. However, the mechanisms through which Green/Blue Space Justice influence residents’ health remain unclear.MethodsThis study aims to explore the impact of green spaces on public psychological responses, physical activity, and mental health from a justice perspective, and to examine the moderating role of blue spaces in this relationship. The research was conducted in selected communities within the Chang-Zhu-Tan urban agglomeration in Hunan Province, China. A total of 801 valid questionnaires were collected through field visits and online surveys. The study uses an improved Gaussian-based two-step floating catchment area (2SFCA) method to assess green space accessibility. Data were analyzed using structural equation modeling (SEM) and moderation effect analysis to reveal the relationships between variables.ResultsThe findings indicate that Green Space Justice has a significant positive impact on psychological responses, physical activity, and mental health; psychological responses and physical activity play crucial mediating roles between Green Space Justice and mental health; and Green Space Justice significantly affects mental health through a chain mediation path involving psychological responses and physical activity. Moreover, Blue Space Justice significantly moderates the impact of Green Space Justice on psychological responses and physical activity, but does not have a significant direct impact on mental health.ConclusionThis study enriches the theory of Green Space Justice by revealing the mechanisms through which it influences mental health via psychological responses and physical activity. It provides a scientific basis for the development of healthy cities. Additionally, it recommends that urban planning should prioritize the equitable distribution and high accessibility of both green and blue spaces to comprehensively enhance residents’ physical and mental well-being. Policymakers should consider prioritizing the accessibility of high-quality green spaces for vulnerable communities during urban renewal and expansion processes to reduce social health inequalities and promote broader public health outcomes.

Lung cancer remains the leading cause of mortality worldwide. Non-small cell lung cancer (NSCLC) is the most common subtype of lung cancer with a generally poor prognosis. In recent years, advances in targeted therapy and sequencing technology have brought significant improvement in the therapeutic outcomes of patients with advanced NSCLC. Targeted inhibitors directed against specific mutated or rearranged oncogenes, such as epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), and receptor tyrosine kinase ROS proto-oncogene 1(ROS1) among others, exhibit promising anti-tumor activity. Unfortunately, some patients develop acquired resistance and disease progression soon after initial remission. Despite the continuous development of new drugs and strategies to overcome drug resistance, it is still a major challenge in the treatment of NSCLC. The landscape of targeted therapy for NSCLC is evolving rapidly in response to the pace of scientific research. This study aimed to provide a comprehensive review of tumor target antigens and agents related to targeted therapy in NSCLC.

Background: The development of tyrosine kinase inhibitor (TKI) therapy has positively impacted the survival rates of patients with chronic myeloid leukemia (CML). It is common in medical practice to adjust the dosage of TKI downward because of TKI-associated adverse events, financial burden, comorbidity, or an attempt at treatment-free remission. Objectives: This investigation sought to explore the feasibility of employing a reduced dosage of TKI for treating CML. Design: This was a retrospective study. Methods: Patients with CML in its chronic phase who had been on a reduced dose of TKI for a minimum of 3 months for various reasons in a practical clinical environment, irrespective of molecular response, were included. Regular molecular monitoring was performed, and changes in adverse events were recorded after dose reduction. Results: This research included a total of 144 participants. Upon reducing the dosage, 136 of 144 patients achieved major molecular response or deeper, and 132 of 144 achieved molecular response 4 (MR4). Following a median observation period of 16 months, the calculated 1- and 2-year survival rates free from MR4 failure were estimated to be 96.5% (95% CI: 90.8–98.7) and 90.5% (95% CI: 81.3–95.3), respectively. MR4 failure-free survival was better in patients with longer MR4 durations (⩾34 months) before dose reduction ( p = 0.02). The median interval from dose reduction to MR4 loss was 15 months. Improved TKI-associated adverse events after dose reduction were observed in 61.3% of patients. Conclusion: Lowering the TKI dose can effectively preserve a deep molecular response over time while relieving adverse events caused by TKIs.

Caviar yield, caviar color, and body weight are crucial economic traits in sturgeon breeding. Understanding the molecular mechanisms behind these traits is essential for their genetic improvement. In this study, we performed whole-genome sequencing on 673 Russian sturgeons, renowned for their high-quality caviar. With an average sequencing depth of 13.69×, we obtained approximately 10.41 million high-quality single nucleotide polymorphisms (SNPs). Using a genome-wide association study (GWAS) with a single-marker regression model, we identified SNPs and genes associated with these traits. Our findings revealed several candidate genes for each trait: caviar yield: TFAP2A, RPS6KA3, CRB3, TUBB, H2AFX, morc3, BAG1, RANBP2, PLA2G1B, and NYAP1; caviar color: NFX1, OTULIN, SRFBP1, PLEK, INHBA, and NARS; body weight: ACVR1, HTR4, fmnl2, INSIG2, GPD2, ACVR1C, TANC1, KCNH7, SLC16A13, XKR4, GALR2, RPL39, ACVR2A, ADCY10, and ZEB2. Additionally, using the genomic feature BLUP (GFBLUP) method, which combines linkage disequilibrium (LD) pruning markers with GWAS prior information, we improved genomic prediction accuracy by 2%, 1.9%, and 3.1% for caviar yield, caviar color, and body weight traits, respectively, compared to the GBLUP method. In conclusion, this study enhances our understanding of the genetic mechanisms underlying caviar yield, caviar color, and body weight traits in sturgeons, providing opportunities for genetic improvement of these traits through genomic selection.

Diagenesis has been demonstrated to significantly affect porosity development in shale reservoirs, however, the effect of diagenetic modifications on shale pore structures is still unclear. For clarifying this issue, this paper focuses on the Upper Ordovician to Lower Silurian Wufeng and Longmaxi shales, which are the only commercially gas-produced shale plays in China. This study aims to reveal the influence of diagenetic alterations on the WF-LMX shale reservoir quality by integrating total organic carbon (TOC) content, X-ray diffraction (XRD), low-temperature gas (N2) and carbon dioxide (CO2) adsorption experiments, field-emission scanning electron microscopy (FE-SEM), energy dispersive X-ray (EDS), and cathodoluminescence (CL) analyses. Three major shale lithofacies were identified, mainly including siliceous, siliceous–argillaceous mixed, and argillaceous shale; the siliceous shale has a relatively high TOC content. The organic pores, intergranular pores, intragranular pores, and fractures are generally developed in the WF-LMX shales. The pore volume (PV) and specific surface area (SSA) of micropores, mesopores, and macropores of siliceous shales are higher than those of mixed shales and argillaceous shales. The TOC content has a strongly positive correlation with PV and SSA for micropores and mesopores. After combustion, the PV and SSA of micropores and mesopores were decreased, whereas the PV and SSA of macropore were significantly increased. In the siliceous shale, organic pore is the dominant pore type due to the fact that a large amount of authigenic microcrystalline quartz aggregates can protect organic pores from compaction. The argillaceous shale has high clay and low TOC content, and the dominant pore type is pores between clay flakes. The siliceous shale has a relatively high TOC content, large PV and SSA, and so are the dessert lithofacies for shale gas exploration.