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Tumor metastasis is a leading cause of breast cancer-related death. Taxane-loaded polymeric formulations, such as Genexol PM and Nanoxel M using poly(ethylene glycol)-poly(d,l-lactide) (PEG-PLA) micelles as drug carriers, have been approved for the treatment of metastatic breast cancer. Unfortunately, the physical instability of PEG-PLA micelles, leading to poor drug loading, premature drug leakage, and consequently limited drug delivery to tumors, largely hinders their therapeutic outcome. Inspired by the enantiomeric nature of PLA, this work developed stereocomplex PEG-PLA micelles through stereoselective interactions of enantiomeric PLA, which are further incorporated with a hypoxia-responsive moiety used as a hypoxia-cleavable linker of PEG and PLA, to maximize therapeutic outcomes. The results showed that the obtained micelles had high structural stability, showing improved drug loading for effective drug delivery to tumors as well as other tissues. Especially, they were capable of sensitively responding to the hypoxic tumor environment for drug release, reversing hypoxia-induced drug resistance and hypoxia-promoted cell migration for enhanced bioavailability under hypoxia. In vivo results further showed that the micelles, especially at a high dose, inhibited the growth of the primary tumor and improved tumor pathological conditions, consequently remarkably inhibiting its metastasis to the lungs and liver, while not causing any systemic toxicity. Hypoxia-responsive stereocomplex micelles thus emerge as a reliable drug delivery system to treat breast cancer metastasis.

Traditional villages, as spatial carriers with rich cultural resources, are important cornerstones for cultural inheritance and promotion, and their ecological and cultural symbiosis has been formed in the process of long historical development, which contains rich ecological wisdom. To comprehensively analyze the development status of traditional villages and plan and design future development, this study is guided by the theory of ecological and cultural health, selects the evaluation elements of the target level, criterion level, and indicator level, and devotes itself to constructing an evaluation system of the healthy development of traditional villages, and applies the hierarchical analysis method and the entropy weight method to determine the index weight, to establish a comprehensive evaluation model of the healthy development of traditional villages. By evaluating the healthy development of traditional villages in Ning’an City, Mudanjiang City, and Heilongjiang Province, the study verifies the feasibility of the evaluation system constructed by the study for the healthy development of traditional villages. It proposes corresponding healthy development strategies for the evaluation analysis to provide reference ideas for traditional villages’ ecological and cultural health and sustainable development.

Residual cancer cells that survive drug treatments with targeted therapies act as a reservoir from which eventual resistant disease emerges. Although there is great interest in therapeutically targeting residual cells, efforts are hampered by our limited knowledge of the vulnerabilities existing in this cell state. Here, we report that diverse oncogene-targeted therapies, including inhibitors of epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), KRAS, and BRAF, induce DNA double-strand breaks and, consequently, ataxia-telangiectasia mutated (ATM)-dependent DNA repair in oncogene-matched residual tumor cells. This DNA damage response, observed in cell lines, mouse xenograft models, and human patients, is driven by a pathway involving the activation of caspases 3 and 7 and the downstream caspase-activated deoxyribonuclease (CAD). CAD is, in turn, activated through caspase-mediated degradation of its endogenous inhibitor, ICAD. In models of EGFR mutant non-small cell lung cancer (NSCLC), tumor cells that survive treatment with small-molecule EGFR-targeted therapies are thus synthetically dependent on ATM, and combined treatment with an ATM kinase inhibitor eradicates these cells in vivo. This led to more penetrant and durable responses in EGFR mutant NSCLC mouse xenograft models, including those derived from both established cell lines and patient tumors. Last, we found that rare patients with EGFR mutant NSCLC harboring co-occurring, loss-of-function mutations in ATM exhibit extended progression-free survival on first generation EGFR inhibitor therapy relative to patients with EGFR mutant NSCLC lacking deleterious ATM mutations. Together, these findings establish a rationale for the mechanism-based integration of ATM inhibitors alongside existing targeted therapies.

Objective To establish a risk prediction model for frailty in patients with inflammatory bowel disease and verify its prediction effect. Methods A classic sampling method was used to collect samples from 360 patients with inflammatory bowel disease who were hospitalized in the Department of Gastroenterology of Peking Union Medical College Hospital from July 2021 to November 2021. According to the evaluation results of the FRAIL Scale (FS), patients were divided into two group: frail group and non-frail group. The differences of demographic factors and disease related factors between the two categories of patients were compared. Randomized number method was used to divide the model group and verification group at a ratio of 8∶2. Logistic regression analysis was used to establish a risk prediction model. Hosmer-Lemeshow χ2 was used to test the prediction model fitting effect, and receiver operator characteristic curve (ROC curve) was drawn. Area under ROC curve (AUC) and Youden index were calculated to evaluate the differentiation ability of the prediction model. Results The incidence of frailty in patients with inflammatory bowel disease was 16.6%. Age (OR=1.041), emaciation (OR=10.135), several times of exercise per month (OR=0.345), ulcerative colitis (OR=2.952), quality of life (OR=0.979), family care index (OR=1.629), depression (OR=1.194) and sleep disorders (OR=1.158) were independent influencing factors (P

Judo is a skills-led sport, which has higher requirements on the athletes’ skills, physical ability, intelligence and psychology, but the athletes’ physical characteristics are still the basis of competitive ability. In this article, 107 male judo athletes were selected as the investigation object, their body shape indexes and some physical quality indexes were measured, the independent sample multiple regression method and T-test were applied to compare and analyze the elite and non-elite athletes, the youth and adult athletes, and the standardized typical discriminant function of athletes’ sports grade was established by stepwise discriminant analysis. Thus, we have a comprehensive understanding of the physical characteristics of the men's judo athletes and provide a reliable basis for the training and selection of basic coaches.