Understanding the interaction between nanoparticles (NPs) and cell membranes is crucial for the design of NP-based drug delivery systems and for the assessment of the risks exerted by the NPs. Recent experimental and theoretical studies have shown that cell membranes can mediate attraction between NPs and form tubular structures to wrap multiple NPs. However, the cooperative wrapping process is still not well understood, and the shape effect of NPs is not considered. In this article, we use largescale coarse-grained molecular dynamics (CGMD) simulations to study the cooperative wrapping of NPs when a varying number of NPs adhered to the membrane. Spherical, prolate and oblate NPs of different sizes are considered in this study. We find that, in addition to tubular structures, the membrane can form a pocket-like and a handle-like structure to wrap multiple NPs depending on the size and shape of the NPs. Furthermore, we find that NPs can mediate membrane hemifusion or fusion during this process.Our findings provide new insights into the interaction of NPs with the cell membrane.

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Background Studies investigating breast cancer polygenic risk score (PRS) in Chinese women are scarce. The objectives of this study were to develop and validate PRSs that could be used to stratify risk for overall and subtype-specific breast cancer in Chinese women, and to evaluate the performance of a newly proposed Artificial Neural Network (ANN) based approach for PRS construction. Methods The PRSs were constructed using the dataset from a genome-wide association study (GWAS) and validated in an independent case-control study. Three approaches, including repeated logistic regression (RLR), logistic ridge regression (LRR) and ANN based approach, were used to build the PRSs for overall and subtype-specific breast cancer based on 24 selected single nucleotide polymorphisms (SNPs). Predictive performance and calibration of the PRSs were evaluated unadjusted and adjusted for Gail-2 model 5-year risk or classical breast cancer risk factors. Results The primary PRSANN and PRSLRR both showed modest predictive ability for overall breast cancer (odds ratio per interquartile range increase of the PRS in controls [IQ-OR] 1.76 vs 1.58; area under the receiver operator characteristic curve [AUC] 0.601 vs 0.598) and remained to be predictive after adjustment. Although estrogen receptor negative (ER−) breast cancer was poorly predicted by the primary PRSs, the ER− PRSs trained solely on ER− breast cancer cases saw a substantial improvement in predictions of ER− breast cancer. Conclusions The 24 SNPs based PRSs can provide additional risk information to help breast cancer risk stratification in the general population of China. The newly proposed ANN approach for PRS construction has potential to replace the traditional approaches, but more studies are needed to validate and investigate its performance.

Purpose/Objective. Inhaled corticosteroids (ICS) are the most effective treatment for asthma. However, some asthmatic patients do not respond to ICS treatment due to insensitivity. Thus, some studies have attempted to identify combination treatments to resolve this clinical problem. Cough variant asthma (CVA) is well established as a specific asthma phenotype. In this study, we examined whether the traditional medicine Suhuang (a combination of several traditional Chinese medicinal plants) could enhance the effect of Budesonide (BUD) by ameliorating corticosteroid insensitivity via p38 MAPK signal pathway in CVA guinea pig. Methods. The CVA guinea pig model was successfully established by use of ovalbumin (OVA) sensitization and cigarette smoke (CS) exposure. The guinea pigs were divided into 6 groups: a control group, an OVA model group, an OVA + CS model group, a Suhuang treatment group, a BUD treatment group, and a combination (Suhuang and BUD) treatment group. The effects of the treatment were determined by measuring lung function (RI/Cydn) and cough symptoms (coughs number/cough latency) as outcome criteria. The levels of inflammatory cytokines in bronchoalveolar lavage fluid (BALF) were determined by ELISA. Lung tissues were stained by hematoxylin and eosin (H&E). The expressions of GR/total p38 MAPK/p-p38 MAPK were detected by Western blot. The MKP-1 mRNA levels were detected by RT-PCR. Results. Combination treatment significantly decreased RI/coughs numbers and increased Cydn/cough latency. Significantly, the results indicated that combination treatment decreased injury to pulmonary tissues. Results also revealed that levels of inflammatory cytokines were reduced in all treatment groups but most markedly in the combination treatment group. Moreover, Suhuang treatment significantly ameliorated corticosteroid insensitivity by improving the expression of glucocorticoid receptors (GR). The expressions of total p38 MAPK and p-p38 MAPK in lung tissue were significantly inhibited in the Suhuang and combination treatment groups. The MKP-1 mRNA levels in Suhuang and combination treatment groups were also increased significantly. Conclusion. Suhuang was effective for reversing corticosteroid insensitivity by regulating the p38 MAPK signal pathway, and combining BUD and Suhuang treatment showed synergistic interactions in CVA guinea pigs. Our findings showed that this combination therapy might be a promising therapeutic agent for CVA and also clarified its underlying mechanism of action, providing a theoretical basis for clinical combination treatment with Suhuang and BUD in CVA patients.