Table_1_Efficacy of EGFR-TKI Plus Chemotherapy or Monotherapy as First-Line Treatment for Advanced EGFR-Mutant Lung Adenocarcinoma Patients With Co-Mutations.docx

BackgroundCo-mutations was associated with poor response to EGFR-TKIs. First-generation EGFR-TKIs combined with chemotherapy was reported to be more effective than TKIs alone in advanced lung adenocarcinoma patients.ObjectiveThis retrospective study aimed to explore whether EGFR-mutant patients with co-mutations can benefit from EGFR-TKIs plus chemotherapy.Patients and MethodsWe retrospectively collected data of 137 EGFR-mutant patients with advanced lung adenocarcinoma who underwent next-generation sequencing in our hospital in 2018. Among them, 96 were treated with EGFR–TKIs alone and 41 received EGFR–TKIs plus chemotherapy. We analyzed the progression-free survival (PFS) of patients with co-mutations using different treatments.ResultsConcurrent TP53 mutations, especially exon 4 and 6, were associated with a markedly shorter time to progression on EGFR-TKI monotherapy (11.4 months vs. 16.6 months, P=0.003), while EGFR–TKIs plus chemotherapy would benefit those patients more (with TP53: 11.4 months vs. 19.1 months, P=0.001, HR=0.407; without TP53: 16.6 months vs. 18.9 months, P=0.379, HR=0.706). The incidence of T790M after resistance was equal in patients treated with different treatments (53% vs. 53%, P=0.985).ConclusionsIn our study, concurrent TP53 mutations were found to be risk factors for EGFR-TKI monotherapy, but TKI combined with chemotherapy could eliminate this heterogeneity.</p

Well-Defined Oligo(azobenzene-<i>graft</i>-mannose): Photostimuli Supramolecular Self-Assembly and Immune Effect Regulation

The immune system can recognize and respond to pathogens of various shapes. Synthetic materials that can change their shape have the potential to be used in vaccines and immune regulation. The ability of supramolecular assemblies to undergo reversible transformations in response to environmental stimuli allows for dynamic changes in their shapes and functionalities. A meticulously designed oligo­(azobenzene-graft-mannose) was synthesized using a stepwise iterative method and “click” chemistry. This involved integrating hydrophobic and photoresponsive azobenzene units with hydrophilic and bioactive mannose units. The resulting oligomer, with its precise structure, displayed versatile assembly morphologies and chiralities that were responsive to light. These varying assembly morphologies demonstrated distinct capabilities in terms of inhibiting the proliferation of cancer cells and stimulating the maturation of dendritic cells. These discoveries contribute to the theoretical comprehension and advancement of photoswitchable bioactive materials

A phylogenetic tree of the microbiota reveals taxa commonly found in the skin and gut.

(TIFF)</p

Demonstrating the cage effect.

(TIFF)</p

Pairwise statistical tests of the 15 most abundant families.

(TIFF)</p

Repeated exposure to oxazolone induces skin thickening and recruitment of immune cells.

OXA-induced inflammation was studied by measuring thickness of epidermis (A) and dermis (B) in H&E-stained skin sections. The number of total cells (C), lymphocytes (D), eosinophils (E) and neutrophils (F) were counted from H&E-stained skin tissue under a light microscope at 1000x magnification. P values for epidermis and dermis were calculated with Brown-Forsythe and Welch ANOVA and Dunnett’s T3 multiple comparison tests and P values for immune cells were calculated with Kruskal-Wallis and Dunn’s multiple comparison tests. Yellow significance stars indicate the test between naïve and positive or naïve and negative, and blue significance stars between negative and positive group. P values: * < 0.05. ** < 0.01, *** < 0.001, **** < 0.0001.</p

Histological ear tissue stainings.

(TIFF)</p

Pairwise statistical test results of microbial abundance of within group timepoints based on HMSC.

Each ASV, its lowest rank, statistical test, comparison, and the result are given in each column. GLMM = generalised linear mixed model.</p

Table_4_Context-Specific Coordinately Regulatory Network Prioritize Breast Cancer Genetic Risk Factors.XLSX

Breast cancer (BC) is one of the most common tumors, leading the causes of cancer death in women. However, the pathogenesis of BC still remains unclear, and the atlas of BC-associated risk factors is far from complete. In this study, we constructed a BC-specific coordinately regulatory network (CRN) to prioritize potential BC-associated protein-coding genes (PCGs) and non-coding RNAs (ncRNAs). We integrated 813 BC sample transcriptome data from The Cancer Genome Atlas (TCGA) and eight types of regulatory relationships to construct BC-specific CRN, including 387 transcription factors (TFs), 174 microRNAs (miRNAs), 407 long non-coding RNAs (lncRNAs), and 905 PCGs. After that, the random walk with restart (RWR) method was performed on the CRN by using the known BC-associated factors as seeds, and potential BC-associated risk factors were prioritized. The leave-one-out cross-validation (LOOCV) was utilized on the BC-specific CRN and achieved an area under the curve (AUC) of 0.92. The performances of common CRN, common protein–protein interaction (PPI) network, and BC-specific PPI network were also evaluated, demonstrating that the context-specific CRN prioritizes BC risk factors. Functional analysis for the top 100-ranked risk factors in the candidate list revealed that these factors were significantly enriched in cancer-related functions and had significant semantic similarity with BC-related gene ontology (GO) terms. Differential expression analysis and survival analysis proved that the prioritized risk factors significantly associated with BC progression and prognosis. In total, we provided a computational method to predict reliable BC-associated risk factors, which would help improve the understanding of the pathology of BC and benefit disease diagnosis and prognosis.</p

Number of BCSSCs signature genes.

Number of BCSSCs signature genes.</p