Omental metastasis occurs frequently in gastric cancer (GC) and is considered one of the major causes of gastric cancer-related mortality. Recent research indicated that omental adipocytes might mediate this metastatic predilection. Phosphatidylinositol transfer protein, cytoplasmic 1 (PITPNC1) was identified to have a crucial role in metastasis. However, whether PITPNC1 participates in the interaction between adipocytes and GC omental metastasis is unclear.Methods: We profiled and analyzed the expression of PITPNC1 through analysis of the TCGA database as well as immunohistochemistry staining using matched GC tissues, adjacent normal gastric mucosa tissues (ANTs), and omental metastatic tissues. The regulation of PITPNC1 by adipocytes was explored by co-culture systems. By using both PITPNC1 overexpression and silencing methods, the role of PITPNC1 in anoikis resistance and metastasis was determined through in vitro and in vivo experiments.Results: PITPNC1 was expressed at higher rates in GC tissues than in ANTs; notably, it was higher in omental metastatic lesions. Elevated expression of PITPNC1 predicted higher rates of omental metastasis and a poor prognosis. PITPNC1 promoted anoikis resistance through fatty acid metabolism by upregulating CD36 and CPT1B expression. Further, PITPNC1 was elevated by adipocytes and facilitated GC omental metastasis. Lastly, in vivo studies showed that PITPNC1 was a therapeutic indicator of fatty acid oxidation (FAO) inhibition.Conclusion: Elevated expression of PITPNC1 in GC is correlated with an advanced clinical stage and a poor prognosis. PITPNC1 promotes anoikis resistance through enhanced FAO, which is regulated by omental adipocytes and consequently facilitates GC omental metastasis. Targeting PITPNC1 might present a promising strategy to treat omental metastasis.

Background: Metastasis and recurrence, wherein circulating tumour cells (CTCs) play an important role, are the leading causes of death in colorectal cancer (CRC). Metastasis-initiating CTCs manage to maintain intravascular survival under anoikis, immune attack, and importantly shear stress; however, the underlying mechanisms remain poorly understood. Methods: In view of the scarcity of CTCs in the bloodstream, suspended colorectal cancer cells were flowed into the cyclic laminar shear stress (LSS) according to previous studies. Then, we detected these suspended cells with a CK8+/CD45−/DAPI+ phenotype and named them mimic circulating tumour cells (m-CTCs) for subsequent CTCs related researches. Quantitative polymerase chain reaction, western blotting, and immunofluorescence were utilised to analyse gene expression change of m-CTCs sensitive to LSS stimulation. Additionally, we examined atonal bHLH transcription factor 8 (ATOH8) expressions in CTCs among 156 CRC patients and mice by fluorescence in situ hybridisation and flow cytometry. The pro-metabolic and pro-survival functions of ATOH8 were determined by glycolysis assay, live/dead cell vitality assay, anoikis assay, and immunohistochemistry. Further, the concrete up-anddown mechanisms of m-CTC survival promotion by ATOH8 were explored. Results: The m-CTCs actively responded to LSS by triggering the expression of ATOH8, a fluid mechanosensor, with executive roles in intravascular survival and metabolism plasticity. Specifically, ATOH8 was upregulated via activation of VEGFR2/AKT signalling pathway mediated by LSS induced VEGF release. ATOH8 then transcriptionally activated HK2-mediated glycolysis, thus promoting the intravascular survival of colorectal cancer cells in the circulation. Conclusions:This study elucidates a novel mechanism that an LSS triggered VEGF-VEGFR2-AKT-ATOH8 signal axis mediates m-CTCs survival, thus providing a potential target for the prevention and treatment of hematogenous metastasis in CRC.

Purpose To classify radiation necrosis versus recurrence in glioma patients using a radiomics model based on combinational features and multimodality MRI images. Methods Fifty-one glioma patients who underwent radiation treatments after surgery were enrolled in this study. Sixteen patients revealed radiation necrosis while 35 patients showed tumor recurrence during the follow-up period. After treatment, all patients underwent T1-weighted, T1-weighted postcontrast, T2-weighted, and fluid-attenuated inversion recovery scans. A total of 41,284 handcrafted and 24,576 deep features were extracted for each patient. The 0.623 + bootstrap method and the area under the curve (denoted as 0.632 + bootstrap AUC) metric were used to select the features. The stepwise forward method was applied to construct 10 logistic regression models based on different combinations of image features. Results For handcrafted features on multimodality MRI, model 7 with seven features yielded the highest AUC of 0.9624, sensitivity of 0.8497, and specificity of 0.9083 in the validation set. These values were higher than the accuracy of using handcrafted features on single-modality MRI (paired t-test, p < 0.05, except sensitivity). For combined handcrafted and AlexNet features on multimodality MRI, model 6 with six features achieved the highest AUC of 0.9982, sensitivity of 0.9941, and specificity of 0.9755 in the validation set. These values were higher than the accuracy of using handcrafted features on multimodality MRI (paired t-test, p < 0.05). Conclusions Handcrafted and deep features extracted from multimodality MRI images reflecting the heterogeneity of gliomas can provide useful information for glioma necrosis/recurrence classification.

With the rapid development of protein-based pharmaceutical products over the past decade, one of the biggest challenges in product development is maintaining the structural stability of proteins during purification, processing, and storage. In this work, the design of a new class of surfactants, polyethermodified N-acyl amino acids, is presented. One surfactant from this series, containing a phenylalanine moiety, demonstrated remarkable stabilization against aggregation of several model protein drugs. Dynamic light scattering, size exclusion chromatography, and circular dichroism all show the rate of thermally accelerated protein aggregation slowed. IgG aggregation was reduced by 3-fold compared to polysorbate controls. Testing of Orencia, a prescription biologic drug for rheumatoid arthritis, demonstrated a 36% improvement in monomer retention upon heat-aging.

Background: Neoadjuvant radiotherapy is a commonly used method for the current standard-of-care for most patients with rectal cancer, when the effects of radioresistance are limited. The phosphatidylinositol transfer protein, cytoplasmic 1 (PITPNC1), a lipid-metabolism-related gene, has previously been proved to manifest pro-cancer effects in multiple types of cancer. However, whether PITPNC1 plays a role for developing radioresistance in rectal cancer patients is still unknown. Therefore, this study aims to investigate the role of PITPNC1 in rectal cancer radioresistance.Methods: Patient-derived tissue were used to detect the difference in the expression level of PITPNC1 between radioresistant and radiosensitive patients. Bioinformatic analyses of high-throughput gene expression data were applied to uncover the correlations between PITPNC1 level and oxidative stress. Two rectal cancer cell lines, SW620, and HCT116, were selected in vitro to investigate the effect of PITPNC1 on radioresistance, reactive oxygen species (ROS) generation, apoptosis, and proliferation in rectal cancer.Results: PITPNC1 is highly expressed in radioresistant patient-derived rectal cancer tissues compared to radiosensitive tissue; therefore, PITPNC1 inhibits the generation of ROS and improves the extent of radioresistance of rectal cancer cell lines and then inhibits apoptosis. Knocking down PITPNC1 facilitates the production of ROS while application of the ROS scavenger, N-acetyl-L-cysteine (NAC), could reverse this effect.Conclusions: PITPNC1 fuels radioresistance of rectal cancer via the inhibition of ROS generation.

This study examines China’s mass innovation/mass entrepreneurship campaign, with particular attention to the community of maker-entrepreneurs in the new techno-political ordering of society and their social territories. This raises the question of the subject-making of maker-entrepreneurs on a massive scale through what we call the new education–incubatory assemblage. How does the new education–incubatory machine assemble a new participatory community, form a production–communications–consumption circuit to imagine the new economy and re-territorialise the techno-political ordering of society? Our study stresses two differences in the social factory. First, by forging a fragmented pattern of production and an individualised society, mass entrepreneurship emphasises social networking. The exploitation of social relations in production has been brought to the foreground. Second, a participatory mass is not only shaped by the new mentality, but also constitutive of the very formation of the new mentality. Such a mass is a collection of actors, from the government, cooperatives, start-ups and individuals. In addition, their agencies vary, from those with a more reified form of power, such as policy, to the mundane, unrehearsed actions of individuals. This process entails the reconfiguration of political apparatus and bio-political power.

Acinetobacter baumannii is an important opportunistic pathogen common in clinical infections. Phage therapy become a hot research field worldwide again after the post-antibiotic era. This review summarizes the important progress of phage treatments for A. baumannii in the last five years, and focus on the new interesting advances including the combination of phage and other substances (like photosensitizer), and the phage encapsulation (by microparticle, hydrogel) in delivery. We also discuss the remaining challenges and promising directions for phage-based therapy of A. baumannii infection in the future, and the innovative combination of materials in this area may be one promising direction.

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