Lung-inspired, fractal flow-fields hold great potential in improving the performance of polymer electrolyte membrane fuel cells (PEMFCs) by providing uniform gas distribution across the electrodes ...and ensuring minimum entropy production in the whole system. However, the inherent susceptibility of the fractal flow-fields to flooding renders their use inadequate at high humidity conditions. In-depth understanding of water management in lung-inspired flow-fields is indispensable for the implementation of alternative outlet channel geometries or engineered water removal strategies to alleviate flooding. Here, liquid water formation and transport across the lung-inspired and serpentine flow-field based PEMFCs are evaluated using neutron radiography. The results reveal a propensity to flooding in the interdigitated outlet channels of the fractal flow-field with N = 4 generations as a result of slow gas velocity and narrow channel dimensions, which leads to significant performance deterioration. Neutron images also elucidate the importance of ensuring a well-defined internal channel structure of the fractal flow-fields to prevent backflow of liquid water via wicking and capillary pressure build-up arising from the narrow inlet gas channels and hydrophobic gas diffusion layer.
•Neutron radiographs are presented for the lung-inspired and serpentine flow-fields.•A well-defined channel structure of the fractal flow-field is indispensable.•Water removal strategies required to alleviate flooding in the fractal flow-field.
Malignant melanoma is a type of highly aggressive tumor, which has a strong ability to metastasize to brain, and 60-70% of patients die from the spread of the tumor into the central nervous system. ...Exosomes are a type of nano-sized vesicle secreted by most living cells, and accumulated studies have reported that they play crucial roles in brain tumor metastasis, such as breast cancer and lung cancer. However, it is unclear whether exosomes also participate in the brain metastasis of malignant melanoma. Here, we established a human blood-brain barrier (BBB) model by co-culturing human brain microvascular endothelial cells, astrocytes and microglial cells under a biomimetic condition, and used this model to explore the potential roles of exosomes derived from malignant melanoma in modulating BBB integrity. Our findings showed that malignant melanoma-derived exosomes disrupted BBB integrity and induced glial activation on the BBB chip. Transcriptome analyses revealed dys-regulation of autophagy and immune responses following tumor exosome treatment. These studies indicated malignant melanoma cells might modulate BBB integrity via exosomes, and verified the feasibility of a BBB chip as an ideal platform for studies of brain metastasis of tumors in vitro.
► We prepare SAC with abundant acid groups from sewage sludge. ► Phenol adsorption on SAC is mainly determined by SAC’s surface area. ► The acid groups on SAC favor the adsorption of nitrobenzene. ► ...Nitrobenzene adsorption on SAC may be attributed to its polarity and hydrophobicity.
The physicochemical properties of an activated carbon produced from sewage sludge (SAC) were determined and compared with those of a market activated carbon (MAC). Phenol and nitrobenzene were selected as the target compounds and their adsorption behaviors in water and cyclohexane were studied and compared. The experimental results showed that the surface area of SAC was only 1/4 of that of the MAC. Functional groups on the SAC are all acid groups while basic groups are the dominant on the MAC. Based on the properties of the activated carbons and the adsorption behaviors of the two organic pollutants, it could be inferred preliminarily that phenol adsorption was mainly affected by surface area but nitrobenzene adsorption was affected by both surface area and surface functional groups. In water, when the initial concentration is between 0.1 and 10mmol/L, the maximum phenol and nitrobenzene adsorption capacity of SAC is 0.48 and 1.26mmol/g respectively, which is 1/4 and 1/3 of that of MAC. In cyclohexane, SAC’s phenol adsorption capacity is higher and nitrobenzene adsorption capacity is lower than that in water; but MAC’s phenol adsorption capacity does not change much and nitrobenzene adsorption capacity decreases a lot compared that in water. The results further indicate that the hydrophobicity and the polarity of the organic pollutants can greatly affect their adsorption in water. For SAC, polar interaction and hydrophobic interaction may be the main mechanisms affecting the sorption of nitrobenzene in water. For MAC, hydrophobic interaction and π–π interaction may be the main mechanisms affecting the sorption of nitrobenzene in water. For both phenol and nitrobenzene, the adsorption capacities of MAC are higher than that of SAC.
The bromodomain and extra-terminal domain (BET) inhibitor is a type of anti-tumor agent, currently being evaluated in phase I and II clinical trials for cancer therapy. It can decrease MYC expression ...levels and cause effective anti-tumor effects in diverse human cancers. However, its cytotoxic effect and related mechanisms of drug resistance are poorly understood in hepatocellular carcinomas (HCC). Here, we investigated the anti-tumor effects of BET inhibitor on HCC and the molecular mechanisms involved in its associated drug resistance.
We assessed the cytotoxicity of BET inhibitor on HCC cells compared with sorafenib by cell viability assay, metastasis assay and reproduced the anti-tumor effect in xenograft mouse model. In addition, the molecular mechanisms involved in drug resistance on JQ1-resistant HCC cells were revealed by western blotting, qRT-PCR, whole exome-sequencing and gene-editing technology. Finally, with specific inhibition of EGFR or ERK activity by interference RNAs or inhibitors, the efficacy of the synergistic treatment was investigated using cell viability assay, colony formation, apoptosis and xenograft mouse model.
We found that JQ1, a commonly used BET bromo-domain inhibitor, offered a better anti-tumor response than sorafenib in MYC-positive HCC cells by inducing apoptosis in vitro and in vivo. Unlike sorafenib, JQ1 treatment significantly impaired mitochondrial respiration and glycolysis in HCC cells. Importantly, we revealed that MAPK activation by a previously undescribed activating mutation of EGFR-I645L, was critical for JQ1 sensitivity through stabilizing oncogenic MYC protein in JQ1-resistant HCC cells. Inhibition of either EGFR or ERK activity overcame the JQ1 resistance and significantly decreased MYC protein level in vitro and in vivo.
Since MYC amplification is frequently identified in HCC, co-occurring with EGFR amplification, our findings suggest that targeting EGFR signaling might be essential for JQ1 therapy in advanced HCC.
Early human brain development can be affected by multiple prenatal factors that involve chemical exposures
in utero,
maternal health characteristics such as psychiatric disorders, and cancer. Breast ...cancer is one of the most common cancers worldwide arising pregnancy. However, it is not clear whether the breast cancer might influence the brain development of fetus. Exosomes secreted by breast cancer cells play a critical role in mediating intercellular communication and interplay between different organs. In this work, we engineered human induced pluripotent stem cells (hiPSCs)-derived brain organoids in an array of micropillar chip and probed the influences of breast cancer cell (MCF-7) derived-exosomes on the early neurodevelopment of brain. The formed brain organoids can recapitulate essential features of embryonic human brain at early stages, in terms of neurogenesis, forebrain regionalization, and cortical organization. Treatment with breast cancer cell derived-exosomes, brain organoids exhibited enhanced expression of stemness-related marker OCT4 and forebrain marker PAX6. RNA-seq analysis reflected several activated signaling pathways associated with breast cancer, medulloblastoma and neurogenesis in brain organoids induced by tumor-derived exosomes. These results suggested that breast cancer cell-derived exosomes might lead to the impaired neurodevelopment in the brain organoids and the carcinogenesis of brain organoids. It potentially implies the fetus of pregnant women with breast cancer has the risk of impaired neurodevelopmental disorder after birth.
The use of acoustic emission as a low-cost, non-destructive, and operando diagnostic tool has been demonstrated for a range of electrochemical energy conversion and storage devices, including polymer ...electrolyte membrane water electrolysers (PEMWEs) and fuel cells. In this work, an abrupt change in acoustic regime is observed during operation of a PEMWE as the current density is increased from 0.5 to 1.0 A cm−2. This regime change is marked by a sudden drop in the number of acoustic hits, while hit duration, amplitude, and energy increase significantly. It is found that the change in acoustic regime coincides with a significant extension of the stagnant bubble region in the flow channels of the PEMWE, observed with high-speed optical imaging. These results demonstrate that acoustic emission can be used effectively as an operando diagnostic tool to monitor bubble formation (two-phase flow conditions) in PEMWEs, facilitating rapid testing or prototyping, and contributing to operational safety.
Bug reports which are written by different people have a variety of styles, and such various styles lead to difficulty in understanding bug reports. To enhance the comprehensibility of bug reports, ...GitHub has proposed a template mechanism to guide how to report the bugs. However, there is no study on the use of bug report templates on GitHub. In this paper, we conduct an empirical study on the bug report templates on GitHub, including the popularity, benefits, and content of the templates. Our empirical study finds that: (1) For popularity, more and more open source projects and bug reports are applying templates over time. (2) For benefits, bug reports written using templates will be resolved quicker and have a higher comment coverage. (3) For content, the most common items for templates are expected behavior, describe the bug and to reproduce etc. Additionally, we summarize a taxonomy of items for bug report templates. Finally, we propose an automatic templating approach for templating an un-templated bug report. Our approach achieves an accuracy of 0.718 and an F1-score of 0.717 on average, which shows that our approach can effectively templatize an un-templated bug report.
•We conduct the first empirical study on the bug report templates on GitHub from three aspects (i.e., popularity, benefit, and content).•For popularity, we find that more and more projects and bug reports are written using templates.•For benefits, we find that bug reports with templates have shorter resolution times and higher comment coverage.•For content, we discover the most commonly used items and summarize the main item categories.•We propose an automatic templating approach to effectively templatize an un-templated bug report.
High IgG-binding capacity of protein A affinity chromatography is crucial to its application in the antibody purification and autoantibody-associated disease treatment. An oriented immobilization ...strategy was used to covalently conjugate the recombinant protein A (rSpA) on the glutaraldehyde activated agarose. By controlling the glutaraldehyde concentration, pH and reactivity time, one or two molecules of glutaraldehyde per primary amino group were anchored on agarose supports. The structure differences of activated supports were evaluated. Moreover, the 3D surface structure of B domain was modeled to explore the distribution of reactive and adsorptive groups. Compared with the monomeric glutaraldehyde agarose (Aga@MG), the dimeric glutaraldehyde agarose (Aga@DG) seems to be involved with more amino acid groups of rSpA during the immobilization. The leaked rSpA of 0.24 ng/mg IgG from Aga@DG@rSpA was slightly lower than that of 0.36 ng/mg IgG from Aga@MG@rSpA. However, Aga@MG is more suitable for oriented immobilization of rSpA which endows the prepared adsorbents to higher IgG-binding capacity. When rSpA was immobilized on Aga@MG at the low and high ionic strength, the maximum capacities from Langmuir model were 56.2 and 59.2 mg/g, respectively. The Aga@MG provided shorter spacer arm compared with the Aga@DG, which contributed to the oriented immobilization of rSpA.
•Aga@MG is more suitable for oriented immobilization of proteins than Aga@DG.•Location of anionic and hydrophobic groups on the surface of B domain was analyzed.•Oriented immobilization of rSpA was achieved by controlling the conditions.•IgG-binding performance of oriented rSpA on supports outperformed the random one.
Purpose. To determine the relationship between Hashimoto’s thyroiditis (HT) and all stages of papillary thyroid carcinoma (PTC) with or without local lymph node metastasis (LNM). Methods. We ...conducted a retrospective study of thyroidectomies from 2008–2013 in First Affiliated Hospital of Nanjing Medical University. We categorized patients according to the presence of histopathologically proven HT. The prevalence of mPTC (maximum diameter ≤ 10 mm) and crPTC (clinical relevant PTC) and local LNM rates were compared. Results. We evaluated 6,432 consecutive thyroidectomies. In total, 1,328 specimens were confirmed as HT. The prevalence of PTC in this HT cohort was 43.8%, significantly higher than non-HT group. After adjustment of gender and age, the prevalence of PTC was still higher in HT group. HT was a risk factor for PTC in multivariate analysis with odds ratio 2.725 (95% CI, 2.390–3.109) ( P < 0.001 ). However, no correlation was found between HT and LNM of PTC. Conclusion. HT was associated with an increased prevalence of all stages of PTC, independent of tumor size, gender, and age. In contrast, locally advanced disease defined by LNM was unrelated to HT. These data suggest an association of HT with low risk PTC and a potential protective immunologic effect from further disease progression.
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