A Scalable and Robust Water Management Strategy for PEMFCs: Operando Electrothermal Mapping and Neutron Imaging Study.

Effective water management is crucial for the optimal operation of low-temperature polymer electrolyte membrane fuel cells (PEMFCs). Excessive liquid water production can cause flooding in the gas diffusion electrodes and flow channels, limiting mass transfer and reducing PEMFC performance. To tackle this issue, a nature-inspired chemical engineering (NICE) approach has been adopted that takes cues from the integument structure of desert-dwelling lizards for passive water transport. By incorporating engraved, capillary microchannels into conventional flow fields, PEMFC performance improves significantly, including a 15% increase in maximum power density for a 25 cm2 cell and 13% for a 100 cm2 cell. Electro-thermal maps of the lizard-inspired flow field demonstrate a more uniform spatial distribution of current density and temperature than the conventional design. Neutron radiography provides evidence that capillary microchannels in the lizard-inspired flow field facilitate the efficient transport and removal of generated liquid water, thereby preventing blockages in the reactant channels. These findings present a universally applicable and highly efficient water management strategy for PEMFCs, with the potential for widespread practical implementation for other electrochemical devices.

Blood-brain barrier injury and neuroinflammation induced by SARS-CoV-2 in a lung-brain microphysiological system.

In some patients, COVID-19 can trigger neurological symptoms with unclear pathogenesis. Here we describe a microphysiological system integrating alveolus and blood-brain barrier (BBB) tissue chips that recapitulates neuropathogenesis associated with infection by SARS-CoV-2. Direct exposure of the BBB chip to SARS-CoV-2 caused mild changes to the BBB, and infusion of medium from the infected alveolus chip led to more severe injuries on the BBB chip, including endothelial dysfunction, pericyte detachment and neuroinflammation. Transcriptomic analyses indicated downregulated expression of the actin cytoskeleton in brain endothelium and upregulated expression of inflammatory genes in glial cells. We also observed early cerebral microvascular damage following lung infection with a low viral load in the brains of transgenic mice expressing human angiotensin-converting enzyme 2. Our findings suggest that systemic inflammation is probably contributing to neuropathogenesis following SARS-CoV-2 infection, and that direct viral neural invasion might not be a prerequisite for this neuropathogenesis. Lung-brain microphysiological systems should aid the further understanding of the systemic effects and neurological complications of viral infection.

Brain organoid-on-chip system to study the effects of breast cancer derived exosomes on the neurodevelopment of brain.

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.

Malignant Melanoma-Derived Exosomes Induce Endothelial Damage and Glial Activation on a Human BBB Chip Model.

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.

EGFR signaling confers resistance to BET inhibition in hepatocellular carcinoma through stabilizing oncogenic MYC.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Oriented covalent immobilization of recombinant protein A on the glutaraldehyde activated agarose support.

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.

Comparison of two different standards of care in detecting malignant thyroid nodules using thyroid fine-needle aspiration.

The aim of the present study was to verify the optimal method to obtain enough fine-needle aspiration (FNA) materials for detecting thyroid malignancy. A prospective study was performed by comparing two different regional standards of care. In one group a traditional FNA method mainly used in Asian countries, including China, was performed in which a single pass of a 22-G needle was applied with or without aspiration. In the other group, the method mainly used in Western countries was performed in which three passes of a 25-G needle with non-aspiration were undertaken for thyroid nodules. The study included 718 thyroid nodules from 695 patients. These nodules were allocated for three different methods of performing thyroid FNA. There were 332 thyroid nodules subjected to the traditional Asian FNA method using a 22-G needle with aspiration for 142 nodules and non-aspiration for 190 nodules. FNA using the Western method was performed with three passes of non-aspiration using 25 G for 386 nodules. All the FNAs were performed with the guidance of ultrasound. The components of the nodules were documented. All the samples were reported using the Bethesda System for Reporting Thyroid Cytopathology. Among the 22 G group, the non-diagnostic rate in the aspiration group was as high as 76.76%, which was significantly higher than 44.21% in the non-aspiration group (P<0.01). For the non-aspiration group, the non-diagnostic rate in the 25 G group was 34.97%, which was significantly lower than 44.21% in the 22 G group. In general, the non-diagnostic rate for the 25-G needle was 34.97%, which was significantly lower than 58.13% in all the 22 G groups. For the solid and mixed nodules, the non-diagnostic rate was lower in the 25-G needle group compared to the 22 G groups with statistical significance. The non-aspiration method using a 25-G needle with multiple passes can result in a higher diagnostic rate for thyroid FNA.

Coexistence of Histologically Confirmed Hashimoto's Thyroiditis with Different Stages of Papillary Thyroid Carcinoma in a Consecutive Chinese Cohort.

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.

Surface properties of SAC and its adsorption mechanisms for phenol and nitrobenzene.

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 10 mmol/L, the maximum phenol and nitrobenzene adsorption capacity of SAC is 0.48 and 1.26 mmol/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.