Perfluoroalkyl Functionalized Superhydrophobic Covalent Organic Frameworks for Excellent Oil-Water Membrane Separation and Anhydrous Proton Conduction.

Rapid economic development has led to oil pollution and energy shortage. Membrane separation has attracted much attention due to its simplicity and efficiency in oil-water-separation. The development of membrane materials with enhanced separation properties is essential to improve the separation-efficiency. Proton exchange membrane fuel cells (PEMFCs) are expected to replace conventional engines due to their high-power-conversion rates and other favorable properties. Anhydrous-proton-conducting materials are vital components of PEMFCs. However, developing stable proton-conducting materials that exhibit high conductivity at varying temperatures remains challenging. Herein, two covalent organic frameworks (COFs) with long-side-chains are synthesized, and their corresponding COF@SSN membranes. Both membranes can effectively separate oil-water mixtures and water-in-oil emulsions. The TFPT-AF membrane achieves a maximum oil-flux of 6.05 × 105 g h-1 m-2 with an oil-water separation efficiency of above 99%, which is almost unchanged after 20 consecutive uses. COF@H3PO4 doped with different ratios of H3PO4 is prepared, the results show that the perfluorocarbon-chain system has  excellent anhydrous proton conductivity , achieving an ultra-high proton-conductivity of 3.98 × 10-1 S cm-1 at 125 °C. This study lays the foundation for tailor-made-functionalization of COF through pre-engineering and surface-modification, highlighting the great potential of COFs for oil-water separation and anhydrous-proton-conductivity.

NDRG1 facilitates self-renewal of liver cancer stem cells by preventing EpCAM ubiquitination.

BACKGROUND: Portal vein tumour thrombus (PVTT) is the main pathway of HCC intrahepatic metastasis and is responsible for the poor prognosis of patients with HCC. However, the molecular mechanisms underlying PVTT vascular metastases have not been fully elucidated. METHODS: NDRG1 expression was assessed by immunohistochemistry and immunoblotting in clinical specimens obtained from curative surgery. The functional relevance of NDRG1 was evaluated using sphere formation and animal models of tumorigenicity and metastasis. The relationship between NDRG1 and EpCAM was explored using molecular biological techniques. RESULTS: NDRG1 protein was upregulated in HCC samples compared to non-tumorous tissues. Furthermore, NDRG1 expression was enhanced in the PVTT samples. Our functional study showed that NDRG1 was required for the self-renewal of tumour-initiating/cancer stem cells (CSCs). In addition, NDRG1 knockdown inhibited the proliferation and migration of PVTT-1 cells in vitro and in vivo. NDRG1 was found to stabilise the functional tumour-initiating cell marker EpCAM through protein-protein interactions and inhibition of EpCAM ubiquitination. CONCLUSION: Our findings suggest that NDRG1 enhances CSCs expansion, PVTT formation and growth capability through the regulation of EpCAM stability. NDRG1 may be a promising target for the treatment of patients with HCC and PVTT.

Establishment of an inducible cell line for Hepatitis B virus genotype C2 and its pharmacological responses to interferons.

Hepatitis B virus (HBV) genotype C is closely associated with poor prognosis, contributing greatly to heavy chronic hepatitis B (CHB)-related liver disease burden in China and worldwide. However, the mechanistic studies on genotype C of HBV remain largely limited, partially because of a long-term lack of genotype C HBV-based stable cellular tools. According to a bioinformatics analysis on the sub-genotype C2 HBV that is predominantly endemic in China, we selected 17.3 strain as a representative isolate. With a Tet-off gene expression system, an inducible viral replication and virion DNA production of genotype C2 HBV were achieved in a cell line carrying persistent rcDNA-cccDNA recycling, termed HepG2-17.3, can be useful for virological studies. Additionally, this cell line has been formatted into cell-based assay that permits particular pharmacological screening of drug candidates, such as interferon regimens, for evaluations of the inhibitory effects on genotype C2 HBV replication.

3D landscape of Hepatitis B virus interactions with human chromatins.

Hepatitis B viral (HBV) DNAs, including covalently closed circular DNA (cccDNA) and integrated HBV DNA forms, are considered to be primary contributors to the development and progression of HBV-associated liver diseases. However, it remains largely unclear how HBV DNAs communicate with human chromatin. Here we employed a highly sensitive technology, 3C-high-throughput genome-wide translocation sequencing (3C-HTGTS), to globally identify HBV DNA-host DNA contacts in cellular models of HBV infection. HBV DNA does not randomly position in host genome but instead preferentially establishes contacts with the host DNA at active chromatin regions. HBV DNA-host DNA contacts are significantly enriched at H3K4me1-marked regions modified by KMT2C/D; this histone modification is also observed in the HBV cccDNA mini-chromosome and strongly influences HBV transcription. On the other hand, chromatin loop formed by integrated HBV DNA with host genomic DNA was found in transcriptionally active regions. Furthermore, HBV infection influences host gene expression accompanied with HBV DNA-host DNA contacts. Our study provides a 3D landscape of spatial organization of cccDNA and integrated HBV DNA within the human genome, which lays the foundation for a better understanding of the mechanisms how HBV involves in liver disease development and progression.

Influence of Foot-and-Mouth Disease Virus O/CHN/Mya98/33-P Strain Leader Protein on Viral Replication and Host Innate Immunity.

Foot-and-mouth disease virus (FMDV) O/CHN/Mya98/33-P strain was isolated from the esophageal-pharyngeal fluid sample of cattle, and was shown to cause persistent infection. Its leader protein contains 200 amino acids with one amino acid deletion, which is upstream and next to the second initiation codon compared with the majority of FMDV Mya98 strains. The FMDV genome includes two initiation codons that can produce two different leader proteins, Lab (from the first AUG) and Lb (from the second AUG). For convenience, the inter-AUG region was named as La. Previously, it was found that a recombinant virus with Lab of FMDV O/CHN/Mya98/33-P strain had higher proliferation efficiency, and better ability to inhibit the host innate immune response. Three full-length infectious cDNA clones-rHN33-Lb, rHN33-La, and rHNGSLX-Lb-containing the FMDV O/CHN/Mya98/33-P strain leader proteins Lb, La, or the FMDV O/GSLX/2010 strain leader protein Lb, respectively, were constructed based on an established infectious clone r-HN rescued from FMDV O/HN/CHN/93 strain. After infecting pig kidney primary cells, rHN33-La showed higher replication efficiency than r-HN, and rHN33-Lb displayed better ability to resist host innate immunity than rHNGSLX-Lb. These results demonstrated that the inter-AUG region of FMDV strain O/CHN/Mya98/33-P leader protein must be involved in increasing viral replication efficiency. Additionally, the Lb of FMDV O/CHN/Mya98/33-P must be involve in increasing its ability to inhibit host innate immune response, and the distinctive amino acids G56 and/or R118 of FMDV leader protein may play essential roles in it.