PRMT5 Cooperates with pICln to Function as a Master Epigenetic Activator of DNA Double-Strand Break Repair Genes

DNA double-strand break (DSB) repair is critical for cell survival and genome integrity. Upon recognition of DSBs, repair proteins are transiently upregulated to facilitate repair through homologous recombination (HR) or non-homologous end joining (NHEJ). We present evidence that PRMT5 cooperates with pICln to function as a master epigenetic activator of DNA damage response (DDR) genes involved in HR, NHEJ, and G2 arrest (including RAD51, BRCA1, and BRCA2) to upregulate gene expression upon DNA damage. Contrary to the predominant role of PRMT5 as an epigenetic repressor, our results demonstrate that PRMT5 and pICln can activate gene expression, potentially independent of PRMT5's obligate cofactor MEP50. Targeting PRMT5 or pICln hinders repair of DSBs in multiple cancer cell lines, and both PRMT5 and pICln expression positively correlates with DDR genes across 32 clinical cancer datasets. Thus, targeting PRMT5 or pICln may be explored in combination with radiation or chemotherapy for cancer treatment

The potential for the treatment of Antimony-containing Wastewater by Iron-based Adsorbents

Antimony (Sb) and its compounds are considered as global priority pollutants. Elevated concentrations of antimony in natural and industrial process wastewater are of global concern, particularly given interest in the potential toxicity and harm to the environment from aquatic exposure. Iron-based materials for treatment by adsorption are widely regarded to have potential merit for the removal of trace contaminants from water and especially in the search for efficient and low-cost techniques. In this paper, we review the application of iron-based materials in the sorption treatment of antimony contaminated water. The interaction of Sb is discussed in relation to adsorption performance, influencing factors, mechanism, modelling of adsorption (isotherm, kinetic and thermodynamic models), advantages, drawbacks and the recent achievements in the field. Although iron-based adsorbents show promise, the following three aspects are in need of further study. Firstly, a select number of iron based binary metal oxide adsorbents should be further explored as they show superior performance compared to other systems. Secondly, the possibility of redox reactions and conversion between Sb(III) and Sb(V) during the adsorption process is unclear and requires further investigation. Thirdly, in order to achieve optimized control of preferential adsorption sites and functional groups, the mechanism of antimony removal has to be qualitatively and quantitatively resolved by combining the advantages of advanced characterization techniques such as Fourier transform infrared spectroscopy(FTIR), X-ray photoelectron spectroscopy (XPS), Atomic force microscope(AFM), X-ray absorption near edge structure(XANES), and other spectroscopic methods. We provide details on the achievements and limitations of each of these stages and point to the need for further research

Impaired dendritic cell maturation and IL-10 production following H. pylori stimulation in gastric cancer patients

The current study was to investigate the interaction between Helicobacter pylori and human dendritic cells (DCs). Whether impaired DC function can influence the outcome of H. pylori infections. Human monocyte-derived DCs (MDDCs) from five gastric cancer patients and nine healthy controls were stimulated with H. pylori. Maturation markers of MDDC were examined by flow cytometry. IL-10 and TNF-α released by MDDCs and IL-17 produced by T cells were measured by ELISA. Regulatory signaling pathways of IL-10 were examined by ELISA, western blotting, and chromatin immunoprecipitation assay. The results showed that as compared with healthy individuals, the maturation marker CD40 in MDDCs, IL-17A expression from T cells, and IL-10 expression from MDDCs were significantly lower in gastric cancer patients. Blocking DC-SIGN, TLR2, and TLR4 could reverse H. pylori-associated IL-10 production. Activation of the p38 MAPK and NF-kB signaling pathways concomitant with decreased tri-methylated H3K9 and increased acetylated H3 accounted for the effect of H. pylori on IL-10 expression. Furthermore, upregulated IL-10 expression was significantly suppressed in H. pylori-pulsed MDDCs by histone acetyltransferase and methyltransferase inhibitors. Taken together, impaired DC function contributes to the less effective innate and adaptive immune responses against H. pylori seen in gastric cancer patients. H. pylori can regulate IL-10 production through Toll-like and DC-SIGN receptors, activates p-p38 MAPK signaling and the transcription factors NF-kB, and modulates histone modification

Treatment of breast deformity with free deep inferior epigastric perforator flap secondary to pectoralis major flap harvesting

SummaryHead and neck cancer is less common in women than in men. Free tissue transfer is the first choice in reconstructive option for head and neck tumor. Pedicle pectoralis major (PM) flap was a common option in head neck reconstruction in the past, but has become the salvage procedure when free flap fails. However, it is not suitable for female patients because of severe breast deformity and induced psychosocial distress. We present a female patient who had breast deformity due to PM flap reconstruction and was successfully treated with free deep inferior epigastric perforator (DIEP) flap. A 48-year-old woman had squamous cell carcinoma in the left side buccal mucosa, T2N0M0, stage II s/p wide excision with partial resection of maxilla and marginal resection of mandible. Free anterolateral thigh flap had been tried but in vain, then alternatively salvaged with a pedicle PM flap 3 years earlier. She presented with malposition of the left breast, nipple retraction, and high riding. We adequately released the contracture and reconstructed with a free DIEP flap. The free DIEP flap survived completely and restored a balanced breast with good shape and symmetry at 1-year follow-up. Although PM flap is a good modality in head and neck reconstruction, it should be used cautiously especially in female patients. The free DIEP flap is not only suitable for breast reconstruction in breast cancer patient, but also a good choice for a different purpose of breast reconstruction such as this patient with breast deformity due to PM flap harvest

Temporal and spatial distribution of phosphorus in the Xiangxi River

The phosphorus in water and sediment collected at different time from the Xiangxi River were analyzed. The results indicated that the phosphorus pollution have significant relations to human activities (especially the phosphorus industry). The concentrations of total-phosphorus (TP), total dissolved phosphorus (TDP) and dissolved phosphorus (DP) in Dec. 2004 were higher than those in Jul. 2005; the TP contents of sites 15 and 16 were much higher than others', the TP content of the largest site 16 was 1946.29 mg/kg in Dec. 2004 and 1756.11 mg/kg in Jul. 2005, respectively, which was much higher than the average (1497.51 mg/kg and 1369.38 mg/kg, respectively). The TP content in the sediment of the Xiangxi River was from 1179.53 mg/kg to 1851. 20 mg/kg. The TP contents of most sites except site 18, 19 and 20 were higher in Dec. 2004 than those in Jul. 2005. The aluminium-phosphorus (Al-P) content in the sediment was obviously higher in Jul. 2005 than that in Dec. 2004, which indicated that the stability of Al-P has a significant relation to the change of season

GESS: a database of global evaluation of SARS-CoV-2/hCoV-19 sequences

The COVID-19 outbreak has become a global emergency since December 2019. Analysis of SARS-CoV-2 sequences can uncover single nucleotide variants (SNVs) and corresponding evolution patterns. The Global Evaluation of SARS-CoV-2/hCoV-19 Sequences (GESS, https://wan-bioinfo.shinyapps.io/GESS/) is a resource to provide comprehensive analysis results based on tens of thousands of high-coverage and high-quality SARS-CoV-2 complete genomes. The database allows user to browse, search and download SNVs at any individual or multiple SARS-CoV-2 genomic positions, or within a chosen genomic region or protein, or in certain country/area of interest. GESS reveals geographical distributions of SNVs around the world and across the states of USA, while exhibiting time-dependent patterns for SNV occurrences which reflect development of SARS-CoV-2 genomes. For each month, the top 100 SNVs that were firstly identified world-widely can be retrieved. GESS also explores SNVs occurring simultaneously with specific SNVs of user's interests. Furthermore, the database can be of great help to calibrate mutation rates and identify conserved genome regions. Taken together, GESS is a powerful resource and tool to monitor SARS-CoV-2 migration and evolution according to featured genomic variations. It provides potential directive information for prevalence prediction, related public health policy making, and vaccine designs.National Institutes of Health [P30CA082709 to J.W.]; Walther Cancer Foundation. Funding for open access charge: National Institutes of Health

Genetic Spectrum and Distinct Evolution Patterns of SARS-CoV-2

Four signature groups of frequently occurred single-nucleotide variants (SNVs) were identified in over twenty-eight thousand high-quality and high-coverage SARS-CoV-2 complete genome sequences, representing different viral strains. Some SNVs predominated but were mutually exclusively presented in patients from different countries and areas. These major SNV signatures exhibited distinguishable evolution patterns over time. A few hundred patients were detected with multiple viral strain-representing mutations simultaneously, which may stand for possible co-infection or potential homogenous recombination of SARS-CoV-2 in environment or within the viral host. Interestingly nucleotide substitutions among SARS-CoV-2 genomes tended to switch between bat RaTG13 coronavirus sequence and Wuhan-Hu-1 genome, indicating the higher genetic instability or tolerance of mutations on those sites or suggesting that major viral strains might exist between Wuhan-Hu-1 and RaTG13 coronavirus.This work was partially supported by the National Institutes of Health (Grant Number: P30CA082709) and Walther Cancer Foundation (Grant Number: 4301-80519/0187.01). Funding for open access charge: National Institutes of Health