Deficiency of polypeptide N-acetylgalactosamine transferase 9 contributes to a risk for Parkinson's disease via mitochondrial dysfunctions.

Polypeptide N-acetylgalactosamine transferase 9 (GALNT9) catalyzes the initial step of mucin-type O-glycosylation via linking N-acetylgalactosamine (GalNAc) to serine/threonine in a protein. To unravel the association of GALNT9 with Parkinson's disease (PD), a progressive neurodegenerative disorder, GALNT9 levels were evaluated in the patients with PD and mice treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, and statistically analyzed based on the GEO datasets of GSE114918 and GSE216281. Glycoproteins with exposing GalNAc were purified using lectin affinity chromatography and identified by LC-MS/MS. The influence of GALNT9 on cells was evaluated via introducing a GALNT9-specific siRNA into SH-SY5Y cells. Consequently, GALNT9 deficiency was found to occur under PD conditions. GALNT9 silencing contributed to a causative factor in PD pathogenesis via reducing the levels of intracellular dopamine, tyrosine hydroxylase and soluble α-synuclein, and promoting α-synuclein aggregates. MS identification revealed 14 glycoproteins. 5 glycoproteins, including ACO2, ATP5B, CKB, CKMT1A, ALDOC, were associated with energy metabolism. GALNT9 silencing resulted in mitochondrial dysfunctions via increasing ROS accumulation, mitochondrial membrane depolarization, mPTPs opening, Ca2+ releasing and activation of the CytC-related apoptotic pathway. The dysfunctional mitochondria then triggered mitophagy, possibly intermediated by adenine nucleotide translocase 1. Our study suggests that GALNT9 is potentially developed into an auxiliary diagnostic index and therapeutic target of PD.

TMEM97 is transcriptionally activated by YY1 and promotes colorectal cancer progression via the GSK-3ß/ß-catenin signaling pathway.

Transmembrane protein 97 (TMEM97) is a conserved integral membrane protein highly expressed in various human cancers, including colorectal cancer (CRC), and it exhibits pro-tumor roles in breast cancer, gastric cancer, and glioma. However, whether TMEM97 participates in CRC progression is not fully understood. The expression of mRNA and protein was evaluated by real-time qPCR, western blotting, immunofluorescent, and immunohistochemical staining. TMEM97 functions in cell proliferation, apoptosis, migration, and invasion were assessed by CCK-8, flow cytometry, and transwell assays. The roles of TMEM97 in CRC cells in vivo was investigated using a subcutaneous xenograft model. The transcriptional regulation of TMEM97 was explored by luciferase reporter and ChIP assays. The silencing of TMEM97 inhibited migration and invasion of CRC cells in vitro and led to suppressed growth and enhanced apoptosis in CRC cells and xenografts, whereas overexpression of TMEM97 displayed opposite effects. Mechanistically, TMEM97 knockdown caused a reduction of the proliferating marker PCNA and an increase of pro-apoptotic proteins (cleaved caspase 8/3/7 and cleaved PARP) in CRC cells. TMEM97 also positively regulated the ß-catenin signaling pathway in CRC cells and xenografts by modulating the phosphorylated-GSK-3ß and active (non-phospho) ß-catenin levels. Interestingly, YY1, a well-recognized oncogenic transcription factor, was identified to bind to the TMEM97 promoter and enhance its transcriptional activity, and silencing of TMEM97 abolished YY1-mediated pro-tumor effects on CRC cells. Our results suggest that TMEM97 is transcriptionally activated by YY1 and promotes CRC progression via the GSK-3ß/ß-catenin signaling pathway, providing that TMEM97 might be a novel therapeutic target for preventing CRC development.

Treatment of groundwater polluted by arsenic compounds by zero valent iron.

Batch experiments were carried out to study the kinetics and efficiency of inorganic arsenic removal by zero valent iron (ZVI) powder, and as well as the effects of pH, anions, and humic material (HM) on this process. Moreover, column experiment was conducted for 31 days to treat arsenate solution of 500 microg As/L using waste iron chippings as filling. Batch experiments showed that both arsenate and arsenite compounds could be removed efficiently from simulated groundwater by ZVI under aerobic and relative anaerobic conditions. Aerobic condition was favorable to arsenic removal especially for arsenate, while arsenite could be removed more rapidly than arsenate in relative anaerobic condition. Oxidation of arsenite to arsenate by iron species in aerobic environment was observed, which is thought to be an important pathway of arsenite removal. In an unsealed system, the removal efficiency of both arsenate and arsenite decreased at higher pH value. In a sealed system, acidic and alkaline condition seemed to be favorable for arsenate and arsenite removal, respectively. Phosphate and low concentration sulfate caused a decrease in arsenate removal, while high concentration sulfate as well as nitrate caused slight increase in arsenate removal. Presence of HM in solution slightly inhibited arsenic removal. Arsenic removal efficiency in column study was influenced by flow rate and work period of the column. More than 98% of arsenate could be removed stably with a hydraulic resident time of 2 h at last, and the effluent meet the drinking water standard.