Microbial population changes and metabolic shift of candidatus accumulibacter under low temperature and limiting polyphosphate.

This study explored the microbial population dynamics of Accumulibacter (Acc) at low temperature and metabolic shift to limiting polyphosphate (Poly-P) in enhanced biological phosphorus removal (EBPR) system. The Accumulibacter-enriched EBPR systems, fed with acetate (HAc) and propionate (HPr) at 10 ± 1 °C respectively, were operated for 60 days in two identical SBR reactors (SBR-1 and SBR-2). The phosphorus removal performance in two systems was stable at 10 ± 1 °C, while the microbial community structure changed. Compared with the population structure in seed sludge, Accumulibacter clades reduced in the HAc system, while Acc I increased significantly in the HPr system. Low temperature was beneficial to the formation of granular sludge in the EBPR system, and the sludge granulation in the HAc system was more homogeneous than that in the HPr system. Accumulibacter in the HPr system can get ATP through glycogen accumulating metabolism (GAM) under limiting Poly-P condition at 10 ± 1 °C, while that in the HAc system cannot. This work suggests that poly-P levels can affect the metabolic pathway of Accumulibacter in EBPR systems under low temperature.

Fast Prediction of RF-induced Heating for Sacral Neuromodulation System Exposed to Multi-Channel 2 RF Field at 3T MRI.

This paper presents a fast method to predict the radiofrequency (RF) induced heating for Sacral Neuromodulation System (SNM) under multi-channel 2 (MC-2) RF field of 3 Tesla (T) magnetic resonance imaging (MRI) system by using the artificial neural network (ANN). The raw computational model for the SNM was based on the transfer function approach. The MC-2 parallel transmission RF field at 3T MRI exposure was considered for 2 independent channels, which have an exposure space of -15 dB to 15 dB magnitude difference and -180 degrees to 170 degrees phase difference. A total number of 535,680 study cases that cover all possible shimming conditions and the corresponding temperature rises are collected from raw calculation data. The ANN was used as the surrogate model to predict the temperature rises against the incident electromagnetic field distributions. 40320 cases were used for training while the rest data sets were used for testing. The ANN can estimate the temperature rises for each human model in a small exposure sampling space. The testing performance of the ANN has a correlation coefficient higher than 0.99 and the mean absolute error was less than 0.12°C. It is demonstrated that the ANN can be used as an efficient tool for quick temperature rise estimation under MRI 3T shimming.

PMPCB Silencing Sensitizes HCC Tumor Cells to Sorafenib Therapy.

Hepatocellular carcinoma (HCC) tumors invariably develop resistance to cytotoxic and targeted agents, resulting in failed treatment and tumor recurrence. Previous in vivo short hairpin RNA (shRNA) screening evidence revealed mitochondrial-processing peptidase (PMPC) as a leading gene contributing to tumor cell resistance against sorafenib, a multikinase inhibitor used to treat advanced HCC. Here, we investigated the contributory role of the ß subunit of PMPC (PMPCB) in sorafenib resistance. Silencing PMPCB increased HCC tumor cell susceptibility to sorafenib therapy, decreased liver tumor burden, and improved survival of tumor-bearing mice receiving sorafenib. Moreover, sorafenib + PMPCB shRNA combination therapy led to attenuated liver tumor burden and improved survival outcome for tumor-bearing mice, and it reduced colony formation in murine and human HCC cell lines in vitro. Additionally, PMPCB silencing enhanced PINK1-Parkin signaling and downregulated the anti-apoptotic protein MCL-1 in sorafenib-treated HCC cells, which is indicative of a healthier pro-apoptotic phenotype. Higher pre-treatment MCL-1 expression was associated with inferior survival outcomes in sorafenib-treated HCC patients. Elevated MCL-1 expression was present in sorafenib-resistant murine HCC cells, while MCL-1 knockdown sensitized these cells to sorafenib. In conclusion, our findings advocate combination regimens employing sorafenib with PMPCB knockdown or MCL-1 knockdown to circumvent sorafenib resistance in HCC patients.

Analysis of Antineutrophil Cytoplasm Antibody from 118 730 Patients in Tertiary Hospitals in Jiangxi Province, China.

BACKGROUND The discovery of antineutrophil cytoplasm antibody (ANCA) makes the early diagnosis of primary vasculitis possible, and also has important guiding significance for the diagnosis and treatment of secondary vasculitis. This study aimed to investigate the clinical significance of ANCA. MATERIAL AND METHODS ANCA was detected by indirect immunofluorescence assay (IIF), and anti-myeloperoxidase (MPO) antibody, and anti-proteinase 3 (PR3) antibody were detected by ELISA. The results were analyzed retrospectively. RESULTS Among 118 730 patients, a total of 5853 (4.93%) were positive for ANCA. In the positive cases, 3.98% were male and 6.33% were female, with significant differences (χ²=123.38, P<0.01). For ANCA, the department with the highest positive rate (15.06%) was the Department of Rheumatology, followed by 7.78% in the Department of Dermatology, 6.79% in the Department of Nephrology, and 5.72% in the Department of Traditional Chinese Medicine (TCM). Anti-PR3 and cANCA were highly specific in primary vasculitis (P<0.01). Anti-MPO and pANCA had high specificity for other autoimmune diseases (P<0.01). CONCLUSIONS ANCA has important guiding significance for vasculitis-related diseases. Therefore, it is important in the diagnosis and treatment of this disease and has value in clinical practice.

Comparative Metabolomic Profiling of Hepatocellular Carcinoma Cells Treated with Sorafenib Monotherapy vs. Sorafenib-Everolimus Combination Therapy.

BACKGROUND: Sorafenib-everolimus combination therapy may be more effective than sorafenib monotherapy for hepatocellular carcinoma (HCC). To better understand this effect, we comparatively profiled the metabolite composition of HepG2 cells treated with sorafenib, everolimus, and sorafenib-everolimus combination therapy. MATERIAL AND METHODS: A 2D HRMAS 1H-NMR metabolomic approach was applied to identify the key differential metabolites in 3 experimental groups: sorafenib (5 µM), everolimus (5 µM), and combination therapy (5 µM sorafenib +5 µM everolimus). MetaboAnalyst 3.0 was used to perform pathway analysis. RESULTS: All OPLS-DA models displayed good separation between experimental groups, high-quality goodness of fit (R2), and high-quality goodness of predication (Q2). Sorafenib and everolimus have differential effects with respect to amino acid, methane, pyruvate, pyrimidine, aminoacyl-tRNA biosynthesis, and glycerophospholipid metabolism. The addition of everolimus to sorafenib resulted in differential effects with respect to pyruvate, amino acid, methane, glyoxylate and dicarboxylate, glycolysis or gluconeogenesis, glycerophospholipid, and purine metabolism. CONCLUSIONS: Sorafenib and everolimus have differential effects on HepG2 cells. Sorafenib preferentially affects glycerophospholipid and purine metabolism, while the addition of everolimus preferentially affects pyruvate, amino acid, and glucose metabolism. This phenomenon may explain (in part) the synergistic effects of sorafenib-everolimus combination therapy observed in vivo.

Genistein modulation of streptozotocin diabetes in male B6C3F1 mice can be induced by diet.

Diet and phytoestrogens affect the development and progression of diabetes. The objective of the present study was to determine if oral exposure to phytoestrogen genistein (GE) by gavage changed blood glucose levels (BGL) through immunomodulation in streptozotocin (STZ)-induced diabetic male B6C3F1 mice fed with three different diets. These three diets were: NTP-2000 diet (NTP), soy- and alfalfa-free 5K96 diet (SOF) and high fat diet (HFD) with 60% of kcal from fat, primarily rendered fat of swine. The dosing regimen for STZ consisted of three 100mg/kg doses (i.p.): the first dose was administered at approximately 2weeks following the initiation of daily GE (20mg/kg) gavage, and the second dose was on day 19 following the first dose, and the third dose was on day 57 following the first dose. In mice on the NTP diet, GE treatment decreased BGL with statistical significances observed on days 33 and 82 following the first STZ injection. In mice fed the HFD diet, GE treatment produced a significant decrease and a significant increase in BGL on days 15 and 89 following the first STZ injection, respectively. In mice fed the SOF diet, GE treatment had no significant effects on BGL. Although GE treatment affected phenotypic distributions of both splenocytes (T cells, B cells, natural killer cells and neutrophils) and thymocytes (CD4/CD8 and CD44/CD25), and their mitochondrial transmembrane potential and generation of reactive oxygen species, indicators of cell death (possibly apoptosis), GE modulation of neutrophils was more consistent with its diabetogenic or anti-diabetic potentials. The differential effects of GE on BGL in male B6C3F1 mice fed with three different diets with varied phytoestrogen contents suggest that the estrogenic properties of this compound may contribute to its modulation of diabetes.

[Randomized control study on the treatment of 26 cases of acne conglobata with encircling acupuncture combined with venesection and cupping].

OBJECTIVE: To observe the curative effect of acne conglobata treated by encircling acupuncture combined with ventouse and cupping. METHODS: A total of 52 acne conglobata patients were randomly divided into acupuncture group (n=26) and Western medicine group (n=26). Patients of acupuncture group were treated with encircling acupuncture around the affected focus. Common acupuncture was applied to Hegu (LI 4), Xuehai (SP 10), Fenglong (ST 40) and Sanyinjiao (SP 6), once daily. Dazhui (GV 14) and Feishu (BL 13) were used for venesection and cupping (twice a week). Patients of medication group were treated with oral administration of Isotretinoin Capsules (10 mg, t.i.d.). The treatment duration of 2 groups was 4 weeks. Serum IL-6 content was detected with double-antibody sandwich elisa enzyme linked immunosorbent assay (ELISA). RESULTS: After the treatment, in acupuncture group and Western medicine group, 3 (11.5%) and 4 (15.4%) cases experienced remarkable relief in their signs, 14 (53.8%) and 11 (42.3%) had marked improvement, 6 (23. 1%) and 7 (26.9%) had improvement, 3 (11.5%) and 4 (15.4%) failed, with the effective rates being 88.5% and 84.6%, respectively. No significant difference was found between two groups in the therapeutic effect (P>0.05). Self-comparison showed that after the treatment, IL-6 in both groups decreased significantly (P<0.01). The therapeutic effect of acupuncture group was significantly superior to that of Western medicine group in lowering serum IL-6 (P<0.05). CONCLUSION: Both acupuncture and medication can effectively promote the recovery of the affected skin, and lower serum IL-6 level in acne conglobata patients. The effect of acupuncture is stronger than that of Isotretinoin Capsules in lowering serum IL-6 content and has fewer adverse effects.