Development of a compact helicon plasma source with two sets of ring array permanent magnets for the study of blue core plasma.

A compact helicon plasma source for the study of helicon plasma, especially for the study of blue core plasma, is designed and developed with permanent magnets (PMs). The structure of the PMs consists of two sets of ring array magnets with opposite magnetization. This structure can provide a higher magnetic field with fewer PMs, which is helpful for controlling the device's mass. A quartz tube with 50 cm in length, 5 cm in outer diameter, and 0.3 cm in thickness is used. Argon helicon plasma is produced at ∼38 sccm (3.4 Pa inlet chamber and 0.122 Pa diffusion chamber) by a radio frequency (RF) power of ∼13.56 MHz using a helical antenna under a high magnetic field (∼1600 G). Preliminary results measured by the Langmuir probe, photomultiplier tube (PMT), CCD, and Hall coil are applied to characterize the helicon plasma in this source, such as the mode transition and the formation of the blue core with the RF power variation. The device generates the blue core (W mode) plasma at a lower power of about 200 W, and the energy coupling efficiency is as high as 65%.

Effect of low-calcium and standard-calcium dialysate on serum calcium, phosphorus and full-segment parathyroid hormone in patients on peritoneal dialysis: A retrospective observational study.

OBJECTIVE: To investigate the effects of low-calcium and standard-calcium dialysate in patients with chronic kidney disease on peritoneal dialysis, and find out which dialysate has less vascular calcification effect. METHODS: A total of 141 patients who had undergone peritoneal dialysis (PD) for 2 years in the PD centre from January 2012 to December 2017 were included and divided into two groups according to the calcium concentration of the PD fluid used. There were 79 cases in the low-calcium group, with a dialysate calcium concentration of 1.25 mmol/L and 62 cases in the standard-calcium group, with a dialysate calcium concentration of 1.75 mmol/L. The demographic characteristics and clinical information before initiation of PD were collected and compared between the two groups. Information on the serum calcium, phosphorus and PTH, systolic and diastolic blood pressures and the use of antihypertensive and phosphate-lowering drugs in the second year of dialysis was also collected and compared between the two groups. Vascular calcification was assessed in patients on PD treatment. RESULTS: The mean serum calcium concentrations before initiation of PD in the low- and standard-calcium groups were 1.94 ± 0.27 and 1.89 ± 0.28 mmol/L, respectively. The serum calcium concentrations after PD were 2.30 ± 0.21 and 2.41 ± 0.23 mmol/L, respectively. After PD, the serum calcium concentration in both groups was significantly increased (p < 0.05). The serum calcium concentration in the low-calcium group after PD treatment was lower than that in the standard-calcium group, and the difference was statistically significant (p < 0.05). Compared with the standard-calcium group, patients in the low-calcium group had significantly higher parathyroid hormone concentrations (p < 0.05). More types of phosphate-lowering drugs were used (59.49%) in the low-calcium group than that in the standard-calcium group (35.48%; p < 0.05). The number of antihypertensive drug usage were also higher in the low-calcium group, and the difference was statistically significant (p < 0.05). As for the vascular calcification effect, the two groups have shown no statistical difference in abdominal aortic calcification rate, carotid arteriosclerosis rate and aortic arch calcification rate (p < 0.05). CONCLUSION: We found that low-calcium PD fluid may increase the PTH level and the proportion of CKD patients using antihypertensive drug and phosphorus-lowering drug, but the vascular calcification effect of the low and standard calcium PD fluid needs further exploration. This paper provides new evidence for the choice of dialysate for PD, low-calcium dialysate has no outstanding advantages for long term dialysis.

A Case-Control Study of the Factors Associated with Anemia in Chinese Children Aged 3-7 years Old.

Background: Anemia in children is still an important public problem in China and can have a profound impact on the physical and mental health of children. The purpose of this study was to explore the risk factors for anemia among Chinese children aged 3-7 years old and to provide some basis for the prevention and control of anemia. Methods: A matched case-control study was conducted and 1104 children (552 cases and 552 controls) were recruited in this study. Cases were children who were diagnosed with anemia by the doctor of physical examination and checked by one deputy chief physician of pediatrics, and controls were healthy children without anemia. Data were collected using a self-designed structured questionnaire. Univariable and multivariable analyses were used to identify independent determinants of anemia. P values less than 0.05 were used to declare statistical significance. Results: In the multivariable analyses, maternal anemia before or during pregnancy and lactation (OR = 2.14, 95% CI: 1.10∼4.15; OR = 2.86, 95% CI: 1.66∼4.94; OR = 2.51, 95% CI: 1.13∼5.60), gestational weeks (OR = 0.72, 95% CI: 0.53∼0.96), having G6PD deficiency or thalassemia (OR = 8.12, 95% CI: 2.00∼33.04; OR = 36.25, 95% CI: 10.40∼126.43), having cold and cough in previous two weeks (OR = 1.56, 95% CI: 1.04∼2.34), family income (OR = 0.80, 95% CI: 0.65∼0.97), and being a picky eater (OR = 1.80, 95% CI: 1.20∼2.71) were determinants of anemia in children aged 3-7 years old. Conclusions: Some of the identified factors are modifiable and could be targeted to reduce childhood anemia. More emphasis should be given by the concerned bodies to intervene in the anemia problem by improving the maternal health education, screening for disease-related anemia, requesting medical services in a timely manner, improving the economic status of households, promoting dietary habits, and improving sanitation and hygiene practices.

The Association Between Anemia and Depressive Symptoms in Non-White Male Adults: National Health and Nutrition Examination Survey (2005-2018).

BACKGROUND: The relationship between anemia and depression remains controversial. This study aimed to investigate the association between hemoglobin (Hb) levels and depressive symptoms. Study Design: A cross-sectional study. METHODS: This study was conducted using National Health and Nutrition Examination Survey data from 2005-2018. Hb levels were obtained from laboratory files, and depressive symptoms were assessed using the Patient Health Questionnaire (PHQ-9). Multivariable logistic regression analysis and smoothing plots were performed to examine the relationship between anemia and depression, including potential nonlinear associations. RESULTS: The study included 6008 male adults. Multivariable analysis revealed that anemia was associated with an increased odds ratio for mild (OR=1.49, 95% CI: 1.06, 2.10) and moderate (OR=2.05, 95% CI: 1.14-3.70) anemia. Additionally, each additional g/dL of Hb was significantly inversely associated with developing depression (OR=0.91, 95% CI: 0.85, 0.96). A nonlinear relationship was detected between Hb and depression, with an inflection point at 15 g/dL. Below this threshold, there was a significantly negative association between Hb and depression (OR=0.88, 95% CI: 0.79, 0.98); no significant relationship was observed above it (OR=1.05, 95% CI: 0.84, 1.31). CONCLUSION: Anemia was positively associated with depression in non-White American men. A nonlinear relationship between Hb and depression was detected, and it had a saturation effect. A significant negative correlation with depression was observed when the Hb level was below 15 g/dL.

Experimental Determination of Hydrogen Isotope Transport Parameters in Vanadium.

Deuterium permeation through vanadium membranes in a wide range of pressures and the temperature range ~250-550 °C was experimentally investigated. Measurements on the same material were carried out in three laboratories with different features for an extended characterization and for cross-check validation. A unified equation for deuterium permeability in pure vanadium (99%) was provided as Φ=1.27×10-4·e-8667/T mol m-1 s-1 Pa-0.5, which represents a significant progress for the characterization of the transport properties in this material, given the spread of data, which can currently be found in the literature. Adsorption and recombination rate constants were also measured for hydrogen and deuterium at low pressure for the same range of temperatures. Finally, the influence of the surface roughness was examined by measuring samples with different surface finish.

Design, Synthesis, and Structure-Activity Relationships of Indoline-Based Kelch-like ECH-Associated Protein 1-Nuclear Factor (Erythroid-Derived 2)-Like 2 (Keap1-Nrf2) Protein-Protein Interaction Inhibitors.

The Keap1 (Kelch-like ECH-associated protein 1)-Nrf2 (nuclear factor erythroid 2-related factor 2)-ARE (antioxidant response element) pathway is the major defending mechanism against oxidative stresses, and directly disrupting the Keap1-Nrf2 protein-protein interaction (PPI) has been an attractive strategy to target oxidative stress-related diseases, including cardiovascular diseases. Here, we describe the design, synthesis, and structure-activity relationships (SARs) of indoline-based compounds as potent Keap1-Nrf2 PPI inhibitors. Comprehensive SAR analysis and thermodynamics-guided optimization identified 19a as the most potent inhibitor in this series, with an IC50 of 22 nM in a competitive fluorescence polarization assay. Further evaluation indicated the proper drug-like properties of 19a. Compound 19a dose-dependently upregulated genes and protein level of Nrf2 as well as its downstream markers and showed protective effects against lipopolysaccharide-induced injury in both H9c2 cardiac cells and mouse models. Collectively, we reported here a novel indoline-based Keap1-Nrf2 PPI inhibitor as a potential cardioprotective agent.

[Removal of Nitrate Nitrogen by Microbial Photoelectrochemical Cell: PANI/TiO2-NTs as a Photoanode].

The use of microbial photoelectrochemical cells (MPECs) for the removal of contaminants is a cost-effective and environment-friendly method. Based on the preparation of polyaniline/titanium dioxide nanotube array (PANI/TiO2-NTs) composite photoelectrodes, an MPEC system comprising PANI/TiO2-NTs photoanode and biocathode was constructed and the removal performance of nitrate nitrogen (NO3--N) was studied. The experimental results showed that the PANI/TiO2-NT electrode exhibited the best photoelectric performance when the PANI loading time was 80 s. Compared with the TiO2-NTs electrode, the photocurrent density doubled. The light-driven MPEC system could realize autotrophic denitrification without an external voltage. The biodegradation of NO3--N conformed to the pseudo first-order kinetics. The higher the photoresponse current density, the better the denitrification performance of the system. When the initial concentration of NO3--N was 25 mg·L-1 and the photoresponse current density increased from 0.17 mA·cm-2 to 0.67 mA·cm-2, the average denitrification rate increased from 0.83 mg·(L·h)-1 to 2.83 mg·(L·h)-1. High-throughput sequencing of the biocathode microbial membranes revealed that Pseudomonas (27.37%) was the dominant bacteria. It was considered that the photogenerated electrons generated by the PANI/TiO2-NTs photoanode were transmitted to the cathode through an external circuit. Pseudomonas and other microorganisms with autotrophic denitrification and electrochemical activity directly used the electrons on the electrode as the sole electron donors for autotrophic denitrification reaction.

Recent progress in the development of small molecule Nrf2 activators: a patent review (2017-present).

Introduction: The transcription factor Nrf2 (nuclear factor erythroid 2-related factor 2) is the first line of defense against a plethora of environmental or endogenous deviations in redox metabolism, proteostasis, inflammation, etc. Therefore, pharmacological activation of Nrf2 is a potential therapeutic approach for several diseases related to oxidative stress and inflammation, such as cancer, cardiovascular, and neurodegenerative diseases.Areas covered: The authors first describe the biological function of Nrf2 and the molecular regulatory mechanism of Keap1-Nrf2-ARE ((Kelch-like ECH-Associating protein 1)-Nrf2-(antioxidant response element)). Then, they review recent progress of covalent activators and non-covalent Keap1-Nrf2 protein-protein interaction (PPI) inhibitors from patents and publications in 2017-present, consisting of new chemical molecules, structure optimization of reported activators and progress in preclinical or clinical trials.Expert opinion: Despite significant achievements in the development of Nrf2 activators, the selectivity is the primary consideration. Due to reacting with redox-sensitive cysteines in proteins except for Keap1, electrophilic activators often exhibit off-target effects. For Keap1-Nrf2 PPI inhibitors, how to enhance in vivo efficacy and/or penetrate blood-brain barrier (BBB) to reach central nervous system (CNS) is also challenging. Fragment-based drug discovery (FBDD), carboxylic acid bioisosteric replacement and prodrug approach might be used to circumvent this challenge. Moreover, the possibility of cancer risk caused by Nrf2 activation needs to be considered carefully.

Discovery of a head-to-tail cyclic peptide as the Keap1-Nrf2 protein-protein interaction inhibitor with high cell potency.

Directly disrupting Keap1-Nrf2 protein-protein interaction (PPI) has emerged as a novel way to activate Nrf2. Peptide Keap1-Nrf2 PPI inhibitors have been reported with high Keap1 binding affinity. However, these peptide inhibitors show weak activity in cells. In this study, the head-to-tail cyclic strategy was applied in the development of peptide inhibitors. The privileged residue sequence with minimal acidic residues was used as the template for the cyclic peptide, and the appropriate conjugation method was designed based on the peptide-Keap1 binding mode. The glycine was introduced as the linker to connect both sides, which can avoid the terminal charge, enhance the peptide stability and constrain the binding conformation simultaneously. The obtained novel cyclic peptide 3 showed high binding affinity with Keap1 and possessed high potency in Nrf2 activation at cellular level. We also showed that peptide 3 exhibited effective anti-inflammatory effects in mouse RAW 264.7 cells by activating the Nrf2-regulated defense system and enhancing the antioxidant capacity. This study proved that the head-to-tail cyclic strategy is quite useful in improving the cell potency of peptide Keap1-Nrf2 inhibitors and provided a possible way to develop drug-like peptides as therapeutic Nrf2 activators.

NRF2 promotes breast cancer cell proliferation and metastasis by increasing RhoA/ROCK pathway signal transduction.

Nuclear factor erythroid 2-related factor (NRF2) is an important transcription factor in oxidative stress regulation. Overexpression of NRF2 is associated with human breast carcinogenesis, and increased NRF2 mRNA levels predict poor patient outcome for breast cancer. However, the mechanisms linking gain of NRF2 expression and poor prognosis in breast cancer are still unclear. Here, we provide evidence that NRF2 deletion inhibits proliferation and metastasis of breast cancer cells by down-regulating RhoA. Restoration of RhoA in MCF7 and MDA-MB-231 cells induced NRF2 knockdown-suppressed cell growth and metastasis in vitro, and NRF2 silencing suppressed stress fiber and focal adhesion formation leading to decreased cell migration and invasion. Mechanistic studies showed that NRF2 binds to the promoter region of estrogen-related receptor α (ERR1) and may function as a silencer. This may enhance RhoA protein stability and lead to RhoA overexpression in breast cancer cell. Our findings indicate that NRF2 silencing-mediated reduction of RhoA expression contributes, at least in part, to the poor outcome of breast cancer patients with high NRF2 expression.

Design, Synthesis, and Initial Evaluation of Affinity-Based Small-Molecule Probes for Fluorescent Visualization and Specific Detection of Keap1.

Keap1 is a pluripotent protein which plays a predominant role in cellular homeostasis and stress responses. Given that the cellular environment is quite dynamic and versatile, further investigation of the function of Keap1 depends on tools for specific and real-time detection of Keap1. Herein, we report the development of functional affinity-based small-molecule probes which can overcome some shortcomings of current methods and be applied in further studying the function of Keap1.

Losartan alleviates renal fibrosis by down-regulating HIF-1α and up-regulating MMP-9/TIMP-1 in rats with 5/6 nephrectomy.

BACKGROUND: This study investigated the effects of losartan intervention on the expressions of hypoxia-inducible factor-1α (HIF-1α), matrix metalloproteinase-9 (MMP-9), and tissue inhibitor of metalloproteinase-1 (TIMP-1) in renal fibrosis in rats with 5/6 nephrectomy. METHODS: Sprague Dawley rats were randomly divided into three groups. Rats in the losartan group were gavaged with losartan (33.3 mg/kg/day) from 1 week after 5/6 nephrectomy, and those in the sham group and the model group only received an equal volume of saline solution by gavage. Rats were sacrificed at the ends of the 4, 8 and 12 weeks, respectively. Urinary N-acetyl-glucosaminidase (NAG), 24-h urinary protein, serum cystatin C, blood urea nitrogen (BUN), and serum creatinine (Scr) levels were assessed. Kidney tissues were observed under light and electron microscope. The expressions of HIF-1α, transforming growth factor-ß1 (TGF-ß1), MMP-9, and TIMP-1 were determined by immunohistochemistry and Western blotting. RESULTS: Twenty-four hour urinary protein, urinary NAG, serum cystatin C, BUN, and Scr levels in the model group were significantly higher than those in the sham group (p < 0.05), but losartan treatment improved these changes. The apparent glomerular sclerosis and tubulointerstitial fibrosis were also found in the model group, which were ameliorated by losartan. The expressions of HIF-1α, TGF-ß1, MMP-9, and TIMP-1 were elevated and MMp-9/TIMP-1 ratio was lowered in the model group (p < 0.05), but losartan increased the expression of MMP-9 and MMp-9/TIMP-1 ratio (p < 0.05) and lessened the expressions of HIF-1α, TGF-ß1, and TIMP-1 (p < 0.05). CONCLUSION: Losartan may ameliorate renal fibrosis partly by down-regulating HIF-1α and up-regulating MMP-9/TIMP-1 in rats with 5/6 nephrectomy.