Low-Protein Diet Supplemented with Keto Acids Is Associated with Suppression of Small-Solute Peritoneal Transport Rate in Peritoneal Dialysis Patients

Objective. We investigate whether low-protein diet would show benefits in suppressing peritoneal transport rate in peritoneal dialysis (PD) patients. Methods. This is a supplemented analysis of our previously published trial, which randomized 60 PD patients to receive low- (LP: dietary protein intake of 0.6–0.8 g/kg/d), keto-acid-supplemented low- (sLP: 0.6–0.8 g/kg/d with 0.12 g/kg/d of keto acids), or high- (HP: 1.0–1.2 g/kg/d) protein diet and lasted for one year. In this study, the variations of peritoneal transport rate were assessed. Results. While baseline D/Pcr (dialysate-to-plasma concentration ratio for creatinine at 4 hour) and D/D0glu (dialysate glucose at 4 hour to baseline dialysate glucose concentration ratio) were similar, D/Pcr in group sLP was lower, and D/D0glu was higher than those in the other two groups (P < 0.05) at 12th month. D/D0glu increased (P < 0.05), and D/Pcr tended to decrease, (P = 0.071) in group sLP. Conclusions. Low-protein diet with keto acids may benefit PD patients by maintaining peritoneum at a lower transport rate

Model for the quasineutral region capacitance of p/n junction devices

The capacitance associated with free-carrier charge storage in the quasineutral region is a primary factor in limiting the switching speed of pin junction devices. This capacitance has been conventionally modeled using assumptions such as low-level injection, nondegeneracy, complete impurity ionization, and no space-charge region thickness modulation. These assumptions can give rise to a large error in device modeling, particularly for modern devices with very small geometry and high bias conditions. In this article, a comprehensive quasineutral region capacitance model including relevant device physics is developed. Comparisons between the present and conventional models are made, and the effects of using these two different models on the total capacitance of junction diode are also investigated

High-Sensitivity C-Reactive Protein: An Independent Risk Factor for Left Ventricular Hypertrophy in Patients with Lupus Nephritis

Objective. To determine the prevalence of left ventricular hypertrophy (LVH) and its associated risk factors in lupus nephritis (LN) patients. Methods. 287 LN patients (age: 38.54 ± 13.31, 262 female) were recruited. Echocardiography and serum high-sensitivity C-reactive protein (hs-CRP) were measured. Their relationship was evaluated by univariate correlation analysis and multivariate regression analysis. Results. The prevalence of LVH in this cohort was 21.25% (n = 61). Serum hs-CRP level was significantly elevated in patients with LVH compared to those without (8.03 (3.22–30.95) versus 3.93 (1.48–9.48) mg/L, P < .01), and correlated with left ventricular mass index (LVMI) (r = 0.314, P = .001). Multivariate regression analysis further confirmed that hs-CRP was an independent risk factor (β = 0.338, P = .002) for LVH in patients with LN. Conclusions. Our findings demonstrated that serum hs-CRP level is independently correlated with LVMI and suggested that measurement of hs-CRP may provide important clinical information to investigate LVH in LN patients

Serum IL-18 Is Closely Associated with Renal Tubulointerstitial Injury and Predicts Renal Prognosis in IgA Nephropathy

Background. IgA nephropathy (IgAN) was thought to be benign but recently found it slowly progresses and leads to ESRD eventually. The aim of this research is to investigate the value of serum IL-18 level, a sensitive biomarker for proximal tubule injury, for assessing the histopathological severity and disease progression in IgAN. Methods. Serum IL-18 levels in 76 IgAN patients and 36 healthy blood donors were measured by ELISA. We evaluated percentage of global and segmental sclerosis (GSS) and extent of tubulointerstitial damage (TID). The correlations between serum IL-18 levels with clinical, histopathological features and renal prognosis were evaluated. Results. The patients were 38.85 ± 10.95 years old, presented with 2.61 (1.43∼4.08) g/day proteinuria. Serum IL-18 levels were significantly elevated in IgAN patients. Baseline serum IL-18 levels were significantly correlated with urinary protein excretion (r = 0.494, P = 0.002), Scr (r = 0.61, P < 0.001), and eGFR (r = −0.598, P < 0.001). TID scores showed a borderline significance with serum IL-18 levels (r = 0.355, P = 0.05). During follow-up, 26 patients (34.21%) had a declined renal function. Kaplan-Meier analysis found those patients with elevated IL-18 had a significant poor renal outcome (P = 0.03), and Cox analysis further confirmed that serum IL-18 levels were an independent predictor of renal prognosis (β = 1.98, P = 0.003)

Direct evidence of ZnO morphology modification via the selective adsorption of ZnO-binding peptides

Biomolecule-mediated ZnO synthesis has great potential for the tailoring of ZnO morphology for specific application in biosensors, window materials for display and solar cells, dye-sensitized solar cells (DSSCs), biomedical materials, and photocatalysts due to its specificity and multi-functionality. In this contribution, the effect of a ZnO-binding peptide (ZnO-BP, G-12: GLHVMHKVAPPR) and its GGGC-tagged derivative (GT-16: GLHVMHKVAPPRGGGC) on the growth of ZnO crystals expressing morphologies dependent on the relative growth rates of (0001) and (10 (1) over bar0) planes of ZnO have been studied. The amount of peptide adsorbed was determined by a depletion method using oriented ZnO films grown by Atomic Layer Deposition (ALD), while the adsorption behavior of G-12 and GT-16 was investigated using XPS and a computational approach. Direct evidence was obtained to show that (i) both the ZnO-BP identified by phage display and its GGGC derivative (GT-16) are able to bind to ZnO and modify crystal growth in a molecule and concentration dependent fashion, (ii) plane selectivity for interaction with the (0001) versus the (10 (1) over bar0) crystal planes is greater for GT-16 than G-12; and (iii) specific peptide residues interact with the crystal surface albeit in the presence of charge compensating anions. To our knowledge, this is the first study to provide unambiguous and direct quantitative experimental evidence of the modification of ZnO morphology via (selective and nonselective) adsorption-growth inhibition mechanisms mediated by a ZnO-BP identified from phage display libraries

Adherence to a healthy lifestyle and its association with cognitive impairment in community-dwelling older adults in Shanghai

IntroductionThere is a growing body of recent literature linking the association of specific or multiple lifestyles with cognitive impairment, but most of these studies have been conducted in Western populations, and it is necessary to study multiple lifestyles and cognitive abilities in different populations, with the primary population of this study being a select group of community-dwelling older adults in Shanghai, China.MethodsThe sample included 2,390 community-dwelling Chinese participants. Their cognitive function was assessed using the Mini-Mental State Examination (MMSE). We defined a healthy lifestyle score on the basis of being non-smoking, performing ≥210 min/wk moderate/vigorous-intensity physical activity, having light to moderate alcohol consumption, eating vegetables and fruits daily, having a body mass index (BMI) of 18.5–23.9 kg/m2, and having a waist-to-hip ratio (WHR) &lt;0.90 for men and &lt;0.85 for women, for an overall score ranging from 0 to 6.ResultsCompared with participants with ≤2 healthy lifestyle factors, the adjusted odds ratio (OR) and 95% confidence interval (CI) for participants with 4, 5, and 6 healthy lifestyle factors were 0.53 (95% CI, 0.29–0.98), 0.40 (95% CI, 0.21–0.75), and 0.36 (95% CI, 0.16–0.79), respectively. Only WHR (OR = 0.54, 95% CI = 0.37–0.78) and physical activity (OR = 0.69, 95% CI = 0.51–0.92) were associated with cognitive impairment. A healthy lifestyle correlated with overall cognition (β = 0.066, orientation (β = 0.049), language ability (β = 0.060), delayed recall (β = 0.045) and executive function (β = 0.044) (P all &lt; 0.05).ConclusionThe study provides evidence on an inverse association between healthy lifestyles and cognitive impairment. We investigated whether healthy lifestyle was related to specific cognitive functions to provide a theoretical basis for accurate clinical prescription

The neutrophil-to-lymphocyte ratio is associated with mild cognitive impairment in community-dwelling older women aged over 70 years: a population-based cross-sectional study

BackgroundThe neutrophil-to-lymphocyte ratio (NLR) is a marker of inflammation that can be obtained quickly, conveniently, and cheaply from blood samples. However, there is no research to explore the effects of sex and age on the relationship between the NLR and mild cognitive impairment (MCI) in community-dwelling older adults.MethodsA total of 3,169 individuals aged over 60 years in Shanghai were recruited for face-to-face interviews, and blood samples were collected. MCI was assessed by the Mini-Mental State Examination (MMSE) and the Instrumental Activities of Daily Living (IADL) scale, and neutrophil count and lymphocyte counts were measured in fasting blood samples. The NLR was calculated by dividing the absolute neutrophil count by the absolute lymphocyte count.ResultsIn females, the NLR in the MCI group was significantly higher than that in the cognitively normal group (2.13 ± 0.94 vs. 1.85 ± 0.83, p &lt; 0.001) but not in men. Logistic regression showed that a higher NLR was an independent risk factor for MCI in women [odds ratio (OR) = 1.28; 95% confidence interval (CI) = 1.09–1.49]. In addition, the elevated NLR quartile was associated with an increased risk of MCI, especially in women older than 70 years (p-value for trend = 0.011).ConclusionCompared with males, female MCI patients had a significantly higher NLR than cognitively normal controls. In addition, elevated NLR was found to be significantly associated with MCI risk in women older than 70 years. Therefore, elderly Chinese women with a higher NLR value may be the target population for effective prevention of MCI

B Cell Adaptor Containing Src Homology 2 Domain (Bash) Links B Cell Receptor Signaling to the Activation of Hematopoietic Progenitor Kinase 1

The B cell adaptor containing src homology 2 domain (BASH; also termed BLNK or SLP-65), is crucial for B cell antigen receptor (BCR)-mediated activation, proliferation, and differentiation of B cells. BCR-mediated tyrosine-phosphorylation of BASH creates binding sites for signaling effectors such as phospholipase Cγ (PLCγ)2 and Vav, while the function of its COOH-terminal src homology 2 domain is unknown. We have now identified hematopoietic progenitor kinase (HPK)1, a STE20-related serine/threonine kinase, as a protein that inducibly interacts with the BASH SH2 domain. BCR ligation induced rapid tyrosine-phosphorylation of HPK1 mainly by Syk and Lyn, resulting in its association with BASH and catalytic activation. BCR-mediated activation of HPK1 was impaired in Syk- or BASH-deficient B cells. The functional SH2 domain of BASH and Tyr-379 within HPK1 which we identified as a Syk-phosphorylation site were both necessary for interaction of both proteins and efficient HPK1 activation after BCR stimulation. Furthermore, HPK1 augmented, whereas its kinase-dead mutant inhibited IκB kinase β (IKKβ) activation by BCR engagement. These results reveal a novel BCR signaling pathway leading to the activation of HPK1 and subsequently IKKβ, in which BASH recruits tyrosine-phosphorylated HPK1 into the BCR signaling complex

Reversible inhibitor of p97, DBeQ, impairs both ubiquitin-dependent and autophagic protein clearance pathways

A specific small-molecule inhibitor of p97 would provide an important tool to investigate diverse functions of this essential ATPase associated with diverse cellular activities (AAA) ATPase and to evaluate its potential to be a therapeutic target in human disease. We carried out a high-throughput screen to identify inhibitors of p97 ATPase activity. Dual-reporter cell lines that simultaneously express p97-dependent and p97-independent proteasome substrates were used to stratify inhibitors that emerged from the screen. N^2,N^4-dibenzylquinazoline-2,4-diamine (DBeQ) was identified as a selective, potent, reversible, and ATP-competitive p97 inhibitor. DBeQ blocks multiple processes that have been shown by RNAi to depend on p97, including degradation of ubiquitin fusion degradation and endoplasmic reticulum-associated degradation pathway reporters, as well as autophagosome maturation. DBeQ also potently inhibits cancer cell growth and is more rapid than a proteasome inhibitor at mobilizing the executioner caspases-3 and -7. Our results provide a rationale for targeting p97 in cancer therapy