Deep learning-based prediction of coronary artery calcium scoring in hemodialysis patients using radial artery calcification.

OBJECTIVE: This study used random forest model to explore the feasibility of radial artery calcification in prediction of coronary artery calcification in hemodialysis patients. MATERIAL AND METHODS: We enrolled hemodialysis patients and performed ultrasound examinations on their radial arteries to evaluate the calcification status using a calcification index. All involved patients received coronary artery computed tomography scans to generate coronary artery calcification scores (CACS). Clinical variables were collected from all patients. We constructed both a random forest model and a logistic regression model to predict CACS. Logistic regression model was used to identify the risk factors of radial artery calcification. RESULTS: One hundred eighteen patients were included in our analysis. In random forest model, the radial artery calcification index, age, serum C-reactive protein, body mass index (BMI), diabetes, and hypertension history were related to CACS based on the average decrease of the Gini coefficient. The random forest model achieved a sensitivity of 76.9%, specificity of 75.0%, and area under receiver operating characteristic of 0.869, while the logistic regression model achieved a sensitivity of 75.2%, specificity of 68.7%, and area under receiver operating characteristic of 0.742 in prediction of CACS. Sex, BMI index, smoking history, hypertension history, diabetes history, and serum total calcium were all the risk factors related to radial artery calcification. CONCLUSIONS: A random forest model based on radial artery calcification could be used to predict CACS in hemodialysis patients, providing a potential method for rapid screening and prediction of coronary artery calcification.

Mononuclear Non-Heme Manganese-Catalyzed Enantioselective cis-Dihydroxylation of Alkenes Modeling Rieske Dioxygenases.

The practical catalytic enantioselective cis-dihydroxylation of olefins that utilize earth-abundant first-row transition metal catalysts under environmentally friendly conditions is an important yet challenging task. Inspired by the cis-dihydroxylation reactions catalyzed by Rieske dioxygenases and non-heme iron models, we report the biologically inspired cis-dihydroxylation catalysis that employs an inexpensive and readily available mononuclear non-heme manganese complex bearing a tetradentate nitrogen-donor ligand and aqueous hydrogen peroxide (H2O2) and potassium peroxymonosulfate (KHSO5) as terminal oxidants. A wide range of olefins are efficiently oxidized to enantioenriched cis-diols in practically useful yields with excellent cis-dihydroxylation selectivity and enantioselectivity (up to 99% ee). Mechanistic studies, such as isotopically 18O-labeled water experiments, and density functional theory (DFT) calculations support that a manganese(V)-oxo-hydroxo (HO-MnV═O) species, which is formed via the water-assisted heterolytic O-O bond cleavage of putative manganese(III)-hydroperoxide and manganese(III)-peroxysulfate precursors, is the active oxidant that effects the cis-dihydroxylation of olefins; this is reminiscent of the frequently postulated iron(V)-oxo-hydroxo (HO-FeV═O) species in the catalytic arene and alkene cis-dihydroxylation reactions by Rieske dioxygenases and synthetic non-heme iron models. Further, DFT calculations for the mechanism of the HO-MnV═O-mediated enantioselective cis-dihydroxylation of olefins reveal that the first oxo attack step controls the enantioselectivity, which exhibits a high preference for cis-dihydroxylation over epoxidation. In this study, we are able to replicate both the catalytic function and the key chemical principles of Rieske dioxygenases in mononuclear non-heme manganese-catalyzed enantioselective cis-dihydroxylation of olefins.

Calcification detection on upper extremity arteries: a comparison of ultrasonic and X-ray methods.

Background: Vascular calcification (VC) has been observed in patients with hemodialysis, whereas few studies have investigated calcification in the upper extremity vasculature. Both ultrasound and X-ray are used to investigate the calcification of arteries in patients. However, there is a lack of data on the consistency between these two methods. The aim of this study was to investigate the occurrence of VC in the radial and ulnar arteries of hemodialysis patients and investigate the detection consistency in VC between ultrasound and X-ray. Methods: Ultrasound and X-ray examinations were performed in the radial and ulnar arteries of both the left and right upper extremities of 40 patients on hemodialysis. The calcification status of arteries was evaluated by the calcification index from ultrasound and X-ray respectively. Clinical variables of patients were collected from all the involved patients. Results: Of the 40 patients, VC was detected in 31 patients by ultrasound, while X-ray detected VC in 22 patients. Compared to ultrasound assessment, X-ray assessment was 73.21% sensitive but only 66.35% specific with a positive predictive value of 53.95% for detecting calcifications in the radial or ulnar artery. The level of agreement between ultrasound and X-ray results was fair. In addition, our data showed that more ulnar arteries had VCs than the corresponding radial arteries. Conclusion: Ultrasound is more sensitive in detecting the presence of calcified atherosclerotic lesions. Ultrasound and X-ray exhibited fair consistency. Ultrasound screening for upper extremity radial and ulnar arteries in hemodialysis patients may deserve attention to explore its clinical significance.

The Effect of Allopurinol on Renal Outcomes in Patients with Diabetic Kidney Disease: A Systematic Review and Meta-Analysis.

BACKGROUND: Hyperuricemia is an independent risk factor for diabetic kidney disease (DKD) progression. Previous animal and cohort studies have reported that allopurinol administration could be of therapeutic benefit in diabetic subjects. However, there has been controversy regarding the effects of allopurinol on DKD. OBJECTIVES: The aim of our study was to investigate the efficacy of allopurinol on renal function in patients with DKD by meta-analysis of randomized controlled trials. METHOD: PubMed, EMBASE, and the Cochrane Library were searched from inception to October 2020. The primary outcome was a change in glomerular filtration rate (GFR). The secondary outcome was the change in albuminuria and serum uric acid (UA). Two reviewers independently assessed for risk of bias and extracted data. Standardized mean difference (SMD) or weighted mean difference (WMD) was calculated with random effects models and was reported with corresponding 95% confidence intervals (CIs). Grading of Recommendations Assessment, Development, and Evaluation (GRADE) of the evidence was performed after meta-analysis. International prospective register of systematic reviews registration CRD42020219132. RESULTS: From 642 potentially relevant citations, 3 studies were ultimately included. Our results showed evident reduction in serum UA after allopurinol intervention (WMD = -103.80, 95% CI -159.05, -48.55, I2 = 76%; p = 0.04), with a high GRADE of evidence. However, allopurinol did not significantly improve GFR (WMD = 1.07, 95% CI -1.68, 3.82, I2 = 33%; p = 0.45), with a moderate GRADE of evidence. There was no significant difference on improvement of albuminuria in patients of allopurinol and those in placebo groups (SMD = -0.26, 95% CI -1.03, 0.52, I2 = 94%; p = 0.52), with a moderate GRADE of evidence. CONCLUSIONS: The present research showed that allopurinol did not significantly improve renal function and albuminuria in patients with DKD.

Role and Mechanism of Epithelial-Mesenchymal Transition Mediated by Inflammatory Stress-Induced TGF-ß1 in Promoting Arteriovenous Fistula Stenosis.

Objective: To explore the role and mechanism of epithelial-mesenchymal transition (EMT) mediated by inflammatory stress-induced TGF-ß1 in promoting arteriovenous fistula stenosis. Methods: The inflammatory cells HK-2 were cultured by adding TGF-ß1. The optimal stimulation time was determined after TGF-ß1 was added. HK-2 cells were divided into two groups, DMEM/F12 medium was added to one group (the control group), and the other group was treated with TGF-ß1 (10 ng/ml) in serum-free DMEM/F12 medium to stimulate cell differentiation to mesenchymal. Results: TGF-ß1 was stably expressed after being transfected into EMT. The expression of TGF-ß1 in the experimental group was higher than that in the control group (P < 0.05) 7 days after transfection. Western blot showed that TGF-ß1 protein expression was higher in the experimental group 7 days after transfection, and no TGF-ß1 protein expression was detected in the control group. The smooth muscle cells showed α-SMA expression in the control group, but no cells with expression of SMA and CD31/vWF were found at the same time; α-SMA expression was shown in smooth muscle cells and proliferative myofibroblasts, but no cells with expressions of SMA and CD31/vWF were found at the same time. The observation group showed that the expression of α-SMA was detected in smooth muscle cells and proliferative myofibroblasts, CD31/vWF was also expressed in endothelial cells, and α-SMA and vWF were also observed in endothelial cells, but no CD31 expression was found. Conclusion: The inflammatory stress-induced TGF-ß1 could act on epithelial-mesenchymal transition and promote the degree of arteriovenous fistula stenosis.

Identification of IκBα in Japanese eel Anguilla japonica that impairs the IKKα-dependent activation of NF-κB, AP1, and type I IFN signaling pathways.

As a member of inhibitory κB family (IκB) family, IκBα is best-characterized and plays a central negative feedback regulator of NF-κB pathway in mammals, but the information about IκBα in the regulation of immune responses is still limited in teleost fishes. In the present study, the full-length cDNA of an IκBα homologue, AjIκBα, was cloned by 5' and 3' SMART RACE from Japanese eel, and its characteristics of expression in response to various PAMPs and A. hydrophila infection were investigated both in vivo and in vitro using quantitative real-time polymerase chain reaction (qRT-PCR). In addition, the subcellular localization of AjIκBα GFP fusion protein and the induction of AjIκBα alone or co-expression with Japanese eel IKKα (AjIKKα) in the activation of NF-κB, type I IFN and AP1 performed using Dual-Glo luciferase assay system were also detected. Sequence comparison analysis revealed that AjIκBα has typical conserved domains, including the N-terminal conserved degradation motif, the ankyrin repeats, and the C-terminal PEST domain. The predicted three-dimensional structure of AjIκBα is similar to that of human IκBα. qRT-PCR analysis revealed a broad expression for AjIκBα in a wide range of tissues, with the highest expression in the spleen, followed by intestine, liver, gills, skin, kidney, and with a lower expression in the heart and muscle. The AjIκBα expressions in the kidney, spleen, and especially in liver were significantly induced following injection with Gram-negative bacterial component LPS, the viral mimic poly I:C and Aeromonas hydrophila infection. In vitro, the AjIκBα transcripts of Japanese eel liver cells were significantly enhanced by the treatment of LPS, poly I:C, or the stimulation of different concentration of Aeromonas hydrophil. Luciferase assays demonstrated that not only could the AjIκBα expression significantly decrease the activation of NF-κB, AP1, and IFNß-responsive promoters in HEK293 cells and EPC cells, but also robustly inhibited the activity of these three promoters in HEK293 cells or NF-κB and AP1-responsive promoters in EPC cells induced by AjIKKα. Additionally, subcellular localization studies showed that AjIκBα was evenly distributed in the cytoplasm and nucleus both in HEK293 cells and EPC cells under natural state. AjIκBα was found to aggregate into spots in the cytoplasm and nucleus stimulated by LPS or mostly aggregate into nucleus with the treatment of poly I:C in HEK293 cells, whereas the elevated expression of AjIκBα was observed in the cytoplasm of EPC cells upon the stimulation of poly I:C. These results collectively indicated that AjIκBα function as an important negative regulation in innate immunity of host against antibacterial and antiviral infection likely via the inhibition of the activation of NF-κB, AP1, and type I IFN signaling pathways.

Fish IKKα from Japanese eel (Anguilla japonica) can activate NF-κB, AP1, and type I IFN signaling pathways.

Inhibitor of nuclear factor kappa-B kinase subunit alpha (IKKα) plays a pivotal role in the activation of nuclear factor kappa-B (NF-κB) pathway in response to pathogens infections in mammals, but the information about IKKα in the regulation of immune responses is still limited in teleost fishes. In the present study, the full-length cDNA of an IKKα homologue, AjIKKα, was cloned by 5' and 3' SMART RACE from Japanese eel, and its characteristics of expression in response to various PAMPs and A. hydrophila infection were investigated both in vivo and in vitro using quantitative real-time polymerase chain reaction (qRT-PCR). In addition, the subcellular localization of AjIKKα GFP fusion protein and the induction of AjIKKα in the activation of NF-κB, type I IFN and AP1 performed using Dual-Glo luciferase assay system were also detected. Sequence comparison analysis revealed that AjIKKα has typical conserved domains, including an N-terminal kinase domain, an ubiquitin-like domain, a scaffold dimerization domain, and a C-terminal NEMO-binding domain. The predicted three-dimensional structure of AjIKKα is similar to that of human IKKα. Quantitative real-time polymerase chain reaction (qRT-PCR) analysis revealed a broad expression for AjIKKα in a wide range of tissues, with the highest expression in the liver, followed by the intestine, gills, and spleen, and with a lower expression in the muscle and heart. The AjIKKα expressions in the liver and kidney were significantly induced following injection with the viral mimic poly I:C and Aeromonas hydrophila infection, whereas the bacterial mimic LPS down-regulated the expression of AjIKKα in the spleen. In vitro, the AjIKKα transcripts of Japanese eel liver cells were significantly enhanced by the treatment of LPS, poly I:C, CpG-DNA, and PGN or the stimulation of different concentration of Aeromonas hydrophila (1 × 106 cfu/mL, 1 × 107 cfu/mL, and 1 × 108 cfu/mL). Luciferase assays demonstrated that AjIKKα expression could significantly induce NF-κB, AP-1 and type I IFN promoter activation in a dose-dependent manner. Additionally, subcellular localization studies showed that AjIKKα was evenly distributed in the cytoplasm in the natural state, but AjIKKα was found to aggregate into spots in the cytoplasm after the stimulation of LPS and poly I:C. These results collectively indicated that AjIKKα plays an important role in innate immunity of host against antibacterial and antiviral infection likely via the activation of NF-κB, AP1and type I IFN signaling pathway.

Electronic Structure and Magnetic Anisotropy of Single-Layer Rare-Earth Oxybromide.

The discovery of intrinsic magnetism in two-dimensional (2D) limit has triggered increasing investigations in layered magnetic materials. However, most of the available candidates involves 3d transition metals, while the layered rare-earth magnetic materials are largely unexplored at present. Here, we proposed a series of 2D rare-earth magnetic semiconductors REOBr (RE = Tb, Dy, Ho, Er and Tm) with large magnetic moments and magnetic anisotropy energies using the PBE + U method. Our calculations indicate a half-metallic meta-stable state and a low-energy semi-conducting ground state in these 4f single-layers, which can be characterized by the location of the two-fold degenerate x(x 2 - 3y 2) orbital. The dynamical stability of single-layer REOBr is further confirmed using phonon dispersions. The predicted energy gaps ranging from 2.47 to 4.26 eV decrease with the atomic number of the rare-earth element. Meanwhile, very large spin moments and orbital moments up to 6.018 and 2.872 µB are found, which seem to be insensitive to the magnetic state. Furthermore, the magnetic anisotropy energies are evaluated and understood by a fourth-order non-uniaxial anisotropy mode. Diverse anisotropy energy landscapes including easy cone, easy plane, and easy axis are found, and an extremely high magnetic anisotropy energy of about 8 meV per RE atom is found in the single-layer DyOBr. Our investigations provide a unique insight into layered rare-earth magnetic materials and suggest the single-layer REOBr as competing candidates for low-dimensional data storage applications.

Spin-dependent Schottky barriers and vacancy-induced spin-selective ohmic contacts in magnetic vdW heterostructures.

2D ferromagnets, such as CrX3 (X = Cl, Br and I), have been attracting extensive attention since they provide novel platforms to fundamental physics and device applications. Integrating CrX3 with other electrodes and substrates is an essential step to their device realization. Therefore, it is important to understand the interfacial properties between CrX3 and other 2D materials. As an illustrative example, we have investigated the heterostructures between CrX3 and graphene (CrX3/Gr) by first-principles calculations. We found a unique Schottky contact type with strongly spin-dependent barriers in CrX3/Gr. This can be understood by synergistic effects between the exchange splitting of the semiconductor band of CrX3 and interlayer charge transfer. The spin-asymmetry of Schottky barriers may result in different tunneling rates of spin-up and down electrons, and then lead to spin-polarized current, namely the spin-filter (SF) effect. Moreover, by introducing X vacancies into CrX3/Gr, an ohmic contact forms in the spin-up direction. It may enhance the transport of spin-up electrons, and improve the SF effect. Our systematic study reveals the unique interfacial properties of CrX3/Gr, and provides a theoretical view of the understanding and designing of spintronic devices based on magnetic vdW heterostructures.

The effects of megestrol acetate on nutrition, inflammation and quality of life in elderly haemodialysis patients.

PURPOSE: Malnutrition, inflammation and poor quality of life are prevalent among elderly haemodialysis patients. Megestrol acetate (MA) is a synthetic progestin that is widely used to increase appetite and weight in various clinical settings. MA has been indicated to be effective in improving quality of life in patients with cancers. The aim of the present study was to evaluate the efficacy and safety of MA in treating malnourished elderly haemodialysis patients. METHODS: A randomized controlled study involving 46 hypoalbuminemia haemodialysis patients aged 70 years or older was conducted. The patients in MA-treated group (n = 23) took 160 mg of MA daily, while those in control group (n = 23) were enrolled without any intervention. Anthropometric parameters and laboratory results, including height, dry weight, body mass index, and modified subjective global assessment score as well as serum albumin, triglyceride, total cholesterol, hsCRP, IL-1b and IL-6 concentrations were measured in all patients before and after the intervention. Health-related quality of life was also evaluated using the KDQOL-SF 1.3. RESULTS: In the MA-treated group, a total of 18 patients finished the therapy over a 3-month period. Appetite was reported as improved by 15 patients, and a statistically significant increase was observed in dry weight (53.36 ± 6.15 vs. 54.24 ± 6.32, P < 0.01) and serum albumin concentration (29.05 ± 3.91 vs. 37.67 ± 4.88, P < 0.01) in the MA-treated group compared to those of the control group. The quality of life in both the physical domain (46.73 ± 18.17 vs. 63.37 ± 22.35, P < 0.01) and the mental domain (50.28 ± 20.36 vs. 68.02 ± 25.48, P < 0.01) was also improved in the same group. There was no significant change in the inflammatory marker concentrations after the intervention. No serious or unexpected adverse events were observed except that one patient who withdrew due to excessive fluid gain between haemodialysis sessions. CONCLUSION: Our data suggest that MA can be effective in improving nutritional status and quality of life by increasing appetite in elderly haemodialysis patients with acceptable side effects; however, MA might not ameliorate inflammation.

The enhanced ferromagnetism of single-layer CrX3 (X = Br and I) via van der Waals engineering.

The recent experimental discovery of intrinsic ferromagnetism in single-layer CrI3 opens a new avenue to low-dimensional spintronics. However, the low Curie temperature, TC ∼ 45 K, is still a large obstacle to its realistic device application. In this work, we demonstrate that the TC and magnetic moment of CrX3 (X = Br, I) can be enhanced simultaneously by coupling them to buckled two-dimensional Mene (M = Si, Ge) to form magnetic van der Waals (vdW) heterostructures. Our first-principles calculations reveal that n-doping of CrX3, induced by a significant spin-dependent interlayer charge-transfer from Mene, is responsible for the drastic enhancement of TC and magnetic moment. Furthermore, the diversified electronic properties including half-metallicity and semi-conductivity with a configuration-dependent energy gap are also predicted in this novel vdW heterostructure, implying broad potential applications in spintronics. Our study suggests that vdW engineering may be an efficient way to tune the magnetic properties of 2D magnets, and Mene/CrX3 magnetic vdW heterostructures are wonderful candidates in spintronics and nanoelectronics devices.

Achieving a direct band gap and high power conversion efficiency in an SbI3/BiI3 type-II vdW heterostructure via interlayer compression and electric field application.

Type-II van der Waals (vdW) heterostructures are considered as a class of competitive candidates of high-efficiency photovoltaic materials, due to their spontaneous electron-hole separation. However, most of the vdW heterostructures possess an indirect gap and a large band offset, which would lead to low photon-to-electron conversion efficiency. Taking an SbI3/BiI3 vdW heterostructure as an illustrative example, we propose interlayer compression and vertical electric field application as two effective strategies to modulate the electronic and photovoltaic properties of type-II vdW heterostructures. Our results reveal that a lattice-matched SbI3/BiI3 vdW heterostructure has an indirect band gap of 1.34 eV with the conduction band minimum (CBM) at the Γ point and the valence band maximum (VBM) between the Γ and M points. The power conversion efficiency (PCE) of an SbI3/BiI3-based excitonic solar cell (XSC) is predicted to be about 14.42%. When compressing the heterostructure along the vdW gap direction, the highest valence band state at the Γ point is lifted significantly and the VBM gradually approaches the Γ point, implying an indirect-direct gap transition. This interesting evolution can be attributed to the increasing k-dependent electronic hybridization of the pz orbitals of interlayer adjacent I atoms with a reduced interlayer distance. Moreover, the interlayer compression also enhances the PCE of the system monotonically. When applying a vertical electric field, the band alignment of the heterostructure undergoes a transition from type-II to type-I and then returns to type-II between 0.1 and 0.6 V Å-1. Meanwhile, the PCE of the SbI3/BiI3 XSC could be enhanced up to 21.63%. This work provides guidance for improving the electronic and photovoltaic properties of type-II vdW heterostructures.

Kinetics of C60 fullerene dispersion in water enhanced by natural organic matter and sunlight.

The industrial-scale production of Buckminster fullerene C60 elicits concerns over its impact on human health and ecosystems because of the reported, albeit debatable, toxicity. Assessment of the overall environment risk requires a good estimate of the level of exposure and careful characterization of the physicochemical properties of C60 in natural aqueous environments. The reported study investigates the role of various environmental factors, i.e., ionic composition, natural organic matter (NOM), and light in dispersion of C60 in the aqueous phase by simple mixing. The presence of NOM greatly enhances C60 dispersion, and the dispersion process is further accelerated by sunlight. At typical NOM concentrations found in natural waters, C60 concentrations of a few to tens of milligrams per liter can occur within 10 days of mixing, regardless of its extremely low water solubility. The rate of dispersing decreases with the increase of ionic strength. However, calcium ions significantly increase C60 concentration in the aqueous phase. Results from UV/vis absorbance characterization strongly suggest that C60 may have been chemically modified when dispersed in an NOM solution in the presence of sunlight. This reaction pathway has significant implication on the fate, transport, and environmental impact of C60 fullerene.