Extreme-high-speed laser cladding (EHLA), as a novel surface treatment technique, has attracted great attention because of its high cladding rate and good performance of cladding coatings. However, ...when depositing coatings with high cracking susceptibility, such as Ni60 coatings, cracks are difficult to avoid. Therefore, an extreme-high-speed laser-induction hybrid cladding technology (EH-LIHC) was innovatively proposed in this study. The effects of different preheating temperatures on the surface morphology, internal defects, microstructure, and mechanical properties of Ni60 coatings that were deposited by EHLA and EH-LIHC were analyzed. The results show that the roughness of the coating deposited by EHLA is 26.228 μm. However, the surface roughness of the coating deposited by EH-LIHC at 400 ℃ decreases to 14.316 μm. Simultaneously, the pores- and cracks-free Ni60 coating was deposited at 400 ℃. The coating dilution rate obviously increases as the preheating temperature rises. When the preheating temperature rises, the size of the grains and precipitates also increases. However, although Fe elemental diffusion is increased, there is no significant effect on the properties of the coating. The hardness of the coating fluctuates between 700 and 900 HV, nearly three times that of the substrate. As the preheating temperature rises, the coating’s wear mechanism shifts from abrasive to abrasive and adhesive wear, and eventually back to abrasive wear. The improvement of wear resistance of the Ni60 coating deposited at 400 ℃ was mainly attributed to its high hardness and uniform and dense microstructure. The proposed EH-LIHC technique provides a promising method for the efficient deposit of crack-free coatings with good properties.
Parathyroid hormone (PTH) plays crucial role in maintaining calcium and phosphorus homeostasis. In the progression of secondary hyperparathyroidism (SHPT), expression of calcium-sensing receptors ...(CaSR) in the parathyroid gland decreases, which leads to persistent hypersecretion of PTH. How to precisely manipulate PTH secretion in parathyroid tissue and underlying molecular mechanism is not clear. Here, we establish an optogenetic approach that bypasses CaSR to inhibit PTH secretion in human hyperplastic parathyroid cells. We found that optogenetic stimulation elevates intracellular calcium, inhibits both PTH synthesis and secretion in human parathyroid cells. Long-term pulsatile PTH secretion induced by light stimulation prevented hyperplastic parathyroid tissue-induced bone loss by influencing the bone remodeling in mice. The effects are mediated by light stimulation of opsin expressing parathyroid cells and other type of cells in parathyroid tissue. Our study provides a strategy to regulate release of PTH and associated bone loss of SHPT through an optogenetic approach.
Objective
We assessed the consistency of noninvasive and invasive measurements of central arterial pressure (CAP) and the difference between peripheral brachial artery pressure and CAP in patients ...with chronic kidney disease (CKD) undergoing versus not undergoing hemodialysis.
Methods
This single-center cross-sectional study was performed from May to December 2018. The patients were divided into a control group (n = 50), CKD group (stages 3–5, n = 50), and dialysis group (n = 20), and all underwent measurement of peripheral humeral arterial pressure and noninvasive and invasive measurement of CAP. Group differences and correlations between CAP and peripheral arterial pressure were assessed.
Results
The consistency between noninvasive and invasive CAP was better in the control and CKD groups than in the dialysis group. In the dialysis group, the noninvasive equipment underestimated the actual CAP. The CAP was close to the peripheral brachial artery pressure in the dialysis group, while the CAP was significantly lower than the peripheral brachial artery pressure in the control and CKD groups.
Conclusion
Noninvasive equipment underestimates the actual CAP in patients undergoing dialysis and should be used with caution. The difference between the peripheral arterial pressure and CAP was smaller in patients undergoing dialysis than in patients with CKD and controls.
FG-4592 (roxadustat) is an oral hypoxia-inducible factor (HIF) prolyl hydroxylase inhibitor (HIF-PHI) promoting coordinated erythropoiesis through the transcription factor HIF. Two Phase 2 studies ...were conducted in China to explore the safety and efficacy of FG-4592 (USAN name: roxadustat, CDAN name: ), a HIF-PHI, in patients with anemia of chronic kidney disease (CKD), both patients who were dialysis-dependent (DD) and patients who were not dialysis-dependent (NDD).
In the NDD study, 91 participants were randomized to low (1.1-1.75 mg/kg) or high (1.50-2.25 mg/kg) FG-4592 starting doses or to placebo. In the DD study, 87 were enrolled to low (1.1-1.8 mg/kg), medium (1.5-2.3 mg/kg) and high (1.7-2.3 mg/kg) starting FG-4592 doses or to continuation of epoetin alfa. In both studies, only oral iron supplementation was allowed.
In the NDD study, hemoglobin (Hb) increase ≥1 g/dL from baseline was achieved in 80.0% of subjects in the low-dose cohort and 87.1% in the high-dose cohort, versus 23.3% in the placebo arm (P < 0.0001, both). In the DD study, 59.1%, 88.9% (P = 0.008) and 100% (P = 0.0003) of the low-, medium- and high-dose subjects maintained their Hb levels after 5- and 6-weeks versus 50% of the epoetin alfa-treated subjects. In both studies, significant reductions in cholesterol were noted in FG-4592-treated subjects, with stability or increases in serum iron, total iron-binding capacity (TIBC) and transferrin (without intravenous iron administration). In the NDD study, hepcidin levels were significantly reduced across all FG-4592-treated arms as compared with no change in the placebo arm. In the DD study, hepcidin levels were also reduced in a statistically significant dose-dependent manner in the highest dose group as compared with the epoetin alfa-treated group. Adverse events were similar for FG-4592-treated and control subjects.
FG-4592 may prove an effective alternative for managing anemia of CKD. It is currently being investigated in a pivotal global Phase 3 program.
Immunoglobulin A nephropathy (IgAN) is the most common primary glomerulopathy worldwide, and lacks the effective treatment. The study was aimed to investigate the clinical efficacy of fluticasone ...propionate aerosol combined with angiotensin converting enzyme inhibitor / angiotensin receptor blocker (ACEI/ARB) in the treatment of IgAN.
142 patients with biopsy-proven IgAN at Shenzhen People?s hospital from June 2018 to June 2020 were enrolled. The patients were randomly divided into the supportive care plus fluticasone group and the supportive care group. The patients of the supportive care plus fluticasone group were treated with fluticasone propionate aerosol (250 ?g Bid) combined with ACEI/ARB, while the supportive care group was merely treated with ACEI/ARB. The patients were followed up at 3, 6 and 9 months after enrollment. Primary outcomes include changes in proteinuria and estimated glomerular filtration rate (eGFR).
The level of proteinuria in the supportive care plus fluticasone group was significantly lower compared with the supportive care group at 0, 3, 6 and 9 months. Meanwhile, during the follow-up period, no serious adverse events were recorded during the study in either group. However, fluticasone treatment did not alleviate the decline in eGFR.
Fluticasone propionate aerosol combined with ACEI/ARB can reduce the level of proteinuria in thetreatment of IgAN, and has no significant effects on renal function.
SLM process parameters such as laser power, scanning speed, layer thickness and hatch spacing play a crucial role in the quality of the processed product. In order to find the parameters suitable for ...SLM process, a finite element model was established to simulate the distribution of temperature field of selective laser melting (SLM) stainless steel 316L (SS316L) parts. After finite element simulation, the optimum factor levels for SLM processing SS316L were as follows: laser power of 100–200 W, scanning speed of 500–1500 mm/s, hatch spacing of 0.04–0.12 mm, and layer thickness of 0.03–0.06 mm. Then, based on a series of experiments, different laser energy densities were divided into three regions corresponding to three melting mechanisms: the partial melting zone (37.88–75.76 J/mm
3
), the full melting zone (75.76–151.52 J/mm
3
), and the over-melting zone (larger than 151.52 J/mm
3
). The surface roughness, density, microstructure and mechanical properties of the SLM SS316L were strongly dependent on the laser energy density. The results showed that an excellent SS316L part with a relative density higher than 99.66% and good mechanical properties could be obtained at a laser energy density of 119.05 J/mm
3
with a laser powder of 200 W, a scanning speed of 700 mm/s, a hatch spacing of 0.08 mm and a layer thickness of 0.03 mm.
The aim of the study was to further explore the pathogenesis of idiopathic membranous nephropathy (IMN), gene-sequencing was used to analyze the differentially expressed circRNAs in exosomes of ...patients with IMN, which may lay the foundation for the research of circRNAs as a new class of exosome-based IMN diagnosis biomarkers.
Ten patients with IMN and ten normal controls were recruited as experimental subjects in our study. The exosomes were extracted from the collected serum and urine. Then, pure circRNAs were extracted from the exosomes with a series of enzymatic reactions. Afterwards, the significantly differentially expressed circRNAs were chosen by the method of gene-sequencing.
Compared with normal controls, the circRNAs were reduced in the exosomes from serum of patients with IMN, which mostly originated from intron gene regions. Meanwhile, a total of 89 circRNAs were significantly differentially expressed, which were also mostly derived from intron gene regions, including 49 up-regulated and 40 down-regulated genes. However, the species were increased in the exosomes from the urine of patients with IMN compared to normal controls, and they mainly originated from exon gene regions. Simultaneously, 60 circRNAs were significantly differentially expressed, which primarily belonged to intron gene regions, including 54 up-regulated and 6 down-regulated regions.
The significant differential and specific expression of circRNAs in the exosomes from patients with IMN were observed. For example, MUC3A, which originated from chr7:100550808|100551062, could be considered a potential diagnostic biomarker of IMN. Furthermore, these figures may be used as a reference or supplement in the research of the pathogenesis of IMN.
A weak alkaline environment is established to facilitate the growth of osteoblasts. Unfortunately, this is inconsistent with the application of biodegradable polymer in bone regeneration, as the ...degradation products are usually acidic. In this study, the variation of the interfacial pH of poly (D, L-lactide) and piperazine-based polyurethane ureas (P-PUUs), as the representations of acidic degradable materials, and the behavior of osteoblasts on these substrates with tunable interfacial pH were investigated in vitro. These results revealed that the release of degraded products caused a rapid decrease in the interfacial pH, and this could be relieved by the introduction of alkaline segments. On the contrary, when culturing with osteoblasts, the variation of the interfacial pH revealed an upward tendency, indicating that cell could construct the microenvironment by secreting cellular metabolites to satisfy its own survival. In addition, the behavior of osteoblasts on substrates exhibited that P-PUUs with the most PP units were better for cell growth and osteogenic differentiation of cells. This is due to the hydrophilic surface and the moderate N% in P-PUUs, key factors in the promotion of the early stages of cellular responses, and the interfacial pH contributing to the enhanced effect on osteogenic differentiation.
It is common for diabetic kidney disease (DKD) to be complicated by abnormal blood glucose, blood lipids, and blood pressure rhythms. Thus, it is essential to examine diagnostic and treatment plans ...from the perspective of circadian disruption. This brief review discusses the clinical relevance of circadian rhythms in DKD and how the core clock gene encoding brain and muscle arnt-like protein 1 (BMAL1) functions owing to the importance of circadian rhythm disruption processes, including the excretion of urinary protein and irregular blood pressure, which occur in DKD. Exploring Bmal1 and its potential mechanisms and signaling pathways in DKD following contact with Sirt1 and NF-κB is novel and important. Finally, potential pharmacological and behavioral intervention strategies for DKD circadian rhythm disturbance are outlined. This review aids in unveiling novel, potential molecular targets for DKD based on circadian rhythms.
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•DKD has abnormality in albuminuria and hypertension rhythm.•Bmal1 deficiency in the renal correlates with low blood pressure and BMAL1 has obesity paradox.•BMAL1 probably modulates BMAL1/SIRT1/NF-κB pathway to reduce kidney injury in DKD.•Targeted therapeutic approaches for DKD rhythm disorders encompass pharmacological intervention and small-molecule targets.•Regulating daily eating pattern, enhancing sleep quality, and scheduling exercise are also critical.
With the rapid development of new-generation cyber–physical system (CPS) technologies, the smart operation and management of the broad bean harvesting system are enabled. This paper proposed a smart ...broad bean harvesting system (SBHS) and a self-adaptive control method based on CPS technologies. Firstly, the overall architecture of the SBHS is designed, which consists of four main components, namely optimal intelligent perception environment configuration, digital twin model construction, virtual simulation and real-time optimization, self-adaptive adjustment and control. Then, three key enabling technologies are discussed in detail, namely, intelligent perception environment configuration for the SBHS, digital twin model construction for the SBHS, colored Petri net (CPN)-based self-adaptive analysis and control of the harvesting system. Lastly, a proof-of-concept experiment based on a cooperative company is presented to illustrate the main work logic and advantage of the proposed SBHS. After the edge–cloud cooperative intelligent harvesting environment is configured, the CPN model for the workflow of the SBHS is created to analyze and optimize the harvesting processes. In addition, a management and control platform are developed to further illustrate the implementation of the proposed SBHS and the self-adaptive control method.
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