Proteomic Analysis of Idiopathic Nephrotic Syndrome Triggered by Primary Podocytopathies in Adults: Regulatory Mechanisms and Diagnostic Implications.

Idiopathic nephrotic syndrome (NS) is a heterogeneous group of glomerular disorders which includes two major phenotypes: minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS). MCD and FSGS are classic types of primary podocytopathies. We aimed to explore the molecular mechanisms in NS triggered by primary podocytopathies and evaluate diagnostic value of the selected proteomic signatures by analyzing blood proteome profiling. Totally, we recruited 90 participants in two cohorts. The first cohort was analyzed using label-free quantitative (LFQ) proteomics to discover differential expressed proteins and identify enriched biological process in NS which were further studied in relation to clinical markers of kidney injury. The second cohort was analyzed using parallel reaction monitoring-based quantitative proteomics to verify the data of LFQ proteomics and assess the diagnostic performance of the selected proteins using receiver-operating characteristic curve analysis. Several biological processes (such as immune response, cell adhesion, and response to hypoxia) were found to be associated with kidney injury during MCD and FSGS. Moreover, three proteins (CSF1, APOC3, and LDLR) had over 90% sensitivity and specificity in detecting adult NS triggered by primary podocytopathies. The identified biological processes may play a crucial role in MCD and FSGS pathogenesis. The three blood protein markers are promising for diagnosing adult NS triggered by primary podocytopathies.

Development of a novel prognostic assessment model for hepatitis B virus-related acute-on-chronic liver failure based on reexamination results.

Acute-on-chronic liver failure (ACLF) is a common clinical emergency and critical illness with rapid progression and poor prognosis. This study aims to establish a more efficient system for the prognostic assessment of hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF), which will provide a guiding scheme for subsequent treatment and improve the survival rate of patients. Data on 623 patients with HBV-ACLF were recorded. Univariate and multivariate analyses were performed to determine the discriminative abilities of the novel prognostic assessment model in predicting 90-day mortality. The area under the receiver operating characteristic curve was used to evaluate the accuracy of the models. Patients were divided into high- and low-scoring groups based on the best critical values, and survival rates were analyzed using Kaplan-Meier survival analysis and compared by applying log-rank tests. The area under the curve of the new scoring system established using the results of the first reexamination, the results of the first examination, the mean daily change in these results (MDCR) and the results of other first examinations were 0.911 (95% confidence interval [CI]: 0.889, 0.933), 0.893 (95% CI: 0.868, 0.917), and 0.895 (95% CI: 0.871, 0.919), respectively. The final prognostic scoring system established using the results of the first reexamination was chosen as a novel prognostic assessment model, and patients with lower scores (first reexamination results [FRER] score ≤ 3.65) had longer survival times (P < .001). The prognostic scoring system established using the FRER combined with other examination results can better assess the prognosis of HBV-ACLF at 90 days.

Dietary thiamine modulates carbohydrate metabolism, antioxidant status, and alleviates hypoxia stress in oriental river prawn Macrobrachium nipponense (de Haan).

Hypoxia is one of the challenges in prawns aquaculture. However, the role of thiamine, which is a coenzyme in carbohydrate metabolism with antioxidant properties, in reducing hypoxia in prawns aquaculture is currently unknown. We investigated the effects of thiamine on antioxidant status, carbohydrate metabolism and acute hypoxia in oriental river prawn, Macrobrachium nipponense. One thousand eight hundred prawns (0.123 ± 0.003 g) were fed five diets (60 prawns each tank, six replicates per diet) supplemented with graded thiamine levels (5.69, 70.70, 133.67, 268.33 and 532.00 mg/kg dry mater) for eight weeks and then exposed to hypoxia stress for 12 h followed by reoxyegnation for 12 h. The results showed that, under normoxia, prawns fed the 133.67 or 268.33 mg/kg thiamine diet had significantly lower glucose 6-phosphatedehydrogenase, succinate dehydrogenase and phosphoenolpyruvate carboxykinase activities than those fed the other diets. Moreover, total antioxidant capacity (T-AOC) increased significantly when prawns were fed the 133.67 mg/kg thiamine diet. Superoxide dismutase (SOD) activity and malonaldehyde (MDA) content also increased significantly when prawns were fed the 268.33 or 532.00 mg/kg thiamine diet under hypoxia. And the significantly increased SOD activity and MDA level also observed in prawns fed 532.00 mg/kg thiamine under reoxygenation. Under normoxia, prawns fed the 70.70 or 133.67 mg/kg thiamine diet decreased the mRNA expressions of AMP-activated protein kinase-alpha (AMPK-α), pyruvate dehydrogenase-E1-α subunit (PDH-E1-α) and hypoxia-inducible factor-1s (HIF-1α, HIF-1ß), but increased the mRNA expressions of phosphofructokinase (PFK) significantly. After 12 h of hypoxia, the energy metabolism related genes (AMPK-ß, AMPK-γ, PFK, PDH-E1-α), hypoxia-inducible factor related genes (HIF-1α, HIF-1ß) and thiamine transporter gene (SLC19A2) were up-regulated significantly in prawns fed the 133.67 or 268.33 mg/kg thiamine diets. After 12 h of reoxygenation, prawns fed the 133.67 or 268.33 mg/kg diet significantly decreased the SOD activity, MDA level and SLC19A2 mRNA expression compared with other diets. The optimum thiamine was 161.20 mg/kg for minimum MDA content and 143.17 mg/kg for maximum T-AOC activity based on cubic regression analysis. In summary, supplementing 143.17 to 161.20 mg/kg thiamine in the diets for M. nipponense improves the antioxidant capacity under normoxia and reduces the oxidative damage under hypoxia stress.

Toughening and Hardening Limited Zone of High-Strength Steel through Geometrically Necessary Dislocation When Exposed to Electropulsing.

The enhancement of both low-temperature impact toughness and the hardness of a high strength steel heat-affected zone (HAZ) is investigated by using high-density electropulsing (EP). The athermal and thermal effects of EP on HAZ microstructure and resultant mechanical properties were examined based on physical metallurgy by electron backscattered diffraction and on tests of hardness and impact toughness at -60 °C, respectively. EP parameters were carefully determined to avoid electro-contraction and excessive pollution of the base metal by using numerical simulation. The EP results show that the mean impact toughness and hardness of HAZ are 2.1 times and 1.4 times improved, respectively. In addition to the contribution of microstructure evolution, geometrically necessary dislocation (GND) is also a contributor with an increase of 1.5 times, against the slight decrease in dislocation line density and dislocation density. The mechanisms behind this selective evolution of dislocation components were correlated with the localized thermal cycle EP, i.e., the competition among thermo- and electro-plasticity, and work-hardening due to local thermal expansion. The selective evolution enables the local thermal cycle EP tailor the martensitic substructure that is most favorable for toughness and less for hardness. This selective span was limited within 4 mm for a 5 mm thick sample. The local thermal cycle EP is confirmed to be capable of enhancing in both toughness and hardness within a millimeter-scale region.

Eliminating the Brittleness Constituent to Enhance Toughness of the High-Strength Steel Weld Heat-Affected Zone Using Electropulsing.

The evolution of the martensite-austenite (MA) constituent in the heat-affected zone (HAZ) of high-strength steel FH690 welds when subjected to electropulsing (EP) treatment was investigated herein, with the aim of eliminating brittle MA to enhance toughness. The features induced by EPT were correlated with the microstructure and fractography through scanning electron microscopy and electron backscatter diffraction analyses, together constituting an impact property evaluation. The Charpy V-notch impact results showed EPT could improve toughness of the HAZ from 34.1 J to 51.8 J (the calibrated value was 46 J). Examinations of EP-treated microstructure showed a preferred Joule heating: at the site of the MA constituent, the cleavage fractography introduced by the MA constituent was substituted with ductile dimples with various sizes. Decreases in grain size of 40% and 47% for the matrix and the retained austenite, respectively, were achieved; while for regions without the MA constituent, microstructural modification was negligible. The temperature rise at sample surface was less than 60 °C. The mechanism behind this favorable Joule heating for the MA constituent was correlated with the electrical properties of the MA constituent in contrast with martensite matrix. The toughness enhancement of the HAZ was thus attributed to the elimination of the coarse MA constituent. The present investigation suggested that electropulsing, characterized as a narrow-duration current, is a promising method for preferred elimination of brittle factors and thus improving the toughness of HAZ of high-strength steel within a limited region with a width less than 2 mm.

On (Non-)Monotonicity and Phase Diagram of Finitary Random Interlacement.

In this paper, we study the evolution of a Finitary Random Interlacement (FRI) with respect to the expected length of each fiber. In contrast to the previously proved phase transition between sufficiently large and small fiber length, for all d≥3, FRI is NOT stochastically monotone as fiber length increases. At the same time, numerical evidence still strongly supports the existence and uniqueness of a critical fiber length, which is estimated theoretically and numerically to be an inversely proportional function with respect to system intensity.