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To explore the clinical characteristics, treatment protocol and prognosis of children with anti-complement factor H (CFH) autoantibody (Ab)-associated hemolytic uremic syndrome (HUS).Clinical data of 8 patients with anti-CFH Ab-associated HUS who were admitted to Shandong Provincial Hospital from January 2011 to December 2020 were collected retrospectively.The age at disease onset ranged between 5.83 and 13.5 years, with a male: female ratio of 1.67:1. The time of onset was distributed from May to June and November to December. Digestive and upper respiratory tract infections were common prodromal infections. Positivity for anti-CFH Ab and reduced C3 levels were observed among all patients. Heterozygous mutation of the CHFR5 gene (c.669del A) and homozygous loss of the CFHR1 gene [loss2(EXON:2-6)] were found in two patients. All patients received early treatment with plasma exchange and corticosteroid therapy. Six patients were given immunosuppressive agents (cyclophosphamide and/or mycophenolate mofetil) for persistent proteinuria. The follow-up period was 12-114 months. Four of 8 patients achieved complete remission, 3 achieved partial remission, and 1 died. Relapse occurred in two patients.Children with anti-CFH Ab-associated HUS were mainly school-aged and predominantly male, with onset times of summer and winter. Digestive and upper respiratory tract infections were common prodromal infections. Plasma exchange combined with methylprednisolone pulse therapy in the acute phase and cyclophosphamide or mycophenolate mofetil treatment for maintenance can be utilized in children with anti-CFH Ab-associated HUS if eculizumab is not available.

Background This study investigated the association between urinary epidermal growth factor (EGF) and complete remission (CR) of proteinuria in children with IgA nephropathy (IgAN). Methods We included 108 patients from the Registry of IgA Nephropathy in Chinese Children. The urinary EGF at the baseline and follow-up were measured and normalized by urine creatinine (expressed as uEGF/Cr). The person-specific uEGF/Cr slopes were estimated using linear mixed-effects models for the subset of patients with longitudinal data of uEGF/Cr. Cox models were used to analyze the associations of baseline uEGF/Cr and uEGF/Cr slope with CR of proteinuria. Results Patients with high baseline uEGF/Cr were more likely to achieve CR of proteinuria (adjusted HR 2.24, 95% CI: 1.05–4.79). The addition of high baseline uEGF/Cr on the traditional parameters significantly improved the model fit for predicting CR of proteinuria. In the subset of patients with longitudinal data of uEGF/Cr, high uEGF/Cr slope was associated with a higher likelihood of CR of proteinuria (adjusted HR 4.03, 95% CI: 1.02–15.88). Conclusions Urinary EGF may be a useful noninvasive biomarker for predicting and monitoring CR of proteinuria in children with IgAN. Impact High levels of baseline uEGF/Cr (>21.45 ng/mg) could serve as an independent predictor for CR of proteinuria. The addition of baseline uEGF/Cr on the traditional clinical pathological parameters significantly improved the fitting ability for the prediction of CR of proteinuria. Longitudinal data of uEGF/Cr were also independently associated with CR of proteinuria. Our study provides evidence that urinary EGF may be a useful noninvasive biomarker in the prediction of CR of proteinuria as well as monitoring therapeutic response, thus guiding treatment strategies in clinical practice for children with IgAN.

This study aims to evaluate the effect of purinergic ligand-gated ion channel 7 receptor (P2X7R) antagonist A438079 in kidneys of children with primary nephrotic syndrome (PNS). In vitro, human podocytes were respectively stimulated with oxLDL (80 µg/ml), A438079 (10 µmol/L), or the compound oxLDL and A438079 together. CXC chemokine ligand 16 (CXCL16) and P2X7R expression levels were detected by Western blot and immunofluorescence assay, respectively. Immunofluorescence assay was used to detect Dil-oxLDL, and a Colorimetric Cholesterol Detection Kit was used for quantitative determination. Our results demonstrated that CXCL16 and P2X7R expression levels were remarkably increased in the renal tissue from children with PNS, particularly in the same location. Furthermore, in contrast to children with minimal change disease, the expressions of P2X7R and CXCL16 in renal tissue of children with focal segmental glomerulosclerosis were more obvious. In vitro, CXCL16 and P2X7R expression levels in human podocytes stimulated with oxLDL were markedly elevated accompanying higher intracellular lipid accumulation compared with the normal control group. In addition, pretreatment of human podocytes with A438079 before the start of oxLDL stimulation causes a significant reduction in CXCL16 expression and a decrease in lipid accumulation. Overall, CXCL16 and P2X7R may participate in the progression of PNS. The lipid accumulation reduction caused by A438079 may be through deregulating the CXCL16 pathway, suggesting that there is a potential role for P2X7R antagonists to remedy PNS.

It was reported that Melatonin (MT) is essential for plants and can mitigate multiple abiotic stresses. However, the mechanism used by endogenous MT to alleviate chromium phytotoxicity is still unclear. In this study, the effects of MT pretreatment on growth, root architecture, subcellular Cr distribution, phytochelatin synthesis and antioxidant metabolism of wheat seedlings under chromium (50 µM Cr6+) stress were researched. Our results showed that Cr stress markedly inhibited seedlings growth and increased ROS accumulation in both roots and leaves. Importantly, growth inhibition and oxidative stress were significantly improved by MT under Cr stress. On the one hand, Cr accumulation and transport from roots to leaves were reduce by MT, which was owed to enhanced vacuolar sequestration via up-regulated phytochelatin (PC) accumulation, which was derived from that MT up-regulated the expression of key genes for PC synthesis (TaPCS and Taγ-ECS). On the other hand, MT pretreatment obviously alleviated Cr-induced oxidative damage, which proved by the diminished lipid peroxidation and cell apoptosis, profiting from the enhanced scavenging ability of reactive oxygen species (ROS) as a result of the MT-induced increment of the activities of superoxide dismutase (SOD), catalase (CAT), ascorbate peroxidase (APX) and glutathione reductase (GR) and the related encoding genes expression levels of TaSOD2, TaCAT, TaAPX and TaGR. Taken together, all these results revealed that MT alleviated Cr toxicity to wheat seedlings probably through altering Cr6+ subcellular distribution and enhancing antioxidant metabolism. And these findings may be helpful to increase wheat production under Cr stress.

Kidney disease is manifested in a wide variety of phenotypes, many of which have an important hereditary component. To delineate the genotypic and phenotypic spectrum of pediatric nephropathy, a multicenter registration system is being implemented based on the Chinese Children Genetic Kidney Disease Database (CCGKDD). In this study, all the patients with kidney and urological diseases were recruited from 2014 to 2020. Genetic analysis was conducted using exome sequencing for families with multiple affected individuals with nephropathy or clinical suspicion of a genetic kidney disease owing to early-onset or extrarenal features. The genetic diagnosis was confirmed in 883 of 2256 (39.1%) patients from 23 provinces in China. Phenotypic profiles showed that the primary diagnosis included steroid-resistant nephrotic syndrome (SRNS, 23.5%), glomerulonephritis (GN, 32.2%), congenital anomalies of the kidney and urinary tract (CAKUT, 21.2%), cystic renal disease (3.9%), renal calcinosis/stone (3.6%), tubulopathy (9.7%), and chronic kidney disease of unknown etiology (CKDu, 5.8%). The pathogenic variants of 105 monogenetic disorders were identified. Ten distinct genomic disorders were identified as pathogenic copy number variants (CNVs) in 11 patients. The diagnostic yield differed by subgroups, and was highest in those with cystic renal disease (66.3%), followed by tubulopathy (58.4%), GN (57.7%), CKDu (43.5%), SRNS (29.2%), renal calcinosis /stone (29.3%) and CAKUT (8.6%). Reverse phenotyping permitted correct identification in 40 cases with clinical reassessment and unexpected genetic conditions. We present the results of the largest cohort of children with kidney disease in China where diagnostic exome sequencing was performed. Our data demonstrate the utility of family-based exome sequencing, and indicate that the combined analysis of genotype and phenotype based on the national patient registry is pivotal to the genetic diagnosis of kidney disease.

Steroid-resistant nephrotic syndrome (SRNS) is one of the major causes of end-stage kidney disease (ESKD) in children and young adults. For approximately 30% of children with SRNS results from a genetic cause. In this study, genotype-phenotype correlations in a cohort of 283 pediatric patients with SRNS or early-onset NS (nephrotic syndrome presenting within the first year of life) from 23 major pediatric nephrology centers in China were analyzed. All patients were performed with next-generation sequencing and Sanger sequencing. The overall mutation detection rate was 37.5% (106 of 283 patients). WT1 was the most frequently detected mutation, followed by NPHS1, NPHS2, and ADCK4, and these four major causative genes (WT1, NPHS1, NPHS2, and ADCK4) account for 73.6% of patients with monogenic SRNS. Thirteen of 106 individuals (12.3%) carried mutations in ADCK4 that function within the coenzyme Q10 biosynthesis pathway. In the higher frequently ADCK4-related SRNS, two mutations, c.737G>A (p.S246N) and c.748G>C (p.D250H), were the most prevalent. Our study provides not only definitive diagnosis but also facilitate available targeted treatment for SRNS, and prediction of prognosis and renal outcome. Our indications for genetic testing are patients with FSGS, initial SRNS, cases of positive family history or those with extra-renal manifestations.

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Nephrotic syndrome (NS) is one of the most common causes of chronic kidney disease in the pediatric population. Hyperlipidemia is one of the main features of NS. The present study investigated the role of CXC motif chemokine ligand 16 (CXCL16) and ADAM metallopeptidase domain 10 (ADAM10) in oxidized low‑density lipoprotein (oxLDL)‑stimualted podocytes and the underlying mechanisms. CXCL16 and ADAM10 expression levels in oxLDL‑treated podocytes were measured via reverse transcription‑quantitative PCR and western blotting. Cell migration assays were conducted to assess the migration of oxLDL‑treated podocytes. CXCL16 or ADAM10 overexpression and knockdown assays were conducted. The results indicated that oxLDL stimulation increased ADAM10 and CXCL16 expression levels, and enhanced podocyte migration compared with the control group. Moreover, CXCL16 and ADAM10 overexpression significantly increased podocyte migration and the expression of actinin‑α4 (ACTN4) compared with the control groups. By contrast, CXCL16 and ADAM10 knockdown significantly reduced podocyte migration and the expression of ACTN4 compared with the control groups. The results suggested that oxLDL promoted podocyte migration by regulating CXCL16 and ADAM10 expression, as well as by modulating the actin cytoskeleton. Therefore, CXCL16 and ADAM10 may serve as novel therapeutic targets for primary nephrotic syndrome in children.

Parthenolide (PTL) is a natural product from the shoots of Tanacetum parthenium, which has immunomodulatory effects in multiply type of diseases. This study aimed to explore the effect and the underlying mechanism of PTL on the anti-apoptotic and anti- inflammatory ability of tweak-induced podocytes. Conditionally immortalized mouse podocytes were incubated with Tumor necrosis factor-like weak inducer of apoptosis (Tweak, 100 ng/ml), PTL(10 µM) or Tweak + PTL for 12 h, 24 and 48 h, respectively. Podocytes viability was detected by CCK-8 assay. Tweak and Cxcl16 expression were evaluated by western blot and immunofluorescence assay. Dil-oxLDL stain was detected by immunofluorescence analysis. Intracellular Total Cholesterol (TC) content was measured through TC detection Kit. These results demonstrated that the podocytes cells viability was gradually decreased after treatment with different concentrations of Tweak (0, 50, 100, 150). Tweak and Cxcl16 protein expression in mouse podocytes treated with tweak were remarkably elevated and were found to have higher intracellular lipid accumulation compared with the control group, whereas co-administration with PTL, tweak and Cxcl16 expression as well as the intracellular lipid accumulation were notablely decreased in tweak-induced podocytes. Therefore, our conclusion was that tweak and Cxcl16 were involved in the regulation of tweak-induced podocytes injury. Meanwhile, the anti-apoptotic and anti-inflammatory effect of PTL may be correlated with the tweak and Cxcl16 expression decreased.

In mainland China, dialysis for children with end-stage renal disease (ESRD) was not introduced until the 1980s. To describe the development of pediatric dialysis in different regions of China, a national pediatric dialysis network, namely, International Pediatric Dialysis Network-China (IPDN-China) ( www.pedpd.org.cn ), was launched in 2012. Original and updated information from the renal centers registered with the IPDN-China was collected between 2012 and 2016 from two sources, namely, the registry and the survey, and demographic features were analyzed. Due to promotion by the IPDN-China, the number of registered renal centers increased from 12 to 39 between 2012 and 2016, with a significant increase in the coverage of the Chinese administrative divisions (from 26.5 to 67.6%) (p < 0.01); and the coverage of the pediatric (0~14 years old) population increased to nearly 90% in 2016. The distribution of renal centers indicated that East China had the highest average number of registered centers per million population (pmp) 0~14-year-old age group. Seventeen relatively large dialysis centers were distributed across 14 divisions. Various modalities of renal replacement therapy (RRT) were available in most centers. The IPDN-China has promoted collaborations between dieticians, psychologists, and social workers on dialysis teams to provide better service to children with ESRD and their families. The proportion of centers with all three types of paramedic support (i.e., dieticians, psychologists, and social workers) as well as the proportion of centers with a partial paramedic team significantly increased between 2012 (25.0%) and 2016 (69.2%) (p < 0.05). In terms of the point prevalent cases of patients (aged < 18 years), data from the survey of 39 registered centers revealed that the number of children with ESRD who were on RRT was 578 (49% received a kidney transplant) at the end of 2016, which was more than that reported in previous surveys. Data from the registry showed that 349 dialysis patients had been enrolled as of the end of 2016. The median age at RRT start was 9.5 years, and the leading cause of ESRD was congenital abnormalities of the kidney and urinary tract (CAKUT). The IPDN-China has helped to promote the development of pediatric dialysis for ESRD in China by improving the organization of care for dialysis patients and increasing the availability and the quality of RRT for patients who need it. To improve knowledge about the epidemiology and outcomes of pediatric RRT around the country, a sustained effort needs to be made by the IPDN-China to increase the enrollment of dialysis patients and increase the number of registered centers in the future.

C4d may be used as a marker to evaluate the condition and prognosis of adults with IgA nephropathy, but there have been few studies of children with IgA nephropathy.C4d immunohistochemical staining was performed on samples from children with IgA nephropathy with C1q-negative immunofluorescence. The clinical and pathological treatment and prognostic characteristics of children in the C4d-positive and -negative groups were compared.A total of sixty-five children with IgA nephropathy were included in the study and were followed up for an average of 37 months. C4d was mainly deposited along the capillary loops. The urinary protein-to-creatinine ratio (UPCR) in the C4d-positive group was significantly higher than that in the C4d-negative group (3.97 vs. 0.81, P 0.001), and the average integrated optical density value of each child was positively correlated with the UPCR (r = 0.441, P 0.001). There was a significant difference in the proportions of children with mesangial hypercellularity (M1) (68.97% vs. 44.44%, P = 0.048) and segmental glomerulosclerosis (S1) (65.52% vs. 33.33%, P = 0.010) between the C4d-positive group and the C4d-negative group. The proportion of children who received immunosuppressants in the C4d-positive group was higher than that in the C4d-negative group (86.21% vs. 36.11%, P 0.001). There was no significant difference in the proportion of children developing kidney failure between the two groups.C4d was found to be associated with proteinuria, segmental lesions, and immunosuppressant treatment. Activation of the lectin pathway may reflect the severity of clinical and pathological manifestations of IgA nephropathy in children. A higher resolution version of the Graphical abstract is available as Supplementary information.

Contains fulltext : 283144.pdf (Publisher’s version ) (Open Access) Primary Coenzyme Q10 (CoQ(10)) deficiency is an ultra-rare disorder caused by defects in genes involved in CoQ(10) biosynthesis leading to multidrug-resistant nephrotic syndrome as the hallmark kidney manifestation. Promising early results have been reported anecdotally with oral CoQ(10) supplementation. However, the long-term efficacy and optimal prescription remain to be established. In a global effort, we collected and analyzed information from 116 patients who received CoQ(10) supplements for primary CoQ(10) deficiency due to biallelic pathogenic variants in either the COQ2, COQ6 or COQ8B genes. Median duration of follow up on treatment was two years. The effect of treatment on proteinuria was assessed, and kidney survival was analyzed in 41 patients younger than 18 years with chronic kidney disease stage 1-4 at the start of treatment compared with that of an untreated cohort matched by genotype, age, kidney function, and proteinuria. CoQ(10) supplementation was associated with a substantial and significant sustained reduction of proteinuria by 88% at 12 months. Complete remission of proteinuria was more frequently observed in COQ6 disease. CoQ(10) supplementation led to significantly better preservation of kidney function (5-year kidney failure-free survival 62% vs. 19%) with an improvement in general condition and neurological manifestations. Side effects of treatment were uncommon and mild. Thus, our findings indicate that all patients diagnosed with primary CoQ(10) deficiency should receive early and life-long CoQ(10) supplementation to decelerate the progression of kidney disease and prevent further damage to other organs.

Primary nephrotic syndrome (PNS) is the commonest glomerular disease affecting children. Previous studies have confirmed that CXC motif chemokine ligand 16 (CXCL16) is involved in the pathogenesis of PNS. However, the exact mechanisms underlying the pathogenesis of PNS remain to be elucidated. Thus, the present study aimed to elucidate the role of CXCL16 in PNS. It was found that the expression of CXCL16 and extracellular signal‑regulated kinases 1 and 2 (ERK1/2) were significantly increased in clinical PNS renal tissues using reverse transcription‑quantitative PCR, western blot analysis and immunohistochemistry. Lentivirus overexpression or short hairpin RNA vector was used to induce the overexpression or knockdown of CXCL16 in podocytes, respectively. Overexpression of CXCL16 in podocytes could decrease the cell proliferation and increase the migration and apoptosis, whereas CXCL16 knockdown increased cell proliferation and decreased cell migration and apoptosis. Results of the present study further demonstrated that ERK2 protein expression was regulated by CXCL16. The knockdown of ERK2 expression reversed the effects of CXCL16 on the proliferation, apoptosis, migration and epithelial mesenchymal transition (EMT) of podocytes. Collectively, the findings of the present study highlighted that the CXCL16/ERK1/2 pathway regulates the growth, migration, apoptosis and EMT of human podocytes.

Behavioral barriers to gene flow often evolve faster than intrinsic incompatibilities and can eliminate the opportunity for hybridization between interfertile species. While acoustic signal divergence is a common driver of premating isolation in birds and insects, its contribution to speciation in mammals is less studied. Here we characterize the incidence of, and potential barriers to, hybridization among three closely related species of grasshopper mice (genus Onychomys). All three species use long‐distance acoustic signals to attract and localize mates; Onychomys arenicola and Onychomys torridus are acoustically similar and morphologically cryptic whereas Onychomys leucogaster is larger and acoustically distinct. We used genotyping‐by‐sequencing (GBS) to test for evidence of introgression in 227 mice from allopatric and sympatric localities in the western United States and northern Mexico. We conducted laboratory mating trials for all species pairs to assess reproductive compatibility, and recorded vocalizations from O. arenicola and O. torridus in sympatry and allopatry to test for evidence of acoustic character displacement. Hybridization was rare in nature and, contrary to prior evidence for O. torridus/O. arenicola hybrids, only involved O. leucogaster and O. arenicola. In contrast, laboratory crosses between O. torridus and O. arenicola produced litters whereas O. leucogaster and O. arenicola crosses did not. Call fundamental frequency in O. torridus and O. arenicola was indistinguishable in allopatry but significantly differentiated in sympatry, a pattern consistent with reproductive character displacement. These results suggest that assortative mating based on a long‐distance signal is an important isolating mechanism between O. torridus and O. arenicola and highlight the importance of behavioral barriers in determining the permeability of species boundaries., Divergence in behavioral traits is fundamental to the evolution of reproductive isolation and maintenance of species barriers. We characterized the incidence of, and potential barriers to, hybridization among three closely related species of grasshopper mice (genus Onychomys). We found little evidence for hybridization and a signature of reproductive character displacement in the mate attractions calls of the species pair with highest ecological and morphological overlap, highlighting the importance of behavioral barriers in determining the permeability of species boundaries.

Renal cell carcinoma (RCC) accounts for 2-3% of adult malignant tumors, and the incidence of RCC worldwide has increased by about 2% over the past two decades. The homeobox protein Six2 has been shown to promote the stemness of breast cancer cells and play a role in kidney development, but its involvement in RCC progression has not previously been investigated. Here, we found that six2 expression was significantly increased in RCC tissues and negatively correlated with the overall survival of patients with RCC. In addition, six2 expression exhibited a remarkably higher level relative to that in normal renal cells. Functional experiments showed that six2 knockdown attenuated the stemness of RCC cells, which was evident by decreased spheroid formation ability and stemness marker (sox2 and nanog) expression. Mechanistic studies indicated that Six2 directly bound to the enhancer of sox2, promoting sox2 expression and downstream effector expression of nanog. Furthermore, overexpression of sox2 rescued the inhibitory effects of six2 on the stemness of RCC cells. Notably, six2 expression is positively correlated with sox2 and nanog expression in RCC tissues. Collectively, our results point toward a six2/sox2 axis responsible for RCC cell stemness.

Evidence to date suggests that β-arrestins act beyond their role as adapter proteins. Arginine vasopressin (AVP) may be a factor in inflammation and fibrosis in the pathogenesis of heart failure. In the present study we investigated the effect of AVP on inflammatory cytokine IL-6 production in murine hearts and the impact of β-arrestin 2-dependent signaling on AVP-induced IL-6 production. We found that administration of AVP (0.5 U/kg, iv) markedly increased the levels of IL-6 mRNA in rat hearts with the maximum level occurred at 6 h. In β-arrestin 2 KO mouse hearts, deletion of β-arrestin 2 decreased AVP-induced IL-6 mRNA expression. We then performed in vitro experiments in adult rat cardiac fibroblasts (ARCFs). We found that AVP (10−9–10−6 M) dose-dependently increased the expression of IL-6 mRNA and protein, activation of NF-κB signaling and ERK1/2 phosphorylation, whereas knockdown of β-arrestin 2 blocked AVP-induced IL-6 increase, NF-κB activation and ERK1/2 phosphorylation. Pharmacological blockade of ERK1/2 using PD98059 diminished AVP-induced NF-κB activation and IL-6 production. The selective V1A receptor antagonist SR49059 effectively blocked AVP-induced NF-κB phosphorylation and activation as well as IL-6 expression in ARCFs. In AVP-treated mice, pre-injection of SR49059 (2 mg/kg, iv) abolished AVP-induced NF-κB activation and IL-6 production in hearts. The above results suggest that AVP induces IL-6 induction in murine hearts via the V1A receptor-mediated β-arrestin2/ERK1/2/NF-κB pathway, thus reveal a novel mechanism of myocardial inflammation in heart failure involving the V1A/β-arrestin 2/ERK1/2/NF-κB signaling pathway.

The purpose of our research is to elucidate whether oxLDL activates P2X7R in cultured human podocytes and if the activation of P2X7R leads to podocyte apoptosis. Additionally, we explore the underlying mechanism involved in podocyte apoptosis. Immortalized human podocytes were incubated with oxLDL (80 µg/ml), P2X7R antagonist A438079 (10 µM), or the compound of A438079 and oxLDL for 48 h, respectively. Cellular apoptosis and ROS were evaluated using flow cytometer. P2X7R, Bax, and Caspase-3 protein expression were detected by western blot and immunofluorescence analysis.The expression of P2X7R, ROS, Bax, and Caspase-3 in human podocytes incubated with oxLDL was significantly up-regulated and was found to have higher intracellular lipid accumulation and podocyte apoptosis compared with the NC group. However, co-administration with A438079, ROS, Bax, and Caspase-3 expression both significantly down-regulate as well as lower lipid accumulation and cellular apoptosis in the oxLDL-induced podocyte group. We revealed that P2X7R is involved in the regulation of oxLDL-treated podocytes. Additionally, we found that the anti-apoptotic effect of A438079 is correlated with ROS, Bax, and Caspase-3 expression down-regulated.

Bcl-2-associated athanogene3(BAG3) protects the heart and cardiomyocytes from ischaemia/reperfusion (I/R) injury. Although the anti-apoptosis effect of BAG3 has been demonstrated in multiple cell types, the structural domain of BAG3, which is responsible for its anti-apoptosis effect, is not well understood. BAG3 protein consists of various characteristic amino acid motifs/regions that permit the interaction of BAG3 with numerous proteins involved in many cellular key pathways. The purpose of this study is to determine whether the proline-rich (PXXP) domain of BAG3 is necessary for its cellular protection against hypoxia-reoxygenation (H/R) stress by binding to its chaperone, heat shock cognate 71 kDa protein (HSC70). Cell apoptosis induced by H/R was evaluated using propidium iodide (PI) staining, caspase 3/7 activation and TUNEL staining in cultured H9C2 cells. The expression levels of BAG3 and HSC70 were manipulated, where BAG3 or its mutant, which lacked the PXXP domain, was overexpressed using a plasmid and adenovirus vector, and HSC70 expression was silenced using siRNA. Co-immunoprecipitation (co-IP) followed by western blot was employed to define the complex of BAG3 binding to its chaperones. The PXXP domain of BAG3 was determined to be critical for BAG3-mediated attenuation of H9C2 cell apoptosis induced by H/R through the binding of PXXP with HSC70. The abolished cellular protection of BAG3 induced by the knockdown of HSC70 is associated with reduced binding to HSC70. Given that the structural domain PXXP of BAG3 is necessary for the cellular protection of BAG3 from I/R injury, the mechanism revealed in this study indicates that BAG3 may be a therapeutic target in patients undergoing reperfusion after myocardial infarction.

Background Several researches have been conducted on the associations between elements and diseases. Few studies have examined trace elements in young people’s hair. The objective of this study is to investigate the influence of age, gender and season on the contents of magnesium (Mg), calcium (Ca), Iron (Fe), copper (Cu), zinc (Zn), manganese (Mn), selenium (Se) and strontium (Sr) as well as to establish the reference intervals (RIs). Methods We conducted a retrospective study of 589 apparently healthy children and adolescents under 19 years old. Quantitative analysis has been carried out using inductively coupled plasma-mass spectrometry (ICP-MS). Eight nutrient elements in peripheral blood of children and adolescents in eastern China were grouped according to age, sex or season, and analyzed using and Mann-Whitney U test and spearman statistical analyses. RIs were defined by using 95% confidence interval. Results Precisions of ICP-MS detecting for Mg, Ca, Fe, Cu, Zn, Mn, Se and Sr are 2.8%~12.2%. The linearity were all > 0.999 and the bias were all within 10%. Differences between contents of particularly Mg, Fe, Cu and Zn in girls’ and boys’ whole blood were found, and higher contents of Mg, Cu for boys were measured in some age groups. Positive correlations for Fe, Zn, Se and Sr, while negative for Ca and Cu were found with age. And substantial differences between age groups were stated. In general, an increasing trend was found for bioelements (Fe, Zn,Se) both for girls and boys in all age groups, while for Ca and Cu changes were even decreasing for children and teenagers. The most frequently correlating element pairs were Fe-Zn, Mg-Se, and Fe-Se in five successive age groups. Lower contents of essential elements (Mg, Ca, Fe, Zn, Se) were found in summer comparing with other seasons. Finally, the reference interval of each element was initially established according to age and gender grouping. Conclusions The contents of elements in whole blood varies depending mainly on the gender and age of children and adolescents. Besides, season is also a factor that affects the contents of elements in the body. The reference intervals of elements in whole blood grouped by age and gender provide a reference basis for clinical diagnosis and treatment of element-related diseases.

In 2018, the policies, contents and resources of China’s film industry all made a joint effort to push China’s film industry to new heights, creating records of an annual box office exceeding 60 billion yuan, monthly box office exceeding 10 billion yuan, and the total screen number exceeding 60,000. This report analyzes and summarizes the state of the Chinese film industry in 2018 in terms of macro-environment, industry scale and layout, online platform and development prospects, with the aim of enhancing current film scholarship on this subject, and providing film-related enterprises and film professionals with up-to-date knowledge and information.

Butyl-biodiesel is produced by the transesterification of waste cooking oil and n-butanol. The sulfamic acid, a kind of heterogeneous acid, is used as the substitute of sulfuric acid to catalyze the reaction. The yield of biodiesel can reach 95.6% at the optimal reaction conditions (molar ratio of n-butanol to oil is 10:1, catalyst amount is 1.0 wt% (based on oil), reaction temperature is 110 °C and reaction time is 2 h). Besides, a pseudo second-order reaction kinetics is also established at the temperature range of 90–110 °C and the activation energy of 80.3 kJ/mol is calculated by the Arrhenius equation. Moreover, when compared with the FAMEs, the cold flow performance of FABEs is improved and the cold filter plugging point (CFPP) of FABEs is significantly decreased from 6.5 °C to 2 °C. Finally, the bench test was also investigated to make a detail comparison of the engine performance and the CH, CO, NOx and PM emissions of FAMEs, FABEs and 0# diesel.

BACKGROUND Synovitis is an important disease that cause intractable pain in temporomandibular joint (TMJ), and the inflammation process played a crucial role in the initiation and development of temporomandibular joint disorder. A series of investigations suggested that the increasing expression of interleukin-(IL) 1β secreted by synovial lining cells plays an important role in synovial inflammation and cartilage destruction in TMJ. In this present study, we investigated the signaling pathways which regulate the expression of IL-1β. MATERIAL AND METHODS The occlusal interference animal model was created to induce synovial injury. Forty-eight rats were divided into 4 groups: 1) control group, 2) occlusal interference group, 3) TAK-242 (a specific inhibitor targeting the Toll-like receptor (TLR)-4) group, and 4) SB203580 (a specific inhibitor targeting the p38) group. The inflammation changes were observed, and the expression of p38 and IL-1β in the synovial membranes were assayed. RESULTS The results showed that downstream p38 MAPK (mitogen-activated protein kinase) signaling was triggered following the activation of TLR4. Moreover, the injection of SB203580 could inhibit the inflammatory reactions and the increased expression of IL-1β at both mRNA and protein levels. CONCLUSIONS The results prompted us that TLR4 may stimulates synovial inflammatory reactions and increased expression of IL-1β in rats through the activation of p38 MAPK signaling pathway, p38 was an important mediator in the mechanisms of the initiation and development of synovial injury by regulating the expression of IL-1β in synovial membranes.

The transesterification of palm oil and mixed dimethyl/diethyl carbonate (DMC/DEC) was investigated to produce glycerol-free biodiesel with improved cold flow performance. The potassium hydroxide (KOH) was used as the cheap heterogeneous catalyst. The biodiesel yield could reach 90.8% and the molar ratio of FAMEs/FAEEs was fixed as 2:1 over the following optimal reaction conditions: Molar ratio of DMC/DEC was 1:1, molar ratio of mixed DMC/DEC and oil was 14:1, KOH amount was 15 wt% (based on the oil), reaction temperature was 100 °C and reaction time was 20 h. The biodiesel had a cold filter plugging point of 3 °C and a solidifying point of −2 °C, which met the cold flow requirements of commercial 0# diesel in China. Finally, the cold flow properties of biodiesel/diesel blends were carefully characterized. Interestingly, due the formation of eutectic mixtures between n-alkanes in diesel and saturated esters in biodiesel, the cold flow performance of diesel could be significantly improved by adding no more than 30 v% of biodiesel.

Mesenchymal stem cells (MSCs) possess reparative and immunoregulatory properties, representing a hope for stem cell‑based treatments. However, the mechanisms by which transplanted MSCs affect T helper (Th)17/regulatory T cell (Treg) balance in asthma patients remain unclear. The aim of the present study was to assess the therapeutic effects of human placenta MSCs (hPMSCs) in asthma, and explore the underlying mechanisms; in addition, the impact of hPMSCs transplantation on Th17/Treg balance in lymph and serum samples from asthmatic animals was evaluated. Sprague‑Dawley rats were sensitized and challenged with ovalbumin (OVA). Administration of hPMSCs from human placenta resulted in increased Th17 and Treg in lymph samples compared with peripheral blood specimens. Enhanced pause values in OVA‑treated animals were significantly higher than those in the control and hPMSCs treatment groups. The numbers of total cells, macrophages, neutrophils, and eosinophils were markedly increased in the OVA group compared with those of control + hPMSCs and control groups. In addition, interleukin 10, forkhead box P3 (Foxp3) and Treg levels in lymph, peripheral blood and lung tissue samples from asthma rats were increased significantly following hPMSC transplantation. Furthermore, Foxp3 protein levels increased, while those of RAR‑related orphan receptor γ (RORγt) decreased after hPMSCs transplantation compared with the asthma group. Reduced IL‑17, RORγt and Th17 levels were accompanied by reduced inflammatory cell infiltration, sub‑epithelial smooth layer attenuation and mucus production in lung tissues. These results suggest that hPMSCs may improve airway hyperresponsiveness and inflammation by regulating the Th17/Treg balance in rats with asthma.

Accumulating studies reported mutations in the gene encoding the proline-rich transmembrane protein 2 (PRRT2) to be causative for several paroxysmal neurological disorders, including paroxysmal kinesigenic dyskinesia (PKD), PKD combined with infantile seizures (ICCA), and benign familial infantile seizures (BFIS). However, the impact of PRRT2 in tumorigenesis is not known. Based on a large-scale data analysis, we found that PRRT2 was down-regulated in glioma tumor tissues compared with normal brain tissue. Dysregulation of PRRT2 was not induced by mutation, copy number variation and epigenetic modification, but modulated by microRNA-30a-5p. Overexpression of PRRT2 strongly impaired the cell viability and promoted cell apoptosis and these anti-tumor effects could be largely reversed by microRNA-30a-5p. Mechanistically, PRRT2 expression was closely correlated genes involved in unfolded protein response (UPR) pathway and introduction of PRRT2 inhibited gene expression in the three branches of UPR, including PERK axis, IRE1 axis and ATF6 axis. Taken together, our findings identify PRRT2 as a tumor suppressor in glioma and provide a promising target for potential therapeutic intervention.

Interleukin 6 (IL-6), which is elevated in patients with congestive heart failure and acts as both a chronic marker of inflammation and an acute-phase reactant, is associated with myocardial damage. Circulating levels of arginine vasopressin (AVP) are elevated during cardiac stress and could be a factor for cardiac inflammation and fibrosis. Our previous study has shown that AVP promotes the proliferation of neonatal rat cardiac fibroblasts (NRCFs) throughV 1A vasopressin receptor-mediated G protein–coupled receptor kinase 2 (GRK2) signaling. In the present study, we investigated the impact of the GRK2-dependent signaling. Using quantitative polymerase chain reaction and enzyme-linked immunosorbent assay, we measured the levels of interleukin-6 (IL-6) mRNA and protein in NRCFs, respectively. Manipulation of GRK2 activation either pharmacologically or through overexpression of GRK2-ct was used to determine the role of GRK2 in regulating the effects of AVP on IL-6 production. Phosphorylation and activation of nuclear factor κ-B (NF- κ B) evoked by AVP stimulation were measured by immunoblot and NF-kB luciferase reporter gene transfected in NRCFs, respectively. Present studies have found that: 1) AVP increased the level of IL-6 protein and mRNA in a dose- and time-dependent manner in NRCFs; 2) inhibition of GRK2 abolished the AVP-induced IL-6 production and NF- κ B activation; and 3) blocking NF- κ B signaling using the pharmacologic approach diminished AVP-induced IL-6 production. In summary, AVP induces IL-6 production of NRCFs by activating V 1A receptor signaling via a GRK2/NF- κ B pathway. These findings provide a possible molecular mechanism for inflammation that occurs in heart failure and other types of cardiac stress.

To investigate the effect of simvastatin on lipid accumulation and the expression of CXCL16 and Nephrin in murine podocytes induced by oxidized LDL (OxLDL) in order to explore the mechanism of protection.Murine podocytes (MPC5) were incubated with OxLDL (80 μg/ml) at different concentrations of simvastatin (0, 1.0, and 2.0 μg/ml) for 48 hours. Oil red O staining was used for the assessment of lipid accumulation in podocytes, and colorimetric cholesterol detection kit was used for the quantitative measurement. CXCL16 and Nephrin expression were detected by using Western blot.OxLDL-treated MPC5 cells exhibited significantly higher intracellular lipid accumulations compared with the untreated group. Colorimetric detection found that total cholesterol was 90.3 ± 30.1 μg/ml in untreated cells and 226.5 ± 21.6 μg/ml in OxLDL-treated cells. The difference was statistically significant (p.01). While cells were treated with both OxLDL and simvastatin, we observed little lipid accumulation. Total cholesterol in OxLDL + simvastatin cells were 151.8 ± 6.8 μg/ml and 135.5 ± 26.9 μg/ml under 1.0 μg/ml or 2.0 μg/ml of simvastatin treatment, respectively. Both were statistically significantly lower than that of the OxLDL treated cells (p.05). Western blot analysis showed that CXCL16 expression was significantly increased (p.05) in OxLDL-treated cells compared with the untreated cells, and was significantly inhibited by application of simvastatin (p.05). The analysis of nephrin expression showed that there were no changes in group simvastatin compared with that of control group (p.05). Nephrin expression was significantly reduced by treatment with OxLDL (p.01), and was significantly increased by application of simvastatin (p.05).Simvastatin treatment could significantly decrease lipid accumulation in murine podocytes and this protective effect was realized through inhibition of the expression of CXCL16 and increase in the expression of nephrin.

The genetic gain of spruce (Picea spp.) breeding programs is impeded by long recurrent selection cycles stemming from biological constraints such as late expression of traits, weak juvenile mature correlations, and late onset of sexual maturity. Genomic selection (GS) is capable of addressing these barriers to improving the rate of genetic gain via early prediction of phenotypes using dense genetic marker arrays. Results from GS studies focused on spruce species in Canada thus far have produced encouraging results to capture additional genetic gain for wood quality, growth, and insect resistance traits either through the re-analysis of existing progeny trials with genomic information or via prediction of phenotypes for untested candidate trees. With the continual improvement of phenotyping technologies and spruce genomic resources, we expect the capability of GS to capture genetic gain to greatly exceed that of traditional pedigree-based selection methods in the future.

Long noncoding RNAs lncRNAs play an essential role in the epigenetic regulation of colorectal cancer CRC. However, the biological function of lncRNA Long Intergenic Noncoding RNA 00511 LINC00511 in the CRC is unclear. Here, present research found that LINC00511 was significantly up-regulated in the CRC tissue samples and cell lines. Consistently, LINC00011 overexpression was correlated with larger tumor size and advanced tumor stage. Functionally, LINC00511 promoted the proliferation and reduced the apoptosis of CRC cells in vitro, and LINC00511 knockdown repressed tumor growth in vivo. Mechanistically, hypoxia-inducible factor 1α (HIF-1α) bound the promoter region of LINC00511 to active tits transcription. Moreover, LINC00511 functioned as the miR-153-5p sponge in the cytoplasmic portion, and miR-153-5p also targeted the 3'-UTR of HIF-1α. In conclusion, this study identifies the roles of LINC00511 in CRC progression and uncovers the positive feedback loop of HIF-1α/LINC00511/miR-153-5p in CRC, providing a potential therapeutic target.

Dent disease is a rare X-linked recessive inherited tubular disease. In this multicenter study, the clinical presentation and genetic background of Chinese children with Dent disease are studied to improve the cognition and diagnostic ability of pediatricians. In this prospective cohort, we described the genotype and phenotype of a national cohort composed of 45 pediatric probands with Dent disease belonging to 45 families from 12 different regions of China recruited from 2014 to 2018 by building up the multicenter registration system. The CLCN5 gene from 32 affected families revealed 28 different mutations. The OCRL gene from 13 affected families revealed 13 different mutations. The incidence of low-molecular-weight proteinuria (LMWP) in both Dent disease type 1 populations and Dent disease type 2 populations was 100.0%; however, the incidence of other manifestations was not high, which was similar to previously reported data. Therefore, LMWP is a key clinical feature that should alert clinicians to the possibility of Dent disease. A high amount of LMWP combined with positive gene test results can be used as the diagnostic criteria for this disease. The diagnostic criteria are helpful in reducing the missed diagnosis of this disease and are beneficial for protecting the renal function of these patients through early diagnosis and early intervention.

To explore the approaches and diagnostic yield of genetic testing for renal disease in children, we describe the genotype and phenotype of the national cohort of children with renal disease from 13 different regions of China recruited from 2014 to 2018 by building up the multicenter registration system (Chinese Children Genetic Kidney Disease Database, CCGKDD). Genetic diagnosis was confirmed in 42.1% of our cohort of 1001 pediatric patients with clinical suspicion of a genetic renal disease. Of the 106 distinct monogenetic disorders detected, 15 accounted for 60.7% of genetic diagnoses. The diagnostic yield was 29.1% in steroid resistant nephritic syndrome (SRNS), 61.4% in cystic renal disease, 17.0% in congenital anomalies of the kidney and urinary tract (CAKUT), 62.3% in renal tubular disease/renal calcinosis, and 23.9% for chronic kidney disease (CKD) 3 to 5 stage with unknown origin. Genetic approaches of target gene sequence (TGS), singleton whole-exome sequencing (WES) and trio-WES were performed with diagnostic rates of 44.8%, 36.2%, and 42.6%, respectively. The early use of trio-WES could improve the diagnostic rate especially in renal tubular disease and calcinosis. We report the genetic spectrum of Chinese children with renal disease. Establishment of the CCGKDD will improve the genetic work on renal disease.

Black ice, a thin sheet of glazed ice on a road surface, is hard to spot by drivers, because it usually has the same color as the road. It is very hazardous and causes many car accidents each year. Unfortunately, the current static road warning signs (such as "Ice May Form on Bridge") may not draw enough attention from drivers. In order to provide in-time warning signals during black ice emergencies, this paper proposes a remote-controlled black-ice detection and warning system with economic black ice detection sensors, Geographic Information System (GIS) based database and a remote control server. This system also provides visualization functions to help users locate the affected sites on a digital map.

In the past two decades, many store-brand products have been introduced by their retailers as having low-cost alternatives to existing brands. However, many store-brand products are perceived with lower quality because their manufacturers do not own the brands. In this paper, we investigate using extended warranties to coordinate the quality decisions of store-brand products. We investigate three extended warranty contracts for the amount of revenue transferred from the retailer to the manufacturer: fixed fee, proportional sharing, and manufacturer direct. Under the fixed fee structure, the transferred amount is pre-negotiated, fixed, and independent of the price of the extended warranty; under the proportional sharing structure, the transferred amount is proportional to the price of the extended warranty; under the manufacturer-direct structure, the retailer let the manufacturer decide the price and collect all the revenue of the extended warranty. Our analytical results show that all three contracts provide incentives for the manufacturer to improve the product quality. In the numerical analysis, we compare the performance of the three extended warranty contracts with the baseline case, where no extended warranty is offered. It shows that the manufacturer-direct contract achieves the highest quality improvement and the highest profit among the three contracts.

In this study, the zein extracted from distillers dried grains with solubles (DDGS) is utilized to produce a fat analogue, by employing a simple ”reduced-pressure distillation microparticulation“ method. The optimal conditions for preparing the fat analogue are as follows: a zein concentration of 3 w/v% (based on 60 v/v% ethanol water), an agitator speed of 200 rpm, a xanthan gum amount of 20 wt% (based on zein mass) and a heating temperature of 50 °C. The zein-based fat analogue obtained has a volume-weighted mean diameter (D[4, 3]) of about 16 μm, which is then applied in the formulation of mayonnaise, at fat substitution ratios of 0% (full-fat), 20%, 40%, 60%, 80% and 100%, respectively. Based on the appearance, stability, total calorific value, as well as rheological, microstructure and sensory analyses, it may be concluded that the fat substitution ratio of no more than 40% is acceptable. This paper illustrates another high-value added use of zein.

P2X3 receptor plays a role in nociception transmission of orofacial pain in temporomandibular disorder patients. A previous study found that P2X3 receptors in masseter muscle afferent neurons and the trigeminal ganglia were involved in masseter muscle pain induced by inflammation caused by chemical agents or eccentric muscle contraction. In this study, we attempted to investigate changes in P2X3 receptors in the trigeminal subnucleus caudalis (Vc) and midbrain periaqueductal gray (PAG) in relation to the hyperalgesia of masseter muscles induced by occlusal interference. Experimental occlusal interference by crown application was established in 30 rats and another 30 rats were treated as sham controls. On days 1, 3, 7, 14, and 28 after crown application, the mechanical pain threshold was examined by von-Frey filaments. The expression of the P2X3 receptor in Vc and PAG was investigated by immunohistochemistry and quantitative PCR. We found that mechanical pain threshold of bilateral masseter muscles decreased significantly after occlusal interference, which remained for the entire experimental period. The mRNA expression of the P2X3 receptor increased significantly and the number of P2X3R-positive neurons increased markedly in Vc and PAG accordingly. These results indicate that the upregulated expression of P2X3 receptors in Vc and PAG may contribute toward the development of orofacial pain induced by occlusal interference and P2X3 receptors in the PAG may play a key role in the supraspinal antiociception effect.

Background WT1 mutations cause a wide spectrum of renal and extrarenal manifestations concerning urogenital development and the development of tumors. Methods We retrospectively collected the information on the genotype and phenotype of WT1 nephropathy from the multicenter registry since 2014 to 2019. All patients were stratified by renal function decline status or by sequence timing. Rapid progressive group was defined as rapidly developing into ERSD within 12 months since disease onset. Early sequencing group was defined as gene mutation identified before ERSD. Results Thirty-three (3.5%) cases were identified with a WT1 mutation in patients with steroid resistant nephrotic syndrome (SRNS), proteinuria and chronic kidney disease (CKD) 3–5 stage of unknown origin. ESRD developed in twenty patients at a median age of 4.3 years old. Comparing study between the rapid progressive group (n = 8) and non-rapid progressive group (n = 25) showed no significant difference in age of onset, gender, syndrome phenotype, genotype and proteinuria except for initial estimated glomerular filtration rate (eGFR) (p = 0.021) or sequencing timing (p = 0.003). In multivariable logistic regression analysis, the delayed sequencing was associated with rapid renal function decline, even after adjusting for established clinical factors including syndromic phenotype, genotype, age onset and eGFR at initial stage (p = 0.019). The renal survival analysis did not show a significantly better outcome in early sequencing group than in delayed sequencing group (p > 0.05). Conclusion Screening for WT1 mutations should be performed in children with Wilms’ tumor, proteinuria/SRNS or CKD. Early diagnosis of WT1 nephropathy through clinical and genetic findings is warranted.

To quickly solve the fractional Black–Scholes (B–S) equation in the option pricing problems, in this paper, we construct pure alternative segment explicit–implicit (PASE-I) and pure alternative segment implicit–explicit (PASI-E) difference schemes for time-space fractional B–S equation. It is a kind of intrinsic parallel difference schemes constructed on the basis of classic explicit scheme and classic implicit scheme combined with alternate segmentation technique. PASE-I and PASI-E schemes are analyzed to be unconditionally stable, convergent with second-order spatial accuracy and $(2-\alpha)$ th-order time accuracy, and they have a unique solution. The numerical experiments show that the two schemes have obvious parallel computing properties, and the computation time is greatly improved compared to Crank–Nicolson (C–N) scheme. The PASE-I and PASI-E intrinsic parallel difference methods are efficient to solve the time-space fractional B–S equation.

BACKGROUND Recovering high value-added substances (oil, zein and carotenoids) from corn distillers dried grains with solubles (DDGS), the major coproduct of bioethanol, is important to enhance the profit of the corn ethanol process. Currently, few studies have been reported on separating high value-added substances in a process suitable for industrialization. In this article, a semi-continuous countercurrent extraction method was investigated to refine the corn DDGS. RESULTS First, an oil yield as high as 94.5% (based on oil content in DDGS) was measured using a series of five packed columns. Second, the DDGS residues after oil extraction were used for zein extraction, obtaining a zein yield of 24.5% (based on protein content in DDGS) with a series of four packed columns. Moreover, the carotenoids in zein were extracted by anhydrous ethanol in a Soxhlet apparatus. The extractives, which accounted for 17% of the original mass of zein, had a carotenoids content of 2.4 mg g−1. Finally, zein was decolored by hydrogen peroxide to form a whiter product. CONCLUSIONS The semi-continuous countercurrent method was developed successfully to refine the corn DDGS. The corn oil with high acid value was a perfect feedstock for biodiesel. The zein obtained achieved the quality of a commercial product. © 2015 Society of Chemical Industry

The corn oil extracted from distillers dried grains with solubles (DDGS), which has a high acid value of 41.6 mg KOH/g and a high water content of 4.5%, is used to produce biodiesel in this article. The transesterification of dimethyl carbonate (DMC) and DDGS-extracted corn oil was studied at the catalysis of Novozym 435. Meanwhile, several water removal agents, which include acrylic super absorbent resin (SAP), 4A-molecular sieve, blue silica-gel and tert-butanol, were added to absorb the water during the reaction. The yield of fatty acid methyl esters (FAMEs) was analyzed by GC with internal standard method. The effect of different reaction conditions (type of water absorbent, molar ratio of DMC to oil, reaction time and temperature, lipase and SAP amount) on the yield of FAMEs were also discussed. Then the highest yield of FAMEs could reach 91.0% at 60 °C for 18 h with molar ratio of DMC to oil 15:1, Novozym 435 amount of 20 wt% and SAP amount of 10 wt% (based on the oil mass). Finally, Novozym 435/SAP showed excellent operational stability without losing any catalytic activity after 8 cycles of repeated use, and the water absorbed by Novozym 435/SAP can be dried at mild temperature (60 °C). Because it is easy to be recycled, the Novozym 435/SAP has a great potential to be used in the continuous biodiesel apparatus such as the fixed bed reactor.

Atypical hemolytic uremic syndrome (aHUS) is associated with defective complement regulation. Anti-complement factor H (CFH) antibodies were thought to participate in the pathogenesis of aHUS. The aim of this study was to address the functions and properties of CFH autoantibodies in a Chinese Han cohort of aHUS patients. Thirty-six anti-CFH antibody-positive aHUS patients at the acute phase of the disease were involved in this study. Clinical data of the patients were collected. Anti-CFH immunoglobulin G (IgG) subclasses and antibody isotypes were detected by ELISA. Epitope mapping was performed using recombinant CFH fragments (SCRs 1–4, SCR 7, SCRs 11–14, and SCRs 19–20). Purified IgG from plasma from seven patients were used for functional analyses. All patients presented with the classic triad of HUS. The anti-CFH autoantibodies mostly bound to the SCRs 19–20 domains of CFH but not the SCRs 1–4 domains. CFI cofactor activity was not disturbed by the anti-CFH antibody in any of the seven patients. Purified IgG interfered with the binding of CFH to C3b and CFH-mediated sheep erythrocyte protection in all seven patients. IgG from 4/5 (80%) patients tested inhibited the binding of CFH to glomerular endothelial cells. Our study suggests that the properties of CFH antibodies from patients with aHUS, including the recognition of SCRs and IgG subclasses, can influence and impair the biological role of CFH and therefore contribute to aHUS susceptibility.

As a hallmark of platelet activation, mean platelet volume (MPV) has been identified to be associated with various malignancies. However, the correlation between MPV, mean platelet volume/platelet count ratio (MPR), and esophageal squamous cell carcinoma (ESCC) remains unclear. The aim of this study is to clarify the relevance of MPV and MPR in patients with locally advanced ESCC. Four hundred and fifty-seven cases with newly diagnosed locally advanced ESCC followed by radical surgery and 240 healthy subjects matched for age and gender were included in this study. We retrospectively compared various hematological variables between groups and analyzed the correlation between MPV, MPR, and patients' clinicopathologic characteristics. Preoperative MPV and MPR were found to be significantly decreased in locally advanced ESCC when compared to healthy controls, they were (8.14 ± 1.09 fL vs. 10.23 ± 0.78 fL, P

The aim of the present study was to analyze the diagnostic value of neutrophil gelatinase-associated lipocalin (NGAL) in renal injury in asphyxiated preterm infants. In total, 48 cases of asphyxiated preterm infants, 45 cases of premature infants and 45 cases of normal newborn infants were included in the study. Using ELISA we evaluated the level of urine NGAL, kidney injury molecule-1 (KIM-1), cystatin C (Cys-C) and serum creatinine (Scr). We also calculated the estimated glomerular filtration rate (eGFR). Our results showed that NGAL, KIM-1 and Cys-C levels in the group of asphyxiant renal injury within 24 and 48 h were markedly higher than the other two groups (P0.05). Scr level in renal injury group within 48 h was markedly elevated while the eGFR level was visibly reduced (P

Anti-complement factor H (CFH) autoantibody-associated hemolytic uremic syndrome (HUS) is a severe sub-type of HUS. We assessed the clinical and renal pathological features, circulating complement levels, and genetic background of Chinese pediatric patients with this sub-type of HUS. Thirty-three consecutive patients with acute kidney injury who tested positive for serum anti-CFH autoantibodies were enrolled in this study. All of the eight patients who underwent renal biopsies presented with changes typical of thrombotic microangiopathy, especially changes in chronic characteristics. Compared to patients in remission and normal control subjects, patients with acute disease had significantly lower plasma CFH levels and significantly higher plasma complement 3a (C3a), C5a, and terminal complement complex (SC5b-9) levels. The CFH–anti-CFH immunoglobin G (IgG) circulating immunocomplex (CFH-CIC) titers were more closely correlated with CFH plasma levels than anti-CFH IgG levels. Of the 22 patients, four (18%) were homozygous for CFHR3–1Δ and ten were heterozygous for CFHR1 or CFHR3 deletions. Most patients responded well to a combination of plasma and immunosuppressive therapies, with a remission rate of 87%. At the end of the follow-up, nine patients reached the combined end-points, including two with end-stage renal disease and seven with relapses. Plasma C3a, C5a, and SC5b-9 levels predicted disease activity in anti-CFH autoantibody-associated HUS patients enrolled in this study. These patients responded well to plasma therapy combined with immunosuppression.