Eccentricity-paced geomagnetic field and monsoon rainfall variations over the last 870 kyr.

Whether there are links between geomagnetic field and Earth's orbital parameters remains unclear. Synchronous reconstructions of parallel long-term quantitative geomagnetic field and climate change records are rare. Here, we present 10Be-derived changes of both geomagnetic field and Asian monsoon (AM) rainfall over the last 870 kyr from the Xifeng loess-paleosol sequence on the central Chinese Loess Plateau. The 10BeGM flux (a proxy for geomagnetic field-induced 10Be production rate) reveals 13 consecutive geomagnetic excursions in the Brunhes chron, which are synchronized with the global records, providing key time markers for Chinese loess-paleosol sequences. The 10Be-derived rainfall exhibits distinct ~100 kyr glacial-interglacial cycles, and superimposed precessional (~23 kyr) cycles that match with those in Chinese speleothem δ18O record. We find that changes in the geomagnetic field and AM rainfall share a common ~100 kyr cyclicity, implying a likely eccentricity modulation of both the geomagnetic field and climate.

Krüppel-like factor 4 modulates the miR-101/COL10A1 axis to inhibit renal fibrosis after AKI by regulating epithelial-mesenchymal transition.

Acute kidney injury (AKI) can progress to renal fibrosis and chronic kidney disease (CKD), which reduces quality of life and increases the economic burden on patients. However, the molecular mechanisms underlying renal fibrosis following AKI remain unclear. This study tested the hypothesis that the Krüppel-like factor 4 (KLF4)/miR-101/Collagen alpha-1X (COL10A1) axis could inhibit epithelial-mesenchymal transition (EMT) and renal fibrosis after AKI in a mouse model of ischemia-reperfusion (I/R)-induced renal fibrosis and HK-2 cells by gene silencing, overexpression, immunofluorescence, immunohistochemistry, real-time quantitative PCR, Western blotting, dual-luciferase reporter assay, fluorescence in situ hybridization (FISH) and ELISA. Compared with the Sham group, I/R induced renal tubular and glomerular injury and fibrosis, and increased the levels of BUN, serum Scr and neutrophil gelatinase-associated lipocalin (NGAL), Col10a1 and Vimentin expression, but decreased E-cadherin expression in the kidney tissues of mice at 42 days post-I/R. Similarly, hypoxia promoted fibroblastic morphological changes in HK-2 cells and enhanced NGAL, COL10A1, Vimentin, and α-SMA expression, but reduced E-cadherin expression in HK-2 cells. These pathological changes were significantly mitigated in COL10A1-silenced renal tissues and HK-2 cells. KLF4 induces miR-101 transcription. More importantly, hypoxia upregulated Vimentin and COL10A1 expression, but decreased miR-101, KLF4, and E-cadherin expression in HK-2 cells. These hypoxic effects were significantly mitigated or abrogated by KLF4 over-expression in the HK-2 cells. Our data indicate that KLF4 up-regulates miR-101 expression, leading to the downregulation of COL10A1 expression, inhibition of EMT and renal fibrosis during the pathogenic process of I/R-related renal fibrosis.

Growth hormone treatment in pre-pubertal short Chinese children with chronic kidney disease prior to transplantation.

BACKGROUND: The effect of recombinant human GH (rhGH) in Chinese children with chronic kidney disease (CKD) is unclear. METHODS: This was a 52-week, multicenter, randomized, open-label, negative-controlled phase 3 study. Prepubertal subjects were randomized 1:1 to either daily subcutaneous injections of rhGH 0.05 mg/kg/day or no treatment for 52 weeks. RESULTS: A total of 68 subjects with a mean age of 7.8 ± 3.27 years were enrolled. At week 52, the height standard deviation score (HT-SDS) in the treated group increased by 0.75 ± 0.58, which was significantly higher compared with 0.17 ± 0.47 in the untreated group (least squares mean 0.58, 95% confidence interval, 0.32-0.84; P < 0.001). At week 52, significant improvements were observed in other growth parameters (height velocity [P < 0.001]), insulin-like growth factor 1 (IGF-1) SDS [P < 0.001], IFG-1/insulin-like growth factor binding protein-3 molar ratio [P < 0.001], and height [P < 0.001]) compared with the untreated control. Seven patients reported treatment-related adverse events (TRAEs) and most TRAEs were mild in severity. Most subjects recovered without further intervention. CONCLUSIONS: Daily rhGH for 52 weeks in children with CKD-induced growth retardation significantly improved HT-SDS and other growth parameters without compromising safety. IMPACT: The efficacy and safety of growth hormone (GH) therapy in Chinese children with chronic kidney disease (CKD) are unclear. This study found that giving short stature Chinese children with CKD daily recombinant human growth hormone (rhGH) for 52 weeks improved growth parameters without compromising safety. This study's information can give physicians the confidence to treat these patients in their clinical practice.

Study on the correlation between maternal serum uric acid and foetal birth weight in Naqu, Tibet.

In high-altitude regions, low birth weight is mainly caused by hypoxia. We aimed to determine whether maternal serum uric acid (SUC) level was associated with decreased foetal birth weight. The relevant data of individual pregnant women who delivered between 37 and 40 weeks in the People's Hospital of Naqu City, Tibet were retrospectively collected. The correlation between maternal SUC and birth weight was examined using multivariate linear regression analysis and subgroup analysis. The results showed that there was a significant negative correlation between SUC and birth weight in pregnant women with proteinuria, female foetuses, and primiparas. Fitting smoothing curve analysis showed that there was a negative linear correlation between SUC and birth weight in primiparas and female foetuses. Maternal SUC is negatively associated with foetal birth weight in a single pregnancy with proteinuria, primipara, or female foetuses in the Naqu region of Tibet, China.IMPACT STATEMENTWhat is already known on this subject? Preeclampsia associated with hyperuricaemia can affect foetal birth weight, foetal birth weight in plains area is negatively correlated with maternal hyperuricaemia.What do the results of this study add? Maternal SUC was negatively correlated with foetal birth weight, especially in primipara, mothers with proteinuria, and pregnant girls.What are the implications of these findings for clinical practice and/or further research? The results suggest that attention should be paid to SUC in pregnant women, especially in primipara, mothers with proteinuria, and pregnant girls, in the prevention of low birth weight infants in Naqu Plateau area of Tibet.

CREG mitigates neonatal HIE injury through survival promotion and apoptosis inhibition in hippocampal neurons via activating AKT signaling.

Neonatal hypoxic ischemic encephalopathy (Neonatal HIE) is a common but serious disease caused by perinatal asphyxia injury in newborns. Elevated neuronal apoptosis plays an important role in the injury process post hypoxia ischemia of the brain, which accurate mechanism is still worthy to be studied. Cellular repressor of E1A-stimulated genes (CREG) possesses the protective effect in ischemia-reperfusion in multiple organs, including livers and hearts. The main purpose of this work was to investigate whether CREG was involved in alleviating neonatal HIE and explore the possible mechanisms. We found that CREG expression was downregulated in the hippocampus of neonatal HIE rats as well as oxygen-glucose deprivation/reperfusion (OGD/R)-treated hippocampal neurons. Besides, CREG overexpression promoted survival while inhibited apoptosis in OGD/R-induced hippocampal neurons accompanied by AKT signaling activation, which could be reversed by CREG silence. In addition, the protective effects of CREG overexpression could be antagonized by AKT deactivation, indicating the function of CREG was attributed by regulating AKT pathway. Collectedly, we demonstrated that CREG protected hippocampal neurons from hypoxic ischemia-induced injury through regulating survival and apoptosis via activating AKT signaling pathway.

The association between skinfold thicknesses and estimated glomerular filtration rate in adolescents: a cross-sectional study.

BACKGROUND: Obesity is one of the causes of glomerular hyperfiltration. Studies on the relationship between body fat content and glomerular hyperfiltration have been limited to special children. Therefore, we aimed to evaluate the correlation between skinfold thickness, which represents body fat content, and estimated glomerular filtration rate (eGFR). METHODS: The cross-sectional study included 6655 participants (3532 boys and 3123 girls; age: 12 - 17.99 years); data was obtained from the National Health and Nutrition Examination Survey (NHANES; 2001-2010). The independent variables were subscapular skinfold thickness and triceps skinfold thickness. The dependent variable was eGFR. We used multivariate linear regression models to evaluate their associations and also performed subgroup analyses. RESULTS: After adjusting for age, standing height, race, family income, blood urea nitrogen and uric acid variables, multivariate regression analysis identified that triceps skinfold thickness and subscapular skinfold thickness were positively correlated with eGFR and glomerular hyperfiltration in boys. In subgroup analyses stratified by age and body mass index, triceps skinfold thickness was also associated with glomerular hyperfiltration in boys. There was a linear relationship between triceps skinfold thickness and eGFR in boys (ß = 0.389, P < 0.001) and girls (ß = 0.159, P = 0.0003). CONCLUSIONS: Triceps skinfold thickness and subscapular skinfold thickness are positively correlated with eGFR and glomerular hyperfiltration in US male adolescents. In all adolescents, there is a linear relationship between triceps skinfold thickness and eGFR.

A potential pathogenic role of interleukin-6 in a child with ANCA-negative pauci-immune crescentic glomerulonephritis: case report and literature review.

BACKGROUND: Crescentic glomerulonephritis is a disease characterized by severe glomerular injuries that is classified into five different pathological types. Patients with type V disease have pauci-immune crescentic glomerulonephritis (PICGN) that is negative for anti-neutrophil cytoplasmic autoantibodies (ANCAs). There are limited clinical data on the manifestations, treatment, and prognosis of type V crescentic glomerulonephritis, especially in children. CASE PRESENTATION: A 13-year-old girl who had an intermittent fever for more than 10 months was admitted to our hospital. She had no gross hematuria, oliguria, edema, or hypertension, but further tests indicated a decreased glomerular filtration rate, hematuria, proteinuria, and an elevated level of IL-6. The antinuclear antibody spectrum test was positive at 1:1000, and the ANCA and anti-glomerular basement membrane antibody tests were negative. A renal biopsy confirmed the diagnosis of ANCA-negative PICGN. We administered methylprednisolone pulse therapy with intravenous cyclophosphamide and oral mycophenolate mofetil. At the 3-month follow-up, her urine protein level was significantly lower, and her serum creatinine level was in the normal range. CONCLUSIONS: Fever may be an extrarenal manifestation of ANCA-negative PICGN, and IL-6 may play a role in the pathogenesis of this disease. Early methylprednisolone pulse therapy with an immunosuppressant may reduce symptoms and improve prognosis.

Silencing of the lncRNA TUG1 attenuates the epithelial-mesenchymal transition of renal tubular epithelial cells by sponging miR-141-3p via regulating ß-catenin.

Renal interstitial fibrosis (RIF) is characterized by excessive extracellular matrix deposition and involves epithelial-mesenchymal transition (EMT). The lncRNA taurine-upregulated gene 1 (TUG1) participates in EMT in several cancers; however, the effect and underlying mechanism of TUG1 in RIF-related EMT remain unclear. Here, we explored the mechanisms by which TUG1 modulates RIF. An in vivo model of renal fibrosis was established by unilateral ureteral obstruction in Balb/c mice. Human renal proximal tubular epithelial (HK-2) cells treated with transforming growth factor (TGF)-ß1 were used to induce the in vitro model. Morphological changes and TUG1 expression were assessed. HK-2 cells were transfected with siRNA to silence TUG1. Western blot analysis, immunofluorescence staining, cell proliferation, and migration assays were performed to examine TGF-ß1-induced changes in EMT markers and EMT-like cell behaviors. TUG1 and ß-catenin (CTNNB1) levels were significantly upregulated, whereas miR-141-3p was significantly downregulated, during EMT in vitro and in vivo. TUG1 knockdown or miR-141-3p overexpression supported the epithelioid morphology of HK-2 cells while enhancing the downregulation of E-cadherin and upregulation of vimentin, α-smooth muscle actin, and ß-catenin levels in TGF-ß1-treated HK-2 cells. TUG1 knockdown promoted the proliferation and decreased the migration of HK-2 cells and enhanced the downregulation of miR-141-3p levels in TGF-ß1-treated HK-2 cells. TUG1 directly targeted miR-141-3p, and miR-141-3p was directly bound to CTNNB1. Downregulation of miR-141-3p inhibited TUG1 silencing-induced suppression of EMT. In conclusion, TUG1 promotes EMT in TGF-ß1-induced HK-2 cells via upregulation of ß-catenin levels by sponging miR-141-3p, suggesting a novel therapeutic candidate for RIF.

IPDN-China promotes the development of pediatric dialysis in China.

BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Dynamic Change of T-Helper Cell Cytokines in Nasal Secretions and Serum after Endoscopic Sinus Surgery in Chronic Rhinosinusitis with Nasal Polyps.

BACKGROUND/AIMS: This study aimed to determine the dynamic change of postoperative T-helper cell cytokines in nasal secretions and serum in chronic rhinosinusitis with nasal polyps (CRSwNP). METHODS: Nasal secretions and serum samples of 30 CRSwNP patients and 10 healthy subjects were collected. Among CRSwNP patients, samples of 30 patients were collected 1 day before endoscopic sinus surgery (ESS) and that of 18 patients (12 asthmatic and 6 non-asthmatic) were collected 4, 8, and 12 weeks after ESS. Concentrations of interleukin (IL)-2, IL-4, IL-5, IL-17, and interferon gamma (IFN-γ) were determined by Cytometric Beads Array. The Sino-Nasal Outcomes Test 22 and Lund-Kennedy endoscopic scoring (LKES) system were collected for all patients. RESULTS: The levels of IL-2 and IL-5 in secretions of CRSwNP were significantly higher than that of healthy control at the baseline. At the 4th and 8th week after ESS, the IL-4 levels in nasal secretions of the asthmatic group were significantly higher than their baseline controls (preoperatively). From the 4th to 12th week after ESS, the IL-2, IFN-γ, IL-4, and IL-17 levels in nasal secretions of the non-asthmatic group were significantly increased as compared to their baseline controls. Postoperative IL-5 levels in serum of the asthmatic group decreased significantly as compared to their baseline controls. There was no significant association between LKES and levels of cytokines in postoperative secretions and serum. CONCLUSIONS: Our results indicate that postoperative endoscopic findings may not directly reflect the underlying mucosal inflammation, and surgery could not change the systemic immunity status. Despite endoscopic resolution of mucosal abnormalities, it may not avert the need for subsequent postoperative medical intervention to treat the underlying mucosal inflammation.

Screening of genes involved in epithelial-mesenchymal transition and differential expression of complement-related genes induced by PAX2 in renal tubules.

AIM: The aim of the present study was to screen and verify downstream genes involved in the epithelial mesenchymal transition (EMT) induced by paired box 2 (PAX2) in NRK-52E cells. METHODS: NRK-52E cells were transfected with lentivirus carrying PAX2 gene or no-load virus respectively. Total RNA was isolated 72 h after transfection from PAX2-overexpressing cells and control cells. Isolated RNA was then hybridized with the Rat OneArray Plus expression profile chip. The chips were examined by Agilent 0.1 XDR to screen for differentially expressed genes, which were further analyzed to investigate complement-related genes as genes of interest. RESULTS: In NRK-52E cells, PAX2 overexpression promoted EMT followed by upregulation of 298 genes and downregulation of 293 genes. KEGG analysis indicated the differential expression of genes related to cytokines and their receptors, extracellular matrix (ECM), MAPKs, local adhesion, cancer, the complement cascade, and coagulation. Gene oncology analysis screened out genes related to molecular functions (e.g., hydrolase activity, phospholipase activity, components of the ECM) and biological processes (e.g., cell development, signal transduction, phylogeny), and cell components (e.g., cytoplasm, cell membrane, and ECM). Analysis of the complement system revealed upregulation of C3 and downregulation of CD55 and complement regulator factor H (CFH). CONCLUSION: PAX2 overexpression upregulates EMT in vitro and may regulate C3, CD55, and CFH.

Association of VEGF gene polymorphisms with sporadic Parkinson's disease in Chinese Han population.

Recent evidence indicates that vascular endothelial growth factor (VEGF) is capable of protecting dopaminergic (DA) neurons. Parkinson's disease (PD) is a progressive neurodegenerative disease caused by the degeneration of nigrostriatal dopaminergic neurons. To evaluate the role of VEGF single nucleotide polymorphisms (SNPs) and haplotypes in PD, we performed a case-control study including 400 PD patients and 400 healthy-matched controls. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis and DNA sequencing were used to detect the rs699947, rs2010963 and rs3025039 polymorphisms of the VEGF gene in cases and controls. Our study revealed that T allelic frequency of rs3025039 polymorphism was significantly higher in PD subjects (OR 1.497, 95 % CI 1.099-2.040, P = 0.013) than that in controls. Significant association for rs3025039 could be found in additive model (TT vs. CT vs. CC: OR 1.489, 95 % CI 1.018-2.177, P = 0.040) and dominant model (TT + CT vs. CC: OR 1.538, 95 % CI 1.068-2.216, P = 0.021). Subgroup analyses performed by gender suggested that this association could be found in male, but not in female. Moreover, it also demonstrated a significant association in the subgroup of late-onset PD (LOPD). However, for rs699947 and rs2010963 polymorphisms, genotype or allele frequencies did not differ between groups. No significant association could be found between rs699947 and rs2010963 polymorphism and PD risk. None of the observed haplotypes showed significant association with PD. Therefore, these results suggested that the VEGF gene might be associated with risk of developing sporadic PD in Han Chinese and the rs3025039 polymorphism may be a risk factor for sporadic PD.

[Influence of PAX2 gene silencing on renal interstitial fibrosis in rats].

OBJECTIVE: To investigate the influence of silencing PAX2 gene in vivo on epithelial-mesenchymal transition (EMT) of renal tubular cells in rats with renal interstitial fibrosis. METHODS: A total of 64 Wistar rats were anaesthetized, and unilateral ureteral obstruction (UUO) was performed to establish a rat model of renal interstitial fibrosis. The 64 rats were randomly divided into negative control and PAX2 gene silencing groups (n=32 each). The rats in the control group were transfected with 200 µL NC-siRNA-in vivo jetPEI(TM) solution. Those in the PAX2 gene silencing group were transfected with 200 µL PAX2-siRNA-in vivo jetPEI(TM) solution. Each group was further divided into 4 subgroups based on the post-transfection time (3, 5, 7 and 14 days after transfection), with 8 rats in each subgroup. Renal tissue samples were harvested in each group. Real-time PCR and Western blot were used to measure the mRNA and protein expression of PAX2 in the renal cortex, as well as the mRNA and protein expression of E-cadherin and α-SMA. RESULTS: Compared with the control group, the PAX2 gene silencing group showed significantly lower mRNA and protein expression of PAX2 (P<0.05). In the two groups, the mRNA and protein expression levels of E-cadherin were gradually reduced over the time of obstruction, while those of α-SMA gradually increased. At 14 days after transfection, the PAX2 gene silencing group had significantly higher mRNA and protein expression of E-cadherin but lower mRNA and protein expression of α-SMA compared with the control group (P<0.05). CONCLUSIONS: PAX2 gene silencing can significantly inhibit the process of EMT of renal tubular cells in rats with advanced fibrosis, suggesting that PAX2 gene silencing may have a therapeutic effect on renal interstitial fibrosis.

Efficient line-based lens distortion correction for complete distortion with vanishing point constraint.

The line-based correction method has been widely researched to improve the performance of lens distortion correction. However, due to the coupling of the distortion parameters and the inaccuracy of line equation estimation, it is difficult to achieve high-accuracy correction under the complete lens distortion (composed of radial, decentering, and prism distortion). Here, we present a method that utilizes two models to resolve these two problems, respectively: the recursive individual optimization model decouples the distortion parameters by applying Levenberg-Marquardt to optimize the parameters individually, and the vanishing point reprojection model improves the accuracy of line equation estimation with the known vanishing points calculated by a proposed expectation-minimization algorithm. Therefore, accurate correction of complete distortion can be achieved by the line information only. The validity of the proposed method was tested by several synthetic and real data, and the results showed that this method can correct the image with the complete and noncomplete distortion effectively.

Apolipoprotein A1, B levels, and their ratio and the risk of a first stroke: a meta-analysis and case-control study.

The associations of levels of apolipoprotein A1 (ApoA1) and apolipoprotein B and ApoB/A1 ratio and risk of a first stroke have not been reliably documented. We performed a meta-analysis to summarize the relationships and confirmed them in a case-control study. We identified relevant publications in PubMed and Embase databases up to June 1, 2015. A Dersimonian-Laird random effects model was used to compute summary relative risks (RRs) and 95 % confidence intervals (CIs). A case-control study was conducted in a southern Chinese population. We included 8 cohort and 4 case-control studies (222,774 subjects; 10,032 first stroke events) in the meta-analysis. Reduced ApoA1 level and increased ApoB level and ApoB/A1 ratio was associated with a first stroke in cohort studies (RR 0.86 [95 % CI 0.79-0.94], 1.66 [1.62-1.69], and 1.66 [1.63-1.70], respectively) and reduced ApoA1 level and increased ApoB/A1 ratio in case-control studies (0.68 [0.47-0.99] and 1.76 [1.50-2.06], respectively). When stratified by stroke type in cohort studies, the RR for ischemic stroke was 0.83 (0.76-0.90), 1.36 (1.32-1.40), and 1.38 (1.35-1.42) for the 3 factors, respectively. In our case-control study (1013 cases; 1029 controls), the OR for a first ischemic stroke was 0.83 (0.74-0.92), 1.33 (1.18-1.48) and 2.10 (1.76-2.51), respectively, with increased ApoA1 level associated with hemorrhagic stroke (1.37 [1.06-1.78]). Meta-analysis suggests that reduced ApoA1 level and increased ApoB level and ApoB/A1 ratio are risk factors for a first ischemic but not hemorrhagic stroke. Elevated ApoA1 level may be a risk factor for a first hemorrhagic stroke.

Due-window assignment scheduling with variable job processing times.

We consider a common due-window assignment scheduling problem jobs with variable job processing times on a single machine, where the processing time of a job is a function of its position in a sequence (i.e., learning effect) or its starting time (i.e., deteriorating effect). The problem is to determine the optimal due-windows, and the processing sequence simultaneously to minimize a cost function includes earliness, tardiness, the window location, window size, and weighted number of tardy jobs. We prove that the problem can be solved in polynomial time.

COPA syndrome caused by a novel p.Arg227Cys COPA gene variant.

BACKGROUND: COPA syndrome is a recently described and rare monogenic autosomal dominant disease caused by heterozygous missense mutations in the Coatomer Protein Subunit alpha (COPA) gene that encodes the alpha subunit of coat protein complex I (COPI). Its main clinical manifestations are inflammatory lung disease, arthritis, and renal disease. The development of inflammation in COPA syndrome maybe due to abnormal autophagic response and abnormal activation of type I interferon pathway. To date, 59 cases of COPA have been reported worldwide. METHODS: In this case, Trio-whole exome sequencing was employed in the proband and her parents to identify the underlying genetic cause. COPA variant were detected and the clinical presentation of the patient was described. RESULTS: Herein, we report a case of a 5-year-old girl with COPA syndrome who presented with symptoms of arthritis combined with Anti-neutrophil Cytoplasmic Antibody (ANCA) associated vasculitis (AAV), and progressive renal decline with minimal pulmonary involvement. Trio-whole exome sequencing was performed which revealed a novel heterozygous likely pathogenic variation in the COPA gene (c.679C>T,p.Arg227Cys), which was maternally inherited. Her mother was a heterozygote, but she had no phenotypic manifestations. No other mutations associated with the clinical phenotype were identified. CONCLUSION: The present identification and characterization of a novel mutation expands the genotypic spectra of the COPA syndrome and provide reference data to guide future clinical diagnosis and treatment of COPA syndrome.

Capturing cerium ions via hydrogel microspheres promotes vascularization for bone regeneration.

The rational design of multifunctional biomaterials with hierarchical porous structure and on-demand biological activity is of great consequence for bone tissue engineering (BTE) in the contemporary world. The advanced combination of trace element cerium ions (Ce3+) with bone repair materials makes the composite material capable of promoting angiogenesis and enhancing osteoblast activity. Herein, a living and phosphorylated injectable porous hydrogel microsphere (P-GelMA-Ce@BMSCs) is constructed by microfluidic technology and coordination reaction with metal ion ligands while loaded with exogenous BMSCs. Exogenous stem cells can adhere to and proliferate on hydrogel microspheres, thus promoting cell-extracellular matrix (ECM) and cell-cell interactions. The active ingredient Ce3+ promotes the proliferation, osteogenic differentiation of rat BMSCs, and angiogenesis of endotheliocytes by promoting mineral deposition, osteogenic gene expression, and VEGF secretion. The enhancement of osteogenesis and improvement of angiogenesis of the P-GelMA-Ce scaffold is mainly associated with the activation of the Wnt/ß-catenin pathway. This study could provide novel and meaningful insights for treating bone defects with biofunctional materials on the basis of metal ions.

All-optical interrogation of brain-wide activity in freely swimming larval zebrafish.

We introduce an all-optical technique that enables volumetric imaging of brain-wide calcium activity and targeted optogenetic stimulation of specific brain regions in unrestrained larval zebrafish. The system consists of three main components: a 3D tracking module, a dual-color fluorescence imaging module, and a real-time activity manipulation module. Our approach uses a sensitive genetically encoded calcium indicator in combination with a long Stokes shift red fluorescence protein as a reference channel, allowing the extraction of Ca2+ activity from signals contaminated by motion artifacts. The method also incorporates rapid 3D image reconstruction and registration, facilitating real-time selective optogenetic stimulation of different regions of the brain. By demonstrating that selective light activation of the midbrain regions in larval zebrafish could reliably trigger biased turning behavior and changes of brain-wide neural activity, we present a valuable tool for investigating the causal relationship between distributed neural circuit dynamics and naturalistic behavior.

A Self-Adaptive Biomimetic Periosteum Employing Nitric Oxide Release for Augmenting Angiogenesis in Bone Defect Regeneration.

The periosteum plays a vital role in the regeneration of critical-size bone defects and highly comminuted fractures, promoting the differentiation of osteoblasts, accelerating the reconstruction of the vascular network, and guiding bone tissue regeneration. However, the materials loaded with exogenous growth factors are limited by the release and activity of the elements. Therefore, the material structure must be carefully designed for the periosteal function. Here, a self-adaptive biomimetic periosteum strategy is proposed, which is a novel interpenetrating double network hydrogel consisting of diselenide-containing gelatin and calcium alginate (modified natural collagen and polysaccharide) to enhance the stability, anti-swelling, and delayed degradation of the hydrogel. The diselenide bond continuously releases nitric oxide (NO) by metabolizing endogenous nitrosated thiols (RSNO), activates the nitric oxide-cycle guanosine monophosphate (NO-cGMP) signal pathway, coordinates the coupling effect of angiogenesis and osteogenesis, and accelerates the repair of bone defects. This self-adaptive biomimetic periosteum with the interpenetrating double network structure formed by the diselenide-containing gelatin and calcium alginate has been proven to be safe and effective in repairing critical-size bone defects and is expected to provide a promising strategy for solving clinical problems.