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Background: Systemic immune-inflammatory markers such as neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR) and systemic immune-inflammatory index (SII) are associated with the prognosis of many cardiovascular and neoplastic diseases. Moyamoya disease (MMD) is associated with inflammation, but the relationship between systemic immune-inflammatory markers between MMD is unclear. The aim of our study was to analyse the association between systemic immune-inflammatory markers and the risk of MMD and its subtypes. Methods: We consecutively recruited 360 patients with MMD and 89 healthy control subjects in a case-control study to calculate and analyse the association of systemic immune-inflammatory markers with the risk of MMD and its subtypes. Results: The risk of MMD increased with higher levels of NLR (OR 1.237, 95% CI [1.008, 1.520], p =.042). When NLR and SII were assessed as quartile-spaced subgroups, the third quartile grouping of NLR and SII had a higher risk of MMD than the first quartile grouping (NLR: OR 3.206, 95% CI [1.271, 8.088], p =.014; SII: OR 3.074,95% CI [1.232,7.672], p =.016). When NLR was combined with SII, the highest subgroup had a higher risk of MMD than the lowest subgroup (OR2.643, 95% CI [1.340, 5.212], p =.005). The risk of subtypes also increased with higher levels of NLR and SII. The association between the levels of NLR and SII with the staging of the Suzuki stage follows an inverted U-shape. The highest levels of NLR and SII were found in patients with MMD at Suzuki stages 3–4. Conclusion: The risk of MMD increases with elevated systemic immune-inflammatory markers. This study analysed the association of systemic immune-inflammatory markers with the risk of developing MMD and its subtypes, and identified novel inflammatory markers for MMD. Systemic immune-inflammatory markers such as neutrophil–lymphocyte ratio and systemic immune-inflammatory index were higher in moyamoya disease (MMD) patients than in normal people. Systemic immune-inflammatory markers may be an independent risk factor for the onset of MMD. Systemic immune-inflammatory markers were associated with the progression of MMD, and their levels showed an inverted U shape with imaging stages. [ABSTRACT FROM AUTHOR]

Mitochondrial DNA (mtDNA) copy number (CN) is a biomarker of mitochondrial function and has been reported associated with kidney disease. However, its association with IgA nephropathy (IgAN), the most common cause of glomerulonephritis (GN), has not been evaluated. We included 664 patients with biopsy-proven IgAN and measured mtDNA-CN in peripheral blood by multiplexed real-time quantitative polymerase chain reaction (RT-qPCR). We examined the associations between mtDNA-CN and clinical variables and found that patients with higher mtDNA-CN had higher estimated glomerular filtration rate (eGFR) (r = 0.1009, p =.0092) and lower serum creatinine (SCr), blood urea nitrogen (BUN), and uric acid (UA) (r=−0.1101, −0.1023, −0.07806, respectively, all p values <.05). In terms of pathological injury, mtDNA-CN was higher in patients with less mesangial hypercellularity (p =.0385, M0 vs. M1 score by Oxford classification). Multivariable logistic regression analyses also showed that mtDNA-CN was lower for patients with moderate to severe renal impairment (defined as eGFR < 60 mL/min/1.73 m2) vs. mild renal impairment, with the odds ratio of 0.757 (95% confidence interval: 0.579–0.990, p =.042). In conclusion, mtDNA-CN was correlated with better renal function and less pathological injury in patients with IgAN, proposing that systemic mitochondrial dysfunction may be involved in or reflect the development of IgAN. [ABSTRACT FROM AUTHOR]

Acute kidney injury (AKI) is a syndrome characterized by an accelerating decrease in renal function in a short time. Thymol is one of the main components of thyme species and has a variety of pharmacological effects. Here, we investigated whether thymol could ameliorate rhabdomyolysis (RM)-induced AKI and its related mechanism. Glycerol was used to induce RM-associated AKI in rats. Rats received thymol (20 mg/kg/day or 40 mg/kg/day) gavage 24 h before glycerol injection until 72 h after injection daily. Kidney injury was identified by measuring serum creatinine (Scr) and urea levels and by H&E and PAS staining and immunohistochemistry (the expression of proliferating cell nuclear antigen (PCNA)). Renal superoxide dismutase (SOD), malondialdehyde (MDA), and oxidative stress-related Nrf2/HO-1 signaling pathways were measured. The expression of the inflammatory markers TNF-α, IL-6, MCP-1, and NF-κB was assessed by ELISA and western blotting. Finally, the expression of the PI3K/Akt signaling pathway was detected by western blotting. Glycerol administration induced obvious renal histologic damage and increased Scr, urea, and PCNA expression. Notably, thymol treatment attenuated these structural and functional changes and prevented renal oxidative stress, inflammatory damage and PI3K/Akt pathway downregulation associated with glycerol-induced AKI. In conclusion, thymol might have potential applications in the amelioration of AKI via its antioxidant and anti-inflammatory effects and upregulation of the PI3K/Akt signaling pathway. [ABSTRACT FROM AUTHOR]

The aims of the study were to explore the potential associations between plasma proprotein convertase subtilisin/kexin type 9 (PCSK9) and coagulation indexes in patients with primary membranous nephropathy (PMN). A total of 87 patients diagnosed with PMN were enrolled in our study. 30 healthy participants were recruited to match PMN participants. Plasma PCSK9 concentrations were tested by enzyme-linked immunosorbent assay (ELISA). Correlations between PCSK9 and coagulation abnormalities in patients with PMN were analyzed using univariate and multiple linear regression analysis. Plasma PCSK9 levels in patients with PMN were significantly higher than that in healthy controls [232.0 (143.5, 359.5) ng/mL vs. 166.8 (129.7, 199.7) ng/mL; p = 0.001]. Plasma levels of PCSK9 were positively correlated with factor VIII, factor IX, factor XI, log-transformed tissue factor, protein C and protein S (r = 0.267, p = 0.013; r = 0.496, p < 0.001; r = 0.217, p = 0.045; r = 0.584, p < 0.001; r = 0.372, p = 0.001; r = 0.282, p = 0.011). In multiple linear regression analysis, PCSK9 concentration was independently and positively correlated with factor VIII, factor IX, and tissue factor (β = 0.186, p = 0.047; β = 0.325, p = 0.001; β = 0.531, p < 0.001; respectively). PCSK9 concentration was independently and negatively correlated with PT (β= −0.343, p = 0.011). Plasma PCSK9 levels had good positive correlations with procoagulant clotting factors and negative correlations with PT in PMN, which might provide novel information with regard to PCSK9 and hypercoagulability in PMN. [ABSTRACT FROM AUTHOR]

Peritoneal fibrosis caused by long-term peritoneal dialysis (PD) is the main reason why patients withdraw from PD treatment. Lipid accumulation in the peritoneum was shown to participate in fibrosis, and klotho is a molecule involved in lipid metabolism. GSK343 (enhancer of zeste 2 polycomb repressive complex 2 subunit (EZH2) inhibitor) has been verified to inhibit epithelial mesenchymal transdifferentiation (EMT) and peritoneal fibrosis, but its related mechanism remains unclear. This study aimed to investigate whether lipid accumulation was involved in the effect of GSK343 and its related mechanism. First, the expression of EZH2, klotho and EMT indices in human peritoneal mesothelial cells (HMrSV5) incubated with high glucose (HG) levels was detected. After EZH2 was inhibited by GSK343, Western blot (WB), wound healing and Transwell assays were used to explore the effect of GSK343. EZH2 and klotho expression was also detected. Oil red O and Nile red staining and triglyceride (TG) detection kits were used to detect lipid accumulation. A rescue experiment with small interfering RNA specific for klotho (si-klotho) on the basis of GSK343 was also conducted to verify that GSK343 exerted its effect via klotho. In in vivo experiments, rats were administered GSK343, and the related index was assessed. In our study, we revealed that the expression of EZH2 was significantly upregulated and klotho was significantly downregulated in HMrSV5 cells induced by high glucose. With the aid of GSK343, we found that lipid deposition caused by HG was significantly decreased. In addition, EMT and fibrosis were also significantly alleviated. Moreover, GSK343 could also restore the downregulation of klotho. To further verify whether klotho mediated the effect of EZH2, a rescue experiment with si-klotho was also conducted. The results showed that si-klotho could counteract the protective effect of GSK343 on high glucose-induced lipid accumulation and fibrosis. In vivo experiments also revealed that GSK343 could relieve peritoneal fibrosis, lipid deposition and EMT by mitigating EZH2 and restoring klotho expression. Combining these findings, we found that EZH2 regulated lipid deposition, peritoneal fibrosis, and EMT mediated by klotho. To our knowledge, this is the first study to demonstrate the effect of the EZH2-klotho interaction on peritoneal fibrosis. Hence, EZH2 and klotho could act as potential targets for the treatment of peritoneal fibrosis. [ABSTRACT FROM AUTHOR]

Ginseng black spot, caused by Alternaria panax, is one of the most common diseases of Panax ginseng, which usually causes serious yield loss of ginseng plants. However, the pathogenic mechanism of A. panax has not been clarified clearly. Mycotoxins produced by phytopathogens play an important role in the process of infection. Previous study reported that dibutyl phthalate (DBP) identified from the metabolites of A. panax is a potent mycotoxin against P. ginseng. However, more evidence suggests that DBP is one of the constituents of plasticisers. To identify mycotoxins from A. panax and evaluate their phytotoxicity on the leaves of P. ginseng, different chromatographic, spectral and bioassay-guided methods were used together in this report. As a result, tyrosol (1), 3-hydroxy-3-(4-methoxyphenyl) propanoic acid (2), and 3-benzylpiperazine-2,5-dione (3) were isolated and characterised from the extract of A. panax, in which compounds 1 and 2 showed phytotoxic activity on ginseng leaves. Furthermore, DBP was confirmed to come from the residue of ethyl acetate through UPLC-MS/MS analysis, and displayed no phytotoxicity on ginseng leaves based on biological experiments. The results in this report first revealed that tyrosol (1), and 3-hydroxy-3-(4-methoxyphenyl) propanoic acid (2) not DBP were the potent mycotoxins of A. panax. [ABSTRACT FROM AUTHOR]

Immune checkpoint inhibitor-associated acute kidney injury (ICI-AKI) is the most common renal complication and has attracted increasing amounts of attention. However, studies on this topic in Chinese cancer patients are very limited. Therefore, we conducted a retrospective study on the incidence, risk factors, clinical features and renal recovery of ICI-AKI in all patients with malignancies treated with ICIs in Shandong Provincial Hospital Affiliated to Shandong First Medical University. In this single-center retrospective cohort study, the data of 904 patients who received immune checkpoint inhibitors (ICIs) treatment were retrospectively analyzed. Multivariable logistic regression was used to identify the predictors of ICI-AKI. A total of 46 of 904 patients receiving ICIs developed ICI-AKI, and the incidence of ICI-AKI was 5.1%. Patients developed ICI-AKI at a median of 9 weeks (IQR 3–23) after ICIs initiation. A lower baseline estimated glomerular filtration rate (eGFR) and use of antibiotics were associated with a higher risk of ICI-AKI. Renal recovery occurred in 17 patients (46%) at a median of 4 weeks (IQR 2–8) after ICI-AKI, including 16 (43%) with complete recovery and 1 (3%) with partial recovery. Of the 14 rechallenged patients, only one developed recurrent ICI-AKI. Patients with ICI-AKI were more likely to have impaired renal function at baseline and after treatment with antibiotics. Approximately half of the patients achieved renal recovery. [ABSTRACT FROM AUTHOR]

Predicting future urban land-use scenarios and assessing their encroachment on ecological land is important for sustainability policy formulation. This study develops a new Futureland model using cellular automata with user-defined transformation rules, graphical neighborhood configuration and matrixed transformation cost to simulate multiple land-use changes. Compared with existing models, Futureland applies different factors to different land-use types in a single simulation experiment. Futureland was developed using Geospatial Data Abstraction Library and parallel computing, which significantly improve the implementation efficiency. The case study of Shanghai 2010–2020 illustrates an overall accuracy of 86.6% and a Kappa simulation of 0.79. The land-use scenarios for 2020–2035 were projected under greenspace planning constraints using Futureland. The results indicate that Shanghai's urban sprawl will gradually slow down by 2030, and the increased urban areas will be mainly in the urban fringes and suburban regions. Futureland can help decision-makers to manage future land-use and optimize urban planning policies. [ABSTRACT FROM AUTHOR]

Linked colour imaging (LCI) is a novel new image-enhanced endoscopy (IEE) technology that produces bright and vivid images. The aim of this study was to assess the ability of LCI to improve the diagnostic accuracy of early gastric cancer (EGC) relative to white light imaging (WLI). We performed this study on patients undergoing screening endoscopy from 12 medical institutions in China. Patients were randomly assigned to receive WLI followed by LCI or LCI followed by WLI. The primary outcome was to compared the diagnostic accuracy between LCI and WLI for EGC/high-grade intraepithelial neoplasms. Secondary outcomes included the numbers of suspicious lesions, neoplastic lesions and examination time by using LCI detected versus using WLI. A total of 1924 patients were randomly selected, and 1828 were included in the analysis. The diagnostic accuracy for EGC, which was 78.8% by using LCI and 68.4% by using WLI (p <.0001). More suspicious lesions were detected by LCI than by WLI (n = 1235 vs. 1036, p =.031), especially among differentiated EGC (p =.013). LCI greatly shortened the examination time compared with WLI (p =.019). LCI has better accuracy and shorter examination time in diagnosing EGC than WLI (Clinical trial registration: NCT03092414). Compared with white light imaging (WLI), the diagnostic accuracy, sensitivity and specificity increased by using LCI. More lesions were detected by LCI alone than by WLI alone, especially among differentiated EGC. LCI may be used as a screening tool for routine clinical observation. [ABSTRACT FROM AUTHOR]

To investigate the clinical manifestations, pathological features, pathogenesis, treatment, and prognosis of anti-glomerular basement membrane (anti-GBM) disease with membranous nephropathy (MN). Seven patients with anti-GBM disease and concurrent MN were enrolled in this study. Control subjects included 13 patients with anti-GBM glomerulonephritis (GN) and 6 with anti-GBM disease and concurrent anti-neutrophil cytoplasmic antibodies-associated disease (anti-GBM + ANCA). Laboratory tests and pathological information were analyzed before immunosuppressive therapy or plasmapheresis administration. Prognosis was assessed in continuous follow-up. In the anti-GBM + MN group, 28.57% of patients exhibited acute kidney disease, lower than that in the anti-GBM GN group (84.62%, p =.022). None of the anti-GBM + MN or + ANCA patients exhibited hemoptysis, but 15.4% of anti-GBM GN patients did, with no significant difference (p =.720). Only 14.3% of anti-GBM + MN patients had crescentic GN. The proportion of necrosis averaged 29.0% in the anti-GBM + MN group. Survival curve analysis revealed that renal outcomes in the anti-GBM + MN group were better than those in the anti-GBM GN group (p =.019). Patients with both anti-GBM disease and MN showed atypical anti-GBM GN. They had a lower proportion of glomerular crescents and a better renal function prognosis than patients with classical anti-GBM GN. To improve renal recovery, early identification and treatment of anti-GBM disease associated with MN is needed. [ABSTRACT FROM AUTHOR]

The aims of the study were to identify whether left renal vein (LRV) entrapment was more prevalent in IgA nephropathy (IgAN) and Henoch–Schönlein purpura nephritis (HSPN) compared with other types of renal diseases, and the association of LRV entrapment with glomerular incidental IgA and galactose-deficient-IgA1 (Gd-IgA1) deposition. A total of 797 patients with biopsy-proven kidney diseases have been screened for LRV entrapment by color Doppler ultrasound, and the prevalence of LRV entrapment in different types of renal diseases were then analyzed. Propensity score matching analysis was used to adjust for age, gender, and body mass index. Immunostaining of Gd-IgA1 with KM55 was performed in paraffin-embedded sections of renal biopsy specimens. LRV entrapment was diagnosed in 47 patients (6%) with several kinds of renal diseases in our cohort. A total of 32 (68%) LRV entrapments were combined with expanded IgAN (idiopathic IgAN and HSPN). The prevalence of LRV entrapment in expanded IgAN was significantly higher than that in non-expanded IgAN (17 vs. 2%, p < 0.001), even after adjustment for age, gender, and body mass index by propensity score matching analysis (13 vs. 2%, p < 0.001). Removing expanded IgAN and LN, glomerular incidental IgA deposition was observed to be significantly more common in patients with LRV entrapment compared with patients without it (43 vs. 9%, p < 0.001). Furthermore, in glomerular diseases with incidental IgA deposits, significantly much larger proportion of patients with LRV entrapment were positive for glomerular Gd-IgA1 in contrast to patients without LRV entrapment (5/5 vs. 5/17, p = 0.01). LRV entrapment coexisted with several kinds of renal diseases, with a significantly higher prevalence in patients with idiopathic IgAN and HSPN. In patients of LN and IgAN-unrelated disease with LRV entrapment, glomerular IgA and Gd-IgA1 deposition was more common compared with patients without LRV entrapment. [ABSTRACT FROM AUTHOR]

Primary membranous nephropathy (PMN) is associated with the highest risk for developing venous thrombosis compared with other nephrotic diseases. The aim of the study was to assess the predictive value of the pathognomonic anti-phospholipase A2 receptor (PLA2R) antibody with regard to incidence of venous thrombosis in PMN. A total of 365 in-hospital patients diagnosed with PMN were enrolled in the study. Anti-PLA2R antibody was detected by commercial enzyme-linked immunosorbent assay. Multivariate logistic regression was used to detect the independent risk factors for venous thrombosis. Thirty-seven patients (10.14%) had venous thrombosis. Patients with venous thrombosis had higher levels of cholesterol (CHOL), low-density lipoprotein (LDL), and D-dimer than those without venous thrombosis (p <.05). Patients with venous thrombosis had significantly lower levels of albumin (23.95 ± 5.53 vs. 26.18 ± 6.59 g/L, p =.049). No significant differences were found in proteinuria, serum creatinine, estimated glomerular filtration rate, platelets, and fibrinogen between patients with and without thrombosis. Anti-PLA2R antibody levels in patients with venous thrombosis were significantly higher than in patients without it (p =.002). In the univariate logistic regression, Ln anti-PLA2R antibody (OR: 1.340; p =.004), albumin (OR: 0.945; p =.050), CHOL (OR: 1.191; p =.006), and LDL (OR: 1.271, p =.006) were associated with venous thrombosis. Ln anti-PLA2R antibody (OR = 1.269; 95%CI: 1.032–1.561), and LDL (OR = 1.213; 95%CI: 1.017–1.448) were the independent risk factors for venous thrombosis (p <.05) in multivariate analysis. Anti-PLA2R antibody was the independent risk factor for venous thrombosis in PMN. Larger prospective studies were warranted to verify the results in future. [ABSTRACT FROM AUTHOR]

Smart structures have the advantages of high system integrity and diverse sensing capabilities. However, the labor-intensive and time-consuming fabrication process hinders the large-scale adoption of smart structures. Despite recent attempts to develop sensor-embedded structures using 3D printing technologies, the reported smart structures generally suffer from the complex fabrication process, constrained part size, and limited sensing modality. Herein, we propose a workflow to design and fabricate novel smart structures via multimaterial fused deposition modeling (FDM)-based 3D printing. More specifically, conductive filaments with tailorable mechanical and electrical properties, e.g. piezoresistive effects, were developed. Additionally, the printing process was optimized for processing soft filaments with Young's modulus around 2 MPa, resolving the issue of filament buckling. Furthermore, the potential applications of the proposed workflow were showcased using three design cases, i.e. biaxial strain sensor, smart tire, and cable-driven soft finger with multiple sensing capabilities. This workflow provides a cost-effective and rapid solution for developing novel smart structures with soft materials. [ABSTRACT FROM AUTHOR]

The production and selection of driving factors are essential to building a strong Cellular Automata (CA) model of dynamic urban growth simulation. A critical issue that should be addressed is how the spatial representation and the generalization scale of driving factors affect the CA modeling and the simulation results. It is challenging to evaluate the effectiveness of the selected driving factors because they have no true values. To explore the impacts of the generalization scales, we produced nine sets of driving factors at nine scales to calibrate the CA models based on the Particle Swarm Optimization (CAPSO) and applied them to simulate urban growth of Suzhou during 2000–2020. Our results show that the driving factors at a smaller scale have much better performance in explaining urban growth simulations as inferred by the Explained Residual Deviance (ERD) of the Generalized Additive Models (GAMs). Specifically, the ERD declined from 51.9% to 45.9% as the factor scale became larger during 2000–2020, but there was a peak value (52.2%) at Scale-2. For all simulations during 2000–2020, the CAPSO models with larger-scale factors have slightly lower overall accuracy and Figure-of-Merit (FOM), which respectively decreased by 3.1% and 4.4% as compared to the CA models with scale-free factors. We concluded that the driving factors at a smaller scale (200 ~ 400 m for point-like facilities and 7 ~ 14 m for line-like facilities) can build more accurate CA models to simulate urban growth patterns, and the optimal scale for factors can be identified using the ERD. This study contributes to the methods of evaluating the effectiveness of driving factor production and reveals the impacts of spatial representation of factors on the CA modeling and simulation considering the factor generalization scales. [ABSTRACT FROM AUTHOR]

Macroautophagy/autophagy-related proteins regulate infectious and inflammatory diseases in autophagy-dependent or -independent manner. However, the role of a newly identified mammalian-specific autophagy protein-BECN2 (beclin 2) in innate immune regulation is largely unknown. Here we showed that loss of BECN2 enhanced the activities of NLRP3, AIM2, NLRP1, and NLRC4 inflammasomes upon ligand stimulations. Mechanistically, BECN2 interacted with inflammasome sensors and mediated their degradation through a ULK1- and ATG9A-dependent, but BECN1-WIPI2-ATG16L1-LC3-independent, non-canonical autophagic pathway. BECN2 recruited inflammasome sensors on ATG9A+ vesicles to form a complex (BECN2-ATG9A-sensors) upon ULK1 activation. Three soluble NSF attachment protein receptor (SNARE) proteins (SEC22A, STX5, and STX6) were further shown to mediate the BECN2-ATG9A-dependent inflammasome sensor degradation. Loss of BECN2 promoted alum-induced peritonitis, which could be rescued by the ablation of CASP1 in Becn2-deficient mice. Hence, BECN2 negatively regulated inflammasome activation to control inflammation, serving as a potential therapeutic target for the treatment of infectious and inflammatory diseases. Abbreviations: AIM2: absent in melanoma 2; ATG: autophagy related; BECN1: beclin 1; BMDC: bone marrow-derived dendritic cells; BMDM: bone marrow-derived macrophages; CASP1: caspase 1; CQ: chloroquine; gMDSC: granulocytic myeloid-derived suppressor cells; IL: interleukin; LPS: lipopolysaccharide; MAP1LC3B: microtubule associated protein 1 light chain 3 beta; mMDSC: monocytic myeloid-derived suppressor cells; NLRC4: NLR family CARD domain containing 4; NLRP1: NLR family pyrin domain containing 1; NLRP3: NLR family pyrin domain containing 3; PECs: peritoneal exudate cells; PYCARD/ASC: apoptosis-associated speck-like protein containing a caspase activation and recruitment domain; SNAREs: soluble NSF attachment protein receptors; STX5: syntaxin 5; STX6: syntaxin 6; ULK1: unc-51 like autophagy activating kinase 1; WIPI: WD repeat domain, phosphoinositide interacting. [ABSTRACT FROM AUTHOR]

A significant decrease in red blood cell (RBC) survival has been observed in patients with renal failure, which is supposed to contribute to renal anemia. The aim of this observational study was to determine RBC survival in hemodialysis (HD) patients treated with roxadustat or recombinant human erythropoietin (rhuEPO) compared with healthy persons. RBC lifespan was measured by Levitt's CO breath test with newly developed automatic instrument ELS Tester. A total of 102 patients receiving long-term HD from two independent dialysis centers enrolled in the study, of whom 62 were treated with rhuEPO and 40 were on roxadustat therapy. A total of 25 healthy participants were recruited to match HD participants according to age and sex. Median RBC survival times in rhuEPO, roxadustat, and control groups were 65.0 (25th–75th percentile, 49.5–77.3), 75.5 (25th–75th percentile, 57.3–99.3), and 108.0 (25th–75th percentile, 89.0–141.5) d, respectively. Patients treated with roxadustat had significantly longer RBC survival time than patients treated with rhuEPO (p <.05). In multivariate analysis of factors affecting RBC lifespan in the whole HD patients, anemia treatment drugs (rhuEPO/roxadustat) and levels of hemoglobin were the significantly independent factors. RBC survival was not found to correlate with either weekly rhuEPO dosage (r = –0.087, p =.500) or weekly roxadustat dosage (r = −0.267, p =.110) in our cohort. HD patients treated with roxadustat had significantly longer RBC survival time than patients treated with rhuEPO, large prospective studies with long-term follow-up are warranted to verify the results in future. Abbreviations RBC: red blood cell; HD: hemodialysis; rhu EPO: recombinant human erythropoietin; ESRD: end-stage renal disease; EPO: erythropoietin; ROS: reactive oxygen species; CKD: chronic kideny disease; ESAs: erythropoiesis-stimulating agents; HIF-PHD: hypoxia-inducible factor prolyl hydroxylase; CO: carbon monoxide; Hb: hemoglobin [ABSTRACT FROM AUTHOR]

The complete mitogenome of Gymnosoma dolycoridis Dupuis, 1960 was determined in this study. It is 15,185 bp in length, consisting of 13 protein-coding genes (PCG), 22 transfer RNA genes, two ribosomal RNA genes and one non-coding control region. The A + T content of the mitogenome is 78.5%. A maximum-likelihood phylogenetic tree built on 13 PCGs of 15 tachinid species indicated that Gymnosoma dolycoridis is clustered with other members of the subfamily Phasiinae as conventional taxonomy predicted. [ABSTRACT FROM AUTHOR]

The mitochondrial genome of Cylindromyia (Calocyptera) intermedia (Meigen, 1824) was sequenced and assembled through high-throughput sequencing techniques and reference-based assembly methods. The mitochondrial genome is 15,114 bp in total, consisting of 13 protein-coding genes, 22 transfer RNA genes, 2 ribosomal RNA genes, and 1 noncoding control region. The nucleotide composition biases toward A and T; the overall A + T content are up to 76.9% of the entire mitogenome. The result of phylogenetic analysis suggested a close relationship between C. intermedia and subfamily Dexiinae. [ABSTRACT FROM AUTHOR]

Inflammation is a defense mechanism that the immune system uses in response to harmful stimuli such as pathogens, damaged cells, toxic compounds, or irradiation. These stimuli may induce inflammatory response and potentially tissue damage in respiratory, cardiovascular, digestive, nervous, endocrine, urinary, or reproductive systems. Inflammatory diseases include a broad array of disorders and conditions that are characterized by inflammation, ranging from autoimmune disease, atopic dermatitis, asthma, chronic obstructive pulmonary disease, inflammatory bowel disease, glomerulonephritis, hepatitis, reperfusion injury, transplant rejection, diabetes, cancer, Parkinson’s disease, multiple sclerosis, to depression. Epigenetic mechanisms play crucial roles in many biological processes by regulating transcriptional activation or repression. Histone post-translational modifications have emerged as prospective therapeutic targets. Methylation of histone 3 at lysine 9 is one of the most highly conserved epigenetic marks that correlate well with gene silencing. The methylation status of H3K9 modulates immune cell differentiation and immune responses and therefore influences the outcome of cancer, infection, and other inflammatory diseases. Here, we review the high impact and innovate discoveries in this field, highlight the critical role of the H3K9 methylation/de-methylation in human inflammatory diseases, discuss potential new therapeutic strategies based on a better understanding of the biology of H3K9 methylation modifications. Abbreviations: 2OG: 2-oxoglutarate; AOL: Amine oxidase-like; ChIP: Chromatin immunoprecipitation; CNS2: conserved noncoding sequence 2; COPD: Chronic obstructive pulmonary disease; CoREST: Corepressor of RE1 silencing transcription factor; CPP: Cell-permeant protein; CTLA4: Cytotoxic T-lymphocyte antigen 4; DCs: Dendritic cells; DN: Diabetic nephropathy; ESRD: End-stage renal disease; ETDB: SET domain bifurcated histone lysine methyltransferase; FAD: Flavin adenine dinucleotide; FEV1%: The percentage of forced expiratory volume in one second; FEV1/FVC: Forced expiratory volume in one second (FEV1)/Forced vital capacity (FVC) value; FOXP3: forkhead/winged helix transcription factor 3; GLP: G9a like protein; GZMB: Granzyme B; H3K27me3: Trimethylation of lysine 27 on histone H3; H3K4me3: Trimethylation of lysine 4 on histone H3; H3K9: Histone 3 Lysine 9; HG: Hyperglycemia; HDAC3: Histone deacetylase 3; HP1: Heterochromatin protein 1; I/R: Ischemia/Reperfusion; IBD: Inflammatory bowel disease; IFN-: Interferon-; IFNG: Interferon Gamma; IL-2: Interleukin-2; ILC2s: Group 2 innate lymphoid cells; JMJD: Jumonji domain-containing protein; iTreg: inducible Treg; KDM: Lysine-specific demethylase; LPS: Lipopolysaccharide; LSD: Lys-specific demethylase; MCP-1: Monocyte chemoattractant protein-1; MCSF: Macrophage colony-stimulating factor; MIP-1: Macrophage inflammatory protein-1; MS: Metabolic syndrome; NAFLD: Non-alcoholic fatty liver disease; NKRF: NF-kappaB repressing factor; NOR: Norisoboldine; NuRD: Nucleosome remodeling and deacetylase; OxLDL: Oxidized low-density lipoprotein; PBMCs: Peripheral blood monocytes; PHD: Plant homology domain; Poly I:C: Polyinosinic:polycytidylic acid; PPARγ: Peroxisome proliferator-activated receptor gamma; PTMs: Post-translational modifications; SUV3-9: Suppressor of variegation3-9; T1D: Type 1 diabetes; TLRs: Toll like receptors; TSDR: TGF-β sensitive region and Treg cell specific demethylated region; Treg: Regulatory T cell; VSMCs: Vascular smooth muscle cells. [ABSTRACT FROM AUTHOR]

In this study, the whole mitochondrial genome of the Purple Spot Mantis Shrimp Gonodactylus smithii from the South China Sea was determined using next-generation sequencing. The circular mitogenome of G. smithii is 16,260 bp long and consists of 13 protein-coding genes (PCGs), 22 tRNA genes, and two rRNA genes. The base composition is AT-rich and has an overall AT content of 67.76% (composition of A, G, T, and C was 35.30%, 12.41%, 32.46%, and 19.83%, respectively). Among 13 PCGs, 12 PCGs shared a common ATN as the start codon except COX1 gene using an abnormal putative first codon GCG. 11 PCGs ended with TAA or TAG, while ND6, COX2 gene terminated with a single T and ND3 gene used a special "GAT" as the stop codon. The phylogenetic tree showed that G. smithii was clustered with Gonodactylus chiragra, then together with Gonodactylaceus randalli. [ABSTRACT FROM AUTHOR]

Context: Danshen tablets (DST), an effective traditional Chinese multi-herbal formula, are often combined with atorvastatin calcium (AC) for treating coronary heart disease in the clinic. Objective: This study investigated the effects of DST on the pharmacokinetics of AC and the potential mechanism. Materials and methods: The pharmacokinetics of AC (1 mg/kg) with or without pretreatment of DST (100 mg/kg) were investigated using LC-MS/MS. The effects of DST (50 μg/mL) on the metabolic stability of AC were also investigated using rat liver microsome incubation systems. Results: The results indicated that Cmax (23.87 ± 4.27 vs. 38.94 ± 5.32 ng/mL), AUC(0-t) (41.01 ± 11.32 vs. 77.28 ± 12.92 ng h/mL), and t1/2 (1.91 ± 0.18 vs. 2.74 ± 0.23 h) decreased significantly (p < 0.05) when DST and AC were co-administered, which suggested that DST might influence the pharmacokinetic behavior of AC when they are co-administered. The metabolic stability (t1/2) of AC was also decreased (25.7 ± 5.2 vs. 42.5 ± 6.1) with the pretreatment of DST. Discussion and conclusions: This study indicated that the main components in DST could accelerate the metabolism of AC in rat liver microsomes and change the pharmacokinetic behaviors of AC. So these results showed that the herb-drug interaction between DST and AC might occur when they were co-administered. Therefore, the clinical dose of AC should be adjusted when DST and AC are co-administered. [ABSTRACT FROM AUTHOR]

Nifedipine is completely absorbed by the gastrointestinal tract and its pharmacokinetics and metabolism may be influenced by microorganisms. If gut microbes are involved in the metabolism of nifedipine, plateau hypoxia may regulate the bioavailability and the therapeutic effect of nifedipine by altering the metabolic activity of the gut microbiota. We herein demonstrated for the first time that gut flora is involved in the metabolism of nifedipine by in vitro experiments. In addition, based on the results of 16S rRNA analysis of feces in rats after acute plateau, we first confirmed that the plateau environment could cause changes in the number and composition of intestinal microbes. More importantly, these changes in flora could lead to a slower metabolic activity of nifedipine in the body after an acute plateau, resulting in increased bioavailability and therapeutic efficacy of nifedipine. Our research will provide basis and new ideas for changes in the fecal flora of human acutely entering the plateau, and contribute to rational drug use of nifedipine. [ABSTRACT FROM AUTHOR]

BECN2 (beclin 2) is a newly identified mammalian-specific macroautophagy/autophagy family member, and plays a critical role in the control of obesity and insulin sensitivity. However, its role in innate immune signaling and inflammation remains elusive. In our recent study, we show that BECN2 functions as a negative regulator in innate immune signaling and tumor development through non-canonical autophagy. Loss of Becn2 causes splenomegaly, lymphadenopathy, elevated proinflammatory cytokine production and spontaneous lymphoma development in mice. Mechanistically, BECN2 mediates the degradation of MAP3K7/TAK1 and MAP3K3/MEKK3 through an ATG9A- and ULK1-dependent but ATG16L1-BECN1-MAP1LC3B/LC3B-independent autophagy pathway to control systemic inflammation. BECN2 interacts with MAP3K7 and MAP3K3 through the engagement of ATG9A+ vesicles upon ULK1 activation, and promotes the fusion of MAP3K3- or MAP3K7-associated ATG9A+ vesicles with phagophores for subsequent degradation. Our findings have identified a previously unrecognized role of BECN2 in innate immune signaling and tumor development through non-canonical autophagy, thus providing a potential target for inflammatory disease and cancer therapy. [ABSTRACT FROM AUTHOR]

Salvia hispanica is an annual food and oil crop native to Mexico and Guatemala. In this study, we report the complete chloroplast genome (plastome) of S. hispanica. The plastome was 150,980 bp in length and comprises a large single-copy region (82,274 bp), a small single-copy region (17,534 bp), and a pair of inverted repeats (25,586 bp). It encodes 114 unique genes, including 80 protein-coding genes (PCGs), 30 tRNAs, and 4 rRNAs. The overall GC content of this plastome was 38.0%. Phylogenomic analysis of all PCGs revealed that S. hispanica was closely related to S. bulleyana. [ABSTRACT FROM AUTHOR]

Eucommia ulmoidesis a small tree that has evolved strong pest resistance. This study investigated the mechanism of this resistance by evaluating pest damage and antifeedant activity of the secondary metabolite gutta-percha. In the field,E. ulmoidesdisplayed an average plant resistance of 93.3%, with most damage confined to leaves. We assessed the effects of gutta-percha as a feeding deterrent againstHyphantria cuneaandAnoplophora glabripennislarvae by mixing it into or daubing it onto the surface of artificial diets. Diets containing more than 6% gutta-percha significantly reduced the amount of feeding byA. glabripennislarvae and the body length ofH. cunealarvae. In addition, approximately 95% of the artificial diet was not consumed compared to the control without gutta-percha. The content, distribution, properties, and dynamics of gutta-percha inE. ulmoidesindicate that gutta-percha may function as a physical-chemical barrier against insect pests. [ABSTRACT FROM AUTHOR]

Chlorophorus caragana(Coleoptera: Cerambycidae) is a trunk borer that feeds onCaraganashrubs in the desert. There are five species ofCaraganaplant in the distribution area ofCh. caragana. We investigated damagedCaraganaplants in the field. Olfactory responses of femaleCh. caraganato plants and identified volatile compounds fromCaraganaplants were further evaluated.Caragana davazamciiwas severely damaged in the field, followed byCaragana microphylla. No damage was found to the other three species. Behavioral experiments showed thatC. davazamcii, C. microphylla, andCaragana korshinskiiwere attractive to female insects.Caragana ordosicacould repel and avoid female insects.Caragana brachypodahad no effect on the orientation behavior of female insects. Seventy volatile components were identified from theCaraganaplants, and (Z)-β-ocimene, 1,3-pentadiene, (Z)-3-hexenyl acetate, perillene, chrysanthenone, and limonene were the most abundant volatiles identified from theCaraganaplants. The volatiles were categorized into three groups. Those most attractive toCh. caraganaconsisted of chrysanthenone, 1,3-pentadiene, and (Z)-β-ocimene. Those repellingCh. caraganaconsisted of perillene, dibutyl phthalate, nonanal, and pentadecane, and those irrelevant to each other consisted of (Z)-3-hexenyl acetate, 1-octene, nonene, decanal, (Z)-3-hexenol, and α-pinene. [ABSTRACT FROM AUTHOR]

The amino acid, protein, carbohydrate, and mineral element contents and composition of the xylem, phloem, and leaves of healthy and insect-damaged Caragana korshinskii plants were analyzed to evaluate the changes in the nutrient content of C. korshinskii after damage by Chlorophorus caragana. The amino acid content decreased in the leaf and phloem but increased in the xylem in response to damage, while the protein content did not change in the leaf, increased in the xylem, and decreased in the phloem. The carbohydrate content increased slightly in the leaf but decreased in the xylem and phloem. The six mineral elements analyzed, namely, phosphorous, potassium, magnesium, zinc, manganese, and iron decreased in the xylem, phloem, and leaf. The present results may provide a basis for understanding the mechanisms underlying the effect of C. caragana on the loss of viability of C. korshinskii. [ABSTRACT FROM AUTHOR]

We propose a novel two-step procedure to combine epidemiological data obtained from diverse sources with the aim to quantify risk factors affecting the probability that an individual develops certain disease such as cancer. In the first step, we derive all possible unbiased estimating functions based on a group of cases and a group of controls each time. In the second step, we combine these estimating functions efficiently to make full use of the information contained in data. Our approach is computationally simple and flexible. We illustrate its efficacy through simulation and apply it to investigate pancreatic cancer risks based on data obtained from the Connecticut Tumor Registry, a population-based case–control study, and the Behavioral Risk Factor Surveillance System which is a state-based system of health surveys. Supplementary materials for this article are available online. [ABSTRACT FROM AUTHOR]

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Alopecurus japonicus is a weed in summer crop field, which is harmful to wheat crops. The complete plastome of A. japonicus was reported in this study. The genome was 136,408 bp in length, consisting of an 80,512 bp large single-copy region, a 12,836 bp small single-copy region, and two 21,530 bp inverted repeat regions. The GC content of this plastome was 38.3%. A total of 112 genes were annotated for the plastome of A. japonicus, containing 78 protein-coding genes (PCGs), 30 tRNAs, and 4 rRNAs. Phylogenetic analysis showed that A. japonicus was sister to Alopecurus aequalis. [ABSTRACT FROM AUTHOR]

Alopecurus aequalis is a predominant weed species that distributes widely in North temperate regions. The complete plastome of A. aequalis is reported here. It is a circular molecular of 136,382 bp in length and consists of a large single-copy region (LSC: 80,455 bp), a small single-copy region (SSC: 12,849 bp), and two inverted repeats regions (IRs: 21,539 bp). GC content is 38.3%. This plastome encodes 112 unique genes, including 78 protein-coding genes, 30 tRNAs, and 4 rRNAs. Phylogenetic tree shows that A. aequalis is sister to Poa annua. [ABSTRACT FROM AUTHOR]

The chloroplast (cp) genome sequence of Vitis amurensis has been characterized from Illumina pair-end sequencing. The complete cp genome was 161,014 bp in length, containing a large single-copy region (LSC) of 89,239 bp and a small single-copy region (SSC) of 19,067 bp, which were separated by a pair of 26,354 bp inverted repeat regions (IRs). The genome contained 133 genes, including 88 protein coding genes, 37 tRNA genes, and 8 rRNA genes. The overall GC content is 37.4%, while the corresponding values of the LSC, SSC, and IR regions are 35.3%, 31.7%, and 43.0%, respectively. Further, phylogenetic analysis suggested that the V. amurensis was sister to Vitis coignetiae. [ABSTRACT FROM AUTHOR]

Individuals carrying a germ line mutation of the breast cancer susceptibility gene BRCA2 are predisposed to breast, ovarian, and other types of cancer. The BRCA2 protein has been proposed to function in the repair of DNA double-strand breaks. Using an immunopurification-mass spectrometry approach to identify novel proteins that associate with the BRCA2 gene product, we found that a deubiquitinating enzyme, USP11, formed specific complexes with BRCA2. Moreover, BRCA2 was constitutively ubiquitinated in vivo in the absence of detectable proteasomal degradation. Mitomycin C (MMC) led to decreased BRCA2 protein levels associated with increased ubiquitination, consistent with proteasome-dependent degradation. While BRCA2 could be deubiquitinated by USP11 in transient overexpression assays, a catalytically inactive USP11 mutant had no effect on BRCA2 ubiquitination or protein levels. Antagonism of USP11 function either through expression of this mutant or through RNA interference increased cellular sensitivity to MMC in a BRCA2-dependent manner. All of these results imply that BRCA2 expression levels are regulated by ubiquitination in the cellular response to MMC-induced DNA damage and that USP11 participates in DNA damage repair functions within the BRCA2 pathway independently of BRCA2 deubiquitination. [ABSTRACT FROM AUTHOR]

Context: Development of a reliable and selective anti-inflammatory agent of cyclooxygenase-2 (COX-2), induced or up-regulated by inflammatory/injury stimulus such as IL-1β, TNF-α and LPS in the various types of organs, tissues and cells, with low side effects is a long-standing medicinal chemistry problem with significant social implications. Objective: To target druggable enzymome COX-2 by exploiting NSAIDs and genipin (GEP) in anti-inflammatory infection. Materials and methods: The compound aspirin GEP ester (AGE) was designed by computer-assisted screening, synthesized in the esterification of the acylate derivative and the methylate derivative with Et3N, and evaluated with 20, 40 and 60 mg/kg from days 18 to 24 after immunization in collagen-induced arthritis (CIA) rats by the sequential enzymatic experiments, western-blot analysis and pathological observation methods. Results: AGE exhibited higher binding affinity with COX-1 and displayed the lowest estimated free energy with COX-2 than other ligands built by hanging NSAIDs with GEP, and was characterized by1H NMR,13C NMR and HRMS. AGE was competed against COX-2 with molecule-dependent potencies and selectivity (IC50: 0.36 mM; selectivity index: 275) in the sequential enzymatic experiments and decreased the expression of COX-2 in peripheral blood lymphocytes of CIA rats. AGE (40 and 60 mg/kg) could significantly relieve the secondary hind paw swelling and arthritis index, along with observing AGE attenuated histopathological changes of fibroblast like synovial tissue (FLST) and mesenteric lymph node lymphocytes (MLNL) in CIA rats. Discussion and conclusion: AGE pharmacophore reported herein may be an effective strategy to develop a novel anti-inflammatory agent and potential inhibitor of COX-2. [ABSTRACT FROM AUTHOR]