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Abstract Teleconnections between the tropics and the Arctic have attracted a lot of scientific interest. However, the mechanisms by which tropical synoptic-scale systems influence the variability of Arctic sea ice remain unknown. In this study, we highlight the impacts of tropical cyclone (TC) activity over the western North Pacific (WNP) on Arctic Sea Ice Concentration (SIC) using observational evidence and climate model simulation experiments. Our findings demonstrate significant positive correlations between Accumulated Cyclone Energy (ACE) in the WNP and SIC in the Arctic-Pacific Sector (APS), particularly when considering a 30-day lag. The TC activity over the WNP induces Rossby wave train propagation towards the Arctic, leading to anomalous cyclonic circulation over the upper troposphere of the APS. The anomalous cyclone over the Arctic, on one hand, signifies the deepening of the Arctic polar vortex and diminishes adiabatic warming over the APS, subsequently inducing cooling and drying of the lower Arctic air. This process reduces downward longwave radiation, promoting an increase in September APS SIC. On the other hand, the anomalous cyclone over the Arctic hinders the export of sea ice and local melting processes throughout the Fram Strait. These findings contribute to a deeper comprehension of tropics-Arctic teleconnections.

Abstract This study focuses on the primary synoptic‐scale patterns and precursors of extreme and non‐extreme precipitation over the Tibetan Plateau (TP). Atmospheric circulation anomalies and their precursors associated with regional extreme precipitation events (REPE) demonstrate distinct precursor wave train and heightened intensity than regional non‐extreme precipitation events (non‐REPE). Specifically, REPE over the northwestern TP (NWTP) exhibits a geopotential height anomaly induced by a latitudinal propagating Rossby wave train along 40°N. In contrast, over the southeastern TP (SETP), REPE is characterized by a geopotential height anomaly caused by a northwest‐southeastward propagating Rossby wave train. The ascending motion anomalies of REPE over both NWTP and SETP are primarily attributed to the geostrophic zonal temperature advection, which is significantly stronger during REPE compared to non‐REPE. This finding provides valuable insights for forecasting summer extreme precipitation over TP.

Introduction: Malignant hypertension (mHTN) is a hypertensive emergency. Thrombotic microangiopathy (TMA) is a widespread complication of mHTN. Few studies have evaluated whether glomerular hematuria provides prognostic information for renal dysfunction in patients with mHTN-associated TMA. Methods: This observational cohort study included 292 patients with mHTN-associated TMA based on renal biopsy. Propensity-score matching (PSM) analysis was conducted to adjust for clinical characteristics in a comparison between with and without glomerular hematuria. Cox regression was employed to identify risk factors for renal prognosis. Results: A total of 70 patients with glomerular hematuria were compared to 222 patients with non-glomerular hematuria. After PSM, 67 pairs of patients with mHTN-associated TMA were matched. Patients with glomerular hematuria exhibited lower serum albumin levels, higher 24-h proteinuria, and a higher prevalence of glomerular sclerosis than those with non-glomerular hematuria. Glomerular hematuria was independently associated with deteriorated renal function compared with non-glomerular hematuria (HR: 0.51; 95% CI: 0.29–0.89, p = 0.019). This association remained significant after PSM (HR: 0.51; 95% CI: 0.28–0.91, p = 0.022). Additionally, glomerular hematuria was independently associated with renal replacement therapy (RRT) (HR: 3.14; 95% CI: 2.06–5.66, p < 0.001). This difference remained significant after PSM comparison (HR: 2.41; 95% CI: 1.34–4.33, p = 0.003). Furthermore, despite intensive blood pressure control, patients with glomerular hematuria experienced a higher incidence of RRT and a poorer recovery in renal function, specifically a 25% reduction of creatinine levels, compared to patients with non-glomerular hematuria. Conclusion: Glomerular hematuria is significantly associated with an increased risk of adverse renal outcomes in patients with mHTN-associated TMA.

Transglutaminase 2 (TGase2) has been shown to contribute to the mesangial IgA1 deposition in a humanized mouse model of IgA nephropathy (IgAN), but the mechanism is not fully understood. In this study, we found that inhibition of TGase2 activity could dramatically decrease the amount of polymeric IgA1 (pIgA1) isolated from patients with IgAN that interacts with human mesangial cells (HMC). TGase2 was expressed both in the cytosol and on the membrane of HMC. Upon treatment with pIgA1, there were more TGase2 recruited to the membrane. Using a cell model of mesangial deposition of pIgA1, we identified 253 potential TGase2-associated proteins in the cytosolic fraction and observed a higher concentration of cellular vesicles and increased expression of Ras homolog family member A (RhoA) in HMC after pIgA1 stimulation. Both the amount of pIgA1 deposited on HMC and membrane TGase2 level were decreased by inhibition of the vesicle trafficking pathway. Mechanistically, TGase2 was found to be coprecipitated with RhoA in the cellular vesicles. Membrane TGase2 expression was greatly increased by overexpression of RhoA, while it was reduced by knockdown of RhoA. Our in vitro approach demonstrated that TGase2 was transported from the cytosol to the membrane through a RhoA-mediated vesicle-trafficking pathway that can facilitate pIgA1 interaction with mesangium in IgAN.

Objective End-stage kidney disease (ESKD) patients have a higher risk of antibiotic-associated encephalopathy (AAE) than other patients. We aimed to evaluate the prevalence, risk factors and outcomes of AAE in ESKD patients.Method A retrospective study of ESKD patients treated with intravenous antibiotics in our hospital from Jan. 1, 2006, to Dec. 31, 2015 was performed. AAE was diagnosed by the modified Delphi method. Control individuals were randomly selected from the remaining patients who did not exhibit neurologic symptoms. Logistic regression analysis was used to identify risk factors for AAE as well as the association between AAE and outcome.Result A total of 2104 patients were included in the study. The prevalence of AAE in our study was 4.4% (92/2104). The multivariate logistic regression analysis revealed that anuria (OR = 8.04, 95% CI: 4.13–15.65, p

Introduction: A previous genome-wide association study has identified CARD9 (caspase recruitment domain family member 9) as a susceptibility gene for Immunoglobulin A nephropathy (IgAN), which encodes an adapter protein and is related to mucosal immunity. This study aims to investigate the association of CARD9 variants with the clinicopathological phenotypes and prognosis of IgAN. Methods: Eight SNPs within CARD9 were genotyped using Sequenom MassARRAY iPLEX for 986 IgAN patients in this study. Logistic and linear regression analyses adjusted for age and gender were performed to evaluate the effects of CARD9 gene polymorphisms on clinicopathological phenotypes. The Kaplan‒Meier method and Cox proportional hazard models were applied to analyse the associations between genetic variants and renal survival. Results: The T allele of rs10747047 was strongly associated with high levels of serum creatinine (P = 0.005) and the lower levels of estimated glomerular filtration rate (P = 0.005). The rs10870149-G and rs10870077-C allele were associated with elevated 24-h urine protein excretion (P = 0.041 and 0.022, respectively) and more serious segmental glomerulosclerosis lesions (P = 0.005 and 0.041, respectively) in IgAN patients. Carriers with the T allele of rs10781533 and the C allele of rs3812552 also presented with severe segmental glomerulosclerosis lesions (P = 0.001 and 0.010, respectively). Additionally, rs10747047-C and rs10870077-C alleles were independently related to the poor prognosis of IgAN patients after adjustments for covariates (TT vs. CC HR = 0.138, 95% CI = 0.022-0.871, P = 0.035; GG vs. CC HR = 0.321, 95% CI = 0.123, 0.836, P = 0.020, respectively). Conclusion: CARD9 variants are associated with disease severity and rapid disease progression for IgAN in a Chinese Han population.

BackgroundPrevious research has supported the association between the triglyceride–glucose index (TyG index) and the incidence and prognosis of cardiovascular disease. However, the association between the TyG index and the prognosis of patients with acute coronary syndrome (ACS) without diabetes mellitus (DM) who underwent emergency percutaneous coronary intervention (PCI) with drug-eluting stents (DESs) has not been thoroughly investigated, and these patients may easily be neglected. Therefore, this study aimed to investigate the association between the TyG index and major adverse cardiovascular and cerebrovascular events (MACCEs) in Chinese ACS patients without DM who underwent emergency PCI with DES.MethodsThe total number of ACS patients without DM who underwent emergency PCI with DES for this study was 1650. Ln [fasting triglycerides (mg/dL) ×fasting plasma glucose (mg/dL)/2] is the formula used to calculate the TyG index. According to the TyG index, we classified the patients into two groups. The frequency of the following endpoint events was calculated and compared between the two groups: all-cause death, non-fatal myocardial infarction (MI), non-fatal ischemia stroke, ischemia-driven revascularization and cardiac rehospitalization.ResultsAfter a median of 47 months of follow-up [47 (40, 54)], 437 (26.5%) endpoint events were recorded in total. The TyG index was further demonstrated to be independent of MACCE by multivariable Cox regression analysis (hazard ratio [HR], 1.493; 95% confidence interval [CI], 1.230–1.812; p

BackgroundIn patients with acute coronary syndrome (ACS), prolonged dual antiplatelet therapy (DAPT) may reduce ischemic events and increase the risks of bleeding events differently in different ethnic groups. However, whether prolonged DAPT in Chinese patients with ACS following emergency percutaneous coronary intervention (PCI) with drug-eluting stents (DES) will be beneficial or dangerous remains unclear. This study aimed to examine the potential benefits and risks of prolonged DAPT in Chinese patients with ACS who have undergone emergency PCI with DES.MethodsThis study included 2,249 patients with ACS who underwent emergency PCI. If DAPT was continued for 12 or 12–24 months, it was classified as the standard (n = 1,011) or prolonged (n = 1,238) DAPT group, respectively. The incidence of the following endpoint events was determined and compared between the two groups: composite bleeding event (BARC 1 or 2 types of bleeding and BARC 3 or 5 types of bleeding) and major adverse cardiovascular and cerebrovascular events (MACCEs) [ischemia-driven revascularization, non-fatal ischemia stroke, non-fatal myocardial infarction (MI), cardiac death, and all-cause death].ResultsAfter a median period of 47 months of follow-up [47 (40, 54)], the rate of composite bleeding events was 13.2% (n = 163) in the prolonged DAPT group and 7.9% (n = 80) in the standard DAPT group [odds ratio (OR) 1.765, 95% confidence interval (CI) 1.332–2.338, p < 0.001]. The rate of MACCEs was 11.1% (n = 138) in the prolonged DAPT group and 13.2% (n = 133) in the standard DAPT group (OR 0.828, 95% CI 0.642–1.068, p = 0.146). The DAPT duration was further shown to be insignificantly correlated with MACCEs as per the multivariable Cox regression model (HR, 0.813; 95% CI, 0.638–1.036; p = 0.094). No statistically significant difference was observed between the two groups. However, the DAPT duration was a separate predictor of composite bleeding events according to the multivariable Cox regression model (HR 1.704, 95% CI 1.302–2.232, p < 0.001). Compared with the standard DAPT group, the prolonged DAPT group had substantially more BARC 3 or 5 types of bleeding events (3.0 vs. 0.9% in those with standard DAPT, OR 3.430, 95% CI 1.648–7.141, p < 0.001) and BARC 1 or 2 types of bleeding events (10.2 vs. 7.0% in those with standard DAPT, OR 1.500, 95% CI 1.107–2.032, p = 0.008).ConclusionThe prolonged DAPT group had a considerably greater incidence of composite bleeding events than the standard DAPT group. No statistically significant difference was observed in the incidence of MACCEs between the two groups.

This paper studies the interdecadal transition of interannual variability of summertime intraseasonal rainfall (SIR) over South China (SC). It is found that after the mid-1990s (1995/96), the interannual oscillation of SIR over SC has significantly enhanced. The inner connection and possible physical processes associated with the atmospheric intraseasonal oscillation (ISO) involved in the interdecadal transition of the interannual variability of SIR over SC are discussed. The results show that the “Silk Road” teleconnection wave trains distributed zonally across Eurasia from western Europe to northeastern China in the mid-to-high latitudes and the intraseasonal component of the western Pacific subtropical high (WPSH) are two major factors that control the increase of SIR interannual oscillation over SC after 1996. In the period after 1996, the low-frequency perturbation kinetic energy of the wave activity flux associated with the “Silk Road” teleconnection converges more significantly over SC. At the same time, note that the positive SIR anomaly years tend to be in the El Niño decaying phase, the eastward-propagating Kelvin waves triggered by the warm Indian ocean can promote the development of the western Pacific anticyclonic anomaly, which subsequently strengthens the WPSH effectively. The interannual variability of the WPSH east-west movement increases the low-level intraseasonal change of atmospheric circulation over SC. Low-level circulation anomalies in the low latitudes combined with the dispersion of Rossby wave energy in the mid-to-high latitudes eventually lead to an increased interannual variability of SIR over SC.

Activation of the alternative pathway (AP) of complement is thought to play an important role in Immunoglobin A nephropathy (IgAN). Our previous study showed that rs4151657 within the complement factor B (CFB) gene increased the risk of IgAN. The protein encoded by the CFB gene is an initial factor that promotes AP activation. The aim of this study was to investigate whether other variants of CFB confer susceptibility to IgAN and elucidate their potential roles in AP activation. A total of 1,350 patients with IgAN and 1,420 healthy controls were enrolled and five tag single-nucleotide polymorphisms were selected for genotyping. The levels of key AP components, such as CFB, complement factor H and complement split product C3a, were measured by enzyme-linked immunosorbent assay. Molecular docking and molecular dynamic simulation were carried out to characterize the mutation of residues in the protein structure and the dynamic properties of wide type and mutation models of CFB protein. The allele-specific effect on CFB expression and its binding affinity to C3b were investigated through cell transfection and surface plasmon resonance analysis, respectively. We found that rs12614 significantly reduced the risk of IgAN (OR = 0.69, 95% CI = 0.52–0.91, P = 0.009), and the rs12614-T (R32W mutation) was correlated with lower CFB levels, higher serum C3 level, and less mesangial C3 deposition in patients with IgAN. The structural model showed that the R32W mutation reduced the structural stability of CFB protein. Furthermore, in vitro study revealed that rs12614-T decreased the expression of CFB and reduced its binding affinity to C3b by four-fold compared with rs12614-C. In conclusion, the rs12614-T in CFB was associated with low risk of IgAN probably by attenuating AP activation.

Recent studies have proposed a relatively reliable metric, i.e., the annual-mean latitude of tropical cyclone (TC) lifetime maximum intensity, to evaluate the observed trend of poleward migration of TC. The documented trend in the existing records of the metric suggests that anthropogenic factors might make considerable contributions to the poleward migration of TC. However, here we show that there is no significant TC migration trend in the western North Pacific (WNP). Instead, large interdecadal variation is found in the WNP TC track over the past 35 years. Rather than the anthropogenic factors, it is the natural variability, especially the Interdecadal Pacific Oscillation (IPO), that plays a key role in modulating the migration of WNP TC track. The IPO-related TC migration is assumed to cause systematic changes (i.e., increases and decreases) in regional hazard exposure and risk. The impact of IPO on the WNP TC migration is attributed to its influences on the large-scale circulation, TC genesis potential index, and the potential intensity in the TC prevailing region of the WNP.

This study focuses on the interdecadal transition of summer rainfall interannual variability over the Yellow-Huaihe River valley (YHRV). It is found that the interannual variability of summer rainfall over the YHRV becomes significantly weakened after the late 2000s. In the decade before the late 2000s (hereafter P1), the variance is 1.28 mm d−1 and the mean value of interannual variability is 1.49 mm d−1. In the decade after the late 2000s (P2), the variance is 0.35 mm d−1 and the mean value of interannual variability is 0.62 mm d−1. The variance and mean value of summer rainfall interannual variability have considerably decreased by 72.7% and 58.4% since the late 2000s, respectively. The reasons for the aforementioned interdecadal transition are explored. The results show that the interdecadal shift of the East Asian jet stream axis and the western Pacific subtropical high (WPSH) are two major factors leading to the interdecadal transition of summer rainfall interannual variability over the YHRV. The northward shift of the jet stream axis, which resembles the Pacific-Japan (PJ) pattern, suppresses the development of summer rainfall over the YHRV. The interannual oscillation of WPSH in P1 is more significant than that in P2, which is consistent with the weakened interannual variability of summer rainfall in P2. Further analysis reveals that the modulation factors responsible for the above changes are El Niño in its decaying phase in the equatorial central eastern Pacific and the warming in the Maritime continent and the western Pacific (WP) in P1. While in P2, the primary modulation factor is La Niña in its developing phase in the equatorial central eastern Pacific. As for the mechanism of the growth of summer rainfall in P1 positive years, the WP warm pool and El Niño in its decaying phase strengthen the Walker circulation in the tropical Pacific and induce Hadley circulation, whose ascending branch over the YHRV provides a favorable condition for the development of rainfall. At the same time, the northward propagation of Rossby waves in response to the above SSTA pattern suppresses convective activities over the Northwestern Pacific (NWP), which indirectly intensifies the WPSH. As a result, the PJ pattern is triggered and provides a favorable large-scale circulation condition for the growth of rainfall.

C9orf72 expansion mutations are the most common genetic cause of ALS and FTD, which have limited therapies. The authors generate stereopure oligonucleotides that selectively deplete expansion-containing transcripts and protect against expansion-associated pathologies in preclinical models.

Background In the first year of dialysis, patients are vulnerable to cardiovascular disease (CVD) hospitalization, but knowledge regarding the risk factors and long-term outcomes of cardiovascular readmission within the first year after dialysis in incident continuous ambulatory peritoneal dialysis (CAPD) patients is limited. Methods This retrospective cohort study was conducted in incident CAPD patients. The demographic characteristics, laboratory parameters, and CVD readmission were collected and analyzed. The primary outcome was all-cause mortality, and the secondary outcomes included CVD mortality, infection-related mortality and technique failure. A logistic regression was used to identify the risk factors associated with CVD readmission within the first year after dialysis. Cox proportional hazards models were used to evaluate the association between CVD readmission and the outcomes. Results In total, 1589 peritoneal dialysis (PD) patients were included in this study, of whom 120 (7.6%) patients had at least one episode of CVD readmission within the first year after dialysis initiation. Advanced age, CVD history, and a lower level of serum albumin were independently associated with CVD readmission. CVD readmission within the first year after dialysis was significantly associated with all-cause (HR 2.66, 95%CI 1.91–3.70, p

Introduction This study aimed to investigate the clinical characteristics, risk factors, and outcomes of infection-related hospitalization (IRH) in patients with lupus nephritis (LN) and ANCA glomerulonephritis after intensive immunosuppressive therapy. Methods Patients diagnosed with LN or ANCA glomerulonephritis who received intensive immunosuppressive therapy at the First Affiliated Hospital of Sun Yat-sen University from 2005 to 2014 were enrolled. Demographics, laboratory parameters, immunosuppressive agents, and IRH details were collected. Multivariable Cox regression was used, and hazard ratios (HRs) and 95% confidence intervals (CIs) were reported. Results Totally, 872 patients with 806 LN and 66 ANCA glomerulonephritis were enrolled, and 304 (34.9%) patients with 433 episodes of IRH were recorded. ANCA glomerulonephritis patients were more vulnerable to IRH than LN patients (53.0% vs. 33.4%, p = .001). Multivariable Cox regression analysis showed that ANCA glomerulonephritis (HR = 1.62, 95% CI: 1.06–2.49, p = .027), diabetes (HR = 1.82, 95% CI: 1.03–3.22, p = .039) and a higher initial dose of prednisone (HR = 1.01, 95% CI: 1.00–1.02, p = .013) were associated with a higher likelihood of IRH. Higher albumin (HR = 0.96, 95% CI: 0.94–0.98, p

Background and Aims. Mean platelet volume to platelet count ratio (MPV/PC) has been found to be an independent risk factor for mortality in various diseases, including cardiovascular disease, cancer, and hemodialysis. We aimed to evaluate the association between MPV/PC and all-cause and cardiovascular (CV) mortality in peritoneal dialysis (PD) patients. Methods and Results. We conducted a retrospective cohort study at a single center and enrolled 1473 PD patients who were catheterized at our PD center from January 1, 2006, to December 31, 2013. All patients were divided into four groups according to the quartiles of baseline MPV/PC levels and followed up until December 31, 2018. A total of 453 patients died, and 221 deaths were caused by cardiovascular disease during a median follow-up time of 48.0 (21.9-82.2) months. There was a significant interaction by age of association between MPV/PC level and all-cause mortality (P=0.009), and multivariate Cox regression analysis showed that higher MPV/PC level was related to a decreased risk of all-cause and CV mortality in PD patients aged

Heavy metal pollution in soils threatens food safety and human health. Calcium sulfate and ferric oxide are commonly used to immobilize heavy metals in soils. However, the spatial and temporal variations of the heavy metals’ bioavailability in soils regulated by a combined material of calcium sulfate and ferric oxide (CSF) remain unclear. In this work, two soil column experiments were conducted to investigate the spatial and temporal variations of CSF immobilized Cd, Pb, and As. In the horizontal soil column, the results showed that CSF’s immobilization range for Cd increased over time, and adding CSF in the center of the soil column decreased the concentrations of bioavailable Cd significantly, up to 8 cm away by day 100. The CSF immobilization effect on Pb and As only existed in the center of the soil column. The CSF’s immobilization depths for Cd and Pb in the vertical soil column increased over time and extended to 20 cm deep by day 100. However, the CSF’s immobilization depths for As only extended to between 5 and 10 cm deep after 100 days of incubation. Overall, the results from this study can serve as a guide to determine the CSF application frequency and spacing distance for the in-situ immobilization of heavy metals in soils.

The current study concentrates on the interdecadal shift in the interannual variability of summertime precipitation (IVSP) over South China (SC). Possible causes for the interdecadal shift are explored. The IVSP on a decadal time scale presents a significant weakening after the mid-2000s. The results show that the variances of the interannual precipitation variability over the SC region between 1993 and 2004 (hereafter S1) and 2005 and 2020 (hereafter S2) are 1.40 mm d−1 and 0.58 mm d−1, respectively. The variance of the IVSP has decreased by 58.6% since the mid-2000s. The current study reveals that the reduction in the IVSP over SC after the mid-2000s is prominently attributed to the weakened impact of the East Asia-Pacific (EAP) teleconnection. Before the mid-2000s, the interannual variation of the east-west movement of the western Pacific subtropical high was more significant. The warming over the tropical central-eastern Pacific (CEP) and cooling over the western Pacific (WP) suppress the Walker cell in the tropical Pacific and induce anomalous Hadley cell with its descending branch over the WP in the wet years. The anomalies of SST and atmospheric circulation show opposite phases in the dry years. This SSTA pattern enhances the northward propagation of the EAP teleconnection through a Rossby-wave-type response, which triggers an ascending/descending branch with active/suppressed convection over the northwestern Pacific in the wet/dry years. Therefore, the cooling WP and El Niño in its developing phase provide an ideal condition for more precipitation over SC. However, the above ocean–atmosphere interactions changed after the mid-2000s. The significant SST changes in the tropical CEP and the WP weaken the EAP teleconnection and atmospheric circulation anomalies over SC, leading to a significant interdecadal reduction in the IVSP over SC after the mid-2000s.

The capability to reproduce tropical cyclones (TCs) realistically is important for climate models. A recent study proposed a method for quantitative evaluation of climate model simulations of TC track characteristics in a specific basin, which can be used to rank multiple climate models based on their performance. As an extension of this method, we propose a more comprehensive method here to evaluate the capability of climate models in simulating multi-faceted characteristics of global TCs. Compared with the original method, the new method considers the capability of climate models in simulating not only TC tracks but also TC intensity and frequency. Moreover, the new method is applicable to the global domain. In this study, we apply this method to evaluate the performance of eight climate models that participated in phase 5 of the Coupled Model Intercomparison Project. It is found that, for the overall performance of global TC simulations, the CSIRO Mk3.6.0 model performs the best, followed by GFDL CM3, MPI-ESM-LR, and MRI-CGCM3 models. Moreover, the capability of each of these models in simulating global TCs differs substantially over different ocean basins.

Precipitation observations collected at weather stations in eastern China, the NCEP/NCAR reanalysis data, the tropical cyclone (TC) Best Track Dataset, and a sensitivity numerical experiment were used in the present study to investigate the role in the East Asian summer monsoon (EASM) system played by frequent TC activities over the western North Pacific (WNP). Results indicated that, in active TC years, the EASM is stronger and the southerly winds in the lower troposphere advance farther north and reach higher latitudes. Meanwhile, the monsoon rain belt remains in the lower and middle reaches of the Yangtze River valley for a relatively short period, leading to less precipitation there. Both the western Pacific subtropical high and the South Asian high weaken with the northward shift of the ridgelines for both high-pressure systems as well as the East Asian subtropical upper-level jet. Therefore, the impacts of frequent TC activities over the WNP on each individual component of the EASM are in phase with those of the stronger EASM itself, amplifying features of the already strengthened EASM.

Background: Increased serum hepcidin-25 level is associated with excess mortality in hemodialysis patients. However, there is a dearth of published information about its predictive effect for survival in patients on peritoneal dialysis (PD). The purpose of this study is to evaluate the association of serum hepcidin-25 with the risk of mortality in PD patients.Methods: Serum hepcidin-25 level was measured using an enzyme-linked immunosorbent assay in a prospective cohort study of PD patients with stored serum samples at baseline. Multivariate linear regression model was used to determine clinical characteristics associated with serum hepcidin-25 concentration. We evaluated the relationship between serum hepcidin-25 and all-cause mortality using a Cox proportional hazards model and the relationship between hepcidin-25 and cardiovascular (CV) and infection-related deaths using competing-risks regression models.Results: In total, 513 PD patients were included in this study. The median serum hepcidin-25 level was 40.9 (17.9–85.9) ng/mL. Body mass index and serum ferritin were positively correlated with serum hepcidin-25 levels. During a median follow-up period of 64.1 months, 122 (24%) patients died, including 61 (50%) CV deaths and 32 (26%) infection-related deaths. In multivariable analysis, patients with the highest tertile of serum hepcidin-25 had a greater risk of all-cause [adjusted hazard ratio (aHR) 1.85, 95% confidence interval (95%CI), 1.14 to 3.00, P = 0.013] and infection-related mortality (adjusted subdistribution hazard ratio [aSHR], 2.61; 95%CI, 1.01 to 6.76, P = 0.049) when compared with those in the second tertile. However, no significant relationship was observed between serum hepcidin-25 and CV mortality.Conclusions: Higher baseline serum hepcidin-25 level was associated with increased risk for all-cause and infection-related mortality in PD patients.

This study reveals the impacts of cumulus parameterization schemes (CPSs) on the simulation of interannual and interdecadal variations of Meiyu in the middle and lower reaches of the Yangtze River valley (Yangtze Meiyu) by using a regional climate model. A multiple 55-year (1955-2009) simulation of Yangtze Meiyu is conducted using RegCM4.6 with different CPSs, including the Emanuel scheme, Kuo scheme, and Grell scheme. It is found that all the CPSs have good performances in simulating the interannual variation of Yangtze Meiyu rainfall amounts. However, a large bias is found in the simulated interdecadal variation of Yangtze Meiyu rainfall amount by the three CPSs. Because the Emanuel CPS has good performance in the simulation of both interannual and interdecadal variations of Yangtze Meiyu, its overall performance in the simulation of the total amount of Yangtze Meiyu is the best among the three CPSs. The second best CPS is the Grell scheme, and the worst is the Kuo scheme. The model convergence in simulating the distribution of Yangtze Meiyu shows an obvious characteristic of interdecadal variation. During the years with strong summer monsoon and northward rain belt, the simulated distributions of Yangtze Meiyu by the three CPSs are quite different, and the model convergence is weak. On the contrary, during the years with weak summer monsoon and southward rain belt, the simulated distributions of Yangtze Meiyu by the three CPSs are similar to each other, and the model convergence is strong. As a result, when the well-known interdecadal change happens in the late 1970s, the monsoon changes from strong to weak, whereas the model convergence changes from weak to strong.

Abstract In this study, we compared the performance of two potential predicators, that is, El Niño–Southern Oscillation (ENSO) index (Niño‐3.4) and mega‐ENSO index, in the seasonal forecast of tropical cyclone (TC) activity and its spatial distribution over the western North Pacific (WNP) during the extended TC season, which is of public concern. Our results clearly show that, although both mega‐ENSO and Niño‐3.4 indices in the preceding May are important predictors for the seasonal predication, the relative‐sea surface temperature (SST)‐dependent mega‐ENSO exhibits a higher skill in the seasonal forecasting compared with the absolute‐SST‐dependent ENSO. Further results show that, despite of stronger destructiveness of TCs in high mega‐ENSO (El Niño) years than in low mega‐ENSO (La Niña) years, more attention should be paid to the TCs in low mega‐ENSO years, which are more likely to occur in coastal areas compared with the TCs in high mega‐ENSO years. Due to the responses of TC genesis, TC potential intensity, and large‐scale flow to the SST change in low mega‐ENSO years, the WNP TCs tend to originate in the northwestern quadrant and intensify at high latitudes and then turn northwestward over the TC prevailing region, which contributes to the northwestward migration of the WNP TC exposure in terms of track density and destructiveness density and thus imposes more risks in the coastal areas in low mega‐ENSO years. In addition, despite the significant predication skill in forecasting TC activity when using mega‐ENSO/Niño‐3.4 as a single predicator, it is still far to predict reliable WNP activity, especially its spatial distribution, without considering other predictors.

Abstract State‐of‐the‐art climate models are extremely useful tools, but they all have biases when simulating tropical cyclone (TC) genesis location. These biases contribute to discrepancies in simulating other characteristics of TC activities (e.g., track, intensity, and duration) and even the surrounding large‐scale circulation. The genesis potential index (GPI) is a useful tool to evaluate the performance of climate models in simulating TC genesis. Here, it is employed to investigate possible causes of simulation biases of TC genesis location in western North Pacific using the downscaled Community Atmosphere Model Version 5 (CAM5) climate model and observations. We find that GPI can reasonably describe the spatial pattern of TC genesis location in either observation or simulation. By having one of GPI‐related variables (i.e., low‐level absolute vorticity, middle‐level relative humidity, vertical wind shear, and potential intensity) change with the others set to stable while testing single variable, the contributions of environmental fields associated with GPI are examined and a possible cause of TC genesis biases is revealed. Due to the overestimated humidity in the east region of western North Pacific, the simulated GPI high value region is to the east of the observed one, and more TCs in the downscaled CAM5 model generate farther east than in observation. These results imply that the biases in simulated humidity and thus TC genesis location may be reduced by correcting the evaporation rate in the deep convection scheme, since the evaporation rate is closely related to environment humidity change as suggested by previous studies.

Abstract The response of tropical cyclone (TC) destructive potential to global warming is an open issue. A number of previous studies have ignored the effect of TC size change in the context of global warming, which resulted in a significant underestimation of the TC destructive potential. The lack of reliable and consistent historical data on TC size limits the confident estimation of the linkage between the observed trend in TC size and that in sea surface temperature (SST) under the background of global climate warming. A regional atmospheric model is used in the present study to investigate the response of TC size and TC destructive potential to increases in SST. The results show that a large-scale ocean warming can lead to not only TC intensification but also TC expansion. The TC size increase in response to the ocean warming is possibly attributed to the increase in atmospheric convective instability in the TC outer region below the middle troposphere, which facilitates the local development of grid-scale ascending motion, low-level convergence and the acceleration of tangential winds. The numerical results indicate that TCs will become stronger, larger, and unexpectedly more destructive under global warming.

Neural stem cells and progenitor cells (NPCs) are increasingly appreciated to hold great promise for regenerative medicine to treat CNS injuries and neurodegenerative diseases. However, evidence for effective stimulation of neuronal production from endogenous or transplanted NPCs for neuron replacement with small molecules remains limited. To identify novel chemical entities/targets for neurogenesis, we had established a NPC phenotypic screen assay and validated it using known small-molecule neurogenesis inducers. Through screening small molecule libraries with annotated targets, we identified BET bromodomain inhibition as a novel mechanism for enhancing neurogenesis. BET bromodomain proteins, Brd2, Brd3, and Brd4 were found to be downregulated in NPCs upon differentiation, while their levels remain unaltered in proliferating NPCs. Consistent with the pharmacological study using bromodomain selective inhibitor (+)-JQ-1, knockdown of each BET protein resulted in an increase in the number of neurons with simultaneous reduction in both astrocytes and oligodendrocytes. Gene expression profiling analysis demonstrated that BET bromodomain inhibition induced a broad but specific transcription program enhancing directed differentiation of NPCs into neurons while suppressing cell cycle progression and gliogenesis. Together, these results highlight a crucial role of BET proteins as epigenetic regulators in NPC development and suggest a therapeutic potential of BET inhibitors in treating brain injuries and neurodegenerative diseases.

AlBeMet 162 (Materion Co., formerly Brush Wellman) has been irradiated with 145MeV protons up to 1.2×1020cm−2 fluence, with irradiation temperatures in the range of 100–220°C. Macroscopic post-irradiation evaluation on the evolution of mechanical and thermal properties was integrated with a comprehensive X-ray- diffraction study using high-energy monochromatic and polychromatic X-ray beams, which offered a microscopic view of the irradiation damage effects on AlBeMet. The study confirmed the stability of the metal–matrix composite, its resistance to proton damage, and the continuing separation of the two distinct phases, fcc aluminum and hcp beryllium, following irradiation. Furthermore, based on the absence of inter-planar distance change during proton irradiation, it was confirmed that the stacking faults and clusters on the Al (111) planes are stable, and thus can migrate from the cascade region and be absorbed at various sinks. XRD analysis of the unirradiated AlBeMet 162 showed clear change in the texture of the fcc phase with orientation especially in the Al (111) reflection which exhibits a “non-perfect” six-fold symmetry, implying lack of isotropy in the composite.

Stabilizing heavy metal contaminated soil is a popular remediation model in China. Many waste biomass materials have been proven to have a stabilizing effect on heavy metals but also have several advantages like environmental friendliness and waste utilization. In this study, the waste crab shells were selected as raw materials for stabilizing agents, and the stabilization effects on different heavy metals after incineration and pyrolysis treatment was explored. The obvious stabilizing effect of pyrolytic crab shell powder on Cr and Cr6+ was observed, and the excellent stabilizing effect of the incinerated crab shell powder on Cu, Zn, Pb, Ni was also confirmed. After mixing the two crab shells, the overall stabilization effect of Cr and Cr6+, Cu, Zn, Pb, Ni and other heavy metals can reach the desired level (The stabilization efficiency of Cr, Cr6+, Cu, Zn, Pb, Ni was 89.0%, 89.1%, 93.3%, 86.1% and 96.1%,respectively).

The Weather Research Forecast model (WRF) is used to examine the destructive potential of tropical cyclone (TC) Shanshan (2006) at various horizontal resolutions (7.5 km⁻1 km) with different cumulus parameterization (CP) schemes. It is found that the calculated Power Dissipation Index (PDI) increases while the size-dependent destructive potential (PDS) decreases as the grid spacing decreases for all CP-scheme simulations, which indicates a weak model convergence in both PDI and PDS calculations. Moreover, it is change of the storm intensity and inner-core size that lead to the non-convergence of PDI and PDS respectively. At a higher resolution, convection becomes more explicitly resolved, which leads to larger diabatic heating. As a result, the radial pressure gradient force (PGF) increases, and the radius of maximum wind (RMW) decreases. The area of strong diabatic heating subsequently becomes closer to the TC center, which further increases the TC intensity and the PGF near the eyewall. With such a positive feedback loop, the PGF increases and the RMW decreases as the resolution increases. Note that a perfect model should converge well in the simulation of both TC intensity and size, and thus converge in the PDS. For some CP experiments, the calculated PDS convergence is relatively strong, but it is a result of offset between the non-convergent simulations of TC intensity and size. In contrast, the Grell⁻Freitas scheme exhibits a stronger convergence in the simulations of TC intensity and size, although the convergence in PDS is relatively weak, but is closer to the truth.

For centuries, mulberry leaf has been used in traditional Chinese medicine for the treatment of diabetes. This study aims to test the prevention effects of a proprietary mulberry leaf extract (MLE) and a formula consisting of MLE, fenugreek seed extract, and cinnamon cassia extract (MLEF) on insulin resistance development in animals. MLE was refined to contain 5% 1-deoxynojirimycin by weight. MLEF was formulated by mixing MLE with cinnamon cassia extract and fenugreek seed extract at a 6:5:3 ratio (by weight). First, the acute toxicity effects of MLE on ICR mice were examined at 5 g/kg BW dose. Second, two groups of normal rats were administrated with water or 150 mg/kg BW MLE per day for 29 days to evaluate MLE's effect on normal animals. Third, to examine the effects of MLE and MLEF on model animals, sixty SD rats were divided into five groups, namely, (1) normal, (2) model, (3) high-dose MLE (75 mg/kg BW) treatment; (4) low-dose MLE (15 mg/kg BW) treatment; and (5) MLEF (35 mg/kg BW) treatment. On the second week, rats in groups (2)-(5) were switched to high-energy diet for three weeks. Afterward, the rats were injected (ip) with a single dose of 105 mg/kg BW alloxan. After four more days, fasting blood glucose, post-prandial blood glucose, serum insulin, cholesterol, and triglyceride levels were measured. Last, liver lysates from animals were screened with 650 antibodies for changes in the expression or phosphorylation levels of signaling proteins. The results were further validated by Western blot analysis. We found that the maximum tolerance dose of MLE was greater than 5 g/kg in mice. The MLE at a 150 mg/kg BW dose showed no effect on fast blood glucose levels in normal rats. The MLE at a 75 mg/kg BW dose and MLEF at a 35 mg/kg BW dose, significantly (p < 0.05) reduced fast blood glucose levels in rats with impaired glucose and lipid metabolism. In total, 34 proteins with significant changes in expression and phosphorylation levels were identified. The changes of JNK, IRS1, and PDK1 were confirmed by western blot analysis. In conclusion, this study demonstrated the potential protective effects of MLE and MLEF against hyperglycemia induced by high-energy diet and toxic chemicals in rats for the first time. The most likely mechanism is the promotion of IRS1 phosphorylation, which leads to insulin sensitivity restoration.

In the servicization business model, a service-oriented manufacturer sells the service derived from its products. Because of the special compensation method, a service-oriented manufacturer is more likely to be underfunded. A Stackelberg game is formulated to investigate the interaction among a bank, a manufacturer, and an operator, in which two financing strategies are considered: bank financing and guaranteed (internal) financing. The difference between these two strategies is who bears the bankruptcy risk of the manufacturer. With bank financing, the bank bears the risk and determines the interest rate, while under guaranteed financing, the operator sets a guaranteed financing interest rate. We find that under bank financing, the low operating efficiency of the manufacturer increases the bank's share of the supply chain benefits. In particular, the service-oriented manufacturer can rarely be financed if the bankruptcy risk is high. However, under guaranteed financing, the operator may, interestingly, even subsidise a manufacturer with high operating efficiency. In this situation, a high bankruptcy risk could incentivize the manufacturer to improve its operating efficiency for the sake of the subsidy. Practically, guaranteed financing could coordinate the supply chain through interest rate adjustments or subsidies when facing different risk levels, which could improve both firms' benefits. [ABSTRACT FROM AUTHOR]

Chronic inflammation is a major contributing factor in the pathogenesis of many age-associated diseases. One central protein that regulates inflammation is NF-κB, the activity of which is modulated by post-translational modifications as well as by association with co-activator and co-repressor proteins. SIRT1, an NAD(+)-dependent protein deacetylase, has been shown to suppress NF-κB signaling through deacetylation of the p65 subunit of NF-κB resulting in the reduction of the inflammatory responses mediated by this transcription factor. The role of SIRT1 in the regulation of NF-κB provides the necessary validation for the development of pharmacological strategies for activating SIRT1 as an approach for the development of a new class of anti-inflammatory therapeutics. We report herein the development of a quantitative assay to assess compound effects on acetylated p65 protein in the cell. We demonstrate that small molecule activators of SIRT1 (STACs) enhance deacetylation of cellular p65 protein, which results in the suppression of TNFα-induced NF-κB transcriptional activation and reduction of LPS-stimulated TNFα secretion in a SIRT1-dependent manner. In an acute mouse model of LPS-induced inflammation, the STAC SRTCX1003 decreased the production of the proinflammatory cytokines TNFα and IL-12. Our studies indicate that increasing SIRT1-mediated NF-κB deacetylation using small molecule activating compounds is a novel approach to the development of a new class of therapeutic anti-inflammatory agents.