Sterile alpha and TIR motif-containing protein 1 is a negative regulator in the anti-bacterial immune responses in nile tilapia (Oreochromis niloticus)

Nile tilapia (Oreochromis niloticus) is one of the most important food fish in the world. However, the farming industry has encountered significant challenges, such as pathogen infections. Toll-like receptors (TLRs) play an essential role in the initiation of the innate immune system against pathogens. Sterile alpha and TIR motif-containing protein 1 (SARM1) is one of the most evolutionarily conserved TLR adaptors, and its orthologs are present in various species from worms to humans. SARM1 plays an important role in negatively regulating TIR domain-containing adaptor proteins inducing IFNβ (TRIF)-dependent TLR signaling in mammals, but its immune function remains poorly understood in fish. In this study, O. niloticus SARM1 (OnSARM1) was cloned and its evolutionary status was verified using bioinformatic analyses. mRNA expression of OnSARM1 was found at a higher level in the trunk kidney and muscle in healthy fish. The examination of its subcellular location showed that the OnSARM1 was detected only in the cytoplasm of THK cells, and colocalized with OnMyD88, OnTRIF and OnTRIF in small speckle-like condensed granules. The transcript levels of OnMyD88, OnTIRAP, OnTRIF, and downstream effectors, including interleukin (IL)-1β, IL-8, IL-12b and type I interferon (IFN)d2.13, were regulated conversely to the expression of OnSARM1 in the head kidney from Aeromonas hydrophila and Streptococcus agalactiae infected fish. Moreover, the treatment of THK cells with lysates from A. hydrophila and S. agalactiae enhanced the activity of the NF-κB promoter, but the effects were inhibited in the OnSARM1 overexpressed THK cells. Overexpression of OnSARM1 alone did not activate the NF-κB-luciferase reporter, but it suppressed OnMyD88- and OnTIRAP-mediated NF-κB promoter activity. Additionally, OnSARM1 inhibited the mRNA expression of proinflammatory cytokines and hepcidin in A. hydrophila lysate stimulated THK cells. Taken together, these findings suggest that OnSARM1 serves as a negative regulator by inhibiting NF-κB activity, thereby influencing the transcript level of proinflammatory cytokines and antimicrobial peptides in the antibacterial responses

Atrasentan and renal events in patients with type 2 diabetes and chronic kidney disease (SONAR): a double-blind, randomised, placebo-controlled trial

Background: Short-term treatment for people with type 2 diabetes using a low dose of the selective endothelin A receptor antagonist atrasentan reduces albuminuria without causing significant sodium retention. We report the long-term effects of treatment with atrasentan on major renal outcomes. Methods: We did this double-blind, randomised, placebo-controlled trial at 689 sites in 41 countries. We enrolled adults aged 18–85 years with type 2 diabetes, estimated glomerular filtration rate (eGFR)25–75 mL/min per 1·73 m 2 of body surface area, and a urine albumin-to-creatinine ratio (UACR)of 300–5000 mg/g who had received maximum labelled or tolerated renin–angiotensin system inhibition for at least 4 weeks. Participants were given atrasentan 0·75 mg orally daily during an enrichment period before random group assignment. Those with a UACR decrease of at least 30% with no substantial fluid retention during the enrichment period (responders)were included in the double-blind treatment period. Responders were randomly assigned to receive either atrasentan 0·75 mg orally daily or placebo. All patients and investigators were masked to treatment assignment. The primary endpoint was a composite of doubling of serum creatinine (sustained for ≥30 days)or end-stage kidney disease (eGFR <15 mL/min per 1·73 m 2 sustained for ≥90 days, chronic dialysis for ≥90 days, kidney transplantation, or death from kidney failure)in the intention-to-treat population of all responders. Safety was assessed in all patients who received at least one dose of their assigned study treatment. The study is registered with ClinicalTrials.gov, number NCT01858532. Findings: Between May 17, 2013, and July 13, 2017, 11 087 patients were screened; 5117 entered the enrichment period, and 4711 completed the enrichment period. Of these, 2648 patients were responders and were randomly assigned to the atrasentan group (n=1325)or placebo group (n=1323). Median follow-up was 2·2 years (IQR 1·4–2·9). 79 (6·0%)of 1325 patients in the atrasentan group and 105 (7·9%)of 1323 in the placebo group had a primary composite renal endpoint event (hazard ratio [HR]0·65 [95% CI 0·49–0·88]; p=0·0047). Fluid retention and anaemia adverse events, which have been previously attributed to endothelin receptor antagonists, were more frequent in the atrasentan group than in the placebo group. Hospital admission for heart failure occurred in 47 (3·5%)of 1325 patients in the atrasentan group and 34 (2·6%)of 1323 patients in the placebo group (HR 1·33 [95% CI 0·85–2·07]; p=0·208). 58 (4·4%)patients in the atrasentan group and 52 (3·9%)in the placebo group died (HR 1·09 [95% CI 0·75–1·59]; p=0·65). Interpretation: Atrasentan reduced the risk of renal events in patients with diabetes and chronic kidney disease who were selected to optimise efficacy and safety. These data support a potential role for selective endothelin receptor antagonists in protecting renal function in patients with type 2 diabetes at high risk of developing end-stage kidney disease. Funding: AbbVie

Peat Swamp Groundwater Treatment: Efficiency of Mixed Citrus Peel and Kernel Activated Carbon Layer

One of the natural water resources is groundwater. Groundwater is another alternative to meet the increasing water demand in Malaysia. Then, the decrease in supplying raw groundwater which may due to depletion of groundwater and hence it is important to maintain the availability of water supply locally and even establish new water source such as from peat swamp to overcome future water crisis. Activated carbon is famous for its characteristic in eliminating various organic contaminants. In this investigation, low cost mixed activated carbon of food waste (citrus peel) and agricultural waste (palm kernel shell) are used as adsorbents in biological sand filter to treat peat swamp groundwater whereby the overall aim of study to evaluate the performance of mixed activated carbon layer of citrus peel and kernel in biological sand filter for peat swamp groundwater treatment.The mixed activated carbon with 1:1 ratio is filled into the biological sand filter. The efficiency of the mixed activated carbon layered biological sand water treatment system is evaluated using parameters pH, Turbidity, Chemical Oxygen Demand (COD), Biological Oxygen Demand (BOD), Total Suspended Solids (TSS) and E. coli and removal of heavy metal ions of peat swamp groundwater. All these parameters follow the Standard Methods for Examination of Water and Wastewater 2005. The implementation of investigation improved the water quality of the peat swamp groundwater, the water treatment technology using combination of activated carbon and biosand filter, human living standards by providing safe and clean water supply

A Study of Knowledge-Based Simulation for Enterprise Resources Planning

The conventional way of using the Enterprise Resources Planning (ERP) applications is inadequate for the highly dynamic, complex and demanding business environment. The efficient use of the ERP system relies heavily on the know-how, experience and quality of the users. Since the knowledge of operating ERP system is difficult to be acquired, shared and diffused among the users, it takes time and money to train well-experienced users. As a result, this paper presents a framework of Knowledge-based Simulation System for Enterprise Resources Planning named KBSimERP. The KBSimERP provides an integrated learning environment for achieving three perspectives, which includes the knowledge acquisition, knowledge diffusion and performance measurement perspectives respectively. Hence, a prototype of the KBSimERP is built for production planning and control, and the performance of the system is preliminarily evaluated. Satisfactory results are obtained.Artificial intelligence, enterprise resources planning, knowledge management, simulation, multi-perspective