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Previous studies have shown that paricalcitol (PA) has a protective effect on the kidneys. However, the exact molecular mechanism by which PA affects diabetic nephropathy (DN) progression remains uncertain. PBMCs of patients with DN were isolated, and CYP2J2 and VDR levels were detected by qPCR. Pearson correlation analysis was utilized to detect the relationship between uACR and CYP2J2 and VDR and between CYP2J2 and VDR. The protective effects of PA on DN have been examined by TUNEL, HE staining, ELISA, and Flow cytometry assays in STZ‐induced mice. Moreover, THP‐1 cells were stimulated with HG/LPS for in vitro studies. ELISA, qPCR, western blot, and Flow cytometry assays were utilized to assess the effects of PA on DN progression by regulating CYP2J2. The interaction between CYP2J2 and VDR was analyzed by CHIP‐qPCR and luciferase experiments. CYP2J2 and VDR levels were downregulated and uACR level was upregulated in DN patients. CYP2J2 and VDR were positively correlated in PBMCs. Both CYP2J2 and VDR are inversely correlated with uACR. Moreover, after PA treatment, 11, 12‐EET levels increased, inflammatory factor levels decreased, and M2 macrophage polarization was promoted in STZ‐induced mice and HG/LPS‐triggered THP‐1 cells. Depletion of CYP2J2 and VDR decreased 11, 12‐EET level, enhanced inflammatory factor levels, and inhibited M2 macrophage polarization, which were reversed by CYP2J2 overexpression in HG/LPS‐treated cells. Furthermore, VDR bound to the CYP2J2 promoter and promoted CYP2J2 transcriptional expression. The present work pointed out a new use for PA to inhibit DN progression by increasing EET level, inhibiting inflammatory response, and inducing M2 macrophage polarization via regulating the VDR/CYP2J2 axis. [ABSTRACT FROM AUTHOR]

The architecture of software‐defined network (SDN)enhances the openness of the network by separating the control and forwarding functions, but the centralized SDN control form is susceptible to distributed denial of service (DDoS) attacks. In this paper, entropy value and back‐propagation neural network (BPNN) were applied to the DDoS attack detection of SDN, and then the two detection algorithms were simulated in MATLAB software and compared with the K‐means algorithm. The results showed that in the face of four DDoS attacks, SYN Flood, ACK Flood, UDP Flood and ICMP Flood, the BPNN‐based DDoS detection had higher accuracy and less detection time; the switch that adopted the BPNN‐based DDoS detection algorithm adjusted the traffic ratio back to normal level faster when facing DDoS attacks, reducing the impact on other switches and maintaining the traffic stability of the network. © 2024 Institute of Electrical Engineer of Japan and Wiley Periodicals LLC. [ABSTRACT FROM AUTHOR]

Aims: To validate cardiovascular risk prediction models for individuals with diabetes using the UK Biobank in order to assess their applicability. Methods: We externally validated 19 cardiovascular risk scores from seven risk prediction models (Chang et al., Framingham, University of Hong Kong‐Singapore [HKU‐SG], Li et al, RECODe [risk equations for complications of type 2 diabetes], SCORE [Systematic Coronary Risk Evaluation] and the UK Prospective Diabetes Study Outcomes Model 2 [UKPDS OM2]), identified from systematic reviews, using UK Biobank data from 2006 to 2021 (n = 23 685; participant age 40–71 years, 63.5% male). We evaluated performance by assessing the discrimination and calibration of the models for the endpoints of mortality, cardiovascular mortality, congestive heart failure, myocardial infarction, stroke, and ischaemic heart disease. Results: Over a total of 269 430 person‐years of follow‐up (median 11.89 years), the models showed low‐to‐moderate discrimination performance on external validation (concordance indices [c‐indices] 0.50–0.71). Most models had low calibration with overprediction of the observed risk. RECODe outperformed other models across four comparable endpoints for discrimination: all‐cause mortality (c‐index 0.67, 95% confidence interval [CI] 0.65–0.69), congestive heart failure (c‐index 0.71, 95% CI 0.69–0.72), myocardial infarction (c‐index 0.67, 95% CI 0.65–0.68); and stroke (c‐index 0.65, 95% CI 0.62–0.68), and for calibration (except for all‐cause mortality). The UKPDS OM2 had comparable performance to RECODe for all‐cause mortality (c‐index 0.67, 95% CI 0.66–0.69) and cardiovascular mortality (c‐index 0.71, 95% CI 0.70–0.73), but worse performance for other outcomes. The models performed better for younger participants and somewhat better for non‐White ethnicities. Models developed from non‐Western datasets showed worse performance in our UK‐based validation set. Conclusions: The RECODe model led to better risk estimations in this predominantly White European population. Further validation is needed in non‐Western populations to assess generalizability to other populations. [ABSTRACT FROM AUTHOR]

Estimating the population of defects is a key reference for completion evaluation in crowdsourced testing. Current studies commonly use the biological capture–recapture model (CRC model) to estimate the population of defects in crowdsourced tests with good results. However, the lack of consideration of false negatives for defects in existing studies leads to imprecise estimation of completion in crowdsourced testing, which in turn influences decision support during crowdsourced testing. This study analyzes the basic assumptions of the CRC model in biology and maps them to the field of crowdsourced testing, improves the Lincoln–Peterson estimator and sample coverage estimator utilizing false negative assumptions, and compares them with original estimators in 29 real crowdsourced testing projects. The experimental results show that our improved estimators can effectively reduce the estimation relative error of the population of defects caused by false negatives. [ABSTRACT FROM AUTHOR]

Summary: The Moringa seed protein (MOS) is a new protein resource, the development and utilisation of MOS is still in its early stages due to the late introduction of its varieties. To improve the range of available MOS protein, this study investigated the effects of different pH levels on the ultrasonic modification of MOS protein (UMOWP), exploring the feasibility of UMOWP emulsion systems in food. The zeta potential analysis revealed that the isoelectric point (pI) of UMOWP was 5.8. The secondary structures of UMOWP could be regulated by pH. Moreover, different secondary structures led to different tertiary structures and chemical bonds in UMOWP. Compared with pH values near pI, surface hydrophobicity significantly increased but the total S–S group and particle size decreased away from pI. Furthermore, UMOWP partially dissociated at pH 3, and the degree of dissociation was weaker at pH 9 and pH 11. These structural changes led to significant improvements in the emulsification properties of UMOWP at pH 11, resulting in better environmental stability of the emulsion. These findings provide a foundation for the potential application of MOS proteins in the food industry. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the effects of lipid microspheres coated with prostaglandin E1 (lipo‐PGE1) on peritoneal transport function and inflammation in patients with end‐stage renal disease undergoing continuous ambulatory peritoneal dialysis (CAPD). Methods: In total, 89 patients were randomly allocated to the lipo‐PGE1 and control groups. All the patients received conventional treatment, and those in the lipo‐PGE1 group received lipo‐PGE1 intravenously for 2 weeks. The levels of β2‐microglobulin (β2‐MG), cystatin C, albumin, urea, creatinine, interleukin‐6 (IL‐6), matrix metalloproteinase‐2 (MMP‐2), and high‐sensitivity C‐reactive protein (hs‐CRP) were measured before and at 1 and 2 weeks after treatment. Results: In the lipo‐PGE1 group, the peritoneal clearance rates of β2‐MG, cystatin C, and albumin were significantly increased comparing with pre‐treatment values, and the IL‐6 appearance rate (AR) in the peritoneal dialysate and the serum levels of IL‐6 and hs‐CRP were markedly decreased (p < 0.05). The lipo‐PGE1 group had significantly higher peritoneal clearance rates of β2‐MG and cystatin C and lower IL‐6 AR in the peritoneal dialysate than the control group (p < 0.05). Conclusions: Lipid microspheres coated with prostaglandin E1 may increase the peritoneal clearance of moderately sized molecules and macromolecules with insignificant effect on the clearance of small molecules. The reduction in IL‐6 level following treatment with lipo‐PGE1 may alleviate inflammation. [ABSTRACT FROM AUTHOR]

Antibody responses of the first wave of survivors infected with SARS-CoV-2 1 year ago Keywords: coronavirus; epidemiology; immunity/immunization; infection; SARS coronavirus; virus classification EN coronavirus epidemiology immunity/immunization infection SARS coronavirus virus classification 1770 1772 3 03/22/22 20220501 NES 220501 As of 6:41 p.m. CEST, August 16, 2021, there have been 207 173 086 confirmed cases of coronavirus disease (COVID-19), inclu ding 4 361 996 deaths worldwide.1 Antibody response is presumed to associate with host resistance to viral diseases and can protect against reinfection.2,3 In view of the emergency and threat caused by the COVID-19 outbreak, it is urgent to understand the host antibody responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Coronavirus, epidemiology, infection, SARS coronavirus, virus classification, immunity/immunization. [Extracted from the article]

Aims: Type 2 diabetes mellitus (T2DM) is commonly complicated by renal impairment. Polyethylene glycol loxenatide (PEX168) is a novel long‐acting glucagon‐like peptide‐1 receptor agonist for T2DM. PEX168 pharmacokinetics was studied to identify requirements for dose‐modification in T2DM complicated by renal impairment. Methods: This was a single‐centre, open‐labelled, parallel‐group, single‐dose, phase I clinical trial of patients with mild and moderate renal impairment, and with or without T2DM. Age‐, sex‐ and body mass index‐matched subjects with normal renal function, and with or without T2DM were recruited as controls. Subjects received a single abdominal subcutaneous injection of PEX168 200 μg. Pharmacokinetic samples were taken at 0, 24, 48, 72, 96, 120, 144, 216, 312, 480, 648 and 720 hours. Results: Twenty‐three patients were included in the pharmacokinetics analysis. Vz/F and CL/F were lower in the moderate impairment group than in the other groups. The mean t1/2 (163 hours) in the moderate impairment group was prolonged compared to the mild impairment (117 hours) and normal (121 hours) groups. AUC0–inf increased by 13 and 100.7% in patients with mild and moderate renal impairment, respectively. Most adverse events were mild gastrointestinal disorders, with only 1 serious adverse event observed. Conclusion: A single dose of 200 μg of PEX168 was in general well tolerated in patients with renal impairment. The in vivo clearance rate of PEX168 in patients with moderate renal impairment is slower than in patients with mild renal impairment and normal renal function and dose adjustment might be required (ClinicalTrials.org #NCT02467790). [ABSTRACT FROM AUTHOR]