Multi-strategy synthetized equilibrium optimizer and application.

Background: Improvement on the updating equation of an algorithm is among the most improving techniques. Due to the lack of search ability, high computational complexity and poor operability of equilibrium optimizer (EO) in solving complex optimization problems, an improved EO is proposed in this article, namely the multi-strategy on updating synthetized EO (MS-EO). Method: Firstly, a simplified updating strategy is adopted in EO to improve operability and reduce computational complexity. Secondly, an information sharing strategy updates the concentrations in the early iterative stage using a dynamic tuning strategy in the simplified EO to form a simplified sharing EO (SS-EO) and enhance the exploration ability. Thirdly, a migration strategy and a golden section strategy are used for a golden particle updating to construct a Golden SS-EO (GS-EO) and improve the search ability. Finally, an elite learning strategy is implemented for the worst particle updating in the late stage to form MS-EO and strengthen the exploitation ability. The strategies are embedded into EO to balance between exploration and exploitation by giving full play to their respective advantages. Result and Finding: Experimental results on the complex functions from CEC2013 and CEC2017 test sets demonstrate that MS-EO outperforms EO and quite a few state-of-the-art algorithms in search ability, running speed and operability. The experimental results of feature selection on several datasets show that MS-EO also provides more advantages.

Efficacy and safety of Abelmoschus manihot in treating chronic kidney diseases: A multicentre, open-label and single-arm clinical trial.

RATIONALE AND OBJECTIVE: The efficacy of Abelmoschus manihot (AM) in treating of chronic kidney disease (CKD) has been confirmed by prior trials. AM is also commonly combined to other medicines among CKD patients in clinic. This trial aimed at evaluating the safety of AM combination application, and further verifying the efficacy of AM in treating various types of CKD. STUDY DESIGN: A multicentre, prospective, open-label, single-arm trial SETTING AND PARTICIPANTS: Approximately 2000 CKD patients with proteinuria (≥ 150 mg/d), from 105 centres across China INTERVENTIONS: AM was administered to patients three times per day for 24 weeks: the daily dose was based on age (> 12 years old: 2.5 g tid; 6∼12 years old: 1.5 g tid; 2∼6 years old: 1 g tid) OUTCOMES: The efficacy outcomes were the change in 24-hour proteinuria and estimated glomerular filtration rate (eGFR) from baseline to week 24. Safety outcomes included adverse events and laboratory tests. RESULTS: 2054 CKD patients from 105 centres were enrolled in this trial, with 1843 (89.7%) completing the 24-week follow-up. The participants' median age was 44 years old and 44.6% were female. Compared to baseline, 24-hour proteinuria decreased 471 mg (95% confident interval, 367 to 575, p < 0.001) at week 24. eGFR did not change significantly relative to baseline with the mean increase as 1.7 ml/min/1.73 m2 (95% confident interval, -0.3 to 3.7, p = 0.09). 902 (43.9%) participants combined medication to AM during follow-up. The total incidence of adverse events was 12.9%; and the most common adverse events were hyperlipidaemia (4.1%), abnormal liver function (2.3%), upper respiratory infection (1.8%), and hyperglycaemia (1.1%). Combined medications did not change the risk for hyperlipidaemia and upper respiratory infection. The combination application with antiplatelet reagents increased the risk of abnormal liver function, and with calcium channel blockers increased the risk of hyperglycaemia. LIMITATIONS: Single-arm clinical trial and short observation time CONCLUSION: We have provided safety information of AM on various types of CKD in a large trial, especially when combination to medications most commonly prescribed to CKD patients. AM also showed to decrease proteinuria with stable kidney function during follow up. AM is a promising treatment for CKD patients.

Drug repositioning of COVID-19 based on mixed graph network and ion channel.

Research on the relationship between drugs and targets is the key to precision medicine. Ion channel is a kind of important drug targets. Aiming at the urgent needs of corona virus disease 2019 (COVID-19) treatment and drug development, this paper designed a mixed graph network model to predict the affinity between ion channel targets of COVID-19 and drugs. According to the simplified molecular input line entry specification (SMILES) code of drugs, firstly, the atomic features were extracted to construct the point sets, and edge sets were constructed according to atomic bonds. Then the undirected graph with atomic features was generated by RDKit tool and the graph attention layer was used to extract the drug feature information. Five ion channel target proteins were screened from the whole SARS-CoV-2 genome sequences of NCBI database, and the protein features were extracted by convolution neural network (CNN). Using attention mechanism and graph convolutional network (GCN), the extracted drug features and target features information were connected. After two full connection layers operation, the drug-target affinity was output, and model was obtained. Kiba dataset was used to train the model and determine the model parameters. Compared with DeepDTA, WideDTA, graph attention network (GAT), GCN and graph isomorphism network (GIN) models, it was proved that the mean square error (MSE) of the proposed model was decreased by 0.055, 0.04, 0.001, 0.046, 0.013 and the consistency index (CI) was increased by 0.028, 0.016, 0.003, 0.03 and 0.01, respectively. It can predict the drug-target affinity more accurately. According to the prediction results of drug-target affinity of SARS-CoV-2 ion channel targets, seven kinds of small molecule drugs acting on five ion channel targets were obtained, namely SCH-47112, Dehydroaltenusin, alternariol 5-o-sulfate, LPA1 antagonist 1, alternariol, butin, and AT-9283.These drugs provide a reference for drug repositioning and precise treatment of COVID-19.

Role of solution chemistry in the attachment of graphene oxide nanoparticles onto iron oxide minerals with different characteristics.

Given the ubiquity and abundance of the iron oxide minerals and their important roles in affecting the environmental fate of graphene oxide (GO) nanoparticles, the attachment of GO onto three iron oxide minerals (i.e., hematite, goethite, and ferrihydrite) under different solution chemistry conditions was investigated in this study. The main mechanism of the attachment of GO was electrostatic interaction. Calculations based on the DLVO theory showed that the attachment was a favorable process. Interestingly, the affinity of GO towards three iron oxide minerals was in the order of ferrihydrite > goethite > hematite. This result indicates that different characteristics of various iron oxides (e.g., specific surface area, crystal structure, and surface charge, and surface hydroxyl densities) can influence their attachment capacities for GO. The attachment of GO depended on the solution pH and ionic strength. Electrostatic attraction and hydrogen bonding were the important retention mechanisms for GO attachment when pH < pHPZC (the point of zero charge) and pH > pHPZC, respectively. The attachment capacities of iron oxides decreased with increasing ionic strength at lower pH because of the decrease of the electrostatic attraction. Meanwhile, the presence of divalent cations (i.e., Ca2+ and Cu2+) could significantly promote GO attachment mainly by the surface-bridging mechanism. Meanwhile, the enhancement effect of Cu2+ was greater than Ca2+ due to the greater complexation affinity of Cu2+. Furthermore, attachment isotherms showed that the presence of phosphate could inhibit the attachment of GO onto minerals obviously. Because phosphate could form inner-sphere surface complex on the iron oxide surface, and consequently decreased the electrostatic attraction between nanoparticles and minerals. Our study has important implications for predicting the fate of GO in natural environment where amounts of iron oxide minerals are present.

Resveratrol improves mitochondrial function in the remnant kidney from 5/6 nephrectomized rats.

Mitochondrial dysfunction is involved in the pathogenesis of chronic kidney disease (CKD). Resveratrol has been demonstrated to be beneficial for the recovery of kidney diseases. In this study, the 5/6 nephrectomized rat was used as a CKD model and the TGF-ß1-exposed mouse mesangial cells were used as an in vitro model. Pathological examination showed that resveratrol treatment attenuated glomerular injury in the remnant kidney of 5/6 nephrectomized rat. Additionally, resveratrol improved mitochondrial function in vivo and in vitro, as evidenced by increasing mitochondrial membrane potential, increasing ATP, decreasing reactive oxygen species production and enhancing activities of complex I and III. Furthermore, the dysregulated expressions of electron transport chain proteins and fission/fusion proteins in the kidney of 5/6 nephrectomize rats and TGF-ß1-exposed mesangial cells were restored by resveratrol. Finally, upregulated sirt1 and PGC-1α deacetylation were found after treatment with resveratrol in vivo and in vitro, which may contribute to the mitochondrial protective effects of resveratrol. The results demonstrate that resveratrol protects the mitochondria of kidney in 5/6 nephrectomized rats and TGF-ß1 induced mesangial cells. The study provides new insights into the renoprotective mechanisms of resveratrol.

Probucol inhibits JAK2-STAT pathway activation and protects human glomerular mesangial cells from tert-butyl hydroperoxide induced premature senescence.

Human mesangial cells (HMCs) have a finite lifespan and eventually enter irreversible growth arrest known as cellular senescence, which is thought to contribute to kidney ageing and age-related kidney disorders such as chronic kidney disease. The JAK2-STAT pathway plays a pivotal role in transmitting cytokine signals, including cell proliferation, apoptosis, and differentiation, but whether it could regulate HMC senescence still remains to be explored. In our study, tert-butyl hydroperoxide (tBHP)-induced cells accelerated HMC senescence, as judged by increased senescence-associated ß-galactosidase stained positive cells, morphological changes, and G0-G1 cell cycle arrest. STAT1 and STAT3 activity were increased in tBHP-induced cells. After tBHP treatment, Bcl-2 protein expression decreased and Bax protein expression increased. Blocking the JAK2-STAT pathway with AG490 and using probucol significantly inhibited the progression of HMC senescence. Bax protein expression decreased, but Bcl-2 protein expression increased after AG490 and probucol treatment. Our results indicated that the JAK2-STAT pathway might mediate tBHP-induced HMC senescence through the Bcl-2-Bax pathway, and that probucol could attenuate HMC senescence by regulating STATs.