Multi-population genetic algorithm with ER network for solving flexible job shop scheduling problems.

A genetic algorithm (GA) cannot always avoid premature convergence, and multi-population is usually used to overcome this limitation by dividing the population into several sub-populations (sub-population number) with the same number of individuals (sub-population size). In previous research, the questions of how a network structure composed of sub-populations affects the propagation rate of advantageous genes among sub-populations and how it affects the performance of GA have always been ignored. Therefore, we first propose a multi-population GA with an ER network (MPGA-ER). Then, by using the flexible job shop scheduling problem (FJSP) as an example and considering the total individual number (TIN), we study how the sub-population number and size and the propagation rate of advantageous genes affect the performance of MPGA-ER, wherein the performance is evaluated by the average optimal value and success rate based on TIN. The simulation results indicate the following regarding the performance of MPGA-ER: (i) performance shows considerable improvement compared with that of traditional GA; (ii) for an increase in the sub-population number for a certain TIN, the performance first increases slowly, and then decreases rapidly; (iii) for an increase in the sub-population size for a certain TIN, the performance of MPGA-ER first increases rapidly and then tends to remain stable; and (iv) with an increase in the propagation rate of advantageous genes, the performance first increases rapidly and then decreases slowly. Finally, we use a parameter-optimized MPGA-ER to solve for more FJSP instances and demonstrate its effectiveness by comparing it with that of other algorithms proposed in other studies

The cytotoxicity and protective effects of Astragalus membranaceus extracts and butylated hydroxyanisole on hydroxyl radical-induced apoptosis in fish erythrocytes

Erythrocytes play an essential role in transporting O2 and CO2 for respiration in fish. However, erythrocytes continuously suffer from reactive oxygen species (ROS) -induced oxidative stress and apoptosis. Thus, it is essential to expand our knowledge of how to protect erythrocytes against ROS-induced oxidative stress and apoptosis in fish. In this study, we explored the cytotoxicity and the effects of butylated hydroxyanisole (BHA), ethyl ether extracts, ethyl acetate extracts, acetone extracts (AE), ethanol extracts, and aqueous extracts of Astragalus membranaceus (EAm) on hydroxyl radical (·≡OH)-induced apoptosis in carp erythrocytes. The rat hepatocytes and carp erythrocytes were incubated with different concentrations of BHA or EAm(0.125 to 1 mg/mL). The toxicity in rat hepatocytes and carp erythrocytes was then measured using a 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay and a haemolysis assay, respectively. The carp erythrocytes were treated with BHA or EAm in the presence of 40 μmol/L FeSO4 and 20 μmol/L H2O2 at 37 °C, except for the control group. Oxidative stress and apoptosis parameters in the carp erythrocytes were then evaluated using the commercial kit. The results indicated that at high concentrations, BHA and EAm could induce toxicity in rat hepatocytes and fish erythrocytes. However, BHA was more toxic than EAm at the same concentrations. Moreover, the toxicity order of BHA and EAm in the fish erythrocytes approximately agreed with that for the rat hepatocytes. Butylated hydroxyanisole and EAm suppressed the ·≡OH-induced phosphatidylserine exposure and DNA fragmentation (the biomarkers of apoptosis) by decreasing the generation of ROS, inhibiting the oxidation of cellular components, and restoring the activities of antioxidants in carp erythrocytes. Of all of the examined EAm, the AE showed the strongest effects. The effects of AE on superoxide anion, H2O2, met-haemoglobin and reduced glutathione levels, as well as glutathione reductase activity and apoptosis were equivalent to or stronger than those of BHA. These results revealed that the AE of Astragalus membranaceus could be used as a potential natural antioxidant or apoptosis inhibitor in fish erythrocytes

Re-evaluation of retested nucleic acid-positive cases in recovered COVID-19 patients: Report from a designated transfer hospital in Chongqing, China

Since the outbreak of coronavirus disease 2019 (COVID-19) in Wuhan, Hubei Province, China [1], a large number of confirmed cases met the discharge criteria (one of which is two consecutive negative nucleic acid tests with an interval of at least 24 h) [2]. Previous studies have paid more attention to the epidemic situation of COVID-19 and patient diagnosis and treatment. Close attention also should be paid to the discharged patients. Surprisingly, a previous follow-up reported that some patients’ nucleic acid retest results were positive again after discharge [3]. Factors impacting these follow-up test results should be further investigated. Since the first confirmed case was diagnosed in our hospital (Chongqing Emergency Medical Center, the designated transfer hospital) on February 4th, we confirmed a total of 17 cases. All patients infected with the novel coronavirus were transferred to a designated hospital in Southwest China’s Chongqing by ambulance with an inbuilt negative-pressure chamber [4]. In the follow-up examination of these patients, RT-PCR tests were conducted again 3 days after discharged from the designated hospital. Four patients showed recurrence of positive results after a few days of discharge. Thus, we examined these cases herein, aiming to provide information for policy formulation and modification of discharge plans

Camptothecin-20(s)-O-[N-(3’α,12’α-dihydroxy-24’-carbonyl-5’β-cholan)]-lysine, a Novel Camptothecin Analogue, Induces Apoptosis towards Hepatocellular Carcinoma SMMC-7721 Cells

Camptothecin-20(s)-O-[N-(3’α,12’α-dihydroxy-24’-carbonyl-5’β-cholan)]-lysine (B2) is a novel camptothecin analogue. Our previous study had shown that it displayed higher cytoxicity activity towards hepatocellular carcinoma SMMC-7721 cells than camptothecin (CPT) in vitro. In this paper, the underlying mechanism of anti-proliferation of B2 towards SMMC-7721 cells was further examined. Cell growth inhibition of B2 was determined using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay; morphological changes were observed under Laser Scanning Confocal Microscope (LSCM); cell cycle distribution, apoptotic population, changes in mitochondrial membrane potential, intracellular calcium concentration and reactive oxygen species (ROS) production were determined by flow cytometry (FCM). Activities of caspase-3 and caspase-9 were measured, and the expression level of Bcl-2 and Bax proteins were analyzed by Western blot. The results suggested that B2 inhibited SMMC-7721 cell growth by causing cell cycle arrest at the S and G2/M phases, and induced apoptosis involving a mitochondrial pathway. B2 appears to cause a high induction of apoptosis on SMMC-7721 cells in vitro, which suggests it might be a potential drug for cancer therapy

Effects of tea tree essential oil supplementation in low fish meal diet on growth, lipid metabolism, anti-oxidant capacity and immunity of largemouth bass (Micropterus salmoides)

This study was conducted to investigate the effects of tea tree essential oil (TTO) supplementation in low fish meal diet on growth, lipid metabolism, anti-oxidant capacity and immunity of largemouth bass (Micropterus salmoides). Five low fish meal (175 g kg−1) diets with grade levels of TTO (0, 0.25, 0.5, 1 and 2 g kg−1) were formulated to feed largemouth bass (initial weight: 15.06 ± 0.05 g) for 56 days. The results indicated that supplementation of dietary 1 g kg−1 TTO could significantly improve the weight gain rate, specific growth rate and protein deposition ratio, and decrease the feed conversion rate. The activities of gastric lipase and intestinal trypsin were enhanced by dietary TTO. The width of the intestinal villus was significantly elevated with dietary TTO level. In lipid metabolism parameters, the whole-body crude lipid content was increased and the liver crude lipid content was decreased in TTO treatment groups. The expression of acetyl-CoA carboxylase beta was downregulated, and the mRNA levels of peroxisome proliferator activated receptor alpha and carnitine palmitoyl-transferase 1 were upregulated in the liver by the addition of TTO. The contents of total cholesterol, triglyceride and low-density lipoprotein cholesterol significantly decreased, and the content of high-density lipoprotein cholesterol significantly increased in serum by dietary TTO. In anti-oxidative parameters, catalase activities in the liver and superoxide dismutase activities in the liver, intestine and serum were elevated with dietary TTO level. Malondialdehyde and protein carbonyl contents in the liver, intestine and serum showed the opposite trend. The nf-e2-related factor 2 (Nrf2) signaling pathways in the liver and intestine were triggered by dietary TTO supplementation. In the immune indices, the contents of total protein and albumin were improved, and the contents of glucose, aspartate aminotransferase and alanine transaminase were declined in TTO treatment groups. However, hepatocyte swelling and nuclear migration were found in the liver sections of all groups. After Aeromonas hydrophila administration, the toll-like receptor 2 (TLR2) signaling pathway was activated in the head-kidney, liver and intestine, and the expression levels of interleukin 10 and transforming growth factor beta 1 were increased in the head-kidney, spleen, liver and intestine by dietary TTO. In conclusion, dietary TTO in low fish meal diet could improve growth, anti-oxidant capacity and immunity, and reduce lipid deposition in the liver and serum of largemouth bass. The optimal level of TTO in low fish meal diet of largemouth bass ranged from 1.33 to 1.34 g kg−1

IL-27 Activates Human Trophoblasts to Express IP-10 and IL-6: Implications in the Immunopathophysiology of Preeclampsia

Purpose. To investigate the effects of IL-27 on human trophoblasts and the underlying regulatory signaling mechanisms in preeclampsia. Methods. The expression of IL-27 and IL-27 receptor (WSX-1) was studied in the placenta or sera from patients with preeclampsia. In vitro, we investigated the effects of IL-27 alone or in combination with inflammatory cytokine tumor necrosis factor (TNF-α) on the proinflammatory activation of human trophoblast cells (HTR-8/SVneo) and the underlying intracellular signaling molecules. Results. The expression of IL-27 and IL-27 receptor α (WSX-1) was significantly elevated in the trophoblastic cells from the placenta of patients with preeclampsia compared with control specimens. In vitro, IL-27 could induce the expression of inflammatory factors IFN-γ-inducible protein 10 (CXCL10/IP-10) and IL-6 in trophoblasts, and a synergistic effect was observed in the combined treatment of IL-27 and TNF-α on the release of IP-10 and IL-6. Furthermore, the production of IP-10 and IL-6 stimulated by IL-27 was differentially regulated by intracellular activation of phosphatidylinositol 3-OH kinase-AKT, p38MAPK, and JAK/STAT pathways. Conclusions. These results provide a new insight into the IL-27-activated immunopathological effects mediated by distinct intracellular signal transduction molecules in preeclampsia

Multidrug-loaded liposomes prevent ischemic stroke through intranasal administration

Baicalin (BA), a multi-target neuroprotective agent, has poor solubility resulting in low bioavailability. In this study, multidrug-loaded liposomes were prepared by encapsulating BA, borneol (BO) and cholic acid (CA) to prevent ischemic stroke. BBC-LP were administered intranasally (i.n.) to deliver into the brain for neuroprotection. Finally, potential mechanism of BBC treating ischemic stroke (IS) was explored by network pharmacology. In this study, BBC-LP was prepared by reverse evaporation method, and the encapsulation efficiency (EE) of the optimized liposomes was 42.69% and the drug loading (DL) was 6.17%. The liposomes had low mean particle size (156.62 ± 2.96 nm), polydispersity index (PDI) (0.195) and zeta potential (−0.99 mv). Compared to BBC, pharmacodynamic studies revealed that BBC-LP significantly improved neurological deficits, brain infarct volume, and cerebral pathology in MCAO rats. Toxicity studies showed that BBC-LP was not irritating to the nasal mucosa. These results suggest that BBC-LP can safely and effectively ameliorate IS injury by i.n. administration. Moreover, it's neuroprotective function may be related to the anti-apoptotic and anti-inflammatory effects exerted by phosphatidylinositol-3-kinase (PI3K)/Akt signaling pathway and mitogen-activated protein kinase (MAPK) signaling pathway

Table_1_Tryptophan metabolism: Mechanism-oriented therapy for neurological and psychiatric disorders.docx

Neurological and psychiatric disorders are a category of chronic diseases that are widespread and pose serious mental and physical health problems for patients. The substrates, products, and enzymes of Tryptophan metabolism all contribute to the development of neurological and psychiatric disorders. This paper deals with three metabolic pathways of tryptophan that produce a series of metabolites called tryptophan Catabolics (TRYCATs). These metabolites are involved in pathological processes such as excitotoxicity, neuroinflammation, oxidative stress, and mitochondrial damage and are closely associated with neurological and psychiatric disorders such as Alzheimer’s disease and depression. Here, we review the elements that affect how tryptophan metabolism is regulated, including inflammation and stress, exercise, vitamins, minerals, diet and gut microbes, glucocorticoids, and aging, as well as the downstream regulatory effects of tryptophan metabolism, including the regulation of glutamate (Glu), immunity, G-protein coupled receptor 35 (Gpr35), nicotinic acetylcholine receptor (nAChR), aryl hydrocarbon receptor (AhR), and dopamine (DA). In order to advance the general understanding of tryptophan metabolism in neurological and psychiatric disorders, this paper also summarizes the current situation and effective drugs of tryptophan metabolism in the treatment of neurological and psychiatric disorders and considers its future research prospects.</p