A Dual-Population-Based NSGA-III for Constrained Many-Objective Optimization.

The main challenge for constrained many-objective optimization problems (CMaOPs) is how to achieve a balance between feasible and infeasible solutions. Most of the existing constrained many-objective evolutionary algorithms (CMaOEAs) are feasibility-driven, neglecting the maintenance of population convergence and diversity when dealing with conflicting objectives and constraints. This might lead to the population being stuck at some locally optimal or locally feasible regions. To alleviate the above challenges, we proposed a dual-population-based NSGA-III, named DP-NSGA-III, where the two populations exchange information through the offspring. The main population based on the NSGA-III solves CMaOPs and the auxiliary populations with different environment selection ignore the constraints. In addition, we designed an ε-constraint handling method in combination with NSGA-III, aiming to exploit the excellent infeasible solutions in the main population. The proposed DP-NSGA-III is compared with four state-of-the-art CMaOEAs on a series of benchmark problems. The experimental results show that the proposed evolutionary algorithm is highly competitive in solving CMaOPs.

Comparison of Robotic-Assisted vs. Conventional Laparoscopy for Para-aortic Lymphadenectomy in Gynecological Malignancies: A Systematic Review and Meta-Analysis.

Background: Robotic-assisted surgery is one of the novel minimally invasive surgical techniques for the treatment of gynecological malignancies. The aim of this systematic review and meta-analysis was to compare the outcomes of robot-assisted vs. conventional laparoscopy for para-aortic lymphadenectomy (PAL) in patients with gynecological malignancies. Methods: An electronic search in PubMed, Scopus, Cochrane Central Register of Controlled Trials (CENTRAL), and Google Scholar databases was performed for articles, published up to 01st November 2021. Outcomes including operating time (OT), total blood loss (TBL), length of stay (LOS), and complication rate (CR) in robot-assisted vs. conventional laparoscopy were investigated. Results: A total of nine studies (7 non-RCTs and 2 RCTs) involving 914 participants were included. Of them, 332 patients underwent robotic laparoscopy (robotic group) and 582-conventional laparoscopy (conventional laparoscopy group). A significant decrease in TBL (MD = -149.1; 95% CI: -218.4 to -79.91) [ml] was observed in the robotic group as compared to the conventional laparoscopy group. However, no significant difference was noted for OT, CR, and LOS in the overall findings. Further subgroup analysis showed that the robotic group had a lower OT in mixed histological populations and studies reporting on the extraperitoneal approach. The lower chance of TBL was observed in mixed histological populations and studies involving extraperitoneal approach, Caucasian population, and non-RCTs design. Conclusions: Robotic laparoscopy has a significant advantage over the conventional laparoscopy approach for PAL in gynecological malignancies. Further prospective observational studies embedded with a large sample size are needed to validate our findings.

The Bloom-Forming Dinoflagellate Karenia mikimotoi Adopts Different Growth Modes When Exposed to Short or Long Period of Seawater Acidification.

Impacts of ocean acidification (OA) on noncalcifying organisms and the possibly responsible mechanism have aroused great research interests with the intensification of global warming. The present study focused on a noxious, noncalcifying, bloom-forming dinoflagellate, Karenia mikimotoi (K. mikimotoi), and its variation of growth patterns exposed to different periods of seawater acidification with stressing gradients was discussed. The dinoflagellates under short-time acidifying stress (2d) with different levels of CO2 presented significant growth inhibition (p < 0.05). The cell cycle was obviously inhibited at S phase, and the photosynthetic carbon fixation was also greatly suppressed (p < 0.05). Apoptosis was observed and the apoptotic rate increased with the increment of pCO2. Similar tendencies were observed in the key components of mitochondrial apoptotic pathway (the mitochondrial membrane potential (MMP), Caspase-3 and -9, and Bax/Bcl-2 ratio). However, under prolonged stressing time (8 d and 15 d), the growth of dinoflagellates was recovered or even stimulated, the photosynthetic carbon fixation was significantly increased (p < 0.05), the cell cycle of division presented little difference with those in the control, and no apoptosis was observed (p > 0.05). Besides, acidification adjusted by HCl addition and CO2 enrichment resulted in different growth performances, while the latter had a more negative impact. The results of present study indicated that (1) the short-time exposure to acidified seawater led to reduced growth performance via inducing apoptosis, blocking of cell cycle, and the alteration in photosynthetic carbon fixation. (2) K. mikimotoi had undergone adaptive changes under long-term exposure to CO2 induced seawater acidification. This further demonstrated that K. mikimotoi has strong adaptability in the face of seawater acidification, and this may be one of the reasons for the frequent outbreak of red tide. (3) Ions that dissociated by the dissolved CO2, instead of H+ itself, were more important for the impacts induced by the acidification. This work thus provides a new perspective and a possible explanation for the dominance of K. mikimotoi during the occurrence of HABs.

De novo synthetic short antimicrobial peptides against cariogenic bacteria.

OBJECTIVE: Antimicrobial peptides (AMPs) have shown the ability to inhibit planktonic bacteria and biofilms. The objectives of this study were to de novo design and synthesize a series of cationic, amphipathic α-helical AMPs that would be shorter, less cytotoxic, and more potent than existing AMPs against cariogenic bacteria. DESIGN: Three short AMPs (GH8, GLLWHLLH-NH2; GH12, GLLWHLLHHLLH-NH2; and GH16, GLLWHLLHHLLHLLHH-NH2) were designed, synthesized and characterized structurally. Minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) against eight major cariogenic bacteria were tested to select the most promising peptide. Scanning electron microscopy (SEM) was used to observe the bacterial membrane after treatment with selected peptides. The bactericidal kinetics, effects on biofilm and cytotoxity were further investigated. RESULTS: Of the three AMPs, GH12 had the most balanced structural parameters and a high content of α-helical structure. GH12 had a MIC of 4.0-8.0µg/mL and MBC of 8.0-32.0µg/mL. The corresponding values for the other two AMPs were 2- to 64- fold higher. In time-kill assays, GH12 killed all bacterial strains within 60min at 4- fold MBC. SEM observed lysis and pore formation of the cytomembrane after treatment with GH12. 8.0µg/mL GH12 inhibited Streptococcus mutans biofilm formation. Confocal laser scanning microscopy showed that GH12 effectively reduced the biomass of 1-day-old S. mutans biofilm. Cytotoxicity assays indicated that GH12 showed little toxic effect on the viability of human gingival fibroblasts. CONCLUSION: These results indicate that GH12 shows antimicrobial activity against cariogenic bacteria and biofilms in vitro.

Promotion of enamel caries remineralization by an amelogenin-derived peptide in a rat model.

OBJECTIVE: An amelogenin-derived peptide has been shown to promote remineralization of demineralized enamel in an in vitro model of initial caries induced by pH cycling. The present study examines whether the peptide exerts similar effects within the complex oral environment in vivo. DESIGN: Specific pathogen-free Sprague-Dawley rats (n=36) were infected with Streptococcus mutans, given ad libitum access to Diet 2000 and drinking water supplemented with sucrose (10%, w/v), and then randomly divided into three groups treated with 25µM peptide solution, 1g/L NaF or deionized water. Molar teeth were swabbed twice daily with the respective solutions for 24days. Then animals were killed, their jaws were removed and caries lesions were analyzed using the quantitative light-induced fluorescence-digital (QLF-D) technique to measure changes in mineral content. To verify QLF-D results, caries were scored for lesion depth and size using the Keyes method, and analyzed using polarized light microscopy (PLM). RESULTS: Mineral gain was significantly higher in teeth treated with peptide or NaF than in teeth treated with water (p<0.05), based on the QLF-D results (ΔF and ΔQ). Incidence of smooth-surface and sulcal caries based on Keyes scores was similar in rats treated with peptide or NaF, and significantly lower in these groups than in rats treated with water (p<0.05). Lesions on teeth treated with peptide or NaF were shallower, based on PLM. No significant differences were observed between molar enamel caries treated with peptide or NaF. CONCLUSIONS: This amelogenin-derived peptide can promote remineralization in a rat caries model, indicating strong potential for clinical use.

Combining structure-based pharmacophore and in silico approaches to discover novel selective serotonin reuptake inhibitors.

Inhibition of human serotonin transporter (hSERT) has been reported to be a potent strategy for the treatment for depression. To discover novel selective serotonin reuptake inhibitors (SSRIs), a structure-based pharmacophore model (SBPM) was developed using the docked conformations of six highly active SSRIs. The best SBPM, consisting of four chemical features: two ring aromatics (RAs), one hydrophobic (HY), and one positive ionizable (PI), was further validated using Gunner-Henry (GH) scoring and receiver operating characteristic (ROC) curve methods. This well-validated SBPM was then used as a 3D-query in virtual screening to identify potential hits from National Cancer Institute (NCI) database. These hits were subsequently filtered by absorption, distribution, metabolism, excretion, and toxicity (ADMET) prediction and molecular docking, and their binding stabilities were validated by 20-ns MD simulations. Finally, only two compounds (NSC175176 and NSC705841) were identified as potential leads, which exhibited higher binding affinities in comparison with the paroxetine. Our results also suggest that cation-π interaction plays a crucial role in stabilizing the hSERT-inhibitor complex. To our knowledge, the present work is the first structure-based virtual screening study for new SSRI discovery, which should be a useful guide for the rapid identification of novel therapeutic agents from chemical database.

The possible structural models for polyglutamine aggregation: a molecular dynamics simulations study.

Huntington's disease is a neurodegenerative disorder caused by a polyglutamine (polyQ) expansion near the N-terminus of huntingtin. Previous studies have suggested that polyQ aggregation occurs only when the number of glutamine (Q) residues is more than 36-40, the disease threshold. However, the structural characteristics of polyQ nucleation in the very early stage of aggregation still remain elusive. In this study, we designed 18 simulation trials to determine the possible structural models for polyQ nucleation and aggregation with various shapes and sizes of initial ß-helical structures, such as left-handed circular, right-handed rectangular, and left- and right-handed triangular. Our results show that the stability of these models significantly increases with increasing the number of rungs, while it is rather insensitive to the number of Qs in each rung. In particular, the 3-rung ß-helical models are stable when they adopt the left-handed triangular and right-handed rectangular conformations due to the fact that they preserve high ß-turn and ß-sheet contents, respectively, during the simulation courses. Thus, we suggested that these two stable ß-helical structures with at least 3 rungs might serve as the possible nucleation seeds for polyQ depending on how the structural elements of ß-turn and ß-sheet are sampled and preserved during the very early stage of aggregation.

[Profit and loss of nutrients in crop-fruit ecosystems].

The analysis on the balance of nutrient's profit and loss in crop-fruit ecosystems of three villges in middle-south Loess Plateau showed that fertilization was the main input of nutrients, of which, chemical fertilizer occupied a larger proportion, while organic manure was relatively insufficient. The quantity of N, P and K spent in interior circulation was far less than that exported from the ecosystem. The ratio of nutrient's output and input in three test villages was differed, but all at a low level.

[Productivity of crop-fruit ecological agriculture in middle-south Loess Plateau].

With the Xipo, Feimahe and Nangou villages as test objects, the productive characteristics of crop-fruit ecological agriculture in the middle-south Loess Plateau were investigated. The results showed that the biomass productivity of a plant was different with its organs, the highest for grain or fruit, and followed by stem, leaf and root. In the crop-fruit ecological agriculture, the higher ratio the crop subsystem, the higher productivity its biomass, the lower economic productivity and lower economic value was; while the fruit subsystem was on the contrary. The productivity of livestock farming subsystem was in a lower level, which restricted the increase of the total ecosystem's productivity. Based on these results, a countermeasure of increasing the ecosystem productivity was put forward.