In silico identification of compounds from Piper sarmentosum Roxb leaf fractionated extract inhibit interleukin-6 to prevent rheumatoid arthritis.

Objective: Medicinal herbs with a phytonutrient background has been applied globally as major alternatives to ameliorate the continuous increase in rheumatoid arthritis cases worldwide. We herein aimed to critically examine the bioactive components of the medicinal herb Piper sarmentosum Roxb leaf fractionated extract for its potential to inhibit the influx of interleukin-6 (IL-6) in rheumatoid arthritis. Methods: The Schrödinger platform was employed as the main computational acumen for the screening of bioactive compounds identified and reference compounds subjected to molecular simulation (MDS) for analyzing the stability of docked complexes to assess fluctuations and conformational changes during protein-ligand interactions. Results: The values of the simulatory properties and principal component analysis (PCA) revealed the good stability of these phytochemicals in the active pocket of interleukin-6 (IL-6). Discussion: Our findings reveal new strategies in which these phytochemicals are potential inhibitory agents that can be modified and further evaluated to develop more effective agents for the management of rheumatoid arthritis, thereby providing a better understanding and useful model for the reproduction and/or discovery of new drugs for the management of rheumatoid arthritis and its complications.

Phytotherapeutic potential of compounds identified from fractionated extracts of Morus alba L., as an inhibitor of interleukin-6 in the treatment of rheumatoid arthritis: computational approach.

The presence of HLA-DRB1 alleles that encode critical points associated with environmental interactions is associated with increased risk of rheumatoid arthritis caused by anti-citrullinated protein antibodies. Therefore, interleukin-6 (IL-6), a multifunctional cytokine that controls both local and systemic acute inflammatory responses through its ability to induce a phase response, plays a serious role. Its overexpression leads to pathological challenges such as rheumatoid arthritis and menopausal osteoporosis. However, targeting the IL-6 receptor and its region could be the major step in controlling the overexpression of this cytokine for therapeutic importance. Therefore, our research explored the computational insight needed to investigate the anti-RFA potential of phytochemicals from fractionated extracts of Morus alba L. against receptors, which have been implicated as druggable targets for the treatment of rheumatoid arthritis. In this study, fifty-nine (59) previously isolated and characterized phytochemicals from M. alba L. were identified from the literature and retrieved from the PubChem database. In silico screening was used to assess the mode of action of these phytochemicals from M. alba L. against receptors that may serve as therapeutic targets for rheumatoid arthritis. Molecular docking studies, toxicity prediction, drug visualization and molecular dynamics simulation (MD) of the ligands together with the receptor-identified target were carried out using the Schrodinger Molecular Drug Discovery Suite. The findings indicated that a selected group of ligands displayed significant binding strength to specific amino acid residues, revealing an important link between the building blocks of proteins (amino acids) and ligands at the inhibitor binding site through traditional chemical interactions, such as interactions between hydrophobic and hydrogen bonds. The binding affinities of the receptors were carefully checked via comparison with those of the approved ligands, and the results suggested structural and functional changes in the lead compounds. Therefore, the bioactive component from M. alba L. could be a lead foot interleukin-6 (IL-6) inhibitor and could be a promising lead compound for the treatment of rheumatoid arthritis and related challenges.Communicated by Ramaswamy H. Sarma.

Identified phytocompounds from the fractionated extract of Morus alba inhibit IL-6 production via molecular docking and molecular simulation analysisChanges in the structure and function of these hit compounds show promising potential in the treatment of rheumatoid arthritis and related challenges.

Morphological, phytochemical and genetic characterization of Centella asiatica accessions collected throughout Vietnam and Laos.

Pennywort (Centella asiatica L.) is commonly grown in the tropical world for its nutritional and medicinal values. Valuable saponins in pennywort are extensively investigated for their anti-tumour activities. The diversity in morphology, phytochemical contents and genetics among pennywort accessions has been extensively studied to identify elite landraces for large-scale production. While pennywort is widely consumed in Vietnam, a systematic characterization of their diverse morphology, secondary metabolites and genetics is lacking. In this work, 26 pennywort accessions were collected across Vietnam and Laos. Their morphological features and yields were characterized under uniform agro-climatic conditions at Hue city in central Vietnam. The highest yield was obtained with HUIB_CA20 (478 g per tray), compared to the lowest yield in HUIB_CA19 (107 g per tray). Furthermore, a range of phytochemical markers, including vitamin C, reducing sugar, carotenoid, tannin, phenolic, flavonoid and saponin contents, were determined. Based on yield, phenolic and flavonoid contents, HUIB_CA20 and HUIB_CA27 were determined to be elite cultivars in this germplasm. Finally, microsatellite analysis was performed to explore the genetic diversity within the germplasm. Using fourteen SSR primer pairs, a total of 47 alleles were identified with 45 alleles (96 %) being polymorphic. These results will be useful for breeding programs aiming to create elite pennywort cultivars with enhanced properties.

Transgenerational exposure to marine heatwaves ameliorates the lethal effect on tropical copepods regardless of predation stress.

Marine heatwaves (MHWs) are emerging as a severe stressor in marine ecosystems. Extreme warm sea surface temperatures during MHWs often exceed the optimal thermal range for more than one generation of tropical coastal zooplankton. However, it is relatively unknown whether transgenerational plasticity (TGP) to MHWs may shape the offspring's fitness, particularly in an ecologically relevant context with biotic interactions such as predation stress. We addressed these novel research questions by determining the survival, reproductive success, and grazing rate of the copepod Pseudodiaptomus incisus exposed to MHW and fish predator cues (FPC) for two generations (F1 and F2). The experiment was designed in a full orthogonal manner with 4 treatments in F1 and 16 treatments in F2 generation. In both generations, MHW reduced P. incisus survival, reproductive parameters, and grazing by 10%-62% in MHW, but these parameters increased by 2%-15% with exposure to FPC, particularly at control temperature. F2 reproductive success and grazing rate as indicated by cumulative fecal pellets were reduced by 20%-30% in F1-MHW, but increased by ~2% in F1-FPC. Strikingly, MHW exposure reduced 17%-18% survival, but transgenerational exposure to MHWs fully ameliorated its lethal effect and this transgenerational effect was independent of FPC. Increased survival came with a cost of reduced reproductive success, constrained by reduced grazing. The rapid transgenerational MHW acclimation and its associated costs are likely widespread and crucial mechanisms underlying the resilience of coastal tropical zooplankton to MHWs in tropical coastal marine ecosystems.

A Variable-Length Chromosome Genetic Algorithm for Time-Based Sensor Network Schedule Optimization.

Scheduling sensor nodes has an important role in real monitoring applications using sensor networks, lowering the power consumption and maximizing the network lifetime, while maintaining the satisfaction to application requirements. Nevertheless, this problem is usually very complex and not easily resolved by analytical methods. In a different manner, genetic algorithms (GAs) are heuristic search strategies that help to find the exact or approximate global optimal solution efficiently with a stochastic approach. Genetic algorithms are advantageous for their robustness to discrete and noisy objective functions, as they are only evaluated at independent points without requirements of continuity or differentiability. However, as explained in this paper, a time-based sensor network schedule cannot be represented by a chromosome with fixed length that is required in traditional genetic algorithms. Therefore, an extended genetic algorithm is introduced with variable-length chromosome (VLC) along with mutation and crossover operations in order to address this problem. Simulation results show that, with help of carefully defined fitness functions, the proposed scheme is able to evolve the individuals in the population effectively and consistently from generation to generation towards optimal ones, and the obtained network schedules are better optimized in comparison with the result of algorithms employing a fixed-length chromosome.

Parental exposures increase the vulnerability of copepod offspring to copper and a simulated marine heatwave.

Extreme temperatures from marine heatwaves (MHWs) and pollution are dominant stressors in tropical marine ecosystems. However, we know little about the role of transgenerational effects of metals and MHWs in shaping the offspring's vulnerability to these stressors. We addressed this fundamental knowledge gap by exposing the planktonic copepod Pseudodiaptomus incisus to copper (Cu: control, 15 and 60 µg L-1) under 2 temperatures (30 and a simulated marine heatwave at 34 °C) in the first generation (F1) and 16 treatments in F2: offspring from each of 4 F1 conditions (control or 15 µg Cu L-1 × 30 or 34 °C) was reared in 4 F2 conditions (control or 15 µg Cu L-1 × 30 or 34 °C). We assessed changes in copepod performance, particularly survival, adult size, grazing, and reproduction. In F1, Cu or marine heatwave (MHW) exposures reduced all fitness traits of F1; the effects were particularly strong when both stressors were present. Transgenerational effects of Cu or MHW also strongly reduced F2 performance. Direct Cu and MHW effects on the offspring were further strengthened by transgenerational effects, resulting in more substantial reductions in F2 performance when both generations were exposed to these stressors. As copepods are major food resources for corals, shrimps, or fish larvae and juveniles, strong transgenerational and direct effects of Cu and MHW can have a cascading effect on entire coastal food webs. These results highlight the importance of considering the interaction of transgenerational and direct effects of multiple stressors, particularly relevant for short-lived organisms in tropical marine ecosystems.

Interactive effects of extreme temperature and a widespread coastal metal contaminant reduce the fitness of a common tropical copepod across generations.

Tropical coastal areas are increasingly exposed to temperature extremes from marine heatwaves and contaminants from anthropogenic activities. The interactive effects of these environmental changes on marine life are understudied. We investigated the direct and cross-generational effects of copper (Cu) on F0 and F1 generations of the common tropical copepod Pseudodiaptomus annandalei under extreme temperatures (30 and 34 °C). In F0, Cu exposure reduced survival and nauplii production; these patterns were more pronounced at 34 °C and in females. F0 Copepods produced more faecal pellets at 34 °C than 30 °C, indicating a higher energetic demand. In F1, the number of F1 adults was lower in CuF0 and at 34 °C. Cu-exposed F0 produced larger adult F1, while exposure to 34 °C resulted in smaller adult F1. Our results show that tropical copepods are highly vulnerable to the interactive effects of contaminants and extreme temperatures.

New insights into the urban washoff process with detailed physical modelling.

Current urban washoff models still rely on empirical catchment-scale functions, that have not been substantially updated during the last 40years. This paper introduce a new approach using the physical model FullSWOF to evaluate urban washoff process. The modelling approach is performed for a Parisian road catchment. Water flow simulation is validated by outlet discharge measurements and local observations of water depth. Water quality modelling of three classes of particles (d50=7µm, 70µm, and 250µm) is applied using the Hairsine-Rose model. Analysis of the washoff process at the catchment scale indicates that most (>90%) of the finest particles are removed at the beginning of a rainfall event, about 10%-20% of medium-sized particles are moved over the latest part of the event, and almost no coarse particles can be transferred into the sewer inlet. Spatial analysis of washoff process reveals that the concentration of suspended solids on road and sidewalk surface is more sensitive to rainfall intensities than that on gutter surface, while coarser particles tend to accumulate in the gutter over the later part of a rainfall event. Investigation of the driving force behind the detachment process indicates that rainfall-driven effects are two orders of magnitude higher than flow-driven effects. Moreover, it is observed that rainfall-driven detachment is considerably decreased with the rising water depth, while flow-driven detachment occurs only in gutter areas. Finally, several controversial arguments on the use of physical models for assessing the washoff process, and perspectives on development of physical urban washoff models are discussed.

A new approach of monitoring and physically-based modelling to investigate urban wash-off process on a road catchment near Paris.

Nowadays, the increasing use of vehicles is causing contaminated stormwater runoff to drain from roads. The detailed understanding of urban wash-off processes is essential for addressing urban management issues. However, existing modelling approaches are rarely applied for these objectives due to the lack of realistic input data, unsuitability of physical descriptions, and inadequate documentation of model testing. In this context, we implement a method of coupling monitoring surveys with the physically-based FullSWOF (Full Shallow Water equations for Overland Flow) model (Delestre et al., 2014) and the process-based H-R (Hairsine-Rose) model (Hairsine and Rose, 1992a, 1992b) to evaluate urban wash-off process on a road catchment near Paris (Le Perreux sur Marne, Val de Marne, France, 2661 m(2)). This work is the first time that such an approach is applied for road wash-off modelling in the context of urban stormwater runoff. On-site experimental measurements have shown that only the finest particles of the road dry stocks could be transferred to the sewer inlet during rainfall events, and most Polycyclic Aromatic Hydrocarbons (PAHs) are found in the particulate phase. Simulations over different rainfall events represent promising results in reproducing the various dynamics of water flows and sediment transports at the road catchment scale. Elementary Effects method is applied for sensitivity analysis. It is confirmed that settling velocity (Vs) and initial dry stocks (S) are the most influential parameters in both overall and higher order effects. Furthermore, flow-driven detachment seems to be insignificant in our case study, while raindrop-driven detachment is shown to be the major force for detaching sediment from the studied urban surface. Finally, a multiple sediment classification regarding the Particle Size Distribution (PSD) can be suggested for improving the model performance for future studies.

Evaluation of extenders and cryoprotectants on motility and morphology of longtooth grouper (Epinephelus bruneus) sperm.

The objective was to evaluate various extenders and cryoprotectants on postthaw motility of longtooth grouper (Epinephelus bruneus) sperm, based on sperm motility ratio (SMR), sperm velocity (SV), and morphological damage after thawing. To evaluate the optimal cryoprotectant for cryopreservation of longtooth grouper sperm, semen was diluted in 0.3 M glucose extender containing one of four cryoprotectants (dimethyl sulfoxide, methanol, ethylene glycol, and glycerol [Gly]) at a final concentration of 10% or 20%, and then frozen in liquid nitrogen vapor (-76 °C for 3 minutes) before storage in liquid nitrogen. Semen diluted in 0.3 M glucose containing 10% Gly had the highest postthaw SMR (57.5 ± 2.5%, mean ± SEM). To identify the optimal extender, semen was diluted in one of two longtooth grouper artificial seminal plasma (LG-ASP; LG-ASP1 and LG-ASP2) extenders containing Gly at concentrations of 0%, 5%, 10%, or 20%, then cryopreserved using the described procedure. Semen diluted with LG-ASP2 extender containing 10% Gly cryoprotectant had the best postthaw SMR (66.3 ± 2.0%) and SV (135.9 ± 4.5 µm/s). Compared with fresh sperm, some structural damage was observed in cryopreserved sperm. We concluded that the combination of LG-ASP2 and 10% Gly (as extender and cryoprotectant, respectively), resulted in high postthaw SMR and SV for cryopreservation of longtooth grouper sperm.

Effects of varying dilutions, pH, temperature and cations on spermatozoa motility in fish Larimichthys polyactis.

The objectives of this present study were to assess the effects of varying dilutions, pH, temperature and cations on spermatozoa motile parameters (SMPs) in fish Larimichthys polyactis. Optimal SMPs were observed when emen was diluted in artificial seawater (ASW) at a ratio of 1 to 100, with temperature of 10 degreesC and pH 8.0. The spermatozoa of L. polyactis were immotile in distilled water and motile in solution containing different cations. Maximum SMPs were obtained in each solution containing 0.4 mol NaCI, 0.4 mol KCI, 0.2 mol CaCI2 and 0.2 mol MgCl2. This study provides baseline knowledge of L. polyactis spermatozoa sensitivity of pH, temperature and cationic effects.

Notes on the diagnosis and treatment of bone fractures of the limbs with injury of peripheral vessels in the Department of traumatology at Viet Tiep Hospital, Hai Phong city

27 patients with the diagnosis of bone fractures of the limbs with injury of peripheral vessels were treated in Viet Tiep Hospital, Hai Phong city from January 2001 to November 2002. Their majority was male persons of productive age and the main cause was traffic casualties 74%, among them underwent early operation within 6 hours. 6 patients underwent a bone combination with intraspinal nail or Kirchner needle. Among 23 preserved cases, only in 8 cases, the function of the limbs was well rehabilitated, the rest were moderate and bad. In 4 cases, it must undergo an amputation at 2nd time because the late diagnosis and had been missing.