Time-dependent Effects Research Articles

Effects of curcumin nanoparticles on the proliferation and migration of human ovarian cancer cells assessed through the NF-κB/PRL-3 signaling pathway

Curcumin (CUR) exhibits potential inhibitory effects on tumor growth; however, its hydrophobicity and instability limit its clinical applications. In the present study, we developed CUR nanoparticles (CUR-NPs) and evaluated their biochemical characteristics. Cell uptake and proliferation were assessed using scratch and Transwell assays, respectively. Western blotting was performed to investigate the expression levels of proteins related to the NF-κB/PRL-3 signaling pathway, inflammatory response, cell proliferation, and cell migration in SKOV3 cells. Our findings showed that the blank vector was not cytotoxic to cells, allowing us to disregard any effects caused by the vector itself. CUR-NPs exhibited concentration- and time-dependent inhibitory effects on cell proliferation, surpassing those of CUR alone. Increasing the concentration of CUR-NPs resulted in a reduced cell scratch-healing ability and lower chamber migration capacity. Compared to the control group, expression levels of proteins associated with NF-κB/PRL-3 signaling pathway, inflammatory response (TNF-α and IL-6), cell proliferation (cyclin E1 and cyclin A1), as well as cell migration (N-cadherin and vimentin) were significantly elevated in the lipopolysaccharide (LPS) stimulation and NF-κB p65 overexpression groups. Conversely, E-cadherin expression was significantly decreased under these conditions. However, treatment with high concentrations of CUR-NPs effectively reversed these changes. These results highlight the significant ability of CUR-NPs to inhibit human ovarian cancer cell proliferation and migration, while suppressing inflammatory responses through the regulation of the NF-κB/PRL-3 signaling pathway.

Synthesis of gold nanoparticles using Ginkgo biloba leaf extract and its in vitro anticancer effects on nasopharyngeal carcinoma cells

Green synthesis of gold nanoparticles (AuNPs) using Ginkgo biloba leaf aqueous extract was optimized by response surface methodology to yield monodispersed, crystalline nanoparticles of 18 ± 4 nm diameter. Fourier transform infrared spectroscopy confirmed capping by flavonoids, terpenoids and polyphenols providing stability for over 6 months. The biosynthesized AuNPs exhibited promising in vitro dose and time-dependent antiproliferative effects against human nasopharyngeal carcinoma CNE1 cells with IC50 reducing from 65.7 to 39.2 μg/mL over 24–72 hrs. Distinct cytoplasmic damage was observed under microscope. Treatment with 50 μg/mL AuNPs for 48 hrs dramatically upregulated pro-apoptotic Bax, Caspase-3 and p53 by 8.7, 6.5 and 4.3 fold respectively while downregulating anti-apoptotic Bcl-2 by 11.2 fold, indicating apoptosis induction via mitochondrial intrinsic pathway. The green fabricated G. biloba AuNPs displayed preferential toxicity towards carcinoma cells compared to normal fibroblasts, indicating potential for targeted nasopharyngeal cancer therapy.

Geraniol Potentiates the Effect of Fluconazole against Planktonic and Sessile Cells of Azole-Resistant Candida tropicalis: In Vitro and In Vivo Analyses.

Candida tropicalis is regarded as an opportunistic pathogen, causing diseases ranging from superficial infections to life-threatening disseminated infections. The ability of this yeast to form biofilms and develop resistance to antifungals represents a significant therapeutic challenge. Herein, the effect of geraniol (GER), alone and combined with fluconazole (FLZ), was evaluated in the planktonic and sessile cells of azole-resistant C. tropicalis. GER showed a time-dependent fungicidal effect on the planktonic cells, impairing the cell membrane integrity. Additionally, GER inhibited the rhodamine 6G efflux, and the molecular docking analyzes supported the binding affinity of GER to the C. tropicalis Cdr1 protein. GER exhibited a synergism with FLZ against the planktonic and sessile cells, inhibiting the adhesion of the yeast cells and the viability of the 48-h biofilms formed on abiotic surfaces. C. tropicalis biofilms treated with GER, alone or combined with FLZ, displayed morphological and ultrastructural alterations, including a decrease in the stacking layers and the presence of wilted cells. Moreover, neither GER alone nor combined with FLZ caused toxicity, and both treatments prolonged the survival of the Galleria mellonella larvae infected with azole-resistant C. tropicalis. These findings indicate that the combination of GER and FLZ may be a promising strategy to control azole-resistant C. tropicalis infections.

Modulation of BDNF Expression by Bryophyllum pinnatum Extract: Implications for Oxidative Stress and Cognitive Function in Pain-induced Wistar Rats

This research work investigated modulatory effects of Bryophylum pinnatum extract on BDNF expression, and cognitive functions in repetitive pain-induced oxidative stress in Wistar rats. Animals weighing between 80–100g were acquired from the animal house of the Department of Human Physiology, Faculty of Basic Medical Sciences, University of Port Harcourt, and all animals received standard laboratory rat feeds and water ad libitum. The study was designed to assess the time dependent effects with a total of 30 rats divided into 6 groups. Group 1(Control), Group 2 (Pain Only), Group 3 (Pain + 5mg/kg Morphine), Group 4 (Pain + 10mg/kg Morphine), Group (Pain + 25mg/kg Bryophylumm Pinnatum), Group 6 (Pain + 50mg/kg Bryophylumm Pinnatum), Hydromethanolic extracts was prepared accordingly, and Gas Chromatography Mass Spectrometry (GC/MS) analysis were carried out. Neurobehavioral studies were conducted weekly to assess the effects of the interventions on cognitive and neurological parameters, using radial maze and navigational maze test. Assay of BDNF was done using the Elisa method. The Results showed that Morphine and Bryophyllum pinnatum both significantly improved BDNF expression, showed antioxidant effects, improved cognitive functions, and provided possible mechanisms of pain relief. Pharmacokinetic studies on the binding affinities and drug-likeness properties of the active compounds from these extracts revealed some favorable properties with regard to management of oxidative stress and promotion of cognitive function in states of pain. The study therefore provide indication of the therapeutic potential of Bryophyllum pinnatum in the effective management of Pain, oxidative stress and cognitive functions.

Contractile effects of stimulation of D1-dopamine receptors in the isolated human atrium.

Dopamine receptors have been claimed not to directly increase contractility in the human heart. Therefore, we performed contraction experiments in isolated electrically driven human atrial preparations (HAP). For comparison, we performed contraction experiments with left atrial preparations of transgenic mice which harbor a cardiac overexpression of human D1-dopamine receptors (D1-TG). In D1-TG, first we noted that dopamine (10nM-10µM cumulatively applied) in the presence of propranolol exerted a concentration- and time-dependent positive inotropic effect in D1-TG. In a similar fashion, dopamine increased force of contraction in the presence of 0.4µM propranolol in HAP and these effects were amplified by pre-treatment with inhibitor of phosphodiesterase III (1µM) cilostamide. Moreover, contractile effects of dopamine in the presence of propranolol 0.4µM in HAP were antagonized by odapipam, haloperidol, or raclopride. Ten micromolars of fenoldopam in the presence of cilostamide increased force of contraction in HAP and this effect was antagonized by SCH23390. We conclude that stimulation of human D1-dopamine receptors can increase force of contraction in the HAP.

Numerical simulation of fabric cold pad-batch winding and quality assessment of fabric in roll

Proper fabric winding quality is crucial for achieving desired finishing effects in cold pad-batch dyeing. In this work, a detailed 3D finite element model and assessment criteria were established to analyze the influences of winding pattern, pick-up, and tension function on fabric winding quality, revealed the complex relationship between winding process and fabric roll shape. Material viscoelasticity’s time-dependent effects on stress distribution were considered. Results show that employing a following roller effectively suppresses tangential creases and axial streaks but increases seam imprints and reduces fabric roundness. Increasing pick-up improves winding quality by reducing creases, streaks, and compression deformations. However, it also elevates internal radial stress, hindering control over seam imprints. Winding with variable tension, conicity coefficient α and power index i have significant impacts on coiling quality. In addition, increasing α or decreasing i effectively enhances winding quality, with the power function performing better in tension adjustment and overall winding quality.

Impacts of exposure to and subsequent discontinuation of clozapine on tripartite synaptic transmission.

Clozapine is an effective antipsychotic for treatment-resistant schizophrenia, but its discontinuation leads to discontinuation syndrome/catatonia complicated by benzodiazepine-resistance and rhabdomyolysis. This study determined time-dependent effects of exposure and subsequent discontinuation of clozapine on expression of connexin43, 5-HT receptors, intracellular L-β-aminoisobutyrate (L-BAIBA) and 2nd-messengers and signalling of AMPK, PP2A and Akt in cultured astrocytes and rat frontal cortex. Intracellular L-BAIBA levels increased during clozapine exposure but immediately recovered after discontinuation. Both exposure to clozapine and L-BAIBA increased connexin43 and signalling of AMPK/Akt time-dependently, but reduced PP2A signalling, 5-HT receptor expression and IP3 level. These changes recovered within 2 weeks after discontinuation, while 5-HT receptors and IP3 transiently increased during the recovery process. L-BAIBA activated AMPK signalling, leading to attenuated PP2A signalling. Astroglial D-serine release was increased by clozapine exposure but continued to increase within 1 week after discontinuation via activation of IP3 receptor function. Clozapine discontinuation restored PP2A signalling due to decreased L-BAIBA, increased 5-HT receptor expression via probably enhanced 5-HT receptor recycling, but increased astroglial D-serine release persisted by transiently activated IP3 receptors via transiently increased IP3 level. Decreased L-BAIBA caused by clozapine discontinuation is, at least partially, involved in the transiently increased 5-HT receptor and astroglial D-serine release.

Abstract Mo056: Cholinergic Activation Suppresses Optogenetic Stimulation of Intrinsic Cardiac Catecholaminergic Neurons in Perfused Mouse Hearts

Balance of cholinergic and catecholaminergic activation is necessary to maintain heart health. Interrogating the acute interaction of these autonomic pathways can be done using optogenetics via selective expression of channelrhodopsin (ChR2) within intrinsic cardiac neurons. We tested the hypothesis that cholinergic activation via exogenous acetylcholine (ACh) would suppress the beta-adrenergic heart rate (HR) acceleration induced by tyrosine hydroxylase (TH) neuron stimulation, with the prominence of AV block increasing with increased ACh concentration. ECGs were recorded during perfused heart studies using wild-type (WT) mice and transgenic mice that selectively expressed ChR2 in TH neurons that secrete norepinephrine (NE). HR responses were measured for WT while increasing [NE] and for TH by illuminating the right atrium (465nm, microLED) at a range duty cycles and frequencies. Duty cycles (at 5Hz) increasing from 5-50% caused proportional increases in HR however HR was unstable at duty cycles >30%. At 20% duty cycle, HR increased by 39.43±6.79% (n=6). HR increased sigmoidally at frequencies from 2.5-15Hz (with 30ms pulse width) but HR was unstable at 15Hz. At 10Hz, heart rate increased by 64.24±13.47% (n=4). When comparing HR increases for TH (n=5) and WT+NE (n=4), optogenetic activation resulted in similar maximum HRs but drastically different rise times (7.6±1.25 vs 46.43±5.01 beats/sec, respectively). HR suppression at increasing doses of ACh was measured while perfusing WT hearts with NE and photostimulating TH hearts. The addition of ACh caused beta-adrenergic HR increases to diminish, eventually reaching below baseline HR. In WT+NE animals this occurred at 400nM ACh and in TH animals this did not occur until 1800nM ACh. As ACh increased in TH animals, onset of AV block occurred sooner and more prominently. In conclusion, optogenetic activation of TH neurons caused rapid HR acceleration that was suppressed by ACh at concentrations much higher than that required to suppress acceleration during NE perfusion. AV block also occurred more rapidly during TH neuron activation as [ACh] increased, demonstrating a time-dependent effect in the interaction of cholinergic and catecholaminergic activation.

Novel chimeric peptides based on endomorphins and ghrelin receptor antagonist produced supraspinal antinociceptive effects with reduced acute tolerance in mice

It is widely recognized that developing bi- or multifunctional opioid compounds could offer a valuable approach to pain management with fewer side effects compared to single-target compounds. In this study, we designed and characterized two novel chimeric peptides, EM-1-DLS and EM-2-DLS, incorporating endomorphins (EMs) and the ghrelin receptor antagonist [D-Lys3]-GHRP-6 (DLS). Functional assays demonstrated that EM-1-DLS and EM-2-DLS acted as κ-opioid receptor (κ-OR)-preferring agonists, weak μ-opioid receptors (μ-OR) and ghrelin receptor (GHSR) agonists. Upon intracerebroventricular (i.c.v.) administration in mice, both EM-1-DLS and EM-2-DLS exhibited dose- and time-dependent antinociceptive effects in the tail withdrawal test. EM-1-DLS demonstrated the highest antinociceptive potency among the peptides, with an ED50 approximately 8-fold greater than EM-1, while EM-2-DLS showed comparable effects to EM-2. The antinociceptive actions of EM-1-DLS involved activation of GHS-R1α, μ-OR, and κ-OR, whereas EM-2-DLS acted via GHS-R1α, δ-OR, and κ-OR pathways. Additionally, acute antinociceptive tolerance was investigated, revealing that EM-1-DLS induced a tolerance ratio of 2.33-fold, significantly lower than the 5.19-fold ratio induced by EM-1. Cross-tolerance ratios between the chimeric peptides and EMs ranged from 0.92 to 1.76, indicating reduced tolerance compared to EMs alone. These findings highlight the potential of these chimeric peptides to mitigate pain with diminished tolerance development, suggesting a promising strategy for the development of new analgesic therapies with improved safety profiles.

Tuina alleviates neuropathic pain through regulate the activation of microglia and the secretion of inflammatory cytokine in spinal cord.

To observe the analgesic effects of Tuina on neuropathic pain (NPP) and the underlying mechanisms. Forty-eight Sprague-Dawley (SD) rats were assigned by random into three treatment groups: sham, chronic constriction injury (CCI), and Tuina. Each group contained sixteen rats. CCI model was generated by ligating the right sciatic nerve. Behavioral changes of CCI were assessed by the paw withdrawal threshold (PWT) and paw withdrawal latency (PWL). In addition, biochemical techniques such as immunofluorescence staining, enzyme-linked immunosorbent assay (ELISA) and Western blotting were used to profile levels of microglia activation and inflammatory factors in the spinal dorsal horn (SDH) of rats. Tuina (clockwise pressing and rubbing) was performed at Chengshan (BL57) to observe the analgesic effects on CCI rats and the underlying mechanisms. Rats with CCI experienced significant reduction in the PWT and PWL of the right hind paw relative to CCI group at day 3. Tuina treatment rescued this situation significantly on days 10 and 14. Besides, Iba-1, microglia M1 receptor CD68, tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β) were higher in the right SDH for CCI group compared to the sham group on day 14. As expected, Tuina partially downregulated the CCI-induced overexpressed Iba-1, CD68, TNF-α, and IL-1β in the SDH of CCI model. Tuina induces a time-dependent cumulative analgesic effect in CCI rats by inhibiting the activation of microglia and the secretion of IL-1β and TNF-α in SDH.

Characterization of a unique catechol-O-methyltransferase as a molecular drug target in parasitic filarial nematodes.

Filarial nematodes cause severe illnesses in humans and canines including limb deformities and disfigurement, heart failure, blindness, and death, among others. There are no vaccines, and current drugs against filarial nematodes infections have only modest effects and are prone to complications. We identified a gene (herein called DiMT) encoding an S-adenosyl-L-methionine (SAM)-dependent methyltransferase with orthologs in parasite filarial worms but not in mammals. By in silico analysis, DiMT possesses catalytic sites for binding SAM and catecholamines with high affinity. We expressed and purified recombinant DiMT protein and used it as an enzyme in a series of SAM-dependent methylation assays. DiMT acted specifically as a catechol-O-methyltransferase (COMT), catalyzing catabolic methylation of dopamine, and depicted Michaelis Menten kinetics on substrate and co-substrate. Among a set of SAM-dependent methyltransferase inhibitors, we identified compounds that bound with high affinity to DiMT's catalytic sites and inhibited its enzymatic activity. By testing the efficacy of DiMT inhibitors against microfilariae of Dirofilaria immitis in culture, we identified three inhibitors with concentration- and time-dependent effect of killing D. immitis microfilariae. Importantly, RNAi silencing of a DiMT ortholog in Caenorhabditis elegans has been shown to be lethal, likely as a result of excessive accumulation of active catecholamines that inhibit worm locomotion, pharyngeal pumping and fecundity. Together, we have unveiled DiMT as an essential COMT that is conserved in parasitic filarial nematodes, but is significantly different from mammalian COMTs and, therefore, is a viable target for development of novel drugs against filarial nematode infections.

Impact of Diafiltration Media and Filtration Modes on Fouling and Performance in Skim Milk Microfiltration: A Comparative Study

This research utilized a customized laboratory setup to compare the filtration performance and fouling buildup during microfiltration with polymeric membranes of skim milk using 2 diafiltration media: ultrafiltration permeate and ultrapure water. Two filtration modes were evaluated: in stage 1, the diafiltration media was added in a 1:1 ratio, with the collection of permeate continuing until the initial protein concentration was restored. In stage 2, retentates and permeates were recycled to simulate fouling accumulation in a steady-state without altering the retentate composition. Utilizing water as the diafiltration medium resulted in higher flux and lower resistance values compared with using ultrafiltration permeate, irrespective of the filtration mode. The concentration had a significant impact on membrane resistance, with no noticeable time-dependent effect on fouling layer development after 60 min of filtration when the retentate composition remained constant. The protein composition of the permeate and extracted foulants were comparable between the 2 media, with caseins predominating in the fouling layer.

Time-Dependent Effects of Altered Prebedtime Light Exposure in Enclosed Spaces on Sleep Performance Associated with Human States.

Exposure to artificial light influences human performance, which is essential for maintaining healthy work and sleep. However, existing research has not explored the intrinsic links between sleep performance and human states over time under prebedtime light exposure interventions (LEIs). To investigate the time-dependent effects of altered prebedtime light exposure, four LEI groupings (#L1 - #L4) and a Time factor (D8, D9, and D10) were chosen for sleep experiments in enclosed spaces. Forty-eight young adults recruited were available for data analysis. Subjective alertness (SA), negative affect (NA), subjective sleep, and objective sleep were measured via the Karolinska Sleepiness Scale, Positive and Negative Affect Schedule, Next-day Self-assessment Sleep Quality, and joint assessment of wrist actigraphy and sleep diaries, respectively. Statistical analysis was used for the effects of light exposure on the human states (corresponding to the SA and NA) and sleep performance, while the process model helped construct the associations between the two. The statistical effects revealed that the Time had a significant main effect on subjective sleep and changes in prebedtime alertness; the LEI had a significant main effect only on sleep onset latency (SOL). After undergoing altered prebedtime light exposure, the mean SA increased at prebedtime of D9 (p = 0.022) and D10 (p = 0.044); No significant effect on the NA was observed; Mean subjective sleep had a significant increase from D8 to D10. Moreover, five actigraphy-estimated sleep parameters were interrelated. In light of this, a chained pathway relationship was identified. The SOL played a mediating predictor between prebedtime state and objective sleep, which was linked to the awakening state through subjective sleep. Our study suggests that time-dependent effects of altered prebedtime light exposure on sleep performance are associated with human states at prebedtime and awakening, with implications for its prediction of sleep health.

Anticancer effect of ethanolic extract of Rheum ribes L. rhizomes: assessment of dose and time-dependent effects in cell-based models

Anticancer effect of ethanolic extract of Rheum ribes L. rhizomes: assessment of dose and time-dependent effects in cell-based models

Apple Cider Vinegar in the Combat Against Type 2 Diabetes and Obesity – An Overview of Recent Research

ABSTRACT Introduction Apple Cider Vinegar, primarily composed of acetic acid, is gaining more recognition for its possible health advantages, especially its anti-diabetic effects and its beneficial impact on weight loss. Aim of this study The aim of this review is to discuss the current state of knowledge regarding the influence of ACV on glycemic indices and weight management in diabetic and obese patients, explore the possibilities of preventing comorbidities, and assess the safety of ACV consumption. Materials and Methods Research was performed based on Pubmed and Google Scholar databases. The literature was reviewed using the keywords : Apple Cider Vinegar, Diabetes, Glucose, Obesity. Results Studies have confirmed that apple cider vinegar exhibits significant anti-obesity and anti-diabetic properties. It demonstrates dose- and time-dependent effects on reducing fasting glucose, postprandial glucose, glycated hemoglobin, and lipid parameters. It positively impacts weight loss, reducing waist and hip circumference, and enhances tissue sensitivity to insulin. Additionally, apple cider vinegar has been shown to potentiate the effects of metformin, with liquid consumption yielding better results than pill form. Conclusions Although initial findings are encouraging, additional research with a larger participant pool and an extended duration of vinegar consumption is necessary. The brevity of the study period restricts the observation of long-term effects, and a larger sample size would improve the applicability of the findings. Key words: apple cider vinegar; diabetes; glucose; obesity

Identification and bioactivity evaluation of twelve previously undescribed depsidone derivatives from Garcinia oligantha

AbstractPhytochemical studies on the leaves and twigs of Garcinia oligantha Merr. led to the isolation of twelve previously undescribed depsidone derivatives (oliganthdepsidones A-L, 1–12). Their structures were elucidated by extensive spectroscopic analysis including 1H and 13C NMR, HSQC, HMBC and NOESY along with HRESIMS. The structures of oliganthdepsidones G and J were finally determined using DFT-NMR chemical shift calculations and DP4+ methods. Cytotoxicity test in four human cancer cell lines indicated that oliganthdepsidone F had relatively strong cytotoxic effect against A375 (melanoma), A549 (lung cancer), HepG2 (liver cancer), and MCF-7 (breast cancer) cell lines with IC50 of 18.71, 15.44, 10.92, and 15.90 μM, respectively. The dose- and time-dependent antiproliferative effects of oliganthdepsidone F on these cell lines were also observed by CCK-8 test. As determined by fluorescent microscopy and flow cytometry in these cell lines, oliganthdepsidone F could promote cell apoptosis, leading to the inhibition of cell proliferation. The results of wound healing assay and transwell assay showed that oliganthdepsidone F could inhibit the migration and invasion of A549 and MCF-7 cell lines in a concentration-dependent manner.

Exploring the Anticancer Potential of Astragalin in Triple Negative Breast Cancer Cells by Attenuating Glycolytic Pathway through AMPK/mTOR.

Aerobic glycolysis is crucial for cancer cells to survive, grow, and progress. In the current study, the anti-cancer effects of astragalin (ASG) on breast cancer cells and in the glycolytic pathway through AMPK/mTOR have been evaluated. The objective of this study was to examine the impact of ASG, a natural flavonoid, on glycolysis via targeting AMPK/mTOR signalling in MDA-MB-231 breast cancer cells. The study utilized ASG, which was isolated from Haplophyllum tuberculatum. The cells were treated with different concentrations of ASG (20 and 40 μg/mL), and anti- glycolytic activities were measured through cell proliferation, expression of glycolytic enzymes (HK-2, LDH-A, GLUT-1), glucose uptake, and lactate concentration assays. The MTT assay was used to assess cellular proliferation, while the glucose uptake and lactate levels were determined by employing colorimetric assays. The mRNA expression of target glycolytic enzymes was determined by qRT-PCR. The protein levels of glycolytic targets, as well as that of AMPK and mTOR, were determined by western blot. in silico docking of ASG was done with mTOR and AMPK proteins. Astragalin exhibited dose- and time-dependent anti-proliferative effects in MDA-MB-231 cells. In breast cancer cells, the mRNA and protein expression of GLUT-1, LDH-A, and HK-2 were all significantly downregulated after receiving ASG treatments. Furthermore, after ASG treatments, MDA-MB231 cells showed a significant decrease in lactate and glucose uptake compared to control cells. Mechanistically, ASG increased AMPK activation and suppressed mTOR activation in these cells. The inhibitory role of ASG on aerobic glycolysis was prevented by treatments with compound C (an AMPK inhibitor). However, combined treatment of compound C and ASG could nullify the ASG-induced anti-glycolysis effect and restore the level of p-AMPK and p-mTOR in MDA-MB231 cells. The results from molecular docking predicted that ASG had the potential to bind AMPK and mTOR, with free energy for binding, -8.2 kcal/mol and -8.1 kcal/mol, respectively. Taken together, the findings from this study indicated that ASG might modulate the AMPK/mTOR pathway to inhibit aerobic glycolysis and proliferation of MDAMB231 breast cancer.

Timing-dependent effects of elevated temperature on reproductive traits in the European corn borer moth.

Elevated temperature often has life stage-specific effects on ectotherms because thermal tolerance varies throughout ontogeny. Impacts of elevated temperature may extend beyond the exposed life stage, if developmental plasticity causes early exposure to carry over, or if exposure at multiple life stages cumulatively produces effects. Reproductive traits may be sensitive to different thermal environments experienced during development, but such effects have not been comprehensively measured in Lepidoptera. In this study, we investigate how elevated temperature at different life stages alters reproduction in the European corn borer moth, Ostrinia nubilalis. We tested effects of exposure to elevated temperature (28°C) separately or additively during larval, pupal, and adult life stages compared to control temperatures (23°C). We found that exposure to elevated pupal and adult temperature decreased the number of egg clusters produced, but exposure limited to a single stage did not significantly impact reproductive output. Furthermore, elevated temperature during the pupal stage led to a faster transition to the adult stage and elevated larval temperature altered synchrony of adult eclosion, either by itself or combined with pupal temperature exposure. These results suggest that exposure to elevated temperature during development alters reproduction in corn borers in multiple ways, including through carry-over and additive effects. Additive effects of temperature across life stages are thought to be less common than stage-specific or carry-over effects, but our results suggest thermal environments experienced at all life stages need to be considered when predicting reproductive responses of insects to heatwaves.

Gaussian process regression driven rapid life-cycle based seismic fragility and risk assessment of laminated rubber bearings supported highway bridges subjected to multiple uncertainty sources

Structural attributes, corrosion of steel rebars in reinforced concrete (RC) columns, thermal oxidative aging of inherent rubber in laminated rubber bearings (LRBs), replacement of LRBs, and the time-dependent seismic hazard level at the bridge site are well recognized as the main factors that affect the accurate assessment of the seismic performance of RC bridges implemented with LRBs. However, the probabilistic seismic demand model (PSDM) and probabilistic structural capacity model (PSCM) of deteriorated bridge components may not exhibit homoscedastic log-linearity. And the expansion of seismic fragility surfaces and seismic risk curves in the temporal dimension requires a considerable computational cost on the nonlinear analysis, which regretfully has not been well addressed in current studies. To fill in this gap, this study proposes a life-cycle based seismic fragility and risk assessment framework for LRBs supported RC bridges considering deterioration mechanisms of bridge components during their life cycles demonstrated by a three-span LRBs supported highway bridge considering multiple uncertainties such as the replacement interval for LRBs. In this framework, Gaussian process regression (GPR) is employed to effectively construct the PSDM and PSCM of deteriorated bridge components, and then the time-dependent seismic fragility surfaces of bridge components and bridge system are established. Life-cycle based seismic risk analysis is conducted to quantify the coupled time-dependent effects of deterioration and site seismic hazard on a newly built bridge during its design service life and a deteriorated bridge within its remaining service life, respectively. Results indicate that GPR can successfully capture the nonlinearity and heteroscedasticity characteristics of PSDM and PSCM, leading to a significant reduced number of nonlinear analysis cases to generate the time-dependent seismic fragility surfaces and seismic risk curves. Consequently, the proposed framework using GPR can significantly improve the accuracy and efficiency of life-cycle based seismic performance assessment when uncertainties of structural attributes, deterioration progress and seismic hazard are taken into consideration.

Cytotoxicity and Chemotaxonomic Significance of Saponins from Wild and Cultured Asparagus Shoots.

The shoots of Asparagus L. are consumed worldwide, although most species belonging to this genus have a restricted range, and several taxa remain unstudied. In this work, a total of four taxa from different locations were scrutinized and compared with cultivated A. officinalis. All shoots were screened for saponins via LC-MS, and in vitro antiproliferative activities against the HT-29 colorectal cancer cell line were assessed via the MTT assay. The total saponins (TS) contained in the crude extracts ranged from 710.0 (A. officinalis) to 1258.6 mg/100 g dw (A. acutifolius). The richness of the compounds detected in this work stands out; a total of 47 saponins have been detected and quantified in the edible parts (shoots) of five taxa of Asparagus. The structure of all the saponins found present skeletons of the furostane and spirostane type. In turn, the structures with a furostane skeleton are divided into unsaturated and dioxygenated types, both in the 20-22 position. The sum of dioscin and derivatives varied largely among the studied taxa, reaching the following percentages of TS: 27.11 (A. officinalis), 18.96 (A. aphyllus), 5.37 (A. acutifolius), and 0.59 (A. albus); while in A. horridus, this compound remains undetected. Aspachiosde A, D, and M varied largely among samples, while a total of seven aspaspirostanosides were characterized in the analyzed species. The hierarchical cluster analysis of the saponin profiles clearly separated the various taxa and demonstrated that the taxonomic position is more important than the place from which the samples were acquired. Thus, saponin profiles have chemotaxonomic significance in Asparagus taxa. The MTT assay showed dose- and time-dependent inhibitory effects of all saponins extracts on HT-29 cancer cells, and the strongest cell growth inhibition was exercised by A. albus and A. acutifolius (GI50 of 125 and 175 µg/mL). This work constitutes a whole approach to evaluating the saponins from the shoots of different Asparagus taxa and provides arguments for using them as functional foods.