Physiological Effects Research Articles

Cardiopulmonary Response in Post-COVID-19 Individuals: A Cross-Sectional Study Comparing the Londrina Activities of Daily Living Protocol, 6-Minute Walk Test, and Glittre Activities of Daily Living Test.

This study addresses the imperative need for reliable assessment protocols in guiding rehabilitation interventions for individuals post-COVID-19, considering the enduring physiological effects of the virus. A cohort of 40 post-COVID-19 individuals underwent assessments using the Londrina ADL protocol, Glittre ADL test, and the 6-minute walk test (6MWT). Physiological parameters were recorded during and after each test, including heart rate, respiratory rate, and oxygen saturation. The post hoc comparisons between the pre-test and post-test cardiopulmonary response of the three tests showed significant differences, except diastolic blood pressure (6MWT vs. Londrina ADL protocol), heart rate (6MWT vs. Londrina ADL protocol), respiratory rate (6MWT vs. Londrina ADL protocol), blood oxygen level (SpO2) (6MWT vs. Londrina ADL protocol), dyspnea (Londrina ADL protocol vs. Glittre ADL test), and fatigue (Londrina ADL protocol vs. Glittre ADL test). The Londrina ADL protocol demonstrated cardio-pulmonary responses comparable to the Glittre ADL test, as well as the 6MWT, emphasizing its effectiveness in evaluating walking-related outcomes. The study concludes that the Londrina ADL protocol is a robust and practical tool for the routine clinical testing of daily living activities in post-COVID-19 individuals. While the 6MWT remains valuable for assessing walking-related outcomes, a combined approach employing the Londrina ADL protocol and 6MWT offers a comprehensive strategy for evaluating multifaceted functional capacities in this population.

Abstract 1251: Tobacco smoke alters the adaptive landscape of lung adenocarcinoma and influences the strength of epistatic interactions

Abstract Tobacco smoke produces both mutagenic and physiological effects, altering the mutation rate of cells and the selection acting on them in the damaged lung environment, and facilitating its role in driving cancer progression. In addition to these gene-by-environment interactions, gene-by-gene epistatic interactions also shape the adaptive landscape, influencing the evolutionary trajectories of cancer. Understanding the influence of tobacco smoke on the epistatic trajectories of lung cancer progression would help guide the development of targeted therapies that are more effective for smoker or never-smoker populations. To address this need, we constructed a continuous-time Markov chain model for the evolutionary trajectories of lung adenocarcinoma (LUAD), the most common subtype of lung cancer and the most frequent subtype among never-smokers. Using thousands of tumor sample sequences aggregated across studies, we profiled the trajectories of LUAD in smokers and never-smokers and estimated the rates at which mutations are gained from each possible set of pre-existing mutations, or genetic states. We then accounted for differences in baseline mutation rates to quantify the selective benefit of mutations. We find that epistasis is prevalent in LUAD, with several strong synergistic interactions—such as between RB1 and EGFR mutations- and antagonistic interactions-such as between EGFR and KEAP1 or KRAS mutations. Additionally, we identify non-additive epistatic effects: STK11 mutations are synergistic with KEAP1 and KRAS mutations but do not experience additional selection when both are mutated. In contrast, GNAS mutations are not synergistic with KEAP1 or RBM10 mutations alone but are synergistic with their co-mutation. Smoking has a large influence on the adaptive landscape, with several common mutations being preferentially selected in never-smoker cancers, including EGFR, SMAD4, GNAS, and PIK3CA mutations. KEAP1, STK11, and KRAS mutations are preferentially selected in smoker cancers. Smoking’s physiological influence also affects the strength of certain epistatic interactions, such as between STK11 and KEAP1 mutations. Overall, we find that smoking not only increases the mutation rate of lung cells but also substantially alters the adaptive landscape of lung adenocarcinoma, leading to clinically relevant differences in selection on mutations between smoker and never-smoker cancers. We additionally detect frequent pairwise and higher-order epistatic effects in LUAD that may inform the personalized application of targeted therapies. Citation Format: Krishna Dasari, Jorge Alfaro-Murillo, Jeffrey Townsend. Tobacco smoke alters the adaptive landscape of lung adenocarcinoma and influences the strength of epistatic interactions [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1251.

Quantifying the long-term changes of terrestrial water storage and their driving factors

Global warming is expected to cause changes in terrestrial water storage (TWS) across the land surface, with widespread impacts on ecosystems and society. Although extensive research has been performed to analyze TWS changes and possible drivers during the post-2000 period, longer-term evolution of TWS and associated environmental forcings remain relatively unexplored. In this study, we evaluated the performance of the Energy Exascale Earth System model (E3SM) land model ELM version 1 (ELM v1) in simulating global TWS, and used factorial simulations of ELMv1 to quantify global TWS changes and their drivers during 1948–2012. We found that ELM’s agreed best with existing satellites and reconstruction datasets in temperate regions unaffected by irrigation. Biome- and climate zone-averaged TWS mainly increased at rates between 0 and 10 mm/year over 1948–2012, but the second half of that period saw smaller positive trends than the first half or even negative trends. Climate change explained >80 % of the TWS trends across most biomes and climate zones, followed by land use and land cover change. The physiological and phenological effects of CO2 primarily induced noticeable TWS trends in the more humid biomes and climate zones across different latitudes. In contrast, nitrogen deposition and aerosol deposition generally had smaller and negative impacts across the biomes and climate regions. Among the meteorological drivers analyzed, the long-term average imbalance between precipitation (P), evapotranspiration (E), and runoff (Q) contributed >50 % of the TWS trends in most biomes and climate zones, with nonlinearity being induced by spatially heterogenous changes in E/P and Q/P ratios. The accumulated detrended anomalies in P, E, and Q also often contributed substantially, while the trends difference between P, E, and Q contributed little. Together, these findings unveiled an intensification of the global TWS and its diverse patterns of climate change and different non-withdrawal human-induced alterations, contributing to a more comprehensive understanding and projection of the global water cycle.

Preparation, Characterization, and Bioactivities of Polysaccharide-Nano-Selenium and Selenized Polysaccharides from Acanthopanax senticosus.

Acanthopanax senticosus polysaccharide-nano-selenium (ASPS-SENPS) and A. selenopanax selenized polysaccharides (Se-ASPS) were synthesized, and their characterization and biological properties were compared. The acid extraction method was used to extract the polysaccharides of A. selenopanax, followed by decolorization using the hydrogen peroxide method and deproteinization based on the Sevage method, and the purification of A. senticosus polysaccharides (ASPS) was carried out using the cellulose DEAE-52 ion column layer analysis method. An A. senticosus polysaccharide-nano-selenium complex was synthesized by a chemical reduction method using ASPS as dispersants. The selenization of polysaccharides from A. selenopanax was carried out using the HNO3-Na2SeO3 method. The chemical compositions, scanning electron microscopy images, infrared spectra, and antioxidant properties of ASPS-SENPS and Se-ASPS were studied, and they were also subjected to thermogravimetric analysis. The results indicated that the optimal conditions for the synthesis of ASPS-SENPS include the following: when ASPS accounts for 10%, the ratio of ascorbic acid and sodium selenium should be 4:1, the response time should be 4 h, and the reaction temperature should be 50 °C. The most favorable conditions for the synthesis of Se-ASPS were as follows: m (Na2SeO3):m (ASPS) = 4:5, response temperature = 50 °C, and response time = 11.0 h. In the in vitro antioxidant assay, when the mass concentration of Se-ASPS and ASPS-SENPS was 5 mg/mL, the removal rates for DPPH free radicals were 88.44 ± 2.83% and 98.89 ± 3.57%, respectively, and the removal rates for ABTS free radicals were 90.11 ± 3.43% and 98.99 ± 1.73%, respectively, stronger than those for ASPS. The current study compares the physiological and bioactivity effects of ASPS-SENPS and Se-ASPS, providing a basis for future studies on polysaccharides.

The Influence of Triphenyltin Exposure on the Osmoregulatory Capacity of Marine Medaka (Oryzias melastigma) at Different Salinities

Triphenyltin (TPT) is an organotin pollutant widely found in the aquatic environment. It has endocrine-disrupting and osmotic pressure toxicity. In this study, the physiological and biochemical effects of TPT and various salinities were investigated in different tissues (gut, gill, and brain) of marine medaka. The exposure experiments were conducted for 42 days in different salinities (0, 15, and 30 ppt) without TPT exposure and in different salinity groups with TPT exposure concentrations of 100 ng/L, respectively. The results showed that the Na+-K+-ATPase (NKA) and Ca2+ATPase activity had significant tissue-specific differences, with the highest activity observed in the gills, indicating their major contribution to osmoregulation. Changes in salinity also resulted in significant alterations in the ion concentrations of the gut and gill tissues in the 0-C and 15-C groups. While the changes in Na+ and Cl− were relatively stable, the presence of TPT disrupted the regulation of Ca2+ and K+. In conclusion, substantial variations were observed in the osmoregulatory capacity of marine medaka tissues. Environmental concentrations of TPT had little effect on osmotic enzyme activity but interfered with the regulation of Ca2+ and K+ concentrations in the tissues. This study provides valuable insights into the osmotic toxicity of TPT in aquatic environments with different salinities.

Temperature influences the toxicity, behavioral, and physiology response of chlorfenapyr, fipronil, imidacloprid, and indoxacarb to Reticulitermes flaviceps

A comprehensive understanding of the interaction between pesticides and climate change is critical to the safety of pesticide applications. Many insecticides are actually more toxic at higher temperatures. However, little is currently known about the effect of temperature on the toxicity of chemicals. In order to fill this knowledge gap and improve our understanding of the mechanisms of temperature effects, the present study investigated the toxic, physiological, and behavioral effects of four insecticides, chlorfenapyr, fipronil, imidacloprid, and indoxacarb, on subterranean termites, Reticulitermes flaviceps at different temperatures (24 to 32 °C). The results show that the sensitivity of R. flaviceps to chrofenapyr (LC50 = 8.67–152.49 mg/L), fipronil (LC50 = 10.14–36.84 mg/L), imidacloprid (LC50 = 184.27–326.47 mg/L) and indoxacarb (LC50 = 12.23–46.23 mg/L) substantially increased when the temperature alters from 24 to 32 °C. Additionally, the activities of three detoxification enzymes [glutathione S-transferases (GSTs), carboxylesterase (CarE), and cytochrome P450 (P450)] of R. flaviceps were also measured of four insecticide at various temperatures. Correlation analysis reveals that changes in GSTs CarE and P450 activities of R. flaviceps are closely related to their sensitivity to chlorfenapyr, fipronil, imidacloprid, and indoxacarb. Meanwhile, the speed of action (LT50 value) of four insecticides is positively affected by temperature. In addition, intoxication, ataxia, and moribundity behaviors were observed in most concentrations and temperature combinations for chlorfenapyr, fipronil, and imidacloprid–exposed termite. The findings of our research emphasize that in the context of global climate change, the development and application of pesticides should consider the temperature dimension.

How much heat does non-photochemical quenching produce?

Non-photochemical quenching (NPQ) is a protective mechanism used by plants to safely dissipate excess absorbed light energy as heat, minimizing photo-oxidative damage. Although the importance of NPQ as a safety valve for photosynthesis is well-known, the physiological and environmental effects of the heat produced remain unclear because the amount of heat produced by NPQ is considered negligible, and its physiological effects have not been directly observed. Here, we calculated the heat produced by NPQ and evaluated its impact on the leaf and global warming based on simplified models. Our evaluation showed that the heat produced by NPQ in a given leaf area is 63.9 W m-2 under direct sunlight. Under the standard condition, NPQ warms up the leaf at less than 0.1°C, but it could be 1°C under particular conditions with low thermal conductance. We also estimated the thermal radiation of vegetation's NPQ to be 2.2 W m-2 par global averaged surface area. It is only 0.55% of the thermal radiation by the Earth's surface, but still significant in the current climate change response. We further discuss the possible function of NPQ to plant physiology besides the safety valve and provide strategies with artificial modification of the NPQ mechanism to increase food production and mitigate global warming.

Modulation of neural gene networks by estradiol in old rhesus macaque females.

The postmenopausal decrease in circulating estradiol (E2) levels has been shown to contribute to several adverse physiological and psychiatric effects. To elucidate the molecular effects of E2 on the brain, we examined differential gene expression and DNA methylation (DNAm) patterns in the nonhuman primate brain following ovariectomy (Ov) and subsequent subcutaneous bioidentical E2 chronic treatment. We identified several dysregulated molecular networks, including MAPK signaling and dopaminergic synapse response, that are associated with ovariectomy and shared across two different brain areas, the occipital cortex (OC) and prefrontal cortex (PFC). The finding that hypomethylation (p = 1.6 × 10-51) and upregulation (p = 3.8 × 10-3) of UBE2M across both brain regions provide strong evidence for molecular differences in the brain induced by E2 depletion. Additionally, differential expression (p = 1.9 × 10-4; interaction p = 3.5 × 10-2) of LTBR in the PFC provides further support for the role E2 plays in the brain, by demonstrating that the regulation of some genes that are altered by ovariectomy may also be modulated by Ov followed by hormone replacement therapy (HRT). These results present real opportunities to understand the specific biological mechanisms that are altered with depleted E2. Given E2's potential role in cognitive decline and neuroinflammation, our findings could lead to the discovery of novel therapeutics to slow cognitive decline. Together, this work represents a major step toward understanding molecular changes in the brain that are caused by ovariectomy and how E2 treatment may revert or protect against the negative neuro-related consequences caused by a depletion in estrogen as women approach menopause.

Ionic complexation, metal coordination, and physiological stress effects of polyborate

Organic agents exhibit efficacy in water quality stabilization, yet entail inherent risks of nitrogen and phosphorus diffusion losses. This work introduces a versatile inorganic polyborate slow-release preparations (PSRPs) agents. The effectiveness of the PSRPs in terms of scale inhibition, corrosion resistance, and antibacterial activity was empirically validated within a simulated cooling station operating at a circulation rate of 6 L/h and 636 L/h. The [BO3] units dissociate from the PSRPs complex with Ca0.8Mg0.2, forming slightly soluble, flocculent complexes. The complexes exhibit flexibility and low adhesiveness, enhancing to settle and separate from aquatic environments. Notably, self-propagating boronizing on carbon steel surfaces is characterized by the coordination of Fe with B and O atoms from polyborates. Such coordination notably hinders the transition of iron into its oxidative and ionic forms. Moreover, the study highlights the significant physiological stress effects exerted by high concentrations of borate salts on algae and bacteria. Under the influence of PSRPs, the deposition of scale decreased from 376.9 g/m2 to 35.3 g/m2, the corrosion rate decreased from 1.60 mm/y to 0.22 mm/y, and the antibacterial efficiency increased to 81.8 %. This work is a significant attempt to develop new multifunctional inorganic water treatment agents.

Novel Human Milk Fat Substitutes Based on Medium- and Long-Chain Triacylglycerol Regulate Thermogenesis, Lipid Metabolism, and Gut Microbiota Diversity in C57BL/6J Mice.

Human milk is naturally rich in medium- and long-chain triacylglycerols (MLCT), accounting for approximately 30% of the total fat. However, infant formula fat is prepared using a physical blend of vegetable oils, which rarely contains MLCT, similar to human milk. The differences in MLCT between human milk and infant formulas may cause different lipid metabolisms and physiological effects on infants, which are unknown. This study aimed to analyze the metabolic characteristics of formula lipid containing novel human milk fat substitutes based on MLCT (FL-MLCT) and compare their effects with those of the physical blend of vegetable oils (FL-PB) on lipid metabolism and gut microbiota in mice. Compared with the FL-PB group, the FL-MLCT group showed increased energy expenditure, decreased serum triacylglycerol level, and significantly lower aspartate aminotransferase level, epididymal and perirenal fat weight, and adipocyte size. Moreover, the abundances of Firmicutes/Bacteroidota, Actinobacteriota, and Desulfovibrionaceae were significantly decreased in the FL-MLCT group. Novel human milk fat substitutes MLCT could inhibit visceral fat accumulation, improve liver function, and modulate the mice gut microbiota composition, which may contribute to controlling obesity.

Abstract P498: Different Metabolomic Associations With Mediterranean Style Diet (MSD) Scores Between Individuals With Normoglycemia vs. Impaired Fasting Glucose (IFG) in the Multi-Ethnic Study of Atherosclerosis Transomic Precision Medicine Initiative (MESA-TOPMed) Data

Diet-metabolite associations for foods high in monounsaturated fatty acids (MUFAs) differ between those with normo- vs. with dys- glycemia. As metabolites represent the physiological effects of food after it has been digested, processed, and absorbed, this suggests that dysglycemia alters how foods are metabolized and thus their potential health impacts. Our goal was to examine whether metabolites associated with adherence to a MSD, a diet high in MUFA, differed by glycemia status (normoglycemia vs. IFG [125<FG≥110 mg/dL]). We leveraged the longitudinal data on diet and plasma metabolites (N=2,816) in MESA-TOPMed, collected at two exams ~10y apart (baseline (BL): 2000-2002, and follow-up (FU): 2010-2011), on ~3,700 multi-ethnic US adults, ages 44-84y at baseline. Between exams, the proportion of the population with IFG increased from 25% to 40% (P<1.0*10 -16 ), providing a natural experiment to examine how MSD-metabolite associations change alongside population-level glycemia changes. We interpreted linear models which specified metabolites values as the outcome, and MSD score as the predictor, and adjusted for demographic (age, gender, race/ethnicity, income level, highest education level) and health behavior (physical activity, energy intake, smoking status, body mass index [BMI]) information, with longitudinal models also including time as a fixed effect (days since BL). Longitudinal random-intercept multi-level models identified 789 compounds associated with MSD at metabolome wide levels of significance (P<1.8*10 -5 ). Significant diet-by-time interactions (P<.05) indicated that the 241 metabolites showed associated with MSD that were time-specific, changing as population dysglycemia increased (alongside changes in other characteristics), and we observed different effect sizes for MSD-metabolite associations in those with IFG vs those with normoglycemia (t = 3.4, df = 145, P = 9.0*10 -4 ). 548 metabolites showed associations with an MSD that were time-invariant, and when analyses were stratified by glycemia status, more of these more ‘universally associated’ metabolites were significantly associated with an MSD in those with IFG and normoglycemia, vs. in just one dysglycemia group (45% vs. 15%; X 2 =117, df=2, P<2.0*10 -16 ). Our longitudinal analyses demonstrated that population-level metabolite associations with an MSD change as the population dysglycemia changes. Of course, other characteristics changed as well, and only some of these (e.g., BMI and age) were controlled for in our analyses. However, our cross-sectional analyses provided additional evidence that MSD-metabolite associations differ between those with normoglycemia vs. IFG. We are now seeking replication in other TOPMed cohorts, to support that notion that tailoring dietary advice to T2D prevention vs. management would be an important direction for future precision nutrition efforts.

Dietary L-Methionine modulates the gut microbiota and improves the expression of tight junctions in an in vitro model of the chicken gastrointestinal tract

BackgroundThe poultry industry encounters a number of factors that affect growth performance and productivity; nutrition is essential for sustaining physiological status and protecting against stressors such as heat, density, and disease. The addition of vitamins, minerals, and amino acids to the diet can help restore productivity and support the body’s defense mechanisms against stress. Methionine (Met) is indispensable for poultry’s energy metabolism, physiology, performance, and feed utilization capacity. Through this study, we aimed to examine the physiological effects of methionine supplementation on poultry as well as alterations of intestinal microbiome.MethodsWe utilized the DL- and L- form of methionine on Caenorhabditis elegans and the FIMM (Fermentor for intestine microbiota model) in-vitro digesting system. A genomic-analysis of the transcriptome confirmed that methionine supplementation can modulate growth-related physiological metabolic pathways and immune responses in the host poultry. The C. elegans model was used to assess the general health benefits of a methionine supplement for the host.ResultsRegardless of the type or concentration of methionine, supplementation with methionine significantly increased the lifespan of C. elegans. Feed grade L-Methionine 95%, exhibited the highest lifespan performance in C. elegans. Methionine supplementation increased the expression of tight junction genes in the primary intestinal cells of both broiler and laying hens, which is directly related to immunity. Feed grade L-Methionine 95% performed similarly or even better than DL-Methionine or L-Methionine treatments with upper doses in terms of enhancing intestinal integrity. In vitro microbial cultures of healthy broilers and laying hens fed methionine revealed changes in intestinal microflora, including increased Clostridium, Bacteroides, and Oscillospira compositions. When laying hens were given feed grade L-Methionine 95% and 100%, pathogenic Campylobacter at the genus level was decreased, while commensal bacteria were increased.ConclusionsSupplementation of feed grade L-Methionine, particularly L-Methionine 95%, was more beneficial to the host poultry than supplementing other source of methionine for maintaining intestinal integrity and healthy microbiome.

Warm-Up Strategies and Effects on Performance in Racing Horses and Sport Horses Competing in Olympic Disciplines.

Warm-up is a standard component of exercise preparation, intended to lower the risk of injury and improve performance. Comprehensive evidence-based guidelines per discipline are missing. This scoping review aimed to describe the physiological effects and strategies of active warm-up in horses according to different equestrian disciplines. The search strategies identified 479 papers for review. After application of selection criteria, 23 articles published from 1996 to January 2024 were included of which 12 discussed the effects of warm-up on physiological parameters and 11 discussed warm-up strategies in different disciplines. As shown in humans, warm-up enhanced aerobic capacity and increased blood and muscle temperatures, independently from its intensity. Riders emphasized the importance of warm-up to prepare horses for physical work and to increase their reactiveness to aids. A canter or trot was the preferred gait in elite or non-elite dressage horses, respectively, while the walk was in show jumping horses. Warm-up duration and intensity increased with increasing competitive level, but a longer and/or more intensive warm-up did not affect the final score. Dressage riders warmed up their horses for a longer time compared to show jumping riders. Future studies should objectively establish the most profitable warm-up strategies per equestrian discipline and level.

Abstract P299: Alteration of Cardiac Autonomic Function Through Inhalation of Biogenic Volatile Organic Compounds

Background: There is an inverse relationship between exposure to greenspaces and prevalence of cardiovascular disease and cardiovascular disease risk factors. More specifically, green exposure is associated with electrocardiogram (ECG) changes, suggesting a potential alteration of cardiac autonomic balance. One proposed mechanism by which cardiac autonomic balance may be altered is a direct physiologic effect of inhalable plant derived compounds, or biogenic volatile organic compounds (bVOCs), including limonene, α- and β-pinene which are commonly released from vegetation. Therefore, we examined the relationship between acute exposure of isolated bVOCs and cardiac autonomic tone. Hypothesis: We hypothesize that controlled exposure to isolated individual bVOCs will decrease cardiac sympathetic tone. Methods: Under controlled conditions after a bVOC washout period, healthy adults ages 18-70 were exposed to limonene (n=32), α-pinene (n=24), β-pinene (n=17), and a control (room air, n=9). Exposure consisted of one inhalation every 30 seconds for a total of 5 minutes (10 inhalations total). Pre- and post-exposure measurements of supine heart rate variability (HRV) were conducted following a 10-minute rest period. HRV was analyzed using a clean, 5-minute epoch with >95% effective data length. Statistical analysis was performed using paired t-tests to determine changes in HR and HRV. Significance level was set at p<0.05, a priori . Results: Our population was primarily female (56%, 18 of 32), white (53%, 17 of 32), high income (47%, 15 of 32), and had an education higher than a 4-year degree (62.5%, 20 of 32). There were significant decreases in HR when exposed to limonene (pre: 64.87±9.86bpm vs. post: 63.26±9.10bpm, p<.001) and α-pinene (pre: 63.98±9.32bpm vs. post: 61.64±9.72bpm, p=.008), along with trends seen in β-pinene (pre: 65.78±10.60bpm vs. post: 63.74±9.65bpm, p=.066). Control exposure showed no difference (pre: 65.40±8.38bpm vs. post: 64.14±9.35bpm, p=.301). Normalized low- (LF) and high-frequency (HF) HRV parameters showed no change across isolated bVOCs, however the LF/HF ratio scores decreased significantly following β-pinene exposure (pre: 1.62±1.69 vs. post: 0.96±0.96, p=.039). HRV time-domain parameters RMSSD and SDNN did not change following isolate exposure. Conclusions: Post-exposure decreases in HR and LFHF ratios indicate the potential for cardiovascular disease risk reduction from bVOC exposure leading to decreased sympathetic tone. Additional work is required to determine the mechanism of exposure-related changes.

Biomimetic nanoparticles for effective Celastrol delivery to targeted treatment of rheumatoid arthritis through the ROS-NF-κB inflammasome axis

Previous study has indicated that Celastrol (Cel) has various physiological and pharmacological effects, including antibacterial, antioxidant, pro-apoptotic, anticancer and anti-rheumatoid arthritis (RA) effects. However, low water solubility, low oral bioavailability, narrow treatment window, and high incidence of systemic adverse reactions still limit the further clinical application of Cel. Here, aiming at effectively overcome those shortcomings of Cel to boost its beneficial effects for treating RA, we developed the leukosome (LEUKO) coated biomimetic nanoparticles (NPs) for the targeted delivery of Cel to arthritis injury area in RA. LEUKO were synthesized using membrane proteins purified from activated J774 macrophage. LEUKO and Cel-loaded LEUKO (Cel@LEUKO) were characterized using dynamic light scattering and transmission electron microscopy. Our results demonstrated that Cel@LEUKO can inhibit the inflammatory response of lipopolysaccharide (LPS) induced mouse monocyte macrophage leukemia cells (RAW264.7 cells) and human rheumatoid arthritis synovial fibroblasts (MH7A) cells through the inhibition of reactive oxygen species (ROS)-NF-κB pathway. In addition, research has shown that LEUKO effectively targets and transports Cel to the inflammatory site of RA, increased drug concentration in affected areas, reduced systemic toxicity of Cel, and reduced clinical symptoms, inflammatory infiltration, bone erosion, and serum inflammatory factors in collagen-induced arthritis (CIA) rats.

Intraspecific trait variation modulates the temperature effect on elemental quotas and stoichiometry in marine Synechococcus.

Diverse phytoplankton modulate the coupling between the ocean carbon and nutrient cycles through life-history traits such as cell size, elemental quotas, and ratios. Biodiversity is mostly considered at broad functional levels, but major phytoplankton lineages are themselves highly diverse. As an example, Synechococcus is found in nearly all ocean regions, and we demonstrate contains extensive intraspecific variation. Here, we grew four closely related Synechococcus isolates in serially transferred cultures across a range of temperatures (16-25°C) to quantify for the relative role of intraspecific trait variation vs. environmental change. We report differences in cell size (p<0.01) as a function of strain and clade (p<0.01). The carbon (QC), nitrogen (QN), and phosphorus (QP) cell quotas all increased with cell size. Furthermore, cell size has an inverse relationship to growth rate. Within our experimental design, temperature alone had a weak physiological effect on cell quota and elemental ratios. Instead, we find systemic intraspecific variance of C:N:P, with cell size and N:P having an inverse relationship. Our results suggest a key role for intraspecific life history traits in determining elemental quotas and stoichiometry. Thus, the extensive biodiversity harbored within many lineages may modulate the impact of environmental change on ocean biogeochemical cycles.

Feasibility study of powdered activated carbon membrane bioreactor (PAC-MBR) for source-separated urine treatment: A comparison with MBR

Micropollutants (MPs) such as pharmaceuticals and personal care products are a group of emerging environmental contaminants, which are structurally complex and can cause adverse physiological effects on human health at low concentration. This study demonstrated that a hybrid process of powdered activated carbon and microfiltration membrane bioreactor (PAC-MBR) could be utilized for efficient removal of metronidazole, acetaminophen, naproxen, ibuprofen, carbamazepine, estriol (> 99 %) from source-separated urine via physical adsorption and biodegradation in a single step, without compromising the operating system stability. PAC addition to MBR improved 5 % of nitrification performance in terms of ammonia to nitrate conversion rate. Further, it improved organic removal efficiency from 88.6 ± 2.9 % to 96.0 ± 1.2 %, promoted rapid biomass growth, increased sludge floc size growth by 17 % and reduced membrane fouling propensities. This study showed the production of a micropollutant-free fertiliser from source-separated urine achieving a complete nutrient recovery in a single stage MBR system.

Physiological and metabolic effects of using interval training loads by athletes specializing in race walking in different training periods

Purpose: to evaluate the efficiency of using interval training loads by athletes specializing in race walking in different training periods using biochemical and physiological indicators.&#x0D; Material and methods. The study included 22 athletes specializing in race walking aged 19-30 years with 6-15 years of sports experience and qualifications of Master of Sports (MS) and International Master of Sports (ICMS). The athletes performed physical tests - 500m x 20 times and 1000m x 12 times. The study was conducted both at rest and during the recovery period after performing the physical tests. Physiological and biochemical control with the determination of lactate content in the blood, heart rate, and sports performance was used to assess the direction and effectiveness of the training process in different periods of athletes' training.&#x0D; Results. Used interval loads confirm the correct choice of the training load program, which has shown its effectiveness in the competitive period of training compared to the preparatory period: it contributed to the improvement of test results, speed capabilities and high-speed endurance of athletes. It has been established that the use of interval training, accompanied by the accumulation of lactate up to 12 mmol·l-1 in the blood and an increase in heart rate over 180 min-1, leads to an improvement in sports performance.&#x0D; Conclusions. The used interval training loads contributed to the improvement of sports result in the competitive period in comparison with the preparatory period when overcoming series of 500 m distance by 2,08s, and 1000 m distance - by 6,56s, that testifies to the improvement of motor qualities - speed and high-speed endurance of sportsmen in the competitive period in comparison with the preparatory period.

The Physiological and Clinical-Behavioral Effects of Heart Rate Variability Biofeedback in Adolescents with Autism: A Pilot Randomized Controlled Trial.

Adolescents with autism present lower levels of cardiac vagal modulation. It was hypothesized that Heart Rate Variability Biofeedback (HRVB) increases cardiac vagal modulation in adolescents with autism, resulting in positive effects on physiological and psychosocial parameters. It was also hypothesized that home-based HRVB training is feasible. In a single-blind, randomized sham-controlled pilot trial, adolescents with autism performed supervised HRVB (n = 24) or sham training (n = 20). Subsequently, half of the adolescents received HRVB training at home, whereas the other subset did not practice. Physiological, cortisol and behavioral data were collected during stress-provoking assessments before and after each training period. Supervised HRVB resulted in a late increase in cardiac vagal modulation in adolescents with autism. Heart rate increased and cortisol decreased significantly immediately after supervised HRVB, but none of these effects remained after follow-up. Following supervised HRVB, no significant change in psychosocial functioning was found. Home-based HRVB was feasible, adolescents reported lower symptoms of stress, but a significant decrease in compliance rate was found. HRVB is feasible and effective in adolescents with autism given the late-emerging increases in cardiac vagal modulation and decrease in stress symptoms. Replicating this study with a larger sample and further exploration of the working mechanisms of HRVB are recommended. ClinicalTrials.gov , NCT04628715.

TARGET ONCOGENIC RECEPTORS IN TUMOURS, FROM ITS INITIAL CLINICAL BREAKTHROUGHS TO CURRENT CLINICAL STANDARD THERAPY

Epidermal growth factor (EGF) is a polypeptide hormone originally isolated from mouse submaxillary gland, which is a potent mitogen for a wide variety of culture cells of both epithelial and mesenchymal origin, and its important role in the proliferation, differentiation, and survival of neural and glial precursor cells. The physiological effects of EGF are mediated by an EGF receptor with tyrosine-specific protein kinase activity. The traditionally accepted view is that normal epidermal growth factor receptor (EGFR) is no tumorigenic, whereas mutated EGFR such as an oncogenic receptor EGFRvIII is oncogenic. In recent, it has been implicated that EGF could be beneficial for burn, wound healing, diabetic foot ulcer, and show an attractive perspective. In addition, cosmetic containing EGF would be effective in improving the plasticity of skin, helps in anti-aging and whitening, and controls the amount of erythema and sebum in the skin. In our team we have successfully prepared a series of 350 bottles of Shampoo liquid and 26 bottles of recombinant human EGF (rhEGF) spray, and 4 bottles of EGF-Silvadence ointment. The initial results indicated that prepared rhEGF is safe and available in clinical use. On the other hand, progress on the interaction of EGF with its altered oncogenic receptor signaling through its downstream molecules such Ras/Raf/MAPK (see figure in the full text, George Zhu,1991) and/or PI3k/akt pathway in the development of some cancers such as A431 human epidermoid carcinoma cells, brain glioblastoma, breast, pancreas and lung cancers. In addition to a series of gefitinib, erlotinib, osimertinib and the CIMA vax-EGF vaccine, an antioncogenic receptor antibody based fusion protein [for example Cetuximab-based IL-10 fusion protein, CmAb-(IL10)2] provide a potential strategy to improve cancer immunotherapy. Peer Review History: Received 1 December 2023; Revised 26 January 2024; Accepted 2 March; Available online 15 March 2024 Academic Editor: Dr. Tamer Elhabibi, Suez Canal University, Egypt, tamer_hassan@pharm.suez.edu.eg Average Peer review marks at initial stage: 6.0/10 Average Peer review marks at publication stage: 8.0/10 Reviewers: Dr. Bilge Ahsen KARA, Ankara Gazi Mustafa Kemal Hospital, Turkey, ahsndkyc@gmail.com Dr. Asia Selman Abdullah, University of Basrah, Iraq, asia_abdullah65@yahoo.com