Conditions Of Depletion Research Articles

Hydrogen sulfide-mediated persulfidation regulates homocysteine metabolism and enhances ferroptosis in non-small cell lung cancer

Hydrogen sulfide (H₂S), a metabolite of the transsulfuration pathway, has been implicated in ferroptosis, a unique form of cell death caused by lipid peroxidation. While the exact mechanisms controlling ferroptosis remain unclear, our study reveals that H₂S sensitizes human non-small cell lung cancer (NSCLC) cells to this process, particularly when cysteine levels are low. Combining H₂S with cystine depletion significantly enhances the effectiveness of ferroptosis-based cancer therapy. Mechanistically, H₂S persulfidates the 195th cysteine on S-adenosyl homocysteine hydrolase (SAHH), reducing its enzymatic activity. This leads to decreased homocysteine levels, subsequently lowering cysteine and glutathione concentrations under cystine depletion conditions. These changes ultimately increase the vulnerability of NSCLC cells to ferroptosis. Our findings establish H₂S as a key regulator of homocysteine metabolism and a critical factor in determining NSCLC cell susceptibility to ferroptosis. These results highlight the potential of H₂S-based therapies to improve the efficacy of ferroptosis-targeted cancer treatments for NSCLC.

Response to the CO2 concentrating mechanisms and transcriptional time series analysis of Ulva prolifera under inorganic carbon limitation

Ulva prolifera is a dominant species in green tides and has been affecting marine ecosystem for many years. Due to the low availability of CO2 in the environment, U. prolifera utilizes the CO2 concentrating mechanisms (CCMs) to increase intracellular inorganic carbon concentration. However, the transcriptional response mechanism and temporal changes of U. prolifera CCMs based on transcriptomics have not been thoroughly described. Therefore, we induced U. prolifera CCMs in a low CO2 environment to explore the dynamic regulation of CCMs expression under inadequate inorganic carbon supply. The results showed that inorganic carbon limitation increased the inorganic carbon affinity of U. prolifera, upregulating CCMs. The first 24 h of inorganic carbon environmental changes were the most active period for U. prolifera's expression regulation. U. prolifera gradually achieved a new steady state by regulating metabolic processes such as nucleic acids, energy, and ethylene-activated signaling pathways. In the carbon fixation system of U. prolifera, there are characteristics of both biophysical and biochemical CCMs. After 24 h of inorganic carbon limitation, the biophysical CCMs becomes more effective under conditions of inorganic carbon depletion. This study aids in exploring the CCMs of U. prolifera and their evolution in response to environmental changes.

Asparagine synthetase and G-protein coupled estrogen receptor are critical responders to nutrient supply in KRAS mutant colorectal cancer.

Survival differences exist in colorectal cancer (CRC) patients by sex and disease stage. However, the potential molecular mechanism(s) are not well understood. Here we show that asparagine synthetase (ASNS) and G protein-coupled estrogen receptor-1 (GPER1) are critical sensors of nutrient depletion and linked to poorer outcomes for females with CRC. Using a 3D spheroid model of isogenic SW48 KRAS wild-type (WT) and G12A mutant (MT) cells grown under a restricted nutrient supply, we found that glutamine depletion inhibited cell growth in both cell lines, whereas ASNS and GPER1 expression were upregulated in KRAS MT versus WT. Estradiol decreased growth in KRAS WT but had no effect on MT cells. Selective GPER1 and ASNS inhibitors suppressed cell proliferation with increased caspase-3 activity of MT cells under glutamine depletion condition particularly in the presence of estradiol. In a clinical colon cancer cohort fromThe Cancer Genome Atlas, both high GPER1 and ASNS expression were associated with poorer overall survival for females only in advanced stage tumors. These results suggest KRAS MT cells have mechanisms in place that respond to decreased nutrient supply, typically observed in advanced tumors, by increasing the expression of ASNS and GPER1 to drive cell growth. Furthermore, KRAS MT cells are resistant to the protective effects of estradiol under nutrient deplete conditions. The findings indicate that GPER1 and ASNS expression, along withthe interaction between nutrient supply and KRAS mutations shed additional light on the mechanisms underlyingsex differences in metabolism and growth in CRC, and have clinical implications in the precision management of KRAS mutant CRC.

Early depletion of gut microbiota shape oligodendrocyte response after traumatic brain injury

White matter injury (WMI) is thought to be a major contributor to long-term cognitive dysfunctions after traumatic brain injury (TBI). This damage occurs partly due to apoptotic death of oligodendrocyte lineage cells (OLCs) after the injury, triggered directly by the trauma or in response to degenerating axons. Recent research suggests that the gut microbiota modulates the inflammatory response through the regulation of peripheral immune cell infiltration after TBI. Additionally, T-cells directly impact OLCs differentiation and proliferation. Therefore, we hypothesized that the gut microbiota plays a critical role in regulating the OLC response to WMI influencing T-cells differentiation and activation. Gut microbial depletion early after TBI chronically reduced re-myelination, acutely decreased OLCs proliferation, and was associated with increased myelin debris accumulation. Surprisingly, the absence of T-cells in gut microbiota depleted mice restored OLC proliferation and remyelination after TBI. OLCs co-cultured with T-cells derived from gut microbiota depleted mice resulted in impaired proliferation and increased expression of MHC-II compared with T cells from control-injured mice. Furthermore, MHC-II expression in OLCs appears to be linked to impaired proliferation under gut microbiota depletion and TBI conditions. Collectively our data indicates that depletion of the gut microbiota after TBI impaired remyelination, reduced OLCs proliferation with concomitantly increased OLC MHCII expression, and required the presence of T cells. This data suggests that T cells are an important mechanistic link by which the gut microbiota modulate the oligodendrocyte response and white matter recovery after TBI.

Amorphous silicon detectors for proton beam monitoring in FLASH radiotherapy

Ultra-high dose rate radiation therapy (FLASH) based on proton irradiation is of major interest for cancer treatments but creates new challenges for dose monitoring. Amorphous hydrogenated silicon is known to be one of the most radiation-hard semiconductors. In this study, detectors based on this material are investigated at proton dose rates similar to or exceeding those required for FLASH therapy. Tested detectors comprise two different types of contacts, two different thicknesses deposited either on glass or on polyimide substrates. All detectors exhibit excellent linear behaviour as a function of dose rate up to a value of 20 kGy/s. Linearity is achieved independently of the depletion condition of the device and remarkably in passive (unbiased) conditions. The degradation of the performance as a function of the dose rate and its recovery are also discussed.

Modeling phase equilibria for a water-CO2-hydrocarbon mixture using CPA equation of state in CO2 injection EOR-storage processes: a Colombian case study

Currently, it is necessary to reduce CO2 emissions into the atmosphere. The oil industry in Colombia can contribute through CO2 injection processes in depleted fields. To achieve this, it is essential to have knowledge of the physicochemical interactions of CO2 with reservoir fluids. To integrate CO2, water and hydrocarbon phases, advanced models are required that capture the phenomenology of thermodynamic equilibrium. The CPA (Cubic-Plus-Association) equation of state is an equation that adds an associative term to model the interaction of water with the hydrocarbon and CO2 phase. In this work, the CO2 injection process is thermodynamically modeled in a depleted Colombian reservoir case study. There is a compositional fluid with a gradient of PVT properties in a vertical relief of 10,000 ft at a depletion condition of 2,000 psi @ 15,374 ft and an oil-water contact (OWC) at 17,000 ft. CO2 injections between 10 and 80 mol% were carried out, and through the CPA equation of state, the swelling conditions of the crude oil, the solubility of CO2 in the formation water and the pressurization of the system were evaluated. The associative parameters of the equation were taken from literature and estimated through molecular dynamics simulations of water-CO2-Hydrocarbon interactions. This thermodynamic modeling with an advanced equation of state and use of molecular dynamics simulations allowed us to simulate different CO2 injection scenarios in a compositional fluid. The development of these types of studies is key to carrying out successful CO2 injection processes focused on enhanced recovery (EOR) and CO2 storage in the porous medium in a Colombian-depleted compositional reservoir.

Основные маршруты экологического туризма в Чеченской Республике

Various approaches to defining ecological tourism as a nature-oriented form of tourism have been investigated. Describes the diverse types and types of ecological tourism and its advantages in comparison with other types of tourism and recreation. The role of ecological tourism in achieving the sustainable development goals of the region is revealed. It has been shown that development cannot be sustainable in conditions of depletion of natural resources and degradation of natural systems. The prerequisites for the development of tourist and recreational activities are disclosed on the example of the Chechen Republic, for which several ecological tourism routes are proposed and described. These routes are mainly laid from the Chechen Plain to the mountainous regions, covering picturesque landscapes and many unique geomorphological, hydrological, geological and historical and cultural objects. In the context of more sustainable development of the region, some recommendations are given to solve the most acute problems of the tourist and recreational industry.

Evaluation of Extraction Techniques for Recovery of Microalgal Lipids under Different Growth Conditions.

Microalgal lipids contain a wide array of liposoluble bioactive compounds, but lipid extraction remains a critical limitation for their commercial use. An accelerated solvent extraction (ASE) was used to extract lipids from Chlamydomonas reinhardtii, Arthrospira platensis (Spirulina), and Chlorella vulgaris grown under either standard or nitrogen depletion conditions. Under standard growth conditions, ASE using methanol:chloroform (2:1), methyl tert-butyl ether (MTBE):methanol:water, and ethanol at 100 °C resulted in the highest recovery of total lipids (352 ± 30, 410 ± 32, and 127 ± 15 mg/g biomass from C. reinhardtii, C. vulgaris, and A. platensis, respectively). Similarly, the highest total lipid and triacylglycerols (TAGs) recovery from biomass cultivated under nitrogen depletion conditions was found at 100 °C using methanol:chloroform, for C. reinhardtii (total, 550 ± 21; TAG, 205 ± 2 mg/g biomass) and for C. vulgaris (total, 612 ± 29 mg/g; TAG, 253 ± 7 mg/g biomass). ASE with MTBE:methanol:water at 100 °C yielded similar TAG recovery for C. reinhardtii (159 ± 6 mg/g) and C. vulgaris (200 ± 4 mg/g). Thus, MTBE:methanol:water is suggested as an alternative substitute to replace hazardous solvent mixtures for TAGs extraction with a much lower environmental impact. The extracted microalgal TAGs were rich in palmitic (C16:0), stearic (C18:0), oleic (C18:1,9), linoleic (C18:2n6), and α-linolenic (C18:3n3) acids. Under nitrogen depletion conditions, increased palmitic acid (C16:0) recovery up to 2-fold was recorded from the biomasses of C. reinhardtii and C. vulgaris. This study demonstrates a clear linkage between the extraction conditions applied and total lipid and TAG recovery.

A novel transcription factor Sdr1 involving sulfur depletion response in fission yeast.

In the fission yeast Schizosaccharomyces pombe, the response to sulfur depletion has been less studied compared to the response to nitrogen depletion. Our study reveals that the fission yeast gene, SPCC417.09c, plays a significant role in the sulfur depletion response. This gene encodes a protein with a Zn2Cys6 fungal-type DNA-binding domain and a transcription factor domain, and we have named it sdr1+ (sulfur depletion response 1). Interestingly, while sulfur depletion typically induces autophagy akin to nitrogen depletion, we found that autophagy was not induced under sulfur depletion in the absence of sdr1+. This suggests that sdr1+ is necessary for the induction of autophagy under conditions of sulfur depletion. Although sdr1+ is not essential for the growth of fission yeast, its overexpression, driven by the nmt1 promoter, inhibits growth. This implies that Sdr1 may possess cell growth-inhibitory capabilities. In addition, our analysis of Δsdr1 cells revealed that sdr1+ also plays a role in regulating the expression of genes associated with the phosphate depletion response. In conclusion, our study introduces Sdr1 as a novel transcription factor that contributes to an appropriate cellular nutrient starvation response. It does so by inhibiting inappropriate cell growth and inducing autophagy in response to sulfur depletion.

Single-base resolution quantitative genome methylation analysis in the model bacterium Helicobacter pylori by enzymatic methyl sequencing (EM-Seq) reveals influence of strain, growth phase, and methyl homeostasis

BackgroundBacterial epigenetics is a rapidly expanding research field. DNA methylation by diverse bacterial methyltransferases (MTases) contributes to genomic integrity and replication, and many recent studies extended MTase function also to global transcript regulation and phenotypic variation. Helicobacter pylori is currently one of those bacterial species which possess the highest number and the most variably expressed set of DNA MTases. Next-generation sequencing technologies can directly detect DNA base methylation. However, they still have limitations in their quantitative and qualitative performance, in particular for cytosine methylation.ResultsAs a complementing approach, we used enzymatic methyl sequencing (EM-Seq), a technology recently established that has not yet been fully evaluated for bacteria. Thereby, we assessed quantitatively, at single-base resolution, whole genome cytosine methylation for all methylated cytosine motifs in two different H. pylori strains and isogenic MTase mutants. EM-Seq reliably detected both m5C and m4C methylation. We demonstrated that three different active cytosine MTases in H. pylori provide considerably different levels of average genome-wide single-base methylation, in contrast to isogenic mutants which completely lost specific motif methylation. We found that strain identity and changed environmental conditions, such as growth phase and interference with methyl donor homeostasis, significantly influenced quantitative global and local genome-wide methylation in H. pylori at specific motifs. We also identified significantly hyper- or hypo-methylated cytosines, partially linked to overlapping MTase target motifs. Notably, we revealed differentially methylated cytosines in genome-wide coding regions under conditions of methionine depletion, which can be linked to transcript regulation.ConclusionsThis study offers new knowledge on H. pylori global and local genome-wide methylation and establishes EM-Seq for quantitative single-site resolution analyses of bacterial cytosine methylation.

Characterizing the Exponential Profile of W' Recovery Following Partial Depletion.

The aim of this study was to characterize W' recovery kinetics in response to a partial W' depletion. We hypothesized that W' recovery following a partial depletion would be better described by a biexponential than by a monoexponential model. Nine healthy men performed a ramp incremental exercise test, three to five constant load trials to determine critical power and W', and 10 experimental trials to quantify W' depletion. Each experimental trial consisted of two constant load work bouts (WB1 and WB2) interspersed by a recovery interval. WB1 was designed to evoke a 25% or 75% W' depletion (DEP 25% and DEP 75% ). Subsequently, participants recovered for 30, 60, 120, 300, or 600 s and then performed WB2 to exhaustion to calculate the observed W' recovery (W' OBS ). W' OBS data were fitted using monoexponential and biexponential models, both with a variable and with a fixed model amplitude. Root mean square error and Akaike information criterion (AIC c ) were calculated to evaluate the models' goodness-of-fit. The biexponential model fits were associated with overall lower root mean square error values (0.4% to 5.0%) when compared with the monoexponential models (2.9% to 8.0%). However, ΔAIC c resulted in negative values (-15.5 and -23.3) for the model fits where the amplitude was kept free, thereby favoring the use of a monoexponential model for both depletion conditions. For the model fits where the amplitude was fixed at 100%, ΔAIC c was negative for DEP 25% (-15.0) but positive for DEP 75% (11.2). W' OBS values were strongly correlated between both depletion conditions ( r = 0.92) and positively associated with V̇O 2peak , critical power, and gas exchange threshold ( r = 0.67 to 0.77). The present study results did not provide evidence in favor of a biexponential modeling technique to characterize W' recovery following a partial depletion. Moreover, we demonstrated that fixed time constants were insufficient to model W' recovery across different depletion levels, and that W' recovery was positively associated with aerobic fitness. These findings underline the importance of employing variable and individualized time constants in future predictive W' models.

High production of ectoine from methane in genetically engineered Methylomicrobium alcaliphilum 20Z by preventing ectoine degradation

BackgroundMethane is a greenhouse gas with a significant potential to contribute to global warming. The biological conversion of methane to ectoine using methanotrophs represents an environmentally and economically beneficial technology, combining the reduction of methane that would otherwise be combusted and released into the atmosphere with the production of value-added products.ResultsIn this study, high ectoine production was achieved using genetically engineered Methylomicrobium alcaliphilum 20Z, a methanotrophic ectoine-producing bacterium, by knocking out doeA, which encodes a putative ectoine hydrolase, resulting in complete inhibition of ectoine degradation. Ectoine was confirmed to be degraded by doeA to N-α-acetyl-L-2,4-diaminobutyrate under nitrogen depletion conditions. Optimal copper and nitrogen concentrations enhanced biomass and ectoine production, respectively. Under optimal fed-batch fermentation conditions, ectoine production proportionate with biomass production was achieved, resulting in 1.0 g/L of ectoine with 16 g/L of biomass. Upon applying a hyperosmotic shock after high–cell–density culture, 1.5 g/L of ectoine was obtained without further cell growth from methane.ConclusionsThis study suggests the optimization of a method for the high production of ectoine from methane by preventing ectoine degradation. To our knowledge, the final titer of ectoine obtained by M. alcaliphilum 20ZDP3 was the highest in the ectoine production from methane to date. This is the first study to propose ectoine production from methane applying high cell density culture by preventing ectoine degradation.

Imaginary impedance due to hopping phenomena and evaluation of dopant ionization time in cryogenic metal-oxide-semiconductor devices on highly doped substrate

MOS capacitors fabricated on substrates with doping concentrations as high as 1018 cm−3 were characterized at 4.2 K. The highly doped substrate exhibited an intrinsic imaginary component of impedance at 4.2 K. The imaginary component is attributed to the time delay induced by hopping phenomena, leading to a decrease in the gate capacitance. Furthermore, we investigated the time constant associated with dopant ionization under depletion conditions and determined it to be 0.35 μs. An equivalent circuit model of the highly doped substrate at 4.2 K is also shown.

Abstract 2651: A selective HPK1 inhibitor FB849 reprograms intratumoral immune cells and elicits strong anti-cancer immunity

Abstract Hematopoietic progenitor kinase 1 (HPK1) is a negative regulator of immune cells and suppresses the immune function of a wide range of cells, including T cells, B cells, and dendritic cells (DCs). Recent studies have shown that HPK1 is correlated with increased T cell exhaustion, one of hallmark phenomena for acquired resistance to immune checkpoint inhibitors (ICIs), that is a major obstacle in the current immunotherapy regimen with an increasing need of novel agent to overcome it. We have discovered FB849, a highly potent, highly selective, and orally available HPK1 inhibitor especially with an excellent selectivity over key immune-related off target kinases. FB849 confers the activation of various human primary immune cells such as T cells, B cells, and DCs in vitro. FB849 elicited robust anti-cancer efficacy in syngeneic mouse models including MC38 and CT26 both as a monotherapy and in combination with a PD-1 antagonist. A dramatic synergistic efficacy with FB849 and PD-1 combination was observed in EMT6. Durable effects possibly through immunological memory were also confirmed in CT26. Under a CD8+ T cell depletion condition in vivo, FB849 still maintained monotherapy efficacy, demonstrating its anti-cancer immunity through CD8+ T cell-independent pathway possibly via efficacy through myeloid lineage. FB849 significantly reduced the LAG3+ and PD-1+ exhausted T cells and CD25+ FoxP3+ regulatory T cells, simultaneously depleted tumor associated macrophages (TAMs), and modulated dendritic cell population in the syngeneic tumors. To better understand how FB849’s effects on human cancer, FB849 was evaluated in isolated TILs (tumor-infiltrating lymphocytes) from patients with renal cell carcinoma and other cancer types. CD8+ T cells from a RCC patient was highly activated evidenced by the increased cell proliferation and the enhanced cytokine secretion by ex vivo treatment of FB849 alone or by the combination with PD-1 antagonist. Similar phenomena were observed in gastric cancer, hepatocellular carcinoma, colorectal cancer, and head and neck cancer. FB849 treatment resulted in the activation of not only stem-like T cells but also in the partial reinvigoration of terminally differentiated T cells from a RCC patient. These data from patient TIL’s together with mouse TIL’s pinpoint unprecedented anti-tumor mechanism by FB849 through modulation of exhausted T cells as well as myeloid cells. Altogether, this study supports the planned clinical development of FB849 as a promising immuno-oncology agent as a monotherapy in the selected cancer types and as post-ICI combination with a PD-1 antagonist. Citation Format: Hyekyoung Kim, Seungmook Lim, A Yeong Park, Jinhwa Lee, Jamie Jae Eun Kim, Seung Hyuck Jeon, Yong Joon Lee, Eui-Cheol Shin, Seongkon Kim. A selective HPK1 inhibitor FB849 reprograms intratumoral immune cells and elicits strong anti-cancer immunity [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 2651.

Effect of air depletion in the preferential oxidation reactor and fuel depletion in a proton exchange membrane fuel cell system fueled by natural gas

This study estimates the steady-state performance of a proton exchange membrane fuel cell (PEMFC) under conditions of air depletion in the preferential oxidation reactor (PrOx) and fuel depletion at the anode, which has not been previously studied. Considering the detailed chemical reactions of the reforming process, the composition of the reformed gas at the anode inlet is determined using the temperature and pressure data measured at various state points in the PEMFC system. To calculate the voltage loss at the anode due to the air depletion in PrOx or reformate gas depletion before the anode, the electrochemical reaction of the reformed gas in the anode catalyst layer is studied. The calculations show that when the fuel entering the anode or air entering the PrOx decreases, the amount of CO at the anode increases depending on the reduction, resulting in activation loss at the anode, and thereby leading to power loss. This analysis of the power loss in a PEMFC due to a lack of air or fuel can serve as an auxiliary diagnostic tool to identify faulty parts in the Balance of Plant (BOP).

Immunoregulatory and neutrophil-like monocyte subsets with distinct single-cell transcriptomic signatures emerge following brain injury.

Monocytes represent key cellular elements that contribute to the neurological sequela following brain injury. The current study reveals that trauma induces the augmented release of a transcriptionally distinct CD115+/Ly6Chi monocyte population into the circulation of mice pre-exposed to clodronate depletion conditions. This phenomenon correlates with tissue protection, blood-brain barrier stability, and cerebral blood flow improvement. Uniquely, this shifted the innate immune cell profile in the cortical milieu and reduced the expression of pro-inflammatory Il6, IL1r1, MCP-1, Cxcl1, and Ccl3 cytokines. Monocytes that emerged under these conditions displayed a morphological and gene profile consistent with a subset commonly seen during emergency monopoiesis. Single-cell RNA sequencing delineated distinct clusters of monocytes and revealed a key transcriptional signature of Ly6Chi monocytes enriched for Apoe and chitinase-like protein 3 (Chil3/Ym1), commonly expressed in pro-resolving immunoregulatory monocytes, as well as granule genes Elane, Prtn3, MPO, and Ctsg unique to neutrophil-like monocytes. The predominate shift in cell clusters included subsets with low expression of transcription factors involved in monocyte conversion, Pou2f2, Na4a1, and a robust enrichment of genes in the oxidative phosphorylation pathway which favors an anti-inflammatory phenotype. Transfer of this monocyte assemblage into brain-injured recipient mice demonstrated their direct role in neuroprotection. These findings reveal a multifaceted innate immune response to brain injury and suggest targeting surrogate monocyte subsets may foster tissue protection in the brain.

The nitric oxide-soluble guanylate cyclase-cGMP pathway in pulmonary hypertension: from PDE5 to soluble guanylate cyclase.

The nitric oxide (NO)-soluble guanylate cyclase (sGC)-cyclic guanosine monophosphate (cGMP) pathway plays a key role in the pathogenesis of pulmonary hypertension (PH). Targeted treatments include phosphodiesterase type 5 inhibitors (PDE5i) and sGC stimulators. The sGC stimulator riociguat is approved for the treatment of pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH). sGC stimulators have a dual mechanism of action, enhancing the sGC response to endogenous NO and directly stimulating sGC, independent of NO. This increase in cGMP production via a dual mechanism differs from PDE5i, which protects cGMP from degradation by PDE5, rather than increasing its production. sGC stimulators may therefore have the potential to increase cGMP levels under conditions of NO depletion that could limit the effectiveness of PDE5i. Such differences in mode of action between sGC stimulators and PDE5i could lead to differences in treatment efficacy between the classes. In addition to vascular effects, sGC stimulators have the potential to reduce inflammation, angiogenesis, fibrosis and right ventricular hypertrophy and remodelling. In this review we describe the evolution of treatments targeting the NO-sGC-cGMP pathway, with a focus on PH.

Microalgae Haemococcus pluvialis, Cultured in OHM Medium under Stressful Conditions: Phenolic Content and Antioxidant Capacity

Haematococcus pluvialis, a unicellular green microalgae, is able to accumulate the large amounts of astaxathin under stress conditions. Nutritional factors such as nitrate or phosphate and light intensity play an important role in the growth, accumulation of phenolic compounds and antioxidant capacity microalgae H. pluvialis. In this study, H. pluvialis was cultured under three conditions of stress, nutrient depletion, denitrification of nitrate and addition of NPK fertilizer, and natural light in OHM medium to investigate the phenolic content and antioxidant capacity of the biomass of H. pluvialis microalgae. The results showed that, under denitrification of nitrate and addition of NPK fertilizer, the phenolic content reached a high value (8.054 µg gallic acid/g) and there was no significant difference with the two conditions of nutrient depletion (4.115 µg gallic acid/g) and natural light (4.707 µg gallic acid/g) (p<0.05). However, no differences were found between the antioxidant capacity under denitrification of nitrate and addition of NPK fertilizer (51.390%) and natural light (52.301%) (p=0.552) that were higher than nutrient depletion (45.257%) (p<0.05). Thus, under the stress conditions of nitrate depletion and high light intensity, H. pluvialis has the ability to synthesize and accumulate high amounts of bioactive compounds and microalgae biomass can be applied in dietary supplement and cosmeticeuticals.

Microglia depletion/repopulation does not affect light-induced retinal degeneration in mice.

Reactive microglia are a hallmark of age-related retinal degenerative diseases including age-related macular degeneration (AMD). These cells are capable of secreting neurotoxic substances that may aggravate inflammation that leads to loss of photoreceptors and impaired vision. Despite their role in driving detrimental inflammation, microglia also play supporting roles in the retina as they are a crucial cellular component of the regulatory innate immune system. In this study, we used the colony stimulating factor 1 receptor (CSF1R)-antagonist PLX3397 to investigate the effects of microglia depletion and repopulation in a mouse model of acute retinal degeneration that mimics some aspects of dry AMD. Our main goal was to investigate whether microglia depletion and repopulation affects the outcome of light-induced retinal degeneration. We found that microglia depletion effectively decreased the expression of several key pro-inflammatory factors but was unable to influence the extent of retinal degeneration as determined by optical coherence tomography (OCT) and histology. Interestingly, we found prominent cell debris accumulation in the outer retina under conditions of microglia depletion, presumably due to the lack of efficient phagocytosis that could not be compensated by the retinal pigment epithelium. Moreover, our in vivo experiments showed that renewal of retinal microglia by repopulation did also not prevent rapid microglia activation or preserve photoreceptor death under conditions of light damage. We conclude that microglia ablation strongly reduces the expression of pro-inflammatory factors but cannot prevent photoreceptor loss in the light-damage paradigm of retinal degeneration.

Effect of Water Adsorption on Lubricating Film Stability in Slippery Coatings.

The absorption of water by slippery coatings is a ubiquitous phenomenon that arises due to small but finite water dissolution during the contact of aqueous media with lubricants. In this study, using the concept of surface forces, we have analyzed the influence of trace amounts of water in lubricants on the stability of slippery coatings for both coatings with hydrophilic porous bases, prone to form hydrogen bonds with water, and those with hydrophobic porous bases. To perform such analysis, we have considered for the first time the electrostatic problem of the distribution of the electric potential and electric field strength in stratified films that contain two thin dielectric layers imitating the lubricant and a hydrophobic layer sandwiched between the porous substrate and air or water. Based on the developed approach, the equations for the calculation of the excess free energy and the disjoining pressure, associated with water dissolution in the lubricant film, were derived. An analysis of the excess film energy and the contribution of the image interaction to the disjoining pressure isotherm indicates that the dissolved water can both stabilize and destabilize the oil film, depending on the ratio of the static and dynamic dielectric permittivities of the lubricant and the phases confining the film. The results of calculations and simple experiments carried out here indicate much better water contact stability of silicone films impregnating a hydrophobized porous substrate than films impregnating a hydrophilic porous substrate. The obtained results indicate the preference for using the hydrophobic bases for the fabrication of long-lived slippery coatings characterized by better preservation of slippery functional properties under conditions of lubricant depletion and prolonged contact with water.