Preservation Of Membrane Integrity Research Articles

Exploring Multitarget Strategies for Membrane Protection in Alzheimer's Disease.

The exploration of multitarget molecules presents a promising avenue in the quest for effective therapeutic strategies against Alzheimer's disease (AD), a multifactorial neurodegenerative disorder. Traditional single-target drugs have shown limited success due to the complex interplay of pathological processes involved in AD. Multitarget-directed ligands (MTDLs), designed to interact with multiple targets simultaneously, offer a more holistic approach to address the multifaceted nature of neurodegenerative diseases. Recent studies have highlighted the potential of chalcones and huprine derivatives in mitigating amyloid-β peptide-associated toxicity and preserving membrane integrity, crucial for cellular homeostasis. The interaction of these compounds with lipid bilayers may modulate biological responses, opening a new realm of investigation in membrane-centric phenomena. This approach not only broadens the mechanistic understanding of bioactive compounds but also underscores the need for a paradigm shift in AD research, focusing on both intracellular targets and plasma membrane protection for more effective treatment strategies.

Methyl salicylate-improved mitochondrial stability obstructed cell death activation in preventing visible chilling injury in sweet basil under cold storage

Mitochondrial stability plays an important part in compelling plant senescence and physiological disorders. The research aimed to investigate the role of mitochondrial reactive oxygen species (ROS) and oxidative damage in mediated cell death and chilling in sweet basil and to investigate the role of methyl salicylate (MeSA) immersion in retarding chilling injury development via activation of antioxidant defense systems to protect mitochondria-induced deterioration. Sweet basils were subjected to a 5-min immersion in 1 mM MeSA and stored at 6 °C for 8 d. In the control group, evident symptoms of chilling injury were observed on day 4, coinciding with a substantial accumulation of mitochondrial ROS and reduction in mitochondrial stability, particularly evident in cytochrome c dissipation. Concurrently, an increase in caspase-like enzyme activities, known to drive cell death, was observed following exposure to low temperatures. In contrast, chilling injury was mitigated in the MeSA-treated leaves. The MeSA treatment significantly enhanced the overall antioxidant capacity of the mitochondria and improved mitochondrial stability, thereby preventing the activation of caspase-like enzymes. Consequently, this treatment preserved membrane integrity and suppressed cell death activation, ultimately leading to a delay in the appearance of cold damage during storage.

Seed Pretreatment by CaCl2 and NaHS Alleviates Oxidative Stress, Preserves Membrane Integrity, and Stimulates Hydrogen Sulfide Biosynthesis in Pea (Pisum sativum L.) Under Nickel Stress

Seed Pretreatment by CaCl2 and NaHS Alleviates Oxidative Stress, Preserves Membrane Integrity, and Stimulates Hydrogen Sulfide Biosynthesis in Pea (Pisum sativum L.) Under Nickel Stress

Effects of Graphene Oxide Nanosheets in Freshwater Biofilms.

Graphene oxide (GO) properties make it a promising material for graphene-based applications in areas such as biomedicine, agriculture, and the environment. Thus, its production is expected to increase, reaching hundreds of tons every year. One GO final destination is freshwater bodies, possibly affecting the communities of these systems. To clarify the effect that GO may impose in freshwater communities, a fluvial biofilm scraped from submerged river stones was exposed to a range (0.1 to 20 mg/L) of GO concentrations during 96 h. With this approach, we hypothesized that GO can: (1) cause mechanical damage and morphological changes in cell biofilms; (2) interfere with the absorption of light by biofilms; (3) and generate oxidative stress, causing oxidative damage and inducing biochemical and physiological alterations. Our results showed that GO did not inflict mechanical damage. Instead, a positive effect is proposed, linked to the ability of GO to bind cations and increase the micronutrient availability to biofilms. High concentrations of GO increased photosynthetic pigment (chlorophyll a, b, and c, and carotenoids) content as a strategy to capture the available light more effectively as a response to the shading effect. A significant increase in the enzymatic (SOD and GSTs activity) and low molecular weight (lipids and carotenoids) antioxidant response was observed, that efficiently reduced oxidative stress effects, reducing the level of peroxidation, and preserving membrane integrity. Being complex entities, biofilms are more similar to environmental communities and may provide more accurate information to evaluate the impact of GO in aquatic systems.

Dextran-Chitosan Composites: Antioxidant and Anti-Inflammatory Properties.

This study presents the development of new formulations consisting of dextran (Dex) and chitosan (Ch) matrices, with fillings such as chitosan stearate (MCh), citric acid, salicylic acid, or ginger extract. These materials were characterized using Fourier-Transform Infrared Spectroscopy (FTIR), Scanning Electron Microscopy (SEM), and mechanical tests, and evaluated for antioxidant properties, including scavenging activities, metal chelation, and ferric ion reducing power, as well as anti-inflammatory properties, measuring the binding affinity between serum albumin and the bioactive substances, which can influence their bioavailability, transport, and overall anti-inflammatory effect. Compounds in ginger such as 6-gingerol reduce inflammation by inhibiting the production of inflammatory substances, such as prostaglandin, cytokines, interleukin-1β, and pro-inflammatory transcription factor (NF-κB) and, alongside citric and salicylic acids, combat oxidative stress, stabilizes cell membranes, and promote membrane fluidity, thereby preserving membrane integrity and function. Incorporating chitosan stearate in chitosan:dextran samples created a dense, stiff film with an elastic modulus approximately seventeen times higher than for the chitosan:dextran matrix. The Dex:Ch:MCh sample exhibited low compressibility at 48.74 ± 1.64 kPa, whereas the Dex:Ch:MCh:citric acid:salicylic acid composite had a compact network, allowing for 70.61 ± 3.9% compression at 109.30 kPa. The lipid peroxidation inhibitory assay revealed that Dex:Ch:MCh:citric acid had the highest inhibition value with 83 ± 0.577% at 24 h. The study highlights that adding active substances like ginger extract and citric acid to Dex:Ch composites enhances antioxidant properties, while modified chitosan improves mechanical properties. These composites may have potential medical applications in repairing cell membranes and regulating antioxidant enzyme activities.

Early Endosomes Act as Local Exocytosis Hubs to Repair Endothelial Membrane Damage.

The plasma membrane of a cell is subject to stresses causing ruptures that must be repaired immediately to preserve membrane integrity and ensure cell survival. Yet, the spatio-temporal membrane dynamics at the wound site and the source of the membrane required for wound repair are poorly understood. Here, it is shown that early endosomes, previously only known to function in the uptake of extracellular material and its endocytic transport, are involved in plasma membrane repair in human endothelial cells. Using live-cell imaging and correlative light and electron microscopy, it is demonstrated that membrane injury triggers a previously unknown exocytosis of early endosomes that is induced by Ca2+ entering through the wound. This exocytosis is restricted to the vicinity of the wound site and mediated by the endosomal soluble N-ethylmaleimide sensitive factor attachment protein receptor (SNARE) VAMP2, which is crucial for efficient membrane repair. Thus, the newly identified Ca2+ -evoked and localized exocytosis of early endosomes supplies the membrane material required for rapid resealing of a damaged plasma membrane, thereby providing the first line of defense against damage in mechanically challenged endothelial cells.

Abstract 115: Comparison Of Di-block Copolymer-based Cell Membrane Stabilizers To The Tri-block Poloxamer 188 In Protecting Coronary Artery Endothelial Cells Against Hypoxia-Reoxygenation Injury

The triblock copolymer-based cell membrane stabilizer (CCMS) Poloxamer (P)188 consists of a central hydrophobic poly-propylene oxide (PPO) block that is flanked by two hydrophilic poly-ethylene oxide (PEO) blocks (PEO 75 -PPO 30 -PEO 75 ). It has been found to protect against various types of ischemia/reperfusion (IR) injury (e.g. stroke, traumatic brain injury, trauma, myocardial infarction) presumably by preserving membrane integrity and function. Modifications of its structure to di-block compounds (PEO-PPO) with a strongly hydrophobic (t) tert-butyl end-terminal were reported to yield even stronger protection. Recently, we demonstrated the critical importance of endothelial cells in mediating protection against IR injury of cardiomyocytes in a co-culture study. Here, we compared the protective effects of custom-made di-blocks (PEO 113 -PPO 10 t, PEO 226 -PPO 18 t and PEO 113 -PPO 20 t) at different concentrations (0 to 300 μM) on cell proliferation, lactate dehydrogenase (LDH) leakage and FM1-43 dye incorporation as markers of cell viability and membrane damage, respectively, to P188 in mouse coronary artery endothelial cells (MCAECs) when given upon the beginning of 2 hrs reoxygenation after 24 hrs hypoxia (HR) vs corresponding control normoxia (CN) conditions. Data are mean +/- standard deviation; statistics: ANOVA and SNK post-hoc testing, alpha = 0.05, # vs CN, * vs 0 mM. P188 as well as all three tested di-blocks significantly attenuated HR-induced cell damage dose-dependently; the figure shows the LDH data. This, for the first time, demonstrates that di-block compounds can protect MCAECs against HR injury as effective and even superior to P188. If translated clinically, di-block CCMS may become effective new compounds mitigating IR injury.

Electronic-level deciphering of the desalination mechanism of high-performance graphenylene membranes

The insufficiency of available freshwater has surged as a major global concern in recent years, and the issue is raising ever more awareness. Meanwhile, the recent experimental synthesis of graphenylene has inspired researchers to pursue its applicative merits. The related properties regarding lithium-ion storage electrodes and gas separation membranes of graphenylene have been reported. However, the suitability of graphenylene as a desalination membrane has yet to be fully established. In the present study, with a view to delineating the action mechanism of graphenylene desalination membrane, we have dissected its structure and properties through first-principles and molecular dynamics. The results illustrate that graphenylene comprising dodecagonal, hexagonal, and tetragonal carbon rings contains 0.55 nm nanopores, which should permit outstanding desalination properties. In addition, the periodic pore distribution should support stress dispersion in service to preserve membrane integrity. The low water-molecule free-energy barrier, remarkable salt ion adsorption properties, and favorable anti-agglomeration ability endow graphenylene with desirable permeability and selectivity. Furthermore, we demonstrate that graphenylene is a 2D Dirac semi-metallic material. The interlinked electronic structure of which confers it with self-cleaning behavior, facilitating the restoration of water flux. The present research has elucidated the mechanism whereby effective desalination may be achieved on graphenylene membranes. Further, it has clarified the potential applicability of such membranes. They show good prospects for the advancement of seawater desalination technology.

Etavopivat, a Pyruvate Kinase Activator in Red Blood Cells, for the Treatment of Sickle Cell Disease

Etavopivat is an investigational, oral, small molecule activator of erythrocyte pyruvate kinase (PKR) in development for the treatment of sickle cell disease (SCD) and other hemoglobinopathies. PKR activation is proposed to ameliorate the sickling of SCD red blood cells (RBCs) through multiple mechanisms, including reduction of 2,3-diphosphoglycerate (2,3-DPG), which consequently increases hemoglobin (Hb)-oxygen affinity; increased binding of oxygen reduces sickle hemoglobin polymerization and sickling. In addition, PKR activation increases adenosine triphosphate (ATP) produced via glycolytic flux, which helps preserve membrane integrity and RBC deformability. We evaluated the pharmacodynamic response to etavopivat in nonhuman primates (NHPs) and in healthy human subjects and evaluated the effects in RBCs from patients with SCD after ex vivo treatment with etavopivat. A single dose of etavopivat decreased 2,3-DPG in NHPs and healthy subjects. Hb-oxygen affinity was significantly increased in healthy subjects after 24 hours. After daily dosing of etavopivat over 5 consecutive days in NHPs, ATP was increased by 38% from baseline. Etavopivat increased Hb-oxygen affinity and reduced sickling in RBCs collected from patients with SCD with either homozygous hemoglobin S or hemoglobin S and C disease. Collectively, these results demonstrate the ability of etavopivat to decrease 2,3-DPG and increase ATP, resulting in increased Hb-oxygen affinity and improved sickle RBC function. Etavopivat is currently being evaluated in clinical trials for the treatment of SCD. SIGNIFICANCE STATEMENT: Etavopivat, a small molecule activator of the glycolytic enzyme erythrocyte pyruvate kinase, decreased 2,3-diphosphoglycerate in red blood cells (RBCs) from nonhuman primates and healthy subjects and significantly increased hemoglobin (Hb)-oxygen affinity in healthy subjects. Using ex vivo RBCs from donors with sickle cell disease (SCD) (homozygous hemoglobin S or hemoglobin S and C genotype), etavopivat increased Hb-oxygen affinity and reduced sickling under deoxygenation. Etavopivat shows promise as a treatment for SCD that could potentially reduce vaso-occlusion and improve anemia.

The Bak core dimer focuses triacylglycerides in the membrane

Apoptosis, the intrinsic programmed cell death process, is mediated by the Bcl-2 family members Bak and Bax. Activation via formation of symmetric core dimers and oligomerization on the mitochondrial outer membrane (MOM) leads to permeabilization and cell death. Although this process is linked to the MOM, the role of the membrane in facilitating such pores is poorly understood. We recently described Bak core domain dimers, revealing lipid binding sites and an initial role of lipids in oligomerization. Here we describe simulations that identified localized clustering and interaction of triacylglycerides (TAGs) with a minimized Bak dimer construct. Coalescence of TAGs occurred beneath this Bak dimer, mitigating dimer-induced local membrane thinning and curvature in representative coarse-grain MOM and model membrane systems. Furthermore, the effects observed as a result of coarse-grain TAG cluster formation was concentration dependent, scaling from low physiological MOM concentrations to those found in other organelles. We find that increasing the TAG concentration in liposomes mimicking the MOM decreased the ability of activated Bak to permeabilize these liposomes. These results suggest that the presence of TAGs within a Bak-lipid membrane preserves membrane integrity and is associated with reduced membrane stress, suggesting a possible role of TAGs in Bak-mediated apoptosis.

Preharvest Application of Hexanal as a Surface Treatment Improved the Storage Life and Quality of Mango Fruits

Mango is a highly preferred seasonal tropical fruit with a maximum shelf-life of five to seven days. Hexanal is a plant volatile compound assayed in green tissues and showing significance in enhancing storage life and fruit quality attributes by preserving membrane integrity. This experiment explored the effect of the pre-harvest application of an aqueous hexanal composition (active ingredient: 0.02% hexanal) in altering the post-harvest storage behavior of four mango cultivars. The pre-harvest application of the hexanal formulation to the fruit surface twice before the harvest date drastically slowed down the physiological loss in weight by 70% to 80%, and reduced the ethylene evolution rate by two to three folds, respectively. The pre-harvest hexanal formulation spray combined with post-harvest cold storage prominently improved the storage life along with the total soluble solids, total sugars, ascorbic acid and carotenoid content compared to untreated fruits stored in ambient conditions. Though ripening coincides with the increased activity of enzymes, the hexanal formulation spray acts predominantly in bringing down the activities of fruit softening enzymes viz. pectinmethlyesterase (43%) and polygalacturonases (37%), and antioxidant enzymes viz. peroxidase (67%) and catalase (45%), respectively.

Endogenous phytosulfokine α (PSKα) signaling delays petals senescence and prolongs vase life of cut rose flowers (Rosa hybrida cv. Angelina)

This study investigated the endogenous phytosulfokine α (PSKα) signaling during opening and senescence in rose flowers. Our results showed that the higher phytosulfokines (PSKs) and tyrosyl protein sulfotransferase (TPST) expression could be responsible for higher endogenous PSKα accumulation in petals during rose flowers opening (stages 2 and 3). By triggering the endogenous PSKα signaling, higher phytosulfokine receptor 1 (PSKR1) expression could be responsible for higher cytosolic cyclic guanosine monophosphate (cGMP) accumulation in petals during rose flowers opening (stages 3 and 4). Higher protein kinase G (PKG) and cyclic nucleotide-gated ion channel 1 (CNGC1) expression accompanying higher plasma membrane intrinsic protein 2 (PIP2) and tonoplast intrinsic protein 1 (TIP1) expression in petals during rose flowers opening may arise from higher cytosolic cGMP accumulation giving rise to higher petals relative water content (RWC) (stage 4). Triggering phosphodiesterase (PDE) expression lay off cytosolic cGMP signaling. Suppressing PKG and CNGC1 expression accompanying lower PIP2 and TIP1 expression accelerates petals senescence in rose flowers representing by deteriorating petals membrane integrity revealed by higher electrolyte leakage and malondialdehyde (MDA) accumulation (stage 5 and 6). For delaying petals senescence and prolonging vase life in cut rose flowers, we employed exogenous PSKα treatment at the commercial harvest stage (stage 3). Our results showed that the suppressing PDE expression in petals by exogenous 150 nM PSKα treatment could be responsible for allowing cytosolic cGMP signaling ongoing for supporting PKG and CNGC1 expression accompanying by higher PIP2 and TIP1 expression. Exogenous 150 nM PSKα treatment, outperforming cut rose flowers by delayed senescence and prolonged vase life to 16 days from 12 days could be ascribed to preserving membrane integrity revealed by lower electrolyte leakage and MDA accumulation. Our results could be proposed that exogenous PSKα treatment and endogenous PSKα signaling for employing in the floriculture industry for delaying petals senescence and prolonging the vase life of cut rose flower.

Poloxamer 188 Dose‐Dependently Protects Adult Mouse Coronary Artery Endothelial Cell Layers from Reoxygenation Injury

Poloxamer (P)188 is a tri-block copolymer shown to provide a cardioprotective effect when administered at the beginning of reoxygenation in adult mouse cardiomyocyte hypoxia/reoxygenation models. It is thought that it seals cells damaged by hypoxia via membrane stabilization, thus, protecting the cells from additional injury during reoxygenation. To further explore the effects of P188 on maintaining endothelial cell layer integrity, we treated confluent adult mouse coronary artery endothelial cell layers with varying concentrations of P188 upon initiation of a 2-hr reoxygenation period immediately following hypoxic periods of 3, 12, and 48 hrs. Using trans-endothelial electrical resistance (TEER), we found that P188 dose-dependently protected cells from further damage after hypoxia, with some doses returning TEER measurements even back to control/normoxia levels. However, we also observed that similar concentrations of P188 varied in effects as hypoxia times increased. Our results indicate that P188 protects the endothelial layer in a dose-dependent manner as long as it is administered after an optimal ischemia time to effectively preserve membrane integrity in tissue barriers. More research will need to be conducted to confirm our findings and determine the optimal combination of dosage and timing of P188 administration.

A vital role of chitosan nanoparticles in improvisation the drought stress tolerance in Catharanthus roseus (L.) through biochemical and gene expression modulation

Drought is a main abiotic stress that restricts plant growth and development. The increased global demand of anti-cancer alkaloids extracted from periwinkle (Catharanthus roseus) is mainly related to plant growth and development, which are severely affected by drought. Chitosan nanoparticles (CSNPs) have been used to boost plant growth and defense mechanism, however their impact to alleviate drought stress of C. roseus has not been investigated yet. In this study, control and stressed plants (100 and 50% of field capacity [FC], respectively) were subjected to CSNPs application at 1%. Drought stress considerably reduced plant growth, relative water content (RWC), stomatal conductance and total chlorophyll; however, CSNPs mitigated these effects. They enhanced proline accumulation and the activity of catalase (CAT) and ascorbate peroxidase (APX) with possible mitigation of drought-induced oxidative stress. Therefore, they reduced H2O2 and malondialdehyde (MDA) accumulation, and eventually preserved membrane integrity. Drought stress increased alkaloid accumulation, and further increase was observed with the application of CSNPs. High alkaloid content was associated with induced gene expression of strictosidine synthase (STR), deacetylvindoline-4-O-acetyltransferase (DAT), peroxidase 1 (PRX1) and geissoschizine synthase (GS) up to 5.6 folds under drought stress, but more accumulation was noticed with the application of CSNPs. Overall, this study is the first on using CSNPs to mitigate drought stress of C. roseus by inducing the antioxidant potential and gene expression of alkaloid biosynthesis.

The effects of melatonin treatment on cap browning and biochemical attributes of Agaricus bisporus during low temperature storage

Exogenous melatonin application at 0, 1, 10, 100, and 1000 µM retarded cap browning of button mushrooms (Agaricus bisporus) by 78.35, 31.40, 30.91, 27.17, and 32.50 %, respectively.Mushrooms treated with 100 µM melatonin also had lower weight loss and higher firmness. During the first 5 days of storage at 4 °C, higher H2O2 accumulation may serve as a signal for promoting endogenous melatonin accumulation by triggering the expression of TDC, T5H, SNAT, and ASMT genes, beneficial for preserving membrane integrity. Besides, the higher accumulation of phenols in mushrooms treated with 100 µM melatonin may be ascribed to higher PAL and lower PPO gene expression and enzyme activity. Moreover, higher DPPH scavenging capacity in mushrooms treated with 100 µM melatonin may be ascribed to the higher accumulation of phenols and ascorbic acid.

In-vitro effect of Peganum harmala total alkaloids on spermatozoa quality and oxidative stress of epididymal ram semen

Objective: To determine the in-vitro effect of the total alkaloid extract of Peganum (P.) harmala seeds on ram epididymal sperm.Methods: Semen was divided into six groups according to the following concentrations of the P. harmala total alkaloids: 1, 5, 10, 50, and 100 μg/mL, and the control group. The samples were incubated at ambient temperature (21 °C-24 °C) for 24 h, and analyzed in terms of motility, membrane integrity, and oxidative status.Results: The sperm kinematic parameters, i.e. straight-line velocity, curvilinear velocity, average path velocity, were significantly higher when treated with P. harmala at concentrations ranging from 1 to 10 μg/mL compared to the control group (P<0.05). In addtion, the highest amplitude of the lateral head displacement value was found in the groups treated with concentrations 1 and 5 μg/mL of P. harmala compared to the control group (P<0.05). Total and progressive motilities showed that the extracts at 1, 5, and 10 μg/mL exhibited a high percentage after 24 h of incubation. The effect of P. harmala extracts on the membrane integrity of ram epididymal sperm was concentration-dependent and significantly different compared to the control group (P<0.05). Non-significantly lower lipid peroxidation levels were observed after 24 h of incubation of ram epididymal sperm treated with concentrations 1, 5, and 10 μg/mL of P. harmala extracts compared to the control group (P>0.05).Conclusions: Low concentrations (1-10 μg/mL) of P. harmala extracts stimulate sperm motility, preserve membrane integrity and protect ram spermatozoa from lipid peroxidation.

Sperm cryopreservation in an Australian skink (Eulamprus quoyii).

Assisted reproductive technologies for population and genetic management for threatened herpetofauna have grown substantially in the past decade. Here we describe experiments to optimise sperm cryopreservation in a model squamate, the eastern water skink Eulamprus quoyii . Small, concentrated volumes of highly motile spermatozoa were reliably collected from adult male E. quoyii by non-lethal ventral massage. Samples were used to: (1) test whether protein-rich diluents, namely Beltsville poultry semen extender (BPSE) and TES and Tris (TEST) yolk buffer (TYB), improve post-thaw quality metrics compared with Dulbecco's phosphate-buffered saline (DPBS); and (2) compare the efficacy of these diluents in combination with either 1.35M glycerol or 1.35M dimethyl sulfoxide (DMSO) at two freezing rates, fast (approximately -20°C min-1 ) versus slow (-6°C min-1 ). Glycerol and DMSO performed equally well in preserving spermatozoa under slow freezing rates. Under these conditions, the use of the complex diluents BPSE and TYB significantly improved post-thaw total motility compared with DPBS. Complex interactions occurred between cryodiluent type, cryoprotectant and freezing rate when testing fast versus slow freezing rates among treatment groups. Under slow freezing rates, DMSO was better at preserving membrane integrity and motility, regardless of diluent type, but successful fast freezing required complex diluents to support motility and membrane integrity, which has implications for implementation in a field setting.

Maintaining phagosome integrity during fungal infection: do or die?

Professional phagocytes represent a critical node in innate immunity and tissue homeostasis through their specialized ability to eat, drink, and digest material from the extracellular milieu. The degradative and microbicidal functions of phagocytes rely on the fusion of lysosomes with endosomal compartments such as phagosomes, resulting in the digestion and recycling of internalized prey and debris. Despite these efforts, several particularly dangerous infections result from a class of tenacious pathogens that resist digestion, often surviving and even proliferating within the confines of the phagosomal membrane. One such example, Candida albicans, is a commensal polymorphic fungus that colonizes ~50% of the population and can cause life-threatening infections in immunocompromised patients. Not only can C. albicans survive within phagosomes, but its ingestion by macropahges triggers a yeast-to-hyphal transition promoting rapid intraphagosomal growth (several microns per hour) while imposing a substantial mechanical burden on the phagosomal membrane surrounding the fungus. Preservation of membrane integrity is essential to maintain the hostile internal environment of the phagosome, a functionality of degradative enzymes and oxidative stress. Yet, biological membranes such as phagosomes have a limited capacity to stretch. Using C. albicans as a model intracellular pathogen, our recent work reveals a mechanism by which phagosomes respond to intraphagosomal growth of pathogens by expanding their surface area, and as a result, maintain the integrity of the phagosomal membrane. We hypothesized that this expansion would be facilitated by the delivery and fusion of membrane from extraneous sources with the phagosome. Consistently, macrophages respond to the yeast-to-hyphal transition through a stretch-induced release of phagosomal calcium, leading to recruitment and insertion of lysosomes that accommodate the expansion of the phagolysosome and preserve its integrity. Below, we discuss this calcium-dependent mechanism of lysosome insertion as a means of avoiding phagosomal rupture. Further, we examine the implications of membrane integrity on the delicate balance between the host and pathogen by focusing on fungal stress responses, nutrient acquisition, inflammasome activation, and cell death.

Lipidomic changes in mouse oocytes vitrified in PEG 8000-supplemented vitrification solutions

Cryopreserved oocytes are inevitably exposed to cold stress, which negatively affects the cellular aspects of the oocytes. Lipidomic analysis of the oocytes reveals quantitative changes in lipid classes under conditions of cold stress, leading to potential freezing-vulnerability. We had previously shown that specific phospholipids are significantly downregulated in vitrified-warmed mouse oocytes compared to those in fresh oocytes. In this study, we examined whether supplementation of polyethylene glycol 8000 (PEG 8000) during vitrification influences the lipidome of the oocytes. We used liquid chromatography with tandem mass spectrometry (LC-MS/MS) to study the alteration in the lipidome in three groups of mouse oocytes: fresh, vitrified-warmed, and vitrified with PEG 8000-warmed during vitrification. In these groups, we targeted to analyze 21 lipid classes. We profiled 132 lipid species in the oocytes and statistical analyses revealed lipid classes that were up- or downregulated in these groups. Overall, our data revealed that several classes of lipids were affected during vitrification, and that oocytes vitrified with PEG 8000 to some extent alleviated the levels of changes in phospholipid and sphingolipid contents during vitrification. These results suggest that phospholipids and sphingolipids are influenced by PEG 8000 during vitrification and that PEG 8000 can be considered as a potential candidate for preserving membrane integrity during oocyte cryopreservation.

Dead-end membrane distillation with localized interfacial heating for sustainable and energy-efficient desalination

Membrane distillation (MD) has the high potential to circumvent conventional desalination limitations in treating highly saline brines. However, the performance of MD is limited by its low thermal efficiencyand temperature polarization (TP) effect. Consequently, the driving force decreases when heat loss increases.In this study, we propose to minimize TP through localized heating where the thin feed channel was heated uniformly at the membrane-liquid interface without changing the properties of the membrane.This concept was further improved by implementing a new dead-end MD configuration. Investigated for the first time,this configuration eliminated circulation heat losses, which cannot be realized in conventional MD due to a rapid temperature stratification. In addition, the accumulation of foulants on the membrane surface was successfully controlled by intermittent flushing. 3-Dimensional conjugate heat transfer modeling revealedmore uniform heat transfer and temperature gradient across the membrane due to the increased feed water temperature over a larger membrane area. The increase of water vapor flux (45%) and the reduction of heat lossobserved in the new dead-end concept led to a decrease of the specific energy consumption by 57%, corresponding to a gain output ratio increase of about 132 %, compared to a conventional bulk heating, while preserving membrane integrity. A conjugate heat transfer model was deployed in ANSYS-Fluent framework to elucidate on the mechanism of flux enhancement associated with the proposed technique. This study provides a framework for future sustainable MD developmentby maintaining a stable vapor flux while minimizing energy consumption.