Cell Longevity Research Articles

Long-term Memory in Immune Cells: An Overview

Long-term memory in immune cells is a pivotal aspect of the adaptive immune response, enabling the host to mount rapid and effective defenses against previously encountered pathogens. This review explores the mechanisms underlying the development and maintenance of immune memory, focusing on memory T cells, memory B cells, and long-lived plasma cells. Following primary infections or vaccinations, a subset of activated lymphocytes transitions into memory cells, which persist long after pathogen clearance. Factors influencing memory cell longevity, such as antigen persistence, cytokine signaling, and homeostatic proliferation, are discussed. Moreover, the review addresses the challenges posed by chronic infections and the potential for immune exhaustion, which can impair memory function. Additionally, the clinical implications of understanding immune memory are highlighted, particularly in vaccine development, cancer immunotherapy, and the management of autoimmune diseases. By synthesizing current knowledge on long-term memory in immune cells, this review aims to provide insights into future research directions and therapeutic strategies to enhance immune responses and improve public health outcomes. Keywords: Long-term memory, immune cells, memory T cells, memory B cells, immune exhaustion, vaccine development.

Triticain alpha represents the major active papain-like cysteine protease in naturally senescing and ozone-treated leaves of wheat

Current background tropospheric ozone (O3) concentrations have significant adverse effects on wheat. O3 generally induces oxidative damages and premature leaf senescence leading to important yield losses. As leaf protein degradation and recycling is involved in both maintaining cell longevity during abiotic stresses and performing efficient nitrogen remobilization during senescence, we aimed to identify proteases involved in acidic endoproteolytic activities during natural and O3-induced leaf senescence in wheat. Field-grown plants of two winter wheat cultivars were exposed to ambient and semi-controlled chronic O3 concentrations, from pre-anthesis to grain harvest. Yield parameters were impacted by the most elevated O3 exposure for both cultivars. At the cellular level, our analysis revealed that both natural leaf senescence and O3 treatments induced a stimulation of acidic (pH 5.5) endoproteolytic activities, mostly due to papain-like cysteine proteases (PLCPs). Identification of active PLCPs using activity-based protein profiling (ABPP) revealed that Triticain α was the major active PLCP in senescing flag leaves and the only PLCP whose abundance increased with O3 stress, a result of positive transcriptional regulation. Our study provides novel insight into the implication of PLCP-mediated proteolysis in O3 sensitivity in a major crop.

Establishment of a cell culture from Daphnia magna as an in vitro model for (eco)toxicology assays: Case study using Bisphenol A as a representative cytotoxic and endocrine disrupting chemical

Bisphenol A (BPA) is a widely used industrial compound found in polycarbonate plastics, epoxy resin, and various polymer materials, leading to its ubiquitous presence in the environment. The toxicity of BPA to aquatic organisms has been well documented following in vivo exposure scenarios, with known cytotoxic and endocrine-disrupting effects. As such, BPA was used in this study as a well-characterized chemical to implement more ethical and resource-efficient scientific practices in toxicity testing through new approach methods (NAMs). Due to the frequent use of Daphnia spp. as a model organism in toxicology, we developed an in vitro cell culture system from Daphnia magna embryos, with optimized medium to support cell longevity. The cultures were maintained for up to two months, demonstrating their stability and suitability for cytotoxicity studies. Using this novel system, lethal concentration 50 (LC50) values were determined at the 24 and 48 h time points following BPA exposure. Subsequently, oxidative stress, endocrine disruption, and DNA damage were assessed through gene expression, activity assays, and a comet assay in BPA-exposed cells. LC50 values of 52 µM and 20 µM BPA were calculated after 24 and 48 h exposures, respectively. BPA cells exposed to 20 and 52 µM had significantly increased GSH, GPx, and GST activity levels. mRNA expression analysis revealed significant upregulations in the mRNA expression of hsp70, hsp90, gst, gpx, vtg1, and cyp4, with downregulations of sod, cat, and ecr following BPA exposure. Furthermore, comet assays showed a significantly higher level of DNA damage induced by BPA compared to controls, with greater comet and tail lengths. This study established a novel in vitro Daphnia model, using BPA as a case study for determining toxic effects, further highlighting the importance and applicability of utilizing alternative methods in ecotoxicological research through reducing animal use.

Mitochondrial-derived compartments are multilamellar domains that encase membrane cargo and cytosol.

Preserving the health of the mitochondrial network is critical to cell viability and longevity. To do so, mitochondria employ several membrane remodeling mechanisms, including the formation of mitochondrial-derived vesicles (MDVs) and compartments (MDCs) to selectively remove portions of the organelle. In contrast to well-characterized MDVs, the distinguishing features of MDC formation and composition remain unclear. Here, we used electron tomography to observe that MDCs form as large, multilamellar domains that generate concentric spherical compartments emerging from mitochondrial tubules at ER-mitochondria contact sites. Time-lapse fluorescence microscopy of MDC biogenesis revealed that mitochondrial membrane extensions repeatedly elongate, coalesce, and invaginate to form these compartments that encase multiple layers of membrane. As such, MDCs strongly sequester portions of the outer mitochondrial membrane, securing membrane cargo into a protected domain, while also enclosing cytosolic material within the MDC lumen. Collectively, our results provide a model for MDC formation and describe key features that distinguish MDCs from other previously identified mitochondrial structures and cargo-sorting domains.

Calorie restriction increases insulin sensitivity to promote beta cell homeostasis and longevity in mice

Caloric restriction (CR) can extend the organism life- and health-span by improving glucose homeostasis. How CR affects the structure-function of pancreatic beta cells remains unknown. We used single nucleus transcriptomics to show that CR increases the expression of genes for beta cell identity, protein processing, and organelle homeostasis. Gene regulatory network analysis reveal that CR activates transcription factors important for beta cell identity and homeostasis, while imaging metabolomics demonstrates that beta cells upon CR are more energetically competent. In fact, high-resolution microscopy show that CR reduces beta cell mitophagy to increase mitochondria mass and the potential for ATP generation. However, CR beta cells have impaired adaptive proliferation in response to high fat diet feeding. Finally, we show that long-term CR delays the onset of beta cell aging hallmarks and promotes cell longevity by reducing beta cell turnover. Therefore, CR could be a feasible approach to preserve compromised beta cell structure-function during aging and diabetes.

Comprehensive study of CeO2/CuFe2O4 nanocomposites: Structural, EPR, magnetic, electrochemical, and cytotoxicity properties

This study dives into the successful synthesis of CeO2/CuFe2O4 nanocomposites using the auto-combustion approach and elucidates their characteristics. The electrochemical analysis of samples calcination produced at 700 °C (CeO2/CuFe2O4) revealed good results, with a specific capacitance (Cs) of 123 F/g at a current density (CD) of 0.25 A g−1 in a 1 M KOH solution. Significantly, these findings emphasize the established technique's potential for producing new, highly active, flexible, and environmentally friendly substrate materials appropriate for a variety of applications in supercapacitors. CeO2/CuFe2O4 nanocomposites may be useful in biological and medicinal research. Despite their extensive use, little study has been conducted to investigate their possible impact on cell viability, in normal cell lines. The positive benefits of the CeO2/CuFe2O4 nanocomposite structure were assessed using X-ray diffraction (XRD). To assess the impact of these nanocomposites, MTT cytotoxicity tests were performed on normal (mouse muscle fibroblast - BLO-11) cell lines. The results show that CeO2/CuFe2O4 nanocomposites have a high potential for biomedical applications, as they had no harmful effects on the cell types evaluated. As a result, the structure of the material appears to be crucial in determining both electrochemical performance and cell longevity. This discovery is significant because it provides useful insights into the morphological engineering of electrodes for a variety of applications and influences future material development.

Effect of Coupled Microstructural Characteristics of Catalyst Layer on High Temperature: Proton Exchange Membrane Fuel Cell Performance

The widespread adoption of High Temperature-Proton Exchange Membrane Fuel Cells (HT-PEMFC) in commercial applications is limited by their performance and durability compared to conventional energy sources. A key factor affecting these cells is the sluggish oxygen reduction reaction (ORR) at the cathode catalyst layer (CL). Optimizing the structural parameters of the cathode CL can enhance cell performance and longevity. Current research on these parameters is mostly descriptive, lacking numerical evidence to quantify their impact. This study develops a three-dimensional, non-isothermal HT-PEMFC numerical model to investigate the sensitivities of coupled structural parameters of the cathode CL, including Pt loading, CL thickness, and Pt particle diameter, at three levels. The orthogonal/Taguchi approach quantitatively assesses the impact of these parameters. The study reveals that Pt loading significantly affects cell voltage and cathode overpotential, while Pt diameter influences the homogeneity of overpotential distribution. The dominant impact of a single parameter decreases at higher current densities, necessitating careful analysis of trade-offs between different structural characteristics to maximize performance. These findings offer valuable insights for future experimental studies to enhance cell performance through adjustments to cathode catalyst characteristics.

Generative adversarial networks for stack voltage degradation and RUL estimation in PEMFCs under static and dynamic loads

Accurately predicting the degradation and remaining useful life (RUL) of Proton Exchange Membrane Fuel Cells (PEMFCs) is crucial for enhancing their reliability, particularly in automotive and energy sectors. Traditional models often fail to capture the complex, non-linear degradation patterns of PEMFCs, resulting in suboptimal predictions. This study addresses these technological gaps by introducing a novel approach, the Self-Attention Temporal Dual Discriminator Generative Adversarial Network (SAT-DD-GAN). This model is designed to overcome the limitations of existing methods by integrating advanced Long Short-Term Memory (LSTM) networks for time-series analysis, a self-attention mechanism to focus on critical degradation signals, and dual discriminators to improve prediction accuracy and robustness. By addressing the gap in handling long-term dependencies and complex degradation patterns, the proposed SAT-DD-GAN bridges the disconnect between traditional models and the real-world degradation behavior of PEMFCs. The SAT-DD-GAN achieved groundbreaking predictive performance, with the lowest RMSE (0.983E-3 for static load, 1.012E-3 for dynamic load), MAPE (0.036E-1 and 0.253E-1), MAE (0.776E-3 and 0.806E-3), and the highest R2-score (0.9998 and 0.9983), alongside zero relative error for both datasets. These results demonstrate the model's ability to capture the intricate degradation dynamics more effectively than existing state-of-the-art methods. By filling the technology gap of accurately modeling PEMFC degradation under varying load conditions, this study establishes a new standard for PEMFC prognostics and paves the way for future innovations in optimizing fuel cell performance and longevity.

Performance evaluation of inorganic Cs3Bi2I9-based perovskite solar cells with BaSnO3 charge transport layer

This research embedded with a novel idea of integration of perovskite material as charge transport layer corresponding to the perovskite absorber layer. The study explores the effectiveness of BaSnO3 perovskite material as an electron transport layer (ETL) in Cs3Bi2I9-based perovskite solar cells, using SCAPS-1D simulations. The research meticulously examines how structural and optical variations in each layer affect the device’s performance indicators, finding the thickness of the Cs3Bi2I9 layer and its defect concentration pivotal for optimal functionality. The highest photovoltaic efficiency, 20.62%, was achieved with an absorber layer thickness of 0.8 micrometers and acceptor and donor concentrations between 1E17 /cm3 and 1E18 /cm3, respectively. The absorber’s bulk defect density optimally ranged from 1E14 /cm3 to 1E15 /cm3. Interface defects between BaSnO3 and Cs3Bi2I9 layers significantly influenced performance, more so than those at the HTL (Cu2O) interface. The study also assesses thermal effects and series and shunt resistances, aiming to mitigate potential induced degradation (PID), a key concern for solar cell longevity and reliability. Nickel (Ni) was chosen as the back contact metal, balancing cost and efficiency. This research intends to clarify PID conditions to enhance the durability and consistent performance of photovoltaic systems.

PPARβ/δ-orchestrated metabolic reprogramming supports the formation and maintenance of memory CD8+ T cells.

The formation of memory T cells is a fundamental feature of adaptative immunity, allowing the establishment of long-term protection against pathogens. Although emerging evidence suggests that metabolic reprogramming is crucial for memory T cell differentiation and survival, the underlying mechanisms that drive metabolic rewiring in memory T cells remain unclear. Here, we found that up-regulation of the nuclear receptor peroxisome proliferator-activated receptor β/δ (PPARβ/δ) instructs the metabolic reprogramming that occurs during the establishment of central memory CD8+ T cells. PPARβ/δ-regulated changes included suppression of aerobic glycolysis and enhancement of oxidative metabolism and fatty acid oxidation. Mechanistically, exposure to interleukin-15 and expression of T cell factor 1 facilitated activation of the PPARβ/δ pathway, counteracting apoptosis induced by antigen clearance and metabolic stress. Together, our findings indicate that PPARβ/δ is a master metabolic regulator orchestrating a metabolic switch that may be favorable for T cell longevity.

Experiments and modeling of solid oxide co-electrolysis: Occurrence of CO2 electrolysis and safe operating conditions

Solid Oxide Electrolysis Cell (SOEC) has attracted considerable attention for its potential scalability and high energy conversion efficiency. It is capable of electrolyzing both H2O and CO2 simultaneously, generating syngas that can be further synthesized into carbon-based fuels, which are good energy carriers for long-term energy storage. However, despite its promise, the understanding of the reaction mechanism crucial for extending cell longevity remains incomplete, and concerns persist regarding carbon deposition during co-electrolysis. A dual approach, combining experiments and Multiphysics simulations was adopted to explore the reaction mechanism and carbon deposition risk across a wide range of operating conditions on industrial-size cells. Both experimental observations and simulation results indicate that CO2 electrolysis and carbon deposition are significantly influenced by the inlet water content and flow rates at the fuel electrode. Increasing the inlet H2O concentration and fuel electrode flow rates lead to CO2 electrolysis occurring at higher current densities. Also, carbon deposition, which was found at the interface of fuel electrode and electrolyte, can be mitigated by controlling the conversion rate relative to the inlet H2O content and by increasing the flow rate at the fuel electrode. Additionally, the current density distribution of H2O electrolysis and CO2 electrolysis across the cell were also investigated. The obtained insights hold significance for the practical operation of SOEC co-electrolysis.

CAR-NKT Cells in Asthma: Use of NKT as a Promising Cell for CAR Therapy.

NKT cells, unique lymphocytes bridging innate and adaptive immunity, offer significant potential for managing inflammatory disorders like asthma. Activating iNKT induces increasing IFN-γ, TGF-β, IL-2, and IL-10 potentially suppressing allergic asthma. However, their immunomodulatory effects, including granzyme-perforin-mediated cytotoxicity, and expression of TIM-3 and TRAIL warrant careful consideration and targeted approaches. Although CAR-T cell therapy has achieved remarkable success in treating certain cancers, its limitations necessitate exploring alternative approaches. In this context, CAR-NKT cells emerge as a promising approach for overcoming these challenges, potentially achieving safer and more effective immunotherapies. Strategies involve targeting distinct IgE-receptors and their interactions with CAR-NKT cells, potentially disrupting allergen-mast cell/basophil interactions and preventing inflammatory cytokine release. Additionally, targeting immune checkpoints like PDL-2, inducible ICOS, FASL, CTLA-4, and CD137 or dectin-1 for fungal asthma could further modulate immune responses. Furthermore, artificial intelligence and machine learning hold immense promise for revolutionizing NKT cell-based asthma therapy. AI can optimize CAR-NKT cell functionalities, design personalized treatment strategies, and unlock a future of precise and effective care. This review discusses various approaches to enhancing CAR-NKT cell efficacy and longevity, along with the challenges and opportunities they present in the treatment of allergic asthma.

Management of diabetes in people with advanced chronic kidney disease.

Diabetes is the commonest cause of end stage kidney disease globally, accounting for almost 40% of new cases requiring renal replacement therapy. Management of diabetes in people with advanced kidney disease on renal replacement therapy is challenging due to some unique aspects of assessment and treatment in this group of patients. Standard glycaemic assessment using glycated haemoglobin may not be valid in such patients due to altered red blood cell turnover or iron/erythropoietin deficiency, leading to changed red blood cell longevity. Therefore, use of continuous glucose monitoring may be beneficial to enable more focussed glycaemic assessment and improved adjustment of therapy. People with advanced kidney disease may be at higher risk of hypoglycaemia due to a number of physiological mechanisms, and in addition, therapeutic options are limited in such patients due to lack of experience or license. Insulin therapy is the basis of treatment of people with diabetes with advanced kidney disease due to many other drugs classes being contraindicated. Targets for glycaemic control should be adjusted according to co-morbidity and frailty, and continuous glucose monitoring should be used in people on dialysis to ensure low risk of hypoglycaemia. Post-transplant diabetes is common amongst people undergoing solid organ transplantation and confers a greater risk of mortality and morbidity in kidney transplant recipients. It should be actively screened for and managed in the post-transplant setting.

Current progress of CAR-T-cell therapy for patients with multiple myeloma.

Currently available chimeric antigen receptor (CAR)-engineered T-cell therapies targeting B-cell maturation antigen (BCMA), namely, idecabtagene vicleucel and ciltacabtagene autoleucel, have shown marked efficacy against relapsed and refractory multiple myeloma. However, further improvement in CAR-T-cell function is warranted as most patients treated with these products eventually relapse due to various mechanisms such as antigen loss and T-cell dysfunction or disappearance. Strategies for improving CAR-T-cell function include targeting of dual antigens, enhancing cell longevity through genetic modification, and eliminating the immunosuppressive tumor microenvironment. Serious side effects can also occur after CAR-T-cell infusions. Although understanding of the molecular pathogenesis of cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome is growing, the unique movement disorder caused by BCMA-targeted therapy is less understood, and its molecular mechanisms must be further elucidated to establish better management strategies. In this article, we will review the current status of BCMA-targeting CAR-T-cell therapy. We will also highlight progress in the development of CAR-T cells targeting other antigens, as well as universal allogeneic CAR-T cells and bispecific antibodies.

Bee honey of the Pajeú hinterland, Pernambuco, Brazil: Physicochemical characterization and biological activity

The state of Pernambuco, in the northeast Brazil, is one the biggest bee honey producers in the country, especially in semiarid microregions called “Sertão", or hinterlands. Its unique biome characterized by xerophyte Caatinga vegetation presents a unique flora with many medicinal properties. One of these microregions, Sertão do Pajeú, has stood out for its growing honey production. The present work reported for the first time a characterization of this honey and evaluated its potential for the production of alternative nutraceutical products. Samples from Sertão do Pajeú and two other regions of the State were collected and subjected to analyses as recommended by the Brazilian legislation. As the most striking characteristics, honeys from this microregion showed darker colour, higher content of phenolic compounds and elevated antioxidant activity than that from other locations. The high content of 5-HMF, together with high diastase activity, indicated that it is an intrinsic property of this honey. And finally, fermented worts containing the probiotic yeast Saccharomyces boulardii were supplemented with honey and sucrose as reference. The results showed that samples stocked in the presence of honey presented high level of cell longevity over 60 days of storage under refrigeration. In addition, those cells became very tolerant to the simulation of the gastrointestinal tract. Therefore, this honey greatly increased the probiotic potential of the yeast. This shows the nutraceutical potential of honey from Sertão do Pajeú.

Design and Optimization of Accumulator Pack

For an electric scooter, a lithium-ion battery with a Acro Butyl-nitrate (ABS) temperature management system was developed. Without the use of active cooling components like a fan, a blower, or a pump used in air/liquid-cooling systems, passive thermal management systems employing ABS can regulate the temperature excursions and maintain temperature uniformity in Li-ion batteries. Therefore, this new type of thermal management system can provide the benefits of a small, light, and energy-efficient system. The simulation results for a Li-ion battery sub-module with twenty 18650 Li-ion cells encased in ABS and a melting point of 114 to 120 °C are displayed. There are many important advantages to using aluminium fins manufactured from 0.7mm thick aluminium sheet between the battery cells in an accumulator pack. The relevance of them is explained in the following ways: Accumulator packs, particularly those used in high-power applications like scooters, can produce large amount of heat when in use. The performance, longevity, and safety of battery cells are all significantly impacted by heat. Aluminium fins serve as heat sinks and enhance heat dissipation by boosting the amount of heat-transfer surface area. Heat can be effectively transferred from the cells to the fins thanks to the thin aluminium sheet. Temperature Control: Battery cell efficiency and longevity depend on maintaining their temperature within a favorable range. By releasing more heat, aluminium fins assist in controlling the temperature. The fins aid in preventing overheating and preserving a more constant operating temperature by efficiently draining heat from the cells. Thermal Uniformity: The accumulator pack's thermal uniformity is enhanced by the inclusion of aluminium fins between the battery cells. Variations in cell temperature can cause performance imbalances and lower pack efficiency because uneven heat distribution can cause temperature differences among the cells. The fins aid in the even distribution of heat throughout the cells, reducing temperature variations and fostering consistent performance. Reduced Hotspots: Hotspots are small, high-temperature regions inside a battery pack that can hasten degradation and pose safety issues. Aluminium fins aid in heat dissipation, which reduces the development of hotspots. The fins' increased surface area enables more effective heat transport, which lowers the possibility of localized temperature accumulation. Improved Safety: Effective heat dissipation with aluminium fins can aid in accumulator packs' increased safety. Battery cells may experience thermal runaway or other dangerous situations as a result of high temperatures. The risk of thermal incidents is decreased by maintaining lower cell temperatures, improving operational safety in general. It's crucial to remember that parameters like spacing, size, and overall pack should be taken into account while designing and using aluminium fins. Additionally, by lowering the amount of heat that is released into the environment, liquid cooled heatsinks can be utilised to lessen the environmental effect of electronic equipment. The following are some benefits of employing liquid-cooled heatsinks: ● more efficient at cooling than heatsinks that use air cooling ● can be used to enhance the functionality and dependability of electronic equipment ● can be used to lessen how harmful electrical devices are to the environment. The following are some drawbacks of employing liquid-cooled heatsinks: ● more expensive than heatsinks that are air-cooled. ● more difficult to install and keep up ● Tend to leak more frequently. Keywords — CFD, 18650,ABS ,ALUMINUM FINS ,DRIVE CYCLE MODELS,EQUIVALENT CIRCUIT MODEL.

Correction to “Assessing Individual Material Degradation toward Organic Solar Cells Using Accelerated Nanolayer Lifetime Protocols: Implications for Solar Cell Longevity”

Correction to “Assessing Individual Material Degradation toward Organic Solar Cells Using Accelerated Nanolayer Lifetime Protocols: Implications for Solar Cell Longevity”

Sirtuins and Cellular Senescence in Patients with Idiopathic Pulmonary Fibrosis and Systemic Autoimmune Disorders.

The sirtuin family is a heterogeneous group of proteins that play a critical role in many cellular activities. Several degenerative diseases have recently been linked to aberrant sirtuin expression and activity because of the involvement of sirtuins in maintaining cell longevity and their putative antiaging function. Idiopathic pulmonary fibrosis and progressive pulmonary fibrosis associated with systemic autoimmune disorders are severe diseases characterized by premature and accelerated exhaustion and failure of alveolar type II cells combined with aberrant activation of fibroblast proliferative pathways leading to dramatic destruction of lung architecture. The mechanisms underlying alveolar type II cell exhaustion in these disorders are not fully understood. In this review, we have focused on the role of sirtuins in the pathogenesis of idiopathic and secondary pulmonary fibrosis and their potential as biomarkers in the diagnosis and management of fibrotic interstitial lung diseases.

External Pressure in Polymer-Based Lithium Metal Batteries: An Often-Neglected Criterion When Evaluating Cycling Performance?

Solid-state batteries based on lithium metal anodes, solid electrolytes, and composite cathodes constitute a promising battery concept for achieving high energy density. Charge carrier transport within the cells is governed by solid-solid contacts, emphasizing the importance of well-designed interfaces. A key parameter for enhancing the interfacial contacts among electrode active materials and electrolytes comprises externally applied pressure onto the cell stack, particularly in the case of ceramic electrolytes. Reports exploring the impact of external pressure on polymer-based cells are, however, scarce due to overall better wetting behavior. In this work, the consequences of externally applied pressure in view of key performance indicators, including cell longevity, rate capability, and limiting current density in single-layer pouch-type NMC622||Li cells, are evaluated employing cross-linked poly(ethylene oxide), xPEO, and cross-linked cyclodextrin grafted poly(caprolactone), xGCD-PCL. Notably, externally applied pressure substantially changes the cell's electrochemical cycling performance, strongly depending on the mechanical properties of the considered polymers. Higher external pressure potentially enhances electrode-electrolyte interfaces, thereby boosting the rate capability of pouch-type cells, despite the fact that the cell longevity may be reduced upon plastic deformation of the polymer electrolytes when passing beyond intrinsic thresholds of compressive stress. For the softer xGCD-PCL membrane, cycling of cells is only feasible in the absence of external pressure, whereas in the case of xPEO, a trade-off between enhanced rate capability and minimal membrane deformation is achieved at cell pressures of ≤0.43 MPa, which is considerably lower and more practical compared to cells employing ceramic electrolytes with ≥5 MPa external pressure.

The risk of acute infections in new users of antidepressants: An observational cohort study

BackgroundPreclinical studies suggested that drugs that functionally inhibit acid sphingomyelinase (FIASMA)may enhance immune cell longevity and potentially offer protection against infections. Many antidepressants have shown FIASMA activity. MethodsWe conducted a cohort study using primary-care data from the UK-based Clinical Practice Research Datalink (2000−2021). We assessed the association of composite diagnosed acute infections in new users of fluoxetine, sertraline, paroxetine, or venlafaxine aged 18–80 years compared to citalopram. We compared SARS-CoV-2 infections between groups in a secondary analysis. We estimated incidence rates (IR) and IR ratios (IRR) of acute infections in four pairwise comparisons using negative binomial regression. We applied propensity score (PS) fine stratification to control for confounding. ResultsIn the PS-weighted cohorts, we included 353,138 fluoxetine, 222,463 sertraline, 69,963 paroxetine, 32,608 venlafaxine, and between 515,996 and 516,583 new citalopram users. PS-weighted IRs ranged between 76.8 acute infections /1000 person-years (py) (sertraline) and 98.9 infections/1000 py (citalopram). We observed PS-weighted IRRs around unity for paroxetine (0.97, 95 % CI, 0.95–1.00), fluoxetine (0.94, 95 % CI, 0.92–0.95), and venlafaxine (0.90, 95 % CI, 0.87–0.94) vs citalopram. Reduced IRR for sertraline vs citalopram (0.84, 95 % CI, 0.82–0.85), became null within subgroups by cohort entry date. In the analysis of SARS-CoV-2 infection, no statistically relevant risk reduction was seen. LimitationsAnalysis not limited to patients with diagnosed depression, possible underestimation of infection incidence, and unclear FIASMA activity of citalopram. ConclusionsFluoxetine, sertraline, paroxetine, and venlafaxine were not associated with a reduced risk of acute infection when compared with the presumably weak FIASMA citalopram.