Short Lifespan Research Articles

Pyrrolic-Nitrogen Chemistry in 1-(2-hydroxyethyl)imidazole Electrolyte Additives toward a 50,000-Cycle-Life Aqueous Zinc-Iodine Battery.

Rechargeable aqueous zinc iodine (Zn-I2) batteries offer benefits such as low cost and high safety. Nevertheless, their commercial application is hindered by hydrogen evolution reaction (HER) and polyiodide shuttle, which result in a short lifespan. In this study, 1-(2-hydroxyethyl)imidazole (HEI) organic molecules featuring pyrrole-N groups are introduced as dually-functional electrolyte additives to simultaneously stabilize Zn anode and confine polyiodide through ion-dipole interactions. The pyrrole-N groups in HEI can preserve the interfacial pH equilibrium at Zn anode by reversibly capturing H+ ions and dynamically neutralizing OH- ions, thereby suppressing the HER. Notably, the H2 evolution rate at the Zn anode is reduced to a mere 2.20 μmol h-1 cm-2. Furthermore, the pyrrole-N moieties in HEI effectively curtail the polyiodide shuttle at I2 cathode, which show adsorption energies of -0.174 eV for I2, -0.521 eV for I3 -, and -0.768 eV for I-, as indicated by density functional theory calculations. Electrochemical testing demonstrates that the Zn//Zn symmetric cell maintains stable cycling for up to 4,200 hours at 1 mA cm-2. Most strikingly, at a high I2 mass loading of 9.7 mg cm-2, the Zn-I2 battery achieves an extraordinary cycle life of 50,000 cycles.

Metabolomic Changes Associated with AGXT2 Genotype Variants and Stone Formation in a Colony of Cats.

The objective of this study was to assess serum chemistries and metabolomic parameters in cats with genetic variants of the alanine-glyoxylate aminotransferase 2 (AGXT2) gene to determine abnormalities associated with urolith formation and better understand effective approaches for the treatment of cats with uroliths. AGXT2 genotypes of 445 cats in the colony at Hill's Pet Nutrition, Inc. (Topeka, KS, USA) were assessed in a genome-wide association study. Additionally, the serum chemistries and metabolic profiles of each cat were determined, along with their lifetime history of stone incidence. Factor analysis was used as a data-reduction method for metabolites in order to perform statistical hypothesis testing and to select significant metabolites from the more than 600 serum metabolites identified. Of the 82 cats forming stones in the colony (18.4%), the majority were calcium oxalate. Results showed that approximately one third of the cats with the AA variant of the AGXT2 gene have stones, that chronic kidney disease (CKD) is more common in cats with stones, and that having stones results in a shorter lifespan. A discriminant variable selection process was performed to determine the complete blood count, serum biochemistries, and serum metabolomic factors that best discriminated among the three genotypes (AA, AG, GG) and between cats forming stones and non-stone formers. Several of the highly ranked discriminating factors included metabolites related to decreased aminotransferase activity in cats with the AA variant of the AGXT2 gene. Another factor that ranked highly for discriminating between stone formers and non-stone formers contained lipid metabolites, consisting of multiple sphingomyelin species and cholesterol. These findings support the results of feeding studies in cats, whereby CKD cats fed food supplemented with betaine and prebiotics have experienced an increase in total body mass, reduced uremic toxins, and altered sphingomyelin concentrations.

Characterization method of conductive film state of micro-cathode arc thrusters

Micro-Cathode Arc Thruster (μCAT) is an advanced electric propulsion system developed in the past decades to meet the maneuvering requirements of space microsatellites. However, the constraint on the its application is the short lifespan of the thruster. This is attributed to the conductive film, a key component of thruster discharge. In this study, we propose a measurement method for μCAT conductive film, and enables the evaluation of the evolution process of film thickness. The method is based on the four-probe resistivity testing theory and size effect fitting model, and establishes a method for characterizing the thickness and resistivity of μCAT conductive films. A comparison was made between the corrected resistivity test results of 1, 2, 5, and 10 μm film and the fitting results of the titanium film, revealing an error ofapproximately 10%. Additionally, a total of 2500 ignition experiments were conducted to verify the film thickness and resistance measurement of this method. This research serves as a valuable basis for the lifetime investigation of μCAT. Consequently, the thickness of the film progressively decreases with each discharge cycle, and the resistivity exhibits a corresponding increase due to the size effect. This method could be used as an effective method for exploring the μCAT lifespan and performance.

Carbon-decorated hydrated V10O24 nanorods for high-performance lithium-ion battery cathodes

This study reports the successful synthesis of carbon-decorated hydrated V10O24 (HVO@C) nanorods using a facile hydrothermal method. The synthesized material was comprehensively characterized using XRD, FTIR, Raman, TGA/DSC, BET, SEM, and HRTEM to reveal its structure and morphology, and the resulting electrode's electrochemical performance as a lithium-ion battery (LIB) cathode was evaluated for the first time. The HVO@C nanorods exhibited a remarkable initial capacity of 292.5 mAh g−1 at 75 mA g−1 current rate, exceeding most of the reported V2O5-based LIB cathodes. Notably, the HVO@C electrode retained a good capacity retention of 67.1 % and a slower capacity loss rate of 0.26 % after 125 cycles compared to most V2O5-based counterparts with shorter lifespans. This outstanding performance could be due to a synergistic interplay of structural characteristics. The large interlayer spacing within the nanorods facilitated unimpeded Li-ion diffusion, while the short diffusion path minimized transport limitations. Furthermore, the strategic incorporation of carbon coating enhanced electrical conductivity and structural stability, leading to enduring LIB battery performance. These results indicate that in-situ carbon-decorated hydrated V10O24 nanoparticles have great potential as a promising cathode electrode for LIBs with exceptional performance.

GBT1118, a Voxelotor Analog, Ameliorates Hepatopathy in Sickle Cell Disease.

Background and Objectives: In sickle cell disease (SCD), hepatopathy is a cumulative consequence of ischemia/reperfusion (I/R) injury from a vaso-occlusive crisis, tissue inflammation, and iron overload due to blood transfusion. Hepatopathy is a major contributing factor of shortened life span in SCD patients. We hypothesized that the voxelotor, a hemoglobin allosteric modifier, ameliorates sickle hepatopathy. Materials and Methods: Townes SCD mice and their controls were treated with either chow containing GBT1118, a voxelotor analog, or normal chow. We evaluated inflammation, fibrosis, apoptosis and ferroptosis in their livers using qPCR, ELISA, histology, and immunohistochemistry. Results: GBT1118 treatment resulted in reduced hemolysis, iron overload and inflammation in the liver of SCD mice. There were significant reductions in the liver enzyme levels and bile acids. Furthermore, GBT1118-treated mice exhibited reduced apoptosis, necrosis, and fibrosis. Increased ferroptosis as evident from elevated 4-hydroxynonenal (4-HNE) staining, malondialdehyde (MDA) levels, and expression of Ptgs2 and Slc7a11 mRNAs, were also significantly reduced after GBT1118 treatment. To explain the increased ferroptosis, we evaluated iron homeostasis markers in livers. SCD mice showed decreased expression of heme oxygenase-1, ferritin, hepcidin, and ferroportin mRNA levels. GBT1118 treatment significantly increased expressions of these genes. Conclusions: Our results suggest GBT1118 treatment in SCD confers the amelioration of sickle hepatopathy by reducing inflammation, fibrosis, apoptosis, iron overload and ferroptosis.

Boosting the Efficiency and Stability of Li-CO2 Batteries via a Ruthenium-Based Olefin-Metathesis Catalyst.

The practical application of Li-CO2 batteries is significantly hindered by high charge potential and short lifespan, mainly due to sluggish reaction kinetics and inadequate reaction reversibility. Homogeneous catalysts added to the electrolyte provide a promising strategy to address these issues. In this work, the third-generation Grubbs catalyst (G-III), which is efficient for olefin metathesis reactions, has been adopted as a homogeneous catalyst for Li-CO2 batteries. Batteries with G-III exhibited a low overpotential of 0.86 V and a lifespan of 1300 h at a current density of 300 mA g-1. Even at a high current density of 2000 mA g-1, the batteries remained stable for over 300 cycles, with an initial overpotential of 1.11 V. A two-step discharge/charge reaction involving Li2C2O4 as an intermediate was well illustrated, attributed to both low overpotentials and high specific capacity. These findings provide insights into catalyst selection and mechanism analysis for Li-CO2 batteries, offering practical strategies for Li-CO2 battery performance enhancement and practical applications.

The regenerative capacity of hepatocyte organoids following long-term cryopreservation in Republic of Korea

Background: Hepatocyte organoids (HOs) are more functionally versatile than bile duct epithelial cell organoids, but have a shorter lifespan. This limitation has been improved by optimizing culture methods, but could remain a barrier to their wider application in research and therapy, especially for use at the appropriate time.Methods: This study aimed to prolong the lifespan of pig HOs and assess their viability and functionality after a year of cryopreservation. Genes involved in apoptosis (TP53, P21, CASP8) and liver function (ALB, CYP3A29, EPCAM) were analyzed to evaluate the impact of adipose-derived mesenchymal stem cell (A-MSC) co-culture before and after freezing on cryoresistance. HOs were cut into fragments, cryopreserved for a year, and cultured alone or co-cultured with A-MSCs in Matrigel post-thawing.Results: After thawing, co-cultured HOs exhibited a higher development rate than those cultured alone. P21 expression increased irrespective of pre-freezing culture conditions. The ALB and CYP3A29 expression patterns resembled those of non-frozen HOs, with similar effects from co-culture. EPCAM expression surged post-freezing.Conclusion: This study demonstrates that HOs maintain liver function post-preservation, showing increased EPCAM expression and enhanced regenerative capacity against cryoinjury. These findings suggest that HOs may be a valuable cell source for drug development in animals and research on medications for human diseases.

Drosophila melanogaster as an Alternative Model to Higher Organisms for In Vivo Lung Research.

COPD and asthma are lung diseases that cause considerable burden to more than 800 million people worldwide. As both lung diseases are so far incurable, it is mandatory to understand the mechanisms underlying disease development and progression for developing novel therapeutic approaches. Exposures to environmental cues such as cigarette smoke in earliest life are known to increase disease risks in the individual's own future. To explore the pathomechanisms leading to later airway disease, mammalian models are instrumental. However, such in vivo experiments are time-consuming and burdensome for the animals, which applies in particular to transgenerational studies. Along this line, the fruit fly Drosophila melanogaster comes with several advantages for research in this field. The short lifespan facilitates transgenerational studies. A high number of evolutionary conserved signaling pathways, together with a large toolbox for tissue-specific gene modification, has the potential to identify novel target genes involved in disease development. A well-defined airway microbiome could help to untangle interactions between disease development and microbiome composition. In the following article, Drosophila melanogaster is therefore presented and discussed as an alternative in vivo model to investigate airway diseases that can complement and/or replace models in higher organisms.

Survival and reproduction tests using springtails reveal weathered petroleum hydrocarbon soil toxicity in boreal ecozone.

Survival and reproduction tests were conducted using two native springtail (subclass: Collembola) species to determine the toxicity of a fine-grained (< 0.005 - 0.425 mm) soil from an industrial site located in the Canadian boreal ecozone. Accidental petroleum hydrocarbon (PHC) release continuously occurred at this site until 1998, resulting in a total hydrocarbon concentration of 12,800mg/kg (soil dry weight). Subfractions of the PHC-contaminated soil were characterized using Canadian Council of Ministers of the Environment Fractions, which are based on effective carbon numbers (nC). Fraction 2 (> nC10 to nC16) was measured at 8400mg/kg and Fraction 3 (> nC16 to nC34) at 4250mg/kg in the contaminated soil. Age-synchronized colonies of Folsomia candida and Proisotoma minuta were subject to 0%, 25%, 50%, 75%, and 100% relative contamination mixtures of the PHC-contaminated and background site soil (< 100mg/kg total PHCs) for 28 and 21days, respectively. Survival and reproduction decreased significantly (Kruskal-Wallis Tests: p < 0.05, df = 4.0) in treatments of the contaminated site soil compared to the background soil. In both species, the most significant decline in survival and reproduction occurred between the 0% and 25% contaminated soil. Toxicity responses in the two springtails were ascribed to the standardized test design, short lifespans, and high fecundity in both species. This study showed that 25 + years of soil weathering has not eliminated the toxicity of fine-grained PHC-contaminated soil on two native terrestrial springtail species. Adverse effects to springtail health were attributed to exposure to soils dominated by genotoxic PHC Fraction 2 compounds and slow weathering processes due to the cold climate at the site.

THE IMPACT OF RECENT LEASING ACTIVITY ON THE FINANCIAL SYSTEM IN THE REPUBLIC OF NORTH MACEDONIA

Leasing is an activity that refers to movable and immovable goods, in which the lessee determines the subject of leasing that is purchased or produced by the lessor and is given to the lessee for use for an agreed period, in exchange for payment of compensation for the use of the subject of leasing, based on the leasing agreement concluded between the provider and the lessee, according to the conditions specified in it. Leasing is an alternative way of financing where it is necessary to emphasize the use of the leased goods, and not the ownership over them (use but not possess), i.e. the philosophy of leasing arises from the idea of profitable use of an investment goods followed by a flexible method of payment that allows investment without the additional engagement of core capital, successful operation and maximum utilization of funds. In addition to the primary financing function that the leasing activity has for the lessee, if he uses the leased goods for business purposes, leasing in that case can also have an investment function. Regulated by the Law on Leasing, leasing activity in the Republic of North Macedonia has a fairly short lifespan, focusing exclusively on financial leasing. Through analysis, synthesis, and statistics, the authors processed the official data of the Ministry of Finance presented by the National Bank in the period mainly of the last decade, which offers a clear picture of the movements of the use of leasing in the country.

Research Progress on Characteristics of On‐Line Hydrogen Production by Methanol Steam Reforming

On‐line hydrogen production via methanol steam reforming (MSR) has gained considerable interest due to its high efficiency, affordability, and eco‐friendliness. Currently, this technology has been widely applied in the industry and has become an important method for hydrogen energy production. However, there are still some issues with this technology, such as short catalyst lifespan and CO pollution, which require further research and improvement. This article provides a comprehensive review of the research progress made in this field, with a particular focus on the catalyst development, reaction mechanism, theoretical calculation, and reactor design. Additionally, the challenges and prospects of on‐line hydrogen production by MSR are also discussed. In conclusion, MSR technology for hydrogen production has vast application prospects and development potential. It will be further explored in‐depth and extensively in future research.

Single housing of juveniles accelerates early-stage growth but extends adult lifespan in African turquoise killifish.

Within the same species, individuals exhibiting faster growth tend to have shorter lifespans, even if their fast growth arises from early-life pharmacological interventions. However, in vertebrates, the impact of the early-life environment on the growth rate and lifespan has not been fully elucidated. In this study, by utilizing the short-lived African turquoise killifish, which is suitable for a comprehensive life-stage analysis in a brief timeframe, we explored the effects of housing density during the juvenile stage on holistic life traits. As a result, we found that lower housing densities resulted in faster growth, but led to longer adult lifespan, which was contrary to the common notion. Furthermore, the single-housed adult fish displayed a longer egg-laying period than did their group-housed counterparts. Our transcriptome analysis also demonstrated that, in terms of internal transcriptional programs, the life stage progression and aging process of single-housed fish were slower than those of group-housed fish. Collectively, our results suggest that sharing housing with others in early life might influence whole-life attributes, potentially leading to specific life history traits beyond the typical relationship between the growth rate and lifespan.

Sabellaria wilsoni Lana and Gruet, 1989 on the Brazilian Amazon coast: Fast growth with high mortality, production, and turnover rate

Given the enormous ecological importance of sabellariid (Annelida: Sabellariidae) reefs for marine environments, data on the life history traits of these reef builders are essential for understanding ecosystem function. We assessed the functional parameters of a population of Sabellaria wilsoni (Annelida: Sabellariidae) on the Brazilian Amazon coast, where this polychaete builds extensive reef systems. The species had fast growth, a relatively short life span (1.30 years), and a high mortality rate (3.87 year−1). The mean annual biomass (58 g AFDM m−2) and production (233 g AFDM m−2 year−1) were very high and resulted in a high production-to-biomass ratio (P/B ratio: 4.02 year−1). The months with the highest productivity were those with the greatest reef coverage and density of worms, which coincided with the periods of reef growth. The high P/B ratio indicates the rapid replacement of biomass in this tropical population. These data support the hypothesis that S. wilsoni is an r-strategist, which is favored by the elevated temperatures and abundance of feeding resources and grains (for tube building) found on the Amazon coast. The present study is the first to produce systematic data on the population dynamics and production of a sabellariid species in the Western Atlantic Ocean. These data provide a baseline for understanding how shallow-water trophic webs function, as well as for monitoring these coastal habitats in the tropics.

A - 45 Duchenne and Becker Muscular Dystrophy: Sibling Case Studies

Abstract Objective Duchenne Muscular Dystrophy (DMD) is an X-linked recessive neuromuscular condition primarily affecting males. Progressive proximal muscle wasting and weakness is seen and a shortened life span can occur due to cardiac involvement. Becker Muscular Dystrophy (BMD) is a milder form of DMD. Non-progressive cognitive impairment (e.g., lower IQ) in DMD has been well established, while the cognitive profile in BMD is less known. DMD/BMD are caused by mutations in the dystrophin protein. Research suggests that mutations downstream of exon 63 in the DMD gene are associated with poorer cognitive outcomes compared to upstream 1–30. Our cases explore the association between genetic/medical factors upon cognitive and behavioral outcomes, and neuropsychological similarities/differences between DMD and BMD. Method The current sibling case studies include one BMD set (mutations at exon 45–49) and two DMD sets (exon 61–74, and 13, respectively). They are part of a larger IRB-approved research dataset. Notably in DMD set two, the siblings have different biological fathers. Results The BMD siblings have comparable neuropsychological profiles (e.g., below average IQ, academic challenges, attention/executive problems). In DMD set one, one sibling has average intelligence with no academic challenges, while the other sibling has a low average IQ with challenges in math and spelling. In DMD set two, one sibling has intact cognitive functioning, while the other sibling performs well below average across neurocognitive domains. Conclusions Our results indicate variabilities in DMD/BMD, highlighting the contributing role of established factors (e.g., mutation location) and additional non-DMD influences (e.g., genetic contributions from biological father) to understand neuropsychological profiles.

Ionic Covalent Organic Framework Membrane as Active Separator for Highly Reversible Zinc-Sulfur Battery.

Zinc-sulfur (Zn-S) batteries exhibit a high theoretical energy density, nontoxicity, and cost-effectiveness, demonstrating significant potential for integration into large-scale energy storage systems. However, the phenomenon of polysulfide (including dissolved S8 and Sx2-) shuttling is a major issue that results in rapid capacity decay and a short lifespan, limiting the practical performance of sulfur-based batteries. Herein, we fabricated an ionic covalent organic framework (iCOF) membrane as an active separator for the Zn-S battery. Sulfonic acid groups were introduced to the COF membrane, providing abundant negative charge sites in its pore wall. By combining size sieving and charge interaction between the polysulfide and pore wall, the iCOF membrane inhibited the crossover of polysulfides to the Zn metal anode without affecting the transport of metal ions. The Zn-S battery with the iCOF membrane as the separator shows a high-performance and low attenuation rate of 0.05% per cycle over 300 cycles at 2.5 A g-1. This study emphasizes the significance of separator design in enhancing Zn-S batteries and showcases the potential of functionalized framework materials for the development of high-performance energy storage systems.

Warmer environmental temperature accelerates aging in mosquitoes, decreasing longevity and worsening infection outcomes

BackgroundMost insects are poikilotherms and ectotherms, so their body temperature is predicated by environmental temperature. With climate change, insect body temperature is rising, which affects how insects develop, survive, and respond to infection. Aging also affects insect physiology by deteriorating body condition and weakening immune proficiency via senescence. Aging is usually considered in terms of time, or chronological age, but it can also be conceptualized in terms of body function, or physiological age. We hypothesized that warmer temperature decouples chronological and physiological age in insects by accelerating senescence. To investigate this, we reared the African malaria mosquito, Anopheles gambiae, at 27 °C, 30 °C and 32 °C, and measured survival starting at 1-, 5-, 10- and 15-days of adulthood after no manipulation, injury, or a hemocoelic infection with Escherichia coli or Micrococcus luteus. Then, we measured the intensity of an E. coli infection to determine how the interaction between environmental temperature and aging shapes a mosquito’s response to infection.ResultsWe demonstrate that longevity declines when a mosquito is infected with bacteria, mosquitoes have shorter lifespans when the temperature is warmer, older mosquitoes are more likely to die, and warmer temperature marginally accelerates the aging-dependent decline in survival. Furthermore, we discovered that E. coli infection intensity increases when the temperature is warmer and with aging, and that warmer temperature accelerates the aging-dependent increase in infection intensity. Finally, we uncovered that warmer temperature affects both bacterial and mosquito physiology.ConclusionsWarmer environmental temperature accelerates aging in mosquitoes, negatively affecting both longevity and infection outcomes. These findings have implications for how insects will serve as pollinators, agricultural pests, and disease vectors in our warming world.

2D heterostructures in photocatalysis for emerging applications: Current Status, challenges, and Prospectives

Photocatalysts for energy conversion and production, pollutants degradation, CO2 reduction, organic synthesis, biomedical, are especially important in a renewable energy-based energy and economic landscape. Due to their larger surface area and efficient capacity to segregate photogenerated electrons and holes, 2D van der Waals (vdW) heterostructures are being investigated to overcome the critical challenge of the short lifespan of photogenerated charges. This study presents the most recent research on 2D photocatalysts, specifically vdW heterostructures, for energy conversion and production, pollutants degradation, CO2 reduction, organic synthesis, biomedical. After presenting the core concepts of the light-driven redox reaction for aforementioned applications, we address a number of interesting 2D vdW heterostructures, highlighting transition metal dichalcogenides and graphene oxide heterostructures from both theoretical and experimental perspectives. In this review, we address the prospects and difficulties within this field of study. The enhanced understanding of 2D vdW heterostructures in photocatalysis presented in this research opens up new possibilities for increasing the efficiency of hydrogen generation. The key issues and future developments in the applications of 2D/2D layered heterojunctions and heterostructures in photocatalysis are explored.

Life in the fastlane? A comparative analysis of gene expression profiles across annual, semi-annual, and non-annual killifishes (Cyprinodontiformes: Nothobranchiidae).

The Turquoise Killifish is an important vertebrate for the study of aging and age-related diseases due to its short lifespan. Within Nothobranchiidae, species possess annual, semi-annual, or non-annual life-histories. We took a comparative approach and examined gene expression profiles (QuantSeq) from 62 individuals from eleven nothobranchid species that span three life-histories. Our results show significant differences in differentially expressed genes (DEGs) across life-histories with non-annuals and semi-annuals being most similar, and annuals being the most distinct. At finer scales, we recovered significant differences in DEGs for DNA repair genes and show that non-annual and semi-annuals share similar gene expression profiles, while annuals are distinct. Most of the GO terms enriched in annuals are related to metabolic processes. However, GO terms, including translation, protein transport, and DNA replication initiation also are enriched in annuals. Non-annuals are enriched in Notch signaling pathway genes and downregulated in the canonical Wnt signaling pathway compared to annual species, which suggests that non-annuals have stronger regulation in cellular processes. This study provides support for congruency in DEGs involved in these life-histories and provides strong evidence that a particular set of candidate genes may be worthy of study to investigate their role in the aging process.

A high-power hybrid carbon nanotube/three-dimensional reduced graphene oxide glucose/O2 enzymatic biofuel cell

Long-lasting, high-performance enzymatic biofuel cells (EBFCs) are among the most promising candidates for renewable and green power generation. There are two main drawbacks to EBFCs: 1) short enzyme lifetime due to the enzyme's (protein) denaturation; and 2) low electron transfer efficiency as the enzyme's active site is deeply buried inside the non-conductive protein structure of the enzyme. In this study, a hybrid of carbon nanotubes (CNT) and three-dimensional graphene (3DG) was used to immobilize the glucose oxidase (GOx) on the surface of a glassy carbon electrode (GCE) to fabricate a modified bioanode in a glucose/O2 EBFC. This facile and low-cost CNT/3DG hybrid is a solution to the problems of instability, short lifespan, and poor electron transport in EBFCs. The exceptional electrocatalytic activity of the porous CNT/3DG hybrid is demonstrated by its effective immobilization of GOx and ability to collect energy from glucose oxidation by direct electron transfer (DET) while preserving the structure of the enzyme. The CNT acts like a tiny electrical wire that reaches and harvests the electron directly from the flavin adenine dinucleotide (FAD) (the redox center of GOx) and transfers it to the electrode surface, thus enhancing the performance of the EBFC. The immobilized GOx lifetime was increased to 210 days with a maximum power density of 253.36 µWcm-2 at 0.65 V. These results demonstrate the attractive capability of the CNT/3DG hybrid in the development of efficient biofuel cells and biosensors that employ enzymes in their structures.

A critical appraisal of geroprotective activities of flavonoids in terms of their bio-accessibility and polypharmacology

Flavonoids, a commonly consumed natural product, elicit health-benefits such as antioxidant, anti-inflammatory, antiviral, anti-allergic, hepatoprotective, anti-carcinogenic and neuroprotective activities. Several studies have reported the beneficial role of flavonoids in improving memory, learning, and cognition in clinical settings. Their mechanism of action is mediated through the modulation of multiple signalling cascades. This polypharmacology makes them an attractive natural scaffold for designing and developing new effective therapeutics for complex neurological disorders like Alzheimer's disease and Parkinson's disease. Flavonoids are shown to inhibit crucial targets related to neurodegenerative disorders (NDDs), including acetylcholinesterase, butyrylcholinesterase, β-secretase, γ-secretase, α-synuclein, Aβ protein aggregation and neurofibrillary tangles formation. Conserved neuro-signalling pathways related to neurotransmitter biogenesis and inactivation, ease of genetic manipulation and tractability, cost-effectiveness, and their short lifespan make Caenorhabditis elegans one of the most frequently used models in neuroscience research and high-throughput drug screening for neurodegenerative disorders. Here, we critically appraise the neuroprotective activities of different flavonoids based on clinical trials and epidemiological data. This review provides critical insights into the absorption, metabolism, and tissue distribution of various classes of flavonoids, as well as detailed mechanisms of the observed neuroprotective activities at the molecular level, to rationalize the clinical data. We further extend the review to critically evaluate the scope of flavonoids in the disease management of neurodegenerative disorders and review the suitability of C. elegans as a model organism to study the neuroprotective efficacy of flavonoids and natural products.