Complex IV subunit isoform COX6A2 protects fast-spiking interneurons from oxidative stress and supports their function.

Parvalbumin-positive (PV+ ) fast-spiking interneurons are essential to control the firing activity of principal neuron ensembles, thereby regulating cognitive processes. The high firing frequency activity of PV+ interneurons imposes high-energy demands on their metabolism that must be supplied by distinctive machinery for energy generation. Exploring single-cell transcriptomic data for the mouse cortex, we identified a metabolism-associated gene with highly restricted expression to PV+ interneurons: Cox6a2, which codes for an isoform of a cytochrome c oxidase subunit. Cox6a2 deletion in mice disrupts perineuronal nets and enhances oxidative stress in PV+ interneurons, which in turn impairs the maturation of their morphological and functional properties. Such dramatic effects were likely due to an essential role of COX6A2 in energy balance of PV+ interneurons, underscored by a decrease in the ATP-to-ADP ratio in Cox6a2-/- PV+ interneurons. Energy disbalance and aberrant maturation likely hinder the integration of PV+ interneurons into cortical neuronal circuits, leading to behavioral alterations in mice. Additionally, in a human patient bearing mutations in COX6A2, we found a potential association of the mutations with mental/neurological abnormalities.

The role of the balance between energy production and ammonia detoxification mediated by key amino acids in divergent hypersaline adaptation among crassostrea oysters.

Global ocean salinity is changing under rapid climate change and intensified anthropogenic activity. Increased differences in salinity threaten marine biodiversity, organismal survival, and evolution, particularly sessile invertebrates dwelling in highly fluctuating intertidal and estuarine environments. Comparing the responses of closely related species to salinity changes can provide insights into the adaptive mechanisms underlying inter- and intraspecific divergence in salinity tolerance, but are poorly understood in marine bivalves. We collected wild individuals of four Crassostrea species, in addition to two populations of the same species from their native habitats and determined the dynamics of hydrolyzed amino acids (HAAs) and transcriptional responses to hypersaline stress. In response to hypersaline stress, species/populations inhabiting natural high-salinity sea environments showed higher survival and less decline in HAAs than that of congeners inhabiting low-salinity estuaries. Thus, native environmental salinity shapes oyster tolerance. Notably, a strong negative correlation between the decline in HAAs and survival indicated that the HAAs pool could predict tolerance to hypersaline challenge. Four HAAs, including glutamine (Glu), aspartic acid (Asp), alanine (Ala) and glycine (Gly), were identified as key amino acids that contributed substantially to the emergency response to hypersaline stress. High-salinity-adapted oyster species only induced substantial decreases in Glu and Asp, whereas low-salinity-adapted congeners further incresaed Ala and Gly metabolism under hypersaline stress. The dynamics of the content and gene expression responsible for key amino acids pathways revealed the importance of maintaining the balance between energy production and ammonia detoxification in divergent hypersaline responses among oyster species/populations. High constructive or plastic expression of evolutionarily expanded gene copies in high-salinity-adapted species may contribute to their greater hypersaline tolerance. Our findings reveal the adaptive mechanism of key amino acids in salinity adaptation in marine bivalves and provide new avenues for the prediction of adaptive potential and aquaculture with high-salinity tolerant germplasms.

Structural Characterization and Physicochemical Properties of Functionally Porous Proton-Exchange Membrane Based on PVDF-SPA Graft Copolymers.

Fluorinated proton-exchange membranes (PEMs) based on graft copolymers of dehydrofluorinated polyvinylidene fluoride (D-PVDF), 3-sulfopropyl acrylate (SPA), and 1H, 1H, 2H-perfluoro-1-hexene (PFH) were prepared via free radical copolymerization and characterized for fuel cell application. The membrane morphology and physical properties were studied via small-(SAXS) and wide-angle X-ray scattering (WAXS), SEM, and DSC. It was found that the crystallinity degree is 17% for PEM-RCF (co-polymer with SPA) and 16% for PEM-RCF-2 (copolymer with SPA and PFH). The designed membranes possess crystallite grains of 5-6 nm in diameter. SEM images reveal a structure with open pores on the surface of diameters from 20 to 140 nm. Their transport and electrochemical characterization shows that the lowest membrane area resistance (0.9 Ωcm2) is comparable to perfluorosulfonic acid PEMs (such as Nafion®) and polyvinylidene fluoride (PVDF) based CJMC cation-exchange membranes (ChemJoy Polymer Materials, China). Key transport and physicochemical properties of new and commercial membranes were compared. The PEM-RCF permeability to NaCl diffusion is rather high, which is due to a relatively low concentration of fixed sulfonate groups. Voltammetry confers that the electrochemical behavior of new PEM correlates to that of commercial cation-exchange membranes, while the ionic conductivity reveals an impact of the extended pores, as in track-etched membranes.

Estrogen-Related Receptor α: A Key Transcription Factor in the Regulation of Energy Metabolism at an Organismic Level and a Target of the ABA/LANCL Hormone Receptor System.

The orphan nuclear receptor ERRα is the most extensively researched member of the estrogen-related receptor family and holds a pivotal role in various functions associated with energy metabolism, especially in tissues characterized by high energy requirements, such as the heart, skeletal muscle, adipose tissue, kidney, and brain. Abscisic acid (ABA), traditionally acknowledged as a plant stress hormone, is detected and actively functions in organisms beyond the land plant kingdom, encompassing cyanobacteria, fungi, algae, protozoan parasites, lower Metazoa, and mammals. Its ancient, cross-kingdom role enables ABA and its signaling pathway to regulate cell responses to environmental stimuli in various organisms, such as marine sponges, higher plants, and humans. Recent advancements in understanding the physiological function of ABA and its mammalian receptors in governing energy metabolism and mitochondrial function in myocytes, adipocytes, and neuronal cells suggest potential therapeutic applications for ABA in pre-diabetes, diabetes, and cardio-/neuroprotection. The ABA/LANCL1-2 hormone/receptor system emerges as a novel regulator of ERRα expression levels and transcriptional activity, mediated through the AMPK/SIRT1/PGC-1α axis. There exists a reciprocal feed-forward transcriptional relationship between the LANCL proteins and transcriptional coactivators ERRα/PGC-1α, which may be leveraged using natural or synthetic LANCL agonists to enhance mitochondrial function across various clinical contexts.

Environmental reporting in Italian thermal power plants: insights from a comprehensive analysis of EMAS environmental statements.

The global energy sector heavily relies on fossil fuels, significantly contributing to climate change. The ambitious European emissions' reduction targets require sustainable processes and alternatives. This study presents a comprehensive analysis of 73 Italian thermal power plants registered to the European Eco-Management and Audit Scheme (EMAS) aimed at assessing EMAS effectiveness in addressing and quantifying the environmental impacts of this relevant industrial sector. The analysis was based on EMAS environmental statements, publicly disclosing verified and certified data, with the secondary objective of evaluating if EMAS could be an efficient tool to improve the plants' environmental performances. An inventory of technical and environmental aspects, adopted indicators, and allocated budgets was based on 2023 data. A strong correlation was found between the significance of the environmental aspects and the number of adopted indicators. Gaps were observed in describing aspects like "biodiversity" and "local issues". Improvement objectives and budget allocation showed discrepancies and lacked correlation with the significance of the related environmental aspects. "Energy production" accounted for 68% of the total allocated budget; "environmental risks", "emissions to air", "electricity consumption", and "local issues" were also key focus areas. Insufficient information on emission control technologies and progress tracking of improvement objectives was detected. This study highlights the need for thermal power installations to improve the selection of appropriate indicators and to better relate allocated budget to improvement objectives when implementing EMAS. Such measures would facilitate the quantification of the effective environmental impacts of the energy production sector, supporting future research on this topic, allowing stakeholders a better comparison among plants, and driving industry-wide improvements.

From single-chamber to multi-anodic microbial fuel cells: A review.

Microbial fuel cells (MFCs) present a promising solution for wastewater treatment with the added benefits of energy generation, less sludge production and less energy consumption. MFCs have demonstrated high efficiency in the degradation of diverse types of wastewater. Nevertheless, the relatively low power density exhibited by MFCs has imposed certain restrictions on their widespread implementation. Consequently, the need for modification of MFC technology led to the development of stack and multi-chambered MFCs. The modified variations exhibit enhanced scalability and demonstrate greater reliability in terms of power output compared to traditional MFCs. In the present review article, different components of MFCs such as anode, cathode, microbial community and membrane have been reviewed and the advancement in design for better scalability of MFCs has been addressed, emphasizing the benefits associated with stacked and multi-anodic MFCs for enhanced performance. Finally, an update of previous large-scale MFC system applications is presented.

Mitochondrial pyruvate carrier blockade results in decreased osteoclastogenesis and bone resorption via regulating mitochondrial energy production.

It's widely accepted that increasing mitochondrial respiration plays a pivotal role during osteoclastogenesis. Mitochondrial pyruvate carrier (MPC) is the key transporter that links glycolysis to mitochondrial respiration but little is known about its role during osteoclastogenesis. Our goal was to determine the effects of its blockade on osteoclastogenesis and bone resorption in vivo and in vitro. To address this issue, we performed gene knockdown or pharmacologically inhibited MPC in primary bone marrow-derived monocytes (BMMs) or in an ovariectomized mouse model. We also studied the metabolic changes in RANKL-induced differentiating BMMs with MPC blockade and performed rescue experiments. We found that MPC blockade resulted in decreased osteoclastogenesis both in vivo and in vitro and inhibiting MPC significantly alleviated ovariectomy-induced trabecular bone loss. Further investigations showed that MPC blockade significantly reversed the metabolic profile related to RANK activation, including decreased intermediates involved in citric acid cycle and glutamine metabolism. Moreover, metabolic flux analysis verified that MPC blockade decreased pyruvate flux into TCA cycle with no significant effect on glycolysis. Besides, MPC blockade resulted in suppressed mitochondrial biogenesis in addition to oxidative phosphorylation. Rescue experiments revealed that inhibiting pyruvate dehydrogenase kinase (PDK) via sodium dichloroacetate (DCA), but not targeting glutamine metabolism, could reverse the effects of MPC blockade on osteoclastogenesis. These implied that the effects of MPC blockade were mediated by reduced pyruvate fuel into citric acid cycle in multiple aspects. Taken together, our data demonstrated the inhibitory effects of MPC blockade on osteoclastogenesis, which was mediated by decreased mitochondrial energy production.

Putting the electro-bugs to work: A systematic review of 22 years of advances in bio-electrochemical systems and the parameters governing their performance.

Wastewater treatment using bioelectrochemical systems (BESs) can be considered as a technology finding application in versatile areas such as for renewable energy production and simultaneous reducing environmental problems, biosensors, and bioelectrosynthesis. This review paper reports and critically discusses the challenges, and advances in bio-electrochemical studies in the 21st century. To sum and critically analyze the strides of the last 20+ years on the topic, this study first provides a comprehensive analysis on the structure, performance, and application of BESs, which include Microbial Fuel Cells (MFCs), Microbial Electrolysis Cells (MECs) and Microbial Desalination Cells (MDCs). We focus on the effect of various parameters, such as electroactive microbial community structure, electrode material, configuration of bioreactors, anode unit volume, membrane type, initial COD, co-substrates and the nature of the input wastewater in treatment process and the amount of energy and fuel production, with the purpose of showcasing the modes of operation as a guide for future studies. The results of this review show that the BES have great potential in reducing environmental pollution, purifying saltwater, and producing energy and fuel. At a larger scale, it aspires to facilitate the path of achieving sustainable development and practical application of BES in real-world scenarios.

Anaerobic membrane bioreactor for carbon-neutral treatment of industrial wastewater containing N, N-dimethylformamide: Evaluation of electricity, bio-energy production and carbon emission.

The feasibility of anaerobic membrane bioreactor (AnMBR) for the treatment of N, N-dimethylformamide (DMF)-containing wastewater was theoretically compared with the conventional activated sludge (CAS) process in this study. The electricity consumption and expenditure, bio-energy production and CO2 emission were investigated using the operational results of a lab-scale AnMBR operated in a long-term operation. The AnMBR was capable of producing bio-methane from wastewater and generated 3.45 kWh/m3 of electricity as recovered bio-energy while the CAS just generated 1.17 kWh/m3 of electricity from the post-treatment of excessive sludge disposal. The large quantity of bio-methane recovered by the AnMBR can also be sold as sustainable bioresource for the use of household natural gas with a theoretical profit gain of 29,821 US$/year, while that of the CAS was unprofitable. The AnMBR was also demonstrated to significantly reduce the carbon emission by obtaining a theoretical negative CO2 production of -2.34 kg CO2/m3 with the recycle of bio-energy while that for the CAS was 4.50 kg CO2/m3. The results of this study demonstrate that the AnMBR process has promising potential for the carbon-neutral treatment of high-strength DMF-containing wastewater in the future.

From Corrective to Predictive Maintenance-A Review of Maintenance Approaches for the Power Industry.

Appropriate maintenance of industrial equipment keeps production systems in good health and ensures the stability of production processes. In specific production sectors, such as the electrical power industry, equipment failures are rare but may lead to high costs and substantial economic losses not only for the power plant but for consumers and the larger society. Therefore, the power production industry relies on a variety of approaches to maintenance tasks, ranging from traditional solutions and engineering know-how to smart, AI-based analytics to avoid potential downtimes. This review shows the evolution of maintenance approaches to support maintenance planning, equipment monitoring and supervision. We present older techniques traditionally used in maintenance tasks and those that rely on IT analytics to automate tasks and perform the inference process for failure detection. We analyze prognostics and health-management techniques in detail, including their requirements, advantages and limitations. The review focuses on the power-generation sector. However, some of the issues addressed are common to other industries. The article also presents concepts and solutions that utilize emerging technologies related to Industry 4.0, touching on prescriptive analysis, Big Data and the Internet of Things. The primary motivation and purpose of the article are to present the existing practices and classic methods used by engineers, as well as modern approaches drawing from Artificial Intelligence and the concept of Industry 4.0. The summary of existing practices and the state of the art in the area of predictive maintenance provides two benefits. On the one hand, it leads to improving processes by matching existing tools and methods. On the other hand, it shows researchers potential directions for further analysis and new developments.

Enzymatic and Bioinspired Systems for Hydrogen Production.

The extraordinary potential of hydrogen as a clean and sustainable fuel has sparked the interest of the scientific community to find environmentally friendly methods for its production. Biological catalysts are the most attractive solution, as they usually operate under mild conditions and do not produce carbon-containing byproducts. Hydrogenases promote reversible proton reduction to hydrogen in a variety of anoxic bacteria and algae, displaying unparallel catalytic performances. Attempts to use these sophisticated enzymes in scalable hydrogen production have been hampered by limitations associated with their production and stability. Inspired by nature, significant efforts have been made in the development of artificial systems able to promote the hydrogen evolution reaction, via either electrochemical or light-driven catalysis. Starting from small-molecule coordination compounds, peptide- and protein-based architectures have been constructed around the catalytic center with the aim of reproducing hydrogenase function into robust, efficient, and cost-effective catalysts. In this review, we first provide an overview of the structural and functional properties of hydrogenases, along with their integration in devices for hydrogen and energy production. Then, we describe the most recent advances in the development of homogeneous hydrogen evolution catalysts envisioned to mimic hydrogenases.

Recent Advances in Processing and Applications of Heterobimetallic Oxide Thin Films by Aerosol-Assisted Chemical Vapor Deposition.

The fabrication of smart, efficient, and innovative devices critically needs highly refined thin-film nanomaterials; therefore, facile, scalable, and economical methods of thin films production are highly sought-after for the sustainable growth of the hi-tech industry. The chemical vapor deposition (CVD) technique is widely implemented at the industrial level due to its versatile features. However, common issues with a precursor, such as reduced volatility and thermal stability, restrict the use of CVD to produce novel and unique materials. A modified CVD approach, named aerosol-assisted CVD (AACVD), has been the center of attention due to its remarkable tendency to fabricate uniform, homogenous, and distinct nano-architecture thin films in an uncomplicated and straightforward manner. Above all, AACVD can utilize any custom-made or commercially available precursors, which can be transformed into a transparent solution in a common organic solvent; thus, a vast array of compounds can be used for the formation of nanomaterial thin films. This review article highlights the importance of AACVD in fabricating heterobimetallic oxide thin films and their potential in making energy production (e. g., photoelectrochemical water splitting), energy storage (e. g., supercapacitors), and environmental protection (e. g., electrochemical sensors) devices. A heterobimetallic oxide system involves two metallic species either in a composite, solid solution, or metal-doped metal oxides. Moreover, the AACVD tunable parameters, such as temperature, deposition time, and precursor, which drastically affect thin films microstructure and their performance in device applications, are also discussed. Lastly, the key challenges and issues of scaling up AACVD to the industrial level and processing for emerging functional materials are also highlighted.

Ion and Water Transport in Ion-Exchange Membranes for Power Generation Systems: Guidelines for Modeling.

Artificial ion-exchange and other charged membranes, such as biomembranes, are self-organizing nanomaterials built from macromolecules. The interactions of fragments of macromolecules results in phase separation and the formation of ion-conducting channels. The properties conditioned by the structure of charged membranes determine their application in separation processes (water treatment, electrolyte concentration, food industry and others), energy (reverse electrodialysis, fuel cells and others), and chlore-alkali production and others. The purpose of this review is to provide guidelines for modeling the transport of ions and water in charged membranes, as well as to describe the latest advances in this field with a focus on power generation systems. We briefly describe the main structural elements of charged membranes which determine their ion and water transport characteristics. The main governing equations and the most commonly used theories and assumptions are presented and analyzed. The known models are classified and then described based on the information about the equations and the assumptions they are based on. Most attention is paid to the models which have the greatest impact and are most frequently used in the literature. Among them, we focus on recent models developed for proton-exchange membranes used in fuel cells and for membranes applied in reverse electrodialysis.

The daily gene transcription cycle in mouse retina.

Many physiological retinal processes, such as outer segment disk shedding and visual sensitivity, exhibit a daily rhythm. However, the detailed transcriptome dynamics and related biological processes of the retina are not fully understood. Retinal tissues were collected from C57BL/6J male mice housed in a 12h light/12h dark (LD) cycle for 4 weeks, at Zeitgeber time (ZT) 0, 4, 8, 12, 16, and 20. Total RNA was extracted from the tissues and used for unique identifier RNA sequencing experiments. The rhythmicity of gene expression was determined using the MetaCycle R package. We found that 1741 genes (10.26%) were rhythmically expressed in the retina. According to the expression patterns, the rhythmically expressed genes were assigned to four clusters, each with about 361-492 genes, using the Mfuzz R package. The Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analyses were conducted to identify pathways and biological processes of the profiled genes. Genes in Clusters 1 and 4 were associated with glycolysis and energy production, showed higher activity at night (from ZT16 to ZT20), and were enriched in the Hif-1α signaling pathway and low-oxygen-related terms. Genes in Cluster 2 were predominantly involved in cilium assembly and organization and were relatively upregulated during the day. Genes in Cluster 3 were associated with ribosome biosynthesis and were highly expressed during the day-night transition period. Taken together, these results demonstrate that a large proportion of retinal genes are expressed rhythmically. Genes involved in energy production and glycolysis are highly expressed at night, leading to relative hypoxia and activation of the Hif-1α signaling pathway. Genes associated with the formation of photoreceptor cilia are expressed during the day.

Intramuscular short-chain acylcarnitines in elderly people are decreased in (pre-)frail females, but not in males.

This study tested the hypothesis that in human aging, a decreased intramuscular acylcarnitine status is associated with (pre-)frailty, reduced physical performance, and altered mitochondrial function. We used a cross-sectional study design with well-matched fit and (pre-)frail old males and females, using young males and females as healthy controls. Frailty was assessed according to the Fried criteria and physical performance was determined by 400 m walk test, short physical performance battery and handgrip strength. Muscle and plasma acylcarnitine status, and muscle mitochondrial gene expression was analyzed. Results showed that intramuscular total carnitine levels and short-chain acylcarnitine levels were lower in (pre-)frail old females compared to fit old females and young females, whereas no differences were observed in males. The low intramuscular short-chain acylcarnitine levels in females correlated with low physical performance, even after correction for muscle mass (%), and were accompanied with lowered expression of genes involved in mitochondrial energy production and functionality. It is, therefore, concluded that in (pre-)frail old females, intramuscular total carnitine levels and short-chain acylcarnitine levels are decreased, and this decrease is associated with reduced physical performance and low expression of a wide range of genes critical for mitochondrial function. The results stress the importance of taking sex differences into account in aging research.

Mass-spectrometry analysis of the human pineal proteome during night and day and in autism.

The human pineal gland regulates day-night dynamics of multiple physiological processes, especially through the secretion of melatonin. Using mass-spectrometry-based proteomics and dedicated analysis tools, we identify proteins in the human pineal gland and analyze systematically their variation throughout the day and compare these changes in the pineal proteome between control specimens and donors diagnosed with autism. Results reveal diverse regulated clusters of proteins with, among others, catabolic carbohydrate process and cytoplasmic membrane-bounded vesicle-related proteins differing between day and night and/or control versus autism pineal glands. These data show novel and unexpected processes happening in the human pineal gland during the day/night rhythm as well as specific differences between autism donor pineal glands and those from controls.

Quantifying Methane and Ozone Precursor Emissions from Oil and Gas Production Regions across the Contiguous US.

We present an updated fuel-based oil and gas (FOG) inventory with estimates of nitrogen oxide (NOx) emissions from oil and natural gas production in the contiguous US (CONUS). We compare the FOG inventory with aircraft-derived ("top-down") emissions for NOx over footprints that account for ∼25% of US oil and natural gas production. Across CONUS, we find that the bottom-up FOG inventory combined with other anthropogenic emissions is on average within ∼10% of top-down aircraft-derived NOx emissions. We also find good agreement in the trends of NOx from drilling- and production-phase activities, as inferred by satellites and in the bottom-up inventory. Leveraging tracer-tracer relationships derived from aircraft observations, methane (CH4) and non-methane volatile organic compound (NMVOC) emissions have been added to the inventory. Our total CONUS emission estimates for 2015 of oil and natural gas are 0.45 ± 0.14 Tg NOx/yr, 15.2 ± 3.0 Tg CH4/yr, and 5.7 ± 1.7 Tg NMVOC/yr. Compared to the US National Emissions Inventory and Greenhouse Gas Inventory, FOG NOx emissions are ∼40% lower, while inferred CH4 and NMVOC emissions are up to a factor of ∼2 higher. This suggests that NMVOC/NOx emissions from oil and gas basins are ∼3 times higher than current estimates and will likely affect how air quality models represent ozone formation downwind of oil and gas fields.

18ß-glycyrrhetinic acid improves high-intensity exercise performance by promoting glucose-dependent energy production and inhibiting oxidative stress in mice.

It has been shown that 18ß-glycyrrhetinic acid (18ß-GA), the main bioactive compound of licorice, can modulate oxidative stress and metabolic processes in liver and skin. Given the critical role of oxidative stress and energy metabolism in exercise-induced fatigue, we hypothesized that 18ß-GA could exert an ergogenic action by inhibiting excess reactive oxygen species (ROS) induction and promoting energy production in muscles. Mice were gavage-fed with 18ß-GA for four consecutive days. Running ability was assessed based on the exhaustive treadmill test with high- and moderate-intensity. Western blot analysis, enzyme-linked immunosorbent assay, and immunofluorescence staining were used to measure the changes of muscle fatigue-related markers, oxidative stress status, and energy metabolism in response to 18ß-GA exposure. Treatment with 18ß-GA significantly increased the exhaustive running distance (~37%) in the high-intensity exercise, but not in the moderate-intensity exercise. Mechanistically, reduction of oxidative stress and induction of antioxidants (SOD, CAT, and GSH) by 18ß-GA were observed. Moreover, 18ß-GA treatment caused an improved preservation of muscle glycogen (12%), which was associated with upregulation of glucose transporter 4 (GLUT4) (91%) and increased insulin level (17%). The findings of the present study clearly suggest that 18ß-GA holds excellent potential as a novel bioactive agent against high-intensity exercise-induced fatigue.

CNPase, a 2',3'-Cyclic-nucleotide 3'-phosphodiesterase, as a Therapeutic Target to Attenuate Cardiac Hypertrophy by Enhancing Mitochondrial Energy Production.

Heart failure is the end-stage of all cardiovascular diseases with a ~25% 5-year survival rate, and insufficient mitochondrial energy production to meet myocardial demand is the hallmark of heart failure. Mitochondrial components involved in the regulation of ATP production remain to be fully elucidated. Recently, roles of 2',3'-cyclic nucleotide-3'-phosphodiesterase (CNPase) in the pathophysiological processes of heart diseases have emerged, implicated by evidence that mitochondrial CNPase proteins are associated with mitochondrial integrity under metabolic stress. In this study, a zebrafish heart failure model was established, by employing antisense morpholino oligonucleotides and the CRISPR-Cas9 gene-editing system, which recapitulates heart failure phenotypes including heart dysfunction, pericardial edema, ventricular enlargement, bradycardia, and premature death. The translational implications of CNPase in the pathophysiological process of heart failure were tested in a pressure overload-induced heart hypertrophy model, which was carried out in rats through transverse abdominal aorta constriction (TAAC). AAV9-mediated myocardial delivery of CNPase mitigated the hypertrophic response through the specific hydrolysis of 2'-3'-cyclic nucleotides, supported by the decrease of cardiac hypertrophy and fibrosis, the integrity of mitochondrial ultrastructure, and indicators of heart contractility in the AAV9-TAAC group. Finally, the biometrics of a mitochondrial respiration assay carried out on a Seahorse cellular energy analyzer demonstrated that CNPase protects mitochondrial respiration and ATP production from AngII-induced metabolic stress. In summary, this study provides mechanistic insights into CNPase-2',3'-cyclic nucleotide metabolism that protects the heart from energy starvation and suggests novel therapeutic approaches to treat heart failure by targeting CNPase activity.

Anaerobic Digestion for Producing Renewable Energy-The Evolution of This Technology in a New Uncertain Scenario.

Anaerobic digestion is a well-known technology with wide application in the treatment of high-strength organic wastes. The economic feasibility of this type of installation is usually attained thanks to the availability of fiscal incentives. In this review, an analysis of the different factors associated with this biological treatment and a description of alternatives available in literature for increasing performance of the process were provided. The possible integration of this process into a biorefinery as a way for producing energy and chemical products from the conversion of wastes and biomass also analyzed. The future outlook of anaerobic digestion will be closely linked to circular economy principles. Therefore, this technology should be properly integrated into any production system where energy can be recovered from organics. Digestion can play a major role in any transformation process where by-products need further stabilization or it can be the central core of any waste treatment process, modifying the current scheme by a concatenation of several activities with the aim of increasing the efficiency of the conversion. Thus, current plants dedicated to the treatment of wastewaters, animal manures, or food wastes can become specialized centers for producing bio-energy and green chemicals. However, high installation costs, feedstock dispersion and market distortions were recognized as the main parameters negatively affecting these alternatives.