Search Results (112)

The focal “hot spot” neuropathologies in COVID-19 infection are revealing footprints of a hidden underlying collapse of a novel ultrafast ultradian Piezo2 signaling system within the nervous system. Paradoxically, the same initiating pathophysiology may underpin the systemic findings in COVID-19 infection, namely the multiorgan SARS-CoV-2 infection-induced vascular pathologies and brain–body-wide systemic pro-inflammatory signaling, depending on the concentration and exposure to infecting SARS-CoV-2 viruses. This common initiating microdamage is suggested to be the primary damage or the acquired channelopathy of the Piezo2 ion channel, leading to a principal gateway to pathophysiology. This Piezo2 channelopathy-induced neural switch could not only explain the initiation of disrupted cell–cell interactions, metabolic failure, microglial dysfunction, mitochondrial injury, glutamatergic synapse loss, inflammation and neurological states with the central involvement of the hippocampus and the medulla, but also the initiating pathophysiology without SARS-CoV-2 viral intracellular entry into neurons as well. Therefore, the impairment of the proposed Piezo2-induced quantum mechanical free-energy-stimulated ultrafast proton-coupled tunneling seems to be the principal and critical underlying COVID-19 infection-induced primary damage along the brain axes, depending on the loci of SARS-CoV-2 viral infection and intracellular entry. Moreover, this initiating Piezo2 channelopathy may also explain resultant autonomic dysregulation involving the medulla, hippocampus and heart rate regulation, not to mention sleep disturbance with altered rapid eye movement sleep and cognitive deficit in the short term, and even as a consequence of long COVID. The current opinion piece aims to promote future angles of science and research in order to further elucidate the not entirely known initiating pathophysiology of SARS-CoV-2 infection. Full article

The GntR is a transcriptional regulator generally known as a gluconate-operon repressor to specifically regulate the transportation and phosphorylation of gluconate. In the present study we report the cloning of the GntR-encoding gene of the industrial 2-ketogluconate (2KGA)-producer Pseudomonas plecoglossicida JUIM01, which is involved in the regulation of gluconate metabolism, along with the identification of some of its target genes and its operator sequence. GntR is a 36.36-kDa cytoplasmic and hydrophobic DNA-binding transcriptional regulator belonging to the LacI family. The knockout of gntR resulted in the significant upregulation of the transcription of the gluconate kinase gene gntK and, to a lesser extent, the permease gene gntP, as well as downregulation of genes involved in glucose uptake (oprB-1, gltB, gltF, gltG, and gltK) and those involved in 2-ketogluconate (2KGA) transport (kguT) and catabolism (kguE, kguK, and kguD). These results indicated that GntR positively regulated glucose and 2KGA transport and catabolism, while negatively affecting GntP-mediated gluconate uptake and gluconate phosphorylation by GntK. Electrophoretic mobility shift assay (EMSA) and DNase I footprinting analyses confirmed that GntR interacted with operator sequences in the divergent promoter regions of gntK and gntP, as well as in the gntR promoter region. A putative operator sequence (consensus 5′-AG-N₂-AGCGCT-N-TCT-3′) was identified. These data suggest that GntR positively regulates genes involved in glucose uptake/transport and 2KGA transport/catabolism, while repressing its own expression as well as that of genes involved in gluconate transport/catabolism. These findings not only elucidate the regulation of GntR and its target genes in P. plecoglossicida, but also provide valuable insights for optimizing industrial 2KGA production. Full article

The sustainable growth of finfish farming relies heavily on reducing the high ecological footprint of sourcing and producing fish feeds that accounts for almost 50% of the total ecological footprint of finfish farming. Sustainable alternatives to fishmeal often pose challenges due to the presence of antinutritional factors and nutrient imbalances that impair fish health and growth. Screening for alternative nutrient sources and adapting to global commodity fluctuations requires modern tools that can predict the physiological responses of fish early and reliably. The present study explores for the first time the potential of fish red blood cell (RBC) transcriptome as a minimally invasive biomarker of physiological responses in gilthead seabream (Sparus aurata) fed either a fishmeal-based (FM) or a plant-protein-based (PP) diet. Blood samples were collected at multiple time points (15, 20, and 30 days post-diet initiation) from genetically diverse full-sib families reared under commercial conditions, integrating transcriptomic analysis with long-term growth assessments. Differential gene expression analysis revealed significant dietary effects on oxidative phosphorylation, ribosomal capacity, and lipid metabolism pathways, highlighting metabolic plasticity and cellular adaptations to plant-based feeds. The downregulation of oxidative phosphorylation genes suggests a metabolic shift in response to altered nutrient composition, while ribosomal pathway modulation indicates potential constraints on protein synthesis. These transcriptomic shifts, conserved across two independent experiments, reinforce the utility of RBCs as a real-time indicator of fish physiological status, offering a tool for monitoring dietary impacts and optimizing feed formulations. Such insights are essential for advancing sustainable, nutritionally balanced aquaculture feeds that support fish welfare and productivity. The minimally invasive sample collection respects the 3Rs (Reduce, Refine, Replace) principle in animal experimentation and allows for frequent screening and generation of refined data. Full article

Ruminal methanogenesis represents considerable energy loss within the fermentative processes mediated by microbial populations, by means of which up to 12% of gross energy intake is driven away from microbial protein synthesis (MPS). This review explores the relationship between methane (CH₄) synthesis and emission with MPS in beef cattle, focusing on the nutritional, biochemical, and microbial factors modulating these processes. The synthesis of CH₄ by ruminal archaea is essential for maintaining redox balance during the fermentation of carbohydrates. This process diverts metabolic H₂ from energy-efficient pathways like propionate synthesis, which could otherwise enhance microbial growth. Dietary factors, including carbohydrate fermentability, N synchronization, and passage rate, modulate MPS. Diets based on roughage might enhance CH₄ synthesis while impairing MPS efficiency by reducing diet digestibility and promoting microbial shifts towards methanogenic populations. Potential mitigation strategies, including plant secondary metabolites, CH₄ inhibitors, and controlled forage-to-concentrate ratios, demonstrate the potential to reduce CH₄ emissions while enhancing nutrient utilization. This review underscores the need for integrated approaches combining dietary strategies, advanced feed additives, and improved prediction models to optimize ruminal fermentation, enhance MPS, and reduce the environmental footprint of beef cattle systems. Full article

Waste biomass deriving from agricultural activities has different destinations depending on the possibility of applying it to specific processes. As the waste biomass is abundant, cheap, and generally safe, it can be used for several applications, biogas production being the most relevant from the quantitative point of view. In this study, we have used a set of agricultural by-products (agro-waste) deriving from the post-harvest treatment of cereals and legumes as the growth substrate for selected biosurfactant-producing microbial strains. The agricultural by-products were easily metabolized and highly effective for the growth of microorganisms and the production of rhamnolipids and surfactin by Pseudomonas aeruginosa and Bacillus subtilis, respectively. In particular, the use of corn chaff (“bee-wings”) was suitable for the production of rhamnolipids. Indeed, in corn-chaff-based media, rhamnolipids yields ranged from 2 to 18 g/L of fermentation broth. This study demonstrated that the use of waste raw materials could be applied to reduce the carbon footprint of the production of biosurfactants without compromising the possibility of having a suitable fermentation medium for industrial production. Full article

Replacing traditional agricultural ingredients with biotechnologically improved agro-industry by-products in fish diets promotes sustainable aquaculture, reduces production costs and carbon footprint, and promotes a circular economy. Brewer’s spent grain (BSG) is one such by-product. Solid-state fermentation (SSF) of BSG with Aspergillus ibericus enhances its nutritional value and digestibility for European seabass. The present study further evaluates the potential of dietary inclusion of BSG-SSF on growth performance, feed utilization, plasma metabolite profile, intermediary metabolism, and oxidative status of European seabass juveniles compared to the unfermented product. A practical diet (45% protein; 18% lipids) was tested against diets incorporating 10% or 20% of BSG or BSG-SSF, replacing plant-protein feedstuffs. Triplicate groups of European seabass juveniles (49 g initial weight) were fed for 10 weeks. Unfermented BSG (10% and 20%) reduced growth and feed efficiency. In comparison, the 20% BSG-SSF diet promoted growth and feed efficiency similar to the control group, while the 10% BSG-SSF diet surpassed the control diet. Whole-body protein content was unaffected, but lipid and energy content decreased with increasing BSG levels, regardless of fermentation. Plasma glucose and phospholipid levels and hepatic activities of glucokinase and malic enzymes decreased with increasing BSG, irrespective of fermentation. BSG-SSF incorporation increased plasma triglyceride levels and decreased hepatic transaminase activities but did not affect hepatic key enzyme activity of β-oxidation or lipogenesis. It also reduced antioxidant enzyme activity and lipid peroxidation. In conclusion, BSG negatively impacted growth performance, while BSG-SSF supported inclusion levels up to 20% without performance loss. Further, the 10% BSG -SSF diet outperformed the control diet. Full article

New psychoactive substances (NPSs) emerged in the 2000s as legal alternatives to illicit drugs and quickly became a huge public health threat due to their easy accessibility online, limited information, and misleading labels. Synthetic cannabinoids and synthetic cathinones are the most reported groups of NPSs. Despite NPSs being widely studied, due to their structural diversity and the constant emergence of novel compounds with unknown properties, the development of new techniques is required to clarify their mode of action and evaluate their toxicological effects. Metabolomics has been a useful tool to evaluate the metabolic effects of several xenobiotics. Herein, a systematic review was performed, following PRISMA guidelines, regarding metabolomic studies on synthetic cathinones and synthetic cannabinoids to evaluate their effects in cellular metabolism. In the studies, in vivo models were the most employed (86%) and the analysis mostly followed untargeted approaches (75%) using LC-MS techniques (67%). Both groups of NPSs seem to primarily interfere with energy metabolism-related pathways. Even though this type of study is still limited, metabolomics holds great promise as a tool to clarify mechanisms of actions, identify biomarkers of exposure, and explain the toxicological effects of NPSs. Full article

The biomarker-based Dutch Newborn Screening (NBS) panel (as of 2024) comprises 19 inherited metabolic disorders (IMDs). With the use of next-generation sequencing (NGS) as a first-tier screen, NBS could expand to include IMDs that lack a reliable biochemical footprint in dried blood spots, while also reducing secondary findings. To be eligible for inclusion in NBS, an IMD needs to fulfill the Wilson and Jungner criteria, with treatability being one of the most important criteria. In this study, we aimed to identify IMDs eligible for DNA-first NBS when considering only treatability in the context of NBS as a prerequisite. First, three independent reviewers performed a systematic literature review of the 1459 genotypic IMDs and their causative gene(s), as described in the International Classification of Inherited Metabolic Disorders (dated 1 February 2021), applying 16 criteria to exclude non-treatable disorders. Eligible disorders were then discussed in three online meetings with a project group of clinical laboratory geneticists, medical laboratory specialists specialized in IMD, and pediatricians with expertise in IMDs. Based on treatability, we identified 100 genes, causing 95 IMDs, as eligible for NBS, including 42 causal genes for the IMDs in the current biomarker-based NBS. The other 58 genes are primarily associated with treatable defects in amino acid metabolism and fatty acid oxidation. Other IMDs were excluded, most often because of insufficient literature. As the evaluation of treatability was not straightforward, we recommend the development of standardized treatability scores for the inclusion of IMDs in NBS. Full article

Analyzing genetic variability and inbreeding trends is essential for effective breed management in animal populations. To this, the characterization of runs of homozygosity (ROH) provides a good genomic approach to study the phenomena. The Polo Argentino (PA) breed, globally recognized as the best adapted to playing polo, is known for its strong influence of Thoroughbreds, intense selective breeding, and extensive use of reproductive biotechnologies. This study investigates the PA’s genomic variability, by characterizing the ROH landscape and identifying ROH islands (ROHi) as potential genomic footprints for the breed. PA horses (n = 506) were genotyped using EquineGGP™ array v5 (70 k). We calculated the inbreeding coefficient based on ROH (F_ROH—ancestral and recent) using a chromosomal approach. Finally, we identified genomic regions with increased ROH frequency (ROHi) and their associated genes. An average of 79.5 ROH per horse was detected, with a mean length of 4.6 Mb. The average F_ROH was 0.151, but most of them (54%) corresponded to ancestral inbreeding (ROH < 5.5 Mb). However, 4 ROHi were identified in ECA 1, 3, 7 and 17, containing 67 genes, some of which were related to behavior, neurodevelopment, and metabolic functions. This genomic analysis determined, for the first time, the length and location of homozygosity segments in the PA breed and identified ROHi associated with potential genomic regions and genes for positive selection in the breed. Full article

Grape pomace (GP), a byproduct of winemaking, has gained significant attention as a sustainable and functional ingredient with applications in the food and nutraceutical industries. This review examines the potential of GP in meat products and analogs, functional foods, and nutraceuticals, highlighting its composition, health benefits, and role in enhancing nutritional and functional properties. Rich in dietary fiber, polyphenols, essential fatty acids, and bioactive compounds, GP exhibits antioxidant, anti-inflammatory, and gut health-promoting effects, making it suitable for various food applications. Its incorporation into meat products, such as sausages and patties, improves texture, enhances shelf life, and increases nutritional value while reducing the environmental footprint. GP is also effective in functional foods such as baked goods, dairy and plant-based yoghurts, smoothies, and snack bars, where it can enrich fiber and polyphenol content, aid in satiety, and provide health benefits beyond basic nutrition. The challenge is how to maintain the sensory properties characteristic of conventional, unmodified products. In nutraceuticals, GP’s polyphenolic compounds and dietary fiber support antioxidant, anti-inflammatory, and metabolic health functions, with applications as antioxidant supplements, gut health boosters, weight management aids, and cardiovascular health supplements. Despite challenges such as taste modification and optimizing bioavailability, GP’s versatility and sustainability highlight its value in developing innovative, health-oriented products. This review emphasizes the promise of GP as a valuable ingredient in functional foods and nutraceutical formulations, contributing to health, sustainability, and resource efficiency. Full article

Vanillin, an aromatic aldehyde, is one of the most popular flavors worldwide, extensively used in the food, cosmetics, pharmaceutical, and agrochemical industries. Despite its widespread use, less than 1% of the total vanillin production is natural, with the majority being synthesized chemically. While chemical synthesis can help to meet the growing demand for vanillin, a strong market trend has rapidly developed for products created from natural ingredients, including natural vanillin. Given the labor-intensive process of extracting vanillin from vanilla pods, there is a critical need for new metabolic engineering platforms to support the biotechnological production of nature-identical vanillin. This review highlights the significance of vanillin in various markets, its diverse applications, and the current state of bio-engineered production using both prokaryotic and eukaryotic biological systems. Although recent advancements have demonstrated successful vanillin production through biocatalytic approaches, our focus was to provide a current and innovative overview of vanillin bioengineering across various host systems with special consideration placed on microalgae, which are emerging as promising platforms for vanillin production through metabolic engineering. The use of these systems to support the biotechnological production of vanillin, while leveraging the photosynthetic capabilities of microalgae to capture CO₂ and convert it into biomass, can significantly reduce the overall carbon footprint. Full article

Androstenedione (AD) is an important intermediate for the production of steroidal drugs. The process of transforming phytosterols into AD by Mycolicibacterium is mainly the degradation process of the phytosterol side chain, and the excessive accumulation of propionyl-CoA produced by Mycobacterium will produce toxic effects, which seriously restricts the transformation performance of strains. In this study, Mycolicibacterium sp. LZ2 (Msp) was used as the research object to study the transcription factor PccD of the TetR family, which has the role of propionyl-CoA metabolism regulation. By constructing overexpression and deletion strains of pccD, it was confirmed that pccD had an inhibitory effect on the transcription of propionyl-CoA carboxylase genes (pccA and pccB). Electrophoretic Mobility Shift Assay (EMSA) and DNase I footprint analysis demonstrated that PccD is directly involved in the transcriptional regulation of pccA and pccB and is a negative transcriptional regulator of the pcc operon. In the study of phytosterol transformation, the growth rate and bacterial viability of Msp-ΔpccD were higher than Msp, but the growth of Msp-pccD was inhibited. As a result of testing of intracellular propionyl-CoA levels and AD production yields, it was found that lower propionyl-CoA levels and higher AD production yields were observed in Msp-ΔpccD. The results expand the cognition of propionyl-CoA metabolism regulation and provide a theoretical basis and reference for the rational transformation of phytosterol transformation strains and secondary metabolite synthesis strains with propionyl-CoA as a substrate, which has important research significance. Full article

The Loess Plateau is one of the most vulnerable areas in the world. Numerous studies have been conducted to investigate alfalfa fields with different planting years. Soil microorganisms and nematodes are vital in ecosystem functionality and nutrient cycling. Therefore, comprehending their response to alfalfa fields with varying years of planting is essential for predicting the direction and trajectory of degradation. Alfalfa fields with different planting years (2 years, 9 years, and 18 years) were used as the research object, and farmland was used as the control (CK). High-throughput sequencing and morphological methods determined the community composition of microorganisms and nematodes. Carbon metabolic footprints, correlation networks, and structural equations were used to study soil microorganisms and nematode interactions. Principal component analysis (PCA) results showed that alfalfa fields with different planting years significantly impacted soil microorganisms and nematode community structures. Planting alfalfa significantly increased the nematode channel ratio (NCR) and Wasilewska index (WI), but significantly reduced the soil nematode PPI/MI and dominance (λ). The correlation network results indicated that, for the 2-year and 18-year treatments, the total number of links and positive links are higher than other treatments. Conversely, the 9-year treatment had fewer positive links and more negative links compared to other treatments. Additionally, the keystone species within each network varied based on the treatment years. Structural equation results show that alfalfa planting years directly impact soil fungal community structure and plant-parasitic nematodes’ carbon metabolism omnivorous-predatory nematodes. Furthermore, the carbon metabolism of omnivorous-predatory nematodes directly influences soil organic carbon fixation. Moreover, as the duration of alfalfa planting increases, the metabolic footprint of plant-parasitic nematodes decreases while that of omnivorous-predatory nematodes rises. Among treatments varying in alfalfa planting durations, the 9-year treatment exhibited the most incredible energy conversion and utilization efficiency within the soil food web, demonstrating the most stable structure. This study reveals optimal alfalfa planting duration for soil ecosystem stability in the Loess Plateau. Future research should explore sustainable crop rotations and alfalfa–soil–climate interactions for improved agricultural management. Full article

Recent studies have identified a urinary microbiome, dispelling the myth of urine sterility. Intravesical bacillus Calmette–Guérin (BCG) therapy is the preferred treatment for intermediate to high-risk non-muscle-invasive bladder cancer (BCa), although resistance occurs in 30–50% of cases. Progression to muscle-invasive cancer necessitates radical cystectomy. Our research uses 16S rRNA gene sequencing to investigate how the urinary microbiome influences BCa and its response to BCG therapy. Urine samples were collected via urethral catheterization from patients with benign conditions and non-muscle-invasive BCa, all of whom underwent BCG therapy. We utilized 16S rRNA gene sequencing to analyze the bacterial profiles and metabolic pathways in these samples. These pathways were validated using a real metabolite dataset, and we developed predictive models for malignancy and BCG response. In this study, 87 patients participated, including 29 with benign diseases and 58 with BCa. We noted distinct bacterial compositions between benign and malignant samples, indicating the potential role of the toluene degradation pathway in mitigating BCa development. Responders to BCG had differing microbial compositions and higher quinolone synthesis than non-responders, with two Bifidobacterium species being prevalent among responders, associated with prolonged recurrence-free survival. Additionally, we developed highly accurate predictive models for malignancy and BCG response. Our study delved into the mechanisms behind malignancy and BCG responses by focusing on the urinary microbiome and metabolic pathways. We pinpointed specific beneficial microbes and developed clinical models to predict malignancy and BCG therapy outcomes. These models can track recurrence and facilitate early predictions of treatment responses. Full article

Flours rich in resistant starch (RS) are crucial for producing low glycemic index foods, as per Commission Regulation (EU) No. 432/2012. This study assessed the environmental profiles of two high-RS fresh pasta variants: one from malted and decorticated Gradoli Purgatory beans, and another from amylose-rich soft wheat flour, using the Product Environmental Footprint standard method. Both pastas had similar carbon footprints, but the overall weighted score of malted bean pasta was 38% higher than that of the high-amylose wheat pasta, making the latter more economically and environmentally viable. Climate change and water use were major contributors to their environmental footprints, influenced by cultivation practices. Mitigation strategies, such as cultivating drought-resistant beans, are recommended. Although greenhouse gas emissions per gram of protein or RS were similar, overall scores varied, emphasizing the need for sustainable crop selection. Consumer preferences may favor high-amylose wheat for glucose metabolism, while gluten-free, protein-rich needs can be met with malted bean flour, despite its higher environmental impact. Full article