Adepu Kiran Kumar

The transformation of biorenewable feedstocks into biocomposites for sound‐insulating applications is a promising alternative to the use of fossil‐derived noise control materials. It is also an innovative strategy for waste‐to‐wealth technologies within the circular economy framework. This study examined the feasibility and techno‐economics of rice straw (RS)‐derived biocomposites for sound‐insulating applications. Bio‐based binders – Protobind‐1000 lignin (PBL) and guar gum (GG) – were used in varying concentrations to develop six biocomposites: RS 0 (100% RS), RS A (50% RS, 25% PBL, 25% GG), RS B (50% RS, 37.5% PBL, 12.5% GG), RS C (50% RS, 12.5% PBL, 37.5% GG), RS D (50% RS, 50% PBL, 0% GG), and RS E (50% RS, 0% PBL, 50% GG). These were evaluated for functional, microstructural, thermal, flammability, mechanical, biodegradability, physical, and acoustic properties. Average sound transmission loss ranged from 28 to 30 dB, and thermal conductivity ranged from 0.255 to 0.315 W m ⁻¹ K ⁻¹ (25–75 °C). Flammability tests confirmed that all samples met horizontal test criteria and achieved V‐0 to V‐2 ratings under vertical conditions. The RS B biocomposite demonstrated the highest mechanical performance, achieving a tensile strength of 13.76 MPa and a flexural strength of 1.30 MPa. Soil burial tests confirmed the biodegradability of all biocomposites, with visible surface cracking and up to 25% weight loss after 85 days. The techno‐economic analysis indicated that repurposing the existing plant for biocomposite production was more financially advantageous than building a new plant. The repurposed plant was projected to generate a net present value of $2.91 million and recoup its initial investment in 3.25 years, outperforming the new plant’s estimated $1.64 million net present value and 5 year payback period.

A canonical view of the primary physiological function of myoglobin (Mb) is that it is an oxygen (O₂) storage protein supporting mitochondrial oxidative phosphorylation, especially as the tissue O₂ partial pressure (Po₂) drops and Mb off-loads O₂. Besides O₂ storage/transport, recent findings support functions for Mb in lipid trafficking and sequestration, interacting with cellular glycolytic metabolites such as lactate (LAC) and pyruvate (PYR), and “ectopic” expression in some types of cancer cells and in brown adipose tissue (BAT). Data from Mb knockout (Mb^−/−) mice and biochemical models suggest additional metabolic roles for Mb, especially regulation of nitric oxide (NO) pools, modulation of BAT bioenergetics, thermogenesis, and lipid storage phenotypes. From these and other findings in the literature over many decades, Mb’s function is not confined to delivering O₂ in support of oxidative phosphorylation but may serve as an O₂ sensor that modulates intracellular Po₂- and NO-responsive molecular signaling pathways. This paradigm reflects a fundamental change in how oxidative metabolism and cell regulation are viewed in Mb-expressing cells such as skeletal muscle, heart, brown adipocytes, and select cancer cells. Here, we review historic and emerging views related to the physiological roles for Mb and present working models illustrating the possible importance of interactions between Mb, gases, and small-molecule metabolites in regulation of cell signaling and bioenergetics.

Metabolomics, the study of small-molecule metabolites within biological systems, has become a potent instrument for understanding cellular processes. Despite its profound insights into health, disease, and drug development, identifying the protein partners for metabolites, especially dietary phytochemicals, remains challenging. In the present study, we introduced an innovative in silico, structure-based target prediction approach to efficiently predict protein targets for metabolites. We analyzed 27 blood serum metabolites from nutrition intervention studies’ blueberry-rich diets, known for their health benefits, yet with elusive mechanisms of action. Our findings reveal that blueberry-derived metabolites predominantly interact with Carbonic Anhydrase (CA) family proteins, which are crucial in acid-base regulation, respiration, fluid balance, bone metabolism, neurotransmission, and specific aspects of cellular metabolism. Molecular docking showed that these metabolites bind to a common pocket on CA proteins, with binding energies ranging from −5.0 kcal/mol to −9.0 kcal/mol. Further molecular dynamics (MD) simulations confirmed the stable binding of metabolites near the Zn binding site, consistent with known compound interactions. These results highlight the potential health benefits of blueberry metabolites through interaction with CA proteins.

Myoglobin (Mb) interaction with the outer mitochondrial membrane (OMM) promotes oxygen (O₂) release. However, comprehensive molecular details on specific contact regions of the OMM with oxygenated (oxy-) and deoxygenated (deoxy-)Mb are missing. We used molecular dynamics (MD) simulations to explore the interaction of oxy- and deoxy-Mb with the membrane lipids of the OMM in two lipid compositions: (a) a typical whole membrane on average, and (b) specifically the cardiolipin-enriched cristae region (contact site). Unrestrained relaxations showed that on average, both the oxy- and deoxy-Mb established more stable contacts with the lipids typical of the cristae contact site, then with those of the average OMM. However, in steered detachment simulations, deoxy-Mb clung more tightly to the average OMM, and oxy-Mb strongly preferred the contact sites of the OMM. The MD simulation analysis further indicated that a non-specific binding, mediated by local electrostatic interactions, existed between charged or polar groups of Mb and the membrane, for stable interaction. To the best of our knowledge, this is the first computational study providing the molecular details of the direct Mb–mitochondria interaction that assisted in distinguishing the preferred localization of oxy- and deoxy-Mb on the OMM. Our findings support the existing experimental evidence on Mb–mitochondrial association and shed more insights on Mb-mediated O₂ transport for cellular bioenergetics.

Previous research has indicated that various metabolites belonging to phenolic acids (PAs), produced by gut microflora through the breakdown of polyphenols, help in promoting bone development and protecting bone from degeneration. Results have also suggested that G-protein-coupled receptor 109A (GPR109A) functions as a receptor for those specific PAs such as hippuric acid (HA) and 3-(3-hydroxyphenyl) propionic acid (3-3-PPA). Indeed, HA has a molecular structural similarity with nicotinic acid (niacin) which has been shown previously to bind to GPR109A receptor and to mediate antilipolytic effects; however, the binding pocket and the structural nature of the interaction remain to be recognized. In the present study, we employed a computational strategy to elucidate the molecular structural determinants of HA binding to GPR109A and GPR109B homology models in understanding the regulation of osteoclastogenesis. Based on the docking and molecular dynamics simulation studies, HA binds to GPR109A similarly to niacin. Specifically, the transmembrane helices 3, 4 and 6 (TMH3, TMH4 and TMH6) and Extracellular loop 1 and 2 (ECL1 and ECL2) residues of GRP109A; R111 (TMH3), K166 (TMH4), ECL2 residues; S178 and S179, and R251 (TMH6), and residues of GPR109B; Y87, Y86, S91 (ECL1) and C177 (ECL2) contribute for HA binding. Simulations and Molecular Mechanics Poisson-Boltzmann solvent accessible area (MM-PBSA) calculations reveal that HA has higher affinity for GPR109A than for GPR109B. Additionally, in silico mutation analysis of key residues have disrupted the binding and HA exited out from the GPR109A protein. Furthermore, measurements of time-resolved circular dichroism spectra revealed that there are no major conformational changes in the protein secondary structure on HA binding. Taken together, our findings suggest a mechanism of interaction of HA with both GPR109A and GPR109B receptors.

Myoglobin (Mb), besides its roles as an oxygen (O₂) carrier/storage protein and nitric oxide NO scavenger/producer, may participate in lipid trafficking and metabolite binding. Our recent findings have shown that O₂ is released from oxy-Mb upon interaction with lactate (LAC, anerobic glycolysis end-product). Since pyruvate (PYR) is structurally similar and metabolically related to LAC, we investigated the effects of PYR (aerobic glycolysis end-product) on Mb using isothermal titration calorimetry, circular dichroism, and O₂-kinetic studies to evaluate PYR affinity toward Mb and to compare the effects of PYR and LAC on O₂ release kinetics of oxy-Mb. Similar to LAC, PYR interacts with both oxy- and deoxy-Mb with a 1:1 stoichiometry. Time-resolved circular dichroism spectra revealed that there are no major conformational changes in the secondary structures of oxy- or deoxy-Mb during interactions with PYR or LAC. However, we found contrasting results with respect to binding affinities and substrate preference, where PYR has higher affinity toward deoxy-Mb when compared with LAC (which prefers oxy-Mb). Furthermore, PYR interaction with oxy-Mb releases a significantly lower amount of O₂ than LAC. Taken together, our findings support the hypothesis that glycolytic end-products play a distinctive role in the Mb-rich tissues by serving as novel regulators of O₂ availability, and/or by impacting other activities related to oxy-/deoxy-Mb toggling in resting vs. exercised or metabolically activated conditions.

Myoglobin (Mb)-mediated oxygen (O₂) delivery and dissolved O₂ in the cytosol are two major sources that support oxidative phosphorylation. During intense exercise, lactate (LAC) production is elevated in skeletal muscles as a consequence of insufficient intracellular O₂ supply. The latter results in diminished mitochondrial oxidative metabolism and an increased reliance on nonoxidative pathways to generate ATP. Whether or not metabolites from these pathways impact Mb-O₂ associations remains to be established. In the present study, we employed isothermal titration calorimetry, O₂ kinetic studies, and UV-Vis spectroscopy to evaluate the LAC affinity toward Mb (oxy- and deoxy-Mb) and the effect of LAC on O₂ release from oxy-Mb in varying pH conditions (pH 6.0–7.0). Our results show that LAC avidly binds to both oxy- and deoxy-Mb (only at acidic pH for the latter). Similarly, in the presence of LAC, increased release of O₂ from oxy-Mb was detected. This suggests that with LAC binding to Mb, the structural conformation of the protein (near the heme center) might be altered, which concomitantly triggers the release of O₂. Taken together, these novel findings support a mechanism where LAC acts as a regulator of O₂ management in Mb-rich tissues and/or influences the putative signaling roles for oxy- and deoxy-Mb, especially under conditions of LAC accumulation and lactic acidosis.

This paper presents a comprehensive techno‐economic evaluation of an integrated natural deep eutectic solvent (NADES)‐based biorefinery – a 1 ton day⁻¹ capacity design plant. The key parameters include payback period, net present value (NPV), and internal rate of return (IRR). These were compared with the parameters of conventional biorefineries. The ‘nth plant’ results clearly revealed that the single product‐based biorefinery is not a sustainable approach. Hence, value‐added products viz., cellulose, lignin, xylan, silica, etc., play a vital role in the cost‐effectiveness of bio‐based biorefineries. Based on ‘base‐case’ experimental results, a pilot‐scale plant design scenario is most feasible, with a NPV of 1.4 million USD, >100% IRR, and a payback period of <2 years. Sensitivity analysis revealed that lignin has the greatest impact on revenue. This report proves that multi‐product biorefineries provide better sustainability. The concepts of solvent recycling and reuse, and key challenges to the commercialization of this design approach, were also discussed. The application of NADES in biorefineries, has several advantages, making the implementation of NADES a key feature for increased sustainability in this industry. © 2020 Society of Chemical Industry and John Wiley & Sons, Ltd