Review
Food Science & Technology
He Liu, Jiaxin Xu, Xinyue Xu, Zhiheng Yuan, Hong Song, Lina Yang, Danshi Zhu
Summary: This review provides a foundation for future research and development of bean polysaccharides. It summarizes the sources, structure, and functions of bioactive bean polysaccharides, focusing on their role in immunology, antioxidant, and anti-diabetic activities. The article offers useful guidance for optimizing polysaccharide structure and developing bean polysaccharides as novel functional materials.
CRITICAL REVIEWS IN FOOD SCIENCE AND NUTRITION
(2023)
Article
Energy & Fuels
Zi-Zhen Wang, Gautier Njiekak, Douglas R. Schmitt, Rui-He Wang
Summary: Laboratory tests were conducted to analyze the ultrasonic velocity response to pressure changes in dry carbonate rocks from the Weyburn oilfield in Canada. Results showed that P- and S-wave velocities in these samples follow a linear relation regardless of pressure changes, with the Vp/Vs ratio being more sensitive to pressure changes. The pressure dependence of velocities (PDV) of Weyburn carbonate rocks varied widely, even for samples from the same formation, and an empirical model for elastic wave velocity was found to fit well for most samples.
Article
Energy & Fuels
Jiabin Huang, Xiaoqing Wu, Qifeng Hou, Mengqi Wu, Jiuzhong Yang, Feng Zhang
Summary: This study measured the PICS of various benzene compounds with different substituents using PIMS, revealing that nitrogen-containing substituents enhance the plateau characteristics of PICS. Molecular orbital analysis elucidates the origin of PICS characteristics of monocyclic substituted aromatic compounds.
Article
Chemistry, Physical
Michael H. Palmer, Marcello Coreno, Monica de Simone, Cesare Grazioli, Nykola C. Jones, Soren Vronning Hoffmann, R. Alan Aitken
Summary: This study presents a synchrotron-based photoionization spectrum of azulene, revealing significant vibrational fine structure compared to previous studies, which was successfully analyzed using Franck-Condon methods. New sequence for ionic states and reliable theoretical values for calculated adiabatic ionization energy and vertical ionization energy were determined through ab initio configuration interaction methods. Various ionization states and electronic excitation involving methods were considered by different computational techniques.
JOURNAL OF CHEMICAL PHYSICS
(2022)
Article
Pharmacology & Pharmacy
Yu Zou, Quan Zhou, Yinan Zhao, Defu Zhi, Huiying Chen, Rui Wang, Benzhi Ju, Shubiao Zhang
Summary: Ionizable lipids, such as the optimized lipid EDM, show efficient gene delivery and gene silencing in A549 cells. EDM is capable of escaping the endosome quickly and releasing the gene in the cytoplasm.
INTERNATIONAL JOURNAL OF PHARMACEUTICS
(2022)
Review
Chemistry, Multidisciplinary
Jia Tan, Binbin Ding, Bo Teng, Ping'an Ma, Jun Lin
Summary: This article reviews nanoadjuvants and their structure-function relationships, as well as their applications in cancer therapy. The article first introduces different types of adjuvants and then discusses their mechanisms. It summarizes the methods for evaluating immune effects of adjuvants. The authors particularly focus on the structure-function relationships of nanoadjuvants and explore their impact on immune activities. Finally, the safety of adjuvants is discussed, and representative advancements of nanoadjuvants in tumor immunotherapy and other therapies are presented.
ADVANCED FUNCTIONAL MATERIALS
(2022)
Article
Biochemistry & Molecular Biology
Luciana Esposito, Nicole Balasco, Giovanni Smaldone, Rita Berisio, Alessia Ruggiero, Luigi Vitagliano
Summary: One of the key features of KCTD proteins is their involvement in various physiological and pathological processes. Despite the lack of structural data, the use of predicted three-dimensional models by AlphaFold has enabled researchers to gain insights into the relationships within the KCTD family. A novel pseudo-phylogenetic tree based on a common structurally similar domain in the C-terminal region has revealed previously undetected similarities among the KCTD proteins, providing a solid foundation for understanding their diverse functions.
Article
Chemistry, Analytical
Hideto Moriyama, Genki Ogata, Haruma Nashimoto, Seishiro Sawamura, Yoshiaki Furukawa, Hiroshi Hibino, Hiroyuki Kusuhara, Yasuaki Einaga
Summary: Monitoring drug concentration in blood is crucial for safe and effective drug treatment. This study introduces a rapid electrochemical method using boron-doped diamond electrodes to determine the unbound drug concentration in human serum. The results show that this method can provide fast and reliable measurement within the clinical concentration range.
Review
Physiology
Erika Moreno, Diana Pacheco-Alvarez, Maria Chavez-Canales, Stephanie Elizalde, Karla Leyva-Rios, Gerardo Gamba
Summary: The thiazide sensitive Na+:Cl- cotransporter (NCC) is crucial for salt reabsorption and blood pressure regulation. It has been extensively studied, with its structure, function, and kinetics elucidated. Cryo-EM has provided high-resolution structures, confirming essential glycosylation sites and the inverted conformation of specific regions. This review provides an overview of the research on the structure-function relationship of NCC, from the early biochemical studies to the recent cryo-EM structures.
FRONTIERS IN PHYSIOLOGY
(2023)
Review
Engineering, Multidisciplinary
Jiaming Zhong, Wei Huang, Huamin Zhou
Summary: Modern material design aims to achieve multifunctionality through integrating structures in a diverse range, resulting in simple materials with embedded functions. This review highlights the multiscale structural and functional integration of representative natural organisms and materials, as well as biomimetic examples. The integration of structure and function is crucial for driving innovations and breakthroughs in modern engineering materials and their applications.
Article
Chemistry, Physical
Abhinav S. Raman, Annabella Selloni
Summary: This study investigates the hydration structure, proton transfer mechanisms, and acid-base properties of the rutile IrO2(110)-water interface using ab initio based deep neural-network potentials and enhanced sampling simulations. The proton affinities of different surface sites are characterized, and a point of zero charge is obtained. Results show a large fraction of adsorbed water dissociation and a short lifetime of resulting hydroxy groups due to rapid surface proton exchanges, supporting recent experimental findings that the rate-determining step in the oxygen evolution reaction may not involve proton transfer into solution.
JOURNAL OF PHYSICAL CHEMISTRY LETTERS
(2023)
Article
Chemistry, Multidisciplinary
Lukasz Kielesinski, Francesco F. Summa, Jeanet Conradie, Hilah C. Honig, Ariel Friedman, Gugliemo Monaco, Lior Elbaz, Abhik Ghosh, Daniel T. Gryko
Summary: The new naphthocorrole ligands combine the cavity size of corroles and the dianionic character of porphyrins. They possess nonaromatic properties but exhibit optical spectra similar to porphyrins, and can be easily synthesized using a simple protocol.
CHEMICAL COMMUNICATIONS
(2023)
Review
Developmental Biology
Sameed Khan, Sarah Fitch, Sarah Knox, Ripla Arora
Summary: Fluid secretion is crucial for the survival of mammals, and each glandular unit has its own unique structure and function. This article reviews the structural characteristics of glandular organs, discusses the impact of developmental defects on secretory function, and explores how knowledge of structure-function relationships can be applied to diagnostics, regenerative approaches, and tissue regeneration.
Article
Chemistry, Medicinal
Shuhua Ma, Jack A. Henderson, Jana Shen
Summary: Continuous constant pH molecular dynamics (CpHMD) simulations were used to investigate the acid/base roles of renin's catalytic dyad and the conformational dynamics of the flap. The calculated pK(4)'s indicate that catalytic Asp38 and Asp226 serve as general base and acid, supporting the hypothesis that renin's neutral optimum pH is due to the substrate-induced pK(4) shifts of the aspartic dyad. Additionally, hydrogen bond formation is identified as the major determinant of the dyad pK(4) order in these simulations.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2021)
Article
Green & Sustainable Science & Technology
Yu Fu, Lingli Wang, Yunjiao Liu, Meiru Hou, Qingchao Li, Xiaodie Li, Dagang Lin, Jialin Chen, Zhaohui Wang, Bing Xie
Summary: The use of waste biomass for the adsorption of toxic Cr(VI) is an eco-friendly technology to remediate chromium-polluted water. However, the role of dissolved organic matter (DOM) released from the waste biomass is often overlooked in Cr(VI) depletion. This study investigated the utilization of plant leaves (PLs) as a resource for Cr(VI) reduction. The experiments showed that freezing enhanced the Cr(VI) reduction with PLs, and the main components responsible for the reduction were identified as D(-)-quinic acid and lignin/carboxyl-rich acyclic molecules (CRAM).
JOURNAL OF CLEANER PRODUCTION
(2023)
Review
Biochemistry & Molecular Biology
Elena Rosini, Loredano Pollegioni
Summary: Oxidases, specifically FAD-containing enzymes such as glucose oxidase, have shown promise in cancer therapy by producing reactive oxygen species in tumors and potentially modulating cytotoxic compound production. Advances in nanotechnologies and protein engineering have improved tumor specificity, making oxidase-based ROS production a mature and applicable approach in clinical settings.
Article
Biochemistry & Molecular Biology
Elena Rosini, Loredano Pollegioni
Summary: This article presents an optimized workflow for the expression and purification of various human proteins using Chinese Hamster Ovary cells (CHO). The workflow allows for high yield and high quality protein production, and can be completed within 2 weeks. The platform has also been successfully adapted for the production of the receptor-binding domain (RBD) in the SARS-CoV-2 S protein, which is crucial for COVID-19 research.
BIOTECHNOLOGY AND APPLIED BIOCHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Valentina Pirillo, Marco Orlando, Caren Battaglia, Loredano Pollegioni, Gianluca Molla
Summary: Improved variants of PET-hydrolysing enzymes were generated by protein engineering. The F243T variant partially depolymerized PET film, while the S101N/F243T double variant showed higher activity. The highest conversion yield for both variants was obtained at 55°C. The S101N/F243T variant is capable of fully depolymerizing untreated postconsumer PET waste within 3 days at 55°C, making it a more ecofriendly and sustainable process.
Article
Chemistry, Multidisciplinary
Filippo Molinari, Loredano Pollegioni, Elena Rosini
Summary: In this study, an efficient and green process was developed to produce valuable compounds from renewable feedstocks through extraction optimization and genetic engineering of E. coli strain. The optimized whole-cell system demonstrated a sustainable and cost-competitive approach for producing high value-added products from renewable resources.
ACS SUSTAINABLE CHEMISTRY & ENGINEERING
(2023)
Article
Biochemistry & Molecular Biology
Valentina Rabattoni, Francesco Marchesani, Giulia Murtas, Silvia Sacchi, Andrea Mozzarelli, Stefano Bruno, Alessio Peracchi, Loredano Pollegioni, Barbara Campanini
Summary: De novo L-serine biosynthesis in mammalian astrocytes involves a linear, three-step pathway that is catalyzed by PHGDH, PSAT, and PSP. The formation of a complex between these enzymes has been observed in human astrocytes and in in vitro experiments.
Review
Biochemistry & Molecular Biology
Marco Orlando, Gianluca Molla, Pietro Castellani, Valentina Pirillo, Vincenzo Torretta, Navarro Ferronato
Summary: The accumulation of synthetic plastic waste in the environment has raised global concerns. Microbial enzymes offer promising biotechnological tools for plastic recycling, but their effectiveness depends on waste management practices. This review highlights the potential of biotechnology in plastic bio-recycling within the European waste management framework. Current biotechnology tools can support polyethylene terephthalate (PET) recycling, but other unrecycled plastics, such as polyurethanes and polyolefins, require further research and optimization of chemoenzymatic technologies. New bio-based technologies with lower environmental impacts should also be developed to efficiently depolymerize both existing and new plastic materials.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Biochemistry & Molecular Biology
Giulia Murtas, Loredano Pollegioni
Summary: D-amino acids have been found to play important roles in specific cancer types, including cancer cell proliferation, cell protection during therapy, and as potential biomarkers. More research is needed on the relationship between D-amino acids, their nutritional value, and cancer cell proliferation and survival.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Correction
Chemistry, Multidisciplinary
Filippo Molinari, Loredano Pollegioni, Elena Rosini
ACS SUSTAINABLE CHEMISTRY & ENGINEERING
(2023)
Review
Multidisciplinary Sciences
Elena Rosini, Loredano Pollegioni, Gianluca Molla
Summary: In this review, the enantiospecific interaction between proteins and chiral amino acids is explored. The molecular basis of the ability of certain enzymes to discriminate opposite enantiomers is described. The analysis showcases the importance of natural evolution in shaping biological processes.
Review
Chemistry, Physical
Elena Rosini, Filippo Molinari, Davide Miani, Loredano Pollegioni
Summary: Lignin, the second most abundant polymer in nature, has the potential to be a valuable feedstock for the production of value-added chemicals, rather than simply being burnt for energy supply. Recent advancements in systems metabolic engineering have allowed for the design of microbial cell factories that efficiently degrade lignin and transform its products into useful compounds. This review focuses on successful case studies, conducted at the laboratory/pilot scale, that demonstrate the generation of value-added and specialty chemicals, with a particular emphasis on the production of cis,cis-muconic acid, an important building block for plastic materials synthesis. The transformation of this waste stream into a sustainable product portfolio awaits the resolution of economic challenges related to process scale-up.
Article
Biotechnology & Applied Microbiology
Elena Rosini, Marta Boreggio, Matteo Verga, Laura Caldinelli, Loredano Pollegioni, Elisa Fasoli
Summary: The study explores a new cancer treatment strategy by using an external enzyme to convert prodrugs into active anticancer compounds directly in tumor sites. It is found that a D-amino acid oxidase variant with five aminoacidic substitutions (mDAAO) has better therapeutic efficacy than the wild-type DAAO (wtDAAO) in catalyzing the oxidative deamination of D-amino acids. Functionalized multi-walled carbon nanotubes (MWCNTs) with polyethylene glycol (PEG) enhance the activity and cytotoxicity of DAAO, with mDAAO showing higher cytotoxicity at low O-2 concentration.
Article
Pharmacology & Pharmacy
Sara Tengattini, Davide Rubes, Massimo Serra, Luciano Piubelli, Loredano Pollegioni, Enrica Calleri, Teodora Bavaro, Gabriella Massolini, Marco Terreni, Caterina Temporini
Summary: Conjugation via disuccinimidyl homobifunctional linkers is a convenient approach for the synthesis of glycoconjugate vaccines. However, the hydrolysis of these linkers makes their purification challenging, resulting in side reactions and impure glycoconjugates. In this study, the conjugation of 3-aminopropyl saccharides via disuccinimidyl glutarate (DSG) was utilized to synthesize glycoconjugates. Through optimization of purification protocols and conjugation conditions, high sugar-loaded and pure glycoconjugates were obtained, making this approach valuable for the production of well-defined glycovaccines.
Article
Biochemistry & Molecular Biology
Francesco Marchesani, Annalisa Michielon, Elisabetta Viale, Annalisa Bianchera, Davide Cavazzini, Loredano Pollegioni, Giulia Murtas, Andrea Mozzarelli, Stefano Bettati, Alessio Peracchi, Barbara Campanini, Stefano Bruno
Summary: The phosphorylated pathway (PP) in humans converts D-3-phosphoglycerate (3-PG) into L-serine through several enzymes. Genetic defects of these enzymes are associated with serine deficiency disorders (SDDs). This study characterizes different PSAT variants associated with SDDs and non-SDDs and shows that the pathogenetic mechanisms in SDDs are diverse. These findings confirm the importance of PSAT dysfunctions as a cause of SSDs.
Article
Biochemistry & Molecular Biology
Siva Santhiya Arul, Brinda Balakrishnan, Savithri S. Handanahal, Sangita Venkataraman
Summary: Viral nanoparticles are self-assembling delivery systems used for vaccines and therapeutic agents. They have improved biocompatibility and are widely used in various biomedical applications. However, large-scale production of VNPs still faces challenges.
Article
Biochemistry & Molecular Biology
Wisely Chua, Carl O. Marsh, Si En Poh, Winston LC. Koh, Melody Li Ying Lee, Li Fang Koh, Xin-Zi Emily Tang, Peter See, Zheng Ser, Shi Mei Wang, Radoslaw M. Sobota, Thomas L. Dawson Jr, Yik Weng Yew, Steven Thng, Anthony J. O'Donoghue, Hazel H. Oon, John E. Common, Hao Li
Summary: In this study, the gene expression of enzymes secreted by Malassezia globosa in the skin was investigated using targeted RNA sequencing. The study found that the expression of these enzymes is regulated by the fungus's environment and differs significantly from healthy skin sites. Additionally, a pseudoprotease MGL_3331 was identified to elicit an immune reaction in patients with atopic dermatitis. This highlights the importance of studying fungal proteins in physiologically relevant environments and their role in host immunity.
Article
Biochemistry & Molecular Biology
Belisa Parmeggiani, Marian Flores Signori, Cristiane Cecatto, Marina Rocha Frusciante, Manuela Bianchin Marcuzzo, Debora Guerini Souza, Rafael Teixeira Ribeiro, Bianca Seminotti, Diogo Onofre Gomes de Souza, Cesar Augusto Joa o Ribeiro, Moacir Wajner, Guilhian Leipnitz
Summary: Non ketotic hyperglycinemia (NKH) is a disorder caused by mutations in the genes encoding glycine cleavage system proteins, leading to severe neurodegeneration and white matter alterations. The study found that glycine affects myelin structure, glutamatergic system, and induces oxidative stress in neonatal rats and MO3.13 oligodendroglial cells.
Review
Biochemistry & Molecular Biology
Marie Rose Ndella Thiaw, Pascal Gantet
Summary: Mini zinc fingers play important roles in plant development, including control of cell division and expansion, meristem state transition, and growth and organ development. They have diverse modes of action, such as direct gene activation, interaction with specific transcription factors, and aggregation of protein complexes for chromatin remodeling. Further research is needed to explore their wider range of biological functions and their involvement in biotic and abiotic stress responses.
Article
Biochemistry & Molecular Biology
Shao-Jui Lai, Takahiro Kameda, Maasa Morita, Yuka Yamagata, Kaoruko Nishizaka, Yuna Horiuchi, Yukihiro Kobayashi, Yoko Usami, Jun-Jen Liu, Takeshi Kasama, Minoru Tozuka, Ryunosuke Ohkawa
Summary: In this study, the co-modification and impact of chymase and MPO on HDL were investigated. Sequential treatment with MPO and chymase generated two novel apoA-I fragments from HDL, one of which has a specific immunological property and can be used to predict patients with normal HDL-C levels and cardiovascular diseases.
Article
Biochemistry & Molecular Biology
Xiao-Mi Sun, Asami Yoshida, Takuya Ishii, Yan-Rong Jiang, Yi-Li Gao, Mikinori Ueno, Katsuya Hirasaka, Kiyoshi Osatomi
Summary: This study found that infection with the causative bacteria of edwardsiellosis, Edwardsiella tarda NUF251, leads to the production of superoxide radicals, causing oxidative stress. The research on the Jfsod1 gene suggests that the transcription factor NF-IL6 plays a significant role in upregulating the transcriptional activity of the gene in response to oxidative stress induced by NUF251 infection.
Article
Biochemistry & Molecular Biology
Shane M. Carey, Sean P. Kearns, Matthew E. Millington, Gregory S. Buechner, Beda E. Alvarez Jr, Leily Daneshian, Brendan Abiskaroon, Maksymilian Chruszcz, Edward L. D'Antonio
Summary: The importance of F337 in TcGlcK was investigated using the hole mutagenesis approach, revealing its key interactions with aromatic tail groups in inhibitor molecules. Mutants retaining activity and structural similarity were obtained, suggesting the possibility of TcHxK existing as a monomer lacking the F337 residue. Similar D-glucosamine inhibitors may bind less strongly to TcHxK due to the absence of van der Waals contacts from residue side chains.
Article
Biochemistry & Molecular Biology
Catia Barria, Diogo Athayde, Guillem Hernandez, Leonor Fonseca, Jorge Casinhas, Tiago N. Cordeiro, Margarida Archer, Cecilia M. Arraiano, Jose A. Brito, Rute G. Matos
Summary: Ribonucleases play a crucial role in RNA regulation by processing, degrading, and quality controlling cellular transcripts. Campylobacter jejuni, the main cause of human gastroenteritis, relies on the exoribonuclease PNPase (CjPNP) for low-temperature survival, virulence factor synthesis, and swimming, cell adhesion/invasion, and chick colonization abilities. The crystallographic structure of CjPNP, along with SAXS analysis, confirms its trimeric arrangement and provides insight into domain arrangement and flexibility. Mutations in highly conserved residues reveal unexpected RNA degradation activity even under conditions favoring polymerization. These findings have significant implications for the development of strategies to combat C. jejuni infections.
Article
Biochemistry & Molecular Biology
Elvira R. Shaykhutdinova, Maria S. Severyukhina, Inna V. Kholoshenko, Elena A. Gondarenko, Irina V. Shelukhina, Elena V. Kryukova, Alina M. Ismailova, Elena S. Sadovnikova, Igor A. Dyachenko, Arkady N. Murashev, Victor I. Tsetlin, Yuri N. Utkin
Summary: Evidence suggests that activating nicotinic acetylcholine receptors (nAChRs) can reduce cardiac injury caused by ischemia and reperfusion. In this study, the expression of a4, a6, and a132 nAChR subunits in the rat heart's left ventricle was demonstrated. The nAChR agonists cytisine and varenicline, commonly used for nicotine addiction treatment, were found to significantly reduce myocardial ischemia-reperfusion injury, with varenicline showing greater protection. The presence of a4132, a7, and/or a6132-containing receptors suggests that the protective effect of varenicline may be mediated by these subunits. These findings indicate a potential new use for cytisine and varenicline as cardioprotective agents.
Article
Biochemistry & Molecular Biology
Xinhai Xiong, Wenjie Chen, Cheng Chen, Qi Wu, Chaopeng He
Summary: This article summarizes the important roles of Cx43 in disease development from the perspective of subcellular localization and provides new ideas for Cx43 as a therapeutic target and the search for related pathological mechanisms.
Article
Biochemistry & Molecular Biology
Veronica Bastos, Simone Pascoal, Kamila Lopes, Marcia Mortari, Helena Oliveira
Summary: Cancer, especially melanoma, is a major global health problem due to its metastatic capacity, treatment resistance, and high mortality rates. The Chartergellus-CP1 peptide isolated from Chartergellus communis wasp venom showed selective cytotoxicity towards melanoma cell lines, inducing apoptosis, cell cycle impairment, and intracellular ROS increase.
Article
Biochemistry & Molecular Biology
Charlotte Claeyssen, Nathan Bulangalire, Bruno Bastide, Onnik Agbulut, Caroline Cieniewski-Bernard
Summary: Maintenance of striated muscle tissue relies on a dynamic network of protein-protein interactions. Desmin intermediate filaments play a crucial role in heart and skeletal muscle by maintaining cell structure and contributing to various cellular processes. The assembly of desmin intermediate filaments requires aB-crystallin, which is involved in multiple cellular functions.
Article
Biochemistry & Molecular Biology
Dhritiman Dey, Adhiraj Dasgupta, Dipanjan Ghosh, Oindrila Bhattacharjee, Abhrajyoti Ghosh, Ayae Honda, Dhrubajyoti Chattopadhyay
Summary: This study successfully identified host factors that interact with Chandipura Virus (CHPV) and play a critical role in infection, including A2M, LRP1, and GRP78. Knocking out A2M has a severe effect on viral infection, indicating the potential role of these host proteins in viral entry into host cells.
Article
Biochemistry & Molecular Biology
Anna Dotsenko, Igor Sinelnikov, Aleksandra Rozhkova, Ivan Zorov, Arkady Sinitsyn
Summary: Xylanases play important roles in various industrial applications, such as feed additives, pulp and paper bleaching, and the production of bread, food, and drinks. Xylanases from the GH10 family show high thermostability and resistance to protein inhibitors, making them promising candidates for these processes. This study successfully improved the thermostability and enzymatic activity of GH10 xylanase, which could enhance its effectiveness as a feed additive and during pulp and paper bleaching.
Article
Biochemistry & Molecular Biology
M. Jaquet, M. Bengue, K. Lambert, G. Carnac, D. Misse, C. Bisbal
Summary: Changes to our environment have led to the emergence of human pathogens such as chikungunya virus, which is now a major public health concern. In this study, the interconnection between skeletal muscle cells metabolism, their differentiation stage, and the infectivity of chikungunya virus was investigated. The results showed that chikungunya virus infectivity is dependent on cell differentiation and metabolism and that the virus interferes with cellular metabolism.