Biomedical subjects

Ye Gao

Publications and source records attributed to Ye Gao.

9 recordsLinked to original sources

PubMed2026

Decoding SUMOylation as a metabolic stress sensor in aging and age-related disorders: Mechanisms, tissue specificity and therapeutic potential.

SUMOylation is a reversible post-translational modification increasingly recognized for its role in coordinating cellular responses to metabolic stress during aging. Emerging evidence indicates that it functions beyond a conventional modification, representing an adaptive stress‑responsive regulatory network that integrates metabolic, oxidative, inflammatory, and proteotoxic signals. Rather than acting on isolated pathways, this network finely tunes mitochondrial function, proteostasis, genome maintenance, immune balance, and epigenetic regulation. Accumulating evidence indicates that SUMO-dependent regulation exhibits remarkable tissue specificity, supporting mitochondrial adaptation and contractile integrity in skeletal muscle, shaping lipid and glucose metabolism in the liver, modulating proteotoxic stress and neuronal resilience in the brain, and contributing to immune cell differentiation and chronic low-grade inflammation during aging. In this review, we summarize current mechanistic insights into SUMO signaling across aging-relevant tissues, with particular emphasis on its functional interplay with other post-translational modifications, including ubiquitination and acetylation. We discuss how SUMOylation operates as a shared regulatory layer while enabling context-dependent outcomes that underlie diverse aging phenotypes and age-related disorders. Finally, we evaluate emerging translational approaches-ranging from pharmacological modulation of SUMO enzymes to lifestyle interventions such as caloric restriction and exercise-that highlight both the opportunities and challenges of targeting SUMO-regulated stress responses in aging. Together, this synthesis provides a framework for understanding how SUMOylation links metabolic stress to tissue-specific aging trajectories and therapeutic potential.

Aging↗

PubMed2025

Laboratory Evolution Reveals Transcriptional Mechanisms Underlying Thermal Adaptation of Escherichia coli.

Adaptive laboratory evolution is able to generate microbial strains, which exhibit extreme phenotypes, revealing fundamental biological adaptation mechanisms. Here, we use adaptive laboratory evolution to evolve Escherichia coli strains that grow at temperatures as high as 45.3 °C, a temperature lethal to wild-type cells. The strains adopted a hypermutator phenotype and employed multiple systems-level adaptations that made global analysis of the DNA mutations difficult. Given the challenge at the genomic level, we were motivated to uncover high-temperature tolerance adaptation mechanisms at the transcriptomic level. We employed independently modulated gene set (iModulon) analysis to reveal five transcriptional mechanisms underlying growth at high temperatures. These mechanisms were connected to acquired mutations, changes in transcriptome composition, sensory inputs, phenotypes, and protein structures. They are as follows: (i) downregulation of general stress responses while upregulating the specific heat stress responses, (ii) upregulation of flagellar basal bodies without upregulating motility and upregulation fimbriae, (iii) shift toward anaerobic metabolism, (iv) shift in regulation of iron uptake away from siderophore production, and (v) upregulation of yjfIJKL, a novel heat tolerance operon whose structures we predicted with AlphaFold. iModulons associated with these five mechanisms explain nearly half of all variance in the gene expression in the adapted strains. These thermotolerance strategies reveal that optimal coordination of known stress responses and metabolism can be achieved with a small number of regulatory mutations and may suggest a new role for large protein export systems. Adaptive laboratory evolution with transcriptomic characterization is a productive approach for elucidating and interpreting adaptation to otherwise lethal stresses.

Escherichia coli↗

PubMed2006

Energetic bicyclic azolium salts.

Bicyclic azoles, 2-methyl-5-(imidazol-1-yl)-2H-tetrazole (1), 2-methyl-5-(1,2,4-triazol-1-yl)-2H-tetrazole (4), 1-methyl-5-(imidazol-1-yl)-1H-tetrazole (7), 1-methyl-5-(1,2,4-triazol-1-yl)-1H-tetrazole (10), 1-methyl-4-nitro-2-(imidazol-1-yl)-1H-imidazole (13), and 1-methyl-4-nitro-2-(1,2,4-triazol-1-yl)-1H-imidazole (16) were prepared. Their thermally stable azolium salts, 3, 6, 9, 12, 15, and 18-21, with densities ranging between 1.519-1.674 g cm-3, were synthesized by quaternization with nitric or perchloric acid or with iodomethane followed by metathesis reactions with silver nitrate and silver perchlorate. The structures of 12 b and 21 b were confirmed by single-crystal X-ray analysis. The standard enthalpies of formation for some of the new salts were calculated by using the computationally feasible DFT(B3LYP) and MP2 methods in conjunction with an empirical approach based on densities of salts. The calculated values range from DeltaHdegreef=209.9 (21 a) to 412.3 (12 b) kJ mol-1 in which the experimental densities are >1.515 g cm-3.

Journal Article↗

PubMed2006

Coordination networks with fluorinated backbones.

Fluorine-containing ligands 2,3,5,6-tetrafluoro-1,4-bis(imidazol-1-yl-methyl)benzene (1) and 2,3,5,6-tetrafluoro-1,4-bis(2-methylimidazol-1-yl-methyl)benzene (2) were prepared and coordinated with AgNO3, Co(ClO4)2 x 6 H2O, and Cd(NO3)2 x 4 H2O, respectively, to form the following structures: 3D channel polymer [Ag2(1)2(NO3)2 x H2O x MeOH]n (3), 2D sheet polymer [Co(1)3(ClO4)2]n (4), 1D chain polymer [Cd(1)3(NO3)2 x 4 H2O]n (5), and a 2D herringbone sheet polymer [Ag(2)NO3 x 1.5 MeOH]n (6). The solid-state crystal structures of 3-6 were studied by single-crystal X-ray crystallography.

Crystallography, X-Ray↗

PubMed2005

Energetic azolium azolate salts.

Energetic salts comprising substituted imidazolium and 1,2,4-triazolium cations and 4,5-dinitro-imidazolate and 5-nitrotetrazolate anions were synthesized and characterized. On the basis of experimentally obtained heats of combustion, the calculated heats of formation range from deltaHf(o) degrees = 80 (3) to 1071 kJ/mol (13). Imidazolate salts are more dense but have lower heats of formation than their tetrazolate analogues. Salts 4, 5, 8, and 11-14 fall into the ionic liquid class (mp < 100 degrees C). The structure of 1,2,4-triazolium 5-nitrotetrazolate (10) was confirmed by X-ray analysis.

Journal Article↗

PubMed2005

Guanidinium-based ionic liquids.

Cyclic (subset=N+<, subset = imidazolidine 3 and 4, hexahydro-pyrimidine 7 and 8, tetrahydro-1,3,5-oxadiazine 12, and triazoline 15 and 16) and acyclic [(R2N)2C=N+<, 19] guanidinium-based salts were synthesized via the quaternization of guanidine derivatives with nitric or perchloric acid or with iodomethane followed by metathesis reaction with silver nitrate, silver perchlorate, or ammonium dinitroamide. The structure of 15d was confirmed by single-crystal X-ray analysis. Most of the salts exhibited low melting points and good thermal stabilities. Their densities range between 1.2 and 1.5 g/cm3. Standard molar enthalpies of formation were calculated from experimentally determined constant-volume combustion energies obtained using an oxygen bomb calorimeter.

Journal Article↗

PubMed2004

The first (ferrocenylmethyl)imidazolium and (ferrocenylmethyl)triazolium room temperature ionic liquids.

N-(Ferrocenylmethyl)imidazole (3a), 1-(ferrocenylmethyl)-1,2,4-triazole (3b), 1,1'-bis[(1H-imidazol-1-yl)methyl]ferrocene (8a), 1,1'-bis([1H-(2-methyl)imidazol-1-yl]methyl]ferrocene (8b), and 1,1'-bis[(1H-1,2,4-triazol-1-yl)methyl]ferrocene (8c) were synthesized in moderate yields. These compounds were quaternized with methyl iodide to form 1-(ferrocenylmethyl)-3-methylimidazolium iodide (4a), 1-(ferrocenylmethyl)-4-methyl-1,2,4-triazolium iodide (4b), 1,1'-bis([1-(2,3-dimethyl)imidazolium]methyl)ferrocene diiodide (9b), and 1,1'-bis([1-(4-methyl)-1,2,4-triazolium]methyl)ferrocene diiodide (9c), respectively, in excellent yields. Compounds 4a, 4b, 9b, and 9c were metathesized with bis(trifluoromethanesulfonyl)amide to give high yields of 5a, 5b, 10b, and 10c. With potassium hexafluorophosphate, 9b forms 10d. Salts 5a, 5b, and 10c are the first room-temperature ionic liquids with cations containing an organometallic moiety that exhibit T(g) values well below room temperature, i.e., -32, -16, and -11 degrees C. The compounds were characterized by (1)H, (19)F, and (13)C NMR, MS, and elemental analyses. T(g) values and melting points were determined by DSC. T(d) values (5% weight loss temperature) were recorded by TGA. X-ray single-crystal structures show that 9c and 10d crystallize in the triclinic space group P.

Journal Article↗

PubMed2003

Quaternary salts containing the pentafluorosulfanyl (SF5) group.

The first quaternary salts of pyridine (2), N-methyl imidazole (3), N-propyl triazole (4), and pyridazine (5) that contain the pentafluorosulfanyl (SF(5)) group were prepared and characterized. Neat reactions of the aromatic nitrogen compounds with SF(5)(CF(2))(n)(CH(2))(m)I (n = 2 or 4, m = 2 or 4) gave quaternary iodides 6a-c, 7a-c, 8a, and 9a,b, which were metathesized with LiN(SO(2)CF(3))(2) to form the bis(trifluoromethylsulfonyl)amides 10a-c, 11a-c, 12a, and 13a,b, in high yields. With the exception of the pyridine bis(trifluoromethylsulfonyl)amide salts, the compounds melted or exhibited a T(g) at <0 degrees C. The methylimidazolium, pyridinium, and pyridazinium salts exhibited densities of approximately 2 g/cm(3). Particularly striking was the density of CF(3)(CF(2))(5)(CH(2))(2)-pyridazinium N(CF(3)SO(2))(2) measured at 2.13 g/cm(3); however, an atypically high density for the 1-CF(3)(CF(2))(5)(CH(2))(2)-3-methyl imidazolium amide (14) was also observed at 1.77 g/cm(3). All quaternary salts were characterized via IR, (19)F, (1)H, and (13)C NMR spectra and elemental analyses.

Journal Article↗

PubMed2003

Unprecedented double C-C bond cleavage of a cyclopentadienyl ligand.

Double C-C bond cleavage of a cyclopentadienyl ligand proceeded to titanacyclopentadienes when 2 equiv of nitriles were added and the resulting two-carbon unit and three-carbon unit were converted into a benzene derivative and a pyridine derivative, respectively, in one-pot.

Journal Article↗