Potential nutritional and functional matters in yeast culture prepared by soybean meal fermentation.

BACKGROUND: Yeast culture (YC) is a product fermented on a specific medium, which is a type of postbiotic of anaerobic solid-state fermentation. Although YC has positive effects on the animal growth and health, it contains a variety of beneficial metabolites as dark matter, which have not been quantified. In the present study, liquid chromatography-tandem mass spectrometry is employed to identify the unknown metabolites. Following their identification, the important chemicals are quantified using HPLC-diode array detection methods. RESULTS: Non-targeted metabolomics studies showed that 670 metabolites in total were identified in YC, of which 23 metabolites significantly increased, including organic acids, amino acids, nucleosides and purines, isoflavones, and other substances. The chemical quantitative analysis showed that the contents of succinic acid, aminobutyric acid, glutamine, purine and daidzein increased by 84.42%, 51.07%, 100%, 68.85% and 4.60%, respectively. CONCLUSION: Therefore, the use of non-targeted metabolomics combined with chemical quantitative analysis to reveal the nutritional and functional substances of YC could help to elucidate the postbiotic mechanism and provide theoretical support for the regulation of the directional accumulation of beneficial metabolites. © 2024 Society of Chemical Industry.

Uncovering phytochemicals quantitative evolution in avocado fruit mesocarp during ripening: A targeted LC-MS metabolic exploration of Hass, Fuerte and Bacon varieties.

Avocado ripening entails intricate physicochemical transformations resulting in desirable characteristics for consumption; however, its impact on specific metabolites and its cultivar dependence remains largely unexplored. This study employed LC-MS to quantitatively monitor 30 avocado pulp metabolites, including phenolic compounds, amino acids, nucleosides, vitamins, phytohormones, and related compounds, from unripe to overripe stages, in three commercial varieties (Hass, Fuerte, and Bacon). Multivariate statistical analysis revealed significant metabolic variations between cultivars, leading to the identification of potential varietal markers. Most monitored metabolites exhibited dynamic quantitative changes. Although phenolic compounds generally increased during ripening, exceptions such as epicatechin and chlorogenic acid were noted. Amino acids and derivatives displayed a highly cultivar-dependent evolution, with Fuerte demonstrating the highest concentrations and most pronounced fluctuations. In contrast to penstemide, uridine and abscisic acid levels consistently increased during ripening. Several compounds characteristic of the Bacon variety were delineated but require further research for identification and role elucidation.

Development of a novel HEK293 cell model lacking SLC29A1 to study the pharmacology of endogenous SLC29A2-encoded equilibrative nucleoside transporter subtype 2.

Equilibrative nucleoside transporters (ENT) mediate the transmembrane flux of endogenous nucleosides and nucleoside analogues used clinically. The predominant subtype, ENT1, has been well characterized. However, the other subtype, ENT2, has been less well characterized in its native milieu due to its relatively low expression and the confounding influence of co-expressed ENT1. We created a cell model where ENT1 was removed from HEK293 cells using CRISPR/cas9 (ENT1KO cells); this cell line has ENT2 as the only functional purine transporter. Transporter function was assessed through measurement of [3H]2-chloroadenosine uptake. ENT1 protein was quantified based on the binding of [3H]nitrobenzylthioinosine, and ENT1/ENT2 protein was detected by immunoblotting. Changes in expression of relevant transporters and enzymes involved in purine metabolism were examined by qPCR. Wildtype HEK293 cells and ENT1KO cells had a similar expression of SLC29A2/ENT2 transcript/protein and ENT2-mediated [3H]2-chloroadenosine transport activity (Vmax values of 1.02 {plus minus} 0.06 and 1.50 {plus minus} 0.22 pmol/µl/s, respectively). Of the endogenous nucleosides/nucleobases tested, adenosine had the highest affinity (Ki) for ENT2 (2.6 µM), while hypoxanthine was the only nucleobase with a sub-millimolar affinity (320 µM). A range of nucleoside/nucleobase analogues were also tested for their affinity for ENT2 in this model, with affinities (Ki) ranging from 8.6 µM for ticagrelor to 2,300 µM for 6-mercaptopurine. Our data suggest that the removal of endogenous ENT1 from these cells does not change the expression or function of ENT2. This cell line should prove useful for the analysis of novel drugs acting via ENT2 and to study ENT2 regulation. Significance Statement We have created a cell line whereby endogenous ENT2 can be studied in detail in the absence of the confounding influence of ENT1. Loss of ENT1 has no impact on the expression and function of ENT2. This novel cell line will provide an ideal model for studying drug interactions with ENT2 as well as the cellular regulation of ENT2 expression and function.

Synthesis of Substituted 1,2,4-Triazole-3-Thione Nucleosides Using E. coli Purine Nucleoside Phosphorylase.

1,2,4-Triazole derivatives have a wide range of biological activities. The most well-known drug that contains 1,2,4-triazole as part of its structure is the nucleoside analogue ribavirin, an antiviral drug. Finding new nucleosides based on 1,2,4-triazole is a topical task. The aim of this study was to synthesize ribosides and deoxyribosides of 1,2,4-triazole-3-thione derivatives and test their antiviral activity against herpes simplex viruses. Three compounds from a series of synthesized mono- and disubstituted 1,2,4-triazole-3-thione derivatives were found to be substrates for E. coli purine nucleoside phosphorylase. Of six prepared nucleosides, the riboside and deoxyriboside of 3-phenacylthio-1,2,4-triazole were obtained at good yields. The yields of the disubstituted 1,2,4-triazol-3-thiones were low due to the effect of bulky substituents at the C3 and C5 positions on the selectivity of enzymatic glycosylation for one particular nitrogen atom in the triazole ring. The results of cytotoxic and antiviral studies on acyclovir-sensitive wild-type strain HSV-1/L2(TK+) and acyclovir-resistant strain (HSV-1/L2/RACV) in Vero E6 cell culture showed that the incorporation of a thiobutyl substituent into the C5 position of 3-phenyl-1,2,4-triazole results in a significant increase in the cytotoxicity of the base and antiviral activity. The highest antiviral activity was observed in the 3-phenacylthio-1-(ß-D-ribofuranosyl)-1,2,4-triazole and 5-butylthio-1-(2-deoxy-ß-D-ribofuranosyl)-3-phenyl-1,2,4-triazole nucleosides, with their selectivity indexes being significantly higher than that of ribavirin. It was also found that with the increasing lipophilicity of the nucleosides, the activity and toxicity of the tested compounds increased.

Production of pyrimidine nucleosides in microbial systems via metabolic engineering: Theoretical analysis research and prospects.

Pyrimidine nucleosides, as intermediate materials of significant commercial value, find extensive applications in the pharmaceutical industry. However, the current production of pyrimidine nucleosides largely relies on chemical synthesis, creating environmental problems that do not align with sustainable development goals. Recent progress in systemic metabolic engineering and synthetic biology has enabled the synthesis of natural products like pyrimidine nucleosides through microbial fermentation, offering a more sustainable alternative. Nevertheless, the intricate and tightly regulated biosynthetic pathways involved in the microbial production of pyrimidine nucleosides pose a formidable challenge. This study focuses on metabolic engineering and synthetic biology strategies aimed at enhancing pyrimidine nucleoside production. These strategies include gene modification, transcriptional regulation, metabolic flux analysis, cofactor balance optimization, and transporter engineering. Finally, this research highlights the challenges involved in the further development of pyrimidine nucleoside-producing strains and offers potential solutions in order to provide theoretical guidance for future research endeavors in this field.

1mΨ influences the performance of various positive-stranded RNA virus-based replicons.

Self-amplifying RNAs (saRNAs) are versatile vaccine platforms that take advantage of a viral RNA-dependent RNA polymerase (RdRp) to amplify the messenger RNA (mRNA) of an antigen of interest encoded within the backbone of the viral genome once inside the target cell. In recent years, more saRNA vaccines have been clinically tested with the hope of reducing the vaccination dose compared to the conventional mRNA approach. The use of N1-methyl-pseudouridine (1mΨ), which enhances RNA stability and reduces the innate immune response triggered by RNAs, is among the improvements included in the current mRNA vaccines. In the present study, we evaluated the effects of this modified nucleoside on various saRNA platforms based on different viruses. The results showed that different stages of the replication process were affected depending on the backbone virus. For TNCL, an insect virus of the Alphanodavirus genus, replication was impaired by poor recognition of viral RNA by RdRp. In contrast, the translation step was severely abrogated in coxsackievirus B3 (CVB3), a member of the Picornaviridae family. Finally, the effects of 1mΨ on Semliki forest virus (SFV), were not detrimental in in vitro studies, but no advantages were observed when immunogenicity was tested in vivo.

[Effect of different initial processing treatments on commercial characters and chemical components of Fritillaria taipaiensis].

To investigate the effects of different initial processing methods on the quality of Fritillaria taipaiensis, this study explored the effects of anti-browning treatment, drying methods, and drying temperatures on the commercial characters, chromaticity values, and alkaloid and nucleoside components of Fritillariae Taipaiensis Bulbus. The results were comprehensively evaluated through correlation analysis(CA), principal component analysis(PCA), and hierarchical clustering analysis(HCA). Compared with those of the direct drying group(WD60), the chromaticity values(ΔE*) of the groups with scraped outer skin( FHB1) and mixed lime powder treatments(FHB2) were significantly reduced, indicating the inhibition of the browning process. The total alkaloid content of the group with mixed raw soil treatment(FHB3) and the FHB2 group showed no significant change, whereas that of the group with 5%Na Cl O solution rinse treatment(FHB4) was the lowest. Compared with air-blast dried(WD50) samples, the ΔE* values of freezedried(FS6) and vacuum-dried(FS5) samples were significantly decreased, with an increase in total alkaloid contents. Conversely,the ΔE* values of shade-dried(FS1) and sun-dried(FS2) samples were significantly increased, with severe browning and low total alkaloid contents. The total alkaloid contents of heat-pump-dried(FS4) samples showed no significant change, and their ΔE* value was significantly decreased, with a light degree of browning and favorable commercial characters. The total alkaloid content of air-blast dried samples initially increased and then decreased within the range of 40-80 ℃, and the highest content was recorded at 70 ℃. The ΔE* values of high-temperature air-blast dried samples(70-80 ℃) were smaller with a light degree of browning, whereas their texture was compact and lacked powder. CA revealed a significant relationship between the uracil content and chromaticity value of the samples(P< 0. 05). The clustering relationships among samples subjected to different treatments were visualized via PCA and HCA. The results showed that FHB2 and air-blast drying(50-60 ℃) were more suitable for large-scale production, and heat pump drying could be a promising direction for future development. This study provides a scientific basis for optimizing the initial processing methods of Fritillaria taipaiensis.

Synthesis and Development of Inverse-Type Nucleoside Diarylethene Photoswitches.

Nucleosidic diarylethenes (DAEs) have evolved from an emerging class of photochromes into a well-established option for integrating photochromic functionalities into biological systems. However, a comprehensive understanding of how chemical structure influences their photochromic properties remains essential. While structural features, such as an inverse connection between the aryl residues and the ethene bridge, are well-documented for classical DAEs, their application to nucleosidic DAEs has been underexplored. In this study, we address this gap by developing three distinct types of inverse nucleosidic DAEs - semi-inverse thiophenes, semi-inverse uridines and inverse uridines. We successfully synthesized these compounds and conducted comprehensive analyses of their photostationary states, thermal stability, reversibility, and reaction quantum yields. Additionally, we conducted an in-depth comparison of their photochromic properties with those of their normal-type counterparts. Among the synthesized compounds, seven semi-inverse thiophenes exhibited the most promising characteristics. Notably, these compounds demonstrated excellent fatigue resistance, with up to 96% retention of photochromic activity over 40 switching cycles, surpassing the performance of all comparable nucleosidic DAEs reported to date. These findings hold significant promise for future applications in various fields.

Regioselective Deacetylation in Nucleosides and Derivatives.

Nucleoside analogues are a promising class of natural compounds in the pharmaceutical industry, and many antiviral, antibacterial and anticancer drugs have been created through structural modification of nucleosides scaffold. Acyl protecting groups, especially the acetyl group, play an important role in the protection of hydroxy groups in nucleoside synthesis and modification; consequently, numerous methodologies have been put forth for the acetylation of free nucleosides. However, for nucleosides that contain different O- and N-based functionalities, selective deprotection of the acetyl group(s) in nucleosides has been studied little, despite its practical significance in simplifying the preparation of partially or differentially substituted nucleoside intermediates. In this mini-review, recent approaches for regioselective deacetylation in acetylated nucleosides and their analogues are summarized and evaluated. Different regioselectivities (primary ester, secondary ester, full de-O-acetylation, and de-N-acetylation) are summarized and discussed in each section.

Two new types of structures from soft coral-associated epiphytic fungus Aspergillus versicolor CGF9-1-2.

Global Natural Products Social (GNPS) molecular networking platform was applied to discovery the undescribed compounds from the common marine fungi Aspergillus versicolor CGF9-1-2, ultimately resulting in isolation of four new polyketides, decumbenone E (1), decumbenone F (2), 2'-epi-8-O-methylnidurufin (6), (-)-phomoindene A (7), one new nucleoside, 3-methyl-9-(2-methylbutene)-xanthine (8), and five known analogues. Their structures were elucidated based on 1D/2D NMR spectroscopic and HRESIMS data analyses, meanwhile, the absolute configurations of new compounds were established based on the X-ray crystallographic experiments, as well as the electronic circular dichroism (ECD) analysis. All compounds were predicted pharmaceutical chemistry with ten commonly disease-related proteins by molecular docking. In addition, all compounds against TDP1 were performed in vitro, which was consistent with the docking result, and compound 6 shown a weak inhibitory activity.

Structure-Function Insights into the Dual Role in Nucleobase and Nicotinamide Metabolism and a Possible Use in Cancer Gene Therapy of the URH1p Riboside Hydrolase.

The URH1p enzyme from the yeast Saccharomyces cerevisiae has gained significant interest due to its role in nitrogenous base metabolism, particularly involving uracil and nicotinamide salvage. Indeed, URH1p was initially classified as a nucleoside hydrolase (NH) with a pronounced preference for uridine substrate but was later shown to also participate in a Preiss-Handler-dependent pathway for recycling of both endogenous and exogenous nicotinamide riboside (NR) towards NAD+ synthesis. Here, we present the detailed enzymatic and structural characterisation of the yeast URH1p enzyme, a member of the group I NH family of enzymes. We show that the URH1p has similar catalytic efficiencies for hydrolysis of NR and uridine, advocating a dual role of the enzyme in both NAD+ synthesis and nucleobase salvage. We demonstrate that URH1p has a monomeric structure that is unprecedented for members of the NH homology group I, showing that oligomerisation is not strictly required for the N-ribosidic activity in this family of enzymes. The size, thermal stability and activity of URH1p towards the synthetic substrate 5-fluoruridine, a riboside precursor of the antitumoral drug 5-fluorouracil, make the enzyme an attractive tool to be employed in gene-directed enzyme-prodrug activation therapy against solid tumours.

Antitumor activity and transcriptome sequencing (RNA-seq) analyses of hepatocellular carcinoma cells in response to exposure triterpene-nucleoside conjugates.

Fifteen betulonic/betulinic acid conjugated with nucleoside derivatives were synthesized to enhance antitumor potency and water solubility. Among these, the methylated betulonic acid-azidothymidine compound (8c) exhibited a broad-spectrum of antitumor activity against three tested tumor cell lines, including SMMC-7721 (IC50 = 5.02 µM), KYSE-150 (IC50 = 5.68 µM), and SW620 (IC50 = 4.61 µM) and along with lower toxicity (TC50 > 100 µM) estimated by zebrafish embryos assay. Compared to betulinic acid (<0.05 µg/mL), compound 8c showed approximately 40-fold higher water solubility (1.98 µg/mL). In SMMC-7721 cells, compound 8c induced autophagy and apoptosis as its concentration increased. Transcriptomic sequencing analysis was used to understand the potential impacts of the underlying mechanism of 8c on SMMC-7721 cells. Transcriptomic studies indicated that compound 8c could activate autophagy by inhibiting the PI3K/AKT pathway in SMMC-7721 cells. Furthermore, in the xenograft mice study, compound 8c significantly slowed down the tumor growth, as potent as paclitaxel treated group. In conclusion, methylated betulonic acid-azidothymidine compound (8c) not only increases water solubility, but also enhances the potency against hepatocellular carcinoma cells by inducing autophagy and apoptosis, and suppressing the PI3K/Akt/mTOR signaling pathway.

Furostanol glycosides, stilbenoids and nucleosides from the roots of Smilax perfoliata, and evaluation of their cytotoxic and anticholinesterase activities.

Three undescribed compounds including two furosteroid glycosides (perfoloside and 22-O-methylperfoloside) and one stilbenedimer (perfolostilbene) together with 21 known compounds were isolated from the roots of Smilax perfoliata. The structural elucidation was established by extensive uses of HRMS, 1D and 2D spectroscopic techniques. The assignment of the stereocenters in perfolostilbene was based on NOESY data and ECD calculation. Among the isolates, two compounds showed marginal cytotoxic activity against KB and Hela cell lines while seven stilbenoids showed strong to weak antiacetylcholinesterase and antibutyrylcholinesterase activities with IC50 ranging between 2-197 µM.

Vibrational circular dichroism of adenosine crystals.

Adenosine is one of the building blocks of nucleic acids and other biologically important molecules. Spectroscopic methods have been among the most utilized techniques to study adenosine and its derivatives. However, most of them deal with adenosine in solution. Here, we present the first vibrational circular dichroism (VCD) spectroscopic study of adenosine crystals in solid state. Highly regular arrangement of adenosine molecules in a crystal resulted in a strongly enhanced supramolecular VCD signal originating from long-range coupling of vibrations. The data suggested that adenosine crystals, in contrast to guanosine ones, do not imbibe atmospheric water. Relatively large dimensions of the adenosine crystals resulted in scattering and substantial orientational artifacts affecting the spectra. Several strategies for tackling the artifacts have been proposed and tested. Atypical features in IR absorption spectra of crystalline adenosine (e.g., extremely low absorption in mid-IR spectral range) were observed and attributed to refractive properties of adenosine crystals.

1,5-disubstituted 1,2,3-triazolylated carbohydrates and nucleosides.

In general, 1,5-disubstituted 1,2,3-triazolyl moiety is much less common in the synthesis and applications in comparison to its regioisomeric counterpart. Moreover, the synthesis of 1,5-disubstituted 1,2,3-triazoles are not so straightforward as is the case for copper catalyzed strategy of 1,4-disubstituted 1,2,3-triazoles. The preparation of 1,5-triazolylated carbohydrates and nucleosides are even more complex because of the difficulties in accessing the appropriate starting materials as well as the compatibility of reaction conditions with the various protecting groups. 1,5-Disubstitution regioisomeric triazoles of carbohydrates and nucleosides were traditionally obtained as minor products through straightforward heating of the mixture of azides and terminal alkynes. However, the separation of isomers was tedious or in some cases futile. On the other hand, regioselective synthesis using ruthenium catalysis triggered serious concern of residual metal content in therapeutically important ingredients. Therefore, serious efforts are being made by several groups to develop non-toxic metal based or completely metal-free synthesis of 1,5-disubstituted 1,2,3-triazoles. This article strives to summarize the pre-Click era as well as the post-2001 reports on the synthesis and potential applications of 1,5-disubstituted 1,2,3-triazoles in biological systems.

Exploiting the roles of nitrogen sources for HEA increment in Cordyceps cicadae.

Cordyceps cicadae, as a new food ingredient, is a valuable edible and medicinal fungi. However, its resources are severely depleted due to environmental limitations and excessive harvesting practices. N6-(2-hydroxyethyl) adenosine (HEA), as an important product of Cordyceps cicadae, has the potential to be used in medical industry due to its diverse disease curing potential. However, the disclosure of HEA synthesis still severely limited its application until now. In this study, the kinetic curves for adenosine and HEA under shaker fermentation were explored. The kinetics of HEA and adenosine production exhibited a competitive pattern, implicating a possibility of sharing a same step during their synthesis. Due to HEA as a derivative of nitrogen metabolism, the effect of different nitrogen sources (peptone, yeast extract, ammonium sulfate, diammonium oxalate monohydrate, ammonium citrate dibasic, and ammonium citrate tribasic) on HEA production in Cordyceps cicadae strain AH 10-4 had been explored under different incubation conditions (shaker fermentation, stationary fermentation, and submerged fermentation). Our results indicated that the complex organic nitrogen sources were found to improve the accumulation of HEA content under shaker fermentation. In contrast, the optimal nitrogen source for the accumulation of HEA under stationary fermentation and submerged fermentation was ammonium citrate tribasic. But submerged fermentation obviously shortened the incubation time and had a comparable capacity of HEA accumulation by 2.578 mg/g compared with stationary fermentation of 2.535 mg/g, implicating a possibility of scaled-up production of HEA in industry by submerged fermentation. Based on the dramatic HEA production by ammonium sulfate as nitrogen resources between stationary and shaker fermentations, alanine, aspartate and glutamate as well as arginine metabolic pathway were related to the production of HEA by comparative transcriptome. Further investigation indicated that glutamic acid, which is an analog of Asp, showed an optimum production of HEA in comparison with other amino acids.

Nitrogen-Centered Radicals Derived from Azidonucleosides.

Azido-modified nucleosides have been extensively explored as substrates for click chemistry and the metabolic labeling of DNA and RNA. These compounds are also of interest as precursors for further synthetic elaboration and as therapeutic agents. This review discusses the chemistry of azidonucleosides related to the generation of nitrogen-centered radicals (NCRs) from the azido groups that are selectively inserted into the nucleoside frame along with the subsequent chemistry and biological implications of NCRs. For instance, the critical role of the sulfinylimine radical generated during inhibition of ribonucleotide reductases by 2'-azido-2'-deoxy pyrimidine nucleotides as well as the NCRs generated from azidonucleosides by radiation-produced (prehydrated and aqueous) electrons are discussed. Regio and stereoselectivity of incorporation of an azido group ("radical arm") into the frame of nucleoside and selective generation of NCRs under reductive conditions, which often produce the same radical species that are observed upon ionization events due to radiation and/or other oxidative conditions that are emphasized. NCRs generated from nucleoside-modified precursors other than azidonucleosides are also discussed but only with the direct relation to the same/similar NCRs derived from azidonucleosides.

Synthesis, conformational analysis and antimicrobial activity of 10-benzyl-1,2,4-triazolo[4,3-b]1,2,4-triazino[5,6-b]indole acyclo C-nucleoside analogs.

Condensation of 5-benzyl-3-hydrazino-1,2,4-triazino[5,6-b]indole with various sugar aldoses or ketoses gave the corresponding sugar hydrazones as single geometrical isomer or exist in E/Z tautomeric isomers. The hydrazones underwent heterocyclization with Fe(Ш)Cl3 to give the N2-adduct acyclo C-nucleosides: 3-(alditol-1yl)-10-benzyl-1,2,4-triazolo[4,3-b]1,2,4-triazino[5,6-b]indoles rather than the N4-adduct: 10-(alditol-1-yl)-3-benzyl-1,2,4-triazolo[3,4-c]1,2,4-triazino[5,6-b] indoles on the basis of chemical and UV spectral proofs. Conformational analysis of their polyacetates were studied. The new acyclo C-nucleosides were evaluated for antimicrobial activity.

Deoxyguanosine kinase deficiency: natural history and liver transplant outcome.

Autosomal recessive pathogenetic variants in the DGUOK gene cause deficiency of deoxyguanosine kinase activity and mitochondrial deoxynucleotides pool imbalance, consequently, leading to quantitative and/or qualitative impairment of mitochondrial DNA synthesis. Typically, patients present early-onset liver failure with or without neurological involvement and a clinical course rapidly progressing to death. This is an international multicentre study aiming to provide a retrospective natural history of deoxyguanosine kinase deficient patients. A systematic literature review from January 2001 to June 2023 was conducted. Physicians of research centres or clinicians all around the world caring for previously reported patients were contacted to provide followup information or additional clinical, biochemical, histological/histochemical, and molecular genetics data for unreported cases with a confirmed molecular diagnosis of deoxyguanosine kinase deficiency. A cohort of 202 genetically confirmed patients, 36 unreported, and 166 from a systematic literature review, were analyzed. Patients had a neonatal onset (≤ 1 month) in 55.7% of cases, infantile (>1 month and ≤ 1 year) in 32.3%, pediatric (>1 year and ≤18 years) in 2.5% and adult (>18 years) in 9.5%. Kaplan-Meier analysis showed statistically different survival rates (P < 0.0001) among the four age groups with the highest mortality for neonatal onset. Based on the clinical phenotype, we defined four different clinical subtypes: hepatocerebral (58.8%), isolated hepatopathy (21.9%), hepatomyoencephalopathy (9.6%), and isolated myopathy (9.6%). Muscle involvement was predominant in adult-onset cases whereas liver dysfunction causes morbidity and mortality in early-onset patients with a median survival of less than 1 year. No genotype-phenotype correlation was identified. Liver transplant significantly modified the survival rate in 26 treated patients when compared with untreated. Only six patients had additional mild neurological signs after liver transplant. In conclusion, deoxyguanosine kinase deficiency is a disease spectrum with a prevalent liver and brain tissue specificity in neonatal and infantile-onset patients and muscle tissue specificity in adult-onset cases. Our study provides clinical, molecular genetics and biochemical data for early diagnosis, clinical trial planning and immediate intervention with liver transplant and/or nucleoside supplementation.

Unraveling the structure-chirality sensing relationship between achiral anthracene-based tetracationic nanotubes and nucleosides in aqueous host-guest complexation.

In biological systems, nucleosides play crucial roles in various physiological processes. In this study, we designed and synthesized four achiral anthracene-based tetracationic nanotubes (1-4) as artificial hosts and chiroptical sensors for nucleosides in aqueous media. Notably, different nanotubes exhibit varied chirality sensing on circular dichroism (CD)/circularly polarized luminescence (CPL) spectra through the host-guest complexation, which prompted us to explore the factors influencing their chiroptical responses. Through systematic host-guest experiments, the structure-chirality sensing relationship between achiral anthracene-based tetracationic nanotubes and nucleosides in the host-guest complexation was unraveled. Firstly, the CD response originates from the anthracene rings situated at the side-wall position, resulting from the right-handed (P)- or left-handed (M)-twisted conformation of the macrocyclic structure. Secondly, the CPL signal is influenced by the presence of anthracene rings at the linking-wall position, which results from intermolecular chiral twisted stacking between these anthracene rings. Therefore, these nanotubes can serve as chiroptical sensor arrays to enhance the accuracy of nucleotide recognition through principal component analysis (PCA) analysis based on the diversified CD spectra. This study provides insights for the construction of adaptive chirality from achiral nanotubes with dynamic conformational nature and might facilitate further design of chiral functional materials for several applications.