PubMed

Int J Mol Sci. 2023 May 24;24(11):9192. doi: 10.3390/ijms24119192.ABSTRACTHypertension affects over a billion adults worldwide and is a major risk factor for cardiovascular disease. Studies have reported that the microbiota and its metabolites regulate hypertension pathophysiology. Recently, tryptophan metabolites have been identified to contribute to and inhibit the progression of metabolic disorders and cardiovascular diseases, including hypertension. Indole propionic acid (IPA) is a tryptophan metabolite with reported protective effects in neurodegenerative and cardiovascular diseases; however, its involvement in renal immunomodulation and sodium handling in hypertension is unknown. In the current study, targeted metabolomic analysis revealed decreased serum and fecal IPA levels in mice with L-arginine methyl ester hydrochloride (L-NAME)/high salt diet-induced hypertension (LSHTN) compared to normotensive control mice. Additionally, kidneys from LSHTN mice had increased T helper 17 (Th17) cells and decreased T regulatory (Treg) cells. Dietary IPA supplementation in LSHTN mice for 3 weeks resulted in decreased systolic blood pressure, along with increased total 24 h and fractional sodium excretion. Kidney immunophenotyping demonstrated decreased Th17 cells and a trend toward increased Treg cells in IPA-supplemented LSHTN mice. In vitro, naïve T cells from control mice were skewed into Th17 or Treg cells. The presence of IPA decreased Th17 cells and increased Treg cells after 3 days. These results identify a direct role for IPA in attenuating renal Th17 cells and increasing Treg cells, leading to improved sodium handling and decreased blood pressure. IPA may be a potential metabolite-based therapeutic option for hypertension.PMID:37298145 | DOI:10.3390/ijms24119192

J Clin Med. 2023 May 29;12(11):3739. doi: 10.3390/jcm12113739.ABSTRACTAdrenal incidentalomas are common findings in clinical practice, with a prevalence of up to 4.2% in radiological studies. Due to the large number of focal lesions in the adrenal glands, it can be challenging to make a definitive diagnosis and determine the appropriate management. The purpose of this review is to present current diagnostic modalities used to preoperatively distinguish between adrenocortical adenoma (ACA) and adrenocortical cancer (ACC). Proper management and diagnosis are crucial in avoiding unnecessary adrenalectomies, which occur in over 40% of cases. A literature analysis was conducted to compare ACA and ACC using imaging studies, hormonal evaluation, pathological workup, and liquid biopsy. Before deciding on surgical treatment, the nature of the tumor can be accurately determined using noncontrast CT imaging combined with tumor size and metabolomics. This approach helps to narrow down the group of patients with adrenal tumors who require surgical treatment due to the suspected malignant nature of the lesion.PMID:37297933 | DOI:10.3390/jcm12113739

J Clin Med. 2023 May 23;12(11):3613. doi: 10.3390/jcm12113613.ABSTRACTThis scoping review summarizes what is known about kidney metabolism during hypothermic perfusion preservation. Papers studying kidney metabolism during hypothermic (<12 °C) perfusion were identified (PubMed, Embase, Web of Science, Cochrane). Out of 14,335 initially identified records, 52 were included [dog (26/52), rabbit (2/52), pig (20/52), human (7/52)]. These were published between 1970-2023, partially explaining study heterogeneity. There is a considerable risk of bias in the reported studies. Studies used different perfusates, oxygenation levels, kidney injury levels, and devices and reported on perfusate and tissue metabolites. In 11 papers, (non)radioactively labeled metabolites (tracers) were used to study metabolic pathways. Together these studies show that kidneys are metabolically active during hypothermic perfusion, regardless of the perfusion setting. Although tracers give us more insight into active metabolic pathways, kidney metabolism during hypothermic perfusion is incompletely understood. Metabolism is influenced by perfusate composition, oxygenation levels, and likely also by pre-existing ischemic injury. In the modern era, with increasing donations after circulatory death and the emergence of hypothermic oxygenated perfusion, the focus should be on understanding metabolic perturbations caused by pre-existing injury levels and the effect of perfusate oxygen levels. The use of tracers is indispensable to understanding the kidney's metabolism during perfusion, given the complexity of interactions between different metabolites.PMID:37297808 | DOI:10.3390/jcm12113613

Healthcare (Basel). 2023 May 30;11(11):1592. doi: 10.3390/healthcare11111592.ABSTRACTAlthough not completely devoid of risk, pregnancy can be managed in virtually all patients affected by even the most complex forms of congenital heart disease. It is not however advisable in patients with any form of pulmonary arterial hypertension. Pregnancy is even manageable in patients with univentricular heart converted to Fontan circulation. A personalised risk stratification should be performed, and patients affected by advanced NYHA functional class appropriately warned of the potential risks. In this setting, metabolomics might represent a novel tool for use in conducting personalised risk stratification. All pregnancies, particularly those at higher risk, should be managed in a tertiary care centre capable of providing the necessary assistance to both the mother and infant. With a few rare exceptions, vaginal delivery is to be preferred over caesarean section due to the lower degree of maternal and foetal complications. The desire for motherhood, at times extreme in women with congenital heart disease, may often be accomplished, thus providing a ray of hope in the lives of these patients.PMID:37297732 | DOI:10.3390/healthcare11111592

Foods. 2023 Jun 3;12(11):2254. doi: 10.3390/foods12112254.ABSTRACTJUNCAO wine fermentation metabolites are closely related to the final quality of the product. Currently, there are no studies of dynamic metabolite changes during fermentation of JUNCAO wine. Here, we used gas chromatography quadrupole time-of-flight mass spectrometry (GC-QTOF-MS) metabolomics and multivariate statistical analysis to explore the relationship between metabolites and fermentation time. A total of 189 metabolites were annotated throughout the fermentation process. The principal component analysis (PCA) revealed a clear separation between the samples in the early and late stages of fermentation. A total of 60 metabolites were annotated as differential during the fermentation (variable importance in the projection, VIP > 1, and p < 0.05), including 21 organic acids, 10 amino acids, 15 sugars and sugar alcohols, and 14 other metabolites. Pathway analysis showed that the most commonly influenced pathways (impact value > 0.1 and p < 0.05) were tricarboxylic acid cycle, alanine, aspartic acid and glutamic acid metabolism, pyrimidine metabolism, and other 10 metabolic pathways. Moreover, integrated metabolic pathways are generated to understand the conversion and accumulation of differential metabolites. Overall, these results provide a comprehensive overview of metabolite changes during fermentation of JUNCAO wine.PMID:37297498 | DOI:10.3390/foods12112254

Foods. 2023 May 31;12(11):2221. doi: 10.3390/foods12112221.ABSTRACTTo overcome the fruit's perishability, mulberry wine has been developed as a method of preservation. However, dynamic changes in metabolites during mulberry wine fermentation have not been reported yet. In the present investigation, UHPLC-QE-MS/MS coupled with multivariate statistical analyses was employed to scrutinize the metabolic profiles, particularly the flavonoid profiles, throughout the process of vinification. In general, the major differential metabolites encompassed organic heterocyclic compounds, amino acids, phenylpropanoids, aromatic compounds, and carbohydrates. The contents of total sugar and alcohol play a primary role that drove the composition of amino acids, polyphenol, aromatic compound, and organic acid metabolites based on the Mantel test. Importantly, among the flavonoids, abundant in mulberry fruit, luteolin, luteolin-7-O-glucoside, (-)-epiafzelechin, eriodictyol, kaempferol, and quercetin were identified as the differential metabolic markers during blackberry wine fermentation and ripening. Flavonoid, flavone and flavonol biosynthesis were also identified to be the major metabolic pathways of flavonoids in 96 metabolic pathways. These results will provide new information on the dynamic changes in flavonoid profiles during black mulberry winemaking.PMID:37297465 | DOI:10.3390/foods12112221

Foods. 2023 May 31;12(11):2209. doi: 10.3390/foods12112209.ABSTRACTNowadays, it is evident that food ingredients have different roles and distinct health benefits to the consumer. Over the past years, the interest in functional foods, especially those targeting gut health, has grown significantly. The use of industrial byproducts as a source of new functional and sustainable ingredients as a response to such demands has raised interest. However, the properties of these ingredients can be affected once incorporated into different food matrices. Therefore, when searching for the least costly and most suitable, beneficial, and sustainable formulations, it is necessary to understand how such ingredients perform when supplemented in different food matrices and how they impact the host's health. As proposed in this manuscript, the ingredients' properties can be first evaluated using in vitro gastrointestinal tract (GIT) simulation models prior to validation through human clinical trials. In vitro models are powerful tools that mimic the physicochemical and physiological conditions of the GIT, enabling prediction of the potentials of functional ingredients per se and when incorporated into a food matrix. Understanding how newly developed ingredients from undervalued agro-industrial sources behave as supplements supports the development of new and more sustainable functional foods while scientifically backing up health-benefits claims.PMID:37297454 | DOI:10.3390/foods12112209

Foods. 2023 May 29;12(11):2178. doi: 10.3390/foods12112178.ABSTRACTE. sinensis, normally harvested in October and November, is an economic aquatic product in China. Pond culture has been widely applied for the production of E. sinensis, wherein a stable food supply for crabs is provided. In order to improve the nutritional quality of E. sinensis products, this study evaluated the effect of the local pond culture on the nutritive profiles of E. sinensis and screened out the best harvest time for the nutrient-rich crabs, thereby guiding the local crab industry to improve its aquaculture mode and harvest strategy. The results indicated that pond culture enhanced the levels of protein, amino acids, and specific organic acid derivatives, and reduced the levels of peptides and polyunsaturated fatty acids (PUFAs). Compared with E. sinensis harvested in October, peptide levels were significantly increased, whereas sugar, phenolic acid, and nucleotide levels were decreased in those harvested in November. Overall, the study revealed that the nutritive profile of the pond-reared E. sinensis was significantly modulated by a high-protein diet, thus lacking the diversity of metabolites. Additionally, October could be more appropriate for harvesting E. sinensis than November.PMID:37297423 | DOI:10.3390/foods12112178

Foods. 2023 May 25;12(11):2140. doi: 10.3390/foods12112140.ABSTRACTVarious fields have been identified in the "omics" era, such as genomics, proteomics, transcriptomics, metabolomics, phenomics, and metagenomics. Among these, metagenomics has enabled a significant increase in discoveries related to the microbial world. Newly discovered microbiomes in different ecologies provide meaningful information on the diversity and functions of microorganisms on the Earth. Therefore, the results of metagenomic studies have enabled new microbe-based applications in human health, agriculture, and the food industry, among others. This review summarizes the fundamental procedures on recent advances in bioinformatic tools. It also explores up-to-date applications of metagenomics in human health, food study, plant research, environmental sciences, and other fields. Finally, metagenomics is a powerful tool for studying the microbial world, and it still has numerous applications that are currently hidden and awaiting discovery. Therefore, this review also discusses the future perspectives of metagenomics.PMID:37297385 | DOI:10.3390/foods12112140

Foods. 2023 May 24;12(11):2105. doi: 10.3390/foods12112105.ABSTRACTIn the present research, we investigated changes in the gut metabolome that occurred in response to the administration of the Laticaseibacillus rhamnosus strain GG (LGG). The probiotics were added to the ascending colon region of mature microbial communities established in a human intestinal microbial ecosystem simulator. Shotgun metagenomic sequencing and metabolome analysis suggested that the changes in microbial community composition corresponded with changes to metabolic output, and we can infer linkages between some metabolites and microorganisms. The in vitro method permits a spatially-resolved view of metabolic transformations under human physiological conditions. By this method, we found that tryptophan and tyrosine were mainly produced in the ascending colon region, while their derivatives were detected in the transverse and descending regions, revealing sequential amino acid metabolic pathways along with the colonic tract. The addition of LGG appeared to promote the production of indole propionic acid, which is positively associated with human health. Furthermore, the microbial community responsible for the production of indole propionic acid may be broader than is currently known.PMID:37297350 | DOI:10.3390/foods12112105

Cancers (Basel). 2023 Jun 1;15(11):3020. doi: 10.3390/cancers15113020.ABSTRACTPancreatic cancer (PC) is one of the deadliest cancers. Developing biomarkers for chemotherapeutic response prediction is crucial for improving the dismal prognosis of advanced-PC patients (pts). To evaluate the potential of plasma metabolites as predictors of the response to chemotherapy for PC patients, we analyzed plasma metabolites using high-performance liquid chromatography-mass spectrometry from 31 cachectic, advanced-PC subjects enrolled into the PANCAX-1 (NCT02400398) prospective trial to receive a jejunal tube peptide-based diet for 12 weeks and who were planned for palliative chemotherapy. Overall, there were statistically significant differences in the levels of intermediates of multiple metabolic pathways in pts with a partial response (PR)/stable disease (SD) vs. progressive disease (PD) to chemotherapy. When stratified by the chemotherapy regimen, PD after 5-fluorouracil-based chemotherapy (e.g., FOLFIRINOX) was associated with decreased levels of amino acids (AAs). For gemcitabine-based chemotherapy (e.g., gemcitabine/nab-paclitaxel), PD was associated with increased levels of intermediates of glycolysis, the TCA cycle, nucleoside synthesis, and bile acid metabolism. These results demonstrate the feasibility of plasma metabolomics in a prospective cohort of advanced-PC patients for assessing the effect of enteral feeding as their primary source of nutrition. Metabolic signatures unique to FOLFIRINOX or gemcitabine/nab-paclitaxel may be predictive of a patient's response and warrant further study.PMID:37296982 | DOI:10.3390/cancers15113020

Diagnostics (Basel). 2023 May 26;13(11):1864. doi: 10.3390/diagnostics13111864.ABSTRACTImprovements in the treatment of childhood cancer have considerably enhanced survival rates over the last decades to over 80% as of today. However, this great achievement has been accompanied by the occurrence of several early and long-term treatment-related complications major of which is cardiotoxicity. This article reviews the contemporary definition of cardiotoxicity, older and newer chemotherapeutic agents that are mainly involved in cardiotoxicity, routine process diagnoses, and methods using omics technology for early and preventive diagnosis. Chemotherapeutic agents and radiation therapies have been implicated as a cause of cardiotoxicity. In response, the area of cardio-oncology has developed into a crucial element of oncologic patient care, committed to the early diagnosis and treatment of adverse cardiac events. However, routine diagnosis and the monitoring of cardiotoxicity rely on electrocardiography and echocardiography. For the early detection of cardiotoxicity, in recent years, major studies have been conducted using biomarkers such as troponin, N-terminal pro b-natriuretic peptide, etc. Despite the refinements in diagnostics, severe limitations still exist due to the increase in the above-mentioned biomarkers only after significant cardiac damage has occurred. Lately, the research has expanded by introducing new technologies and finding new markers using the omics approach. These new markers could be used not only for early detection but also for the early prevention of cardiotoxicity. Omics science, which includes genomics, transcriptomics, proteomics, and metabolomics, offers new opportunities for biomarker discovery in cardiotoxicity and may provide an understanding of the mechanisms of cardiotoxicity beyond traditional technologies.PMID:37296716 | DOI:10.3390/diagnostics13111864

Cells. 2023 Jun 4;12(11):1540. doi: 10.3390/cells12111540.ABSTRACTZebrafish (Danio rerio) assays provide a versatile pharmacological platform to test compounds on a wide range of behaviors in a whole organism. A major challenge lies in the lack of knowledge about the bioavailability and pharmacodynamic effects of bioactive compounds in this model organism. Here, we employed a combined methodology of LC-ESI-MS/MS analytics and targeted metabolomics with behavioral experiments to evaluate the anticonvulsant and potentially toxic effects of the angular dihydropyranocoumarin pteryxin (PTX) in comparison to the antiepileptic drug sodium valproate (VPN) in zebrafish larvae. PTX occurs in different Apiaceae plants traditionally used in Europe to treat epilepsy but has not been investigated so far. To compare potency and efficacy, the uptake of PTX and VPN into zebrafish larvae was quantified as larvae whole-body concentrations together with amino acids and neurotransmitters as proxy pharmacodynamic readout. The convulsant agent pentylenetetrazole (PTZ) acutely reduced the levels of most metabolites, including acetylcholine and serotonin. Conversely, PTX strongly reduced neutral essential amino acids in a LAT1 (SLCA5)-independent manner, but, similarly to VPN specifically increased the levels of serotonin, acetylcholine, and choline, but also ethanolamine. PTX dose and time-dependent manner inhibited PTZ-induced seizure-like movements resulting in a ~70% efficacy after 1 h at 20 µM (the equivalent of 4.28 ± 0.28 µg/g in larvae whole-body). VPN treated for 1 h with 5 mM (the equivalent of 18.17 ± 0.40 µg/g in larvae whole-body) showed a ~80% efficacy. Unexpectedly, PTX (1-20 µM) showed significantly higher bioavailability than VPN (0.1-5 mM) in immersed zebrafish larvae, possibly because VPN in the medium dissociated partially to the readily bioavailable valproic acid. The anticonvulsive effect of PTX was confirmed by local field potential (LFP) recordings. Noteworthy, both substances specifically increased and restored whole-body acetylcholine, choline, and serotonin levels in control and PTZ-treated zebrafish larvae, indicative of vagus nerve stimulation (VNS), which is an adjunctive therapeutic strategy to treat refractory epilepsy in humans. Our study demonstrates the utility of targeted metabolomics in zebrafish assays and shows that VPN and PTX pharmacologically act on the autonomous nervous system by activating parasympathetic neurotransmitters.PMID:37296660 | DOI:10.3390/cells12111540

Cells. 2023 May 29;12(11):1501. doi: 10.3390/cells12111501.ABSTRACTGlycyrrhiza inflata Batalin is a medicinal licorice species that has been widely used by humans for centuries. Licochalcone A (LCA) is a characteristic flavonoid that accumulates in G. inflata roots with high economical value. However, the biosynthetic pathway and regulatory network of its accumulation remain largely unknown. Here we found that a histone deacetylase (HDAC) inhibitor nicotinamide (NIC) could enhance the accumulation of LCA and total flavonoids in G. inflata seedlings. GiSRT2, a NIC-targeted HDAC was functionally analyzed and its RNAi transgenic hairy roots accumulated much more LCA and total flavonoids than its OE lines and the controls, indicating a negative regulatory role of GiSRT2 in the accumulation of LCA and total flavonoids. Co-analysis of transcriptome and metabolome of RNAi-GiSRT2 lines revealed potential mechanisms in this process. An O-methyltransferase gene, GiLMT1 was up-regulated in RNAi-GiSRT2 lines and the encoded enzyme catalyzed an intermediate step in LCA biosynthesis pathway. Transgenic hairy roots of GiLMT1 proved that GiLMT1 is required for LCA accumulation. Together, this work highlights the critical role of GiSRT2 in the regulation of flavonoid biosynthesis and identifies GiLMT1 as a candidate gene for the biosynthesis of LCA with synthetic biology approaches.PMID:37296622 | DOI:10.3390/cells12111501

Cells. 2023 May 24;12(11):1462. doi: 10.3390/cells12111462.ABSTRACTThe ABC transporter ABCA7 has been found to be aberrantly expressed in a variety of cancer types, including breast cancer. We searched for specific epigenetic and genetic alterations and alternative splicing variants of ABCA7 in breast cancer and investigated whether these alterations are associated with ABCA7 expression. By analyzing tumor tissues from breast cancer patients, we found CpGs at the exon 5-intron 5 boundary aberrantly methylated in a molecular subtype-specific manner. The detection of altered DNA methylation in tumor-adjacent tissues suggests epigenetic field cancerization. In breast cancer cell lines, DNA methylation levels of CpGs in promoter-exon 1, intron 1, and at the exon 5-intron 5 boundary were not correlated with ABCA7 mRNA levels. By qPCR involving intron-specific and intron-flanking primers, we identified intron-containing ABCA7 mRNA transcripts. The occurrence of intron-containing transcripts was neither molecular subtype-specific nor directly correlated with DNA methylation at the respective exon-intron boundaries. Treatment of breast cancer cell lines MCF-7, BT-474, SK-BR3, and MDA-MB-231 with doxorubicin or paclitaxel for 72 h resulted in altered ABCA7 intron levels. Shotgun proteomics revealed that an increase in intron-containing transcripts was associated with significant dysregulation of splicing factors linked to alternative splicing.PMID:37296582 | DOI:10.3390/cells12111462

J Appl Microbiol. 2023 Jun 9:lxad120. doi: 10.1093/jambio/lxad120. Online ahead of print.ABSTRACTAIM: Metabolomics analysis using LC-HRESIMS of twelve extracts of Spongia irregularis associated actinomycetes for dereplication purposes in addition to evaluation of cytotoxic and antiviral activities of the extracts.METHODS AND RESULTS: In the present study, three actinomycetes belonging to the genera Micromonospora, Streptomyces, and Rhodococcus were recovered from the marine sponge Spongia irregularis. Applying OSMAC approach, each strain was fermented on four different media resulting in twelve extracts. All extracts were subjected to metabolomics analysis using LC-HRESIMS for dereplication purposes. Multivariate data statistical analysis was carried out for the differentiation between extracts. Additionally, the cytotoxic and anti-HCV potentials of extracts were evaluated. Most of extracts showed strong to moderate cytotoxicity effects against HepG-2, CACO-2 and MCF-7 cell lines with general IC50 range of 2.8-8.9 µg/mL. Moreover, the extracts of Micromonospora sp. UR44 using ISP2 and OLIGO media and Streptomyces sp. UR32 using ISP2 medium exhibited anti-HCV activity with IC50 of 4.5 ± 0.22, 3.8 ± 0.18 and 5.7 ± 0.15 µM, respectively.CONCLUSION: Metabolomic analysis of twelve extracts of Spongia irregularis associated actinomycetes led to identification of large number of secondary metabolites. Morever, investigation of cytotoxic and antiviral activities of the extracts revealed that only three extracts exhibited antiviral activity and 7 extracts exhibited cytotoxic activity.PMID:37296319 | DOI:10.1093/jambio/lxad120

Nat Commun. 2023 Jun 9;14(1):3390. doi: 10.1038/s41467-023-38859-x.ABSTRACTElucidating intracellular drug targets is a difficult problem. While machine learning analysis of omics data has been a promising approach, going from large-scale trends to specific targets remains a challenge. Here, we develop a hierarchic workflow to focus on specific targets based on analysis of metabolomics data and growth rescue experiments. We deploy this framework to understand the intracellular molecular interactions of the multi-valent dihydrofolate reductase-targeting antibiotic compound CD15-3. We analyse global metabolomics data utilizing machine learning, metabolic modelling, and protein structural similarity to prioritize candidate drug targets. Overexpression and in vitro activity assays confirm one of the predicted candidates, HPPK (folK), as a CD15-3 off-target. This study demonstrates how established machine learning methods can be combined with mechanistic analyses to improve the resolution of drug target finding workflows for discovering off-targets of a metabolic inhibitor.PMID:37296102 | DOI:10.1038/s41467-023-38859-x

Nat Commun. 2023 Jun 9;14(1):3403. doi: 10.1038/s41467-023-39040-0.ABSTRACTSquamous cell carcinoma antigen recognized by T cells 3 (SART3) is an RNA-binding protein with numerous biological functions including recycling small nuclear RNAs to the spliceosome. Here, we identify recessive variants in SART3 in nine individuals presenting with intellectual disability, global developmental delay and a subset of brain anomalies, together with gonadal dysgenesis in 46,XY individuals. Knockdown of the Drosophila orthologue of SART3 reveals a conserved role in testicular and neuronal development. Human induced pluripotent stem cells carrying patient variants in SART3 show disruption to multiple signalling pathways, upregulation of spliceosome components and demonstrate aberrant gonadal and neuronal differentiation in vitro. Collectively, these findings suggest that bi-allelic SART3 variants underlie a spliceosomopathy which we tentatively propose be termed INDYGON syndrome (Intellectual disability, Neurodevelopmental defects and Developmental delay with 46,XY GONadal dysgenesis). Our findings will enable additional diagnoses and improved outcomes for individuals born with this condition.PMID:37296101 | DOI:10.1038/s41467-023-39040-0

Nat Commun. 2023 Jun 9;14(1):3385. doi: 10.1038/s41467-023-39091-3.ABSTRACTSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19, generates multiple protein-coding, subgenomic RNAs (sgRNAs) from a longer genomic RNA, all bearing identical termini with poorly understood roles in regulating viral gene expression. Insulin and interferon-gamma, two host-derived, stress-related agents, and virus spike protein, induce binding of glutamyl-prolyl-tRNA synthetase (EPRS1), within an unconventional, tetra-aminoacyl-tRNA synthetase complex, to the sgRNA 3'-end thereby enhancing sgRNA expression. We identify an EPRS1-binding sarbecoviral pan-end activating RNA (SPEAR) element in the 3'-end of viral RNAs driving agonist-induction. Translation of another co-terminal 3'-end feature, ORF10, is necessary for SPEAR-mediated induction, independent of Orf10 protein expression. The SPEAR element enhances viral programmed ribosomal frameshifting, thereby expanding its functionality. By co-opting noncanonical activities of a family of essential host proteins, the virus establishes a post-transcriptional regulon stimulating global viral RNA translation. A SPEAR-targeting strategy markedly reduces SARS-CoV-2 titer, suggesting a pan-sarbecoviral therapeutic modality.PMID:37296097 | DOI:10.1038/s41467-023-39091-3

J Dairy Sci. 2023 Jun 7:S0022-0302(23)00332-6. doi: 10.3168/jds.2023-23226. Online ahead of print.ABSTRACTProton nuclear magnetic resonance (1H NMR) spectroscopy is acknowledged as one of the most powerful analytical methods with cross-cutting applications in dairy foods. To date, the use of 1H NMR spectroscopy for the collection of milk metabolic profile is hindered by costly and time-consuming sample preparation and analysis. The present study aimed at evaluating the accuracy of mid-infrared spectroscopy (MIRS) as a rapid method for the prediction of cow milk metabolites determined through 1H NMR spectroscopy. Bulk milk (n = 72) and individual milk samples (n = 482) were analyzed through one-dimensional 1H NMR spectroscopy and MIRS. Nuclear magnetic resonance spectroscopy identified 35 milk metabolites, which were quantified in terms of relative abundance, and MIRS prediction models were developed on the same 35 milk metabolites, using partial least squares regression analysis. The best MIRS prediction models were developed for galactose-1-phosphate, glycerophosphocholine, orotate, choline, galactose, lecithin, glutamate, and lactose, with coefficient of determination in external validation from 0.58 to 0.85, and ratio of performance to deviation in external validation from 1.50 to 2.64. The remaining 27 metabolites were poorly predicted. This study represents a first attempt to predict milk metabolome. Further research is needed to specifically address whether developed prediction models may find practical application in the dairy sector, with particular regard to the screening of dairy cows' metabolic status, the quality control of dairy foods, and the identification of processed milk or incorrectly stored milk.PMID:37296050 | DOI:10.3168/jds.2023-23226