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D-allulose, a naturally occurring monosaccharide, is present in small quantities in nature. It is considered a valuable low-calorie sweetener due to its low absorption in the digestive tract and zero energy for growth. Most of the recent efforts to produce D-allulose have focused on in vitro enzyme catalysis. However, microbial fermentation is emerging as a promising alternative that offers the advantage of combining enzyme manufacturing and product synthesis within a single bioreactor. Here, a novel approach was proposed for the efficient biosynthesis of D-allulose from glycerol using metabolically engineered Escherichia coli. FbaA, Fbp, AlsE, and A6PP were used to construct the D-allulose synthesis pathway. Subsequently, PfkA, PfkB, and Pgi were disrupted to block the entry of the intermediate fructose-6-phosphate (F6P) into the Embden−Meyerhof−Parnas (EMP) and pentose phosphate (PP) pathways. Additionally, GalE and FryA were inactivated to reduce D-allulose consumption by the cells. Finally, a fed-batch fermentation process was implemented to optimize the performance of the cell factory. As a result, the titer of D-allulose reached 7.02 g/L with a maximum yield of 0.287 g/g. • Design of a synthesis pathway capable of producing only D-allulose from glycerol. • Enhancing cell factory performance by gene knockout and fermentation optimization. • Substrate conversion was dramatically increased compared to Izumoring epimerization. • Using glycerol rather than hexoses theoretically facilitates product purification. • Development of a green route that is widely applicable to synthesizing rare sugars. [ABSTRACT FROM AUTHOR]

In classic galactosemia (CG) patients, aldose reductase (AR) converts galactose to galactitol. In a phase 1/2, placebo‐controlled study (NCT04117711), safety, pharmacokinetics (PK), and pharmacodynamics (PD) of govorestat were evaluated after single and multiple ascending doses (0.5‐40 mg/kg) in healthy adults (n = 81) and CG patients (n = 14). Levels of govorestat in plasma and cerebrospinal fluid (CSF) and blood levels of galactitol, galactose, and galactose‐1‐phosphate (Gal‐1p) were measured for population PK and PK/PD analyses. Govorestat was well tolerated. Adverse event frequency was comparable between placebo and govorestat. Govorestat PK displayed a 2‐compartment model with sequential zero‐ and first‐order absorption, and no effect of demographic factors. Multiple‐dose PK of govorestat was linear in the 0.5‐40 mg/kg range, and CSF levels increased dose dependently. Elimination half‐life was ∼10 h. PK/PD modeling supported once‐daily dosing. Change from baseline in galactitol was −15% ± 9% with placebo and −19% ± 10%, −46% ± 4%, and −51% ± 5% with govorestat 5, 20, and 40 mg/kg, respectively, thus was similar for 20 and 40 mg/kg. Govorestat did not affect galactose or Gal‐1p levels. In conclusion, govorestat displayed a favorable safety, PK, and PD profile in humans, and reduced galactitol levels in the same magnitude (∼50%) as in a rat model of CG that demonstrated an efficacy benefit on neurological, behavioral, and ocular outcomes. [ABSTRACT FROM AUTHOR]

IgA nephropathy (IgAN) is a genetically complex multifactorial trait. Over the past decade, population-based genome-wide association studies (GWAS) have identified more than 30 IgAN risk loci, providing novel perspectives on both the epidemiology of the disease and its underlying molecular mechanisms. In addition, the association between IgAN and galactose-deficient IgA1 (Gd-IgA1) presented another avenue for genetic exploration due to the heritability of the elevated serum Gd-IgA1 levels. These endeavors also yielded and enabled refinement of polygenic risk scores, which may help identify specific groups of individuals at significantly increased risks, leading to stratifications of medical treatments. In this review, we aim to explore the existing evidence for genetic causation in IgAN. We summarize the state of genetic research in IgAN and how it has led to the reformulation of the new pathogenesis model and novel therapeutic targets. [ABSTRACT FROM AUTHOR]

Aging is characterized by molecular damage from free radicals, leading to neural dysfunction and memory impairment. This study investigated using bioceramic material and colored light to mitigate neurodegenerative symptoms in aging rats. We assessed the effects of different color light spectrums on D-galactose-induced aging rats using the Morris water maze, novel object recognition, and open field tests. Findings revealed that bioceramic material with various light wavelengths improved activity, recognition, and memory in aging rats. Significant enhancements were observed in the open field and novel object recognition tests, with a trend toward improvement in the Morris water maze. These effects are attributed to the antioxidant properties and microcirculation enhancement associated with bioceramic materials. Color stimulation may impact enzymes, human physiology, psychological activity, and the autonomic nervous system. This study highlights the significance of exploring novel interventions for neurodegenerative symptoms and memory deficits in aging rats. Results indicate that bioceramic material with different colored light spectrums positively influences cognitive function. These findings contribute to our understanding of the therapeutic potential of bioceramic materials and emphasize the need for further research in this area. [ABSTRACT FROM AUTHOR]

Pseudomonas putida have emerged as promising biocatalysts for the conversion of sugars and aromatic compounds obtained from lignocellulosic biomass. Understanding the role of carbon catabolite repression (CCR) in these strains is critical to optimize biomass conversion to fuels and chemicals. The CCR functioning in P. putida M2, a strain capable of consuming both hexose and pentose sugars as well as aromatic compounds, was investigated by cultivation experiments, proteomics, and CRISPRi-based gene repression. Strain M2 co-utilized sugars and aromatic compounds simultaneously; however, during cultivation with glucose and aromatic compounds (p-coumarate and ferulate) mixture, intermediates (4-hydroxybenzoate and vanillate) accumulated, and substrate consumption was incomplete. In contrast, xylose-aromatic consumption resulted in transient intermediate accumulation and complete aromatic consumption, while xylose was incompletely consumed. Proteomics analysis revealed that glucose exerted stronger repression than xylose on the aromatic catabolic proteins. Key glucose (Eda) and xylose (XylX) catabolic proteins were also identified at lower abundance during cultivation with aromatic compounds implying simultaneous catabolite repression by sugars and aromatic compounds. Reduction of crc expression via CRISPRi led to faster growth and glucose and p-coumarate uptake in the CRISPRi strains compared to the control, while no difference was observed on xylose+p-coumarate. The increased abundances of Eda and amino acid biosynthesis proteins in the CRISPRi strain further supported these observations. Lastly, small RNAs (sRNAs) sequencing results showed that CrcY and CrcZ homologues levels in M2, previously identified in P. putida strains, were lower under strong CCR (glucose+p-coumarate) condition compared to when repression was absent (p-coumarate or glucose only).IMPORTANCEA newly isolated Pseudomonas putida strain, P. putida M2, can utilize both hexose and pentose sugars as well as aromatic compounds making it a promising host for the valorization of lignocellulosic biomass. Pseudomonads have developed a regulatory strategy, carbon catabolite repression, to control the assimilation of carbon sources in the environment. Carbon catabolite repression may impede the simultaneous and complete metabolism of sugars and aromatic compounds present in lignocellulosic biomass and hinder the development of an efficient industrial biocatalyst. This study provides insight into the cellular physiology and proteome during mixed-substrate utilization in P. putida M2. The phenotypic and proteomics results demonstrated simultaneous catabolite repression in the sugar-aromatic mixtures, while the CRISPRi and sRNA sequencing demonstrated the potential role of the crc gene and small RNAs in carbon catabolite repression.

Summary: This study investigated the effects of reducing sugars and protein‐to‐sugar ratios on generating volatile compounds from nutritional yeast hydrolysates after Maillard reaction. Nutritional yeast extract (NYE) was cleaved using Flavourzyme® at an enzyme‐to‐substrate ratio of 0.5% w/w, followed by heat treatment with varying concentrations of reducing sugars (i.e., hexoses: glucose and fructose and pentoses: xylose and ribose). The results showed that pentoses generate higher numbers and concentrations of volatiles than hexoses, especially furans, Strecker aldehydes, and sulphur‐containing compounds such as dimethyl disulphide. However, hexoses produced higher concentrations of pyrazines. Strecker aldehydes and pyrazines served as key aroma‐active compounds in meat aroma. Likewise, sulphur‐containing compounds played an important role in meat aroma due to their low detection threshold. The results showed that reducing sugars significantly impacts the volatile profile of NYE, potentially influencing the formation of meaty aroma compounds. These findings demonstrate the potential of MRPs to enhance meaty flavours due to the presence of volatile compounds with characteristics of cooked meat. [ABSTRACT FROM AUTHOR]

Summary: The 'assimilates inhibition hypothesis' posits that accumulation of nonstructural carbohydrates (NSCs) in leaves reduces leaf net photosynthetic rate, thus internally regulating photosynthesis. Experimental work provides equivocal support mostly under controlled conditions without identifying a particular NSC as involved in the regulation.We combined 3‐yr in situ leaf gas exchange observations (natural dynamics) in the upper crown of mature Betula pendula simultaneously with measurements of concentrations of sucrose, hexoses (glucose and fructose), and starch, and similar measurements during several one‐day shoot girdling (perturbation dynamics). Leaf water potential and water and nitrogen content were measured to account for their possible contribution to photosynthesis regulation.Leaf photosynthetic capacity (A/Ci) was temporally negatively correlated with NSC accumulation under both natural and perturbation states. For developed leaves, leaf hexose concentration explained A/Ci variation better than environmental variables (temperature history and daylength); the opposite was observed for developing leaves.The weaker correlations between NSCs and A/Ci in developing leaves may reflect their strong internal sink strength for carbohydrates. By contrast, the strong decline in photosynthetic capacity with NSCs accumulation in mature leaves, observed most clearly with hexose, and even more tightly with its constituents, provides support for the role of assimilates in regulating photosynthesis under natural conditions. [ABSTRACT FROM AUTHOR]

Background: This study aimed to identify the specific areas of knowledge gaps regarding lactose intolerance among neonatologists in Chinese outpatient settings as well as to assess the availability of lactose intolerance testing in hospitals. Methods: A total of 278 neonatologists in outpatient settings from 144 hospitals were surveyed. To explore the awareness level, diagnosis, and treatment of neonatal lactose intolerance among neonatologists in outpatient settings, a multicenter cross-sectional survey was designed. Descriptive analysis based on frequency and percent distribution was performed for all variables. Results: Most respondents were senior doctors (256, 92.09%) from general hospitals and maternity/maternal and child health hospitals, had over 10 years of experience, and were dominantly associate chief physicians and chief physicians (211, 75.90%). A significant proportion of the participants (236, 84.89%) believed that neonatal lactose intolerance tends to be overlooked during clinical practice. When the most common symptoms of neonatal lactose intolerance were surveyed, diarrhea was selected by 142 (51.08%) respondents, followed by bloating and milk regurgitation or emesis (71, 25.54%). Other symptoms included unexplained crying (36, 12.85%), stool with milk flap or foam (15, 5.40%), and increased venting (14, 5.04%). Furthermore, the survey results indicated that the most common method for diagnosing neonatal lactose intolerance in the respondents' hospitals was qualitative test for urinary galactose (78, 28.06%). Of the respondents, 137 (49.28%) stated that their hospital could not test for lactose intolerance. For treating lactose intolerance, the neonatologists primarily opted for exogenous lactase rather than lactose-free formula milk. Conclusions: This study sheds light on Chinese neonatologists' awareness of neonatal lactose intolerance, revealing some knowledge gaps. The expeditious popularization and conduct of lactose intolerance-related examinations in hospitals will have a positive stimulative effect on the management of lactose intolerance in newborns. [ABSTRACT FROM AUTHOR]

Agave tequilana stems store fructan polymers, the main carbon source for tequila production. This crop takes six or more years for industrial maturity. In conducive conditions, agave wilt disease increases the incidence of dead plants after the fourth year. Plant susceptibility induced for limited photosynthates for defense is recognized in many crops and is known as "sink-induced loss of resistance". To establish whether A. tequilana is more prone to agave wilt as it ages, because the reduction of water-soluble carbohydrates in roots, as a consequence of greater assembly of highly polymerized fructans, were quantified roots sucrose, fructose, and glucose, as well as fructans in stems of agave plants of different ages. The damage induced by inoculation with Fusarium solani or F. oxysporum in the roots or xylem bundles, respectively, was recorded. As the agave plant accumulated fructans in the stem as the main sink, the amount of these hexoses diminished in the roots of older plants, and root rot severity increased when plants were inoculated with F. solani, as evidence of more susceptibility. This knowledge could help to structure disease management that reduces the dispersion of agave wilt, dead plants, and economic losses at the end of agave's long crop cycle. [ABSTRACT FROM AUTHOR]

Anti-proliferative and antioxidant activities of Pleurotus pulmonarius and P. citrinopileatus water-soluble polysaccharides were examined using human colon adenocarcinoma (HT29) and human normal colonic epithelial (CCD841 CoTr) cell lines in vitro. Polysaccharides were prepared by cold and hot water extraction methods and chemically characterized. The monosaccharide analysis showed that all the preparations contained hexoses--mannose, glucose, galactose, and 3-O-methyl-hexose (identified as 3-O-methyl-galactose)--as well as trace amounts of pentose identified as arabinose. Linkage analysis, on the other hand, revealed a wide variety of monosaccharide linking bonds in the studied polysaccharides, depending on the polymer source and the method of isolation. Both fungal polysaccharide preparations with increasing concentrations showed lower DPPH free radical reducing activity. The degree of reduction depended on the origin of the compounds and the method of their preparation. Stimulation of nitric oxide (NOx) production by the tested cells was observed after their incubation with the polysaccharides. The tested compounds at lower concentrations (up to 500 µg/mL) did not significantly influence the metabolic activity of the tumor and normal cells after 24 h of incubation. The viability of the tumor and normal cells was limited after the impact of the polysaccharides in the concentration range of 25-1000 µg/mL. The hot and cold water isolated polysaccharides did not induce changes in the normal and tumor cell cytoskeleton organization. The paper presents newly prepared and characterized hot and cold isolated water-soluble polysaccharides with promising pro-health potential against tumor and normal human colon epithelium cells. [ABSTRACT FROM AUTHOR]

Hexose transporters (HXT) play a crucial role in the pathogenicity of Magnaporthe oryzae, serving not only as key facilitators for acquiring and transporting sugar nutrients to support pathogen development, but also as sugar sensors which receive transduction signals. The objective of this study is to investigate the impact of MoHXT1-3 on rice pathogenicity and hexose affinity. MoHXT1-3 deletion mutants were generated using CRISPR/Cas9 technology, and their affinity for hexose was evaluated through yeast complementation assays and electrophysiological experiments in Xenopus oocytes. The results suggest that MoHXT1 does not contribute to melanin formation or hexose transportation processes. Conversely, MoHXT2, despite displaying lower affinity towards the hexoses tested in comparison to MoHXT3, is likely to have a more substantial impact on pathogenicity. The analysis of the transcription profiles demonstrated that the deletion of MoHXT2 caused a decrease in the expression of MoHXT3, whereas the knockout of MoHXT3 resulted in an upregulation of MoHXT2 transcription. It is noteworthy that the MoHXT2M145K variant displayed an incapacity to transport hexoses. This investigation into the functional differences in hexose transporters in Magnaporthe oryzae provides insights into potential advances in new strategies to target hexose transporters to combat rice blast by blocking carbon nutrient supply. [ABSTRACT FROM AUTHOR]

Sugar transport proteins (STPs) are high‐affinity H+‐coupled hexose symporters. Recently, the contribution of STP13 to bacterial and fungal pathogen resistance across multiple plant species has garnered significant interest. Quantitative PCR analysis of source leaves, developing embryos, and seed coats of Phaseolus vulgarisL. (common bean) revealed that PvSTP13.1 was expressed in source leaves and seed coats throughout seed development. In contrast, PvSTP13.1 transcripts were detected at exceedingly low levels in developing embryos. To characterize the transport mechanism, PvSTP13.1 was expressed in Xenopus laevis oocytes, and inward‐directed currents were analyzed using two‐electrode voltage clamping. PvSTP13.1 was shown to function as an H+‐coupled monosaccharide symporter exhibiting a unique high affinity for hexoses and aldopentoses at depolarized membrane potentials. Specifically, of the 31 assessed substrates, which included aldohexoses, deoxyhexoses, fructose, 3‐O‐methyl‐D‐glucose, aldopentoses, polyols, glycosides, disaccharides, trisaccharides, and glucuronic acid, PvSTP13.1 displayed the highest affinity (K0.5) for glucose (43 μM), mannose (92 μM), galactose (145 μM), fructose (224 μM), xylose (1.0 mM), and fucose (3.7 mM) at pH 5.6 at a depolarized membrane potential of −40 mV. The results presented here suggest PvSTP13.1 contributes to retrieval of hexoses from the apoplasmic space in source leaves and coats of developing seeds. [ABSTRACT FROM AUTHOR]

Single-cell RNA sequencing (scRNAseq) is a crucial tool in kidney research. These technologies cluster cells based on transcriptome similarity, irrespective of the anatomical location and order within the nephron. Thus, a transcriptome cluster may obscure the heterogeneity of the cell population within a nephron segment. Elevated dietary fructose leads to salt-sensitive hypertension, in part, through fructose reabsorption in the proximal tubule (PT). However, the organization of the four known fructose transporters in apical PTs (SGLT4, SGLT5, GLUT5, and NaGLT1) remains poorly understood. We hypothesized that cells within each subsegment of the proximal tubule exhibit complex, heterogeneous fructose transporter expression patterns. To test this hypothesis, we analyzed rat kidney transcriptomes and proteomes from publicly available scRNAseq and tubule microdissection databases. We found that microdissected PT-S1 segments consist of 81% ± 12% cells with scRNAseq-derived transcriptional characteristics of S1, whereas PT-S2 express a mixture of 18% ± 9% S1, 58% ± 8% S2, and 19% ± 5% S3 transcripts, and PT-S3 consists of 75% ± 9% S3 transcripts. The expression of all four fructose transporters was detectable in all three PT segments, but key fructose transporters SGLT5 and GLUT5 progressively increased from S1 to S3, and both were significantly upregulated in S3 vs. S1/S2 (Slc5a10: 1.9 log2FC, p < 1 × 10−299; Scl2a5: 1.4 log2FC, p < 4 × 10−105). A similar distribution was found in human kidneys. These data suggest that S3 is the primary site of fructose reabsorption in both humans and rats. Finally, because of the multiple scRNAseq transcriptional phenotypes found in each segment, our findings also imply that anatomical labels applied to scRNAseq clusters may be misleading. [ABSTRACT FROM AUTHOR]

Four new iridoid glycosides (1–4), rehmaglutosides L–O, were isolated from the air-dried roots of Rehmannia glutinosa. Their structures were established from the spectroscopic data obtained and by chemical evidence. The known mellittoside (5) and ajugol (6) were also obtained in the current investigation, and the structure of mellittoside was unequivocally defined using X-ray diffraction data. Compounds 1–6 were tested for their cytotoxicity against five human tumor cell lines and proliferation effects on Lactobacillus Reuteri. [ABSTRACT FROM AUTHOR]

Vitamaize lines (VMLs) were created by backcrossing the pigmented aleurone trait into Centro Internacional de Mejoramiento de Maíz y Trigo (CIMMYT) maize lines (CMLs). This study evaluates metabolic differences between the VMLs and their original CMLs. Direct infusion mass spectrometry (DIMS) analyses, carotenoid profiling, total anthocyanins content (TAC) determination, and biochemical evaluation of the quality protein maize (QPM) endosperm trait allowed a comprehensive chemical characterization of the maize lines. DIMS data indicate higher hexoses and trigonelline content for most VMLs; the carotenoid profile revealed a decrease in β-cryptoxanthin to less than half of the original parent content for two VMLs but an augmentation for one VML. The pigmented aleurone VMLs did not inherit the complex QPM endosperm trait of the QPM CMLs. Except for anthocyanin accumulation, no other metabolites were consistently modified across all the backcross-generated maize lines with a pigmented aleurone trait. These findings suggest using genetic or metabolic markers rather than morphological or visual traits for future breeding programs. [ABSTRACT FROM AUTHOR]

Vinyl‐substituted carbohydrates have been synthesized from glycals derived from hexoses and pentoses. Key step is the radical reaction of xanthates in the presence of triethylborane, a non‐toxic reagent. The mechanism has been investigated by isolation of various side products, which speak for a reversibility of the cyclopropylmethyl radical ring‐opening. Compared to reactions with tributyltin hydride, higher regioselectivities in favor of the 2‐vinyl‐substituted sugars have been obtained. Yields are slightly lower with triethylborane, but all products have been isolated in analytically pure form. The new reaction is applicable to benzyl‐ and silyl‐protected carbohydrates, which makes free sugars accessible as well. Overall, more than 15 1,2‐dideoxy‐2‐vinyl carbohydrates have been synthesized from simple precursors in only few steps. [ABSTRACT FROM AUTHOR]

Background: D-mannose, an epimer of glucose, which is abundant in some fruits, such as cranberry, has been previously reported to inhibit urinary tract infection. In recent years, the potential function of D-mannose has been broadened into the regulation of other inflammation diseases and cancer. It was reported that D-mannose can increase reactive oxygen species (ROS) production, while IDH2 is important for the generation of NADPH, the crucial reducing factor. These findings prompted us to determine whether D-mannose can regulate IDH2 and IDH2-mediated NADPH production in tumor. Methods: The breast cancer cell line MDA-MB-231 was cultured and treated with 100mM D-mannose. IDH2 expression was detected by Western Blot and qRT-PCR. RNA-seq was conducted to identify the differentially expressed genes. BioGRID database was used to find the IDH2 interactors. Tumor cells were collected to measure the NADPH production using the NADP+/NADPH detection Kit. Colony formation assay and CCK-8 assay were conducted to evaluate the proliferation of cells. Results: D-mannose can promote IDH2 protein degradation through ubiquitination-proteasome pathway. Mechanistically, D-mannose treatment upregulated the expression of an E3 ligase - RNF185, which can interact with IDH2 and promotes its proteasomal degradation. Consequently, IDH2-mediated NADPH production was inhibited by D-mannose, the proliferation of breast cancer cells was retarded, and the sensitivity to pro-oxidant of breast cancer cells was elevated. Conclusions: Our study demonstrated that D-mannose can degrade IDH2 and inhibit the production of NADPH to suppress the proliferation of breast cancer cells and render the breast cancer cells more sensitive to pro-oxidant treatment. Furthermore, we illustrated the E3 ligase RNF185 plays an important role in D-mannose-mediated proteasomal degradation of IDH2. [ABSTRACT FROM AUTHOR]

Successful yield in orchards is the culmination of a series of events that start with plants entering dormancy with adequate energy reserves (non-structural carbohydrates; NSC). These NSC are responsible for the maintenance of activities during dormancy and extending onto the period of activeness. Using multi-year yield information and monthly NSC content in twigs, we show that high levels of carbohydrate in Prunus dulcis, Pistachio vera, and Juglans regia during the winter months are indeed associated with high yield, while high levels of the NSC in late summer often correlate with low yield. An evaluation of monthly NSC level importance on yield revealed that for P. dulcis high levels in February were a good predictor of yield and that low levels throughout summer were associated with high yield. In P. vera, high levels of NSC in December were best predictors of yield. J. regia exhibited peculiar patterns; while high pre-budbreak reserves were associated with high yields they only played a minor role in explaining crop, the most important months for predicting yields were June and July. Results suggest that NSC levels can serve as good predictors of orchard yield potential and should be monitored to inform orchard management.

Background: Alzheimer's disease (AD) is the most prevalent neurodegenerative and remains incurable. Aluminum is a potent neurotoxin associated with AD. The main pathological features of AD are extracellular amyloid-β protein deposition and intracellular hyperphosphorylated Tau protein. A body of evidence suggest that oxidative stress and autophagy are involved in the pathogenesis of AD. Andrographis paniculata (AP) is a native plant with anti-inflammatory, anti-oxidative stress, and regulation of autophagy properties. AP significantly alleviated cognitive impairments, reduced Aβ deposition and has neuroprotective effect. However, its effects on aluminum-induced AD model have not been studied much. In this study, we investigated whether AP protect against aluminum-induced neurotoxicity through regulation of p62-Kelch-like ECH-associated protein 1(Keap1)-Nuclear factor E2 related factor 2 (Nrf2) pathway and activation autophagy in vivo and in vitro. Methods: UPLC-ESI-qTOF-MS/MS was used to identify the chemical constituents of AP ethanol extract. The mice with cognitive deficit were established by injecting aluminum chloride and D-galactose, and treated with either AP extract (200, 400, or 600 mg/kg/d) or andrographolide (2 mg/kg/2d).The spatial memory ability was detected by Morris water maze, HE staining were used to detect in brain tissue,Oxidative stress indexs and SOD activity in both serum and brain tissue were detected by kit.The expression of p62-Nrf2 pathway proteins were measured via western blotting. Furthermore, the neurotoxicity model was induced by aluminum maltolate (700 µM) in PC12 cells. Following AP and andrographolide treatment, the cell viability was detected. The relevant mRNA and protein expressions were detected in cells transfected with the p62 siRNA. Results: The main active components of AP included andrographolide, neoandrographolide and deoxyandrographolide as identified. AP and andrographolide significantly improved the spatial memory ability of mice, attenuated pathological changes of hippocampal cells, reduced the level of malondialdehyde, and increased superoxide dismutase activity in serum or brain tissue as compared to model control. In addition, the Nrf2, p62 and LC3B-II proteins expression were increased, and p-Tau and Keap1 proteins were decreased in the hippocampus after AP and andrographolide treatment.Furthermore, AP increased aluminum maltolate-induced cell viability in PC12 cells. Silencing p62 could reverse the upregulation expression of Nrf2 and downregulation of Keap1 and Tau proteins induced by AP in aluminum maltolate-treated cells. Conclusions: AP had neuroprotective effects against aluminum -induced cognitive dysfunction or cytotoxicity, which was involved in the activation of the p62-keap1-Nrf2 pathway and may develop as therapeutic drugs for the treatment of AD. However, this study has certain limitations, further optimize the protocol or model and study the molecular mechanism of AP improving AD. [ABSTRACT FROM AUTHOR]

Background: Distal symmetric sensorimotor polyneuropathy (DSPN) is a common neurologic complication of type 2 diabetes mellitus (T2DM), but the underlying mechanisms and changes in serum metabolites remain largely undefined. This study aimed to characterize the plasma metabolite profiles of participants with T2DM using targeted metabolomics analysis and identify potential biomarkers for DSPN. Methods: A combined liquid chromatography MS/MS and direct flow injection were used to quantify plasma metabolite obtained from 63 participants with T2DM, 81 with DSPN, and 33 nondiabetic control participants. A total of 130 metabolites, including amino acids, biogenic amines, sphingomyelins (SM), phosphatidylcholines, carnitines, and hexose, were analyzed. Results: A total of 16 plasma metabolites and 3 cholesterol‐related laboratory parameters were found to have variable importance in the projection score >1.0 and false discovery rate <5.0% between control, T2DM, and DSPN. Among these variables, five serum metabolites, including phenylalanine (AUC = 0.653), alanine (AUC = 0.630), lysine (AUC = 0.622) tryptophan (AUC = 0.620), and SM C16:0 (AUC = 0.630), are potential biomarkers (all p <.05) in distinguishing T2DM with DSPN from those without (AUC = 0.720). Conclusions: In this cross‐sectional study, derangement of several metabolites in the plasma was observed in T2DM with and without DSPN, and these metabolites may be potential biomarkers for predicting DSPN. Longitudinal studies are warranted. [ABSTRACT FROM AUTHOR]

Numerous studies have depicted the role of diet and environmental toxins in aging. Melamine (Mel) is a globally known notorious food adulterant, and its toxicity has been shown in several organs including the brain. However, till now, there are no reports regarding Mel neurotoxicity in aging neurons. So, this study examined the in vitro neurotoxicity caused by Mel in the D-galactose (DG)-induced aging model of neuronal SH-SY5Y cells. In the present study, the neuronal SH-SY5Y cells were treated with DG and Mel separately and in combination to assess the neurotoxicity potential using MTT assay and neurite length measurement. Further, the superoxide dismutase (SOD), catalase (CAT), and total antioxidant activities were evaluated followed by the determination of the intracellular reactive oxygen species (ROS), mitochondrial membrane potential (MMP), and caspase3 (Casp3) activity. The cotreatment of Mel and DG in neuronal SH-SY5Y cells showed maximum cell death than the cells treated with DG or Mel individually and untreated control cells. The neurite length shrinkage and ROS production were maximum in the DG and Mel cotreated cells showing exacerbated toxicity of Mel. The activity of SOD, CAT, and total antioxidants was also found to be lowered in the cotreatment group (Mel + DG) than in Mel- or DG-treated and untreated cells. Further, the combined toxicity of Mel and DG also elevated the Casp3 activity more than any other group. This is the first study showing the increased neurotoxic potential of Mel in an aging model of neuronal SH-SY5Y cells which implicates that Mel consumption by the elderly may lead to increased incidences of neurodegeneration like Alzheimer's disease and Parkinson's disease. [ABSTRACT FROM AUTHOR]

Background: This study investigated the effect of uteroplacental insufficiency (UPI) on renal development by detecting metabolic alterations in the kidneys of rats with intrauterine growth restriction (IUGR). Methods: On gestational day 17, pregnant Sprague Dawley rats were selected and allocated randomly to either the IUGR group or the control group. The IUGR group received a protocol involving the closure of bilateral uterine vessels, while the control group underwent a sham surgery. The rat pups were delivered on gestational day 22 by natural means. Pups were randomly recruited from both the control and IUGR groups on the seventh day after birth. The kidneys were surgically removed to conduct Western blot and metabolomic analyses. Results: IUGR was produced by UPI, as evidenced by the significantly lower body weights of the pups with IUGR compared to the control pups on postnatal day 7. UPI significantly increased the levels of cleaved caspase-3 (p < 0.05) and BAX/Bcl-2 (p < 0.01) in the pups with IUGR. Ten metabolites exhibited statistically significant differences between the groups (q < 0.05). Metabolic pathway enrichment analysis demonstrated statistically significant variations between the groups in the metabolism related to fructose and mannose, amino and nucleotide sugars, and inositol phosphate. Conclusions: UPI alters kidney metabolism in growth-restricted newborn rats and induces renal apoptosis. The results of our study have the potential to provide new insights into biomarkers and metabolic pathways that are involved in the kidney changes generated by IUGR. [ABSTRACT FROM AUTHOR]

The use of all sugars from biomass fractionation – that is, hexoses and pentoses – is essential to develop feasible processes in a biorefinery context. Hexoses are converted into different products by most microorganisms. The main issue is the conversion of pentoses, especially when mixed with hexoses. Improving sugar conversion in co‐fermentation is a major challenge, which was explored in this work. Co‐culture using Saccharomyces cerevisiae and evolved Kluyveromyces marxianus strains was evaluated by screening using 24 deep‐well plates. Glucose depletion and 83% of xylose conversion were achieved with supplemented hemicellulosic hydrolysate medium (medium volume corresponding to 2/5 of deep‐well volume), and initial cell concentrations of 2.5 g L‐1 for each yeast, incubated at 150 rpm. The screening strategy provided reliable data that confirmed the co‐culture as a promising approach for the co‐assimilation of biomass‐derived sugars. The importance of aeration control for effective xylose assimilation was also pointed out. [ABSTRACT FROM AUTHOR]

The nature of alpha-D-mannose—natural aldohexose sugar, C-2 glucose epimer, whose intended use is for preventing urinary tract infections—in the interaction with E. coli is addressed in order to drive the issue of its regulatory classification as a medicinal product or medical device. PRISMA systematic review approach was applied; Delphi Panel method was used to target consensus on statements retrieved from evidence. Based on regulatory definitions and research evidence, the mechanism of D-mannose does not involve a metabolic or immunological action while there is uncertainty regarding the pharmacological action. Specific interaction between the product and the bacteria within the body occurs, but its nature is inert: it does not induce a direct response activating or inhibiting body processes. Moreover, the action of D-mannose takes place, even if inside the bladder, outside the epithelium on bacteria that have not yet invaded the urothelial tissue. Therefore, its mechanism of action is not directed to host structures but to structures (bacteria) external to the host's tissues. On the basis of current regulation, the uncertainty as regard a pharmacological action of alpha-D-mannose makes possible its medical device classification: new regulations and legal judgments can add further considerations. From a pharmacological perspective, research is driven versus synthetic mannosides: no further considerations are expected on alpha-D-mannose. [ABSTRACT FROM AUTHOR]

An artificial CO 2 -to-sugars roadmap displayed high CO 2 -sugar conversion rate and great degree of control over the product stereochemistry. [Display omitted] Developing artificial "CO 2 -sugar" platforms is meaningful for addressing challenges posed by land scarcity and climate change to the supply of dietary sugar. However, upcycling CO 2 into complex polyoxygenated carbohydrates involves several major challenges, including achieving enantioselective and thermodynamically driven transformation and expanding product repertoires while reducing energy consumption. We present a versatile chemoenzymatic roadmap based on aldol condensation, iso/epimerization, and dephosphorylation reactions for asymmetric CO 2 and H 2 assembly into sugars with perfect stereocontrol. In particular, we developed a minimum ATP consumption and the shortest pathway for bottom-up biosynthesis of the fundamental precursor, fructose-6-phosphate, which is valuable for synthesizing structure-diverse sugars and derivatives. Engineering bottleneck–associated enzyme catalysts aided in the thermodynamically driven synthesis of several energy-dense and functional hexoses, such as glucose and D -allulose, featuring higher titer (63 mmol L−1) and CO 2 -product conversion rates (25 mmol C L−1 h−1) compared to established in vitro CO 2 -fixing pathways. This chemical–biological platform demonstrated greater carbon conversion yield than the conventional "CO 2 -bioresource-sugar" process and could be easily extended to precisely synthesize other high-order sugars from CO 2. [ABSTRACT FROM AUTHOR]

As photoautotrophic organisms, plants produce an incredible spectrum of pigments, anti-herbivory compounds, structural materials and energic intermediates. These biosynthetic routes help plants grow, reproduce and mitigate stress. HEXOKINASE1 (HXK1), a metabolic enzyme and glucose sensor, catalyzes the phosphorylation of hexoses, a key introductory step for many of these pathways. However, previous studies have largely focused on the glucose sensing and signaling functions of HXK1, and the importance of the enzyme's catalytic function is only recently being connected to plant development. In this brief Spotlight, we describe the developmental significance of plant HXK1 and its role in plant metabolic pathways, specifically in glucose-6-phosphate production. Furthermore, we describe the emerging connections between metabolism and development and suggest that HXK1 signaling and catalytic activity regulate discrete areas of plant development. [ABSTRACT FROM AUTHOR]

Propolis samples were extracted from beehives using sharp knife the conventional method in the apiaries located in the Governorates of Sohag, Beheira, Qalubia, Ismailia, and Zagazig. Additionally, two varieties of bee propolis were collected using traps in this investigation as follows: Hand-cut fiber screens with circular holes in a diameter of 1 mm., Fiber mesh sheets (45*35 cm) were put onto the top bar of the combs. Hand - cut polypropylene plastic screens with round holes in diameter of 2mm. Plastic mesh sheets (45*35 cm) were set onto the top bar of the combs inside the honeybee hive presented. Eighty percent methanol was used to extract the samples. Bee propolis was analyzed using LC-MS spectral database, displayed the composition scrape that follows for each Governorate Sohag: ester or ether of tamarixetin - syringic, caffeic-hexose-tartaric, caffeic-quinic acids, gallic-vanillin and acetyl gallate. In Beheira: quinic-hexose, ferulic-hexose, synapticpentose or apigenin or one of its isomer malonate, apigenin and vanillic acid. In Qalubia: myricetin, coumaric-hexose-malonate, ferulic-hexose, synaptic pentose or apigenin or one of its isomer malonate. In Ismailia: ferulic-hexose, synaptic-pentose or apigenin or one of its isomer malonate. In Zagazig: Cyanidin, pelargonidin or apigeninidin with benzoic, hydroxyl benzoic. Based on the results of analysis the biological effect of each separated component has been studied. [ABSTRACT FROM AUTHOR]

Simple Summary: In recent years, there has been a notable rise in the incidence of breast cancer among young patients. These young patients exhibit worse survival outcomes and distinct characteristics compared to intermediate and elderly patients. To address this issue, our study focuses on discerning the clinicopathological, genomics, transcriptional features unique to breast cancer in young patients. The ultimate goal is to explore potential therapeutic strategies that can enhance survival outcomes for this particular demographic. Notably, our work identified the novel correlations between galactose metabolism pathways, stemness, and survival outcomes, providing potential therapeutic interventions for young patients. In recent years, there has been a notable rise in the incidence of breast cancer among young patients, who exhibit worse survival outcomes and distinct characteristics compared to intermediate and elderly patients. Therefore, it is imperative to identify the specific features unique to young patients, which could offer insights into potential therapeutic strategies and improving survival outcomes. In our study, we performed an integrative analysis of bulk transcriptional and genomic data from extensive clinical cohorts to identify the prognostic factotrs. Additionally, we analyzed the single-cell transcriptional data and conducted in vitro experiments. Our work confirmed that young patients exhibited higher grading, worse disease-free survival (DFS), a higher frequency of mutations in TP53 and BRCA1, a lower frequency of mutations in PIK3CA, and upregulation of eight metabolic pathways. Notably, the galactose metabolism pathway showed upregulation in young patients and was associated with worse DFS. Further analysis and experiments indicated that the galactose metabolism pathway may regulate the stemness of cancer cells and ultimately contribute to worse survival outcomes. In summary, our finding identified distinct clinicopathological, transcriptional, and genomics features and revealed a correlation between the galactose metabolism pathway, stemness, and poor disease-free survival of breast cancer in young patients. [ABSTRACT FROM AUTHOR]

Sustainably produced renewable biomass has the potential to replace fossil-based feedstocks, for generation of biobased fuels and chemicals of industrial interest, in biorefineries. In this context, seaweeds contain a large fraction of carbohydrates that are a promising source for enzymatic and/or microbial biorefinery conversions. The thermoanaerobe Thermoanaerobacterium AK17 is a versatile fermentative bacterium producing ethanol, acetate and lactate from various sugars. In this study, strain AK17 was engineered for more efficient production of ethanol by knocking out the lactate and acetate side-product pathways. This was successfully achieved, but the strain reverted to acetate production by recruiting enzymes from the butyrate pathway. Subsequently this pathway was knocked out and the resultant strain AK17_M6 could produce ethanol close to the maximum theoretical yield (90%), leading to a 1.5-fold increase in production compared to the wild-type strain. Strain AK17 was also shown to successfully ferment brown seaweed hydrolysate from Laminaria digitata to ethanol in a comparatively high yield of 0.45 g/g substrate, with the primary carbon sources for the fermentations being mannitol, laminarin-derived glucose and short laminari-oligosaccharides. As strain AK17 was successfully engineered and has a wide carbohydrate utilization range that includes mannitol from brown seaweed, as well as hexoses and pentoses found in both seaweeds and lignocellulose, the new strain AK17_M6 obtained in this study is an interesting candidate for production of ethanol from both second and third generations biomass. [ABSTRACT FROM AUTHOR]

Objective: To explore the possible effects and mechanism of Zhizhu Decoction (ZZD) on the pathophysiology of slow transit constipation (STC). Methods: A total of 54 C57BL/6 mice was randomly divided into the following 6 groups by a random number table, including control, STC model (model), positive control, and low-, medium- and high-doses ZZD treatment groups (5, 10, 20 g/kg, namely L, M-, and H-ZZD, respectively), 9 mice in each group. Following 2-week treatment, intestinal transport rate (ITR) and fecal water content were determined, and blood and colon tissue samples were collected. Hematoxylin-eosin and periodic acid-Schiff staining were performed to evaluate the morphology of colon tissues and calculate the number of goblet cells. To determine intestinal permeability, serum levels of lipopolysaccharide (LPS), low-density lipoprotein (LDL) and mannose were measured using enzyme-linked immunosorbent assay (ELISA). Western blot analysis was carried out to detect the expression levels of intestinal tight junction proteins zona-occludens-1 (ZO-1), claudin-1, occludin and recombinant mucin 2 (MUC2). The mRNA expression levels of inflammatory cytokines including tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, IL-4, IL-10 and IL-22 were determined using reverse transcription-quantitative reverse transcription reaction. Colon indexes of oxidative stress were measured by ELISA, and protein expression levels of colon silent information regulator 1/forkhead box O transcription factor 1 (SIRT1/FoxO1) antioxidant signaling pathway were detected by Western blot. Results: Compared with the model group, ITR and fecal moisture were significantly enhanced in STC mice in the M-ZZD and H-ZZD groups (P<0.01). Additionally, ZZD treatment notably increased the thickness of mucosal and muscular tissue, elevated the number of goblet cells in the colon of STC mice, reduced the secretion levels of LPS, LDL and mannose, and upregulated ZO-1, claudin-1, occludin and MUC2 expressions in the colon in a dose-dependent manner, compared with the model group (P<0.05 or P<0.01). In addition, ZZD significantly attenuated intestinal inflammation and oxidative stress and activated the SIRT1/FoxO1 signaling pathway (P<0.05 or P<0.01). Conclusion: ZZD exhibited beneficial effects on the intestinal system of STC mice and alleviated intestinal inflammation and oxidative stress via activating SIRT1/FoxO1 antioxidant signaling pathway in the colon. [ABSTRACT FROM AUTHOR]

Reaction of glucose or galactose was performed in arginine solution or phosphate buffer (pH 7.0) using a batch reactor at 110°C. The yields of products, pH, and absorbances at 280 and 420 nm were measured during the reaction. Fructose, mannose, and allulose were formed from glucose; tagatose, talose, and sorbose were done from galactose. The reaction proceeded more rapidly in arginine solution than in phosphate buffer. In arginine solution, yields of fructose and tagatose were 20% and 16%, respectively, after 30-min reaction; in phosphate buffer, they were 14% and 10%, respectively. However, in both reaction media, the pH drop and increase in absorbances continued even after the yield became almost constant. The absorbance increased particularly in the latter half of the reaction due to formation of browning products. Therefore, to avoid browning, the reaction should be stopped as soon as possible after the yield approaches its maximum value. [ABSTRACT FROM AUTHOR]

Simple Summary: There is a need to identify new translational prognostic biomarkers in head and neck cancer. Metabolomics, the study of small molecules resulting from cellular metabolism, is an emerging and promising field regarding head and neck cancer. We performed metabolomics on patients' blood prior to treatment and found that it can divide patients into high-risk and low-risk groups based on their cancer progression and survival. We believe our study provides compelling results to consider metabolomics as a translational prognostic biomarker and that it may offer novel information for patient risk stratification. With continued research, we hope to gain a fuller understanding of how metabolomics may aid in the early detection, prognosis, treatment monitoring, and targeted therapies of head and neck cancer. There is growing evidence that the metabolism is deeply intertwined with head and neck squamous cell carcinoma (HNSCC) progression and survival but little is known about circulating metabolite patterns and their clinical potential. We performed unsupervised hierarchical clustering of 209 HNSCC patients via pre-treatment plasma metabolomics to identify metabolic subtypes. We annotated the subtypes via pathway enrichment analysis and investigated their association with overall and progression-free survival. We stratified the survival analyses by smoking history. High-resolution metabolomics extracted 186 laboratory-confirmed metabolites. The optimal model created two patient clusters, of subtypes A and B, corresponding to 41% and 59% of the study population, respectively. Fatty acid biosynthesis, acetyl-CoA transport, arginine and proline, as well as the galactose metabolism pathways differentiated the subtypes. Relative to subtype B, subtype A patients experienced significantly worse overall and progression-free survival but only among ever-smokers. The estimated three-year overall survival was 61% for subtype A and 86% for subtype B; log-rank p = 0.001. The association with survival was independent of HPV status and other HNSCC risk factors (adjusted hazard ratio = 3.58, 95% CI: 1.46, 8.78). Our findings suggest that a non-invasive metabolomic biomarker would add crucial information to clinical risk stratification and raise translational research questions about testing such a biomarker in clinical trials. [ABSTRACT FROM AUTHOR]

Mammalian meat allergy can develop after tick bites that introduce the allergen galactose-α-1,3-galacotose, which is also found in non-primate mammalian meat. It is characterized by a delayed onset allergic reaction that can result in dermatological, gastrointestinal and/or anaphylactic symptoms. The condition is managed by avoiding the allergen (i.e. by abstaining from mammalian meat consumption) and further sensitization via tick bites; pharmacological options may be of use for symptom management. [ABSTRACT FROM AUTHOR]

Galactose and its metabolites, primarily derived from lactose, may have toxic effects on the ovary. We aimed to prospectively examine the associations of galactose and lactose intakes with the onset of natural menopause. The data of a population-based cohort study in a Japanese community (the Takayama study) initiated in 1992 were analysed, with follow-up data collected in 2002. Among the participants of the Takayama study, premenopausal women (n 3115) aged 35–56 years at baseline were included in this study. Dietary intake, including lactose and galactose was assessed only at baseline using a FFQ. The menopausal status and age at menopause were determined based on the participants' self-reports, and natural menopause was defined as the absence of menstruation for 12 months or more. Cox proportional hazards models were used to estimate the hazard ratios (HR) and 95 % CI. A total of 1790 women experienced natural menopause within the 10-year follow-up. Lactose and galactose intakes were associated with a later onset of natural menopause after adjusting for potential confounding factors and the HR (95 % CI) for the highest v. lowest quartile were 0·80 (0·69, 0·92) (P -trend = 0·001) in lactose and 0·86 (0·74, 1·00) in galactose (P -trend = 0·036), respectively. High intakes of lactose and galactose were associated with a later onset of natural menopause. Despite the presumed ovotoxicity effects, lactose and galactose intakes at usual levels may not be deleterious to the ovarian aging process among Japanese community-dwelling women. [ABSTRACT FROM AUTHOR]

Several sulfonated polymers, which are typical Brønsted acid catalysts, have been employed in the production of two biofuels: 5-ethoxymethylfurfural (EMF) and ethyl levulinate (EL) as main byproduct, and the catalytic results have been attributed to their different chemical and morphological properties. The Purolite CT275DR attained the best results from 5-hydroxymethylfurfural (HMF) with a 63% EMF yield after 16 h at 100 °C thanks to their more abundant superficial acid sites. Moreover, Purolite CT275DR was able to efficiently dehydrate and etherify fructose, with a total EMF plus EL yield of 65% after 24 h at 100 °C. When glucose or galactose were used as feedstock, alumina was utilized to provide Lewis acid sites, necessary for the transformation of aldoses in solution enabling a combined biofuel yield (EMF plus EL) of 40% from glucose after 24 h at 140 °C. With the study of the role of each catalyst, both Brønsted and Lewis acid catalysts (resin and alumina, respectively) were required to obtain considerable EMF yields from aldoses. The reutilization of the catalysts employed for 5 catalytic runs demonstrated that Purolite CT275DR suffers no appreciable loss of activity, but alumina showed progressive losses in activity in each cycle due to carbonaceous deposits and catalyst loss. [Display omitted] [ABSTRACT FROM AUTHOR]

Simple Summary: 5-fluorouracil (5-FU) has been the treatment of choice against colorectal cancer (CRC) for the past six decades. However, 5-FU exhibits high toxicity and drug resistance in CRC patients, highlighting the need for less toxic and more efficient treatments. The pentose phosphate pathway (PPP) is upregulated in cancer cells and promotes their survival. Recently, mannose has been reported to halt tumor growth and impair the PPP. We studied the effect of mannose, alone and in combination with 5-FU in human CRC cells and animal models. We have shown that mannose alone or in combination with 5-FU downregulated the PPP and enhanced the sensitivity of CRC cancer cells and tumors in mice to 5-FU. Therefore, this research may pave the way for better patient care. Colorectal cancer (CRC) is one of the leading cancers and causes of death in patients. 5-fluorouracil (5-FU) is the therapy of choice for CRC, but it exhibits high toxicity and drug resistance. Tumorigenesis is characterized by a deregulated metabolism, which promotes cancer cell growth and survival. The pentose phosphate pathway (PPP) is required for the synthesis of ribonucleotides and the regulation of reactive oxygen species and is upregulated in CRC. Mannose was recently reported to halt tumor growth and impair the PPP. Mannose inhibitory effects on tumor growth are inversely related to the levels of phosphomannose isomerase (PMI). An in silico analysis showed low PMI levels in human CRC tissues. We, therefore, investigated the effect of mannose alone or in combination with 5-FU in human CRC cell lines with different p53 and 5-FU resistance statuses. Mannose resulted in a dose-dependent inhibition of cell growth and synergized with 5-FU treatment in all tested cancer cell lines. Mannose alone or in combination with 5-FU reduced the total dehydrogenase activity of key PPP enzymes, enhanced oxidative stress, and induced DNA damage in CRC cells. Importantly, single mannose or combination treatments with 5-FU were well tolerated and reduced tumor volumes in a mouse xenograft model. In summary, mannose alone or in combination with 5-FU may represent a novel therapeutic strategy in CRC. [ABSTRACT FROM AUTHOR]

Background: Surface polysaccharides (SPs), such as lipopolysaccharide (O antigen) and capsular polysaccharide (K antigen), play a key role in the pathogenicity of Escherichia coli (E. coli). Gene cluster for polysaccharide antigen biosynthesis encodes various glycosyltransferases (GTs), which drive the process of SP synthesis and determine the serotype. Results: In this study, a total of 7,741 E. coli genomic sequences were chosen for systemic data mining. The monosaccharides in both O and K antigens were dominated by D-hexopyranose, and the SPs in 70–80% of the strains consisted of only the five most common hexoses (or some of them). The linkages between the two monosaccharides were mostly α-1,3 (23.15%) and β-1,3 (20.49%) bonds. Uridine diphosphate activated more than 50% of monosaccharides for glycosyltransferase reactions. These results suggest that the most common pathways could be integrated into chassis cells to promote glycan biosynthesis. We constructed a database (EcoSP, http://ecosp.dmicrobe.cn/) for browse this information, such as monosaccharide synthesis pathways. It can also be used for serotype analysis and GT annotation of known or novel E. coli sequences, thus facilitating the diagnosis and typing. Conclusions: Summarizing and analyzing the properties of these polysaccharide antigens and GTs are of great significance for designing glycan-based vaccines and the synthetic glycobiology. [ABSTRACT FROM AUTHOR]

Heat stress (HS) during late gestation implies unfavorable effects on dairy cows and their in-utero heat stressed offspring. The objective of the present study was to elucidate the effect of intrauterine (maternal) HS during the last week of gestation on blood metabolite concentrations of female dairy calves during their first week of life. We defined the mean temperature humidity index (mTHI) during the last gestation week of ≥60 as threshold for maternal HS. In this regard, we compared differences in metabolite concentrations of maternally heat stressed (MHSCALVES) (n = 14) and not heat stressed (NMHSCALVES) (n = 33) calves. We identified 15 metabolites from five different biochemical classes (phosphatidylcholines, cholesteryl esters, sphingomyelins, cresols and hexoses) as potential biomarkers for maternal HS in calves. The plasma concentrations of all significantly affected metabolites were lower in MHSCALVES when compared to NMHSCALVES. The effect of maternal HS during the last week of gestation on blood metabolite concentrations of the female offspring during the first week after birth might be due to HS induced intergenerational physiological alterations, impaired colostrum quality or epigenetic modifications of the calf genome. The results of this pilot study should be validated in ongoing fully standardized studies. [ABSTRACT FROM AUTHOR]

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Enzymatic hydrolysis of lactose is a crucial step to improve the efficiency and selectivity of membrane-based separations toward the recovery of milk oligosaccharides free from simple sugars. Response surface methodology was used to investigate the effects temperature (25.9 to 54.1 °C) and amount of enzyme (0.17 to 0.32% w/w) at 1, 2, and 4 h of reaction on the efficiency of lactose hydrolysis by Aspergillus oryzae β-galactosidase, preservation of major goat whey oligosaccharides, and on the de-novo formation of oligosaccharides. Lactose hydrolysis above 99% was achieved at 1, 2, and 4 h, not being significantly affected by temperature and amount of enzyme within the tested conditions. Formation of 4 Hexose (Hex) and 4 Hex 1 Hex and an increased de-novo formation of 2 Hex 1 N-Acetyl-Neuraminic Acid (NeuAc) and 2 Hex 1 N-Glycolylneuraminic acid (NeuGc) was observed in all treatments. Overall, processing conditions using temperatures ≤40 °C and enzyme concentration ≤0.25% resulted in higher preservation/formation of goat whey oligosaccharides.

Glucose, alcohol stillage and glycerol were used as substrates for bio-hydrogen production by the newly isolated strain Clostridium beijerinckii 6A1 under batch conditions. High molar yields of hydrogen from the studied organic substrates were observed. There was a neat difference in the metabolic pathways of substrate digestion when hexose-based substrate or glycerol were used. The products of glycerol digestion showed that a pathway with no formic acid formation as intermediate was probable. In this case, considerable concentrations of acetic and propionic acid (up to 6 g dm−3) and small amounts of butanol were observed after 48 h. When glucose or hexose-based substrates were used, considerable amounts of formic acid (up to 6 g dm−3), i.e., the pathway proposed for Clostridia mixed cultures, were appropriate for the observed process of hydrogen release. For these substrates, considerable amounts of propionic acid in concentrations up to 1 g dm−3 were observed. That is why the pathway proposed for mixed cultures seemed more appropriate for our experiments carried out with hexose-based substrates. When hexoses were used, substrate digestion stopped the formation of acetic acid, propionic acid and ethanol. Probably, these intermediates are inhibitors to the further digestion to other products. [ABSTRACT FROM AUTHOR]

Saccharomyces cerevisiae (S. cerevisiae) is the most widely used yeast in biotechnology in the world because its well-known metabolism and physiology as well as its recognized ability to ferment sugars such as hexoses. However, it does not metabolize pentoses such as arabinose and xylose, which are present in lignocellulosic biomass. Lignocellulose is a widely available raw material, with xylose content of approximately 35% of total sugars. This xylose fraction could be used to obtain high added-value chemical products such as xylitol. One of these yeasts isolated from a Colombian locality, designated as 202-3, showed interesting properties. 202-3 was identified through different approaches as a strain of S. cerevisiae, with an interesting consumption of xylose metabolizing into xylitol, in addition with excellent ability as a hexose fermenter with high ethanol yields and shows resistance to inhibitors present in lignocellulosic hydrolysates. The xylose metabolization by the 202-3 strain and their kinetics parameters had not been previously reported for any other natural strain of S. cerevisiae. These results suggest the great potential of natural strains for obtaining high value-added chemical products using sugars available in lignocellulosic biomass. [ABSTRACT FROM AUTHOR]

Different fractions of organic matter in surface sediments from three transects along the eastern margin of the Arabian Sea (AS) were quantified to determine the sources of organic matter, and also to study its impact on microbial community structure. From the extensive analyses of different biochemical parameters, it was evident that the distribution of total carbohydrate (TCHO), total neutral carbohydrate (TNCHO), proteins, lipids, and uronic acids (URA) concentrations and yield (% TCHO-C/TOC) are affected by organic matter (OM) sources and microbial degradation of sedimentary OM. Monosaccharide compositions from surface sediment was quantified to assess the sources and diagenetic fate of carbohydrates, suggesting that the deoxysugars (rhamnose plus fucose) had significant inverse relationship (r = 0.928, n = 13, p < 0.001) with hexoses (mannose plus galactose plus glucose) and positive relationship (r = 0.828, n = 13, p < 0.001) with pentoses (ribose plus arabinose plus xylose). This shows that marine microorganisms are the source of carbohydrates and there is no influence of terrestrial OM along the eastern margin of AS. During the degradation of algal material, the hexoses seem to be preferentially used by heterotrophic organisms in this region. Arabinose plus galactose (glucose free wt %) values between 28 and 64 wt% indicate that OM was derived from phytoplankton, zooplankton, and non-woody tissues. In the principal component analysis, rhamnose, fucose, and ribose form one cluster of positive loadings while glucose, galactose, and mannose form another cluster of negative loadings which suggest that during OM sinking process, hexoses were removed resulting in increase in bacterial biomass and microbial sugars. Results indicate sediment OM to be derived from marine microbial source along the eastern margin of AS. [ABSTRACT FROM AUTHOR]

N-(2-thioethyl)-2-aminobenzamide (TEAB), a novel glycan auxiliary, was synthesized and its utility was evaluated. The auxiliary was conjugated to glycans by reductive amination with the water-stable reagent 2-picoline borane complex. Glycan products, which ranged from 1 to 7 linked hexoses, were all isolated in yields ranging from 60% to 90% after purification by reverse-phase chromatography. The novel conjugate introduces a convenient, shelf-stable thiol directly onto the desired free glycans with purification advantages and direct modification with efficient reactions through alkenes, halides, epoxides, disulfides, and carboxylates in yields of 49% to 93%. Subsequently, a thiol-selective modification of the BSA protein was used to generate a neoglycoprotein with a bifunctional PEG–maleimide linker. To further illustrate the utility of a thiol motif, 2-thiopyridine activation of a thiol-containing support facilitated the covalent chromatographic purification of labeled glycans in yields up to 63%. Finally, initial proof of concept of implementation in a light printed microarray was explored and validated through FITC-labeled concanavalin A binding. In conclusion, the thiol-functionalized glycans produced greatly expand the diversity of bioconjugation tools that can be developed with glycans and enable a variety of biological investigations. [ABSTRACT FROM AUTHOR]

Background & Objective: Aging is a natural phenomenon which can cause changes in most organs and cells. Numerous mechanisms including oxidative stress and free radical generation is involved in the progression of the aging process. Pomegranate seed oil (PSO), has different therapeutic properties including anti)oxidant and anti-inflammatory effects. In this research, the effect of PSO against D)galactose-induced aging is investigated. Materials & Methods: D-galactose, 500 mg/kg, injected subcutaneously (S.C.) to induce aging in rats. Animals in treatment groups received PSO, 0.4 and 0.8 ml/kg intraperitoneally (i.p.). After 42 days, behavioral test was evaluated by passive avoidance (PA). Then animals killed, blood samples collected by cardiac puncture, and brain and liver removed. Levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) measured in serum. Malondialdehyde (MDA) and thiol contents of brain and liver homogenized tissue samples were determined. Results: D-galactose increased lipid-peroxidation in liver and brain tissues as well as elevation of ALT, AST, but the level of thiol contents decreased in homogenized tissues. Both doses of PSO attenuated d-galactose-induced injury in liver and brain by decreasing ALT, AST, MDA and elevation of thiol content. The PA test showed that PSO increased the latency time to enter the dark chamber compared to the control group. Conclusion: PSO decreased D-galactose-induced aging in rats via prevention of oxidative stress. This effect may be related to the presence of various compounds and their anti-oxidant properties, which is found in PSO. [ABSTRACT FROM AUTHOR]

The valorization of lignocellulosic biomass (LCB) holds critical importance within the circular economy framework. Xylose, a five-carbon monosaccharide and the second most abundant sugar in LCB, represents a versatile building block for industrial applications. However, its use in fermentation processes is less efficient compared to hexoses like glucose, primarily due to the yeast Saccharomyces cerevisiae inability to metabolize this pentose. As a result, current industrial processes for xylose often rely on chemical catalysis methods, such as reduction and hydrogenation, which can have significant environmental impacts. Transitioning to sustainable processes requires both effective xylose recovery from LCB and enhanced fermentation efficiency. This review highlights LCB deconstruction techniques that yield high xylose concentrations and explores the potential of various yeast species to produce biofuels and value-added biomolecules from this pentose. This review summarizes recent advancements and highlights the potential for developing highly efficient xylose bioprocessing methodologies for sustainable biomass utilization. [ABSTRACT FROM AUTHOR]

Maize, one of the most important crops in the food chain, is facing severe threats from the escalating incidence of drought stress worldwide. Maize grain development requires assimilate uptake from the attached cob, however, the spatial distribution of sugars (the main carbon assimilate) within ear and its relationship with grain development under drought stress remain unclear. Here, we systematically investigated the dynamics of sugars and starch in different sub-tissues of cob (pith, woody ring, pedicel, and glume) and grain at different regions (the apical, middle and basal) of the developing ear under drought stress during grain filling. Results showed that the major sugar within cob was sucrose, followed by hexoses (fructose and glucose) and starch. Spatially, sucrose was highest in the woody ring and decreased toward the pedicel and then grain, whilst the hexoses were higher in the grain and then the cob center (pith) but gradually decreased towards the pedicel. Under drought, sucrose and hexoses were significantly accumulated in the pedicel but reduced in the grain, revealing that sugar uptake from the pedicel by grain was blocked. Moreover, sugars were reduced in the apical and middle regions of cob but were promoted in the basal region by drought, suggesting a drought-suppressed sugar translocation within cob. Accordingly, grain weight in the apical, middle, and basal regions were reduced by 18.9 %, 11.3 %, and 10.8 %, with starch weight decreased by 25.2 %, 21.4 %, and 2.0 %, respectively, at maturity. Collectively, these results support that sugar uptake from the pedicel by the grain and upward translocation along the cob are associated with grain weight in response to drought. These findings firstly uncover the spatial patterns for sugars within ear to respond to drought stress and highlight the importance of sugar availability within cob in grain yield formation. • Spatial-temporal distributions of sugars in maize ear in response to drought. • Drought hinders assimilate uptake by grain from pedicel. • Drought hinders upward translocation of assimilate along the cob. • Grain weight loss is associated with stuck sugar translocation under drought. [ABSTRACT FROM AUTHOR]

Plants modify their carbon allocation as a response to low water availability. The objective of this study was to evaluate, using a 14CO2 pulse‐chase analysis, the effect of moisture restriction on biomass production in common bean plants var. OTI. The plants were maintained with irrigation until the beginning of pods filling; then, three groups were formed, kept at 100%, 75% or 50% field capacity (FC). After 10 days, 14CO2 gas was supplied to the plants for 4 hr. The plants were harvested at 1, 3 and 7 days after applying the label. Ripe fruits imported more than 50% of the total 14C. Particularly, the label presented greater changes in pericarps of stage III of pod development. The fructose concentration doubled that of the glucose and decreased with the pod age; sucrose concentration increased in pericarps in stages III and IV of pod development in relation to those in stage II. The sucrose decrease only in stage II pericarps on day 7, as well as the starch concentration that decreased by half in the 50% FC condition. The latter coincided with the highest amylolytic activity as evaluated in native gels. These findings open new opportunities to research the carbon allocation mechanism under moisture restriction. [ABSTRACT FROM AUTHOR]

Background: Current cancer immunotherapies have made tremendous impacts but generally lack high response rates, especially in ovarian cancer. New therapies are needed to provide increased benefits. One understudied approach is to target the large population of immunosuppressive tumor-associated macrophages (TAMs). Using inducible transgenic mice, we recently reported that upregulating nuclear factor-kappaB (NF-κB) signaling in TAMs promotes the M1, anti-tumor phenotype and limits ovarian cancer progression. We also developed a mannose-decorated polymeric nanoparticle system (MnNPs) to preferentially deliver siRNA payloads to M2, pro-tumor macrophages in vitro. In this study, we tested a translational strategy to repolarize ovarian TAMs via MnNPs loaded with siRNA targeting the inhibitor of NF-κB alpha (IκBα) using mouse models of ovarian cancer.Methods: We evaluated treatment with MnNPs loaded with IκBα siRNA (IκBα-MnNPs) or scrambled siRNA in syngeneic ovarian cancer models. ID8 tumors in C57Bl/6 mice were used to evaluate consecutive-day treatment of late-stage disease while TBR5 tumors in FVB mice were used to evaluate repetitive treatments in a faster-developing disease model. MnNPs were evaluated for biodistribution and therapeutic efficacy in both models.Results: Stimulation of NF-κB activity and repolarization to an M1 phenotype via IκBα-MnNP treatment was confirmed using cultured luciferase-reporter macrophages. Delivery of MnNPs with fluorescent payloads (Cy5-MnNPs) to macrophages in the solid tumors and ascites was confirmed in both tumor models. A three consecutive-day treatment of IκBα-MnNPs in the ID8 model validated a shift towards M1 macrophage polarization in vivo. A clear therapeutic effect was observed with biweekly treatments over 2-3 weeks in the TBR5 model where significantly reduced tumor burden was accompanied by changes in immune cell composition, indicative of reduced immunosuppressive tumor microenvironment. No evidence of toxicity associated with MnNP treatment was observed in either model.Conclusions: In mouse models of ovarian cancer, MnNPs were preferentially associated with macrophages in ascites fluid and solid tumors. Evidence of macrophage repolarization, increased inflammatory cues, and reduced tumor burden in IκBα-MnNP-treated mice indicate beneficial outcomes in models of established disease. We have provided evidence of a targeted, TAM-directed approach to increase anti-tumor immunity in ovarian cancer with strong translational potential for future clinical studies. [ABSTRACT FROM AUTHOR]