Ultra-high Performance Research Articles

Optimization of Ultra-High Performance Concrete Based on Response Surface Methodology and NSGA-II.

This study systematically investigated three influential factors-water-to-binder ratio, cement/sand ratio, and steel fiber content-that significantly impact the performance of ultra-high-performance concrete (UHPC). Utilizing the Response Surface Methodology (RSM) with a Central Composite Design (CCD), 20 carefully designed mix proportions underwent comprehensive experimental testing. Through rigorous statistical analysis, models were established to elucidate the complex relationships between the specified factors and the overall properties of UHPC. Variance analysis reveals significant effects of the three factors on UHPC performance, with workability and compressive strength increasing with higher cement/sand ratios while flexural strength decreases. Moreover, increased water-to-binder ratios exhibit substantial negative impacts on both 28-day compressive and flexural strengths. Despite adversely affecting workability, higher steel fiber dosages contribute positively to mechanical performance. Furthermore, Monte Carlo sampling and the multi-objective non-dominated sorting genetic algorithm-II (NSGA-II) were employed to validate the reliability of the statistical model and to conduct multi-objective optimization. The final UHPC mix design obtained consists of a cement/sand ratio of 1.12, a water/binder ratio of 0.16, and a steel fiber content of 2.94%. Experimental results yielded a slump flow of 802 mm, compressive strength of 122.7 MPa, and flexural strength of 24.3 MPa.

Experimental study on the seismic performance of two-storey UHPC modular building structure

Ultra-high performance concrete modular building is a new structural system in which the module units made by the factory with UHPC materials are transported to the site for assembly. To study the seismic performance of UHPC module building structures, a two-story full-scale module building structure made by UHPC is designed in this study. Lateral cyclic loading tests are performed to investigate the seismic performance of the module building structures. The bearing capacity, failure mode, stiffness degradation, hysteretic performance, residual deformation, and strain skeleton curve are analyzed. Results indicate that the specimen undergoes three stress stages: elasticity, yield, and ultimate under lateral cyclic loading. At ultimate load capacity, the maximum inter-story drift ratio reached 1/57, and the load-bearing capacity was approximately 1.20 times the yield strength. The average ductility factor of the specimens was 3.42. The cracks mainly appear at the bottom and top of the walls of the module unit, and initial cracks occur at the top of the wall of the upper module unit. The specimen exhibits excellent seismic performance, full hysteretic curves, good dissipation capacity and ductility. The four corners between module units are connected by grouting sleeves in a reliable way to transfer force, which can ensure the overall deformation requirements of the structure.

Bamboo fiber-enhanced UHPC: Early hydration and microstructural/mesoscale analysis

This study investigates the impact of incorporating bamboo fibers, a natural and renewable material, into ultra-high performance concrete (UHPC) on its early hydration, mechanical properties, internal relative humidity, autogenous shrinkage, and microstructure. The results show that adding bamboo fibers significantly improves various UHPC properties. Bamboo fibers regulate hydration and prolong the hydration process through their water absorption and retention abilities. With a fiber content of 1.0 vol percent (vol%), the compressive strength increases by 10.2 %, reaching 97.1 MPa, and at 2.0 vol%, flexural strength and toughness increase by 37.9 % and 739.5 %, respectively. Additionally, bamboo fibers help maintain internal relative humidity above 98 % during the first 7 days of curing and reduce autogenous shrinkage by up to 55.9 %. The fibers also optimize the microstructure by minimizing voids, with a 1.0 % fiber content reducing the void ratio to 1.64 %. This reduces large voids and improves the material's density. Overall, bamboo fibers show great promise in enhancing UHPC's structural performance and environmental adaptability while being a sustainable and cost-effective material.

Characterising and preventing the gut microbiota's inactivation of trifluridine, a colorectal cancer drug

The gut microbiome can metabolise hundreds of drugs, potentially affecting their bioavailability and pharmacological effect. As most gut bacteria reside in the colon, drugs that reach the colon in significant proportions may be most impacted by microbiome metabolism. In this study the anti-colorectal cancer drug trifluridine was used as a model drug for characterising metabolism by the colonic microbiota, identifying correlations between bacterial species and individuals’ rates of microbiome drug inactivation, and developing strategies to prevent drug inactivation following targeted colonic delivery. High performance liquid chromatography and ultra-high performance liquid chromatography coupled with high resolution tandem mass spectrometry demonstrated trifluridine's variable and multi-route metabolism by the faecal microbiota sourced from six healthy humans. Here, four drug metabolites were linked to the microbiome for the first time. Metagenomic sequencing of the human microbiota samples revealed their composition, which facilitated prediction of individual donors’ microbial trifluridine inactivation. Notably, the abundance of Clostridium perfringens strongly correlated with the extent of trifluridine inactivation by microbiota samples after 2 hours (R2 = 0.8966). Finally, several strategies were trialled for the prevention of microbial trifluridine metabolism. It was shown that uridine, a safe and well-tolerated molecule, significantly reduced the microbiota's metabolism of trifluridine by acting as a competitive enzyme inhibitor. Further, uridine was found to provide prebiotic effects. The findings in this study greatly expand knowledge on trifluridine's interactions with the gut microbiome and provide valuable insights for investigating the microbiome metabolism of other drugs. The results demonstrate how protection strategies could enhance the colonic stability of microbiome-sensitive drugs.

Experimental study on the flexural behavior of reinforced concrete beam strengthened with novel prefabricated HSSM-UHPC thin plate

Ultra-high performance concrete (UHPC) has been used to strengthen reinforced concrete (RC) structures recently. Although UHPC has high compressive strength, the tensile strength is still low and, the high curing condition on site requirements of UHPC may hinder the further application in complex condition. In this study, a novel prefabricated UHPC thin plate, which is reinforced with high-strength steel wire strand meshes (HSSM), is proposed for rapidly strengthening RC beams. In order to understand the flexural performance of RC beams strengthened with the prefabricated HSSM-UHPC thin plate, four-point bending tests were conducted on three beams including one unstrengthened RC control beam (CB), one cast-in-place HSSM-UHPC strengthened beam (SUB) and one prefabricated HSSM-UHPC strengthened beam (PSUB). The failure modes of the beams were investigated and, the crack development process of the test beams was detailly observed by digital image correlation (DIC). Experiment results showed that compared with CB, the cracking, peak load of SUB and PSUB increased by 25.30%, 28.5% and 19.8%, 26.4%, respectively. However, the deflection ductility of the strengthened beams slightly decreased. Finally, calculation model and theoretical equation for predicting the cracking as well as peak flexural capacity of HSSM-UHPC plate strengthened beams were proposed. Comparison between theoretical and test results showed that the proposed model can accurately predict the cracking and peak capacity of the strengthened beams, and can be used for strengthening design.

Seismic behavior of composite shear walls with post-casting UHPC boundary elements and CRB600H steel bars

This study investigates the seismic behavior of composite shear walls reinforced with post-casting Ultra-High Performance Concrete (UHPC) boundary elements and Colded-Rolled Ribbed Bars (CRB600H). The research aims to explore the synergistic effects of UHPC and CRB600H bars on seismic performance. Six shear wall specimens with a shear span ratio of 1.56 were subjected to cyclic loading to evaluate their failure modes, crack patterns, hysteresis behavior, stiffness degradation, ductility, residual deformation, and energy dissipation capacity. The results demonstrated that the use of CRB600H bars in boundary elements of normal concrete specimens improved post-yield stiffness and reduced residual deformation. Conversely, incorporating UHPC in boundary elements enhanced load-bearing capacity and crack control but slightly reduced ductility due to the weaker interfacial connection between UHPC and the foundation. Additionally, CRB600H bars in the web region improved load-bearing capacity while maintaining ductility comparable to HRB400 bars. The findings suggest that substituting CRB600H for HRB400 in shear-dominant regions can enhance the seismic performance of shear walls. Finally, the multi-layer shell element numerical model validated by the experimental results was encouraged to conduct parametric analysis in the future. This research supports the development of more resilient building structures by integrating high-performance materials in key structural components.

Synergizing Proton‐Dominated Storage and Electron Transfer for High‐Loading, Fast‐Rate Organic Anode in Metal‐Free Aqueous Zinc‐Ion Batteries

AbstractDeveloping suitable anode materials to fabricate metal‐free Zinc ion battery is a promising strategy to solve the issues of Zn metal anode, such as dendrite growth and side reactions. However, the reported anode materials face shortcomings such as unsatisfactory rate performance, low mass loading, etc. Herein, featuring synergetic proton‐dominated storage and electron transfer, a conjugated polyimide nanocomposite trapped by multi‐walled carbon nanotubes (PPN‐MWCNT) is developed for high‐loading, fast‐rate organic anode materials in metal‐free Zinc ion battery. Specifically, abundant hydrophilic active sites and nonplaner conjunctional structure in PPN achieve proton‐dominated storage with two steps four electrons mechanism, leading to fast ion diffusion, and the intimate contact between the polymer and MWCNT via in situ polymerization ensures the excellent charge transfer and robust structure. Thus, the PPN‐MWCNT electrode delivers low redox potential, ultrahigh rate performance (50 A g−1), superior loading capability (≈40 mg cm−2) and exceptional long‐term cyclability (over 12 000 cycles). More importantly, the full batteries assembled with PPN‐MWCNT anode and different cathodes deliver a high energy density of 106.4 Wh kg−1 (PPN‐MWCNT//MnO2) and 83.7 Wh kg−1 (PPN‐MWCNT//active carbon‐I2), exceeding the most reported metal‐free Zinc ion batteries.

B-170 Age-Specific reference intervals for ethanolamine plasmalogen species in red blood cells using liquid chromatography tandem mass spectrometry

Abstract Background Plasmalogens are critical membrane structural components that are mainly generated by de novo synthesis starting in peroxisomes. Hence, patients with defects in peroxisome biogenesis (PBD) exhibit markedly reduced plasmalogen levels. Plasmalogen ratios are traditionally measured by gas chromatography-mass spectrometry (GC-MS); however, this method entails a lengthy sample extraction and derivatization and does not report concentrations of individual plasmalogen species. We have developed a robust and easy-to-implement liquid chromatography-tandem mass spectrometry (LC-MS/MS) method to quantify the 18 most abundant ethanolamine plasmalogen (PlsEtn) species in packed red blood cells (RBCs). However, no reference intervals have been published for individual PlsEtn. Here, we describe the establishment of age-specific reference intervals for individual PlsEtn species and their total values (16:0, 18:0, 18:1 species, and total plasmalogens). Methods Plasmalogens were extracted using methanol containing two labeled internal standards, shaking for one hour at room temperature. Chromatographic separation was performed using an Acquity Premier BEH C18 UPLC column with a binary gradient of 5 mM ammonium acetate in water:methanol (15:85) and 5 mM ammonium acetate in methanol. Analysis was performed using a XEVO TQ-XS Mass Spectrometer with Ultra-High Performance Liquid Chromatography (Waters) in multiple reaction monitoring mode. Eighteen PlsEtn species were quantified using four commercially available standards; additionally, totals were calculated for 16:0, 18:0 or 18:1 species, and for total plasmalogens. Reference intervals were established using 376 RBCs from self-reported healthy volunteers and de-identified clinical samples referred for unrelated testing (182 females and 194 males; range 0 to 88 years). Data was analyzed using the R programming language. The study was approved by the Institutional Review Board of the University of Utah. Results Initial age groups were identified using a model-based clustering algorithm followed by iterative Harris-Boyd analysis. Finally, the adjacent groups were merged if their means differed by less than 10%. Once the final age groups were partitioned, data in each individual age group were analyzed using parametric or non-parametric statistics to determine reference intervals (95%, with 90%confidence intervals). PlsEtn species displayed the lowest concentration in the first few months of life, which increased in childhood until adolescence or adulthood (depending on PlsEtn). For most species, the concentrations increased over time reaching a plateau between 18 and 48 years of age, and then starting to decrease. The total values followed the same trend, with neonates showing significantly lower values compared to other age groups. Conclusions We applied a novel statistical approach to identify age groups and determine age-specific reference intervals for 18 individual PlsEtn in RBC and their totals. Lacking previously published data, this study is critical for supporting test implementation in clinical laboratories.

Quantification of Total Ketone Bodies in Biological Matrices Using Stable Isotope-Labeled Internal Standards and RP-UHPLC-MS/MS.

Acetoacetate (AcAc) and D-beta-hydroxybutyrate (D-βOHB), the two major ketone bodies found in circulation, are linked to multiple physiological and pathophysiological states. Therefore, analytical methodologies surrounding the quantification of total ketone body (TKB) concentrations in biological matrices are paramount. Traditional methods to quantify TKBs relied on indirect spectrophotometric assays with narrow dynamic ranges, which have been significantly improved upon by modern mass spectrometry (MS)-based approaches. However, the lack of stable isotope-labeled internal standards (ISs) for AcAc and the need to distinguish D-βOHB from its closely related structural and enantiomeric isomers pose significant obstacles. Here, we provide a protocol to synthesize and quantify a [13C] stable isotope-labeled IS for AcAc, which, in conjunction with a commercially available [2H] stable isotope-labeled IS for βOHB, allows TKBs to be measured across multiple biological matrices. This rapid (7min) analysis employs reverse phase ultra-high performance liquid chromatography (RP-UHPLC) coupled to tandem MS (MS/MS) to distinguish βOHB from three structural isomers using parallel reaction monitoring (PRM), providing excellent specificity and selectivity. Finally, a method is provided that distinguishes D-βOHB from L-βOHB using a simple one-step derivatization to produce the corresponding diastereomers, which can be chromatographically resolved using the same rapid RP-UHPLC separation with new PRM transitions. In summary, this method provides a rigorous analytical pipeline for the analysis of TKBs in biological matrices via leveraging two authentic stable isotope-labeled ISs and RP-UHPLC-MS/MS.

Chebulinic acid isolated from aqueous extracts of Terminalia chebula Retz inhibits Helicobacter pylori infection by potential binding to Cag A protein and regulating adhesion.

Terminalia chebula Retz, known as the King of Tibet, is considered a functional food in China, celebrated for its antioxidant, immune-modulating, antibacterial, and anti-inflammatory properties. Chebulinic acid, derived from aqueous extracts of Terminalia chebula Retz, is known for its anti-inflammatory properties. However, its potential as an anti-Helicobacter pylori (HP) agent has not been fully explored. Herein, we extracted the main compound from Terminalia chebula Retz using a semi-preparative liquid chromatography (LC) system and identified compound 5 as chebulinic acid through Ultra-high performance liquid chromatography-MS/MS (UPLC-MS/MS) and Nuclear Magnetic Resonance (NMR). To evaluate its role, we conducted minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) assays, scanning electron microscope (SEM) imaging, inhibiting kinetics curves, urea fast test, cell counting kit-8 (CCK-8) assay, western blot analysis, griess reagent system, and molecular docking. Our results showed that chebulinic acid effectively inhibited the growth of the HP strain ATCC 700392, damaged the HP structure, and exhibited selective antimicrobial activity without affecting normal epithelial cells GES-1. Importantly, it suppressed the expression of Cytotoxin-associated gene A (Cag A) protein, a crucial factor in HP infection. Molecular docking analysis predicted a strong affinity (-9.7 kcal/mol) between chebulinic acid and Cag A protein. Overall, our findings suggest that chebulinic acid acts as an anti-adhesive agent, disrupting the adhesion of HP to host cells, which is a critical step in HP infection. It also suppresses the Cag A protein. These results highlight the potential of chebulinic acid against HP infections.

A-066 Does essential fatty acid deficiency alter ethanolamine plasmalogen concentrations in red blood cells? Implications for clinical testing

Abstract Background Plasmalogens are glycerophospholipids characterized by a fatty alcohol at the sn-1 position, a polyunsaturated fatty acid at the sn-2 position, most commonly docosahexaenoic acid (DHA) or arachidonic acid, and a polar head group at the sn-3 position, mainly phosphoethanolamine. Markedly reduced plasmalogens are seen in peroxisome biogenesis defects, including Zellweger spectrum disorders (ZSD), since the first two steps of plasmalogen synthesis occur in peroxisomes. Disruption of the peroxisomal β-oxidation pathway also causes DHA deficiency in ZSD patients. Since plasmalogens are composed of fatty acids, the deficiency of DHA or other essential fatty acids could further decrease the plasmalogen level in ZSD patients and lower the results of plasmalogen testing in patients without ZSD. To test this hypothesis, we evaluated the impact of essential fatty acid (EFA) deficiency on plasmalogens in patients with ZSD and individuals with EFA deficiency due to unrelated causes. Methods Red blood cell (RBC) samples were obtained from individuals without ZSD referred to ARUP laboratories for clinical EFA testing (n = 80; age range: birth - 89 years), and from patients with ZSD (n = 7; age range birth - 9 years). Three ZSD patients were older and with a less severe phenotype. A total of 18 intact ethanolamine plasmalogen species were extracted from packed RBCs and quantified using a XEVO TQ-XS Mass Spectrometer in conjunction with Ultra-High Performance Liquid Chromatography (Waters). Total plasmalogen values were also calculated; plasmalogen deficiency was defined as ≤60% of age-matched control median. Fatty acids (FAs) were quantified by gas chromatography negative chemical ionization-mass spectrometry (GC-NCI-MS). EFA deficiency was diagnosed by increased Triene/Tetraene ratio (Mead acid/Arachidonic acid). Data was analyzed using Prism v.8.3.0 software (La Jolla, CA). The study was approved by the Institutional Review Board of the University of Utah. Results Out of the 80 samples from individuals without ZSD referred for EFA testing, 18% had normal fatty acid profile, 57% were receiving dietary supplements and 25% had elevated Triene/Tetraene ratio suggesting EFA deficiency. EFA deficiency was accompanied by low DHA only in two individuals without ZSD, whereas it was present in most of the samples from ZSD patients evaluated (5/7). None of the individuals without ZSD were deficient in plasmalogens. Moreover, when compared to individuals without ZSD with a normal FA profile, there was no significant difference observed with EFA deficiency or FA supplementation. Although our ZSD cohort is small, no correlation between EFA deficiency and plasmalogen levels was also seen in ZSD: 2 patients with milder phenotype had EFA deficiency but normal plasmalogens, 2 patients had EFA deficiency and low plasmalogens, 2 patients with low plasmalogens had low DHA without EFA deficiency, and 1 patient had low plasmalogens but normal EFA. Conclusions Plasmalogen quantitation in RBCs by LC-MS/MS is not significantly affected by EFA deficiency. Although more data is warranted to elucidate the correlation between plasmalogen levels and ZSD phenotype, plasmalogens can be within normal reference intervals in ZSD regardless of EFA status.

Biomass-based three-dimensional network porous carbon anodes derived from discontinuous activation for high performance Li-ion batteries

An approach of discontinuous activation and frozon-dry pretreatment toward a three-dimensional network porous carbon was proposed by using apple as the carbon source. The porous carbon, characterized by its high surface area and abundant porosity, was optimized through the manipulation of temperature and activator quantities during the activation process. The sample obtained by first calcining at 500 °C and then at 800 °C shows ultra-high rate electrochemical performance of over 900 mA h g−1 after 100 cycles and over 500 mA h g−1 after 500 cycles under the condition of charging and discharging current density of 0.2 A g−1 due to the high porosity. It is ascribed to the unique porous structure that can make the electrolyte and lithium ion transport and path short on the surface and inside the electrode material, further enhance its fast transport ability. The described approach represents an innovative and potentially impactful method for producing porous carbon electrodes with excellent electrochemical performance, particularly in the context of high-rate capability lithium-ion batteries.

Ultrahigh room and high − temperature mechanical properties of SiCf/SiC composites prepared by hybrid CVI and PIP methods: Effects of PIP temperature

Unidirectional (UD) SiCf/SiC composites were prepared using chemical vapor infiltration (CVI)-polymer infiltration and pyrolysis (PIP) hybrid procedure at different PIP temperatures of 1100 °C (1100PIP), 1300 °C (1300PIP), and 1500 °C (1500PIP). The effect of PIP temperature on the microstructure of each component was studied. Results showed that SiC fiber strength and interfacial shear strength (IFSS) were the main factors affecting the mechanical properties of the composite. At 1100 °C, the fiber was thermally stable and IFSS was high, due to which 1100PIP achieved ultrahigh mechanical performance with tensile strength of 901.0 ± 87.7 MPa, flexural strength of 2186.5 ± 192.5 MPa, and toughness of 80.6 ± 12.0 MPa·m1/2. At 1300 °C, IFSS decreased slightly, due to the crystallization of BN interphase. Hence, the mechanical performance of 1300PIP decreased slightly to 789.8 ± 42.9 MPa, 1935.9 ± 163.2 MPa, and 58.2 ± 4.0 MPa·m1/2, respectively. At 1500 °C, severe fiber ceramization and decrease in IFSS caused severe decline in mechanical performance to about half of that of 1100PIP. The crack could be deflected not only at the fiber/BN (F/B) interface, but also at the CVI SiC/PIP SiC (C/P) interface, due to the existence of free carbon layers at the C/P interface, which played an important role in improving the strength and toughness of the composite. 1300PIP also showed excellent strength at high − temperature. At 1350 °C and 1500 °C, its flexural strengths were as high as 1529.0 ± 73.0 MPa and 1223.1 ± 81.1 MPa, respectively. The thermal conductivity and thermal expansion coefficient were also tested. Their values were mainly affected by the grain size and thermal stabilities of the SiC fiber and PIP matrix.

Achieving ultra-high energy storage performance in simple systems through minimal element substitution

Dielectric capacitors are essential components of modern advanced electronic devices and power systems based on their ultra-fast charging and discharging speeds and supreme power densities. Nevertheless, how to comprehensively boost their energy storage density and storage efficiency is still an insurmountable challenge. Here, we report a simple micro-chemical polarizability modulation strategy that enables SrTiO3-based dielectric materials to achieve excellent energy storage properties. The energy density and energy efficiency are increased to as high as 76 J∙cm−3 and 72 % from 0.4 J∙cm−3 and 46.7 % of pure STO, respectively, which is the largest value in micro-substitution (less than 3 %). Our results show that the introduction of trace amounts of elements with high ionic polarizabilities (Mn, V) facilitates the increase of chemical disorder and the formation of stable and highly dynamic polar nanoregions (PNRs), which reduces the hysteresis of the polarization switching and improves the polarization at the breakdown field strength, synergistically fostering the energy storage performance. The results of X-ray photoelectron spectroscopy and scanning electron microscopy reveal that the micro-substitution of Mn and V promote the reduction of oxygen vacancies and grain size, improving the breakdown resistance and stability of the capacitor. This present approach is expected to be widely used in the development of high-performance dielectrics.

Monosaccharide composition and glycosidic linkages analysis by ultra high performance liquid chromatography-triple quadrupole tandem mass spectrometry—Case study of plant polysaccharides

Monosaccharide composition and glycosidic linkages analysis are essential for the structural characterization and biological activity research of polysaccharides. To simplify the analysis steps and improve detection efficiency, this study developed monosaccharide compositions and glycosidic linkages detection methods based on UPLC-QqQ-MS/MS, and established a plant polysaccharide glycosidic linkages library. Furthermore, the detailed analysis process of monosaccharide compositions and glycosidic linkages was presented through a plant polysaccharide (Chinese bayberry wine polysaccharide, CPW) example. The results showed that the monosaccharide analysis method could identify and quantify 20 monosaccharides within 13 min by 6 chromatograms. By this method, 7 monosaccharides were detected in CPW, which was consistent with previous results obtained using ion chromatography. Meanwhile, the UPLC-QqQ-MS/MS based method could analyze 112 glycosidic linkages of 9 plant monosaccharides within 30 min, and the results were distributed on 11 chromatograms. According to the approach, 44 different glycosidic linkages were identified in CPW. Based on Congo red assay and molecular weight as well as our findings of monosaccharide composition and glycosidic linkages, we proposed that CPW may consist of two distinct sugar chains: One composed of 1–2,4-Rha, 1–3,4-GalA, and 1-F-Ara, and the other composed of 1–3,4-Gal, 1–4-Gal, 1–3,4,6-Gal, and 1-F-Ara.

Low polarity fraction of Radix Bupleuri alleviates chronic unpredictable mild stress-induced depression in rats through FXR modulating bile acid homeostasis in liver, gut, and brain

Radix Bupleuri (BR, Bupleurum chinense DC.) is a well-known traditional Chinese medicine (TCM) known for its effects on soothing the liver and alleviating depression, and is widely used in clinical settings to manage depressive symptoms. A dosage of 12.5g crude drug/kg/d of the low-polarity fraction of Radix Bupleuri (LBR) demonstrated effectiveness in treating depression in our previous study. However, the mechanism through which BR ameliorates depression remains unclear. This study aimed to explore the polar fractions of BR and their mechanisms of action in the treatment of depression. Chronic unpredictable mild stress (CUMS) rats were continuously administered BR by oral gavage for 4 weeks. Behavioral and biochemical indicators were evaluated to assess the antidepressant effects of LBR, and transcriptomics was used to explore the relevant pathways. In addition, pseudo-targeted bile acid (BA) metabonomics was used to quantify the BA profiles. Molecular biology techniques have been used to investigate the underlying mechanisms. LBR serves as a more effective active fraction with antidepressant activity. Intervention with LBR, which is characterized by a clearly defined chemical composition, significantly ameliorated depression-like behavior and biochemical indicators in rats subjected to CUMS. Notably, marked improvements were observed in the levels of total bile acids (TBAs) in the blood, liver, and ileum. Mechanistically, liver transcriptome analysis suggested that bile secretion may be a crucial pathway for alleviating depression after LBR treatment. Ultra-high performance liquid chromatography-mass spectrometry (UPLC-MS) BA metabonomics indicated that TCA, β-MCA, γ-MCA, Tβ-MCA, and UDCA in the liver, Tβ-MCA, TCA, βMCA, GHDCA, and GLCA in the ileum, and β-MCA, CA, and DCA in the hippocampus were the potential therapeutic targets. In addition, molecular biology experiments showed that LBR exerts antidepressant effects by regulating the FXR/SHP/CYP7A1 pathway in the liver, the FXR/FGF15/ASBT pathway in the ileum, and the FXR/CREB/BDNF pathway in the hippocampus. In conclusion, LBR attenuated depression by moderating BA homeostasis through FXR and related genes within the liver-gut-brain axis.

Metabolomics of basal tears in amyotrophic lateral sclerosis: a cross-sectional study

PurposeAmyotrophic lateral sclerosis (ALS) clinical variability, along with the lack of conclusive diagnostic instruments, result in average diagnosis delays of 9 months. This study aimed to assess whether metabolomic profiling of basal tears in ALS patients could act as a biological marker for diagnosing ALS, predicting prognosis, and discriminating between endophenotypes. MethodsA single-center prospective case-control study was conducted in France from September 2021 to March 2023 including patients with ALS according to the revised EI Escorial criteria. Two microliters of basal tears were collected using microcapillary glass tubes and analyzed with ultra-high performance liquid chromatography coupled with mass spectrometry. Both univariate and multivariate analyses were performed. ResultsTwenty-five patients with ALS and 30 controls were included. No significant differences in metabolite levels were found between ALS and control groups (p>0.05). The basal tear metabolome significantly discriminated bulbar and spinal forms of ALS based on 6 metabolites, among which 5 were decreased (aniline, trigonelline, caffeine, theophylline and methyl beta-D-galactoside) in the bulbar form and 1 was decreased in the spinal form (dodecanedioic acid). ConclusionThis study represents the first prospective analysis of basal tear metabolomics in individuals with ALS. Despite the inability to distinguish between ALS patients and controls based on metabolic signatures, these findings could contribute to understanding the phenotypic diversity of ALS. Notably, distinct metabolic profiles were identified that differentiate between the bulbar and spinal forms of the disease.

Metabolic and cannflavin profiles of germinated hemp seed (Cannabis sativa L.)

This study aimed to identify the optimal germination period for maximizing cannflavin A (CFL-A) and cannflavin B (CFL-B) production in hemp seeds. Utilizing ultra-high performance liquid chromatograph with orbitrap mass spectrometry (uHPLCOrbitrap-MS/MS), the research measured metabolomic activities, complemented by spectrophotometric analysis of antioxidant activity. The findings indicated that CFL-A and CFL-B concentrations progressively increased, reaching a peak at 72 h. Notably, the polar compounds saw the emergence of 4-hydroxybenzaldehyde, a derivative of enzymatic sugar-to-aldehyde conversion. In contrast, the non-polar fraction exhibited a decrease in cannabidiolic acid levels. The study also noted the potential formation of alpha-linolenic acid (omega-3 fatty acid) through hydrolysis, which serves as an energy source for germination. Metabolomic profiles were categorized by Agglomerative Hierarchical Clustering (AHC) and Principal Component Analysis (PCA), revealing significant changes from Day 0 to Day 1, followed by relative stability until Day 3. A substantial reduction in DPPH IC50 values was observed from 93.00 mg/kg (Day 0) to 43.18 mg/kg (Day 3), indicated stronger radical scavenging capacity. The highest FRAP and TPC value was recorded on Day 3, reflecting the accumulation of bioactive compounds, resulting in improved antioxidant activity.

Development of an untargeted DNA adductomics method by ultra-high performance liquid chromatography coupled to high-resolution mass spectrometry

Genotoxicants originating from inflammation, diet, and environment can covalently modify DNA, possibly initiating the process of carcinogenesis. DNA adducts have been known for long, but the old methods allowed to target only a few known DNA adducts at a time, not providing a global picture of the “DNA adductome”. DNA adductomics is a new research field, aiming to screen for unknown DNA adducts by high resolution mass spectrometry (HRMS). However, DNA adductomics presents several analytical challenges such as the need for high sensitivity and for the development of effective screening approaches to identify novel DNA adducts. In this work, a sensitive untargeted DNA adductomics method was developed by using ultra-high performance liquid chromatography (UHPLC) coupled via an ESI source to a quadrupole-time of flight mass spectrometric instrumentation. Mobile phases with ammonium bicarbonate gave the best signal enhancement. The MS capillary voltage, cone voltage, and detector voltage had most effect on the response of the DNA adducts. A low adsorption vial was selected for reducing analyte loss. Hybrid surface-coated analytical columns were tested for reducing adsorption of the DNA adducts. The optimized method was applied to analyse DNA adducts in calf thymus, cat colon, and human colon DNA by performing a MSE acquisition (all-ion fragmentation acquisition) and screening for the loss of deoxyribose and the nucleobase fragment ions. Fifty-four DNA adducts were tentatively identified, hereof 38 never reported before. This is the first untargeted DNA adductomics study on human colon tissue, and one of the few untargeted DNA adductomics studies in the literature reporting the identification of such a high number of unknowns. This demonstrates promising results for the application of this sensitive method in future human studies for investigating novel potential cancer-causing factors.

The impact protection behavior of UHPC composite structure on RC columns

In order to prevent the reinforced concrete (RC) structures from being damaged under the overload impact, a new type of composite structure—ultra-high performance concrete (UHPC)–Bio-inspired honeycomb column thin-walled structure (BHTS) was designed in this paper. A scale model with a scaling factor of 1:10 was made. The experimental tests and numerical simulations of RC column and UHPC composite structure were carried out. By comparing the impact force, displacement, shear force, bending moment and energy absorption, the protective effect of the UHPC-BHTS composite structure on RC columns under lateral impact load was evaluated. Then, the failure process of RC column was analyzed, the UHPC-BHTS composite structure absorbed 76.42% of the impact kinetic energy under the higher energy input condition, the shear failure with large damage to the RC column can be converted into bending failure with small damage. At the same time, a new damage assessment method was used to evaluate the RC column. The results show that the RC column with UHPC-BHTS composite structure can effectively protects the RC column structural integrity under impact. The design and modeling methods in this research can provide a useful reference for anti-collision design in practical engineering.