Least-squares Analysis Research Articles

A comprehensive quality evaluation of Cimicifugae Rhizoma using UPLC-Q-Orbitrap-MS/MS coupled with multivariate chemometric methods.

Cimicifugae Rhizoma, known in Chinese as Shengma, is a common medicinal material in traditional Chinese medicine (TCM), mainly used for treating wind-heat headaches, sore throat, uterine prolapse, and other diseases. An approach using a combination of ultra-performance liquid chromatography (UPLC), mass spectrometry (MS), and multivariate chemometric methods was designed to assess the quality of Cimicifugae Rhizoma. All materials were crushed into powder and the powdered sample was dissolved in 70% aqueous methanol for sonicating. Chemometric methods, including hierarchical cluster analysis (HCA), principal component analysis (PCA), and orthogonal partial least squares discriminant analysis (OPLS-DA), were adopted to classify and perform a comprehensive visualization study of Cimicifugae Rhizoma. The unsupervised recognition models of HCA and PCA obtained a preliminary classification and provided a basis for classification. In addition, we constructed a supervised OPLS-DA model and established a prediction set to further validate the explanatory power of the model for the variables and unknown samples. Exploratory work research found that the samples were divided into two groups, and the differences were related to appearance traits. The correct classification of the prediction set also demonstrates a strong predictive ability of the models for new samples. Subsequently, six chemical makers were characterized by UPLC-Q-Orbitrap-MS/MS, and the content of four components was determined. The results of the content determination revealed the distribution of representative chemical markers caffeic acid, ferulic acid, isoferulic acid, and cimifugin in two classes of samples. This strategy can provide a reference for assessing the quality of Cimicifugae Rhizoma, which is significant for the clinical practice and quality control of Cimicifugae Rhizoma.

Physiological Changes and Antioxidative Mechanisms of Alternanthera philoxeroides in Phytoremediation of Cadmium.

This study evaluated the physiological characteristics (e.g., growth parameters, chlorophyll content, metabolites and antioxidative enzymes activity) of Alternanthera philoxeroides (A. philoxeroides), as a hyperaccumulator plant, during the phytoremediation of cadmium (Cd) from water. After cultivating A. philoxeroides in a Cd-containing medium for 30 days, the growth rate was inhibited by up to 33.5% as the exposed Cd concentration increased to 0.80 mmol·L-1. Cd exposure interfered with the photosynthesis of A. philoxeroides and caused oxidative stress as indicated by the rise of malondialdehyde (MDA) and H2O2, which increased by 8 times and 3 times compared to the control group. Moreover, high exposure concentrations of Cd also reduced the activities of multiple antioxidants (e.g., GSH and AsA), indicating the inhibition of Cd on the plant's ability to mitigate oxidative damage. Finally, the fluorescent patterns of the rhizosphere dissolved organic matter (rDOM) revealed three major components (humic, fulvic substances and protein-like substances) well correlated with the changes in antioxidant activities. Partial least-squares discriminant analysis (PLS-DA) visualized the difference in the activity of the antioxidative enzymes between different groups. The study unravelled deep insights into the potential mechanisms of tolerance and resistance of A. philoxeroides for phytoremediation of Cd pollution.

Metabolomic analysis of Mycobacterium tuberculosis reveals metabolic profiles for identification of drug-resistant tuberculosis

The detection of pre-extensively (pre-XDR) and extensively drug-resistant tuberculosis (XDR-TB) is challenging. Drug-susceptibility tests for some anti-TB drugs, especially ethambutol (ETH) and ethionamide (ETO), are problematic due to overlapping thresholds to differentiate between susceptible and resistant phenotypes. We aimed to identify possible metabolomic markers to detect Mycobacterium tuberculosis (Mtb) strains causing pre-XDR and XDR-TB. The metabolic patterns of ETH- and ETO-resistant Mtb isolates were also investigated. Metabolomics of 150 Mtb isolates (54 pre-XDR, 63 XDR-TB and 33 pan-susceptible; pan-S) were investigated. Metabolomics of ETH and ETO phenotypically resistant subgroups were analyzed using UHPLC-ESI-QTOF-MS/MS. Orthogonal partial least-squares discriminant analysis revealed distinct separation in all pairwise comparisons among groups. Two metabolites (meso-hydroxyheme and itaconic anhydride) were able to differentiate the pre-XDR and XDR-TB groups from the pan-S group with 100% sensitivity and 100% specificity. In comparisons of the ETH and ETO phenotypically resistant subsets, sets of increased (ETH = 15, ETO = 7) and decreased (ETH = 1, ETO = 6) metabolites specific for the resistance phenotype of each drug were found. We demonstrated the potential for metabolomics of Mtb to differentiate among types of DR-TB as well as between isolates that were phenotypically resistant to ETO and ETH. Thus, metabolomics might be further applied for DR-TB diagnosis and patient management.

Application of untargeted volatile profiling in inflammatory bowel disease research

Inflammatory bowel disease (IBD) diagnosis depends on criteria based on histological, endoscopic, radiological, and clinical results. These studies show drawbacks as being expensive, invasive, and time-consuming. In this work, an untargeted metabolomic strategy based on the monitoring of volatile compounds in serum by headspace gas chromatography–mass spectrometry is proposed as a complementary, fast, and efficient test for IBD patient diagnosis. To develop the method and build a chemometric model that allows the IBD diagnosis, serum samples including IBD patients and healthy volunteers were collected. Analyses were performed by incubating 400 µL of serum for 10 min at 90 °C. For data processing, an untargeted metabolomic strategy was used. A total of 96 features were detected, of which a total of 10 volatile compounds could be identified and confirmed by means of the analysis of real standards. The chemometric treatment consisted of a discriminant analysis of orthogonal partial least squares (OPLS-DA) obtaining a 100% of classification rate, since all the analyzed samples were correctly classified.Graphical abstract

Volatile Components’ Variation Analysis on Ginseng Stems and Leaves at Different Growth Ages by HS-SPME-GC-MS

Panax ginseng is a famous valuable folk herb, the price of which particularly depends on its cultivation age. Since the classical chemical analysis usually needs to destroy the plants which is not suitable for the old wild ginseng due to the huge cost, in the current study, we employed the headspace solid-phase microextraction (HS-SPME) GC-MS methodology which has the advantage of time-saving, nondestructive, and green to analyze the growth age of ginseng (roots) via determining the volatile components of ginseng stem and leaves (GSLs) combined with metabolic profiles way. 100 mg of finely ground GSL samples (3–7 years) were extracted by a 65 μm PDMS-DVB fiber in the headspace and then analyzed within 20 mins. The content assay of total saponins, crude polysaccharides, and total protein was also included. As a result of GC-MS-based profiling, the orthogonal partial least-squares discriminant analysis’ (OPLS-DA) score plots showed excellent classification of four comparison groups (the 3- and 4-, 3-and 5-, 3- and 6-, and 3- and 7-year-old GSL) with 100% discrimination rate, respectively. 263 common differential variables were gained referring to the VIP and P values. 32 volatile metabolites were identified and showed good age discrimination capacities with an area under the curve (AUC) value of more than 0.8 by the receiver operating characteristic (ROC) analysis. Remarkably, there was one volatile component of sesquiterpenes, 1-cyclohexene-1-carboxaldehyde, 2, 6, 6-trimethyl-, which showed an excellent prediction with the AUC value of 1.0 among all the four compared groups, which could be the potential biomarker to distinguish all the four compared groups. The total contents of different growth ages of components of ginseng stems and leaves were distinct. The contents of total protein (4.80 ± 0.27%) and crude polysaccharide (24.15 ± 0.89%) in the 4th year of GSLs were the highest among the five cultivation years. The content of total saponins (4.66 ± 0.38%) in the 5th year of GSLs was the highest. These results could provide a novel reference for the GSLs’ harvest and application periods. Moreover, the current study could also supply a promising way to set up a nondestructive, in situ, and green approach to discriminate the growth age of Panax ginseng rapidly without digging the roots out instead of detecting the VOCs of GSLs.

Associations between Borg's rating of perceived exertion and changes in urinary organic acid metabolites after outdoor weight-bearing hiking.

Developing methods to monitor exercise load and evaluate body fatigue and muscle injury over time in hiking training remains a key problem to be solved. A widely used psycho-physical tool to assess the subjective perception of effort during exercise is Borg's rating of perceived exertion (BRPE) scale. Data on the relationships and validity of the BRPE compared to objectively assessed metabolic criteria are still lacking, especially urinary organic acid concentrations. To verify whether the BRPE scale could be used in the prescription of outdoor hiking with weight-bearing and reveal the relationship between the BRPE scale and urinary physiological measures. Eighty-nine healthy men (average age: 22 years) were enrolled in a 40 km (6 h) hiking training exercise with a 20 kg load. After training, the BRPE scale (6-20) was completed. All participants were divided into three groups according to the rating of the BRPE scale. Urine samples were collected before and after training. Urinary myoglobin levels were measured immediately using the fluorescent immunoassay method. The remaining urine was subpacked and frozen for the subsequent detection of urinary organic acids using gas chromatography and mass spectrometry. The contents of organic acids and myoglobin in urine were significantly increased after participants hiked 40 km (6 h) with a 20 kg load. Only orthogonal partial least-squares discrimination analysis performed well in separating the group with a BRPE score of 6-12 from the group with a BRPE score of 13-20. Significant differences in the urine levels of several organic acids were observed between the two groups, and the heatmap also presented different metabolic profiles based on BRPE. According to the standard of a variable importance in the projection > 1, fold change > 1.5 and P < 0.05, 19 different metabolites of urinary organic acids were screened and enriched in pathways mainly including the citrate cycle (tricarboxylic acid cycle) and alanine, aspartate and glucose metabolism. The BRPE scale identified significantly different urinary organic acid profiles between the higher and lower BRPE value groups, and, thus, could be used to monitor body fatigue in individuals participating in long-distance outdoor hiking with weight bearing.

A Novel Serum Metabolomic Panel for the Diagnosis of Crohn's Disease.

A distinctive metabolic phenotype provides the opportunity to discover noninvasive biomarkers for the diagnosis of Crohn's disease (CD) and for differentiating it from other intestinal inflammatory diseases. The study sought to identify new biomarkers for CD diagnosis. Serum metabolites from 68 newly diagnosed and treatment-naïve patients with CD and 56 healthy control (HC) subjects were profiled using targeted liquid chromatography-mass spectrometry. Five metabolic biomarkers were identified to distinguish patients with CD from the HC subjects and validated in a separate cohort consisting of 110 patients with CD and 90 HC subjects using a combination of univariate analysis, orthogonal partial least-squares discriminant analysis, and receiver-operating characteristic curve analysis. Differences in the 5 metabolites were evaluated among patients with CD and patients with ulcerative colitis (n = 62), intestinal tuberculosis (n = 48), and Behçet's disease (n = 31). Among the 185 quantified metabolites, a panel of 5 (pyruvate, phenylacetylglutamine, isolithocholic acid, taurodeoxycholic acid, and glycolithocholic acid) were found to distinguish patients with CD with high accuracy from HC subjects, with an area under the curve of 0.861 (P < .001). The performance of the model in assessing clinical disease activity was comparable to that of the present biomarkers: C-reactive protein and erythrocyte sedimentation rate. The 5 metabolites were significantly different among the patients and were valuable in the differentiation between CD and other chronic intestinal inflammatory diseases. The combination of 5 serum metabolite biomarkers for the diagnosis of CD has the potential to provide an accurate, noninvasive, and inexpensive alternative to conventional tests and might be valuable for the differentiation from other diagnostically challenging intestinal inflammatory diseases.

Analisis Tingkat Kepercayaan dan Tingkat Pendapatan Muzaki Terhadap Minat Membayar Zakat kepada Amil Zakat di Yogyakarta

Zakat is the fourth pillar of Islam which is considered to have a significant role in overcoming various kinds of economic problems. Management of zakat in Indonesia has been regulated in Law no. 38/1998 concerning the management of zakat which regulates all activities related to the organization, planning, implementation, and supervision of the collection and distribution and utilization of zakat funds. Amil plays a role in connecting the muzaki with the mustahik. As a financial intermediary, amil is required to apply the principle of trust (trust). The purpose of this study was to analyze the level of trust and income level of muzakki on interest in paying zakat to amil field research (field research). The population is all muzaki in Yogyakarta City. The number of samples in this study as many as 100 people were taken using purposive sampling technique. The research instrument is a questionnaire. Analysis of the data used in this study is the analysis of Weight Least Squares (WLS). The results showed that the level of trust of muzaki to amil zakat in Yogyakarta was in the high category as many as 14 people or 14%, for the moderate category of trust as many as 74 people or 74%, and for the unbelief category as many as 12 people (12%). the t-count value on the confidence level variable is -0.071 with Sig. t is 0.943 (p&gt;0.05). And at the level of income to interest in paying zakat, the t-count value is 2.575 with Sig. t is 0.011 (p&lt;0.05). The conclusion in this study is that there is no effect of the level of trust on the interest in paying zakat and the effect of the level of income of the muzaki on the interest in paying zakat to the amil.

Comprehensive analysis of untargeted metabolomics and lipidomics in girls with central precocious puberty.

Central precocious puberty (CPP) is a rare condition that causes early sexual development in children. Although the cure is effective, the etiology of central precocious puberty is unclear. In total, 10 girls with central precocious puberty and same number of age-matched female controls were enrolled. Plasma samples were collected from each participant and subjected to untargeted metabolomics and lipidomics. Student's t-tests were employed to compare the mean of each metabolite and lipid. Furthermore, orthogonal partial least-squares discriminant analysis was conducted and the variable importance in the projection was calculated to identify differentially expressed metabolites or lipids. Subsequent bioinformatics was conducted to investigate the potential function of differentially expressed metabolites and lipids. Fifty-nine differentially expressed metabolites were identified based on the criteria used (variable importance in the projection >1 and a P value < 0.05). Kyoto Encyclopedia Genes and Genome (KEGG) enrichment analysis showed that differentially expressed metabolites were enriched in four pathways: beta-alanine metabolism, histidine metabolism, bile secretion, and steroid hormone biosynthesis. As for the lipidomics, 41 differentially expressed lipids were observed and chain length analysis and lipid saturation analysis yielded similar results. Significant differences between the two groups were only observed in (O-acyl) ω-hydroxy fatty acids (OAHFA). The present study showed that antibiotic overuse, increased meat consumption, and obesity may have potential roles in the development of central precocious puberty in girls. Several metabolites have diagnostic value but further research is required.

The serum proteome of VA-ECMO patients changes over time and allows differentiation of survivors and non-survivors: an observational study

BackgroundVeno-arterial extracorporeal membrane oxygenation (VA-ECMO) is applied in patients with refractory hemodynamic failure. Exposure of blood components to high shear stress and the large extracorporeal surfaces in the ECMO circuit trigger a complex inflammatory response syndrome and coagulopathy which are believed to worsen the already poor prognosis of these patients. Mass spectrometry-based proteomics allow a detailed characterization of the serum proteome as it provides the identity and concentration of large numbers of individual proteins at the same time. In this study, we aimed to characterize the serum proteome of patients receiving VA-ECMO.MethodsSerum samples were collected on day 1 and day 3 after initiation of VA-ECMO. Samples underwent immunoaffinity based depletion for the 14 most abundant serum proteins, in-solution digestion and PreOmics clean-up. A spectral library was built with multiple measurements of a master-mix sample using variable mass windows. Individual samples were measured in data independent acquisition (DIA) mode. Raw files were analyzed by DIA-neural network. Unique proteins were log transformed and quantile normalized. Differential expression analysis was conducted with the LIMMA—R package. ROAST was applied to generate gene ontology enrichment analyses.ResultsFourteen VA-ECMO patients and six healthy controls were recruited. Seven patients survived. Three hundred and fifty-one unique proteins were identified. One hundred and thirty-seven proteins were differentially expressed between VA-ECMO patients and controls. One hundred and forty-five proteins were differentially expressed on day 3 compared to day 1. Many of the differentially expressed proteins were involved in coagulation and the inflammatory response. The serum proteomes of survivors and non-survivors on day 3 differed from each other according to partial least-squares discriminant analysis (PLS-DA) and 48 proteins were differentially expressed. Many of these proteins have also been ascribed to processes in coagulation and inflammation (e.g., Factor IX, Protein-C, Kallikrein, SERPINA10, SEMA4B, Complement C3, Complement Factor D and MASP-1).ConclusionThe serum proteome of VA-ECMO patients displays major changes compared to controls and changes from day 1 until day 3. Many changes in the serum proteome are related to inflammation and coagulation. Survivors and non-survivors can be differentiated according to their serum proteomes using PLS-DA analysis on day 3. Our results build the basis for future studies using mass-spectrometry based serum proteomics as a tool to identify novel prognostic biomarkers.Trial registration: DRKS00011106.

Metabolomic analysis reveals the metabolic disturbance in aortic dissection: Subtype difference and accurate diagnosis

Background and aimsAortic dissection (AD), a severe clinical emergency with high mortality, is easily misdiagnosed as are other cardiovascular diseases. This study aimed at discovering plasma metabolic markers with the potential to diagnose AD and clarifying the metabolic differences between two subtypes of AD. Methods and resultsTo facilitate the diagnosis of AD, we investigated the plasma metabolic profile by metabolomic approach. A total 482 human subjects were enrolled in the study: 80 patients with AD (50 with Stanford type A and 30 with Stanford type B), 198 coronary artery disease (CAD) patients, and 204 healthy individuals. Plasma samples were submitted to targeted metabolomic analysis. The partial least-squares discriminant analysis models were constructed to illustrate clear discrimination of AD patients with CAD patients and healthy control. Subsequently, the metabolites that were clinically relevant to the disturbances in AD were identified. Twenty metabolites induced the separation of AD patients and healthy control, 9 of which caused the separation of CAD patients and healthy control. There are 11 metabolites specifically down-regulated in AD group. Subgroup analysis showed that the levels of glycerol and uridine were dramatically lower in the plasma of patients with Stanford type A AD than those in the healthy control or Stanford type B AD groups. ConclusionThis study characterized metabolomic profiles specifically associated with the pathogenesis and development of AD. The findings of this research may potentially lead to earlier diagnosis and treatment of AD.

Differences in the Volatilomic Urinary Biosignature of Prostate Cancer Patients as a Feasibility Study for the Detection of Potential Biomarkers.

Prostate cancer (PCa) continues to be the second most common malignant tumour and the main cause of oncological death in men. Investigating endogenous volatile organic metabolites (VOMs) produced by various metabolic pathways is emerging as a novel, effective, and non-invasive source of information to establish the volatilomic biosignature of PCa. In this study, headspace solid-phase microextraction combined with gas chromatography-mass spectrometry (HS-SPME/GC-MS) was used to establish the urine volatilomic profile of PCa and identify VOMs that can discriminate between the two investigated groups. This non-invasive approach was applied to oncological patients (PCa group, n = 26) and cancer-free individuals (control group, n = 30), retrieving a total of 147 VOMs from various chemical families. This included terpenes, norisoprenoid, sesquiterpenes, phenolic, sulphur and furanic compounds, ketones, alcohols, esters, aldehydes, carboxylic acid, benzene and naphthalene derivatives, hydrocarbons, and heterocyclic hydrocarbons. The data matrix was subjected to multivariate analysis, namely partial least-squares discriminant analysis (PLS-DA). Accordingly, this analysis showed that the group under study presented different volatomic profiles and suggested potential PCa biomarkers. Nevertheless, a larger cohort of samples is required to boost the predictability and accuracy of the statistical models developed.

Liver Metabolic Dysregulation Induced by Polypropylene Nano- and Microplastics in Nile Tilapia Using Internal Extractive Electrospray Ionization Mass Spectrometry.

Understanding the metabolic disorders induced by nano- and microplastics in aquatic organisms at the molecular level could help us understand the potential toxicity of nano- and microplastics more thoroughly and provide a fundamental scientific basis for regulating the usage and management of plastic products. In this research, the effect of polypropylene nanoplastics (PP-NPs) and microplastics (PP-MPs) on metabolites in the tilapia liver was comprehensively investigated by internal extractive electrospray ionization mass spectrometry (iEESI-MS). A partial least-squares discriminant analysis (PLS-DA) and a one-component analysis of variance (ANOVA) were used for selecting 46 differential metabolites, including phospholipids, amino acids, peptides, carbohydrates, alkaloids, purines, pyrimidines, and nucleosides. Pathway enrichment analysis showed significant effects on glycerophospholipid metabolism, arginine and proline metabolism, and aminoacyl-tRNA biosynthesis after tilapia were exposed to PP-N/MPs. Dysregulation of these metabolites is mainly reflected in the possible induction of hepatitis, oxidative stress, and other symptoms. The application of iEESI-MS technology without sample pretreatment to the study of metabolic disorders in aquatic organisms under the interference of nano- and microplastics provides a promising analytical method for environmental toxicology research.

Comprehensive Metabolite Profiling of Two Edible Garcinia Species Based on UPLC-ESI-QTOF-MSE Coupled with Bioactivity Assays.

In China, the endemic species Garcinia yunnanensis and native Garcinia xanthochymus are known as edible and medicinal plants. However, a systematic metabolomic and bioactivity evaluation of different plant parts from both species is lacking. In this study, comprehensive investigations of 11 plant parts of G. yunnanensis and 10 of G. xanthochymus employing UPLC-ESI-QTOF-MSE-based metabolomic analysis in conjunction with three bioactivity assays were undertaken. A customized chemotaxonomic-based in-house library containing 6456 compounds was constructed and coupled to the Progenesis QI informatic platform for metabolite annotations. From these two species, a total of 235 constituents were characterized using multiple criteria. Differences in metabolite profiles between the plant parts within each species were uncovered using multivariate analysis. Based on orthogonal partial least-squares discriminant analysis (OPLS-DA), 23 markers were identified as highly differential metabolites from G. xanthochymus and 20 from G. yunnanensis. Comparative assessment of the biological assays revealed the activity variations among different plant parts. The seeds of both species and G. yunnanensis latex exhibited excellent cytotoxic and antibacterial activities, while G. xanthochymus roots and G. yunnanensis arils showed strong anti-inflammatory effects. S-plot analysis identified 26 potential biomarkers for the observed activities, including the known cytotoxic agent cycloxanthochymol and the anti-inflammatory compound garcimultiflorone B, which likely explains some of the potent observed bioactivity.

Influence of Sowing Date on Phenology, Biometric, and Yield of Mungbean (Vigna radiata) Cultivars in Chitwan, Nepal

Mungbean is a commercially promising legume crop, accounting for a very low productivity of approximately 0.5 tons ha1 in the Terai region of Nepal. This study aimed to achieve the potential yield of mungbean promising cultivars planting at optimum sowing time. An experiment was conducted at the Agriculture and Forestry University (AFU), Rampur, Chitwan, during the spring of 2019 in a split-plot design (SPD) with three replications and 16 treatment combinations. Four sowing dates at 15 days intervals (13th February, 28th February, 15th March, and 30th March) of 2019; cultivars viz. Kalyan, Pratikshya, Pratigya, and Pant-5 are considered as main and subplot factors. The Dunken test was carried out to compare the mean in R-software at p ≤ 0.05 level of significance. The results revealed that earlier planting (Feb 13 planting) resulted in delayed emergence, slower growth, and the lowest yield (1.79 tons/ha). The March 15 to March 30 plantations resulted in significantly faster emergence, germination, and growth showing a higher yield. Pant-5 yielded a higher grain yield, which was statistically at par with Partigya (2.08 tons/ha) and Partikshya (1.983 tons/ha). Vigna radiata plantations from March 15 to March 30 are the optimum sowing times for higher productivity (2.119 tons/hectare) and high potential yield, which can be applied for perfect decision-making in mungbean plantations. Future work on least-squares analysis for understanding the genotypic-environment interaction of economic traits and the effect of different nutrient sources on cultivars has scope.

Validating metrics for reward alignment in human-autonomy teaming

Alignment of human and autonomous agent values and objectives is vital in human-autonomy teaming settings which require collaborative action toward a common goal. In order to characterize the impact of alignment on team dynamics, a means to quantify and evaluate this alignment is critical. However, few alignment metrics have been proposed to date, and none have been validated through human-subject experiments. Individual and team goals can often be represented as reward functions the team must jointly optimize, so in this paper we focus on the alignment of these reward functions in particular. We propose four individual assessments and associated metrics for alignment between reward functions, along with three composite metrics. We then validate these metrics through a survey-based human-subject experiment. Results from a factor analysis of the data collected in the experiment provide empirical support for the existence of two latent constructs related to alignment, which we name “feature alignment” and “policy alignment,” and a subsequent partial least-squares analysis further supports the existence of a second-order formative construct, which we name “reward alignment.” These findings suggest the applicability of the proposed metrics for future evaluation of reward alignment, as well as its feature- and policy-based components. We also provide potential directions for future research into alignment in human-autonomy teaming.

Inertial effects in just-saturated axisymmetric column collapses

This work introduces a scaling analysis of sub-aerial axisymmetric column collapses of glass beads and Newtonian glycerol-water solutions mimicking some of the behaviours of debris flows. The beads were in a size range where their inertia partly decouples their collapse behaviour from the water column. Experiments explored a range of viscous, surface tension and particle inertia effects through systematic variation of particle size and fluid viscosity. Crucially a geotechnical centrifuge was used to access elevated effective gravitational accelerations driving the collapse, allowing field-scale viscous and surface tension effects to be replicated. Temporal pore pressure and run out front position evolution data was extracted using a pressure transducer and high speed imaging, respectively. A least-squares fitted scale analysis demonstrated that all characteristic dimensionless quantities of the acceleration phase could be described as a function of the column-scale Bond number text{ Bo }, the Capillary number text{ Ca }, the system size r^*, and the grain-fluid density ratio rho ^*. This analysis demonstrated that collapses as characterised by pore pressure evolution and front positions were controlled by the ratio of text{ Bo}/text{Ca}. This indicates that grain-scale surface tension effects are negligible in such inertial column collapses where they may dominate laboratory-scale granular-fluid flow behaviour where geometric similarity between grain and system size is preserved.Graphical abstract

Untargeted metabolomics analysis of serum and follicular fluid samples from women with polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is a complex endocrine disorder with well-established metabolic abnormalities. In the present study, untargeted metabolomics technology was applied to analyze the serum and follicular fluid samples from women with polycystic ovary syndrome and healthy controls using 1H nuclear magnetic resonance (NMR). Seventy samples for PCOS analysis were collected in hospital of Shandong University of Traditional Chinese Medicine (Jinan, China), NMR was used as analytical technology and multivariate analysis was applied to analyze metabolomics difference in PCOS and healthy controls. Significant metabolic differences were found in both serum and follicular fluid samples with orthogonal partial least-squares discriminant analysis (OPLS-DA). Three discriminated metabolites (1-Methylhistidine, threonine and Citrate) in both serum and follicular fluid were altered in PCOS patients. Abnormal energy metabolism, lipid metabolism and amino acid metabolism were detected in PCOS patients. Furthermore, more significantly changed amino acids were discovered in follicular fluid samples. Our findings would provide a resource for further investigations on metabolic disturbance in PCOS patients.

A unified strategy to rebalance multifactorial designs with unequal group sizes: application to analysis of variance multiblock orthogonal partial least squares

BackgroundAdequately handling unbalanced groups remains one of the major challenges for the analysis of multivariate data collected from multifactorial experimental designs. While partial least squares-based methods, such as analysis of variance multiblock orthogonal partial least squares (AMOPLS), can offer better discrimination between factor levels, they can be more heavily affected by this issue, and unbalanced designs of experiments may lead to a substantial confusion of the effects. Even state-of-the-art analysis of variance (ANOVA) decomposition methodologies using general linear models (GLM) lack the ability to efficiently disentangle these sources of variation when combined with AMOPLS. ResultsA versatile solution developed as an extension of a prior rebalancing strategy is proposed for the first decomposition step based on ANOVA. This approach has the advantage of yielding an unbiased estimation of the parameters and retaining the within-group variation in the rebalanced design, while preserving the orthogonality of effect matrices, even in presence of unequal group sizes. This property is of utmost importance for model interpretation because it avoids mixing sources of variation related to the different effects in the design. A real case study involving metabolomic data from in vitro toxicological experiments was used to demonstrate the potential of this strategy to handle unequal group sizes using a supervised approach. Primary 3D rat neural cell cultures were exposed to trimethyltin following a multifactorial design of experiments involving three fixed effect factors. Significance and NoveltyThe rebalancing strategy was demonstrated as a novel and potent solution to handle unbalanced experimental designs by offering unbiased parameter estimators and orthogonal submatrices, thus avoiding confusion of the effects and facilitating model interpretation. Moreover, it can be combined with any multivariate method used for the analysis of high-dimensional data collected from multifactorial designs.

Mechanism of acupuncture-moxibustion with "Biao-Ben" acupoint combination in treating irritable bowel syndrome rats by regulating serum metabolites and metabolic pathway based on TM widely targeted metabolomics method

To investigate the effect of acupuncture-moxibustion with "Biao-Ben" acupoint combination (BB) on the serum metabolites and metabolic pathway in irritable bowel syndrome (IBS) model rats, so as to explore the mechanisms of BB in the prevention and treatment of IBS. Thirty SD rats were randomly divided into three groups: control group, model group, and BB group, with 10 rats in each group. The IBS model was established by the combination of acute stress method and chronic stress method, and the success of the model establishment was evaluated by abdominal wall reflex (AWR). BB group received acupuncture-moxibustion treatment at "Neiguan" (PC6), "Zusanli" (ST36), and "Guanyuan" (CV4) for 15 min, once a day, for a total of 28 days. Bristol's fecal character score was evaluated, and intestinal propulsion rate was calculated. The open-field experiment was used to observe the behaviour of rats. Pathological changes in the colon were observed by H.E. staining. TM widely targeted metabolomics technology was used to detect the metabolic profile of serum samples from 3 groups of rats. Principal component analysis and orthogonal partial least-squares discrimination analysis techniques were combined with database screening to screen differential metabolites, and the KEGG database was utilized to map the enriched metabolic pathway. Compared with the control group, AWR, and the total distance, speed, duration traveled autonomously, the distance of central grid traveling, the number of central grid crossings of the open-field experiment were significantly decreased (P<0.01，P<0.05), while Bristol's fecal character score, intestinal propulsion rate and rest duration in the open-field experiment were significantly increased(P<0.01) in the model group. Compared with the model group, Bristol's fecal character score, the intestinal propulsion rate, rest duration, and rest episode were significantly decreased(P<0.01, P<0.05), while AWR, the total distance, speed, duration traveled autonomously, the distance of central grid traveling, the number of central grid crossings, and the residence time of the central grid were significantly increased(P<0.01，P<0.05) in the BB group. H.E. staining showed a discontinuous mucosal layer of colon tissue, a slightly disordered arrangement of glands, and more inflammatory cell infiltration in the submucosa and muscle layer in the model group, which was relatively milder in the BB group. After comparing the model and control group, 123 differential metabolites were screened, while 57 were screened after comparing the model and BB group. Six differential metabolic pathways were acquired when comparing the model and the control group, while 8 were acquired when comparing the model and BB group using KEGG enrichment analysis, both of which included the arachidonic acid metabolism pathway. "Biao-Ben" acupoint combination can improve symptoms of IBS by regulating metabolites of the arachidonic acid metabolism pathway, which may be a potential target for the treatment of IBS.