Multivariate Statistical Analysis Research Articles

Biological and metabolomics-guided isolation of tetrahydrofurofuran lignan from Croton spp. with antiproliferative activity against human melanoma cell line

The Croton genus (Euphorbiaceae) is recognized as a promising source for identifying bioactive compounds with antiproliferative activity. However, knowledge on the chemical composition and activity of Croton floribundus, Croton echinocarpus, and Croton zehntneri is limited. Thus, this study aimed to investigate the antiproliferative activity of these species on cells derived from tumoral breast, lung, and melanoma cells, and primary fibroblasts derived from human skin. Metabolomic strategies were applied via ultra-performance liquid chromatography coupled with high-resolution mass spectrometry and multivariate statistical analysis to target the main active compound. The C. floribundus leaf extract exhibited the highest activity, with an IC50 value lower than that of the reference drug – temozolomide – in the most responsive cell line – SK-MEL-147 – and in all the evaluated melanoma cell lines (SK-MEL-147, CHL-1 and WM-1366). Four tetrahydrofurofuran lignans were isolated for the first time from the most promising fraction of the C. floribundus extract. According to the metabolomic and multivariate statistical analyses, the isolated lignan epi-yangambin constituted the main antiproliferative compound against SK-MEL-147; furthermore, it exhibited selective antiproliferative activity for this cell line (IC50 = 13.09 μg/mL and selectivity index = 3.82; temozolomide, IC50 = 121.50 μg/mL) due to, at least in part, its ability to inhibit cell cycle progression at G2/M. This is especially relevant considering the high resistance of melanoma cells to available drugs. Thus, epi-yangambin can serve as a prototype for further antiproliferative investigations.

Revealing the comprehensive effect of mechanization on sauce-flavor Daqu through high-throughput sequencing and multi-dimensional metabolite profiling

Mechanization has emerged as a focal point in the modernization of traditional enterprises, offering standardized production and labor reduction benefits. However, little is known about how mechanization affects the microbiota and metabolite profiles of Daqu. To address this gap, we conducted a comprehensive comparison between traditional and mechanical sauce-flavor Daqu using a multi-omics approach. Results showed that mechanical Daqu exhibited higher acidity, amino acid nitrogen and enzyme activity, alongside lower fat and moisture levels. Following mechanization, lactic acid bacteria (LAB), Staphylococcus, Aspergillus and Saccharomycopsis were enriched and identified as biomarkers, whereas Oceanobacillus, Monascus and Scopulariopsis were notably decreased. Furthermore, significant disparities in metabolic profiles were observed between the two types of Daqu based on GC–MS, GC-IMS, and LC-MS/MS analyses. The content of volatile compounds was significantly higher in mechanical Daqu (332.82 ± 22.69 mg/kg), while that of non-volatile compounds was higher in traditional Daqu (753.44 ± 41.82 mg/kg). Moreover, OPLS-DA models identified 44 volatile and 31 non-volatile compounds as differential metabolites. Multivariate statistical analysis indicated that bacteria and fungi primarily contributed to protease and saccharification activities, respectively. Additionally, the co-occurrence network revealed that Oceanobacillus and Scopulariopsis were closely associated with non-volatile compound formation, while LAB and Rhizopus significantly influenced volatile compound production. These findings elucidate the multi-dimensional relationship between mechanization and Daqu quality, offering insights to advance the modernization of traditional industries.

Analysis of metabolic characteristics of metabolic syndrome in elderly patients with gastric cancer by non-targeted metabolomics.

The relationship between metabolic syndrome (MetS) and gastric cancer (GC), which is a common metabolic disease, has attracted much attention. However, the specific metabolic characteristics of MetS in elderly patients with GC remain unclear. To investigate the differentially abundant metabolites and metabolic pathways between preoperative frailty and MetS in elderly patients with GC based on nontargeted metabolomics techniques. In this study, 125 patients with nonfrail nonmeal GC were selected as the control group, and 50 patients with GC in the frail group were selected as the frail group. Sixty-five patients with GC combined with MetS alone were included in the MetS group, and 50 patients with GC combined with MetS were included in the MetS group. Nontargeted metabolomics techniques were used to measure plasma metabolite levels by ultrahigh-performance liquid chromatography-mass spectrometry. Multivariate statistical analysis was performed by principal component analysis, orthogonal partial least squares, pattern recognition analysis, cluster analysis, and metabolic pathway annotation. A total of 125 different metabolites, including amino acids, glycerophospholipids, sphingolipids, fatty acids, sugars, nucleosides and nucleotides, and acidic compounds, were identified via nontargeted metabolomics techniques. Compared with those in the control group, there were 41, 32, and 52 different metabolites in the MetS group, the debilitated group, and the combined group, respectively. Lipid metabolites were significantly increased in the MetS group. In the weak group, amino acids and most glycerol phospholipid metabolites decreased significantly, and fatty acids and sphingosine increased significantly. The combined group was characterized by significantly increased levels of nucleotide metabolites and acidic compounds. The alanine, aspartic acid, and glutamate metabolic pathways were obviously enriched in the asthenic group, and the glycerol and phospholipid metabolic pathways were obviously enriched in the combined group. Elderly GC patients with simple frailty, simple combined MetS, and frailty combined with MetS have different metabolic characteristics, among which amino acid and glycerophospholipid metabolite levels are significantly lower in frail elderly GC patients, and comprehensive supplementation of fat and protein should be considered. Many kinds of metabolites, such as amino acids, lipids, nucleotides, and acidic compounds, are abnormally abundant in patients with MetS combined with fthenia, which may be related to tumor-related metabolic disorders.

Sensory and chemical characterization of chestnuts processed in different methods using instrumental analyses and the Check-all-that-apply method

Chestnuts are known for their unique sensory characteristics and nutritional value. However, the changes in their sensory attributes after processing remain unclear. This study used instrumental analysis and sensory evaluation combined with multivariate statistical analysis to investigate the effect of packaging and thermal sterilization procedures on the sensory characteristics of chestnuts. The results showed that the significant variations (p < 0.05) between the different processing methods for chestnuts were revealed via the texture analysis, headspace solid-phase microextraction gas chromatography × gas chromatography-time of flight-mass spectrometry (HS-SPME-GC×GC-TOF-MS), and check-all-that-apply (CATA) sensory evaluation. The packaging had a more significant influence on the sensory quality of the chestnuts than thermal sterilization procedures. The HS-SPME-GC×GC-TOF-MS identified 116 volatile compounds, and the partial least squares-discriminant analysis (PLS-DA) identified the 28 volatile compounds responsible for the similarities and differences among different processing methods of chestnuts. Principal component analysis (PCA) combined with texture analysis and the fingerprint of HS-SPME-GC×GC-TOF-MS, as well as the correspondence analysis (CA) analysis of CATA, could discriminate samples from different packaging of chestnuts. This study provides chestnuts processing recommendations for satisfying consumer preferences and predicting possible related quality changes.

Holistic vibrational spectromics assessment of human cartilage for osteoarthritis diagnosis.

Osteoarthritis (OA) is the most common degenerative joint disease, presented as wearing down of articular cartilage and resulting in pain and limited mobility for 1 in 10 adults in the UK [Osteoarthr. Cartil.28(6), 792 (2020)10.1016/j.joca.2020.03.004]. There is an unmet need for patient friendly paradigms for clinical assessment that do not use ionizing radiation (CT), exogenous contrast enhancing dyes (MRI), and biopsy. Hence, techniques that use non-destructive, near- and shortwave infrared light (NIR, SWIR) may be ideal for providing label-free, deep tissue interrogation. This study demonstrates multimodal "spectromics", low-level abstraction data fusion of non-destructive NIR Raman scattering spectroscopy and NIR-SWIR absorption spectroscopy, providing an enhanced, interpretable "fingerprint" for diagnosis of OA in human cartilage. This is proposed as method level innovation applicable to both arthro- or endoscopic (minimally invasive) or potential exoscopic (non-invasive) optical approaches. Samples were excised from femoral heads post hip arthroplasty from OA patients (n = 13) and age-matched control (osteoporosis) patients (n = 14). Under multivariate statistical analysis and supervised machine learning, tissue was classified to high precision: 100% segregation of tissue classes (using 10 principal components), and a classification accuracy of 95% (control) and 80% (OA), using the combined vibrational data. There was a marked performance improvement (5 to 6-fold for multivariate analysis) using the spectromics fingerprint compared to results obtained from solely Raman or NIR-SWIR data. Furthermore, clinically relevant tissue components were identified through discriminatory spectral features - spectromics biomarkers - allowing interpretable feedback from the enhanced fingerprint. In summary, spectromics provides comprehensive information for early OA detection and disease stratification, imperative for effective intervention in treating the degenerative onset disease for an aging demographic. This novel and elegant approach for data fusion is compatible with various NIR-SWIR optical devices that will allow deep non-destructive penetration.

Insights into the usage of biobased organic acids for treating municipal solid waste incineration bottom ash towards metal removal and material recycling

The recycling of incineration bottom ash (IBA) is crucial for sustainable municipal solid waste (MSW) management and alleviating landfill burdens. However, limited environmentally friendly methods exist to effectively treat IBA for safe recycling. This study systematically examined the performance of biobased organic acids, namely citric acid (CA), oxalic acid (OA), lactic acid (LA), and levulinic acid (LEA), for IBA treatment. CA shows high extraction efficiency for most trace metals (e.g., Mn > 65 %, Pb > 50 %, Co approx.100 %, Cd > 85 %, Zn > 80 %, Ni > 80 %), while OA performs better for certain trace metals (e.g., Sn approx.99 %, Sb > 70 %, Mo > 70 %, Cr > 50 %). Multivariate statistical analysis and instrumental techniques were used to gain deeper insights into the critical mechanisms, including proton promoted dissolution, ligand related dissolution and precipitation/co-precipitation. The latter two mechanisms are distinctive metal extraction behaviours by organic acids compared to their inorganic counterparts. Both CA- and OA-treated alkaline-washed IBA residues demonstrate high leaching reduction efficiency (>99.9 %) of the critical heavy metals, making the treated IBA residues suitable for safe recycling as construction materials. This study highlights the potential of environmentally friendly organic acids which can be derived from bio-wastes for treating and repurposing IBA as resources for construction materials, promoting sustainable waste management for MSW incineration ash.

Enhancing postgraduate education quality: a comprehensive analysis of factors influencing students’ satisfaction in university-business cooperation

ABSTRACT This study investigates the critical factors influencing students’ satisfaction with university-business cooperation (UBC) in postgraduate education, focusing on Chinese universities of applied sciences. Employing a comprehensive research model, we utilised multivariate statistical analysis methods, including canonical correlation analysis, partial correlation analysis, principal component analysis (PCA), and cluster analysis, to validate our measurement and hypotheses. Our findings reveal that teaching, tutor supervision, practical relevance, and individual development are primary determinants of students’ satisfaction with UBC in postgraduate education. Additionally, significant correlations exist between these factors, consistent with our proposed research model. The study emphasises the importance of fostering effective UBC for enhancing postgraduate education quality. Practical implications and recommendations for stakeholders are discussed, contributing both to the academic understanding of UBC and offering actionable insights for educational institutions and businesses. Future research directions in this field are also suggested.

Perfluoroalkyl compounds in groundwater alter the spatial pattern of health risk in an arsenic‑cadmium contaminated region

Integrated health risk assessment strategies for emerging organic pollutants and heavy metals that coexist in water/soil media are lacking. Contents of perfluoroalkyl compounds and potentially toxic elements in multiple media were determined by investigating a county where a landfill and a tungsten mine coexist. The spatial characteristics and sources of contaminants were predicted by Geostatistics-based and multivariate statistical analysis, and their comprehensive health risks were assessed. The average contents of perfluorooctane acid, perfluorooctanesulfonic acid, arsenic, and cadmium in groundwater were 3.21, 0.77, 1.69, and 0.14 μg L−1, respectively; the maximum content of cadmium in soils and rice highly reached 2.12 and 1.52 mg kg−1, respectively. In soils, the contribution of mine lag to cadmium was 99 %, and fertilizer and pesticide to arsenic was 59.4 %. While in groundwater, arsenic, cadmium and perfluoroalkyl compounds near the landfill mainly came from leachate leakage. Significant correlations were found between arsenic in groundwater and arsenic and cadmium in soils, as well as perfluoroalkyl compounds in groundwater and pH and sulfate. Based on these correlations, the geographically optimal similarity model predicted high-level arsenic in groundwater near the tungsten mine and cadmium/perfluoroalkyl compounds around the landfill. The combination of analytic network process, entropy weighting method and game theory-based trade-off method with risk assessment model can assess the comprehensive risks of multiple pollutants. Using this approach, a high health-risk zone located around the landfill, which was mainly attributed to the presence of arsenic, cadmium and perfluorooctanesulfonic acid, was found. Overall, perfluoroalkyl compounds in groundwater altered the spatial pattern of health risks in an arsenic‑cadmium contaminated area.

Effects and mechanisms of using “clean” smoke particles in the smoking process on the formation of β-carboline heterocyclic amines (β-CHAs) in smoked meat patties

β-Carboline heterocyclic amines (β-CHAs), known for their synergistic neurotoxic and carcinogenic effects, are predominantly produced by humans through cigarette smoke and food and are found particularly in meats cooked at high temperatures. Few studies have explored the differences in the mechanisms of accumulation of β-CHAs in smoked meat and meat processed at high temperatures. In this research, the concentration of β-CHAs in smoked meats prepared using a variety of wood materials was measured using LCMS/MS. Additionally, key volatile organic compound markers associated with β-CHAs accumulation in smoke were identified through GCMS and multivariate statistical analysis and subsequently confirmed in a chemical simulation system. Three types of strainers, each with a distinct aperture size, were used to assess the efficacy of particle filtration in reducing β-CHAs levels in smoked meat. The findings indicated that smoke exposure indeed increases the β-CHAs content of meat. However, only the strainer capable of filtering PM2.5-sized particles reduced the amount of β-CHAs present compared to the control group. In contrast, strainers with larger pore sizes facilitated excessive accumulation of β-CHAs. The presence of aldehydes such as 1 H-pyrrole-2-carboxaldehyde, 5-methylfurfural, benzaldehyde, furfural, and nonanal exhibited a positive correlation with the accumulation of β-CHAs. Conversely, phenolic compounds, including 2-methoxy-4-vinylphenol, 2-methoxy-5-methylphenol, p-cresol, phenol, 2-methoxy-4-(1-propenyl)-, (Z)-, phenol, 3-ethyl-, and phenol, 4-ethyl-2-methoxy-, showed a negative correlation. Thus, filters made from chelated carbonyl trap materials both chemically and physically disrupt the buildup of β-CHAs in smoked meats. The use of this approach will not only improve the quality of these products but will also contribute to decreasing the amount of inhalation pollutants released into the environment.

A hyaena on stilts: comparison of the limb morphology of Ictitherium ebu (Mammalia: Hyaenidae) from the Late Miocene of Lothagam, Turkana Basin, Kenya with extant Canidae and Hyaenidae.

The long, gracile morphology of the limb bones of the Late Miocene hyaenid Ictitherium ebu has led to the hypothesis that this animal was cursorial. The forelimb and femur of the holotype were compared with specimens of extant Hyaenidae and Canidae. Two morphometric methods were used. The first used measurements to calculate indices of different morphological characters. The second method involved capturing photographs of the anterior distal humerus of each specimen, mapping six landmarks on them, and calculating truss distances. These distances represent a schematic reproduction of the elbow. Multivariate statistical analysis primarily separated the data based on taxonomy, yet locomotor and habitat categories were also considered. Ictitherium ebu has an overall morphology similar to that of the maned wolf and a distal humerus reminiscent of that of the aardwolf. The long, gracile limb bones of I. ebu are suggested to be adaptations for pouncing on prey, for locomotor efficiency, and for looking over the tall grass of the open environments the animal lived in, much like the present-day maned wolf.

Research Advances of Groundwater Nitrate Pollution and Source Apportionment in China

Groundwater nitrate (NO3-) contamination in China has become a serious environmental problem, especially in agricultural production areas, which greatly affects the safety of drinking groundwater and requires urgent attention. In this study, the main sources of groundwater nitrate in China were reviewed, including atmospheric deposition, soil nitrogen, agricultural fertilization, and fecal sewage, among which fecal sewage and agricultural fertilization were the main reasons for the excessive groundwater nitrate. The application of hydrochemical analysis, multivariate statistical analysis, stable isotope tracer method, and microbial source tracking in the source apportionment of groundwater nitrate was summarized. All types of source apportionment methods had certain limitations. It is suggested that a variety of methods should be used to identify the source of groundwater nitrate, and the contribution rate of different pollution sources should be calculated using multivariate statistical analysis and isotope quantitative analysis models. The source apportionment of nitrate pollution has undergone a process from qualitative to quantitative research. At present, the SIAR and MixSIAR models based on δ15N-NO3-and δ18O-NO3- have been used widely to analyze the source of nitrate. However, due to the overlap of isotope characteristic values of different input end-members, the difference in δ15N-NO3-and δ18O-NO3- values under different spatial and temporal changes, and the influence of isotope fractionation in the process of nitrogen migration and transformation, the results calculated by the model remain uncertain. It is necessary to further optimize the analytical method of the model to obtain the source of nitrate pollution and its contribution rate more accurately to further aid in the scientific management of groundwater resources.

Water residence time is an important predictor of dissolved organic matter composition and drinking water treatability

Freshwater ecosystems are critical resources for drinking water. In recent decades, dissolved organic matter (DOM) inputs into aquatic systems have increased significantly, particularly in central and northern Europe, due to climatic and anthropogenic drivers. The associated increase in dissolved organic carbon (DOC) concentration can change lake ecosystem services and adversely affect drinking water treatment processes. In this study, we examined spatial and temporal patterns of DOM treatability with granular activated carbon (GAC) and biological reactivity based on 14-day bacterial respiration incubations at 11 sites across Mälaren during six-time points between July 2019 and February 2021. Mälaren is the third largest lake in Sweden and provides drinking water for over 2 million people including the capital city Stockholm. In our spatio-temporal analysis, we assessed the influence of phytoplankton abundance, water chemistry, runoff, and climate on DOM composition, GAC removal efficiency, and biological reactivity. Variations in DOM composition were characterized using optical measurements and Orbitrap mass spectrometry. Multivariate statistical analyses indicated that DOM produced during warmer months was easier to remove by GAC. Removal efficiency of GAC varied from 41 to 87 %, and the best predictor of treatability using mass spectrometry was double bond equivalents (DBE), while the best optical predictors were specific UV absorbance (SUVA), and freshness index. The oxygen consumption rate (k) from the bacterial respiration incubations ranged from 0.04 to 0.71 d−1 and higher in warmer months and at deeper basins and was associated with more aliphatic and fresh DOM. The three deepest lake basins with the longest water residence time (WRT) were temporally the most stable in terms of DOM composition and had the highest DOC removal efficiency and k rates. DOM composition in these three lake basins was optically clearer than in basins located closer to terrestrial inputs and had a signature suggesting it was derived from in-lake processes including phytoplankton production and bacterial processing of terrestrial DOM. This means that with increasing WRT, DOM derived from terrestrial sources shifts to more aquatically produced DOM and becomes easier to remove with GAC. These findings indicate WRT can be highly relevant in shaping DOM composition and thereby likely to affect its ease of treatability for drinking water purposes.

Identification of characteristic volatiles of Zhenjiang aromatic vinegar using HS‐SPME‐GC/MS coupled with multivariate analysis

AbstractThis study employed headspace solid phase micro‐extraction gas chromatography mass spectrometry (HS‐SPME‐GC–MS) coupled with multivariate statistical analysis to identify volatile markers in various levels of Zhenjiang Aromatic Vinegar (ZAV). A full range of 40 volatile organic compounds (VOCs) were identified and categorized into acids, alcohols, esters, aldehydes, ketones, heterocyclic compounds and others. Principal component analysis (PCA) and hierarchical cluster analysis (HCA) demonstrated a clear clustering effect among different levels of ZAV, indicating distinct volatile characteristics at the relative content level. Furthermore, using Orthogonal partial least squares discrimination analysis (OPLS‐DA), 20 significant volatile organic compounds (VOCs) were identified as markers for distinguishing between the various levels of ZAV. To differentiate among the levels of ZAV, two volatile compounds, acetic acid and n‐hexanol, were identified as characteristic volatile compounds using a combination of Venn diagram, analysis of variance (ANOVA) and boxplot analysis. The results showed notable variations in VOCs among ZAV samples of different grades. Acetic acid and n‐hexanol can serve as reliable markers for grade distinction, providing valuable technical and theoretical support for the production and quality control of ZAV.

Multivariate statistical regression analysis and relative quantification based on dimensional-reduction method to compare the taste-active components of different chicken breeds

To compare the difference of non-volatile taste-active flavor components of different chicken breeds, four Chinese native yellow feather broilers including Langshan chicken, Chongren chicken, Luyuan chicken and Wenchang chicken were used in the experiment. The contents of free amino acids, 5'-nucleotides and minerals were determined by standard method, and then five principal components were extracted from the multi-index system based on the principal component analysis (PCA). Combined with the Mahalanobis distance analysis method and sensory evaluation results, the advantages and characteristics of each chicken breed were evaluated. The results showed that different kinds of chicken had their own advantages in different evaluation dimensions. The Equivalent umami concentration (ECU) of Wenchang chicken, which had the highest content of amino acids, was 12 g monosodium glutamate (MSG)/100 g, indicating the umami taste of it was very intense. The indexes of Langshan chicken were relatively uniform, with slightly higher mineral content, its overall Mahalanobis distance score was more similar to the "best standard". According to the Mahalanobis distance score, although the difference in amino acid content among each species was the largest, the overall score was more affected by the content of minerals and nucleotides, and there was interaction between each nutrient, which had an impact on the overall Mahalanobis distance score. The sensory evaluation results indicated that Wenchang chicken was the most superior among the taste of the four varieties investigated. Finally, taste compounds affecting the difference of chicken varieties were analyzed by partial least squares regression (PLS), resulting in order of mineral (Ca2+, Mg2+, PO43−) > nucleotide (AMP, IMP) > amino acid. This could provide a theoretical basis for quantitative oriented flavor processing and consumer choice of chicken.Graphical

Urinary metabolome of infants with colic treated with Lactobacillus reuteri DSM 17938: a pilot randomized trial.

Lactobacillus reuteri DSM 17938 is the only probiotic recommended for treatment of colicky infants, but its mechanism of action is not clear. The study aim was to examine urinary metabolomic fingerprint of colicky breastfed infants before and after 1 month of orally administered Lactobacillus reuteri DSM 17938 or placebo. This randomized, blinded, placebo-controlled clinical trial was carried out with a well-documented probiotic. Thirty-two infants were enrolled, 16 in the probiotic group and 16 in the placebo group. Urine samples were collected from each subject before starting supplementation and at the end of the study period. Metabolomic profiles were obtained using a gas chromatography/mass spectrometry instrument. Subsequently, to compare groups before and after probiotic supplementation, univariate and multivariate statistical analysis were performed. In the L. reuteri treated group all metabolites for all class of nutrients (sugars, amino acids, carboxylic acids) resulted more abundant after the study period. The comparison with a control group (placebo treated), confirmed this effect on urines. The metabolomic analysis of urine samples from infants treated with L. reuteri DSM 17938 allowed to detect some interesting features related to the effect of this treatment on urinary metabolome. To validate the results, a test on a larger cohort is required.

Effectiveness and safety of medication abortion via telemedicine versus in-person: A cohort of pregnant people in Colombia

ObjectiveTo compare the effectiveness and safety of medication abortion (MAB) via telemedicine versus in-person in pregnant people with less than 12 gestational weeks in Colombia. Study designA retrospective cohort study was conducted with 23,362 pregnant people who requested MAB service from Profamilia (a Colombian non-governmental organization) in 2021–2022. The outcomes were success and safety of MAB. We performed a descriptive and a multivariate statistical analysis using the binary regression model to obtain an adjusted Odds Ratio (aOR) to identify factors associated with abortion success. ResultsIn comparison to in-person care (n = 20,289), individuals in telemedicine (n = 3073) were predominantly from urban areas, belonged to a lower socioeconomic stratum, single and did not identify with any ethnic group. In-person users tended to have higher levels of education and accessed the service through private insurance (p < 0,05). There were no differences in the odd of a successful abortion based on the modality of care (aOR 1.18; 95% CI=0.87–1.59). The results were also the same with sensitivity analysis stratified: pregnant people who were nine weeks gestation or less (aOR 0.86; 95% CI=0.63–1.17) or more (aOR 0.87; 95% CI=0.28–2.65). ConclusionTelemedicine is an effective and safe option for MAB, as in-person care. Telemedicine has the potential to increase abortion access by extending the availability of providers and offering people a new option for obtaining care conveniently and privately, especially for women with disadvantaged socioeconomic and educational background. ImplicationsThis study demonstrates that medication abortion (MAB) administered via telemedicine produces outcomes akin to those of in-person care, providing a compelling rationale for its adoption, particularly in underserved regions. This approach can be replicated in other countries in Latin America and the Caribbean.

Regulatory effect of Tingli Dazao Xiefei Decoction on asthmatic rats by urine metabolomics

Urine metabolomics based on ultra-performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry(UHPLC-Q-TOF-MS) was utilized to investigate the metabolic regulation mechanism of Tingli Dazao Xiefei Decoction(TLDZ) in rats with allergic asthma. SD male rats were divided into a normal group, a model group, a dexamethasone group, and a TLDZ group. The allergic asthma model was established by intraperitoneal injection of ovalbumin(OVA) to induce allergy, combined with atomization excitation. Urine metabolites from all rats were collected by UHPLC-Q-TOF-MS. The metabolic profiles of rats in each group were built by principal component analysis(PCA). Besides, the differential metabolites between the model group and the TLDZ group were selected by orthogonal partial least squares discriminant analysis(OPLS-DA), t-test(P&lt;0.05), and variable importance in the projection(VIP) values of more than 3. The differential metabolites were identified through HMDB, METLIN, and other online databa-ses. Heat maps and clustering analysis for relative quantitative information of biomarkers in each group were drawn by MeV 4.8.0 software. Finally, MetaboAnalyst, MBRole, and KEGG databases were used to enrich related metabolic pathways and construct metabolic networks. The result demonstrated that TLDZ could effectively regulate the disordered urine metabolic profiles of asthmatic rats. Combined with multivariate statistical analysis and online databases, a total of 45 differential metabolites with significant changes(P&lt;0.05) between the model group and the TLDZ group were screened out. Metabolic pathways including histidine metabolism, tryptophan metabolism, and arginine and proline metabolism were enriched. TLDZ could improve asthma by regulating related metabolic pathways and interfering with pathological processes such as immune homeostasis airway inflammation. The study investigates the molecular mechanism of anti-asthma of TLDZ from the perspective of urine metabolomics, and combined with previous pharmacological studies, it provides a scientific basis for the clinical development and application of TLDZ in the treatment of asthma.

Linking the companion diagnostic function of cancer genome profiling to therapy: Investigation of TMB-high predictors.

e13033 Background: Based on the companion diagnostic function of the Comprehensive Cancer Genome Profiling (CGP) test in Japan, pembrolizumab is the standard treatment for patients with Tumor Mutational Burden (TMB)-high (H) solid tumors. In this report, we attempted to extract predictive factors of TMB-H from CGP test results. Methods: We carried out a retrospective cohort study of 42 patients with malignant breast tumors (excluding circulating tumor DNA in the blood) who underwent CGP testing between June 1, 2019, and November 30, 2023, at our hospital and affiliated institutions. We analyzed the association between clinicopathological factors, the number of analyzed cancer-related gene mutations (SNV, InDel), and TMB-H using univariate and multivariate statistical analysis. Results: Of the 42 cases (27 positive and 15 negative for estrogen receptor (ER), respectively), seven (16.7%) were TMB-H. Samples significantly associated with TMB-H according to univariate analysis were submitted as pathology specimens (non-primary (16.7%) vs. primary (0%), p = 0.011), ER (positive (16.7%) vs. negative (0%), p = 0.044), letrozole (LET) (yes (11.9%) vs. no (4.8%), p = 0.008), and previous treatment (after 6th line (14.3%) vs. before (2.4%), p = 0.041). Multivariate analysis showed that LET had a significant effect on TMB-H in Aromatase inhibitor agents (LET + Anastrozole + Exemestane) (LET: OR, 19.9; 95% CI, 2.2–183.5; p = 0.008) and the number of cancer-related gene mutations (PIK3CA+TP53) were significantly affected (PIK3CA: OR, 3.8; 95% CI, 1.1–13.2; p = 0.032. TP53: OR, 0.08; 95% CI, 0.01–0.66; p = 0.015). Single regression analysis showed a significant association between the number of PIK3CA mutations and LET. (β, 0.31; SE, 0.11; p = 0.008). Conclusions: ER positivity, history of LET use, prior therapy after the 6th line, and submission of pathology specimens from non-primary tumors to CGP testing are predictive factors for TMB-H. In multivariate analysis, the history of LET use and the number of PIK3CA mutations were significantly associated with TMB-H. Research shows that PIK3CA mutations are most frequent in patients who have undergone preoperative endocrine therapy with LET (Breast Cancer Res Treat. 2020 Nov;184(1):123–133.), suggesting that an increased number of PIK3CA mutations due to LET contributed to TMB-H. Although immune checkpoint inhibitors (ICIs) are not indicated for ER-positive breast cancer, TMB-H may be a predictor of ICI efficacy in such cases. The limitations of our research were the small sample size, and the study population only included Japanese. For the next steps needed to continue in this research, clinical trials should take place to test whether TMB-H is a predictor of ICIs in a wider population of ER-positive breast cancer.

Investigating the effects of low-salt processing on the umami peptides of dry-cured ham using peptidomics techniques

This study investigated the effect of low-salt processing on the umami peptide profile of dry-cured hams. Peptidomics data showed 633 umami peptides in the low- and full-salt groups. Among them, 36.2% and 26.5% of shared umami peptides in the low-salt group were significantly down- and up-regulated in relative abundance. Multivariate statistical analysis showed 1011 significantly different umami peptides (SDUPs) in the low- and full-salt groups. Creatine kinase M-type (CKM) and fast skeletal muscle troponin T (TnTf) were the main precursor proteins of these SDUPs. At the end of processing, the relative expression of CKM was lower in the low-salt group than in the full-salt group (P < 0.05), but there was no significant difference in TnTf. More dipeptidyl peptidase cleavage sites were observed in CKM and TnTf proteins in the low-salt group.

Authenticity discrimination for Galli Gigerii Endothelium Corneum based on UPLC-MS/MS and peptidomics

Peptidomics was employed to systematically analyze the characteristic peptides in Galli Gigerii Endothelium Corneum and its adulterants and establish a method for distinguishing Galli Gigerii Endothelium Corneum from its adulterants, including the gizzard membranes from ducks, geese, and pigeons. UPLC-Q-Exactive Orbitrap-MS was combined with multivariate statistical analysis to analyze the peptides in Galli Gigerii Endothelium Corneum and its adulterants. The structures of peptides were identified by pNovo combined with manual recognition of spectra, and synthetic peptide standards were used for validation. LC-MS/MS was used to optimize the sample pre-processing conditions, including the extraction procedure, extraction time, extraction solvents, and solvent volumes, for the characteristic peptide LESY in Galli Gigerii Endothelium Corneum. Multiple reaction monitoring(MRM) in the ESI~+ mode with m/z 511.24→269.11 and 511.24→243.13 as detection ions was employed for qualitative and quantitative analyses. The established UPLC-MS/MS method demonstrated good specificity, stability, and durability. The content of LESY in 16 batches of Galli Gigerii Endothelium Corneum samples ranged from 55.03 to 113.36 μg·g~(-1). Additionally, a qualitative detection method for the common peptide RDPVLVSR in adulterants was established with m/z 471.28→785.45 and 471.28→670.41 as the detection ions. This study established a convenient, rapid, and accurate detection method for the characteristic peptides in Galli Gigerii Endothelium Corneum and its adulterants. The method possesses good specificity, stability, and durability, providing a valuable reference for the identification and quality control of Galli Gigerii Endothelium Corneum and other traditional Chinese medicines derived from animal sources.