Cluster Heat Map Research Articles

Impact of must clarification treatments on chemical and sensory profiles of kiwifruit wine

This study examined the effect of various clarification treatments on the physicochemical properties, volatile compounds, and sensory attributes of kiwi wines produced from five different kiwifruit (Actinidia deliciosa) varieties. The degree of clarification had a minimal impact on physicochemical parameters, including the content of residual sugar, ethanol, volatile acid, titratable acidity (except for the kiwifruit variety ‘Qinmei’), and the pH value. However, wines made from unclarified juices (muddy juice and pulp) displayed a higher glycerol content than those made from clarified juices. The cluster heat map and principal component analyses (PCA) demonstrated that kiwi wines produced from clarified kiwi juices possessed a higher ester content, whereas muddy juice and pulp wines contained elevated levels of higher alcohols. Quantitative descriptive analysis (QDA) indicated that clarified juice wines outperformed muddy juice and pulp wines in terms of purity, typicality, harmony, intensity, and freshness, with negligible differences in terms of palate acidity. Moreover, the clarified juice wines featured more characteristic kiwi wine aromas (kiwifruit, passionfruit, and pineapple) compared with that of the muddy juice and pulp wines, which exhibited an increased grassy flavour. Although the 100-NTU kiwifruit juice-fermented wine did not show an advantage in the cluster heat map and PCA, it presented better freshness, typicality, and intensity in the QDA, as well as a more passionfruit aroma. Based on the orthogonal partial least-squares discriminant analysis, A. deliciosa ‘Xuxiang’ was deemed to be the most suitable variety for vinification. This study provides crucial insights for enhancing the production of high-quality kiwi wine.

Use of GC-IMS and Stoichiometry to Characterize Flavor Volatiles in Different Parts of Lueyang Black Chicken during Slaughtering and Cutting.

Chilled and cut chicken is preferred by consumers for its safeness and readiness to cook. To evaluate the quality characteristics of various chilled chicken products, differences in volatile organic components (VOCs) of six different cut parts (breast, back, leg, heart, liver, and gizzard) of Lueyang black chicken were characterized through gas chromatography-ion mobility spectroscopy (GC-IMS) combined with stoichiometry. A total of 54 peaks in the signal of VOCs were detected by GC-IMS, and 43 VOCs were identified by qualitative analysis. There were 22 aldehydes (20.66-54.07%), 8 ketones (25.74-62.87%), 9 alcohols (4.17-14.69%), 1 ether (0.18-2.22%), 2 esters (0.43-1.54%), and 1 furan (0.13-0.52%), in which aldehydes, ketones, and alcohols were the main categories. Among the six cut parts, the relative content of aldehydes (54.07%) was the highest in the gizzard, and the relative content of ketones (62.87%) was the highest in the heart. Meanwhile, the relative content of alcohols (14.69%) was the highest in the liver. Based on a stable and reliable predictive model established by orthogonal partial least squares-discriminant analysis (OPLS-DA), 3-hydroxy-2-butanone (monomer and dimer), acetone, 2-butanone monomer, hexanal (monomer and dimer), isopentyl alcohol monomer, and n-hexanol monomer were picked out as characteristic VOCs based on variable importance in projection (VIP value > 1.0, p < 0.05). Principal component analysis (PCA) and the clustering heatmap indicated that the characteristic VOCs could effectively distinguish the six cut parts of Lueyang black chicken. The specific VOCs responsible for flavor differences among six different cut parts of Lueyang black chicken were hexanal (monomer and dimer) for the gizzard, 2-butanone monomer and hexanal dimer for the breast, hexanal monomer for the back, 3-hydroxy-2-butanone monomer for the leg, 3-hydroxy-2-butanone (monomer and dimer) for the heart, and acetone and isopentyl alcohol monomer for the liver. These findings could reveal references for quality assessment and development of chilled products related to different cut parts of Lueyang black chicken in the future.

Pan-cancer B- and T-cell transcriptome analysis of CXCL13 as a predictive marker for immune checkpoint inhibitor response.

2626 Background: Maturation of lymphoid structures and tumor-antigen presentation via B cells in the tumor microenvironment (TME) have been recognized as factors in tumor immunity. The presence of B cells and tertiary lymphoid structures appears to result in better prognosis in patients with cancer but their role in response to immunotherapy remains subject to research. This study aimed to leverage the transcriptome expression of B and T cell markers and elucidate their impact on response to immune checkpoint inhibitors (ICIs). Methods: Among 514 patients with cancer included in the Profile-Related Evidence determining Individualized Cancer therapy study (NCT02478931), 208 with advanced cancer and available date treated with ICIs were analyzed. Patients were divided into responders (progression-free survival [PFS] after initiation of ICI therapy: 6 or more months) and non-responders (PFS: less than 6 months). Transcriptome expression of 34 immunoregulatory markers associated with B and T cells was compared between these groups using odds ratios (ORs) of “High” transcriptome expression [“High” (75-100 percentile), “Intermediate” (25-74), and “Low” (0-24), rank compared to 735 controls] of each immune marker for immunotherapy responders. A logistic regression model was used to perform a multivariable analysis of ORs. Clinical characteristics between responders and non-responders were summarized, and rate of “High” transcriptome expression of identified markers contributing to immunotherapy response was summarized by cancer type. Results: In total, 82 and 126 patients were classified into responder and non-responder groups. Median age was 65.0 and 61.0, and women were 58.5% (48/82) and 54.8% (69/126) in each group, respectively. Cancer type in both groups was well balanced. In univariate analysis, “High” transcriptome expression of CXCL13, CD3, BTLA, CTLA-4, and PD-1 was significantly more frequent in the responder than non-responder group. Cluster heatmaps in both groups revealed more B and T cell enriched population in the responder group. In multivariable analysis, patients with “High” CXCL13 expression were more likely to be immunotherapy responders (OR: 3.91, 95% confidence interval [CI]=1.02-15.04, p=0.044). High CXCL13 transcriptome expression was most common in head and neck (25%, 3/12), breast (22.4%, 11/49), neuroendocrine (20%, 3/15), and lung (20%, 4/20) tumors. Conclusions: This pan-cancer analysis found an association between high CXCL13 mRNA expression and better response to ICI therapy. CXCL13 role in promoting a lymphoid structure in the TME by facilitating B-cell recruitment could enable anti-tumor immunity, resulting in better response to immunotherapy. This indicates that dissection of not only T cell but also B cell regulatory factors is necessary to cancer immunotherapy response and resistance mechanisms. Clinical trial information: NCT02478931 .

Assessing the role of the graphene family nanomaterials (GFNs: Graphene, GO, rGO) in modifying the toxicity potential and environmental risk of flame retardant, tetrabromobisphenol-A (TBBPA) in the marine microalgae Chlorella sp.

In recent years, a growing concern has emerged regarding the environmental implications of flame retardants (FRs) like tetrabromobisphenol-A (TBBPA) and graphene family nanomaterials (GFNs), such as graphene, graphene oxide (GO), and reduced graphene oxide (rGO), on marine biota. Despite these substances' well-established individual toxicity profiles, there is a notable gap in understanding the physicochemical interactions within the binary mixtures and consequent changes in the toxicity potential. Therefore, our research focuses on elucidating the individual and combined toxicological impacts of TBBPA and GFNs on the marine alga Chlorella sp. Employing a suite of experimental methodologies, including Raman spectroscopy, contact angle measurements, electron microscopy, and chromatography, we examined the physicochemical interplay between the GFNs and TBBPA. The toxicity potentials of individual constituents and their binary combinations were assessed through growth inhibition assays, quantifying reactive oxygen species (ROS) generation and malondialdehyde (MDA) production, photosynthetic activity analyses, and various biochemical assays. The toxicity of TBBPA and graphene-based nanomaterials (GFNs) was examined individually and in combinations. Both pristine TBBPA and GFNs showed dose-dependent toxicity. While lower TBBPA concentrations exacerbated toxicity in binary mixtures, higher TBBPA levels reduced the toxic effects compared to pristine TBBPA treatments. The principal mechanism underlying toxicity was ROS generation, resulting in membrane damage and perturbation of photosynthetic parameters. Cluster heatmap and Pearson correlation were employed to assess correlations between the biological parameters. Finally, ecological risk assessment was undertaken to evaluate environmental impacts of the individual components and the mixture in the algae.

Research on the Effects of the Relationship between Agronomic Traits and Dwarfing Genes on Yield in Colored Wheat.

This research focuses on 72 approved varieties of colored wheat from different provinces in China. Utilizing coefficients of variation, structural equation models, and correlation analyses, six agronomic traits of colored wheat were comprehensively evaluated, followed by further research on different dwarfing genes in colored wheat. Using the entropy method revealed that among the 72 colored wheat varieties, 10 were suitable for cultivation. Variety 70 was the top-performing variety, with a comprehensive index of 87.15%. In the final established structural equation model, each agronomic trait exhibited a positive direct effect on yield. Notably, plant height, spike length, and flag leaf width had significant impacts on yield, with path coefficients of 0.55, 0.40, and 0.27. Transcriptome analysis and real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) validation were used to identify three dwarfing genes controlling plant height: Rht1, Rht-D1, and Rht8. Subsequent RT-qPCR validation clustering heatmap results indicated that Rht-D1 gene expression increased with the growth of per-acre yield. Rht8 belongs to the semi-dwarf gene category and has a significant positive effect on grain yield. However, the impact of Rht1, as a dwarfing gene, on agronomic traits varies. These research findings provide crucial references for the breeding of new varieties.

Examining the Alterations in Metabolite Constituents and Antioxidant Properties in Mountain-Cultivated Ginseng (Panax ginseng C.A. Meyer) Organs during a Two-Month Maturation Period

The current research was the first to prove the existence of fluctuations in the metabolite constituents and antioxidant properties in different organs (leaves, stems, and roots) of the mountain-cultivated ginseng (MCG) plant during a two-month maturation period. Four metabolites, including fatty acids, amino acids, ginsenosides, and phenolic phytochemicals, exhibited considerable differences in organs and maturation times with the following order: leaves &gt; stems &gt; roots. The predominant metabolite contents were found in leaves, with fatty acid (1057.9 mg/100 g) on 31 May, amino acid (1989.2 mg/100 g) on 13 July, ginsenosides (88.7 mg/g) on 31 May, and phenolic phytochemical (638.3 μg/g) on 31 May. Interestingly, ginsenoside content in leaves were highest, with 84.8 → 88.7 → 82.2 → 78.3 mg/g. Specifically, ginsenosides Re, Rd, and F2 showed abundant content ranging from 19.1 to 16.9 mg/g, 8.5 to 14.8 mg/g, and 9.5 to 13.1 mg/g, respectively. Phenolic phytochemicals exhibited remarkable differences in organs compared to maturation periods, with the highest total phenolic content and total flavonoid content recorded at 9.48 GAE and 1.30 RE mg/g in leaves on 31 May. The antioxidant capacities on radical, FRAP, and DNA protection differed significantly, with leaves on 31 May exhibiting the highest values: 88.4% (DPPH), 89.5% (ABTS), 0.84 OD593 nm (FRAP) at 500 μg/mL, and 100% DNA protection at 50 μg/mL. Furthermore, principal cluster analysis revealed metabolite variability as follows: ginsenoside (83.3%) &gt; amino acid (71.8%) &gt; phenolic phytochemical (61.1%) &gt; fatty acid (58.8%). A clustering heatmap highlighted significant changes in metabolite components under the maturation times for each organ. Our findings suggest that MCG leaves on 31 May may be a potential source for developing nutraceuticals, offering highly beneficial components and strong antioxidants.

Analysis of VOCs in Lueyang Black Chicken Breast Meat during the Steaming Process with GC-IMS and Stoichiometry

Steamed chicken breast meat attracts people for its unique flavor and nutritional benefits. In this study, the sensory evaluation of Lueyang black chicken breast meat during steaming was first performed, and their volatile organic compounds (VOCs) were further analyzed by gas chromatography-ion mobility spectroscopy (GC-IMS) combined with stoichiometry. The sensory results demonstrated that the Lueyang black chicken breast meat steamed for 15–30 min was more acceptable in taste, flavor, and chewiness. A total of 60 volatile flavor signal peaks were obtained, and 46 VOCs were recognized from qualitative analysis, containing 24 aldehydes (51.19–72.57%), 8 ketones (10.15–16.97%), 9 alcohols (7.98-13.16%), 2 furans (2.24–10.85%), 2 esters (0.54–1.56%), and 1 ether (0.05–2.47%). A stable and reliable prediction model was set up by orthogonal partial least squares-discriminant analysis (OPLS-DA), and 18 characteristic VOCs (including 10 aldehydes, 3 alcohols, 3 ketones, 1 furan, and 1 ether) were picked out through variable importance in the projection (VIP&gt;1.0 and p&lt;0.05). Principal component analysis (PCA) results indicated that the cumulative contribution ratio was 92% with PC1 68.7% and PC2 23.3%, respectively, indicating that these characteristic VOCs could well discriminate the steaming time of Lueyang black chicken breast meat. Heatmap clustering analysis also demonstrated a similar distinguishing effect. These results could provide references for the research, development, and quality control of ready-to-eat steamed products for Lueyang black chicken breast meat in the future.

Effects of Different Storage Times on the Stability of 12 Traditional Chinese Medicine Decoction Pieces.

As storage time increases, the quality of traditional Chinese medicines (TCMs) may change, and stability is an essential aspect of ensuring the safety and efficacy of TCMs. In this study, the effects of different storage times on the stability of 12 decoction pieces were evaluated. High-performance liquid chromatography was used to determine the contents of the active components in the 12 decoction pieces. The chemical composition data were analyzed using fingerprinting and clustering heatmap (CH). Results showed that during storage, significant variations (relative standard deviation > 10%) were observed in the levels of paeoniflorin in Paeoniae Radix Alba and Paeoniae Radix Rubra, hesperidin in Citri Reticulatae Pericarpium and Citri Reticulatae Pericarpium Viride, bufothionine in Siccus Bufo and chlorogenic acid in White Chrysanthemi Flos and Lonice Raejaponicae Caulis. However, calycosin-7-glucoside and calycosin in Astragali Radix Praeparata Cum Melle and chlorogenic acid in Lonicerae Japonicae Flos, Yellow Chrysanthemi Flos and Mori Folium were all <10%, which is consistent with the CH. Decoction pieces can be stored for up to sixmonths, but it is recommended that volatile oil-containing and animal-based decoction pieces should not be stored for more than one month. This study provides new perspectives for the stability and quality control studies of TCM.

Peripheral Blood Gene Expression Profiling Reveals Molecular Pathways Associated with Cervical Artery Dissection.

Cervical artery dissection (CeAD) is the primary cause of ischemic stroke in young adults. Monogenic heritable connective tissue diseases account for fewer than 5% of cases of CeAD. The remaining sporadic cases have known risk factors. The clinical, radiological, and histological characteristics of systemic vasculopathy and undifferentiated connective tissue dysplasia are present in up to 70% of individuals with sporadic CeAD. Genome-wide association studies identified CeAD-associated genetic variants in the non-coding genomic regions that may impact the gene transcription and RNA processing. However, global gene expression profile analysis has not yet been carried out for CeAD patients. We conducted bulk RNA sequencing and differential gene expression analysis to investigate the expression profile of protein-coding genes in the peripheral blood of 19 CeAD patients and 18 healthy volunteers. This was followed by functional annotation, heatmap clustering, reports on gene-disease associations and protein-protein interactions, as well as gene set enrichment analysis. We found potential correlations between CeAD and the dysregulation of genes linked to nucleolar stress, senescence-associated secretory phenotype, mitochondrial malfunction, and epithelial-mesenchymal plasticity.

Spatiotemporal variation in methylmercury and related water quality variables in a temperate river under highly dynamic hydrologic conditions

The understanding of the essential environmental factors affecting the spatiotemporal variation in methylmercury (MeHg) in river water is limited to date, despite its importance for predicting the effect of ongoing climate change on MeHg accumulation in freshwater ecosystems. This study aimed to explore the variation in MeHg concentration and related environmental factors in the downstream zone of the Yeongsan River under highly dynamic hydrologic conditions by using water quality and hydrologic data collected from 1997 to 2022, and Hg and MeHg data collected from 2017 to 2022. The mean concentration of unfiltered MeHg was 35.7 ± 13.7 pg L−1 (n = 24) in summer and 26.7 ± 7.43 pg L−1 (n = 24) in fall. Dissolved oxygen (DO), conductivity, nitrate, and dissolved organic carbon (DOC) were determined to be the most influential variables in terms of MeHg variation based on the partial least squares regression model, and their effects on the MeHg concentration were negative, except for DOC. Heatmaps representing the similarity distances between temporal trends of hydrologic and water quality variables were constructed to determine fundamental factors related to the time-based variations in DO, conductivity, nitrate, and DOC using a dynamic time warping algorithm. The heatmap cluster analysis showed that the temporal trends of these variables were closely related to rainfall variation rather than irradiance or water temperature. Overall, biogeochemical factors directly related to in situ methylation rate of Hg(II)—rather than transport of Hg(II) and MeHg from external sources—mainly control the spatiotemporal variation of MeHg in the downstream zone of the Yeongsan River.

AI-Enhanced evaluation of YouTube content on post-surgical incontinence following pelvic cancer treatment

BackgroundSeveral pelvic area cancers exhibit high incidence rates, and their surgical treatment can result in adverse effects such as urinary and fecal incontinence, significantly impacting patients' quality of life. Post-surgery incontinence is a significant concern, with prevalence rates ranging from 25 to 45% for urinary incontinence and 9–68% for fecal incontinence. Cancer survivors are increasingly turning to YouTube as a platform to connect with others, yet caution is warranted as misinformation is prevalent. ObjectiveThis study aims to evaluate the information quality in YouTube videos about post-surgical incontinence after pelvic area cancer surgery. MethodsA YouTube search for "Incontinence after cancer surgery" yielded 108 videos, which were subsequently analyzed. To evaluate these videos, several quality assessment tools were utilized, including DISCERN, GQS, JAMA, PEMAT, and MQ-VET. Statistical analyses, such as descriptive statistics and intercorrelation tests, were employed to assess various video attributes, including characteristics, popularity, educational value, quality, and reliability. Also, artificial intelligence techniques like PCA, t-SNE, and UMAP were used for data analysis. HeatMap and Hierarchical Clustering Dendrogram techniques validated the Machine Learning results. ResultsThe quality scales presented a high level of correlation one with each other (p < 0.01) and the Artificial Intelligence-based techniques presented clear clustering representations of the dataset samples, which were reinforced by the Heat Map and Hierarchical Clustering Dendrogram. ConclusionsYouTube videos on "Incontinence after Cancer Surgery" present a "High" quality across multiple scales. The use of AI tools, like PCA, t-SNE, and UMAP, is highlighted for clustering large health datasets, improving data visualization, pattern recognition, and complex healthcare analysis.

Toxicity evaluation of neonicotinoids to earthworm (Eisenia fetida) behaviors by a novel locomotion tracking assay

Pesticides are substances used for controlling, preventing, and repelling pests in agriculture. Among them, neonicotinoids have become the fastest-growing class of insecticides because of their efficiency in targeting pests. They work by strongly binding to nicotinic acetylcholine receptors (nAChRs) in the central nervous system of insects, leading to receptor blockage, paralysis, and death. Despite their selectivity for insects, these substances may be hazardous to non-target creatures, including earthworms. Although earthworms may be invasive in some regions like north America, they contribute to the development of soil structure, water management, nutrient cycling, pollution remediation, and cultural services, positively impacting the environment, particularly in the soil ecosystem. Thus, this study aimed to develop a novel earthworm behavior assay since behavior is a sensitive marker for toxicity assay, and demonstrated its application in evaluating the toxicity of various neonicotinoids. Here, we exposed Eisenia fetida to 1 and 10 ppb of eight neonicotinoids (acetamiprid, clothianidin, dinotefuran, imidacloprid, nitenpyram pestanal, thiacloprid, thiametoxam, and sulfoxaflor) for 3 days to observe their behavior toxicities. Overall, all of the neonicotinoids decreased their locomotion, showed by a reduction of average speed by 24.94–68.63% and increment in freezing time movement ratio by 1.51–4.25 times, and altered their movement orientation and complexity, indicated by the decrement in the fractal dimension value by 24–70%. Moreover, some of the neonicotinoids, which were acetamiprid, dinotefuran, imidacloprid, nitenpyram, and sulfoxaflor, could even alter their exploratory behaviors, which was shown by the increment in the time spent in the center area value by 6.94–12.99 times. Furthermore, based on the PCA and heatmap clustering results, thiametoxam was found as the neonicotinoid that possessed the least pronounced behavior toxicity effects among the tested pesticides since these neonicotinoid-treated groups in both concentrations were grouped in the same major cluster with the control group. Finally, molecular docking was also conducted to examine neonicotinoids' possible binding mechanism to Acetylcholine Binding Protein (AChBP), which is responsible for neurotransmission. The molecular docking result confirmed that each of the neonicotinoids has a relatively high binding energy with AChBP, with the lowest binding energy was possessed by thiametoxam, which consistent with its relatively low behavior toxicities. Thus, these molecular docking results might hint at the possible mechanism behind the observed behavior alterations. To sum up, the present study demonstrated that all of the neonicotinoids altered the earthworm behaviors which might be due to their ability to bind with some specific neurotransmitters and the current findings give insights into the toxicities of neonicotinoids to the environment, especially animals in a soil ecosystem.

Abstract PO4-05-14: Gene expression in metastatic breast cancer – patterns and prognostic potential

Abstract Introduction Metastatic breast cancer (mBC) is the leading cause of breast cancer mortality. However, mBC has a considerable variance in prognosis and course of disease, reflecting a substantial biological heterogeneity. Despite this, there is a lack of prognostic biomarkers validated for mBC. New prognostic markers and improved understanding of the molecular variants of mBC could aid in prognostication and personalizing treatments, and lead to the discovery of novel drug targets. The primary objective of this study was to explore the prognostic value of gene expression (GEX) in the distant metastasis (DM) of mBC. Secondly, we aimed to identify molecular subtypes of mBC, and describe their biological niches. Methods We used a cohort of mBC patients enrolled in a prospective trial (NCT01322893) that includes tissue from primary tumor (PT) and matched lymph node metastasis (LNM) and/or DM (1). The inclusion criteria were diagnosed mBC with a life expectancy of &amp;gt;2 months, ECOG score of 0-2, and an age of &amp;gt;18 years. RNA was extracted from formalin-fixed, paraffin-embedded tumor tissue. GEX data were acquired for n=123 PT, n=71 LNM, and n=74 DM using the NanoString Breast Cancer 360 assay, which comprises 758 genes and &amp;gt;30 GEX signatures. The relationships between GEX and the endpoints overall survival (OS) and progression-free survival (PFS) were assessed using cox proportional hazards regression with GEX as a continuous score. Multivariable cox regressions were adjusted for PAM50 of the DM, number of metastatic sites, visceral metastasis, ECOG, and age at mBC diagnosis. Visualization by heatmap and k-means clustering were used to identify GEX patterns. When clustering single genes, we included only the 100 genes with the highest standard deviation. Results In relation to PFS, we found prognostically unfavorable roles of DM GEX of the signatures for Treg cells (HR=1.3, p=0.02), cytotoxicity (HR=1.3, p=0.03), and p53 (HR=1.3, p=0.02). Further, our data indicate prognostically favorable value of DM GEX of ESR1 (HR=0.77, p=0.02), PGR (HR=0.65, p=0.002), FOXA1 (HR=0.76, p=0.02), and AR (HR=0.68, p=0.0006). The prognostic value of AR remained in multivariable analysis. In relation to OS the first 2 years after mBC prognosis, we found prognostically favorable value of DM GEX of B7H3 (HR=0.65, p=0.04), TGFB (HR=0.53, p=0.02) and the signatures for stroma (HR=0.7, p=0.05) and claudin-low (HR=0.61, p=0.02). Finally, our data suggests that the previously published PAM50MET panel performs well as a prognostic indicator, especially when considered on a continuous scale, for PFS (HR=1.3, p=0.0023) and OS (HR=1.3, p=0.003) (2). Based on the 100 most highly variable genes, we identified five stable tumor clusters with distinct GEX profiles, where some strongly associated with metastatic site. Using the same approach on the GEX signatures, we established four GEX profiles able to outperform PAM50 in identifying tumors with poor OS in this material. Conclusion In this study, we demonstrate prognostic value for GEX-based panels in DM samples. First, we find GEX signatures related to hormone responsiveness to be favorable, and genetic instability to be unfavorable for mBC prognosis. We also demonstrate AR to be an independent marker for better PFS. Further, we confirm the prognostic value of PAM50MET, a previously published panel with the advantage of including only PAM50 genes and clinical parameters. Finally, we identify new GEX profiles related to metastatic site and outcome. These results illuminate the biological differences between mBC in relation to outcome and metastatic site. Better understanding of the mBC GEX subtypes may open new venues for tailored treatment.

A comparative study on the protective effects of cuminaldehyde, thymoquinone, and gallic acid against carbon tetrachloride-induced pulmonary and renal toxicity in rats by affecting ROS and NF-κB signaling

CCl4 toxicity is a fatal condition that can cause numerous organ dysfunctions. We evaluated and compared the protective effects of cuminaldehyde (CuA), thymoquinone (TQ), and gallic acid (GA) on CCl4-induced pulmonary and renal toxicity in rats. The impacts of these compounds on CCl4-induced oxidative stress, inflammation, and morphological alterations were examined. The results showed that the compounds under investigation prevented CCl4 from significantly increasing pulmonary and renal lipid peroxidation and NO levels, as well as massively depleting GSH levels and GPX and SOD activities. Moreover, they suppressed the CCl4-induced increase in mucus secretion in the lung and upregulated the gene expression of pulmonary and renal NF-ҡB, iNOS, TNF-α, and COX-2. The heatmap cluster plots showed that GA and TQ had better protective potencies than CuA. The external organ morphology, histopathological results, and chest X-ray analysis confirmed the toxicity of CCl4 and the protective influences of the tested compounds in both the lungs and kidneys of rats. These compounds displayed predicted competitive inhibitory effects on iNOS activity and may block the IL-13α2 receptor, as revealed by molecular docking analysis. Thus, CuA, TQ, and GA, particularly the latter two, are prospective protective compounds against the pulmonary and renal toxicity caused by CCl4.

Molecular diversity of Klebsiella pneumoniae clinical isolates: antimicrobial resistance, virulence, and biofilm formation

One of the mechanisms responsible for antibiotic resistance in Klebsiella pneumoniae is the enzymes produced by the bacteria; another important mechanism is the ability to form biofilm. In this study, antibiotic resistance, genes associated with virulence, and biofilm-forming properties of K. pneumoniae strains were investigated. A total of 100 K. pneumoniae isolates were obtained from different clinical samples identified by Matrix-Assisted Laser Desorption/Ionization time-of-flight Mass Spectrometry. Antimicrobial susceptibility testing was performed with the Phoenix 100 apparatus. The biofilm forming properties of strains were determined by the microtiter plate method. For molecular analysis, genes encoding the carbapenemase enzyme (bla OXA-48, bla NDM-1, bla IMP, and bla VIM) and biofilm-related genes (treC, luxS, mrkA, and wza) were investigated by polymerase chain reaction (PCR). While 76% of clinical isolates were resistant to three or more antimicrobials, 24% were classified as non-multidrug resistant (non-MDR). When biofilm-forming capacities of clinical isolates were tested, it was determined that the resistant-isolates produced 59.2% strong biofilm, and susceptible-isolates produced 12.5% strong biofilm. According to PCR results, carbapenemase genes were determined as follows: bla OXA−48-70%, bla NDM-49%, and bla KPC-19%, bla OXA-48/bla NDM/bla KPC-12%, bla OXA-48/bla NDM-26%, and bla OXA-48/bla KPC-4%. The biofilm-associated genes in bacterial isolates were determined as follows: luxS-98%, treC-94%, mrkA-88%, and wza-15%. In addition, Hierarchical Clustering Tree and Heatmap analysis revealed an association between isolates that lacks resistance genes and isolates lacks biofilm-formation related genes that were included in MDR or non-MDR classes. As a result, biofilm should be considered in the treatment of MDR infections, and therapy should be planned accordingly. In addition, pursuing the data and genes of antibiotic resistance is significant for combating resistance.

The physicochemical components, amino acids, organic acids, phenolic compounds and antioxidant capacity of apple ciders: According to geographical origin and altitude of Fuji apple

This study aimed to analyze the physicochemical parameters, amino acids, organic acids, total phenols, total flavonoids and antioxidant capacity of apple ciders fermented with Fuji apple from different regions. The results showed that there are differences in the composition and quality characteristics of ciders fermented with Fuji apple from different regions. The apple ciders fermented with Fuji apple from 11 different producing areas were divided into three categories by cluster heat map analysis. The samples belonging to category I are from Zhaotong. Category II comprises samples from Changli, Weihai, Xingcheng, and Qingyang, while category III includes samples from Liangshan, Yuncheng, Luochuan, Aksu, Jinzhong, and Lingbao. The altitude of the apple production area has an impact on the quality of the apples, consequently affecting the distinctive characteristics of the final apple cider. This research aims to provide a theoretical basis for the development and production of high-quality apple ciders.

Unveiling the transformations in phytochemicals and grape features: a thorough examination of 'Italia' and 'Bronx Seedless' cultivars throughout multiple berry development stages

Understanding the physical and phytochemical characteristics of grape cultivars across different berry development stages is crucial for optimizing grape production and quality in the agricultural and viticultural industries. The study, therefore, investigated the physical characteristics and phytochemical composition of 'Italia' and 'Bronx Seedless' grape cultivars harvested across six distinct periods. In grape cultivars displayed an intriguing journey in terms of resveratrol, ranging from 5.96 mg/kg in Period I to 11.59 mg/kg in Period VI. These vital compounds known for contributing to grape color and potential health benefits showed substantial variation across the grape cultivars and harvest periods. In addition, significant variations in phytochemical compositions were observed between 'Italia' and 'Bronx Seedless' grape cultivars, with 'Italia' generally exhibiting higher concentrations of key compounds such as resveratrol, pterostilbene, anthocyanidins, and flavonoids. The longitudinal analysis across six berry developmental periods highlighted a progressive increase in the concentrations of these phytochemicals in cultivar, indicating a dynamic evolution of grape biochemistry over time. Particularly, delphinidin-3-O-glycoside, cyanidin-3-O-glycoside, and petunidin-3-O-glycoside showed marked increases, indicating significant growth in anthocyanin content from Period I to Period VI. Utilizing PCA biplots and a hierarchical clustering heatmap, the study visually represented the relationships and variances among various phytochemical components. The insights revealed how certain compounds clustered together, suggesting similarities and dissimilarities. The positioning of compounds on these plots indicated their significance in characterizing grape cultivars and their maturation over time. In summary, the data underlined the strong influence of berry development time on phytochemical composition, emphasizing the importance of strategic grape harvesting to attain desired phytochemical profiles for wine or other grape products. The findings provide valuable insights for grape growers, winemakers, and researchers aiming to exploit the full potential of these compounds in grape-based products and for those interested in understanding the dynamics of grape phytochemistry.

Genetic Variability and Multivariate Analysis of Physio-Biochemical Traits in Coloured Grape Genotypes

Twenty-two coloured grape accessions were screened for various physio-biochemical traits. The genetic variability and multivariate analysis were carried out for growth and biochemical parameters of grape accessions grown under Pune conditions. High genotypic and phenotypic coefficient of variations were observed in average bunch weight, berry weight, proline and total tannin. All the biochemical parameters showed very high estimated heritability for broad sense (h2b.s.). Higher genetic gain was recorded for average bunch weight, total tannin, proline and protein while low genetic gain was observed in berry diameter and seeds/berry. The multivariate analysis revealed that biochemical parameters could be potentially used for discrimination of grape genotype. The heat map cluster analysis showed higher biochemical parameters in Kali Sahebi, Kishmish Maldovski, Red Ficosa, H-516 and Omania Black. Among the accessions studied, Kali Sahebi performed better concerning growth attributes like average bunch weight, berry diameter, berry and seed weight, days to harvest and biochemical constituents like total phenol, anthocyanin and colour intensity. A very close association was observed between phenotypic and genotypic variation, particularly for biochemical parameters. Therefore, very high heritability and genetic advance were recorded in these parameters. It can be concluded that the parameters governing the very close association between phenotypic and genotypic variation can contribute to the varietal selection and trait-specific varietal development programmes.

SingmiR: a single-cell miRNA alignment and analysis tool.

Single-cell RNA sequencing(RNA-seq) has revolutionized our understanding of cell biology, developmental and pathophysiological molecular processes, paving the way toward novel diagnostic and therapeutic approaches. However, most of the gene regulatory processes on the single-cell level are still unknown, including post-transcriptional control conferred by microRNAs (miRNAs). Like the established single-cell gene expression analysis, advanced computational expertise is required to comprehensively process newly emerging single-cell miRNA-seq datasets. A web server providing a workflow tailored for single-cell miRNA-seq data with a self-explanatory interface is currently not available. Here, we present SingmiR, enabling the rapid (pre-)processing and quantification of human miRNAs from noncoding single-cell samples. It performs read trimming for different library preparation protocols, generates automated quality control reports and provides feature-normalized count files. Numerous standard and advanced analyses such as dimension reduction, clustered feature heatmaps, sample correlation heatmaps and differential expression statistics are implemented. We aim to speed up the prototyping pipeline for biologists developing single-cell miRNA-seq protocols on small to medium-sized datasets. SingmiR is freely available to all users without the need for a login athttps://www.ccb.uni-saarland.de/singmir.

Aromatic Characterization of Graševina Wines from Slavonia and Podunavlje Sub-Regions

This study investigated the chemical aromatic profiles of 60 volatile organic compounds (VOCs), including 21 terpenes, 6 norisoprenoids, 6 volatile phenols, 4 C-6 alcohols, and 23 esters, in Graševina wines originating from Slavonia and Podunavlje sub-regions (Croatia). Headspace solid-phase microextraction gas chromatography coupled with mass spectrometric detection (HS-SPME-GCMS) was used to assess 60 VOCs, and a novel HS-SPME-GCMS method for the determination of terpenes and norisoprenoids was developed and validated. Statistical analysis found no significant differences between VOCs present in Graševina wines and others wines (Chardonnay and Pinot gris); nonetheless, comparison of VOC fingerprints between different wines from the same producer showed that four terpenes (α-terpinene, γ-terpinene, 1,4-cineol, and 4-terpineol) were present in higher amounts in Graševina wines when compared to other wines. By exclusively examining VOCs within Graševina wines through the utilization of a heatmap and hierarchical clustering, a distinct visualization of samples and VOCs emerged, highlighting the vintage effect. Simultaneously, a partial least squares discriminant analysis model was developed with a confidence interval of 95%, demonstrating a noticeable distinction between samples originating from the western and eastern regions. Furthermore, by employing the heatmap using only VOCs from the terpene and norisoprenoidic groups, a clear separation of samples into two groups was observed based on geographical origin; namely, higher concentrations of norisoprenoids and terpenes were observed in the Slavonia sub-region. These results suggest that terpenes and norisoprenoids to a lower extent may be valuable aromatic markers for the regional typicality of Graševina wines.