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Numerous factors, ranging from genetics, age, lifestyle, and dietary habits to local environments, contribute to the heterogeneity of the microbiota in humans. Understanding the variability of a "healthy microbiota" is a major challenge in scientific research. The gut microbiota profiles of 148 healthy Italian volunteers were examined by 16S rRNA gene sequencing to determine the range and diversity of taxonomic compositions in the gut microbiota of healthy populations. Possible driving factors were evaluated through a detailed anamnestic questionnaire. Microbiota reference intervals were also calculated. A "scaffold" of a healthy Italian gut microbiota composition was identified. Differences in relative quantitative ratios of microbiota composition were detected in two clusters: a bigger cluster (C 2 ), which included 124 subjects, was characterized by more people from the northern Italian regions, who habitually practised more physical activity and with fewer dietary restrictions. Species richness and diversity were significantly higher in this cluster (C 2 ) than in the other one (C 1 ) (C 1 : 146.67 ± 43.67; C 2 : 198.17 ± 48.47; F = 23.40; P < 0.001 and C 1 : 16.88 ± 8.66; C 2 : 35.01 ± 13.40; F = 40.50; P < 0.001, respectively). The main contribution of the present study was the identification of the existence of a primary healthy microbiological framework that is only marginally affected by variations. Taken together, our data help to contextualize studies on population-specific variations, including marginal aspects, in human microbiota composition. Such variations must be related to the primary framework of a healthy microbiota and providing this perspective could help scientists to better design experimental plans and develop strategies for precision tailored microbiota modulation., (© 2022. The Author(s).)

The paper analyzes the process of incongruent dissolution of silicates taking place in close proximity to a talc mine. The chemical and phase composition as well as the concentrations and mobility of potentially toxic elements (PTE) in research material with varying levels of weathering were determined using instrumental (XRF, XRD) and chemical methods (extractions: BCR, aqua regia, water leaching, 0.05 M EDTA). It was demonstrated that the predominant minerals in the weathering crust include weathering-resistant minerals (i.e. quartz and muscovite) and secondary minerals (kaolinite, illite and interstratified minerals, vermiculite/chlorite) and that the predominant processes are hydrolysis and oxidation. The weathering process has an impact on the complexity of the chemical and mineral composition and the diverse structure of the weathering crust. A layer of Fe and Al oxides and hydroxides forms in the upper part of the weathering crust, while the amount of silica decreases. Low-mobility elements (i.e. Si, Al and Fe) react on the phase separation surface, causing the formation of clay minerals (i.e. vermiculite, montmorillonite) or Al and Fe hydroxides (e.g. goethite). The duration of weathering causes an increase in the content of PTEs in solid materials: multifold in the case of Cr (15), Ba (9), Pb (7), Zn (6) and considerably lower in the case of V (1.3), Sr (0.8) and Co (0.4). It was demonstrated that PTEs co-occur in several chemical fractions in the weathering crust and that the highest share of their total concentration are cations incorporated in the crystal lattice of minerals and bound by strong crystalline bonds (F4 46%). The lowest share was observed for the reducible fraction (9%) and the share of the oxidizable fraction was 29% The most mobile cations connected by the weakest bonds comprised only 16% of the total concentration. Based on the content of the readily soluble fraction of PTEs, it was concluded that the degree of weathering does not increase the environmental risk, but actually reduces it for Cr, Cr and Pb. The obtained Ecological Risk Index (ERI) values indicate that the ecological risk associated with the elements tested is low for the entire area, which means that natural weathering processes do not have any impact on environmental pollution. [ABSTRACT FROM AUTHOR]

The metabolic network of a living cell is highly intricate and involves complex interactions between various pathways. In this study, we propose a computational model that integrates glycolysis, the pentose phosphate pathway (PPP), the fatty acids beta-oxidation, and the tricarboxylic acid cycle (TCA cycle) using queueing theory. The model utilizes literature data on metabolite concentrations and enzyme kinetic constants to calculate the probabilities of individual reactions occurring on a microscopic scale, which can be viewed as the reaction rates on a macroscopic scale. However, it should be noted that the model has some limitations, including not accounting for all the reactions in which the metabolites are involved. Therefore, a genetic algorithm (GA) was used to estimate the impact of these external processes. Despite these limitations, our model achieved high accuracy and stability, providing real-time observation of changes in metabolite concentrations. This type of model can help in better understanding the mechanisms of biochemical reactions in cells, which can ultimately contribute to the prevention and treatment of aging, cancer, metabolic diseases, and neurodegenerative disorders. [ABSTRACT FROM AUTHOR]

Seismic reflection (2D/3D), borehole and bathymetric data are used to recognize a new gravitational complex in the Gulf of Squillace, Southern Italy, named the Squillace Complex. The complex has a NE-striking headwall connected to a basal detachment formed between Messinian evaporites and Tortonian shales. Its sense of movement changes to a W–E direction in the toe region. In plan view, the Squillace Complex is marked by the presence of sinuous and continuous seafloor scarps, just a few kilometers offshore, over an elongated morphological high. Seismic-well ties reveal that the complex was initiated in the Zanclean (~ 4 Ma) and continued its movement into the Gelasian (~ 2.1 Ma) at an average rate of 1.9 mm/year. Movement slowed down in the Calabrian (middle Pleistocene) and continued until the present day at a lower rate of 0.1 mm/year. Gravitational collapse of the Squillace Complex correlates with discrete contractional/transpressional events affecting the Calabrian region, which caused basin shortening and the temporary arrest of Calabrian Arc migration. These episodes resulted in tectonic uplift in the study area after 0.45 Ma (Late Pleistocene). Conversely, the complex's slower movement recorded since the Calabrian (middle Pleistocene) is associated with slab rollback of the Ionian plate under the Calabrian Arc. [ABSTRACT FROM AUTHOR]

Our work group designed and synthesized a promissory compound N-(2-hydroxyphenyl)-2-propylpentanamide (HO-AAVPA). The HO-AAVPA is a HDAC1 inhibitor and antiproliferative in cancer cell lines. However, HO-AAVPA is poor water solubility and enzymatically metabolized. In this work, the fourth-generation poly(amidoamine) dendrimer (PAMAM-G4) was used as a drug deliver carrier of HO-AAVPA. Moreover, HO-AAVPA and HO-AAVPA-PAMAM complex were submitted to forced degradation studies (heat, acid, base, oxidation and sunlight). Also, the HO-AAVPA-PAMAM-G4 complex was assayed as antiproliferative in a breast cancer cell line (MCF-7). The HO-AAVPA-PAMAM-G4 complex was obtained by docking and experimentally using three pH conditions: acid (pH = 3.0), neutral (pH = 7.0) and basic (pH = 9.0) showing that PAMAM-G4 captureand protect the HO-AAVPA from forced degradation, it is due to sunlight yielded a by-product from HO-AAVPA. In addition, the PAMAM-G4 favored the HO-AAVPA water solubility under basic and neutral pH conditions with significant difference (F(2,18) = 259.9, p < 0.001) between the slopes of the three conditions being the basic condition which solubilizes the greatest amount of HO-AAVPA. Finally, the HO-AAVPA-PAMAM-G4 complex showed better antiproliferative effects on MCF-7 (IC50 = 75.3 μM) than HO-AAVPA (IC50 = 192 μM). These results evidence that PAMAM-G4 complex improve the biological effects of HO-AAVPA. [ABSTRACT FROM AUTHOR]

Silica cycling in the world's oceans is not straightforward to evaluate on a geological time scale. With the rise of radiolarians and sponges from the early Cambrian onward, silica can have two depositional origins, continental weathering, and biogenic silica. It is critical to have a reliable method of differentiating amorphous silica and crystalline silica to truly understand biogeochemical and inorganic silica cycling. In this study, opal-A is mapped across the Western Canada Sedimentary Basin in the Late Devonian Duvernay Formation shales using longwave hyperspectral imaging alongside geochemical proxies that differentiate between crystalline and amorphous SiO2, during the expansion of the world's early forests. Signaled by several carbon isotope excursions in the Frasnian, the punctata Event corresponds to the expansion of forests when vascular land plants develop seeds and deeper root networks, likely resulting in increased pedogenesis. Nutrients from thicker soil horizons entering the marine realm are linked to higher levels of primary productivity in oceans and subsequent oxygen starvation in deeper waters at this time. The results of this study reveal, for the first time, the spatial distribution of amorphous SiO2 across a sedimentary basin during this major shift in the terrestrial realm when forests expand and develop deeper root networks. [ABSTRACT FROM AUTHOR]

The rapid development and mutations have heightened ceramic industrialization to supply the countries' requirements worldwide. Therefore, the continuous exploration for new reserves of possible ceramic-raw materials is needed to overwhelm the increased demand for ceramic industries. In this study, the suitability assessment of potential applications for Upper Cretaceous (Santonian) clay deposits at Abu Zenima area, as raw materials in ceramic industries, was extensively performed. Remote sensing data were employed to map the Kaolinite-bearing formation as well as determine the additional occurrences of clay reserves in the studied area. In this context, ten representative clayey materials from the Matulla Formation were sampled and examined for their mineralogical, geochemical, morphological, physical, thermal, and plasticity characteristics. The mineralogical and chemical compositions of starting clay materials were examined. The physicochemical surface properties of the studied clay were studied utilizing SEM–EDX and TEM. The particle-size analysis confirmed the adequate characteristics of samples for white ceramic stoneware and ceramic tiles manufacturing. The technological and suitability properties of investigated clay deposits proved the industrial appropriateness of Abu Zenima clay as a potential ceramic raw material for various ceramic products. The existence of high kaolin reserves in the studied area with reasonable quality and quantity has regional significance. It would significantly help reduce the manufacturing cost and overwhelm the high consumption rate. The ceramic manufacturers in the investigated areas are expected to bring steady producers into the industry in the long term to gain the advantage of low-cost raw materials, labor, and factory construction. [ABSTRACT FROM AUTHOR]

DNA copy number aberrated regions in cancer are known to harbor cancer driver genes and the short non-coding RNA molecules, i.e., microRNAs. In this study, we integrated the multi-omics datasets such as copy number aberration, DNA methylation, gene and microRNA expression to identify the signature microRNA-gene associations from frequently aberrated DNA regions across pan-cancer utilizing a LASSO-based regression approach. We studied 7294 patient samples associated with eighteen different cancer types from The Cancer Genome Atlas (TCGA) database and identified several cancer-specific and common microRNA-gene interactions enriched in experimentally validated microRNA-target interactions. We highlighted several oncogenic and tumor suppressor microRNAs that were cancer-specific and common in several cancer types. Our method substantially outperformed the five state-of-art methods in selecting significantly known microRNA-gene interactions in multiple cancer types. Several microRNAs and genes were found to be associated with tumor survival and progression. Selected target genes were found to be significantly enriched in cancer-related pathways, cancer hallmark and Gene Ontology (GO) terms. Furthermore, subtype-specific potential gene signatures were discovered in multiple cancer types. [ABSTRACT FROM AUTHOR]

A new 16 X-short tandem repeat (STR) multiplex PCR system has recently been developed for Sr Lankans, though its applicability in evolutionary genetics and forensic investigations has not been thoroughly assessed. In this study, 838 unrelated individuals covering all four major ethnic groups (Sinhalese, Sri Lankan Tamils, Indian Tamils and Moors) in Sri Lanka were successfully genotyped using this new multiplex system. The results indicated a high forensic efficiency for the tested loci in all four ethnicities confirming its suitability for forensic applications of Sri Lankans. Allele frequency distribution of Indian Tamils showed subtle but statistically significant differences from those of Sinhalese and Moors, in contrast to frequency distributions previously reported for autosomal STR alleles. This suggest a sex biased demographic history among Sri Lankans requiring a separate X-STR allele frequency database for Indian Tamils. Substantial differences observed in the patterns of LD among the four groups demand the use of a separate haplotype frequency databases for each individual ethnicity. When analysed together with other 14 world populations, all Sri Lankan ethnicities except Indian Tamils clustered closely with populations from Indian Bhil tribe, Bangladesh and Europe reflecting their shared Indo-Aryan ancestry. [ABSTRACT FROM AUTHOR]

Deterministic models have been widely applied in landslide risk assessment (LRA), but they have limitations in obtaining various geotechnical and hydraulic properties. The objective of this study is to suggest a new deterministic method based on machine learning (ML) algorithms. Eight crucial variables of LRA are selected with reference to expert opinions, and the output value is set to the safety factor derived by Mohr–Coulomb failure theory in infinite slope. Linear regression and a neural network based on ML are applied to find the best model between independent and dependent variables. To increase the reliability of linear regression and the neural network, the results of back propagation, including gradient descent, Levenberg–Marquardt (LM), and Bayesian regularization (BR) methods, are compared. An 1800-item dataset is constructed through measured data and artificial data by using a geostatistical technique, which can provide the information of an unknown area based on measured data. The results of linear regression and the neural network show that the special LM and BR back propagation methods demonstrate a high determination of coefficient. The important variables are also investigated though random forest (RF) to overcome the number of various input variables. Only four variables—shear strength, soil thickness, elastic modulus, and fine content—demonstrate a high reliability for LRA. The results show that it is possible to perform LRA with ML, and four variables are enough when it is difficult to obtain various variables. [ABSTRACT FROM AUTHOR]

DNA methylation could provide a link between environmental, genetic factors and weight control and can modify gene expression pattern. This study aimed to identify genes, which are differentially expressed and methylated depending on adiposity state by evaluating normal weight women and obese women before and after bariatric surgery (BS). We enrolled 24 normal weight (BMI: 22.5 ± 1.6 kg/m2) and 24 obese women (BMI: 43.3 ± 5.7 kg/m2) submitted to BS. Genome-wide methylation analysis was conducted using Infinium Human Methylation 450 BeadChip (threshold for significant CpG sites based on delta methylation level with a minimum value of 5%, a false discovery rate correction (FDR) of q < 0.05 was applied). Expression levels were measured using HumanHT-12v4 Expression BeadChip (cutoff of p ≤ 0.05 and fold change ≥2.0 was used to detect differentially expressed probes). The integrative analysis of both array data identified four genes (i.e. TPP2, PSMG6, ARL6IP1 and FAM49B) with higher methylation and lower expression level in pre-surgery women compared to normal weight women: and two genes (i.e. ZFP36L1 and USP32) that were differentially methylated after BS. These methylation changes were in promoter region and gene body. All genes are related to MAPK cascade, NIK/NF-kappaB signaling, cellular response to insulin stimulus, proteolysis and others. Integrating analysis of DNA methylation and gene expression evidenced that there is a set of genes relevant to obesity that changed after BS. A gene ontology analysis showed that these genes were enriched in biological functions related to adipogenesis, orexigenic, oxidative stress and insulin metabolism pathways. Also, our results suggest that although methylation plays a role in gene silencing, the majority of effects were not correlated. [ABSTRACT FROM AUTHOR]

Radiotherapy has a central role in the treatment of head and neck squamous cell carcinoma (HNSCC). Activation of the PI3K/AKT/mTOR pathway can decrease the efficiency of radiotherapy via the promotion of cell survival and DNA repair. Here, the influence of PI3K pathway inhibition on radiotherapy response was investigated. Two PI3K inhibitors were investigated and both BKM120 and GDC0980 effectively inhibited cellular and clonogenic growth in 6 HNSCC cells, both HPV-positive as well as HPV-negative. Despite targeted inhibition of the pathway and slight increase in DNA damage, PI3K inhibition did not show significant radiosensitization. Currently only one clinical trial is assessing the effectiveness of combining BKM120 with RT in HNSCC (NCT02113878) of which the results are eagerly awaited. [ABSTRACT FROM AUTHOR]

Estrogen receptor-positive breast cancers are treated with tamoxifen, a drug that competitively inhibits the binding of estrogen to its receptor. Resistance to tamoxifen is a major hurdle in effective management of target breast cancer patient population. A number of dynamic changes within the tumor microenvironment, including the phenomenon of epithelial to mesenchymal transition (EMT), determine the response to endocrine therapy. EMT is marked by silencing or suppression of epithelial marker, E-Cadherin and we found significantly down-regulated E-Cadherin, among other epithelial markers, and a significantly up-regulated mesenchymal marker, Twist, among other mesenchymal markers, in a model system that comprised of tamoxifen sensitive MCF-7 cells and their tamoxifen-resistant counterparts, MCF-7-TAM, developed by chronic and escalating exposure of parental cells to tamoxifen. Further, E-cadherin, but not Twist, was differentially expressed in MCF-7-TAM cells because of differential methylation. Treatment with demethylating agent 5-azacytidine increased the expression of E-cadherin thus verifying a role of methylation in its silencing and, moreover, 5-azacytidine treatment also re-sensitized MCF-7-TAM cells to tamoxifen, as evaluated by assays for viability, apoptosis and migration potential. The 5-azacytidine effects were similar to effects of E-cadherin overexpression in MCF-7-TAM cells. This work describes novel mechanism of E-cadherin downregulation in tamoxifen resistant breast cancer cells. Further studies are needed to exploit this information for betterment of breast cancer therapy. [ABSTRACT FROM AUTHOR]

The risk of gastric cancer (GC) declines after Helicobacter pylori (H. pylori) eradication and long-term aspirin use. We evaluated the effects of H. pylori eradication (Cohort 1) and aspirin use (Cohort 2) on the methylation of microRNAs (miRNAs), such as miR-34c, miR-124a-3, miR-129-2, and miR-137, in the gastric mucosa with and without GC, i.e., in atrophic mucosal glands without intestinal metaplasia (non-IM) and intestinal metaplastic glands (IM). DNA was isolated from non-IM and IM separately using laser caption microdissection. In Cohort 1, H. pylori eradication was associated with a significant reduction of miR-124a-3 methylation only in non-IM, but not in IM. miR-129-2 methylation in non-IM may be a surrogate marker of GC in H. pylori-infected patients. In Cohort 2, aspirin did not reverse miRNA methylation in either non-IM or IM, irrespective of H. pylori infection. miR-129-2 methylation in non-IM was an independent predictive marker of GC in H. pylori-infected but not -eradicated patients. These results indicate that H. pylori eradication and aspirin use were less effective for improving methylation in IM than in non-IM; thus, these interventions are recommended at an early stage prior to the development of IM to prevent GC development. In addition, the effects of the interventions were not uniform for each miRNA gene. [ABSTRACT FROM AUTHOR]

Development of personalised cancer models to predict response to radiation would benefit patient care; particularly in malignancies where treatment resistance is prevalent. Herein, a robust, easy to use, tumour-on-a-chip platform which maintains precision cut head and neck cancer for the purpose of ex vivo irradiation is described. The device utilises sintered discs to separate the biopsy and medium, mimicking in vivo microvascular flow and diffusion, maintaining tissue viability for 68 h. Integrity of tissues is demonstrated by the low levels of lactate dehydrogenase release and retained histology, accompanied by assessment of cell viability by trypan blue exclusion and flow cytometry; fluid dynamic modelling validates culture conditions. An irradiation jig is described for reproducible delivery of clinically-relevant doses (5 × 2 Gy) to newly-presenting primary tumours (n = 12); the addition of concurrent cisplatin is also investigated (n = 8) with response analysed by immunohistochemistry. Fractionated irradiation reduced proliferation (BrdU, p = 0.0064), increased DNA damage (ƴH2AX, p = 0.0043) and caspase-dependent apoptosis (caspase-cleaved cytokeratin-18) compared to control; caspase-dependent apoptosis was further increased by concurrent cisplatin compared to control (p = 0.0063). This is a proof of principle study showing the response of cancer tissue to irradiation ex vivo in a bespoke system. The novel platform described has the potential to personalise treatment for patients in a cost-effective manner with applicability to any solid tumour. [ABSTRACT FROM AUTHOR]

The risk of gastric cancer (GC) remains in precancerous conditions, including atrophic mucosa and intestinal mucosa (IM), even after H. pylori treatment. To define the molecular changes following H. pylori eradication, molecular alterations in the gastric mucosa with and without GC were evaluated in a long-term follow-up study. A total of 232 biopsy specimens from 78 consecutive patients, including atrophic gastritis patients with follow-up ≥3 y after successful H. pylori eradication (AG group), patients who developed early GC after successful eradication (≥3 y) (GC group), and patients with H. pylori-positive atrophic gastritis (Hp group), were analyzed. H. pylori eradication was associated with significant reductions of methylation of several genes/loci in atrophic mucosa (non-IM), but not in IM. In contrast, the incidence of CpG island methylator phenotype (CIMP) in IM was significantly higher in the GC group than in the AG group. miR-124a-3 methylation and miR-34c methylation were more frequently identified in IM, with very few in non-IM mucosa among the three groups. H. pylori eradication can reverse methylation only in non-IM mucosa. CIMP in IM may have potential as a surrogate maker of GC development, and methylation of miR-124a-3 and miR-34c is a molecular event in IM that may not be associated with GC development. [ABSTRACT FROM AUTHOR]