Levels Of Enrichment Research Articles

Fast and Cost-Efficient 17 O-Isotopic Labeling of Carboxylic Groups in Biomolecules: From Free Amino Acids to Peptide Chains.

17 O NMR spectroscopy is a powerful technique, which can provide unique information regarding the structure and reactivity of biomolecules. However, the low natural abundance of 17 O (0.04 %) generally requires working with enriched samples, which are not easily accessible. Here, we present simple, fast and cost-efficient 17 O-enrichment strategies for amino acids and peptides by using mechanochemistry. First, five unprotected amino acids were enriched under ambient conditions, consuming only microliter amounts of costly labeled water, and producing pure molecules with enrichment levels up to ∼40 %, yields ∼60-85 %, and no loss of optical purity. Subsequently, 17 O-enriched Fmoc/tBu-protected amino acids were produced on a 1 g/day scale with high enrichment levels. Lastly, a site-selective 17 O-labeling of carboxylic functions in peptide side-chains was achieved for RGD and GRGDS peptides, with ∼28 % enrichment level. For all molecules, 17 O ssNMR spectra were recorded at 14.1 T in reasonable times, making this an important step forward for future NMR studies of biomolecules.

Nutrient enrichment drives the sediment microbial communities in Chinese mitten crab Eriocheir sinensis culture

Microbial communities play a critical role in aquaculture ecosystems. To identify the influence of sediment nutrient levels on microbial communities, sediment and water samples were collected from Chinese mitten crab Eriocheir sinensis culture ponds with different nutrient enrichment levels. Relevant physicochemical properties were measured, and 16 S rRNA gene sequencing was applied to identify relevant bacterial communities in the sediments. The results showed that the diversity and composition of microbial communities in sediments with different levels of nutrient enrichment varied considerably. Proteobacteria was the most abundant phylum in all samples, followed by Bacteroidetes, and Desulfobacterota with relative abundances of 23.5–40.9%, 9.8–21.5%, and 9.6–18.1%, respectively. Notably, total nitrogen (TN), organic matter (OM), and pH were important factors driving sediment bacterial community aggregation, the TN concentration explaining 61.5% of the microbial community variation. This study highlights that long-term culture activities alter the degree of sediment nutrient enrichment, which in turn affects microbial community composition and may ultimately have an impact on culture efficiency.

Abstracting Data in Distributed Ledger Systems for Higher Level Analytics and Visualizations

By design, distributed ledger technologies persist low-level data, which makes conducting complex business analysis of the recorded operations challenging. Existing blockchain visualization and analytics tools such as block explorers tend to rely on this low-level data and complex interfacing to provide an enriched level of analytics. The ability to derive richer analytics could be improved through the availability of a higher level abstraction of the data. This article proposes an abstraction layer architecture that enables the design of high-level analytics of distributed ledger systems and the decentralized applications that run on top. Based on the analysis of existing initiatives and identification of the relevant user requirements, this work aims to establish key insights and specifications to improve the auditability and intuitiveness of distributed ledger systems by leveraging the development of future user interfaces. To illustrate the benefits offered by the proposed abstraction layer architecture, a regulated sector use case is explored.

Occurrence, geochemical characteristics, enrichment, and ecological risks of rare earth elements in sediments of “the Yellow river−Estuary−bay” system

Recent studies have suggested that rare earth elements (REEs) are contaminants of emerging concern. Moreover, the understanding of the occurrence and risks of REEs in river-estuary-bay systems is limited. The present study investigated the distributions, geochemical characteristics, and ecological risks of Y and 14 REEs (La, Ce, Pr, Nd, Sm, Eu, Gd, Tb, Dy, Ho, Er, Tm, Yb, and Lu) in sediments from the Yellow River to its estuary and adjacent Laizhou Bay. The average total concentrations of Y and REEs in the sediments generally increased from the Yellow River (149 mg/kg) to the estuary (165 mg/kg) and Laizhou Bay (173 mg/kg). In the estuarine core sediments, the concentrations of Y, light REEs (LREEs), and heavy REEs (HREEs) were in the ranges of 19.5–31.4 mg/kg, 58.6–156 mg/kg, and 12.3–19.1 mg/kg, respectively, from the 1700s to 2018, showing no obvious increasing or decreasing trends. The surface and core sediments from the river to the bay were characterized by obvious fractionation between LREEs and HREEs. In sediments, Fe minerals and clay are believed to promote the accumulation of REEs, especially HREEs. The enrichment levels of REEs generally increased from the middle reaches of the Yellow River to the bay, and Gd, Tb, Dy, Ho, Yb, and Lu were the most enriched elements in the sediments. Lu had moderate potential ecological risks in sediments of “the Yellow River−estuary−bay” system, and other REEs had relatively low ecological risks. The potential ecological risk indices of Y and REEs ranged from 78.7 to 144, showing increasing trends from the Yellow River to its estuary and adjacent bay, which should raise concerns regarding emerging contaminant management around estuarine and coastal regions.

Screening and identifying a novel M-MDSCs-related gene signature for predicting prognostic risk and immunotherapeutic responses in patients with lung adenocarcinoma.

Background: Lung adenocarcinoma (LUAD) shows intratumoral heterogeneity, a highly complex phenomenon that known to be a challenge during cancer therapy. Considering the key role of monocytic myeloid-derived suppressor cells (M-MDSCs) in the tumor microenvironment (TME), we aimed to build a prognostic risk model using M-MDSCs-related genes. Methods: M-MDSCs-related genes were extracted from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Utilized univariate survival analysis and random forest algorithm to screen candidate genes. A least absolute shrinkage and selection operator (LASSO) Cox regression analysis was selected to build the risk model. Patients were scored and classified into high- and low-risk groups based on the median risk scores. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis along with R packages "estimate" and "ssGSEA" were performed to reveal the mechanism of risk difference. Prognostic biomarkers and tumor mutation burden (TMB) were combined to predict the prognosis. Nomogram was carried out to predict the survival probability of patients in 1, 3, and 5years. Results: 8 genes (VPREB3, TPBG, LRFN4, CD83, GIMAP6, PRMT8, WASF1, and F12) were identified as prognostic biomarkers. The GEO validation dataset demonstrated the risk model had good generalization effect. Significantly enrichment level of cell cycle-related pathway and lower content of CD8+ T cells infiltration in the high-risk group when compared to low-risk group. Morever, the patients were from the intersection of high-TMB and low-risk groups showed the best prognosis. The nomogram demonstrated good consistency with practical outcomes in predicting the survival rate over 1, 3, and 5years. Conclusion: The risk model demonstrate good prognostic predictive ability. The patients from the intersection of low-risk and high-TMB groups are not only more sensitive response to but also more likely to benefit from immune-checkpoint-inhibitors (ICIs) treatment.

Identifying Immune-Specific Subtypes of Adrenocortical Carcinoma Based on Immunogenomic Profiling

The tumor immune microenvironment (TIME) of adrenocortical carcinoma (ACC) is heterogeneous. However, a classification of ACC based on the TIME remains unexplored. We hierarchically clustered ACC based on the enrichment levels of twenty-three immune signatures to identify its immune-specific subtypes. Furthermore, we comprehensively compared the clinical and molecular profiles between the subtypes. We identified two immune-specific subtypes of ACC: Immunity-H and Immunity-L, which had high and low immune signature scores, respectively. We demonstrated that this subtyping method was stable and reproducible by analyzing five different ACC cohorts. Compared with Immunity-H, Immunity-L had lower levels of immune cell infiltration, worse overall and disease-free survival prognosis, and higher tumor stemness, genomic instability, proliferation potential, and intratumor heterogeneity. Furthermore, the ACC driver gene CTNNB1 was more frequently mutated in Immunity-L than in Immunity-H. Several proteins, such as mTOR, ERCC1, Akt, ACC1, Cyclin_E1, β-catenin, FASN, and GAPDH, were more highly expressed in Immunity-L than in Immunity-H. In contrast, p53, Syk, Lck, PREX1, and MAPK were more highly expressed in Immunity-H. Pathway and gene ontology analysis showed that the immune, stromal, and apoptosis pathways were highly enriched in Immunity-H, while the cell cycle, steroid biosynthesis, and DNA damage repair pathways were highly enriched in Immunity-L. ACC can be classified into two stable immune-related subtypes, which have significantly different antitumor responses, molecular characteristics, and clinical outcomes. This subtyping may provide clinical implications for prognostic and immunotherapeutic stratification of ACC.

Omega-3 meat enrichment and L-FABP, PPARA, and LPL genes expression are modified by the level and period of tuna oil supplementation in slow-growing chickens.

This study proposes a strategy to manipulate the fatty acid (FA) content in slow-growing Korat chicken (KRC) meat using tuna oil (TO). To determine the optimal level and feeding period of TO supplementation, we conducted a study investigating the effects of dietary TO levels and feeding periods on meat quality, omega-3 polyunsaturated fatty acid (n-3 PUFA) composition, and gene expression related to FA metabolism in KRC breast meat. At 3 wk of age, 700 mixed-sex KRC were assigned to seven augmented factorial treatments with a completely randomized design, each consisting of four replicate pens containing 25 chickens per pen. The control group received a corn-soybean-based diet with 4.5% rice bran oil (RBO), while varying amounts of TO (1.5%, 3.0%, or 4.5%) replaced a portion of the RBO content in the experimental diets. The chickens were fed these diets for 3 and 6 wk, respectively, before being slaughtered at 9 wk. Our results indicated no significant interactions between TO levels and feeding periods on the growth performance or meat quality of KRC (P > 0.05). However, the liver fatty acid-binding protein gene (L-FABP, also known as FABP1), responsible for FA transport and accumulation, showed significantly higher expression in the chickens supplemented with 4.5% TO (P < 0.05). The chickens supplemented with 4.5% TO for a longer period (3 to 9 wk of age) exhibited the lowest levels of n-6 PUFA and n-6 to n-3 ratio, along with the highest levels of eicosapentaenoic acid, docosahexaenoic acid, and n-3 PUFA in the breast meat (P < 0.05). However, even a short period of supplementation with 4.5% TO (6 to 9 wk of age) was adequate to enrich slow-growing chicken meat with high levels of n-3 PUFA, as recommended previously. Our findings indicated that even a short period of tuna oil supplementation could lead to desirable levels of omega-3 enrichment in slow-growing chicken meat. This finding has practical implications for the poultry industry, providing insights into optimal supplementation strategies for achieving desired FA profiles without adversely affecting growth performance or meat quality.

Investigation of Radioisotopes Produced in the Core of a Navy Nuclear Reactor with Low- and High-Enriched Uranium Flues During One Cycle

ABSTRACT Today, nuclear reactors, especially small reactors, have been significantly welcomed in different countries and have various applications, including use as desalination plants, naval propulsions, etc. During the operation of the reactor, different types of radioisotopes are produced, some of which have very high activity and half-life. The type and amount of radioisotopes produced depends on the type of fuel used, the level of enrichment and the operating time of the reactor. The atomic density and activity of the most important radioisotopes for a typical reactor with two types of high and low enrichment fuel have been calculated in terms of time using MCNPX and CINDER codes. The activity of some of these radioisotopes is high and it is necessary to pay attention to possible environmental hazards. In this research, using the MCNPX Monte Carlo code, the core of a small nuclear reactor proposed as a Virginia class submarine propulsion with a power of 150 MWth was modeled. Using the BURN and KCODE cards in this code as well as the CINDER code, the fuel burnup calculations of the core of this naval reactor have been performed. For this reactor, there are two types of metal alloy fuels, including the high-enrichment UO2-Zr fuel and the low-enrichment U-10Mo fuel, and fuel burnup calculations have been performed for both fuels. After calculations, different types of radioisotopes were identified and changes in atomic density and activity quantities were calculated for the most important of these radioisotopes with high half-life during cycle and compared.

Trait adaptation enhances species coexistence and reduces bistability in an intraguild predation module.

Disentangling how species coexist in an intraguild predation (IGP) module is a great step toward understanding biodiversity conservation in complex natural food webs. Trait variation enabling individual species to adjust to ambient conditions may facilitate coexistence. However, it is still unclear how coadaptation of all species within the IGP module, constrained by complex trophic interactions and trade-offs among species-specific traits, interactively affects species coexistence and population dynamics. We developed an adaptive IGP model allowing prey and predator species to mutually adjust their species-specific defensive and offensive strategies to each other. We investigated species persistence, the temporal variation of population dynamics, and the occurrence of bistability in IGP models without and with trait adaptation along a gradient of enrichment represented by carrying capacity of the basal prey for different widths and speeds of trait adaptation within each species. Results showed that trait adaptation within multiple species greatly enhanced the coexistence of all three species in the module. A larger width of trait adaptation facilitated species coexistence independent of the speed of trait adaptation at lower enrichment levels, while a sufficiently large and fast trait adaptation promoted species coexistence at higher enrichment levels. Within the oscillating regime, increasing the speed of trait adaptation reduced the temporal variability of biomasses of all species. Finally, species coadaptation strongly reduced the presence of bistability and promoted the attractor with all three species coexisting. These findings resolve the contradiction between the widespread occurrence of IGP in nature and the theoretical predictions that IGP should only occur under restricted conditions and lead to unstable population dynamics, which broadens the mechanisms presumably underlying the maintenance of IGP modules in nature. Generally, this study demonstrates a decisive role of mutual adaptation among complex trophic interactions, for enhancing interspecific diversity and stabilizing food web dynamics, arising, for example, from intraspecific diversity.

Avaliação de risco ecológico em potencial avaliação de metal tóxico (chumbo) em prados contaminados nas proximidades da cidade suburbana: solo x forragens x gado

Heavy metal toxicity is becoming an increasing concern for environmental, human and animal health. The current research analyzed the lead (Pb) contamination in the food chain under three different irrigation sources (ground, canal, and wastewater). Soil, plant and animal samples were collected from the Jhang district of Pakistan and processed with an atomic absorption spectrophotometer. Lead concentration varied in the samples as: 5.22-10.73 mg/kg in soil, 2.46-10.34 mg/kg in forages and 0.736-2.45 mg/kg in animal samples. The observed lead concentration in forage and animal blood samples was higher than the standard limits. The pollution load index (0.640-1.32) in soil showed that lead contamination mainly took place at the wastewater irrigating sites. Bio-concentration factor values (0.313-1.15) were lower than one in all samples except Zea mays, showing that lead metal was actively taken up by Zea mays tissues from the soil. Enrichment factor values ranged from 0.849-3.12, showing a moderate level of lead enrichment. Daily intake and health risk index varied between 0.004-0.020 mg/kg/day and 0.906-4.99, respectively. All the samples showed maximum lead concentration at the wastewater irrigating site compared to the ground or canal water application sites. These results recommended that consistent application of wastewater for forage irrigation must be avoided to prevent health hazards associated with lead in the animal and human food chain. Government must implement adequate strategies to protect the animal and human health from the harms of toxic heavy metals.

Correlation of Reduced PTGER3 Expression with Prognosis and Immune Infiltration in Clear Cell Renal Carcinoma.

Prostaglandin E2 receptor 3 (PTGER3, EP3) is essential for many malignancies growth and metastasis. The role of PTGER3 in kidney renal clear cell carcinoma (KIRC) was assessed in terms of its prognosis and its association with immune infiltration. Transcriptomic expression profiles of PTGER3 were acquired from The Cancer Genome Atlas (TCGA) database. Comparative analysis was performed to evaluate the disparity in PTGER3 expression between KIRC and normal tissues. The discriminative potential of PTGER3 as a distinguishing determinant was assessed through receiver operating characteristic (ROC) curves. Prognostic factors were evaluated employing COX regression and logistic models. Furthermore, the impact of PTGER3 on survival was ascertained utilizing the Kaplan-Meier method. A protein-protein interaction (PPI) network was constructed utilizing the STRING database. To investigate the correlation between immune infiltration levels and PTGER3 expression, a single-sample Gene Set Enrichment Analysis (GSEA) method was employed, employing the Gene Set Variation Analysis (GSVA) package and the Tumor Immune Estimation Resource (TIMER) database. Bioinformatics analysis unveiled a significant downregulation of PTGER3 expression in KIRC tissues compared to paraneoplastic tissues (p < 0.001). Furthermore, quantitative reverse transcription polymerase chain reaction (qRT-PCR) experiments demonstrated a reduction in PTGER3 expression in 786-O cells in contrast to paraneoplastic tissues (p < 0.01). The ROC curve, employing PTGER3 as a potential diagnostic biomarker, exhibited a substantial area under the curve (AUC) value of 0.929. According to the Kaplan-Meier survival analysis, reduced PTGER3 expression increased the chance of negative overall survival (OS) (p = 0.019). A PPI network was constructed, elucidating the interaction patterns between PTGER3 and the top 10 co-expressed genes. An examination of gene enrichment and immune infiltration levels found a link between PTGER3 transcription and immune infiltration levels. Notably, high B cell counts and low Mast cell counts were connected to a poor prognosis in KIRC patients. The expression of PTGER3 was found to be diminished in KIRC in comparison to paracancerous tissue. This observation exhibited a correlation with both prognosis and immune cell infiltration. As a result, our findings suggest that PTGER3 could be considered a promising biomarker to forecast KIRC prognosis and as a possible target for immunotherapy.

Periphyton responses to enrichment and nutrient dilution in two mesocosm experiments in a shallow hypereutrophic reservoir

Periphyton can contribute to maintaining oligotrophic conditions in restored shallow lakes and reservoirs. In two mesocosm experiments, we evaluated the periphyton responses to enrichment and nutrient dilution in a hypereutrophic reservoir. Effects of the isolated and combined N and P enrichment and dilution levels on periphyton biomass and structure on artificial substrate were investigated. For colonization of periphyton, glass slides were exposed for 14 days (enrichment experiment) and 21 days (dilution experiment) at 20 cm deep. We monitored the effects of N and P enrichment and dilution on the algal biomass, density, and species composition in the periphyton. P was a primary limiting factor for periphyton development. Periphyton algal density and biomass increased in response to combined and isolated P enrichment. Only the 75 % dilution had a positive and significant effect on biomass and algal density in the periphyton. In both mesocosm experiments, the periphyton structure changed, with Nitzschia palea (Kutz.) Smith responding positively to P enrichment and negatively to dilution. Achnanthidium minutissimum Complex becoming dominant following 50 % and 75 % eutrophic water dilution. Our results suggest that major environmental changes are necessary for a heterogeneous algal community structure in the periphyton in hypereutrophic con¬ditions. We conclude that, after a restoration process that reduces P-competition with phytoplankton and shading, periphyton can become an important primary producer in a hypereutrophic reservoir.

Healthy Human Fecal Microbiota Transplantation into Mice Attenuates MPTP-Induced Neurotoxicity via AMPK/SOD2 Pathway.

Increasing evidence has shown that gut dysbacteriosis may play a crucial role in neuroinflammation in Parkinson's disease (PD). However, the specific mechanisms that link gut microbiota to PD remain unexplored. Given the critical roles of blood-brain barrier (BBB) dysfunction and mitochondrial dysfunction in the development of PD, we aimed to evaluate the interactions among the gut microbiota, BBB, and mitochondrial resistance to oxidation and inflammation in PD. We investigated the effects of fecal microbiota transplantation (FMT) on the physiopathology of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mice. The aim was to explore the role of fecal microbiota from PD patients and healthy human controls in neuroinflammation, BBB components, and mitochondrial antioxidative capacity via the AMPK/SOD2 pathway. Compared to control mice, MPTP-treated mice exhibited elevated levels of Desulfovibrio, whereas mice given FMT from PD patients exhibited enriched levels of Akkermansia and mice given FMT from healthy humans showed no significant alterations in gut microbiota. Strikingly, FMT from PD patients to MPTP-treated mice significantly aggravated motor impairments, dopaminergic neurodegeneration, nigrostriatal glial activation and colonic inflammation, and inhibited the AMPK/SOD2 signaling pathway. However, FMT from healthy human controls greatly improved the aforementioned MPTP-caused effects. Surprisingly, the MPTP-treated mice displayed a significant loss in nigrostriatal pericytes, which was restored by FMT from healthy human controls. Our findings demonstrate that FMT from healthy human controls can correct gut dysbacteriosis and ameliorate neurodegeneration in the MPTP-induced PD mouse model by suppressing microgliosis and astrogliosis, ameliorating mitochondrial impairments via the AMPK/SOD2 pathway, and restoring the loss of nigrostriatal pericytes and BBB integrity. These findings raise the possibility that the alteration in the human gut microbiota may be a risk factor for PD and provide evidence for potential application of FMT in PD preclinical treatment.

КЕНЖЕ МЕКТЕП ОКУУЧУЛАРЫНДАГЫ ОРИГАМИНИ КОЛДОНУУ МОТИВАЦИЯЛАРДЫН КАЛЫПТАНЫШЫНЫН ДЕҢГЭЭЛДЕРИ

In the process of practical and experimental work, we set the task to check the effectiveness of the work carried out to develop the creative abilities of younger students. The main indicator of the development of creative activity of younger students is the constant interest in the educational process, readiness to complete tasks, and their attitude to non- standard solution of tasks. The structural level of mutual enrichment in the development of the creative personality of a junior schoolchild is considered as a property that is equally applicable to everyone, emotional expressiveness, creative activity, freedom of thought and behavior. This is the formation of readiness for creativity, the search for new, non-standard ways of solving problems; the formation of communication skills in the classroom. To improve the motivational perception of learning based on interest and the desire to acquire new knowledge, concentration and stability of attention will contribute to a more intensive development of spatial and figurative thinking.

Organic matter accumulation of the Upper Triassic Ma'antang shales in the Longmenshan Foreland Basin (western Sichuan, China)

The Upper Triassic Ma'antang Formation is not only an important set of source rocks in the Sichuan Basin but may also be a successor for shale gas in China. In this study, the provenance, tectonic setting, chemical weathering, environment and productivity of the middle–late Carnian (Tuvalian) are reconstructed from petrological and geochemical data to determine the origin of the Ma'antang shales. The brachiopod-dominated fossil composition, type II-dominated organic matter, and fluctuating water salinity reflect that the shale formed in a marine environment influenced by terrestrial influx. TiO2 vs. Zr and La/Th vs. Hf diagrams, as well as the combination of major elements indicate that the Sichuan Basin was a collisional setting in the Tuvalian, and the provenance was felsic igneous source rocks. Redox-sensitive elements indicate dysoxic–anoxic conditions. Samples with Cd/Mo < 0.1 and Co*Mn > 0.4 show normal levels of Cd and relative enrichment of Mn and Co, which supports that the shale is more likely to be a product of anoxic preservation mode associated with the restricted basin. In contrast, the moderate productivity conditions reflected by Babio and P/Ti are also positive factors for organic matter accumulation. Based on the reconstruction of these environmental parameters, several driving factors that promote the formation of high TOC shales are explored. It is believed that the rapid tectonic subsidence in the early stage of foreland basin evolution (undercompensation period) created accommodation space for the shale, and the deep water also promoted anoxic bottom water, which facilitated the preservation of organic matter. The Carnian Pluvial Episode (CPE) increased global weathering and rainfall, allowing the oceans to receive more terrestrial nutrients, and freshwater influx caused stratification due to differences in salinity between the surface water and bottom water. Volcanic ash from the Wrangellia Large Igneous Province (W-LIP) and volcanic ash from local volcanoes were transported over long distances in the Late Triassic megamonsoons. Both were able to stimulate marine productivity, maintain and expand oceanic anoxia, and were beneficial for organic matter accumulation.

Occurrence and Distribution of Heavy Metals in Mining Degraded Soil and Medicinal Plants: A Case Study of Pb/Zn Sulfide Terrain Northern Areas, Pakistan

Mining activities have serious environmental impacts, thus releasing heavy metals (HMs) such as cadmium (Cd), lead (Pb), chromium (Cr), zinc (Zn) and nickel (Ni) into the surrounding environment. The current paper investigated the impacts of mining activities of Pb-Zn sulfide on soil and medicinal plants. Hence, soil samples (n = 36) and medicinal plants (n = 36) samples were collected, acid extracted and were analyzed through Inductively Coupled Plasma Mass Spectrometry (ICP-MS) for HMs quantification. Our results showed that mineralized zones showed high HMs enrichment levels as compared to non-mineralized zones. Various Indices for HMs assessment revealed that the contaminated soil of the study area had low to extreme level. The mean concentrations of HMs in mining degraded soil and medicinal plants were significantly higher (p ≤ 0.01) and were found in order of Zn > Pb > Cr > Ni > Cd and Cr > Zn > Pb > Ni > Cd respectively. Similarly, some widely consumable medicinal plants showed good metal accumulation for Cd, Cr and Pb i.e., 3.57mg kg1, 350mg kg-1 and 335mg kg-1 in C. sativa, while 5.9mg kg-1, 276.9mg kg-1 and 188.7mg kg-1 in R. hestatus respectively. Hence, the present study recommended that medicinal plants grown in mining areas should be analyzed for HMs concentration before consumption.

Systematic comparison of differential expression networks in MTB mono-, HIV mono- and MTB/HIV co-infections for drug repurposing.

The synergy between human immunodeficiency virus (HIV) and Mycobacterium tuberculosis (MTB) could accelerate the deterioration of immunological functions. Previous studies have explored the pathogenic mechanisms of HIV mono-infection (HMI), MTB mono-infection (MMI) and MTB/HIV co-infection (MHCI), but their similarities and specificities remain to be profoundly investigated. We thus designed a computational framework named IDEN to identify gene pairs related to these states, which were then compared from different perspectives. MMI-related genes showed the highest enrichment level on a greater number of chromosomes. Genes shared by more states tended to be more evolutionarily conserved, posttranslationally modified and topologically important. At the expression level, HMI-specific gene pairs yielded higher correlations, while the overlapping pairs involved in MHCI had significantly lower correlations. The correlation changes of common gene pairs showed that MHCI shared more similarities with MMI. Moreover, MMI- and MHCI-related genes were enriched in more identical pathways and biological processes, further illustrating that MTB may play a dominant role in co-infection. Hub genes specific to each state could promote pathogen infections, while those shared by two states could enhance immune responses. Finally, we improved the network proximity measure for drug repurposing by considering the importance of gene pairs, and approximately ten drug candidates were identified for each disease state.

The cGAS-STING pathway-related gene signature can predict patient prognosis and immunotherapy responses in prostate adenocarcinoma

The cyclic GMP-AMP synthase-stimulator of the interferon genes (cGAS-STING) pathway is essential in inflammation-driven tumor occurrence and progression. However, the prognostic roles and immune functions of cGAS-STING pathway-related genes in patients with prostate adenocarcinoma (PRAD) remain unclear. cGAS-STING pathway-related genes were obtained from the gene set enrichment analysis (GSEA) website. Univariate Cox regression analysis was performed to screen the prognosis-related hub genes in the cancer genome atlas (TCGA) and GSE116918 datasets. Unsupervised clustering analysis was performed to identify different clusters. The least absolute shrinkage and selection operator and multivariate Cox regression analyses were applied to develop a prognostic risk model. The prognostic values and predictive performance of risk signature were assessed by the Kaplan-Meier curve and receiver operating characteristic curve. The IMvigor210 cohort was used to investigate the potential values of the risk score in immunotherapeutic responses. Two clusters were identified based on the expression matrix of 12 prognosis-related genes. Specifically, better overall survival was observed in cluster 2 than cluster 1 in both datasets. Inflammation-related pathway enrichment and immune cell infiltration levels were altered between 2 clusters. Moreover, 6 genes (CASP8, GRK6, IL3RA, PLCB1, TBKBP1, and TNFSF10) were identified to generate a cGAS-STING pathway-related signature (CPRS). Survival analysis showed that patients in the high-risk group showed a more dismal survival than those in the low-risk group in TCGA and GSE116918 datasets. Notably, the CPRS can differentiate responsive patients from non-responsive individuals treated with PD-L1 blockades in an independent cohort. In addition, higher CPRS was associated with a more favorable prognosis. The proposed risk model was developed based on 6 cGAS-STING pathway related-genes, which can be used as a promising predictor for patient survival and immunotherapeutic responses in PRAD, contributing to treatment strategy-related decision-making.

PENGARUH STABILITAS PEKERJAAN, PENGAYAAN PEKERJAAN DAN KEPUASAN KERJA TERHADAP KOMITMEN KARYAWAN

&lt;p class="TableParagraph"&gt;&lt;em&gt;The purpose of this thesis is to investigate the mediating effect of job satisfaction on the relationships between job stability and job enrichment on employee commitment of clinic in the health organization. Data were collected from 54 clinic employees working in Mutiara Medika Rangkasbitung Clinic of Lebak Regency. Partial Least Squares were used for analysis since it is considered the best method to analyze the data containing both reflective and formative indicators. Results suggest that job satisfaction fully mediates the effects of job stability and job enrichment on employee commitment and the positive effects of the job stability and job enrichment on job satisfaction. This thesis confirms that job stability and job enrichment on employee commitment affect employee commitment via job satisfaction. Hence, job stability and job enrichment embed clinic employees in their jobs, and they are likely to improve their commitment. Furthermore, low levels of job stability and job enrichment must be addressed with a good environment clime in order to increase job satisfaction..&lt;/em&gt;&lt;/p&gt;

Surface electrostatics dictate RNA-binding protein CAPRIN1 condensate concentration and hydrodynamic properties

Biomolecular condensates concentrate proteins, nucleic acids, and small molecules and play an essential role in many biological processes. Their formation is tuned by a balance between energetically favorable and unfavorable contacts, with charge-charge interactions playing a central role in some systems. The positively charged intrinsically disordered carboxy-terminal region of the RNA-binding protein CAPRIN1 is one such example, phase separating upon addition of negatively charged ATP or high concentrations of sodium chloride (NaCl). Using solution NMR spectroscopy, we measured residue-specific near-surface electrostatic potentials (ϕENS) of CAPRIN1 along its NaCl-induced phase separation trajectory to compare with those obtained using ATP. In both cases, electrostatic shielding decreases ϕENS values, yet surface potentials of CAPRIN1 in the two condensates can be different, depending on the amount of NaCl or ATP added. Our results establish that even small differences in ϕENS can significantly affect the level of protein enrichment and the mechanical properties of the condensed phase, leading, potentially, to the regulation of biological processes.