Circulating tumor DNA (ctDNA) is a type of cell-free DNA released by tumor cells after necrosis and apoptosis, and it can be actively secreted by tumor cells. Since ctDNA is derived from various ...tumor sites, it can provide far more comprehensive genomic and epigenomic information than a single-site biopsy. Therefore, ctDNA can overcome tumor heterogeneity, which is the major limitation of a traditional tissue biopsy approach. Noninvasive ctDNA assays allow continuous real-time monitoring of the molecular status of cancers. Recently, ctDNA assays have been widely used in clinical practice, including cancer diagnosis, evaluation of therapeutic efficacy and prognosis, and monitoring of relapse and metastasis. Although ctDNA shows a high diagnostic performance in advanced esophageal cancer, it is far from satisfactory for early diagnosis of esophageal cancer. Monitoring the dynamic changes of ctDNA is beneficial for the evaluation of therapeutic efficacy and prediction of early recurrence in esophageal cancer. It is necessary to establish standards for individualized ctDNA detection in the evaluation of treatment response and surveillance of esophageal cancer and to develop clinical practice guideline for the systemic treatment of patients with "ctDNA recurrence." This review aims to provide an update on the role of ctDNA in the diagnosis and monitoring of esophageal cancer.
•Ethanol production by thermophilic bacteria especially via consolidated bioprocessing is reviewed.•Butanol production by thermophilic bacteria is reviewed and compared.•Further prospects on ...improvement of butanol production is proposed.
Biofuels, including ethanol and butanol, are mainly produced by mesophilic solventogenic yeasts and Clostridium species. However, these microorganisms cannot directly utilize lignocellulosic materials, which are abundant, renewable and non-compete with human demand. More recently, thermophilic bacteria show great potential for biofuels production, which could efficiently degrade lignocellulose through the cost effective consolidated bioprocessing. Especially, it could avoid contamination in the whole process owing to its relatively high fermentation temperature. However, wild types thermophiles generally produce low levels of biofuels, hindering their large scale production. This review comprehensively summarizes the state of the art development of biofuels production by reported thermophilic microorganisms, and also concludes strategies to improve biofuels production including the metabolic pathways construction, co-culturing systems and biofuels tolerance. In addition, strategies to further improve butanol production are proposed.
Co-occurrence networks inferred from the abundance data of microbial communities are widely applied to predict microbial interactions. However, the high workloads of bacterial isolation and the ...complexity of the networks themselves constrained experimental demonstrations of the predicted microbial associations and interactions. Here, we integrate droplet microfluidics and bar-coding logistics for high-throughput bacterial isolation and cultivation from environmental samples, and experimentally investigate the relationships between taxon pairs inferred from microbial co-occurrence networks. We collected Potamogeton perfoliatus plants (including roots) and associated sediments from Beijing Olympic Park wetland. Droplets of series diluted homogenates of wetland samples were inoculated into 126 96-well plates containing R2A and TSB media. After 10 days of cultivation, 65 plates with > 30% wells showed microbial growth were selected for the inference of microbial co-occurrence networks. We cultivated 129 bacterial isolates belonging to 15 species that could represent the zero-level OTUs (Zotus) in the inferred co-occurrence networks. The co-cultivations of bacterial isolates corresponding to the prevalent Zotus pairs in networks were performed on agar plates and in broth. Results suggested that positively associated Zotu pairs in the co-occurrence network implied complicated relations including neutralism, competition, and mutualism, depending on bacterial isolate combination and cultivation time.
Biobutanol production directly from lignocellulose, known as consolidated bioprocessing (CBP), is expected to be much less expensive than a process where hydrolytic enzyme production, cellulose ...saccharification, and microbial fermentation are accomplished separately. However, few microbes possess both cellulolytic and solventogenic properties in nature. Current research aims to endow cellulolytic microorganisms with butanol-producing ability or to set up microbial consortia for CBP. This review comprehensively details current achievements attempting to confer butanol-generating ability, not only to cellulolytic Clostridium strains but also to microbial consortia, to address and overcome major challenges in butanol production from cellulose. Recent advances in improving cellulosome activities within cellulolytic Clostridium strains are also emphasized.
Isobutanol and butanol can be produced from cellulose in mesophilic Clostridium cellulolyticum and Clostridium cellulovorans by introducing butanol synthesis modules.
Thermophilic Clostridium thermocellum shows increased cellulose degradation efficiency.
Microbial consortia including cellulolytic and solventogenic strains represent a simple and efficient method to achieve butanol production from cellulose in CBP. Multivariate modular metabolic engineering (MMME) provides a versatile tool to optimize the pathway and strain interactions.
Cohesin fusion of β-glucosidase into the Clostridium cellulosome can eliminate the cellobiose inhibition effect, improving the cellulose degradation efficiency of C. thermocellum.
Lytic polysaccharide monooxygenases (LPMOs) have been described as ‘cellulase boosters’. Integrating bacterial LPMOs into cellulosomes increases the levels of soluble sugars released from cellulose.
Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive disease with limited therapy. Renshen Pingfei Formula (RPFF), a classic Chinese medicine derivative formula, has been shown to exert ...therapeutic effects on IPF.
The study aimed to explore the anti-pulmonary fibrosis mechanism of RPFF through network pharmacology, clinical plasma metabolomics, and in vitro experiment.
Network pharmacology was used to study the holistic pharmacological mechanism of RPFF in the treatment of IPF. The differential plasma metabolites for RPFF in the treatment of IPF were identified by untargeted metabolomics analysis. By integrated analysis of metabolomics and network pharmacology, the therapeutic target of RPFF for IPF and the corresponding herbal ingredients were identified. In addition, the effects of the main components of the formula, kaempferol and luteolin, which regulate the adenosine monophosphate (AMP)-activated protein kinase (AMPK)/peroxisome proliferator-activated receptor γ (PPAR-γ) pathway were observed in vitro according to the orthogonal design.
A total of 92 potential targets for RPFF in the treatment of IPF were obtained. The Drug–Ingredients–Disease Target network showed that PTGS2, ESR1, SCN5A, PPAR-γ, and PRSS1 were associated with more herbal ingredients. The protein–protein interaction (PPI) network identified the key targets of RPFF in IPF treatment, including IL6, VEGFA, PTGS2, PPAR-γ, and STAT3. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis acquired the main enriched pathways, and PPAR-γ involved in multiple signaling pathways, including the AMPK signaling pathway. Untargeted clinical metabolomics analysis revealed plasma metabolite variations in patients with IPF versus controls and before versus after RPFF treatment for patients with IPF. Six differential metabolites were explored as differential plasma metabolites for RPFF in IPF treatment. Combined with network pharmacology, a therapeutic target PPAR-γ of RPFF in IPF treatment and the corresponding herbal components were identified. Based on the orthogonal experimental design, the experiments showed that kaempferol and luteolin can decrease the mRNA and protein expression of α-smooth muscle actin (α-SMA), and the combination of lower dose can inhibit α-SMA mRNA and protein expression by promoting the AMPK/PPAR-γ pathway in transforming growth factor beta 1 (TGF-β1)-treated MRC-5 cells.
This study revealed that the therapeutic effects of RPFF are due to multiple ingredients and have multiple targets and pathways, and PPAR-γ is one of therapeutic targets for RPPF in IPF and involved in the AMPK signaling pathway. Two ingredients of RPFF, kaempferol and luteolin, can inhibit fibroblast proliferation and the myofibroblast differentiation of TGF-β1, and exert a synergistic effect through AMPK/PPAR-γ pathway activation.
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•Untarget clinical metabolomics analysis revealed the six differential metabolites, as plasma differential metabolites for RPFF in the treatment of IPF.•PPAR-γ is one of therapeutic targets for RPPF in IPF, and involved in AMPK signaling pathway integrated metabolomics and network pharmacology analysis.•The ingredients of RPFF, kaempferol and luteolin could inhibit TGF-β1 induced fibroblast proliferation and myofibroblast differentiation and exert a synergistic effect through AMPK/PPAR-γ pathway activation.
This study investigates the relationship between supervisory behavior, conflict management strategies, and sustainable employee performance and inquires the mediating effect of conflict management ...strategies. Data were collected from the SMEs of the manufacturing industry of Pakistan. The significance of the model was assessed using the PLS-SEM (structural equation modeling). The findings of the study revealed a positive and significant relationship between supervisory behavior and sustainable employee behavior. Similarly, conflict management strategies had a positive effect on the relationship between supervisory behavior and sustainable employee behavior. This study adds in the current literature of supervisory behavior as a critical predictor of sustainable employee performance in two ways. Firstly, this study validates Conflict management strategies as an influential mediator between the relationship of supervisory behavior and sustainable employee performance. Secondly, this study provides substantial practical implications for managers at SMEs to enhance sustainable employee performance through supervisory behavior, stimulated by conflict management strategies. This study is based on cross-sectional data; more longitudinal studies can further strengthen the generalizability of relationships between the constructs. The study adds in the current literature of PLS-SEM as an assessment model for direct and mediation relationships.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Oxidative stress is a major cause of adverse outcomes in preeclampsia (PE). Ferroptosis, i.e. programmed cell death from iron-dependent lipid peroxidation, likely mediates PE pathogenesis. We ...evaluated specific markers for ferroptosis in normal and PE placental tissues, using in vitro (trophoblasts) and in vivo (rat) models. Increase in malondialdehyde content and total Fe2+ along with reduced the glutathione content and glutathione peroxidase activity was observed in PE placenta. While the trophoblasts experienced death under hypoxia, inhibitors of ferroptosis, apoptosis, autophagy, and necrosis increased the cell viability. Microarrays, bioinformatic analysis, and luciferase reporter assay revealed that upregulation of miR-30b-5p in PE models plays a pivotal role in ferroptosis, by downregulating Cys2/glutamate antiporter and PAX3 and decreasing ferroportin 1 (an iron exporter) expression, resulting in decreased GSH and increased labile Fe2+. Inhibition of miR-30b-5p expression and supplementation with ferroptosis inhibitors attenuated the PE symptoms in rat models, making miR-30b-5p a potential therapeutic target for PE.
A UiO type MOF with Lewis basic bipyridyl sites was synthesized and structurally characterized. After being activated by Soxhlet-extraction, this MOF exhibits high storage capacities for H2, CH4 and ...CO2, and shows unusual stepwise adsorption for liquid CO2 and solvents, indicating a sequential filling mechanism on different adsorption sites.
The construction of acyclic, non‐adjacent 1,3‐stereogenic centers, prevalent motifs in drugs and bioactive molecules, has been a long‐standing synthetic challenge due to acyclic nucleophiles being ...distant from the chiral environment. In this study, we successfully synthesized highly valuable 1,2‐bis(boronic) esters featuring acyclic and nonadjacent 1,3‐stereocenters. Notably, this reaction selectively produces migratory coupling products rather than alternative deborylative allylation or direct allylation byproducts. This approach introduces a new activation mode for selective transformations of gem‐diborylmethane in asymmetric catalysis. Additionally, we found that other gem‐diborylalkanes, previously challenging due to steric hindrance, also successfully participated in this reaction. The incorporation of 1,2‐bis(boryl)alkenes facilitated the diversification of the alkenyl and two boron moieties in our target compounds, thereby enabling access to a broad array of versatile molecules. DFT calculations were performed to elucidate the reaction mechanism and shed light on the factors responsible for the observed excellent enantioselectivity and diastereoselectivity. These were determined to arise from ligand‐substrate steric repulsions in the syn‐addition transition state.
We have developed an efficient method for synthesizing chiral 1,2‐bis(boronic) esters bearing non‐adjacent, acyclic 1,3‐stereocenters. Notably, a novel activation mode for gem‐diborylalkanes in asymmetric catalysis has been uncovered, avoiding two potential side‐products encountered when using classical conditions. This innovative approach exhibits excellent chemo‐, regio‐, enantio‐ and diastereoselectivity.
MicroRNA (miRNA or miR) has been shown to play an important role in the initiation and development in many different cancers. Here, we demonstrated down‐regulated expression of miR‐27a‐3p in ...hepatocellular carcinoma (HCC) tissues in comparison with that in adjacent normal liver tissues based on the TCGA database. Cells viability and apoptosis was measured by CCK‐8 and flow cytometry assay. Cell invasion and migration was measured by Transwell and wound healing assay. The effect of miR‐27a‐3p on DUSP16 expression was evaluated by luciferase assays, and western blot assay. miR‐27a‐3p up‐regulation by transfection with miR‐27a‐3p mimics attenuated SMMC‐7721 and HepG2 cell viability, invasion as well as migration, obviously. Moreover, we found that dual specificity phosphatase 16 (DUSP16), also known as mitogen‐activated protein kinase phosphatase 7 (MKP‐7), is a target of miR‐27a‐3p. DUSP16 expression was obvious decrease by miR‐27a‐3p at both transcriptional and protein levels in both SMMC‐7721 and HepG2 cells. DUSP16 expression in tissues of HCC was up‐regulated in comparison with that in tissues of adjacent liver based on the TCGA database. Overexpression of DUSP16 significantly reversed the cell changes in viability, invasion and migration which resulted from miR‐27a‐3p up‐regulation in SMMC‐7721 and HepG2 cells. Our findings contribute to current understanding of the functions of miR‐27a‐3p and suggest a mechanism by which miR‐27a‐3p plays an anti‐tumor role in the development of HCC by targeting DUSP16.
miR‐27a‐3p induces cell apoptosis and inhibits cell invasion and migration of HCC. miR‐27a‐3p negative regulates DUSP16 expression. DUSP16 overexpression inhibits miR‐27a‐3p‐induced cell apoptosis and decreased cell invasion and migration of HCC.
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