Radiotherapy (RT) is a highly effective multimodal nonsurgical treatment that is essential for patients with advanced colorectal cancer (CRC). Nevertheless, cell subpopulations displaying intrinsic ...radioresistance survive after RT. The reactivation of their proliferation and successful colonization at local or distant sites may increase the risk of poor clinical outcomes. Recently, radioresistant cancer cells surviving RT were reported to exhibit a more aggressive phenotype than parental cells, although the underlying mechanisms remain unclear.
By investigating public databases containing CRC patient data, we explored potential radioresistance-associated signaling pathways. Then, their mechanistic roles in radioresistance were investigated through multiple validation steps using patient-derived primary CRC cells, human CRC cell lines, and CRC xenografts.
Janus kinase (JAK)/signal transducer and activator of transcription (STAT) signaling was activated in radioresistant CRC tissues in correlation with local and distant metastases. JAK2 was preferentially overexpressed in the CRC stem cell subpopulation, which was accompanied by the phosphorylation of STAT proteins, especially STAT3. JAK2/STAT3 signaling played an essential role in promoting tumor initiation and radioresistance by limiting apoptosis and enhancing clonogenic potential. Mechanistically, the direct binding of STAT3 to the cyclin D2 (CCND2) promoter increased CCND2 transcription. CCND2 expression was required for persistent cancer stem cell (CSC) growth via the maintenance of an intact cell cycle and proliferation with low levels of DNA damage accumulation.
Herein, we first identified JAK2/STAT3/CCND2 signaling as a resistance mechanism for the persistent growth of CSCs after RT, suggesting potential biomarkers and regimens for improving outcomes among CRC patients.
Although there have been attempts to use non‐lead based halide perovskite materials as insulating layers for resistive switching memory, the ratio of low resistance state (LRS) to high resistance ...state (HRS) ( = ON/OFF ratio) and/or endurance is reported to be mostly lower than 103. Resistive switching memory characteristics of layered (BzA)2CuBr4 (BzA = C6H5CH2NH3) perovskite with high ON/OFF ratio and long endurance are reported here. The X‐ray diffraction (XRD) pattern of the deposited (BzA)2CuBr4 layer shows highly oriented (00l) planes perpendicular to a Pt substrate. An Ag/PMMA/(BzA)2CuBr4/Pt device shows bipolar switching behavior. A forming step at around +0.5 V is observed before the repeated bipolar switching at the SET voltage of +0.2 V and RESET voltage of ‐0.3 V. The ON/OFF ratio as high as =108 is monitored along with an endurance of ≈2000 cycles and retention time over 1000 s. The high ON/OFF ratio enables multilevel storage characteristics as confirmed by changing the compliance currents. Ohmic conduction at the LRS and Schottky emission at HRS are involved in electrochemical metallization process. The bipolar resistive switching property is retained after storing the device at ambient condition under relative humidity of about 50% for 2 weeks, which indicates that (BzA)2CuBr4 is stable memory material.
The layered (BzA)2CuBr4 (BzA = C6H5CH2NH3) perovskite is developed for an environmentally friendly multilevel data storage memristor, which exhibits a stable bipolar switching behavior at the SET voltage of +0.2 V and RESET voltage of −0.3 V, leading to ON/OFF ratio as high as 108 and endurance of 2000 cycles.
Aims
Dispersal effects on biofilms have not been adequately studied despite their strong potential impacts on biofilm development. We investigated the effects of dispersal on biofilm metacommunity.
...Methods and results
A bacterial consortium was allowed to form biofilms on 12 glass beads attached to disposable plates (compartmentalized or not), and biofilms were scrutinized on days 5, 10 and 15 using quantitative PCR and MiSeq sequencing. Biofilm population density was lesser by 2 orders of magnitude on day 5 when dispersal was allowed (p < 0.05). Then, the population rapidly increased by 4.4 orders with dispersal (p < 0.05) but did not change without dispersal. Community analyses revealed that dispersal increased the species diversity at all sampling times (p < 0.05). Dispersal affected the community structure and increased the homogeneity of local communities (p < 0.05). Distance–decay analysis showed that dispersal reduced the dissimilarity among local communities at all distance levels. Furthermore, dispersal reduced the variability of diversity, population and community structure. Network analysis revealed that dispersal increased the clustering coefficient, network density and connectivity.
Conclusions
Dispersal increased the species diversity, population and interaction and reduced the variability of the diversity, population and structure among local communities.
Significance and Impact of Study
Our results suggest that dispersal can induce the niche complementarity and mass effects.
Response of microbial community to nutrient availability in anaerobic digestion (AD) remains elusive. Prokaryotic communities in AD batch cultures with 0, 1, 3, 5, 7, 11, 15, 20, and 25 g/L peptone ...were monitored using massive parallel sequencing and quantitative PCR over a 34-day experimental period. Methane production displayed a hump-shaped response to the nutrient gradient (peaking at 15 g/L peptone). Moreover, total and acetoclastic methanogens showed hump-shaped responses (both peaking at 11 g/L peptone). However, prokaryotic population increased with nutrient concentration (linear regression, R2 = 0.86) while diversity decreased (R2 = 0.94), and ordination analysis showed a gradual succession of community structure along the first axis. Network analysis revealed that extent of interspecific interactions (e.g., edge number and clustering coefficient) exhibited a hump-shaped response. The combined results indicate that abundant species became more dominated with increasing nutrient, which can result in a gain or loss of interspecific interaction within the community. Network module analysis showed that one module dominated the network at each nutrient level (comprising 41%–65% of the nodes), indicating that AD community formed a core microbial guild. The most abundant phylotypes, Macellibacteroides and Butyricicoccaceae, were consistently negative with acetoclastic methanogens in the dominant modules. Their predominance at ≥15 g/L peptone can explain the hump-shaped responses of methanogenesis and methanogens. Collectively, methanogenesis and microbial network exhibited hump-shaped responses, although microbial community exhibited monotonic responses. Therefore, nutrient availability can determine the methanogenesis through regulating the relative fitness of methanogens within the community.
Display omitted
•Prokaryotic community displayed a monotonic response to a nutrient gradient.•Methanogenesis and interspecific interaction showed hump-shaped responses.•The prokaryotic community formed a core microbial guild for anaerobic digestion.•Suppression of methanogens by specific bacteria was greater at higher nutrients.•Nutrient availability can determine the relative fitness of methanogens.
We compared surgical resection (SR) and radiofrequency ablation (RFA) as first-line treatment in patients with hepatocellular carcinoma (HCC) based on the risk of microvascular invasion (MVI).
The ...best curative treatment modality between SR and RFA in patients with HCC with MVI remains unclear.
Data from 2 academic cancer center-based cohorts of patients with a single, small (≤3 cm) HCC who underwent SR were used to derive (n = 276) and validate (n = 101) prediction models for MVI using clinical and imaging variables. The MVI prediction model was developed using multivariable logistic regression analysis and externally validated. Early recurrence (<2 years) based on risk stratification between SR (n = 276) and RFA (n = 240) was evaluated via propensity score matching.
In the multivariable analysis, alpha-fetoprotein (≥15 ng/mL), protein induced by vitamin K absence-II (≥48 mAU/mL), arterial peritumoral enhancement, and hepatobiliary peritumoral hypointensity on magnetic resonance imaging were associated with MVI. Incorporating these factors, the area under the receiver operating characteristic curve of the predictive model was 0.87 (95% confidence interval: 0.82-0.92) and 0.82 (95% confidence interval: 0.74-0.90) in the derivation and validation cohorts, respectively. SR was associated with a lower rate of early recurrence than RFA based on the risk of MVI after propensity score matching (P < 0.05).
Our model predicted the risk of MVI in patients with a small (≤ 3 cm) HCC with high accuracy. Patients with MVI who had undergone RFA were more vulnerable to recurrence than those who had undergone SR.
The dry process is a promising fabrication method for all‐solid‐state batteries (ASSBs) to eliminate energy‐intense drying and solvent recovery steps and to prevent degradation of solid‐state ...electrolytes (SSEs) in the wet process. While previous studies have utilized the dry process to enable thin SSE films, systematic studies on their fabrication, physical and electrochemical properties, and electrochemical performance are unprecedented. Here, different fabrication parameters are studied to understand polytetrafluoroethylene (PTFE) binder fibrillation and its impact on the physio‐electrochemical properties of SSE films, as well as the cycling stability of ASSBs resulting from such SSEs. A counter‐balancing relation between the physio‐electrochemical properties and cycling stability is observed, which is due to the propagating behavior of PTFE reduction (both chemically and electrochemically) through the fibrillation network, resulting in cell failure from current leakage and ion blockage. By controlling PTFE fibrillation, a bilayer configuration of SSE film to enable physio‐electrochemically durable SSE film for both good cycling stability and charge storage capability of ASSBs is demonstrated.
Physical and electrochemical properties as well as cycling stability of dry‐processed solid‐state electrolyte films are systematically evaluated by using polytetrafluoroethylene binder. This study provides insight into binder fibrillation in designing all‐solid‐state architecture to achieve ease of fabrication and stable cycling performance.
The NLRP3 inflammasome is upregulated by various agents, such as nuclear factor-kappa B (NF-κB), lipopolysaccharide (LPS), and adenosine triphosphate (ATP). The NLRP3 inflammasome facilitations the ...maturation of interleukin (IL)-1β, a proinflammatory cytokine that is critically involved in the pathogenesis of atopic dermatitis (AD). Although the NLRP3 inflammasome clearly exacerbates AD symptoms such as erythema and pruritus, drugs for AD patients targeting the NLRP3 inflammasome are still lacking. Based on the previous findings that
essential oil (MAEO) possesses strong anti-inflammatory and anti-AD properties through its inhibition of the ERK/NF-κB signaling pathway, we postulated that MAEO might be capable of modulating the NLRP3 inflammasome in AD. The aim of this research was to investigate whether MAEO affects the inhibition of NLRP3 inflammasome activation in murine bone marrow-derived macrophages (BMDMs) stimulated with LPS + ATP in vitro and in a murine model displaying AD-like symptoms induced by 2,4-dinitrochlorobenzene (DNCB) in vivo. We found that MAEO inhibited the expression of NLRP3 and caspase-1, leading to the suppression of NLRP3 inflammasome activation and IL-1β production in BMDMs stimulated with LPS + ATP. In addition, MAEO exhibited efficacy in ameliorating AD symptoms in a murine model induced by DNCB, as indicated by the reduction in dermatitis score, ear thickness, transepidermal water loss (TEWL), epidermal thickness, and immunoglobulin E (IgE) levels. Furthermore, MAEO attenuated the recruitment of NLRP3-expressing macrophages and NLRP3 inflammasome activation in murine dorsal skin lesions induced by DNCB. Overall, we provide evidence for the anti-AD effects of MAEO via inhibition of NLRP3 inflammasome activation.
Operation of membrane bioreactors (MBRs) for wastewater treatment is hampered by the membrane biofouling resulting from microbial activities. However, the knowledge of the microbial ecology of both ...biofilm and activated sludge in MBRs has not been sufficient. In this study, we scrutinized microbial communities of biofilm and activated sludge from 10 full-scale MBR plants. Overall, Flavobacterium, Dechloromonas and Nitrospira were abundant in order of abundance in biofilm, whereas Dechloromonas, Flavobacterium and Haliscomenobacter in activated sludge. Community structure was analyzed in either biofilm or activated sludge. Among MBRs, as expected, not only diversity of microbial community but also its composition was different from one another (p < 0.05). Between the biofilm and activated sludge, community composition made significant difference, but its diversity measures (i.e., alpha diversity, e.g., richness, diversity and evenness) did not (p > 0.05). Effects of ten environmental factors on community change were investigated using Spearman correlation. MLSS, HRT, F/M ratio and SADm explained the variation of microbial composition in the biofilm, whereas only MLSS did in the activated sludge. Microbial networks were constructed with the 10 environmental factors. The network results revealed that there were different topological characteristics between the biofilm and activated sludge networks, in which each of the 4 factors had different associations with microbial nodes. These results indicated that the different microbial associations were responsible for the variation of community composition between the biofilm and activated sludge.
Display omitted
•Microbial communities of ten actual MBRs were scrutinized using Miseq sequencing.•Both microbial composition and structure differed among the MBRs.•Some environmental factors could explain the compositional variation among the MBRs.•Both microbial composition and networks were different between the biofilm and activated sludge.•It was confirmed that the variation in microbial association resulted in the compositional difference.
Non-alcoholic fatty liver disease (NAFLD) is a dominant cause of chronic liver disease, but the exact mechanism of progression from simple steatosis to nonalcoholic steatohepatitis (NASH) remains ...unknown. Here, we investigated the role of exosomes in NAFLD progression. Exosomes were isolated from a human hepatoma cell line treated with palmitic acid (PA) and their miRNA profiles examined by microarray. The human hepatic stellate cell (HSC) line (LX-2) was then treated with exosome isolated from hepatocytes. Compared with controls, PA-treated hepatocytes displayed significantly increased CD36 and exosome production. The microarray analysis showed there to be distinctive miRNA expression patterns between exosomes from vehicle- and PA-treated hepatocytes. When LX-2 cells were cultured with exosomes from PA-treated hepatocytes, the expression of genes related to the development of fibrosis were significantly amplified compared to those treated with exosomes from vehicle-treated hepatocytes. In conclusion, PA treatment enhanced the production of exosomes in these hepatocytes and changed their exosomal miRNA profile. Moreover, exosomes derived from PA-treated hepatocytes caused an increase in the expression levels of fibrotic genes in HSCs. Therefore, exosomes may have important roles in the crosstalk between hepatocytes and HSCs in the progression from simple steatosis to NASH.
Conventional deep learning (DL) algorithm requires full supervision of annotating the region of interest (ROI) that is laborious and often biased. We aimed to develop a weakly-supervised DL algorithm ...that diagnosis breast cancer at ultrasound without image annotation. Weakly-supervised DL algorithms were implemented with three networks (VGG16, ResNet34, and GoogLeNet) and trained using 1000 unannotated US images (500 benign and 500 malignant masses). Two sets of 200 images (100 benign and 100 malignant masses) were used for internal and external validation sets. For comparison with fully-supervised algorithms, ROI annotation was performed manually and automatically. Diagnostic performances were calculated as the area under the receiver operating characteristic curve (AUC). Using the class activation map, we determined how accurately the weakly-supervised DL algorithms localized the breast masses. For internal validation sets, the weakly-supervised DL algorithms achieved excellent diagnostic performances, with AUC values of 0.92-0.96, which were not statistically different (all Ps > 0.05) from those of fully-supervised DL algorithms with either manual or automated ROI annotation (AUC, 0.92-0.96). For external validation sets, the weakly-supervised DL algorithms achieved AUC values of 0.86-0.90, which were not statistically different (Ps > 0.05) or higher (P = 0.04, VGG16 with automated ROI annotation) from those of fully-supervised DL algorithms (AUC, 0.84-0.92). In internal and external validation sets, weakly-supervised algorithms could localize 100% of malignant masses, except for ResNet34 (98%). The weakly-supervised DL algorithms developed in the present study were feasible for US diagnosis of breast cancer with well-performing localization and differential diagnosis.
PDF
