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Abstract Alcoholic liver disease (ALD) accounts for a large fraction of patients with cirrhosis and hepatocellular carcinoma. In the present study we investigated the involvement of Brahma‐related gene 1 (Brg1) in ALD pathogenesis and implication in ALD intervention. We report that Brg1 expression was elevated in mouse models of ALD, in hepatocyte exposed to alcohol, and in human ALD specimens. Manipulation of Brg1 expression in hepatocytes influenced the development of ALD in mice. Flow cytometry showed that Brg1 deficiency specifically attenuated hepatic infiltration of Ly6G+ neutrophils in the ALD mice. RNA‐seq identified C‐X‐C motif chemokine ligand 14 (CXCL14) as a potential target for Brg1. CXCL14 knockdown alleviated whereas CXCL14 over‐expression enhanced ALD pathogenesis in mice. Importantly, pharmaceutical inhibition of Brg1 with a small‐molecule compound PFI‐3 or administration of an antagonist to the CXCL14 receptor ameliorated ALD pathogenesis in mice. Finally, a positive correlation between Brg1 expression, CXCL14 expression, and neutrophil infiltration was detected in ALD patients. In conclusion, our data provide proof‐of‐concept for targeting the Brg1‐CXCL14 axis in ALD intervention.

This study assesses the impact of a service-learning (SL) initiative at a coastal university in East China, analyzing data from 232 students enrolled in five pilot SL courses over the 2017–2020 academic years. Utilizing the Intended Learning Outcomes (ILO) questionnaire and the Community Service Attitudes Scale (CSAS), it explores changes in students' intellectual and civic development through SL. The findings reveal significant improvements in the intellectual/cognitive dimension of the ILO, confirming SL's efficacy in bridging theoretical learning with practical application, enhancing critical thinking, and fostering problem-solving skills. The study finds a positive shift in students' attitudes towards local community engagement, evidenced by improvements in six out of ten CSAS components. This contrasts with the relatively unchanged aspects of broader civic responsibilities, particularly in the civic dimension of the ILO and four CSAS sub-scales. Additionally, a gender gap in community service attitudes exists, with female students displaying more favorable views towards service than male students. The study also shows that first year students demonstrated a stronger positive assessment of benefits from community service compared to senior students. These findings suggest that in the Chinese context, SL's impact on students' sense of broader civic responsibility, empathetic understanding, and overall assessment of the costs and benefits of serving the community is more intricate and varies across student groups. The study concludes with recommendations for future SL program design and implementation strategies, emphasizing the importance of addressing the identified gaps in civic and empathy areas. [ABSTRACT FROM AUTHOR]

RNA-binding proteins (RBPs) make vital impacts on tumor progression and are important potential targets for tumor treatment. Previous studies have shown that RBP regulator of differentiation 1 (ROD1), enriched in the nucleus, is abnormally expressed and functions as a splicing factor in tumors; however, the mechanism underlying its involvement in gastric cancer (GC) is unknown. In this study, ROD1 is found to stimulate GC cell proliferation and metastasis and is related to poor patient prognosis. In vitro experiments showed that ROD1 influences GC proliferation and metastasis through modulating the imbalance of the level of the oncogenic gene OIP5 and the tumor suppressor gene GPD1L. Further studies showed that the N6-methyladenosine (m6A) “reader” protein YTHDC1 can interact with ROD1 and regulate the balance of the expression of the downstream molecules OIP5/GPD1L by promoting the nuclear enrichment of ROD1. Therefore, YTHDC1 stimulates GC development and progression through modulating nuclear enrichment of the splicing factor ROD1. [ABSTRACT FROM AUTHOR]

Pulmonary fibrosis (PF) is a severe chronic interstitial lung disease with high mortality, and there is currently a lack of definite and effective treatment methods. Studies have found that gentiopicroside, a secoiridoid glycoside compound derived from plants of the Gentiana genus, can significantly improve pulmonary inflammation and fibrosis lesions in mice with pulmonary fibrosis. However, the mechanism of its anti-fibrotic effect is unclear. Therefore, in this study, we employed network pharmacology's virtual computer technology to investigate the potential mechanism underlying the anti-pulmonary fibrosis effect of Gentianae Radix et Rhizome (Longdan in Chinese, GRR). Our findings offer valuable theoretical insights and serve as a guiding reference for future experimental investigations. A total of 10 active compounds and 920 drug-target proteins were identified from the TCMSP database. The compound-target-pathway-disease network showed that GRR could potentially treat PF by regulating the MDM2, ERBB2 and VEGFA, signaling pathways through its key targets, including AKT1, TNF, and MAPK1. The protein‒protein interaction network revealed that these targets had strong interactions with each other, indicating a potential synergistic effect of GRR in treating PF. The GO and KEGG enrichment analyses further supported the potential anti-pulmonary fibrosis mechanisms of GRR, including regulating the inflammatory response, ECM-receptor interaction, and TGF-beta signaling pathways. Our study provides a systematic analysis of the potential anti-pulmonary fibrosis mechanisms of GRR based on network pharmacology. These findings could contribute to the development of novel treatments for PF and provide a basis for further experimental studies.Article highlights: The anti-pulmonary fibrosis mechanism of GRR was investigated using network pharmacology methods An effective pathway involving the interaction of compound-target-pathway-disease was identified Several key target proteins were successfully identified, providing a basis for subsequent pharmaceutical experiments. [ABSTRACT FROM AUTHOR]

Bacterial infection has been considered as a serious problem posing health and economic risks worldwide. Although certain materials like antibiotics have been widely used as antimicrobial products, their cytotoxicity and drug resistance effect remain challenges. Fullerene (C60) has been proven as a safe antibacterial material via photodynamic therapy (PDT), but its strong hydrophobicity and limited bactericidal efficiency prevent its biomedical application. Herein, we report a facile strategy in producing ultrasmall (ca. 3 nm) zinc nanoparticle-decorated hydroxylated C60 (ZnNPs/fullerenol), which possesses high solubility and stability in water. Efficient antibacterial performances of ZnNPs/fullerenol were achieved under a visible light irradiation for only 15 min that the inhibition rate for E. coli and S. aureus could reach to 99 and 80%, respectively. This is attributed to the strong synergism of ZnNPs and fullerenol, leading to a large radical oxygen species (ROS) generation under visible light. In vivo tests further indicated excellent wound healing functionality of our composite. This work may shed light on the innovation for next generation of nanoscale antibacterial agents. [ABSTRACT FROM AUTHOR]

Epigallocatechin-3-gallate, as a representative amyloid inhibitors, has shown a promising ability against A β fibrillation by directly degradating the mature fibrils. Most previous studies have been focusing on its functional mechanisms, meanwhile its optimal dosage has been seldom considered. To solve this critical issue, we refer to the generalized Logistic model for amyloid fibrillation and inhibition and adopt the optimal control theory to balance the effectiveness and cost (or toxicity) of inhibitors. The optimal control trajectory of inhibitors is analytically solved, based on which the influence of model parameters, the difference between the optimal control strategy and several other traditional drug dosing strategies are systematically compared and validated through experiments. It is found that the strategy of multiple-times adding is more suitable for a long-term disease treatment, while single high-dose therapy is preferred for a short-term treatment. We hope our findings can shed light on the rational usage of amyloid inhibitors in clinic. [ABSTRACT FROM AUTHOR]

The effect of polydopamine (PDA) modification on aminated Fe3O4 nanoparticles (Fe3O4-NH2)/graphite oxide (GO)/β-cyclodextrin polymer cross-linked by citric acid (CDP-CA) composites were studied for the removal of a cationic dye (methylene blue, MB) and an anionic dye (Congo red, CR) from waters. The micro-structural and magnetic characterizations confirmed the successful preparation of Fe3O4-NH2/GO/CDP-CA and PDA/Fe3O4-NH2/GO/CDP-CA composites. The maximum MB and CR adsorption capacities of Fe3O4-NH2/GO/CDP-CA were 75 mg/g and 104 mg/g, respectively, while the corresponding amounts for PDA/Fe3O4-NH2/GO/CDP-CA composite were 195 mg/g and 64 mg/g, respectively. The dye sorption behaviors of these two composites were explained by their corresponding surface-charged properties according to the measured zeta potential results. Moreover, the high saturation magnetizations and the stable dye removal rate in the adsorption–desorption cycles indicated the good recyclability and reusability of the fabricated composites. [ABSTRACT FROM AUTHOR]

While children and adolescents' education has been significantly affected during the COVID-19 pandemic and school closures, how they are impacted remains unknown. Based on Bourdieu's theory, this paper aims to examine whether cultural capital mediates the association between economic capital and academic achievement during the crisis. Using a longitudinal dataset from the Chinese high school and the moderated mediation model, the result showed that economic capital had a total effect on academic achievement, especially on the students' academic ranks. Meanwhile, economic-related inequality in education seemed to be mediated by cultural capital. Interestingly, the finding further indicated that the indirect effect was mainly attributable to exam-oriented cultural capital, compared with quality-based cultural capital. we discussed the theoretical contributions and policy implications in the end. [ABSTRACT FROM AUTHOR]

Light initiates chloroplast biogenesis in Arabidopsis by eliminating PHYTOCHROME-INTERACTING transcription FACTORs (PIFs), which in turn de-represses nuclear photosynthesis genes, and synchronously, generates a nucleus-to-plastid (anterograde) signal that activates the plastid-encoded bacterial-type RNA polymerase (PEP) to transcribe plastid photosynthesis genes. However, the identity of the anterograde signal remains frustratingly elusive. The main challenge has been the difficulty to distinguish regulators from the plethora of necessary components for plastid transcription and other essential chloroplast functions, such as photosynthesis. Here, we show that the genome-wide induction of nuclear photosynthesis genes is insufficient to activate the PEP. PEP inhibition is imposed redundantly by multiple PIFs and requires PIF3's activator activity. Among the nuclear-encoded components of the PEP holoenzyme, we identify four light-inducible, PIF-repressed sigma factors as anterograde signals. Together, our results elucidate that light-dependent inhibition of PIFs activates plastid photosynthesis genes via sigma factors as anterograde signals in parallel with the induction of nuclear photosynthesis genes. Photoreceptors in the nucleus control plastid transcription by utilizing sigma factors as nucleus-to-plastid signals in parallel with the light regulation of nuclear photosynthesis genes. [ABSTRACT FROM AUTHOR]

Fullerene (C60) has been regarded as an effective radical scavenger for many years, but the highly hydrophobic nature strongly limits its application in biological fields. Herein, a simple and green strategy for synthesizing water-soluble fullerene derivative was reported, in which intrinsic C60 was grafted by amine oxide functional group (AO-C60). In addition to its excellent aqueous dispersion, AO-C60 exhibited extremely low toxicity to mice macrophage cell RAW264.7. Further experiments have confirmed the prominent antioxidative ability of AO-C60 towards typical free radicals including 1,1-diphenyl-2-picrylhydrazy (DPPH) radical, hydroxyl radical (•OH) and nitric oxide (•NO) without the help of metal loading, while the IC50 could be as low as 0.09 mg/mL. Our work will shed light on the development of anti-oxidative nanoagents with both effectiveness and bio-safety. [ABSTRACT FROM AUTHOR]

This paper investigates how peer social capital mediates associations between socioeconomic status and quality of life among adolescents during the COVID-19 pandemic. Using survey data and school administration records collected at a high school (N = 1,736) in a coastal province in China, the results demonstrate that adolescents' socioeconomic status is associated strongly with their quality of life. When students were learning at home during COVID-19 school closures, peer social capital exerted a mediating effect on the association between socioeconomic status and quality of life. Most importantly, while peer social capital rooted in the real world seemed to be related positively to higher quality of life, peer social capital in the virtual world led to lower quality of life. These findings suggest that peer social capital might manifest different impact mechanisms for adolescents during the pandemic. Theoretical contributions and policy implications are discussed in this paper. [ABSTRACT FROM AUTHOR]

In vivo optogenetics and photopharmacology are two techniques for controlling neuronal activity that have immense potential in neuroscience research. Their applications in tether-free groups of animals have been limited in part due to tools availability. Here, we present a wireless, battery-free, programable multilateral optofluidic platform with user-selected modalities for optogenetics, pharmacology and photopharmacology. This system features mechanically compliant microfluidic and electronic interconnects, capabilities for dynamic control over the rates of drug delivery and real-time programmability, simultaneously for up to 256 separate devices in a single cage environment. Our behavioral experiments demonstrate control of motor behaviors in grouped mice through in vivo optogenetics with co-located gene delivery and controlled photolysis of caged glutamate. These optofluidic systems may expand the scope of wireless techniques to study neural processing in animal models. Wireless delivery of both light and pharmacological agents is important for optogenetic and other mechanistic experiments in the brain. Here the authors present a wireless real-time programmable optofluidic platform that enables optogenetics and photopharmacology experiments that require real-time precise control of light and drug delivery. [ABSTRACT FROM AUTHOR]

Notch ligands are expression changes in a great many malignancies including gastric cancer (GC) frequently. The prognostic value of each Notch ligands in GC patients remains lack of large sample data results. In present research, we researched the prognostic value of Notch ligands in GC patients in order to fill the shortage areas. We used an online database (http://kmplot.com/analysis/index.php?p=service&cancer=gastric) to identify the relationship between mRNA expression of each Notch ligand and overall survival (OS) in GC. We analyze the relevance of overall survival and clinical data which includes gender, Lauren's classification, differentiation, clinical stage and treatment. The study found that high DLL1, DLL3, DLL4 and JAG2 mRNA expression were tied to worse OS in all GC patients followed up for 10 years. There is no significant relevance to the expression of JAG1 mRNA and OS in patients with GC. We also did a survey of each Notch ligands in different clinical and pathological features present different prognosis. The information will help to better understand the biology of gastric cancer heterogeneity, provide more accurate prognostic evaluation tools and provide new targets for targeted drug development besides. [ABSTRACT FROM AUTHOR]

Tryptophol (TOL) is a metabolic derivative of tryptophan (Trp) and shows pleiotropic effects in humans, plants and microbes. In this study, the effect of Trp and phenylalanine (Phe) on TOL production in Saccharomyces cerevisiae was determined, and a systematic interpretation of TOL accumulation was offered by transcriptomic and metabolomic analyses. Trp significantly promoted TOL production, but the output plateaued (231.02–266.31 mg/L) at Trp concentrations ≥ 0.6 g/L. In contrast, Phe reduced the stimulatory effect of Trp, which was strongly dependent on the Phe concentration. An integrated genomic, transcriptomic, and metabolomic analysis revealed that the effect of Trp and Phe on TOL production was mainly related to the transamination and decarboxylation of the Ehrlich pathway. Additionally, other genes, including thiamine regulon genes (this), the allantoin catabolic genes dal1, dal2, dal4, and the transcriptional activator gene aro80, may play important roles. These findings were partly supported by the fact that the thi4 gene was involved in TOL production, as shown by heterologous expression analysis. To the best of our knowledge, this novel biological function of thi4 in S. cerevisiae is reported here for the first time. Overall, our findings provide insights into the mechanism of TOL production, which will contribute to TOL production using metabolic engineering strategies. [ABSTRACT FROM AUTHOR]

Poverty is an objective state, as well as a set of subjective experiences. This study explored how low-income seniors in urban China make meaning under the pressures of poverty-related shame. Based on two rounds of in-depth interviews with participants in Beijing, spanning 9 years, the researchers concluded that low-income seniors feel deprivation, experiences of being belittled and inferior and a sense of self-deprecation due to material scarcity. Under such pressures, the seniors actively reconstruct poverty-related experiences, demonstrating that older people living in poverty have a powerful meaning-making system, which serves as evidence of their resilience. However, reconstructing experiences of poverty should not be taken for granted, but be regarded as an appeal for dignity-oriented social policies. This rich meaning-making system could be a foundation upon which anti-poverty advocates adopt and advance various strengths-based interventions. These findings also point to implications for quality of life research with older people living in poverty and anti-poverty measures for this population in other developing contexts. [ABSTRACT FROM AUTHOR]

Cadmium (Cd) has been widely studied as an environmental pollutant for many years. Numerous studies have reported that Cd exposure causes damage to the heart, liver, kidneys, and thyroid in vivo. The emerging evidence suggests that Cd exposure induces damage on male reproductive system, which is related to oxidative stress, inflammation, steroidogenesis disruption, and epigenetics. Current preclinical animal studies have confirmed a large number of proteins and intracellular signaling pathways involved in the pathological process of Cd-induced male reproductive damage and potential measures for prophylaxis and treatment, which primarily include antioxidants, anti-inflammatory agents, and essential ion supplement. However, explicit pathogenesis and effective treatments remain uncertain. This review collects data from the literatures, discusses the underlying mechanisms of Cd-induced toxicity on male reproductive function, and summarizes evidence that may provide guidance for the treatment and prevention of Cd-induced male reproductive toxicity. [ABSTRACT FROM AUTHOR]

Relationships between stem growth and climatic and edaphic factors, notably air temperatures and soil moisture for different slopes, are not completely understood. Stem radial variations were monitored at the bottom and top slope positions in a Larix principis-rupprechtii plantation during the 2017 and 2018 growing seasons. Total precipitation during the growing season in 2017 and 2018 was 566 mm and 728 mm, respectively. Stem contractions typically occurred after mid-morning followed by swelling in the late afternoon in both plots, reflecting the diurnal cycle of water uptake and loss. Trees at the two locations showed the same growth initiation (mid-May) because of the small differences in air and soil temperatures. There were no significant differences in cumulative stem radial growth between the bottom plot (1.57 ± 0.34 mm) and the top plot (1.55 ± 0.26 mm) in 2018. However, in 2017, the main growth period of the bottom plot ceased 17 days earlier than in the top plot, while cumulative seasonal growth of the bottom plot (1.08 ± 0.25 mm) was significantly less than the top plot (1.54 ± 0.43 mm). Maximum daily stem shrinkage was positively correlated with air and soil temperatures, solar radiation, vapor pressure deficits, and negatively correlated with volumetric soil moisture content. The maximum daily shrinkage reflected transpiration rates as affected by environmental factors. Daily radial stem increment was correlated with precipitation and volumetric soil moisture in both years, but with air temperatures only in 2017. The seasonal growth of L. principis-rupprechtii Mayr thus shows interannual dynamics, while precipitation constitutes a key driving factor. [ABSTRACT FROM AUTHOR]

The finite difference scheme is now widely used in the reverse time migration and full waveform inversion. Their results are dependent on the accuracy of finite difference operators. In this paper, we combine the cosine function with the original window function to construct a new window function, in order to obtain higher precision finite difference operators. The absolute error curves of the optimized finite difference operators are close to zero for low wavenumbers. In other words, we do not observe an oscillating curve of absolute errors produced by other optimized methods. In order to overcome the limitations of a single graphics processing unit (GPU), we developed the multiple-GPU method for the elastic wave equation. Numerical experimental results show that our new window function can control the numerical dispersion better than the binomial window and scaled binomial window, and the multiple-GPU computation is very stable. [ABSTRACT FROM AUTHOR]

Purpose: Poor sleep quality is common in medical students and is associated with a number of negative health outcomes. However, the prevalence estimates of poor sleep quality in medical students vary widely across studies. We thus conducted a meta-analysis of the prevalence of poor sleep quality and its mediating factors in medical students. Methods: A systematic literature search of PubMed, EMBASE, Web of Science, PsycINFO, and Medline Complete was performed. The random-effects model was used to analyze the pooled prevalence of poor sleep quality and its 95% confidence intervals (CIs). Results: A total of 57 studies with 25,735 medical students were included. The pooled prevalence of poor sleep quality was 52.7% (95% CI: 45.3% to 60.1%) using the Pittsburgh Sleep Quality Index (PSQI). The pooled mean total PSQI score across 41 studies with available data was 6.1 (95% CI: 5.6 to 6.5). Subgroup analyses found that PSQI cutoff value and study region were associated with the prevalence of poor sleep quality (P = 0.0003 VS. P = 0.005). Across the continents, poor sleep quality was most common in Europe, followed by the Americas, Africa, Asia, and Oceania. Meta-regression analyses found that smaller sample size (slope = − 0.0001, P = 0.009) was significantly associated with higher prevalence of poor sleep quality. Conclusions: Poor sleep quality is common among medical students, especially in Europe and the Americas continets. Due to the negative health outcomes, regular screening of poor sleep quality and effective interventions are needed for medical students. [ABSTRACT FROM AUTHOR]

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Using a hand-collected data, we provide evidence of extensive use of commodity derivative in hedging among U.S. oil and gas producers. We find large variations in hedging intensity and hedging profits while on average they generate significant positive profits. The profits relate positively to the intensity of hedging. We further decompose the hedge ratio into two components: the pure hedging component and the market timing component. We find that the hedging profits relate strongly and positively to the market timing component. We also identify a group of firms that can consistently generate profits from their hedging activities. Among firms who actively change their hedging positions, the winners tend to be larger firms. The hedging outcome does not increase equity beta while the pure hedging component tends to decrease equity beta. The positive profits are exclusive for the commodity derivative transactions of the oil and gas producers, while they do not profit from their interest rate or foreign exchange derivative transactions. [ABSTRACT FROM AUTHOR]

Large earthquake-triggered landslides near a seismogenic fault are usually closely linked to fault slipping. Therefore, it is important to research the relationship between the landslide movement and the deformation pattern of faults to better understand the location and influencing factors related to the large landslides. A large landslide, on the right bank of the Clarence River, New Zealand, was reactivated during the 2016 Mw 7.8 Kaikoura earthquake. The landslide is located in close proximity to the Papatea Fault which ruptured during the earthquake. The special tectonic location of this landslide provided favorable conditions to research the failure mechanism of earthquake-triggered landslides. Field investigation and remote-sensing images revealed that the co-seismic surface rupture zone of the Papatea Fault is relatively complicated and characterized by a wide deformation zone with a width of ~80–170 m. The northern section showed as left-lateral strike-slip and thrust-slip, with a vertical displacement of up to 4–6 m. However, it exhibited thrust motion in the Clarence landslide area. The Clarence landslide was a reactivation of a pre-existing landslide. The thrust faulting of the Papatea Fault produced a wide deformation and fractured zone near the top of the landslide mass, and resulted in over-steepened topography in the landslide area. It should be noted that long-team seismic shaking, especially the main frequency of the seismic acceleration and rapid co-seismic vertical slip of the fault, played the principal role in further accelerating topographic instability during the earthquake. The landslide body thus started to slide along a pre-existing sliding surface under these actions. Our results indicate that the deformation pattern of the seismogenic fault could also play an important role in the occurrence of earthquake-triggered landslides, in addition to geological and geomorphological conditions and local seismic acceleration. [ABSTRACT FROM AUTHOR]

Hypoxia inducible factor-1α (HIF-1α) is a central molecule involved in mediating cellular processes. Alterations of HIF-1α and hypoxically regulated microRNAs (miRNAs) are correlated with patients' outcome in various cancers, indicating their crucial roles on cancer development. Recently, an increasing number of studies have revealed the intricate regulations between miRNAs and HIF-1α in modulating a wide variety of processes, including proliferation, metastasis, apoptosis, and drug resistance, etc. miRNAs are a class of small noncoding RNAs which function as negative regulators by directly targeting mRNAs. Evidence shows that miRNAs can be regulated by HIF-1α at transcriptional level. In turn, HIF-1α itself can be modulated by many miRNAs whose alterations have been implicated in tumorigenesis, thus forming a reciprocal regulation network. These findings add a new layer of complexity to our understanding of HIF-1α regulatory networks. Here, we will provide a comprehensive overview of the current advances about the bidirectional interactions between HIF-1α and miRNAs in human cancers. Besides, the review will summarize the roles of miRNAs/HIF-1α crosstalk according to various cellular processes. Finally, the potential values of miRNAs/HIF-1α loops in clinical applications are discussed. [ABSTRACT FROM AUTHOR]

The power of synthetic biology has enabled the expression of heterologous pathways in cells, as well as genome-scale synthesis projects. The complexity of biological networks makes rational de novo design a grand challenge. Introducing features that confer genetic flexibility is a powerful strategy for downstream engineering. Here we develop an in vitro method of DNA library construction based on structural variation to accomplish this goal. The “in vitro SCRaMbLE system” uses Cre recombinase mixed in a test tube with purified DNA encoding multiple loxPsym sites. Using a β-carotene pathway designed for expression in yeast as an example, we demonstrate top-down and bottom-up in vitro SCRaMbLE, enabling optimization of biosynthetic pathway flux via the rearrangement of relevant transcription units. We show that our system provides a straightforward way to correlate phenotype and genotype and is potentially amenable to biochemical optimization in ways that the in vivo system cannot achieve. [ABSTRACT FROM AUTHOR]

1-Butyl 3-methylimidazolium bis(trifluoromethylsulfonyl) imide (BMI)-modified multiwalled carbon nanotubes (MWCNTs) were used as nanofillers for the hydrogenated carboxylated nitrile-butadiene rubber/hydrogenated nitrile-butadiene rubber (HXNBR/HNBR) blends. The multifunctional properties of rubber nanocomposites with various filler loadings were investigated. It was found that in the presence of BMI-MWCNTs, the mechanical strength, dielectric properties, electrical and thermal conductivities of HXNBR/HNBR were significantly improved due to the better dispersibility as well as the intrinsic reinforcement effect of MWCNTs. Particularly, in comparison with unfilled rubber blend, the electrical conductivity of BMI-MWCNTs-filled HXNBR/HNBR composites exhibited three orders of magnitude enhancement with a lower electrical percolation threshold. The tensile strength and thermal conductivity of composites filled with 5 phr (parts per hundred rubber) BMI-MWCNTs increased by 52 and 23%, respectively. In addition, the polarizability of composites was also intensified under the applied electric field, which resulted in remarkable dielectric relaxation compared to neat rubber. Our experimental data have indicated that BMI-MWCNTs can be used as a promising candidate for fabricating multifunctional HXNBR/HNBR nanocomposites. [ABSTRACT FROM AUTHOR]

Accurate prenatal diagnosis of complex congenital cardiovascular anomalies, vascular ones in particular, is still challenging. A fetal cardiovascular cast model can provide a copy of the cardiac chambers and great vessels with normal or pathological structures. This study was aimed to demonstrate three-dimensional anatomy of complex congenital cardiovascular anomalies in fetuses by means of corrosion casting. Twenty fetuses with prenatal-ultrasound-diagnosed complex cardiovascular anomalies were enrolled in this study (19 to 35 gestational weeks). Fetal cardiovascular cast models were made by a corrosion casting technique. The specimens were injected with casting material via the umbilical vein, and then immersed in strong acid after casting fluid was solidified, to disclose the geometries of cardiovascular cavities. Nineteen cast models were successfully made from 20 specimens. The casts distinctly showed the morphological malformations and spatial relationship between cardiac chambers and great vessels. One hundred and eleven abnormalities were revealed by casting in the 19 specimens, including 34 abnormalities located in the cardiac chambers (3, 4 and 27 anomalies in the atria, atrioventricular valves and ventricles, respectively), and 77 in the great vessels (28, 20, 24 and 5 anomalies in the aorta and its branches, the pulmonary artery, the ductus arteriosus and the major veins, respectively). Corrosion casting can display three-dimensional anatomy of fetal complex cardiovascular anomalies. This improves our understanding of related pathomorphology and prenatal diagnosis. [ABSTRACT FROM AUTHOR]

Inflammatory bowel diseases (IBD), mainly including Crohn's disease and ulcerative colitis, are characterized by chronic inflammation of the gastrointestinal tract. Despite improvements in detection, drug treatment and surgery, the pathogenesis of IBD has not been clarified. A number of miRNAs have been found to be involved in the initiation, development and progression of IBD, and they may have the potential to be used as biomarkers and therapeutic targets. Here, we have summarized the recent advances about the roles of miRNAs in IBD and analyzed the contribution of miRNAs to general diagnosis, differential diagnosis and activity judgment of IBD. Furthermore, we have also elaborated the promising role of miRNAs in IBD-related cancer prevention and prognosis prediction. [ABSTRACT FROM AUTHOR]

Background: The National Comprehensive Cancer Network (NCCN) recommends that at least 15 lymph nodes (LNs) be removed during radical gastrectomy. This study aims to investigate the optimal number of LNs resected for radical gastrectomy. Patients and Methods: From September 2008 to March 2015, a total of 1990 gastric cancer patients were enrolled in this study. Clinicopathological features and survivals were recorded, and the association between the number of LNs resected and the prognosis of gastric cancer were analyzed. Results: Overall, 1520 males (76.4%) and 470 females (23.6%) were included in the study, with a median age of 57 years (range 20-90). The median number of LNs resected was 24 (range 15-83) for stage N1, 25 (range 15-62) for stage N2, 25 (range 15-88) for stage N3a, and 28 (range 16-73) for stage N3b. The optimal cut-off value for the number of LNs resected was 22 for stage N3a ( p = 0.000) and N3b ( p = 0.003) patients, while no other cut-off value was significantly superior to 15 for stage N1-2 patients (both p > 0.05). Age, tumor size, tumor depth, and number of LNs resected were independent prognostic predictors for stage N3a patients, while resection type and number of LNs resected were independent prognostic predictors for stage N3b patients. Removing more than 22 LNs exhibited a significant survival benefit compared with removing 15-22 LNs for stage N3a and N3b patients (29.7 vs. 21.6%, p = 0.000; 12.9% vs. 0%, p = 0.003, respectively). Conclusion: Removing at least 23 LNs could yield better survival outcomes in stage N3 gastric cancer patients. [ABSTRACT FROM AUTHOR]

Employing cost-effective biomaterials to deliver chemically modified ribonucleic acid (cmRNA) in a controlled manner addresses the high cost, safety concerns, and lower transfection efficiency that exist with protein and gene therapeutic approaches. By eliminating the need for nuclear entry, cmRNA therapeutics can potentially overcome the lower transfection efficiencies associated with non-viral gene delivery systems. Here, we investigated the osteogenic potential of cmRNA-encoding BMP-9, in comparison to cmRNA-encoding BMP-2. Polyethylenimine (PEI) was used as a vector to increase in vitro transfection efficacy. Complexes of PEI-cmRNA (encoding BMP-2 or BMP-9) were fabricated at an amine (N) to phosphate (P) ratio of 10 and characterized for transfection efficacy in vitro using human bone marrow stromal cells (BMSCs). The osteogenic potential of BMSCs treated with these complexes was determined by evaluating the expression of bone-specific genes as well as through the detection of bone matrix deposition. It was found that alkaline phosphatase (ALP) expression 3 days post transfection in the group treated with BMP-9-cmRNA was significantly higher than that in the group that received BMP-2-cmRNA treatment. Alizarin red staining and atomic absorption spectroscopy demonstrated enhanced osteogenic differentiation as evidenced by increased bone matrix production by the BMSCs treated with BMP-9-cmRNA when compared to cells treated with BMP-2-cmRNA. In vivo studies showed increased bone formation in calvarial defects treated with the BMP-9-cmRNA and BMP-2-cmRNA collagen scaffolds when compared to empty defects. The connectivity density of the regenerated bone was higher (2-fold-higher) in the group that received BMP-9-cmRNA compared to BMP-2-cmRNA. Together, these findings suggest that cmRNA-activated matrix encoding osteogenic molecules can provide a powerful strategy for bone regeneration with significant clinical translational potential. [ABSTRACT FROM AUTHOR]

Gene delivery to bone is a potential therapeutic strategy for directed, sustained, and regulated protein expression. Tissue engineering strategies for bone regeneration include delivery of proteins, genes (viral and non-viral-mediated delivery), and/or cells to the bone defect site. In addition, biomimetic scaffolds and scaffolds incorporating bone anabolic agents greatly enhance the bone repair process. Regional gene therapy has the potential of enhancing bone defect healing and bone regeneration by delivering osteogenic genes locally to the osseous lesions, thereby reducing systemic toxicity and the need for using supraphysiological dosages of therapeutic proteins. By implanting gene-activated matrices (GAMs), sustained gene expression and continuous osteogenic protein production in situ can be achieved in a way that stimulates osteogenesis and bone repair within osseous defects. Critical parameters substantially affecting the therapeutic efficacy of gene therapy include the choice of osteogenic transgene(s), selection of non-viral or viral vectors, the wound environment, and the selection of ex vivo and in vivo gene delivery strategies, such as GAMs. It is critical for gene therapy applications that clinically beneficial amounts of proteins are synthesized endogenously within and around the lesion in a sustained manner. It is therefore necessary that reliable and reproducible methods of gene delivery be developed and tested for their efficacy and safety before translating into clinical practice. Practical considerations such as the age, gender, and systemic health of patients and the nature of the disease process also need to be taken into account in order to personalize the treatments and progress towards developing a clinically applicable gene therapy for healing bone defects. This review discusses tissue engineering strategies to regenerate bone with specific focus on non-viral gene delivery systems. [ABSTRACT FROM AUTHOR]

NOx removal from flue gas using direct current (DC) narrow pulsed discharge-induced non-thermal plasma (NTP) was experimentally investigated. Factors such as additives, NOx initial concentrations, residence time, reaction temperatures inside the NTP reactor, and so on were investigated to evaluate their effects on NOx removal efficiencies. The focus was on the effects of additives containing amino groups. The results showed that HO addition enhanced NOx removal, NH could further increase the NOx removal efficiencies under the same conditions without an obvious NH slip, and NH was the most effective additive by reducing NO to N. X-Ray diffraction (XRD) analysis of the products collected from the NTP reactor demonstrated that NOx removal inside the NTP reactor was mainly based on NOx oxidation when ammonia or HO was used as an additive, while NOx removal was mainly based on NOx reduction with the NH additive. [ABSTRACT FROM AUTHOR]

To investigate the application and effectiveness of vascular corrosion technique in preparing fetal cardiovascular cast models, 10 normal fetal heart specimens with other congenital disease (control group) and 18 specimens with severe congenital heart disease (case group) from induced abortions were enrolled in this study from March 2013 to June 2015 in our hospital. Cast models were prepared by injecting casting material into vascular lumen to demonstrate real geometries of fetal cardiovascular system. Casting effectiveness was analyzed in terms of local anatomic structures and different anatomical levels (including overall level, atrioventricular and great vascular system, left-sided and right-sided heart), as well as different trimesters of pregnancy. In our study, all specimens were successfully casted. Casting effectiveness analysis of local anatomic structures showed a mean score from 1.90±1.45 to 3.60±0.52, without significant differences between case and control groups in most local anatomic structures except left ventricle, which had a higher score in control group ( P=0.027). Inter-group comparison of casting effectiveness in different anatomical levels showed no significant differences between the two groups. Intra-group comparison also revealed undifferentiated casting effectiveness between atrioventricular and great vascular system, or left-sided and right-sided heart in corresponding group. Third-trimester group had a significantly higher perfusion score in great vascular system than second-trimester group ( P=0.046), while the other anatomical levels displayed no such difference. Vascular corrosion technique can be successfully used in fabrication of fetal cardiovascular cast model. It is also a reliable method to demonstrate three-dimensional anatomy of severe congenital heart disease and normal heart in fetus. [ABSTRACT FROM AUTHOR]

The connection between inflammation and tumourigenesis has been well established. However, the detailed molecular mechanism underlying inflammation-associated tumourigenesis remains unknown because this process involves a complex interplay between immune microenvironments and epithelial cells. To obtain a more systematic understanding of inflammation-associated tumourigenesis as well as to identify novel therapeutic approaches, we constructed a knowledge-based network describing the development of colitis-associated colon cancer (CAC) by integrating the extracellular microenvironment and intracellular signalling pathways. Dynamic simulations of the CAC network revealed a core network module, including P53, MDM2, and AKT, that may govern the malignant transformation of colon epithelial cells in a pro-tumor inflammatory microenvironment. Furthermore, in silico mutation studies and experimental validations led to a novel finding that concurrently targeting ceramide and PI3K/AKT pathway by chemical probes or marketed drugs achieves synergistic anti-cancer effects. Overall, our network model can guide further mechanistic studies on CAC and provide new insights into the design of combinatorial cancer therapies in a rational manner. [ABSTRACT FROM AUTHOR]

The Mg-doped materials are synthesized by a novel ionothermal method using a kind of imidazolium-based ionic liquids as both reaction medium and structure-directing agent and successively followed by a calcination process. The tests show that the Mg-doped materials present uniform particles about 150 nm which are smaller than that of LiNiMnO. The result can be mostly due to MgCl, which restrains the growth of the particles at high temperature. The electrochemical testing results demonstrate LiNiMgMnO material has the capacity retention of higher than 96.9 % after 100 cycles, and high capacity of 105.3 mAh g at 10 C rate, in comparison with the capacity retention of 91.2 % and capacity of 82.4 mAh g for the pristine one. The excellent rate performance and cycling stability can be attributed to the small and uniform nanostructure, which can make the lithium-ion diffusion and electron transfer more easily across the LiNiMgMnO/electrolyte interfaces. [ABSTRACT FROM AUTHOR]

In this article, the controllability of asynchronous Boolean multiplex control networks (ABMCNs) with time delay is studied. Firstly, dynamical model of Boolean multiplex control networks is constructed, which is assumed to be under Harvey' asynchronous update and time delay is introduced both in states and controls. By using of semi-tensor product (STP) approach, the logical dynamics is converted into an equivalent algebraic form by obtaining the control-depending network transition matrices of delayed system. Secondly, a necessary and sufficient condition is proved that only control-depending fixed points of the studied dynamics can be controlled with probability one. Thirdly, respectively for two types of controls, the controllability of dynamical control system is investigated. When initial states and time delay are given, formulae are obtained to show a) the reachable set at time s under specified controls; b) the reachable set at time s under arbitrary controls; c) the reachable probabilities to different destination states. Furthermore, an approach is discussed to find a precise control sequence which can steer dynamical system into a specified target with the maximum reachable probability. Examples are shown to illustrate the feasibility of the proposed scheme. [ABSTRACT FROM AUTHOR]