The diagnosis of biliary atresia (BA) remains a clinical challenge because affected infants have signs, symptoms, and serum liver biochemistry that are also seen in those with other causes of ...neonatal cholestasis (non‐BA). However, an early diagnosis and prompt surgical treatment are required to improve clinical outcome. Recently, the relative abundance of serum matrix metalloproteinase‐7 (MMP‐7) was suggested to have discriminatory features for infants with BA. To test the hypothesis that elevated serum concentration of MMP‐7 is highly diagnostic for BA, we determined the normal serum concentration of MMP‐7 in healthy control infants, and then in 135 consecutive infants being evaluated for cholestasis. The median concentration for MMP‐7 was 2.86 ng/mL (interquartile range, IQR: 1.32‐5.32) in normal controls, 11.47 ng/mL (IQR: 8.54‐24.55) for non‐BA, and 121.1 ng/mL (IQR: 85.42‐224.4) for BA (P < 0.0001). The area under the curve of MMP‐7 for the diagnosis of BA was 0.9900 with a cutoff value of 52.85 ng/mL; the diagnostic sensitivity and specificity were 98.67% and 95.00%, respectively, with a negative predictive value of 98.28%. Conclusion: Serum MMP‐7 assay has high sensitivity and specificity to differentiate BA from other neonatal cholestasis, and may be a reliable biomarker for BA.
► ANCR level is significantly decreased during osteoblastic differentiation. ► ANCR downregulation promotes osteoblastic differentiation. ► ANCR is associated with enhancer of zeste homolog 2 (EZH2). ...► ANCR regulates Runx2 expression and osteoblast differentiation by EZH2.
Long noncoding RNAs (lncRNAs) are key regulators of diverse biological processes such as transcriptional regulation, cell growth and differentiation. Previous studies have demonstrated that the lncRNA-ANCR (anti-differentiation ncRNA) is required to maintain the undifferentiated cell state within the epidermis. However, little is known about whether ANCR regulates osteoblast differentiation. In this study, we found that the ANCR expression level is significantly decreased during hFOB1.19 cell differentiation. ANCR-siRNA blocks the expression of endogenous ANCR, resulting in osteoblast differentiation, whereas ANCR overexpression is sufficient to inhibit osteoblast differentiation. We further demonstrated that ANCR is associated with enhancer of zeste homolog 2 (EZH2) and that this association results in the inhibition of both Runx2 expression and subsequent osteoblast differentiation. These data suggest that ANCR is an essential mediator of osteoblast differentiation, thus offering a new target for the development of therapeutic agents to treat bone diseases.
Microplastics, which are plastic debris with a particle diameter of less than 5 mm, have attracted growing attention in recent years. Its widespread distributions in a variety of habitats have urged ...scientists to understand deeper regarding their potential impact on the marine living resources. Most studies on microplastics hitherto are focused on the marine environment, and research on risk assessment methodology is still limited. To understand the distribution of microplastics in urban rivers, this study investigated river sediments in Shanghai, the largest urban area in China. Seven sites were sampled to ensure maximum coverage of the city's central districts, and a tidal flat was also included to compare with river samples. Density separation, microscopic inspection and μ-FT-IR analysis were conducted to analyze the characteristics of microplastics and the type of polymers. The average abundance of microplastics in six river sediment samples was 802 items per kilogram of dry weight. The abundance in rivers was one to two orders of magnitude higher than in the tidal flat. White microplastic spheres were most commonly distributed in river sediments. Seven types of microplastics were identified, of which polypropylene was the most prevailing polymers presented. The study then conducted risk assessment of microplastics in sediments based on the observed results, and proposed a framework of environmental risk assessment. After reviewing waste disposal related legislation and regulations in China, this study conclude that in situ data and legitimate estimations should be incorporated as part of the practice when developing environmental policies aiming to tackle microplastic pollution.
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•Rivers in urban areas suffered from more human activities than tidal flats.•Microplastic abundance in urban rivers was one to two orders of magnitude higher than in the tidal flat.•White spherical microplastics were widely distributed in urban river sediments.•Risk assessment was conducted, and a framework for environmental risk assessment for microplastics was proposed.•Waste disposal related legislation and regulations in China were summarized.
Microplastic abundance in rivers was one to two orders of magnitude higher than in the tidal flat, and a framework of risk assessment was proposed.
Abstract
Vasoactive intestinal polypeptide receptor (VIP1R) is a widely expressed class B G protein-coupled receptor and a drug target for the treatment of neuronal, metabolic, and inflammatory ...diseases. However, our understanding of its mechanism of action and the potential of drug discovery targeting this receptor is limited by the lack of structural information of VIP1R. Here we report a cryo-electron microscopy structure of human VIP1R bound to PACAP27 and Gs heterotrimer, whose complex assembly is stabilized by a NanoBiT tethering strategy. Comparison with other class B GPCR structures reveals that PACAP27 engages VIP1R with its N-terminus inserting into the ligand binding pocket at the transmembrane bundle of the receptor, which subsequently couples to the G protein in a receptor-specific manner. This structure has provided insights into the molecular basis of PACAP27 binding and VIP receptor activation. The methodology of the NanoBiT tethering may help to provide structural information of unstable complexes.
Plastic pollution, including microplastics (MPs), poses a global threat to environmental and human health. Studies on the transference of MPs along marine food webs are limited. In the present study, ...we investigated MP pollution in 11 wild fish species (193 individuals) and 8 wild crustacean species (136 individuals) captured from the Zhoushan fishing ground, off the East China Sea. The average abundance of MPs found in two main tissues, the gill and gastrointestinal (GI) tract, were 0.77 ± 1.25 and 0.52 ± 0.90 items/individual, respectively. The MPs we found were predominantly fiber-shaped, blue, and composed of polyester polymers. Our results suggest that MP pollution is ubiquitous in the East China Sea. We suggest that MPs are likely aggregated in the higher trophic level fish species throughout the marine food web. Furthermore, we suggest that marine organisms which occupy higher trophic levels might be suitable MP indicator species.
•MP pollution is ubiquitous marine fish and crustacean species in the East China Sea.•MPs were predominantly fiber-shaped, blue, and composed of polyester.•Marine organisms which occupy higher trophic levels are suitable MP indicator species.
Maternal seeding of the microbiome in neonates promotes a long-lasting biological footprint, but how it impacts disease susceptibility in early life remains unknown. We hypothesized that feeding ...butyrate to pregnant mice influences the newborn's susceptibility to biliary atresia, a severe cholangiopathy of neonates. Here, we show that butyrate administration to mothers renders newborn mice resistant to inflammation and injury of bile ducts and improves survival. The prevention of hepatic immune cell activation and survival trait is linked to fecal signatures of Bacteroidetes and Clostridia and increases glutamate/glutamine and hypoxanthine in stool metabolites of newborn mice. In human neonates with biliary atresia, the fecal microbiome signature of these bacteria is under-represented, with suppression of glutamate/glutamine and increased hypoxanthine pathways. The direct administration of butyrate or glutamine to newborn mice attenuates the disease phenotype, but only glutamine renders bile duct epithelial cells resistant to cytotoxicity by natural killer cells. Thus, maternal intake of butyrate influences the fecal microbial population and metabolites in newborn mice and the phenotypic expression of experimental biliary atresia, with glutamine promoting survival of bile duct epithelial cells.
To the Editor： Mantle cell lymphoma （MCL） is a non-Hodgkin＇s lymphoma （NHL） subtype and considered one of the most aggressive lyrnphomas with worse prognosis than other subtypes ofN H L. Despite the ...great progress over the last several decades, treatment of MCL still has troubles in survival, relapse, and drug resistance.
The role of rivers as a major transport pathway for all sizes of plastic debris into the ocean is widely recognized. Global modelling studies ranked the Changjiang River as the largest contributor of ...plastic waste to the marine environment, but these estimates were based on insufficient empirical data. To better understand the role of rivers in delivering terrestrial plastic debris to the ocean, the spatial and temporal patterns of microplastics (MP) in the Changjiang Estuary (CE) and the East China Sea (ECS) were studied based on surface water samples in February, May, and July 2017. A total of 3225 MP (60–5000 μm) were identified by Fourier-transform infrared (FTIR) spectrometry. MP abundance in July was higher than in February and May due to higher river discharge. Density stratification in CE significantly influenced the surface MP abundances. A temporal accumulation zone within the river-sea interface for plastics was indicated by stations with apparently higher abundances in the river plume. Fibers were the most common MP (>80%) over three months. Small MP (<1000 μm) composed 75.0% of the total plastics on average. The average mass of MP was 0.000033 g/particle, which was two orders of magnitude lower than the empirical mass in literature. Without considering tidal effects, we estimate 16–20 trillion MP particles, weighing 537.6–905.9 tons, entered the sea through the surface water layer of the Changjiang River in 2017. These findings of this study provide reliable information on MP waste in a large river, which should be considered in further studies for estimating the riverine plastic loads.
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•MP abundance and size exhibited distinct seasonality in the Changjiang Estuary.•A ‘Patchiness’ in distribution of MP were observed in the Changjiang River plume.•The water density stratification impacted suspended microplastic abundances.•MP in our study averagely weighed 0.000033 g.•The annually MP load in the top layer of the Changjiang River is 537.6–905.9 tons.
Immune system evasion, distance tumor metastases, and increased cell proliferation are the main reasons for the progression of non-small cell lung cancer (NSCLC) and the death of NSCLC patients. ...Dysregulation of circular RNAs plays a critical role in the progression of NSCLC; therefore, further understanding the biological mechanisms of abnormally expressed circRNAs is critical to discovering novel, promising therapeutic targets for NSCLC treatment.
The expression of circular RNA fibroblast growth factor receptor 1 (circFGFR1) in NSCLC tissues, paired nontumor tissues, and cell lines was detected by RT-qPCR. The role of circFGFR1 in NSCLC progression was assessed both in vitro by CCK-8, clonal formation, wound healing, and Matrigel Transwell assays and in vivo by a subcutaneous tumor mouse assay. In vivo circRNA precipitation, RNA immunoprecipitation, and luciferase reporter assays were performed to explore the interaction between circFGFR1 and miR-381-3p.
Here, we report that circFGFR1 is upregulated in NSCLC tissues, and circFGFR1 expression is associated with deleterious clinicopathological characteristics and poor prognoses for NSCLC patients. Forced circFGFR1 expression promoted the migration, invasion, proliferation, and immune evasion of NSCLC cells. Mechanistically, circFGFR1 could directly interact with miR-381-3p and subsequently act as a miRNA sponge to upregulate the expression of the miR-381-3p target gene C-X-C motif chemokine receptor 4 (CXCR4), which promoted NSCLC progression and resistance to anti-programmed cell death 1 (PD-1)- based therapy.
Taken together, our results suggest the critical role of circFGFR1 in the proliferation, migration, invasion, and immune evasion abilities of NSCLC cells and provide a new perspective on circRNAs during NSCLC progression.
The synergistic impact of salts and organic matter on adsorption of ibuprofen and sulfamethoxazole by three types of biochar and an activated carbon was investigated using reclaimed water reverse ...osmosis (RO) concentrate and synthetic solutions spiked with target organic compounds and non-target water constituents (e.g., Na+, Ca2+, Mg2+, K+, Cl−, SO42−, alkalinity, humic acid (HA), and bovine serum albumin (BSA)). Kinetic modeling was used to better understand the adsorption process between the carbon adsorbents and pharmaceuticals and to elucidate the impact of water chemistry on pharmaceuticals adsorption. The adsorption capacity of pharmaceuticals by biochar was affected by their physicochemical properties including ash content, specific surface area, charge, pore volume, as well as hydrophobicity, π-energy, and speciation of pharmaceuticals. The adsorption of pharmaceuticals in concentrate was pH-dependent, the kinetic rate constant increased with deceasing pH due to the electrical interactions between pharmaceutical molecules and adsorbents. High salinity and electrolyte ions in RO concentrate improved adsorption, whereas the presence of carbonate species, HA, and BSA hindered the removal of ibuprofen and sulfamethoxazole. This study revealed the correlation of concentrate water quality on adsorption of pharmaceuticals by biochar and activated carbon. Biochar provides a promising alternative to activated carbon for removal of organic contaminants of emerging concerns in various wastewater and concentrate streams.
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•Limited option of concentrate management is a barrier for water reuse & desalination.•Biochar is a promising alternative adsorbent for organic contaminants removal.•Biochar with larger surface area and pore volume has higher adsorption capacity.•High ionic strength in concentrate increases ibuprofen & sulfamethoxazole removal.•Carbonate species and organic matter hinder ibuprofen & sulfamethoxazole removal.
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