The dielectric constant ε of interfacial water has been predicted to be smaller than that of bulk water (ε ≈ 80) because the rotational freedom of water dipoles is expected to decrease near surfaces, ...yet experimental evidence is lacking. We report local capacitance measurements for water confined between two atomically flat walls separated by various distances down to 1 nanometer. Our experiments reveal the presence of an interfacial layer with vanishingly small polarization such that its out-of-plane ε is only ~2. The electrically dead layer is found to be two to three molecules thick. These results provide much-needed feedback for theories describing water-mediated surface interactions and the behavior of interfacial water, and show a way to investigate the dielectric properties of other fluids and solids under extreme confinement.
Microplastic pollution in inland waters is receiving growing attentions. Reservoirs are suspected to be particularly vulnerable to microplastic pollution. However, very limited information is ...currently available on pollution characteristics of microplastics in reservoir ecosystems. This work studied the distribution and characteristics of microplastics in the backwater area of Xiangxi River, a typical tributary of the Three Gorges Reservoir. Microplastics were detected in both surface water and sediment with concentrations ranging from 0.55 × 105 to 342 × 105 items km–2 and 80 to 864 items m–2, respectively. Polyethylene, polypropylene, and polystyrene were identified in surface water, whereas polyethylene, polypropylene, and polyethylene terephthalate, and pigments were observed in sediment. In addition, microplastics were also detected in the digestion tracts of 25.7% of fish samples, and polyethylene and nylon were identified. Redundancy analysis indicates a weak correlation between microplastics and water quality variables but a negative correlation with water level of the reservoir and Secchi depth. Results from this study confirm the presence of high abundance microplastics in reservoir impacted tributaries, and suggest that water level regulated hydrodynamic condition and input of nonpoint sources are important regulators for microplastic accumulation and distribution in the backwater area of reservoir tributaries.
Establishing the appropriate theoretical framework for unconventional superconductivity in the iron-based materials requires correct understanding of both the electron correlation strength and the ...role of Fermi surfaces. This fundamental issue becomes especially relevant with the discovery of the iron chalcogenide superconductors. Here, we use angle-resolved photoemission spectroscopy to measure three representative iron chalcogenides, FeTe0.56Se0.44, monolayer FeSe grown on SrTiO3 and K0.76Fe1.72Se2. We show that these superconductors are all strongly correlated, with an orbital-selective strong renormalization in the dxy bands despite having drastically different Fermi surface topologies. Furthermore, raising temperature brings all three compounds from a metallic state to a phase where the dxy orbital loses all spectral weight while other orbitals remain itinerant. These observations establish that iron chalcogenides display universal orbital-selective strong correlations that are insensitive to the Fermi surface topology, and are close to an orbital-selective Mott phase, hence placing strong constraints for theoretical understanding of iron-based superconductors.
Aims/hypothesis
FTO
harbours the strongest known obesity-susceptibility locus in Europeans. While there is growing evidence for a role for
FTO
in obesity risk in Asians, its association with type 2 ...diabetes, independently of BMI, remains inconsistent. To test whether there is an association of the
FTO
locus with obesity and type 2 diabetes, we conducted a meta-analysis of 32 populations including 96,551 East and South Asians.
Methods
All studies published on the association between
FTO
-rs9939609 (or proxy
r
2
> 0.98) and BMI, obesity or type 2 diabetes in East or South Asians were invited. Each study group analysed their data according to a standardised analysis plan. Association with type 2 diabetes was also adjusted for BMI. Random-effects meta-analyses were performed to pool all effect sizes.
Results
The
FTO
-rs9939609 minor allele increased risk of obesity by 1.25-fold/allele (
p
= 9.0 × 10
−19
), overweight by 1.13-fold/allele (
p
= 1.0 × 10
−11
) and type 2 diabetes by 1.15-fold/allele (
p
= 5.5 × 10
−8
). The association with type 2 diabetes was attenuated after adjustment for BMI (OR 1.10-fold/allele,
p
= 6.6 × 10
−5
). The
FTO
-rs9939609 minor allele increased BMI by 0.26 kg/m
2
per allele (
p
= 2.8 × 10
−17
), WHR by 0.003/allele (
p
= 1.2 × 10
−6
), and body fat percentage by 0.31%/allele (
p
= 0.0005). Associations were similar using dominant models. While the minor allele is less common in East Asians (12–20%) than South Asians (30–33%), the effect of
FTO
variation on obesity-related traits and type 2 diabetes was similar in the two populations.
Conclusions/interpretation
FTO
is associated with increased risk of obesity and type 2 diabetes, with effect sizes similar in East and South Asians and similar to those observed in Europeans. Furthermore,
FTO
is also associated with type 2 diabetes independently of BMI.
Amelogenesis imperfecta (AI) is a diverse group of inherited diseases featured by various presentations of enamel malformations that are caused by disturbances at different stages of enamel ...formation. While hypoplastic AI suggests a thickness defect of enamel resulting from aberrations during the secretory stage of amelogenesis, hypomaturation AI indicates a deficiency of enamel mineralization and hardness established at the maturation stage. Mutations in ENAM, which encodes the largest enamel matrix protein, enamelin, have been demonstrated to cause generalized or local hypoplastic AI. Here, we characterized 2 AI families with disparate hypoplastic and hypomaturation enamel defects and identified 2 distinct indel mutations at the same location of ENAM, c588+1del and c.588+1dup. Minigene splicing assays demonstrated that they caused frameshifts and truncation of ENAM proteins, p.Asn197Ilefs*81 and p.Asn197Glufs*25, respectively. In situ hybridization of Enam on mouse mandibular incisors confirmed its restricted expression in secretory stage ameloblasts and suggested an indirect pathogenic mechanism underlying hypomaturation AI. In silico analyses indicated that these 2 truncated ENAMs might form amyloid structures and cause protein aggregation with themselves and with wild-type protein through the added aberrant region at their C-termini. Consistently, protein secretion assays demonstrated that the truncated proteins cannot be properly secreted and impede secretion of wild-type ENAM. Moreover, compared to the wild-type, overexpression of the mutant proteins significantly increased endoplasmic reticulum stress and upregulated the expression of unfolded protein response (UPR)–related genes and TNFRSF10B, a UPR-controlled proapoptotic gene. Caspase, terminal deoxynucleotidyl transferase UTP nick-end labeling (TUNEL), and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assays further revealed that both truncated proteins, especially p.Asn197Ilefs*81, induced cell apoptosis and decreased cell survival, suggesting that the 2 ENAM mutations cause AI through ameloblast cell pathology and death rather than through a simple loss of function. This study demonstrates that an ENAM mutation can lead to generalized hypomaturation enamel defects and suggests proteinopathy as a potential pathogenesis for ENAM-associated AI.
Conventional strategies for mycotoxin reduction includes both prevention and decontamination strategies. Decontamination of aflatoxin has been a continuing challenge for the food industry. Novel ...processing methods are continuously explored to achieve complete aflatoxin degradation in food products.
The present review provides an update on recent research for aflatoxin decontamination by conventional methods including thermal processing and chemical treatments. Novel aflatoxin decontamination technologies like microwave heating, gamma and electron beam irradiation, ultraviolet and pulsed light, electrolyzed water and cold plasma are reviewed in detail. This review provides a brief introduction, decontamination mechanism, degradation efficiency, advantages and limitations of these novel technologies.
Although conventional thermal technologies are known to cause aflatoxin degradation, they are not adequate for complete aflatoxin degradation in food products. Novel technologies like pulsed light, electrolyzed water and cold plasma have shown complete degradation of aflatoxin on different substrates. However, application on food products need further studies along with the degradant toxicology and its interaction with food components. Novel processing technologies shows significant potential for future applications in decontaminating aflatoxin in the food industry.
•Thermal processing is not adequate for complete aflatoxin degradation in food.•Novel processing methods have shown significant potential for decontamination.•Pulsed light, electrolyzed water and cold plasma can cause aflatoxin degradation.•Aflatoxin degradation mechanism by these technologies are also discussed.
Summary
Background
Hepatitis B virus (HBV) infection is common with major clinical consequences. In Asian Americans, the HBsAg carrier rate ranges from 2% to 16% which approximates the rates from ...their countries of origin. Similarly, HBV is the most important cause of cirrhosis, hepatocellular carcinoma (HCC) and liver related deaths in HBsAg positive Asians worldwide.
Aim
To generate recommendations for the management of Asian Americans infected with HBV.
Methods
These guidelines are based on relevant data derived from medical reports on HBV from Asian countries as well as from studies in the HBsAg positive Asian Americans. The guidelines herein differ from other recommendations in the treatment of both HBeAg positive and negative chronic hepatitis B (CHB), in the approach to HCC surveillance, and in the management of HBV in pregnant women.
Results
Asian American patients, HBeAg positive or negative, with HBV DNA levels >2000 IU/mL (>104 copies/mL) and ALT values above normal are candidates for anti‐viral therapy. HBeAg negative patients with HBV DNA >2000 IU/mL and normal ALT levels but who have either serum albumin <3.5 g/dL or platelet count <130 000 mm3, basal core promoter (BCP) mutations, or who have first‐degree relatives with HCC should be offered treatment. Patients with cirrhosis and detectable HBV DNA must receive life‐long anti‐viral therapy. Indications for treatment include pregnant women with high viraemia, coinfected patients, and those requiring immunosuppressive therapy. In HBsAg positive patients with risk factors, life‐long surveillance for HCC with alpha‐fetoprotein (AFP) testing and abdominal ultrasound examination at 6‐month intervals is required. In CHB patients receiving HCC treatments, repeat imaging with contrast CT scan or MRI at 3‐month intervals is strongly recommended. These guidelines have been assigned to a Class (reflecting benefit vs. risk) and a Level (assessing strength or certainty) of evidence.
Conclusions
Application of the recommendations made based on a review of the relevant literature and the opinion of a panel of Asian American physicians with expertise in HBV treatment will inform physicians and improve patient outcomes.
Linked ContentThis article is linked to Ebel and Rosenthal, and Tong and Pan papers. To view these articles visit https://doi.org/10.1111/apt.14620 and https://doi.org/10.1111/apt.14662.
Autosomal dominant hypocalcified amelogenesis imperfecta (ADHCAI; OMIM #130900) is a genetic disorder exhibiting severe hardness defects and reduced fracture toughness of dental enamel. While the ...condition is nonsyndromic, it can be associated with other craniofacial anomalies, such as malocclusions and delayed or failed tooth eruption. Truncation mutations in FAM83H (OMIM *611927) are hitherto the sole cause of ADHCAI. With human genetic studies, Fam83h knockout and mutation–knock-in mouse models indicated that FAM83H does not serve a critical physiologic function during enamel formation and suggested a neomorphic mutation mechanism causing ADHCAI. The function of FAM83H remains obscure. FAM83H has been shown to interact with various isoforms of casein kinase 1 (CK1) and keratins and to mediate organization of keratin cytoskeletons and desmosomes. By considering FAM83H a scaffold protein to anchor CK1s, further molecular characterization of the protein could gain insight into its functions. In this study, we characterized 9 kindreds with ADHCAI and identified 3 novel FAM83H truncation mutations: p.His437*, p.Gln459*, and p.Glu610*. Some affected individuals exhibited hypoplastic phenotypes, in addition to the characteristic hypocalcification enamel defects, which have never been well documented. Failed eruption of canines or second molars in affected persons was observed in 4 of the families. The p.Glu610* mutation was located in a gap area (amino acids 470 to 625) within the zone of previously reported pathogenic variants (amino acids 287 to 694). In vitro pull-down studies with overexpressed FAM83H proteins in HEK293 cells demonstrated an interaction between FAM83H and SEC16A, a protein component of the COP II complex at endoplasmic reticulum exit sites. The interaction was mediated by the middle part (amino acids 287 to 657) of mouse FAM83H protein. Results of this study significantly extended the phenotypic and genotypic spectrums of FAM83H-associated ADHCAI and suggested a role for FAM83H in endoplasmic reticulum–to–Golgi vesicle trafficking and protein secretion (dbGaP phs001491.v1.p1).
An energy gap can be opened in the spectrum of graphene reaching values as large as 0.2 eV in the case of bilayers. However, such gaps rarely lead to the highly insulating state expected at low ...temperatures. This long-standing puzzle is usually explained by charge inhomogeneity. Here we revisit the issue by investigating proximity-induced superconductivity in gapped graphene and comparing normal-state measurements in the Hall bar and Corbino geometries. We find that the supercurrent at the charge neutrality point in gapped graphene propagates along narrow channels near the edges. This observation is corroborated by using the edgeless Corbino geometry in which case resistivity at the neutrality point increases exponentially with increasing the gap, as expected for an ordinary semiconductor. In contrast, resistivity in the Hall bar geometry saturates to values of about a few resistance quanta. We attribute the metallic-like edge conductance to a nontrivial topology of gapped Dirac spectra.
Epidermal growth factor receptor (EGFR) mutations typically occur in exons 18-21 and are established driver mutations in non-small cell lung cancer (NSCLC)
. Targeted therapies are approved for ...patients with 'classical' mutations and a small number of other mutations
. However, effective therapies have not been identified for additional EGFR mutations. Furthermore, the frequency and effects of atypical EGFR mutations on drug sensitivity are unknown
. Here we characterize the mutational landscape in 16,715 patients with EGFR-mutant NSCLC, and establish the structure-function relationship of EGFR mutations on drug sensitivity. We found that EGFR mutations can be separated into four distinct subgroups on the basis of sensitivity and structural changes that retrospectively predict patient outcomes following treatment with EGFR inhibitors better than traditional exon-based groups. Together, these data delineate a structure-based approach for defining functional groups of EGFR mutations that can effectively guide treatment and clinical trial choices for patients with EGFR-mutant NSCLC and suggest that a structure-function-based approach may improve the prediction of drug sensitivity to targeted therapies in oncogenes with diverse mutations.
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