Complex-Shape Solid-State Photonic Droplets Prepared via Phase Separation and Microfluidics.

Complex-shape solid-state cholesteric liquid crystal (CLCsolid) droplets were prepared via solvent removal, phase separation, and photopolymerization of uniformly sized reactive CLC (rCLC)/fluorocarbon oil (FCO)/dichloromethane (solvent) droplets produced via a microfluidic method. The interfacial energies between rCLC and FCO, rCLC and water, and FCO and water of a rCLC/FCO droplet in an aqueous solution were precisely controlled through the specified surfactants. The shape of the rCLC/FCO droplet was strongly dependent on the balances among these interfacial energies, enabling the preparation of complex-shape droplets through the controlled concentration of the used surfactants. The complex-shape rCLC/FCO droplets showed photonic patterns consisting of a central reflection from a convex surface, cross-communication from a convex surface between adjacent particles, a photonic reflection band from the outer upward-facing concave surface, and total internal reflection from the inner upward-facing surface. Complex-shape CLCsolid particles obtained after photopolymerization and extraction of a nonreactive chiral dopant and FCO showed photonic patterns similar to those before photopolymerization without much deterioration of the photonic structure. These complex patterns make CLCsolid and rCLC/FCO droplets promising anticounterfeiting materials.

Determination of ovalbumin sensing response of protein-imprinted bilayered hydrogel strips via measurement of mechanically driven bending angles based on swelling-induced deformation.

Novel detection method has been developed to explore changes in mechanical bending angles on a bilayer of polyethylene terephthalate (PET) and molecularly imprinted polymer (MIP). For an ovalbumin (OVA)-imprinted hydrogel layer, functional monomers were employed to achieve sufficient binding effect in the polymer matrix. The OVA amount added in the MIP precursor solution and the dimensions of OVA-imprinted hydrogel (MIH) strips were controlled to maximize the change in bending angles as an OVA sensing response within a valid detection range. The sensing behaviors were determined by monitoring the difference in the bending angles via protein adsorption based on the swelling-induced deformation of the OVA-extracted hydrogel (E-MIH) strip. The equilibrium adsorption capacity of the E-MIH strip was calculated via the Bradford protein assay. The detection limit, quantification limit, and imprinting factor were calculated. To compare the selectivity coefficients, the adsorption behaviors of three proteins were investigated. Finally, the reusability of the E-MIH strip was explored via repeated adsorption and extraction. Based on the results, the E-MIH strips demonstrated a promising protein sensing platform monitoring mechanical bending angles affected by swelling deformation.

Comparative Effectiveness of Entecavir Versus Tenofovir for Preventing Hepatocellular Carcinoma in Patients with Chronic Hepatitis B: A Systematic Review and Meta-Analysis.

BACKGROUND AND AIMS: Chronic hepatitis B (CHB) can lead to hepatocellular carcinoma (HCC). While both tenofovir disoproxil (TDF) and entecavir (ETV) have been shown to reduce the risk of HCC, their comparative effectiveness is unclear. We estimated the comparative effectiveness of these two agents in reducing the risk of HCC in patients with CHB, through a systematic review and meta-analysis. APPROACH AND RESULTS: We searched multiple electronic databases from January 1, 1998, to October 31, 2019, for randomized controlled trials and observational comparative effectiveness studies in adults with CHB treated with ETV compared to TDF, reporting the incidence of HCC (minimum follow-up 12 months). Primary outcome was incidence of HCC, calculated as incidence rate ratio (IRR) with 95% confidence interval (CI, unadjusted analysis) and hazard ratio (HR) with 95% CI (adjusted analysis, where reported). Of 1,971 records identified, 14 studies (263,947 person-years) were included for quantitative analysis. On unadjusted meta-analysis of 14 studies, the risk of HCC was not statistically different between ETV and TDF (IRR, 1.28; 95% CI, 0.99-1.66). When using available adjusted data (multivariate or propensity-matched data), the risk of HCC among patients treated with ETV was 27% higher when compared to TDF (seven studies; 95% CI, 1.01-1.60, P = 0.04). Additional analysis of adjusted data when separately reported among patients with cirrhosis demonstrated an adjusted HR of 0.90 (95% CI, 0.66-1.23), suggesting no difference between ETV-treated and TDF-treated groups. The overall confidence in estimates was very low (observational studies, high heterogeneity). CONCLUSIONS: TDF may be associated with lower risk of HCC when compared to ETV.

Impact of COVID-19 Pandemic on Biomedical Publications and Their Citation Frequency.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has resulted in enormous related publications. However, the citation frequency of these documents and their influence on the journal impact factor (JIF) are not well examined. We aimed to evaluate the impact of COVID-19 on biomedical research publications and their citation frequency. METHODS: We searched publications on biomedical research in the Web of Science using the search terms "COVID-19," "SARS-Cov-2," "2019 corona*," "corona virus disease 2019," "coronavirus disease 2019," "novel coronavirus infection" and "2019-ncov." The top 200 journals were defined as those with a higher number of COVID-19 publications than other journals in 2020. The COVID-19 impact ratio was calculated as the ratio of the average number of citations per item in 2021 to the JIF for 2020. RESULTS: The average number of citations for the top 200 journals in 2021, per item published in 2020, was 25.7 (range, 0-270). The average COVID-19 impact ratio was 3.84 (range, 0.26-16.58) for 197 journals that recorded the JIF for 2020. The average JIF ratio for the top 197 journals including the JIFs for 2020 and 2021 was 1.77 (range, 0.68-8.89). The COVID-19 impact ratio significantly correlated with the JIF ratio (r = 0.403, P = 0.010). Twenty-five Korean journals with a COVID-19 impact ratio > 1.5 demonstrated a higher JIF ratio (1.31 ± 0.39 vs. 1.01 ± 0.18, P < 0.001) than 33 Korean journals with a lower COVID-19 impact ratio. CONCLUSION: COVID-19 pandemic infection has significantly impacted the trends in biomedical research and the citation of related publications.

Hydrogen-Bond-Modulated Nucleofugality of SeIII Species to Enable Photoredox-Catalytic Semipinacol Manifolds.

Chemical bond activations mediated by H-bond interactions involving highly electronegative elements such as nitrogen and oxygen are powerful tactics in modern catalysis research. On the contrary, kindred catalytic regimes in which heavier, less electronegative elements such as selenium engage in H-bond interactions to co-activate C-Se σ-bonds under oxidative conditions are elusive. Traditional strategies to enhance the nucleofugality of selenium residues predicate on the oxidative addition of electrophiles onto SeII -centers, which entails the elimination of the resulting SeIV moieties. Catalytic procedures in which SeIV nucleofuges are substituted rather than eliminated are very rare and, so far, not applicable to carbon-carbon bond formations. In this study, we introduce an unprecedented combination of O-H⋅⋅⋅Se H-bond interactions and single electron oxidation to catalytically generate SeIII nucleofuges that allow for the formation of new C-C σ-bonds by means of a type I semipinacol process in high yields and excellent selectivity.

Dependence of the viewing angle control property of a guest-host liquid crystal cell on the extinction coefficient of the mixture.

The theoretical prediction of a display viewing angle control using a guest-host (GH) liquid crystal (LC) cell has been reported by Chen et al. [Jpn. J. Appl. Phys.48, 062401 (2009)JJAPA50021-492210.1143/JJAP.48.062401]. We experimentally confirmed the viewing angle control property of the GH cell and also investigated its dependence on the extinction coefficient of the GH mixture. The GH cell with a negative dielectric anisotropy and a vertical orientation was attached on front of the display panel, resulting in narrow viewing (NV) property at the field-off state. The GH molecules were switched to a planar orientation, which is also orthogonal to the polarization direction of light at the field-on state, showing wide viewing (WV) property. We varied the concentration of a guest dichroic dye in a host LC and measured the extinction coefficients of the mixtures. We simulated the viewing control property using the measured extinction coefficients and found that the horizontal viewing angle can be controlled using the GH cell, but the vertical viewing angle cannot be controlled. Then, we experimentally confirmed the horizontal viewing angle control using the GH cell. The extinction between the NV and the WV states was increased with a greater extinction coefficient of the GH molecules, but the transmittance was decreased.

Recruitment and Retention of Asian Americans in Web-Based Physical Activity Promotion Programs: A Discussion Paper.

Web-based interventions that promote physical activity have been tested in various populations and proven effective. However, information on recruiting and retaining ethnic minorities in these interventions is limited. This study discusses practical issues in recruitment and retention of Asian Americans using three strategies: (1) only Web-based intervention (Group 1), (2) one with Fitbit Charge HR (Group 2), and (3) one with Fitbit Charge HR and office visits (Group 3). Recruitment and retention rates, minutes of weekly research team meetings, and the researchers' memos were collected. Retention rates were analyzed using descriptive statistics, and the minutes and memos were content analyzed following Weber's methods. Retention rates varied by the end of the first (12% in Group 3, 36.9% in Group 2) and third month (0% in Group 3, 36.9% in Group 2). The practical issues were (1) difficulties in recruitment across strategies, (2) the necessity of using community consultants/leaders across strategies, (3) subethnic differences across strategies, (4) timing issues across strategies, (5) Fitbit as a facilitator with several hindrances, and (6) office visits as an inhibitor. Fitbits with user guidelines and community consultants'/leaders' involvement are proposed for future Web-based interventions to promote physical activity in Asian Americans.

In vitro detection of allergen sensitized basophils by HSA-DNP antigen-anchored liquid crystal microdroplets.

A simple and easy to handle biosensing technique for in vitro detection of HSA-DNP antigen induced allergen reactions in patients has been developed through the detection of sensitized basophils expressed with anti-IgE receptor (FcεRI) by using human serum albumin-dinitrophenol (HSA-DNP) antigen-anchored liquid crystal (LC) microdroplets emulsion. The radial to bipolar transition in nematic 4-cyano-4'-pentyl biphenyl liquid crystal molecules (5CB) confined in HSA-DNP antigen anchored LC microdroplets (8.5 pg HSA-DNP/LC microdroplet) is found to be sensitive in PBS solution in detection of allergen sensitized basophils expressed with a minimum amount of anti HSA-DNP (anti-IgE) receptor (≥4.5 pg/basophil). The detection of allergen sensitized basophils was possible within a contact time of 30 min in presence of control cells and with 10% solution of human blood plasma. The HSA-DNP antigen anchored LC microdroplets in presence of macrophages or non-sensitized basophils did not show radial to bipolar transition in 5CB molecules in PBS or solution with 10 wt% human blood plasma. Thus HSA-DNP antigen anchored LC microdroplets biosensor may be used for in vivo detection of stage I allergen reaction basophils in blood samples.

FOXP3 mutations causing early-onset insulin-requiring diabetes but without other features of immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome.

Diabetes occurs in 1/90 000 to 1/160 000 births and when diagnosed under 6 months of age is very likely to have a primary genetic cause. FOXP3 encodes a transcription factor critical for T regulatory cell function and mutations are known to cause "immune dysregulation, polyendocrinopathy (including insulin-requiring diabetes), enteropathy, X-linked" (IPEX) syndrome. This condition is often fatal unless patients receive a bone-marrow transplant. Here we describe the phenotype of male neonates and infants who had insulin-requiring diabetes without other features of IPEX syndrome and were found to have mutations in FOXP3. Whole-exome or next generation sequencing of genes of interest was carried out in subjects with isolated neonatal diabetes without a known genetic cause. RT-PCR was carried out to investigate the effects on RNA splicing of a novel intronic splice-site variant. Four male subjects were found to have FOXP3 variants in the hemizygous state: p.Arg114Trp, p.Arg347His, p.Lys393Met, and c.1044+5G>A which was detected in 2 unrelated probands and in a brother diagnosed with diabetes at 2.1 years of age. Of these, p.Arg114Trp is likely a benign rare variant found in individuals of Ashkenazi Jewish ancestry and p.Arg347His has been previously described in patients with classic IPEX syndrome. The p.Lys393Met and c.1044+5G>A variants are novel to this study. RT-PCR studies of the c.1044+5G>A splice variant confirmed it affected RNA splicing by generating both a wild type and truncated transcript. We conclude that FOXP3 mutations can cause early-onset insulin-requiring diabetes with or without other features of IPEX syndrome.

In vivo measurement and biological characterisation of the diabetes-associated mutant insulin p.R46Q (GlnB22-insulin).

AIMS/HYPOTHESIS: Heterozygous mutations in the insulin gene that affect proinsulin biosynthesis and folding are associated with a spectrum of diabetes phenotypes, from permanent neonatal diabetes to MODY. In vivo studies of these mutations may lead to a better understanding of insulin mutation-associated diabetes and point to the best treatment strategy. We studied an 18-year-old woman with MODY heterozygous for the insulin mutation p.R46Q (GlnB22-insulin), measuring the secretion of mutant and wild-type insulin by LC-MS. The clinical study was combined with in vitro studies of the synthesis and secretion of p.R46Q-insulin in rat INS-1 insulinoma cells. METHODS: We performed a standard 75 g OGTT in the 18-year-old woman and measured plasma glucose and serum insulin (wild-type insulin and GlnB22-insulin), C-peptide, proinsulin, glucagon and amylin. The affinity of GlnB22-insulin was tested on human insulin receptors expressed in baby hamster kidney (BHK) cells. We also examined the subcellular localisation, secretion and impact on cellular stress markers of p.R46Q-insulin in INS-1 cells. RESULTS: Plasma GlnB22-insulin concentrations were 1.5 times higher than wild-type insulin at all time points during the OGTT. The insulin-receptor affinity of GlnB22-insulin was 57% of that of wild-type insulin. Expression of p.R46Q-insulin in INS-1 cells was associated with decreased insulin secretion, but not induction of endoplasmic reticulum stress. CONCLUSIONS/INTERPRETATION: The results show that beta cells can process and secrete GlnB22-insulin both in vivo and in vitro. Our combined approach of immunoprecipitation and LC-MS to measure mutant and wild-type insulin may be useful for the study of other mutant insulin proteins. The ability to process and secrete a mutant protein may predict a more benign course of insulin mutation-related diabetes. Diabetes develops when the beta cell is stressed because of increased demand for insulin, as observed in individuals with other insulin mutations that affect the processing of proinsulin to insulin or mutations that reduce the affinity for the insulin receptor.

Evidence of non-pancreatic beta cell-dependent roles of Tcf7l2 in the regulation of glucose metabolism in mice.

Non-coding variation within TCF7L2 remains the strongest genetic determinant of type 2 diabetes risk in humans. A considerable effort has been placed in understanding the functional roles of TCF7L2 in pancreatic beta cells, despite evidence of TCF7L2 expression in various peripheral tissues important in glucose homeostasis. Here, we use a humanized mouse model overexpressing Tcf7l2, resulting in glucose intolerance, to infer the contribution of Tcf7l2 overexpression in beta cells and in other tissues to the metabolic phenotypes displayed by these mice. Restoring Tcf7l2 expression specifically in beta cells to endogenous levels, in face of its overexpression elsewhere, results in impaired insulin secretion, reduced beta cell number and islet area, corroborating data obtained in humans showing similar phenotypes as a result of manipulations leading to Tcf7l2 loss of function. Interestingly, the persistent overexpression of Tcf7l2 in non-pancreatic tissues results in a significant worsening in glucose tolerance in vivo, indicating that Tcf7l2 overexpression in beta cells does not account for the glucose intolerance in the Tcf7l2 overexpression mouse model. Collectively, these data posit that Tcf7l2 plays key roles in glucose metabolism through actions beyond pancreatic beta cells, and further points to functionally opposing cell-type specific effects for Tcf7l2 on the maintenance of balanced glucose metabolism, thereby urging a careful examination of its role in non-pancreatic tissues as well as its composite metabolic effects across distinct tissues. Uncovering these roles may lead to new therapeutic targets for type 2 diabetes.

Fabrication of water-dispersible single-walled carbon nanotube powder using N-methylmorpholine N-oxide.

Dispersion of nanocarbon materials in liquid media, via solution processing such as spraying, printing, spinning, etc. is one of the prerequisites for practical applications. Here we report that water-dispersible single-walled carbon nanotubes (SWCNTs) were prepared through successive treatments with chlorosulfuric acid (CSA)/H2O2 and N-methylmorpholine N-oxide (NMO) monohydrate. The powder of the CSA/H2O2- and NMO-treated SWCNTs (N-SWCNTs) could be readily redispersed in water in concentrations as high as 1 g l-1 without requiring a dispersant. The mechanism responsible for the high dispersity of the N-SWCNT powder in polar solvents, including water, was elucidated based on the high polarity of the NMO molecule. In order to highlight the wide applicability of the N-SWCNTs, they were used successfully to prepare conducting thin films by spray-coating plastic substrates with an aqueous hybrid solution containing the N-SWCNTs and Ag nanowires (NWs). In addition, a flexible, large-area thin-film heater was prepared based on the N-SWCNT/AgNW hybrid film with a transmittance of 93% and sheet resistance of 30 Ω sq-1.

TCF7L2 is a master regulator of insulin production and processing.

Genome-wide association studies have revealed >60 loci associated with type 2 diabetes (T2D), but the underlying causal variants and functional mechanisms remain largely elusive. Although variants in TCF7L2 confer the strongest risk of T2D among common variants by presumed effects on islet function, the molecular mechanisms are not yet well understood. Using RNA-sequencing, we have identified a TCF7L2-regulated transcriptional network responsible for its effect on insulin secretion in rodent and human pancreatic islets. ISL1 is a primary target of TCF7L2 and regulates proinsulin production and processing via MAFA, PDX1, NKX6.1, PCSK1, PCSK2 and SLC30A8, thereby providing evidence for a coordinated regulation of insulin production and processing. The risk T-allele of rs7903146 was associated with increased TCF7L2 expression, and decreased insulin content and secretion. Using gene expression profiles of 66 human pancreatic islets donors', we also show that the identified TCF7L2-ISL1 transcriptional network is regulated in a genotype-dependent manner. Taken together, these results demonstrate that not only synthesis of proinsulin is regulated by TCF7L2 but also processing and possibly clearance of proinsulin and insulin. These multiple targets in key pathways may explain why TCF7L2 has emerged as the gene showing one of the strongest associations with T2D.

Displacement measurement using an optoelectronic oscillator with an intra-loop Michelson interferometer.

We report on measurement of small displacements with sub-nanometer precision using an optoelectronic oscillator (OEO) with an intra-loop Michelson interferometer. In comparison with conventional homodyne and heterodyne detection methods, where displacement appears as a power change or a phase shift, respectively, in the OEO detection, the displacement produces a shift in the oscillation frequency. In comparison with typical OEO sensors, where the frequency shift is proportional to the OEO oscillation frequency in radio-frequency domain, the frequency shift in our method with an intra-loop interferometer is proportional to an optical frequency. We constructed a hybrid apparatus and compared characteristics of the OEO and heterodyne detection methods.

Continued lessons from the INS gene: an intronic mutation causing diabetes through a novel mechanism.

BACKGROUND: Diabetes in neonates usually has a monogenic aetiology; however, the cause remains unknown in 20-30%. Heterozygous INS mutations represent one of the most common gene causes of neonatal diabetes mellitus. METHODS: Clinical and functional characterisation of a novel homozygous intronic mutation (c.187+241G>A) in the insulin gene in a child identified through the Monogenic Diabetes Registry (http://monogenicdiabetes.uchicago.edu). RESULTS: The proband had insulin-requiring diabetes from birth. Ultrasonography revealed a structurally normal pancreas and C-peptide was undetectable despite readily detectable amylin, suggesting the presence of dysfunctional ß cells. Whole-exome sequencing revealed the novel mutation. In silico analysis predicted a mutant mRNA product resulting from preferential recognition of a newly created splice site. Wild-type and mutant human insulin gene constructs were derived and transiently expressed in INS-1 cells. We confirmed the predicted transcript and found an additional transcript created via an ectopic splice acceptor site. CONCLUSIONS: Dominant INS mutations cause diabetes via a mutated translational product causing endoplasmic reticulum stress. We describe a novel mechanism of diabetes, without ß cell death, due to creation of two unstable mutant transcripts predicted to undergo nonsense and non-stop-mediated decay, respectively. Our discovery may have broader implications for those with insulin deficiency later in life.

Direct Fabrication of Free-Standing MOF Superstructures with Desired Shapes by Micro-Confined Interfacial Synthesis.

Recently, metal-organic frameworks (MOFs) with multifunctional pore chemistry have been intensively investigated for positioning the desired morphology at specific locations onto substrates for manufacturing devices. Herein, we develop a micro-confined interfacial synthesis (MIS) approach for fabrication of a variety of free-standing MOF superstructures with desired shapes. This approach for engineering MOFs provides three key features: 1) in situ synthesis of various free-standing MOF superstructures with controlled compositions, shape, and thickness using a mold membrane; 2) adding magnetic functionality into MOF superstructures by loading with Fe3 O4 nanoparticles; 3) transferring the synthesized MOF superstructural array on to flat or curved surface of various substrates. The MIS route with versatile potential opens the door for a number of new perspectives in various applications.

Dual transcriptional activator and repressor roles of TBX20 regulate adult cardiac structure and function.

The ongoing requirement in adult heart for transcription factors with key roles in cardiac development is not well understood. We recently demonstrated that TBX20, a transcriptional regulator required for cardiac development, has key roles in the maintenance of functional and structural phenotypes in adult mouse heart. Conditional ablation of Tbx20 in adult cardiomyocytes leads to a rapid onset and progression of heart failure, with prominent conduction and contractility phenotypes that lead to death. Here we describe a more comprehensive molecular characterization of the functions of TBX20 in adult mouse heart. Coupling genome-wide chromatin immunoprecipitation and transcriptome analyses (RNA-Seq), we identified a subset of genes that change expression in Tbx20 adult cardiomyocyte-specific knockout hearts which are direct downstream targets of TBX20. This analysis revealed a dual role for TBX20 as both a transcriptional activator and a repressor, and that each of these functions regulates genes with very specialized and distinct molecular roles. We also show how TBX20 binds to its targets genome-wide in a context-dependent manner, using various cohorts of co-factors to either promote or repress distinct genetic programs within adult heart. Our integrative approach has uncovered several novel aspects of TBX20 and T-box protein function within adult heart. Sequencing data accession number (http://www.ncbi.nlm.nih.gov/geo): GSE30943.

Liquid crystal-based proton sensitive glucose biosensor.

A transmission electron microscopy (TEM) grid filled with 4-cyno-4-pentylbiphenyl (5CB) on the octadecyltrichloro silane-coated glass in an aqueous medium was developed to construct a glucose biosensor by coating poly(acrylicacid-b-4-cynobiphenyl-4-oxyundecylacrylate) (PAA-b-LCP) at the aqueous/5CB interface and immobilizing glucose oxidase (GOx) covalently to the PAA chains. The glucose was detected from a homeotropic to planar orientational transition of 5CB by polarized optical microscopy under crossed polarizers. The maximum immobilization density of the GOx, 1.3 molecules/nm(2) obtained in this TEM grid cell enabled the detection of glucose at concentrations as low as 0.02 mM with a response time of 10 s. This liquid crystal-based glucose sensor provided a linear response of birefringence of the 5CB to glucose concentrations ranging from 0.05 to 2 mM with a Michaelis-Menten constant (Km) of 0.32 mM. This new and sensitive glucose biosensor has the merits of low production cost and easy detection through the naked eye and might be useful for prescreening the glucose level in the human body.

Alterations in TCF7L2 expression define its role as a key regulator of glucose metabolism.

Genome-wide association studies (GWAS) have consistently implicated noncoding variation within the TCF7L2 locus with type 2 diabetes (T2D) risk. While this locus represents the strongest genetic determinant for T2D risk in humans, it remains unclear how these noncoding variants affect disease etiology. To test the hypothesis that the T2D-associated interval harbors cis-regulatory elements controlling TCF7L2 expression, we conducted in vivo transgenic reporter assays to characterize the TCF7L2 regulatory landscape. We found that the 92-kb genomic interval associated with T2D harbors long-range enhancers regulating various aspects of the spatial-temporal expression patterns of TCF7L2, including expression in tissues involved in the control of glucose homeostasis. By selectively deleting this interval, we establish a critical role for these enhancers in robust TCF7L2 expression. To further determine whether variation in Tcf7l2 expression may lead to diabetes, we developed a Tcf7l2 copy-number allelic series in mice. We show that a null Tcf7l2 allele leads, in a dose-dependent manner, to lower glycemic profiles. Tcf7l2 null mice also display enhanced glucose tolerance coupled to significantly lowered insulin levels, suggesting that these mice are protected against T2D. Confirming these observations, transgenic mice harboring multiple Tcf7l2 copies and overexpressing this gene display reciprocal phenotypes, including glucose intolerance. These results directly demonstrate that Tcf7l2 plays a role in regulating glucose tolerance, suggesting that overexpression of this gene is associated with increased risk of T2D. These data highlight the role of enhancer elements as mediators of T2D risk in humans, strengthening the evidence that variation in cis-regulatory elements may be a paradigm for genetic predispositions to common disease.

Poly(acrylic acid)-grafted graphene oxide as an intracellular protein carrier.

A pH-sensitive poly(acrylic acid)-grafted graphene oxide (GO-PAA) nanocarrier was synthesized by in situ atom transfer radical polymerization to allow the oral delivery of hydrophilic macromolecular proteins in their active forms to specific cells or organs. The synthesis, morphology, and physiochemical properties of GO-PAA were examined. A model protein, bovine serum albumin (BSA) labeled with fluorescein isothiocyanate (FITC) (BSAFITC), was loaded onto GO-PAA through noncovalent interactions and its release was arrested at acidic pH similar to stomach, whereas at pH similar to intestine it was reduced, which paves way for site specific delivery without its degradation in the gastrointestinal tract. Confocal laser microscopy showed that the BSAFITC-loaded GO-PAA was internalized by KB cells by endocytosis and released into cytoplasm. Thus the GO-PAA as a transmembrane transporter is a new class of drug transporters with potential protein delivery applications.