Regulation of Betaine Homocysteine Methyltransferase by Liver Receptor Homolog-1 in the Methionine Cycle.

Betaine-homocysteine S-methyltransferase (BHMT) is one of the most abundant proteins in the liver and regulates homocysteine metabolism. However, the molecular mechanisms underlying Bhmt transcription have not yet been elucidated. This study aimed to assess the molecular mechanisms underlying Bhmt transcription and the effect of BHMT deficiency on metabolic functions in the liver mediated by liver receptor homolog-1 (LRH-1). During fasting, both Bhmt and Lrh-1 expression increased in the liver of Lrh-1f/f mice; however, Bhmt expression was decreased in LRH-1 liver specific knockout mice. Promoter activity analysis confirmed that LRH-1 binds to a specific site in the Bhmt promoter region. LRH-1 deficiency was associated with elevated production of reactive oxygen species (ROS), lipid peroxidation, and mitochondrial stress in hepatocytes, contributing to hepatic triglyceride (TG) accumulation. In conclusion, this study suggests that the absence of an LRH-1-mediated decrease in Bhmt expression promotes TG accumulation by increasing ROS levels and inducing mitochondrial stress. Therefore, LRH-1 deficiency not only leads to excess ROS production and mitochondrial stress in hepatocytes, but also disrupts the methionine cycle. Understanding these regulatory pathways may pave the way for novel therapeutic interventions against metabolic disorders associated with hepatic lipid accumulation.

Photonic Interpenetrating Polymer Network Fibers Comprising Intertwined Solid-State Cholesteric Liquid Crystal and Polyelectrolyte Networks for Sensor Applications.

Uniform-sized photonic interpenetrating polymer network (IPN) fibers comprising intertwined solid-state cholesteric liquid crystal (CLCsolid) and anionic poly(acrylic acid) (PAA) or cationic poly(2-dimethylaminoethyl methacrylate) (PDMAEMA) networks (photonic IPNPAA or IPNPDMAEMA fibers) were developed for sensor applications. IPNPAA or IPNPDMAEMA fibers with a perfect photonic structure were fabricated inside Teflon tube templates without any treatments for realizing a planar orientation in those fibers. The dominant wavelength of the photonic color from a photograph taken with a cellular phone was used to measure the photonic color change. Photonic IPNPAA fibers treated with KOH (IPNKOH fibers) were used for sensing humidity and divalent metal ions. The linear ranges for relative humidity and Ca2+ detection were 21-92% and 0.5-3.5 mM, and their limits of detection (LODs) were 7.86% and 0.07 mM, respectively. The photonic IPNPAA (or IPNPDMAEMA) fiber immobilized with urease (IPNPAA-urease) (or glucose oxidase (IPNPDMAEMA-GOx)) was used for urea (or glucose) biosensor application. The photonic IPNPAA-urease (or IPNPDMAEMA-GOx) fiber was red-shifted in response to urea (or glucose) in the linear range of 10-60 mM (or 2-16 mM) with an LOD of 2.54 mM (or 0.76 mM). These photonic IPN fibers are promising because of their easy fabrication and miniaturization, battery-free device, cost-effectiveness, and visual detection without using sophisticated analytical instruments. The developed photonic IPN fibers provide new possibilities for the widespread use of photonic sensors in cutting-edge wearable technology and beyond.

Light-Responsive Actuator of Azobenzene-Containing Main-Chain Liquid Crystal Elastomers with Allyl Sulfide Dynamic Exchangeable Linkages.

Herein, a light-responsive and light-induced bond-exchange-reaction (BER)-capable actuator of the monodomain liquid crystal elastomer (xMLCEazo), developed using main-chain mesogenic oligomers containing azobenzene and allyl sulfide linkages, is investigated. Large quantities of the azobenzene and allyl dithiol linkages are incorporated into the main-chain mesogenic oligomer prepared via thiol-acrylate Michael addition polymerization (TAMAP). The xMLCEazo film is generated via visible-light-induced BER of the drawn polydomain xLCEazo (xPLCEazo) film prepared via TAMAP of tetrathiol cross-linkers and diacrylate-terminated mesogenic oligomers. The xMLCEazo film exhibits large length actuation (38%) through the photothermal effect, along with excellent self-healing and reprogramming properties, under ultraviolet (UV) light irradiation. UV light induced BER of the xMLCEazo film is used to develop complex-shaped actuators with a bilayer film, containing the xMLCEazo and xPLCEazo films, which are bonded by the UV light induced BER without glue. The individual arm of the complex eight-arm flower is remotely actuated under UV light irradiation, and a circular band is rolled under blue laser light irradiation, demonstrating the local remote-controlled actuation and fuel-free motion of the motile soft robot using light irradiation, respectively. Thus, the xMLCEazo film can be expanded to other interesting applications requiring reprogrammable, self-healing, reprocessable, patternable, and remote-controlled light-triggered elastic, rubber-like actuators.

Expression of EGFR, PD-L1, and the mismatch repair proteins before and following therapy in malignant serous effusions with metastatic high-grade serous tubo-ovarian carcinoma.

AIM: To compare the immunochemical expression of EGFR, PD-L1, and the mismatch repair (MMR) proteins MLH1, PMS2, MSH2, and MSH6 between matched malignant effusions obtained before and following the administration of chemotherapy in patients with high-grade serous tubo-ovarian carcinoma (HGSC). METHODS: In the enrolled HGSCs, matched formalin-fixed and paraffin-embedded cell blocks (CBs) from effusions sampled before (treatment-naïve patients) and during recurrence (following chemotherapy administration), in addition to their matched HGSC tissues obtained from the ovaries at initial diagnosis (treatment-naïve patients), were subjected to EGFR, PD-L1, and MMR immunochemical analysis. RESULTS: EGFR was more often overexpressed in effusions obtained after chemotherapy administration compared to both effusions (100% vs. 57.1%) and their matched tubo-ovarian tumors (100% vs. 7.1%) from treatment-naïve patients, respectively. EGFR immunochemistry was concordant in just 9.1% of the effusions sampled during recurrence and their paired ovarian samples before recurrence. Whereas all HGSC treatment-naïve samples (ovarian lesions and effusions) were PD-L1 negative, 3/11 (27.3%) malignant effusions obtained during recurrence showed PD-L1 overexpression. Lastly, none of the tested HGSC samples exhibited MMR deficiency. CONCLUSION: Measuring biomarkers using CBs from malignant effusions may provide clinicians with significant information related to HGSC prognosis and therapy selection, especially in patients with resistance to chemotherapy.

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.

Bilayer Actuator Film for Urea Biosensing with Dual Responsiveness: Bending Actuation and Photonic Color Change.

A noninvasive sweat-based biosensor was developed for urea detection using a photonic bilayer actuator film (BAF) consisting of an interpenetrating polymer network (IPN) as the active layer and a flexible poly(ethylene terephthalate) (PET) substrate as the passive layer (IPN/PET). The active IPN layer comprises intertwined solid-state cholesteric liquid crystal and poly(acrylic acid) (PAA) networks. Urease was immobilized in the PAA network in the IPN layer of the photonic BAF. The interaction with aqueous urea altered the curvature and photonic color of the photonic urease-immobilized IPN/PET (IPNurease/PET) BAF. The curvature (and wavelength of the photonic color) of the IPNurease/PET BAF increased linearly with urea concentration (Curea) in the range of Curea = 20-65 (and 30-65) mM with a limit of detection value of 1.42 (and 1.34) mM. The developed photonic IPNurease/PET BAF exhibited high selectivity toward urea and excellent spike test results with real human sweat. This novel IPNurease/PET BAF is promising because it enables battery-free, cost-effective, and visual detection-based analysis without the use of sophisticated instruments. Furthermore, the application of this photonic IPN/PET BAF can be easily extended to other biosensors by immobilizing other receptors on the IPN.

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.

Laminin-α4 Negatively Regulates Adipocyte Beiging Through the Suppression of AMPKα in Male Mice.

Laminin-α4 (LAMA4) is an extracellular matrix protein implicated in the regulation of adipocyte differentiation and function. Prior research describes a role for LAMA4 in modulating adipocyte thermogenesis and uncoupling protein-1 (UCP1) expression in white adipose; however, the mechanisms involved are poorly understood. Here, we describe that Lama4 knockout mice (Lama4-/-) exhibit heightened mitochondrial biogenesis and peroxisome proliferator-activated receptor γ coactivator-1 (PGC-1) expression in subcutaneous white adipose tissue (sWAT). Furthermore, the acute silencing of LAMA4 with small interfering RNA in primary murine adipocytes was sufficient to upregulate the expression of thermogenic markers UCP1 and PR domain containing 16 (PRDM16). Silencing also resulted in an upregulation of PGC1-α and adenosine 5'-monophosphate-activated protein kinase (AMPK)-α expression. Subsequently, we show that integrin-linked kinase (ILK) is downregulated in the sWAT of Lama4-/- mice, and its silencing in adipocytes similarly resulted in elevated expression of UCP1 and AMPKα. Last, we demonstrate that treatment of human induced pluripotent stem cell-derived thermogenic adipocytes with LAMA4 (LN411) inhibited the expression of thermogenic markers and AMPKα. Overall, our results indicate that LAMA4 negatively regulates a thermogenic phenotype and pathways involving mitochondrial biogenesis in adipocytes through the suppression of AMPKα.

Prognostic Impact of Myosteatosis on Mortality in Hospitalized Patients with COVID-19.

Body composition, including sarcopenia, adipose tissue, and myosteatosis, is associated with unfavorable clinical outcomes in patients with coronavirus disease (COVID-19). However, few studies have identified the impact of body composition, including pre-existing risk factors, on COVID-19 mortality. Therefore, this study aimed to evaluate the effect of body composition, including pre-existing risk factors, on mortality in hospitalized patients with COVID-19. This two-center retrospective study included 127 hospitalized patients with COVID-19 who underwent unenhanced chest computed tomography (CT) between February and April 2020. Using the cross-sectional CT images at the L2 vertebra level, we analyzed the body composition, including skeletal muscle mass, visceral to subcutaneous adipose tissue ratio (VSR), and muscle density using the Hounsfield unit (HU). Of 127 patients with COVID-19, 16 (12.6%) died. Compared with survivors, non-survivors had low muscle density (41.9 vs. 32.2 HU, p < 0.001) and high proportion of myosteatosis (4.5 vs. 62.5%, p < 0.001). Cox regression analyses revealed diabetes (hazard ratio [HR], 3.587), myosteatosis (HR, 3.667), and a high fibrosis-4 index (HR, 1.213) as significant risk factors for mortality in patients with COVID-19. Myosteatosis was associated with mortality in hospitalized patients with COVID-19, independent of pre-existing prognostic factors.

Photonic Cholesteric Liquid-Crystal Elastomers with Reprogrammable Helical Pitch and Handedness.

The unique combination of the rubber-like property and the photonic helicoidal structure of cholesteric liquid-crystal elastomers (CLCEs) results in one-handed circular polarized light reflection, the wavelength of which is dictated by the Bragg relationship. Herein, a highly stretchable mechanochromic photonic CLCE film was fabricated by cross-linking mesogenic oligomers having thiol terminal groups, which further reacted to form disulfide (-S-S-) linkages. The mechanically stretched photonic CLCE film reflected both right- and left-handed circular polarized lights with a blue-shifted color. The helicoidal pitch and handedness controlled by the applied strain were programmed through a dynamic exchange reaction between the -S-S- linkages, thus realizing the patterning at selective regions. The pattern almost vanished under unpolarized daylight but was visible under circularly polarized light when the patterned photonic CLCE film had been heated above its isotropic temperature. The hidden patterns of the heat-treated CLCE film reappeared under unpolarized daylight when stretched, demonstrating a data encryption ability. These patterned photonic elastomers can be uniquely used in sensors, actuators, soft robotics, flexible displays, data encryption, and anticounterfeiting applications with a mechanochromic camouflage response.

Developmental defects and impaired network excitability in a cerebral organoid model of KCNJ11 p.V59M-related neonatal diabetes.

The gene KCNJ11 encodes Kir6.2 a major subunit of the ATP-sensitive potassium channel (KATP) expressed in both the pancreas and brain. Heterozygous gain of function mutations in KCNJ11 can cause neonatal diabetes mellitus (NDM). In addition, many patients exhibit neurological defects ranging from modest learning disorders to severe cognitive dysfunction and seizures. However, it remains unclear to what extent these neurological deficits are due to direct brain-specific activity of mutant KATP. We have generated cerebral organoids derived from human induced pluripotent stem cells (hiPSCs) possessing the KCNJ11 mutation p.Val59Met (V59M) and from non-pathogenic/normal hiPSCs (i.e., control/WT). Control cerebral organoids developed neural networks that could generate stable synchronized bursting neuronal activity whereas those derived from V59M cerebral organoids showed reduced synchronization. Histocytochemical studies revealed a marked reduction in neurons localized to upper cortical layer-like structures in V59M cerebral organoids suggesting dysfunction in the development of cortical neuronal network. Examination of temporal transcriptional profiles of neural stem cell markers revealed an extended window of SOX2 expression in V59M cerebral organoids. Continuous treatment of V59M cerebral organoids with the KATP blocker tolbutamide partially rescued the neurodevelopmental differences. Our study demonstrates the utility of human cerebral organoids as an investigative platform for studying the effects of KCNJ11 mutations on neurophysiological outcome.

Association of Skeletal Muscle and Adipose Tissue Distribution with Histologic Severity of Non-Alcoholic Fatty Liver.

Adipose tissue and skeletal muscle is associated with non-alcoholic fatty liver disease (NAFLD). This study evaluates the association between body composition and histologic severity in patients with NAFLD. Using the cross-sectional CT images at the level of L3 vertebra and the histologic findings of 178 patients with biopsy-proven NAFLD, we analyzed the correlation of the histologic findings to the skeletal muscle index (SMI), subcutaneous adipose tissue index (SATI), and visceral adipose tissue index (VATI), which is defined as the body composition area (cm2) by height squared (m2). The clinical and laboratory features with body composition were analyzed to determine the risk factors for advanced fibrosis. The VATI significantly increased in severe non-alcoholic steatohepatitis (NASH) or advanced fibrosis. In addition, the VATI was correlated with the NAFLD activity score (NAS) and the fibrosis stage. In multivariate analyses, age (odds ratio (OR), 1.09; 95% confidence interval (CI), 1.02-1.19; p = 0.025), severe NASH (OR, 8.66; 95% CI, 2.13-46.40; p = 0.005), and visceral adiposity (OR, 6.77; 95% CI, 1.81-29.90; p = 0.007) were independently associated with advanced fibrosis in patients with NAFLD. Visceral adiposity is correlated with the histologic severity of NAFLD, which is independently associated with advanced fibrosis.

In celebration of a century with insulin - Update of insulin gene mutations in diabetes.

BACKGROUND: While insulin has been central to the pathophysiology and treatment of patients with diabetes for the last 100 years, it has only been since 2007 that genetic variation in the INS gene has been recognised as a major cause of monogenic diabetes. Both dominant and recessive mutations in the INS gene are now recognised as important causes of neonatal diabetes and offer important insights into both the structure and function of insulin. It is also recognised that in rare cases, mutations in the INS gene can be found in patients with diabetes diagnosed outside the first year of life. SCOPE OF REVIEW: This review examines the genetics and clinical features of monogenic diabetes resulting from INS gene mutations from the first description in 2007 and includes information from 389 patients from 292 families diagnosed in Exeter with INS gene mutations. We discuss the implications for diagnosing and treating this subtype of monogenic diabetes. MAJOR CONCLUSIONS: The dominant mutations in the INS gene typically affect the secondary structure of the insulin protein, usually by disrupting the 3 disulfide bonds in mature insulin. The resulting misfolded protein results in ER stress and beta-cell destruction. In contrast, recessive INS gene mutations typically result in no functional protein being produced due to reduced insulin biosynthesis or loss-of-function mutations in the insulin protein. There are clinical differences between the two genetic aetiologies, between the specific mutations, and within patients with identical mutations.

Poly(acrylic acid) Hydrogel Microspheres for a Metal-Ion Sensor.

Monodispersed cross-linked poly(acrylic acid) (PAA) droplets (PAA X-droplets), prepared using the microfluidic method with in situ ultraviolet curing, were used as small spherical sensors to simultaneously detect both Ca2+ and Mg2+ in human saliva and serum. The PAA X-droplet treated with KOH (PAAKOH X-droplet) was used as a reference droplet because of its highly swollen state. The PAAKOH X-droplets shrunk in response to the presence of divalent metal ions (Ms) by forming a bridged structure of COO-M-OOC. The sizes of the PAAKOH X-droplets were precisely and dynamically monitored in the poly(dimethylsiloxane) (PDMS) channel with passing time when the aqueous metal-ion solutions were flowing at a controlled flow rate. The sizes of the PAAKOH X-droplets continuously decreased to the saturated constant size. The saturated size of the PAAKOH X-droplet did not change; however, the speed of size reduction increased with an increase in the concentration of the divalent metal ion. The saturated size was studied using the saturated diameter ratio (Rsat-dia) with respect to the initial diameter of the PAAKOH X-droplet before the metal-ion treatment, and the speed of the size reduction was investigated using the inverse time to reach half the saturated diameter reduction (T1/2-1). Ca2+ and Mg2+ exhibited Rsat-dia values of 75.9 and 83.6%, respectively, when the flow rate was 5 µL min-1, regardless of the metal concentration. The T1/2-1s for the Ca2+ and Mg2+ linearly increased with an increase in their concentrations. The Rsat-dia of the aqueous Ca2+/Mg2+ mixture solution had a linear relationship with φ [= CCa/(CCa + CMg), where CCa and CMg are the molar concentrations of Ca2+ and Mg2+, respectively]. The T1/2-1 of the aqueous Ca2+, Mg2+ mixture solution was calculated by adding the individual T1/2-1s of pure aqueous Ca2+ and Mg2+ solutions. Using the Rsat-dia and T1/2-1 of the Ca2+/Mg2+ mixture aqueous solution, the individual CCa and CMg in the mixture solution were successfully calculated. This method was applied to the human saliva and serum in which the major metal ions are Ca2+ and Mg2+, and other metal ions existed in undetectable amounts by the PAAKOH X-droplets. This method is simple, cost-effective, and highly accurate and solves the hurdles of separating the interference effect of a Mg2+ ion when a Ca2+ ion is measured in biofluids.

Optical anticounterfeiting photonic bilayer film based on handedness of solid-state helicoidal structure.

Anticounterfeiting photonic bilayer films were fabricated by sandwiching two solid-state cholesteric liquid crystal films having different handedness. The fabricated photonic bilayer films were successfully applied to patterning by selective photopolymerization. This photonic bilayer film as a new cryptographic technology is of interest for its anticounterfeiting application.

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.

Sweat-Based Noninvasive Skin-Patchable Urea Biosensors with Photonic Interpenetrating Polymer Network Films Integrated into PDMS Chips.

A wearable noninvasive biosensor for in situ urea detection and quantification was developed using a urease-immobilized photonic interpenetrating polymer network (IPNurease) film. The photonic IPN film was intertwined with solid-state cholesteric liquid crystals (CLCsolid) and a poly(acrylic acid) (PAA) network on a flexible poly(ethylene terephthalate) substrate adhered to a poly(dimethylsiloxane) (PDMS) chip that was fabricated using an aluminum mold. The presence of urea in the chemical matrix of human sweat red-shifted the reflected color of the photonic IPNurease film, and quantification was achieved by observing the wavelength at the photonic band gap (λPBG) with a limit of detection of 0.4 mM and a linear range of 0.9-50 mM. The color changes observed in the photonic IPN film were digitalized using the CIE 1931 xy coordinates on a cell phone image, thereby enabling fast, direct diagnosis via a downloadable app. This novel PDMS chip can be expanded for use with other biosensors.

Optical Multisensor Array with Functionalized Photonic Droplets by an Interpenetrating Polymer Network for Human Blood Analysis.

Photonic solid-state cholesteric liquid crystal (CLCsolid) droplets intertwined with a poly(acrylic acid) (PAA) network that has an interpenetrating polymer network (IPN) structure (referred to as photonic IPN CLCsolid-PAA droplets) were used as individual sensors in the dots of a PAA-patterned array film after functionalization via immobilization of the receptors and a metal-ion treatment. The photonic IPN CLCsolid-PAA droplets in the PAA-patterned array film were pH-responsive and showed an observable change in the reflected central color. This "smart" property, coupled with the photonic color response, makes these devices ideal photonic sensors. The immobilization of urease and phenylboronic acid on the PAA network allowed for the application of several 10 µm photonic IPN CLCsolid-PAA droplets to the optical photonic biosensors through facilitated volumetric changes in the PAA network in response to urea and glucose analytes, with high selectivity for major components in human serum, acceptable sensitivity for use with human serum, and extreme stability due to a solid-state structure. The blueshift of the reflected color of the KOH-treated photonic IPN CLCsolid-PAA droplets could be used for divalent metal-ion detection. The compartmentalized photonic IPN CLCsolid-PAA droplets in the patterned array film could be used for multiple detection applications, as evidenced by the ability to conduct pH, divalent metal ion, urea, and glucose detections in one patterned array film. This new platform opens the door for many interesting applications with numerous combinations of responsive hydrogel matrices and receptors.