Dipole moment as the underlying mechanism for enhancing the immobilization of glucose oxidase by ferrocene-chitosan for superior specificity non-invasive glucose sensing.

Non-invasive methods for sensing glucose levels are highly desirable due to the comfortableness, simplicity, and lack of infection risk. However, the insufficient accuracy and ease of interference limit their practical medical applications. Here, we develop a non-invasive salivary glucose biosensor based on a ferrocene-chitosan (Fc-Chit) modified carbon nanotube (CNT) electrode through a simple drop-casting method. Compared with previous studies that relied mainly on trial and error for evaluation, this is the first time that dipole moment was proposed to optimize the electron-mediated Fc-Chit, demonstrating sturdy immobilization of glucose oxidase (GOx) on the electrode and improving the electron transfer process. Thus, the superior sensing sensitivity of the biosensor can achieve 119.97 µA mM-1 cm-2 in phosphate buffered saline (PBS) solution over a wide sensing range of 20-800 µM. Additionally, the biosensor exhibited high stability (retaining 95.0% after three weeks) and high specificity toward glucose in the presence of various interferents, attributed to the specific sites enabling GOx to be sturdily immobilized on the electrode. The results not only provide a facile solution for accurate and regular screening of blood glucose levels via saliva tests but also pave the way for designing enzymatic biosensors with specific enzyme immobilization through fundamental quantum calculations.

Novel GdTaO4 phase for efficient photocatalytic degradation of organic dye under visible light irradiation: An X-ray spectroscopic investigation.

The novel GdTaO4 phase exhibits good photocatalytic activity under visible light irradiation and holds great promise for the removal of organic dyes from industrial wastes. The GdTaO4 samples were synthesized using the hydrothermal and calcination process with different weight ratios of gadolinium nitrate hydrate (G) and tantalum pentachloride (T), and their structural studies confirmed the formation of the GdTaO4 (GT) phase. Among the samples, GT-4 (with a weight ratio of 4:1) exhibited the highest photocatalytic activity for the degradation of Methyl Orange (MO) dye under visible light irradiation. To enhance the photocatalytic performance, H2O2 was used as a green additive, and the photocatalytic abilities were examined by varying dye types and concentrations. X-ray photoelectron spectroscopy (XPS) and X-ray absorption spectroscopy (XAS) revealed the local atomic and electronic structures around Ta and Gd and highlighted the contribution of Gd3+ to the GT system, which is a crucial factor in supporting the enhanced photocatalytic performance. Moreover, in-situ XAS at Gd M5-edge and O K-edge were examined under illumination/dark conditions to explore the electronic structures of photo-excited electron transition in the photocatalytic process. The analytical results provided strong evidence correlating the electronic structure and photocatalytic property of the GT. This study demonstrates that GdTaO4 exhibits good photocatalytic activity under visible light irradiation, making it a promising new Ta-based photocatalyst for the effective removal of organic dyes from industrial wastes.

Layered Double Hydroxides for Regulating Phosphate in Water to Achieve Long-Term Nutritional Management.

Hunger and undernourishment are increasing global challenges as the world's population continuously grows. Consequently, boosting productivity must be implemented to reach the global population's food demand and avoid deforestation. The current promising agricultural practice without herbicides and pesticides is fertilizer management, particularly that of phosphorus fertilizers. Layered double hydroxides (LDHs) have recently emerged as favorable materials in phosphate removal, with practical application possibilities in nanofertilizers. This review discusses the fundamental aspects of phosphate removal/recycling mechanisms and highlights the current endeavors on the development of phosphate-selective sorbents using LDH-based materials. Specific emphasis is provided on the progress in designing LDHs as the slow release of phosphate fertilizers reveals their relevance in making agro-practices more ecologically sound. Relevant pioneering efforts have been briefly reviewed, along with a discussion of perspectives on the potential of LDHs as green nanomaterials to improve food productivity with low eco-impacts.

The Drosophila AWP1 ortholog Doctor No regulates JAK/STAT signaling for left-right asymmetry in the gut by promoting receptor endocytosis.

Many organs of Drosophila show stereotypical left-right (LR) asymmetry; however, the underlying mechanisms remain elusive. Here, we have identified an evolutionarily conserved ubiquitin-binding protein, AWP1/Doctor No (Drn), as a factor required for LR asymmetry in the embryonic anterior gut. We found that drn is essential in the circular visceral muscle cells of the midgut for JAK/STAT signaling, which contributes to the first known cue for anterior gut lateralization via LR asymmetric nuclear rearrangement. Embryos homozygous for drn and lacking its maternal contribution showed phenotypes similar to those with depleted JAK/STAT signaling, suggesting that Drn is a general component of JAK/STAT signaling. Absence of Drn resulted in specific accumulation of Domeless (Dome), the receptor for ligands in the JAK/STAT signaling pathway, in intracellular compartments, including ubiquitylated cargos. Dome colocalized with Drn in wild-type Drosophila. These results suggest that Drn is required for the endocytic trafficking of Dome, which is a crucial step for activation of JAK/STAT signaling and the subsequent degradation of Dome. The roles of AWP1/Drn in activating JAK/STAT signaling and in LR asymmetric development may be conserved in various organisms.

Characterization and Structural Determination of CmnG-A, the Adenylation Domain That Activates the Nonproteinogenic Amino Acid Capreomycidine in Capreomycin Biosynthesis.

Capreomycidine (Cap) is a nonproteinogenic amino acid and building block of nonribosomal peptide (NRP) natural products. We report the formation and activation of Cap in capreomycin biosynthesis. CmnC and CmnD catalyzed hydroxylation and cyclization, respectively, of l-Arg to form l-Cap. l-Cap is then adenylated by CmnG-A before being incorporated into the nonribosomal peptide. The co-crystal structures of CmnG-A with l-Cap and adenosine nucleotides provide insights into the specificity and engineering opportunities of this unique adenylation domain.

A Green Approach for High Oxidation Resistance, Flexible Transparent Conductive Films Based on Reduced Graphene Oxide and Copper Nanowires.

Copper nanowires (CuNWs)-based thin film is one of the potential alternatives to tin-doped indium oxide (ITO) in terms of transparent conductive films (TCFs). However, the severe problem of atmospheric oxidation restricts their practical applications. In this work, we develop a simple approach to fabricate highly stable TCFs through the dip-coating method using reduced graphene oxide (rGO) and CuNWs as the primary materials. Compared with previous works using toxic reduction agents, herein, the CuNWs are synthesized via a green aqueous process using glucose and lactic acid as the reductants, and rGO is prepared through the modified Hummers' method followed by a hydrogen-annealing process to form hydrogen-annealing-reduced graphene oxide (h-rGO). In the rGO/CuNWs films, the dip-coated graphene oxide layer can increase the adhesion of the CuNWs on the substrate, and the fabricated h-rGO/CuNWs can exhibit high atmospheric oxidation resistance and excellent flexibility. The sheet resistance of the h-rGO/CuNWs film only increased from 25.1 to 42.2 Ω/sq after exposure to ambient atmosphere for 30 days and remained almost unchanged after the dynamic bending test for 2500 cycles at a constant radius of 5.3 mm. The h-rGO/CuNWs TCF can be not only fabricated via a route with a superior inexpensive and safe method but also possessed competitive optoelectronic properties with high electrical stability and flexibility, demonstrating great opportunities for future optoelectronic applications.

ECIS Based Electric Fence Method for Measurement of Human Keratinocyte Migration on Different Substrates.

Electric Cell-substrate Impedance Sensing (ECIS) is an impedance-based, real-time, and label-free measuring system for monitoring cellular activities in tissue culture. Previously, ECIS wound healing assay has been used to wound cells with high electric current and monitor the subsequent cell migration. In this study, we applied ECIS electric fence (EF) method, an alternative to electrical wounding, to assess the effects of different surface coatings on human keratinocyte (HaCaT) migration. The EF prevents inoculated cells from attaching or migrating to the fenced electrode surface while maintaining the integrity of the surface coating. After the EF is turned off, cells migrate into the cell-free area, and the increase in measured impedance is monitored. We cultured HaCaT cells on gold electrodes without coating or coated with poly-L-lysin (PLL), poly-D-lysine (PDL), or type-I collagen. We quantified migration rates according to the different slopes in the impedance time series. It was observed that either poly-L-lysine (PLL) or poly-D-lysine (PDL) limits cell adhesion and migration rates. Furthermore, the surface charge of the coated substrate in the culture condition positively correlates with the cell adhesion and migration process. Our results indicate that the EF method is useful for determining cell migration rates on specific surface coatings.

Proteolytic activity accelerates the TH17/TH22 recall response to an epicutaneous protein allergen-induced TH2 response.

Epicutaneous exposure to protein allergens, such as papain, house dust mite (HDM), and ovalbumin (OVA), represents an important mode of sensitization for skin diseases including protein contact dermatitis, immunologic contact urticaria, and atopic dermatitis. These diseases are inducible by re-exposure to an allergen at both original skin sensitization and distant skin sites. In this study, we examined the serum IgE/IgG1 response, differentiation of T-helper (TH) cells, and epicutaneous TH recall response in mice pre-sensitized with protein allergens through the back skin and subsequently challenged on the ear skin. Repeated epicutaneous sensitization with allergenic proteins including papain, HDM, OVA, and protease inhibitor-treated papain, but not bovine serum albumin, induced serum allergen-specific antibody production, passive cutaneous anaphylaxis responses, and TH2 differentiation in the skin draining lymph node (DLN) cells. Sensitization with papain or HDM, which have protease activity, resulted in the differentiation of TH17 as well as TH2. In papain- or HDM-sensitized mice, a subsequent single challenge on the ear skin induced the expression of TH2 and TH17/TH22 cytokines. These results suggest that allergenic proteins induce the differentiation of TH2 in skin DLN cells and an antibody response. These findings may be useful for identifying proteins of high and low allergenic potential. Moreover, allergenic proteins containing protease activity may also differentiate TH17 and induce TH2 and TH17/TH22 recall responses at epicutaneous challenge sites. This suggests that allergen protease activity accelerates the onset of skin diseases caused by protein allergens.

Eight-Fold Interpenetrating Diamondoid Coordination Polymers for Sensing Volatile Organic Compounds and Metal Ions.

Reactions of divalent metal salts with 4,4-oxybis(N-(pyridine-4-yl)-benzamide), L, and naphthalene-1,4-dicarboxylic acid (1,4-H2NDC) in various solvents gave [Zn(L)(1,4-NDC)·H2O]n, 1, [Cd(L)(1,4-NDC)(H2O)·MeOH]n, 2, and [Co(L)(1,4-NDC)(H2O)0.5·MeOH]n, 3, which have been structurally characterized. Complexes 1-3 show eight-fold interpenetrating frameworks with the dia topology, which exhibit porosities substantiated by CO2 adsorption, whereas 1 and 2 manifest stability in aqueous environments and show high selectivity toward sensing of mesitylene molecules and Fe3+ ions with low detection limits and good reusability up to five cycles.

CCL2 associated with CD38 expression during ex vivo expansion in human cord blood-derived hematopoietic stem cells.

To date, different experimental strategies have been developed for the ex vivo expansion of human hematopoietic stem cells (HSCs) for clinical applications. However, differences in the genomic function of expanded HSCs under different culture systems remain unclear. In this study, we compared the gene expression profiles of HSCs in ex vivo expanded serum (10% FBS, fetal bovine serum) and serum-free culture systems and analyzed the molecular functions of differentially expressed genes using microarray chips. We identified 839 differentially expressed genes between the two culture systems. These genes were enriched in the TNF -regulated inflammatory pathway in an FBS culture system. In addition, the mRNA expression of CCL2 (C-C motif chemokine ligand 2), TNF (tumor necrosis factor) and FOS (FBJ murine osteosarcoma viral oncogene homolog) was validated by RT-qPCR. Our data revealed that ex vivo expansion of HSCs using the FBS culture system induces an inflammatory response and high CD38 expression, indicating that this system might activate an inflammatory pathway and induce expression of the cancer marker CD38 during ex vivo expansion of HSCs. This study provides a transcriptional profile and new insights into the genomic functions of HSCs under different expanded cultures.

Women's Cognition and Attitude with Eco-Friendly Menstrual Products by Consumer Lifestyle.

With rapid technology developments and the convenient and fast pace of life in recent years, many people are using disposable products, which cause environmental and ecological damages. A variety of eco-friendly menstrual products have been launched on the market, and "menstrual pads" now have a large market share in Taiwan's menstrual product industry. This study interviewed experts and collected questionnaires for qualitative and quantitative investigation and analysis. The results show that women have positive and open concepts regarding sustainability, as well as a good understanding of their body and are very interested in the performance and usage efficiency of products. The results also indicate that consumers purchase based on their lifestyles; most women collected enough product information before purchasing while overcoming the difficulties in dealing with the environment and learning to adapt them, and the majority of consumers attach importance to comfort, volume, and duration of blood absorption. The results suggest that the government and private enterprises should increase and improve sanitation education and sanitary facilities and guide the approach and serve as an important reference index for the promotion of eco-friendly menstrual products for environmental benefits.

A Triple-Mode Midinfrared Modulator for Radiative Heat Management of Objects with Various Emissivity.

Thermal management is ubiquitous in the modern world and indispensable for a sustainable future. Radiative heat management provides unique advantages because the heat transfer can be controlled by the surface. However, different object emissivities require different tuning strategies, which poses challenges to develop dynamic and universal radiative heat management devices. Here, we demonstrate a triple-mode midinfrared modulator that can switch between passive heating and cooling suitable for all types of object surface emissivities. The device comprises a surface-textured infrared-semiabsorbing elastomer coated with a metallic back reflector, which is biaxially strained to sequentially achieve three fundamental modes: emission, reflection, and transmission. By analyzing and optimizing the coupling between optical and mechanical properties, we achieve a performance as follows: emittance contrast Δε = 0.58, transmittance contrast Δτ = 0.49, and reflectance contrast Δρ = 0.39. The device can provide a new design paradigm of radiation heat regulation for wearable, robotics, and camouflage technologies.

Detecting Effects of Low Levels of FCCP on Stem Cell Micromotion and Wound-Healing Migration by Time-Series Capacitance Measurement.

Electric cell-substrate impedance sensing (ECIS) has been used as a real-time impedance-based method to quantify cell behavior in tissue culture. The method is capable of measuring both the resistance and capacitance of a cell-covered microelectrode at various AC frequencies. In this study, we demonstrate the application of high-frequency capacitance measurement (f = 40 or 64 kHz) for the sensitive detection of both the micromotion and wound-healing migration of human mesenchymal stem cells (hMSCs). Impedance measurements of cell-covered electrodes upon the challenge of various concentrations of carbonyl cyanide 4-(trifluoromethoxy)phenylhydrazone (FCCP), from 0.1 to 30 µM, were conducted using ECIS. FCCP is an uncoupler of mitochondrial oxidative phosphorylation (OXPHOS), thereby reducing mitochondrial ATP production. By numerically analyzing the time-series capacitance data, a dose-dependent decrease in hMSC micromotion and wound-healing migration was observed, and the effect was significantly detected at levels as low as 0.1 µM. While most reported works with ECIS use the resistance/impedance time series, our results suggest the potential use of high-frequency capacitance time series for assessing migratory cell behavior such as micromotion and wound-healing migration.

Association of UBE3C Variants with Reduced Kidney Function in Patients with Diabetic Kidney Disease.

Diabetic kidney disease (DKD) is the leading cause of morbidity and mortality in patients with diabetes mellitus (DM) and the most common variant of end-stage renal disease (ESRD) globally. The economic burden of ESRD treatment with dialysis is substantial. The incidence and prevalence of ESRD in Taiwan remain the highest worldwide. Therefore, identifying genetic factors affecting kidney function would have valuable clinical implications. We performed microarray experiments and identified that ubiquitin protein ligase E3C (UBE3C) is differentially expressed in two DKD patient groups with extreme (low and high) urine protein-to-creatinine ratios. A follow-up genotyping study was performed in a larger group to investigate any specific variants of UBE3C associated with DKD. A total of 263 patients were included in the study, comprising 172 patients with DKD and 91 control subjects (patients with DM without chronic kidney disease (CKD)). Two UBE3C variants (rs3802129(AA) and rs7807(CC)) were determined to be associated with reduced kidney function. The haplotype analysis revealed that rs3802129/rs3815217 (block 1) with A/G haplotype and rs8101/rs7807 (block 2) with T/C haplotype were associated with higher risks of CKD phenotypes. These findings suggest a clinical role of UBE3C variants in DKD risk.

Gender Differences in Genetic Associations of RAB38 with Urinary Protein-to-Creatinine Ratio (UPCR) Levels in Diabetic Nephropathy Patients.

Renal dysfunction is common in patients with diabetes mellitus (DM). Previous findings from a meta-analysis of GWAS indicated that the variation of RAB38/CTSC is highly associated with the urinary albumin-to-creatinine ratio (UACR) in European populations. In addition, RAB38 knockout rats showed an increase in urinary albumins. Although the prevalence of chronic kidney disease is high in Taiwan, the role of genetic variants in diabetic renal function is still unclear. In the current study, 275 diabetic nephropathy (DN) patients were recruited to perform a genetic association study. Our results indicated that rs1027027, rs302647, and rs302646 in RAB38 were significantly associated with urinary protein-to-creatinine ratio (UPCR) levels in DN patients. Importantly, after analysis stratified by gender, a significant genetic influence on UPCR levels was observed in the male population. The findings confirmed the roles of gender and variants of RAB38 in the risk of UPCR in Diabetic Nephropathy patients.

Green Treatment of Phosphate from Wastewater Using a Porous Bio-Templated Graphene Oxide/MgMn-Layered Double Hydroxide Composite.

Excessive phosphorus in water is the primary culprit for eutrophication, which causes approximately $2.2 billion annual economic loss in the United States. This study demonstrates a phosphate-selective sustainable method by adopting Garcinia subelliptica leaves as a natural bio-template, where MgMn-layered double hydroxide (MgMn-LDH) and graphene oxide (GO) can be grown in situ to obtain L-GO/MgMn-LDH. After calcination, the composite shows a hierarchical porous structure and selective recognition of phosphate, which achieves significantly high and recyclable selective phosphate adsorption capacity and desorption rate of 244.08 mg-P g-1 and 85.8%, respectively. The detail variation of LDHs during calcination has been observed via in situ transmission electron microscope (TEM). Moreover, the roles in facilitating phosphate adsorption and antimicrobial ability of chemical constituents in Garcinia subelliptica leaves, biflavonoids, and triterpenoids have been investigated. These results indicate the proposed bio-templated adsorbent is practical and eco-friendly for phosphorus sustainability in commercial wastewater treatment.

Genotypic Regulation of Type I Interferon Induction Pathways by Frameshift (F) Proteins of Hepatitis C Virus.

Hepatitis C virus (HCV) has evolved mechanisms to evade innate immunity that are leading to chronic infections. The immunological function of the HCV frameshift (F) protein, which is a frameshift product of core coding sequences, has not been well characterized. The HCV F protein is produced during natural HCV infections and is found most commonly in genotype 1 HCV. In this study, we investigated whether the F protein plays a role in type I interferon (IFN) induction pathways. We engineered F expression constructs from core coding sequences of 4 genotypes (1a, 2a, 3a, and 4a) of HCV as well as the sequences which would only be able to produce core proteins. The peptide lengths and amino acids sequences of F proteins are highly variable. We hypothesized that F proteins from different genotypes might control the type I IFN production and response differently. We found that both IFN-beta (IFN-ß) promoter activities are significantly higher in genotype 1a F protein (F1a)-expressing cells. Conversely, the IFN-ß promoter activities are lower in genotype 2a F (F2a) protein-expressing cells. We also used real-time PCR to confirm IFN-ß mRNA expression levels. By generating chimera F proteins, we discovered that the effects of F proteins were determined by the amino acid sequence 40 to 57 of genotype 1a. The regulation of type I IFN induction pathway is related but not limited to the activity of F1a to interact with proteasome subunits and to disturb the proteasome activity. Further molecular mechanisms of how F proteins from different genotypes of HCV control these pathways differently remain to be investigated.IMPORTANCE Although naturally present in HCV infection patient serum, the virological or immunological functions of the HCV F protein, which is a frameshift product of core coding sequences, remain unclear. Here, we report the effects of the HCV F protein between genotypes and discuss a potential explanation for the differential responses to type I IFN-based therapy among patients infected with different genotypes of HCV. Our study provides one step forward to understanding the host response during HCV infection and new insights for the prediction of the outcome of IFN-based therapy in HCV patients.

Targeted photoresponsive carbazole-coumarin and drug conjugates for efficient combination therapy in leukemia cancer cells.

Phototriggered drug delivery systems (PTDDSs) facilitate controlled delivery of drugs loaded on photoactive platform to the target region under light stimulation. The present study investigated the synthesis and efficacy of carbazole-coumarin (CC)-fused heterocycles as a PTDDS platform for the photocontrolled release of a chemotherapeutic agent, chlorambucil, in an in vitro model of human breast and leukemia cancer cells. CC-fused heterocycles were constructed using 4-hydroxycarbazole as the starting material, and further modification of these heterocycles yielded two CC derivatives. CC-7 with an additional - COOH group and CC-8 with the triphenylphosphonium (TPP) group, a mitochondria-targeting ligand introduced in the carbazole ring, dissolved in polar solvents and exhibited emission bands at 360 and 450 nm, respectively. The results indicate that visible light of 405 nm triggers the photolysis of the CC-drug conjugate and efficiently delivers the drug in both in vitro cancer cell models. Cytotoxicity evaluation indicates the suppression of proliferation of both types of cells treated with CC-8 under synergy effect combining drug potency and photosensitization. Further, the lower IC50 of CC-8 toward leukemia cells suggests the efficacy of the TPP ligand in increasing the bioavailability of CC-drug conjugates in leukemia treatment. Studies on mitochondria-targeting drug delivery systems are required for improving the performance of anticancer drugs.

Using UPLC-MS/MS to Evaluate the Dissemination of Pyriproxyfen by Aedes Mosquitoes to Combat Cryptic Larval Habitats after Source Reduction in Kaohsiung in Southern Taiwan.

The policy regarding mosquito control strategies in Taiwan is based on integrated vector management (IVM). The major approach is source reduction via collaboration by both residents and governments. However, small and cryptic habitats of dengue vectors are hard to find and eliminate in urban communities. Therefore, this study evaluated a complementary approach that targeted cryptic habitats by utilizing mosquitoes themselves as vehicles to transfer an insect growth regulator, pyriproxyfen (PPF), to their breeding sites; the amount of PPF in breeding water was determined with ultra-performance liquid chromatography coupled with tandem mass spectrometry (UPLC-MS/MS). A bioassay conducted by introducing ten late-instar larvae into PPF solution was performed to assess emergence inhibition (EI). PPF was found at 0.56 ± 0.04 ng in 25 mL of water by dissemination via ten Aedes aegypti mosquitoes exposed to 0.01% PPF, leading to 100% EI. After the community-level source reduction, a field trial in Kaohsiung in Southern Taiwan showed that 30.8%-31.5% of cryptic ovitraps reached EI ≥ 50% one month after spraying 0.01% PPF in microhabitats favored by mosquitoes. IVM in parallel with residual spraying of PPF on resting surfaces of mosquitoes could serve as a simple and complementary approach to reduce cryptic larval sources in urban communities in Southern Taiwan.