Precise tuning of interlayer electronic coupling in layered conductive metal-organic frameworks.

Two-dimensional conjugated metal-organic frameworks (2D c-MOFs) have attracted increasing interests for (opto)-electronics and spintronics. They generally consist of van der Waals stacked layers and exhibit layer-depended electronic properties. While considerable efforts have been made to regulate the charge transport within a layer, precise control of electronic coupling between layers has not yet been achieved. Herein, we report a strategy to precisely tune interlayer charge transport in 2D c-MOFs via side-chain induced control of the layer spacing. We design hexaiminotriindole ligands allowing programmed functionalization with tailored alkyl chains (HATI_CX, X = 1,3,4; X refers to the carbon numbers of the alkyl chains) for the synthesis of semiconducting Ni3(HATI_CX)2. The layer spacing of these MOFs can be precisely varied from 3.40 to 3.70 Å, leading to widened band gap, suppressed carrier mobilities, and significant improvement of the Seebeck coefficient. With this demonstration, we further achieve a record-high thermoelectric power factor of 68 ± 3 nW m-1 K-2 in Ni3(HATI_C3)2, superior to the reported holes-dominated MOFs.

Synthetic Nuances to Maximize n-Type Organic Electrochemical Transistor and Thermoelectric Performance in Fused Lactam Polymers.

A series of fully fused n-type mixed conduction lactam polymers p(g7NCnN), systematically increasing the alkyl side chain content, are synthesized via an inexpensive, nontoxic, precious-metal-free aldol polycondensation. Employing these polymers as channel materials in organic electrochemical transistors (OECTs) affords state-of-the-art n-type performance with p(g7NC10N) recording an OECT electron mobility of 1.20 × 10-2 cm2 V-1 s-1 and a µC* figure of merit of 1.83 F cm-1 V-1 s-1. In parallel to high OECT performance, upon solution doping with (4-(1,3-dimethyl-2,3-dihydro-1H-benzoimidazol-2-yl)phenyl)dimethylamine (N-DMBI), the highest thermoelectric performance is observed for p(g7NC4N), with a maximum electrical conductivity of 7.67 S cm-1 and a power factor of 10.4 µW m-1 K-2. These results are among the highest reported for n-type polymers. Importantly, while this series of fused polylactam organic mixed ionic-electronic conductors (OMIECs) highlights that synthetic molecular design strategies to bolster OECT performance can be translated to also achieve high organic thermoelectric (OTE) performance, a nuanced synthetic approach must be used to optimize performance. Herein, we outline the performance metrics and provide new insights into the molecular design guidelines for the next generation of high-performance n-type materials for mixed conduction applications, presenting for the first time the results of a single polymer series within both OECT and OTE applications.

Determination of N-acetyl-DL-leucine in the saliva of healthy volunteers and diabetic patients using ultra-performance liquid chromatography with fluorescence detection.

BACKGROUND: Recent studies have indicated that N-acetyl-leucine (N-Ac-Leu) is a potential biomarker of diabetes. This study aimed to measure the levels of enantiomers of the chiral molecule N-Ac-DL-Leu in the saliva of patients with type 2 diabetes and further determine the potential association between them. METHOD: A novel validated method was established using ultra-performance liquid chromatography (UPLC) with fluorescence (FL) detection, in which precolumn derivatization of (R)-(-)-4-(N, N-dimethylaminosulfonyl)-7-(3-aminopyrrolidin-l-yl)-2,1,3-benzoxadiazole [(R)-(-)-DBD-APy] was used for the simultaneous determination and chiral separation of N-Ac-DL-Leu in human saliva. RESULTS: The labeled N-Ac-DL-Leu diastereomers were completely separated, with a resolution value of 1.93. Additionally, excellent linearity for N-Ac-DL-Leu was observed, with high coefficients of correlation (r2 ≥ 0.9999) in the range of 10-300 µM; the limit of quantitation (signal-to-noise ratio = 10) was 40-120 pmol/mL, and the mean recoveries of N-Ac-L-Leu and N-Ac-D-Leu were 102.48% and 104.68%, respectively. The levels of N-Ac-Leu in the saliva of diabetic patients and healthy volunteers were determined, and it was found that the levels of N-Ac-DL-Leu in the saliva of diabetic patients were significantly lower than those in healthy volunteers. (p < 0.01). CONCLUSIONS: The proposed method was successfully applied for the measurement of N-Ac-DL-Leu enantiomers in the saliva of diabetic patients and healthy volunteers.

Influence of Molecular Weight on the Organic Electrochemical Transistor Performance of Ladder-Type Conjugated Polymers.

Organic electrochemical transistors (OECTs) hold promise for developing a variety of high-performance (bio-)electronic devices/circuits. While OECTs based on p-type semiconductors have achieved tremendous progress in recent years, n-type OECTs still suffer from low performance, hampering the development of power-efficient electronics. Here, it is demonstrated that fine-tuning the molecular weight of the rigid, ladder-type n-type polymer poly(benzimidazobenzophenanthroline) (BBL) by only one order of magnitude (from 4.9 to 51 kDa) enables the development of n-type OECTs with record-high geometry-normalized transconductance (gm,norm  ≈ 11 S cm-1 ) and electron mobility × volumetric capacitance (µC* ≈ 26 F cm-1  V-1 s-1 ), fast temporal response (0.38 ms), and low threshold voltage (0.15 V). This enhancement in OECT performance is ascribed to a more efficient intermolecular charge transport in high-molecular-weight BBL than in the low-molecular-weight counterpart. OECT-based complementary inverters are also demonstrated with record-high voltage gains of up to 100 V V-1 and ultralow power consumption down to 0.32 nW, depending on the supply voltage. These devices are among the best sub-1 V complementary inverters reported to date. These findings demonstrate the importance of molecular weight in optimizing the OECT performance of rigid organic mixed ionic-electronic conductors and open for a new generation of power-efficient organic (bio-)electronic devices.

Development and validation of a simple and noninvasive method for salivary uric acid: potential applications for monitoring the salivary uric acid level in healthy volunteers and gout patients

Abstract Serum uric acid (UA) is a traditional biomarker in the clinical diagnosis of gout and hyperuricemia. However, serum treatment and storage are cumbersome, and wounds are susceptible to infection. Therefore, in this study, a simple and noninvasive method was developed to detect the UA in human saliva to monitor the gout. An Inertsil ODS-3 column was used for the analysis under the condition of isocratic elution with the mixed solution phosphate buffer (74 mM, pH=2.2): Methanol=98:2 (v:v) and the UV detection at 284 nm. Using salivary UA data from healthy volunteers (HVs) (n=68) and gout patients (GPs) (n=14), we examined the salivary UA difference in their content. The intra-and inter-day accuracy and precision (RSD %) were less than 2.56%, the limit of detection (LOD) of UA was 5.0 ng/mL, the mean recoveries of the corresponding compounds were 102.48%. Saliva levels of UA in HVs and GPs were 35.26±14.06 µg/mL and 91.96±23.90 µg/mL, respectively. The concentrations of salivary UA in GPs were significantly higher than those in HVs ( p < 0.001). This method was also expected to monitor the hyperuricemia and other metabolic disorders in the future

An Oligonucleotide-Distortion-Responsive Organic Transistor for Platinum-Drug-Induced DNA-Damage Detection.

Organic transistor with DNA-damage evaluation ability can open up novel opportunities for bioelectronic devices. Even though trace amounts of drugs can cause cumulative gene damage in vivo, the extremely low occurrence proportion makes them hardly transduced into detectable electric signals. Here, an ultrasensitive DNA-damage sensor based on an oligonucleotide-distortion-responsive organic transistor (DROT) is reported by creating controllable conformation change of double-stranded DNA on the surface of organic semiconductors. In combination with interfacial charge redistribution and efficient signal amplification, the DROT provides an ultrasensitive single-site DNA-damage response with 20.5 s even upon 1 × 10-12 m cisplatin. The high generalizability of this DROT to three generations of classical platinum drugs and gene-relevant DNA damage is demonstrated. A biochip is further designed for intelligent damage analysis in complex environments, which holds the potential for high-throughput biotoxicity evaluation and drug screening in the future.

Curcumin Can Activate the Nrf2/HO-1 Signaling Pathway and Scavenge Free Radicals in Spinal Cord Injury Treatment.

Spinal cord injury (SCI) is a devastating event that often leads to permanent neurological deficits. Evidence from emerging studies has implicated oxygen-derived free radicals and high-energy oxidants as mediators of secondary SCI. Therefore, targeting these mediators using antioxidants could be beneficial for the disease. Several signaling pathways, such as the nuclear factor erythroid-2-related factor 2/heme oxygenase 1 (Nrf2/HO-1), have been associated with the regulation of some pathophysiological features of SCI. Curcumin is a plant medicinal agent whose diverse pharmacological properties have been extensively investigated and reported, notably its ability to curtail inflammatory damage by inhibiting the nuclear factor-κ-light-chain-enhancer of activated B cells. In this review, we analyze the role of curcumin in activating Nrf2/HO-1 and scavenging free radicals to repair SCI. With its minimal side effects, curcumin could be a potential therapy for SCI treatment.

A convenient sampling and noninvasive dried spot method of uric acid in human saliva: Comparison of serum uric acid value and salivary uric acid in healthy volunteers and hyperuricemia patients.

Concentration of uric acid (UA) in serum is one of the markers used to diagnose gout and hyperuricemia. However, serum treatment and storage are cumbersome, and wounds are susceptible to infection. Therefore, a new sampling and analysis method using noninvasive biological samples has been developed, called the dried spot method of UA in human saliva (DSM-UHS). Saliva (5 µL) was dropped on filter paper (a spot with a diameter of 5 mm) containing hypoxanthine (IS) (5 µL) and dried at room temperature for 30 min. The filter paper was immersed in 200 µL of lithium carbonate solution and shaken in a block bath shaker for 5 min at 30 °C. Afterward, the extraction was concentrated and reconstituted with 100 µL of lithium carbonate solution analyzed by HPLC-UV. When comparing the concentration of UA in the human saliva of hyperuricemia patients (HPs) and with that of healthy volunteers (HVs), we observed the concentration of UA was higher in the HPs than in the HVs (p < 0.0001). In addition, the results showed a significant linear relationship between the content of UA in saliva and the content of UA in the serum (r = 0.6243). The content of UA in human saliva could indirectly reflect the content of UA in human serum. Then DSM-UHS could be used to determine the content of UA in the saliva of HVs and HPs. This study provides a new research method and strategy for the determination of human UA content and the clinical prewiring of hyperuricemia.

Persistent Conjugated Backbone and Disordered Lamellar Packing Impart Polymers with Efficient n-Doping and High Conductivities.

Solution-processable highly conductive polymers are of great interest in emerging electronic applications. For p-doped polymers, conductivities as high a nearly 105 S cm-1 have been reported. In the case of n-doped polymers, they often fall well short of the high values noted above, which might be achievable, if much higher charge-carrier mobilities determined could be realized in combination with high charge-carrier densities. This is in part due to inefficient doping and dopant ions disturbing the ordering of polymers, limiting efficient charge transport and ultimately the achievable conductivities. Here, n-doped polymers that achieve a high conductivity of more than 90 S cm-1 by a simple solution-based co-deposition method are reported. Two conjugated polymers with rigid planar backbones, but with disordered crystalline structures, exhibit surprising structural tolerance to, and excellent miscibility with, commonly used n-dopants. These properties allow both high concentrations and high mobility of the charge carriers to be realized simultaneously in n-doped polymers, resulting in excellent electrical conductivity and thermoelectric performance.

Enhanced Thermoelectric Performance of n-Type Organic Semiconductor via Electric Field Modulated Photo-Thermoelectric Effect.

Modulating photophysical processes is a fundamental way for tuning performance of many organic devices. However, it has not been explored as an effective strategy to manipulate the thermoelectric (TE) conversion of organic semiconductors (OSCs) owing to their critical requirement to carrier concentration (>1018 cm-3 ) and the fact of low exciton separation efficiency in single element OSCs. Here, an electric field modulated photo-thermoelectric (P-TE) effect in an n-type OSC is demonstrated to realize a significant improvement of TE performance. The electrical and spectroscopy characterizations reveal that the electric field gating generates combined modulation of exciton separation, charge screening, and carrier recombination, which produces a more than ten times improvement of photoinduced carrier concentration. These coupled processes contribute to the unconventional Seebeck coefficient (S)-electrical conductivity (σ) trade-off relationship of the photoexcited films, therefore leading to a more than 500% enhancement in the power factor for n-type OTE semiconductors. This work opens a unique way toward state-of-the-art organic P-TE materials for energy harvesting applications.

Mimicking Sensory Adaptation with Dielectric Engineered Organic Transistors.

Mimicking sensory adaptation with transistors is essential for developing next-generation smart circuits. A key challenge is how to obtain controllable and reversible short-term signal decay while simultaneously maintaining long-term electrical stability. By introducing a buried dynamic-trapping interface within the dielectric layer, an organic adaptive transistor (OAT) with sensory adaptation functionality is developed. The device induces self-adaptive interfacial trapping to enable volatile shielding of the gating field, thereby leading to rapid and temporary carrier concentration decay in the conductive channel without diminishing the mobility upon a fixed voltage bias. More importantly, the device exhibits a fine-tuned decay constant ranging from 50 ms to 5 s, accurately matching the adaptation timescales in bio-systems. This not only suggests promising applications of OATs in flexible artificial intelligent elements, but also provides a strategy for engineering organic devices toward novel biomimetic functions.

Selenium-Substituted Diketopyrrolopyrrole Polymer for High-Performance p-Type Organic Thermoelectric Materials.

Development of high-performance organic thermoelectric (TE) materials is of vital importance for flexible power generation and solid-cooling applications. Demonstrated here is the significant enhancement in TE performance of selenium-substituted diketopyrrolopyrrole (DPP) derivatives. Along with strong intermolecular interactions and high Hall mobilities of 1.0-2.3 cm2 V-1 s-1 in doping-states for polymers, PDPPSe-12 exhibits a maximum power factor and ZT of up to 364 µW m-1 K-2 and 0.25, respectively. The performance is more than twice that of the sulfur-based DPP derivative and represents the highest value for p-type organic thermoelectric materials based on high-mobility polymers. These results reveal that selenium substitution can serve as a powerful strategy towards rationally designed thermoelectric polymers with state-of-the-art performances.

MiR-1281, a p53-responsive microRNA, impairs the survival of human osteosarcoma cells upon ER stress via targeting USP39.

MicroRNAs (miRNAs) are small regulatory non-coding RNAs that have been reported to play an important role in a variety of cellular functions. Recent studies indicated that some miRNAs are involved in regulating endoplasmic reticulum (ER) stress adaptation. However, the miRNAs were still unknown in osteosarcoma. In this study, we demonstrated that miR-1281 induced by ER stress promoted cell apoptosis and decreased ER stress adaptation of osteosarcoma in vitro and in vivo. Further mechanistic studies revealed that p53, an important tumor suppressor, directly bound to the promoter of miR-1281, leading to its increase under ER stress. Additionally, our data suggest that USP39 was the target of miR-1281 and participated in ER stress-induced cell apoptosis. Thus, our findings suggest a new role for miR-1281 in osteosarcoma and suggest that the p53-dependent, miR-1281-mediated USP39 pathway inhibits the survival of human osteosarcoma cells under ER stress.

Exploring Peltier effect in organic thermoelectric films.

Organic materials are emerging thermoelectric candidates for flexible power generation and solid-cooling applications. Although the Peltier effect is a fundamental thermoelectric effect that enables site-specific and on-demand cooling applications, the Peltier effect in organic thermoelectric films have not been investigated. Here we experimentally observed and quasi-quantitatively evaluated the Peltier effect in a poly(Ni-ett) film through the fabrication of thermally suspended devices combined with an infrared imaging technique. The experimental and simulation results confirm effective extraction of the Peltier effect and verify the Thomson relations in organic materials. More importantly, the working device based on poly(Ni-ett) film yields maximum temperature differences as large as 41 K at the two contacts and a cooling of 0.2 K even under heat-insulated condition. This exploration of the Peltier effect in organic thermoelectric films predicts that organic materials hold the ultimate potential to enable flexible solid-cooling applications.

Enhancing the n-Type Conductivity and Thermoelectric Performance of Donor-Acceptor Copolymers through Donor Engineering.

Conjugated polymers with high thermoelectric performance enable the fabrication of low-cost, large-area, low-toxicity, and highly flexible thermoelectric devices. However, compared to their p-type counterparts, n-type polymer thermoelectric materials show much lower performance, which is largely due to inefficient doping and a much lower conductivity. Herein, it is reported that the development of a donor-acceptor (D-A) polymer with enhanced n-doping efficiency through donor engineering of the polymer backbone. Both a high n-type electrical conductivity of 1.30 S cm-1 and an excellent power factor (PF) of 4.65 µW mK-2 are obtained, which are the highest reported values among D-A polymers. The results of multiple characterization techniques indicate that electron-withdrawing modification of the donor units enhances the electron affinity of the polymer and changes the polymer packing orientation, leading to substantially improved miscibility and n-doping efficiency. Unlike previous studies in which improving the polymer-dopant miscibility typically resulted in lower mobilities, the strategy maintains the mobility of the polymer. All these factors lead to prominent enhancement of three orders magnitude in both the electrical conductivity and the PF compared to those of the non-engineered polymer. The results demonstrate that proper donor engineering can enhance the n-doping efficiency, electrical conductivity, and thermoelectric performance of D-A copolymers.

Deficiency of the AIM2-ASC Signal Uncovers the STING-Driven Overreactive Response of Type I IFN and Reciprocal Depression of Protective IFN-γ Immunity in Mycobacterial Infection.

The nucleic acids of Mycobacterium tuberculosis can be detected by intracellular DNA sensors, such as cyclic GMP-AMP synthase and absent in melanoma 2 (AIM2), which results in the release of type I IFN and the proinflammatory cytokine IL-1ß. However, whether cross-talk occurs between AIM2-IL-1ß and cyclic GMP-AMP synthase-type I IFN signaling upon M. tuberculosis infection in vivo is unclear. In this article, we demonstrate that mycobacterial infection of AIM2-/- mice reciprocally induces overreactive IFN-ß and depressive IFN-γ responses, leading to higher infection burdens and more severe pathology. We also describe the underlying mechanism whereby activated apoptosis-associated speck-like protein interacts with a key adaptor, known as stimulator of IFN genes (STING), and inhibits the interaction between STING and downstream TANK-binding kinase 1 in bone marrow-derived macrophages and bone marrow-derived dendritic cells, consequently reducing the induction of type I IFN. Of note, apoptosis-associated speck-like protein expression is inversely correlated with IFN-ß levels in PBMCs from tuberculosis patients. These data demonstrate that the AIM2-IL-1ß signaling pathway negatively regulates the STING-type I IFN signaling pathway by impeding the association between STING and TANK-binding kinase 1, which protects the host from M. tuberculosis infection. This finding has potential clinical significance.

Conjugated-Backbone Effect of Organic Small Molecules for n-Type Thermoelectric Materials with ZT over 0.2.

Conjugated backbones play a fundamental role in determining the electronic properties of organic semiconductors. On the basis of two solution-processable dihydropyrrolo[3,4-c]pyrrole-1,4-diylidenebis(thieno[3,2-b]thiophene) derivatives with aromatic and quinoid structures, we have carried out a systematic study of the relationship between the conjugated-backbone structure and the thermoelectric properties. In particular, a combination of UV-vis-NIR spectra, photoemission spectroscopy, and doping optimization are utilized to probe the interplay between energy levels, chemical doping, and thermoelectric performance. We found that a moderate change in the conjugated backbone leads to varied doping mechanisms and contributes to dramatic changes in the thermoelectric performance. Notably, the chemically doped A-DCV-DPPTT, a small molecule with aromatic structure, exhibits an electrical conductivity of 5.3 S cm-1 and a high power factor (PF373 K) up to 236 µW m-1 K-2, which is 50 times higher than that of Q-DCM-DPPTT with a quinoid structure. More importantly, the low thermal conductivity enables A-DCV-DPPTT to possess a figure of merit (ZT) of 0.23 ± 0.03, which is the highest value reported to date for thermoelectric materials based on organic small molecules. These results demonstrate that the modulation of the conjugated backbone represents a powerful strategy for tuning the electronic structure and mobility of organic semiconductors toward a maximum thermoelectric performance.

Circulating soluble form of LR11, a regulator of smooth muscle cell migration, is a novel marker for intima-media thickness of carotid arteries in type 2 diabetes.

BACKGROUND: Smooth muscle cell (SMC) migration from the media to the intima, a process affecting plaque stability in advanced-stage atherosclerosis, is under the control of LR11. To delineate the clinical significance of the circulating soluble form of LR11 (sLR11) in patients with type 2 diabetes (T2D), we analyzed the correlation of sLR11 levels with intima-media thickness (IMT) of carotid arteries. METHODS: Plasma sLR11 levels were measured in 165 patients with T2D (mean age 56.2±10.4 y, 58.2% males, and BMI 24.6±3.6) by ELISA. Averaged IMT levels of common carotid arteries were determined by ultrasonography. RESULTS: Circulating sLR11 levels were 9.8±3.5ng/ml, and correlated positively with the classical atherosclerosis risk factors age, sex, systolic blood pressure, low-density lipoprotein-cholesterol (LDL-C), fasting plasma-glucose (FPG), and glycosylated hemoglobin. Multivariate linear regression analysis indicated that only FPG was associated with sLR11; sLR11 correlated positively with IMT, together with age and FPG, but less with LDL-C. Among the serum risk factors for IMT, multivariate linear regression analysis uncovered that sLR11 was independently associated with IMT. Subsequent logistic analysis revealed that FPG correlated best with IMT values at a cut-off of 0.80mm and sLR11 at a cut-off of 0.90mm, respectively, while LDL-C showed lower discriminatory power at any IMT cut-off values. CONCLUSION: Increased sLR11 concentrations are highly associated with increased IMT as well as with FPG in middle-aged, non-obese patients with T2D. Circulating sLR11 may be a novel marker representing the pathophysiology of intimal SMCs in patients with T2D.

Uric acid quantification in fingernail of gout patients and healthy volunteers using HPLC-UV.

The presence of elevated uric acid (UA) levels is a sign of gout, that is, hyperuricemia. In this study the monitoring of the UA levels in less-invasive biological samples, such as the human fingernail, is suggested for the diagnosis and therapy of gout. Twenty-six healthy volunteers (HV) and 22 gout patients (GP) were studied. The UA was extracted from human fingernail samples, then separated on an Inertsil ODS-3 column (250 × 4.6 mm i.d., 4.0 µm, GL Sciences) by isocratic elution using methanol-74 mm phosphate buffer (pH 2.2) 2:98 (v/v). A UV detector was used to monitor the samples at 284 nm. Using the developed method, different UA concentrations were found in the GP and HV. When comparing the concentrations from GP with those from HV, a statistically significant correlation was observed between the UA (p < 0.01). In this study, the UA was confirmed as a potential biomarker for the diagnosis and therapy of gout. We have developed a novel sensitive, and simple method for the determination of UA in the fingernails of GP and HV. The human fingernail may serve as a noninvasive biosample for the diagnosis of gout. Copyright © 2016 John Wiley & Sons, Ltd.