Safety, tolerability, pharmacokinetics and pharmacodynamics of multiple ascending doses of the novel long-acting glucagon analogue HM15136 in overweight and obese patients with co-morbidities.

AIM: To evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of multiple ascending doses of the novel long-acting glucagon analogue HM15136 in overweight/obese patients with co-morbidities, with and without type 2 diabetes (T2D). MATERIALS AND METHODS: This was a phase 1, double-blind, randomized, placebo-controlled, two-part trial with a 12-week treatment period of once-weekly subcutaneous HM15136 (0.02/0.04/0.06 mg/kg). Part 1 included patients with dyslipidaemia and/or hypertension and no T2D. Part 2 included patients with dyslipidaemia and/or hypertension plus T2D. RESULTS: In part 1, 23/27 (85.2%) patients receiving HM15136 and all patients receiving placebo (9/9 [100%]) experienced a treatment-emergent adverse event (TEAE). Five of 27 (18.5%) patients receiving HM15136 developed anti-HM15136 antibodies. Dose-dependent increases in mean HM15136 serum concentration and fasting plasma glucose (FPG) were observed, as were dose-dependent weight reductions of 0.5%/2.3%/2.6% at doses of 0.02/0.04/0.06 mg/kg, respectively. In part 2, 8/12 (66.7%) patients receiving HM15136 and all patients receiving placebo (4/4 [100.0%]) reported a TEAE. Two (16.7%) patients developed anti-HM15136 antibodies. Dose-dependent increases in mean HM15136 serum concentration were observed. FPG of more than 200 mg/dL was reported in 4/9 (44.4%) and 2/3 (66.7%) patients receiving 0.02 and 0.06 mg/kg, respectively. The 0.06 mg/kg dose was not tolerated in part 2 because of hyperglycaemia. Patients receiving 0.02 mg/kg showed a 0.9% weight reduction. No serious TEAEs leading to discontinuation were reported in either study part. CONCLUSIONS: This study of HM15136 provides a preliminary safety and tolerability profile with initial insights into its efficacy profile.

Thermopower of Molecular Junction in Harsh Thermal Environments.

Molecular junctions can be miniaturized devices for heat-to-electricity conversion application, yet these operate only in mild thermal environments (less than 323 K) because thiol, the most widely used anchor moiety for chemisorption of active molecules onto surface of electrode, easily undergoes thermal degradation. N-Heterocyclic carbene (NHC) can be an alternative to traditional thiol anchor for producing ultrastable thermoelectric molecular junctions. Our experiments showed that the NHC-based molecular junctions withstood remarkably high temperatures up to 573 K, exhibiting consistent Seebeck effect and thermovoltage up to approximately |1900 µV|. Our work advances our understanding of molecule-electrode contact in the Seebeck effect, providing a roadmap for constructing robust and efficient organic thermoelectric devices.

Superexchange Coupling-Induced Enhancements of Thermoelectric Performance in Saturated Molecules.

To develop thermoelectric devices, it is of the utmost importance to design organic building blocks to have efficient thermopower. Whereas conjugated and aromatic molecules with intrinsic narrow band gaps are attractive candidates to achieve efficient thermoelectric properties, saturated molecules are usually avoided owing to intrinsically poor thermopower. Here we demonstrate that thermopower of saturated molecules can be enhanced by superexchange coupling. Specifically, thermoelectric properties of large-area junctions that contain self-assembled monolayers of oligo(ethylene glycol) thiolates and alkanethiolates are compared. Through large-area thermopower measurements using a liquid metal top electrode, we show that the superexchange coupling enhances the Seebeck coefficient and counterintuitively leads to an increase in the Seebeck coefficient with increasing the length in a certain conformation. The improved thermoelectric performance is attributed to the superexchange-induced enhanced ability to mediate metal wave function in junctions. Our work offers new insights for improving the thermoelectric performance of nonconjugated, saturated molecules.

Ga-Based Liquid Metal Micro/Nanoparticles: Recent Advances and Applications.

Liquid metals are emerging as fluidic inorganic materials in various research fields. Micro- and nanoparticles of Ga and its alloys have received particular attention in the last decade due to their non toxicity and accessibility in ambient conditions as well as their interesting chemical, physical, mechanical, and electrical properties. Unique features such as a fluidic nature and self-passivating oxide skin make Ga-based liquid metal particles (LMPs) distinguishable from conventional inorganic particles in the context of synthesis and applications. Here, recent advances in the bottom-up and top-down synthetic methods of Ga-based LMPs, their physicochemical properties, and their applications are summarized. Finally, the current status of the LMPs is highlighted and perspectives on future directions are also provided.

Recent Progress in the Chemistry of Pyridazinones for Functional Group Transformations.

While N-hetereocycles have received significant attention in organic synthesis and other research fields, the chemistry of pyridazine, a six-membered aromatic ring with two adjacent nitrogen atoms, and its derivatives has been relatively little understood. This Synopsis describes recent progress made in the synthesis of pyridazine derivatives-particularly, pyridazin-3(2H)-ones-and their utility as efficient and recyclable functional group carriers for various important organic reactions.

Applicability Evaluation of Male-Specific Coliphage-Based Detection Methods for Microbial Contamination Tracking.

Outbreaks of food poisoning due to the consumption of norovirus-contaminated shellfish continue to occur. Male-specific (F+) coliphage has been suggested as an indicator of viral species due to the association with animal and human wastes. Here, we compared two methods, the double agar overlay and the quantitative real-time PCR (RT-PCR)-based method, for evaluating the applicability of F+ coliphage-based detection technique in microbial contamination tracking of shellfish samples. The RT-PCR-based method showed 1.6-39 times higher coliphage PFU values from spiked shellfish samples, in relation to the double agar overlay method. These differences indicated that the RT-PCR-based technique can detect both intact viruses and non-particle-protected viral DNA/RNA, suggesting that the RT-PCR based method could be a more efficient tool for tracking microbial contamination in shellfish. However, the virome information on F+ coliphage-contaminated oyster samples revealed that the high specificity of the RT-PCR- based method has a limitation in microbial contamination tracking due to the genomic diversity of F+ coliphages. Further research on the development of appropriate primer sets for microbial contamination tracking is therefore necessary. This study provides preliminary insight that should be examined in the search for suitable microbial contamination tracking methods to control the sanitation of shellfish and related seawater.

Power Factor of One Molecule Thick Films and Length Dependence.

There is a rapidly increasing interest in organic thin film thermoelectrics. However, the power factor of one molecule thick organic film, the self-assembled monolayer (SAM), has not yet been determined. This study describes the experimental determination of the power factor in SAMs and its length dependence at an atomic level. As a proof-of-concept, SAMs composed of n-alkanethiolates and oligophenylenethiolates of different lengths are focused. These SAMs were electrically and thermoelectrically characterized on an identical junction platform using a liquid metal top-electrode, allowing the straightforward estimation of the power factor of the monolayers. The results show that the power factor of the alkyl SAMs ranged from 2.0 × 10-8 to 8.0 × 10-12 µW m-1 K-2 and exhibited significant negative length dependence, whereas the conductivity and thermopower of the conjugated SAMs are the two opposing factors that balance the power factor upon an increase in molecular length, exhibiting a maximum power factor of 3.6 × 10-8 µW m-1 K-2. Once correction factors about the ratio of effective contact area to geometrical contact area are considered, the values of power factors can be increased by several orders of magnitude. With a newly derived parametric semiempirical model describing the length dependence of the power factor, it is investigated that one molecule thick films thinner than 10 nm composed of thiophene units can yield power factors rivaling those of famed organic thermoelectric materials based on poly(3,4-ethylenedioxythiophene)/polystyrenesulfonate (PEDOT/PSS) and polyaniline/graphene/double-walled carbon nanotube. Furthermore, how the transition of the transport regime from tunneling to hopping as molecules become long affects power factors is examined.

Tunneling and thermoelectric characteristics of N-heterocyclic carbene-based large-area molecular junctions.

Reported herein are tunneling and thermoelectric characteristics of large-area molecular junctions formed with N-heterocyclic carbene (NHC)-based self-assembled monolayers on gold.