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The paper presents the results on numerical simulation of the temperature field of a cold plate type liquid heat exchanger for a multichannel transmitter/receiver module. Each side of the cold plate carries 8 local microwave fuel elements with a heat dissipation capacity of 11 W each and one block with low-power electronic elements (total power of all elements — 50 W), installed symmetrically on both sides. The total heat dissipation capacity is 276 W. The cold plate is cooled by pumping a liquid heat carrier (Antifreeze A 65) through a curved cooling channel of rectangular cross-section made inside the liquid heat exchanger. The study was conducted at a working fluid flow rate of 2, 4, 6, 8 and 10 l/min. Numerical simulation allowed obtaining the temperature distribution of the mounting surfaces of the cold plate and determining the values of the working fluid flow rate, which provide effective cooling of the mounting surfaces. It is shown that at a flow rate of 4 l/min, the temperature values at the installation sites of local microwave elements do not exceed 64°C. The total thermal resistance of the cooling system based on a liquid heat exchanger is from 0.063 to 0.028°C/W with a flow rate from 2 to 10 l/min, respectively.

Frequency multipliers are used in electronic devices to generate spectrally pure sinusoidal signals in the frequency range from a few to tens of GHz. The multipliers are used to multiply the frequency of highly stable but more low-frequency devices with the subsequent extraction of the necessary harmonics from the frequency spectrum of the received microwave range. The frequencies selected after multiplication (set) have significantly higher energy, spectral and range characteristics, which allows them to be used as local oscillators and synthesizers in receiving and transmitting systems. The authors of this paper theoretically substantiate and practically demonstrate the possibility of an unconventional implementation of a microstrip multiplier of the microwave range based on a directional traveling wave filter. The proposed implementation does not require the use of active semiconductor elements. The well-known circuit and technological principles for the creation of microstrip microwave multipliers are considered in the paper. The features, problems and shortcomings arising from their implementation are analyzed. The effectiveness of using the balanced circuit for frequency multiplication is confirmed. A list of mandatory requirements and conditions necessary for the implementation of the microwave multipliers is given. It is demonstrated that the features of the microstrip travelling-wave filter are identical to the conditions and requirements for the implementation of balanced multipliers. It is shown and substantiated how an unconventional implementation of a passive microwave multiplier is possible due to the electromagnetic interaction of the input and output nodes of such a filter with an annular travelling-wave resonator. Using the example of modifying a block diagram of a directional filter into a multiplier circuit, the possibility of creating a microwave doubler is confirmed by separating a given frequency from the frequency spectrum of a traveling-wave ring resonator.

Differences in plant organs that are used as sources of explants can cause differences in callus growth and synthesized bioactive compounds. The objective of this study was to induce calli from different sources of explants and analyze their growth and bioactive compounds in the calli from leaf and stem explants of kaffir lime seedlings. Kaffir lime seeds were germinated until they grew into seedlings. On day 35, the leaves and stems of seedlings were harvested and callus was induced. Results showed that callus initiation time of stem explants was 5.66 days faster than that of leaf explants, which required 12.42 days. The colors of these calli were slightly different. Furthermore, callus fresh weight of leaf explants was less than that of stem explants, and the stationary phase of leaf explant-derived callus was earlier than for those from stem explant. Bioactive compounds detected in calli derived from leaf and stem explants were different. The main compounds found in the leaf explant-derived callus were n-decanoic acid and hexanedioic acid, bis (2-ethylhexyl) esters, while stem explant-derived callus had n-hexadecanoid acid. The presence of various bioactive compounds in these calli indicates potential for use as a natural medicine.

Abstract Background Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a familial cardiac disease associated with ventricular arrhythmias and an increased risk of sudden cardiac death. Currently, there are no approved treatments that address the underlying genetic cause of this disease, representing a significant unmet need. Mutations in Plakophilin-2 (PKP2), encoding a desmosomal protein, account for approximately 40% of ARVC cases and result in reduced gene expression. Methods Our goal is to examine the feasibility and the efficacy of adeno-associated virus 9 (AAV9)-mediated restoration of PKP2 expression in a cardiac specific knock-out mouse model of Pkp2. Results We show that a single dose of AAV9:PKP2 gene delivery prevents disease development before the onset of cardiomyopathy and attenuates disease progression after overt cardiomyopathy. Restoration of PKP2 expression leads to a significant extension of lifespan by restoring cellular structures of desmosomes and gap junctions, preventing or halting decline in left ventricular ejection fraction, preventing or reversing dilation of the right ventricle, ameliorating ventricular arrhythmia event frequency and severity, and preventing adverse fibrotic remodeling. RNA sequencing analyses show that restoration of PKP2 expression leads to highly coordinated and durable correction of PKP2-associated transcriptional networks beyond desmosomes, revealing a broad spectrum of biological perturbances behind ARVC disease etiology. Conclusions We identify fundamental mechanisms of PKP2-associated ARVC beyond disruption of desmosome function. The observed PKP2 dose-function relationship indicates that cardiac-selective AAV9:PKP2 gene therapy may be a promising therapeutic approach to treat ARVC patients with PKP2 mutations.

Abstract Heart failure with preserved ejection fraction (HFpEF) poses therapeutic challenges due to the limited treatment options. Building upon our previous research that demonstrates the efficacy of histone deacetylase 6 (HDAC6) inhibition in a genetic cardiomyopathy model, we investigate HDAC6’s role in HFpEF due to their shared mechanisms of inflammation and metabolism. Here, we show that inhibiting HDAC6 with TYA-018 effectively reverses established heart failure and its associated symptoms in male HFpEF mouse models. Additionally, in male mice lacking Hdac6 gene, HFpEF progression is delayed and they are resistant to TYA-018’s effects. The efficacy of TYA-018 is comparable to a sodium-glucose cotransporter 2 (SGLT2) inhibitor, and the combination shows enhanced effects. Mechanistically, TYA-018 restores gene expression related to hypertrophy, fibrosis, and mitochondrial energy production in HFpEF heart tissues. Furthermore, TYA-018 also inhibits activation of human cardiac fibroblasts and enhances mitochondrial respiratory capacity in cardiomyocytes. In this work, our findings show that HDAC6 impacts on heart pathophysiology and is a promising target for HFpEF treatment.