Abstract: Background: Irreversible electroporation (IRE) is a form of non-thermal ablation that delivers pulses of high voltage electrical current between electrodes. The role of IRE in the treatment of colorectal hepatic metastases is unestablished. This study is an international ques-tionnaire survey of the use of IRE for colorectal hepatic metastases. Methods: A questionnaire addressing views on the use of IRE for colorectal liver metastases was circulated to clinicians with an interest and/or expertise in this technique. Results: 64 clinicians from 17 different countries replied to the questionnaire. Thirty-six (56%) had experience of treating patients with colorectal liver metastases with IRE. The preferred mode of delivery of IRE was percutaneous treatment under CT guidance. Thirty-three (70% respondents) used IRE exclusively for lesions in proximity to inflow or outflow structures. Twenty (43% respondents) used IRE as their sole ablative treat-ment whilst 19 (40% respondents) used IRE in combination with thermal ablation. The maximum number of lesions that could be treated by IRE was two and preferred size of lesion was

We consider an autonomous heat engine in simultaneous contact with a hot and a cold reservoir, and described within a linear-irreversible framework. In the tight-coupling approximation, the rate of entropy generation is effectively written in terms of a single thermal flux which is a homogeneous function of the hot and cold fluxes. The specific algebraic forms of the effective flux are deduced in scenarios containing internal and external irreversibilities for the typical example of a thermoelectric generator.

Re-shaping of thermodynamics with the graph theory and Ramsey theory is suggested. Maps built of thermodynamic states are addressed. Thermodynamic states may be attainable and non-attainable by the thermodynamic process in the system of constant mass. We address the following question how large should be a graph describing connections between discrete thermodynamic states to guarantee the appearance of thermodynamic cycles? The Ramsey theory supplies the answer to this question. Direct graphs emerging from the chains of irreversible thermodynamic processes are considered. In any complete directed graph, representing the thermodynamic states of the system the Hamiltonian path is found. Transitive thermodynamic tournaments are addressed. The entire transitive thermodynamic tournament built of irreversible processes does not contain a cycle of length 3, or in other words, the transitive thermodynamic tournament is acyclic and contains no directed thermodynamic cycles.

The time’s arrow of macroscopic physical phenomenon is reflected by irreversible physical process, which essentially occurs from small probability state to high probability state. In this paper, simplified models are proposed to understand the macroscopic physical process. In order to describe the information of a physical system, we defined the full self-information as "information height" to describe the complexity or difficulty of a macrostate of physical system. In this way, the direction of macroscopic physical process is from high information height to low information height. We can judge the direction of physical process by the information height. If we want the macroscopic physical process to evolve from the low information height state to the high information height state, the system need to add extra information and corresponding energy to increase the information height.

Vopson and Lepadatu recently proposed the Second Law of Infodynamics. The law states that while total entropy increases, information entropy declines over time. They state that the law has applications over a wide range of disciplines, but they leave many key questions unanswered. This article analyzes and reformulates the law based on the thermocontextual interpretation (TCI). The TCI generalizes Hamiltonian mechanics by defining states and transitions thermocontextually, with respect to an ambient-temperature reference state. The TCI partitions energy into ambient heat, which is thermally random and unknowable, and exergy, which is knowable and usable. The TCI is further generalized here to account for a reference observer’s actual knowledge. This enables partitioning exergy into accessible exergy, which is known and accessible for use, and configurational energy, which is knowable but unknown and inaccessible. The TCI is firmly based on empirically validated postulates. The Second Law of thermodynamics and its information-based analogue, MaxEnt are logically derived corollaries. Another corollary is a reformulated Second Law of Infodynamics. It states that an external agent seeks to increase its access to exergy by narrowing its information gap with a potential exergy source. The principle is key to the origin of self-replicating chemicals and life.

SPH5030 is developed to improve the selectivity of irreversible HER2 inhibitors, which shows excellent activity and better HER2 selectivity against four common HER2 mutants than neratinib and pyrotinib, and consumed to attenuate the off-target adverse events in patients. To comprehensively evaluate SPH5030, the preclinical pharmacokinetic studies of SPH5030 were systematically completed, including in vivo pharmacokinetic, tissue distribution and excretion in Sprague Dawley rats and Cynomolgus monkeys, as well as in vitro drug-drug interaction assessment and metabolite identification in different species. The results showed low clearance, reasonable bioavailability and widely tissues distributed properties, and mainly excreted in the feces in rats. In vitro studies SPH5030 showed stable metabolism and metabolized mainly by CYP3A4/5 and CYP2C8, with no or weak inhibitory potential on CYP450 enzymes and efflux transporters. In Phase I clinical trials, SPH5030 also showed well tolerated at doses ranging from 50 to 600mg and is expected to have an ideal clinical application prospect in the future.

The current study aimed to investigate the antitumor effects and potent mechanism of cytokine-induced killer (CIK) cells combined with irreversible electroporation (IRE) via an in vitro function assay in an in vivo Panc02 cell–bearing mouse model. We established an in vitro culture assay for CIK cells and determined the proportions of different peripheral lymphocytes. The antitumor effect of the combination of IRE and CIK cells in a Panc02 pancreatic-cancer (PC) subcutaneous-xenograft model was investigated; tumor size and mouse survival rates were recorded. We used flow cytometry (FCM) to analyze the proportion of intratumoral lymphocytes, the expression of chemokine receptors, and the proliferative activity of CIK cells. The proportion of cells that were positive for clusters of differentiation 3 and 8 (CD3+CD8+) and the proportion of CD3+CD56+ cells were both significantly increased after 21 days of in vitro culture. Combined IRE/CIK cell treatment significantly inhibited tumor growth and increased the survival rate of Panc02 cell–bearing mice. Furthermore, infiltration of lymphocytes into tumor tissue was significantly increased by this combination therapy compared with the untreated group or monotherapy group. In addition, IRE significantly enhanced the expression of chemokine receptors elicited by, and the proliferative activity of, CIK cells. In conclusion, IRE combined with CIK cells showed superior antitumor efficacy in a PC subcutaneous-xenograft model, which we attributed to the promotion of lymphocytic infiltration, as well as to upregulation of chemokine receptor expression and of regulators of CIK cell proliferation.

A partial or complete pulpotomy is a type of vital pulp therapy (VPT) that aims to remove the in-flamed, infected pulp, leaving behind healthy, vital pulp that is capable of healing. VPT has gained renewed popularity as a treatment option in permanent mature posterior teeth with irre-versible/moderate-severe pulpitis, its high success rates matching that of root canal treatment (RCT). There is currently no consensus regarding diagnostic and prognostic predictors of success of pulpotomies for managing such cases. Therefore, we conducted a scoping review to identify and analyze how these factors affect the outcome of treatment. A literature search using the PRISMA guidelines was undertaken using PubMed and Scopus on July 7, 2023. A total of 22 studies met the inclusion criteria and were qualitatively analyzed by two reviewers. The follow-ing diagnostic and prognostic factors were recognized and discussed; presenting signs and symptoms, periapical diagnosis, bleeding time, indicators of inflammation (bleeding time, con-centration of inflammatory biomarkers), patient age and medical status, the depth, activity and location of caries, and restorative factors. Based on the studies assessed, there is limited evidence to support their prognostic value. Further research is necessary to identify solid predictors of outcome.

Exploring the dynamic behavior of cellular metabolism requires a standard laboratory method that guarantees rapid sampling and extraction of the cellular content. We propose a versatile sampling technique applicable to cells with different cell wall and cell membrane properties. The technique is based on irreversible electroporation with simultaneous quenching and extraction by using a microfluidic device. By application of electric pulses in the millisecond range, permanent lethal pores are formed in the cell membrane of Escherichia coli and Saccharomyces cerevisiae, facilitating the release of the cellular contents; here demonstrated by the measurement of glucose-6-phosphate and the activity of the enzyme glucose-6-phosphate dehydrogenase. The successful application of this device was demonstrated by pulsed electric field treatment in a flow-through configuration of the microfluidic chip in combination with sampling, inactivation, and extraction of the intracellular content in a few seconds. Minimum electric field strengths of 10 kV/cm for E. coli and 7.5 kV/cm for yeast S. cerevisiae were required for successful cell lysis. The results are discussed in the context of applications in industrial biotechnology, where metabolomics analyses are important.

The heat and matter transfer during glucose catabolism in living systems and their relation with entropy production are a challenging subject of the classical thermodynamics applied to biology. In this respect, an analogy between mechanics and thermodynamics has been performed via the definition of the entropy density acceleration expressed by the time derivative of the rate of entropy density and related to heat and matter transfer in minimum living systems. Cells are regarded as open thermodynamic systems that exchange heat and matter resulting from irreversible processes with the intercellular environment. Prigogine’s minimum energy dissipation principle is reformulated using the notion of entropy density acceleration applied to glucose catabolism. It is shown that, for out-of-equilibrium states, the calculated entropy density acceleration is finite and negative and approaches as a function of time a zero value at global thermodynamic equilibrium for heat and matter transfer independently of the cell type and the metabolic pathway. These results could be important for a deeper understanding of entropy generation and its correlation with heat transfer in cell biology with special regard to glucose catabolism representing the prototype of irreversible reactions and a crucial metabolic pathway in stem cells and cancer stem cells.

Chagas disease, caused by Trypanosoma cruzi, presents a significant challenge in global health due to the parasite's complex life cycle and its persistence in human tissues. In contrast, advances in treating Trypanosoma brucei infections, notably through the use of irreversible enzyme inhibitors like eflornithine, offer valuable insights into therapeutic strategies. This article explores how artificial intelligence (AI) can aid in identifying crucial metabolic and biochemical pathways in T. cruzi that could serve as targets for irreversible enzymatic inhibitors, drawing parallels to the successful inhibition of T. brucei’s ornithine decarboxylase. By employing AI for data mining, drug-target interaction prediction, pathway modelling, and drug repurposing, researchers can accelerate the discovery of novel treatments. We compare the biological and biochemical differences between T. cruzi and T. brucei, highlighting how AI can bridge the gap in drug discovery and offer new possibilities for Chagas disease treatment.

In this study, we mainly focus on the behavior of an electron gas produced by argon plasma that is bounded by a moving rigid flat plate. The effects of an external magnetic field on the electrons collected with each other, with positive ions, and with neutral atoms in the plasma fluid are investigated. We used the BGK model of the Boltzmann kinetic equation, which is fundamental in the study of the gas dynamics from the continuum flow to the free-molecular regimes with Maxwellian velocity distribution functions of the various species. An exact analytical solution of the model equations for the unsteady flow is given using the moment and the traveling wave methods. The behavior of the mean velocity of electrons is illustrated, which compatible with the variation of the shear stress, viscosity coefficient, and the initial and boundary conditions. Besides, the thermodynamic prediction is investigated by applying the principles of irreversible thermodynamics and Gibbs formula. It is found that the thermodynamic variables verify the Boltzmann’s H–theorem, the principle of Le Chatelier, and the Thermodynamics Second Law for the non-equilibrium processes of the system. Qualitative agreements with previous related papers are introducing. 3-Dimensional graphics for the calculating variables are offering, and their behavior is deeply discussed.

The new coronavirus SARS-CoV-2 is the cause of the COVID-19 pandemic, which has created an incomparable global health problem. PLpro is a key protein involved in viral polyprotein processing and immune system evasion, making it a prime target for the development of antiviral drugs to combat COVID-19. The review begins by elucidating the functional and structural properties of SARS-CoV-2 PLpro, underscoring its significance in viral pathogenicity and replication. Employing homology modeling, a tertiary structure model of PLpro is constructed, laying the groundwork for subsequent investigations. To expedite the search for potential therapeutic candidates, the study harnesses computational methodologies. Molecular docking techniques are employed to explore binding sites for antiviral drugs within the catalytic region of PLpro. This computational approach not only aids in drug development but also provides crucial preliminary data before experimental research commences. The stability of drug-PLpro complexes is assessed through comprehensive all-atom molecular dynamics (MD) simulations, affording dynamic insights into drug-PLpro interactions. By evaluating binding energy estimates from MD simulations, stable drug-PLpro complexes with potential antiviral properties are identified. However, it is emphasized that experimental validation is imperative to confirm these computational findings, necessitating in vitro and in vivo tests to assess safety and efficacy. This pivotal stage bridges the computational realm with real-world clinical applications. The review emphasizes the imperative need for enhancements in the existing PLpro-targeting drugs currently on the market. Their actions are insufficient for clinical use and necessitate thorough characterization and improvement. The Supervised Molecular Dynamics (SuMD) simulation technique reveals critical information about drug unbinding pathways, shedding light on opportunities for refinement. In addition to optimizing existing drugs, the investigation of sub-structurally similar molecules emerges as a promising avenue for drug development. In conclusion, the review underscores the pivotal role of targeting SARS-CoV-2 PLpro in the ongoing battle against COVID-19. By integrating molecular dynamics simulations, structural modeling, and computational insights, a robust foundation is established for identifying promising antiviral drug candidates. The continual need for improvement in existing drugs and the exploration of novel compounds remain paramount in the global effort to combat COVID-19. The evolution and management of COVID-19 hinge on the symbiotic relationship between computational insights and experimental validation, illustrating the interdisciplinary synergy crucial to this endeavor.

In the present paper, the effect of the non-linear thermal radiation on the neutral gas mixture in the unsteady state is investigated for the first time. The unsteady BGK technique of the Boltzmann kinetic equations for a neutral non-homogenous gas is solved. The solution of the unsteady case makes the problem more general significance than the stationary one. For this purpose, the moments' method, together with the traveling wave method, is applied. The temperature and concentration are calculated for each gas component and mixture for the first time.Furthermore, the study is held for aboard range of temperatures ratio parameter and a wide range of the molar fraction. The distribution functions are calculated for each gas component and the gas mixture. The significant non-equilibrium irreversible thermodynamic characteristics the entire system is acquired analytically. That technic allows us to investigate the consistency of Boltzmann's H-theorem, Le Chatelier principle, and thermodynamics laws. Moreover, the ratios among the different participation of the internal energy alteration are evaluated via the Gibbs formula of total energy. The final results are utilized to the argon-helium non-homogenous gas at different magnitudes of radiation force strength and molar fraction parameters. 3D-graphics are presented to predict the behavior of the calculated variables, and the obtained results are theoretically discussed.