The present study investigates the chemical composition variances among Pinelliae Rhizoma, a widely used Chinese herbal medicine, and its common adulterants including Typhonium flagelliforme, Arisaema erubescens, and Pinellia pedatisecta. Utilizing the non-targeted metabolomics technique of employing UHPLC-Q-Orbitrap HRMS, this research aims to comprehensively delineate the metabolic profiles of Pinelliae Rhizoma and its adulterants. Multivariate statistical methods including PCA and OPLS-DA are employed for the identification of differential metabolites. Volcano plot analysis is utilized to discern upregulated and downregulated compounds. KEGG pathway analysis is conducted to elucidate the differences in metabolic pathways associated with these compounds, and significant pathway enrichment analysis is performed. A total of 769 compounds are identified through metabolomics analysis, with alkaloids being predominant, followed by lipids and lipid molecules. Significant differential metabolites were screened out based on VIP > 1 and p-value < 0.05 criteria, followed by KEGG enrichment analysis of these differential metabolites. Differential metabolites between Pinelliae Rhizoma and Typhonium flagelliforme, as well as between Pinelliae Rhizoma and Pinellia pedatisecta, are significantly enriched in the biosynthesis of amino acids and protein digestion and absorption pathways. Differential metabolites between Pinelliae Rhizoma and Arisaema erubescens are mainly enriched in tyrosine metabolism and phenylalanine metabolism pathways. These findings aim to provide valuable data support and theoretical references for further research on the pharmacological substances, resource development and utilization, and quality control of Pinelliae Rhizoma. Full article

The automobile industry relies primarily on spot welding operations, particularly resistance spot welding (RSW). The performance and durability of the resistance spot-welded joints are significantly impacted by the welding quality outputs, such as the shear force, nugget diameter, failure mode, and the hardness of the welded joints. In light of this, the present study sought to determine how the aforementioned welding quality outputs of 0.5 and 1 mm thick austenitic stainless steel AISI 304 were affected by RSW parameters, such as welding current, welding time, pressure, holding time, squeezing time, and pulse welding. In order to guarantee precise evaluation and experimental analysis, it is essential that they are supported by a numerical model using an intelligent model. The primary objective of this research is to develop and enhance an intelligent model employing artificial neural network (ANN) models. This model aims to provide deeper knowledge of how the RSW parameters affect the quality of optimum joint behavior. The proposed neural network (NN) models were executed using different ANN structures with various training and transfer functions based on the feedforward backpropagation approach to find the optimal model. The performance of the ANN models was evaluated in accordance with validation metrics, like the mean squared error (MSE) and correlation coefficient (R²). Assessing the experimental findings revealed the maximum shear force and nugget diameter emerged to be 8.6 kN and 5.4 mm for the case of 1–1 mm, 3.298 kN and 4.1 mm for the case of 0.5–0.5 mm, and 4.031 kN and 4.9 mm for the case of 0.5–1 mm. Based on the results of the Pareto charts generated by the Minitab program, the most important parameter for the 1–1 mm case was the welding current; for the 0.5–0.5 mm case, it was pulse welding; and for the 0.5–1 mm case, it was holding time. When looking at the hardness results, it is clear that the nugget zone is much higher than the heat-affected zone (HZ) and base metal (BM) in all three cases. The ANN models showed that the one-output shear force model gave the best prediction, relating to the highest R and the lowest MSE compared to the one-output nugget diameter model and two-output structure. However, the Levenberg–Marquardt backpropagation (Trainlm) training function with the log sigmoid transfer function recorded the best prediction results of both ANN structures. Full article

Ionizing radiation induces many different types of DNA lesions. But one of its characteristics is to produce complex DNA damage, of which tandem DNA damage has received much attention, owing to its promise of distinctive biological properties. Oxidative stresses in response to inflammation in tissues and metal-catalyzed reactions that result in generation of radicals also form these DNA lesions. In this minireview, we have summarized the formation of the tandem lesions as well as the replication and repair studies carried out on them after site-specific synthesis. Many of these lesions are resistant to the traditional base excision repair, so that they can only be repaired by the nucleotide excision repair pathway. They also block DNA replication and, when lesion bypass occurs, it may be significantly error-prone. Some of these tandem DNA lesions may contribute to ageing, neurological diseases, and cancer. Full article

This article discusses the enculturated Catholic ethics of martyrdom embodied by the Martyrs of Fraternity of Burundi, a group of students whose cause is now before the Vatican’s Congregation for the Causes of Saints for refusing to separate into Hutus and Tutsis during Burundi’s 1993–2005 civil war. Engaging Fratelli Tutti from a local African perspective, it considers how the conviction that all human beings are brothers and sisters is to find concrete embodiment. Its argument develops Emmanuel Katongole’s assertion that the African church provides a living witness of what hope looks like in contexts of violence and war, drawing on Burundian scholarship and more than sixty interviews conducted in Burundi from 2018 to 2024 to develop a thick narrative of fraternal martyrdom and the ethics of Ubuntu. By placing sacrificial solidarity rather than violence at the center of the story of the Martyrs of Fraternity, Burundian Catholics reimagine their civil war in ethical terms. This Burundian embodiment of an ethics of sacrificial solidarity, solidly grounded in its original cultural substratum, stands as a resource for a world increasingly engulfed by war, refusing to let violence have the last word in a story of fraternal love hallowed by sacrifice. Full article

New antimicrobial molecules effective against Pseudomonas aeruginosa, known as an antibiotic-resistant “high-priority pathogen”, are urgently required because of its ability to develop biofilms related to healthcare-acquired infections. In this study, for the first time, the anti-biofilm and anti-virulence activities of a polyphenolic extract of extra-virgin olive oil as well as purified oleocanthal and oleacein, toward P. aeruginosa clinical isolates were investigated. The main result of our study was the anti-virulence activity of the mixture of oleacein and oleocanthal toward multidrug-resistant and intermediately resistant strains of P. aeruginosa isolated from patients with ventilator-associated pneumonia or surgical site infection. Specifically, the mixture of oleacein (2.5 mM)/oleocanthal (2.5 mM) significantly inhibited biofilm formation, alginate and pyocyanin production, and motility in both P. aeruginosa strains (p < 0.05); scanning electron microscopy analysis further evidenced its ability to inhibit bacterial cell adhesion as well as the production of the extracellular matrix. In conclusion, our results suggest the potential application of the oleacein/oleocanthal mixture in the management of healthcare-associated P. aeruginosa infections, particularly in the era of increasing antimicrobial resistance. Full article

Viral infection can regulate the cell cycle, thereby promoting viral replication. Hijacking and altering the cell cycle are important for the virus to establish and maintain a latent infection. Previously, Spodoptera exigua multiple nucleopolyhedrovirus (SeMNPV)-latently infected P8-Se301-C1 cells, which grew more slowly than Se301 cells and interfered with homologous SeMNNPV superinfection, were established. However, the effects of latent and superinfection with baculoviruses on cell cycle progression remain unknown. In this study, the cell cycle profiles of P8-Se301-C1 cells and SeMNPV or Autographa californica multiple nucleopolyhedrovirus (AcMNPV)-infected P8-Se301-C1 cells were characterized by flow cytometry. The results showed that replication-related genes MCM4, PCNA, and BAF were down-regulated (p < 0.05) in P8-Se301-C1 cells, and the S phase of P8-Se301-C1 cells was longer than that of Se301 cells. P8-Se301-C1 cells infected with SeMNPV did not arrest in the G2/M phase or affect the expression of Cyclin B and cyclin-dependent kinase 1 (CDK1). Furthermore, when P8-Se301-C1 cells were infected with SeMNPV after synchronized treatment with hydroxyurea and nocodazole, light microscopy and qRT-PCR analysis showed that, compared with unsynchronized cells and S and G2/M phase cells, SeMNPV-infected P8-Se301-C1 cells in G1 phase induced G2/M phase arrest, and the amount of virus adsorption and intracellular viral DNA replication were significantly increased (p < 0.05). In addition, budded virus (BV) production and occlusion body (OB)-containing cells were both increased at 120 h post-infection (p < 0.05). The expression of Cyclin B and CDK1 was significantly down-regulated at 48 h post-infection (p < 0.05). Finally, the arrest of SeMNPV-infected G1 phase cells in the G2/M phase increased BV production (p < 0.05) and the number of OB-containing cells. In conclusion, G1 phase infection and G2/M arrest are favorable to SeMNPV proliferation in P8-Se301-C1 cells, thereby alleviating the homologous superinfection exclusion. The results contribute to a better understanding of the relationship between baculoviruses and insect cell cycle progression and regulation. Full article

Dimensional measurements are fundamental in microfluidic device manufacturing and performance. The main focus of this study is the measurement of the connection port sizes in microfluidic devices and components and, accordingly, the possible existence of fluid leaks determined using the flow rate error. The sizes associated with three different microfluidic systems were determined using laser interferometry and through an optical measuring instrument, with metrological traceability to national length standards. It was possible to infer the method with the greatest accuracy and lowest measurement uncertainty for characterizing this kind of system. In conclusion, the results of this work directly address the current lack of dimensions measuring methods of microfluidic components by providing a comprehensive comparison of different protocols, ultimately suggesting a preferred option for immediate application within the microfluidic industry. Full article

Lyme disease is a zoonotic infectious disease. Increased public interest in Lyme disease has caused increased efforts by researchers for its surveillance and control. The main concept for this paper is to determine the mammalian species composition of areas at high risk for Lyme disease utilizing GIS-based (Geographic Information Systems) techniques coupled with k-means clustering, random forest, and multinomial logistic regression. Cluster analysis results were similar to previous work involving maps that display areas where people are at high risk for developing Lyme disease. There were differences in which mammal species presence had associations with Lyme disease risk observed at the two different scales within this analysis, with some overlap observed between the national scale and the smaller regions, as well as some overlap between the Rocky Mountain and Southeast regions that was not found at the national scale. This is an investigative analysis to determine which species are needed for habitat suitability analyses in efforts to prioritize vaccine deployment locations. There has been limited research on vaccine deployment for Lyme disease. Increasing our understanding of not only the vaccine but also the interactions between the components of disease transmission is necessary to control this infectious disease successfully. Full article

A geometric approach to the integrability and reduction of dynamical systems, both when dealing with systems of differential equations and in classical physics, is developed from a modern perspective. The main ingredients of this analysis are infinitesimal symmetries and tensor fields that are invariant under the given dynamics. A particular emphasis is placed on the existence of alternative invariant volume forms and the associated Jacobi multiplier theory, and then the Hojman symmetry theory is developed as a complement to the Noether theorem and non-Noether constants of motion. We also recall the geometric approach to Sundman infinitesimal time-reparametrisation for autonomous systems of first-order differential equations and some of its applications to integrability, and an analysis of how to define Sundman transformations for autonomous systems of second-order differential equations is proposed, which shows the necessity of considering alternative tangent bundle structures. A short description of alternative tangent structures is provided, and an application to integrability, namely, the linearisability of scalar second-order differential equations under generalised Sundman transformations, is developed. Full article

Under the dual pressures of climate change and human activities, the restrictions imposed by conservation policies, along with the increasing overlap between wildlife protected areas (PAs) and community living areas, have intensified the contradictions and conflicts between PAs and surrounding communities. Effective governance of such conflicts is particularly crucial to reconciling the contradictions between conservation and development. This study takes the Mikumi–Selous region in Tanzania, Africa, as a case study. Through questionnaires and semi-structured interviews, it explores the current state of conflicts between PAs and communities in the region and summarizes conflict governance measures. Moreover, this research focuses on identifying various factors that influence the conservation willingness and action of community residents, further validating the relationships between residents’ household characteristics, conservation costs and benefits, conservation cognition, willingness, and behaviors through empirical analysis methods. The results indicate that residents’ conservation cognition significantly positively impacts their conservation willingness and behaviors, while conservation willingness also positively affects their conservation behaviors. Additionally, it was found that conservation costs inhibit residents’ conservation willingness and behaviors. This study primarily explores, from a community governance perspective, the participation willingness and behaviors of core stakeholders in conflict governance, emphasizing the critical role of community involvement in achieving biodiversity conservation and coordinated community development and providing a new perspective for alleviating conservation and development issues. Full article

The valuation of ecosystem services (ESs) is crucial for preserving ecosystems, assessing natural resources, and making decisions regarding compensation. In this study, we employed the InVEST model’s habitat quality (HQ) module to calculate the HQ and degradation levels in the study area using land use/land cover (LULC) data from 2000 to 2020. Our analysis utilized quantitative methods, including spatial correlation, hotspot analysis, and geo-probing, to determine the value of ESs and identify trends. Furthermore, we examined the spatial and temporal variation in the significance of ESs and their driving factors. The results show the following. (1) The primary LULC types in the Zhundong coalfield from 2000 to 2020 are grassland and barren areas. (2) The average value of the HQ index in the study area exhibited a generally decreasing trend. Between 2000 and 2010, HQ significantly declined, particularly in the region’s large barren industrial and mining zones. However, over time, the proportion of sites with minimal degradation improved steadily, resulting in better overall HQ in the study area by 2020. This pertains to the measures put in place by the local government to safeguard and rehabilitate the ecosystem. (3) The spatial distribution of the ecosystem service value (ESV) aligns with changes in HQ and LULC, with significant hotspots primarily observed in forest and grassland areas, nature reserves, and areas around water sources. (4) LULC, temperature, annual precipitation, and elevation are the main drivers of spatial variation in the ESV in the Zhundong area; the spatial variation in the ESV in the Zhundong coalfield is primarily influenced by the interaction between human factors and natural factors, in which LULC plays a dominant role. This study’s findings can guide the development of rational ecological planning, integrating resource conservation mining with effective zoning management. Full article

There is a huge reservation of loess in the Shanxi mining area in China, which has great potential for preparing supplementary cementitious materials. Loess was modified via mechanical and thermal activation, and the pozzolanic activity was evaluated using an Inductively Coupled Plasma Optical Emission Spectrometer (ICP-OES). Moreover, the workability of grouting materials prepared using modified loess was assessed. The experimental results revealed that the number of ultrafine particles gradually increased with the grinding time, enhancing the grouting performance. The coordination number of Al decreased upon the breakage of the Al–O–Si bond post-calcination at 400 °C, 550 °C, 700 °C, and 850 °C. Moreover, the breaking of the Si–O covalent bond produced Si-phases, and the pozzolanic activity of loess increased. Furthermore, the modified loess was hydrated with different cement proportions. With increasing grinding time, the overall setting time increased until the longest time of 14.5 h and the fluidity of the slurry decreased until the lowest fluidity of 9.7 cm. However, the fluidity and setting time decreased with increasing calcination temperature. The lowest values were 12.03 cm and 10.05 h. With the increase in pozzolanic activity, more ettringite was produced via hydration, which enhanced the mechanical properties. The maximum strength of the hydrated loess after grinding for 20 min reached 16.5 MPa. The strength of the hydrated loess calcined at 850 °C reached 21 MPa. These experimental findings provide theoretical support for the practical application of loess in grouting. Full article

Front loaders used in agriculture are characterized by a compact structure, which limits the scope of their application. The loading possibilities are expanded by designing front loaders equipped with telescopic arms. This design increases the loader’s working area, making it easier to load trucks. It is necessary to work on the arm extension drive and perform strength analyses on the new structures. This article presents a FEM numerical analysis of the structure of an extending front loader and an assessment of the state of stress and the value of displacements under the influence of load. This study discusses the advantages and disadvantages of front loaders compared to telehandlers and the legal requirements and standards for the design of front loaders in Europe. This work presents the concept of loader arm movement and assesses the effectiveness of using hydraulic motors coupled with a screw gear. The obtained results prove that the newly designed extending front loader system is safe and stable. Full article

Ullazines and their π-expanded derivatives have gained much attention as active components in various applications, such as in organic photovoltaic cells or as photosensitizers for CO₂ photoreduction. Here, we report the divergent synthesis of functionalized diazaullazines by means of two different domino-reactions consisting of either a Povarov/cycloisomerization or alkyne–carbonyl metathesis/cycloisomerization protocol. The corresponding quinolino-diazaullazine and benzoyl-diazaullazine derivatives were obtained in moderate to good yields. Their optical and electronic properties were studied and compared to related, literature-known compounds to obtain insights into the impact of nitrogen doping and π-expansion. Full article

This study is based on the need to improve packaging sustainability in the food industry. Its aim was to assess the performance of a recyclable plastic material for semi-hard sheep’s cheese wedges packaging as an alternative to conventional non-sustainable plastic materials. Four different packaging treatments (air, vacuum, and CO₂/N₂ gas mixtures 50/50 and 80/20% (v/v)) were studied. Changes in gas headspace composition, sensory properties, cheese gross composition, weight loss, pH, colour, and texture profile were investigated at 5 ± 1 °C storage for 56 days. The sensory analysis indicated that vacuum packaging scored the worst in paste appearance and holes, and air atmosphere the worst in flavour; it was concluded that cheeses were unfit from day 14–21 onwards. Air and vacuum packaging were responsible for most of the significant changes identified in the texture profile analysis, and most of these happened in the early stages of storage. The colour parameters a* and b* differentiated the air packaging from the rest of the conditions. As in previous studies using conventional plastic materials, modified atmosphere packaging, either CO₂/N₂ 50/50 or 80/20% (v/v), was the most effective preserving technique to ensure the quality of this type of cheese when comparing air and vacuum packaging treatments. Full article

Fresh aquatic products, due to their high water activity, are susceptible to microbial contamination and spoilage, resulting in a short shelf life. Drying is a commonly used method to extend the shelf life of these products by reducing the moisture content, inhibiting microbial growth, and slowing down enzymatic and chemical reactions. However, the drying process of aquatic products involves chemical reactions such as oxidation and hydrolysis, which pose challenges in obtaining high-quality dried products. This paper provides a comprehensive review of drying processing techniques for aquatic products, including drying preprocessing, drying technologies, and non-destructive monitoring techniques, and discusses their advantages and challenges. Furthermore, the impact of the drying process on the quality attributes of dried products, including sensory quality, nutritional components, and microbial aspects, is analyzed. Finally, the challenges faced by drying processing techniques for aquatic products are identified, and future research prospects are outlined, aiming to further advance research and innovation in this field. Full article

Prior studies into fatigue crack growth (FCG) in fibre-reinforced polymer composites have shown that the two methodologies of Simple-Scaling and the Hartman–Schijve crack growth equation, which is based on relating the FCG rate to the Schwalbe crack driving force, Δκ, were able to account for differences observed in the measured delamination growth curves. The present paper reveals that these two approaches are also able to account for differences seen in plots of the rate of crack growth, da/dt, versus the range of the imposed stress intensity factor, ΔK, associated with fatigue tests on different grades of high-density polyethylene (HDPE) polymers, before and after electron-beam irradiation, and for tests conducted at different R ratios. Also, these studies are successfully extended to consider FCG in an acrylonitrile butadiene styrene (ABS) polymer that is processed using both conventional injection moulding and additive-manufactured (AM) 3D printing. Full article

For hybrid direct sequence/frequency hopping (DS/FH) spread spectrum signals, even if the relative motion speed between the transmitter and receiver remains constant, the Doppler frequency will vary due to the continuous hopping of the carrier frequency. Under high dynamic conditions, the first-order and second-order change rates of the Doppler frequency attached to the received signal further increase the Doppler frequency agility, making it difficult for the carrier tracking loop to maintain steady-state tracking. To address these issues, a high dynamic velocity locked loop (HD-VLL) is proposed in this paper. Specifically, the accumulated phase tracking error caused by acceleration and jerk is first analyzed. Subsequently, to compensate for this phase tracking error with the system clock, the proposed loop adds an acceleration compensation module and a jerk compensation module. However, this results in the output of the high dynamic loop filter being updated with the system clock, which contradicts the multiplexing design of a traditional loop filter for parallel signal processing, making the hardware implementation of an HD-VLL impractical. Therefore, this contradiction leads us to design an HD-VLL-based multi-carrier NCO (HD-VLL-NCO). The HD-VLL and HD-VLL-NCO are simulated, revealing the HD-VLL’s superior dynamic adaptability and steady-state tracking, while the HD-VLL-NCO achieves comparable accuracy with the appropriate truncation bit width. Full article

Cutaneous leishmaniasis (CL) is a zoonotic disease, manifested as chronic ulcers, potentially leaving unattractive scars. There is no preventive vaccination or optimal medication against leishmaniasis. Chemotherapy generally depends upon a small group of compounds, each with its own efficacy, toxicity, and rate of drug resistance. To date, no standardized, simple, safe, and highly effective regimen for treating CL exists. Therefore, there is an urgent need to develop new optimal medication for this disease. Sesquiterpen thio-alkaloids constitute a group of plant secondary metabolites that bear great potential for medicinal uses. The nupharidines found in Nuphar lutea belong to this group of compounds. We have previously published that Nuphar lutea semi-purified extract containing major components of nupharidines has strong anti-leishmanial activity in vitro. Here, we present in vivo data on the therapeutic benefit of the extract against Leishmania major (L. major) in infected mice. We also expanded these observations by establishing the therapeutic effect of the extract-purified nupharidine 6,6′-dihydroxythiobinupharidine (DTBN) in vitro against promastigotes and intracellular amastigotes as well as in vivo in L. major-infected mice. The results suggest that this novel anti-parasitic small molecule has the potential to be further developed against Leishmania. Full article

Alterations in a mother’s metabolism and endocrine system, due to unbalanced nutrition, may increase the risk of both metabolic and non-metabolic disorders in the offspring’s childhood and adulthood. The risk of obesity in the offspring can be determined by the interplay between maternal nutrition and lifestyle, intrauterine environment, epigenetic modifications, and early postnatal factors. Several studies have indicated that the fetal bowel begins to colonize before birth and that, during birth and nursing, the gut microbiota continues to change. The mother’s gut microbiota is primarily transferred to the fetus through maternal nutrition and the environment. In this way, it is able to impact the establishment of the early fetal and neonatal microbiome, resulting in epigenetic signatures that can possibly predispose the offspring to the development of obesity in later life. However, antioxidants and exercise in the mother have been shown to improve the offspring’s metabolism, with improvements in leptin, triglycerides, adiponectin, and insulin resistance, as well as in the fetal birth weight through epigenetic mechanisms. Therefore, in this extensive literature review, we aimed to investigate the relationship between maternal diet, epigenetics, and gut microbiota in order to expand on current knowledge and identify novel potential preventative strategies for lowering the risk of obesity in children and adults. Full article

Rice (Oryza sativa) is one of the most important staple foods worldwide. However, rice blast disease, caused by the ascomycete fungus Magnaporthe oryzae, seriously affects the yield and quality of rice. Calmodulin-binding transcriptional activators (CAMTAs) play vital roles in the response to biotic stresses. In this study, we showed that OsCAMTA3 and CAMTA PROTEIN LIKE (OsCAMTAPL), an OsCAMTA3 homolog that lacks the DNA-binding domain, functioned together in negatively regulating disease resistance in rice. OsCAMTA3 associated with OsCAMTAPL. The oscamta3 and oscamtapl mutants showed enhanced resistance compared to wild-type plants, and oscamta3/pl double mutants showed more robust resistance to M. oryzae than oscamta3 or oscamtapl. An RNA-Seq analysis revealed that 59 and 73 genes, respectively, were differentially expressed in wild-type plants and oscamta3 before and after inoculation with M. oryzae, including OsALDH2B1, an acetaldehyde dehydrogenase that negatively regulates plant immunity. OsCAMTA3 could directly bind to the promoter of OsALDH2B1, and OsALDH2B1 expression was decreased in oscamta3, oscamtapl, and oscamta3/pl mutants. In conclusion, OsCAMTA3 associates with OsCAMTAPL to regulate disease resistance by binding and activating the expression of OsALDH2B1 in rice, which reveals a strategy by which rice controls rice blast disease and provides important genes for resistance breeding holding a certain positive impact on ensuring food security. Full article

Epigenetic alterations my play a role in the aggressive behavior of Non-Small Cell Lung Cancer (NSCLC). Treatment with the histone deacetylase inhibitor suberoylanilide hydroxamic acid (SAHA, vorinostat) has been reported to interfere with the proliferative and invasive potential of NSCLC cells. In addition, the DNA methyltransferase inhibitor azacytidine (AZA, vidaza) can modulate the levels of the metastasis suppressor KiSS-1. Thus, since cisplatin is still clinically available for NSCLC therapy, the aim of this study was to evaluate drug combinations between cisplatin and SAHA as well as AZA using cisplatin-sensitive H460 and -resistant H460/Pt NSCLC cells in relation to KiSS-1 modulation. An analysis of drug interaction according to the Combination-Index values indicated a more marked synergistic effect when the exposure to SAHA or AZA preceded cisplatin treatment with respect to a simultaneous schedule. A modulation of proteins involved in apoptosis (p53, Bax) was found in both sensitive and resistant cells, and compared to the treatment with epigenetic agents alone, the combination of cisplatin and SAHA or AZA increased apoptosis induction. The epigenetic treatments, both as single agents and in combination, increased the release of KiSS-1. Finally, the exposure of cisplatin-sensitive and -resistant cells to the kisspeptin KP10 enhanced cisplatin induced cell death. The efficacy of the combination of SAHA and cisplatin was tested in vivo after subcutaneous inoculum of parental and resistant cells in immunodeficient mice. A significant tumor volume inhibition was found when mice bearing advanced tumors were treated with the combination of SAHA and cisplatin according to the best schedule identified in cellular studies. These results, together with the available literature, support that epigenetic drugs are amenable for the combination treatment of NSCLC, including patients bearing cisplatin-resistant tumors. Full article