This study investigated the effects of the dietary protein level and rumen-protected methionine and lysine (RPML) on the growth performance, rumen fermentation, and serum indexes of yaks. Thirty-six male yaks were randomly assigned to a two by three factorial experiment with two protein levels, 15.05% and 16.51%, and three RPML levels: 0% RPML; 0.05% RPMet and 0.15% RPLys; and 0.1% RPMet and 0.3% RPLys. The trial lasted for sixty days. The results showed that the low-protein diet increased the DMI and feed conversion ratio of yaks. The diet supplemented with RPML increased the activities of IGF1 and INS and nutrient digestibility. The high-protein diet decreased the rumen butyrate concentration and increased the rumen isovalerate concentration. The low-protein diet supplemented with RPML increased the rumen pH and the concentrations of total volatile fatty acids, butyrate and NH₃-N; the high-protein diet supplemented with a high level of RPML decreased the rumen pH and the concentrations of isobutyrate, isovalerate, propionate and NH₃-N. The low-protein diet supplemented with RPML increased the total antioxidant capacity and glutathione peroxidase activity, along with the concentrations of malondialdehyde and amino acids such as aspartic acid, lysine, cysteine, etc. In conclusion, a low-protein diet supplemented with RPML is beneficial for rumen and body health, physiological response, and metabolic status in yaks. Full article

The intestine of living organisms harbors different microbiota associated with the biological functioning and health of the host and influences the process of ecological adaptation. Here, we studied the intestinal microbiota’s composition and functional differences using 16S rRNA and metagenomic analysis in the wild, farm, and released Chinese three-keeled pond turtle (Mauremys reevesii). At the phylum level, Bacteroidota dominated, followed by Firmicutes, Fusobacteriota, and Actinobacteriota in the wild group, but Chloroflexi was more abundant in the farm and released groups. Moreover, Chryseobacterium, Acinetobacter, Comamonas, Sphingobacterium, and Rhodobacter were abundant in the released and farm cohorts, respectively. Cetobacterium, Paraclostridium, Lysobacter, and Leucobacter showed an abundance in the wild group. The Kyoto Encyclopedia of Genes and Genomes (KEGG) database revealed that the relative abundance of most pathways was significantly higher in the wild turtles (carbohydrate metabolism, lipid metabolism, metabolism of cofactors, and vitamins). The comprehensive antibiotic resistance database (CARD) showed that the antibiotic resistance gene (ARG) subtype macB was the most abundant in the farm turtle group, while tetA was higher in the wild turtles, and srpYmcr was higher in the released group. Our findings shed light on the association between the intestinal microbiota of M. reevesii and its habitats and could be useful for tracking habitats to protect and conserve this endangered species. Full article

The potentials of ABO replacer of ENZ and DFM on growth performance, AID, colonic VFAs, gut morphology, fecal score and diarrhea incidence were evaluated. We randomly assigned 120 piglets to four experimental diets that included: (1) control diet (CON), fed the basal ration; (2) ABO was added at 250 ppm of in-feed ABO; (3) ENZ was added at a rate of 3 kg/ton feed; (4) DFM was added with 50 × 10⁶ cfu/g of Bacillus subtilis and 2 × 10⁶ cfu/g of Lactobacillus spp. at a rate of 1.2 kg/ton feed. A complete randomized design used six pens per treatment with five pigs per pen. Pigs had ad libitum access to feed and water throughout the 6-week trial. Feed intake and BW were recorded on weeks 0, 2, 4 and 6, as well as fecal scores and diarrhea incidences (visually recorded and calculated). At weeks 2 and 4, a sub-sample of pigs (n = 6) was sacrificed for intestinal morphology, enzyme activity and VFAs. The results of the study demonstrated that DFM piglets showed increased final BW (3 kg) (p < 0.001) vs. CON. Likewise, ADG was positively affected by the incorporation of ABO, ENZ and DFM in the diets, with an average increase of 8 to 17% on ADG compared with CON (p < 0.001). The AID of gross energy, organic matter, CP and EAAs in piglets fed ENZ and DFM were significantly higher (p < 0.05) than those of CON and ABO at weeks 2 and 4. Inclusion of DFM increased intestinal morphology, enzymatic activities and propionic and butyric acid more than in pigs fed CON, ABO and ENZ (p < 0.05). The fecal score and diarrhea incidence generally decreased over time in pigs fed DFM (p < 0.05). These findings indicate that dietary supplementation with DFM has better effects at any period on growth performance, CP and AA digestibility and beneficially altered the intestinal health in weanling piglets. Full article

The Huitang duck (HT), a long-domesticated elite local breed from Hunan Province, China, with excellent meat quality, has not had its population genetic structure and genomic selective sweeps extensively studied to date. This study measured the phenotypic characteristics of HT and conducted comparative analysis between HT and 16 different duck breeds, including wild, indigenous, and meat breeds, to characterize its population structure and genetic potential. The results revealed that HT is a dual-purpose indigenous breed with a genetic background closely related to the Youxian sheldrake and Linwu ducks. In the selective sweep analysis between HT and Linwu ducks, genes such as PLCG2, FN1, and IGF2BP2, which are associated with muscle growth and development, were identified near the 27 selection signals. The comparison between HT and Jinding ducks revealed 68 selective signals that contained important genes associated with ovarian development (GRIK4, MAP3K8, and TGIF1) and egg-laying behaviors (ERBB4). Selective sweep analysis between HT and Youxian sheldrake ducks found 93 selective regions covering genes related to both meat (IGF1R and IGFBP5) and egg-production (FOXO3 and ITPR1) traits. Our study may provide novel knowledge for exploring the population structure and genetic potential of HT, offering a theoretical basis for its breeding strategies in the future. Full article

Xinjiang Brown cattle are a unique and widely distributed breed of dual-purpose cattle in the Xinjiang area of China, whose milk production performance differs from Holstein cattle. It has been known that variations in bacterial species of the gastrointestinal tract influence milk protein, fat, and lactose synthesis. However, the microbiota differences between Xinjiang Brown and Holstein cattle are less known. This study aims to compare the bacterial community composition of the rumen and feces of these two cattle breeds under the same dietary and management conditions. The 16s rRNA sequencing data and milk production of 18 Xinjiang Brown cows and 20 Holstein cows on the same farm were obtained for analysis. The results confirmed differences in milk production between Xinjiang Brown and Holstein cattle. Microbiota with different relative abundance between these two cattle breeds were identified, and their biological functions might be related to milk synthesis. This study increases the understanding of the differences in microbiota between Xinjiang Brown and Holstein cattle and might provide helpful information for microbiota composition optimization of these dairy cattle. Full article

Cooked sausages packaged in a modified atmosphere (MAP: 20% CO_2, 70% N₂, <0.2% O₂) with evident yellow stains were analyzed. The aims of this work were to study the microbial cause of the spoilage and to evaluate different antimicrobial compounds to prevent it. Leuconostoc gelidum was identified as the primary cause of the yellow coating in spoiled cooked sausage, as confirmed by its intentional inoculation on slices of unspoiled sausage. Leuconostoc gelidum was the main bacteria responsible for the yellow coating in spoiled cooked sausage, as confirmed by its intentional inoculation on slices of unspoiled sausage. The yellow color was also evident during growth in the model system containing cooked sausage extract, but the colonies on MRS agar appeared white, demonstrating that the food substrate stimulated the production of the yellow pigment. The spoilage was also characterized by different volatile compounds, including ketones, ethanol, acetic acid, and ethyl acetate, found in the spoiled cooked sausage packages. These compounds explained the activity of Leuc. gelidum because they are typical of heterofermentative LAB, cultivated either on food substrates or in artificial broths. Leuc. gelidum also produced slight swelling in the spoiled packages. The efficacy of different antimicrobials was assessed in model systems composed of cooked sausage extract with the antimicrobials added at food product concentrations. The data showed that sodium lactate, sodium acetate, and a combination of sodium lactate and sodium diacetate could only slow the growth of the spoiler—they could not stop it from occurring. Conversely, hop extract inhibited Leuc. gelidum, showing a minimal inhibitory concentration (MIC) of approximately 0.008 mg CAE/mL in synthetic broth and 4 mg CAE/kg in cooked sausage slices. Adding hop extract at the MIC did not allow Leuc. gelidum growth and did not change the sensorial characteristics of the cooked sausages. To our knowledge, this is the first report of the antimicrobial activities of hop extracts against Leuc. gelidum either in vitro or in vivo. Full article

Orchids are crucial for the horticulture industry. Mycorrhizal fungi benefit crops by improving nutrition, plant growth, and disease resistance. However, the mycorrhizal association of horticultural hybrid orchids is poorly understood. To address this, we investigated mycorrhizal colonization in the entire root system and assessed the mycorrhizal community using a Dendrobium cultivar, D. Stardust ‘Firebird’, obtained from three nurseries. Additionally, we isolated and tested mycorrhizal fungi in symbiotic culture to assess their role in the seed germination and growth of Dendrobium species. All plants were colonized by mycorrhizal fungi, with a higher colonization rate in mature than in juvenile plants. Molecular identification of mycorrhizal fungi by Sanger and high-throughput sequencing revealed that the cultivar was associated with a phylogenetically diverse group of fungi, including mycorrhizal fungi from Tulasnellaceae, and several wood-decaying fungi. The Tulasnellaceae isolates significantly enhanced the seed germination of three Dendrobium species and increased the survival rate and growth of asymbiotic seedlings of D. moniliforme. This study is the first comprehensive examination of mycorrhizal associations in horticultural orchid hybrids, providing valuable insights for commercial production. Full article

With the advent of new sustainable construction materials, self-healing concrete has been used and tested in the last decade, raising the question of the efficacy of said mechanisms to prevent water permeation after crack formation. Thus, new novel mechanical methodologies have been introduced to induce controlled cracks in concrete specimens to improve the standardisation and effectiveness of permeability tests. This research explores those new mechanical techniques to create consistent and reproducible crack patterns, crucial for assessing the efficacy of self-healing mechanisms in concrete. This study systematically evaluates how different crack configurations influence the self-healing ability of the material. Findings from this research are expected to aid in refining testing protocols and to contribute significantly to the field of material science within civil engineering by demonstrating the potential of self-healing concrete to revolutionise building practices. Full article

This study examines the use of SrAl₂O₄: Eu²⁺, Dy³⁺ long-afterglow materials doped into g-C₃N₄/TiO₂ coatings for photodegradation. The prepared sample was tested for the purification of automotive exhaust fumes, with the optimal mass ratio of g-C₃N₄/TiO₂ and SrAl₂O₄: Eu²⁺, Dy³⁺ determined to be 1:1. Characterization tests, including XRD, FT-IR, XPS, and TG-DSC, were conducted to evaluate the microstructure and properties of the samples. Under poor lighting conditions, g-C₃N₄/TiO₂ reduced CH and NO_x by 59 ppm and 13 ppm within 4 h, respectively, while g-C₃N₄/TiO₂/SrAl₂O₄: Eu²⁺, Dy³⁺ decreased CH and NO_x by 98ppm and 34ppm, respectively, resulting in a significant improvement in degradation efficiency. The addition of long-afterglow materials significantly improves the efficiency of photocatalysts in purifying exhaust fumes in low-light environments, providing potential value for all-weather exhaust treatment in the future. Full article

This study focuses on an overview of two programs applied to the residential building stock of Bucharest (Romania), namely, the seismic strengthening program and the thermal rehabilitation program. The methodology for seismic risk assessment given in the current generation of Romanian codes, as well as in previous regulations, is examined. A brief review of other seismic risk assessment methodologies currently applied in various seismically prone countries is also presented. Examples of high-rise buildings in Bucharest that suffered significant damage during the Vrancea 1977 earthquake and that were thermally rehabilitated without any strengthening works are shown in this paper. The consistent differences between the current outcomes of the two programs are presented and discussed. Finally, this review paper highlights the lack of coherence in terms of seismic risk assessments for the same class of buildings, inducing, in some situations, a false feeling of safety in the building inhabitants. In addition, a combined procedure for both seismic strengthening and thermal rehabilitation is mandatory, considering the seismicity of Romania, as well as ongoing climate change. Full article

Taking an actual 3MW steel–concrete composite wind turbine tower as an example, a finite element model of the tower structure was established, and static bearing capacity and dynamic time history response analyses were performed to identify the locations where the structure is prone to failure. On this basis, the fatigue lives of the turbine tower at the most unfavorable locations were predicted using linear cumulative damage theory, and the fatigue reliability at the corresponding locations of the structure was calculated using the kriging–subset simulation method. The most dangerous locations of the tower that are most prone to failure are as follows: the bottom of the leeward side of the upper steel tube, the flange of the steel tube, the bolt-hole imprinting surface of the flange, the leeward side of the transition tube, and the top of the leeward side of the concrete tube. The failure risk of the flange and bolt-hole imprinting surface of the upper steel tube is relatively high, followed by that of the transition tube. This indicates that special attention should be given to the design and daily maintenance of this part. The fatigue resistance of the tower can be enhanced by improving the strength of the flange plate or increasing the number of bolts and strengthening the transition tube. Full article

This study introduces a new internal diaphragm joint to connect steel beams with wall-type concrete-filled steel tubular (WCFST) columns. This study combines experimental research with numerical simulations for analysis. Firstly, one full-scale test specimen was designed and subjected to cyclic loading. The obtained failure mode and hysteresis curves illustrate that the joint specimens exhibit ample energy dissipation capacities. Subsequently, a reliable FE model was obtained based on experimental verification, and parametric analysis was conducted. The findings indicate that axial compression ratios critically affect the load-carrying capacity and displacement at failure, with a 2% reduction in capacity for each 0.1 increment in the ratio. The thicknesses of the column web and flange in the joint area are recommended to be 0.85 to 1.2 times and 1 to 1.2 times the beam flange thickness, respectively. The length of the internal diaphragm is advised to be between 0.2 and 0.3 times the width of the cross-section. Overall, these results significantly enrich our understanding of WCFST systems and will inform future design and construction best practices. Full article

Steel slag is a significant environmental liability generated by pyrometallurgical processes. Residue generation, such as granulated blast furnace slag and basic oxygen slag (BOF), is intrinsic in steel production. Blast furnace slag, generated in the carbothermal reduction of iron ore, is almost entirely used as a supplementary cement material in Portland cement. BOF slag, produced in the conversion of pig iron into steel in a basic oxygen converter, is still not consolidated or valued for reuse. This research proposes the reuse and valorization of BOF slag combined with blast furnace slag in clinker-free cement production. Cement formulations were produced with different slag and gypsum contents, ranging from 80 to 90% blast furnace slag, 10 to 20% gypsum, and 10 to 15% BOF slag. All formulations were evaluated for compressive strength at ages of 3, 7, 14, 28, 91, and 180 days of curing. At the initial ages, the cement formulations exhibited high resistance. On the 3rd day, the cement formulations reached up to 10 MPa, and on the 7th day, 40 MPa. At late ages, the best-performing formulation, ECO2, showed, after 28 days of hydration, a compressive strength greater than 50 MPa, and at 180 days, a compressive strength greater than 80 MPa. It was possible to understand that BOF slag acts in cement alkaline activation with pH increase, more or less actively due to the presence of lime, portlandite, and calcite. Full article

Lianas are a crucial component of karst seasonal rainforests, yet research on them has predominantly focused on non-karst regions. Consequently, their abundance and species richness remain relatively understudied within karst ecosystems. We aimed to document the abundance and species richness of lianas and investigate their relationships with abiotic and biotic factors, based on data from a fully mapped 15 ha plot in a karst seasonal rainforest of Nonggang (SW China). Structural equation models (SEMs) were employed to estimate the path coefficients and variation of dependent variables, enabling a comprehensive analysis of the factors affecting the abundance and species richness of liana. Within the 15 ha plot, a total of 23,819 lianas were identified, encompassing 113 species from 34 families. These lianas constituted 24.16% of the total woody plant density and 33.44% of the species present, but only 4.32% of the total woody plant basal area. Lianas are primarily influenced by abiotic factors, especially elevation and phosphorus (P), with less impact from biotic factors. Our findings reveal that lianas, despite constituting a relatively small percentage of the total woody plant basal area, significantly contribute to the density and diversity of the forest. Notably, abiotic factors such as elevation and phosphorus availability predominantly shape the distribution and richness of lianas, highlighting the importance of these environmental variables. The findings offer valuable insights for future liana studies and the preservation of karst forests’ biodiversity. Full article

This paper assessed and evaluated the river and groundwater quality of five major catchments in the Mzimvubu to Tsitsikamma Water Management Area (WMA7). The river assessment and evaluation considered the present state maximum, minimum and mean seasonal values of physiochemical parameters (EC, NO₃ + NO₂, Cl, pH, NH₄-N, PO₄-P and Mg). The study was able to successfully make use of statistical analysis and a water quality index in order to explain seven-year trends and the present state of all five catchments within the study area. The statistical analysis results showed that water quality parameters such as PO₄, NH₄ and NO₃ + NO₂ were not complying with the South African Water Quality Guidelines (SAWQG) limits, suggesting that the study area was impacted by anthropogenic activities such as agriculture, sewage works, etc. The application of WQI showed that the Gamtoos catchment was in a good water quality state (49.71) while the other four catchments were in a poor to very poor state, according to the WQI classification. Based on the groundwater quality assessment, the physicochemical parameters (NH₄, EC, Ca, NO₃ + NO₂, pH, Na, Cl, Mg, F, K, SO₄ and CaCO₃) were selected and the main parameters of concern were EC (salinity), NO₃ + NO₂ and SO₄. However, groundwater assessment revealed that groundwater quality was chemically suitable for drinking purposes in most parts of the study area. Therefore, the study recommended resource-directed measures to improve surface and groundwater resource protection, especially in areas where surface and groundwater quality for other uses remains a challenge. Further, strong water resource compliance monitoring and enforcement to control water resource pollution sources is critical. Full article

Oil-degrading bacteria have the ability to degrade alkanes present in crude oil because of a special enzymatic system, the alkane hydroxylase complex (AlkH). The mechanism for the transport and degradation of alkanes present in crude oil remains unclear, especially related to the first step in hydrocarbons oxidation. In this work, we present a novel model of the crude oil biodegradation mechanism by considering the contact between the oil drop and the cell and calculating the mass transfer coefficients in three oleophilic bacteria (B. licheniformis, P. putida and P. glucanolyticus). The mass transfer coefficients are evaluated under critical time conditions, when the kinetics and mass transport are in balance, and the difference in the values obtained (k_L α = 1.60 × 10⁻³, 5.25 × 10⁻⁴ and 6.19 × 10⁻⁴ m/d, respectively) shows the higher value of the mass transfer coefficient and higher biodegradation potential for B. licheniformis. Because the morphology of the cells has been analyzed by optical and electron microscopy, in the proposed model, the increase in the size of the cells in P. glucanolyticus compared to P. putida exhibits higher values of the mass transfer coefficients and this is attributed, as a novel statement, to a bigger window for alkanes transport (contact area) when the external area of the cell is bigger. Full article

Very little is known about the preservation and storage of fresh medicinal and aromatic plants (MAPs) and/or herbs. As with many leafy vegetables, i.e., lettuce, fresh spearmint is a very perishable product throughout the production line and requires special handling/processing. The current study aimed to examine the antibacterial activity of selected MAPs (Origanum dubium, Salvia fruticosa and Sideritis cypria) grown in Cyprus towards foodborne pathogens. Then, the most effective MAPs’ essential oil (EO) and hydrosol (at different doses; combination of concentration and time of dipping submerge) were tested to preserve fresh spearmint quality and safety. The results showed that O. dubium EO and hydrosol presented great in vitro antibacterial activity against four foodborne pathogens and those products were further selected for application on fresh spearmint. During sensory evaluation, it was observed that higher O. dubium EO concentrations and longer time of application resulted into a less marketable product (less acceptable with less spearmint-like aroma), while hydrosol resulted in a more marketable product even at high doses. In general, EO and hydrosol applications increased spearmint’s antioxidants (including polyphenols, flavonoids, and ascorbic acid), resulting in a product of increased nutritional value. The bacterial populations of Salmonella enterica and Listeria monocytogenes inoculated on fresh spearmint were decreased with the EO and hydrosol application doses applied, and their effects were evident even after six days of storage at 4 °C. From the findings of this study, it can be concluded that O. dubium EO and hydrosol could be a potential sanitation method for fresh spearmint preservation. Full article

Grading tea leaves efficiently in a natural environment is a crucial technological foundation for the automation of tea-picking robots. In this study, to solve the problems of dense distribution, limited feature-extraction ability, and false detection in the field of tea grading recognition, an improved YOLOv8n model for tea grading and counting recognition was proposed. Firstly, the SPD-Conv module was embedded into the backbone of the network model to enhance the deep feature-extraction ability of the target. Secondly, the Super-Token Vision Transformer was integrated to reduce the model’s attention to redundant information, thus improving its perception ability for tea. Subsequently, the loss function was improved to MPDIoU, which accelerated the convergence speed and optimized the performance. Finally, a classification-positioning counting function was added to achieve the purpose of classification counting. The experimental results showed that, compared to the original model, the precision, recall and average precision improved by 17.6%, 19.3%, and 18.7%, respectively. The average precision of single bud, one bud with one leaf, and one bud with two leaves were 88.5%, 89.5% and 89.1%. In this study, the improved model demonstrated strong robustness and proved suitable for tea grading and edge-picking equipment, laying a solid foundation for the mechanization of the tea industry. Full article

Premature leaf failure is one of the major factors contributing to crop yield reduction. High-yielding soybean cultivars exhibit a longer leaf lifespan during the reproductive period, promoting higher yields. In this experiment, physiological indexes and transcriptomics analysis were carried out on leaves of different canopy parts of two soybean cultivars with different senescence sensitivities of LD32 and SND28 as test materials. The results showed that the leaf senescence rates of the two soybean cultivars, tested at the grain-filling stage, were significantly different, and the senescence rates of the upper and middle canopy leaves of LD32 were significantly lower than those of SND28. In comparison to SND28, LD32 exhibited slower decreases in chlorophyll, net photosynthetic rate, and SPAD values in the upper and middle canopy leaves. The differentially expressed genes for senescence of upper and middle canopy leaves of both cultivars were enriched in four pathways: the photosynthesis pathway, the photosynthesis–antenna protein pathway, the MAPK signaling pathway–plant hormone signal transduction pathway, and the plant hormone signal transduction pathway. The differential expression of 20 genes (Ribose-5-phosphate isomerase, fructose-1,6-bisphosphatase, etc.) in the “carbon fixation in photosynthetic organisms” pathway of LD32 may be involved in the regulation of reducing the rate of leaf senescence in the middle of the canopy at the grain-filling stage of LD32. Ribose-5-phosphate isomerase and fructose-1,6-bisphosphatase in LD32 may reduce the rate of leaf senescence in the middle of the canopy during seed filling. Full article

Herbicide-resistant corn poppy (Papaver rhoeas L.) is one of the most important broadleaved weeds and the number of resistant cases is still growing. The aims of this study were to confirm the resistance of P. rhoeas from Tunisia to ALS inhibitors and auxin mimics and investigate the mechanisms of Target-Site Resistance (TSR) and Non-Target Site Resistance (NTSR) involved. Dose–response trials to determine cross-resistance patterns for ALS inhibitors and auxin mimics were conducted in a greenhouse. In this study, multiple resistance to tribenuron-methyl and dicamba but not to 2,4-D was found in P. rhoeas populations. Cross-resistance to imazamox was confirmed as well. Sequence analysis of the ALS gene detected target-site mutations in codon 197 of the ALS gene, namely, Pro197His, Pro197Thr, Pro197Leu, and Pro197Asn. In this study, the metabolism experiments with malathion (a cytochrome P450 inhibitor) showed that malathion reduced resistance to imazamox, indicating that P450 is involved in the resistance. TSR and NTSR mechanisms to ALS inhibitors likely coexist. The findings of this study revealed a significant synergistic interaction between malathion and dicamba in particular populations, suggesting that the resistance to auxin mimics can be conferred by enhanced metabolism. Full article

This manuscript explores the intricate role of acetylcholine-activated inward rectifier potassium (K_ACh) channels in the pathogenesis of atrial fibrillation (AF), a common cardiac arrhythmia. It delves into the molecular and cellular mechanisms that underpin AF, emphasizing the vital function of K_ACh channels in modulating the atrial action potential and facilitating arrhythmogenic conditions. This study underscores the dual nature of K_ACh activation and its genetic regulation, revealing that specific variations in potassium channel genes, such as Kir3.4 and K_2P3.1, significantly influence the electrophysiological remodeling associated with AF. Furthermore, this manuscript identifies the crucial role of the K_ACh-mediated current, I_KACh, in sustaining arrhythmia through facilitating shorter re-entry circuits and stabilizing the re-entrant circuits, particularly in response to vagal nerve stimulation. Experimental findings from animal models, which could not induce AF in the absence of muscarinic activation, highlight the dependency of AF induction on K_ACh channel activity. This is complemented by discussions on therapeutic interventions, where K_ACh channel blockers have shown promise in AF management. Additionally, this study discusses the broader implications of K_ACh channel behavior, including its ubiquitous presence across different cardiac regions and species, contributing to a comprehensive understanding of AF dynamics. The implications of these findings are profound, suggesting that targeting K_ACh channels might offer new therapeutic avenues for AF treatment, particularly in cases resistant to conventional approaches. By integrating genetic, cellular, and pharmacological perspectives, this manuscript offers a holistic view of the potential mechanisms and therapeutic targets in AF, making a significant contribution to the field of cardiac arrhythmia research. Full article

Hepatocellular carcinoma (HCC) development is associated with altered modifications in DNA methylation, changing transcriptional regulation. Emerging evidence indicates that DNA methyltransferase 1 (DNMT1) plays a key role in the carcinogenesis process. This study aimed to investigate how pirfenidone (PFD) modifies this pathway and the effect generated by the association between c-Myc expression and DNMT1 activation. Rats F344 were used for HCC development using 50 mg/kg of diethylnitrosamine (DEN) and 25 mg/kg of 2-Acetylaminofluorene (2-AAF). The HCC/PFD group received simultaneous doses of 300 mg/kg of PFD. All treatments lasted 12 weeks. On the other hand, HepG2 cells were used to evaluate the effects of PFD in restoring DNA methylation in the presence of the inhibitor 5-Aza. Histopathological, biochemical, immunohistochemical, and western blot analysis were carried out and our findings showed that PFD treatment reduced the amount and size of tumors along with decreased Glipican-3, β-catenin, and c-Myc expression in nuclear fractions. Also, this treatment improved lipid metabolism by modulating PPARγ and SREBP1 signaling. Interestingly, PFD augmented DNMT1 and DNMT3a protein expression, which restores global methylation, both in our in vivo and in vitro models. In conclusion, our results suggest that PFD could slow down HCC development by controlling DNA methylation. Full article