Randomised control trial data support the use of stereotactic radiosurgery (SRS) in up to 4 brain metastases (BMs), with non-randomised prospective data complementing this for up to 10 BMs. There is debate in the neuro-oncology community as to the appropriateness of SRS in patients with >10 BMs. We present data from a large single-centre cohort, reporting survival in those with >10 BMs and in a >20 BMs subgroup. A total of 1181 patients receiving SRS for BMs were included. Data were collected prospectively from the time of SRS referral. Kaplan–Meier graphs and logrank tests were used to compare survival between groups. Multivariate analysis was performed using the Cox proportional hazards model to account for differences in group characteristics. Median survival with 1 BM (n = 379), 2–4 BMs (n = 438), 5–10 BMs (n = 236), and >10 BMs (n = 128) was 12.49, 10.22, 10.68, and 10.09 months, respectively. Using 2–4 BMs as the reference group, survival was not significantly different in those with >10 BMs in either our univariable (p = 0.6882) or multivariable analysis (p = 0.0564). In our subgroup analyses, median survival for those with >20 BMs was comparable to those with 2–4 BMs (10.09 vs. 10.22 months, p = 0.3558). This study contributes a large dataset to the existing literature on SRS for those with multi-metastases and supports growing evidence that those with >10 BMs should be considered for SRS. Full article

Expansive soils commonly encountered beneath foundations often lead to structural issues inducing expensive repairs. With the increase of the frequency of dry summers and irregular rainfall patterns, the clayey and marly soils become more and more sensitive to shrinking and swelling phenomena. So to find solutions and improve the knowledge on such phenomena especially in temperate countries where the saturation state is considered as the usual soil state, the impact of the soil density on shrinkage was studied by varying the compaction mode and introducing a swelling step before shrinkage. As expected, dynamically or statically compacted clayey or marly soils exhibited high shrinkage deformation when the soil had a low density. The swelling before shrinkage impacted the soil structure but ultimately had a low effect on shrinkage deformation. Swelling deformation was also influenced by density; the denser the soil, the more sensitive the compacted soil became to swelling. Furthermore, compaction modes induced differences in swelling or shrinkage amplitude that couldn’t be explained by microstructural observations. Finally, results demonstrated that intact soil behavior after shrinkage could be extrapolated from swelling–shrinkage tests conducted on remolded soil samples, thus decreasing the cost of field investigations. Full article

Gd/Fe-SnO₂ nanopowders as novel photocatalysts for the active removal of Rose Bengal dye and methyl parathion pesticide were synthesized with a low-cost coprecipitation route. The X-ray diffraction analysis of SnO₂, Sn_0.96Gd_0.02Fe_0.02O₂ and Sn_0.94Gd_0.02Fe_0.04O₂ nanopowders proved the formation of a tetragonal phase of tin oxide with average crystallite sizes in the range of 13–18 nm. The Fourier transform infrared (FTIR) spectra of all samples displayed the characteristic absorption bands of SnO₂. The nanopowder of the pure SnO₂ sample, as seen in its transmission electron microscope (TEM) image, contains spherical-like particles of variable sizes. The TEM images of the Sn_0.96Gd_0.02Fe_0.02O₂ and Sn_0.94Gd_0.02Fe_0.04O₂ powders revealed the synthesis of fine spherical nanoparticles. Based on the TEM images, the average particle size of the pure, (Gd, 2 wt% Fe) and (Gd, 4 wt% Fe) codoped SnO₂ nanopowders was estimated to be 14, 10 and 12 nm, respectively. After the addition of (Gd, 2 wt% Fe) and (Gd, 4 wt% Fe) to the SnO₂ structure, the band gap energy of SnO₂ was reduced from 3.4 eV to 2.88 and 2.82 eV, respectively. Significantly, the Sn_0.96Gd_0.02Fe_0.02O₂ nanocatalyst exhibited a high removal efficiency of 98 and 96% for Rose Bengal dye and methyl parathion pesticide after activation by sunlight for 35 and 48 min, respectively. Furthermore, this catalyst has shown perfect mineralization as well as high stability properties for the treatment of Rose Bengal dye and methyl parathion pesticide. These results suggest the suitability of the Sn_0.96Gd_0.02Fe_0.02O₂ nanocatalyst for the treatment of agriculture and industrial effluent under sunlight light energy. Full article

CuO is recognized as a promising anode material for sodium-ion batteries because of its impressive theoretical capacity of 674 mAh g⁻¹, derived from its multiple electron transfer capabilities. However, its practical application is hindered by slow reaction kinetics and rapid capacity loss caused by side reactions during discharge/charge cycles. In this work, we introduce an innovative approach to fabricating large-area CuO and CuO@Al₂O₃ flakes through a combination of magnetron sputtering, thermal oxidation, and atomic layer deposition techniques. The resultant 2D CuO flakes demonstrate excellent electrochemical properties with a high initial reversible specific capacity of 487 mAh g⁻¹ and good cycling stability, which are attributable to their unique architectures and superior structural durability. Furthermore, when these CuO flakes are coated with an ultrathin Al₂O₃ layer, the integration of the 2D structures with outer nanocoating leads to significantly enhanced electrochemical properties. Notably, even after 70 rate testing cycles, the CuO@Al₂O₃ materials maintain a high capacity of 525 mAh g⁻¹ at a current density of 50 mA g⁻¹. Remarkably, at a higher current density of 2000 mA g⁻¹, these materials still achieve a capacity of 220 mAh g⁻¹. Moreover, after 200 cycles at a current density of 200 mA g⁻¹, a high charge capacity of 319 mAh g⁻¹ is sustained. In addition, a full cell consisting of a CuO@Al₂O₃ anode and a NaNi_1/3Fe_1/3Mn_1/3O₂ cathode is investigated, showcasing remarkable cycling performance. Our findings underscore the potential of these innovative flake-like architectures as electrode materials in high-performance sodium-ion batteries, paving the way for advancements in energy storage technologies. Full article

It is possible to identify sub-populations of sows in every pig herd that consistently give birth to low birth weight (BW) piglets, irrespective of the litter size. A previous study from our group demonstrated that placental development is a main factor affecting the litter birth weight phenotype (LBWP) in sows, thereby impacting the BW of entire litters, but the biological and molecular pathways behind this phenomenon are largely unknown. The aim of this study was to investigate the differential gene expression in placental tissues at day 30 of gestation between low LBWP (LLBWP) vs. high LBWP (HLBWP) sows from a purebred Large White maternal line. Using mRNA sequencing, we found 45 differentially expressed genes (DEGs) in placental tissues of LLBWP and HLBWP sows. Furthermore, (GO) enrichment of upregulated DEGs predicted that there were two biological processes significantly related to cornification and regulation of cell population proliferation. To better understand the molecular interaction between cell proliferation and cornification, we conducted transcriptional factor binding site (TFBS) prediction analysis. The results indicated that a highly significant TFBS was located at the 5′ upstream of all four upregulated genes (CDSN, DSG3, KLK14, KRT17), recognized by transcription factors EGR4 and FOSL1. Our findings provide novel insight into how transcriptional regulation of two different biological processes interact in placental tissues of LLBWP sows. Full article

We investigated the type of blood component transfusion associated with increased postoperative delirium. Adult patients who underwent total knee arthroplasty (TKA) or total hip arthroplasty (THA) between 2017 and 2022 were included. Delirium was evaluated and treated within two days after surgery. A total of 6737 patients (4112 TKA/2625 THA) were retrospectively studied; 2.48% of patients in the TKA (n = 102) and THA (n = 65) groups had postoperative delirium. The blood transfusion (BT) and non-BT groups had similar percentages of patients who experienced postoperative delirium (3.34 vs. 2.35%, p = 0.080). In the multivariable logistic regression model, BT was not associated with postoperative delirium—adjusted odds ratio (aOR): 1.03, confidence interval (CI): 0.62, 1.71; p = 0.917. Moreover, transfusion of packed red blood cells (p = 0.651), platelets (p = 0.998), and cryoprecipitate (p = 0.999) were not associated with delirium. However, transfusion of fresh frozen plasma was associated with a 5.96-fold higher incidence of delirium—aOR: 5.96, 95% CI: 2.72, 13.04; p < 0.001. In conclusion, perioperative BT was not associated with postoperative delirium in patients who underwent TKA or THA. However, FFP transfusion was associated with an increased incidence of postoperative delirium. Full article

Curcumin (Curcumin) belongs to the polyphenol family. It is extracted by drying the root of a plant of Asian origin, belonging to the Zingiberaceae family. The best-known species is Curcumincuma Longa. Curcumin has been recognized as having great therapeutic powers since ancient times. Studies on curcumin have since confirmed its powerful antioxidant properties, preventing both the formation of free radicals and their neutralization, having anti-inflammatory, antibacterial, immunological, and neuroprotective properties, as well as being a regulator of the intestinal microbiota with beneficial effects on the clinical manifestations of metabolic syndrome. Our study aimed to highlight how all these therapeutic aspects could benefit oral health, both preventing and improving the course of pathological processes. The effect of mouthwashes, and curcumin-based gels on the regulation of bacterial plaque and in the control of gingivitis, was largely comparable to that of using 0.20% chlorhexidine, with fewer side effects. Being a highly hydrophobic substance, it has a high permeability to cross the cell membrane. Bioavailability increases when combined with liposoluble substances (e.g., olive oil) and piperine, which improves absorption. Curcumin also has a negligible degree of toxicity, making it an excellent alternative to the use of gold standard products for oral disinfection. Full article

The maximum thickness for ferritic steel specimens’ residual stress measurements using neutron diffraction is known to be about 80 mm. This paper proposes a new neutron diffraction configuration of residual stress measurements for cases that are over 80 mm thick. The configuration utilizes a neutron beam with a wavelength of 1.55 Å diffracted from the (220) plane with a diffraction angle (2θ) of 99.4°. The reason for the deep penetration capability is attributed to the chosen wavelength having enough intensities due to the low cross-section near the Bragg edge and the reduced beam path length (~16 mm) reflected by the large diffraction angle. Neutron diffraction experiments with this configuration can decrease strain errors up to ±150 με, corresponding to a stress of about ±30 MPa. Full article

Approximately half of the cases of chronic kidney disease (CKD) in childhood are caused by congenital anomalies of the kidney and urinary tract (CAKUT). Specific genes were identified as having significant importance in regard to the underlying genetic factors responsible for the CAKUT phenotype, and in our research, we focused on analyzing and comparing the expression levels of ectodysplasin A2 receptor (EDA2R), protocadherin9 (PCDH9), and TNF receptor-associated factor 7 (TRAF7) proteins in the cortex and medulla of healthy control kidneys during developmental phases 2, 3, and 4. We also performed an analysis of the area percentages of the mentioned proteins in the cortical and medullary sections of healthy embryonic and fetal kidneys compared to those affected by CAKUT, including duplex kidneys (DK), horseshoe kidneys (HK), hypoplastic kidneys (HYP), and dysplastic kidneys (DYS). We found that the CAKUT candidate gene proteins EDA2R, PCDH9, and TRAF7 are all expressed during normal human kidney development stages. In DYS, the expression of EDA2R was higher than in normal kidneys, likely due to EDA2R’s role in apoptosis, which was upregulated in specific cases and could possibly contribute to the formation of DYS. The expression of PCDH9 was lower in HK, which can be attributed to the possible role of PCDH9 in cell migration suppression. Decreased PCDH9 expression is linked to increased cell migration, potentially contributing to the development of HK. The level of TRAF7 expression was reduced in all examined kidney disorders compared to normal kidneys, suggesting that this reduction might be attributed to the crucial role of TRAF7 in the formation of endothelium and ciliogenesis, both of which are essential for normal kidney development. Further research is required to ascertain the function of these proteins in both the typical development of the kidney and in CAKUT. Full article

The purpose of this paper is to automate the interpretation of data during ultrasonic diffraction using a non-destructive testing (NDT) technique to accurately size defects for assisting in decision-making. A convolutional neural network (CNN) architecture was developed to automatically measure the length of the defect. Using the architecture, the population of A-scan signals in the scanning path was classified. The defect region was extracted and its size in the scanning direction was obtained by the connected region solution algorithm based on the classification results. The arrival time of diffraction waves was accurately identified by the intelligent denoising framework proposed, combined with Hilbert transform, and then the height of defects was calculated by corresponding geometric relations. The estimation results demonstrate that the measurement method can be considered as a useful technique for crack sizing in industrial structures, even in the case of complex noise. Full article

This manuscript presents the use of three novel technologies for the implementation of wireless green battery-less sensors that can be used in agriculture. The three technologies, namely, additive manufacturing, energy harvesting, and wireless power transfer from airborne transmitters carried from UAVs, are considered for smart agriculture applications, and their combined use is demonstrated in a case study experiment. Additive manufacturing is exploited for the implementation of both RFID-based sensors and passive sensors based on humidity-sensitive materials. A number of energy-harvesting systems at UHF and ISM frequencies are presented, which are in the position to power platforms of wireless sensors, including humidity and temperature IC sensors used as agriculture sensors. Finally, in order to provide wireless energy to the soil-based sensors with energy harvesting features, wireless power transfer (WPT) from UAV carried transmitters is utilized. The use of these technologies can facilitate the extensive use and exploitation of battery-less wireless sensors, which are environmentally friendly and, thus, “green”. Additionally, it can potentially drive precision agriculture in the next era through the implementation of a vast network of wireless green sensors which can collect and communicate data to airborne readers so as to support, the Artificial Intelligence and Machine Learning-based decision-making with data. Full article

Childhood stunting is a significant public health concern in Bangladesh. This study analysed the data from the Healthy Village programme, which aims to address childhood stunting in southern coastal Bangladesh. The aim was to assess childhood stunting prevalence over time and explore the risk factors in the programme areas. A cross-sectional, secondary data analysis was conducted for point-prevalence estimates of stunting from 2018 to 2021, including 132,038 anthropometric measurements of under-five children. Multivariate logistic regression analyses were conducted for risk factor analysis (n = 20,174). Stunting prevalence decreased from 51% in 2018 to 25% in 2021. The risk of stunting increased in hardcore poor (aOR: 1.46, 95% CI: 1.27, 1.68) and poor (aOR: 1.50, 95% CI: 1.33, 1.70) versus rich households, children with mothers who were illiterate (aOR: 1.25, 95% CI: 1.09, 1.44) and could read and write (aOR: 1.35, 95% CI: 1.16, 1.56) versus mothers with higher education, and children aged 1–2 years compared with children under one year (aOR: 1.32, 95% CI: 1.20, 1.45). The stunting rate was halved over three years in programme areas, which is faster than the national trend. We recommend addressing socioeconomic inequalities when tackling stunting and providing targeted interventions to mothers during the early weaning period. Full article

The autonomous vehicle is an innovative field for the application of machine learning algorithms. Controlling an agent designed to drive safely in traffic is very complex as human behavior is difficult to predict. An individual’s actions depend on a large number of factors that cannot be acquired directly by visualization. The size of the vehicle, its vulnerability, its perception of the environment and weather conditions, among others, are all parameters that profoundly modify the actions that the optimized model should take. The agent must therefore have a great capacity for adaptation and anticipation in order to drive while ensuring the safety of users, especially pedestrians, who remain the most vulnerable users on the road. Deep reinforcement learning (DRL), a sub-field that is supported by the community for its real-time learning capability and the long-term temporal aspect of its objectives looks promising for AV control. In a previous article, we were able to show the strong capabilities of a DRL model with a continuous action space to manage the speed of a vehicle when approaching a pedestrian crossing. One of the points that remains to be addressed is the notion of discrete decision-making intrinsically linked to speed control. In this paper, we will present the problems of AV control during a pedestrian crossing, starting with a modelization and a DRL model with hybrid action space adapted to the scalability of a vehicle-to-pedestrian (V2P) encounter. We will also present the difficulties raised by the scalability and the curriculum-based method. Full article

Herbal teas have attracted attention as functional beverages containing luteolin and apigenin, which exhibit antioxidant and anti-inflammatory effects. The objective of this study was to develop a sensitive online automated method to determine these flavones’ contents in herbal teas using in-tube solid-phase microextraction (IT-SPME) coupled with liquid chromatography–tandem mass spectrometry (LC–MS/MS). These compounds were extracted and concentrated by IT-SPME using a Supel Q PLOT capillary column and then separated and detected within 6 min using a CAPCELL PAK C18 MG III analytical column and a negative electrospray ionization-mode multiple-reaction monitoring system by LC–MS/MS. The detection limits (S/N = 3) for luteolin and apigenin were 0.4 and 0.8 pg mL⁻¹, respectively, and the calibration curves were linear in the range of 2–2000 pg mL⁻¹ with correlation coefficients above 0.9995, and intra-day and inter-day precisions with relative standard deviations below 2.9 and 3.6% (n = 6), respectively. The luteolin and apigenin in herbal tea were quantified using IT-SPME/LC-MS/MS following the acid hydrolysis of their glycosides. Among the 10 herbal teas tested, luteolin was detected in peppermint and sage at concentrations of 375 and 99 µg mL⁻¹, respectively, while apigenin was detected in German chamomile at 110 µg mL⁻¹, which were higher than in the other herbal teas. The method is expected to be a useful method for evaluating the efficacy of luteolin and apigenin in herbal teas as functional beverages. Full article

Despite recent advances, the prognosis of acute myeloid leukemia (AML) remains unsatisfactory due to disease recurrence and the development of resistance to both conventional and novel therapies. Engineered T cells expressing chimeric antigen receptors (CARs) on their cellular surface represent one of the most promising anticancer agents. CAR-T cells are increasingly used in patients with B cell malignancies, with remarkable clinical results despite some immune-related toxicities. However, at present, the role of CAR-T cells in myeloid neoplasms, including AML, is extremely limited, as specific molecular targets for immune cells are generally lacking on AML blasts. Besides the paucity of dispensable targets, as myeloid antigens are often co-expressed on normal hematopoietic stem and progenitor cells with potentially intolerable myeloablation, the AML microenvironment is hostile to T cell proliferation due to inhibitory soluble factors. In addition, the rapidly progressive nature of the disease further complicates the use of CAR-T in AML. This review discusses the current state of CAR-T cell therapy in AML, including the still scanty clinical evidence and the potential approaches to overcome its limitations, including genetic modifications and combinatorial strategies, to make CAR-T cell therapy an effective option for AML patients. Full article

The Epstein-Barr virus (EBV) is frequently found in endomyocardial biopsies (EMBs) from patients with heart failure, but the detection of EBV-specific DNA has not been associated with progressive hemodynamic deterioration. In this paper, we investigate the use of targeted next-generation sequencing (NGS) to detect EBV transcripts and their correlation with myocardial inflammation in EBV-positive patients with heart failure with reduced ejection fraction (HFrEF). Forty-four HFrEF patients with positive EBV DNA detection and varying degrees of myocardial inflammation were selected. EBV-specific transcripts from EMBs were enriched using a custom hybridization capture-based workflow and, subsequently, sequenced by NGS. The short-read sequencing revealed the presence of EBV-specific transcripts in 17 patients, of which 11 had only latent EBV genes and 6 presented with lytic transcription. The immunohistochemical staining for CD3⁺ T lymphocytes showed a significant increase in the degree of myocardial inflammation in the presence of EBV lytic transcripts, suggesting a possible influence on the clinical course. These results imply the important role of EBV lytic transcripts in the pathogenesis of inflammatory heart disease and emphasize the applicability of targeted NGS in EMB diagnostics as a basis for specific treatment. Full article

The Côa region in inner-northern Portugal heavily relies on viticulture, which is a cornerstone of its economy and cultural identity. Understanding the intricate relationship between climatic variables and wine production (WP) is crucial for adapting management practices to changing climatic conditions. This study employs machine learning (ML), specifically random forest (RF) regression, to predict grapevine yields in the Côa region using high-resolution climate data for 2004–2020. SHAP (SHapley Additive exPlanations) values are used to potentially explain the non-linear relationships between climatic factors and WP. The results reveal a complex interplay between predictors and WP, with precipitation emerging as a key determinant. Higher precipitation levels in April positively impact WP by replenishing soil moisture ahead of flowering, while elevated precipitation and humidity levels in August have a negative effect, possibly due to late-season heavy rainfall damaging grapes or creating more favorable conditions for fungal pathogens. Moreover, warmer temperatures during the growing season and adequate solar radiation in winter months favor higher WP. However, excessive radiation during advanced growth stages can lead to negative effects, such as sunburn. This study underscores the importance of tailoring viticultural strategies to local climatic conditions and employing advanced analytical techniques such as SHAP values to interpret ML model predictions effectively. Furthermore, the research highlights the potential of ML models in climate change risk reduction associated with viticulture, specifically WP. By leveraging insights from ML and interpretability techniques, policymakers and stakeholders can develop adaptive strategies to safeguard viticultural livelihoods and stable WP in a changing climate, particularly in regions with a rich agrarian heritage, such as the Côa region. Full article

We reanalyze the phenomenon of verbal (non)agreement with the 2SG tu in a megacorpus of Brazilian Portuguese compiled from the web. Unlike previous research, which has analyzed sociolinguistic interview data and regional differences, we examine these data with a focus on the internal linguistic factors that constrain the variability. Our analysis of 4860 tokens of tu + verb reveals that non-agreement with the 3SG verb form is by far the most common pattern, 2SG agreement being relatively infrequent. Individual verb lexemes show highly distinct rates of (non)agreement. In addition, the specific tense/aspect/mood forms and main/auxiliary status are likewise significant factors affecting the variation. We conclude that future studies of this phenomenon should not ignore these internal linguistic factors. We situate our study within a group of other recent studies in Romance linguistics, which have found that individual verbal and constructional patterns can have diverse effects on morphosyntactic variation. Full article

With an ageing global population, healthcare systems confront challenges unique to the elderly. Current care models primarily manage health–illness shifts but frequently miss developmental transitions, particularly for older adults. Meleis’s transition theory offers an underutilized framework to rejuvenate our gerontogeriatric nursing approach. This article aims to articulate and advocate the value of Meleis’s transition theory as a framework for gerontogeriatric nursing, focusing on developmental transitions, thereby seeking a transformative change in the quality of elderly care. The article delves into Meleis’s transition theory’s vital components—transition types, conditions, and nursing therapeutics. It explores how these can be a multifaceted guide for gauging and overseeing ageing’s developmental shifts; adopting this theoretical perspective deepens our comprehension and bears tangible implications. Nurses versed in this theory could appreciate the benefits of a nuanced approach to the elderly, distinguishing it from the conventional biomedical stance. As the demands of an ageing populace grow, the integration of Meleis’s transition theory into nursing practices is not merely beneficial but imperative, setting a new standard for comprehensive and specialized elderly care. Full article

Malawi has the potential to explore the utilization of biogas technology. The technology has existed in the country for decades. However, the uptake has been lower than expected. Further, there has been a high rate of dis-adoption of the installed systems. To deal with the problem, this study explored the opportunities and barriers to biogas technology to enhance biogas adoption and utilization in Malawi. Qualitative research methods using key informant interviews were employed to collect the data from biogas adopters, dis-adopters, potential adopters, and experts. A total of 22 households and 6 experts were interviewed. The findings of the study show that the country has opportunities for biogas adoption and utilization. The most mentioned opportunities were livestock farming practices, constraints to access to reliable energy sources, associated benefits of biogas technology, and land holding. However, the adoption of the technology has faced several challenges. Commonly cited barriers were the high installation and maintenance costs, inadequate feedstock, inappropriate dissemination approaches, lack of training after installation services and expertise, lack of reliable water sources, absence of ownership, lack of cooperation amongst institutions involved in biogas promotion, lack of a coordinating body for institutions involved in biogas dissemination, lack of standards, and socio-cultural factors. To overcome the challenges, strategies were identified, and these include the provision of incentives, loans and subsidies, provision of technical support services, having demonstration sites, employing suitable dissemination approaches, co-digestion or diversification of raw materials, awareness campaigns, and collaboration amongst sectors involved in biogas dissemination. Full article

In modern agricultural production, where a small number of commercial cultivars dominate, the collection, evaluation, and preservation of germplasm are important tasks to reduce the erosion of genes and preserve biodiversity. The aim of this study is to characterize the morphological and fruit chemical properties of the pomegranate germplasm grown on the East Adriatic coast, including the commercial cultivars ‘Hicaznar’, ‘Granada’, and ‘Wonderful’, and to highlight the characteristics with the greatest discriminating power. The characterization of the tree, leaf, flower, arils, seed, and juice was carried out using the UPOV descriptor. The colors of the peel, arils, and juice were analyzed according to the CIEL*a*b* method, total soluble solids were measured using refractometers, and total acidity was determined by titration with 0.1 M NaOH. The research results showed significant diversity between the cultivars, which were grouped into several clusters using an unsupervised analysis technique. Factors such as plant vigor, plant growth habit, predominant number of leaves per node on young shoots, crown type, fruit shape, fruit shape in cross-section, peel weight, total aril weight, aril weight, number of arils per fruit, seed length and width, seed yield, total acidity, TSS/TA ratio, and color parameters of the peel, arils, and juice showed high variability, indicating their strong discriminating power in determining the phenotypic diversity of pomegranate. Full article

Keloids, marked by abnormal cellular proliferation and excessive extracellular matrix (ECM) accumulation, pose significant therapeutic challenges. Ethyl pyruvate (EP), an inhibitor of the high-mobility group box 1 (HMGB1) and TGF-β1 pathways, has emerged as a potential anti-fibrotic agent. Our research evaluated EP’s effects on keloid fibroblast (KF) proliferation and ECM production, employing both in vitro cell cultures and ex vivo patient-derived keloid spheroids. We also analyzed the expression levels of ECM components in keloid tissue spheroids treated with EP through immunohistochemistry. Findings revealed that EP treatment impedes the nuclear translocation of HMGB1 and diminishes KF proliferation. Additionally, EP significantly lowered mRNA and protein levels of collagen I and III by attenuating TGF-β1 and pSmad2/3 complex expression in both human dermal fibroblasts and KFs. Moreover, metalloproteinase I (MMP-1) and MMP-3 mRNA levels saw a notable increase following EP administration. In keloid spheroids, EP induced a dose-dependent reduction in ECM component expression. Immunohistochemical and western blot analyses confirmed significant declines in collagen I, collagen III, fibronectin, elastin, TGF-β, AKT, and ERK 1/2 expression levels. These outcomes underscore EP’s antifibrotic potential, suggesting its viability as a therapeutic approach for keloids. Full article