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Fasciolosis, a globally re-emerging zoonotic disease, is mostly caused by the parasitic infection with Fasciola hepatica, often known as the liver fluke. This disease has a considerable impact on livestock productivity. This study aimed to evaluate the fluke burdens and faecal egg counts in goats that were administered phage clones of cathepsin L mimotopes and then infected with F. hepatica metacercariae. Additionally, the impact of vaccination on the histology of the reproductive system, specifically related to egg generation in adult parasites, was examined. A total of twenty-four goats, which were raised in sheds, were divided into four groups consisting of six animals each. These groups were randomly assigned. The goats were then subjected to two rounds of vaccination. Each vaccination involved the administration of 1 × 10¹³ phage particles containing specific mimotopes for cathepsin L2 (group 1: PPIRNGK), cathepsin L1 (group 2: DPWWLKQ), and cathepsin L1 (group 3: SGTFLFS). The immunisations were carried out on weeks 0 and 4, and the Quil A adjuvant was used in combination with the mimotopes. The control group was administered phosphate-buffered saline (PBS) (group 4). At week 6, all groups were orally infected with 200 metacercariae of F. hepatica. At week 22 following the initial immunisation, the subjects were euthanised, and adult F. hepatica specimens were retrieved from the bile ducts and liver tissue, and subsequently quantified. The specimens underwent whole-mount histology for the examination of the reproductive system, including the testis, ovary, vitellaria, Mehlis’ gland, and uterus. The mean fluke burdens following the challenge were seen to decrease by 50.4%, 62.2%, and 75.3% (p < 0.05) in goats that received vaccinations containing cathepsin L2 PPIRNGK, cathepsin L1 DPWWLKQ, and cathepsin L1 SGTFLFS, respectively. Animals that received vaccination exhibited a significant reduction in the production of parasite eggs. The levels of IgG1 and IgG2 isotypes in vaccinated goats were significantly higher than in the control group, indicating that protection is associated with the induction of a mixed Th1/Th2 immune response. The administration of cathepsin L to goats exhibits a modest level of efficacy in inducing histological impairment in the reproductive organs of liver flukes, resulting in a reduction in egg output. Full article

This study was designed to compare the antioxidant, antitumor and anti-inflammatory effects of essential oils from the bark and flower of Magnolia officinalis Rehd. et Wils. Distillation extraction and steam distillation were used to extract EOs from the bark and flower. The results showed that the contents of EOs of SDE-F and SDE-B were much higher than that of SD-F and SD-B. EOs from the bark were rich in eudesmol (especially α-eudesmol) and exhibited a stronger antioxidant effect than the flower. The anti-tumor effects of SD-B and SD-F on HepG2 and MDA-MB-231 cells were better than that of SDE-B and SDE-F. The inhibitory rates of SD-B and SD-F on MDA-MB-231 cells were 59.21% and 48.27%, exceeding that of positive control 5-fluorouracil (47.04%) at 50 μg/mL. All four EOs exhibited excellent anti-inflammatory activities through the regulation of nitric oxide production and pro-inflammation cytokines in LPS-induced RAW 264.7 cells and they also remarkably suppressed the mRNA expressions of nitric oxide synthase, IL-6 and TNF-α at the concentration higher than that of positive control dexamethasone. These results indicated significant differences in the composition, and anti-inflammatory and anti-tumor activities of EOs extracted by different methods and provided a theoretical basis for their development and utilization. Full article

Saline–alkali stress is a significant abiotic stress that restricts plant growth globally. Basic region leucine zipper (bZIP) transcription factor proteins are widely involved in plants in response to abiotic stress such as saline–alkali stress. Based on transcriptome and quantitative real-time PCR (qRT-PCR), we found that the MhbZIP23 gene could respond to saline–alkali stress. Despite this discovery, the underlying mechanism by which the MhbZIP23 transcription factor responds to saline–alkaline stress remains unexplored. To address this gap in knowledge, we successfully cloned the MhbZIP23 (MD05G1121500) gene from Malus halliana for heterologous expression in Arabidopsis thaliana, facilitating the investigation of its functional role in stress response. Compared to the wild type (WT), Arabidopsis plants demonstrated enhanced growth and a lower degree of wilting when subjected to saline–alkali stress. Furthermore, several physiological indices of the plants altered under such stress conditions. The transgenic Arabidopsis plants (OE-5, 6, and 8), which grew normally, exhibited a higher chlorophyll content and had greater root length in comparison to the control check (CK). MhbZIP23 effectively regulated the levels of the osmoregulatory substance proline (Pro), enhanced the activities of antioxidant enzymes such as peroxidase (POD) and superoxide dismutase (SOD), and reduced the levels of malondialdehyde (MDA) and relative conductivity (REC). These actions improved the ability of plant cells in transgenic Arabidopsis to counteract ROS, as evidenced by the decreased accumulation of O₂^- and hydrogen peroxide (H₂O₂). In summary, the MhbZIP23 gene demonstrated effectiveness in alleviating saline–alkali stress in M. halliana, presenting itself as an outstanding resistance gene for apples to combat saline–alkali stress. Full article

Brown tumors, an exceptional bone complication of severe primary (PHP) or renal (secondary) hyperparathyroidism (RHP), are caused by long-standing, elevated parathormone (PTH)-induced osteoclast activation causing multinucleated giant cell conglomerates with hemosiderin deposits in addition to the local production of cytokines and growth factors. We aim to present an adult case series including two females displaying this complication as part of a multidisciplinary complex panel in high PTH-related ailments. The approach was different since they had distinct medical backgrounds and posed a wide area of challenges amid real-life settings, namely, a 38-year-old lady with PHP and long-term uncontrolled hypercalcemia (with a history of pregnancy-associated PHP, the removal of a cystic jaw tumor, as well as a family and personal positive diagnosis of polycystic kidney disease, probably a PHP-jaw tumor syndrome), as well as, a 26-year-old woman with congenital single kidney and chronic renal disease-associated RHP who was poorly controlled under dialysis and developed severe anemia and episodes of metabolic acidosis (including one presentation that required emergency hemodialysis and was complicated with convulsive seizures, followed by resuscitated respiratory arrest). Both subjects displayed a severe picture of PHP/RHP with PTH levels of >1000 pg/mL and >2000 pg/mL and elevated serum bone turnover markers. Additionally, they had multiple brown tumors at the level of the ribs and pelvis (asymptomatically) and the spine, skull, and pelvis (complicated with a spontaneous cervical fracture). As an endocrine approach, the control of the underlying parathyroid disease was provided via surgery in PHP (for the postparathyroidectomy hungry bone syndrome) via medical intervention (with vitamin D analogs) in RHP. Additionally, in this case, since the diagnosis was not clear, a multidisciplinary decision to perform a biopsy was taken (which proved inconclusive), and the resection of the skull tumor to confirm the histological traits. This series highlights the importance of addressing the entire multidisciplinary panel of co-morbidities for a better outcome in patients with PHP/RHP-related brown tumors. However, in the instance of real-life medicine, poor compliance and reduced adherence to recommendations might impair the overall health status. Thus, sometimes, a direct approach at the level of cystic lesion is taken into consideration; this stands for a narrow frame of decision, and it is a matter of personalized decision. As seen here, brown tumors represent the hidden face of PHP/RHP, primarily the complex and severe forms, and awareness is essential even in the modern era. Full article

Abstract: Arsenic-containing hydrocarbons (AsHCs) are common in marine organisms. However, there is little research on their effects on the central nervous system's advanced activities, such as cognition. Bidirectional synaptic plasticity dynamically regulates cognition through the balance of long-term potentiation (LTP) and long-term depression (LTD). However, the effects of AsHCs on bidirectional synaptic plasticity and the underlying molecular mechanisms remain unexplored. This study provides the first evidence that 15 μg As L^-1 AsHC 360 enhances bidirectional synaptic plasticity, occurring during the maintenance phase rather than the baseline phase. Further calcium gradient experiments hypothesize that AsHC 360 may enhance bidirectional synaptic plasticity by affecting calcium ion levels. The enhancement of bidirectional synaptic plasticity by 15 μg As L^-1 AsHC 360 holds significant implications in improving cognitive function, treating neuro-psychiatric disorders, promoting neural recovery, and enhancing brain adaptability. Full article

The atavistic theory of cancer posits that cancer emerges and progresses through the reversion of cellular phenotypes to more ancestral types with genomic and epigenetic changes deactivating recently evolved genetic modules and activating ancient survival mechanisms. This theory aims at explaining the known cancer hallmarks and the paradox of cancer’s predictable progression despite the randomness of genetic mutations. Lineweaver and colleagues recently proposed the Serial Atavism Model (SAM), an enhanced version of the atavistic theory, which suggests that cancer progression involves multiple atavistic reversions where cells regress through evolutionary stages, losing recently evolved traits first and reactivating primitive ones later. The Warburg effect, where cancer cells upregulate glycolysis and lactate production in the presence of oxygen instead of using oxidative phosphorylation, is one of the key feature of the SAM. It is associated with the metabolism of ancient cells living on Earth before the oxygenation of the atmosphere. This review addresses the question of whether cancer metabolism can be considered as an atavistic reversion. By analyzing several known characteristics of cancer metabolism, we reach the conclusion that this version of the atavistic theory does not provide an adequate conceptual frame for cancer research. Cancer metabolism spans a whole spectrum of metabolic states which cannot be fully explained by a sequential reversion to an ancient state. Moreover, we interrogate the nature of cancer metabolism and discuss its characteristics within the framework of the SAM. Full article

(1) Background: Among the chronic complications of type 2 diabetes mellitus, cancer has become the leading cause of death in several countries. Our objective was to determine whether prevalent type 2 diabetes mellitus is associated with a higher incidence of cancer. (2) Methods: This study comprised a nationwide analysis conducted in Hungary. The study population was divided into two groups: a type 2 diabetes mellitus group vs. a non-diabetic group. The primary outcome was the risk related to overall cancer incidence; a key secondary outcome was the overall incidence of cancer in distinct study years; and a further outcome was the annual percent changes. (3) Results: The odds ratio related to the overall incidence of cancer was 2.50 (95% confidence interval: 2.46–2.55, p < 0.0001) in patients with diabetes as related to non-diabetic controls. The odds ratio was higher in males than in females [OR_males: 2.76 (2.70–2.82) vs. OR_females: 2.27 (2.22–2.33), p < 0.05 for male-to-female comparison]. The annual cancer incidence rate declined in non-diabetic controls, but not in patients with diabetes [−1.79% (−2.07–−1.52%), p < 0.0001] vs. −0.50% (−1.12–+0.10%), p = 0.0991]. Several types of cancer showed a decreasing tendency in non-diabetic controls, but not in patients with type 2 diabetes. (4) Conclusions: Type 2 diabetes is associated with a higher risk of cancer. While the cancer incidence decreased for non-diabetic individuals with time, it remained unchanged in patients with T2DM. Full article

Drought stress is a major meteorological threat to crop growth and yield. Barley (Hordeum vulgare L.) is a vital cereal crop with strong drought tolerance worldwide. However, the underlying growth properties and metabolomic regulatory module of drought tolerance remains less known. Here, we investigated the plant height, spike length, effective tiller, biomass, average spikelets, 1000-grain weight, number of seeds per plant, grain weight per plant, ash content, protein content, starch content, cellulose content, and metabolomic regulation mechanisms of drought stress in barley. Our results revealed that the growth properties were different between ZDM5430 and IL-12 under drought stress at different growth stages. We found that a total of 12,235 metabolites were identified in two barley genotype root samples with drought treatment. More than 50% of these metabolites showed significant differences between the ZDM5430 and IL-12 roots. The Kyoto Encyclopedia of Genes and Genomes pathway analysis identified 368 differential metabolites mainly involved in starch and sucrose metabolism, the pentose phosphate pathway, pyrimidine metabolism, phenylalanine, tyrosine, and tryptophan biosynthesis in ZDM5430 under drought stress, whereas the different metabolites of IL-12 under drought stress related to starch and sucrose metabolism, the pentose phosphate pathway, 2-oxocarboxylic acid metabolism, cutin, suberine and wax biosynthesis, carbon metabolism, fatty acid biosynthesis, and C5-branched dibasic acid metabolism. These metabolites have application in the tricarboxylic cycle, the urea cycle, the met salvage pathway, amino acid metabolism, unsaturated fatty acid biosynthesis, phenolic metabolism, and glycolysis. On the other hand, the expression patterns of 13 genes related to the abovementioned bioprocesses in different barley genotypes roots were proposed. These findings afford an overview for the understanding of barley roots’ metabolic changes in the drought defense mechanism by revealing the differently accumulated compounds. Full article

Artificial intelligence (AI) has helped enhance the management of software development projects through automation, improving efficiency and enabling project professionals to focus on strategic aspects. Despite its advantages, applying AI in software development project management still faces several challenges. Thus, this study investigates key obstacles to applying artificial intelligence in project management, specifically in the project planning phase. This research systematically reviews the existing literature. The review comprises scientific articles published from 2019 to 2024 and, from the inspected records, 17 papers were analyzed in full-text form. In this review, 10 key barriers were reported and categorized based on the Technology–Organization–Environment (TOE) framework. This review showed that eleven articles reported technological challenges, twelve articles identified organizational challenges, and six articles reported environmental challenges. In addition, this review found that there was relatively little interest in the literature on environmental challenges, compared to organizational and technological barriers. Full article

The aim of this study was to assess the level of contamination of the common dandelion—Taraxacum officinale—with selected metals (Mn, Fe, Ni, Cu, Zn, Cd, and Pb) and to demonstrate that this plant can be used in passive biomonitoring of industrial sites. Two sample transects (the first was near a forest, an area potentially uncontaminated by analytes [A], while the second ran near a steel mill, a contaminated area [B]), each about 1.5 km long, located in Ozimek, Opole Province, Poland, were used in this study. Metals in plant and soil samples were determined by atomic absorption spectroscopy (AAS). Based on the analysis of the obtained results to determine the concentration of metals, plants at site A were more contaminated with Mn (240 mg/kg d.m.) and those at site B with Fe (635 mg/kg d.m.). Mean Pb values (8.39 mg/kg d.m.) were higher at the industrial site (B) and statistically significant at the forest site (A), together with Mn and Fe at the p < 0.001 level. The BCF values for T. officinale showed that Cu (0.473) and Zn (0.785) accumulated to an average degree on both transects. This shows that dandelion is heavily loaded with these metals. Both dandelion and soil samples showed the highest concentrations of Mn, Fe, and Zn, especially in the polluted area B, which is the result of pollution not only from the smelter (dust from electric arc furnaces in steel smelting, extraction installations in production halls transmitting pollutants into the air from molding sand, or waste from molding and core masses dumped on the heap and blown by the wind from the landfill) but also from the high anthropopressure caused by human activity—for example, heating processes or road transport. Our results confirmed that Taraxacum officinale can be successfully used as a herbal plant in passive biomonitoring to assess the quality of the environment, but it must be collected from uncontaminated areas if we want to use it like a medicinal plant. Full article

The E6 and E7 oncoproteins of high-risk types of human papillomavirus (HR-HPV) are crucial for the development of cervical cancer (CC). Small interfering RNAs (siRNAs) are explored as novel therapies that silence these oncogenes, but their clinical use is hampered by inefficient delivery systems. Modification (pegylation) with polyethylene glycol (PEG) of liposomal siRNA complexes (siRNA lipoplexes) may improve systemic stability. We studied the effect of siRNA targeting HPV16 E6, delivered via cationic liposomes (lipoplexes), on cellular processes in a cervical carcinoma cell line (CaSki) and its potential therapeutic use. Lipoplexes-PEG-HPV16 E6, composed of DOTAP, Chol, DOPE, and DSPE-PEG2000 were prepared. The results showed that pegylation (5% DSPE-PEG2000) provided stable siRNA protection, with a particle size of 86.42 ± 3.19 nm and a complexation efficiency of over 80%; the siRNA remained stable for 30 days. These lipoplexes significantly reduced HPV16 E6 protein levels and restored p53 protein expression, inhibiting carcinogenic processes such as proliferation by 25.74%, migration (95.7%), and cell invasion (97.8%) at concentrations of 20 nM, 200 nM, and 80 nM, respectively. In conclusion, cationic lipoplexes-PEG-HPV16 E6 show promise as siRNA carriers for silencing HPV16 E6 in CC. Full article

Background/Objectives: This study aims to analyze the efficacy and safety of the two pelvic fixation systems, S-hooks (SH) and lumbar-sacral-alar-iliac (SAI) screws, when used in association with magnetically controlled growing rods (MCGRs) in non-ambulatory children with severe neuromuscular scoliosis (NMS). Methods: Forty-one patients were retrospectively examined and subdivided corresponding to ilium hook fixation or SAI screws. The major curve correction (%) and pelvic obliquity (PO) correction (%) were assessed utilizing scoliosis plain film radiographs over time. Complications and unplanned return to the operating room (UPROR) were recorded. Patient-specific pre- and postoperative values were included in a backward stepwise regression model to assess UPROR. Results: Mean age at index intervention was 9.4 years. Preoperative main curve was 81° and PO was 22°. 21 and 20 patients were categorized into the SH and SAI subgroups, respectively. Initial curve correction was significantly better in the SAI subgroup (63 vs. 42% in the SH, p = 0.045), while PO correction was equally good. Curve and PO correction were maintained throughout the follow-up period of 55 months. UPROR rate was 38% in the SH subgroup, and 5% in the SAI subgroup (p = 0.010). Regression analysis identified postoperative curve correction as predictive value for UPROR (p = 0.006). Conclusion: SAI screw fixation has a low UPROR rate and achieves superior curve correction. S-hooks are a viable option to correct PO and NMS in children with high operative risk to reduce operative time, but revision surgery is not uncommon. Full article

Climate change is causing permafrost in the Qinghai–Tibet Plateau to degrade, triggering thermokarst hazards and impacting the environment. Despite their ecological importance, the distribution and risks of thermokarst lakes are not well understood due to complex influencing factors. In this study, we introduced a new interpretable ensemble learning method designed to improve the global and local interpretation of susceptibility assessments for thermokarst lakes. Our primary aim was to offer scientific support for precisely evaluating areas prone to thermokarst lake formation. In the thermokarst lake susceptibility assessment, we identified ten conditioning factors related to the formation and distribution of thermokarst lakes. In this highly accurate stacking model, the primary learning units were the random forest (RF), extremely randomized trees (EXTs), extreme gradient boosting (XGBoost), and categorical boosting (CatBoost) algorithms. Meanwhile, gradient boosted decision trees (GBDTs) were employed as the secondary learning unit. Based on the stacking model, we assessed thermokarst lake susceptibility and validated accuracy through six evaluation indices. We examined the interpretability of the stacking model using three interpretation methods: accumulated local effects (ALE), local interpretable model-agnostic explanations (LIME), and Shapley additive explanations (SHAP). The results showed that the ensemble learning stacking model demonstrated superior performance and the highest prediction accuracy. Approximately 91.20% of the total thermokarst hazard points fell within the high and very high susceptible areas, encompassing 20.08% of the permafrost expanse in the QTP. The conclusive findings revealed that slope, elevation, the topographic wetness index (TWI), and precipitation were the primary factors influencing the assessment of thermokarst lake susceptibility. This comprehensive analysis extends to the broader impacts of thermokarst hazards, with the identified high and very high susceptibility zones affecting significant stretches of railway and highway infrastructure, substantial soil organic carbon reserves, and vast alpine grasslands. This interpretable ensemble learning model, which exhibits high accuracy, offers substantial practical significance for project route selection, construction, and operation in the QTP. Full article

Few young Japanese adults regularly consume a well-balanced diet composed of staples, main courses, and sides. We hypothesised that adopting the recommended planetary health diet with regular breakfast consumption would promote well-balanced diets among young Japanese male undergraduates. This study aimed to examine the structural association between the planetary health diet with regular breakfast consumption and a well-balanced diet intake. This cross-sectional study included 142 male engineering undergraduates who completed a 2022 online questionnaire via Google Forms at a public university in Hyogo Prefecture. The planetary health diet comprises the consumption of the recommended eight items. A covariance structure analysis was performed in a hypothetical model with factors (regular breakfast consumption and eight items) potentially associated with the intake of a well-balanced diet at least twice daily. After excluding chicken dishes and nuts from the eight recommended items of the planetary health diet, goodness-of-fit became acceptable. Frequent consumption of the remaining six recommended items (fish, eggs, soybeans/soybean products, dairy foods, vegetables, and fruits) was significantly positively correlated with regular breakfast consumption and a significant positive path to a well-balanced diet. Among male university students, regular breakfast consumption and the planetary health diet may lead to a well-balanced diet. Full article