Role of bone marrow mesenchymal stem cell-derived exosomes in reducing neurotoxicity and depression-like behaviors induced by doxorubicin in rats.

Background: Doxorubicin (DOX) is a broad-spectrum antitumor drug while its use is limited nowadays due to its neurobiological side effects associated with depression. Bone marrow mesenchymal stem cells (BM-MSCs) derived exosomes are a promising regenerative therapy. In this study, we investigated the therapeutic potentiality of BM-MSCs derived exosomes against the neurotoxicity induced by DOX. Methods: Twenty-four male albino rats were divided equally in to three groups as follow: group 1 (control), group 2 (rats injected intraperitoneally (i.p|) with DOX at a dose 2.5mg/Kg), and group 3 (rats injected with DOX and BM-MSCs derived exosomes i.p at a dose 1.5ml/Kg). During the experiment the behavior tests were noted, after three weeks rats were sacrificed, serum and brain samples were collected for biochemical, molecular and histopathological examinations. Results: The results revealed that DOX causing impairment of the locomotor and increasing the anxiety like behavior of rats, marked neuropathological changes, significant elevation of MDA content and TNF-α concentration, reduction of phospholipase (PLD) and acetylcholinesterase (AChE) protein concentration in addition, there were up regulation of JNK, NF-κB and p38 genes and down regulation of Erk1. Conclusion: Exosomal therapy improved the substantial neurotoxicity of DOX through modulating the markers involved in the neurotoxic signalling pathway of DOX that resulting in improving the pathological lesions and the animal behaviours.

Inoculation with Jeotgalicoccus sp. improves nutritional quality and biological value of Eruca sativa by enhancing amino acid and phenolic metabolism and increasing mineral uptake, unsaturated fatty acids, vitamins, and antioxidants.

Plant growth-promoting bacteria (PGPB) are considered a promising tool for triggering the synthesis of bioactive compounds in plants and to produce healthy foods. This study aimed to demonstrate the impact of PGPB on the growth, accumulation of primary and secondary metabolites, biological activities, and nutritional qualities of Eruca sativa (arugula), a key leafy vegetable worldwide. To this end, Jeotgalicoccus sp. (JW0823), was isolated and identified by using partial 16S rDNA-based identification and phylogenetic analysis. The findings revealed that JW0823 significantly boosted plant biomass production by about 45% (P<0.05) and enhanced pigment contents by 47.5% to 83.8%. JW0823-treated plants showed remarkable improvements in their proximate composition and vitamin contents, with vitamin E levels increasing by 161.5%. JW0823 induced the accumulation of bioactive metabolites including antioxidants, vitamins, unsaturated fatty acids, and essential amino acids, thereby improving the nutritional qualities of treated plants. An increase in the amounts of amino acids was recorded, with isoleucine showing the highest increase of 270.2%. This was accompanied by increased activity of the key enzymes involved in amino acid biosynthesis, including glutamine synthase, dihydrodipicolinate synthase, cystathionine γ-synthase, and phenylalanine ammonia-lyase enzymes. Consequently, the total antioxidant and antidiabetic activities of the inoculated plants were enhanced. Additionally, JW0823 improved antimicrobial activity against several pathogenic microorganisms. Overall, the JW0823 treatment is a highly promising method for enhancing the health-promoting properties and biological characteristics of E. sativa, making it a valuable tool for improving the quality of this important leafy vegetable.

Quality of life and psychological distress in end-stage renal disease patients undergoing hemodialysis and transplantation.

BACKGROUND: Among diverse profound impacts on patients' quality of life (QoL), end-stage renal disease (ESRD) frequently results in increased levels of depression, anxiety, and stress. Renal replacement therapies such as hemodialysis (HD) and transplantation (TX) are intended to enhance QoL, although their ability to alleviate psychological distress remains uncertain. This research posits the existence of a significant correlation between negative emotional states and QoL among ESRD patients, with varying effects observed in HD and TX patients. AIM: To examine the relationship between QoL and negative emotional states (depression, anxiety, and stress) and predicted QoL in various end-stage renal replacement therapy patients with ESRD. METHODS: This cross-sectional study included HD or TX patients in the Eastern Region of Saudi Arabia. The 36-item Short Form Survey and Depression Anxiety Stress Scale (DASS) was used for data collection, and correlation and regression analyses were performed. RESULTS: The HD and TX transplantation groups showed statistically significant inverse relationships between QoL and DASS scores. HD patients with high anxiety levels and less education scored low on the physical component summary (PCS). In addition, the results of the mental component summary (MCS) were associated with reduced depression. Compared with older transplant patients, TX patients' PCS scores were lower, and depression, stress, and negative working conditions were highly correlated with MCS scores. CONCLUSION: The findings of this study revealed notable connections between well-being and mental turmoil experienced by individuals undergoing HD and TX. The PCS of HD patients is affected by heightened levels of anxiety and lower educational attainment, while the MCS of transplant patients is influenced by advancing age and elevated stress levels. These insights will contribute to a more comprehensive understanding of patient support.

Elevated concentrations of soil carbon dioxide with partial root-zone drying enhance drought tolerance and agro-physiological characteristics by regulating the expression of genes related to aquaporin and stress response in cucumber plants.

Water scarcity and soil carbon dioxide elevation in arid regions are considered the most serious factors affecting crop growth and productivity. This study aimed to investigate the impacts of elevated CO2 levels (eCO2 at rates of 700 and 1000 ppm) on agro-physiological attributes to induce drought tolerance in cucumbers by activating the expression of genes related to aquaporin and stress response, which improved the yield of cucumber under two levels of irrigation water conditions [75% and 100% crop evapotranspiration (ETc)]. Therefore, two field experiments were conducted in a greenhouse with controlled internal climate conditions, at the Mohamed Naguib sector of the national company for protected agriculture, during the winter seasons of 2021-2022 and 2022-2023. The treatments included eCO2 in soil under normal and partial root zoon drying (PRD, 100% ETc Full irrigations, and 75% ETc). All the applied treatments were organized as a randomized complete block design (RCBD) and each treatment was replicated six times. Untreated plants were designed as control treatment (CO2 concentration was 400 ppm). The results of this study showed that elevating CO2 at 700 and 1000 ppm in soil significantly increased plant growth parameters, photosynthesis measurements, and phytohormones [indole acetic acid (IAA) and gibberellic acid (GA3)], under partial root-zone drying (75% ETc) and full irrigation conditions (100% ETc). Under PRD condition, eCO2 at 700 ppm significantly improved plant height (13.68%), number of shoots (19.88%), Leaf greenness index (SPAD value, 16.60%), root length (24.88%), fresh weight (64.77%) and dry weight (61.25%) of cucumber plant, when compared to untreated plants. The pervious treatment also increased photosynthesis rate, stomatal conductance, and intercellular CO2 concentration by 50.65%, 15.30% and 12.18%; respectively, compared to the control treatment. Similar findings were observed in nutrient concentration, carbohydrate content, Proline, total antioxidants in the leaf, and nutrients. In contrast, eCO2 at 700 ppm in the soil reduced the values of transpiration rate (6.33%) and Abscisic acid (ABA, 34.03%) content in cucumber leaves compared to untreated plants under both water levels. Furthermore, the results revealed that the gene transcript levels of the aquaporin-related genes (CsPIP1-2 and CsTIP4) significantly increased compared with a well-watered condition. The transcript levels of CsPIP improved the contribution rate of cell water transportation (intermediated by aquaporin's genes) and root or leaf hydraulic conductivity. The quantitative real-time PCR expression results revealed the upregulation of CsAGO1 stress-response genes in plants exposed to 700 ppm CO2. In conclusion, elevating CO2 at 700 ppm in the soil might be a promising technique to enhance the growth and productivity of cucumber plants in addition to alleviating the adverse effects of drought stresses.

A comparative study between current and past Helicobacter pylori infection in terms of microalbuminuria in patients with type 2 diabetes.

BACKGROUND: The prevalence of Helicobacter pylori (H. pylori) infection and its potential relationship to various diseases is currently a focus of attention. The aim of this study is to investigate the association between current and past H. pylori infections and elevated levels of microalbuminuria in type 2 diabetic patients. METHODS: Two hundred patients with type 2 diabetes mellitus were tested for the presence of H. pylori infection. They were divided into three groups: 52 had a current H. pylori infection, 38 had a past H. pylori infection, and 110 had no H. pylori infection. All study participants underwent assessments of plasma glucose levels, glycated hemoglobin (HbA1c), albuminuria levels, inflammatory markers such as erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP), as well as other relevant investigations. RESULTS: The prevalence of H. pylori infection (current and past) was detected in 90 out of 200 diabetic patients (45%). There was no statistically significant difference between the three groups in terms of age, diabetes duration, family history of DM, family history of hypertension, residence, or dyspeptic symptoms, indicating that current or past infection with H. pylori has no association with these variables. The current H. pylori infection group showed the highest levels of inflammatory markers, ESR and CRP, which were significantly different from those in the non-infected group (p = 0.013 and p < 0.001, respectively). The median (IQR) of albuminuria levels in the current H. pylori infection group, the past H. pylori infection group, and the non-infected group were 125 (4.8-290), 7.6 (2.4-271), and 5.1 (1.2-173), respectively. The current H. pylori infection group showed the highest albuminuria level, which was significantly different from that of the non-infected group (p = 0.001). CONCLUSION: There might be an association between microalbuminuria levels, general inflammatory markers (ESR and CRP), and current H. pylori infection in type 2 diabetic patients.

Red Bull Energy Drink Impact on Salivary Glands in Wistar Rats: Can Blueberry Extract Reverse the Damage?

Energy drink (ED) consumption has become increasingly popular. Due to a lack of evidence, it was crucial to assess the effects of Red Bull (RB) consumption on the rat submandibular salivary gland and the potential therapeutic impact of blueberry (BB). Thirty rats were randomly assigned to five groups. Group 1 (Control) received distilled water. Group 2 (RB) received RB (10 mL/100 g/day) for 8 weeks. Group 3 (BB) rats were administered BB (500 mg/day for 8 weeks). Group 4 (RB + BB (L)) received RB for 8 weeks, and from the 5th week, were concurrently given BB (250 mg/day) for 4 weeks. Group 5 (RB + BB (H)) received RB for 8 weeks, and from the 5th week, were concurrently given BB (500 mg/day) for 4 weeks. At the end of the experiment, blood samples were collected, the animals were euthanized, and their submandibular salivary glands were harvested. Oxidative stress markers (MDA, GPx, CAT, and SOD) were assessed in both serum and tissue. Inflammatory markers (TNF-α, IL-6, and IL-10) were quantified in tissue. Submandibular gland specimens were prepared for light microscopy, and immunohistochemical staining was performed using anti-α-SMA. RB consumption resulted in a significant increase in MDA, TNF-α, IL-6, and IL-10, while GPx, CAT, and SOD levels decreased significantly. Degenerative changes in the gland's structure were observed in the RB group. A significant increase in α-SMA immunoreaction was detected in myoepithelial cells. Administration of BB, particularly at a high dose, ameliorated the aforementioned findings. In conclusion, blueberry administration exhibited therapeutic effects due to its antioxidative and anti-inflammatory properties.

Revisiting surgical margins for invasive breast cancer patients treated with breast conservation therapy - Evidence for adopting a 1 mm negative width.

Clinical trials have demonstrated conclusively the non-inferiority of breast-conserving surgery followed by breast radiation therapy (BCT) compared with mastectomy for the treatment of early-stage invasive breast cancer (BC). The definition of the required surgical margin to ensure adequate removal of the cancer by BCT to obtain an acceptable low local recurrence (LR) rate remains controversial. Meta-analyses published by Houssami et al. in 2010 and 2014 demonstrated significantly lower LR rates for patients with a negative margin compared with those with positive (ink on tumour) or close (defined as ≤1 mm or ≤2 mm) margins. Neither meta-analysis addressed whether 'no ink on tumour' was adequate to define a negative margin because of a lack of data. Nevertheless, in 2014, the Society of Surgical Oncology (SSO) and the American Society for Radiation Oncology (ASTRO) with advice from pathologists reviewed these data together and published guidelines recommending that a margin of 'no ink on tumour' was sufficient to define a clear margin in BCT. Subsequently, clinical practice has varied with some national and international bodies endorsing 'no ink on tumour', whilst others have recommended a ≥1 mm margin as acceptable margins for BCT. A more recent meta-analysis conducted by Bundred and colleagues in 2022 did have sufficient data to compare 'no ink on tumour' and 1 mm and concluded that 1 mm rather than 'no ink on tumour', should be used as a minimum negative margin, and recommended that international guidelines be revised. The current review presents a balanced assessment of the evidence relating margin width and local recurrence after BCT. This review concludes that guidelines should consider re-defining a negative margin as ≥1 mm rather than 'no ink on tumour' in the context of BCT, recognising there will be variation to tailor therapy for any individual patient situation to ensure optimal patient care.

HER2-positive grade 1 invasive carcinomas of the breast.

AIMS: The American Society of Clinical Oncology and College of American Pathologists HER2-guidelines recommend repeat testing for most grade 1 mammary carcinomas that are HER2-positive in the core biopsy. This study aimed to assess the value of repeat HER2-testing and the histological features of HER2-positive grade 1 carcinomas. METHODS AND RESULTS: A case-series of HER2-results of grade 1 carcinomas was conducted of patients with no pre-operative systemic treatment over a 5-year period. HER2-positive carcinomas had histological review. Twelve HER2-positive carcinomas were initially reported as grade 1. On review, two were reclassified as grade 2. The remaining 10 carcinomas represented 2% of the 508 grade 1 carcinomas. Eight HER2-positive grade 1 carcinomas from other years were also studied. HER2-positive carcinomas more often had marked nuclear pleomorphism (50 versus 6%) and were more often oestrogen receptor-negative (17 versus 0.8%) and progesterone receptor-negative (28 versus 8%) compared with HER2-negative grade 1 carcinomas. Six carcinomas that were HER2 3+ in the core biopsy were also 3+ on repeat assessment. Five of seven carcinomas that were 2+ amplified in the core biopsy were also HER2-positive in the excision. CONCLUSIONS: HER2-positive grade 1 carcinomas are uncommon, and more often have marked nuclear pleomorphism and lack oestrogen receptor and progesterone receptor expression compared with HER2-negative grade 1 carcinomas. A HER2-poitive result in the core biopsy was confirmed in 11 of 13 tumours that had repeat testing.

Corrigendum: Role of dietary fiber and lifestyle modification in gut health and sleep quality.

[This corrects the article DOI: 10.3389/fnut.2024.1324793.].

Marine Bioactive Molecules as Inhibitors of the Janus Kinases: A Comparative Molecular Docking and Molecular Dynamics Simulation Approach.

A treasure trove of naturally occurring biomolecules can be obtained from sea living organisms to be used as potential antioxidant and anti-inflammatory agents. These bioactive molecules can target signaling molecules involved in the severity of chronic autoimmune diseases such as rheumatoid arthritis (RA). The intracellular tyrosine kinases family, Janus kinases (JAKs, includes JAK1, JAK2, and JAK3), is implicated in the pathogenesis of RA through regulating several cytokines and inflammatory processes. In the present study, we conducted molecular docking and structural analysis investigations to explore the role of a set of bioactive molecules from marine sources that can be used as JAKs' specific inhibitors. Around 200 antioxidants and anti-inflammatory molecules out of thousands of marine molecules found at the Comprehensive Marine Natural Products Database (CMNPD) website, were used in that analysis. The details of the interacting residues were compared to the recent FDA approved inhibitors tofacitinib and baricitinib for data validation. The shortlisted critical amino acids residues of our pharmacophore-based virtual screening were LYS905, GLU957, LEU959, and ASP1003 at JAK1, GLU930 and LEU932 at JAK2, and GLU905 and CYS909 of JAK3. Interestingly, marine biomolecules such as Sargachromanol G, Isopseudopterosin E, Seco-Pseudopterosin, and CID 10071610 showed specific binding and significantly higher binding energy to JAK1 active/potential sites when being compared with the approved inhibitors. In addition, Zoanthoxanthin and Fuscoside E bind to JAK2's critical residues, GLU930 and LEU932. Moreover, Phorbaketal and Fuscoside E appear to be potential candidates that can inhibit JAK3 activity. These results were validated using molecular dynamics simulation for the docked complexes, JAK1(6sm8)/SG, JAK2 (3jy9)/ZAX, and JAK3 (6pjc)/Fuscoside E, where stable and lower binding energy were found based on analyzing set of parameters, discussed below (videos are attached). A promising role of these marine bioactive molecules can be confirmed in prospective preclinical/clinical investigations using rheumatoid arthritis models.

Hybrid computing framework security in dynamic offloading for IoT-enabled smart home system.

In the distributed computing era, cloud computing has completely changed organizational operations by facilitating simple access to resources. However, the rapid development of the IoT has led to collaborative computing, which raises scalability and security challenges. To fully realize the potential of the Internet of Things (IoT) in smart home technologies, there is still a need for strong data security solutions, which are essential in dynamic offloading in conjunction with edge, fog, and cloud computing. This research on smart home challenges covers in-depth examinations of data security, privacy, processing speed, storage capacity restrictions, and analytics inside networked IoT devices. We introduce the Trusted IoT Big Data Analytics (TIBDA) framework as a comprehensive solution to reshape smart living. Our primary focus is mitigating pervasive data security and privacy issues. TIBDA incorporates robust trust mechanisms, prioritizing data privacy and reliability for secure processing and user information confidentiality within the smart home environment. We achieve this by employing a hybrid cryptosystem that combines Elliptic Curve Cryptography (ECC), Post Quantum Cryptography (PQC), and Blockchain technology (BCT) to protect user privacy and confidentiality. Additionally, we comprehensively compared four prominent Artificial Intelligence anomaly detection algorithms (Isolation Forest, Local Outlier Factor, One-Class SVM, and Elliptic Envelope). We utilized machine learning classification algorithms (random forest, k-nearest neighbors, support vector machines, linear discriminant analysis, and quadratic discriminant analysis) for detecting malicious and non-malicious activities in smart home systems. Furthermore, the main part of the research is with the help of an artificial neural network (ANN) dynamic algorithm; the TIBDA framework designs a hybrid computing system that integrates edge, fog, and cloud architecture and efficiently supports numerous users while processing data from IoT devices in real-time. The analysis shows that TIBDA outperforms these systems significantly across various metrics. In terms of response time, TIBDA demonstrated a reduction of 10-20% compared to the other systems under varying user loads, device counts, and transaction volumes. Regarding security, TIBDA's AUC values were consistently higher by 5-15%, indicating superior protection against threats. Additionally, TIBDA exhibited the highest trustworthiness with an uptime percentage 10-12% greater than its competitors. TIBDA's Isolation Forest algorithm achieved an accuracy of 99.30%, and the random forest algorithm achieved an accuracy of 94.70%, outperforming other methods by 8-11%. Furthermore, our ANN-based offloading decision-making model achieved a validation accuracy of 99% and reduced loss to 0.11, demonstrating significant improvements in resource utilization and system performance.

Protein Tyrosine Kinase 7 (PTK7) in Breast Cancer: A Retrospective Analysis of Tumour Expression and Association with Clinical Outcome.

Protein tyrosine kinase 7 (PTK7), originally known as colon carcinoma kinase (CCK4), is an evolutionary conserved, catalytically defective transmembrane receptor involved in Wnt signalling. PTK7 has been identified as a potential therapeutic target, and a PTK7 antibody drug conjugate (PF-06647020; cofetuzumab pelidotin) has been investigated in phase I clinical trials for triple-negative breast cancer, ovarian cancer, and non-small cell lung cancer. PTK7 protein expression was evaluated in 1136 early-stage invasive breast tumours by immunohistochemistry. In addition, PTK7 mRNA expression in the METABRIC (n = 1980) and the TCGA breast cancer cohorts (n = 1082) was evaluated. Associations between PTK7 expression and clinicopathological criteria and patient outcome were determined. No association between PTK7 protein expression and breast cancer-specific survival was observed; however, PTK7 mRNA expression in the METABRIC cohort was associated with breast cancer-specific survival (p < 0.001). PTK7 protein and mRNA expression were associated with breast cancer-specific survival of patients with a poor prognostic Nottingham Prognostic Index (NPI) and a moderate prognostic NPI, respectively. Taken together, these data indicate that PTK7 expression is associated with patient outcome in subgroups of breast cancer patients.

A novel two-parameter unit probability model with properties and applications.

This paper develops a novel two-parameter unit probability model which is the generalized form Kumaraswami distribution that exhibits greater flexibility compared to well-known existing distributions, attributed to its distinct hazard and density function shapes. Extensive analysis has been conducted to explore numerous statistical features of the specified distribution, specifically moments, and order statistics providing explicit expressions for these measures. The maximum likelihood estimation is employed to estimate the model parameters and a numerical simulation analysis confirms the consistency of this estimation approach. Furthermore, the applicability of the specified model is demonstrated by considering four real data sets, showcasing its effectiveness in capturing the characteristics of real life data. The proposed model shows promise as a versatile tool for analyzing diverse data sets in a wide range of fields.

Microstructural Changes in the Corpus Callosum in Neurodegenerative Diseases.

The corpus callosum, the largest white matter structure in the brain, plays a crucial role in interhemispheric communication and cognitive function. This review examines the microstructural changes observed in the corpus callosum across various neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis (ALS). New neuroimaging studies, mainly those that use diffusion tensor imaging (DTI) and advanced tractography methods, were put together to show how changes have happened in the organization of white matter and the connections between them. Some of the most common ways the corpus callosum breaks down are discussed, including less fractional anisotropy, higher mean diffusivity, and atrophy in certain regions. The relationship between these microstructural changes and cognitive decline, motor dysfunction, and disease progression is explored. Additionally, we consider the potential of corpus callosum imaging as a biomarker for early disease detection and monitoring. Studies show that people with these disorders have lower fractional anisotropy and higher mean diffusivity in the corpus callosum, often in ways that are specific to the disease. These changes often happen before gray matter atrophy and are linked to symptoms, which suggests that the corpus callosum could be used as an early sign of neurodegeneration. The review also highlights the implications of these findings for understanding disease mechanisms and developing therapeutic strategies. Future directions, including the application of advanced imaging techniques and longitudinal studies, are discussed to elucidate the role of corpus callosum degeneration in neurodegenerative processes. This review underscores the importance of the corpus callosum in understanding the pathophysiology of neurodegenerative diseases and its potential as a target for therapeutic interventions.

Miniplates versus Headless Screws for Fixation of Displaced Radial Head Fractures: A Randomized Controlled Trial.

BACKGROUND: Fixation of displaced radial head fractures using miniplates is technically challenging and has some drawbacks like hardware prominence and limitation of forearm rotation. Fixation by headless compression screws has emerged as a less invasive alternative to miniplates. This study compares the radiological and functional outcomes of both methods of fixation. METHODS: This single-center, prospective, randomized controlled trial was conducted at an academic level 1 trauma center. Sixty patients with displaced isolated radial head fractures were randomized to treatment using either headless compression screws or miniplates in 2 parallel groups. At the final follow-up of 18 months, patients were evaluated radiologically for union and clinically using the Mayo Elbow Performance Score (MEPS), elbow range of motion, grip strength, the visual analogue scale (VAS) for pain, and the Disabilities of the Shoulder, Arm, and Hand (DASH) score. RESULTS: Union was achieved after 8±1.7 weeks in the screw group and after 8.5±2.7 weeks in the plate group. The MEPS was significantly better in the screw group (87.7±10.7) than in the plate group (80.5±13.9). However, this difference is below the minimum clinically important difference (MCID) for the MEPS and as such may not be clinically meaningful. No significant differences were observed between both groups regarding flexion, extension ranges, VAS, grip strength, or the DASH score. However, supination and pronation were significantly better in the screw group. The rate of complications was higher in the plate group (26.7%) than in the screw group (3.3%). CONCLUSION: Both techniques yielded comparable outcomes with better forearm rotation, a lower complication rate, and a lower hardware removal rate in the screw group.

Controversies regarding encapsulated papillary carcinoma of the breast: an approach to evaluation and categorisation.

Malignant papillary lesions, and in particular, encapsulated papillary carcinoma (EPC) of the breast, continue to present diagnostic challenges for the practising pathologist. In addition to the relative rarity of these lesions, the lack of evidence-based diagnostic criteria, differences in the biological characteristics, and the clinical behaviour of in situ and invasive forms, variable use of immunohistochemical markers, and overlap with other tumour types including high-grade circumscribed forms of invasive breast carcinomas has resulted in diagnostic discordance with potentially significant clinical and management implications. Pathologists should be familiar with the range of morphology observed in malignant papillary tumours, EPC, and EPC-like tumours and the existence of tumours with overlapping features. In this review we summarize the common diagnostic pitfalls in malignant papillary tumours and provide an approach to the diagnostic evaluation and categorisation of these enigmatic entities.

Impact of ginger powder (Zingiber officinale) supplementation on the performance, biochemical parameters, antioxidant status, and rumen fermentation in Ossimi rams.

Background and Aim: Ginger (Zingiber officinale) has great potential as a growth promoter and immunostimulant in ruminant nutrition. This study assessed the impact of ginger powder supplementation on Ossimi rams' rumen fermentation, biochemical parameters, and antioxidant levels. Materials and Methods: Fifteen Ossimi rams, aged 10 ± 1.3 months and weighing 30 ± 1.5 kg. Rams were randomly divided into three experimental groups: The control group (G1) received standard feed, while ginger powder (5 g and 7 g/kg body weight [BW] for G2 and G3, respectively) mixed in water was administered to groups G2 and G3 before their standard feed. Results: The control group recorded higher dry matter (DM) intake values (p < 0.05) than the ginger-treated groups. The ginger-treated groups showed superiority (p < 0.05) in weight gain and feed conversion compared to the control group. The digestion coefficients of DM, crude protein, and crude fiber were significantly (p < 0.05) increased by a high dose (7 g/Kg BW) of ginger supplementation, whereas organic matter, ether extract, and nitrogen-free extract digestibility remained unchanged. Compared to the control group, the rams given 5 g of ginger had significantly less (p < 0.05) total protein and globulin in their serum, but the rams given 7 g of ginger had significantly more (p < 0.05) of these proteins. In the ginger groups, these levels were significantly (p < 0.01) lower than those in the control group for serum creatinine, uric acid, urea, total lipids, triglycerides, total cholesterol, glucose, serum alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and gamma-glutamyl transferase. Rams given ginger had significant growth hormone, insulin-like growth factor-1, total superoxide dismutase, GSH-Px, TAC, immunoglobulin (Ig) A, and IgG enhancement (p < 0.01), and a decrease (p < 0.01) in malondialdehyde concentration compared to the control group. Significant increases in total short-chain volatile fatty acids, acetic, propionic, and isovaleric acids (p < 0.05), and significant decreases in NH3N and protozoa (p < 0.01). Conclusion: Ginger powder (5 g and 7 g) can improve growth, immune responses, antioxidant status, and ruminal parameters in rams. Further study is needed to evaluate the effect of ginger on different types of animals (cow, buffalo, and goat) to develop new feed additives.

Machine Learning-Based Prediction Models for Punching Shear Strength of Fiber-Reinforced Polymer Reinforced Concrete Slabs Using a Gradient-Boosted Regression Tree.

Fiber-reinforced polymers (FRPs) are increasingly being used as a composite material in concrete slabs due to their high strength-to-weight ratio and resistance to corrosion. However, FRP-reinforced concrete slabs, similar to traditional systems, are susceptible to punching shear failure, a critical design concern. Existing empirical models and design provisions for predicting the punching shear strength of FRP-reinforced concrete slabs often exhibit significant bias and dispersion. These errors highlight the need for more reliable predictive models. This study aims to develop gradient-boosted regression tree (GBRT) models to accurately predict the shear strength of FRP-reinforced concrete panels and to address the limitations of existing empirical models. A comprehensive database of 238 sets of experimental results for FRP-reinforced concrete slabs has been compiled from the literature. Different machine learning algorithms were considered, and the performance of GBRT models was evaluated against these algorithms. The dataset was divided into training and testing sets to verify the accuracy of the model. The results indicated that the GBRT model achieved the highest prediction accuracy, with root mean square error (RMSE) of 64.85, mean absolute error (MAE) of 42.89, and coefficient of determination (R2) of 0.955. Comparative analysis with existing experimental models showed that the GBRT model outperformed these traditional approaches. The SHapley Additive exPlanation (SHAP) method was used to interpret the GBRT model, providing insight into the contribution of each input variable to the prediction of punching shear strength. The analysis emphasized the importance of variables such as slab thickness, FRP reinforcement ratio, and critical section perimeter. This study demonstrates the effectiveness of the GBRT model in predicting the punching shear strength of FRP-reinforced concrete slabs with high accuracy. SHAP analysis elucidates key factors that influence model predictions and provides valuable insights for future research and design improvements.

Microstructure and Microhardness Evolution of Mg-8Al-1Zn Magnesium Alloy Processed by Differential Speed Rolling at Elevated Temperatures.

Mg-8Al-1Zn magnesium alloy was successfully processed using deferential speed rolling (DSR) at temperatures of 400 and 450 °C for thickness reduction of 30, 50, and 70% with no significant grain growth and dynamic recrystallization. Using optical microscopy (OM), scanning electron microscopy (SEM), and transmission electron microscopy (TEM), the rolled microstructures were examined. Although the results indicate a slight reduction in grain size from the initial condition, the DSR processing of alloy at an elevated temperature was associated with a significant number of twins and a distribution of the fine particles of the second phase. The strength in terms of microhardness measurements and strain hardening in terms of shear punch testing was significantly improved in the rolled microstructure at room temperature. The existence of twins and widely distributed second-phase fine particles at twin boundaries reflected positively on the extent of the elongations in terms of shear displacements when microstructures were tested at elevated temperatures in the shear punch testing.

Ameliorative effects of undifferentiated and differentiated BM-MSCs in MIA-induced osteoarthritic Wistar rats: roles of NF-κB and MMPs signaling pathways.

OBJECTIVES: Osteoarthritis (OA) is a degenerative joint condition that is persistent. OA affects millions of people throughout the world. Both people and society are heavily economically burdened by osteoarthritis. There is currently no medication that can structurally alter the OA processes or stop the disease from progressing. Stem cells have the potential to revolutionize medicine due to their capacity to differentiate into chondrocytes, capacity to heal tissues and organs including osteoarthritic joints, and immunomodulatory capabilities. Therefore, the goal of the current investigation was to determine how bone marrow-derived mesenchymal stem cells (BM-MSCs) and chondrogenic differentiated mesenchymal stem cells (CD-MSCs) affected the treatment of OA in rats with monosodium iodoacetate (MIA)-induced osteoarthritis. METHODS: Male Wistar rats were injected three times with MIA (1 mg)/100 µL isotonic saline to induce osteoarthritis in the ankle joint of the right hind leg. Following the MIA injection, the osteoarthritic rats were given weekly treatments of 1 × 106 BM-MSCs and CD-MSCs into the tail vein for three weeks. RESULTS: The obtained results showed that in osteoarthritic rats, BM-MSCs and CD-MSCs dramatically decreased ankle diameter measurements, decreased oxidized glutathione (GSSG) level, and boosted glutathione peroxidase (GPx) and glutathione reductase (GR) activities. Additionally, in rats with MIA-induced OA, BM-MSCs and CD-MSCs dramatically boosted interleukin-10 (IL-10) serum levels while considerably decreasing serum anticitrullinated protein antibodies (ACPA), tumour necrosis factor-α (TNF-α), and interleukin-17 (IL-17) levels as well as ankle transforming growth factor-ß1 (TGF-ß1) expression. Analysis of histology, immunohistochemistry, and western blots in osteoarthritic joints showed that cartilage breakdown and joint inflammation gradually decreased over time. CONCLUSIONS: It is possible to conclude from these results that BM-MSCs and CD-MSCs have anti-arthritic potential in MIA-induced OA, which may be mediated via inhibitory effects on oxidative stress, MMPs and inflammation through suppressing the NF-κB pathway. In osteoarthritis, using CD-MSCs as a treatment is more beneficial therapeutically than using BM-MSCs.