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As spillways are hydraulic structures constructed for the safe release of floodwater from the upstream (US) side of a dam to the downstream side, or from the end of canals and drains to a lower stream, the upstream water flow of such structures gains significant amounts of potential energy. As this water flows over a spillway or escapes, the gained potential energy is converted into kinetic energy, resulting in the water gaining an increasing velocity, thereby enhancing the flow's destructive potential. This can have a harmful impact on the hydraulic performance and the structural stability of the spillway itself. To avoid such harmful effects, engineers and designers of such structures usually provide the spillways and water escapes with some tools for dissipating that kinetic energy and decreasing the flowing water's velocity. The present study aims to enhance the performance efficiency of such dissipating tools, as well as to improve the quality of the flowing water by leveraging the significant turbulence generated by the existing energy dissipators on the back of the spillway body. The aeration process enabled by this turbulence increases the dissolved oxygen contents, thereby enhancing the water quality, which is one of the main objectives of this work. On the back surface of the spillway, various dissipater shapes with different geometrical configurations, dimensions, and combinations were tested, in order to determine the most suitable engineering treatments for maximizing the dissolved oxygen content and improving the water quality for various uses, as the study's main goal. By testing 21 different model configurations with the available laboratory discharges, the study successfully identified the most effective shape and properties of the desired dissipator, which increased the dissolved oxygen content by an average of 21.70% and dissipated water energy by about 69%. [ABSTRACT FROM AUTHOR]

Globalization's impact on design has raised concerns about the erosion of local cultural identities, particularly in interior design. This study examines the preservation of cultural identity in interior design amidst the homogenizing forces of globalization, emphasizing heritage-inspired critical regionalism and reflexive modernism. A literature review addresses the interconnected themes of globalization, design identity, reflexive modernism, and critical regionalism forming the theoretical foundation of this research. Through a qualitative systematic review, three core strategies are identified as essential for preserving local identity: Historical Revival, Eclectic Historicism, and Free Historicism. These strategies offer innovative approaches to integrating heritage elements within contemporary interiors, balancing cultural preservation with modern functionality. Selected case studies illustrate the successful application of these strategies in interior projects, underscoring their significance in maintaining cultural identity and advancing material heritage research. This study contributes to the state of research by synthesizing and contextualizing these strategies within the discourse on interior design, providing actionable insights for professionals navigating global trends. [ABSTRACT FROM AUTHOR]

Background/Objectives: The antioxidant/antiapoptotic features of dapagliflozin (DPG) have mediated its beneficial actions against several experimental models. However, no studies have been conducted to determine whether DPG mitigates the renal injury triggered by cadmium (Cd). Herein, DPG was studied for its potential to attenuate kidney damage in Cd-intoxicated rats, as well as to unravel the mechanisms involving oxidative events, autophagy, and apoptosis. Methods: Histopathological analysis, immunohistochemical staining, and ELISA were conducted on kidney tissue samples. Results: Cd administration (5 mg/kg/day; p.o.) prompted significant renal damage, as evidenced by histopathological changes, elevated kidney injury molecule-1 (KIM-1) expression, and increased serum creatinine and urea. Interestingly, DPG (1 mg/kg/day; p.o.) significantly mitigated these harmful effects without affecting renal Cd metal accumulation. Mechanistically, DPG curbed Cd-induced renal pro-oxidant response and stimulated the antioxidant sirtuin 1 (SIRT1)/nuclear factor (erythroid-derived 2)-like 2 (Nrf2)/heme oxygenase 1 (HO-1) axis. Moreover, DPG restored autophagy by decreasing sequestosome-1/protein 62 (SQSTM-1/p62) accumulation and stimulating the AMP-activated protein kinase (AMPK)/mechanistic target of rapamycin (mTOR) pathway. In tandem, DPG suppressed Cd-induced apoptosis by lowering renal Bcl-2 associated-x protein (Bax) and cytochrome C (Cyt C) levels and caspase 3 activity. Conclusions: These findings indicate that DPG attenuates Cd-induced nephrotoxicity by enhancing the SIRT1/Nrf2/HO-1 antioxidant pathway, promoting AMPK/mTOR-directed autophagy, and inhibiting apoptotic cell death. [ABSTRACT FROM AUTHOR]

Anemia and mineral and bone disorder (MBD) are significant complications of chronic kidney disease (CKD). The erythropoietin (Epo) pathway plays a key role in both of these processes in CKD. Another molecule that plays an important role in CKD-MBD is fibroblast growth factor (FGF)-23, whose main role is to maintain serum phosphate levels in the normal range, acting via its co-receptor Klotho; however, its activity may also be related to anemia and inflammation. In this review, the regulation of Epo and FGF-23 and the molecular mechanisms of their action are outlined. Furthermore, the complex interaction between EPO and FGF-23 is discussed, as well as their association with other anemia-related factors and processes such as Klotho, vitamin D, and iron deficiency. Together, these may be part of a "kidney–bone marrow–bone axis" that promotes CKD-MBD. [ABSTRACT FROM AUTHOR]

The correlation between epigenetic alterations and the pathophysiology of human infertility is progressively being elucidated with the discovery of an increasing number of target genes that exhibit altered expression patterns linked to reproductive abnormalities. Several genes and molecules are emerging as important for the future management of human infertility. In men, microRNAs (miRNAs) like miR-34c, miR-34b, and miR-122 regulate apoptosis, sperm production, and germ cell survival, while other factors, such as miR-449 and sirtuin 1 (SIRT1), influence testicular health, oxidative stress, and mitochondrial function. In women, miR-100-5p, miR-483-5p, and miR-486-5p are linked to ovarian reserve, PCOS, and conditions like endometriosis. Mechanisms such as DNA methylation, histone modification, chromatin restructuring, and the influence of these non-coding RNA (ncRNA) molecules have been identified as potential perturbators of normal spermatogenesis and oogenesis processes. In fact, alteration of these key regulators of epigenetic processes can lead to reproductive disorders such as defective spermatogenesis, failure of oocyte maturation and embryonic development alteration. One of the primary factors contributing to changes in the key epigenetic regulators appear to be oxidative stress, which arises from environmental exposure to toxic substances or unhealthy lifestyle choices. This evidence-based study, retracing the major epigenetic processes, aims to identify and discuss the main epigenetic biomarkers of male and female fertility associated with an oxidative imbalance, providing future perspectives in the diagnosis and management of infertile couples. [ABSTRACT FROM AUTHOR]

In this work, the nonlinear optical (NLO) properties of CuO nanoparticles (CuO NPs) were studied experimentally using the pulsed laser ablation (PLA) technique. A nanosecond Nd: YAG laser was employed as the ablation excitation source to create CuO NPs in distilled water. Various CuO NPs samples were prepared at ablation periods of 20, 30, and 40 min. Utilizing HR-TEM, the structure of the synthesized CuO NPs samples was verified. In addition, a UV–VIS spectrophotometer was used to investigate the linear features of the samples. The Z-scan technique was utilized to explore the NLO properties of CuO NPs samples, including the nonlinear absorption coefficient (β) and nonlinear refractive index ( n 2 ). An experimental study on the NLO features was conducted at a variety of excitation wavelengths (750–850 nm), average excitation powers (0.8–1.2 W), and CuO NPs sample concentrations and sizes. The reverse saturable absorption (RSA) behavior of all CuO NPs samples differed with the excitation wavelength and average excitation power. In addition, the CuO NPs samples demonstrated excellent optical limiters at various excitation wavelengths, with limitations dependent on the size and concentration of CuO NPs. [ABSTRACT FROM AUTHOR]

Background: The treatment of psoriasis has made considerable progress with biologicals, including tumor necrosis factor inhibitors, and recently, monoclonal antibodies inhibiting directly interleukin (IL) 17, IL-23, or both IL-12/23. Newer biologicals are directed to the interleukin pathway and appear to improve complete or near-complete clearance. The newer biologicals have also been shown to have an excellent safety profile. However, despite experience with patients having confirmed the results obtained in clinical trials, there are still few data on using the newer biologicals. Methods: The present active study aimed to prospectively evaluate safety profiles and persistence of some biologicals in a multicenter pharmacovigilance study, that enrolled 733 patients treated with a biologic drug in five Calabrian hospital units. Informative and treatment persistence evaluations with predictors for suspension and occurrence of adverse events (AEs) were executed. In particular, reasons for treatment discontinuation in our program take account of primary/secondary failure or development of an AE. Results: AEs occurred in 187/733 patients and serious AEs (SAEs) were identified in 5/733 patients. An number of 182/733 patients showed a primary/secondary inefficacy. The AEs and SAEs were described with adalimumab, infliximab, and etanercept but not with abatacept, brodalumab, tildrakizumab, golinumab, ixekizumab, guselkumab, risankizumab, secukinumab, and ustekinumab. Conclusions: Our analysis, although limited by a small sample size and a short-term follow-up period, offers suitable data on commonly used biological agents and their safety, interruption rate, and the attendance of SAEs. Real-world studies should be carried out to evaluate other safety interests. [ABSTRACT FROM AUTHOR]

Over the past 40 years, global plastic production has increased twenty-fold, prompting efforts to mitigate plastic waste. Recycling has emerged as the predominant strategy for sustainable plastic waste management. As additive manufacturing (AM) continues to evolve, integrating recycled plastics with various additives has gained significant attention. This systematic literature review, conducted in full accordance with the PRISMA guidelines, aims to evaluate and compare the properties and effects of recycled plastics and their additives in AM. Specifically, it examines the thermal, mechanical, and rheological properties of these materials, along with their life cycle environmental and economic implications. A total of 88 research publications, spanning from 2013 to 2023, were analyzed. The databases searched include Scopus, Web of Science, ProQuest, and Google Scholar, with the final search conducted in December 2023. Studies were selected through a four-stage process—identification, screening, eligibility, and inclusion—based on predefined inclusion and exclusion criteria. The risk of bias was assessed using five criteria: credibility, scope, clarity, methodology, and analysis quality. The results show that most research focuses on the mechanical properties of recycled plastics, with significant gaps in understanding their thermal and rheological properties. Additionally, there is limited research on the environmental and economic viability of these materials, highlighting the need for integrated life cycle assessments and eco-efficiency analyses. This review offers additive manufacturing professionals a comprehensive understanding of the thermal, mechanical, and rheological performance of recycled plastics and additives, supporting efforts to improve sustainability in the industry. [ABSTRACT FROM AUTHOR]

The design of water structures is crucial for efficient hydraulic performance. Open irrigation canals are designed with specific inside slopes to ensure maximum stability, while the wing walls of water structures constructed across the canal are designed to maximize hydraulic performance. Therefore, ensuring compatibility between the canal inside slopes and the wing wall types used on both the upstream and downstream sides is of great importance for achieving optimum hydraulic performance. However, our literature review indicates that this necessary compatibility between the canal inside slope and the wing wall type has not been adequately researched and studied. This present study aims to numerically investigate the relationship between open canals inside slopes and wing wall types, as well as examine the impact of using different wing wall types with varying canals inside slopes on hydraulic performance efficiency. Four canal inside slope ratios (Z) (H: V = 2:1, 1.5:1, 1:1, and 0.75:1) are simulated using the HEC-RAS program, along with two types of water structure wing walls (box and broken). The HEC-RAS numerical model provides accurate and reliable estimations of the hydraulic characteristics of flowing water through the structure, and the results are verified using previous experimental measurements available in the literature. The variation (ε%) between the measured and computed results is consistent for estimating specific energy, velocity, heading (afflux), and water depths. The simulation results demonstrate that changing the canal inside slope (Z) from 0.75:1 to 2:1 results in a relative increase of approximately 27.84% in heading up and 15.06% in velocity. Additionally, the broken wing wall proves to be more effective than the box type. The study confirms that the optimal configuration for the most efficient performance of water structures involves utilizing broken-type wing walls on the upstream side, along with a 1H:1V canal inside slope. This configuration reduces the relative velocity and relative heading by approximately 12% and 20%, respectively, which is considered highly favorable. [ABSTRACT FROM AUTHOR]

Background: Stress urinary incontinence (SUI) affects around 35% of adult women and has a significant impact on quality of life. A single incision sling (SIS), such as Altis®, was introduced to improve original slings and avoid complications. The present study aimed to evaluate the SIS Altis® subjective and objective cure rates of women with SUI, mixed urinary incontinence (MUI), recurrent SUI, and SUI with concomitant prolapse and report its complications from one single medical center. Methodology: A retrospective cohort, unsponsored study was conducted at the Jordan University Hospital. All women patients were treated with the SIS Altis® procedure, and prolapse procedures were also completed as necessary. The chi square analysis for the cure rates was conducted between the subgroups. Results: From June 2016 to June 2019, 111 women patients with a mean age of 48.0 ± 11.3 years underwent a SIS Altis® procedure. The overall outcome resulted in 81% and 85% of patients being subjectively and objectively cured. The subjectively cured MUI patients were significantly fewer than SUI patients (70% versus 86%, p < 0.05), and patients with recurrent SUI had significantly lower rates (56% for subjective and objective cure rates; p < 0.01 and 0.001). Of the 44 patients who underwent SIS Altis® and concomitant vaginal repair surgery, no significant differences in subjective and objective cure rates were observed. Only 2.7% of women had mild pain, 2.7% had vaginal tape erosion, and 9% had to be re-operated on. Conclusions: The Altis® procedure is effective in women who suffer from SUI for a 19-month follow-up period. However, recurrent SUI patients had lower subjective and objective cure rates than primary SUI patients. Further research is needed with a larger sample size in a prospective study design to determine the effectiveness of single SIS in patients with recurrent SUI. [ABSTRACT FROM AUTHOR]

Carotid stenosis is characterized by the progressive narrowing of the carotid arteries due to the formation of atherosclerotic plaque, which can lead to stroke and death as major complications. Numerous biomarkers allow for its study and characterization, particularly those related to "omics" sciences. Through the most common research databases, we report representative studies about carotid stenosis biomarkers based on genomics, transcriptomics, proteomics, and metabolomics in a narrative review. To establish a priority among studies based on their internal validity, we used a quality assessment tool, the Scale for the Assessment of Narrative Review Articles (SANRA). Genes, transcriptomes, proteins, and metabolites can diagnose the disease, define plaque connotations, predict consequences after revascularization interventions, and associate carotid stenosis with other patient comorbidities. It also emerged that many aspects determining the patient's psychological and social sphere are implicated in carotid disease. In conclusion, when taking the multidisciplinary approach that combines human sciences with biological sciences, it is possible to comprehensively define a patient's health and thus improve their clinical management through precision medicine. [ABSTRACT FROM AUTHOR]

Digital twin (DT) is recognized as a pillar in the transition from traditional to digital construction, yet the risks (opportunities and threats) associated with its implementation have not been thoroughly determined in the literature. In addition, there is a scarcity of research relating the risks of DT implementation to DT maturity levels, which has hindered the optimum consideration of such risks when DT is adopted at different maturity levels. To address these gaps, this study conducted a literature review of 1889 documents from Scopus and Web of Science databases. After rigorous filtration, 72 documents were selected and comprehensively reviewed. A total of 47 risk factors (RFs) were identified and categorized into opportunities (economic, technical, environmental and sustainability, monitoring and safety, and management) and threats (economic, technical, and policy and management). Subsequently, these RFs were mapped onto the five-level DT maturity model, providing users with insights into opportunities and threats on each level. The exhaustive list of RFs and proposed integration of a DT maturity model with corresponding RFs enables stakeholders to identify the risks in their specific use cases and facilitate the decision-making and success in transition across various levels of DT in real-life construction projects. [ABSTRACT FROM AUTHOR]

The interior design sector within the construction industry plays a pivotal role in economic development and significantly contributes to environmental degradation. Unlike broader architectural assessments that emphasize structural and external elements, this study highlights the unique challenges and opportunities within interior design. By examining trends and gaps in sustainable interior design criteria from 2013 to 2023, the research provides a foundation for developing specific actionable standards for this often-overlooked sector. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist guided the review process. Data were collected from recognized indexing databases using rigorous inclusion criteria. Selected studies were analyzed based on a mixed-methods approach. The study aims to highlight key trends and synthesize research themes. This systematic review addresses the critical gap in the literature regarding the sustainability of interior design. The findings reveal a lack of comprehensive criteria and tailored guidelines for assessing interior design sustainability, which hinders the effective implementation of sustainable practices. This review underscores the necessity of micro-scale analysis in interior design, providing new insights into sustainable practices and contributing to the broader discourse on sustainable architecture. The study proposes a guideline as a foundation for developing specific actionable standards for assessing sustainability in interior design. [ABSTRACT FROM AUTHOR]

Clostridium histolyticum is a Gram-positive anaerobic bacterium belonging to the Clostridium genus. It produces collagenase, an enzyme involved in breaking down collagen which is a key component of connective tissues. However, antimicrobial resistance (AMR) poses a great challenge in combating infections caused by this bacteria. The lengthy nature of traditional drug development techniques has resulted in a shift to computer-aided drug design and other modern drug discovery approaches. The above method offers a cost-effective means for gathering comprehensive information about how ligands interact with their target proteins. The objective of this study is to create novel, explicit drugs that specifically inhibit the C. histolyticum collagenase enzyme. Through structure-based virtual screening, a library containing 1830 compounds was screened to identify potential drug candidates against collagenase enzymes. Following that, molecular dynamic (MD) simulation was performed in an aqueous solution to evaluate the behavior of protein and ligand in a dynamic environment while density functional theory (DFT) analysis was executed to predict the molecular properties and structure of lead compounds, and the WaterSwap technique was utilized to obtain insights into the drug–protein interaction with water molecules. Furthermore, principal component analysis (PCA) was performed to reveal conformational changes, salt bridges to express electrostatic interaction and protein stability, and absorption, distribution, metabolism, excretion, and toxicity (ADMET) to assess the pharmacokinetics profile of top compounds and control molecules. Three potent drug candidates were identified MSID000001, MSID000002, MSID000003, and the control with a binding score of −10.7 kcal/mol, −9.8 kcal/mol, −9.5 kcal/mol, and −8 kcal/mol, respectively. Furthermore, Molecular Mechanics Poisson–Boltzmann Surface Area (MMPBSA) analysis of the simulation trajectories revealed energy scores of −79.54 kcal/mol, −73.99 kcal/mol, −62.26 kcal/mol, and −70.66 kcal/mol, correspondingly. The pharmacokinetics properties exhibited were under the acceptable range. The compounds hold the potential to be novel drugs; therefore, further investigation needs to be conducted to find out their anti-collagenase action against C. histolyticum infections and antibiotic resistance. [ABSTRACT FROM AUTHOR]

Climate change is causing a range of environmental impacts, including increased flood frequency and intensity, posing significant risks to human populations and transportation infrastructure. Assessing flood risk under climate change is critical, but it is challenging due to uncertainties associated with climate projections and the need to consider the interactions between different factors that influence flood risk. Geographic Information Systems (GISs) are powerful tools that can be used to assess flood risk under climate change by gathering and integrating a range of data types and sources to create detailed maps of flood-prone areas. The primary goal of this research is to create a comprehensive GIS-based flood risk map that includes various climate change scenarios derived from the Coupled Model Intercomparison Project Phase 6 (CMIP6) models. This goal will leverage the Analytic Hierarchy Process (AHP) methodology to better understand the impacts of these climate change scenarios on the transportation network. Furthermore, this study aims to evaluate the existing flood risk map and assess the potential impacts of prospective climate scenarios on the levels of flood risk. The results showed that the northern and coastal regions of the United Arab Emirates (UAE) are at higher risk of flooding, with the majority of the population living in these areas. The projections for future flood risk levels indicate that under the SSP245 scenario, flood risk levels will generally be low, but some areas in the northern and eastern regions of the UAE may still face high to very high flood risk levels due to extensive urbanization and low-lying coastal regions. Under the SSP585 scenario, flood risk levels are projected to be significantly higher, with a widespread distribution of very high and high flood risk levels across the study area, leading to severe damage to infrastructure, property, and human lives. The recent publication of the CMIP6 models marks a significant advancement, and according to the authors' knowledge, there have been no studies that have yet explored the application of CMIP6 scenarios. Consequently, the insights provided by this study are poised to be exceptionally beneficial to researchers globally, underscoring the urgent necessity for holistic sustainable flood risk management approaches for geography, planning, and development areas. These approaches should integrate both sustainable transportation infrastructure development and risk mitigation strategies to effectively address the anticipated impacts of flooding events within the study region. [ABSTRACT FROM AUTHOR]

The Mpox virus (MPXV) is known to cause zoonotic disease in humans. The virus belongs to the genus Orthopoxvirus, of the family Poxviridae, and was first reported in monkeys in 1959 in Denmark and in humans in 1970 in the Congo. MPXV first appeared in the U.S. in 2003, re-emerged in 2017, and spread globally within a few years. Wild African rodents are thought to be the reservoir of MPXV. The exotic trade of animals and international travel can contribute to the spread of the Mpox virus. A phylogenetic analysis of MPXV revealed two distinct clades (Central African clade and West African clade). The smallpox vaccine shows cross-protection against MPXV infections in humans. Those who have not previously been exposed to Orthopoxvirus infections are more vulnerable to MPXV infections. Clinical manifestations in humans include fever, muscle pain, headache, and vesicle formation on the skin of infected individuals. Pathognomonic lesions include ballooning degenerations with Guarnieri-like inclusions in vesicular epithelial cells. Alterations in viral genome through genetic mutations might favor the re-emergence of a version of MPXV with enhanced virulence. As of November 2023, 92,783 cases and 171 deaths have been reported in 116 countries, representing a global public health concern. Here, we provide insights on the re-emergence of MPXV in humans. This review covers the origin, emergence, re-emergence, transmission, pathology, diagnosis, control measures, and immunomodulation of the virus, as well as clinical manifestations. Concerted efforts of health professionals and scientists are needed to prevent the disease and stop its transmission in vulnerable populations. [ABSTRACT FROM AUTHOR]

Acute limb ischemia (ALI) is defined as a sudden reduction in blood flow to a limb, resulting in cessation of blood flow and, therefore, cessation of the delivery of nutrients and oxygen to the tissues of the lower limb. Despite optimal treatment to restore blood flow to ischemic tissues, some patients may suffer from ischemia/reperfusion (I/R) syndrome, the most severe complication after a revascularization procedure used to restore blood flow. There are multiple molecular and cellular factors that are involved in each phase of ALI. This review focuses firstly on molecular and cellular factors of arterial thrombosis, highlighting the role of atherosclerotic plaques, smooth muscle cells (SMCs), and cytokine which may alter key components of the extracellular matrix (ECM). Then, molecular and cellular factors of arterial embolism will be discussed, highlighting the importance of thrombi composition. Molecular and cellular factors of ischemia/reperfusion syndrome are analyzed in depth, highlighting several important mechanisms related to tissue damage, such as inflammation, apoptosis, autophagy, necrosis, and necroptosis. Furthermore, local and general complications of ALI are discussed in the context of molecular alterations. Ultimately, the role of novel biomarkers and targeted therapies is discussed. [ABSTRACT FROM AUTHOR]

The reproductive system of males is adversely impacted by lead (Pb), a toxic heavy metal. The present study examined arbutin, a promising hydroquinone glycoside, for its potential ameliorative impact against Pb-induced testicular impairment in rats. The testicular injury was induced by the intraperitoneal administration of Pb acetate (20 mg/kg/day) for 10 consecutive days. Thirty-six rats were divided into six experimental groups (n = 6 per group): control, control treated with oral arbutin (250 mg/kg), control treated with intraperitoneal arbutin (75 mg/kg), untreated Pb, Pb treated with oral arbutin, and Pb treated with intraperitoneal arbutin. The treatments were administered daily for 10 days. Arbutin was administered by the oral and intraperitoneal routes to compare the efficacy of both routes in mitigating Pb acetate-induced testicular dysfunction. The current data revealed that both oral and intraperitoneal administration of arbutin significantly enhanced serum testosterone and sperm count/motility, indicating the amelioration of testicular dysfunction. In tandem, both routes lowered testicular histopathological aberrations and Johnsen's damage scores. These favorable outcomes were driven by dampening testicular oxidative stress, evidenced by lowered lipid peroxidation and increased glutathione and catalase antioxidants. Moreover, arbutin lowered testicular p-JAK2 and p-STAT3 levels, confirming the inhibition of the JAK2/STAT3 pro-inflammatory pathway. In tandem, arbutin suppressed the testicular NLRP3/caspase-1/NF-B axis and augmented the cytoprotective PK2/PKR2 pathway. Notably, intraperitoneal arbutin at a lower dose prompted a more pronounced mitigation of Pb-induced testicular dysfunction compared to oral administration. In conclusion, arbutin ameliorates Pb-evoked testicular damage by stimulating testicular antioxidants and the PK2/PKR2 pathway and inhibiting the JAK2/STAT3 and NLRP3/caspase-1 pro-inflammatory pathways. Hence, arbutin may be used as an adjunct agent for mitigating Pb-induced testicular impairment. [ABSTRACT FROM AUTHOR]

Over the past two decades, rapid climate change has severely impacted people's lives globally, affecting their safety and sustainability. Water, a vital human resource, has been severely affected, with drought and high temperatures leading to desertification, the drying up of rivers and lakes, spontaneous fires in forests, and massive floods and torrents due to melting ice and rising sea and ocean surface water levels. The expected impacts of climate change on the Nile, Egypt's primary water source, are significant. These impacts can vary across regions, depending on factors like local climate, socio-economic dynamics, topography, and environmental nature. Upper Egypt, characterized by arid and semi-arid regions, faces water scarcity and socio-economic development challenges. Climate change exacerbates these issues, posing significant threats to the region's ecological sustainability and socio-economic development. Therefore, it is crucial to address these impacts to ensure the Nile's continued vitality and sustainability. The study aims to analyze the climate change data over the past few decades, analyze its characteristics, and model its effects on Upper Egypt's water sources. The study expected a big decrease in the water resources of the Nile. While what is currently occurring in terms of fluctuating rainfall rates between scarcity and severity contradicts the results of those studies, that is the best evidence of the need for further research and studies to obtain more reliable and consistent results with the reality that it may help decision-makers to develop scenarios to manage climate change effectively, preventing or reducing negative effects, and finding suitable alternatives. Studies predict a 10% decrease in Nile revenue at Aswan High Dam Lake by 2095, with some predicting a 30% increase. This lack of credibility underscores the need for more comprehensive studies. [ABSTRACT FROM AUTHOR]

Despite being an effective chemotherapeutic agent, the clinical use of doxorubicin (DOX) is limited by several organ toxicities including hepatic injury. Pentoxifylline (PTX) is a methylxanthine derivative with marked anti-inflammatory and anti-apoptotic features. It is unknown, however, whether PTX can mitigate DOX-evoked hepatotoxicity. This study aims to explore the potential hepatoprotective impact of PTX in DOX-induced hepatic injury and the underlying molecular mechanisms. Histopathology, immunohistochemistry, and ELISA were used to examine liver tissues. The current findings revealed that PTX administration to DOX-intoxicated rats mitigated the pathological manifestations of hepatic injury, reduced microscopical damage scores, and improved serum ALT and AST markers, revealing restored hepatic cellular integrity. These favorable effects were attributed to PTX's ability to mitigate inflammation by reducing hepatic IL-1β and TNF-α levels and suppressing the pro-inflammatory HMGB1/TLR4/NF-κB axis. Moreover, PTX curtailed the hepatic apoptotic abnormalities by suppressing caspase 3 activity and lowering the Bax/Bcl-2 ratio. In tandem, PTX improved the defective autophagy events by lowering hepatic SQSTM-1/p62 accumulation and enhancing the AMPK/mTOR pathway, favoring autophagy and hepatic cell preservation. Together, for the first time, our findings demonstrate the ameliorative effect of PTX against DOX-evoked hepatotoxicity by dampening the hepatic HMGB1/TLR4/NF-κB pro-inflammatory axis and augmenting hepatic AMPK/mTOR-driven autophagy. Thus, PTX could be utilized as an adjunct agent with DOX regimens to mitigate DOX-induced hepatic injury. [ABSTRACT FROM AUTHOR]

Huntington's disease (HD) is a chronic, inherited neurodegenerative condition marked by chorea, dementia, and changes in personality. The primary cause of HD is a mutation characterized by the expansion of a triplet repeat (CAG) within the huntingtin gene located on chromosome 4. Despite substantial progress in elucidating the molecular and cellular mechanisms of HD, an effective treatment for this disorder is not available so far. In recent years, researchers have been interested in studying cerebrospinal fluid (CSF) as a source of biomarkers that could aid in the diagnosis and therapeutic development of this disorder. Immunoglobulin heavy constant gamma 1 (IGHG1) is one of the CSF proteins found to increase significantly in HD. Considering this, it is reasonable to study the potential involvement of deleterious mutations in IGHG1 in the pathogenesis of this disorder. In this study, we explored the potential impact of deleterious mutations on IGHG1 and their subsequent association with HD. We evaluated 126 single-point amino acid substitutions for their impact on the structure and functionality of the IGHG1 protein while exploiting multiple computational resources such as SIFT, PolyPhen-2, FATHMM, SNPs&Go mCSM, DynaMut2, MAESTROweb, PremPS, MutPred2, and PhD-SNP. The sequence- and structure-based tools highlighted 10 amino acid substitutions that were deleterious and destabilizing. Subsequently, out of these 10 mutations, eight variants (Y32C, Y32D, P34S, V39E, C83R, C83Y, V85M, and H87Q) were identified as pathogenic by disease phenotype predictors. Finally, two pathogenic variants (Y32C and P34S) were found to reduce the solubility of the protein, suggesting their propensity to form protein aggregates. These variants also exhibited higher residual frustration within the protein structure. Considering these findings, the study hypothesized that the identified variants of IGHG1 may compromise its function and potentially contribute to HD pathogenesis. [ABSTRACT FROM AUTHOR]

Featured Application: The bio-based food additives obtained from upcycling grapefruit peels can be used mainly in the food industry as natural antioxidant and antimicrobial alternatives. Additionally, these ingredients also show anti-inflammatory potential, underscoring their potential as a nutraceutical. Grapefruit (GF) processing generates significant nutrient and economic losses due to the production of 50% by-products, primarily peels. GF peels are a rich and sustainable source of bioactive compounds (BCs), such as essential oils (EOs) and phenolic compounds. Thus, finding value-added solutions based on a circular economy is paramount. This research aims to assess the antioxidant, anti-inflammatory, and antimicrobial properties of a hydroethanolic polyphenol-rich extract from crude GF peels (GF-CE), essential oil (GF-EO), and polyphenol-rich extract from GF peels after essential oil extraction (GF-PE). The GF-CE and GF-PE showed high concentrations of naringenin (7.71 and 48.60 mg/g dry extract (DE)), narirutin (15.03 and 28.73 mg/g DE), and hesperidin (0.67 and 0.29 mg/mL), respectively. Extracting firstly EOs from GF improved the release of phenolic acids (p-coumaric, ferulic, and chlorogenic acid). The GF-CE exhibited stronger free radical scavenging activity mainly in DPPH (IC50 = 75.69 ± 0.81 µg/mL) than GF-EO (1271 ± 0.85 µg/mL) and GF-PE (113.45 ± 0.85 µg/mL). The GF-EO demonstrated moderate antimicrobial activity against Gram-positive bacteria compared to the reference standard (amoxicillin) and strong activity against the yeast Candida albicans (inhibition zone of 16 mm). The major compounds in the GF-EO included D-limonene (25%), nootkatone (24%), and β-pinene (8%). Both polyphenol-rich extracts showed promising activities as COX1 and COX2 inhibitors with IC50 values of 25 ± 0.1 and 0.28 ± 0.00 µg/mL (compared to celecoxib (97.5 ± 0.1 and 0.31 ± 0.01 µg/mL) and indomethacin (6.25 ± 0.00 and 0.52 ± 0.01 µg/mL) as the standards), respectively. The study concludes that GF peels are a valuable source of BCs with significant bioactivities, offering a sustainable multi-cascade approach to recovering value-added compounds from GF peels in alignment with circular economy principles and open opportunities as functional ingredients for food applications. [ABSTRACT FROM AUTHOR]

Citrus peels are an important by-product of citrus processing industries, but a large part is considered waste. There has been increased attention in the last five years on these industrial by-products, especially those containing residual essential oils (EOs). Lemon, orange, and mandarin peels from Egypt were subjected to hydro-distillation to obtain EOs, which were analyzed via mass spectrometry (GC/MS) and by building Global Natural Products Social Molecular Networking (GNPS-MN) for the purpose of visually exploring the volatile components of citrus species. The constructed MN revealed that D-Limonene, α-pinene, and β-pinene are the dominant volatile constituents in the three Egyptian citrus species. The EOs from three citrus peels exhibited promising activities as antioxidants using two tested methods: 1,1-diphenyl-2-picryl-hydrazil (DPPH) and nitric oxide (NO) compared with vitamin C. Lemon EO proved excellent antimicrobial activity against Gram-positive and negative bacteria. Additionally, the three citrus EOs showed good activities against the yeast Candida albicans. Regarding the anti-inflammatory assay, the three citrus EOs showed promising activities as COX-1 and COX-2 inhibitors. This study concludes that EOs extracted from citrus peel waste can be valorized as an innovative strategy for food preservation or may be incorporated in cosmetics and pharmaceutical formulations in alignment with circular economy principles. [ABSTRACT FROM AUTHOR]

Over the past two decades, extensive research has been conducted to explore alternative supplementary cementitious materials (SCMs) in order to address the environmental concerns associated with the cement industry. Bricks, which are frequently preferred in the construction sector, generate a lot of waste during the production and demolition of existing buildings, requiring environmentally sustainable recycling practices. Therefore, many studies have been carried out in recent years on the use of brick waste as supplementary cementitious materials (SCMs) in cement mortar and concrete production. This critical review evaluates the impact of waste brick powder (WBP) on the mechanical and durability properties of mortar and concrete when used as a partial replacement for cement. It was observed that the properties of WBP-blended cement mortar or concrete depend on several factors, including WBP particle size, replacement ratio, pozzolanic activity, and mineralogical structure. The findings indicate that WBP with a particle size range of 100 µm to 25 µm, with a maximum cement replacement level of 10–20%, exhibits a positive impact on the compressive strength of both mortars and concretes. However, it is crucial to emphasize that a minimum curing duration of 28 days is imperative to facilitate the development of a pozzolanic reaction. This temporal requirement plays a vital role in realizing the optimal benefits of utilizing waste brick powder as a supplementary cementitious material in mortars and concretes. [ABSTRACT FROM AUTHOR]

Integration of the Internet of Things (IoT) into the fields of wastewater treatment and water quality prediction has the potential to revolutionize traditional approaches and address urgent challenges, considering the global demand for clean water and sustainable systems. This comprehensive article explores the transformative applications of smart IoT technologies, including artificial intelligence (AI) and machine learning (ML) models, in these areas. A successful example is the implementation of an IoT-based automated water quality monitoring system that utilizes cloud computing and ML methods to effectively address the above-mentioned issues. The IoT has been employed to optimize, simulate, and automate various aspects, such as monitoring and managing natural systems, water-treatment processes, wastewater-treatment applications, and water-related agricultural practices like hydroponics and aquaponics. This review presents a collection of significant water-based applications, which have been combined with the IoT, artificial neural networks, or ML and have undergone critical peer-reviewed assessment. These applications encompass chlorination, adsorption, membrane filtration, monitoring water quality indices, modeling water quality parameters, monitoring river levels, and automating/monitoring effluent wastewater treatment in aquaculture systems. Additionally, this review provides an overview of the IoT and discusses potential future applications, along with examples of how their algorithms have been utilized to evaluate the quality of treated water in diverse aquatic environments. [ABSTRACT FROM AUTHOR]

Simple Summary: A study was conducted to investigate five semen traits in Egyptian buffalo bulls using a single-step genome-wide association study for genomic evaluation. The study aimed to identify associated genomic regions and potential candidate genes. The X-chromosome was the most crucial, accounting for 23.43% of the overall genomic variance observed in these semen traits. Numerous potential candidate genes associated with the examined semen traits were identified within the genomic regions under investigation. In addition, a total of five new candidate genes were discovered within the genomic area examined for semen traits in Egyptian buffalo bulls. The present study aimed to contribute to the limited research on buffalo (Bubalus bubalis) semen traits by incorporating genomic data. A total of 8465 ejaculates were collected. The genotyping procedure was conducted using the Axiom® Buffalo Genotyping 90 K array designed by the Affymetrix Expert Design Program. After conducting a quality assessment, we utilized 67,282 SNPs genotyped in 192 animals. We identified several genomic loci explaining high genetic variance by employing single-step genomic evaluation. The aforementioned regions were located on buffalo chromosomes no. 3, 4, 6, 7, 14, 16, 20, 22, and the X-chromosome. The X-chromosome exhibited substantial influence, accounting for 4.18, 4.59, 5.16, 5.19, and 4.31% of the genomic variance for ejaculate volume, mass motility, livability, abnormality, and concentration, respectively. In the examined genomic regions, we identified five novel candidate genes linked to male fertility and spermatogenesis, four in the X-chromosome and one in chromosome no. 16. Additional extensive research with larger sample sizes and datasets is imperative to validate these findings and evaluate their applicability for genomic selection. [ABSTRACT FROM AUTHOR]

This review examines the impact of childhood obesity on the kidney from an epidemiological, pathogenetic, clinical, and pathological perspective, with the aim of providing pediatricians and nephrologists with the most current data on this topic. The prevalence of childhood obesity and chronic kidney disease (CKD) is steadily increasing worldwide, reaching epidemic proportions. While the impact of obesity in children with CKD is less pronounced than in adults, recent studies suggest a similar trend in the child population. This is likely due to the significant association between obesity and the two leading causes of end-stage renal disease (ESRD): diabetes mellitus (DM) and hypertension. Obesity is a complex, systemic disease that reflects interactions between environmental and genetic factors. A key mechanism of kidney damage is related to metabolic syndrome and insulin resistance. Therefore, we can speculate about an adipose tissue–kidney axis in which neurohormonal and immunological mechanisms exacerbate complications resulting from obesity. Adipose tissue, now recognized as an endocrine organ, secretes cytokines called adipokines that may induce adaptive or maladaptive responses in renal cells, leading to kidney fibrosis. The impact of obesity on kidney transplant-related outcomes for both donors and recipients is also significant, making stringent preventive measures critical in the pre- and post-transplant phases. The challenge lies in identifying renal involvement as early as possible, as it is often completely asymptomatic and not detectable through common markers of kidney function. Ongoing research into innovative technologies, such as proteomics and metabolomics, aims to identify new biomarkers and is constantly evolving. Many aspects of pediatric disease progression in the population of children with obesity still require clarification. However, the latest scientific evidence in the field of nephrology offers glimpses into various new perspectives, such as genetic factors, comorbidities, and novel biomarkers. Investigating these aspects early could potentially improve the prognosis of these young patients through new diagnostic and therapeutic strategies. Hence, the aim of this review is to provide a comprehensive exploration of the pathogenetic mechanisms and prevalent pathological patterns of kidney damage observed in children with obesity. [ABSTRACT FROM AUTHOR]

Cathepsin L (CTSL) expression is dysregulated in a variety of cancers. Extensive empirical evidence indicates their direct participation in cancer growth, angiogenic processes, metastatic dissemination, and the development of treatment resistance. Currently, no natural CTSL inhibitors are approved for clinical use. Consequently, the development of novel CTSL inhibition strategies is an urgent necessity. In this study, a combined machine learning (ML) and structure-based virtual screening strategy was employed to identify potential natural CTSL inhibitors. The random forest ML model was trained on IC50 values. The accuracy of the trained model was over 90%. Furthermore, we used this ML model to screen the Biopurify and Targetmol natural compound libraries, yielding 149 hits with prediction scores >0.6. These hits were subsequently selected for virtual screening using a structure-based approach, yielding 13 hits with higher binding affinity compared to the positive control (AZ12878478). Two of these hits, ZINC4097985 and ZINC4098355, have been shown to strongly bind CTSL proteins. In addition to drug-like properties, both compounds demonstrated high affinity, ligand efficiency, and specificity for the CTSL binding pocket. Furthermore, in molecular dynamics simulations spanning 200 ns, these compounds formed stable protein-ligand complexes. ZINC4097985 and ZINC4098355 can be considered promising candidates for CTSL inhibition after experimental validation, with the potential to provide therapeutic benefits in cancer management. [ABSTRACT FROM AUTHOR]

Background: Type 2 diabetes mellitus (T2DM) is a chronic progressive disease due to insulin resistance. Oxidative stress complicates the etiology of T2DM. Saxagliptin is a selective dipeptidyl peptidase-4 (DPP-4) inhibitor, while Pioglitazone is a thiazolidinedione insulin sensitizer. This study aimed to assess the effect of Saxagliptin and Pioglitazone monotherapy and combination therapy on the biochemical and biological parameters in streptozotocin (STZ)-induced diabetic rats. Methods: The study included thirty-five male albino rats. Diabetes mellitus was induced by intraperitoneal STZ injection (35 mg/kg). For a 1-month duration, rats were divided into five groups. Glucose homeostasis traits, lipid profiles, kidney functions, liver enzymes, and oxidative stress markers were measured. Gene expression of miRNA-29a, phosphoenolpyruvate carboxykinase (PEPCK), phosphoinositide-3-kinase (PI3K), and interleukin 1 beta (IL-1β) was assessed using qRT-PCR. Results: At a 1-month treatment duration, combination therapy improves oxidative stress markers more than either drug alone. The combination therapy had significantly higher levels of SOD, catalase, and GSH and lower levels of MDA compared to the monotherapy. Additionally, the diabetic group showed a significant increase in the expression levels of miRNA-29a, PEPCK, and IL-1β and a significant decrease in PI3K compared to the normal control group. However, combination therapy of Saxagliptin and Pioglitazone was more effective than either Saxagliptin or Pioglitazone alone in reversing these results, especially for PEPCK and IL-1β. Conclusions: Our findings revealed that combining Saxagliptin and Pioglitazone improves glycemic control and genetic and epigenetic expression profiles, which play an essential regulatory role in normal metabolism. [ABSTRACT FROM AUTHOR]

Over the past few decades, the production of metal oxide nanoparticles (MONPs) has developed into an exciting and sophisticated research area. Green metal oxide nanoparticles have played an extremely imperative role in various fields, including biomedical, environmental, energy, agricultural applications, catalytic, bioactive, antibacterial, poisonous, and biocompatible. To achieve sustainability and adopt environmentally friendly practices, the production of MONPs is now increasingly focused on exploring green chemistry and alternative pathways. When made using green synthesis techniques, the metal oxide nanoparticles are especially important because they do not require external stabilizers, capping agents, dangerous chemicals, or harsh operating conditions (high pressure and temperature). Plant-mediated synthesis of different MONPs using either whole cells or extracts has several advantages, including rapid synthesis (compared with other biogenic processes (using fungi and bacteria)), being more stable than other types, being available in nature, and being non-toxic. This review provides a comprehensive overview of the green synthesis of MONPs using plant parts, factors affecting the synthesis, and the characterization of synthesized NPs. Additionally, it highlights the potential of these environmentally friendly nanoparticles that are widely used to treat environmental pollutants, including the removal of heavy metals, antibacterials, and the degradation of organic pollutants. [ABSTRACT FROM AUTHOR]

Due to its ecological and financial benefits, earth building has gained global attention, with earth bricks being extensively used. Shrinkage and crack development have a considerable impact on the performance and quality of earth bricks. This study employs laboratory experiments to examine the shrinkage behavior of earth bricks reinforced with wheat and barley straw. In addition to this, the impact of cement and gypsum additives is examined. The obtained results indicate that increased fiber content reduces crack formation effectively. However, higher levels of cohesive soil have been shown to have a negative influence on shrinkage behavior. In general, higher fiber contents contribute to the improvement of earth brick performance. These findings offer useful insights for improving the composition and characteristics of reinforced earth bricks, resulting in enhanced performance and quality in sustainable construction practices. [ABSTRACT FROM AUTHOR]

In this study, the chemical investigation of Tetraena aegyptia (Zygophyllaceae) led to the identification of a new megastigmene derivative, tetraenone A ((2S, 5R, 6R, 7E)-2-hydroxy-5,6-dihydro-β-ionone) (1), along with (3S, 5R, 6S, 7E)-3-hydroxy-5,6-epoxy-5,6-dihydro-β-ionone- (2), 3,4-dihydroxy-cinnamyl alcohol-4-glucoside (3), 3β,19α-dihydroxy-ursan-28-oic acid (4), quinovic acid (5), p-coumaric acid (6), and ferulic acid (7), for the first time. The chemical structures of 1–7 were confirmed by analysis of their 1D and 2D NMR and HRESIMS spectra and by their comparison with the relevant literature. The absolute configurations of 1 and 2 were assigned based on NOESY interactions and ECD spectra. Conformational analysis showed that 1 existed exclusively in one of the two theoretically possible chair conformers with a predominant s-trans configuration for the 3-oxobut-1-en-1-yl group with the ring, while the half-chair conformer had a pseudo-axial hydroxy group that was predominant over the other half-chair conformation. Boat conformations were not among the most stable conformations, and the s-trans isomerism was in favor of s-cis configuration. In silico investigation revealed that 1 and 2 had more favorable binding interactions with Mpro rather than with TMPRSS2. Accordingly, molecular dynamic simulations were performed on the complexes of compounds 1 and 2 with Mpro to explore the stability of their interaction with the target protein structure. Compounds 1 and 2 might offer a possible starting point for developing covalent inhibitors of Mpro of SARS-CoV-2. [ABSTRACT FROM AUTHOR]

The protective effect of biochanin A (BCA) on the histopathology, immunohistochemistry, and biochemistry of thioacetamide (TAA)-induced liver cirrhosis in vivo was investigated. There was a significant reduction in liver weight and hepatocyte propagation, with much lower cell injury in rat groups treated with BCA (25 mg/kg and 50 mg/kg) following a TAA induction. These groups had significantly lower levels of proliferating cell nuclear antigen (PCNA) and α-smooth muscle actin (α-SMA). The liver homogenates showed increased antioxidant enzyme activity of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx), as well as decreased malondialdehyde (MDA) levels. The serum biomarkers associated with liver function, namely alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma glutamyl transaminase (GGT), returned to normal levels, comparable to those observed in both the normal control group and the reference control group. Taken together, the normal microanatomy of hepatocytes, the inhibition of PCNA and α-SMA, improved antioxidant enzymes (SOD, CAT, and GPx), and condensed MDA with repairs of liver biomarkers validated BCA's hepatoprotective effect. [ABSTRACT FROM AUTHOR]

Obesity has reached an epidemic proportion in the last thirty years, and it is recognized as a major health issue in modern society now with the possibility of serious social and economic consequences. By the year 2030, nearly 60% of the global population may be obese or overweight, which emphasizes a need for novel obesity treatments. Various traditional approaches, such as pharmacotherapy and bariatric surgery, have been utilized in clinical settings to treat obesity. However, these methods frequently show the possibility of side effects while remaining ineffective. There is, therefore, an urgent need for alternative obesity treatments with improved efficacy and specificity. Polymeric materials and chemical strategies are employed in emerging drug delivery systems (DDSs) to enhance therapy effectiveness and specificity by stabilizing and controlling the release of active molecules such as natural ingredients. Designing DDSs is currently a top priority research objective with an eye towards creating obesity treatment approaches. In reality, the most recent trends in the literature demonstrate that there are not enough in-depth reviews that emphasize the current knowledge based on the creation and design of DDSs for obesity treatment. It is also observed in the existing literature that a complex interplay of different physical and chemical parameters must be considered carefully to determine the effectiveness of the DDSs, including microneedles, for obesity treatment. Additionally, it is observed that these properties depend on how the DDS is synthesized. Although many studies are at the animal-study stage, the use of more advanced DDS techniques would significantly enhance the development of safe and efficient treatment approaches for obese people in the future. Considering these, this review provides an overview of the current anti-obesity treatment approaches as well as the conventional anti-obesity therapeutics. The article aims to conduct an in-depth discussion on the current trends in obesity treatment approaches. Filling in this knowledge gap will lead to a greater understanding of the safest ways to manage obesity. [ABSTRACT FROM AUTHOR]

Cognitive decline and Alzheimer-like neuropathology are common manifestations of cadmium toxicity. Thanks to its antioxidant/anti-apoptotic features, dapagliflozin has demonstrated promising neuroprotective actions. However, its effect on cadmium-induced neurotoxicity is lacking. The present work aimed to examine whether dapagliflozin could protect rats from cadmium-evoked cognitive decline. In this study, the behavioral disturbances and hippocampal biomolecular alterations were studied after receiving dapagliflozin. Herein, cadmium-induced memory/learning decline was rescued in the Morris water maze, novel object recognition task, and Y-shaped maze by dapagliflozin. Meanwhile, the hippocampal histopathological abnormalities were mitigated. The molecular mechanisms revealed that dapagliflozin lowered hippocampal expression of p-tau and Aβ42 neurotoxic proteins while augmenting acetylcholine. The cognitive enhancement was triggered by hippocampal autophagy stimulation, as indicated by decreased SQSTM-1/p62 and Beclin 1 upregulation. Meanwhile, a decrease in p-mTOR/total mTOR and an increase in p-AMPK/total AMPK ratio were observed in response to dapagliflozin, reflecting AMPK/mTOR cascade stimulation. Dapagliflozin, on the other hand, dampened the pro-apoptotic processes in the hippocampus by downregulating Bax, upregulating Bcl-2, and inactivating GSK-3β. The hippocampal oxidative insult was mitigated by dapagliflozin as seen by lipid peroxide lowering, antioxidants augmentation, and SIRT1/Nrf2/HO-1 pathway activation. In conclusion, dapagliflozin's promising neuroprotection was triggered by its pro-autophagic, anti-apoptotic, and antioxidant properties. [ABSTRACT FROM AUTHOR]

The rise of antimicrobial resistance, particularly from extended-spectrum β-lactamase producing Enterobacteriaceae (ESBL-E), poses a significant global health challenge as it frequently causes the failure of empirical antibiotic therapy, leading to morbidity and mortality. The E. coli- and K. pneumoniae-derived CTX-M genotype is one of the major types of ESBL. Mobile genetic elements (MGEs) are involved in spreading ESBL genes among the bacterial population. Due to the rapidly evolving nature of ESBL-E, there is a lack of specific standard examination methods. Carbapenem has been considered the drug of first choice against ESBL-E. However, carbapenem-sparing strategies and alternative treatment options are needed due to the emergence of carbapenem resistance. In South Asian countries, the irrational use of antibiotics might have played a significant role in aggravating the problem of ESBL-induced AMR. Superbugs showing resistance to last-resort antibiotics carbapenem and colistin have been reported in South Asian regions, indicating a future bleak picture if no urgent action is taken. To counteract the crisis, we need rapid diagnostic tools along with efficient treatment options. Detailed studies on ESBL and the implementation of the One Health approach including systematic surveillance across the public and animal health sectors are strongly recommended. This review provides an overview of the background, associated risk factors, transmission, and therapy of ESBL with a focus on the current situation and future threat in the developing countries of the South Asian region and beyond. [ABSTRACT FROM AUTHOR]

Featured Application: Creation of statistically significant reference sample sets for validation, optimization, and demonstration of non-destructive testing techniques, particularly for the additive manufacturing sector. Techniques for the controlled seeding and growth of cracks are urgently required for non-destructive testing technique evaluation, particularly for additive manufactured (AM) samples. This paper describes a method that uses a combination of the tensile load and the resonance excitation of notched AM samples, with in situ monitoring of the resonance frequency serving to track the crack dimensions. Mechanical low-cycle fatigue cracks, ranging in length from ~0.3 mm to ~5 mm, were successfully created in five AM samples using this technique. The samples were non-destructively characterized using optical microscopy and Nonlinear Resonance (NLR) testing. The exploitation of resonance enabled the concentration of a significant number of stress cycles on the samples in much shorter timespans than conventional fatigue testing, enabling a high throughput while utilizing compact components. Furthermore, the tracking of the resonance frequency shift throughout the process enabled non-invasive and no-contact real-time condition monitoring. [ABSTRACT FROM AUTHOR]

Gas sensing is of significant importance in a wide range of disciplines, including industrial safety and environmental monitoring. In this work, a low-cost SILAR (Successive Ionic Layer Adsorption and Reaction) technique was employed to fabricate pure CuO, Zn-doped CuO, and Na-doped CuO nanotextured films to efficiently detect CO2 gas. The structures, morphologies, chemical composition, and optical properties of all films are characterized using different tools. All films exhibit a crystalline monoclinic phase (tenorite) structure. The average crystallite size of pure CuO was 83.5 nm, whereas the values for CuO/Zn and CuO/Na were 73.15 nm and 63.08 nm, respectively. Subsequently, the gas-sensing capabilities of these films were evaluated for the detection of CO2 in terms of sensor response, selectivity, recovery time, response time, and limits of detection and quantification. The CuO/Na film offered the most pronounced sensitivity towards CO2 gas, as evidenced by a sensor response of 12.8% at room temperature and a low limit of detection (LoD) of 2.36 SCCM. The response of this sensor increased to 64.5% as the operating temperature increased to 150 °C. This study thus revealed a brand-new CuO/Na nanostructured film as a highly effective and economically viable sensor for the detection of CO2. [ABSTRACT FROM AUTHOR]

Simple Summary: Currently, Stereotactic Body Radiation Therapy (SBRT) is reserved for head and neck cancer (HNC) patients who are not suitable candidates for conventional radiation therapy and should not be considered as a first line of treatment option and as a boost. It should be performed in the context of clinical trial. This review aims to explore SBRT's role in different HNC scenarios. It has the potential to greatly impact the clinical practice by providing valuable insights into the appropriate indications for SBRT in HNC treatment; as well as the practical and technical considerations involved in administering SBRT for HNC; SBRT dosage for various HNC scenarios; and treatment results. However, further research is needed to fully investigate these applications. Stereotactic body radiation therapy (SBRT) is a precise and conformal radiation therapy (RT) that aims to deliver a high dose of radiation to the tumor whilst sparing surrounding normal tissue, making it an attractive option for head and neck cancer (HNC) patients who are not suitable for the traditional long course of RT with comprehensive RT target volume. Definitive SBRT for HNC has been investigated in different settings, including early stage glottis cancer, and as an alternative to brachytherapy boost after external beam RT. It is also used as a primary treatment option for elderly or medically unfit patients. More recently, an SBRT combination with immunotherapy in the neoadjuvant setting for HNC showed promising results. Salvage or adjuvant SBRT for HNC can be used in appropriately selected cases. Future studies are warranted to determine the optimum dose and fractionation schedules in any of these indications. [ABSTRACT FROM AUTHOR]

Cyclin-dependent kinase 5 (CDK5) plays a crucial role in various biological processes, including immune response, insulin secretion regulation, apoptosis, DNA (deoxyribonucleic acid) damage response, epithelial−mesenchymal transition (EMT), cell migration and invasion, angiogenesis, and myogenesis. Overactivation of CDK5 is associated with the initiation and progression of cancer. Inhibiting CDK5 has shown potential in suppressing cancer development. Despite advancements in CDK5-targeted inhibitor research, the range of compounds available for clinical and preclinical trials remains limited. The marine environment has emerged as a prolific source of diverse natural products with noteworthy biological activities, including anti-cancer properties. In this study, we screened a library of 47,450 marine natural compounds from the comprehensive marine natural product database (CMNPD) to assess their binding affinity with CDK5. Marine compounds demonstrating superior binding affinity compared to a reference compound were identified through high-throughput virtual screening, standard precision and extra-precision Glide docking modes. Refinement of the selected molecules involved evaluating molecular mechanics–generalized born surface area (MM/GBSA) free binding energy. The three most promising compounds, (excoecariphenol B, excoecariphenol A, and zyzzyanone B), along with the reference, exhibiting favorable binding characteristics were chosen for molecular dynamics (MD) simulations for 200 nanoseconds. These compounds demonstrated interaction stability with the target during MD simulations. The marine compounds identified in this study hold potential as effective CDK5 inhibitors and warrant subsequent experimental validation. [ABSTRACT FROM AUTHOR]

Egyptian policymakers and researchers have been working to address the challenge of bridging the gap between limited water resources and the growing population's needs for agricultural and food production. The National Great Project for Lining and Rehabilitation of All Open Canals of the Irrigation Network aims to reduce irrigation water losses through seepage, evaporation, and evapotranspiration. This study evaluated water losses from the Al Maanna canal network in the Assiut governorate, Middle Egypt, using empirical formulas and field ponding methods. The results show the Moleth–Worth formula was more compatible with field measurements, with estimated seepage losses of 2.07 and 2.20 million m3/month, respectively. Moreover, maximum evaporation and evapotranspiration losses were 0.086 and 1.133 million m3/month, respectively. Consequently, total water losses from the Al Maanna canal are estimated to be 3.42 million m3/month, accounting for 13.63% of the total discharge. After canal rehabilitation, evaporation and evapotranspiration losses significantly decreased, while seepage losses were lowered to 0.472 million m3/month, as estimated using the field ponding method. Hence, lining the Al Maanna canal network could reduce water losses by 84%, promoting lining processes that yield significant benefits such as moral, cultural, and environmental benefits. This approach outweighs implementation expenses and ensures a sustainable water supply. [ABSTRACT FROM AUTHOR]

Cadmium is an environmental toxicant that instigates cognitive deficits with excessive glutamate excitatory neuroactivity in the brain. Topiramate, a glutamate receptor antagonist, has displayed favorable neuroprotection against epilepsy, cerebral ischemia, and Huntington's disease; however, its effect on cadmium neurotoxicity remains to be investigated. In this study, topiramate was tested for its potential to combat the cognitive deficits induced by cadmium in rats with an emphasis on hippocampal oxidative insult, apoptosis, and autophagy. After topiramate intake (50 mg/kg/day; p.o.) for 8 weeks, behavioral disturbances and molecular changes in the hippocampal area were explored. Herein, Morris water maze, Y-maze, and novel object recognition test revealed that topiramate rescued cadmium-induced memory/learning deficits. Moreover, topiramate significantly lowered hippocampal histopathological damage scores. Mechanistically, topiramate significantly replenished hippocampal GLP-1 and dampened Aβ42 and p-tau neurotoxic cues. Notably, it significantly diminished hippocampal glutamate content and enhanced acetylcholine and GABA neurotransmitters. The behavioral recovery was prompted by hippocampal suppression of the pro-oxidant events with notable activation of SIRT1/Nrf2/HO-1 axis. Moreover, topiramate inactivated GSK-3β and dampened the hippocampal apoptotic changes. In tandem, stimulation of hippocampal pro-autophagy events, including Beclin 1 upregulation, was triggered by topiramate that also activated AMPK/mTOR pathway. Together, the pro-autophagic, antioxidant, and anti-apoptotic features of topiramate contributed to its neuroprotective properties in rats intoxicated with cadmium. Therefore, it may be useful to mitigate cadmium-induced cognitive deficits. [ABSTRACT FROM AUTHOR]

There have been concerns about the potential health risks posed by microplastics (MP). The detection of MP in a variety of food products revealed that humans are ingesting MP. Nevertheless, there is a paucity of data about their impacts, as well as their uptake, on intestinal barrier integrity. This study examined the toxic effects of oral administration of two doses of polyethylene microplastics (PE-MP) (3.75 or 15 mg/kg/day for 5 weeks; mean particle size: 4.0–6.0 µm) on the intestinal barrier integrity in rats. Moreover, the effect of melatonin treatment with MP exposure was also assessed. The PE-MP particle uptake, histopathological changes, Alcian blue staining, Muc2 mRNA, proinflammatory cytokines (IL-1β and TNF-α), and cleaved caspase-3, as well as tight junction proteins (claudin-1, myosin light-chain kinase (MLCK), occludin, and zonula occludens-1 (ZO-1)) were assessed. Oral administration of PE-MP resulted in apparent jejunal histopathological alterations; significantly decreased mucin secretion, occludin, ZO-1, and claudin-1 expression; and significantly upregulated MLCK mRNA, IL-1β concentration, and cleaved caspase-3 expression. Melatonin reversed these altered parameters and improved the PE-MP-induced histopathological and ultrastructure changes. This study highlighted the PE-MP's toxic effect on intestinal barrier integrity and revealed the protective effect of melatonin. [ABSTRACT FROM AUTHOR]

Canine parvovirus (CPV-2) is one of the most important pathogens of dogs of all ages, causing pandemic infections that are characterized by fatal hemorrhagic enteritis. The CPV-2 vaccine is recommended as a core vaccine for pet animals. Despite the intensive practice of active immunization, CPV-2 remains a global threat. In this study, a multi-epitope vaccine against CPV-2 was designed, targeting the highly conserved capsid protein (VP2) via in silico approaches. Several immunoinformatics methods, such as epitope screening, molecular docking, and simulation were used to design a potential vaccine construct. The partial protein sequences of the VP2 gene of CPV-2 and protein sequences retrieved from the NCBI were screened to predict highly antigenic proteins through antigenicity, trans-membrane-topology screening, an allergenicity assessment, and a toxicity analysis. Homologous VP2 protein sequences typically linked to the disease were identified using NCBI BLAST, in which four conserved regions were preferred. Overall, 10 epitopes, DPIGGKTGI, KEFDTDLKP, GTDPDDVQ, GGTNFGYIG, GTFYFDCKP, NRALGLPP, SGTPTN, LGLPPFLNSL, IGGKTG, and VPPVYPN, were selected from the conserved regions to design the vaccine construct. The molecular docking demonstrated the higher binding affinity of these epitopes with dog leukocyte antigen (DLA) molecules. The selected epitopes were linked with Salmonella enterica flagellin FliC adjuvants, along with the PADRE sequence, by GGS linkers to construct a vaccine candidate with 272 nucleotides. The codon adaptation and in silico cloning showed that the generated vaccine can be expressed by the E. coli strain, K12, and the sequence of the vaccine construct showed no similarities with dog protein. Our results suggest that the vaccine construct might be useful in preventing canine parvoviral enteritis (CPE) in dogs. Further in vitro and in vivo experiments are needed for the validation of the vaccine candidate. [ABSTRACT FROM AUTHOR]

Cadmium is an environmental contaminant associated with marked neurotoxicity and cognitive impairment. Linagliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor, has demonstrated promising neuroprotection against cerebral ischemia and diabetic dementia. However, there has been no study of its effect on cadmium-induced cognitive deficits. In the present work, linagliptin's prospective neuroprotective effects against cadmium-evoked cognitive decline were examined in vivo in rats. The molecular pathways related to oxidative stress, apoptosis, and autophagy were investigated. Histology, immunohistochemistry, ELISA, and biochemical assays were performed on brain hippocampi after receiving linagliptin (5 mg/kg/day). The current findings revealed that cadmium-induced learning and memory impairment were improved by linagliptin as seen in the Morris water maze, Y-maze, and novel object recognition test. Moreover, linagliptin lowered hippocampal neurodegeneration as seen in histopathology. At the molecular level, linagliptin curtailed hippocampal DPP-4 and augmented GLP-1 levels, triggering dampening of the hippocampal neurotoxic signals Aβ42 and p-tau in rats. Meanwhile, it enhanced hippocampal acetylcholine and GABA and diminished the glutamate spike. The behavioral recovery was associated with dampening of the hippocampal pro-oxidant response alongside SIRT1/Nrf2/HO-1 axis stimulation. Meanwhile, linagliptin counteracted hippocampal apoptosis markers and inhibited the pro-apoptotic kinase GSK-3β. In tandem, linagliptin activated hippocampal autophagy by lowering SQSTM-1/p62 accumulation, upregulating Beclin 1, and stimulating AMPK/mTOR pathway. In conclusion, linagliptin's antioxidant, antiapoptotic, and pro-autophagic properties advocated its promising neuroprotective impact. Thus, linagliptin may serve as a management approach against cadmium-induced cognitive deficits. [ABSTRACT FROM AUTHOR]