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Metabolic dysregulation causes diseases like diabetes and cancer, making PDKs attractive targets. However, a thorough investigation into the unique roles played by the different members of the PDK family, especially PDK3, about memory loss and related diseases like Alzheimer's disease (AD) is still lacking. The current study investigates PF's potential to reduce PDK3-associated toxicity in neurodegenerative illnesses, including AD. The association between PF and PDK3 presents a significant opportunity for medication development and AD therapy approaches. PF efficiently suppresses PDK3 activity, as demonstrated by molecular docking and biophysical characterization, providing an in-depth understanding of their molecular interactions. PF significantly inhibited PDK3 in a concentration-dependent manner with an IC50 value of 4.88 µM. Considering this, the current investigation also explores the biological component of PF, which exhibits potential in treating AD and is primarily associated with neuroprotection. In the present study, a 3-hour pre-treatment of PF was administered at varying concentrations (4, 6, and 8 µM) in response to the 24-hour SCP (2 mM)-mediated toxicity. Based on the results of in silico and biophysical characterization, it is concluded that PF inhibits the PDK3 activity. Additionally, it can enhance cell viability, suppress ROS expression, impede apoptosis, and downregulate TNF-α expression. When combined, these actions help to prevent neuronal death in an in vitro model of SCP. PF strengthens the memory marker, which is confirmed through BDNF expression. This study found that all results were more effective at lower and moderate doses of PF. Our research indicates that PF boosts memory, decelerates the progression of oxidative stress, and could potentially serve as a dose-dependent treatment for AD., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025. Published by Elsevier B.V.)

This study explores the potential antagonistic effects of selenium-doped zinc oxide nanoparticles (Se-ZnO NPs), synthesized through a sustainable approach, on maize charcoal rot induced by the fungus Macrophomina phaseolina. Se-ZnO-NPs were prepared using the rhizobium extract of Curcuma longa and characterized for their physicochemical properties. Characterization included various in vitro parameters such as FTIR, ICP-MS, particle size, PDI, and zeta potential. ICP-MS analysis revealed Se and Zn ion concentrations of 54.43 mg L -1 and 71.70 mg L -1 , respectively. SEM analysis indicated a size of 37 nm with polyhedral morphology for the Se-ZnO-NPs. Additionally, EDX spectra confirmed the presence of Se and Zn in the nanoparticles. In vitro assays demonstrated that the highest nanoparticle concentration significantly inhibited M. phaseolina growth and spore germination, accompanied by increased enzyme activities. Greenhouse experiments were conducted to assess the efficacy of Se-ZnO-NPs in reducing charcoal rot severity in maize plants under controlled conditions. Furthermore, a second study evaluated various growth parameters of maize plants, such as shoot and root length, and biomass after 45 days of germination. Physiological attributes such as total chlorophyll content and reducing sugar were examined, while biochemical traits including total protein content, catalase, and polyphenol oxidase were assessed after the same germination period. The results indicated that soil amended with various concentrations (0.8-12.5 μg/ml) of NPs significantly enhanced maize plant growth compared to the respective positive control. The antifungal activity of the Se-ZnO-NPs against M. phaseolina showed a significant reduction in growth. Thus, the findings suggest that green-synthesized Se-ZnO-NPs could effectively combat the charcoal rot pathogen. However, further field experiments are needed to explore the activity of doped nanoparticles in soil against pathogens., Competing Interests: Declaration of competing interest The corresponding author declared no conflict of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Naringenin (Nrg) is the most abundant natural dietary flavonoid with promising anti-inflammatory potential. However, its therapeutic application is limited due to poor absorption, low bioavailability, and inability to cross physiological barriers. Herein, we designed biocompatible solid lipid nanoparticles (SLNs) to overcome these challenges and to enhance the oral bioavailability and therapeutic potential of Nrg. Nrg-loaded solid lipid nanoparticles (Nrg-SLNs) were fabricated from natural fatty acids, stearic (Nrg-SANPs), or a combination of stearic and lauric acid as binary nanoparticles (Nrg-SLNPs) by the hot melt encapsulation technique. The optimized Nrg-loaded nanoparticles exhibited a hydrodynamic diameter of 74 nm for SANPs and 91 nm for SLNPs, a zeta potential of -25 mV to -37 mV, and entrapment efficiency ranging from 79 % to 85 %. Electron paramagnetic resonance (EPR) spectroscopy indicated an in vitro radical protection factor (RPF) of 215 ± 2 × 10 14 radicals/mg for Nrg-SLNPs, which was significantly higher than free Nrg and Nrg-SANPs. Almost 87 % reduction in oxidative stress was recorded with Nrg-SLNPs in a stress-induced lymphocyte model. In vivo studies using the Wistar rat model exhibited around 9-12-fold higher oral bioavailability of Nrg after nanoencapsulation in SLNs, as determined by high-performance liquid chromatography (HPLC). Whereas, hematological and histopathological analysis did not show any damage to the vital organs in vivo. This study presents Nrg-SLNPs as an efficient and biocompatible carrier to enhance the oral bioavailability and therapeutic activity of the natural flavonoids and warrants their further exploration in humans., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background and Objective: Accurate prediction of perioperative major adverse cardiovascular events (MACEs) is crucial, as it not only aids clinicians in comprehensively assessing patients' surgical risks and tailoring personalized surgical and perioperative management plans, but also for information-based shared decision-making with patients and efficient allocation of medical resources. This study developed and validated a machine learning (ML) model using accessible preoperative clinical data to predict perioperative MACEs in stable coronary artery disease (SCAD) patients undergoing noncardiac surgery (NCS)., Methods: We collected data from 9171 adult SCAD patients who underwent NCS and extracted 64 preoperative variables. First, the optimal data imputation, resampling, and feature selection methods were compared and selected to deal with missing data values and imbalances. Then, nine independent machine learning models (logistic regression (LR), support vector machine, Gaussian Naive Bayes (GNB), random forest, gradient boosting decision tree (GBDT), extreme gradient boosting (XGBoost), light gradient boosting machine, categorical boosting (CatBoost), and deep neural network) and a stacking ensemble model were constructed and compared with the validated Revised Cardiac Risk Index's (RCRI) model for predictive performance, which was evaluated using the area under the receiver operating characteristic curve (AUROC), the area under the precision-recall curve (AUPRC), calibration curve, and decision curve analysis (DCA). To reduce overfitting and enhance robustness, we performed hyperparameter tuning and 5-fold cross-validation. Finally, the Shapley additive interpretation (SHAP) method and a partial dependence plot (PDP) were used to determine the optimal ML model., Results: Of the 9,171 patients, 514 (5.6 %) developed MACEs. 24 significant preoperative features were selected for model development and evaluation. All ML models performed well, with AUROC above 0.88 and AUPRC above 0.39, outperforming the AUROC (0.716) and AUPRC (0.185) of RCRI (P < 0.001). The best independent model was XGBoost (AUROC = 0.898, AUPRC = 0.479). The calibration curve accurately predicted the risk of MACEs (Brier score = 0.040), and the DCA results showed that XGBoost had a high net benefit for predicting MACEs. The top-ranked stacking ensemble model, consisting of CatBoost, GBDT, GNB, and LR, proved to be the best (AUROC 0.894, AUPRC 0.485). We identified the top 20 most important features using the mean absolute SHAP values and depicted their effects on model predictions using PDP., Conclusions: This study combined missing-value imputation, feature screening, unbalanced data processing, and advanced machine learning methods to successfully develop and verify the first ML-based perioperative MACEs prediction model for patients with SCAD, which is more accurate than RCRI and enables effective identification of high-risk patients and implementation of targeted interventions to reduce the incidence of MACEs., Competing Interests: Declaration of competing interest The authors declare that they have no competing financial interests or personal relationships that may have influenced the work reported in this study., (Copyright © 2024. Published by Elsevier B.V.)

Autophagy is a critical cellular process that maintains homeostasis by recycling damaged or aberrant components. This process is orchestrated by a network of proteins that form autophagosomes, which engulf and degrade intracellular material. In cancer, autophagy plays a dual role: it suppresses tumor initiation in the early stages but supports tumor growth and survival in advanced stages. Chronic myeloid leukemia (CML), a hematological malignancy, is characterized by the Philadelphia chromosome, a chromosomal abnormality resulting from a translocation between chromosomes 9 and 22. Autophagy has emerged as a key factor in CML pathogenesis, promoting cancer cell survival and contributing to resistance against tyrosine kinase inhibitors (TKIs), the primary treatment for CML. Targeting autophagic pathways is being actively explored as a therapeutic approach to overcome drug resistance and enhance cancer cell death. Recent research highlights the intricate interplay between autophagy and CML progression, underscoring its role in disease biology and treatment outcomes. This review aims to provide a comprehensive analysis of the molecular and cellular mechanisms underlying CML, with a focus on the therapeutic potential of targeting autophagy.

Purpose of Review: Acute postsurgical pain after cardiac surgery is challenging to treat. Adverse effects related to the high dose opioids which have traditionally been used perioperatively in cardiac surgery have led to the adoption of alternative analgesic strategies. This review aims to highlight current evidence-based approaches to managing pain after cardiac surgery., Recent Findings: Current evidence and international guidelines support the use of multimodal analgesics for managing perioperative pain after cardiac surgery. Regional anaesthesia in the form of fascial plane blocks, such as the erector spinae plane and parasternal intercostal plane blocks, are effective and safe techniques for anticoagulated cardiac surgery patients. Transitional pain services are multidisciplinary programmes that bridge the gap between inpatient and outpatient care for these patients., Summary: This paper reviews advancements in perioperative pain management for cardiac surgery patients, emphasising the shift from high-dose opioids to multimodal analgesia and regional anaesthetic techniques, and highlighting the role of multidisciplinary transitional pain services., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

In recent times, neurodegenerative diseases (NDs), such as Alzheimer's disease (AD), Parkinson's disease (PD) and others, represent a major global health challenge with increasing prevalence and significant socio-economic impact. These diseases, characterized by progressive neuronal loss, currently lack effective therapies. Phytochemicals offer promising therapeutic potential due to their diverse bioactive properties. Mangiferin, a glucosylxanthone found in mangoes and other plants, has shown significant therapeutic potential in NDs. Human transferrin (Tf), an iron-binding protein crucial for iron homeostasis, is implicated in ND pathogenesis. This study delineates the interaction between Mangiferin and Tf. Molecular docking revealed Mangiferin predominantly interacts with Tf's binding site, engaging critical residues. Molecular dynamics simulations over 200 ns demonstrated the stability of the Tf-Mangiferin complex without major deviations. Fluorescence binding assays confirmed the strong binding affinity of Mangiferin to Tf. Additionally, Isothermal titration calorimetry (ITC) validated the spontaneous binding of Mangiferin with Tf, providing detailed thermodynamic parameters. The findings highlight the therapeutic potential of Mangiferin in NDs treatment through its interaction with Tf, offering insights into novel mechanisms of action and pathways for disease modification., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

We present a challenging case of infective endocarditis (IE) diagnosed after visual loss from bilateral ocular choroidal infarction in the absence of retinal vasculitis, typical retinal embolic phenomenon, clinical cardiac features or obvious medical history.Our case illustrates the difficulties in diagnosing IE and a high index of clinical suspicion is needed., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2025. No commercial re-use. See rights and permissions. Published by BMJ Group.)

Zircaloy-4 (Zr-4) is widely used as the cladding material in nuclear power plants (NPPs) due to its excellent corrosion resistance and low neutron absorption cross-section. Under Loss of Coolant Accident (LOCA) conditions, oxidation of Zr-4 can compromise the safety of the NPPs by accelerating hydrogen production. Therefore, enhancing the oxidation resistance of Zr-4 is a critical research focus. Surface modification through a facile method offers a promising approach to address this issue. This study explores the impact of chemical, mechanical, and electropolishing (EP) pre-treatments on Zr-4 morphology before and after anodization. EP conducted in ethylene glycol monobutyl ether-perchloric acid electrolyte produced a mirror-like surface finish with hexagonal nanopattern formation under optimized conditions, as revealed by SEM studies. Anodization of the patterned surface in a glycerol-based electrolyte resulted in a hybrid (nanoporous and nanotubular) structure, unlike the nanotubular-only morphology observed in the chemically or mechanically polished samples. EDAX and XRD analyses confirmed the formation of ZrO 2 . The hexagonal nanopattern generated by EP suppressed the dissolution of the nanotube during anodization, resulting in a hybrid nanostructure. Additionally, the chemical polishing of EP-treated Zr-4 in HF : HNO 3  : H 2 O generated a porous particulate structure due to selective etching. This work demonstrates that the surface pre-treatment significantly influences the morphology of anodized Zr-4 nanostructures and suggests the potential use of EP in other materials for hexagonal nanopattern generation., Competing Interests: The authors declare that they have no competing interests., (This journal is © The Royal Society of Chemistry.)

Aluminum (Al) toxicity is a major constraint to crop productivity in acidic soils, frequently encountered in banana-growing regions. This study investigates physiological and biochemical responses to Al stress in two Cavendish banana genotypes, Baodao and Baxi ( Musa acuminata L.), which exhibit contrasting levels of Al tolerance. Banana plantlets were grown hydroponically under three AlCl 3 concentrations (0, 100, and 500 μM) for 24, 48, and 72 h. Root elongation was progressively inhibited with increasing Al concentrations, with Baodao showing greater inhibition than Baxi. Al primarily accumulated in roots and displayed genotype-specific distribution patterns: Baodao concentrated more Al in root tips, suggesting lower exclusion efficiency. In contrast, Baxi, the Al-tolerant genotype, translocated Al from roots to shoots more effectively, indicating potential sequestration mechanisms in less sensitive tissues. Al stress influenced enzyme activities, with Baxi exhibiting higher phosphoenolpyruvate carboxylase and citrate synthase activities at 100 µM Al, while both genotypes showed similar reductions at 500 µM. Baodao experienced more pronounced reductions in H + -ATPase activity. At 100 µM Al, Baxi retained higher levels of key nutrients (P, Zn, Mg, Mn, Fe, K, and B) in essential tissues than Baodao. However, nutrient levels were reduced in both genotypes at 500 µM Al. These findings highlight Baxi's superior resilience under Al stress, making it a suitable genotype for cultivation and breeding in acidic soils.

The quality of Coffee arabica L. beans, particularly the aroma, is a key determinant of commercial value. Fatty acids, as precursors of volatile aroma compounds, play a crucial role in this quality. Screening and identification of their related genes are of particular significance. This study identified 21 members of the CaFAD gene family in the C. arabica genome using bioinformatics tools. Gene duplication events observed in the CaFAD gene family were likely driven by natural selection and mutation pressure, with natural selection being more prominent. Transcriptome sequencing, qRT-PCR, and fatty acid profiling across four fruit developmental stages revealed that CaFAD8 was closely associated with fatty acid synthesis regulation. Fatty acid content was initially high but decreased during the later stages, while CaFAD8 expression showed an inverse pattern. Subcellular localization indicated that CaFAD8 functions primarily on the inner membrane. CaFAD8-OE heterologous expression experiment in Arabidopsis thaliana reduced the total fatty acid content in seeds but increased unsaturated fatty acids, including oleic, linoleic, and linolenic acids. These findings suggest that CaFAD8 promotes fatty acid unsaturation and provides insights into fatty acid metabolism in C. arabica. This study offers a foundation for understanding CaFAD gene regulation and supports breeding strategies for high-oil C. arabica varieties.

Cryptosporidiosis is a zoonotic protozoan parasite-born disease, equally significant in both animals and humans, especially affecting immunocompromised individuals (e.g., AIDS patients) and neonates. The prime concerns of this review article are to demonstrate the disruption of the intestinal barrier and variations in the gut microbiome during cryptosporidiosis, and to explore host gut-parasite interactions that can lead to the development of novel therapeutics. The review concluded that the enteric barrier is particularly maintained by tight junction proteins (e.g., occludin, claudin, and ZO-1, etc.) and mucosal immunity, both of which are severely compromised during Cryptosporidium spp. infections, resulting in increased intestinal barrier permeability, inflammatory responses, diarrhea, and ultimately death in severe cases. Cryptosporidium -induced dysbiosis is characterized by reduced microbial diversity and richness, a shift from commensal to pathogenic bacteria, as evidenced by increased pro-inflammatory taxa like Proteobacteria, and reduced proportions of beneficial SCFAs producing bacteria, e.g., Firmicutes. Recent investigations have highlighted the interrelations between gut microbiota and epithelial barrier integrity, especially during cryptosporidiosis, demonstrating the modulations regarding tight junctions (TJs), immune reactions, and SCFA production, all of which are main players in alleviating this protozoal parasitic infection. This review comprehensively describes the fine details underlying these impairments, including autophagy-mediated TJs' degradation, inflammasome activation, and gut microbiome-driven alterations in metabolic pathways, providing the latest relevant, and well-organized piece of knowledge regarding intestinal barrier alterations and microbial shifts during cryptosporidiosis. This work emphasizes the future need for longitudinal studies and advanced sequencing techniques to understand host gut microbiota-parasite interactions, aiming to formulate innovative strategies to mitigate cryptosporidiosis.

Diabetic neuropathy is one of the severe complications of diabetes, which affects the quality of life in a patient and increases the risk of amputations and chronic wounds. Current therapeutic approaches are symptomatically oriented, focusing on comfort and non-inflammatory aspects without addressing the mechanism or molecular target of the disease. The present study investigates the therapeutic effects of an ethanolic polyherbal extract from Citrullus colocynthis (Bitter Apple), Curcuma longa (Turmeric), and Myristica fragrans (Nutmeg) using advanced in silico and analytical methods. According to the findings, PHE showed the presence of a total of 39 bioactive compounds in GC-MS analysis, which include alcohols, fatty acids, terpenoids, esters, neolignans, phenylpropanoids, and steroids. Three of the compounds--4-isopropyl-1,6-dimethyl-1,2,3,4-tetrahydronaphthalene (-11.4 kcal/mol), (1S,2R)-2-(4-allyl-2,6-dimethoxyphenoxy)-1-(3,4,5-trimethoxyphenyl)-1-propanol (-9.8 kcal/mol) and (S)-5-Allyl-2-((1-(3,4-dimethoxyphenyl)propan-2-yl)oxy)-1,3-dimethoxybenzene (-10.3 kcal/mol)-followed the Lipinski rule and showed the binding affinity with aldol reductase. Docking experiments showed that compound 4-isopropyl-1,6-dimethyl-1,2,3,4-tetrahydronaphthalene (-11.4 kcal/mol) has high-affinity binding to aldose reductase, an enzyme involved in diabetic neuropathy pathophysiology, whereas molecular dynamics simulations show long-range persistence of the interaction of (S)-5-Allyl-2-((1-(3,4-dimethoxyphenyl)propan-2-yl)oxy)-1,3-dimethoxybenzene with aldol reductase in physiological conditions. Therefore, this combination of herbal therapy and advanced computational/analytical techniques could be leading towards innovative, multi-targeted therapies against diabetic neuropathy. Nevertheless, further studies in vivo are required to confirm the efficacy, safety, and pharmacokinetics of the PHE in biological systems.

Apigenin, a dietary flavonoid with notable anti-cancer properties, has emerged as a promising candidate for the treatment of neurodegenerative disorders, particularly Alzheimer's disease (AD). While extensively studied for its ability to modulate key molecular pathways in cancers, apigenin also exerts neuroprotective effects by reducing neuroinflammation, protecting neurons from oxidative stress, and enhancing neuronal survival and synaptic plasticity. This dual functionality makes apigenin an intriguing therapeutic option for diseases like AD, where kinase dysregulation plays a central role. In this study, we focus on Microtubule Affinity-Regulating Kinase 4 (MARK4), a key enzyme implicated in tauopathies associated with AD, as well as in cancer progression. Through in silico analysis, we explore the interaction between apigenin and MARK4, revealing significant structural changes within the kinase domain upon ligand binding. These computational findings were confirmed via experimental assays using purified recombinant MARK4, where apigenin demonstrated potent inhibition with an IC 50 value of 2.39 µM. Fluorescence binding assays further confirmed a strong binding affinity (Ka = 10 8  M -1 ), indicating that apigenin efficiently occupies the MARK4 active site, thereby suppressing its enzymatic activity. These results position apigenin as a potent inhibitor of MARK4, offering a dual therapeutic advantage-both as an anti-cancer agent and as a neuroprotective compound for the potential treatment of AD. This study opens new avenues for the development of apigenin-based therapeutics targeting kinase dysregulation in cancer and neurodegeneration., Competing Interests: Declarations. Competing interest: The authors declare no competing interests. Ethical approval: Not applicable. Consent to participate: Not applicable. Consent to publish: Not applicable., (© 2025. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Alzheimer's disease (AD) is a chronic neurologic disease characterized by the deposition of Aβ amyloid and tau protein in the neural tissue, which leads to gradual and irreversible deterioration of memory. Positron emission tomography (PET) showed high potential in diagnosing AD. It provided a unique opportunity to assess cerebral amyloid plaques and tau neurofibrillary tangle deposits in the brain tissue without invasive procedures in vivo. Many studies have been focused on PET diagnosis of AD in recent years, which has significantly improved diagnosis and treatment strategies. This review study aims to summarize the role and emphasize the benefits of PET detection of AD biomarkers in early stages, clinical and histological progression assessment, and predicting AD outcomes. Relevant articles published in the last five years, from September 1, 2019, to October 30, 2024, were searched through authentic databases such as PubMed, PubMed Central, Europe PubMed Central, Science Direct, Cochrane Library, and Google Scholar. In this systematic review, we included articles published in English, with available full text, based on human trials, with relevant information regarding participants who underwent PET of the brain to diagnose AD biomarkers. The study strictly followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines and recommendations. The Joanna Briggs Institute (JBI) critical appraisal methods were used to evaluate all selected cross-sectional research, and the Newcastle-Ottawa Scale (NOS) was used to assess the cohort and longitudinal studies. Eleven relevant articles were included in this systematic review, and 2,203 males and females participated. The study revealed that the detection of beta-amyloid PET showed high-precious results in early diagnosis of AD. The detection of tau protein showed a high potential for estimation of the clinical and histological progression and prognosis of AD in longitudinal studies. Identifying amyloid and tau protein accumulation and glucose metabolism alterations is highly predictive of neurodegeneration in preclinical and mild cognitive impairment stages., Competing Interests: Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2025, Zarovniaeva et al.)

Estrogen, a steroid hormone synthesized by both gonadal and nongonadal tissues, plays a pivotal role in modulating immune responses, including reducing relapse rates in relapsing-remitting multiple sclerosis (MS). This study explored the expression of aromatase, the enzyme responsible for estrogen synthesis, in lymph nodes (LNs) and its potential role in the pathogenesis of MS using a mouse model. We utilized Cyp19-RFP mice where cells that express or have previously expressed the Cyp19 gene (encoding aromatase) are marked by red fluorescent protein (RFP). RFP was detected in the high endothelial venules of all morphologically identifiable LNs, indicating aromatase activity within these tissues. We discovered that LNs actively synthesize 17β-estradiol, but this activity declines with age. Targeted delivery of an aromatase inhibitor specifically to LNs induced an interferon-β-resistant experimental autoimmune encephalomyelitis (EAE) phenotype. This phenotype was accompanied by significant gray matter atrophy in the spinal cord. These findings underscore LNs as crucial sites of de novo 17β-estradiol production, potentially contributing to nonremitting EAE phenotypes. The observed decline in 17β-estradiol likely exacerbates MS pathogenesis in aging mice. Importantly, aromatase expression in human cervical LNs suggests that these sites may similarly contribute to estrogen synthesis in humans, potentially opening new avenues for understanding and treating MS., (© The Author(s) 2025. Published by Oxford University Press on behalf of National Academy of Sciences.)

Introduction: Alzheimer's disease (AD) is a neurodegenerative disorder that significantly impacts the cognitive function and memory of a person. Despite the significant research efforts, the ability to completely prevent or effectively treat AD and its related dementias remains limited. Protein kinases are integral to AD pathology and represent promising targets for therapeutic intervention., Methods: A series of pyrimidine-based compounds 4-(4-(arylsulfonyl)piperazin-1-yl)-6-(thiophen-3-yl)pyrimidine derivatives ( 8 - 14 ) were synthesized and characterised. ATPase inhibition was carried out against the MARK4 enzyme. Molecular docking and molecular dynamics (MD) simulation at 500 ns was carried out against MARK4 (PDB: 5ES1). The drug-likeness feature and toxicity of the molecules were evaluated using QikProp and other tools., Results: Compounds were synthesized following a multi-step approach and characterized using multi-nuclear magnetic resonance ( 1 H/ 13 C-NMR) and mass spectrometry. ATPase inhibition assay of the compounds against MARK4 showed an IC 50 value in the micromolar (μM) range. The results of the docking studies were consistent with the in-vitro experiments and identified ( 9 ) and ( 14 ) as the candidates with the highest affinity towards MARK4. MD simulation further supported these results, showing that the binding of ligands stabilises the target protein., Conclusion: Using experimental and theoretical approaches, we demonstrated that the reported class of pyrimidine derivatives are an excellent starting point for developing the next-generation anti-AD drugs., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2025 Haque, Alenezi, Rasheed, Rahman, Anwar, Ahamad and Gupta.)

Anemia is a prevalent complication of chronic kidney disease (CKD) and is associated with increased mortality and reduced health-related quality of life. The iron-rich protein hemoglobin, which the body utilizes to carry oxygen, deteriorates in anemia. Because hemoglobin is a protein that contains iron, disturbances in iron homeostasis can lead to iron-deficiency anemia (IDA). CKD frequently results in anemia, which is linked to a poor prognosis. Nevertheless, whether anemia per se or other comorbidities are the reason for this connection remains unclear. Uncertainty surrounds whether distinct forms of IDA can forecast CKD outcomes. Physicians, nurse practitioners, physician assistants, and registered nurses work as a team to manage anemia in patients with CKD. Individuals with CKD can benefit from the involvement of different specialties along the treatment continuum, and dietitians/nutritionists can play a significant role in enhancing management through multidisciplinary care. This literature review aims to deliver a comprehensive overview of IDA in CKD, concentrating on its diagnosis. It addresses the pathophysiology, complications associated with iron deficiency, and the available diagnostic tests for IDA in CKD. Furthermore, we analyze the literature that has contributed to developing current practice guidelines for treating IDA in CKD and encouraging multidisciplinary team collaboration in managing IDA in CKD., Competing Interests: Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2025, Kazmi et al.)

Cryptococcal-associated immune reconstitution inflammatory syndrome (C-IRIS) is a clinical worsening or new presentation of cryptococcal disease following the initiation of antiretroviral therapy. C-IRIS is primarily driven by an influx of pathological CD4 + T cells, which triggers a hyperinflammatory response. The murine model of C-IRIS is a way to study the disease in mice and understand how the immune system triggers life-threatening outcomes in patients. We previously developed a murine C-IRIS model and demonstrated that C-IRIS is triggered by pathological CD4 + T cells, particularly Th1 cells, in the brain, which triggers neurodegeneration and pulmonary dysfunction. Using this unique mouse model, we tested the therapeutic effect of a star-shaped glatiramer acetate (sGA), which is a more effective isomeric form than linear GA. Here, we observed that sGA suppresses Th1 differentiation in the lung tissues, reducing CD4 + T cell and Th1 cell count. It also reduced microglia populations in the brain. Together, these changes improved respiratory dysfunction caused by C-IRIS, lowered mortality rate, and reduced brain neurodegeneration. These findings suggest that sGA could be an effective therapeutic strategy for managing C-IRIS.

Enhanced Recovery After Surgery (ERAS) protocols aim to improve perioperative outcomes and expedite recovery across various surgical specialties. While ERAS protocols have shown significant benefits in gastrointestinal and cardiovascular surgeries, their impact and effectiveness require further synthesis. This systematic review and meta-analysis evaluated the efficacy of ERAS protocols in enhancing recovery and reducing complications in gastrointestinal and cardiovascular surgeries. High-quality studies were selected based on adherence to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and quality assessment using the Newcastle-Ottawa Scale (NOS). A systematic review and meta-analysis of six high-quality studies involving 45,678 patients were conducted using databases such as PubMed, MEDLINE, EMBASE, and Cochrane Central. Data on length of hospital stay (LOS), complications, 30-day readmissions, and mortality were extracted. Statistical analysis employed random-effects models to calculate pooled effect sizes, odds ratios (ORs), and hazard ratios. Subgroup analyses were performed based on surgery type, patient age, comorbidities, and follow-up duration. ORs for postoperative complications varied across subgroups (e.g., urgent vs. elective surgeries), with some ranges (e.g., 0.65-1.02) reflecting mixed effects; sensitivity analyses confirmed the robustness of pooled outcomes. Recovery times ranged from 1 to 3 days for gastrointestinal surgeries and 4 to 9 days for cardiovascular surgeries, demonstrating clinically meaningful variability. ERAS protocols showed greater recovery benefits in urgent surgeries (HR = 1.42, 95% CI: 1.15-1.75) and in patients with comorbidities (HR = 1.62, 95% CI: 1.33-1.96), likely due to their emphasis on rapid stabilization of perioperative care, including early mobilization and nutritional support. Heterogeneity, assessed through sensitivity analyses, ranged from moderate to substantial across subgroup analyses. ERAS protocols consistently enhance recovery outcomes, minimize complications, and reduce hospital stays in gastrointestinal and cardiovascular surgeries, demonstrating their utility in optimizing perioperative care. Future research should explore long-term outcomes and tailored implementation strategies to address patient-specific needs., Competing Interests: Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2025, Noor et al.)

A key challenge in using melt electrowriting (MEW) technology is incorporating large amounts of bioactive inorganic materials, such as hydroxyapatite (HA). In the present study, following optimization of the fabrication parameters, 40 %-HA (HA40) nanoparticles were pre-mixed into medical-grade polycaprolactone (PCL) and processed using the MEW (MEW) technique to mimic the structure and function of the natural extracellular matrix (ECM) for bone regeneration. The HA40 fibrous composite scaffolds showed continuous writing and obtained a well-connected and orderly stacked fibre with a small diameter size (67 ± 8.5 µm). A major result of the present study was the successful enrichment and accumulation of the HA particles, which mostly occurred on the MEW fibre external surfaces. This design allows for direct interfacial interaction with human periodontal ligament cells (hPDLCs). We systematically investigated the behaviour and function of hPDLCs on the HA40 composite scaffold, alongside parameters related to mineralization. The HA40 scaffold demonstrated significantly higher metabolic activity and enhanced expression of osteopontin compared to PCL-only scaffolds, as well as increased levels of ALP and COL1. The study's findings demonstrate that bioactive composite scaffolds, incorporating 40 % HA into m-PCL via MEW, effectively enhance the biological response of the ECM and are promising for potential applications in bone regeneration., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Fluorescence spectroscopy employed to compute the antibacterial potential of pure ZnO and Titania (TiO 2 ) loaded ZnO (TiO 2 : 2%, 4%, 6%, and 8%) electrospun nanofibers. The study of electrospun nanofibers followed by their structural, morphological and antibacterial properties has been revealed through fluorescence spectroscopy. X-ray diffraction (XRD) analysis of nanofibers calcinated at 600 °C revealed the presence of polycrystalline wurtzite hexagonal crystallographic planes of ZnO with preferred orientation along (101) direction. Scanning electron microscopy (SEM) confirmed that calcination of electrospun nanofibers resulted in smooth and pure ZnO nanofibers due to ethanol evaporation and polyvinylpyrrolidone (PVP) decomposition. Two bacterial strains Escherichia coli and Pseudomonas aeruginosa were used for fluorescence spectroscopy-based evaluation of antibacterial activity of ZnO and TiO 2 -ZnO nanofibers. Agar well technique was employed to investigate the antibacterial activity and functioning mechanism of nanofibers against Escherichia coli and Pseudomonas aeruginosa. The consistent zones of inhibition have been observed for pure ZnO and Titania loaded ZnO nanofibers. Fluorescence spectroscopy revealed the insights of bacterial killing with nanofibers. The mechanistic study of interaction between nanofibers and bacterial cells leads to cell membrane breakdown and confirmed with SEM imaged micrographs. Furthermore, the nanofibers calcinated at 600 °C efficiently ruptured the bacteria resulting in higher antibacterial phenomenon as compare to the other nanofiber structures., Competing Interests: Declarations. Ethical Approval: No ethical approval is required because there was no human and animal subject involved in study. Competing Interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Dysferlinopathies are debilitating autosomal recessive muscular dystrophies caused by mutations in the DYSF gene, encoding dysferlin, a protein crucial for sarcolemmal homeostasis and membrane resealing. Currently, no therapies exist for dysferlinopathies. Dysferlin features a modular structure with multiple calcium-dependent C2 lipid-binding domains. Clinical reports of mild, late-onset phenotypes suggest partial retention of functionality despite missing C2 domains, supporting exon-skipping therapies using antisense oligonucleotides (ASOs). In this study, we identified a patient-derived muscle cell line with a splice site mutation in DYSF intron 26, causing exon 26 exclusion, an out-of-frame transcript, and no detectable dysferlin protein. We hypothesized that skipping DYSF exon 27 could restore the reading frame and membrane repair function. Using an in-house in silico tool, we designed ASOs targeting exon 27. Treatment resulted in 65%-92% exon 27 skipping in myoblasts and myotubes, leading to a 39%-51% rescue of normal dysferlin expression, demonstrating robust efficacy of our designed ASOs. Two-photon laser-based assays indicated functional membrane repair. Additionally, we observed improved myotube fusion, cell vitality, and reduced apoptosis levels post-treatment. These findings provide proof of concept that DYSF exon 27 skipping restores functional dysferlin in patient-derived cells, paving the way for future in vivo and clinical studies., Competing Interests: T.Y. and R.M. are cofounders of OligomicsTx., (© 2025 The Authors. Published by Elsevier Inc. on behalf of The American Society of Gene and Cell Therapy.)

Lower gastrointestinal bleeding (LGIB) is a challenging and potentially life-threatening medical condition that often necessitates prompt intervention. In the quest to improve patient outcomes, one therapeutic agent has garnered significant attention - tranexamic acid (TXA). The basic aim of the study is to systematically review the role of TXA in LGIB. This systematic review adheres to the guidelines outlined in The Checklist for critical Appraisal and data extraction for systematic Reviews of prediction Modelling Studies, known as the CHARMS checklist, to ensure the rigorous and reproducible evaluation of predictive models. The study extends beyond the initial protocol to include a report on calibration, in addition to the originally planned assessments of discrimination, validation, and model quality. The findings revealed diverse effect sizes and precision in TXA's impact on LGIB outcomes across the studies. While some studies reported substantial effects, others exhibited more modest results, emphasizing the complexity of LGIB management. Risk of bias assessments unveiled variations in methodological quality, urging caution in interpretation. It is concluded that the role of TXA in LGIB is complex, with diverse findings and methodological considerations., Competing Interests: Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Khalid et al.)

The ability of right-angled synchronous fluorescence spectroscopy (SFS) was explored to analyse the bacterial load in water treated with green synthesized silver nanoparticles (AgNPs) coated polyurethane foam (PUF). Gram negative (Escherichia coli, Pseudomonas aeruginosa) and Gram positive (Staphylococcus aureus) bacteria cultured in nutrient broth were diluted in autoclaved water containing NPs-coated PUF. The survival rate of S. aureus and E. coli lowered after ten minutes as compared to P. aeruginosa; however, after thirty minutes, the percentage viability dropped and recorded as 3.4%, 0.9%, and 0.1% for E. coli, P. aeruginosa and S. aureus respectively in the treated suspensions. No spectral change was observed in the fluorescence emission from the positive control and treated bacterial suspension owing to the masking effect of the emission from nutrient broth. In parallel, SF spectra recorded for directly picked bacterial colony dissolved in water showed remarkable drop in tryptophan emission after treatment with NPs-coated PUF. The SF data changes were assisted by hierarchical cluster analysis, which also made it possible to distinguish between positive control and treated bacterial suspensions. SFS has shown to be a reliable substitute for the culture plate approach for the quick identification of bacterial contamination in water., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

A superoleophilic free-standing three-dimensional covalent organic framework membrane (TAM-DNDC 3D-COFM) with hydroxyl functionalized naphthalene is fabricated interfacially. The enhanced oil-wettability and anti-fouling properties of the 3D-COFM exhibited gravity-based efficient demulsification flux at a four-order magnitude compared to the phenyl cored-congener. The continuous demulsification efficiency (76 400 L m -2 ) will inspire large-scale applications.

Silver nanoparticles (AgNPs), widely utilized nanomaterials, can negatively affect crop growth and development. However, it remains unclear whether crops exhibit similar responses to AgNPs stress at seed germination and seedling stages. In this study, rice seeds and seedlings were exposed to AgNPs, and their growth, photosynthetic efficiency, and antioxidant systems were recorded. demonstrated significant AgNPs accumulation in rice tissues, with notable higher accumulation in seedlings exposed to AgNPs after germination compared to AgNPs exposure during germination. The roots exhibited greater AgNPs accumulation than shoots across both stages. Exposure to AgNPs during the seed germination stage, even at concentrations up to 2 mg/L, did not significantly affect growth, physiological indices, or oxidative stress. In contrast, seedlings exposed to 1 and 2 mg/L AgNPs showed significant reductions in shoot length, biomass, nutrient content, and photosynthetic efficiency. At low AgNPs concentrations, the maximum relative electron transport rate (rETR max ) was significantly reduced, while the higher concentrations caused pronounced declines in the chlorophyll a fluorescence transient curves (OJIP) compared to the control group. Antioxidant enzyme activities increased in both leaves and roots in a dose-dependent manner, with roots exhibiting significantly higher activity, suggesting that roots are the primary site of AgNPs stress responses. In conclusion, rice responds differently to AgNPs exposure at distinct developmental stages, with the seedling stage being more susceptible to AgNPs-induced stress than the seed germination stage. These findings underscore the importance of considering growth stages when assessing the food safety and environmental risks associated with AgNPs exposure.

High-density maize cultivation can enhance yield, but water scarcity on the Loess Plateau may limit this potential. Mulching is a sustainable practice that conserves soil moisture, yet limited studies exist on the combined effects of planting densities and mulching types on maize performance in this region. Over two years, an experiment investigated the effects of mulching (no mulching (NM), plastic film mulching (PM), and straw mulching (SM)) at various densities (60,000 to 90,000 plants ha -1 ). The results showed that mulching significantly improved grain yield and other metrics compared to NM. PM and SM enhanced yields notably at 75,000 plants ha -1 , while NM was more favorable at 67,500 plants ha -1 . Physiological responses varied with density, showing a decreased photosynthesis rate alongside an increased transpiration rate. PM exhibited a 32 and 13% increase in catalase and superoxide dismutase activities, while malondialdehyde content was reduced by 7% compared to NM. The average of both years indicates that PM significantly increased the grain yield, net photosynthesis rate, and chlorophyll content by 5.8, 26.8, and 26.9%, while SM showed a 3, 12, and 12% increase, respectively, compared to NM. In conclusion, the combination of mulching and optimized planting density could enhance maize cultivation in the Loess Plateau.

Intercropping systems offer substantial benefits in crop yield nd nutrient absorption. Utilizing logistic models, we simulated the dynamic of nutrient uptake and accumulation in spring wheat and the impact of different planting patterns and compound fertilizer application rates on spring wheat yield. We conducted a field experiment involving two planting patterns: spring wheat monoculture (MS) and spring wheat-pea intercropping (MI), with five compound fertilizer applications: C0 (0 kg ha-1), C1 (480 kg ha-1), C2 (540 kg ha-1), C3 (600 kg ha-1), and C4 (660 kg ha-1). We assessed spring wheat yield and aboveground nitrogen (N) and phosphorus (P) accumulation under different planting patterns and fertilization treatments. Results revealed that intercropping significantly increased spike number, grains per spike, and grain yield of spring wheat by 3.7%, 6.3%, and 13.3%, respectively, compared to monoculture. Fertilization treatments notably enhanced average spring wheat grain yield, with C2 performing optimally. Logistic model analysis indicated that under intercropping, the maximum accumulated aboveground N and N uptake rate (v) of spring wheat was 11.4% and 13.2% higher, and the maximum accumulated P and maximum P uptake rate (Vmax) were 11.3% and 9.5% higher, respectively, compared to monoculture. Intercropped spring wheat under C2 exhibited the highest P accumulation among all treatments. In conclusion, both intercropping and fertilization can enhance N and P uptake and accumulation in spring wheat, thereby boosting yield. Optimized yield can be achieved under C2 (540 kg h-1) with a 10% reduction in fertilizer application. Thus effective control of fertilizer application is pivotal for maximizing the yield advantage of the spring wheat/pea intercropping system., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Feng et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

People of all ages can contract pneumonia, and it can cause mild to severe disease and even death. In addition to being a major cause of death for elderly people and those with prior medical conditions such as diabetes, it isthe world's biggest infectious cause of death for children. Diabetes mellitus is a metabolic condition with a high glucose level and is a leading cause of lower limb amputation, heart attacks, strokes, blindness, and renal failure. Hyperglycemia is known to impair neutrophil activity, damage antioxidant status, and weaken the humoral immune system. Therefore, diabetic patients are more susceptible to pneumonia than people without diabetes and linked fatalities. The absence of quick, precise, simple, and affordable ways to identify the etiologic agents of community-acquired pneumonia has made diagnostic studies' usefulness contentious. Improvements in biological markers and molecular testing techniques have significantly increased the ability to diagnose pneumonia and other related respiratory infections. Identifying the risk factors for developing severe pneumonia and early testing in diabetic patients might lead to a significant decrease in the mortality of diabetic patients with pneumonia. In this regard, various risk factors, traditional testing techniques, and pathomechanisms are discussed in this review. Further, biomarkers and next-generation sequencing are briefly summarized. Finding biomarkers with the ability to distinguish between bacterial and viral pneumonia could be crucial because identifying the precise pathogen would stop the unnecessary use of antibiotics and effectively save the patient's life.

The waning immunity following the COVID-19 vaccination become a significant concern and the immunological dynamics of vaccine-induced antibodies after vaccination need to be explored. The aim of this study was to compare anti-SARS-CoV-2 receptor-binding domain (RBD) antibody levels before and after a booster dose with heterologous COVID-19 vaccine and to identify factors influencing the levels after receiving the booster dose. A cross-sectional study was conducted in which individuals who received primary doses of CoronaVac and a booster dose with an mRNA-based vaccine were recruited using a purposive sampling technique. The titers of anti-SARS-CoV-2 RBD antibodies were measured using an enzyme-linked immunosorbent assay (ELISA), and plausible associated factors were collected using a questionnaire-assisted face-to-face interview. The Wilcoxon test was used to compare the titers before and after the booster dose, while the Kruskal-Wallis and Mann-Whitney tests, followed by multivariate linear regression, were used to assess the factors associated with RBD total antibody titers. The results showed that there was a significant increase of anti-SARS-CoV-2 RBD total antibody titers before and after receiving the booster dose (1,558.7 binding antibody units (BAU)/mL vs 140.6 BAU/mL, p <0.001). The analysis revealed that age ( p =0.555), sex ( p =0.254), type of vaccine ( p =0.914), presence of hypertension ( p =0.541), diabetes ( p =0.975), chronic obstructive pulmonary disease (COPD, p =0.620), and gout ( p =0.364) were not associated with anti-SARS-CoV-2 RBD total antibody titers. However, the titers of anti-SARS-CoV-2 RBD total antibody were significantly different between those with and without hyperlipidemia ( p =0.021). This study suggests that a booster dose with a heterologous COVID-19 vaccine could significantly enhance immune responses against COVID-19, and therefore, this strategy may be recommended as part of preventive measures to strengthen immunity against COVID-19., Competing Interests: All the authors declare that there are no conflicts of interest., (© 2024 The Author(s).)

Background: Nitrous oxide (N 2 O) is a potent greenhouse gas that contributes significantly to the healthcare sector's carbon footprint. Pre-utilisation losses of N 2 O are up to 95%. Decommissioning manifolds can reduce these losses., Methods: Hospitals in our Greater London research network with at least one active N 2 O manifold were included in the Nitrous Oxide Manifold and Other Reduction of Emissions (NoMoreGas) study. N 2 O utilisation data were collected continuously over 5 days and extrapolated over a year, in addition to collecting procurement records from the preceding financial year. The primary outcome was the discrepancy between clinically utilised N 2 O and the quantity procured by hospitals, referred to as the 'N 2 O gap'. Secondary outcomes included anaesthetists' self-reported utilisation of N 2 O and their opinions on manifold decommissioning., Results: Eighteen of 53 hospitals were included. In total, 6 487 200 L of N 2 O were procured with a median (IQR) of 304 200 (183 600-473 400) L per site. During the 5-day data collection period, sites utilised a median (IQR) of 501 (42-1409) L of N 2 O. Extrapolating over a year resulted in a median (IQR) annual utilisation of 36 573 (3066-102 857) L per site and a total of 1 175 348 L. This represented an estimated 18% of the N 2 O procured, suggesting pre-utilisation losses of 5 311 852 L. Among surveyed anaesthetists, 70% (n=309) reported using N 2 O within the previous year, with one-third (n=97) using it once a week or more. There was widespread support for decommissioning manifolds., Conclusions: Consistent with other reports, the data demonstrate a substantial discrepancy between the quantities of N 2 O procured and utilised clinically, indicative of significant pre-utilisation losses. Our findings support the decommissioning of N 2 O manifolds for environmental and economic benefits., (Copyright © 2024 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.)

Phytoextraction of lead (Pb) is a challenging task due to its extremely low mobility within soil and plant systems. In this study, we tested the influence of some novel chelating agents for Pb-phytoextraction using sunflower. The Pb was applied at control (0.0278 mM) and 4.826 mM Pb as Pb(NO 3 ) 2 through soil-spiking. After 10 days of Pb addition, four different organic ligands (aspartic, ascorbic, tartaric, and pantothenic acids) were added to the soil at 1 mM concentration each. respectively. In the absence of any chelate, sunflower plants grown at 4.826 mM Pb level accumulated Pb concentrations up to 104 µg g -1 DW in roots, whereas 64 µg g -1 DW in shoot. By contrast, tartaric acid promoted significantly Pb accumulation in roots (191 µg g -1 DW; + 45.5%) and shoot (131.6 µg g -1 DW; + 51.3%). Pantothenic acid also resulted in a significant Pb-uptake in the sunflower shoots (123 µg g -1 DW; + 47.9%) and in roots (177.3 µg g -1 DW; + 41.3%). The least effective amongst the chelates tested was aspartic acid, but it still contributed to + 40.1% more Pb accumulation in the sunflower root and shoots. In addition, plant growth, biochemical, and ionomic parameters were positively regulated by the organic chelates used. Especially, an increase in leaf Ca, P, and S was evident in Pb-stressed plants in response to chelates. These results highlight that the use of biocompatible organic chelates positively alters plant physio-biochemical traits contributing to higher Pb-sequestration in sunflower plant parts., Competing Interests: Declarations. Competing interests: The authors declare that they have no competing financial interests of any sort. Ethical approval: Not applicable. Consent to participate: Not applicable. Consent to publications: All the authors agree to its submission and publication in BioMetals., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Ageing is a major risk factor for various chronic diseases and offers a potential target for developing novel and broadly effective preventatives or therapeutics for age-related conditions, including those affecting the brain. Mechanisms contributing to ageing have been summarized as the hallmarks of ageing, with iron imbalance being one of the major factors. Ferroptosis, an iron-mediated lipid peroxidation-induced programmed cell death, has recently been implicated in neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD) and Huntington's disease (HD). Addressing ferroptosis offers both opportunities and challenges for treating neurodegenerative diseases, though the specific mechanisms remain unclear. This research explores the key processes behind how ferroptosis contributes to brain ageing, with a focus on the complex signaling networks that are involved. The current article aims to uncover that how ferroptosis, a specific type of cell death, may drive age-related changes in the brain. Additionally, the article also unveils its role in neurodegenerative diseases, discussing how understanding these mechanisms could open up new therapeutic avenues., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Annona squamosa L. (Annonaceae) is a versatile tree with an edible fruit showing abundant medicinal and industrial applications. The nutritional values of this plant are due to carbohydrates, proteins, amino acids, and vitamins. Ethnopharmacological uses referred to treatment of dysentery, headlice, cancer sores, purgative, and tonic effects. The main reported biological activities for A. squamosa L. were cytotoxic, antidiabetic, antimicrobial, antiparasitic, antioxidant, antimalarial, molluscidal, anthelmintic and insecticidal activities, and its chemical classes encompassed alkaloids, diterpenes, acetogenins, and cyclopeptides. The nutritional content of A. squamosa L. and their main chemical components, biological effects, and the different applications were discussed in this review. This comprehensive review strived to compile all the relevant data in the period between 1990 and 2023 covering databases PubMed, ScienceDirect, Web of Science, Googlescholar and Reaxys concerning A. squamosa L. different parts with their reported phytochemical constituents and biological activities to integrate a better understanding of the medicinal values., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

With the expansion of the manufacturing sector, it has become crucial to incorporate sustainable production methods in order to remain competitive in the market. This study focuses on addressing the needs of the manufacturing industry by conducting a sustainability analysis of electric discharge machining for SS310 alloy. The analysis explores the impact of various electrode materials, for instance, copper and brass, as well as different machining variables, including discharge current (I = 4-12 A), spark gap (SG = 6-12 mu), pulse duration (Pon = 15-45 μs), and duty cycle (DC = 75-85%) using Taguchi method. The objective is to optimize the machining performance measures, which includes material removal rate (MRR), surface roughness (Ra), electrode wear (EW), and energy consumption (EC). In addition, the economic analysis of the machining process takes into account factors such as energy cost, dielectric consumption cost, EW cost, labor cost, and machine depreciation cost for both types of electrodes. Furthermore, the study investigates the carbon emissions resulting from EC, dielectric consumption, and EW to assess the environmental impact of the machining process. Multi-criteria decision-making approach is employed to assess the sustainability of the machining process by taking into account several performance, cost and environmental factors simultaneously. From empirical analysis, it has been observed that the copper electrode outperformed the brass electrode in terms of MRR (2.67 mm 3 /min), Ra (3.36 µm), EW (0.272 g), and EC (145.08 kJ) due to its superior electrical and thermal characteristics. In the cost analysis, copper offered lower costs for EC (2.02 PKR) attributed to its higher electrical conductivity while higher costs in terms of EW (5.5 PKR) and dielectric consumption (5.2 PKR) than brass. However, the analysis of labor and machine depreciation costs revealed that the application of copper electrode results in lower costs (80.1 and 99.3 PKR, respectively) than the brass electrode primarily due to its shorter machining time. The analysis of the environmental impact showed that the utilization of a copper electrode leads to reduced carbon emissions of 9.8 g CO 2 due to its lower EC during the machining process. However, the copper electrode results in higher emissions from EW (5.07 g CO 2 ) and dielectric consumption (54.58 g CO 2 ) compared to the brass electrode. Based on the multi-criteria decision-making using the composite desirability function approach, it is evident that the copper electrode exhibits superior performance in terms of MRR, Ra, and total machining cost. Conversely, the brass electrode demonstrates better performance in terms of overall carbon emissions., Competing Interests: Declarations. Competing interests: The authors declare no competing interests. Ethics approval: Not applicable. Consent to participate: Not applicable. Consent for publication: All authors agreed upon the current version of submission for publication., (© 2024. The Author(s).)

Background: The 2020 cancer report states that breast cancer remains a significant cause of death for females, despite the use of various strategies for early detection and treatment. However, there are still gaps in the fight against this disease. Researchers are exploring the hippo pathway, one of eight significant pathways involved in cancer progression, for potential biomarkers to use in personalized therapeutics., Methods: The current study used bioinformatic tools such as DEGs analysis, Methsurv, Km Plotter to generate data that can predict molecular biomarkers associated with hippo pathway in breast cancer development and treatment. The protein-protein interaction pathway was generated using the STRING database to find associations of hippo pathway genes with other dysregulated genes in breast cancer datasets. A disease enrichment study was also done to explore the potential of the hippo pathway in various aspects., Results: LATS2 and FAT4 genes of the hippo pathway have shown an interesting association with overall survival, hypermethylation, genetic alterations, and decreased expression levels in the breast cancer cohort. Our findings suggest that both of these genes are associated with breast cancer progression and diagnosis and can be utilized as predictive biomarkers by oncologists for personalized therapy in patients., Competing Interests: Declarations. Ethics approval and consent to participate: Not Applicable. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

This study reviews the studies utilizing Artificial Intelligence (AI) and AI-driven tools and methods in managing Acute Kidney Injury (AKI). It categorizes the studies according to medical specialties, analyses the gaps in the existing research, and identifies opportunities for future research directions. PRISMA guidelines were adopted using the three most common databases (PubMed, Scopus, and EBSCO), which resulted in 27 eligible studies, published between 2012 and 2023. The study showed significant heterogeneity in the design of the models, with variations in clinical settings, patient characteristics, cohort regions, and statistical methods. Most models were developed for AKI in hospitalized patients, particularly those undergoing surgery or in intensive care units. Compact models with a subset of significant predictors were deemed more clinically applicable than full models with all predictors. The findings suggest that AI tools, such as machine learning (ML) algorithms, have high prediction capabilities despite the dynamic and complex association among the influencing factors and AKI. Based on these findings and the recognized need for broader inclusivity, future studies should consider adopting a more inclusive approach by incorporating diverse healthcare settings, including resource-limited or developing countries. This inclusivity will lead to a more holistic understanding of AKI management challenges and facilitate the development of adaptable and universally applicable AI-driven solutions. Additionally, further investigations should focus on refining AI models to enhance their accuracy and interpretability, promoting seamless integration and implementation of AI-based tools in real-world clinical practice. Addressing these key aspects will elevate the effectiveness and impact of AI-driven approaches in managing AKI., Competing Interests: Declarations Ethics approval and consent to participate Not applicable. Consent for publication Not applicable. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

In plants, the BAX inhibitor-1 (BI-1) gene plays a crucial part in controlling cell death under stress conditions. This mechanism of Programmed Cell Death (PCD) is genetically regulated and is crucial for the elimination of unwanted or damaged cells in a controlled manner, which is essential for normal development and tissue maintenance. A study on cucumber identified and characterized five BI-1 genes: CsBI1, CsBI2, CsBI3, CsBI4, and CsBI5. These genes share conserved domains, indicating common evolutionary history and function. Physicochemical analysis revealed their molecular weights and isoelectric points, while subcellular localization showed their presence in different cellular compartments. The phylogenetic analysis highlighted evolutionary relationships with related crops. Chromosomal distribution and synteny analysis suggested segmental or tandem duplications within the gene family. Protein-protein interaction analysis revealed extensive interactions with other cucumber proteins. Cis-regulatory elements in the promoter regions provided insights into potential functions and transcriptional regulation. miRNAs showed diverse regulatory mechanisms, including mRNA cleavage and translational inhibition. The CsBI3, CsBI4 and CsBI5 genes exhibit elevated expression levels during cold stress, suggesting their vital involvement in cucumber plant defense mechanisms. The application of chitosan oligosaccharides externally confirms their distinct expression patterns. The qRT-PCR confirms the upregulation of CsBI genes in ToLCNDV-infected plants, indicating their potential to mitigate biotic and abiotic stresses. The comprehensive genome-wide exploration provides opportunities for the development of cold-tolerant and virus-resistant cucumber variants by traditional breeding or gene., (© 2024. The Author(s).)

Overview: Urethral stricture in male patients is a common problem, often necessitating surgical intervention. Sushruta has described Mootra marg sankoch (~urethral stricture) as a type of Mootraghat (~urinary retention). Pathologically, it involves the progressive fibrous narrowing of the urethral lumen. Generally, Balanitis Xerotica Obliterans begins at the prepuce and glans and gradually affects the entire urethra., Case Report: We treated a 32-year-old male patient who had undergone repeated surgical interventions over the past nine years for urethral stricture. ., Intervention: The patient was managed with Ayurvedic Uttar Basti therapy (procedure in which medicated oil is administered through urethral route) over approximately nine months., Result: During this period, significant improvements were observed in Uroflowmetry (UFM) parameters. Retrograde urethrography returned to normal after seven sessions of Ayurvedic Uttar Basti therapy. Specifically, there was approximately a 25% improvement in Maximum Flow rate, a 143% improvement in Average Flow Rate, and a 35.66% reduction in Voiding time. Additionally, the pin-hole meatus normalized, and the patient avoided further surgical procedures., Conclusion: The use of Uttar Basti, a traditional Ayurvedic treatment, in multiple sessions, provided significant improvement in flow rate and voiding time in this case, highlighting an effective alternative therapeutic approach for a condition typically managed with surgery.

As one of the most prevalent malignancies, lung cancer displays considerable biological variability in both molecular and clinical characteristics. Lung cancer is broadly categorized into small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC) with the latter being most prevalent. The primary histological subtypes of NSCLC are lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC). In the present work, we primarily extracted mRNA count data from a publicly accessible database followed by differentially expressed genes (DEGs) and differentially expressed mitophagy-related genes (DEMRGs) identification in case of both LUAD and LUSC cohorts. Next, we identified important DEMRGs via clustering approach followed by enrichment, survival, and mutational analyses. Lastly, the finalized prognostic biomarker was validated using wet-lab experimentations. Primarily, we obtained 986 and 1714 DEGs across LUAD and LUSC cohorts. Only 7 DEMRGs from both cohorts had significant membership values as indicated by the clustering analysis. Most significant pathway, Gene Ontology (GO)-biological process (BP), GO-molecular function (MF), GO-cellular compartment (CC) terms were macroautophagy, GTP metabolic process, magnesium ion binding, mitochondrial outer membrane. Among all, only TDRKH reported significant overall survival (OS) and 14% amplification across LUAD patients. Lastly, we validated TDRKH via immunohistochemistry (IHC) and semi-quantitative polymerase chain reaction (PCR). In conclusion, our findings advocate for the exploration of TDRKH and their genetic alterations in precision oncology therapeutic approaches for LUAD, emphasizing the potential for target-driven therapy and early diagnostics ., Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-024-04127-y., Competing Interests: Conflict of interestThe authors declare that they have no conflict of interest., (© King Abdulaziz City for Science and Technology 2024. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

This study explores the phytochemical composition and biological activities of Verbascum yemenense, a plant known for its medicinal properties. The plant extract revealed a rich presence of bioactive compounds that exhibited significant antioxidant properties against free radicals. The enzyme inhibition potential was particularly notable against cholinesterases (AChE: 2.56 mg GALAE/g; BChE: 1.98 mg GALAE/g), and tyrosinase (87.94 mg KAE/g), α-glucosidase suggesting potential therapeutic applications in neurodegenerative diseases, skin disorders and diabetes. Molecular docking studies and Molecular Dynamics simulations, providing insights into the interaction mechanisms of the identified compounds with the target proteins. Molecular docking studies revealed high binding affinities of the phytoconstituents, with compounds like VY4 and phyllanthusol-A (VY15) showing substantial docking scores against AChE (-9.840 kcal/mol) and BChE (-9.853 kcal/mol), respectively. For instance, the RMSD values during the MD simulations for compound VY17 in the AML complex showed a stable conformation, fluctuating within a range of 0.75 Å to 1.75 Å, indicating a strong and consistent interaction with the enzyme. MESP studies highlighted VY17's distinctive electrostatic features, notably a pronounced electronegative region, which might contribute to its binding efficiency. These findings suggest that V. yemenense is a promising candidate for developing novel therapeutic agents., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Importance: The ability to predict sudden cardiac death (SCD) in children and adolescents with hypertrophic cardiomyopathy (HCM) is currently inadequate. Late gadolinium enhancement (LGE) by cardiovascular magnetic resonance (CMR) imaging is associated with SCD events in adults with HCM., Objective: To examine the prognostic significance of LGE in patients with HCM who are younger than 21 years., Design, Setting, and Participants: This multicenter, retrospective cohort study was conducted from April 8, 2015, to September 12, 2022, in patients with HCM who were younger than 21 years and had undergone CMR imaging across multiple sites in the US, Europe, and South America. Observers of CMR studies were masked toward outcomes and demographic characteristics., Exposure: Natural history of HCM., Main Outcome and Measures: The primary outcome was SCD and surrogate events, including resuscitated cardiac arrest and appropriate discharges from an implantable defibrillator. Continuous and categorical data are expressed as mean (SD), median (IQR), or number (percentage), respectively. Survivor curves comparing patients with and without LGE were constructed by the Kaplan-Meier method, and likelihood of subsequent clinical events was further evaluated using univariate and multivariable Cox proportional hazards models., Results: Among 700 patients from 37 international centers, median (IQR) age was 14.8 (11.9-17.4) years, and 518 participants (74.0%) were male. During a median (IQR) [range] follow-up period of 1.9 (0.5-4.1) [0.1-14.8] years, 35 patients (5.0%) experienced SCD or equivalent events. LGE was present in 230 patients (32.9%), which constituted an mean (SD) burden of 5.9% (7.3%) of left ventricular myocardium. The LGE amount was higher in older patients and those with greater left ventricular mass and maximal wall thickness; patients with LGE had lower left ventricular ejection fractions and larger left atrial diameters. The presence and burden of LGE was associated with SCD, even after correcting for existing risk stratification tools. Patients with 10% or more LGE, relative to total myocardium, had a higher risk of SCD (unadjusted hazard ratio [HR], 2.19; 95% CI, 1.59-3.02; P < .001). Furthermore, the addition of LGE burden improved the performance of the HCM Risk-Kids score (before LGE addition: 0.66; 95% CI, 0.58-0.75; after LGE addition: 0.73; 95% CI, 0.66-0.81) and Precision Medicine in Cardiomyopathy score (before LGE addition: 0.68; 95% CI, 0.49-0.77; after LGE addition: 0.73; 95% CI, 0.64-0.82) SCD predictive models., Conclusions and Relevance: In this retrospective cohort study, quantitative LGE was a risk factor for SCD in patients younger than 21 years with HCM and improved risk stratification.

The goal of achieving autonomous navigation for agricultural robots poses significant challenges, mostly arising from the substantial natural variations in crop row images as a result of weather conditions and the growth stages of crops. The processing of the detection algorithm also must be significantly low for real-time applications. In order to address the aforementioned requirements, we propose a crop row detection algorithm that has the following features: Firstly, a projective transformation is applied to transform the camera view and a color-based segmentation is employed to distinguish crop and weed from the background. Secondly, a clustering algorithm is used to differentiate between the crop and weed pixels. Lastly, a robust line-fitting approach is implemented to detect crop rows. The proposed algorithm is evaluated throughout a diverse range of scenarios, and its efficacy is assessed in comparison to four distinct existing solutions. The algorithm achieves an overall intersection over union (IOU) of 0.73 and exhibits robustness in challenging scenarios with high weed growth. The experiments conducted on real-time video featuring challenging scenarios show that our proposed algorithm exhibits a detection accuracy of over 90% and is a viable option for real-time implementation. With the high accuracy and low inference time, the proposed methodology offers a viable solution for autonomous navigation of agricultural robots in a crop field without damaging the crop and thus can serve as a foundation for future research., Competing Interests: MK was employed at 84.51°. VR was employed at Equipment Technologies. This study received funding from ET Sprayers, Inc.. The funder had the following involvement in the study: Setting the overall study goals and project guidance. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Khan, Rahi, Rajendran, Al Hasan and Anwar.)

A new aluminum complex (NSO)AlMe 2 featuring a hydrogen bond donor on the ligand backbone has been synthesized via the reaction of AlMe 3 with 1-((2-(isopropylamino)phenyl)thio)propan-2-ol (NSO-H) and spectroscopically characterized. In the complex, the aluminum atom is in a distorted tetrahedral coordination sphere determined by the anionic oxygen and neutral nitrogen atoms of the ligand and by the two carbon atoms of the alkyl groups. After proper activation, the complex (NSO)AlMe 2 was able to promote the ring-opening polymerization of L -, rac -lactide, ε -caprolactone and rac - β -butyrolactone. The polymerization of rac -lactide was faster than that of L -lactide: in a toluene solution at 80 °C, the high monomer conversion of 100 equivalents was achieved in 1.5 h, reaching a turnover frequency of 63 mol LA ·mol Al -1 ·h -1 . The experimental molecular weights of the obtained polymers were close to those calculated, assuming the growth of one polymer chain for one added alcohol equivalent and the polydispersity indexes were monomodal and narrow. The kinetic investigation of the polymerization led to the determination of the apparent propagation constants and the Gibbs free energies of activation for the reaction; the terminal groups of the polymers were also identified. The complex (NSO)AlMe 2 was active in harsh conditions such as at a very low concentration or in the melt using technical-grade rac -lactide. A relatively high level of activity was observed in the ring-opening polymerization of ε -caprolactone and rac - β -butyrolactone. DFT calculations were performed and revealed the central role of the NH function of the coordinated ligand. Acting as a hydrogen bond donor, it docks the monomer in the proximity of the metal center and activates it toward the nucleophilic attack of the growing polymer chain.

The objective of this study was to find out the effect of the myofascial release technique combined with valgus correction exercise on the pain, range of motion, balance, and quality of life in participants with grade II knee osteoarthritis. Forty participants with grade II knee osteoarthritis were randomly assigned into two treatment groups in the present clinical trial; group A was the myofascial release group, and group B was the myofascial release with valgus correction exercises group. Measurement included pain, balance, range of motion, and quality of life, as measured through the visual analog scale (VAS), Berg balance scale (BBS), goniometer, and knee injury and osteoarthritis outcome score (KOOS), respectively. The data were collected at the baseline and 3rd and 6th weeks. The between-groups comparison at the end of the 6th week showed significant results in the iliotibial band myofascial release with the valgus correction exercise group ( p < 0.001). The within-group difference showed improvement in both groups individually, with more significant values in group B. The current study showed that the myofascial release combined with valgus correction exercises can effectively improve the pain, range of motion, balance, and quality of life in participants with grade II knee osteoarthritis. Trial Registration: IRCT20230216057434N3.

Introduction: The epidermal growth factor receptor (EGFR) presents a crucial target for combatting cancer mortality., Methods: This study employs a suite of computational techniques, including 3D-QSAR, ligand-based virtual screening, molecular docking, fingerprinting analysis, ADME, and DFT-based analyses (MESP, HOMO, LUMO), supplemented by molecular dynamics simulations and MMGB/PBSA free energy calculations, to explore the binding dynamics of quinazoline derivatives with EGFR. With strong q2 and r2 values from CoMFA and CoMSIA models, our 3D- QSAR models reliably predict EGFR inhibitors' efficacy., Results and Discussion: Utilizing a potent model compound as a reference, an E-pharmacophore model was developed to sift through the eMolecules database, identifying 19 virtual screening hits based on ShapeTanimoto, ColourTanimoto, and TanimotoCombo scores. These hits, assessed via 3D- QSAR, showed pIC 50 predictions consistent with experimental data. Our analyses elucidate key features essential for EGFR inhibition, reinforced by ADME studies that reveal favorable pharmacokinetic profiles for most compounds. Among the primary phytochemicals examined, potential EGFR inhibitors were identified. Detailed MD simulation analyses on three select ligands-1Q1, 2Q17, and VS1-demonstrated their stability and consistent interaction over 200 ns, with MM/GBSA values corroborating their docking scores and highlighting 1Q1 and VS1's superior EGFR1 affinity. These results position VS1 as an especially promising lead in EGFR1 inhibitor development, contributing valuable insights towards crafting novel, effective EGFR1 inhibitors., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Anwar, Alanazi, Ahemad, Raza, Chohan and Saleem.)

The diagnosis of pulmonary hypertension in non-Hodgkin's lymphoma confers a relatively poor prognosis, emphasizing the critical need for early recognition and tailored management strategies. Standard pulmonary hypertension treatments may yield suboptimal responses due to the underlying neoplastic origin, highlighting the importance of prompt initiation of chemotherapy. We present a unique case of pulmonary hypertension in marginal zone lymphoma along with a comprehensive review of reported non-Hodgkin's lymphoma cases associated with pulmonary hypertension, shedding light on the diagnostic and therapeutic challenges encountered in clinical practice., (© 2024 The Authors. Published by Elsevier Inc. on behalf of University of Washington.)