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In light of the escalating global concern regarding adaptation and resilience to elevated temperatures due to climate change, this experiment was designed to assess the thermo-physiological attributes of two native sheep breeds (Najdi and Naimi) and to delineate potential genetic factors conferring heat tolerance amidst acute exposure to elevated ambient temperatures. Meteorological and thermo-physiological parameters were scrutinized at distinct intervals (0 min, 30 min, 120 min, 24 hr, and 48 hr), alongside the analysis of heat-responsive gene expression at 0 min, 30 min, and 120 min, following the exposure of nine healthy male lambs from each breed (mean body weight: 25 kg; age: 4 months) to a bio-meteorologically-simulated environment, maintaining an average ambient temperature of 45 °C (approximately 93 units in the temperature-humidity index). In addition, blood samples were collected from each lamb, with total RNA isolated and purity assessed, followed by qRT-PCR analysis of 16 heat stress candidate genes using validated primers and standardized thermocycling protocols, including controls to ensure accuracy. Data were analyzed using statistical methods, including PROC GLM and PROC MEANS in SAS, one-way ANOVA, and pairwise differences with the LSD test for significance, while gene expression differences were calculated using the comparative Ct method and 2^ (−ΔΔCt) for relative quantification. The findings elucidate that the Najdi breed manifests heightened thermotolerance relative to the Naimi breed, as evidenced by diminished indicators of heat stress, encompassing skin temperature, respiratory rate, packed cell volume, adaptability coefficient, serum total protein, glucose levels, and triiodothyronine concentration. Moreover, analysis of gene expression patterns revealed widespread activation of heat stress-responsive genes in both breeds under thermal stress conditions; however, Najdi lambs consistently exhibited elevated expression levels of these genes compared to their Naimi counterparts. Notably, genes including HSP90AB1, HSPB6, HSF1, STIP1, HSP60, HSP90, and HSPB1 demonstrated particularly pronounced upregulation in Najdi lambs. In conclusion, the integrative thermo-physiological and molecular profiling highlights the superior thermotolerance and evolutionary adaptation of the Najdi breed to the hot climate of the KSA, in contrast to the Naimi breed.

This study was conducted to evaluate how sterubin affects rotenone-induced Parkinson's disease (PD) in rats. A total of 24 rats were distributed into 4 equal groups: normal saline control and rotenone control were administered saline or rotenone (ROT), respectively, orally; sterubin 10 received ROT + sterubin 10 mg/kg po; and sterubin alone was administered to the test group (10 mg/kg). Rats of the normal saline and sterubin alone groups received sunflower oil injection (sc) daily, 1 h after receiving the treatments cited above, while rats of the other groups received rotenone injection (0.5 mg/kg, sc). The treatment was continued over the course of 28 days daily. On the 29th day, catalepsy and akinesia were assessed. The rats were then euthanized, and the brain was extracted for estimation of endogenous antioxidants (MDA: malondialdehyde, GSH: reduced glutathione, CAT: catalase, SOD: superoxide dismutase), nitrative (nitrite) stress markers, neuroinflammatory cytokines, and neurotransmitter levels and their metabolites (3,4-dihydroxyphenylacetic acid (DOPAC), dopamine (DA), norepinephrine (NE), serotonin (5-HT), 5-hydroxyindoleacetic acid (5-HIAA), and homovanillic acid (HVA)). Akinesia and catatonia caused by ROT reduced the levels of endogenous antioxidants (GSH, CAT, and SOD), elevated the MDA level, and altered the levels of nitrites, neurotransmitters, and their metabolites. Sterubin restored the neurobehavioral deficits, oxidative stress, and metabolites of altered neurotransmitters caused by ROT. Results demonstrated the anti-Parkinson's activities of sterubin in ROT-treated rats.

In 2021 JET exploited its unique capabilities to operate with T and D–T fuel with an ITER-like Be/W wall (JET-ILW). This second major JET D–T campaign (DTE2), after DTE1 in 1997, represented the culmination of a series of JET enhancements—new fusion diagnostics, new T injection capabilities, refurbishment of the T plant, increased auxiliary heating, in-vessel calibration of 14 MeV neutron yield monitors—as well as significant advances in plasma theory and modelling in the fusion community. DTE2 was complemented by a sequence of isotope physics campaigns encompassing operation in pure tritium at high T-NBI power. Carefully conducted for safe operation with tritium, the new T and D–T experiments used 1 kg of T (vs 100 g in DTE1), yielding the most fusion reactor relevant D–T plasmas to date and expanding our understanding of isotopes and D–T mixture physics. Furthermore, since the JET T and DTE2 campaigns occurred almost 25 years after the last major D–T tokamak experiment, it was also a strategic goal of the European fusion programme to refresh operational experience of a nuclear tokamak to prepare staff for ITER operation. The key physics results of the JET T and DTE2 experiments, carried out within the EUROfusion JET1 work package, are reported in this paper. Progress in the technological exploitation of JET D–T operations, development and validation of nuclear codes, neutronic tools and techniques for ITER operations carried out by EUROfusion (started within the Horizon 2020 Framework Programme and continuing under the Horizon Europe FP) are reported in (Litaudon et al Nucl. Fusion accepted), while JET experience on T and D–T operations is presented in (King et al Nucl. Fusion submitted).

JET, the world’s largest operating tokamak with unique Be/W wall and tritium handling capability, completed a Deuterium-Tritium (D-T) campaign in 2021 (Maggi et al 29th Fusion Energy Conf. ) following a decade of preparatory experiments, dedicated enhancements, technical rehearsals and training (Horton et al 2016 Fusion Eng. Des. 109–111 925). Operation with tritium raises significant technical, safety and scientific challenges not encountered in standard protium or deuterium operation. This contribution describes the tritium operational requirements, pulses and technical preparations, new operating procedures, lessons learned and details on the achieved operational availability and performance. The preparation and execution of the recent JET tritium experiments benefitted from the previous experience in 1991 (Preliminary Tritium Experiment), 1997 (DTE1 campaign) and 2003 (Trace Tritium Campaigns) and consisted of the following five phases: technical rehearsals and scenario preparation, tritium commissioning, 100% tritium campaign, D-T campaign (DTE2), tritium clean-up. Following the clean-up JET resumed normal operation and is currently undertaking a further D-T campaign (DTE3).

Production of 155Tb radioisotope for medical purposes is still a challenge. In this regard the present study has been done using 16O beam and 146Nd target within the 3–7 MeV/nucleon energy range. The γ-ray spectrometry has been used to identify the residues produced in the reaction. The EF measurements have been done and cross-sections of 155Tb have been reported and compared with the theoretical model code PACE 4. A strong indication of the occurrence of incomplete fusion has been realized within the energy range considered. The highest cross-section of 124 ± 12 mb has been obtained at Elab 101.7 ± 0.5 MeV. [ABSTRACT FROM AUTHOR]

Vision impairment resulting from optic nerve damage poses a significant clinical challenge, often stemming from both direct and indirect traumatic injuries. In this article, we address the complexities involved in diagnosing and managing optic nerve damage, particularly in cases of blunt trauma-induced compression. We highlight the potential delay in diagnosis due to concurrent life-threatening conditions and the difficulties in assessing severely affected patients. Additionally, we present a case series involving three individuals who experienced vision loss secondary to optic nerve compression following blunt trauma. Through this analysis, we underscore the importance of timely recognition and appropriate management strategies in optimizing outcomes for patients with optic nerve injuries. [ABSTRACT FROM AUTHOR]

Sphingolipids are eighteen carbon alcohol lipids synthesized from non-sphingolipid precursors in the endoplasmic reticulum (ER). The sphingolipids serve as precursors for a vast range of moieties found in our cells that play a critical role in various cellular processes, including cell division, senescence, migration, differentiation, apoptosis, pyroptosis, autophagy, nutrition intake, metabolism, and protein synthesis. In CVDs, different subclasses of sphingolipids and other derived molecules such as sphingomyelin (SM), ceramides (CERs), and sphingosine-1-phosphate (S1P) are directly related to diabetic cardiomyopathy, dilated cardiomyopathy, myocarditis, ischemic heart disease (IHD), hypertension, and atherogenesis. Several genome-wide association studies showed an association between genetic variations in sphingolipid pathway genes and the risk of CVDs. The sphingolipid pathway plays an important role in the biogenesis and secretion of exosomes. Small extracellular vesicles (sEVs)/ exosomes have recently been found as possible indicators for the onset of CVDs, linking various cellular signaling pathways that contribute to the disease progression. Important features of EVs like biocompatibility, and crossing of biological barriers can improve the pharmacokinetics of drugs and will be exploited to develop next-generation drug delivery systems. In this review, we have comprehensively discussed the role of sphingolipids, and sphingolipid metabolites in the development of CVDs. In addition, concise deliberations were laid to discuss the role of sEVs/exosomes in regulating the pathophysiological processes of CVDs and the exosomes as therapeutic targets.

The rising problem of plastic pollution is becoming one of the major environmental issues for the world. In the ocean, plastics undergo degradation into smaller microplastics (MPs) and nanoplastics (NPs). Wild fish and farmed salmon would likely be exposed to these NPs and MPs both through skin and through skin wounds. Keratocyte cells, located in the skin epithelial layer, are scavenger cells which may remove foreign materials and maintain the salmon’s health. They are therefore first in line to handle and to suffer from MP and NP exposure. While the impacts of MPs have been well studied in many different organisms, much less is known about the effects of NP exposure, particularly at the subcellular level. Here, we have used holotomographic and fluorescence microscopy to show that both skin and corneal salmon keratocyte cells fully internalize 500–1000 nm polystyrene particles, as well as inorganic 500 nm silica particles. The fact that corneal epithelial cells also take up particles is novel. Furthermore, some of these particles likely end up in lysosomal compartments within 2 hours of exposure. Here, we show that both conventional and new modalities of microscopy have a role to play to understand how micro- and nano particles affect epithelial cells.

Abstract Viral clearance, antibody response and the mutagenic effect of molnupiravir has not been elucidated in at-risk populations. Non-hospitalised participants within 5 days of SARS-CoV-2 symptoms randomised to receive molnupiravir (n = 253) or Usual Care (n = 324) were recruited to study viral and antibody dynamics and the effect of molnupiravir on viral whole genome sequence from 1437 viral genomes. Molnupiravir accelerates viral load decline, but virus is detectable by Day 5 in most cases. At Day 14 (9 days post-treatment), molnupiravir is associated with significantly higher viral persistence and significantly lower anti-SARS-CoV-2 spike antibody titres compared to Usual Care. Serial sequencing reveals increased mutagenesis with molnupiravir treatment. Persistence of detectable viral RNA at Day 14 in the molnupiravir group is associated with higher transition mutations following treatment cessation. Viral viability at Day 14 is similar in both groups with post-molnupiravir treated samples cultured up to 9 days post cessation of treatment. The current 5-day molnupiravir course is too short. Longer courses should be tested to reduce the risk of potentially transmissible molnupiravir-mutated variants being generated. Trial registration: ISRCTN30448031

Aim: Nitrogen and sulfur-containing compounds are the core components utilized for synthesis of different heterocyclic moieties., Methods & Results: In this research, a series of new analogues containing thiazolidinone have been synthesized (1-20) in order to evaluate their activity against acetylcholinesterase and butyrylcholinesterase. Potent analogues were further subjected for molecular docking in order to study their protein-ligand interactions. The highly active analogues were also subjected for DFT, which confirmed the binding properties, electrical properties, and nature with the targeted enzyme. ADMET analysis also confirms the druglikeness properties of the synthesized series., Conclusion: Analog 5 (IC 50  =  1.2 ± 0.1 µM and 1.8 ± 0.2 µM) exhibit excellent inhibition in comparison with the standard drug donepezil in view of inhibiting Alzheimer's disease.

The lipocalin carrier protein, β-lactoglobulin (β-lg), stands out as a crucial protein in the food industry, known for its ability to effectively bind with hydrophobic small molecules. However, it was unclear how β-lg interacts with macrocyclic molecules. In this research, we focused on two key aspects. First, we synthesized a 24-membered macrocycle 4d by modifying a natural product chalcone to create a macrocycle by connecting two ortho-hydroxyl groups of each phenyl ring of two chalcone units with alkyl chains. To enhance solubility, we converted the chalcone CC bonds to epoxide rings. Second, we investigated the binding ability and mechanism of binding of the compound with the β-lg. The β-lg and 4d interaction shows an isoemissive point at 382 nm with K b  = 4.64 ± 0.02 × 10 5 at 298 K, indicating the excellent protein binding ability of 4d. Remarkably, despite its size, 4d binds to the protein without altering its conformation, suggesting the availability of a spacious binding site on the protein where the molecule fits well. Molecular docking analysis confirmed the presence of such a site at the mouth of the calyx. Additionally, our 200 ns molecular dynamics simulation demonstrated that 4d adopts a conformation to interact with the hydrophobic amino acids of the binding site, ultimately stabilizing the protein., 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.)

At present, a major effort in biophysical studies has been paid towards exploring the interactions and release of therapeutic payloads to the specific site leaving behind healthy cells unaffected and hence, lower the drug-induced toxicity. For the purpose, interaction of β-bound CUR with calf thymus DNA (ctDNA) has been examined intensely using a series of biophysical methods like absorption, steady state fluorescence emission, and circular dichroism together with molecular docking study. The experimental analysis divulge that CUR interacts with both β-CD (although with different molar ratio) and DNA. However, the binding affinity of CUR with the target (DNA) is higher than it does with the β-CD. When β-CD-carried (10 mM) CUR (μM) (inclusion complex) comes near DNA (15-372 μM), CUR gets out from β-CD's void and approaches to binds with the DNA. The relocation of the probe occurred due to competitive binding of the CUR between β-CD and the DNA. The present investigation may provide a simple yet probable route for the transfer of encapsulated therapeutic payload of β-CD to the most relevant biomolecular target DNA., 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: The exact role of different immune cells and cytokines in control or promotion of intracellular growth of leishmania has still remained a controversial topic. The aim of the present study was to study effects of cellular changes and relevant cytokines in cell mediated immunity by diphencyprone (DCP) in pathogenicity of acute L.major infection in BALB/c mice., Methods: 45 healthy female BALB/c mice were injected with L. major promastigotes under the base of tail. The mice were randomly divided to three groups of 15 mice: (1) control group without any treatment. (2) acetone group: Acetone was applied topically on the cutaneous lesions weekly and (3) DCP group: DCP was applied topically on the cutaneous lesions with increasing concentrations to induce local allergy. The mice were followed by the end of eighth week, and then macroscopic changes, histopathology, immunology studies, and organ parasite burden were determined., Results: In DCP group, in comparison to other groups the ulcer size and parasite burden in ulcer site and spleen increased, significantly. There was a deep lymphohistiocytic infiltration in the ulcer site. Total IgG, IgG1, and IgG2a levels as well as IgG2a/IgG1 ratio and intracellular IFN-gamma in CD8 + lymphocytes were significantly higher. IL4 and T CD8 + lymphocytes were significantly lower in DCP group. The IgG2a/IgG1 ratio was more than 1 in all groups., Conclusion: Our findings demonstrated that DCP reduced the CD8 + lymphocytes and IL-4 production. In spite of increased IgG2a/IgG1 ratio, the parasite burden and inflammation severity increased in infected mice. The results can show the pivotal role of CD8 + lymphocytes in conjunction with Th1 lymphocytes in the control of acute leishmania infection in mice., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Sirtuin 1 (SIRT1), an NAD+-dependent deacetylase, has emerged as a key regulator of cellular processes linked to ageing and neurodegeneration. SIRT1 modulates various signalling pathways, including those involved in autophagy, oxidative stress, and mitochondrial function, which are critical in the pathogenesis of neurodegenerative diseases. This review explores the therapeutic potential of SIRT1 in several neurodegenerative disorders, including Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and Amyotrophic Lateral Sclerosis (ALS). Preclinical studies have demonstrated that SIRT1 activators, such as resveratrol, SRT1720, and SRT2104, can alleviate disease symptoms by reducing oxidative stress, enhancing autophagic flux, and promoting neuronal survival. Ongoing clinical trials are evaluating the efficacy of these SIRT1 activators, providing hope for future therapeutic strategies targeting SIRT1 in neurodegenerative diseases. This review explores the role of SIRT1 in ageing and neurodegenerative diseases, with a particular focus on its molecular mechanisms, therapeutic potential, and clinical applications., 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.)

Conventional drug delivery systems often suffer from non-specific distribution and limited therapeutic efficacy, leading to significant side effects. To address these challenges, we developed magnetoelectric, cobalt ferrite@barium titanate (CFO@BTO) nanofibers, with a core-shell structure for targeted anticancer drug delivery. The electrospinning method was employed to synthesize polymeric nanofibers based on magnetoelectric core-shell nanostructures. The Scanning electron microscopy (SEM), Transmission electron microscopy (TEM), X-ray diffraction (XRD) and Vibrating sample magnetometer (VSM) analysis confirmed the successful loading of nanostructures on polymeric nanofiber, the core-shell morphology and magnetoelectric phase of cobalt ferrite@barium titanate CFO@BTO, respectively. To verify the drug attachment, the optimization of drug release in an applied external magnetic field, and the time required for control drug release, UV-Vis spectroscopy was used. The effectiveness of magnetic field-assisted controlled drug release was demonstrated by achieving a 95 ± 1.03% drug release from magnetoelectric nanofibers (MENFs) within 30 minutes under a magnetic field of 4mT. In vitro cytotoxicity assay on human skin cancer (SK-MEL-28) cell lines exhibited a maximum 90 ± 2% cytotoxicity with 2±0.03 cm of drug loaded MENFs. Furthermore, the Hemolysis assay was carried out to affirm the biocompatibility and non-toxicity of drug loaded MENFs, which is suitable for anticancer therapy., (© 2024 IOP Publishing Ltd. All rights, including for text and data mining, AI training, and similar technologies, are reserved.)

Mitochondrial dysfunction and cognitive impairment are widespread phenomena among the elderly, being crucial factors that contribute to neurodegenerative diseases. Nuclear factor erythroid 2-related factor 2 (Nrf2) is an important regulator of cellular defense systems, including that against oxidative stress. As such, increased Nrf2 activity may serve as a strategy to avert mitochondrial dysfunction and cognitive decline. Scientific data on Nrf2-mediated neuroprotection was collected from PubMed, Google Scholar, and Science Direct, specifically addressing mitochondrial dysfunction and cognitive impairment in older people. Search terms included "Nrf2", "mitochondrial dysfunction," "cognitive impairment," and "neuroprotection." Studies focusing on in vitro and in vivo models and clinical investigations were included to review Nrf2's therapeutic potential comprehensively. The relative studies have demonstrated that increased Nrf2 activity could improve mitochondrial performance, decrease oxidative pressure, and mitigate cognitive impairment. To a large extent, this is achieved through the modulation of critical cellular signalling pathways such as the Keap1/Nrf2 pathway, mitochondrial biogenesis, and neuroinflammatory responses. The present review summarizes the recent progress in comprehending the molecular mechanisms regarding the neuroprotective benefits mediated by Nrf2 through its substantial role against mitochondrial dysfunction and cognitive impairment. This review also emphasizes Nrf2-target pathways and their contribution to cognitive function improvement and rescue from mitochondria-related abnormalities as treatment strategies for neurodegenerative diseases that often affect elderly individuals., 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 Inc. All rights reserved.)

Background: Globally, many women express the desire to avoid immediate pregnancy for 24 months postdelivery, and only forty percent use contraceptives during this period. There is an enormous demand for postpartum family planning, particularly in developing countries with low- or middle-income grades. Postpartum intrauterine devices such as long-acting reversible contraceptives (LARCs) are among the most effective methods of family planning in the immediate postpartum period, yet their effectiveness is hindered because of a lack of availability and training. Strategies to increase access to LARCs are essential. Hence, the purpose of the current study is to determine the barriers among healthcare providers in providing immediate postpartum family planning services., Methods: A cross-sectional study was conducted in the Department of Obstetrics and Gynaecology at SIMS, a tertiary care teaching hospital, from January to March 2024. Approximately 293 healthcare providers who fulfilled the inclusion criteria were provided an online questionnaire in the form of a Google Forms link, which included a structured questionnaire focusing on various aspects, including demographics, knowledge, practices, and barriers in their practice. The data collected were analysed through SPSS version 26, which employs chi-square tests and Pearson's correlation to determine any significant associations among them. Based on the key statistical outcomes and the significant correlations observed related to the data, a thematic analysis through SWOT (strengths, weaknesses, opportunities, threats) was conducted. The study adhered to the method outlined by Braun and Clarke (2006) and compiled with the COREQ (consolidated criteria for reporting qualitative research) checklist to uphold methodological integrity., Results: Among the participants, 92.4% provided family planning counselling after childbirth, predominantly during the antenatal period (75.1%), and the provision of immediate postnatal family planning was reported in 76.1% of the participants, with PPIUDs identified as the most utilized method by 52.6%. Various barriers were identified, including insufficient training on Implanon (33.4%) and the PPIUCD (12.6%), the unavailability of implants (59.0%), and a lack of interest among patients (46.1%). Statistically significant associations were observed between the practice setting and knowledge of postpartum family planning ( p = 0.002), as well as deficiencies in training for the PPIUCD ( p < 0.001). The study highlights the place of practice and the practitioners' experience as significant strengths in offering immediate postpartum contraception and referring patients for family planning. However, qualification was identified as a limiting factor for practicing immediate postpartum family planning., Conclusions: This study revealed significant difficulty in delivering prompt postpartum long-acting reversible contraceptives (LARCs), underscoring the necessity of improved education and training for professionals. Focusing on these challenges is important in enhancing postpartum family planning acceptance and decreasing unfulfilled requirements in resource-limited settings.

Background and Objectives: Rosiridin is a monoterpene with outstanding monoamine inhibitory activity that is useful to treat depressive episodes and rapid-onset dementia. The current investigation aims to evaluate the neurologically protective impact of rosiridin, which opposes aluminum chloride (AlCl 3 ) and causes memory dysfunction in rats. Materials and Methods: Memory impairment was developed in Wistar rats by administering AlCl 3 (100 mg/kg p.o.) orally for 42 days and then supplemented with rosiridin at 10 and 20 mg/kg/p.o. Upon completion of the investigation, the behavior factor was performed utilizing the Y-maze, Morris Water Maze, and open field tests. Estimating numerous biological factors, such as nitric oxide (NO), oxidative stress (malondialdehyde MDA), acetylcholinesterase (AChE), butyrylcholinesterase levels (BuChE), antioxidants (glutathione GSH, catalase CAT, and superoxide dismutases SODs) and neurotransmitter (serotonin-5HT, dopamine-DA, acetylcholine-Ach) in the brain. Furthermore, interleukin-6 (IL-6), IL-1β, tumor necrosis factor (TNF-α), brain-derived neurotrophic factor (BNDF), nuclear factor kappa B (NFᴋB), phosphatidylinositol 3-kinase (PI3K), and pAkt were assessed in the diffused brain cells. Results: The rosiridin-treated group significantly improved in terms of behavioral parameters, including in the Y-maze, Morris Water Maze, and open field tests. Further, rosiridin restored biochemical parameters, including NO, oxidative stress AChE, BuChE, antioxidants, neurotransmitters, IL-6, IL-1β, TNF-α, BNDF, NFᴋB, PI3K, and pAkt compared to AlCl 3 . Conclusions: The current investigation reveals that rosiridin could ameliorate the impairment of memory that AlCl3 causes in rats via improvements in behavioral and restored biochemical parameters.

Competing Interests: Conflict of Interest All authors have no conflicts of interest to declare.

Lung cancer remains an intractable malignancy worldwide, prompting novel therapeutic modalities. Pyroptosis, a lethal form of programmed cell death featured by inflammation, has been involved in cancer progression and treatment response. Simultaneously, non-coding RNA has been shown to have important roles in coordinating pattern formation and oncogenic pathways, including long non-coding RNA (lncRNAs), microRNA (miRNAs), circular RNA (circRNAs), and small interfering RNA (siRNAs). Recent studies have revealed that ncRNAs can promote or inhibit pyroptosis by interacting with key molecular players such as NLRP3, GSDMD, and various transcription factors. This dual role of ncRNAs offers a unique therapeutic potential to manipulate pyroptosis pathways, providing opportunities for innovative cancer treatments. In this review, we integrate current research findings to propose novel strategies for leveraging ncRNA-mediated pyroptosis as a therapeutic intervention in lung cancer. We explore the potential of ncRNAs as biomarkers for predicting patient response to treatment and as targets for overcoming resistance to conventional therapies., 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 GmbH. All rights reserved.)

Introduction: Fustin, a photogenic flavanol found in the plant Rhus verniciflua Stokes, has been involved in multiple disease ailments and has a beneficial pharmacological effect and a history of use in traditional medicine. The present research aimed to study the impact of fustin on scopolamine (SCOP)-induced memory impairment and neurodegeneration by modulating neuroinflammation and neurotransmitters in rats., Methods: A total of 30 healthy Wistar rats were allocated into five groups (n=6). Group I- served as control and received saline solution (1mL/kg i.p.), group -II- fustin (100 mg/kg, orally), group -III -SCOP (1 mg/kg, i.p.), and group -IV and V were given fustin (50 and 100 mg/kg/p.o.) with SCOP (1 mg/kg, i.p.) for 14-days. After 14 days, 2 hours after SCOP injection, the Y-maze and Morris water maze (MWM) tests were performed. After behavioral tests rats were subsequently euthanized, and brain supernatants were used to estimate choline-acetyltransferase (ChAT), acetylcholinesterase (AChE), antioxidant [superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH)], and total protein, oxidative stress markers [nitrate and malondialdehyde (MDA)], pro-inflammatory markers [tumor necrosis factor (TNF-α), and Interleukins-1β (IL-1β) and IL-6]. Also, neurotransmitters such as serotonin (5-HT), dopamine (DA), ϒ-amino butyric acid (GABA), acetylcholine (Ach), and noradrenaline (NA) contents were performed., Results: Fustin exhibited substantial behavioral improvement in the Y-maze measures spontaneous alterations percentage (SA%) and decreased latency time following the acquisition and prolonged time spent in the probe trial in the MWM test. Moreover, fustin inhibits enhanced neuroinflammatory cytokines and oxidative stress markers and improves the neurotransmitters., Conclusion: The findings of this study suggest that fustin inhibits SCOP impact on cognitive abilities in rats. The present investigation demonstrates that fustin, a potent phytochemical, effectively mitigated the behavioral and physiological changes induced by SCOP in rats. This was primarily achieved by modulating the levels of inflammatory response and neurotransmitters., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Objective: Data-driven methodologies in healthcare necessitate labeled data for effective decision-making. However, medical data, particularly in unstructured formats, such as clinical notes, often lack explicit labels, making manual annotation challenging and tedious., Methods: This paper introduces a novel deep active learning framework designed to facilitate the annotation process for multiclass text classification, specifically using the SOAP (subjective, objective, assessment, plan) framework, a widely recognized medical protocol. Our methodology leverages transformer-based deep learning techniques to automatically annotate clinical notes, significantly easing the manual labor involved and enhancing classification performance. Transformer-based deep learning models, with their ability to capture complex patterns in large datasets, represent a cutting-edge approach for advancing natural language processing tasks., Results: We validate our approach through experiments on a diverse set of clinical notes from publicly available datasets, comprising over 426 documents. Our model demonstrates superior classification accuracy, with an F1 score improvement of 4.8% over existing methods but also provides a practical tool for healthcare professionals, potentially improving clinical documentation practices and patient care., Conclusions: The research underscores the synergy between active learning and advanced deep learning, paving the way for future exploration of automatic text annotation and its implications for clinical informatics. Future studies will aim to integrate multimodal data and large language models to enhance the richness and accuracy of clinical text analysis, opening new pathways for comprehensive healthcare insights., Competing Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)

One of the most complex human physiological processes to study is pregnancy. Standard animal models, as well as two-dimensional models, lack the complexity and biological relevance required to accurately study such a physiological process. Recent studies have focused on the development of three-dimensional models based on microfluidic systems, designated as placental microphysiological systems (PMPSs). PMPS devices provide a model of the placental barrier through culturing relevant cell types in specific arrangements and media to mimic the in vivo environment of the maternal-fetal circulation. Here, recent developments of PMPS models for embryo uterine implantation, preeclampsia evaluation, and toxicological screening are presented. Studies that use bioprinting techniques are also discussed. Lastly, recent developments in endometrium microphysiological systems are reviewed. All these presented models showed their superiority compared to standard models in recapitulating the biological environment seen in vivo . However, several limitations regarding the types of cells and materials used for these systems were also widely reported. Despite the need for further improvements, PMPS models contribute to a better understanding of the biological mechanisms surrounding pregnancy and the respective pathologies.

The analysis aimed to prepare an in-situ implant (ISFI) formulation holding dimethyl fumarate as (a model drug) using cross-linked gellan gum by homogenization method. Cross-linking of gellan gum was done with L-cysteine to improve its gelation properties. Fourier transform infrared spectroscopy (FTIR) and (DSC) Differential scanning calorimetry were used to test the compatibility of the drug-polymer. The diverse formulations were prepared and tested using Design Expert® ver 8.0.1 software to optimize the experiment technique and employ the response surface. The tissue compatibility of the test verified the existence of non-irritants in the established formulation. All preparations contained the drug content from approximately 97.98 to 99.88%. Viscosities are ideal for injection in the optimized formulation (1,55 percent w/w in water). The optimized formula was monitored, and up to 156hours, it was found to be 95.7%. The result was that ISFI can effectively monitor and control the delivery of several powerful drug products., (Copyright © 2024 Académie Nationale de Pharmacie. Published by Elsevier Masson SAS. All rights reserved.)

This review article aims to summarize broadly recent developments in the treatment of HPV-associated cancers, including cervical cancer and head and neck squamous cell carcinoma. Relatively new treatments targeting the key HPV E6 and E7 oncoproteins, including gene editing with TALENs and CRISPR/Cas9, are discussed. Given the increased immunogenicity of HPV-related diseases, other therapies such as PRR agonists, adoptive cell transfer, and tumor vaccines are reaching the clinical trial phase. Due to the mechanism, immunogenicity, and reversibility of HPV carcinogenesis, HPV-related cancers present unique targets for current and future therapies.

This work demonstrates the facile one step hydrothermal synthesis of carbon dots doped with nitrogen and sulfur (SCDs). The carbon dots have various uses, including their use as molecular payloads for antioxidant and drug delivery purposes. The sizes of the CDs were determined using transmission electron microscopy (TEM), which revealed an average size of 4.2 nm. The successful sulfur doping was confirmed by Fourier-transform infrared (FTIR) spectroscopy and X-ray photoelectron spectroscopy (XPS), which identified typical functional groups and elemental composition. UV-vis and photoluminescence (PL) spectroscopy revealed a wide absorption peak at 280 nm and a pronounced blue emission at 440 nm. Colloidal stability was confirmed by dynamic light scattering (DLS) and zeta potential analysis. The antioxidant characteristics were evaluated through the use of electron paramagnetic resonance (EPR) spectroscopy, which confirmed a notable ability to scavenge radicals which revealed more than 80% radical scavenging capability. The SCDs also showed nontoxic behavior against living cells. The findings emphasize the potential of SCDs in the fields of bioimaging, drug delivery, and as potent antioxidant agents., Competing Interests: The authors declare no conflict of interest., (This journal is © The Royal Society of Chemistry.)

Background/Objectives: 6-Shogaol is a comparatively innovative anti-Parkinson's remedy with antioxidant and anti-inflammatory characteristics. This investigation intended to determine the role of 6-shogaol in the Parkinson's disease (PD) paradigm in rotenone-induced rats. Methods: Thirty male Wistar rats (10-12 weeks old; 180 ± 20 g) were divided into five groups. Animals with rotenone-induced experimental PD were subsequently treated with 6-shogaol-10 at 20 mg/kg for 28 days. After the experimental duration, behavioural investigations were performed, i.e., open field test, forced swim test, rotarod test, and catalepsy test. Biochemical assessments like AChE, GSH, CAT, SOD, MDA, nitrite, ceruloplasmin, proinflammatory markers such as IL-1β, NF-κB, TNF-α, and catecholamines markers (DA, GABA, and MAO-B) were determined. The docking procedure was conducted using the AutoDock Vina docking protocol. Furthermore, histopathology was performed. Results: Rotenone significantly increased the level of MAO-B, oxidative, nitrative, and pro-inflammatory markers. However, there was a decline in ceruloplasmin, dopamine, and endogenous antioxidants. Treatment with 6-shogaol (10 and 20 mg/kg) considerably sustained the elevation of oxidative stress and inflammatory indicators and decreased AChE activity and dopamine levels. In the histology of the brain, 6-shogaol improved the neuronal structure and reduced the degeneration of neurons. Based on the binding energy values, compound 6-shogaol demonstrates a favourable binding affinity to AChE, MAO-B, DA, and GABA with respective binding energies of -8.214, -8.133, -7.396 and -6.189 kcal/mol. Conclusions: In this study, 6-shogaol exhibited neuroprotective properties against PD, which could be employed as a prospective medication for PD.

Background: Infective endocarditis (IE) poses significant clinical challenges, often necessitating surgical intervention for improved patient outcomes. The choice between mitral valve repair (MVP) and mitral valve replacement (MVR) is crucial in managing IE. This systematic review and meta-analysis aims to compare the effectiveness of MVP and MVR in treating IE, focusing on outcomes such as postoperative bleeding, mortality, recurrent endocarditis, and stroke., Main Text: A comprehensive literature search was conducted following PRISMA guidelines. Studies directly comparing MVP and MVR in IE patients were included. Data extraction and quality assessment were performed, and meta-analysis was conducted using RevMan software. Thirty-two studies involving 82,123 patients were included. MVP was associated with significantly lower rates of postoperative bleeding (OR: 0.58, 95% CI: 0.40-0.84) and reduced long-term mortality (OR: 0.40, 95% CI: 0.32-0.51) compared to MVR. However, MVR showed lower rates of recurrent endocarditis. MVP was also associated with a decreased likelihood of postoperative stroke (OR: 0.52, 95% CI: 0.40-0.68).2, 4 CONCLUSIONS: MVP demonstrates advantages over MVR in reducing postoperative bleeding, long-term mortality, and stroke risk in IE patients. However, individual patient factors and surgical expertise must be considered in treatment decisions. Further research, including randomized controlled trials, is needed to validate these findings and refine treatment algorithms for IE management., (© 2024. The Author(s).)

Huntington's disease (HD) is a devastating neurodegenerative disease that is manifested by a gradual loss of physical, cognitive, and mental abilities. As the disease advances, age has a major impact on the pathogenic signature of mutant huntingtin (mHTT) protein aggregation. This review aims to explore the intricate relationship between aging, mHTT toxicity, and cellular senescence in HD. Scientific data on the interplay between aging, mHTT, and cellular senescence in HD were collected from several academic databases, including PubMed, Google Scholar, Google, and ScienceDirect. The search terms employed were "AGING," "HUNTINGTON'S DISEASE," "MUTANT HUNTINGTIN," and "CELLULAR SENESCENCE." Additionally, to gather information on the molecular mechanisms and potential therapeutic targets, the search was extended to include relevant terms such as "DNA DAMAGE," "OXIDATIVE STRESS," and "AUTOPHAGY." According to research, aging leads to worsening HD pathophysiology through some processes. As a result of the mHTT accumulation, cellular senescence is promoted, which causes DNA damage, oxidative stress, decreased autophagy, and increased inflammatory responses. Pro-inflammatory cytokines and other substances are released by senescent cells, which may worsen the neuronal damage and the course of the disease. It has been shown that treatments directed at these pathways reduce some of the HD symptoms and enhance longevity in experimental animals, pointing to a new possibility of treating the condition. Through their amplification of the harmful effects of mHTT, aging and cellular senescence play crucial roles in the development of HD. Comprehending these interplays creates novel opportunities for therapeutic measures targeted at alleviating cellular aging and enhancing HD patients' quality of life., (© 2024 The Author(s). CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.)

Background: Type 2 diabetes mellitus (T2DM) is defined by a wide variety of metabolic abnormalities, persistent hyperglycemia, and a slew of other complications. Catharanthus roseus L. (apocyanaceae), remarkably notable as Vinca Rosea , appears to be the source of the active component hirsutidin, which is reported in various diseases., Objective: The study intended to appraise the antidiabetic capability of hirsutidin in a high-fat diet (HFD) and streptozotocin (STZ) induced diabetes in experimental rats., Materials and Methods: An experimental rodent T2DM model was elicited by consuming an HFD regimen with STZ 50 mg/kg, i.p. dose formulated in a 0.1 M cold citrate buffer (pH 4.5). The test drug hirsutidin (10 and 20 mg/kg) and the standard drug glimeclamide (5 mg/kg) were administered daily for six weeks. The efficacy of hirsutidin was observed on several diabetes parameters. The average body weight and an array of biochemical markers were determined, including blood glucose, insulin, dyslipidemia (lipid profile), total protein (TP), liver injury [aspartate aminotransferase (AST), alanine aminotransferase (ALT)], inflammation [IL-6, IL-1β, tumor necrosis factor-α (TNF-α)], oxidative stress [malondialdehyde (MDA)] and antioxidant status [catalase (CAT), glutathione (GSH), and superoxide dismutase (SOD)]. In addition, the concentrations of leptin, adiponectin, and resistin were also assessed. Also, molecular docking studies were undertaken to investigate critical targets associated with diabetes, including TNF-α, insulin, adiponectin, and leptin., Results: Diabetes induction with HFD/STZ resulted in hyperglycemia (significantly reduced blood glucose and increased insulin level), dyslipidemia (significantly reduced TC, TG and increased HDL), total protein (significantly reduced), oxidative stress and antioxidant status (significantly reduced MDA and increased CAT, SOD and GSH levels), inflammation (significantly decreased IL-6, IL-1β, TNF-α), liver damage (significantly reduced AST, ALT), and specific hormones such as adiponectin, leptin significantly improved and resistin significantly reduced as evidenced by biochemical data in this study. Intermolecular interactions of ligands and docking score, hirsutidin proteins TNF-α (2AZ5), Insulin (4IBM), Adiponectin (6KS1), Leptin (7Z3Q) with binding energy of -6.708, -7.674, -7.2 and -7.547 Kcal/mol., Conclusion: Hirsutidin may have an evidential hypoglycemic outcome and may exhibit potent antidiabetic activity in HFD/STZ-induced T2DM in rats. Treatment with hirsutidin significantly improved glycemic control, lipid metabolism, oxidative stress, inflammation, and liver function. Additionally, it normalized dysregulated levels of adiponectin, leptin, and resistin. Molecular docking confirmed its strong binding affinity to key diabetic targets., Competing Interests: 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., (© 2024 The Authors.)

With the advent rise is in urbanization and industrialization, heavy metals (HMs) such as lead (Pb) and cadmium (Cd) contamination have increased considerably. It is among the most recalcitrant pollutants majorly affecting the biotic and abiotic components of the ecosystem like human well-being, animals, soil health, crop productivity, and diversity of prokaryotes (bacteria) and eukaryotes (plants, fungi, and algae). At higher concentrations, these metals are toxic for their growth and pose a significant environmental threat, necessitating innovative and sustainable remediation strategies. Bacteria exhibit diverse mechanisms to cope with HM exposure, including biosorption, chelation, and efflux mechanism, while fungi contribute through mycorrhizal associations and hyphal networks. Algae, especially microalgae, demonstrate effective biosorption and bioaccumulation capacities. Plants, as phytoremediators, hyperaccumulate metals, providing a nature-based approach for soil reclamation. Integration of these biological agents in combination presents opportunities for enhanced remediation efficiency. This comprehensive review aims to provide insights into joint action of prokaryotic and eukaryotic interactions in the management of HM stress in the environment., (© 2024. Institute of Microbiology, Academy of Sciences of the Czech Republic, v.v.i.)

Long non-coding RNAs (lncRNAs) have emerged as crucial regulators in various cellular processes, including cancer progression and stress response. Recent studies have demonstrated that copper accumulation induces a unique form of cell death known as cuproptosis, with lncRNAs playing a key role in regulating cuproptosis-associated pathways. These lncRNAs may trigger cell-specific responses to copper stress, presenting new opportunities as prognostic markers and therapeutic targets. This paper delves into the role of lncRNAs in cuproptosis-mediated cancer, underscoring their potential as biomarkers and targets for innovative therapeutic strategies. A thorough review of scientific literature was conducted, utilizing databases such as PubMed, Google Scholar, and ScienceDirect, with search terms like 'lncRNAs,' 'cuproptosis,' and 'cancer.' Studies were selected based on their relevance to lncRNA regulation of cuproptosis pathways and their implications for cancer prognosis and treatment. The review highlights the significant contribution of lncRNAs in regulating cuproptosis-related genes and pathways, impacting copper metabolism, mitochondrial stress responses, and apoptotic signaling. Specific lncRNAs are potential prognostic markers in breast, lung, liver, ovarian, pancreatic, and gastric cancers. The objective of this article is to explore the role of lncRNAs as potential prognostic markers and therapeutic targets in cancers mediated by cuproptosis., (© 2024. The Author(s).)

Given the suboptimal performance of Boolean searching to identify methodologically sound and clinically relevant studies in large bibliographic databases, exploring machine learning (ML) to efficiently classify studies is warranted. To boost the efficiency of a literature surveillance program, we used a large internationally recognized dataset of articles tagged for methodological rigor and applied an automated ML approach to train and test binary classification models to predict the probability of clinical research articles being of high methodologic quality. We trained over 12,000 models on a dataset of titles and abstracts of 97,805 articles indexed in PubMed from 2012-2018 which were manually appraised for rigor by highly trained research associates and rated for clinical relevancy by practicing clinicians. As the dataset is unbalanced, with more articles that do not meet the criteria for rigor, we used the unbalanced dataset and over- and under-sampled datasets. Models that maintained sensitivity for high rigor at 99% and maximized specificity were selected and tested in a retrospective set of 30,424 articles from 2020 and validated prospectively in a blinded study of 5253 articles. The final selected algorithm, combining a LightGBM (gradient boosting machine) model trained in each dataset, maintained high sensitivity and achieved 57% specificity in the retrospective validation test and 53% in the prospective study. The number of articles needed to read to find one that met appraisal criteria was 3.68 (95% CI 3.52 to 3.85) in the prospective study, compared with 4.63 (95% CI 4.50 to 4.77) when relying only on Boolean searching. Gradient-boosting ML models reduced the work required to classify high quality clinical research studies by 45%, improving the efficiency of literature surveillance and subsequent dissemination to clinicians and other evidence users., Competing Interests: McMaster University, a not-for-profit institution, has contracts, managed by the Health Information Research Unit, supervised by AI, RBH, and LL, with several professional and commercial publishers, to supply newly published studies and systematic reviews that are critically appraised for research methods and assessed for clinical relevance through the McMaster Premium Literature Service (McMaster PLUS). TN, RP, CC, and CL are partly paid through these contracts and RBH receives remuneration for supervisory time and royalties. WA, EB, FG, LC, and MA are not affiliated with McMaster PLUS., (Copyright: © 2024 Lokker 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.)

Atrial fibrillation (AF) is the most common cardiac arrhythmia in the United States, affecting 2.7-6.1 million people. AF can cause symptoms, but when it triggers a rapid ventricular response (RVR), most patients suffer from decompensation. Therefore, we performed an umbrella review of systematic reviews and meta-analyses comparing intravenous (IV) metoprolol and diltiazem to identify discrepancies, fill in knowledge gaps, and develop standardized decision-making guidelines for physicians to manage AF with RVR. A comprehensive search was conducted in PubMed, the Cochrane Library, and Scopus to identify studies for this umbrella review. The overall certainty of the evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation method, while the quality of the included reviews was evaluated using AMSTAR 2, the Cochrane Collaboration tool, and the Newcastle-Ottawa scale. This study comprehensively analyzed four meta-analyses covering 11 randomized controlled trials and 19 observational studies. The analysis showed that IV diltiazem treatment was significantly more successful in rate control for AF with rapid ventricular response (RVR) than IV metoprolol (risk ratio [RR], 1.30; 95% confidence interval [CI], 1.09-1.56; I 2 = 0%; P = .003). IV diltiazem also led to a significantly greater reduction in ventricular rate (mean difference, -14.55; 95% CI, -16.93 to -12.16; I 2 = 72%; P < .00001), particularly at 10 min. The analysis also revealed a significantly increased risk of hypotension associated with treatment with IV diltiazem (RR, 1.43; 95% CI, 1.14-1.79; I 2 = 0%; P = .002). In conclusion, IV diltiazem therapy achieved better rate control and ventricular rate decrease than metoprolol therapy in AF with RVR. Future clinical trials should compare calcium channel blockers and β-blockers for heart rate control efficacy and safety, considering adverse events., Competing Interests: The authors report no conflicts of interest for the published content. No funding information was provided., (Copyright: © 2024 Innovations in Cardiac Rhythm Management.)

Neuropathic pain, a debilitating condition, remains challenging to manage effectively. An insight into neuropharmacological mechanisms is critical for optimizing treatment strategies. This systematic review aims to evaluate the role of neuropharmacological agents based on their efficacy, involved neurotransmitters, and receptors. A manual literature search was undertaken in PubMed including Medline, Cochrane Library, Google Scholar, Plos One, Science Direct, and clinicaltrials.gov from 2013 until 2023. Out of the 13 included studies, seven evaluated the role of gabapentinoids. Two main drugs from this group, gabapentin and pregabalin, function by binding voltage-gated calcium channels, lowering neuronal hyperexcitability and pain signal transmission, thereby relieving neuropathic pain. Four of the pooled studies reported the use of tricyclic antidepressants (TCAs) including amitriptyline and nortriptyline which work by blocking the reuptake of norepinephrine and serotonin, their increased concentration is thought to be central to their analgesic effect. Three articles assessed the use of serotonin-norepinephrine reuptake inhibitors (SNRIs) and reported them as effective as the TCAs in managing neuropathic pain. They work by augmenting serotonin and norepinephrine. Three studies focused on the use of selective serotonin reuptake inhibitors (SSRIs), modulating their effect by increasing serotonin levels; however, they were reported as not a highly effective treatment option for neuropathic pain. One of the studies outlined the use of cannabinoids for neuropathic pain by binding to cannabinoid receptors with only mild adverse effects. It is concluded that gabapentinoids, TCAs, and SNRIs were reported as the most effective therapy for neuropathic pain; however, for trigeminal neuralgia, anticonvulsants like carbamazepine were considered the most effective. Opioids were considered second-line drugs for neuropathic pain as they come with adverse effects and a risk of dependence. Ongoing research is exploring novel drugs like ion channels and agents modulating pain pathways for neuropathic pain management. Our review hopes to inspire further research into patient stratification by their physiology, aiding quicker and more accurate management of neuropathic pain while minimizing inadvertent side effects., 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, Mian et al.)

Cardiovascular disease (CVD) remains one of the major causes of sickness and death in the world. However, lifestyle modifications, such as exercise, can significantly reduce the risk of this disease. This study aimed to assess the effectiveness of various forms of physical activity in reducing CVD risk factors among adults. A comprehensive search of the databases PubMed, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Cochrane Central Register of Controlled Trials (CENTRAL), and Excerpta Medica Database (EMBASE) databases was conducted between January 1, 2014, and May 31, 2024, as per Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Randomized controlled trials (RCTs), cohort studies, and observational studies on the impact of aerobic, resistance, or combined training on cardiovascular risk factors in adults (≥18 years) were considered for inclusion. Data relating to primary outcomes, including stroke and myocardial infarction rates, BP, cholesterol levels, and BMI were collected. The Cochrane risk-of-bias tool and the Methodological Index for Non-Randomized Studies (MINORS) checklist were used for quality and bias assessment. Meta-analyses were performed using the RevMan software, with heterogeneity evaluated by I² statistics; 17 studies, including 11 RCTs and six cohort studies, met the inclusion criteria. There was a significant reduction in the mean systolic BP (SBP) by 3.32 mmHg [95% confidence interval (CI): 0.85-5.78 mmHg; p<0.0001] and mean diastolic BP (DBP) by 2.99 mmHg (95% CI: 2.34-3.64 mmHg; p < 0.00001) after exercise interventions. Moreover, cholesterol levels and BMI values improved with exercise. Those who exercised had a lower risk of stroke or heart attack compared with the controls [odds ratio (OR): 0.57; 95% CI: 0.28-1.14; p >0.0001], although there was substantial heterogeneity in effect size across the studies (I² = 98%). Different types of physical activity (i.e., aerobic, resistance, or combined exercise) can effectively reduce key cardiovascular risk factors, including BP, cholesterol levels, and BMI values. Regular physical activity is still regarded as the most effective preventive measure against CVD, despite inconsistencies in research findings. Future studies should aim to identify optimal exercise programs and their long-term effects on diverse populations., 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, Masmoum et al.)

Herbs have been used as medicines since antiquity, and it has been discovered that the human body responds well to herbal remedies. Research on the effect of butin was conducted in the current study in the alloxan-induced diabetic rat paradigm. A total of 30 Wistar rats were randomly assigned into the following groups (n = 6): I-Normal; II-Alloxan-induced (50 mg/kg); III-Alloxan + butin 25 mg/kg; IV-Alloxan + butin 50 mg/kg; V-Butin per se 50 mg/kg. Various diabetic parameters (blood glucose, insulin, HbA1c), lipid profile, inflammatory (TNF-α, IL-1β, IL-6 and NF-κB), antioxidant enzymes (CAT, SOD and GSH), oxidative stress indicators (MDA), apoptosis marker (caspase-3), hepatic markers (ALT and AST), and histopathological changes were assessed. Additionally, molecular docking and dynamics were performed to evaluate the interaction of butin with target proteins. Butin treatment, at both doses, significantly restored biochemical parameters and preserved pancreatic histopathology in diabetic rats. It effectively modulated blood parameters, lipid profiles, inflammatory markers, apoptosis, antioxidant enzyme activity, oxidative stress, and hepatic markers. Molecular docking revealed that butin binds to proteins such as caspase-3 (1NME), NF-κB (1SVC), and serum insulin (4IBM) with binding affinities of - 7.4, - 6.5, and - 8.2 kcal/mol, respectively. Molecular dynamics simulations further suggested that butin induces significant conformational changes in these proteins. Butin exhibits potential effects against alloxan-induced diabetic rats by restoring biochemical balance, reducing inflammation, and protecting pancreatic tissue. Its binding to key proteins involved in apoptosis and inflammation highlights its therapeutic potential in diabetes management., (© 2024. The Author(s).)

Cardiovascular diseases remain the leading cause of global mortality, underscoring the critical need for accurate and timely diagnosis. This narrative review examines the current applications and future potential of artificial intelligence (AI) and machine learning (ML) in cardiovascular imaging. We discuss the integration of these technologies across various imaging modalities, including echocardiography, computed tomography, magnetic resonance imaging, and nuclear imaging techniques. The review explores AI-assisted diagnosis in key areas such as coronary artery disease detection, valve disorders assessment, cardiomyopathy classification, arrhythmia detection, and prediction of cardiovascular events. AI demonstrates promise in improving diagnostic accuracy, efficiency, and personalized care. However, significant challenges persist, including data quality standardization, model interpretability, regulatory considerations, and clinical workflow integration. We also address the limitations of current AI applications and the ethical implications of their implementation in clinical practice. Future directions point towards advanced AI architectures, multimodal imaging integration, and applications in precision medicine and population health management. The review emphasizes the need for ongoing collaboration between clinicians, data scientists, and policymakers to realize the full potential of AI in cardiovascular imaging while ensuring ethical and equitable implementation. As the field continues to evolve, addressing these challenges will be crucial for the successful integration of AI technologies into cardiovascular care, potentially revolutionizing diagnostic capabilities and improving patient outcomes., 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, Reza-Soltani et al.)

Parkinson's disease is one of the vital neurodegenerative ailments attributed to a rise in Alpha-synuclein proteins leading to the advancement of motor and cognitive deterioration. Interestingly, in PD lncRNAs, miRNAs and siRNAs are also key regulators of SNCA and alpha-synuclein aggregation. This review will focus on the roles of these three types of small RNAs in trebling the development of PD through regulating SNCA expression or alpha-synuclein protein mediating the RNA from acting. Parkinson's disease is defined by the build-up of alpha-synuclein protein resulting predominantly from the elevated expression level of the SNCA gene. Non-coding RNAs have gained broad appeal as fundamental modulators of gene expression and protein aggregation dynamics, with significant implications on the aetiology of PD. LncRNAs modulate SNCA transcription and edit epigenetic modifications, while miRNA target mRNA is involved in the stability and translation of count alpha-synuclein. Considering all these data, siRNAs can achieve the precise gene silencing effect that directly induces the downregulation of SNCA mRNA. This review also summarizes some recent reports about the interaction between these ncRNAs with the SNCA gene and alpha-synuclein protein, each through its independent in addition to synergistic mechanisms. This review highlights the possibility of therapeutic interventions to perturb SNCA expression to prevent alpha-synuclein aggregation via targeting ncRNAs that might be spun off novel drug development for PD., 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 GmbH. All rights reserved.)

Water pollution caused by antibiotics and synthetic dyes and imminent energy crises due to limited fossil fuel resources are issues of contemporary decades. Herein, we address them by enabling the multifunctionality in dual Z-scheme MoS 2 /WO 3-x /AgBiS 2 across photolysis, photo Fenton-like, and night catalysis. Defect, basal, and facet-engineered WO 3-x is modified with MoS 2 and AgBiS 2 , which extended its photoresponse from the UV-NIR region, inhibited carrier recombination, and reduced carrier transfer resistance. The electric field rearrangement leads to a flow of electrons from MoS 2 and AgBiS 2 to WO 3-x and intensifies the electron population, which is crucial for night catalysis. When MoS 2 /WO 3-x /AgBiS 2 was employed against doxycycline hydrochloride (DOXH), it removed 95.65, 81.11, and 77.92 % of DOXH in 100 min during photo-Fenton (PFR), night-Fenton (NFR), and photocatalytic (PCR) reactions, respectively. It also effectively removed 91.91, 98.17, 99.01, and 98.99 % of rhodamine B (RhB), Congo red (CR), methylene blue (MB), and methylene orange (MO) in Fenton reactions, respectively. ESR analysis consolidates the ROS generation feature of MoS 2 /WO 3-x /AgBiS 2 using H 2 O 2 with and without irradiation. This work provides a strategy to eliminate the deficiencies of WO 3-x and is conducive to the evolution of applications seeking to combat environmental and energy crises., 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.)