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Introduction: Astrocytes, specialized glial cells, are essential for maintaining the central nervous system homeostasis. Inflammatory conditions can disrupt neurotrophic factors and receptor expression in astrocytes, leading to potential central nervous system damage. Itaconate, recently identified for its anti-inflammatory properties, was investigated in this study for its effects on neurotrophic factors in LPS-stimulated primary rat astrocytes. Methods: Primary rat astrocyte cells were isolated from one-day-old Wistar rats and exposed to 1 µg/ml lipopolysaccharide (LPS) for 6 h to stimulate inflammation. The effect of DMI (62.5, 125, and 250 µM for 18 h) on the cell viability of astrocyte cells exposed to LPS was evaluated by the MTT assay. The effects of DMI on the mRNA and protein levels of NGF, BDNF, and GDNF were evaluated using ELISA and qRT-PCR assays. Protein and mRNA levels of neurotrophic factor receptors (TrkA, TrkB, and P75) were evaluated using qRT-PCR and Western blot analyses. Results: The results showed that DMI suppressed astrocytes cell death induced by LPS in a dose-dependent manner. DMI dose-dependently restored the reduced mRNA and protein levels of NGF, BDNF, GDNF, and TrkA and TrkB receptors in LPS-treated astrocytes, but it significantly decreased the p75 expression in the same condition. Conclusion: In conclusion, DMI may be able to support astrocyte survival and functions based on the restoration of neurotrophic factors and their receptors expression in LPS-stimulated astrocyte cells. This suggests that DMI could be a promising therapeutic option for neurodegenerative diseases characterized by inflammation-induced astrocyte dysfunction.

Breast cancer is a cause of death in women, making it a significant issue in women's health. The aim of this study was to evaluate the effects of nanoparticles (NPs) of Fe 3 O 4 NPs@pectin and Fe 3 O 4 NPs@SiO 2 on MCF-7 cells. Fe 3 O 4 NPs@pectin and Fe 3 O 4 NPs@SiO 2 NPs were prepared using the chemical coprecipitation technique. The characteristics of the NPs were determined using physical methods. The cytotoxic effects of the NPs were assessed by the MTT assay. The expression levels of BAX, BCL2, and TPX1 genes were determined using real-time PCR. The results indicated a density ratio of 0.11, a saturation magnetism value of 68.5 emu/g, and a spherical with sizes of 98 nm for the NPs. The MTT assay showed that 500 μg/mL of NPs had 75 % toxicity on MCF-7 cells after five days. The increased expression of BAX with 250 μg/mL of Fe 3 O 4 @pectin showed a significant relationship (p-value = 0.0030). Down-regulated expression of BCL2 showed a significant relationship between the three groups treated with 250 μg/mL and 500 μg/mL of Fe 3 O 4 @SiO 2 and 250 μg/mL of Fe 3 O 4 @pectin (p-values of 0.0014, 0.0009 and 0.0030, respectively). Additionally, decreased TPX indicated a significant relationship between treatment at 125, 250 and 500 μg/mL of Fe 3 O 4 @SiO 2 (p-values of 0.0388, 0.0063 and 0.0496, respectively)., 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: Multiple sclerosis (MS) is a chronic and progressive neurological autoimmune disease that affects the central nervous system. There are two types of drugs used to treat this disease: injectable and oral drugs. The present study aimed at systematically reviewing the cost effectiveness of oral versus injectable drugs., Methods: The researchers searched the PubMed, Scopus, and Web of Science databases to find relevant studies. After removing the duplicates, two authors independently assessed the records. The studies that had conducted full economic evaluations of oral versus injectable drugs in MS patients were included. The Quality of Health Economic Studies (QHES) tool was also used to assess the quality of the studies., Results: Thirty studies that had conducted the economic analysis of oral versus injectable therapies in MS patients were included in this review. The QHES scores for all records were generally high (≥ 77) and they were of good quality. The lowest and highest levels of incremental net monetary benefit were respectively obtained through the comparison of Fingolimod and Alemtuzumab (-1,419,333) and the comparison of Teriflunomide and Interferon β-1a (1,792,810). The amount of INMB (incremental net monetary benefit) in the comparisons between oral and injectable drugs showed that the highest and lowest amount of INMB calculated between) Fingolimod and injectable drugs, respectively, compared to (interferon β-1a) 98,253 and (Ocrelizumab) -212,417, the highest amount in dimethyl fumarate is also against (peginterferon β-1a) 191,470 and the lowest against (alemtuzumab) -124,333, Teriflunomide against injectable drugs is the highest against (peginterferon β-1a) 89,956 and the lowest (Ocrelizumab) - 194,169, as well as Cladribine compared to injectable drugs, the highest was compared to (interferon β-1a) 236,430 and the lowest (Ocrelizumab) was 23,965., Conclusion: A large number of health economic evaluations of disease-modifying therapies (DMTs) in MS were available at the international level, the comparison of which was difficult and sometimes contradictory. However, despite the difference in the results, Cladribine tablets were cost-effective in all studies compared with injectable drugs. In addition, the present study could be of great importance for policymakers and other beneficiaries regarding the cost-effectiveness of the aforementioned drugs., (© 2024. The Author(s).)

Dose rate is one of the important parameters in radiation-induced biomolecular damage. The effects of dose rate have been known to modify radiation toxicity in biological systems. The rate and extent of sublethal DNA damage (e.g., base damage and single-strand breaks) repair and those of cell proliferation have been manifested by dose rate. However, the recent preclinical application of ultrahigh dose rate [(UHDR) ca. 40 Gy/s and higher] radiation modalities have been shown to lower the type and extent of radiation damage to biological systems. At these UHDR, radiation-induced physicochemical and chemical processes are expected to differ from those observed after irradiation at conventional dose rates (CONV). It is unclear whether these UHDR conditions can affect the quality (type) and quantity (extent) of biomolecular damage such as DNA lesions. Here, we comparatively study the influence of indirect effects of CONV and UHDR on the formation of DNA strand breaks and clustered damage including densely accumulated lesions in an aerated and an anoxic dilute aqueous solution of a plasmid DNA model under low and high hydroxyl radical (•OH) scavenging conditions. Aqueous solutions of purified supercoiled plasmid DNA (pUC19) were prepared in either air- or nitrogen-saturated conditions, with Tris buffer added as the radiation-produced •OH scavenger at low and high scavenging capacities. These DNA samples were irradiated using kV X-ray systems at CONV (0.1 Gy/s) and high dose rate (HDR, 25 Gy/s) as well as UHDR (55 and 125 Gy/s) under different scavenging and environmental conditions. DNA lesions including strand breaks and clustered damage including densely accumulated lesions were quantified by gel electrophoresis and the yields of these lesions were calculated from the dose-response curve. Non-DSB clustered damage including densely accumulated lesions were evaluated by treating DNAs using bacterial endonuclease enzymes (Fpg and Nth) prior to gel electrophoresis. UHDR of 55 and 125 Gy/s induced lower amounts of both isolated strand breaks and clustered DNA damage including densely accumulated lesions at doses >40 Gy in the presence of oxygen, compared to the abundance of these lesions induced by 0.1 and 25 Gy/s irradiation under the same dose conditions. Overall, the strand break and clustered damage including densely accumulated lesions yields decreased by factors of 1.3-3.5 after UHDR. We did not observe these differences either via •OH scavenging or by removing oxygen from the solution. In addition, our results point out that the inter-track recombination reactions did not contribute to the observed dose-rate effects on DNA damage. The effects of dose rate on DNA damage are highly dependent on the total dose, as expected, but also on the •OH scavenging capacity that is employed in the aqueous DNA solutions. These important variables may be relevant in biological systems as well. On a practical level, our in vitro plasmid DNA model, which permits to precisely vary the scavenging capacity and gassing conditions (air saturated vs. N2 saturated) can help to differentiate dose-rate effects on biomolecular damage. Our results indicate that the radical-radical reactions are important in understanding the dose-rate effect on DNA damage., (© 2024 by Radiation Research Society. All rights of reproduction in any form reserved.)

Curcumin (CUR) has been considered a potential therapeutic agent for allergic reactions due to its antioxidant and anti-inflammatory activities. Nanofibers have attracted increasing attention in drug delivery. The aim of this study was to investigate the combined therapeutic effects of curcumin and allergen in nanofiber-based treatments in order to increase the effectiveness of sublingual immunotherapy (SLIT) efficacy in a mouse model of allergic rhinitis. Nanofibers containing CUR (1.25% and 2.5%) and ovalbumin 2% (OVA) as an allergen were prepared via electrospinning and characterized. BALB/c mice were sensitized with OVA to the induced allergic rhinitis model. SLIT with free and/or nanofibers was carried out. IL-4, INF-γ, and IgE serum levels were measured using ELISA. Splenocyte proliferation was evaluated by the MTT assay. Lung and nasal histological examinations and nasal lavage fluid (NALF) cell counting were carried out. Nanofibers containing 1.25% CUR and 2% OVA were chosen as the optimal formulations. SLIT treatment with the CUR and OVA nanofiber co-administration led to a significantly decreased serum IgE. Nanofiber containing 2.5 µg of CUR/mouse combined with OVA nanofiber showed a significant decrease in IL-4 and an increase in IFN-γ compared to other groups. NALF assessment showed a significant decrease in specific cell and eosinophil counts in the treated nanofiber groups. The histopathological results of NAL in the optimal formulations were near normal, with diminished cellular infiltration and inflammation. Our findings suggest that co-sublingual administration of allergen and CUR nanofibers can be considered as potential immunomodulatory agents., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Cardiovascular progenitor cells (CPCs) derived from human embryonic stem cells (hESCs) are considered valuable cell sources for investigating cardiovascular physiology in vitro. Meeting the diverse needs of this application requires the large-scale production of CPCs in an in vitro environment. This study aimed to use an effective culture system utilizing signaling factors for the large-scale expansion of hESC-derived CPCs with the potential to differentiate into functional cardiac lineage cells., Methods and Results: Initially, CPCs were generated from hESCs using a 4-day differentiation protocol with a combination of four small molecules (CHIR99021, IWP2, SB-431542, and purmorphamine). These CPCs were then expanded and maintained in a medium containing three factors (bFGF, CHIR, and A83-01), resulting in a > 6,000-fold increase after 8 passages. These CPCs were successfully cryopreserved for an extended period in late passages. The expanded CPCs maintained their gene and protein expression signatures as well as their differentiation capacity through eight passages. Additionally, these CPCs could differentiate into four types of cardiac lineage cells: cardiomyocytes, endothelial cells, smooth muscle cells, and fibroblasts, demonstrating appropriate functionality. Furthermore, the coculture of these CPC-derived cardiovascular lineage cells in rat tail collagen resulted in cardiac microtissue formation, highlighting the potential of this 3D platform for studying cardiovascular physiology in vitro., Conclusion: In conclusion, expandable hESC-derived CPCs demonstrated the ability to self-renewal and differentiation into functional cardiovascular lineage cells consistently across passages, which may apply as potential cell sources for in vitro cardiovascular studies., (© 2024. The Author(s).)

A leading cause of global warming is the increase of carbon dioxide (CO 2 ) emissions due to anthropogenic activities which prompts an urgent need for substantial reduction. Recently, CO 2 absorption in deep eutectic solvents (DESs) has attracted scientific attention, because of their adaptability compared to traditional ionic liquids and aqueous amine solutions. This study employs the heating method to synthesize DESs using tetrapropylammonium bromide (TPAB) and formic acid (Fa) with molar ratios of TPAB-Fa (1:1) and TPAB-Fa (1:2). Absorption experiments by static method quantified CO 2 solubility in the DESs under varied pressures and temperatures. TPAB-Fa (1:2) at 25.0 °C was the most efficient with the CO 2 solubility of 0.218. Thermodynamic modeling was performed by employing the nonrandom two liquids activity coefficient model and the Peng-Robinson equation of state for the liquid and gas phases, respectively. The Henry's law constant was determined from experimental data. CO 2 physical absorption was confirmed via nuclear magnetic resonance (NMR) and Fourier-transform infrared (FT-IR) analyses. TPAB-Fa (1:2), as the superior DES, exhibited regeneration efficiency of 99% after five absorption/desorption cycles., (© 2024. The Author(s).)

Objective: Pain often accompanies carpal tunnel syndrome and affects patients' health-related quality of life. The aim was to develop and validate a predictive model for the pain intensity of carpal tunnel syndrome using demographic, clinical, electrophysiological, and ultrasound findings., Methods: We conducted a secondary analysis of data from a large sample of patients (May 2017 to December 2022) with carpal tunnel syndrome. A total of 520 (53.0 %) mild, 276 (28.1 %) moderate, and 186 (18.9 %) severe syndromes were included in the complete data set of 982 hands (61.1 % female). The mean age was 57.8 (10.7) years and the median duration [interquartile range] of the symptoms was 4 [2,10] months. A regression model was developed and validated to predict pain intensity on a numerical rating scale using a tree-based machine learning algorithm., Results: The validation of the regression model showed good performance with a root mean squared error, R-squared, and mean absolute error of 1.35, 0.42, and 1.05, respectively. Overall, the top significant predictors of pain intensity were compound motor nerve action potential latency, nocturnal pain, and thenar weakness. These were followed by the cross-sectional area of the median nerve, sensory nerve action potential, bowing of the flexor retinaculum, disease duration, and body mass index. We did not find strong associations between the median nerve transcarpal latency, age, sex, and diabetes with the pain intensity of carpal tunnel syndrome., Conclusion: Our model showed good performance in predicting the subjective pain intensity of carpal tunnel syndrome, even in the context of non-linear relations., Competing Interests: Competing interests The authors declare that they have no competing interests., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Head computed tomography (CT) is the preferred imaging modality for mild traumatic brain injury (mTBI). The routine use of head CT in low-risk individuals with mild TBI offers no clinical benefit but also causes notable health and financial burden. Despite the availability of related guidelines, studies have reported considerable rate of non-indicated head CT requests. The objectives were to provide an overall estimate for the head CT overutilization rate and to identify the factors contributing to the overuse. A systematic review of PubMed, Scopus, Web of Science, and Embase databases was conducted up to November 2023, following PRISMA and MOOSE guidelines. Two reviewers independently selected eligible articles and extracted data. Quality assessment was performed using a bias risk tool, and a random-effects model was used for data synthesis. Fourteen studies, encompassing 28,612 patients, were included, with 27,809 undergoing head CT scans. Notably, 75% of the included studies exhibited a moderate to high risk of bias. The overutilization rate for pediatric and adult patients was 27% (95% CI: 5-50%) and 32% (95% CI: 21-44%), respectively. An alternative rate, focusing on low-risk pediatric patients, was 54% (95% CI: 20-89%). Overutilization rates showed no significant difference between teaching and non-teaching hospitals. Patients with mTBI from falls or assaults were less likely to receive non-indicated scans. There was no significant association between physician specialty or seniority and overuse, nor between patients' age or sex and the likelihood of receiving a non-indicated scan. Approximately one-third of head CT scans in mTBI cases are avoidable, underscoring the necessity for quality improvement programs to reduce unnecessary imaging and its associated burdens., (© 2024. The Author(s), under exclusive licence to American Society of Emergency Radiology (ASER).)

The emergence and development of antibiotic resistance in bacteria is a serious threat to global public health. Antibiotic resistance genes (ARGs) are often located on mobile genetic elements (MGEs). They can be transferred among bacteria by horizontal gene transfer (HGT), leading to the spread of drug-resistant strains and antibiotic treatment failure. CRISPR (clustered regularly interspaced short palindromic repeats)-Cas (CRISPR-associated genes) is one of the many strategies bacteria have developed under long-term selection pressure to restrict the HGT. CRISPR-Cas systems exist in about half of bacterial genomes and play a significant role in limiting the spread of antibiotic resistance. On the other hand, bacteriophages and other MGEs encode a wide range of anti-CRISPR proteins (Acrs) to counteract the immunity of the CRISPR-Cas system. The Acrs could decrease the CRISPR-Cas system's activity against phages and facilitate the acquisition of ARGs and virulence traits for bacteria. This review aimed to assess the relationship between the CRISPR-Cas systems and Acrs with bacterial antibiotic resistance. We also highlighted the CRISPR technology and Acrs to control and prevent antibacterial resistance. The CRISPR-Cas system can target nucleic acid sequences with high accuracy and reliability; therefore, it has become a novel gene editing and gene therapy tool to prevent the spread of antibiotic resistance. CRISPR-based approaches may pave the way for developing smart antibiotics, which could eliminate multidrug-resistant (MDR) bacteria and distinguish between pathogenic and beneficial microorganisms. Additionally, the engineered anti-CRISPR gene-containing phages in combination with antibiotics could be used as a cutting-edge treatment approach to reduce antibiotic resistance., 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.)

Cardiovascular diseases (CVDs) are the leading causes of death and illness worldwide. While there have been advancements in the treatment of CVDs using medication and medical procedures, these conventional methods have limited effectiveness in halting the progression of heart diseases to complete heart failure. However, in recent years, the hormone melatonin has shown promise as a protective agent for the heart. Melatonin, which is secreted by the pineal gland and regulates our sleep-wake cycle, plays a role in various biological processes including oxidative stress, mitochondrial function, and cell death. The Sirtuin (Sirt) family of proteins has gained attention for their involvement in many cellular functions related to heart health. It has been well established that melatonin activates the Sirt signaling pathways, leading to several beneficial effects on the heart. These include preserving mitochondrial function, reducing oxidative stress, decreasing inflammation, preventing cell death, and regulating autophagy in cardiac cells. Therefore, melatonin could play crucial roles in ameliorating various cardiovascular pathologies, such as sepsis, drug toxicity-induced myocardial injury, myocardial ischemia-reperfusion injury, hypertension, heart failure, and diabetic cardiomyopathy. These effects may be partly attributed to the modulation of different Sirt family members by melatonin. This review summarizes the existing body of literature highlighting the cardioprotective effects of melatonin, specifically the ones including modulation of Sirt signaling pathways. Also, we discuss the potential use of melatonin-Sirt interactions as a forthcoming therapeutic target for managing and preventing CVDs., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

FLASH radiotherapy (RT) is emerging as a potentially revolutionary advancement in cancer treatment, offering the potential to deliver RT at ultra-high dose rates (>40 Gy/s) while significantly reducing damage to healthy tissues. Democratizing FLASH RT by making this cutting-edge approach more accessible and affordable for healthcare systems worldwide would have a substantial impact in global health. Here, we review recent developments in FLASH RT and present perspective on further developments that could facilitate the democratizing of FLASH RT. These include upgrading and validating current technologies that can deliver and measure the FLASH radiation dose with high accuracy and precision, establishing a deeper mechanistic understanding of the FLASH effect, and optimizing dose delivery conditions and parameters for different types of tumors and normal tissues, such as the dose rate, dose fractionation, and beam quality for high efficacy. Furthermore, we examine the potential for democratizing FLASH radioimmunotherapy leveraging evidence that FLASH RT can make the tumor microenvironment more immunogenic, and parallel developments in nanomedicine or use of smart radiotherapy biomaterials for combining RT and immunotherapy. We conclude that the democratization of FLASH radiotherapy represents a major opportunity for concerted cross-disciplinary research collaborations with potential for tremendous impact in reducing radiotherapy disparities and extending the cancer moonshot globally., Competing Interests: Declaration of competing interest We have no conflicts of interest., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objectives: Metastatic prostate cancer is the most common malignant cancer and the second leading cause of death due to various types of cancer among men after lung cancer. This study aimed to analyze the cost-effectiveness of triptorelin, goserelin, and leuprolide in the treatment of the patients with metastatic prostate cancer from the societal perspective in Iran in 2020., Methods: This is a cost-effectiveness study in which a 20-year Markov transition modeling was applied. In this study, local cost and quality-of-life data of each health state were gathered from cohort of patients. The TreeAge pro 2020 and Microsoft Excel 2016 software were used to simulate cost-effectiveness of each treatment in the long term. The one-way and probabilistic sensitivity analyses were also performed to measure robustness of the model outputs., Results: The findings indicated that the mean costs and utility gained over a 20-year horizon for goserelin, triptorelin, and leuprolide treatments were $ 13 539.13 and 6.365 quality-adjusted life-years (QALY), $ 18 124.75 and 6.658 QALY, and $ 26 006.92 and 6.856 QALY, respectively. Goserelin was considered as a superior treatment option, given the estimated incremental cost-effectiveness ratio. The one-way and probabilistic sensitivity analyses confirmed the robustness of the study outcomes., Conclusions: According to the results of the present study, goserelin was the most effective and cost-effective strategy versus 2 other options. It could be recommended to policy makers of the Iran healthcare system to prioritize it in clinical guidelines and reimbursement policies., Competing Interests: Author Disclosures Author disclosure forms can be accessed below in the Supplemental Material section., (Copyright © 2024 International Society for Health Economics and Outcomes Research. Published by Elsevier Inc. All rights reserved.)

Neurological disorders are a heterogeneous group of central or peripheral nervous disorders of which the main symptoms include impaired walking and balance. One of the main interventions for neurological disorders is the use of assistive devices, and it is necessary to consider the psychosocial effects of these devices on users. The psychometric properties of the Persian version of the Psychosocial Impact of Assistive Devices Scale (PIADS) were evaluated in patients with neurological disorders. After translating the scale into Persian based on IQULA, face and content validity were determined. The divergent validity of the scale was examined through its relationship with the Orthotics and Prosthetics Users' Survey (OPUS). Reliability of the tool was evaluated using an internal consistency and test-retest method over two weeks with 50 patients with neurological disorders and a history of using assistive devices for at least six months. The face and content validity of the PIADS was confirmed. The ICC for all subscales was higher than 0.78, which indicates a good correlation. However, the divergent validity of the scale with the OPUS scale was not confirmed. The Persian version of PIADS is a valid and reliable measure for patients with neurological disorders in Iran.

Tissue engineering as an interdisciplinary field of biomedical sciences has raised many hopes in the treatment of cardiovascular diseases as well as development of in vitro three-dimensional (3D) cardiac models. This study aimed to engineer a cardiac microtissue using a natural hybrid hydrogel enriched by granulocyte colony-stimulating factor (G-CSF), a bone marrow-derived growth factor. Cardiac ECM hydrogel (Cardiogel: CG) was mixed with collagen type I (ColI) to form the hybrid hydrogel, which was tested for mechanical and biological properties. Three cell types (cardiac progenitor cells, endothelial cells and cardiac fibroblasts) were co-cultured in the G-CSF-enriched hybrid hydrogel to form a 3D microtissue. ColI markedly improved the mechanical properties of CG in the hybrid form with a ratio of 1:1. The hybrid hydrogel demonstrated acceptable biocompatibility and improved retention of encapsulated human foreskin fibroblasts. Co-culture of three cell types in G-CSF enriched hybrid hydrogel, resulted in a faster 3D structure shaping and a well-cellularized microtissue with higher angiogenesis compared to growth factor-free hybrid hydrogel (control). Immunostaining confirmed the presence of CD31 + tube-like structures as well as vimentin + cardiac fibroblasts and cTNT + human pluripotent stem cells-derived cardiomyocytes. Bioinformatics analysis of signaling pathways related to the G-CSF receptor in cardiovascular lineage cells, identified target molecules. The in silico -identified STAT3, as one of the major molecules involved in G-CSF signaling of cardiac tissue, was upregulated in G-CSF compared to control. The G-CSF-enriched hybrid hydrogel could be a promising candidate for cardiac tissue engineering, as it facilitates tissue formation and angiogenesis., (© The Author(s) 2024. Published by Oxford University Press.)

Background: Coronary artery disease (CAD) is known as the leading cause of disability and death globally. Anxiety disorders are also recognized as common types of mental disorders that substantially impact global health. Iran ranks among the countries with a high incidence of CAD and anxiety disorders. Therefore, the present study aims to determine the potential association and epidemiological aspects of anxiety and CAD within the population of Mashhad, the second most popoulos city in Iran., Methods: The present study is based on extracted data from the Mashhad stroke and heart atherosclerotic disorder (MASHAD) study which is a 10-year prospective cohort study intended to assess the effects of various CAD risk factors among Mashhad city residents. Anxiety scores were assessed at the baseline using Beck Anxiety Inventory and individuals were classified based on the BAI 4-factor structure model which included autonomic, cognitive, panic, and neuromotor components. Accordingly, the association between baseline anxiety scores and the BAI four-factor model with the risk of CAD events was analyzed using SPSS software version 21., Results: Based on the results, 60.4% of the sample were female, and 5.6% were classified as having severe forms of anxiety. Moreover, severe anxiety was more prevalent in females. Results showed a 1.7% risk of CAD (p-value < 0.001) over 10 years with one unit increase in anxiety score. Based on the 4-factor model structure, we found that only panic disorder could significantly increase the risk of CAD by 1.1% over the 10-year follow-up (p-value < 0.001)., Conclusion: Anxiety symptoms, particularly panic disorder, are independently and significantly associated with an increased overall risk of developing CAD over a 10-year period. Therefore, further studies are warranted to investigate the mechanisms through which anxiety may cause CAD, as well as possible interventions to mitigate these processes., (© 2024. The Author(s).)

Most patients with lung squamous cell carcinoma (LSCC) undergo chemotherapy, radiotherapy, and adjuvant immunotherapy for locally advanced disease. The efficacy of these treatments is still limited because of dose-limiting toxicity or locoregional recurrence. New combination approaches and targets such as actionable oncogenic drivers are needed to advance treatment options for patients with LSCC. Moreover, other options for chemotherapy-ineligible patients are limited. As such, there is a critical need for the development of selective and potent chemoradiosensitizers for locally advanced LSCC. In this study, we investigated inhibiting TRAF2- and NCK-interacting protein kinase (TNIK), which is amplified in 40% of patients with LSCC, as a strategy to sensitize LSCC tumors to chemotherapy and radiotherapy. Employing a range of human LSCC cell lines and the TNIK inhibitor NCB-0846, we investigated the potential of TNIK as a chemo- and radiosensitizing target with in vitro and in vivo preclinical models. The combination of NCB-0846 with cisplatin or etoposide was at best additive. Interestingly, pre-treating LSCC cells with NCB-0846 prior to ionizing radiation (IR) potentiated the cytotoxicity of IR in a TNIK-specific fashion. Characterization of the radiosensitization mechanism suggested that TNIK inhibition may impair the DNA damage response and promote mitotic catastrophe in irradiated cells. In a subcutaneous xenograft in vivo model, pretreatment with NCB-0846 significantly enhanced the efficacy of IR and caused elevated necrosis in TNIKhigh LK2 tumors but not TNIKlow KNS62 tumors. Overall, these results indicate that TNIK inhibition may be a promising strategy to increase the efficacy of radiotherapy in patients with LSCC with high TNIK expression., (©2024 The Authors; Published by the American Association for Cancer Research.)

Background and Objective(s): CRISPR-Cas is a prokaryotic adaptive immune system that protects bacteria and archaea against mobile genetic elements (MGEs) such as bacteriophages plasmids, and transposons. In this study, we aimed to assess the prevalence of the CRISPR-Cas systems and their association with antibiotic resistance in one of the most challenging bacterial pathogens, Klebsiella pneumoniae., Materials and Methods: A total of 105 K. pneumoniae isolates were collected from various clinical infections. Extended-spectrum β-lactamases (ESBLs) phenotypically were detected and the presence of ESBL, aminoglycoside-modifying enzymes (AME), and CRISPR-Cas system subtype genes were identified using PCR. Moreover, the diversity of the isolates was determined by enterobacterial repetitive intergenic consensus (ERIC)-PCR., Results: Phenotypically, 41.9% (44/105) of the isolates were found to be ESBL producers. A significant inverse correlation existed between the subtype I-E CRISPR-Cas system's presence and ESBL production in K. pneumoniae isolates. Additionally, the frequency of the ESBL genes bla CTX-M1 (3%), bla CTX-M9 (12.1%), bla SHV (51.5%), and bla TEM (33.3%), as well as some AME genes such as aac(3)-Iva (21.2%) and ant(2'')-Ia (3%) was significantly lower in the isolates with the subtype I-E CRISPR-Cas system in comparison to CRISPR-negative isolates. There was a significant inverse correlation between the presence of ESBL and some AME genes with subtype I-E CRISPR-Cas system., Conclusion: The presence of the subtype I-E CRISPR-Cas system was correlated with the antibiotic-resistant gene (ARGs). The isolates with subtype I-E CRISPR-Cas system had a lower frequency of ESBL genes and some AME genes than CRISPR-negative isolates., (© 2024. The Author(s).)

Single-walled carbon nanotube (SWCNT) thin films were synthesized by using a floating catalyst chemical vapor deposition (FCCVD) method with a low flow rate (200 sccm) of mixed gases (Ar and H 2 ). SWCNT thin films with different thicknesses can be prepared by controlling the collection time of the SWCNTs on membrane filters. Transmission electron microscopy (TEM) showed that the SWCNTs formed bundles and that they had an average diameter of 1.46 nm. The Raman spectra of the SWCNT films suggested that the synthesized SWCNTs were very well crystallized. Although the electrical properties of SWCNTs have been widely studied so far, the Hall effect of SWCNTs has not been fully studied to explore the electrical characteristics of SWCNT thin films. In this research, Hall effect measurements have been performed to investigate the important electrical characteristics of SWCNTs, such as their carrier mobility, carrier density, Hall coefficient, conductivity, and sheet resistance. The samples with transmittance between 95 and 43% showed a high carrier density of 10 21 -10 23 cm -3 . The SWCNTs were also treated using Brønsted acids (HCl, HNO 3 , H 2 SO 4 ) to enhance their electrical properties. After the acid treatments, the samples maintained their p-type nature. The carrier mobility and conductivity increased, and the sheet resistance decreased for all treated samples. The highest mobility of 1.5 cm 2 /Vs was obtained with the sulfuric acid treatment at 80 °C, while the highest conductivity (30,720 S/m) and lowest sheet resistance (43 ohm/square) were achieved with the nitric acid treatment at room temperature. Different functional groups were identified in our synthesized SWCNTs before and after the acid treatments using Fourier-Transform Infrared Spectroscopy (FTIR).

Defects and dysfunctions of temporomandibular joint (TMJ) disc are responsible for the majority of TMJ diseases. Current treatments in this matter are usually short-term and only palliative, thus an alternative treatment that offers long-lasting repair is in great demand. In recent years great attempts have been made to prepare an ideal scaffold, which best resembles the native TMJ disc in characteristics such as mechanical, physical and biological properties. This narrative review focuses on developments of the recent ten years in fabrication of scaffolds using decellularized tissues, natural and synthetic biomaterials for regeneration of TMJ disc and compared their properties. PubMed and Google Scholar databases were searched using the following keywords ("TMJ" OR "temporomandibular joint" OR "TMD" OR "temporomandibular disease") AND ("scaffold" OR "hydrogels"). Randomized controlled trials, randomized clinical trials, case-controls, case reports, and animal studies were included. Comments, systematic reviews, meta-analyses, and non-English papers were excluded. The study concluded that hybrid scaffolds have exhibited favorable cell attachment and proliferation. Synthetic scaffolds have shown promise in providing better control over structural properties; however, additional processes are often required to provide biomimetic cell signaling. While there is still much to learn about the ideal scaffold for TMJ disc regeneration, both natural and synthetic scaffolds have shown promise in achieving the functional, structural, biological, and mechanical properties of a native TMJ disc., Competing Interests: The authors declare no conflict of interest., (Copyright: © Journal of Dentistry.)

Background: Gold nanoparticles (GNPs) have previously been suggested as appropriate carriers for allergen-specific immunotherapy (AIT). In this study, we assessed efficacy of GNPs and dendritic cells (DC)-specific aptamer-modified GNPs (Apts-GNP) for epicutaneous immunotherapy (EPIT) in the case of pollen allergen extracts containing a variety of allergenic and non-allergenic components., Methods: BALB/c mice were sensitized to the total protein extract of Platanus orientalis pollen and epicutaneously treated in different groups either with free P. orientalis total pollen extract, naked GNPs, total extract loaded GNPs, and total extract loaded Apts-GNPs with and without skin-penetrating peptides (SPPs). Then, the specific IgE level (sIgE), total IgE concentration (tIgE) in the serum sample, IL-4, IL-17a, IFN-γ, and IL-10 cytokine concentrations in re-stimulated splenocytes with the total extract and mixture of recombinant allergens, nasopharyngeal lavage fluid (NALF) analysis, and histopathological analysis of lung tissue were evaluated., Results: This study indicated the total extract-loaded GNPs, especially Pla. ext (50 μg)-GNPs, significantly decreased sIgE, tIgE, IL-17a, and IL-4 concentrations, immune cells and eosinophils infiltration in NALF, and increased IL-10 and IFN-γ concentrations compared with the PBS-treated group. In addition, the histopathological analysis of lung tissue showed a significant decrease in allergic inflammation and histopathological damage. The DC-targeted group revealed the most significant improvement in allergic-related immune factors with no histopathological damage compared with the same dose without aptamer., Conclusion: Loading total protein extract on the GNPs and the Apt-modified GNPs could be an effective approach to improve EPIT efficacy in a pollen-induced allergic mouse model., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Although predictors and outcomes of postoperative atrial fibrillation (POAF) are well studied, evidence is lacking concerning postdischarge late/recurrent atrial fibrillation (AF). This study evaluated factors affecting late/recurrent AF and its association with coronary artery bypass grafting (CABG) outcomes in a real-world setting., Methods: From 2012 through 2016, 5175 patients were included. Independent factors associated with late/recurrent AF were identified in a competing risk setting. Cox proportional hazard regression was used to evaluate the association between late/recurrent AF and study outcomes, consisting of all-cause mortality, major adverse cardio-cerebrovascular events, acute coronary syndrome, cerebrovascular events, and heart failure admissions., Results: During a median follow-up of 60 months (quartile 1-quartile 3, 59.3-60.7 months), late/recurrent AF developed in 85 patients (1.64%). Independent factors associated with late/recurrent AF were age (subdistribution hazard ratio [sHR], 1.04; 95% CI, 1.02-1.07), left-ventricular ejection fraction (sHR, 0.97; 95% CI, 0.95-0.99), length of stay (sHR, 1.02; 95% CI, 1.01-1.04), and POAF (sHR, 4.02; 95% CI, 2.50-6.45). Late/recurrent AF was not significantly associated with all-cause mortality and major adverse cardio-cerebrovascular events at unadjusted or adjusted levels (adjusted hazard ratio, 0.80 [95% CI, 0.50-1.28] and 0.74 [95% CI, 0.48-1.13], respectively). Nevertheless, it significantly increased the unadjusted risk of cerebrovascular events (hazard ratio, 2.28; 95% CI, 01.07-4.87), which disappeared after adjustments., Conclusions: Patients with advanced age, a lower left-ventricular ejection fraction, and POAF are more likely to have late/recurrent clinical AF. Albeit counterintuitive, late/recurrent AF was not independently associated with worse midterm post-CABG outcomes. These observations need to be further elucidated in larger-scale studies and interpreted in the context of a developing country with limited resources for late AF surveillance., (Copyright © 2024 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Current therapeutic approaches for Huntington's disease (HD) focus on symptomatic treatment. Therefore, the unavailability of efficient disease-modifying medicines is a significant challenge. Regarding the molecular etiology, targeting the mutant gene or advanced translational steps could be considered promising strategies. The evidence in gene therapy suggests various molecular techniques, including knocking down mHTT expression using antisense oligonucleotides and small interfering RNAs and gene editing with zinc finger proteins and CRISPR-Cas9-based techniques. Several post-transcriptional and post-translational modifications have also been proposed. However, the efficacy and long-term side effects of these modalities have yet to be verified. Currently, cell therapy can be employed in combination with conventional treatment and could be used for HD in which the structural and functional restoration of degenerated neurons can occur. Several animal models have been established recently to develop cell-based therapies using renewable cell sources such as embryonic stem cells, induced pluripotent stem cells, mesenchymal stromal cells, and neural stem cells. These models face numerous challenges in translation into clinics. Nevertheless, investigations in Advanced Therapy Medicinal Products (ATMPs) open a promising window for HD research and their clinical application. In this study, the ATMPs entry pathway in HD management was highlighted, and their advantages and disadvantages were discussed., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

In this study, the conformational potential energy surfaces of Amylmetacresol, Benzocaine, Dopamine, Betazole, and Betahistine molecules were scanned and analyzed using the neural network architecture ANI-2 × and ANI-1ccx, the force field method OPLS, and density functional theory with the exchange-correlation functional B3LYP and the basis set 6-31G(d). The ANI-1ccx and ANI-2 × methods demonstrated the highest accuracy in predicting torsional energy profiles, effectively capturing the minimum and maximum values of these profiles. Conformational potential energy values calculated by B3LYP and the OPLS force field method differ from those calculated by ANI-1ccx and ANI-2x, which account for non-bonded intramolecular interactions, since the B3LYP functional and OPLS force field weakly consider van der Waals and other intramolecular forces in torsional energy profiles. For a more comprehensive analysis, electronic parameters such as dipole moment, HOMO, and LUMO energies for different torsional angles were calculated at two levels of theory, B3LYP/6-31G(d) and ωB97X/6-31G(d). These calculations confirmed that ANI predictions are more accurate than density functional theory calculations with B3LYP functional and OPLS force field for determining potential energy surfaces. This research successfully addressed the challenges in determining conformational potential energy levels and shows how machine learning and deep neural networks offer a more accurate, cost-effective, and rapid alternative for predicting torsional energy profiles., (© 2024. The Author(s).)

Background: Esophageal adenocarcinoma (EAC) is a common cancer with a poor prognosis in advanced stages. Therefore, early EAC diagnosis and treatment have gained attention in recent decades. It has been found that various pathological changes, particularly Barrett's Esophagus (BE), can occur in the esophageal tissue before the development of EAC. In this study, we aimed to identify the molecular contributor in BE to EAC progression by detecting the essential regulatory genes that are differentially expressed in both BE and EAC., Materials and Methods: We conducted a comprehensive bioinformatics analysis to detect BE and EAC-associated genes. The common differentially expressed genes (DEGs) and common single nucleotide polymorphisms (SNPs) were detected using the GEO and DisGeNET databases, respectively. Then, hub genes and the top modules within the protein-protein interaction network were identified. Moreover, the co-expression network of the top module by the HIPPIE database was constructed. Additionally, the gene regulatory network was constructed based on miRNAs and circRNAs. Lastly, we inspected the DGIdb database for possible interacted drugs., Results: Our microarray dataset analysis identified 92 common DEGs between BE and EAC with significant enrichment in skin and epidermis development genes. The study also identified 22 common SNPs between BE and EAC. The top module of PPI network analysis included SCEL, KRT6A, SPRR1A, SPRR1B, SPRR3, PPL, SPRR2B, EVPL, and CSTA . We constructed a ceRNA network involving three specific mRNAs, 23 miRNAs, and 101 selected circRNAs. According to the results from the DGIdb database, TD101 was found to interact with the KRT6A gene., Conclusion: The present study provides novel potential candidate genes that may be involved in the molecular association between Esophageal adenocarcinoma and Barrett's Esophagus, resulting in developing the diagnostic tools and therapeutic targets to prevent progression of BE to EAC., 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.)

Effective relief reduces damages and protects people during natural disasters, such as earthquakes. This research proposes a data-driven model based on sustainability, taking into account the pre and post-crisis simultaneously. Real data was used to validate the model in various earthquake scenarios. The study addresses questions regarding the amount and allocation of relief goods during earthquakes. This research is carried out in two phases: simulation and modeling. The purpose of the simulation phase is to estimate the number of relief goods in different scenarios. Additionally, in the modeling phase, a data-based multi-objective model is presented, considering sustainability, to minimize the lack of relief goods, the number of untreated wounded, and supply chain costs. Using the dynamic simulation system, and after designing the structure of the earthquake effects on urban infrastructure, the actions and effects of the earthquake on vital arteries are investigated in different scenarios, and scenarios with a higher degree of risk are identified. The results showed that the highest and lowest demands for relief goods were related to the "Mosha-day fault" and "North Tehran-night fault" scenarios, respectively., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Like almost all cancer types, timely diagnosis is needed for leukemias to be effectively cured. Drug efflux, attenuated drug uptake, altered drug metabolism, and epigenetic alterations are just several of the key mechanisms by which drug resistance develops. All of these mechanisms are orchestrated by up- and downregulators, in which non-coding RNAs (ncRNAs) do not encode specific proteins in most cases; albeit, some of them have been found to exhibit the potential for protein-coding. Notwithstanding, ncRNAs are chiefly known for their contribution to the regulation of physiological processes, as well as the pathological ones, such as cell proliferation, apoptosis, and immune responses. Specifically, in the case of leukemia chemo-resistance, ncRNAs have been recognized to be responsible for modulating the initiation and progression of drug resistance. Herein, we comprehensively reviewed the role of ncRNAs, specifically its effect on molecular mechanisms and signaling pathways, in the development of leukemia drug resistance., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Most patients with lung squamous cell carcinoma (LSCC) undergo chemotherapy, radiotherapy, and adjuvant immunotherapy for locally advanced disease. The efficacy of these treatments is still limited due to dose-limiting toxicity or locoregional recurrence. New combination approaches and targets such as actionable oncogenic drivers are needed to advance treatment options for LSCC patients. Moreover, other options for chemotherapy-ineligible patients are also limited. As such there is a critical need for the development of selective and potent chemoradiosensitizers for locally advanced LSCC. Here, we investigated inhibiting TRAF2 and NCK-interacting protein kinase (TNIK), which is amplified in 40% of LSCC patients, as a strategy to sensitize LSCC tumors to chemo- and radiotherapy. Employing a range of human LSCC cell lines and the TNIK inhibitor NCB-0846, we investigated the potential of TNIK as a chemo- and radiosensitizing target with in vitro and in vivo preclinical models. The combination of NCB-0846 with cisplatin or etoposide was at best additive. Interestingly, pre-treating LSCC cells with NCB-0846 prior to ionizing radiation (IR) potentiated the cytotoxicity of IR in a TNIK-specific fashion. Characterization of the radiosensitization mechanism suggested that TNIK inhibition may impair the DNA damage response and promote mitotic catastrophe in irradiated cells. In a subcutaneous xenograft in vivo model, pretreatment with NCB-0846 significantly enhanced the efficacy of IR and caused elevated necrosis in TNIKhigh LK2 tumors but not TNIKlow KNS62 tumors. Overall, these results indicate that TNIK inhibition may be a promising strategy to increase the efficacy of radiotherapy in LSCC patients with high TNIK expression.

Background: The diverse and complex attributes of cancer have made it a daunting challenge to overcome globally and remains to endanger human life. Detection of critical cancer-related gene alterations in solid tumor samples better defines patient diagnosis and prognosis, and indicates what targeted therapies must be administered to improve cancer patients' outcome., Materials and Methods: To identify genes that have aberrant expression across different cancer types, differential expressed genes were detected within the TCGA datasets. Subsequently, the DEGs common to all pan cancers were determined. Furthermore, various methods were employed to gain genetic alterations, co-expression genes network and protein-protein interaction (PPI) network, pathway enrichment analysis of common genes. Finally, the gene regulatory network was constructed., Results: Intersectional analysis identified UBE2C as a common DEG between all 28 types of studied cancers. Upregulated UBE2C expression was significantly correlated with OS and DFS of 10 and 9 types of cancer patients. Also, UBE2C can be a diagnostic factor in CESC, CHOL, GBM, and UCS with AUC = 100% and diagnose 19 cancer types with AUC ≥90%. A ceRNA network constructed including UBE2C, 41 TFs, 10 shared miRNAs, and 21 circRNAs and 128 lncRNAs., Conclusion: In summary, UBE2C can be a theranostic gene, which may serve as a reliable biomarker in diagnosing cancers, improving treatment responses and increasing the overall survival of cancer patients and can be a promising gene to be target by cancer drugs in the future., (© 2024 The Authors. Cancer Reports published by Wiley Periodicals LLC.)

Greenhouse gases are major contributors to global warming, and their concentration is increasing due to the widespread use of fossil fuels. Coal bed methane (CBM) offers a potential solution to this issue. However, the gas adsorption mechanisms of CBM, particularly in the context of coal-derived asphaltenes, are not fully understood. This study provides a comprehensive theoretical investigation of the competitive adsorption of carbon dioxide (CO 2 ), methane (CH 4 ), and nitrogen (N 2 ) in the processes of CO 2 - and N 2 -enhanced coalbed methane recovery, with a focus on coal-derived asphaltenes functionalized with CH 4 , NH, O, and S groups. Using the Grand Canonical Monte Carlo (GCMC) simulation method and performing Molecular Dynamics (MD) simulations, we studied the adsorption process. To investigate the electronic effects and nature of the interactions, we performed density functional theory (DFT) calculations. The adsorption energy values and non-covalent interactions (NCI) for the adsorption of gases signify the physical adsorption (van der Waals interaction), with CO 2 exhibiting the highest (absolute) adsorption energy. The Monte Carlo results indicated that elevated temperatures led to a reduction in adsorption capacity. Coal-derived asphaltenes demonstrated greater selectivity for CO 2 compared to CH 4 and N 2 in competitive adsorption, especially at elevated temperatures. Our findings highlight the significant potential of our asphaltene model, not only in mitigating CO 2 greenhouse gas emissions but also in recovering CH 4 , which is a valuable resource., (© 2024. The Author(s).)

Background: The rapid uptake of antigens by antigen-presenting cells (APCs) and their migration to draining lymph nodes in the initial hours after antigen administration in epicutaneous allergen specific immunotherapy (EPIT) prompted us to investigate whether the topical administration of allergens without patch application could alleviate allergy in pollen-sensitized mice. We evaluated the immunotherapeutic effect of topically administering hydrogel-based Gold nanoparticles (AuNPs) loaded with a total extract of Platanus orientalis pollen (Pla. ext (50 μg)-AuNPs) on intact skin., Methods: Mice sensitized to P. orientalis pollen were divided into three groups and treated with Pla. ext (50 μg)-AuNPs: 1) patch with Pla. ext (50 μg)-AuNPs, 2) patch with Pla. ext (50 μg)-AuNPs in combination with hydrogel, and 3) topical application of Pla. ext (50 μg)-AuNPs in combination with hydrogel. The immunotherapeutic effects were evaluated by measuring serum specific and total IgE antibodies, total cell and eosinophil count in nasopharyngeal lavage fluid, cytokines in the supernatants of re-stimulated splenocytes by the total extract, and histological examination of lung and nasal mucosa., Results: Topical administration of Pla. ext (50 μg)-AuNPs, like patch-based administration, significantly downregulated specific and total IgE and IL-4 production, promoted secretion of IFN-γ and IL-10, markedly reduced the number of inflammatory cells, particularly eosinophils, in nasopharyngeal lavage fluid ( p  < .05), and inhibited inflammation and pathological damage in lung and nasal mucosa., Conclusion: Our results suggest that topical administration of AuNPs loaded with P. orientalis total pollen extract on intact skin could be a potential application for EPIT in the P. orientalis pollen -sensitized mice.

To determine the frequency of TB among patients with interstitial lung diseases (ILDs).We performed a comprehensive search in the PubMed/Medline, EMBASE and Scopus databases up to 1 August 2023 of studies reporting on the prevalence of TB among patients with ILDs.Twelve studies comprising 3,817 patients with ILD were found: the pooled prevalence of TB among ILD patients was 11.0% (95% CI 5.4-21.0). In the subgroup analysis, the TB rate among patients with silicosis and idiopathic pulmonary fibrosis (IPF) was respectively 35.6% (95% CI 32.6-38.8) and 4.4% (95% CI 3.6-5.3) ( P = 0.00). The frequency of TB among ILD patients was higher in high TB burden countries than in low/intermediate-burden countries: 26.3%, 95% CI 17.7-37.3 vs. 4.9%, 95% CI 3.3-7.2; P = 0.00.This study shows the frequency of TB among ILD patients. The meta-analysis reveals a significantly increased prevalence of TB among ILD patients with silicosis compared to IPF, and among individuals in high TB burden countries than in those with low/intermediate burden. The study results can help physicians and policymakers make efficient decisions for prompt screening and anti-TB treatment initiation in ILD patients..

Motivation: Clustered DNA-lesions are predominantly induced by ionizing radiation, particularly by high-LET particles, and considered as lethal damage. Quantification of this specific type of damage as a function of radiation parameters such as LET, dose rate, dose, and particle type can be informative for the prediction of biological outcome in radiobiological studies. This study investigated the induction and complexity of clustered DNA damage for three different types of particles at an LET range of 0.5-250 keV/μm., Methods: Nanometric volumes (36.0 nm 3 ) of 15 base-pair DNA with its hydration shell was modeled. Electron, proton, and alpha particles at various energies were simulated to irradiate the nanometric volumes. The number of ionization events, low-energy electron spectra, and chemical yields for the formation of °OH, H°, e aq - , and H 2 O 2 were calculated for each particle as a function of LET. Single- and double-strand breaks (SSB and DSB), base release, and clustered DNA-lesions were computed from the Monte-Carlo based quantification of the reactive species and measured yields of the species responsible for the DNA lesion formation., Results: The total amount of DNA damage depends on particle type and LET. The number of ionization events underestimates the quantity of DNA damage at LETs higher than 10 keV/μm. Minimum LETs of 9.4 and 11.5 keV/μm are required to induce clustered damage by a single track of proton and alpha particles, respectively. For a given radiation dose, an increase in LET reduces the number of particle tracks, leading to more complex clustered DNA damage, but a smaller number of separated clustered damage sites., Conclusions: The dependency of the number and the complexity of clustered DNA damage on LET and fluence suggests that the quantification of this damage can be a useful method for the estimation of the biological effectiveness of radiation. These results also suggest that medium-LET particles are more appropriate for the treatment of bulk targets, whereas high-LET particles can be more effective for small targets., Competing Interests: Conflicts of Interest: The authors declare no conflict of interest.

Myocardial infarction (MI) is the leading cause of heart failure (HF), accounting for high mortality and morbidity worldwide. As a consequence of ischemia/reperfusion injury during MI, multiple cellular processes such as oxidative stress-induced damage, cardiomyocyte death, and inflammatory responses occur. In the next stage, the proliferation and activation of cardiac fibroblasts results in myocardial fibrosis and HF progression. Therefore, developing a novel therapeutic strategy is urgently warranted to restrict the progression of pathological cardiac remodeling. Recently, targeting long non-coding RNAs (lncRNAs) provided a novel insight into treating several disorders. In this regard, numerous investigations have indicated that several lncRNAs could participate in the pathogenesis of MI-induced cardiac remodeling, suggesting their potential therapeutic applications. In this review, we summarized lncRNAs displayed in the pathophysiology of cardiac remodeling after MI, emphasizing molecular mechanisms. Also, we highlighted the possible translational role of lncRNAs as therapeutic targets for this condition and discussed the potential role of exosomes in delivering the lncRNAs involved in post-MI cardiac remodeling., 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 Masson SAS.. All rights reserved.)

Background: Different populations and areas of the world experienced diverse COVID-19 hospitalization and mortality rates. Claims data is a systematically recorded source of hospitalized patients' information that could be used to evaluate the disease management course and outcomes. We aimed to investigate the hospitalization and mortality patterns and associated factors in a huge sample of hospitalized patients., Methods: In this retrospective registry-based study, we utilized claim data from the Iran Health Insurance Organization (IHIO) consisting of approximately one million hospitalized patients across various hospitals in Iran over a 26-month period. All records in the hospitalization dataset with ICD-10 codes U07.1/U07.2 for clinically/laboratory confirmed COVID-19 were included. In this study, a case referred to one instance of a patient being hospitalized. If a patient experienced multiple hospitalizations within 30 days, those were aggregated into a single case. However, if hospitalizations had longer intervals, they were considered independent cases. The primary outcomes of study were general and intensive care unit (ICU) hospitalization periods and case fatality rate (CFR) at the hospital. Besides, various demographic and hospitalization-associated factors were analyzed to derive the associations with study outcomes using accelerated failure time (AFT) and logistic regression models., Results: A total number of 1 113 678 admissions with COVID-19 diagnosis were recorded by IHIO during the study period, defined as 917 198 cases, including 51.9% females and 48.1% males. The 61-70 age group had the highest number of cases for both sexes. Among defined cases, CFR was 10.36% (95% CI: 10.29-10.42). The >80 age group had the highest CFR (26.01% [95% CI: 25.75-26.27]). The median of overall hospitalization and ICU days were 4 (IQR: 3-7) and 5 (IQR: 2-8), respectively. Male patients had a significantly higher risk for mortality both generally (odds ratio (OR) = 1.36 [1.34-1.37]) and among ICU admitted patients (1.12 [1.09-1.12]). Among various insurance funds, Foreign Citizens had the highest risk of death both generally (adjusted OR = 2.06 [1.91-2.22]) and in ICU (aOR = 1.71 [1.51-1.92]). Increasing age groups was a risk of longer hospitalization, and the >80 age group had the highest risk for overall hospitalization period (median ratio = 1.52 [1.51-1.54]) and at ICU (median ratio = 1.17 [1.16-1.18]). Considering Tehran as the reference province, Sistan and Balcuchestan (aOR = 1.4 [1.32-1.48]), Alborz (aOR = 1.28 [1.22-1.35]), and Khorasan Razavi (aOR = 1.24 [1.20-1.28]) were the provinces with the highest risk of mortality in hospitalized patients., Conclusion: Hospitalization data unveiled mortality and duration associations with variables, highlighting provincial outcome disparities in Iran. Using enhanced registry systems in conjunction with other studies, empowers policymakers with evidence for optimizing resource allocation and fortifying healthcare system resilience against future health challenges., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Mehrizi 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.)

Role of clustered regularly interspaced short palindromic repeats (CRISPR)-like sequences in antibiotic resistance and biofilm formation isn't clear. This study investigated association of CRISPR-like sequences with antibiotic resistance and biofilm formation in H. pylori isolates. Thirty-six of H. pylori isolates were studied for existence of CRISPR-like sequences using PCR method and their correlation with biofilm formation and antibiotic resistance. Microtiter-plate technique was utilized for investigating antibiotic resistance profile of isolates against amoxicillin, tetracycline, metronidazole and clarithromycin. Biofilm formation of isolates was analyzed by microtiter-plate-based-method. Out of 23 CRISPR-like positive isolates, 19 had ability of biofilm formation and 7 of 13 CRISPR-like negative isolates were able to form biofilm (P value  = 0.445). In CRISPR-like positive isolates, 11 (48%), 18 (78%), 18 (78%) and 23 (100%) were resistant to amoxicillin, tetracycline, metronidazole and clarithromycin, respectively. Since CRISPR-like sequences have role in antibiotic resistance, may be applied as genetic markers of antibiotic resistance. But there was no substantial correlation between biofilm formation and existence of CRISPR-like sequences. These results indicate possible importance of CRISPR-like sequences on acquisition of resistance to antibiotics in this bacterium., 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.)

Background and Aims: Fragmented QRS (fQRS), which is associated with rhythm disturbances, can predispose the heart to fatal ventricular arrhythmias. Recently, accumulating studies indicates that fQRS is associated with poor prognosis in various types of cardiomyopathies. Therefore, we assessed the association between fQRS with all-cause mortality and major arrhythmic events (MAEs) in patients with nonischemic cardiomyopathy, in this systematic review and meta-analysis study., Methods: We performed a comprehensive search in databases of PubMed/Medline, EMBASE, and Web of Science from the beginning to December 31, 2022. Published observational studies (cohorts, case-control, or analytical cross-sectional studies) were included that report the prognostic value of fQRS in patients with different types of nonischemic cardiomyopathies for MAEs (sudden cardiac death, sudden cardiac arrest, sustained ventricular tachycardia [VT], ventricular fibrillation [VF], and appropriate shock) and all-cause mortality. We pooled risk ratios (RRs) through raw data and adjusted hazard ratios (aHRs) using "Comprehensive Meta-Analysis" software, Version 2.0., Results: Nineteen cohort and three analytical cross-sectional studies were included in this meta-analysis involving a total of 4318 subjects with nonischemic cardiomyopathy (1279 with fQRS and 3039 without fQRS). FQRS was significantly associated with an increased risk of all-cause mortality in patients with nonischemic cardiomyopathy (pooled RR: 1.920; 95% confidence interval [CI]: 1.388-2.656, p  < 0.0001/pooled HR: 1.729; 95% CI: 1.327-2.251, p  < 0.0001). Also, the risk of developing MAEs in the presence of fQRS was significantly increased (pooled RR: 2.041; 95% CI: 1.644-2.533, p  < 0.0001/pooled HR: 3.626; 95% CI: 2.119-6.204, p  < 0.0001). In the subgroup analysis, the strongest association between fQRS presence and increased MAEs was observed in patients with hypertrophic cardiomyopathy (HCM) (pooled RR: 3.44; 95% CI: 2.07-5.71, p  < 0.0001/pooled HR: 3.21; 95% CI: 2.04-5.06, p  < 0.0001)., Conclusion: Fragmented QRS could be a prognostic marker for all-cause mortality and MAEs in patients with various types of nonischemic cardiomyopathies, particularly HCM., Competing Interests: The authors declare no conflict of interest., (© 2024 The Authors. Health Science Reports published by Wiley Periodicals LLC.)

Background: During a COVID-19 pandemic, it is imperative to investigate the outcomes of all non-COVID-19 diseases. This study determines hospital admissions and mortality rates related to non-COVID-19 diseases during the COVID-19 pandemic among 41 million Iranians., Method: This nationwide retrospective study used data from the Iran Health Insurance Organization. From September 23, 2019, to Feb 19, 2022, there were four study periods: pre-pandemic (Sept 23-Feb 19, 2020), first peak (Mar 20-Apr 19, 2020), first year (Feb 20, 2020-Feb 18, 2021), and the second year (Feb 19, 2021-Feb 19, 2022) following the pandemic. Cause-specific hospital admission and in-hospital mortality are the main outcomes analyzed based on age and sex. Negative binomial regression was used to estimate the monthly adjusted Incidence Rate Ratio (IRR) to compare hospital admission rates in aggregated data. A logistic regression was used to estimate the monthly adjusted in-hospital mortality Odds Ratio (OR) for different pandemic periods., Results: During the study there were 6,522,114 non-COVID-19 hospital admissions and 139,679 deaths. Prior to the COVID-19 outbreak, the standardized hospital admission rate per million person-month was 7115.19, which decreased to 2856.35 during the first peak (IRR 0.40, [0.25-0.64]). In-hospital mortality also increased from 20.20 to 31.99 (OR 2.05, [1.97-2.13]). All age and sex groups had decreased admission rates, except for females at productive ages. Two years after the COVID-19 outbreak, the non-COVID-19 hospital admission rate (IRR 1.25, [1.13-1.40]) and mortality rate (OR 1.05, [1.04-1.07]) increased compared to the rates before the pandemic. The respiratory disease admission rate decreased in the first (IRR 0.23, [0.17-0.31]) and second years (IRR 0.35, [0.26-0.47] compared to the rate before the pandemic. There was a significant reduction in hospitalizations for pneumonia (IRR 0.30, [0.21-0.42]), influenza (IRR 0.04, [0.03-0.06]) and COPD (IRR 0.39, [0.23-0.65]) during the second year. There was a significant and continuous rise in the hematological admission rate during the study, reaching 186.99 per million person-month in the second year, reflecting an IRR of 2.84 [2.42-3.33] compared to the pre-pandemic period. The mortality rates of mental disorders (OR 2.15, [1.65-2.78]) and musculoskeletal (OR 1.48, [1.20-1.82), nervous system (OR 1.42, [1.26-1.60]), metabolic (OR 1.99, [1.80-2.19]) and circulatory diseases (OR 1.35, [1.31-1.39]) increased in the second year compare to pre-pandemic. Myocardial infarction (OR 1.33, [1.19-1.49]), heart failure (OR 1.59, [1.35-1.87]) and stroke (OR 1.35, [1.24-1.47]) showed an increase in mortality rates without changes in hospitalization., Conclusions: In the era of COVID-19, the changes seem to have had a long-term effect on non-COVID-19 diseases. Countries should prepare for similar crises in the future to ensure medical services are not suspended., (© 2024. The Author(s).)

Purpose: Most current research toward ultra-high dose rate (FLASH) radiation is conducted with advanced proton and electron accelerators, which are of limited accessibility to basic laboratory research. An economical alternative to charged particle accelerators is to employ high-capacity rotating anode x-ray tubes to produce kilovoltage x-rays at FLASH dose rates at short source-to-surface distances (SSD). This work describes a comprehensive dosimetric evaluation of a rotating anode x-ray tube for potential application in laboratory FLASH study., Methods and Materials: A commercially available high-capacity fluoroscopy x-ray tube with 75 kW input power was implemented as a potential FLASH irradiator. Radiochromic EBT3 film and thermoluminescent dosimeters (TLDs) were used to investigate the effects of SSD and field size on dose rates and depth-dose characteristics in kV-compatible solid water phantoms. Custom 3D printed accessories were developed to enable reproducible phantom setup at very short SSD. Open and collimated radiation fields were assessed., Results: Despite the lower x-ray energy and short SSD used, FLASH dose rates above 40 Gy/s were achieved for targets up to 10-mm depth in solid water. Maximum surface dose rates of 96 Gy/s were measured in the open field at 47 mm SSD. A non-uniform high-to-low dose gradient was observed in the planar dose distribution, characteristic of anode heel effects. With added collimation, beams up to 10-mm diameter with reasonable uniformity can be produced. Typical 80%-20% penumbra in the collimated x-ray FLASH beams were less than 1 mm at 5-mm depth in phantom. Ramp-up times at the maximum input current were less than 1 ms., Conclusion: Our dosimetric characterization demonstrates that rotating anode x-ray tube technology is capable of producing radiation beams in support of preclinical FLASH radiobiology research., (© 2023 American Association of Physicists in Medicine.)

Background: Acute kidney injury (AKI) is one of the preventable complications of percutaneous coronary intervention (PCI). This study aimed to develop machine learning (ML) models to predict AKI after PCI in patients with acute coronary syndrome (ACS)., Methods: This study was conducted at Tehran Heart Center from 2015 to 2020. Several variables were used to design five ML models: Naïve Bayes (NB), Logistic Regression (LR), CatBoost (CB), Multi-layer Perception (MLP), and Random Forest (RF). Feature importance was evaluated with the RF model, CB model, and LR coefficients while SHAP beeswarm plots based on the CB model were also used for deriving the importance of variables in the population using pre-procedural variables and all variables. Sensitivity, specificity, and the area under the receiver operating characteristics curve (ROC-AUC) were used as the evaluation measures., Results: A total of 4592 patients were included, and 646 (14.1%) experienced AKI. The train data consisted of 3672 and the test data included 920 cases. The patient population had a mean age of 65.6 ± 11.2 years and 73.1% male predominance. Notably, left ventricular ejection fraction (LVEF) and fasting plasma glucose (FPG) had the highest feature importance when training the RF model on only pre-procedural features. SHAP plots for all features demonstrated LVEF and age as the top features. With pre-procedural variables only, CB had the highest AUC for the prediction of AKI (AUC 0.755, 95% CI 0.713 to 0.797), while RF had the highest sensitivity (75.9%) and MLP had the highest specificity (64.35%). However, when considering pre-procedural, procedural, and post-procedural features, RF outperformed other models (AUC: 0.775). In this analysis, CB achieved the highest sensitivity (82.95%) and NB had the highest specificity (82.93%)., Conclusion: Our analyses showed that ML models can predict AKI with acceptable performance. This has potential clinical utility for assessing the individualized risk of AKI in ACS patients undergoing PCI. Additionally, the identified features in the models may aid in mitigating these risk factors., (© 2024. The Author(s).)

The most prevalent and severe malignancy of the central nervous system within the brain is glioma. Glioma is a vascularized cancer, and angiogenesis is necessary for glioma growth, invasion, and recurrence. It is also believed that this factor is this factor to be accountable for therapy resistance in many cancers, including glioma. The process of angiogenesis, which plays a crucial role in both health and disease situations such as cancer, involves the creation of new blood vessels from pre-existing ones. Non-coding RNAs (ncRNAs) are unique molecules that have been found to possess a wide range of abilities to modify the expression of various genes. They carry out their gene-modulating roles at a variety of distinct levels, including post-transcriptional and post-translational levels. Long ncRNAs (lncRNAs) and circular RNAs (circRNAs) are a group of ncRNA that have attracted particular attention and are involved in the angiogenesis mechanism in cancer. Understanding the regulatory mechanisms of these RNAs in the angiogenesis process in gliomas provides unique fundamental information about the process of tumor-associated neovascularization. On the other hand, due to developments in the characterisation of lncRNAs and circRNAs, these novel structures may potentially be used in clinics as possible biomarkers for treatment strategies that target tumor angiogenesis. Throughout the review, new knowledge and views about the angioregulatory function of circRNAs and lncRNAs in gliomas have been presented. Additionally, we talk about the novel idea of ncRNA-based therapeutics for gliomas in the future., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: This study aims to present the feasibility of developing a synchrotron-based proton ultra-high dose rate (UHDR) pencil beam scanning (PBS) system., Methods: The RF extraction power in the synchrotron system was increased to generate 142.4 MeV pulsed proton beams for UHDR irradiation at ~100 nA beam current. The charge per spill was measured using a Faraday cup. The spill length and microscopic time structure of each spill was measured with a 2D strip transmission ion chamber. The measured UHDR beam fluence was used to derive the spot dwell time for pencil beam scanning. Absolute dose distributions at various depths and spot spacings were measured using Gafchromic films in a solid-water phantom., Results: For proton UHDR beams at 142.4 MeV, the maximum charge per spill is 4.96 ± 0.10 nC with a maximum spill length of 50 ms. This translates to an average beam current of approximately 100 nA during each spill. Using a 2 × 2 spot delivery pattern, the delivered dose per spill at 5 cm and 13.5 cm depth is 36.3 Gy (726.3 Gy/s) and 56.2 Gy (1124.0 Gy/s), respectively., Conclusions: The synchrotron-based proton therapy system has the capability to deliver pulsed proton UHDR PBS beams. The maximum deliverable dose and field size per pulse are limited by the spill length and extraction charge.

Introduction: It has been demonstrated that an increase in the diameter of the right ventricle or pulmonary artery in COVID-19 patients could be associated with the severity of lung involvement and may lead to unfavorable outcomes, particularly in the presence of pulmonary vascular diseases. This study investigated the relationship between these right heart strain features, the extent of lung involvement, and their prognostic values in patients without vascular comorbidities., Methods: This study selected 154 consecutive patients with positive chest computed tomography (CT) findings and no evidence of concurrent pulmonary disease. Clinical characteristics and adverse outcomes in in-hospital settings were collected retrospectively. Diameters of cardiac ventricles and arteries, along with lung opacification scores, were obtained using CT pulmonary angiography (CTPA) findings, and the association of these variables was evaluated., Results: An increase in pulmonary artery (PA) to ascending aorta (AO) diameter ratio and lung parenchymal damage were significantly and positively correlated ( P =0.017), but increased right ventricle (RV) to left ventricle (LV) diameter ratio showed no association with the extent of chest opacification ( P =0.098). Evaluating the prognostic ability of both ratios using logistic regression and receiver operating characteristic (ROC) analysis proved no significant class separation in regards to predicting adverse outcomes (PA/AO: OR:1.081, P Value:0.638, RV/LV: OR:1.098, P Value:0.344)., Conclusion: In COVID-19 patients without vascular comorbidities, a higher PA/AO diameter ratio was significantly associated with increased lung involvement severity on CT imaging but not with adverse in-hospital outcomes. Conversely, an increased RV/LV ratio on CTPA did not correlate significantly with adverse outcomes or the severity of parenchymal lung damage., Competing Interests: The authors declare no conflict of interest., (© 2024 The Author(s).)

Heart failure (HF) is a public health issue that imposes high costs on healthcare systems. Despite the significant advances in therapies and prevention of HF, it remains a leading cause of morbidity and mortality worldwide. The current clinical diagnostic or prognostic biomarkers, as well as therapeutic strategies, have some limitations. Genetic and epigenetic factors have been identified to be central to the pathogenesis of HF. Therefore, they might provide promising novel diagnostic and therapeutic approaches for HF. Long non-coding RNAs (lncRNAs) belong to a group of RNAs that are produced by RNA polymerase II. These molecules play an important role in the functioning of different cell biological processes, such as transcription and regulation of gene expression. LncRNAs can affect different signaling pathways by targeting biological molecules or a variety of different cellular mechanisms. The alteration in their expression has been reported in different types of cardiovascular diseases, including HF, supporting the theory that they are important in the development and progression of heart diseases. Therefore, these molecules can be introduced as diagnostic, prognostic, and therapeutic biomarkers in HF. In this review, we summarize different lncRNAs as diagnostic, prognostic, and therapeutic biomarkers in HF. Moreover, we highlight various molecular mechanisms dysregulated by different lncRNAs in HF., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Heavy-fermion metals are prototype systems for observing emergent quantum phases driven by electronic interactions 1-6 . A long-standing aspiration is the dimensional reduction of these materials to exert control over their quantum phases 7-11 , which remains a significant challenge because traditional intermetallic heavy-fermion compounds have three-dimensional atomic and electronic structures. Here we report comprehensive thermodynamic and spectroscopic evidence of an antiferromagnetically ordered heavy-fermion ground state in CeSiI, an intermetallic comprising two-dimensional (2D) metallic sheets held together by weak interlayer van der Waals (vdW) interactions. Owing to its vdW nature, CeSiI has a quasi-2D electronic structure, and we can control its physical dimension through exfoliation. The emergence of coherent hybridization of f and conduction electrons at low temperature is supported by the temperature evolution of angle-resolved photoemission and scanning tunnelling spectra near the Fermi level and by heat capacity measurements. Electrical transport measurements on few-layer flakes reveal heavy-fermion behaviour and magnetic order down to the ultra-thin regime. Our work establishes CeSiI and related materials as a unique platform for studying dimensionally confined heavy fermions in bulk crystals and employing 2D device fabrication techniques and vdW heterostructures 12 to manipulate the interplay between Kondo screening, magnetic order and proximity effects., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: Mortality rate in rural areas is a useful measure of the health of the population and the function of the health system, which varies over space and time. The objective of this research is to explore the spatial and temporal variations in the rural mortality rate in Iran at the county level in 2006, 2011, and 2016., Methods: data were gathered from the rural population and mortality statistics published by the Statistical Centre of Iran (SCI) and the National Organization for Civil Registration (NOCR). Global spatial patterns were assessed using the global Moran's I and local clusters through the local Moran's I., Results: Spatial distribution of rural mortality rate shows that during the years under study the number of counties with a lower rate has increased. The counties with rate of less form continuous areas in the southwest, central and east regions. The excess risk map reveals significant variations in both value and extent. Also, the values of Moran's index increased from 0.1848 in 2006 to 0.4041 in 2016, which indicates the strengthening of the cluster spatial pattern of the overall rural mortality rate. Local patterns have undergone substantial changes over space and time., Conclusion: The findings indicate significant spatial and temporal variations in rural mortality rates in Iran. Policy-makers can use this information to plan and enhance healthcare infrastructure in specific counties. The findings serve for evaluating the effectiveness of health policies, enabling policy-makers to make informed decisions, allocate resources efficiently and design targeted interventions for improved public health outcomes., (© 2024 The Author(s); Published by Kerman University of Medical Sciences This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.)

Thyroid and gonadotropin hormones play an essential role in the regulation of regulating various physiological functions. The effects of melatonin and zinc (Zn) on these hormones have already been investigated. The aim of the present study was to investigate the effect of melatonin with and without zinc on the levels of gonadotropin hormones and thyroid hormones (triiodothyronine (T 3 ), thyroxine (T 4 ) and thyroid-stimulating hormone (TSH)) in female rats. In general, 35 sexually mature female rats were randomly divided into five treatment groups, with each group comprising 7 rats, in a completely randomized design (CRD) during the research. The rats were treated daily with Zn and melatonin via gavage as follows T1 (control 1, basal diet), T2 (control 2, treatment with normal saline) and the other experimental groups, including T 3 , T 4 and T 5 , were treated with Zn (40 ppm), melatonin (5 mg/kg) or a combination of Zn and melatonin at the same dose. The administration of the drugs was continued for 20 days (daily) . Plasma samples were then taken for the determination of LH, FFH, LH/FSH, estrogen, progesterone, T 3 , T 4 and TSH levels. The results showed no significant differences in FSH and LH levels between treatments. Estrogen, progesterone and TSH levels were higher in the rats receiving 5 mg melatonin per day than in the other groups, but not statistically significant ( P >0.05). However, T 3 levels decreased significantly in the group receiving 40 mg/kg Zn compared to the other experiments. ( P <0.05). The results showed no significant difference between the treatments in terms of T 4 levels ( P >0.05). In conclusion, no remarkable changes in other variables were observed in female rats receiving melatonin, Zn or a combination of melatonin and Zn, with the exception of T 3 ., Competing Interests: The writers declare to the fact that they have no conflict of interest.

Objectives: We aimed to assess the therapeutic effects of a topical probiotic nano-formulation derived from Lactobacillus reuteri on treating recurrent aphthous stomatitis., Materials and Methods: 60 participants were randomly allocated into two groups (control and probiotic). Probiotic group administered topical probiotic nano-formulation three times a day for seven days. The control group administered a standard analgesic oral rinse. The size of ulcer(s) and pain severity were recorded on days 0, 3, 5, and 7 after intervention., Results: Before the intervention, the groups had no significant differences in terms of pain severity (P-value = 0.28) and lesion size (P-value = 0.24). Both groups exhibited significant reductions in pain severity and lesion size over the course of the intervention. After one week, the probiotic group had a notably larger lesion size reduction than the control group (P-value = 0.01). The probiotic group also showed a significantly greater reduction in pain severity than the control group (P-value = 0.04)., Conclusions: Applying topical probiotic nano-formulation derived from Lactobacillus reuteri three times a day decreased lesion size and pain severity in RAS patients faster than the local analgesic oral rinse., Clinical Relevance: Lactobacillus reuteri-derived probiotic nano-formulation might be a promising treatment option for RAS., (© 2023. The Author(s).)