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Introduction: Teriparatide is a recombinant analog of the parathyroid hormone and an anabolic treatment modality for osteoporosis. This study aimed to evaluate the effectiveness of biosimilar teriparatide (CinnoPar®, CinnaGen Co., Iran) in osteoporotic patients after at least one year of treatment. Methods: In this multi-center, single-arm study, 239 eligible patients received subcutaneous injections of biosimilar teriparatide 20 μg once daily for at least one year. The main outcome measure was the change in bone mineral density (BMD) T-score from baseline (pre-treatment) to end of the study (post-treatment). In addition, the change in the fracture risk assessment tool (FRAX) score was calculated to estimate the 10-year probability of major and hip fractures pre-and post-treatment. Results: A total of 239 patients (age, 63 ± 12.14 years; female, 88.28 %) were included, of which 27.62 % (66/239), 14.64 % (35/239), and 57.74 % (138/239) received biosimilar teriparatide for 12–16 months, 17–20 months, and 21–24 months, respectively. From baseline to end of the study, the T-score at the lumbar spine increased from −2.67 ± 1.04 to −2.26 ± 1.11 (mean percent change, 13.07 ± 62.89; p-value

In this research paper, a new methodology to design a progressive and win-win royalty model for upstream fiscal systems is developed. The proposed royalty model is designed as a function of different boundary conditions of the market and the productive resources. These boundary conditions include the associated exploration and production risks, commodity prices, the extraction costs, besides the expected production and depletion rate. The behavior of the proposed royalty model under different oil prices, development costs, production rates, and exploration risks is investigated using deterministic and stochastic analysis. Our results prove that the applicable royalty rate increases with both the price and production rate while it decreases with increasing the development costs and the associated exploration and production risks. In addition, the proposed royalty model provides the contractor with sufficient incentives to develop marginal or low profitability fields and the development of deep offshore or frontier fields with high development and operating costs.

Humanity has suffered from the coronavirus disease 2019 (COVID-19) pandemic over the past two years, which has left behind millions of deaths. Azithromycin (AZ), an antibiotic used for the treatment of several bacterial infections, has shown antiviral activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) as well as against the dengue, Zika, Ebola, and influenza viruses. Additionally, AZ has shown beneficial effects in non-infective diseases such as cystic fibrosis and bronchiectasis. However, the systemic use of AZ in several diseases showed low efficacy and potential cardiac toxicity. The application of nanotechnology to formulate a lung delivery system of AZ could prove to be one of the solutions to overcome these drawbacks. Therefore, we aimed to evaluate the attenuation of acute lung injury in mice via the local delivery of an AZ nanoformulation. The hot emulsification–ultrasonication method was used to prepare nanostructured lipid carrier of AZ (AZ-NLC) pulmonary delivery systems. The developed formulation was evaluated and characterized in vitro and in vivo. The efficacy of the prepared formulation was tested in the bleomycin (BLM) -mice model for acute lung injury. AZ-NLC was given by the intratracheal (IT) route for 6 days at a dose of about one-eighth oral dose of AZ suspension. Samples of lung tissues were taken at the end of the experiment for immunological and histological assessments. AZ-NLC showed an average particle size of 453 nm, polydispersity index of 0.228 ± 0.07, zeta potential of −30 ± 0.21 mV, and a sustained release pattern after the initial 50% drug release within the first 2 h. BLM successfully induced a marked increase in pro-inflammatory markers and also induced histological changes in pulmonary tissues. All these alterations were significantly reversed by the concomitant administration of AZ-NLC (IT). Pulmonary delivery of AZ-NLC offered delivery of the drug locally to lung tissues. Its attenuation of lung tissue inflammation and histological injury induced by bleomycin was likely through the downregulation of the p53 gene and the modulation of Bcl-2 expression. This novel strategy could eventually improve the effectiveness and diminish the adverse drug reactions of AZ. Lung delivery could be a promising treatment for acute lung injury regardless of its cause. However, further work is needed to explore the stability of the formulation, its pharmacokinetics, and its safety.

Iminodipropionitrile (IDPN) is known to produce axonopathy and vestibular hair cell degeneration. Recent histopathological studies have shown IDPN-induced liver and kidney toxicities in rodents; however, the associated mechanisms are not clearly understood. We investigated the role of proinflammatory cytokines in IDPN-induced liver and kidney toxicities in rats. Rats were treated with saline (control) and IDPN (100 mg/kg, intraperitoneally) daily for 1, 5, and 10 days, respectively. Animals were killed 24 hours after the last dose and liver and kidneys were collected for histopathology and interleukin-1β (IL-1β), IL-6, and tumor necrosis factor-α messenger RNA expression analysis. Serum aspartate aminotransferase and alanine aminotransferase activities were significantly increased after 10 doses of IDPN. The level of serum creatinine was initially increased after the first dose of IDPN but subsided on days 5 and 10. Blood urea nitrogen levels were significantly increased on days 5 and 10 following IDPN exposure. Histopathology showed dose-dependent hepatotoxicity in IDPN-treated rats. Iminodipropionitrile-induced expression of proinflammatory cytokines peaked after day 1 in liver and after day 5 in kidneys. In conclusion, repeated exposure of IDPN for 10 days produced significant structural and functional damages in rat liver whereas kidneys showed gradual recovery with time. These findings point toward the role of inflammatory mediators in IDPN-induced toxicity in rats.

This study compared the efficiency of commercial egg yolk-free (AndroMed, OPTIXcell) and egg yolk-supplemented (Triladyl, Steridyl) Tris-based extenders for semen cryopreservation in seven adult dromedary camels. The camel-specific extender SHOTOR was used as control. The collected semen samples were evaluated and diluted with SHOTOR, Triladyl, Steridyl, AndroMed, or OPTIXcell. The diluted semen was gradually cooled and equilibrated for two hours before liquid nitrogen freezing. Semen was evaluated prior to freezing and after freeze-thawing cycles for motility, kinetics, vitality, abnormality, plasma membrane integrity, and DNA fragmentation using computer-assisted sperm analysis. In pre-freezing evaluation, progressive sperm motility was higher in SHOTOR-diluted samples (21.54 ± 1.83) than in samples diluted with Steridyl, OPTIXcell, or AndroMed (15.76 ± 1.80, 17.43 ± 1.10, and 13.27 ± 1.07, respectively). Moreover, Triladyl and SHOTOR resulted in significantly (p < 0.05) better sperm vitality and DNA integrity than all other diluents, but Triladyl resulted in a significantly (p < 0.05) better plasma membrane integrity (87.77 ± 0.31) than SHOTOR (85.48 ± 0.58). In the post-thawing evaluation, Triladyl led to significantly (p < 0.05) higher sperm motility (38.63 ± 0.81%; p < 0.05) when compared to SHOTOR, Steridyl or AndroMed (35.09 ± 1.341%, 34.4 ± 0.84%, and 31.99 ± 1.48%, respectively), with OPTIXcell being the least efficient (28.39 ± 0.86%). Progressive sperm motility was the highest when using Triladyl. Post-thawing curvilinear, straight line and average path sperm velocities were highest with Triladyl and lowest with AndroMed. Triladyl led to the highest linearity coefficient and straightness sperm coefficient, while SHOTOR to the highest DNA and plasma membrane integrity. OPTIXcell and AndroMed resulted in poor post-thawing sperm vitality, while Steridyl was less efficient than Triladyl. The highest rate of sperm abnormalities was recorded with OPTIXcell and the lowest with SHOTOR or Triladyl. In conclusion, SHOTOR, Triladyl, Steridyl, AndroMed, and OPTIXcell can all be used for camel semen cryopreservation; however, SHOTOR and Triladyl provided the best post-thawing sperm quality. Based on our findings, Triladyl is the best commercially available extender for dromedary camel semen cryopreservation to date.

Retinoic acid (RA) is an indigenous metabolite and descriptive physiologically functioning constituent of vitamin A. Retinoids were documented as vital regulators for cell development and distinction, embryonic growth, and reproductive function in both male and female livestock. Previously, RA has been shown to have several positive impacts in vivo and in vitro and critically control many reproductive events, such as oocyte development, follicular growth, and early embryonic growth. In addition, RA manages apoptotic signaling and oxidative damages in cells. Recently, RA has been used widely in assisted reproductive technology fields, especially during in vitro embryo development in various mammalian species, including buffaloes, bovine, goats, sheep, pigs, and rabbits. However, the optimum concentration of RA greatly differs based on the condition of maturation media and species. Based on the obtained findings, it was generally accepted that RA enhances nuclear oocyte maturation, cleavage and maturation rates, blastocyst formation, and embryo development. As such, it possesses antioxidant properties against reactive oxygen species (ROS) and an anti-apoptotic effect through enhancing the transcription of some related genes such as superoxide dismutase, prostaglandin synthase, glutathione peroxidase, peroxiredoxins, and heme oxygenase. Therefore, the current review concludes that an addition of RA (up to 50 nM) has the potential to improve the oocyte maturation media of various species of livestock due to its antioxidant activity.

Virtual Reality (VR) is a key industry for the development of the digital economy in the future. Mobile VR has advantages in terms of mobility, lightweight and cost-effectiveness, which has gradually become the mainstream implementation of VR. In this paper, a mobile VR video adaptive transmission mechanism based on intelligent caching and hierarchical buffering strategy in Mobile Edge Computing (MEC)-equipped 5G networks is proposed, aiming at the low latency requirements of mobile VR services and flexible buffer management for VR video adaptive transmission. To support VR content proactive caching and intelligent buffer management, users' behavioral similarity and head movement trajectory are jointly used for viewpoint prediction. The tile-based content is proactively cached in the MEC nodes based on the popularity of the VR content. Second, a hierarchical buffer-based adaptive update algorithm is presented, which jointly considers bandwidth, buffer, and predicted viewpoint status to update the tile chunk in client buffer. Then, according to the decomposition of the problem, the buffer update problem is modeled as an optimization problem, and the corresponding solution algorithms are presented. Finally, the simulation results show that the adaptive caching algorithm based on 5G intelligent edge and hierarchical buffer strategy can improve the user experience in the case of bandwidth fluctuations, and the proposed viewpoint prediction method can significantly improve the accuracy of viewpoint prediction by 15%.

Abstract Background Epigenome‐wide association studies have identified multiple DNA methylation sites (CpGs) associated with alcohol consumption, an important lifestyle risk factor for cardiovascular diseases. This study aimed to test the hypothesis that an alcohol consumption epigenetic risk score (ERS) is associated with blood pressure (BP) traits. Results We implemented an ERS based on a previously reported epigenetic signature of 144 alcohol-associated CpGs in meta-analysis of participants of European ancestry. We found a one-unit increment of ERS was associated with eleven drinks of alcohol consumed per day, on average, across several cohorts (p

Abstract Recently, significant efforts have been exerted to replace mineral oil with environmentally friendly oils due to safety and environmental issues. However, there is a need to clarify the physical mechanisms behind the ageing impact of these oils. The authors use advanced optical spectroscopy techniques in correlation with dielectric measurements to understand the ageing processes in environmentally friendly oils as well as mineral oil. Firstly, different samples of environmentally friendly oils and mineral oil were utilised to investigate the ageing mechanism. The samples were subjected to different ageing periods using a thermal accelerated ageing process. Secondly, the severity of the produced byproducts due to the oil degradation is examined based on several measured properties representing macroscopic and microscopic categories. The macroscopic category was evaluated through dielectric properties, including breakdown voltage, dielectric permittivity, and dissipation factor. The microscopic category, on the other hand, was assessed using techniques such as ultraviolet–visible absorption spectroscopy and photoluminescence spectroscopy. These techniques enabled a deep understanding of the molecular‐level changes occurring in the oil under ageing conditions, thereby getting new insights into oil ageing mechanisms. It is worth mentioning that natural ester oil demonstrated the most favourable performance across various properties under ageing conditions.

Abstract The development of efficient and environmentally sustainable materials for white light-emitting diodes (WLEDs) is of paramount importance in the field of lighting technology. In this study, we present a solvent-modulated synthesis approach for the fabrication of multicolor narrow-bandwidth emissive carbon quantum dots (CQDs) as a promising solution for constructing WLEDs. The synthesis method involves the controlled reaction of organic precursors in different solvent environments, leading to the formation of CQDs with distinct emission wavelengths with a relatively small full width at half maximum, ranging from 28 to 42 nm. Moreover, these synthesized multicolor CQDs demonstrate a remarkably high fluorescence quantum yield of up to 65%, indicating their potential for constructing efficient WLED when incorporated in polymer matrix and coated on the surface of blue light-emitting diode (LED).

Abstract Epilepsy, a widespread neural ailment considered by prolonged neuronal depolarization and repetitive discharge, has been linked to extreme stimulus of N-methyl-D-aspartate receptors (NMDARs). Despite the availability of approved anti-seizure medications (ASMs) in many developed nations, approximately 30% of epilepsy patients continue to experience drug-resistant seizures. Thus, a growing interest in discovering natural compounds as potential sources for new medications is growing. Sinapinic acid, a natural derivative of cinnamic acid found in food sources, is known for its neuroprotective properties. This study investigated how sinapinic acid interacts with NMDA receptors and its potential role in providing anticonvulsant effects. Male mice were randomly allocated into nine groups: a control group receiving normal saline (1 ml/kg), groups treated with sinapinic acid at doses of 1, 3, and 10 mg/kg, a group treated with diazepam at 10 mg/kg, a group treated with an NMDA agonist at 75 mg/kg, a group treated with an NMDA antagonist at 0.5 mg/kg, a group receiving the ineffective dose of sinapinic acid (1 mg/kg) along with the NMDA antagonist, and a group receiving the effective dose of sinapinic acid (10 mg/kg) along with the NMDA agonist. Sinapinic acid and other treatments were administered intraperitoneally 30 min prior to inducing seizures with PTZ injection. Seizure onset time was recorded following PTZ injection. Blood and brain samples were collected after anesthesia to determine serum and brain nitrite levels. Real-time PCR assessed NMDAR gene expression in the prefrontal cortex (PFC). Data were analyzed using Prism software. The time seizures began was notably extended in groups treated with sinapinic acid at doses of 3 and 10 mg/kg compared to those treated with saline (P

Abstract Background MicroRNAs (miRNAs) are small non-coding RNAs that post-transcriptionally regulate gene expression. Perturbations in plasma miRNA levels are known to impact disease risk and have potential as disease biomarkers. Exploring the genetic regulation of miRNAs may yield new insights into their important role in governing gene expression and disease mechanisms. Results We present genome-wide association studies of 2083 plasma circulating miRNAs in 2178 participants of the Rotterdam Study to identify miRNA-expression quantitative trait loci (miR-eQTLs). We identify 3292 associations between 1289 SNPs and 63 miRNAs, of which 65% are replicated in two independent cohorts. We demonstrate that plasma miR-eQTLs co-localise with gene expression, protein, and metabolite-QTLs, which help in identifying miRNA-regulated pathways. We investigate consequences of alteration in circulating miRNA levels on a wide range of clinical conditions in phenome-wide association studies and Mendelian randomisation using the UK Biobank data (N = 423,419), revealing the pleiotropic and causal effects of several miRNAs on various clinical conditions. In the Mendelian randomisation analysis, we find a protective causal effect of miR-1908-5p on the risk of benign colon neoplasm and show that this effect is independent of its host gene (FADS1). Conclusions This study enriches our understanding of the genetic architecture of plasma miRNAs and explores the signatures of miRNAs across a wide range of clinical conditions. The integration of population-based genomics, other omics layers, and clinical data presents opportunities to unravel potential clinical significance of miRNAs and provides tools for novel miRNA-based therapeutic target discovery.

Abstract Kojic acid (KA) has gained significant attention due to its widespread use in the food and cosmetics industries. However, concerns about its potential carcinogenic effects have heightened the need for sensitive detection methods. This study introduces a fluorescence-based optical sensor for the quantification of KA in food samples, utilizing fluorescent carbon dots (CDs) synthesized from pomegranate peel via a hydrothermal method. The Stern–Volmer plot demonstrated a linear response for KA in the range of 120 to 1200 µM, with a Pearson correlation coefficient (r) of 0.9999 and. The sensor exhibited a detection limit of 30 ± 0.04 µM and a limit of quantification (LOQ) of 90 ± 0.14 µM. Application of the developed method to soy sauce and vinegar samples yielded accurate KA determinations, with recoveries of 103.11 ± 0.96% and 104.45 ± 2.15%, respectively. These findings highlight the potential of the proposed sensor for practical applications in food quality and safety assessment, offering valuable insights into the presence of KA in food products.

Abstract Neurofilament light chain (NfL) levels in circulation have been established as a sensitive biomarker of neuro-axonal damage across a range of neurodegenerative disorders. Elucidation of the genetic architecture of blood NfL levels could provide new insights into molecular mechanisms underlying neurodegenerative disorders. In this meta-analysis of genome-wide association studies (GWAS) of blood NfL levels from eleven cohorts of European ancestry, we identify two genome-wide significant loci at 16p12 (UMOD) and 17q24 (SLC39A11). We observe association of three loci at 1q43 (FMN2), 12q14, and 12q21 with blood NfL levels in the meta-analysis of African-American ancestry. In the trans-ethnic meta-analysis, we identify three additional genome-wide significant loci at 1p32 (FGGY), 6q14 (TBX18), and 4q21. In the post-GWAS analyses, we observe the association of higher NfL polygenic risk score with increased plasma levels of total-tau, Aβ-40, Aβ-42, and higher incidence of Alzheimer’s disease in the Rotterdam Study. Furthermore, Mendelian randomization analysis results suggest that a lower kidney function could cause higher blood NfL levels. This study uncovers multiple genetic loci of blood NfL levels, highlighting the genes related to molecular mechanism of neurodegeneration.

With the aim of investigating the efficiency of biochar for desalination, experiments with adsorbent treatment at four levels including sesame flour, biochar at temperatures of 400, 500 and 600 ℃ and salt water treatment at four levels including 5, 10, 20 and 35 dS/m were conducted in three replications as a factorial experiment in the form of a completely randomized design in a discontinuous environment. The adsorption of the salinity factor ions was studied in the presence and absence of copper ions. The results showed that the desalination capacity without the presence of copper ions in the best adsorbent (Biochar 600) was obtained at the studied salinities of 411.6 mg/g. While the desalination capacity in the presence of copper ions using the same adsorbent at the studied salinities was 382.2 mg/g, indicating competition between ions and 8.0% decrease in adsorption capacity for salinity 35 dS/m. In both the presence and absence of copper, the highest adsorption was assigned to chlorine and sodium ions and the lowest to potassium ion. In summary, sesame flour biochar, owing to its high active surface area, porous structure, and suitable functional groups on the surface, effectively adsorbs salt ions in the presence of copper ions during the adsorption process.

Introduction: Processes that generate systemic inflammation are strongly associated with neurodegenerative diseases. This study aimed to explore the potential anti-oxidative and anti-inflammatory effects of fasudil and its role in modulating aquaporin-4 (AQP-4) to improve cognitive impairment in a systemic inflammation model induced by lipopolysaccharide (LPS). Method: fourty C57BL/6 mice were assigned to four groups, including sham, LPS, sham+fasudil, and LPS+fasudil). Intraperitoneal LPS was given (500 μg/kg/day) at hours 0, 24, 48, and 72, and fasudil (30 mg/kg) administered intraperitoneal injections 2 hours after LPS injection. The open field, Y-maze, and Novel object tasks was used to assess learning and memory. The levels of malondialdehyde (MDA), superoxide dismutase (SOD), interleukin-10 (IL-10), and tumor necrosis factor-α (TNF-α) in the hippocampus also measured as markers of oxidative stress and inflammation. Furthermore, the expression of AQP-4 measured in the intact and experimental groups. Results: The results showed that Fasudil significantly improved memory and anxiety behavior induced by LPS in the open field maze, spatial recognition memory in the Y-maze, and performance in the novel object recognition task. It also mitigates hippocampal MDA and SOD levels. Additionally, fasudil ameliorated LPS-induced hippocampal levels of TNFα and IL-10 and increased hippocampal levels of AQP-4 expression in mice. Conclusion: Our results suggest that fasudil in the LPS model of systemic inflammation could improve cognition by suppressing oxidative stress and inflammation and increasing AQP-4 protein expression. These findings highlighted the potential of fasudil as a neuroprotective agent. However, further research is required to fully understand its neuroprotective properties in the treatment of neurodegenerative disorders.

The severe respiratory effects of the coronavirus disease 2019 (COVID-19) pandemic have necessitated the immediate development of novel treatments. The majority of COVID-19-related fatalities are due to acute respiratory distress syndrome (ARDS). Consequently, this virus causes massive and aberrant inflammatory conditions, which must be promptly managed. Severe respiratory disorders, notably ARDS and acute lung injury (ALI), may be treated safely and effectively using cell-based treatments, mostly employing mesenchymal stem cells (MSCs). Since the high potential of these cells was identified, a great deal of research has been conducted on their use in regenerative medicine and complementary medicine. Multiple investigations have demonstrated that MSCs and their products, especially exosomes, inhibit inflammation. Exosomes serve a critical function in intercellular communication by transporting molecular cargo from donor cells to receiver cells. MSCs and their derived exosomes (MSCs/MSC-exosomes) may improve lung permeability, microbial and alveolar fluid clearance, and epithelial and endothelial repair, according to recent studies. This review focuses on COVID-19-related ARDS clinical studies involving MSCs/MSC-exosomes. We also investigated the utilization of Nano-delivery strategies for MSCs/MSC-exosomes and anti-inflammatory agents to enhance COVID-19 treatment.

Despite significant advances in the prevention, diagnosis, and treatment of cardiac diseases, this condition is still considered one of the major challenges facing the global healthcare system. According to the World Health Organization (WHO) statistics, cardiovascular diseases (CVD) are among the leading causes of mortality worldwide. It is predicted that in the future, due to population aging, urbanization, and lifestyle changes, the mortality rate from cardiac diseases will increase. Current pharmacological approaches only extend the lifespan of patients without providing cardiac tissue repair. In the advanced stages of these diseases, apart from heart transplantation, there is no curative treatment available. However, due to limited suitable donors and post-operative risks and complications such as graft rejection, primary graft failure, and common infections after heart transplant, transplantation is not always feasible. Stem cells have created a wide range of hope in the world since their discovery. With increased research on stem cells and cell therapy in recent decades, researchers have found that utilizing this innovative therapeutic approach can increase lifespan and improve patient outcomes. Various countries have invested millions of dollars in the application of stem cells for treating various diseases in recent years. Embryonic stem cells (ESCs) have great differentiation potential, but their medical application faces severe ethical and religious constraints. The identification of potent induced pluripotent stem cells has revolutionized regenerative medicine. These cells possess all the capabilities of embryonic stem cells and can easily differentiate into cardiac myocytes. Furthermore, the paracrine effects of induced pluripotent stem cells (iPSCs) and extracellular vesicles (EVs) secreted from these cells in regenerative medicine have garnered significant attention. Among extracellular secretory vesicles, researchers have focused more on exosomes. Exosomes are vesicles ranging from 30 to 100 nanometers that have a plasma membrane-like topology and can enter target cells and deliver their cargo. Cardiac patches are a novel achievement resulting from the integration of tissue engineering and cell sciences and are used to improve cardiac injuries. Cardiac patches consist of a natural or synthetic scaffold designed to support and restore myocardial tissue following injury, and they are implanted into the heart tissue. The primary approach to using cardiac patches is to provide physical support to damaged heart tissue. Nowadays, the combination of cardiomyocytes derived from potent induced pluripotent stem cells along with biocompatible materials and growth factors has created specialized cardiac patches capable of precise delivery of many cells and minimizing cellular damages in vivo conditions. This review article aims to explore the latest advances in cardiac regenerative medicine through the use of cardiac patches, induced pluripotent stem cells, and exosomes derived from them; as well as to assess the challenges ahead in cardiac regenerative medicine using the mentioned items to alleviate and improve tissue damage to the heart, and ultimately provide an overview of new perspectives for future research in cardiac regenerative medicine.

Abstract Packetized energy encapsulates energy into modulated, routable, and trackable energy packets, enhancing the flexibility of managing distributed energy resources and expediting prosumers’ participation in transactive energy markets. In the context of packetized energy trading (PET), energy prosumers are naturally deemed as self‐interested agents seeking to obtain their own benefits. To align with prosumers’ demand, supply, quality of service (QoS), and system‐level social welfare, it is necessary to explore the design of prosumers’ bidding strategies and the market clearing methods, considering prosumers’ utility and the best demand response to markets. This study addresses challenges arising from prosumers’ selfishness and asymmetric preferences by proposing a PET‐oriented iterative double auction (IDA‐PET) design, where prosumers are allowed to iteratively change the bids before the auctioneer clears the market. Moreover, IDA‐PET accommodates system capacity constraints, energy balance, and economic constraints, providing cooperative strategies for both prosumers and the auctioneer. To validate the effectiveness of IDA‐PET, a novel and dedicated co‐simulation platform based on the hierarchical engine for large‐scale infrastructure co‐simulation platform is developed and case studies are conducted within a residential microgrid. The simulation results demonstrate that IDA‐PET can efficiently enhance the revenue of the auction market while meeting prosumers’ QoS requirements.

Abstract Background The plasma metabolome reflects the physiological state of various biological processes and can serve as a proxy for disease risk. Plasma metabolite variation, influenced by genetic and epigenetic mechanisms, can also affect the cellular microenvironment and blood cell epigenetics. The interplay between the plasma metabolome and the blood cell epigenome remains elusive. In this study, we performed an epigenome-wide association study (EWAS) of 1183 plasma metabolites in 693 participants from the LifeLines-DEEP cohort and investigated the causal relationships in DNA methylation–metabolite associations using bidirectional Mendelian randomization and mediation analysis. Results After rigorously adjusting for potential confounders, including genetics, we identified five robust associations between two plasma metabolites (l-serine and glycine) and three CpG sites located in two independent genomic regions (cg14476101 and cg16246545 in PHGDH and cg02711608 in SLC1A5) at a false discovery rate of less than 0.05. Further analysis revealed a complex bidirectional relationship between plasma glycine/serine levels and DNA methylation. Moreover, we observed a strong mediating role of DNA methylation in the effect of glycine/serine on the expression of their metabolism/transport genes, with the proportion of the mediated effect ranging from 11.8 to 54.3%. This result was also replicated in an independent population-based cohort, the Rotterdam Study. To validate our findings, we conducted in vitro cell studies which confirmed the mediating role of DNA methylation in the regulation of PHGDH gene expression. Conclusions Our findings reveal a potential feedback mechanism in which glycine and serine regulate gene expression through DNA methylation.

Abstract MicroRNAs (miRNAs) are small non-coding RNAs involved in post-transcriptional regulation of gene expression. Mounting evidence underscores the dysregulation of miRNAs to be associated with cancer development and progression by acting as tumour suppressors and oncogenes. However, their potential as biomarkers for early diagnosis of different cancers remains incompletely unraveled. We explored the relationship between plasma circulatory miRNAs and cancer risk within the population-based Rotterdam Study cohort. Plasma samples were collected at baseline (between 2002 and 2005) and miRNA levels were measured in 1,999 participants, including 169 prevalent cancer cases. The occurrence of cancer was assessed by continuous monitoring of medical records in 1,830 cancer-free participants until January 1, 2015. We assessed the association between incidence of five common cancers (blood, lung, breast, prostate, and colorectal) and 591 miRNAs well-expressed in plasma, using adjusted Cox proportional-hazards regression models. Our longitudinal analysis identified 13 miRNAs significantly associated with incident hematologic tumors surpassing the Bonferroni-corrected P

Background: Learning life skills can improve students' performance. This study aimed to investigate the effect of online life skills training courses on resilience, locus of control, general health, and academic performance at Yazd University of Medical Sciences.Method: This intervention study was performed on 70 third and higher-semester students. For the experimental group, a life skills training program was performed in five sessions during the five weeks. Data collection tools included Connor and Davidson resilience questionnaires, Rutter locus of control, and Goldberg general health and average grade points of the student in the previous and new semester, completed before and one month after the training program. The data were analyzed using SPSS.v22 descriptive statistics and independent and paired t-tests.Results: Before the study, the mean resilience scores of the intervention and control groups were 57.17±2.40 and 58.70±3.58, respectively. After the study, the mean resilience scores of the intervention and control groups were 73.13±2.27 and 59.50±3.50, respectively. Also, the mean scores of the locus of control before and after the study in the intervention and control groups were 10.22 ± 2.04, 11.59 ± 1.32, and 9.02 ± 3.50, 8.95 ± 2.32, respectively. Statistical analysis showed that there was a significant difference between the two groups in terms of all mentioned variables (P

Life cycle assessment is a suitable tool to examine and measure of the environmental aspects of the production of a product from the beginning to its formation. In this study, the environmental impacts of the production process of 1 ton of formalin in an industrial unit producing formalin with the approach of life cycle assessment and the requirements of the international standard ISO14040:2006, the use of SimaPro9 software and three evaluation methods Eco-indicator 99, IMPACT 2002+ and EDIP 2003 were investigated in the period of 2019-2020. The results of modeling with the Eco-indicator 99 method showed that the environmental impact of using methanol is 86% of the total environmental impact of the formalin production process. 80% of this impact comes from the consumption of fossil fuels in the production of methanol. The results obtained from the modeling of the formalin production process by applying the characteristic coefficients of the EDIP 2003 method indicate that the destruction of the ozone layer is the most important effect of the formalin production process and methanol has an 82% effect on the environmental effects of the formalin production process. Among them, more than 28% of the harmful effect of methanol consumption is on the destruction of the ozone layer. The results of modeling with the IMPACT 2002+ method show that 83% of the environmental impacts of the life cycle of formalin production are caused by the consumption of methanol, and the consumption of non-renewable energy sources has an impact of 60% on this value.

This article aims to illuminate temporality in value determination and stratification of value and price in the transformation of value into price. This leads to an understanding of value-relocating through the two concepts presented in this study: current-value-relocating (CVR) and integrated-value-relocating (IVR). Based on Marx’s exploration of the labor process and social reproduction and focusing on two components of a commodity’s value and the relation between the individual and aggregate level, the article seeks to propose a non-linear conception of temporality in value determination, which justifies the application of simultaneous equations in value determination. Furthermore, through the depiction of the stratification of value and price, the study insists on retaining the relations among their components in different layers. Lastly, the research attempts to explain all price-value deviations at the aggregate and individual levels in two forms: CVR and IVR.

Despite its rarity, pulmonary capillary hemangiomatosis (PCH) presents a significant diagnostic challenge. Due to its similarity to other pulmonary vascular diseases, such as pulmonary veno-occlusive disease, it is characterized by abnormal pulmonary capillary proliferation, which is a rare cause of primary pulmonary hypertension. This case was the first reported instance of PCH in Shahid Rajaee Heart Hospital in Tehran, Iran, in 2023, which was confirmed by genetic testing. It highlighted the importance of considering PCH among the differential diagnoses for pulmonary hypertension, even in adolescent patients. The 13-year-old patient’s main complaints were progressive exertional dyspnea and chest pain. He had no previous medical history and had not taken any pharmaceutical or herbal medications. Critical clinical findings included a heart murmur, an electrocardiogram revealing right ventricular hypertrophy, and echocardiogram evidence of pulmonary hypertension. The main diagnosis was PCH, as shown by CT findings of pulmonary artery dilatation and diffuse nodular ground glass opacities. Genetic tests indicated pathogenic EIF2AK4 mutations and suspicion of PCH. Therapeutic intervention included vasodilator therapy, which exacerbated the patient’s condition. This case emphasized the importance of maintaining a high index of suspicion for rare causes of pulmonary hypertension, such as PCH. The outcome was to prepare the patient for lung transplantation. To differentiate PCH from other pulmonary vascular diseases, a combination of clinical presentation, radiologic studies, genetic analysis, and response to treatment is required to determine appropriate management, particularly lung transplantation.

Objective: Diabetic patients with COVID-19 are at the higher risk of clinical complications and intensive care unit )ICU( admission. There is limited information available on the risk factors of mortality in diabetic patients with COVID-19 admitted to the ICUs. The aim of this study was identifying the mortality risk factors in diabetic patients with COVID-19 who are admitted to the ICU. Materials and Methods: In this study, we conducted a descriptive-analytical observational analysis on 391 patients admitted to the ICU for 18 months. We assessed the demographic, clinical, pharmaceutical, laboratory and imaging data of diabetic patients and statistically analyzed them to identify mortality risk factors. Results: The study found 156 (39.89%) diabetic out of 391 patients. The group of diabetic patients had significantly higher rates of endotracheal intubation (P< 0.001), mortality (P< 0.001), and complications during hospitalization due to COVID-19, including secondary bacterial infections (P = 0.005), venous thrombosis (P = 0.008), and gastrointestinal bleeding (P = 0.011), compared to the nondiabetic patient. Conclusion: Patients with diabetes who also have COVID-19 tend to experience more severe clinical outcomes and a higher mortality rate when admitted to the intensive care unit. The likelihood of mortality in these patients is closely associated with factors such as stroke occurrence, oxygenation levels, and the presence of secondary infections at the time of admission.

Abstract The surface micromorphology and roughening of the thermal evaporation-coated FTO/ZnS bilayer thin films annealed at 300, 400, 500, and $$550\,^\circ{\text{C}}$$ 550 ∘ C for 1 h have been studied. AFM images of the prepared samples were analysed by the MountainsMap software, and the effects of the annealing temperature on the surface texture of the FTO/ZnS thin film’s surface were investigated. Stereometric and advanced fractal analyses showed that the sample annealed at $$500\,^\circ{\text{C}}$$ 500 ∘ C exhibited greater surface roughness and greater skewness and kurtosis. This film also has the most isotropic surface and exhibits the highest degree of heterogeneity. Also, despite the decrease in surface roughness with increasing temperature from 500 to $$550 \,^\circ{\text{C}}$$ 550 ∘ C , the fractal dimension tends to increase. The static water contact angle measurements indicate that the film annealed at $$500 \,^\circ{\text{C}}$$ 500 ∘ C exhibits higher hydrophobicity, which can be attributed to its greater topographic roughness. Our research indicates that the surface morphology of FTO/ZnS bilayer thin films is influenced by the annealing temperature. Changing factors such as roughness, fractality, and wettability parameters to help improve surface performance make the FTO/ZnS bilayer suitable for application in electronic and solar systems.

Abstract Glioblastoma is a rare and deadly malignancy with a low survival rate. Emerging evidence has shown that aberrantly expressed circular RNAs (circRNAs) play a critical role in the initiation and progression of GBM tumorigenesis. The oncogenic function of circZNF609 and circNFIX is involved in several types of cancer, but the role and underlying mechanism of these circRNAs in glioblastoma remain unclear. In this study, we hypothesized that circZNF609 and circNFIX may regulate EGFR through sponging miR-145-5p. Herein, we assessed the expression levels of circZNF609, circNFIX, miR-145-5p, and EGFR using quantitative polymerase chain reaction in glioblastoma patients and normal brain samples. The results showed that circZNF609, circNFIX, and EGFR expression levels were upregulated and miR145-5p was downregulated (p = 0.001, 0.06, 0.002, and 0.0065, respectively), while there was no significant association between clinicopathological features of the patients and the level of these genes expression. We also found a significant inverse correlation between miR145-5p and the expression of cZNF609, cNFIX and EGFR (p = 0.0003, 0.0006, and 0.009, respectively). These findings may open a new window for researchers to better understand the potential pathways involved in GBM pathogenesis. In conclusion, it may provide a new potential pathway for the development of effective drugs for the treatment of GBM patients.

Abstract Background Cost-effectiveness analyses rarely offer useful insights to policy decisions unless their results are compared against a benchmark threshold. The cost-effectiveness threshold (CET) represents the maximum acceptable monetary value for achieving a unit of health gain. This study aimed to identify CET values on a global scale, provide an overview of using multiple CETs, and propose a country-specific CET framework specifically tailored for Egypt. The proposed framework aims to consider the globally identified CETs, analyze global trends, and consider the local structure of Egypt’s healthcare system. Methods We conducted a literature review to identify CET values, with a particular focus on understanding the basis of differentiation when multiple thresholds are present. CETs of different countries were reviewed from secondary sources. Additionally, we assembled an expert panel to develop a national CET framework in Egypt and propose an initial design. This was followed by a multistakeholder workshop, bringing together representatives of different governmental bodies to vote on the threshold value and finalize the recommended framework. Results The average CET, expressed as a percentage of the gross domestic product (GDP) per capita across all countries, was 135%, with a range of 21 to 300%. Interestingly, while the absolute value of CET increased with a country’s income level, the average CET/GDP per capita showed an inverse relationship. Some countries applied multiple thresholds based on disease severity or rarity. In the case of Egypt, the consensus workshop recommended a threshold ranging from one to three times the GDP per capita, taking into account the incremental relative quality-adjusted life years (QALY) gain. For orphan medicines, a CET multiplier between 1.5 and 3.0, based on the disease rarity, was recommended. A two-times multiplier was proposed for the private reimbursement threshold compared to the public threshold. Conclusion The CET values in most countries appear to be closely related to the GDP per capita. Higher-income countries tend to use a lower threshold as a percentage of their GDP per capita, contrasted with lower-income countries. In Egypt, experts opted for a multiple CET framework to assess the value of health technologies in terms of reimbursement and pricing.

Abstract Body weight is an important economic trait for sheep meat production, and its genetic improvement is considered one of the main goals in the sheep breeding program. Identifying genomic regions that are associated with growth-related traits accelerates the process of animal breeding through marker-assisted selection, which leads to increased response to selection. In this study, we conducted a weighted single-step genome-wide association study (WssGWAS) to identify potential candidate genes for direct and maternal genetic effects associated with birth weight (BW) and weaning weight (WW) in Baluchi sheep. The data used in this research included 13,408 birth and 13,170 weaning records collected at Abbas-Abad Baluchi Sheep Breeding Station, Mashhad-Iran. Genotypic data of 94 lambs genotyped by Illumina 50K SNP BeadChip for 54,241 markers were used. The proportion of variance explained by genomic windows was calculated by summing the variance of SNPs within 1 megabase (Mb). The top 10 window genomic regions explaining the highest percentages of additive and maternal genetic variances were selected as candidate window genomic regions associated with body weights. Our findings showed that for BW, the top-ranked genomic regions (1 Mb windows) explained 4.30 and 4.92% of the direct additive and maternal genetic variances, respectively. The direct additive genetic variance explained by the genomic window regions varied from 0.31 on chromosome 1 to 0.59 on chromosome 8. The highest (0.84%) and lowest (0.32%) maternal genetic variances were explained by genomic windows on chromosome 10 and 17, respectively. For WW, the top 10 genomic regions explained 6.38 and 5.76% of the direct additive and maternal genetic variances, respectively. The highest and lowest contribution of direct additive genetic variances were 1.37% and 0.42%, respectively, both explained by genomic regions on chromosome 2. For maternal effects on WW, the highest (1.38%) and lowest (0.41%) genetic variances were explained by genomic windows on chromosome 2. Further investigation of these regions identified several possible candidate genes associated with body weight. Gene ontology analysis using the DAVID database identified several functional terms, such as translation repressor activity, nucleic acid binding, dehydroascorbic acid transporter activity, growth factor activity and SH2 domain binding.

Abstract In the area of energy storage and conversion, Metal-Organic Frameworks (MOFs) are receiving more and more attention. They combine organic nature with long-range order and low thermal conductivity, giving them qualities to be potentially attractive for thermoelectric applications. To make the framework electrically conductive so far, thermoelectricity in this class of materials requires infiltration by outside conductive guest molecules. In this study, an in-situ polymerization of conductive polyaniline inside the porous structure of MOF-801 was conducted to synthesize PANi@MOF-801 nanocomposites for thermoelectrical applications. The growth of polyaniline chains of different loadings inside the host MOF matrix generally enhanced bulk electrical conductivity by about 6 orders of magnitude, leading to Seebeck coefficient value of -141 µVK−1 and improved thermal stability. The unusual increase in electrical conductivity was attributed to the formation of highly oriented conductive PANi chains inside the MOF pores, besides host–guest physical interaction, while the Seebeck coefficient enhancement was because of the energy filtering effect of the developed structure. Modulating the composition of PANi@MOF-801 composites by varying the aniline: MOF-801 ratio in the synthesis bath from 2:1 and 1:1 to 1:2 leads to a change in the semiconductor properties from p-type semiconductor to n-type. Among the examined composites with n-type semiconducting properties exhibited the highest ZT value, 0.015, and lowest thermal conductivity, 0.24 Wm−1 K−1. The synthesized composites have better performance than those recently reported for a similar category of thermoelectric materials related to MOF-based composites.

Summary: MicroRNAs, crucial in regulating protein-coding gene expression, are implicated in various diseases. We performed a genome-wide association study of plasma miRNAs (ex-miRNAs) in 3,743 Framingham Heart Study (FHS) participants and identified 1,027 cis-ex-miRNA-eQTLs (cis-exQTLs) for 37 ex-miRNAs, with 55% replication in an independent study. Colocalization analyses suggested potential genetic coregulation of ex-miRNAs with whole blood mRNAs. Mendelian randomization indicated 29 ex-miRNAs potentially influencing 35 traits. Notably, the chromosome 14q23 and 14q32 miRNA clusters emerged as the top signal, contributing over 50% of the significant cis-exQTL results, and were associated with a diverse range of traits including platelet count. Correlations of 10 ex-miRNAs (such as miR-376c-3p) in 14q32 with platelet count and volume were confirmed in FHS participants. These findings shed light on the genetic basis of ex-miRNA expression and their involvement in complex traits.

BackgroundAnimal-induced ocular injuries represent an under-documented health problem that may pose significant visual complications. This study aimed to investigate the clinical characteristics and outcomes of ocular injuries caused by animals.MethodsThis multicenter prospective study enrolled patients with a history of animal-induced ocular injuries presenting to the ophthalmology departments of two tertiary hospitals over a one-year period. All participants underwent comprehensive assessments by ophthalmologists, and the following data were collected: demographic information, animal species involved, injury details, pre- and post-treatment visual data, management strategies, and follow-up outcomes.ResultsSeventy-two patients (62.5% male) were included in the study. Insects were the most common species, causing 37.5% of ocular injuries. The type of animal involved was significantly associated with injury patterns (p

Summary: Background: 1H-NMR metabolomics and DNA methylation in blood are widely known biomarkers predicting age-related physiological decline and mortality yet exert mutually independent mortality and frailty signals. Methods: Leveraging multi-omics data in four Dutch population studies (N = 5238, ∼40% of which male) we investigated whether the mortality signal captured by 1H-NMR metabolomics could guide the construction of DNA methylation-based mortality predictors. Findings: We trained DNA methylation-based surrogates for 64 metabolomic analytes and found that analytes marking inflammation, fluid balance, or HDL/VLDL metabolism could be accurately reconstructed using DNA-methylation assays. Interestingly, a previously reported multi-analyte score indicating mortality risk (MetaboHealth) could also be accurately reconstructed. Sixteen of our derived surrogates, including the MetaboHealth surrogate, showed significant associations with mortality, independent of relevant covariates. Interpretation: The addition of our metabolic analyte-derived surrogates to the well-established epigenetic clock GrimAge demonstrates that our surrogates potentially represent valuable mortality signal. Funding: BBMRI-NL, X-omics, VOILA, Medical Delta, NWO, ERC.