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Background: High-flow nasal cannula (HFNC) systems employ different methods to provide aerosol to patients. This study compared delivery efficiency, particle size, and regional deposition of aerosolized bronchodilators during HFNC in neonatal, pediatric, and adult upper-airway and lung models between a proximal aerosol adapter and distal aerosol circuit chamber., Methods: A filter was connected to the upper airway to a spontaneously breathing lung model. Albuterol was nebulized using the aerosol adapter and circuit at different clinical flow settings. The aerosol mass deposited in the upper airway and lung was quantified. Particle size was measured with a laser diffractometer. Regional deposition was assessed with a gamma camera at each nebulizer location and patient model with minimum flow settings., Results: Inhaled lung doses ranged from 0.2-0.8% for neonates, 0.2-2.2% for the small child, and 0.5-5.2% for the adult models. Neonatal inhaled lung doses were not different between the aerosol circuit and adapter, but the aerosol circuit showed marginally greater lung doses in the pediatric and adult patient models. Impacted aerosols and condensation in the non-heated HFNC and aerosol delivery components contributed to the dispersion of coarse liquid droplets, high deposition (11-44%), and occlusion of the supine neonatal upper airway. In contrast, the upright pediatric and adult upper-airway models had minimal deposition (0.3-7.0%) and high fugitive losses (∼24%) from liquid droplets leaking out of the nose. The high impactive losses in the aerosol adapter (56%) were better contained than in the aerosol circuit, resulting in less cannula sputter (5% vs 22%), fewer fugitive losses (18% vs 24%), and smaller inhaled aerosols (5 µm vs 13 µm)., Conclusions: The inhaled lung dose was low (1-5%) during HFNC. Approaches that streamline aerosol delivery are needed to provide safe and effective therapy to patients receiving aerosolized medications with this HFNC system., Competing Interests: Mr DiBlasi discloses relationships with Medtronic, ABM Respiratory Care, Vapotherm, Dräger, and Aerogen Pharma. The remaining authors have disclosed no conflicts of interest., (Copyright © 2024 by Daedalus Enterprises.)

Introduction: Many physicians administer steroids after radiofrequency ablation (RFA) to mitigate postprocedural inflammation and decrease postprocedural pain. However, robust evidence supporting the benefits of steroids after RFA is lacking and steroids have risks., Methods: This study was a single-center, prospective, observational study designed to assess whether RFA alone is inferior to RFA with steroids for postprocedure pain. Eligible patients were at least 18 years of age and scheduled to undergo cervical or lumbar RFA. The primary outcome measure was the average pain score on the numeric rating scale (NRS) 7 days after the RFA. The secondary outcome measures included anxiety, depression and physical function, measured via the Patient-Reported Outcomes Measurement Information System short forms. All outcome measures were completed prior to the procedure and at 7 and 60 days postprocedure., Results: Out of the 365 participants who completed baseline assessments, 175 received steroids and 190 did not receive steroids. The pain intensity at 7 days postprocedure was similar between the steroid and non-steroid groups (mean difference (steroid-non-steroid): -0.23). The 95% CI of the estimate (-0.76 to 0.30) was within the prespecified non-inferiority margin of 1.5 NRS points. Similar results were obtained for pain at 60 days (mean difference: 0.09; 95% CI -0.48 to 0.65). No significant differences between groups were observed for anxiety, depression or physical function at either 7 or 60 days., Conclusion: This study suggests that the addition of steroids to the RFA procedure does not provide added benefits and is therefore not worth the additional risks that they pose., Competing Interests: Competing interests: JG has received compensation from Neurometrix for serving on a scientific advisory board (past relationship) and grant funding for an investigator-initiated trial in an unrelated indication. Neurometrix had no influence over the design, analysis, interpretation or writing of this manuscript. In the past 36 months, JG has also received consulting income from Algo Therapeutix, Eikonizo Therapeutics, Eli Lilly, GW Pharma, Hoba Therapeutics and Saluda Medical. She owns vesting shares in Eisana Corp. She has also received personal compensation for serving as Associate Editor for the Clinical Journal of Pain., (© American Society of Regional Anesthesia & Pain Medicine 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Neurophysiological brain activity underpins cognitive functions and behavioural traits. Here, we sought to establish to what extent individual neurophysiological traits spontaneously expressed in ongoing brain activity are primarily driven by genetic variation. We also investigated whether changes in such neurophysiological features observed across the lifespan are supported by longitudinal changes in cortical gene expression. We studied the heritability of neurophysiological traits from task-free brain activity of monozygotic and dizygotic twins as well as non-related individuals recorded with magnetoencephalography. We found that these traits were more similar between monozygotic twins compared to dizygotic twins, and that these heritable core dynamical properties of brain activity are predominantly influenced by genes involved in neurotransmission processes. These genes are expressed in the cortex along a topographical gradient aligned with the distribution of major cognitive functions and psychological processes. Our data also show that the impact of these genetic determinants on cognitive and psychological traits increases with age. These findings collectively highlight the persistent genetic influence across the lifespan on neurophysiological brain activity that supports individual cognitive and behavioural traits.

This letter proposes a novel synthetic aperture radar (SAR) time series analysis method based on the scattering power decomposition algorithm with a reasonable ensemble average in both temporal and spatial domains. We reveal that the ensemble average is effective not only in the spatial domain but also in the temporal–spatial domains in the scattering power decomposition. That is, if we extend the ensemble average window in the temporal domain, the proposed method can accurately achieve volume scattering power with a higher spatial resolution than conventional approaches. The precise volume scattering power serves accurate forest monitoring. As an application, we performed forest disturbance detection in the Amazon rainforest using Sentinel-1 time series data. The proposed method detected the disturbances earlier, in less than 2 months, compared to other methods that take about 3 months. [ABSTRACT FROM AUTHOR]

Synthesis and maturation of Okazaki Fragments is an incessant and highly efficient metabolic process completing the synthesis of the lagging strands at replication forks during S phase. Accurate Okazaki fragment maturation (OFM) is crucial to maintain genome integrity and, therefore, cell survival in all living organisms. In eukaryotes, OFM involves the consecutive action of DNA polymerase Pol ∂, 5' Flap endonuclease Fen1 and DNA ligase I, and constitutes the best example of a sequential process coordinated by the sliding clamp PCNA. For OFM to occur efficiently, cooperation of these enzymes with PCNA must be highly regulated. Here, we present evidence of a role for the K164-PCNA-deubiquitylase Ubp10 in the maturation of Okazaki fragments in the budding yeast Saccharomyces cerevisiae. We show that Ubp10 associates with lagging-strand DNA synthesis machineries on replicating chromatin to ensure timely ligation of Okazaki fragments by promoting PCNA dissociation from chromatin requiring lysine 164 deubiquitylation. Synthesis and maturation of Okazaki fragments is crucial for lagging strand DNA replication. Here the authors find that the ubiquitin-specific protease Ubp10 works with the DNA synthesis machinery to promote Okazaki fragments joining by removal of PCNA through deubiquitylation of PCNA-K164. [ABSTRACT FROM AUTHOR]

Pd-catalyzed regioselective amination of unactivated alkene remains a challenge and is of great interest. Herein, a palladium-catalyzed and ligand-controlled strategy for the Markovnikov selective oxidative amination of 4-pentenoic acid has been described. The protocol effectively reverses the carboxylic acid-directed anti-Markovnikov selectivity in oxidative amination of 4-pentenoic acid, successfully constructing γ-ketoamide derivatives. [ABSTRACT FROM AUTHOR]

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In recent years, metaphors have been used to understand how abstract concepts are processed, and developing metaphorical database can aid this research agenda. Accordingly, the present study aimed to produce a broad Chinese olfactory and gustatory database of metaphors. Expressions for two sensory types (olfaction/gustation) were compiled and classified according to two conditions (metaphorical/literal) and three parts of speech (adjective/noun/verb). To test the validity of this database, we enrolled 199 participants, of whom 97 completed the olfactory test (319 items) and 102 completed the gustatory test (352 items). Each item was rated on seven dimensions: familiarity, meaningfulness, figurativeness, valence, difficulty, imageability, and naturalness. Descriptive statistics and reliability and correlation analyses were conducted for the items under the two sensory types, two conditions, three parts of speech, and seven dimensions mentioned above. The results showed high internal consistency and split-half reliability for the participants' scores; the correlations between the seven dimensions resembled those of previous studies. We concluded by suggesting several ways the database might be applied to aid future research efforts. [ABSTRACT FROM AUTHOR]

Proteins play a key role in biological electron transport, but the structure-function relationships governing the electronic properties of peptides are not fully understood. Despite recent progress, understanding the link between peptide conformational flexibility, hierarchical structures, and electron transport pathways has been challenging. Here, we use single-molecule experiments, molecular dynamics (MD) simulations, nonequilibrium Green's function-density functional theory (NEGF-DFT), and unsupervised machine learning to understand the role of secondary structure on electron transport in peptides. Our results reveal a two-state molecular conductance behavior for peptides across several different amino acid sequences. MD simulations and Gaussian mixture modeling are used to show that this two-state molecular conductance behavior arises due to the conformational flexibility of peptide backbones, with a high-conductance state arising due to a more defined secondary structure (beta turn or 310 helices) and a low-conductance state occurring for extended peptide structures. These results highlight the importance of helical conformations on electron transport in peptides. Conformer selection for the peptide structures is rationalized using principal component analysis of intramolecular hydrogen bonding distances along peptide backbones. Molecular conformations from MD simulations are used to model charge transport in NEGF-DFT calculations, and the results are in reasonable qualitative agreement with experiments. Projected density of states calculations and molecular orbital visualizations are further used to understand the role of amino acid side chains on transport. Overall, our results show that secondary structure plays a key role in electron transport in peptides, which provides broad avenues for understanding the electronic properties of proteins. [ABSTRACT FROM AUTHOR]

Objective: Common Variable Immunodeficiency (CVID) is the most prevalent symptomatic primary immunodeficiency in adults. This study evaluates the clinical, immune, and immunohistological characteristics of hepatic involvement in CVID. Materials and Methods: Medical records of 72 CVID patients, including 7 with liver biopsies, were retrospectively reviewed. Immunohistochemical staining was performed to identify immune cell infiltration. Results: We enrolled 72 patients with a median age of 38 (22--77) years, and 47% (n = 34) were female. Elevated alkaline phosphatase (ALP) levels were found in 58.3% (n=42) of the patients. Hepatic involvement was more prevalent among females, and those with hepatic involvement displayed a higher incidence of autoimmune disease. Splenomegaly was identified in 85% of the patients with hepatic involvement. Notably, switched memory B cells (IgD- CD19+ CD27+) and the CD4+/CD8+ ratio were statistically lower in patients with hepatic involvement (p=0.031, p=0.047). Liver biopsies were performed on 7 patients, revealing minimal to severe chronic hepatitis. Immunohistologic analysis of these liver biopsies revealed varying degrees of positivity of CD8+, CD4+, and CD16+. However, staining for CD21, CD56, and CD138 yielded negative results. Conclusion: Our findings suggest that immune cells, particularly CD8+, CD4+, and CD16+ cells, may play a role in developing hepatic involvement. Understanding the underlying causes and mechanisms of hepatic involvement in CVID patients can lead to early diagnosis and targeted treatments, ultimately improving the prognosis. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Traditional Medical Complementary Therapies is the property of Turkiye Klinikleri and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

DNA replication and transcription occur in all living cells across all domains of life. Both essential processes occur simultaneously on the same template, leading to conflicts between the macromolecular machines that perform these functions. Numerous studies over the past few decades demonstrate that this is an inevitable problem in both prokaryotic and eukaryotic cells. We have learned that conflicts lead to replication fork reversal, breaks in the DNA, R-loop formation, topological stress, and mutagenesis and can ultimately impact evolution. Recent studies have also provided insight into the various mechanisms that mitigate, resolve, and allow tolerance of conflicts and how conflicts result in pathological consequences across divergent species. In this review, we summarize our current knowledge regarding the outcomes of the encounters between replication and transcription machineries and explore how these clashes are dealt with across species. [ABSTRACT FROM AUTHOR]

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Postacute sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (PASC) represent an urgent public health challenge and are estimated to affect more than 60 million individuals globally. Although a growing body of evidence suggests that dysregulated immune reactions may be linked with PASC symptoms, most investigations have primarily centered around blood-based studies, with few focusing on samples derived from affected tissues. Furthermore, clinical studies alone often provide correlative insights rather than causal mechanisms. Thus, it is essential to compare clinical samples with relevant animal models and conduct functional experiments to understand the etiology of PASC. In this study, we comprehensively compared bronchoalveolar lavage fluid single-cell RNA sequencing data derived from clinical PASC samples and a mouse model of PASC. This revealed a pro-fibrotic monocyte-derived macrophage response in respiratory PASC, as well as abnormal interactions between pulmonary macrophages and respiratory resident T cells, in both humans and mice. Interferon-γ (IFN-γ) emerged as a key node mediating the immune anomalies in respiratory PASC. Neutralizing IFN-γ after the resolution of acute SARS-CoV-2 infection reduced lung inflammation and tissue fibrosis in mice. Together, our study underscores the importance of performing comparative analysis to understand the cause of PASC and suggests that the IFN-γ signaling axis might represent a therapeutic target. Editor's summary: The term "Long Covid" covers a myriad of symptoms that a person may experience after an acute infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and is also referred to as postacute sequelae of SARS-CoV-2 (PASC). The specific drivers of these symptoms are unclear, complicating the development of therapeutics for those suffering from this condition. Here, Li et al. used comparative analysis to interrogate a potential driver of respiratory PASC, one of the most debilitating types of PASC. The authors found that humans with respiratory PASC had evidence of an enhanced monocyte-derived macrophage response in their bronchoalveolar lavage fluid. A similar phenotype was observed in aged C57BL/6 mice infected with mouse-adapted SARS-CoV-2. This phenotype in mice could be reduced by anti–interferon-γ (anti–IFN-γ) treatment initiated after the resolution of acute disease, suggesting that the IFN-γ signaling pathway may represent a potential therapeutic target for humans. —Courtney Malo [ABSTRACT FROM AUTHOR]

Background: One of the most widely used medicinal plants in Iranian traditional medicine, Rosa × damascena Herrm. (mohammadi flower) that the people of Kashan use as a sedative and to treat nervous diseases and constipation. In this research, the yield, chemical composition and antimicrobial activity of the essential oil of this plant were evaluated for the first time from Azaran region, Kashan. Methods: The essential oil was extracted by means of hydrodistillation (Clevenger), and its chemical compounds were identified and determined by GC/MS. The antimicrobial activity of the essential oil was determined by the diffusion method in agar, the minimum growth inhibitory concentration (MIC) and the minimum concentration capable of killing bacterial/fungal microorganisms (MBC/MFC). Results: The results showed that the yield of essential oil was 0.1586 ± 0.0331% (w/w). Based on the results of the chemical composition analysis of R. x damascena essential oil, 19 different compounds (98.96%) were identified. The dominant and main components of the essential oil were oleic acid (48.08%), palmitic acid (15.44%), stearic acid (10.17%), citronellol (7.37%) and nonadecane (3.70%). Based on the results of diffusion in agar, the highest zone of inhibition against Candida albicans (ATCC 10231) was ~ 9.5 mm. The strongest inhibitory activity of R. x damascena essential oil against Gram-negative Proteus mirabilis (ATCC 43071) was with the diameter of the inhibition zone (~ 9 mm), which was equal to the strength of rifampin (~ 9 mm). Conclusion: Therefore, this essential oil is a promising natural option rich in fatty acids, which can be a potential for the production of natural antimicrobials against infectious diseases, especially urinary tract infections. [ABSTRACT FROM AUTHOR]

Copyright of Revista Foco (Interdisciplinary Studies Journal) is the property of Revista Foco and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

This article provides a model-based design method for heading control based autonomous trajectory tracking of a KVLCC2 ship. Kinematics, dynamics, and hydrodynamic force subsystems are used to represent the ship's motion equations. By contrasting the outcomes with experimental data received from the maneuvering modelling group, the accuracy of the model is confirmed. Heading angle of the ship is controlled by a linear cascade controller, and the settings of the controller are modified by using two separate heuristic optimization techniques: particle swarm optimization and genetic algorithm. The comparison of the findings demonstrates that the particle swarm optimization approach is computationally more effective than the genetic algorithm. Performance in the presence of disturbance has been investigated using the controller parameters discovered using particle swarm optimization. A suitable guidance algorithm is incorporated into the architecture of a trajectory tracking system to establish the necessary heading angle for travel between waypoints. We use a real-time simulator to visualize the ship motion on a graphical environment. [ABSTRACT FROM AUTHOR]

Grey wolf optimizer (GWO) is a highly valued heuristic algorithm in many fields. However, for some complex problems, especially high‐dimensional and multimodal problems, the basic algorithm has limited computational power and cannot get a satisfactory answer. In order to find a better solution, an improved algorithm based on GWO is proposed herein. Gaussian barebone, random selection and chaotic game mechanisms are introduced into the GWO algorithm to enhance the global search ability. The GWO enhanced by three mechanisms is called CBRGWO. To verify the performance of CBRGWO, using IEEE CEC 2017 as a test function, CBRGWO is compared to five GWO variants, five basic algorithms, six advanced algorithms, and four champion algorithms. CBRGWO is evaluated using the Friedman test and Wilcoxon signed‐rank test. Then, the stability of CBRGWO is analyzed. To verify that CBRGWO is still effective in practical application, CBRGWO is applied to five engineering problems and a water quality prediction problem. The experimental findings indicate that CBRGWO maintains excellent optimization ability in practical engineering problems. [ABSTRACT FROM AUTHOR]

DNA base damage is a major source of oncogenic mutations1. Such damage can produce strand-phased mutation patterns and multiallelic variation through the process of lesion segregation2. Here we exploited these properties to reveal how strand-asymmetric processes, such as replication and transcription, shape DNA damage and repair. Despite distinct mechanisms of leading and lagging strand replication3,4, we observe identical fidelity and damage tolerance for both strands. For small alkylation adducts of DNA, our results support a model in which the same translesion polymerase is recruited on-the-fly to both replication strands, starkly contrasting the strand asymmetric tolerance of bulky UV-induced adducts5. The accumulation of multiple distinct mutations at the site of persistent lesions provides the means to quantify the relative efficiency of repair processes genome wide and at single-base resolution. At multiple scales, we show DNA damage-induced mutations are largely shaped by the influence of DNA accessibility on repair efficiency, rather than gradients of DNA damage. Finally, we reveal specific genomic conditions that can actively drive oncogenic mutagenesis by corrupting the fidelity of nucleotide excision repair. These results provide insight into how strand-asymmetric mechanisms underlie the formation, tolerance and repair of DNA damage, thereby shaping cancer genome evolution.How strand-asymmetric processes such as replication and transcription interact with DNA damage to drive mechanisms of repair and mutagenesis is explored. [ABSTRACT FROM AUTHOR]

Psycholinguistic models of metaphor processing remain a subject of debate. A prime-probe design using Chinese materials with a specific time span (300 ms) was applied to test the mechanisms of metaphor processing. Conventional and familiarized metaphors were designed as primes, followed by a probe word semantically related to the prime metaphor (MT), a probe word related to the literal meaning of the final word of the prime metaphor (LT), control/unrelated probe word (UT), or non-word. Event-related potentials (ERPs) elicited by the probes were recorded to examine metaphor processing. In N400, results revealed that UT and LT elicited significantly more negative waveforms than MT in both primes. MTs and LTs showed no di [ABSTRACT FROM AUTHOR]

An organelle-selective vision provides insights into the physiological response of plants and crops to environmental stresses in sustainable agriculture ecosystems. Biological applications often require two-photon excited fluorophores with low phototoxicity, high brightness, deep penetration, and tuneable cell entry. We obtained three aniline-based squaraines (SQs) tuned from hydrophobic to hydrophilic characteristics by modifying terminal pendant groups and substituents, and investigated their steady-state absorption and far-red-emitting fluorescence properties. The SQs exhibited two-photon absorption (2PA) ranging from 750 to 870 nm within the first biological spectral window; their structure–property relationships, corresponding to the 2PA cross sections (δ2PA), and structure differences were demonstrated. The maximum δ2PA value was ∼1220 GM at 800 nm for hydrophilic SQ3. Distinct biological staining efficiency and selective SQ bioimaging were evaluated utilizing the onion epidermal cell model. Contrary to the hydrophobic SQ1 results in the onion epidermal cell wall, amphiphilic SQ2 tagged the vacuole and nucleus and SQ3 tagged the vacuole. Distinguishable staining profiles in the roots and leaves were achieved. We believe that this study is the first to demonstrate distinct visualisation efficiency induced by the structure differences of two-photon excited SQs. Our results can help establish the versatile roles of novel near-infrared-emitting SQs in biological applications. [ABSTRACT FROM AUTHOR]

Bacteria use various motility mechanisms to explore their environments. Chemotaxis is the ability of a motile bacterial cell to direct its movement in response to chemical gradients. A number of methods have been developed and widely used to study chemotactic responses to chemoeffectors including capillary, agar plug, microscopic slide, and microfluidic assays. While valuable, these assays are primarily designed to monitor rapid chemotactic responses to chemoeffectors on a small scale, which poses challenges in collecting large quantities of attracted bacteria. Consequently, these setups are not ideal for experiments like forward genetic screens. To overcome this limitation, we developed the Large Scale Bacterial Attraction assay (LSBA), which relies on the use of a Nalgene™ Reusable Filter Unit and other materials commonly found in laboratories. We validate the LSBA by investigating chemoeffector kinetics in the setup and by using chemoattractants to quantify the chemotactic response of wild-type, and motility impaired strains of the plant pathogenic bacterium Xanthomonas campestris pv. campestris and the environmental bacterium Shewanella oneidensis. We show that the LSBA establishes a long lasting chemoeffector gradient, that the setup can be used to quantify bacterial migration over time and that the LSBA offers the possibility to collect high numbers of attracted bacteria, making it suitable for genetic screens. [ABSTRACT FROM AUTHOR]

Clinical evidence indicates a close association between muscle dysfunction and bone loss; however, the underlying mechanisms remain unclear. Here, we report that muscle dysfunction–related bone loss in humans with limb-girdle muscular dystrophy is associated with decreased expression of folliculin-interacting protein 1 (FNIP1) in muscle tissue. Supporting this finding, murine gain- and loss-of-function genetic models demonstrated that muscle-specific ablation of FNIP1 caused decreased bone mass, increased osteoclastic activity, and mechanical impairment that could be rescued by myofiber-specific expression of FNIP1. Myofiber-specific FNIP1 deficiency stimulated expression of nuclear translocation of transcription factor EB, thereby activating transcription of insulin-like growth factor 2 (Igf2) at a conserved promoter-binding site and subsequent IGF2 secretion. Muscle-derived IGF2 stimulated osteoclastogenesis through IGF2 receptor signaling. AAV9-mediated overexpression of IGF2 was sufficient to decrease bone volume and impair bone mechanical properties in mice. Further, we found that serum IGF2 concentration was negatively correlated with bone health in humans in the context of osteoporosis. Our findings elucidate a muscle-bone cross-talk mechanism bridging the gap between muscle dysfunction and bone loss. This cross-talk represents a potential target to treat musculoskeletal diseases and osteoporosis. Editor's summary: Musculoskeletal homeostasis is maintained by mechanical and signaling cross-talk between skeletal muscle and bone. Mao et al. report that patients with limb-girdle muscular dystrophy (LGMD) have decreased skeletal muscle expression of folliculin-interacting protein 1 (FNIP1) accompanied by decreased bone mineral density. In murine models, skeletal muscle–specific deletion of FNIP1 similarly led to decreased bone density. Muscle-specific FNIP1 deficiency led to nuclear translocation of transcription factor EB (TFEB) in mice, which stimulated muscle expression of insulin-like growth factor 2 (IGF2). FNIP1 deficiency and increased IGF2 both stimulated osteoclastic activity and decreased bone mass in mice. Elevated IGF2 was further associated with LGMD and osteoporosis in humans. These findings may provide new therapeutic targets for mitigating bone loss in human disease. —Molly Ogle [ABSTRACT FROM AUTHOR]

In view of the competing assignments regarding the most stable isomer of the B70 boron cluster including the quasi-planar and bilayer structures, we reinvestigated the structural motifs of B70 using a genetic algorithm for structure search (MEGA) in conjunction with density functional theory computations using the PBE functional. The quasi-planar structure was also constructed using the topological leapfrog algorithm. The latter search aimed to give us unique insight into its formation and the growth pattern of boron clusters. Also, the di-anionic state of B70 was explored. Our extensive search suggested a competition between the quasi-planar, tubular and bilayer isomers for the ground state of B70 in both neutral and dianionic states. While the bilayer form is more stable in the neutral state, the quasi-planar counterpart becomes more stable in the dianionic B702−. The stability arises due to the fact that the B702− dianion possesses 50 π electrons that satisfy the disk aromaticity model rule. These results tend to extend the stabilization of the quasi-planar structure upon negative charge addition previously found in small size boron clusters to larger sizes. [ABSTRACT FROM AUTHOR]

BRCA2 is a tumor suppressor protein responsible for safeguarding the cellular genome from replication stress and genotoxicity, but the specific mechanism(s) by which this is achieved to prevent early oncogenesis remains unclear. Here, we provide evidence that BRCA2 acts as a critical suppressor of head-on transcription-replication conflicts (HO-TRCs). Using Okazaki-fragment sequencing (Ok-seq) and computational analysis, we identified origins (dormant origins) that are activated near the transcription termination sites (TTS) of highly expressed, long genes in response to replication stress. Dormant origins are a source for HO-TRCs, and drug treatments that inhibit dormant origin firing led to a reduction in HO-TRCs, R-loop formation, and DNA damage. Using super-resolution microscopy, we showed that HO-TRC events track with elongating RNA polymerase II, but not with transcription initiation. Importantly, RNase H2 is recruited to sites of HO-TRCs in a BRCA2-dependent manner to help alleviate toxic R-loops associated with HO-TRCs. Collectively, our results provide a mechanistic basis for how BRCA2 shields against genomic instability by preventing HO-TRCs through both direct and indirect means occurring at predetermined genomic sites based on the pre-cancer transcriptome. BRCA2 has essential roles in suppressing genome instability at stalled replication forks, but how this is achieved remains unclear. Here, the authors apply Okazaki-fragment sequencing to predict sites of genomic instability caused by head-on transcription-replication conflicts upon BRCA2 loss. [ABSTRACT FROM AUTHOR]

Background/Objectives: The anxiolytic effect of transcutaneous electrical nerve stimulation (TENS) is associated with the activation of endogenous inhibitory mechanisms in the central nervous system. Both low-frequency, high-amplitude TENS (LF-TENS) and high-frequency, low-amplitude TENS (HF-TENS) are capable of activating opioid, GABA, serotonin, muscarinic, and cannabinoid receptors. However, there has been no comparative analysis of the effectiveness of HF-TENS and LF-TENS in the treatment of GAD. The purpose of our research was to study the effectiveness of direct HF-TENS and LF-TENS of the right median nerve in the treatment of patients with GAD compared with sham TENS. Methods: The effectiveness of direct HF-TENS and LF-TENS of the right median nerve in the treatment of GAD was studied using Generalized Anxiety Disorder 7-item scale (GAD-7) and the Hamilton Anxiety Rating Scale (HAM-A). 40 patients underwent sham TENS, 40 patients passed HF-TENS (50 Hz—50 μs—sensory response) and 41 patients completed LF –TENS (1 Hz—200 μs—motor response) for 30 days daily. After completion of treatment, half of the patients received weekly maintenance therapy for 6 months. Electroencephalography was performed before and after treatment. Results: Our study showed that a significant reduction in the clinical symptoms of GAD as assessed by GAD-7 and HAM-A was observed after HF-TENS and LF-TENS by an average of 42.4%, and after sham stimulation only by 13.5% for at least 2 months after the end of treatment. However, LF-TENS turned out to be superior in effectiveness to HF-TENS by 51% and only on electroencephalography leads to an increase in PSD for the alpha rhythm in the occipital regions by 24% and a decrease in PSD for the beta I rhythm in the temporal and frontal regions by 28%. The prolonged effect of HF-TENS and LF-TENS was maintained without negative dynamics when TENS treatment was continued weekly throughout the entire six-month observation period. Conclusions: A prolonged anxiolytic effect of direct TENS of the right median nerve has been proven with greater regression of clinical and neurophysiological manifestations of GAD after LF-TENS compared to HF-TENS. Minimal side effects, low cost, safety, and simplicity of TENS procedures are appropriate as a home treatment modality. [ABSTRACT FROM AUTHOR]

To date, imogolite nanotubes (INTs) have been primarily used for environmental applications such as dye and pollutant degradation. However, imogolite's well‐defined porous structure and distinctive electro‐optical properties have prompted interest in the system's potential for energy‐relevant chemical reactions. The imogolite structure leads to a permanent intrawall polarization arising from the presence of bifunctional surfaces at the inner and outer tube walls. Density functional theory simulations suggest such bifunctionality to encompass also spatially separated band edges. Altogether, these elements make INTs appealing candidates for facilitating chemical conversion reactions. Despite their potential, the exploitation of imogolite's features for photocatalysis is at its infancy, thence relatively unexplored. This perspective overviews the basic physical‐chemical and optoelectronical properties of imogolite nanotubes, emphasizing their role as wide bandgap insulator. Imogolite nanotubes have multifaceted properties that could lead to beneficial outcomes in energy‐related applications. This work illustrates two case studies demonstrating a step‐forward on photocatalytic hydrogen production achieved through atomic doping or metal co‐catalyst. INTs exhibit potential in energy conversion and storage, due to their ability to accommodate functions such as enhancing charge separation and influencing the chemical potentials of interacting species. Yet, tapping into potential for energy‐relevant application needs further experimental research, computational, and theoretical analysis. [ABSTRACT FROM AUTHOR]

α-Actinin-4 is an actin-binding protein involved in a wide range of cellular processes. Along with actin and other proteins of the actin cytoskeleton, α-actinin-4 is found not only in the cytoplasm, but also in the nucleus of various types of cells. As a nuclear protein, it takes part in regulating the activity of some transcription factors. In particular, it can regulate the activity of the NF-kB factor, which largely determines the resistance of cancer cells to apoptosis and anticancer therapy. Our previous studies revealed that α-actinin-4 can influence the resistance of cancer cells to topoisomerase II inhibitors and determine the efficiency of DNA double-strand break repair by regulating the assembly of HRR and NHEJ protein complexes. In this work, we tried to answer the question of how α-actinin-4 is involved in the regulation of the double-stranded DNA breaks repair under genotoxic stress. Our results indicate that the effect of α-actinin-4 on the repair process in H1299 non-small-cell lung-cancer cells does not depend on the activity of the transcription factor NF-kB. We found that, in the nucleus of H1299 cells, α-actinin-4 is localized not only in the nucleoplasm, but also shows close association with chromatin. [ABSTRACT FROM AUTHOR]

Checkpoint kinase 1 (CHK1) is critical for cell survival under replication stress (RS). CHK1 inhibitors (CHK1i's) in combination with chemotherapy have shown promising results in preclinical studies but have displayed minimal efficacy with substantial toxicity in clinical trials. To explore combinatorial strategies that can overcome these limitations, we perform an unbiased high-throughput screen in a non-small cell lung cancer (NSCLC) cell line and identify thioredoxin1 (Trx1), a major component of the mammalian antioxidant-system, as a determinant of CHK1i sensitivity. We establish a role for redox recycling of RRM1, the larger subunit of ribonucleotide reductase (RNR), and a depletion of the deoxynucleotide pool in this Trx1-mediated CHK1i sensitivity. Further, the TrxR inhibitor auranofin, an approved anti-rheumatoid arthritis drug, shows a synergistic interaction with CHK1i via interruption of the deoxynucleotide pool. Together, we show a pharmacological combination to treat NSCLC that relies on a redox regulatory link between the Trx system and mammalian RNR activity. The clinical application of inhibitors targeting checkpoint kinase 1 (CHK1) is challenged by limited efficacy. Here, the authors identify that thioredoxin (Trx) system inhibition mediates sensitivity to CHK1 inhibitor via regulating the activity of ribonucleotide reductase, demonstrating the synergistic effect of CHK1 inhibitor and inhibitors targeting Trx system in lung cancer models. [ABSTRACT FROM AUTHOR]

This aimed to develop a comprehensive theoretical protocol for examining substitution reaction processes. The researchers used a theoretical quantum-mechanical protocol based on the QM-ORSA approach, which estimates the kinetic parameters of thermodynamically favourable reaction pathways. This theoretical protocol was validated by experimentally investigating substitution mechanisms in two previously synthesised Pd(II) complexes: chlorido-[(3-(1-(2-hydroxypropylamino)ethylidene)chroman-2,4-dione)]palladium(II) (C1) and chlorido-[(3-(1-(2-mercaptoethylamino)-ethylidene)-chroman-2,4dione)]palladium(II) (C2), along with biologically relevant nucleophiles, namely L -cysteine (L -Cys), L -methionine (L -Met), and guanosine-5′-monophosphate (5′-GMP). Reactions were investigated under pseudo-first-order conditions, monitoring nucleophile concentration and temperature changes using stopped-flow UV-vis spectrophotometry. All reactions were conducted under physiological conditions (pH = 7.2) at 37 °C. The reactivity of the studied nucleophiles follows the order: L -Cys > L -Met > 5′-GMP, and the reaction mechanism is associative based on the activation parameters. The experimental and theoretical data showed that C2 is more reactive than C1, confirming that the complexes' structural and electronic properties greatly affect their reactivity with selected nucleophiles. The study's findings have confirmed that the primary interaction occurs with the acid–base species L -Cys, mostly through the involvement of the partially negative sulfur atom (87.2%). On the other hand, C2 has a higher propensity for reacting with L -Cys−, primarily through the partially negative oxygen atom (92.6%). The implementation of this theoretical framework will significantly restrict the utilization of chemical substances, hence facilitating cost reduction and environmental protection. [ABSTRACT FROM AUTHOR]

Metaphor and simile, two prevalent forms of figurative language widely employed in daily communication, serve as significant research subjects in linguistics. The Career of Metaphor Theory in cognitive linguistics posits that as conventionality increases, the cognitive mechanisms of metaphor comprehension shift from "comparison" to "categorization." In line with this notion, prior electrophysiological investigations have revealed that novel metaphors elicit a stronger N400 brain response compared to conventional metaphors. However, the observed N400 difference between conventional and novel metaphors may merely stem from the familiarity contrast between them, as conventional metaphors are typically more familiar than novel ones. To address this dichotomy, the present study not only compared the N400 responses between conventional and novel metaphors but also between conventional and novel similes. While conventional and novel similes differ in familiarity, similar to conventional and novel metaphors, both are processed via "comparison" mechanisms. The results revealed that novel metaphors elicited larger N400 amplitudes compared to conventional metaphors, aligning with previous findings. In contrast, no significant N400 differences were observed between conventional and novel similes, suggesting that familiarity disparity is unlikely to account for N400 distinctions. Our findings imply that conventional and novel metaphors undergo distinct cognitive processing mechanisms ("comparison" versus "categorization"), thereby providing further empirical validation for the Career of Metaphor Theory. [ABSTRACT FROM AUTHOR]

The most common life-threatening disease, acute lymphoblastic leukemia (ALL), can be lethal within a few weeks if untreated. The early detection and analysis of leukemia is a key dilemma in the field of disease diagnosis, and the methods available for the classification process are time-consuming. To overcome the issues, this paper develops a robust classification technique named Horse Herd Whale Optimization-enabled Deep Neuro-Fuzzy Network (HHWO-enabled DNFN method) for ALL classification and severity analysis using the MapReduce framework. The input image is first preprocessed and segmented, and the useful features necessary for improving the classification performance are extracted during the mapper phase, known as HHWO, which incorporates Horse Herd Optimization Algorithm (HOA) and Whale Optimization Algorithm (WOA). Finally, severity analysis of ALL is done to classify the levels of leukemia to offer optimal treatment. As a result, the developed method performed better than other existing methods, achieving superior performance with a greater testing accuracy of 0.959, sensitivity of 0.965, and specificity of 0.966, respectively. [ABSTRACT FROM AUTHOR]

A thorough understanding of the fundamental electrochemical and chemical processes in batteries is crucial to advancing energy density and power density. However, the characterizations of such processes are complex. In-situ electrochemical nuclear magnetic resonance (EC-NMR) offers the capability to collect real-time data during battery operation, furnishing insights into the local structures and ionic dynamics of materials by monitoring changes in the chemical environment around the nuclei. EC-NMR also has the advantages of being both quantitative and non-destructive. This paper systematically reviews the design of EC-NMR approach, and delves into the applications and progress of EC-NMR concerning battery reaction mechanisms, failure mechanisms, and overall battery systems. The review culminates in a comprehensive summary of the perspective and challenges associated with EC-NMR. [ABSTRACT FROM AUTHOR]

Inborn errors of T cell development present a pediatric emergency in which timely curative therapy is informed by molecular diagnosis. In 11 affected patients across four consanguineous kindreds, we detected homozygosity for a single deleterious missense variant in the gene NudC domain–containing 3 (NUDCD3). Two infants had severe combined immunodeficiency with the complete absence of T and B cells (T -B- SCID), whereas nine showed classical features of Omenn syndrome (OS). Restricted antigen receptor gene usage by residual T lymphocytes suggested impaired V(D)J recombination. Patient cells showed reduced expression of NUDCD3 protein and diminished ability to support RAG-mediated recombination in vitro, which was associated with pathologic sequestration of RAG1 in the nucleoli. Although impaired V(D)J recombination in a mouse model bearing the homologous variant led to milder immunologic abnormalities, NUDCD3 is absolutely required for healthy T and B cell development in humans. Editor's summary: Severe combined immunodeficiency (SCID) and Omenn syndrome (OS) are two related inborn errors of immunity that continue to inform our understanding of how human lymphocytes develop. Chen et al. report the existence of 11 patients with SCID or OS who have a single homozygous deleterious missense variant (G52D) of the gene NUDCD3. These NUDCD3G52D patients showed defects in RAG-mediated V(D)J recombination, a critical step in B and T cell development, namely, the pathological sequestration of RAG1 in the nucleoli and reduced recombinase activity. Mice with a knock-in Nudcd3G52D variant also exhibited altered B and T cell development but to a lesser degree than in the human patients or in other RAG-deficient mouse models. These findings suggest that NUDCD3 may be an important cochaperone in RAG2-mediated egress of RAG1 from the nucleoli. —Seth Thomas Scanlon [ABSTRACT FROM AUTHOR]

The formation of microbial biofilm is a self-organizing process among bacterial cells, regulated by quorum-sensing (QS) mechanisms, contributing to development of infections. These processes, either separately or in combination, significantly contribute to bacterial resistance to antibiotics and disinfectants. A novel approach to addressing the challenge of treating infections due to antibacterial resistance involves the use of plant metabolites. In recent years, there has been increasing recognition of different phytochemicals as potential modulators. In our study, we evaluated the synergistic effect of chloroform and methanol extracts from Inula species against key virulence factors, including biofilm formation, violacein production, and swarming motility. Each of the 11 examined plant extracts demonstrated the ability to reduce biofilms and pigment synthesis in C. violaceum. Two of the extracts from I. britannica exhibited significant anti-biofilm and anti-quorum-sensing effects with over 80% inhibition. Their inhibitory effect on violacein synthesis indicates their potential as anti-QS agents, likely attributed to their high concentration of terpenoids (triterpenoids, sesquiterpene lactones, and diterpenoids). Scanning electron microscopy revealed a notable reduction in biofilm biomass, along with changes in biofilm architecture and cell morphology. Additionally, fluorescence microscopy revealed the presence of metabolically inactive cells, indicating the potent activity of the extracts during treatment. These new findings underscore the effectiveness of the plant extracts from the genus Inula as potential anti-virulent agents against C. violaceum. They also propose a promising strategy for preventing or treating its biofilm formation. [ABSTRACT FROM AUTHOR]

Background/Aim: Dynamic DNA sequences (i.e. sequences capable of forming hairpins, G-quadruplexes, imotifs, and triple helices) can cause replication stress and associated mutations. One example of such a sequence occurs in the RACK7 gene in human DNA. Since this sequence forms i-motif structures at neutral pH that cause replication stress and result in spontaneous deletions in prostate cancer cells, our initial aim was to determine its potential utility as a biomarker of prostate cancer. Materials and Methods: We cloned and sequenced the region in RACK7 where i-motif deletions often occur in DNA obtained from eight individuals. Expressed prostatic secretions were obtained from three individuals with a positive biopsy for prostate cancer and two with individuals with a negative biopsy for prostate cancer. Peripheral blood specimens were obtained from two control healthy bone marrow donors and a marrow specimen was obtained from a third healthy marrow donor. Follow-up computer searches of the genomes of 74 mammalian species available at the NCBI ftp site or frequencies of 6 dynamic sequences known to produce mutations or replication stress using a program written in Mathematica were subsequently performed. Results: Deletions were found in RACK7 in specimens from both older normal adults, as well as specimens from older patients with cancer, but not in the youngest normal adult. The deletions appeared to show a weak trend to increasing frequency with patient age. This suggested that endogenous mutations associated with dynamic sequences might accumulate during aging and might serve as biomarkers of biological age rather than direct biomarkers of cancer. To test that hypothesis, we asked whether or not the genomic frequencies of several dynamic sequences known to produce replication stress or mutations in human DNA were inversely correlated with maximum lifespan in mammals. Conclusion: Our results confirm this correlation for six dynamic sequences in 74 mammalian genomes studied, thereby suggesting that spontaneously induced replication stress and mutations linked to dynamic sequence frequency may limit lifespan by limiting genome stability. [ABSTRACT FROM AUTHOR]

Zeolites are a class of catalysts with specific pore structures as well as different pore sizes, which are now widely used in various shape-selective catalytic reactions. In this paper, a uniform micro/mesoporous core–shell composite HZSM-@MCM-41 comprising zeolite was successfully prepared by coating mesoporous MCM-41 shells on nanosized ZSM-5 cores using a two-step hydrothermal method. Nanoscale ZSM-5 cores with different acidity were successfully prepared by changing the Si/Al of the initial solution of pristine ZSM-5, and three different thicknesses of MCM-41 shell layers were easily encapsulated on the surface of ZSM-5 with different acidity by varying the amount of silicon source added in the secondary hydrothermal crystallization process. The synthesized series of micro-mesoporous core–shell catalysts were also applied to the catalytic fast pyrolysis in lignin. In the catalytic fast pyrolysis of lignin, the mesoporous structure promoted the transition of biomass pyrolysis intermediate to liquid products, and the acidity of the HZSM-5 core facilitated their catalytic transformation to aromatic hydrocarbons. Among all the tested catalysts, the HZ@M-80-ll catalyst with an internal Si/Al = 80 and MCM-41 shell thickness of ∼25 nm exhibited the highest production of light aromatics and phenols. [ABSTRACT FROM AUTHOR]

Spatial compartmentalization is a key facet of protein quality control that serves to store disassembled or non-native proteins until triage to the refolding or degradation machinery can occur in a regulated manner. Yeast cells sequester nuclear proteins at intranuclear quality control bodies (INQ) in response to various stresses, although the regulation of this process remains poorly understood. Here we reveal the SUMO modification of the small heat shock protein Btn2 under DNA damage and place Btn2 SUMOylation in a pathway promoting protein clearance from INQ structures. Along with other chaperones, and degradation machinery, Btn2-SUMO promotes INQ clearance from cells recovering from genotoxic stress. These data link small heat shock protein post-translational modification to the regulation of protein sequestration in the yeast nucleus. Maintaining a healthy nuclear proteome during DNA damage is important but its regulation is poorly understood. The authors here show that a SUMO modification of the small heat shock protein Btn2 regulates yeast nuclear protein sequestration during stress. [ABSTRACT FROM AUTHOR]

In this work, a hydrophobic diamine-functionalized ionic liquid [MAMIm][PF6] was easily synthesized for the transformation of CO2 and halohydrins to cyclic carbonates, serving as a dual catalyst and acid-acceptor. Benefitting from the basic –N(CH3)2 site, this IL could promote this reaction under mild conditions with a high yield of cyclic carbonates. More importantly, by virtue of its hydrophobicity, the IL could be readily recycled and reused by simple washing. The synergistic effect of the basic –N(CH3)2 site and hydrophobic anion is expected to provide new insight in the development of novel catalysts for this reaction. [ABSTRACT FROM AUTHOR]

Background: Pseudomonas aeruginosa is an opportunistic, resistant and highly pathogenic bacteria, responsible for severe nosocomial infections in humans. There is need to search new antimicrobials to target P. aeruginosa strains. Cistus munbyi is used in traditional medicine to manage infections. Objectives: This work aims to investigate the antimicrobial, antibiofilm and other antivirulence effects of essential oil from C. munbyi against P. aeruginosa. Materials and methods: Essential oil (EO) was prepared by hydro-distillation from C. munbyi, characterized by GC–MS and evaluated for its antimicrobial, antibiofilm and anti-virulence effects against clinical isolates of P. aeruginosa. Results: 100% of compounds were identified with Terpinen-4-ol (33.20%), Sabinene (13.20%), α-Thujene (11.30%), and p-Cymene (9.94%) being the major constituents. The EO had good antimicrobial activity determined by diameters of inhibition zones and broth dilution. At minimal inhibitory concentration (MIC), the EO eliminated more that 70% of young biofilms in 19 strains out of 24 tested strains while at 2MIC, only one strain had biofilm inhibition below 70%. The EO eliminated more than 50% of mature biofilms in 13 strains out of 24 tested. Biofilm disruption was concentration-dependent at sub-MIC and indicated good potential of C. munbyi EO as P. aeruginosa antibiofilm agent. Scanning electron microscopy (SEM) images revealed that untreated colonies had a well-developed biofilm while there was significant reduction of biofilms with distorted architecture and cell shrinkage upon treatment with EO. The C. munbyi EO at MIC and sub-MIC was able to reduce quorum-sensing (QS) virulence factors such as pyocyanin production, exopolysaccharides matrix and elastase secretion. Significant QS revealed by reduction of violacein in C. violaceum (CV12472 and CV026) was observed. Conclusion: The overall results show good anti-pseudomonal effects of C. munbyi EO which makes it a potential agent to reduce the spread of infections and resistance to antibiotics from P. aeruginosa strains. [ABSTRACT FROM AUTHOR]

Introduction and Objective: Bee venom is a liquid, colorless and acidic mixture (pH 4.5-5.5) that contains 18 different compounds such as enzymes, peptides and biological amino acids. Some of these compounds have anti-inflammatory properties and some have toxic and allergenic properties. Bee venom is produced by female worker bees. The most important peptides in bee venom are melittin, apamin, adolapin and mast cell degranulating (MCD) peptide. The most important enzymes in bee venom can be called hyaluronidase and phospholipase A2 (PLA2). Bee venom has been used in the past, especially in traditional medicine, as a medicine to treat various diseases such as rheumatoid arthritis and also to reduce muscle pain. Massive bee attacks are considered one of the Public Health problems in some countries in the world, including Iran. No specific therapy is available for bee stings and the treatment is done by chemical drugs, leading us to develop Fabbased antivenom as a potential new treatment. So far in Iran, no action has been taken to produce Fab-based antivenom to save people who are sensitive to bee stings. Therefore, the aim of this research was to produce an effective and safe horse serum antidote against the Iranian honey bee (Apis mellifera meda). Material and Methods: Crude bee venom (BV) was prepared from Iranian bees (Apis mellifera meda) using an electric bee venom collecting machine. The poison dries quickly in the air. The dried venom was collected from the glass plates every day with the help of special spatulas and stored in dark glasses in a freezer at -20 ºC for future experiments. To remove mucus and extra substances, the poison is dissolved in a ratio of 1:1 with saline (physiological serum) and centrifuged at high speed. After centrifugation, the upper clear solution is separated and filtered with a 0.2 micron filter. The amount of protein in the crude venom solution was determined by the Bradford protein assay method and based on the standard curve obtained by measuring different concentrations of bovine serum albumin (BSA) solution. The median lethal dose (LD50) value of BV was determined with 24 male mice. Mice were divided into 4 groups. Then 0.5 ml of different doses of venom (60, 70, 80, 90, 100 and 110 μg/ml) dissolved in sterile normal saline were injected intravenously. Control group were injected with 0.5 ml saline solution. Mortality was recorded after 24 hours and LD50 was calculated based on probit analysis. In this research, 3 horses were used to produce antivenom against honey bee venom. For this purpose, horses were immunized with Iranian bee venom 7 times with 7-day intervals, and immunogenicity was evaluated in laboratory conditions with ELISA test. The precipitated antivenom with saturated ammonium sulfate was also used to perform the neutralizing test in mice. To check the quality of antivenom, the neutralization of phospholipase A2 activity was performed using different concentrations of antivenom. Finally, for determining the efficiency of the prepared antivenom, the median effective dose (ED50) value was calculated by probit analysis. In this research, three adult mares (three years old, 400 to 450 kg) were used. To immunize the horses, bee venom was injected with complete and incomplete Freund's adjuvant. Complete Freund's adjuvant was used in the first and second inoculations, and incomplete Freund's adjuvant was used in subsequent inoculations. Venom inoculation was carried out incrementally from 50, 100, 250, 500, 1000, 2000 and 4000 micrograms in 7 times with 7 days intervals. The injection was done subcutaneously (in the neck). Isolation of horse antibody was performed with the standard protocol of the saturated ammonium sulfate method. Evaluation of immunogenicity in laboratory conditions was done by ELISA test. The serum of immunized horses and the precipitated antivenom with saturated ammonium sulfate were was also used to perform the neutralizing test in mice. To check the quality of antivenom, the neutralization of phospholipase A2 activity was performed using different concentrations of antivenom. Finally, for determining the efficiency of the prepared antivenom, the median effective dose (ED50) value was calculated by probit analysis. To determine the effectiveness of the prepared horse antivenom, bee venom was mixed with a constant amount of antivenom in increasing doses and injected into mice. Results: The total protein in the crude BV solution was calculated to be 56 mg/ml. Also, the LD50 of the crude BV was obtained as 4.84 μg/g. ELISA test results showed an immune response that increased more during the immunization schedule. Neutralization of phospholipase A2 activity using different concentrations of antivenom showed that Iranian bee venom has phospholipase activity and 120 μg/ml of this antidote is able to completely neutralize the activity of phospholipase A2. It is clear that, firstly, Iranian honey bee venom has phospholipase activity, and secondly, 55 micrograms of antivenom are needed to neutralize 50% of phospholipase A2 activity in 100 micrograms of venom. The ED50 value will be approximately 54 times the LD50. This means that the antivenom can neutralize up to 54 times the LD50. Therefore, the death caused by 4 mg of bee venom is neutralized by 1 ml of antivenom, so the average effective dose ED50 will be 4 mg/ml. If 100 micrograms of venom enters the body in each bee sting, then 1 ml of produced antivenom can neutralize 40 bee stings. Conclusion: The result showed that horse antivenom against honey bee venom is capable to neutralize the crude venom in mice model. [ABSTRACT FROM AUTHOR]

Chronic adipose tissue inflammation accompanied by macrophage accumulation and activation is implicated in the pathogenesis of insulin resistance and type 2 diabetes in humans. The transcriptional coregulator CREBZF is a key factor in hepatic metabolism, yet its role in modulating adipose tissue inflammation and type 2 diabetes remains elusive. The present study demonstrates that overnutrition‐induced CREBZF links adipose tissue macrophage (ATM) proinflammatory activation to insulin resistance. CREBZF deficiency in macrophages, not in neutrophils, attenuates macrophage infiltration in adipose, proinflammatory activation, and hyperglycemia in diet‐induced insulin‐resistant mice. The coculture assays show that macrophage CREBZF deficiency improves insulin sensitivity in primary adipocytes and adipose tissue. Mechanistically, CREBZF competitively inhibits the binding of IκBα to p65, resulting in enhanced NF‐κB activity. In addition, bromocriptine is identified as a small molecule inhibitor of CREBZF in macrophages, which suppresses the proinflammatory phenotype and improves metabolic dysfunction. Furthermore, CREBZF is highly expressed in ATM of obese humans and mice, which is positively correlated with proinflammatory genes and insulin resistance in humans. This study identifies a previously unknown role of CREBZF coupling ATM activation to systemic insulin resistance and type 2 diabetes. [ABSTRACT FROM AUTHOR]

Spatial and temporal uncertainties are found in data for many critical applications. This paper describes the use of interval-based representations of some spatial and temporal information. Uncertainties in the information can arise from multiple sources in which degrees of support and non-support occur in evaluations. This motivates the use of intuitionistic fuzzy sets to permit the use of the positive and negative memberships to capture these uncertainties. The interval representations will include both simple and complex or nested intervals. The relationships between intervals such as overlapping, containing, etc. are then developed for both the simple and complex intervals. Such relationships are required to support the aggregation approaches of the interval information. Both averaging and merging approaches to interval aggregation are then developed. Furthermore, potential techniques for the associated aggregation of the interval intuitionistic fuzzy memberships are provided. A motivating example of maritime depth data required for safe navigation is used to illustrate the approach. Finally, some potential future developments are discussed. [ABSTRACT FROM AUTHOR]

The mitochondrial genome (mitogenome) of Actinidia macrosperma, a traditional medicinal plant within the Actinidia genus, remains relatively understudied. This study aimed to sequence the mitogenome of A. macrosperma, determining its assembly, informational content, and developmental expression. The results revealed that the mitogenome of A. macrosperma is circular, spanning 752,501 bp with a GC content of 46.16%. It comprises 63 unique genes, including 39 protein-coding genes (PCGs), 23 tRNA genes, and three rRNA genes. Moreover, the mitogenome was found to contain 63 SSRs, predominantly mono-nucleotides, as well as 25 tandem repeats and 650 pairs of dispersed repeats, each with lengths equal to or greater than 60, mainly comprising forward repeats and palindromic repeats. Moreover, 53 homologous fragments were identified between the mitogenome and chloroplast genome (cp-genome), with the longest segment measuring 4296 bp. This study represents the initial report on the mitogenome of the A. macrosperma, providing crucial genetic materials for phylogenetic research within the Actinidia genus and promoting the exploitation of species genetic resources. [ABSTRACT FROM AUTHOR]