Cyclic diarylheptanoids from Myrica javanica: isolation, transformation, and bioactivity evaluation.

Three cyclic diarylheptanoids, myricanol (1), myricanone (2), and porson (3), were isolated from Myrica javanica (Myricaceae). As a major component, myricanol (1) was obtained from dry powdered bark and twigs (up to 1.6%). Transformation of myricanol (1) afforded 5-prenylmyricanol (4) and 5-benzylmyricanol (5) in 84.5% and 65% yields, respectively. The bioactivities of the isolated cyclic diarylheptanoids and their derivatives were investigated to determine their cytotoxicity and DPPH (2,2-diphenyl-1-picrylhydrazyl) scavenging activities. The cytotoxicity assay against murine leukaemia P-388 cells demonstrated that compounds 4 and 5 showed an almost two-fold increase in the activity of their parent molecule (1), with an IC50 value of 12 µM. Furthermore, the free radical scavenging assay showed that myricanol (1) had the highest radical scavenging activity, revealing the importance of the free phenolic group (IC50 39.3 µM).

Influence of the brushing motions on the dynamic cyclic fatigue resistance of the Reciproc Blue instrument: In vitro study.

INTRODUCTION: This study aimed to evaluate the dynamic cyclic fatigue resistance of Reciproc® Blue files subjected to brushing motion. METHODS: Twenty Reciproc® Blue files (R25, VDW, Munich, Germany) were employed for chemical-mechanical preparation in root canals of 3D printed replicas of mandibular molars. The instruments were divided into two groups (n=10): Group BM, instrumentation with brushing motions; Group WBM, instrumentation without brushing motions. Subsequently, the same instruments underwent cyclic fatigue testing using artificial canals consisting of a stainless-steel plate and an apical segment with a 45° curvature. Data regarding the time to fracture, number of cycles to fracture (NCF), and length of the fractured fragment were collected and subjected to statistical analysis using the t-test or Mann-Whitney test, with a significance level of 5%. Additionally, the fractured fragments were examined under a scanning electron microscope. RESULTS: No statistical differences were observed between the groups in terms of time to fracture (p<0.05), NCF (p<0.05), and length of the fractured fragment (p<0.05). CONCLUSION: The brushing motion did not affect the dynamic cyclic fatigue resistance of Reciproc Blue files.

The formation of aggregated chromatin/chromosomes in mouse oocytes treated with high concentration of IBMX as a model for a chromosome transfer in human.

The presence of cyclic adenosine monophosphate (cAMP) has been considered to be a fundamental factor in ensuring meiotic arrest prior to ovulation. cAMP is regarded as a key molecule in the regulation of oocyte maturation. However, it has been reported that increased levels of intracellular cAMP can result in abnormal cytokinesis, with some MI oocytes leading to symmetrically cleaved 2-cell MII oocytes. Consequently, we aimed to investigate the effects of elevated intracellular cAMP levels on abnormal cytokinesis and oocyte maturation during the meiosis of mouse oocytes. This study found that a high concentration of isobutylmethylxanthine (IBMX) also caused chromatin/chromosomes aggregation (AC) after the first meiosis. The rates of AC increased the greater the concentration of IBMX. In addition, AC formation was found to be reversible, showing that the re-formation of the spindle chromosome complex was possible after the IBMX was removed. In human oocytes, the chromosomes aggregate after the germinal vesicle breakdown and following the first and second polar body extrusions (the AC phase), while mouse oocytes do not have this AC phase. The results of our current study may indicate that the AC phase in human oocytes could be related to elevated levels of intracytoplasmic cAMP.

CYCLOPEp Builder: Facilitating cyclic peptide and nanotube research through a user-friendly web platform.

The study of cyclic peptides (CPs) and self-assembling cyclic peptide nanotubes (SCPNs) is pivotal in advancing applications in diverse fields such as biomedicine, nanoelectronics, and catalysis. Recognizing the limitations in the experimental study of these molecules, this article introduces CYCLOPEp Builder, a comprehensive web-based application designed to facilitate the design, simulation, and visualization of CPs and SCPNs. The tool is engineered to generate molecular topologies, essential for conducting Molecular Dynamics simulations that span All-Atom to Coarse-Grain resolutions. CYCLOPEp Builder's user-friendly interface simplifies the complex process of molecular modeling, providing researchers with the ability to readily construct CPs and SCPNs. The platform is versatile, equipped with various force fields, and capable of producing structures ranging from individual CPs to complex SCPNs with different sequences, offering parallel and antiparallel orientations among them. By enhancing the capacity for detailed visualization of molecular assemblies, CYCLOPEp Builder improves the understanding of CP and SCPN molecular interactions. This tool is a step forward in democratizing access to sophisticated simulations, offering an invaluable resource to the scientific community engaged in the exploration of supramolecular structures. CYCLOPEp is accessible at http://cyclopep.com/.

Endoscopic Management of Boerhaave Syndrome: Are Outcomes Better Than Surgery? A Case Report and Review of Literature.

Boerhaave syndrome (BS) is a rare clinical diagnosis associated with a high morbidity and mortality rate. Diagnosis of this condition is usually delayed which can lead to a very poor outcome. The timing of presentation and time to management plays a very important role in the prognosis and selection of the management method. With the advances seen in therapeutic endoscopy, many authors have been exploring the possibility of shifting the focus of management from surgery to interventional endoscopy. We present a case report of a patient presenting with BS that was successfully managed endoscopically. We also reviewed the literature on how surgical management compares to endoscopic management and attempted to establish general recommendations from available literature on management of BS.

Simultaneously Enhanced Catalytic Activity and Thermostability of a Baeyer-Villiger Monooxygenase from Oceanicola granulosus by Reshaping the Binding Pocket.

Enzymatic oxygenation of various cyclic ketones into lactones via Baeyer-Villiger monooxygenases (BVMOs) could provide a promising route for synthesizing fragrances and pharmaceutical ingredients. However, unsatisfactory catalytic activity and thermostability restricted their applications in the pharmaceutical and food industries. In this study, we successfully improved the catalytic activity and thermostability of a Baeyer-Villiger monooxygenase (OgBVMO) from Oceanicola granulosus by reshaping the binding pocket. As a result, mutant OgBVMO-Re displayed a 1.0- to 6.4-fold increase in the activity toward branched cyclic ketones tested, accompanied by a 3 °C higher melting point, and a 2-fold longer half-life time (t1/2 (45 °C)). Molecular dynamics simulations revealed that reshaping the binding pocket achieved strengthened motion correlation between amino acid residues, appropriate size of the substrate-binding pocket, beneficial surface characteristics, lower energy barriers, and shorter nucleophilic distance. This study well demonstrated the trade-off between the enzyme activity and thermostability by reshaping the substrate-binding pocket, paving the way for further engineering other enzymes.

The Influence of Disulfide, Thioacetal and Lanthionine-Bridges on the Conformation of a Macrocyclic Peptide.

Cyclisation of peptides by forming thioether (lanthionine), disulfide (cystine) or methylene thioacetal bridges between side chains is established as an important tool to stabilise a given structure, enhance metabolic stability and optimise both potency and selectivity. However, a systematic comparative study of the effects of differing bridging modalities on peptide conformation has not previously been carried out. In this paper, we have used the NMR deconvolution algorithm, NAMFIS, to determine the conformational ensembles, in aqueous solution, of three cyclic analogues of angiotensin(1-7), incorporating either disulfide, or non-reduceable thioether or methylene thioacetal bridges. We demonstrate that the major solution conformations are conserved between the different bridged peptides, but the distribution of conformations differs appreciably. This suggests that subtle differences in ring size and bridging structure can be exploited to fine-tune the conformational properties of cyclic peptides, which may modulate their bioactivities.

A solid state electrolyte based enzymatic acetone sensor.

This paper introduces a novel solid-state electrolyte-based enzymatic sensor designed for the detection of acetone, along with an examination of its performance under various surface modifications aimed at optimizing its sensing capabilities. To measure acetone concentrations in both liquid and vapor states, cyclic voltammetry and amperometry techniques were employed, utilizing disposable screen-printed electrodes consisting of a platinum working electrode, a platinum counter electrode, and a silver reference electrode. Four different surface modifications, involving different combinations of Nafion (N) and enzyme (E) layers (N + E; N + E + N; N + N + E; N + N + E + N), were tested to identify the most effective configuration for a sensor that can be used for breath acetone detection. The sensor's essential characteristics, including linearity, sensitivity, reproducibility, and limit of detection, were thoroughly evaluated through a range of experiments spanning concentrations from 1 µM to 25 mM. Changes in acetone concentration were monitored by comparing currents readings at different acetone concentrations. The sensor exhibited high sensitivity, and a linear response to acetone concentration in both liquid and gas phases within the specified concentration range, with correlation coefficients ranging from 0.92 to 0.98. Furthermore, the sensor achieved a rapid response time of 30-50 s and an impressive detection limit as low as 0.03 µM. The results indicated that the sensor exhibited the best linearity, sensitivity, and limit of detection when four layers were employed (N + N + E + N).

The specifics of the Galois field GF(257) and its use for digital signal processing.

An algorithm of digital logarithm calculation for the Galois field G F ( 257 ) is proposed. It is shown that this field is coupled with one of the most important existing standards that uses a digital representation of the signal through 256 levels. It is shown that for this case it is advisable to use the specifics of quasi-Mersenne prime numbers, representable in the form p = 2 n + 1 , which includes the number 257. For fields G F ( 2 n + 1 ) , an alternating encoding can be used, in which non-zero elements of the field are displayed through binary characters corresponding to the numbers + 1 and - 1. In such an encoding, multiplying a field element by 2 is reduced to a quasi-cyclic permutation of binary symbols (the permuted symbol changes sign). Proposed approach makes it possible to significantly simplify the design of computing devices for calculation of digital logarithm and multiplication of numbers modulo 257. A concrete scheme of a device for digital logarithm calculation in this field is presented. It is also shown that this circuit can be equipped with a universal adder modulo an arbitrary number, which makes it possible to implement any operations in the field under consideration. It is shown that proposed digital algorithm can also be used to reduce 256-valued logic operations to algebraic form. It is shown that the proposed approach is of significant interest for the development of UAV on-board computers operating as part of a group.

Prevalence of chronic pelvic pain and associated factors among indigenous women of reproductive age in Ecuador.

BACKGROUND: Chronic pelvic pain is a common disease that affects approximately 4% of women of reproductive age in developed countries. This number is estimated to be higher in developing countries, with a significant negative personal and socioeconomic impact on women. The lack of data on this condition in several countries, particularly those in development and in socially and biologically vulnerable populations such as the indigenous, makes it difficult to guide public policies. OBJECTIVES: To evaluate the prevalence of chronic pelvic pain (dysmenorrhea, dyspareunia, non-cyclical pain) and identify which variables are independently associated with the presence of the condition in indigenous women from Otavalo-Ecuador. DESIGN: A cross-sectional study was carried out including a sample of 2429 women of reproductive age between 14 and 49 years old, obtained from April 2022 to March 2023. A directed questionnaire was used, collected by bilingual interviewers (Kichwa and Spanish) belonging to the community itself; the number of patients was selected by random sampling proportional to the number of women estimated by sample calculation. Data are presented as case prevalence, odds ratio, and 95% confidence interval, with p < 0.05. RESULTS: The prevalence of primary dysmenorrhea, non-cyclic pelvic pain, and dyspareunia was, respectively, 26.6%, 8.9%, and 3.9%.all forms of chronic pain were independently associated with each other. Additionally, dysmenorrhoea was independently associated with hypertension, intestinal symptoms, miscegenation, long cycles, previous pregnancy, use of contraceptives and pear body shape. Pain in other sites, late menarche, exercise, and pear body shape were associated with non-cyclic pelvic pain. And, urinary symptoms, previous pregnancy loss, miscegenation, and pear body shape were associated with dyspareunia. CONCLUSION: The prevalence of primary dysmenorrhea and non-cyclical chronic pelvic pain was notably high, in contrast with the frequency of reported dyspareunia. Briefly, our results suggest an association between dysmenorrhoea and conditions related to inflammatory and/or systemic metabolic disorders, including a potential causal relationship with other manifestations of pelvic pain, and between non-cyclical pelvic pain and signs/symptoms suggesting central sensitization. The report of dyspareunia may be influenced by local cultural values and beliefs.

A cyclic lipopeptide from Fusarium graminearum targets plant membranes to promote virulence.

Microbial plant pathogens deploy amphipathic cyclic lipopeptides to reduce surface tension in their environment. While plants can detect these molecules to activate cellular stress responses, the role of these lipopeptides or associated host responses in pathogenesis are not fully clear. The gramillin cyclic lipopeptide is produced by the Fusarium graminearum fungus and is a virulence factor and toxin in maize. Here, we show that gramillin promotes virulence and necrosis in both monocots and dicots by disrupting ion balance across membranes. Gramillin is a cation-conducting ionophore and causes plasma membrane depolarization. This disruption triggers cellular signaling, including a burst of reactive oxygen species (ROS), transcriptional reprogramming, and callose production. Gramillin-induced ROS depends on expression of host ILK1 and RBOHD genes, which promote fungal induction of virulence genes during infection and host susceptibility. We conclude that gramillin's ionophore activity targets plant membranes to coordinate attack by the F. graminearum fungus.

Anterior variable angle locking neutralisation plate superiority over traditional tension band wiring for treating transverse patella fractures.

Purpose: This paper investigates the biomechanical benefits of using hybrid constructs that combine cannulated screws with tension band wiring (TBW) cerclage compared to cannulated screws with anterior Variable Angle locking neutralisation plates (VA LNP). These enhancements can bear heavier loads and maintain the repaired patella's integrity, in contrast to traditional methods. Method: Eighteen fresh-frozen human cadaver patellae were carefully fractured transversely at their midpoints using a saw. They were then divided into two groups of nine for subsequent utilisation. Fixation methods included Cannulated Screw Fixation added with either TBW or VA LNP Fixation Technique. Cyclic loading simulations (500 cycles) were conducted to mimic knee motion, tracking fracture displacement with Optotrak. After that, the constructs were secured over a servo-hydraulic testing machine to determine the load-to-failure on axial mode. Results: The average fracture displacement for the anterior neutralisation plate group was 0.09 ± 0.12 mm, compared to 0.77 ± 0.54 mm for the tension band wiring with cannulated screw group after 500 cyclic loading. This result is statistically significant (p = 0.004). The anterior neutralisation plate group exhibited a mean load-to-failure of 1359 ± 21.53 N, whereas the tension band wiring group showed 780.1 ± 22.62 N, resulting in a significant difference between the groups (p = 0.007). Conclusion: This research highlights the superior biomechanical advantage of VA LNP over TBW for treating simple transverse patella fractures with two cannulated screws. It also highlights how the TBW is still a valuable option considering the load-to-failure limit. Level of Evidence: Not Applicable.

A 1:1 flavone cocrystal with cyclic trimeric perfluoro-o-phenyl-enemercury.

The title compound, systematic name tris-(µ2-perfluoro-o-phenyl-ene)(µ2-3-phenyl-4H-chromen-4-one)-triangulo-trimercury, [Hg3(C6F4)3(C15H10O2)], crystallizes in the monoclinic P21/n space group with one flavone (FLA) and one cyclic trimeric perfluoro-o-phenyl-enemercury (TPPM) mol-ecule per asymmetric unit. The FLA mol-ecule is located on one face of the TPPM acceptor and is linked in an asymmetric coordination of its carbonyl oxygen atom with two Hg centers of the TPPM macrocycle. The angular-shaped complexes pack in zigzag chains where they stack via two alternating TPPM-TPPM and FLA-FLA stacking patterns. The distance between the mean planes of the neighboring TPPM macrocycles in the stack is 3.445 (2) Å, and that between the benzo-γ-pyrone moieties of FLA is 3.328 (2) Å. The neighboring stacks are inter-digitated through the shortened F⋯F, CH⋯F and CH⋯π contacts, forming a dense crystal structure.

A hybrid finite-discrete element method for modelling cracking processes in sandy mudstone containing a single edge-flaw under cyclic dynamic loading.

Rock mass deformation and failure are macroscopic manifestations of crack initiation, propagation, and coalescence. However, simulating the transition of rocks from continuous to discontinuous media under cyclic dynamic loading remains challenging. This study proposes a hybrid finite-discrete element method (HFDEM) to model crack propagation, incorporating a frequency-dependent cohesive-zone model. The mechanical properties of standard sandy mudstone under quasi-static and cyclic dynamic loading were simulated using HFDEM, and the method's reliability was verified through experimental comparison. The comparative analysis demonstrates that HFDEM successfully captures crack interaction mechanisms and accurately simulates the overall failure behavior of specimens. Additionally, the effects of pre-existing flaw inclination angle and dynamic loading frequency on rock failure mechanisms were investigated. The numerical results reveal that rock samples exhibit significantly higher compressive strength under dynamic loading compared to quasi-static loading, with compressive strength increasing with higher cyclic dynamic load frequencies. Furthermore, by analyzing the strength characteristics, crack propagation, and failure modes of the samples, insights into the failure mechanisms of rocks under different frequency loads were obtained. This study provides valuable insights into crack development and failure of rocks under seismic loads, offering guidance for engineering practices.

HCN channels in the lateral habenula regulate pain and comorbid depressive-like behaviors in mice.

AIMS: Comorbid anxiodepressive-like symptoms (CADS) in chronic pain are closely related to the overactivation of the lateral habenula (LHb). Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels have been implicated to play a key role in regulating neuronal excitability. However, the role of HCN channels in the LHb during CADS has not yet been characterized. This study aimed to investigate the effect of HCN channels in the LHb on CADS during chronic pain. METHODS: After chronic neuropathic pain induction by spared nerve injury (SNI), mice underwent a sucrose preference test, forced swimming test, tail suspension test, open-field test, and elevated plus maze test to evaluate their anxiodepressive-like behaviors. Electrophysiological recordings, immunohistochemistry, Western blotting, pharmacological experiments, and virus knockdown strategies were used to investigate the underlying mechanisms. RESULTS: Evident anxiodepressive-like behaviors were observed 6w after the SNI surgery, accompanied by increased neuronal excitability, enhanced HCN channel function, and increased expression of HCN2 isoforms in the LHb. Either pharmacological inhibition or virus knockdown of HCN2 channels significantly reduced LHb neuronal excitability and ameliorated both pain and depressive-like behaviors. CONCLUSION: Our results indicated that the LHb neurons were hyperactive under CADS in chronic pain, and this hyperactivation possibly resulted from the enhanced function of HCN channels and up-regulation of HCN2 isoforms.

Structure-activity relationships of middle-size cyclic peptides, KRAS inhibitors derived from an mRNA display.

Cyclic peptides are attracting attention as therapeutic agents due to their potential for oral absorption and easy access to tough intracellular targets. LUNA18, a clinical KRAS inhibitor, was transformed-without scaffold hopping-from the initial hit by using an mRNA display library that met our criteria for drug-likeness. In drug discovery using mRNA display libraries, hit compounds always possess a site linked to an mRNA tag. Here, we describe our examination of the Structure-Activity Relationship (SAR) using X-ray structures for chemical optimization near the site linked to the mRNA tag, equivalent to the C-terminus. Structural modifications near the C-terminus demonstrated a relatively wide range of tolerance for side chains. Furthermore, we show that a single atom modification is enough to change the pharmacokinetic (PK) profile. Since there are four positions where side chain modification is permissible in terms of activity, it is possible to flexibly adjust the pharmacokinetic profile by structurally optimizing the side chain. The side chain transformation findings demonstrated here may be generally applicable to hits obtained from mRNA display libraries.

Connect attack in IoT-WSN detect through cyclic analysis based on forward and backward elimination.

IoT-wireless sensor networks (WSN) have extensive applications in diverse fields such as battlegrounds, commercial sectors, habitat monitoring, buildings, smart homes, and traffic surveillance. WSNs are susceptible to various types of attacks, such as malicious attacks, false data injection attacks, traffic attacks, and HTTP flood attacks. CONNECT attack is a novel attack in WSN. CONNECT attack plays a crucial role through disrupting packet transmission and node connections and significantly impacts CPU performance. Detecting and preventing CONNECT attacks is imperative for enhancing WSN efficiency. During a CONNECT attack, nodes fail to respond to legitimate requests, resulting in connectivity delays, acknowledgment delays, and packet drop attacks in IoT-WSN nodes. This article introduces an Intrusion Detection Algorithm based on the Cyclic Analysis Method (CAM), which incorporates a forward selection approach and backward elimination method. CAM analyzes routing information and behavior within the WSN, facilitating the identification of malicious paths and nodes. The proposed approach aims to pinpoint and mitigate the risks associated with CONNECT attacks, emphasizing the identification of malevolent pathways and nodes while establishing multiple disjoint loop-free routes for seamless data delivery in the IoT-WSN. Furthermore, the performance of CAM is assessed based on metrics such as malicious node detection accuracy, connectivity, packet loss, and network traffic. Simulation results using Matlab software demonstrate superior accuracy in malicious node detection, achieving accuracy in attack detection of approximately 99%, surpassing traditional algorithms accuracy of attack detection.

Synthesis of cyclic ß-1,6-oligosaccharides from glucosamine monomers by electrochemical polyglycosylation.

The synthesis of protected precursors of cyclic ß-1,6-oligoglucosamines from thioglycosides as monomers is performed by electrochemical polyglycosylation. The monomer with a 2,3-oxazolidinone protecting group afforded the cyclic disaccharide exclusively. Cyclic oligosaccharides up to the trisaccharide were obtained using the monomer with a 2-azido-2-deoxy group.

Predicting bond dissociation energies of cyclic hypervalent halogen reagents using DFT calculations and graph attention network model.

Although hypervalent iodine(III) reagents have become staples in organic chemistry, the exploration of their isoelectronic counterparts, namely hypervalent bromine(III) and chlorine(III) reagents, has been relatively limited, partly due to challenges in synthesizing and stabilizing these compounds. In this study, we conduct a thorough examination of both homolytic and heterolytic bond dissociation energies (BDEs) critical for assessing the chemical stability and functional group transfer capability of cyclic hypervalent halogen compounds using density functional theory (DFT) analysis. A moderate linear correlation was observed between the homolytic BDEs across different halogen centers, while a strong linear correlation was noted among the heterolytic BDEs across these centers. Furthermore, we developed a predictive model for both homolytic and heterolytic BDEs of cyclic hypervalent halogen compounds using machine learning algorithms. The results of this study could aid in estimating the chemical stability and functional group transfer capabilities of hypervalent bromine(III) and chlorine(III) reagents, thereby facilitating their development.

Electro-oxidation of ammonia nitrogen using W, Ti-doped IrO2 DSA as a treatment method for mariculture and livestock wastewater.

Animal farming wastewater is one of the most important sources of ammonia nitrogen (NH4+-N) emissions. Electro-oxidation can be a viable solution for removing NH4+-N in wastewater. Compared with other treatment methods, electro-oxidation has the advantages of i) high removal efficiency, ii) smaller size of treatment facilities, and iii) complete removal of contaminant. In this study, a previously prepared DSA (W, Ti-doped IrO2) was used for electro-oxidation of synthetic mariculture and livestock wastewater. The DSA was tested for chlorine evolution reaction (CER) activity, and the reaction kinetics was investigated. CER current efficiency reaches 60-80% in mariculture wastewater and less than 20% in livestock wastewater. In the absence of NH4+-N, the generation of active chlorine follows zero-order kinetics and its consumption follows first-order kinetics, with cathodic reduction being its main consumption pathway, rather than escape or conversion to ClO3-. Cyclic voltammetry experiments show that NH4+-N in the form of NH3 can be oxidized directly on the anode surface. In addition, the generated active chlorine combines with NH4+-N at a fast rate near the anode, rather than in the bulk solution. In electrolysis experiments, the NH4+-N removal rate in synthetic mariculture wastewater (30-40 mg/L NH4+-N) and livestock wastewater (~ 450 mg/L NH4+-N) is 112.9 g NH4+-N/(m2·d) and 186.5 g NH4+-N/(m2·d), respectively, which is much more efficient than biological treatment. The specific energy consumption (SEC) in synthetic mariculture wastewater is 31.5 kWh/kg NH4+-N, comparable to other modified electro-catalysts reported in the literature. However, in synthetic livestock wastewater, the SEC is as high as 260 kWh/kg NH4+-N, mainly due to the suppression of active chlorine generation by HCO3- and the generation of NO3- as a by-product. Therefore, we conclude that electro-oxidation is suitable for mariculture wastewater treatment, but is not recommended for livestock wastewater. Electrolysis prior to urea hydrolysis may enhance the treatment efficiency in livestock wastewater.