Probable Mechanism Research Articles

Computer-aided Design of Wide-spectrum Coronavirus Helicase NSP13 Cage Inhibitors: A Molecular Modelling Approach.

The coronavirus helicase NSP13 plays a critical role in its life cycle. The found NSP13 inhibitors have been tested only in vitro but they definitely have the potential to become antiviral drugs. Thus, the search for NSP13 inhibitors is of great importance. The goal of the present work was to develop a general approach to the design of ligands of coronaviral NSP13 helicase and to propose on its basis potential inhibitors. The structure of the NSP13 protein was refined by molecular dynamics and the cavity, responsible for RNA binding, was chosen as the inhibitor binding site. The potential inhibitor structures were identified by molecular docking and their binding was verified by molecular dynamics simulation. A number of potential NSP13 inhibitors were identified and the binding modes and probable mechanism of action of potential inhibitors was clarified. Using the molecular dynamics and molecular docking techniques, we have refined the structure of the coronavirus NSP13 helicase, a number of potential inhibitors, containing cage fragment were proposed and their probable mechanism of action was clarified. The proposed approach is also suitable for the design of ligands interacting with other viral helicases.

Clitoria ternatea L. (Butterfly Pea) Flower Against Endometrial Pain: Integrating Preliminary In Vivo and In Vitro Experimentations Supported by Network Pharmacology, Molecular Docking, and Molecular Dynamics Simulation Studies

Clitoria ternatea L. (CT) is a perennial herbaceous plant with deep blue flowers native to tropical Asia. This work explores the endometrial pain (EP) regulation of CT flower through a multifaceted approach. Phytochemical screening unveiled the presence of alkaloids, steroids, flavonoids, glycosides, and tannins in CT flower methanolic extract (ME). In the in vitro membrane stabilizing experiment, the ME demonstrated 91.47% suppression of heat-induced hemolysis. Upon carrageenan-induced paw edema assay conducted on male Swiss albino mice at doses of 200 mg/kg and 400 mg/kg, 65.28% and 81.89% inhibition rates, respectively, of paw edema were reported. For the same doses, upon acetic acid-induced-writhing assay, 75.6% and 76.78% inhibition rates, respectively, were observed. For network pharmacology analyses, a protein–protein interaction network was constructed for 92 overlapping gene targets of CT and EP, followed by GO and KEGG pathway enrichment analyses. Network pharmacology-based investigation identified the anti-EP activity of CT to be mostly regulated by the proteins SRC homology, ESR1, and PI3KR1. Physicochemical, pharmacokinetic, and toxicity property predictions for the compounds with stable ligand–target interactions and a molecular dynamics simulation for the highest interacting complex further validated these findings. This work affirmed the anti-EP role of CT flower against EP, suggesting a probable molecular mechanism involved.

Flowslide on a fill slope triggered by a burst water pipe: a case history

This paper presents a case study in Hong Kong of a flowslide occurred on a fill slope triggered by a burst water pipe buried near the slope crest. The onset of failure was recorded by nearby pedestrians and the video was immediately posted in social media which had caught noticeable public attention. The flowslide resulted in a temporary closure of an undermined road section at the slope crest. The debris travelled over 500 m down the natural hillside within a country park. No casualties were reported. History of the site was studied. Information was collected to establish the chronological order of events happened before the flowslide. Post-landslide investigations including field mapping in the source area and along the debris trail, ground investigations, and a fluid-coupled numerical study were undertaken to examine the probable cause and mechanism of the failure. It is diagnosed that the high mobility of this landslide would be caused by the saturation of a loose fill layer in the slope due to water egress from the burst pipe which in turn might have triggered a static liquefaction of the loose fill. Lessons learnt from this case history and measures to minimize similar landslide hazard on other fill slopes with similar settings are discussed.

Protective effects of a lactobacilli mixture against Alzheimer’s disease-like pathology triggered by Porphyromonas gingivalis

Porphyromonas gingivalis (P. gingivalis) is one of the pathogens involved in gingival inflammation, which may trigger neuroinflammatory diseases such as Alzheimer’s disease (AD). This study aimed to investigate the protective (preventive and treatment) effects of a lactobacilli mixture combining Lactobacillus reuteri PTCC1655, Lactobacillus brevis CD0817, Lacticaseibacillus rhamnosus PTCC1637, and Lactobacillus plantarum PTCC1058 against P. gingivalis-induced gingival inflammation and AD-like pathology in rats. These probiotic strains exhibited cognitive enhancement effects, but this study proposed to assess their activity in a mixture. To propose a probable mechanism for P. gingivalis cognitive impairments, the TEs balance were analyzed in hippocampus and cortex tissues. Animals were divided into five groups: the control, lactobacilli, P. gingivalis, lactobacilli + P. gingivalis (prevention), and P. gingivalis + lactobacilli group (treatment) groups. The behavioral and histopathological changes were compared among them. Finally, The Trace elements (TEs) levels in the hippocampus and cortex tissues were analyzed. The palatal tissue sections of the P. gingivalis infected rats showed moderate inflammation with dense infiltration of inflammatory cells, a limited area of tissue edema, and vascular congestion. Additionally, passive avoidance learning and spatial memory were impaired. Histopathological tests revealed the presence of Aβ-positive cells in the P. gingivalis group. While the Aβ-positive cells decreased in the treatment group, their formation was inhibited in the preventive group. Administration of a mixture of lactobacilli (orally) effectively mitigated the gingival inflammation, Aβ production, and improved learning and memory functions. Moreover, Zn, Cu, and Mn levels in the hippocampus were dramatically elevated by P. gingivalis infection, whereas lactobacilli mixture mitigated these disruptive effects. The lactobacilli mixture significantly prevented the disruptive effects of P. gingivalis on gingival and brain tissues in rats. Therefore, new formulated combination of lactobacilli may be a good candidate for inhibiting the P. gingivalis infection and its subsequent cognitive effects. The current study aimed to evaluate the effects of a lactobacilli mixture to manage the disruptive effects of P. gingivalis infection on memory.

Metabolite Profiling and Integrated Network Pharmacology Based Mechanism of Benincasa hispida (Thunb.) Cogn. Fruit Against Non-insulin-Dependent Diabetes Mellitus.

Benincasa hispida (Thunb.) Cogn. (Cucurbitaceae) is an essential food plant in India possessing antihyperglycemic and antihyperlipidemic activities. The objective included comparative estimation of α-glucosidase and α-amylase enzyme inhibition potential of B. hispida fractions prepared by microwave-assisted extraction and prediction of metabolite interaction against non-insulin-dependent diabetes mellitus by metabolite profiling based network pharmacology analysis. A validated microwave-assisted extraction method was employed to obtain different fractions of B. hispida fruits. The invitro enzyme assay was done with p-nitrophenyl-α-D-glucopyranoside and acarbose as standard to evaluate antidiabetic potential. The phytomolecules present in the active fraction wereidentified by UHPLC-QToF-MS/MS analysis. Network pharmacology analysis gave possible gene and disease association, combination synergy network, and predicted probable mechanism of action. The highest enzyme inhibition potential (IC50) was shown by the ethyl acetate fraction (0.546 ± 0.17 mg/mL and 1.134 ± 0.42 mg/mL) compared to acarbose (0.298 ± 0.08 mg/mL and 0.532 ± 0.38 mg/mL), respectively, for α-glucosidase and α-amylase addressing the potential role in ameliorating non-insulin-dependent diabetes mellitus. Metabolite profiling resulted in the identification of 17 metabolites, and a synergy between the identified molecules suggested multimolecule action in the amelioration of non-insulin-dependent diabetes mellitus through insulin resistance pathway, AMPK signaling pathway, PPAR signaling pathway, and PI3K-Akt signaling pathway. Combination synergy of identified molecules was observed through a multitarget approach to manage non-insulin-dependent diabetes mellitus. Polyphenol-enriched fraction of B. hispida fruits and identified phytocompounds ameliorate non-insulin-dependent diabetes mellitus. Thus, enriched extract of B. hispida can be further investigated in order to develop high-quality, safe, and effective products for the management of non-insulin-dependent diabetes mellitus.

The interplay of oxidative stress, apoptotic signaling, and impaired mitochondrial function in the pyrethroid-induced cardiac injury: Alleviative role of curcumin-loaded chitosan nanoparticle

This study assessed the consequence of exposure to a pyrethroid insecticide, fenpropathrin (FPN), on the heart and the probable underlying mechanisms in rats. Moreover, the probable protective effect of curcumin-loaded chitosan nanoparticles (CMN-CNP) was evaluated. Forty male Sprague Dawley rats were distributed into four groups orally given corn oil, CMN-CNP (50 mg/kg b.wt), FPN (15 mg/kg b.wt), or CMN-CNP + FPN for 60 days. The results revealed that FPN exposure increased serum cardiac damage indicators. In addition, a substantial increase in the reactive oxygen species and malondialdehyde content but reduced enzymatic and non-enzymatic antioxidants and altered architecture was recorded in the cardiac tissue of FPN-exposed rats. Additionally, a significant down-regulation of expression of the mitochondrial complexes I–V, mitochondrial dynamics, and antioxidants-related genes but up-regulation of apoptosis-related genes was detected in the FPN-exposed group. Immunofluorescence analyses revealed higher amounts of the harmful protein 4-hydroxynonenal in the heart tissue of FPN-exposed rats. Nevertheless, the earlier disturbances were significantly rescued in the FPN + CMN-CNP treated group. Conclusively, our findings reported the cardiotoxic activity of FPN and the involvement of several mitochondrial imbalances as a probable underlying mechanism. Also, the study findings proved the efficacy of CMN-CNP in combating FPN cardiotoxic effects.

A novel maximum likelihood based probabilistic behavioral data fusion algorithm for modeling residential energy consumption.

The current research effort is focused on improving the effective use of the multiple disparate sources of data available by proposing a novel maximum likelihood based probabilistic data fusion approach for modeling residential energy consumption. To demonstrate our data fusion algorithm, we consider energy usage by fuel type variables (for electricity and natural gas) in residential dwellings as our dependent variable of interest, drawn from residential energy consumption survey (RECS) data. The national household travel survey (NHTS) dataset was considered to incorporate additional variables that are not available in the RECS data. With a focus on improving the model for the residential energy use by fuel type, our proposed research provides a probabilistic mechanism for appropriately fusing records from the NHTS data with the RECS data. Specifically, instead of strictly matching records with only common attributes, we propose a flexible differential weighting method (probabilistic) based on attribute similarity (or dissimilarity) across the common attributes for the two datasets. The fused dataset is employed to develop an updated model of residential energy use with additional independent variables contributed from the NHTS dataset. The newly estimated energy use model is compared with models estimated RECS data exclusively to see if there is any improvement offered by the newly fused variables. In our analysis, the model fit measures provide strong evidence for model improvement via fusion as well as weighted contribution estimation, thus highlighting the applicability of our proposed fusion algorithm. The analysis is further augmented through a validation exercise that provides evidence that the proposed algorithm offers enhanced explanatory power and predictive capability for the modeling energy use. Our proposed data fusion approach can be widely applied in various sectors including the use of location-based smartphone data to analyze mobility and ridehailing patterns that are likely to influence energy consumption with increasing electric vehicle (EV) adoption.

Rutin reduces inflammation and fibrosis via TGF-β/SMAD pathways in IgA nephropathy induced rats.

Rutin is a flavonoid glycoside obtained from the plant Ruta graveolens. It was known to have immunosuppressant activities. This study was focused on effect of rutin against immunoglobulin A (IgA) nephropathy. IgA nephropathy was induced in Sprague-Dawley rats with various inducing agents described in text. During the later part of the induction phase, rutin was administered. Control group rats did not receive any treatment or inducing agent, induced group rats received only the inducing agents, whereas treatment group received the inducing agents as well as rutin. During the study, various biochemical parameters pertaining to kidney function were evaluated and also, the expression of proteins and cytokines responsible for inflammation and fibrosis were assessed. The effect of rutin in IgA nephropathy was promising as treatment with rutin reduced the deposition of IgA in the glomeruli of rats. Along with this we also tried to establish the probable mechanism of action of rutin and based on the summary of the results it was concluded that rutin reduced the inflammation and fibrosis related to IgA nephropathy by inhibiting the TGF-β/SMAD pathways and ultimately reducing the expression of α-smooth muscle actin (α-SMA). Comprehending all the above consideration, it may be safely said that that rutin alleviated inflammation and also fibrosis mediated by IgA, by suppressing the transforming growth factor-β (TGF-β) activities through suppressor of mothers against decapentaplegic pathways and reduced the epithelial-to-mesenchymal transition by downregulating the α-SMA which is a marker for fibrosis.

Ameliorative Effects of Essential Oils on Diabetes Mellitus: A Review.

Diabetes mellitus (DM) is a metabolic disorder and is responsible for the death of more than 4.2 million people in 2019. Synthetic drugs for DM like metformin have been reported to induce numerous complications and side effects. Reports suggested that essential plant oil has been used as an herbal remedy to lower blood glucose levels. Essential oils (EOs) are complex combinations of small molecules obtained from plants via the process of steam distillation and several solvents. EOs have already shown great efficacy as antimicrobials, anti-inflammatory, hepatoprotective, and anti-hypertensive. This review aims to summarize some potential EOs that have been reported to have anti-diabetic activity both in preclinical and clinical aspects while summarizing the probable mechanism of action. The authors went through a vast number of articles from various scientific databases like Google Scholar, PubMed, and Web of Science. It was found that EO from a total of 20 plants has been pre-clinically investigated to have anti-diabetic potential. Besides this, clinical studies have reported the antidiabetic efficacy of EOs from Nigella sativa and Cuminum cyminum at different concentrations. Bioactive phytoconstituents like carvacrol, thymol, α- pinene, via . obtained from EOs ameliorate DM by inhibiting α-GLUC, α-amylase, lipase enzymes and increasing GLUT-4 expression, AKT phosphorylation, via . Although fewer in number, EOs from plant sources have demonstrated significant efficacy in DM. Proper elucidation of the anti-diabetic efficacy of the EOs may open up new avenues for drug discovery and development subjected to clinical studies.

Utilizing Fe2O3-β-CD magnetic nanocomposite for efficient removal of MG dye and Gunner 500 pesticide from wastewater

Among various techniques used for wastewater treatment, photocatalysis is one of the most preferred technique. Here, synthesis of a magnetic β-Cyclodextrin (β-CD) based Fe2O3 nanocomposite was carried out. The characterization of the synthesized materials were carried out by using P-XRD, TGA-DTA, FT-IR, PL, DRS, XPS,TEM and SEM-EDAX to study their different properties. Model pollutants Malachite green (MG) dye and Gunner 500 pesticide were selected for photocatalytic activity. These model pollutants were analysed in presence of Fe2O3 and Fe2O3-β-CD under visible light. Performance was monitored through measuring removal efficiency using UV–Visible spectrophotometer. 89.4 and 88.0 % degradation was observed with MG in 120 min and Gunner 500 in 100 min. Photocatalytic degradation efficiency was observed with initial pollutant concentration MG (10 mg L−1) and Gunner 500 (10 mg L−1) at neutral pH value. Reaction kinetics was measured and first order rate law is applicable with both pollutants. Probable mechanism and degradation pathway of pollutants were proposed. COD also favours degradation and demineralization. Reusability was also studied.

Fabrication of core–shell nickel ferrite@polypyrrole composite for broadband and efficient electromagnetic wave absorption

Herein, nickel ferrite@polypyrrole (NiFe2O4@PPy) composite was prepared by a simple two-step route of solvothermal synthesis and in-situ oxidation polymerization reaction. The results of micromorphology analysis showed that the obtained NiFe2O4@PPy composite had a unique core–shell structure, good magnetic performance and electrical conductivity. Furthermore, the as-prepared magnetic/conductive NiFe2O4@PPy composite exhibited notably enhanced electromagnetic wave (EMW) absorption performance than pure NiFe2O4 and PPy. When the filling ratio was 17.5 wt% and the matching thickness was 2.24 mm, the optimal minimum reflection loss (RLmin) of −56.25 dB and a broad effective absorption bandwidth (EAB) of 5.2 GHz were achieved for NiFe2O4@PPy composite. With slightly increasing the matching thickness to 2.6 mm, the maximum EAB of 7.12 GHz could be reached. Additionally, the probable EMW absorption mechanism was elucidated. Therefore, this work could provide a valuable reference for the preparation of magnetic ferrite/conductive polymer composites as broadband and high-efficiency EMW absorbers.

Angular anisotropy of hard x rays produced by laboratory atmospheric discharges

The temporal, spectral, and angular characteristics of the x-ray emissions (photons with energies within 5–1000 keV) are exhaustively investigated during the discharge formation at voltages up to 1 MV in approximately 55 cm air gaps. The temporal correlations between the x-ray emissions and discharge voltage and current waveforms are established. The evolution of the discharge plasma structures developing in the time periods of the x-ray generation is traced with a nanosecond resolution. Based on statistical data, theoretical analysis, and estimates the regularities in the x-ray emission characteristics are revealed together with their relationship with the ionization processes occurring in the gas-discharge medium. On the basis of the obtained experimental data, the probable x-ray generation mechanisms are discussed. The findings can provide a deeper understanding of the physics behind the sources of hard x rays arising during the development of laboratory and atmospheric discharges.

An Update on Clinically Evaluated Medicinal Plants for Psoriasis Management.

Psoriasis is a prevalent inflammatory disease affecting almost 0.5-5 % of the world population. Multiple treatment approaches have been developed to manage psoriasis so far. Although concerns exist in the long-term usage of conventional and biological agents in terms of safety, effectiveness, expensiveness, and tolerability, complementary and alternative medicine (CAM) is a promising point of view for future psoriasis management. In this study, databases including Scopus, PubMed, Google Scholar, and Web of Science were searched for relevant literature on herbal medications clinically evaluated for psoriasis, especially those originating from traditional medicine. About 40 relevant papers were selected by March 2023. Most of the studies were clinical trials on poly-herbal formulations from traditional Chinese medicine (TCM). There are controversial results regarding the efficacy of these herbal formulations in psoriasis mainly due to the variation in the study design. Moreover, the probable protective mechanisms and responsible herbal metabolites of these formulations are summarized. There is a global need for more in-vitro and in-vivo studies based on the standard protocols in terms of the evaluation of the safety and efficacy of topical/ systemic herbal preparations for psoriasis.

Does Peer Socialization Within Cohorts Foster Political Attitudes? A Longitudinal Study of Elite Business Students

AbstractThe association between higher education and political attitudes is well-recognized, and research suggests that socialization amongst peers is one of the most probable mechanisms explaining a possible attitudinal change. However, identifying a socialization effect is difficult due to self-selection mechanisms and limitations in data availability. This article empirically investigates the underlying peer socialization by employing a longitudinal network study of undergraduate students in Swedish and Finnish top-ranked business schools (N = 2651). The study tests the hypotheses that (1) attitudes within a cohort converge over time, and (2) socially embedded students experience more attitudinal change during their studies than students who do not engage with their peers. The paper leverages the Covid-19 pandemic as an exogenous shock that severely affected the networking dynamics of specific cohorts since it moved their education off campus. It is thereby among the first studies to directly test the relationship between socializing behaviors within higher education and political attitudes using both subjective and objective measurements. Contrary to previous conjectures, the findings challenge a general socialization mechanism to foster political attitudes. Instead, they point toward the importance of self-selection mechanisms in studies of higher education and for the specific student composition.

MPSA-Conformer-CTC/Attention: A High-Accuracy, Low-Complexity End-to-End Approach for Tibetan Speech Recognition.

This study addresses the challenges of low accuracy and high computational demands in Tibetan speech recognition by investigating the application of end-to-end networks. We propose a decoding strategy that integrates Connectionist Temporal Classification (CTC) and Attention mechanisms, capitalizing on the benefits of automatic alignment and attention weight extraction. The Conformer architecture is utilized as the encoder, leading to the development of the Conformer-CTC/Attention model. This model first extracts global features from the speech signal using the Conformer, followed by joint decoding of these features through CTC and Attention mechanisms. To mitigate convergence issues during training, particularly with longer input feature sequences, we introduce a Probabilistic Sparse Attention mechanism within the joint CTC/Attention framework. Additionally, we implement a maximum entropy optimization algorithm for CTC, effectively addressing challenges such as increased path counts, spike distributions, and local optima during training. We designate the proposed method as the MaxEnt-Optimized Probabilistic Sparse Attention Conformer-CTC/Attention Model (MPSA-Conformer-CTC/Attention). Experimental results indicate that our improved model achieves a word error rate reduction of 10.68% and 9.57% on self-constructed and open-source Tibetan datasets, respectively, compared to the baseline model. Furthermore, the enhanced model not only reduces memory consumption and training time but also improves generalization capability and accuracy.

Modulating the chemical environment of Ni2+ for the oxidative dehydrogenation of ethane: The formation of LAS(Al3+/Ga3+)-Ni-OH site

The oxidative dehydrogenation of ethane to ethylene (ODHE) usually suffers from the issues of ethane conversion-ethylene selectivity seesaw. Herein, a series of alumina-supported Ni and Ga catalysts with different molar ratios of Ni to Ga were synthesized by facile impregnation method constructing the Lewis acid site (LAS) strategy to obtain great ethylene selectivity (97 %). The variation of Ni:Ga ratio adjusted the ionic substitution ability, redox ability and acidity, thus regulate the chemical environment of Ni2+ to the formation of LAS(Al3+/Ga3+)-Ni-OH structure, which was proposed to be the active site for selective oxidation of ethane to ethylene, as proved by H2-TPR, ToF-SIMS, quasi in-situ XPS and in-situ FTIR. Moreover, the probable mechanism of ODHE reaction was proposed that C2H6 molecules were mainly adsorbed on LAS sites and activated on Ni-OH site of the catalyst. The pulse test further suggested that O- was mainly associated with the generation of CO2 and Ni(2-n)+ was connected with the production of CH4. It is highlighted that adjusting the Ni-related species and oxygen species on the catalyst surface are crucial to further improve the ethylene selectivity.

PMformer: A novel informer-based model for accurate long-term time series prediction

When applied to long-term time series forecasting, Informer struggles to capture temporal dependencies effectively, leading to suboptimal forecasting accuracy. To address this issue, we propose PMformer, a novel model based on Informer for long-term time series prediction. First, we introduce a probabilistic patch sampling attention mechanism that utilizes a patch-based strategy to compute attention scores within randomly selected sequence patches. This localized approach enhances the model's capability to capture local temporal dependencies, allowing it to better understand and process critical local features in time series while reducing computational complexity. Additionally, we propose a multi-scale scaling sparse attention technique that balances attention distribution by combining coarse- and fine-grained attention scores, thereby improving the model's ability to capture global sequence information. Finally, we design a dilated causal pooling layer and a multilayer perceptual cross self-attention decoder to further enhance the model's prediction accuracy by capturing key information in long-term correlations and precisely focusing on sequences. We conducted experiments on both multivariate and univariate time series forecasting tasks. The results show that PMformer outperforms six baseline models, including PatchTST and FEDformer, in terms of MAE and MSE metrics. This demonstrates its superior ability to capture temporal dependencies, achieving more accurate predictions.

The Therapeutic Effects of Lycopene Against Experimental Giardiasis in Mice

ABSTRACTGiardia duodenalis is a protozoan parasite that infects approximately one billion people worldwide. In this study, the effects of lycopene on experimental giardiasis in mice were investigated by evaluating cyst shedding rate, weight changes, duodenal antioxidant status, and histopathological alteration. Ninety‐five male mice aged four to six weeks were divided into six groups of 15 and one group of 5 as the negative control. All mice were infected with 2 × 105 Giardia duodenalis (B genotype) cysts except for the negative control. The treatment groups were treated with metronidazole, mixed lycopene‐metronidazole, and 5, 10, and 20 mg/kg lycopene for 7 days. The mice treated with lycopene 20 and mixed lycopene‐metronidazole had no cyst shedding from the 7th day of treatment. The mildest lesions were observed in the mixed lycopene‐metronidazole group. Results showed that treatment with mixed lycopene‐metronidazole significantly increased TAC and decreased MDA levels as compared with the positive control. It seems that the antigiardial effect of lycopene is related to its antioxidant properties. Nevertheless, direct effect of lycopene on Giardia and its probable mechanism remain to be investigated.

High‐temperature deformation and consolidation of polycrystalline α‐SiC by spark plasma sintering

AbstractThe main objective of this investigation is the consolidation and flexural strength of alpha silicon carbide ceramics produced without additives by spark plasma sintering. Using the design of the experiment method, we optimized temperature and dwell to achieve fully dense silicon carbide bulks. The consolidation process of silicon carbide was analyzed similarly to the creep of bulk ceramics, and it was determined that the activation energy for the densification process was 596 ± 39 kJ/mol, while the stress exponent n was below 2. Bulk additive‐free silicon carbide ceramics gradually increased flexural strength as the temperature rose to 2000°C. The flexural strength at 2000°C was influenced by the loading rate, and under 2.5 mm/min, it reached a maximum of 2.08 GPa. To explain this phenomenon, a deformation mechanisms map was created, indicating that diffusion creep is the most probable mechanism for the strain sensitivity of SiC at 2000°C. Transmission electron microscopy indicated a substantial rise in twin density within the α‐SiC grains at 2000°C, indicating the activation of a previously unreported self‐reinforcing mechanism.

Diacerein and myo-inositol alleviate letrozole-induced PCOS via modulation of HMGB1, SIRT1, and NF-kB: A comparative study.

Polycystic ovary syndrome (PCOS) is the most prevalent cause of anovulatory infertility in women. Myo-inositol supplementation has displayed effectiveness in curing PCOS patients. Diacerein, an anti-inflammatory medication, has not been extensively studied in the context of reproductive disorders. This study aimed to compare the role of myo-inositol and diacerein in PCOS and the probable mechanisms mediating their actions. Forty adult female rats were divided equally into the following: control, PCOS, PCOS+Myo-inositol, and PCOS+Diacerein groups. Rats were subjected to arterial blood pressure (ABP), electromyography (EMG), and uterine reactivity measurements. Blood samples were collected for measuring hormonal assays, glycemic state, lipid profile, oxidative stress, and inflammatory markers. Ovaries and uteri were extracted for histological examination, including hematoxylin and eosin staining, Masson's trichrome staining, immunohistochemistry, and rt-PCR analysis of ovarian tissues. PCOS was associated with significant increases in ABP, uterine frequency and amplitude of contraction, luteinizing hormone, testosterone, lipid, glycemic and inflammatory markers, malondialdehyde, high-mobility group box 1 (HMGB1), nuclear factor kappa (NF-kB), ovarian fibrosis, and endometrial thickening. In contrast, there was a significant reduction in follicular stimulating hormone, reduced glutathione, and Sirtuin 1 (SIRT1) when compared with control group. Both myo-inositol and diacerein counteract PCOS changes; but diacerein's effectswere superiorto myo-inositol's for all parameters, except for lipid and glycemic markers. Diacerein possessed anti-inflammatory properties and showed significant efficacy in mitigating the endocrinal, metabolic, and ovarian structural alterations linked to PCOS. Its beneficial actions likely stem from reducing oxidative stress, dyslipidemia, and hyperglycemia, potentially through the modulation of HMGB1, SIRT1, and NF-kB pathways.