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Organic inhibitors are valuable tools for preventing the corrosion of metals. Consequently, the effectiveness of 42-(bis((3,5-dimethyl-1H-pyrazol-1-yl)methyl)amino)anthracene-9,10-dione, and its corrosion resistance for mild steel in an acidic solution of 1M HCl, was assessed. In addition to analyzing the morphological surface properties and using theoretical techniques, the current study employed polarization curves and electrochemical impedance spectroscopy for analysis. Quantum chemical calculations, including DFT calculations at B3LYP 6-311G (d,p) and Monte Carlo simulations, were used to establish a link between the electronic characteristics of the compound and the experimental findings. The results demonstrated that these compounds were efficient corrosion inhibitors, with an inhibition efficiency of 96% as determined by the EIS method. To understand the corrosion resistance behavior of the anthraquinone inhibitor, the surface morphology of mild steel was examined using scanning electron microscopy in the presence and absence of the inhibitor. It was also found that the inhibitor functions as a mix-type inhibitor. Finally, a strong correlation was discovered between the experimental and theoretical outcomes. [ABSTRACT FROM AUTHOR]

One of the main abiotic stresses that affect plant development and lower agricultural productivity globally is salt in the soil. Organic amendments, such as compost and biochar can mitigate the opposing effects of soil salinity (SS) stress. The purpose of this experiment was to look at how tomato growth and yield on salty soil were affected by mineral fertilization and manure-biochar compost (MBC). Furthermore, the study looked at how biochar (organic amendments) work to help tomato plants that are stressed by salt and also a mechanism by which biochar addresses the salt stress on tomato plants. Tomato yield and vegetative growth were negatively impacted by untreated saline soil, indicating that tomatoes are salt-sensitive. MBC with mineral fertilization increased vegetative growth, biomass yield, fruit yield, chlorophyll, and nutrient contents, Na/K ratio of salt-stressed tomato plants signifies the ameliorating effects on tomato plant growth and yield, under salt stress. Furthermore, the application of MBC with mineral fertilizer decreased H2O2, but increased leaf relative water content (RWC), leaf proline, total soluble sugar, and ascorbic acid content and improved leaf membrane damage, in comparison with untreated plants, in response to salt stress. Among the composting substances, T7 [poultry manure-biochar composting (PBC) (1:2) @ 3 t/ha + soil-based test fertilizer (SBTF)] dose exhibited better-improving effects on salt stress and had maintained an order of T7 > T9 > T8 > T6 in total biomass and fruit yield of tomato. These results suggested that MBC might mitigate the antagonistic effects of salt stress on plant growth and yield of tomatoes by improving osmotic adjustment, antioxidant capacity, nutrient accumulation, protecting photosynthetic pigments, and reducing ROS production and leaf damage in tomato plant leaves. [ABSTRACT FROM AUTHOR]

Field pea (Pisum sativum L.) needs improvement to increase productivity due to its high price and demand. However, the incidence of powdery mildew (PM) disease limits its production. This study aimed to analyze the diversity of qualitative and quantitative traits against powdery mildew resistance by utilizing cluster and principal component analysis to explore PM resistance high-yield potential field peas. Shannon–Weaver's diversity index (Hʹ) displayed high intra-genotype diversity for quantitative and qualitative aspects. Heterogeneity was identified for resistance against powdery mildew infections. Eighty-five genotypes were divided into five groups using Mohalanobis generalized distance (D2) statistics. The highest inter-cluster D2 value was observed between clusters 2 and 3 (11.89) while the lowest value was found between clusters 3 and 4 (2.06). Most of the genotypes had noticeable differences, so these could be employed in a crossing scheme. Twelve genotypes were extremely resistant, 29 genotypes were resistant, 25 genotypes were moderately resistant, 18 genotypes were fairly susceptible, and 1 genotype was susceptible to powdery mildew disease. Among 29 resistant genotypes, BFP77, BFP74, BFP63, BFP62, BFP43, and BFP80 were high yielders and, could be used directly and/or transferred through hybridization to high-yielding disease-susceptible genotypes. Among the 25 moderately resistant genotypes, BFP78, BFP45, BFP79, and BFP48 were found to be high yielders. In principal component analysis (PCA), the first four PCs with Eigen values > 1 accounted for 88.4% variability for quantitative traits. Clustering sorted genotypes into five groups, where groups 1 to 5 assembled 37, 28, 1, 8, and 11 genotypes, respectively. Genotypes of cluster 4 were identified as high yielders with its attributes. Pearson correlation significantly and positively correlated across all traits except for PM. This variation suggested that there is a mechanism to select promising genotypes for field pea breeding. Considering all features, BFP78, BFP77, BFP74, BFP63, BFP62, BFP45, BFP79, and BFP80 could be preferred as high yielders and PM resistance owing to longer pod lengths, seeds per pod and pods per plant. [ABSTRACT FROM AUTHOR]

Climate change has brought an alarming situation in the scarcity of fresh water for irrigation due to the present global water crisis, climate variability, drought, increasing demands of water from the industrial sectors, and contamination of water resources. Accurately evaluating the potential of future rice genotypes in large-scale, multi-environment experiments may be challenging. A key component of the accurate assessment is the examination of stability in growth contexts and genotype-environment interaction. Using a split-plot design with three replications, the study was carried out in nine locations with five genotypes under continuous flooding (CF) and alternate wet and dry (AWD) conditions. Utilizing the web-based warehouse inventory search tool (WIST), the water status was determined. To evaluate yield performance for stability and adaptability, AMMI and GGE biplots were used. The genotypes clearly reacted inversely to the various environments, and substantial interactions were identified. Out of all the environments, G3 (BRRI dhan29) had the greatest grain production, whereas G2 (Binadhan-8) had the lowest. The range between the greatest and lowest mean values of rice grain output (4.95 to 4.62 t ha-1) was consistent across five distinct rice genotypes. The genotype means varied from 5.03 to 4.73 t ha-1 depending on the environment. In AWD, all genotypes out performed in the CF system. With just a little interaction effect, the score was almost zero for several genotypes (E1, E2, E6, and E7 for the AWD technique, and E5, E6, E8, and E9 for the CF method) because they performed better in particular settings. The GGE biplot provided more evidence in support of the AMMI study results. The study's findings made it clear that the AMMI model provides a substantial amount of information when evaluating varietal performance across many environments. Out of the five accessions that were analyzed, one was found to be top-ranking by the multi-trait genotype ideotype distance index, meaning that it may be investigated for validation stability measures. The study's findings provide helpful information on the variety selection for the settings in which BRRI dhan47 and BRRI dhan29, respectively, performed effectively in AWD and CF systems. Plant breeders might use this knowledge to choose newer kinds and to design breeding initiatives. In conclusion, intermittent irrigation could be an effective adaptation technique for simultaneously saving water and mitigating GHG while maintaining high rice grain yields in rice cultivation systems. [ABSTRACT FROM AUTHOR]

Purpose: Moderate-to-severe hallux rigidus is a debilitating pathology that is optimally treated with surgical intervention. Arthrodesis produces reliable clinical outcomes but is limited by restriction in 1st metatarsophalangeal joint range of motion. The advent of polyvinyl alcohol hydrogel (PVA) implants have produced early promise based on initial trials, but more recent studies have called into question the efficacy of this procedure. The purpose of this systematic review was to evaluate the clinical and radiological outcomes following the use of PVA for hallux rigidus. Methods: The MEDLINE, EMBASE and Cochrane library databases were systematically reviewed using the preferred reporting items for systematic reviews and meta-analyses guidelines. 18 studies were included. Results: In total, 1349 patients (1367 feet) underwent PVA at a weighted mean follow-up of 24.1 ± 11.1 months. There were 168 patients (169 feet) included in the cheilectomy cohort and 322 patients (322 feet) included in the arthrodesis cohort. All 3 cohorts produced comparable improvements in subjective clinical outcomes. Postoperative imaging findings in the PVA cohort included joint space narrowing, peri-implant fluid, peri-implant edema and erosion of the proximal phalanx. The complication rate in the PVA cohort, cheilectomy cohort and arthrodesis cohort was 27.9%, 11.8% and 24.1%, respectively. The failure rates in the PVA cohort, cheilectomy cohort and arthrodesis cohort was 14.8%, 0.3% and 9.0%, respectively. Conclusion: This systematic review demonstrated that PVA produced a high complication rate (27.9%) together with concerning postoperative imaging findings at short-term follow-up. In addition, a moderate failure rate (14.8%) and secondary surgical procedure rate (9.5%) was noted for the PVA cohort. The findings of this review calls into question the efficacy and safety of PVA for the treatment of hallux rigidus. Level of evidence: IV. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this systematic review and meta-analysis was to evaluate the prevalence and clinical significance of heterotopic ossification (HO) following total ankle replacement (TAR). Methods: During August 2023, the PubMed, Embase and Cochrane library databases were systematically reviewed to identify clinical studies reporting HO following TAR. Data regarding surgical characteristics, pathological characteristics, subjective clinical outcomes, ankle range of motion, radiographic outcomes, reoperation rates were extracted and analysed. Results: Twenty-seven studies with 2639 patients (2695 ankles) at a weighed mean follow-up time of 52.8 ± 26.9 months were included. The pooled prevalence rate was 44.6% (0.25; 0.66). The implant with the highest rate of HO was the INBONE I (100%) and BOX (100%) implants. The most common modified Brooker staging was grade 1 (132 patients, 27.0%). Random effects models of standardized mean differences found no difference in American orthopedic foot and ankle society (AOFAS) scores, visual analog scale scores (VAS) and ankle range of motion (ROM) between patients with HO and patients without HO. Random effects models of correlation coefficients found no correlation between AOFAS, VAS and ROM and the presence of HO. The surgical intervention rate for symptomatic HO was 4.2%. Conclusion: This systematic review and meta-analysis found that HO is a common finding following TAR that is not associated with inferior clinical outcomes. Surgical intervention was required only for moderate-to-severe, symptomatic HO following TAR. This study is limited by the marked heterogeneity and low level and quality of evidence of the included studies. Further higher quality studies are warranted to determine the precise prevalence and impact of HO on outcomes following TAR. Level of evidence III.: [ABSTRACT FROM AUTHOR]

Uneven rainfall and high temperature cause drought in tropical and subtropical regions which is a major challenge to cultivating summer mung bean. Potassium (K), a major essential nutrient of plants can alleviate water stress (WS) tolerance in plants. A field trial was executed under a rainout shelter with additional K fertilization including recommended K fertilizer (RKF) for relieving the harmful impact of drought in response to water use efficiency (WUE), growth, yield attributes, nutrient content, and yield of mung bean at the Regional Agricultural Research Station, BARI, Ishwardi, Pabna in two successive summer season of 2018 and 2019. Drought-tolerant genotype BMX-08010-2 (G1) and drought-susceptible cultivar BARI Mung-1 (G2) were grown by applying seven K fertilizer levels (KL) using a split-plot design with three replications, where mung bean genotypes were allotted in the main plots, and KL were assigned randomly in the sub-plots. A considerable variation was observed in the measured variables. Depending on the different applied KL and seed yield of mung bean, the water use efficiency (WUE) varied from 4.73 to 8.14 kg ha−1 mm−1. The treatment applying 125% more K with RKF (KL7) under WS gave the maximum WUE (8.14 kg ha−1 mm−1) obtaining a seed yield of 1093.60 kg ha−1. The treatment receiving only RKF under WS (KL2) provided the minimum WUE (4.73 kg ha−1 mm−1) attaining a seed yield of 825.17 kg ha−1. Results showed that various characteristics including nutrients (N, P, K, and S) content in stover and seed, total dry matter (TDM) in different growth stages, leaf area index (LAI), crop growth rate (CGR), root volume (RV), root density (RD), plant height, pod plant−1, pod length, seeds pod−1, seed weight, and seed yield in all pickings increased with increasing K levels, particularly noted with KL7. The highest grain yield (32.52%) was also obtained from KL7 compared to lower K with RKF. Overall, yield varied from 1410.37 kg ha−1 using 281 mm water (KL1; well-watered condition with RKF) to 825.17 kg ha−1 using 175 mm water (KL2). The results exhibited that the application of additional K improves the performance of all traits under WS conditions. Therefore, mung beans cultivating under WS requires additional K to diminish the negative effect of drought, and adequate use of K contributes to accomplishing sustainable productivity. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this systematic review was to evaluate the clinical and radiological outcomes together with the complication rates and failure rates at short‐term follow‐up following particulated juvenile cartilage allograft (PJCA) for the management of osteochondral lesions of the talus (OLT). Methods: During October 2023, the PubMed, Embase and Cochrane library databases were systematically reviewed to identify clinical studies examining outcomes following PJCA for the management of OLTs. Data regarding study characteristics, patient demographics, lesion characteristics, subjective clinical outcomes, radiological outcomes, complications and failures were extracted and analysed. Results: Twelve studies were included. In total, 241 patients underwent PJCA for the treatment of OLT at a weighted mean follow‐up of 29.0 ± 24.9 months. The weighted mean lesion size was 138.3 ± 59.6 mm2. Prior surgical intervention was recorded in seven studies, the most common of which was microfracture (65.9%). The weighted mean American Orthopaedic Foot and Ankle Society score improved from a preoperative score of 58.5 ± 3.2 to a postoperative score of 83.9 ± 5.3. The weighted mean postoperative magnetic resonance observation of cartilage repair tissue (MOCART) score was 48.2 ± 3.3. The complication rate was 25.2%, the most common of which was allograft hypertrophy (13.2%). Thirty failures (12.4%) were observed at a weighted mean time of 9.8 ± 9.6 months following the index procedure. Conclusion: This systematic review demonstrated a moderate improvement in subjective clinical outcomes following PJCA for the treatment of OLT at short term follow‐up. However, postoperative MOCART scores were reported as poor. In addition, a high complication rate (25.2%) and a high failure rate (12.4%) at short‐term follow‐up was observed, calling into question the efficacy of PJCA for the treatment of large OLTs. In light of the available evidence, PJCA for the treatment of large OLTs cannot be currently recommended. Level of Evidence: Level IV. [ABSTRACT FROM AUTHOR]

The assembly of cluster-based π-stacked porous supramolecular frameworks presents daunting challenges, including the design of suitable cluster building units, control of the sufficient C-H···π interactions, trade-off between structural dynamics and stability as well as understanding the resulting collective properties. Herein, we report a cluster-based C-H···π interaction-stacked porous supramolecular framework, namely, Cu12a-π, consisting of Cu12 nanocluster as a 6-connected node, which is further propagated to a dynamic porous supramolecular frameworks via dense intralayer C-H···π interactions, yielding permanent porosity. In addition, Cu12a-π can be transformed into cluster-based nonporous adaptive crystals (Cu12b-NACs) via ligand-exchange following a dissociation-reassembly mechanism. Moreover, Cu12a-π can efficiently remove 97.2% of iodine from saturated iodine aqueous solutions with a high uptake capacity of 2.96 g·g−1. These prospective results positioned at cluster-based porous supramolecular framework and enlighten follow-up researchers to design and synthesize such materials with better performance. The assembly of cluster-based π-stacked porous supramolecular frameworks presents daunting challenges. Here, the authors report a dynamic and transformable supramolecular framework based on Cu12 cluster and C-H···π-stacking with permanent porosity [ABSTRACT FROM AUTHOR]

Purpose: To systematically review and evaluate the current meta-analyses for the treatment of acute Achilles tendon rupture (AATR). This study can provide clinicians with a clear overview of the current literature to aid clinical decision-making and the optimal formulation of treatment plans for AATR. Methods: Two independent reviewers searched PubMed and Embase on June 2, 2022 based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Assessment of evidence was twofold: level of evidence (LoE) and quality of evidence (QoE). LoE was evaluated using published criteria by The Journal of Bone and Joint Surgery and the QoE by the Assessing the Methodological Quality of Systematic Reviews (AMSTAR) scale. Pooled complication rates were highlighted for significance in favour of one treatment arm or no significance. Results: There were 34 meta-analyses that met the eligibility criteria, with 28 studies of LoE 1, and the mean QoE was 9.8 ± 1.2. Significantly lower re-rupture rates were reported with surgical (2.3–5%) versus conservative treatment (3.9–13%), but conservative treatment was favoured in terms of lower complication rates. The re-rupture rates were not significantly different between percutaneous repair or minimally invasive surgery (MIS) compared to open repair, but MIS was favoured in terms of lower complication rates (7.5–10.4%). When comparing rehabilitation protocols following open repair (four studies), conservative treatment (nine studies), or combined (three studies), there was no significant difference in terms of re-rupture or obvious advantage in terms of lower complication rates between early versus later rehabilitation. Conclusion: This systematic review found that surgical treatment was significantly favoured over conservative treatment for re-rupture, but conservative treatment had lower complication rates other than re-rupture, notably for infections and sural nerve injury. Open repair had similar re-rupture rates to MIS, but lower complication rates; however, the rate of sural nerve injuries was lower in open repair. When comparing earlier versus later rehabilitation, there was no difference in re-rupture rates or obvious advantage in complications between open repair, conservative treatment, or when combined. The findings of this study will allow clinicians to effectively counsel their patients on the postoperative outcomes and complications associated with different treatment approaches for AATR. Level of evidence: IV. [ABSTRACT FROM AUTHOR]

Purpose: Acute Achilles tendon ruptures (AATRs) are a common sporting injury, whether for recreational athletes or elite athletes. Prior research has shown returning to physical activity after extended periods of inactivity leads to increased rates of musculoskeletal injuries. The purpose of this study was to investigate rates of acute Achilles' tendon ruptures at a single academic institute in the peri-COVID era, with corollary to the recent NFL season. Methods: A retrospective search was conducted using current procedural terminology to identify the total number of Achilles acute primary repair surgeries performed from years 2017 to 2021. Non-operatively managed AATRs were identified from the same electronic medical record using ICD-10 codes. NFL data were obtained from publicly available sites according to previously validated studies. Results: A total of 588 patients who sustained AATRs and underwent primary surgical repair were identified, primarily men (75.7%, n = 445), with an average age of 43.22 ± 14.4 years. The number and corresponding incidence of AATR repairs per year was: 2017: n = 124 (21.1%), 2018: n = 110 (18.7%), 2019: n = 130 (22.1%), 2020: n = 86 (14.6%), 2021: n = 138 (23.5%), indicating a 7.5% decrease in rate of AATRs from 2019 to 2020, followed by an 8.9% increase in incidence from 2020 to 2021. Within the NFL, the number of AATRs resulting in an injured reserve stint increased every regular season from 2019 to 2020: n = 11 (21.2%), to 2020–2021: n = 17 (32.7%), to this past 2021–2022 season: n = 24 (46.2%). Conclusion: AATR surgeries seem to have increased in 2021 following a 2020 COVID pandemic-induced quarantine for recreational athletes at a single academic institution and for professional athletes in the NFL, although these results are of questionable clinical significance. This provides prognostic information when counseling patients and athletes on return to activity or sport. Level of evidence: Level IV. [ABSTRACT FROM AUTHOR]

Recently, cancer research protocols have introduced clinical-stage spirooxindole-based MDM2 inhibitors. However, several studies reported tumor resistance to the treatment. This directed efforts to invest in designing various combinatorial libraries of spirooxindoles. Herein, we introduce new series of spirooxindoles via hybridization of the chemically stable core spiro[3H-indole-3,2′-pyrrolidin]-2(1H)-one and the pyrazole motif inspired by lead pyrazole-based p53 activators, the MDM2 inhibitor BI-0252 and promising molecules previously reported by our group. Single crystal X-ray diffraction analysis confirmed the chemical identity of a representative derivative. Fifteen derivatives were screened for cytotoxic activities via MTT assay against a panel of four cancer cell lines expressing wild-type p53 (A2780, A549, HepG2) and mutant p53 (MDA-MB-453). The hits were 8h against A2780 (IC50 = 10.3 µM) and HepG2 (IC50 = 18.6 µM), 8m against A549 (IC50 = 17.7 µM), and 8k against MDA-MB-453 (IC50 = 21.4 µM). Further MTT experiments showed that 8h and 8j potentiated doxorubicin activity and reduced its IC50 by at least 25% in combinations. Western blot analysis demonstrated that 8k and 8m downmodulated MDM2 in A549 cells. Their possible binding mode with MDM2 were simulated by docking analysis. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this systematic review was to evaluate both the clinical and radiographic outcomes following supramalleolar osteotomy (SMO) in patients with ankle osteoarthritis, and to analyse the level of evidence (LOE) and quality of evidence (QOE) of the included studies. Methods: A systematic review of the MEDLINE, EMBASE, and Cochrane Library databases was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Studies reporting clinical data following SMO for the treatment of ankle osteoarthritis were included and assessed. The level and quality of evidence of the included studies were also evaluated. Results: Twenty-four studies with 1160 patients (1182 ankles) were included. Overall, 78.8% patients presented with post-traumatic ankle osteoarthritis. The weighted mean AOFAS score improved from 52.6 ± 9.7 (range 33.8–78.4) preoperatively to 78.1 ± 5.7 postoperatively at weighted mean follow-up of 50.4 ± 18.6 months (range 24.5–99.0). The most frequently utilised radiographic parameter was the tibial anterior surface angle, which improved from a preoperative weighted mean of 86.3° ± 5.6° (range 76.0°–102.0°) to a postoperative weighted mean of 89.9° ± 3.7° (range 84.9°–99.6°). The complication rate was 5.1% with non-union as the most commonly reported complication (1.6%). Secondary procedures were carried out in 28.2% of patients, the most common of which was implant and hardware removal (17.6%). The failure rate was 6.8%. Two studies were LOE II, 3 studies were LOE III, and 19 studies were LOE IV. The mean Modified Coleman Methodology Score was 59.3 ± 6.6 and the mean MINORS criteria score of all the included studies was 9.5 ± 3.7. Conclusion: This systematic review demonstrates good clinical and radiological outcomes, together with a low failure rate at mid-term follow-up following supramalleolar osteotomy in patients with ankle osteoarthritis. However, a moderate reoperation rate (28.2%) was reported. A low failure rate (6.8%) was reported, which must be interpreted in light of the shortcomings of the design of the included studies and a relatively short follow-up period. In addition, there is a low level and quality of evidence in the current literature with inconsistent reporting of data which underscores the need for further higher quality research to be conducted. Our review highlights that SMO may be an effective and safe procedure in the setting of early-to-intermediate-stage ankle osteoarthritis. Level of evidence: IV [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the complication rates, continuous functional outcome scores, and return to play data following bone marrow stimulation (BMS) versus biologics ± BMS for the treatment of osteochondral lesion of the talus (OLT). Methods: A systematic review was performed. The PubMed and Embase databases were searched using specific search terms and eligibility criteria according to the PRISMA guidelines. The level of evidence was assessed using published criteria by The Journal of Bone & Joint Surgery, and the quality of evidence using the Modified Coleman Methodology Score. Continuous variables were presented as mean ± standard deviation and categorical variables as frequencies (percentages). Results: BMS versus BMS + hyaluronic acid (HA): no complications in either treatment arm were reported. The mean American Orthopaedic Foot and Ankle Society score was 43.5 to 67.3 points and 44.0 to 72.4 points, respectively. The mean 10 mm Visual Analogue Scale pain score was 7.7 to 3.8 points and 7.5 to 2.5 points, respectively. BMS versus BMS + concentrated bone marrow aspirate (CBMA): the pooled overall complication rate was 17/64 (26.6%) versus 11/71 (15.5%), respectively (non-significant). The pool revision rate was 15/64 (23.4%) versus 6/71 (8.5%), respectively (p = 0.016). There has been a notable poor reporting of complication rates for the use of ADSC and PRP as adjuvant biological therapies to BMS for the treatment of OLT. Conclusion: There was an overall limited comparative clinical evidence of adjuvant biologics with BMS versus BMS alone for the treatment of OLT. BMS + HA and BMS + CBMA can provide superior outcomes, albeit the currently limited evidence. Further studies are warranted to establish the true clinical superiority of the various biologics ± BMS versus BMS alone. These studies must also compare the various biologics against one another to determine, if any, the optimal biologic for OLT. Clinicians should counsel patients accordingly on these findings as required. Level of evidence: Level III. [ABSTRACT FROM AUTHOR]

This paper investigates the free vibration of square plate with side through crack at different angle for six different edge conditions. The six edge conditions are simply supported (SSSS), free (FFFF), Clamped (CCCC), clamped-simply supported (CCSS), clamped-free (CCFF) and simply supported-clamped-free (SCSF). Finite element method has been carried out for the formulation of the cracked plate based on Mindlin plate theory that take into account the shear deformation and rotary inertia. Effect of crack length, orientation of crack and edge conditions on natural frequencies of plate are analysed. Some results obtained in this paper are compared with the published results for SSSS and FFFF edge conditions. Very good agreement between results is observed. Most of the vibration data of side cracked plate for CCCC, CCSS, CCFF and SCSF are new and not reported in literature. These data are important in analysing the frequency based crack detection in plated structure. [ABSTRACT FROM AUTHOR]

The biological activities of some ternary nickel complexes with a Schiff base obtained from 4-dimethylaminobenzaldehyde and 2-aminophenol have been reported. The Schiff base (HL1) acts as a primary ligand whereas, anthranilic acid (HL2), 2-nitroaniline (HL3), alanine (HL4) and histidine (HL5) act as secondary ligand or co-ligand. The anticancer activity of these compounds was studied against human colon carcinoma (HCT-116), human hepatocellular liver carcinoma (HEPG-2) and human breast carcinoma (MCF-7) cell lines. As per the results, the compounds were active against the cell lines. The antioxidant activity of the same compounds was evaluated using DPPH (1,1-diphenyl-2-picryl-hydrazyl) radical scavenging and compared with ascorbic acid. The DFT computations for these compounds were made to understand the bonding mode by a GAUSSIAN 09 program. Moreover, a docking analysis using Autodock 4.2 software package was carried out against the tyrosine kinase receptor (PDB ID: 1M17). In addition, QSAR investigation was also performed to understand the biological potency of the ligand. [ABSTRACT FROM AUTHOR]

A novel series of mononuclear transition metal complexes, [Cu(L)Cl] 1, [Zn(L)Cl] 2, [Pd(L)Cl] 3, [Cd(L)I] 4, [Pt(L)Cl] 5, and [Hg(L)Cl] 6, was constructed from a pyrazole-derived Schiff ligand, HL, and characterized by physicochemical and spectroscopic methods. Fourier-transform infrared (FT-IR) spectral data showed the studied ligand to be tridentate and coordinated to the metal ions via ONO donor atoms, whereas powder X-ray diffraction (PXRD) analysis revealed the crystalline nature of all the complexes. The in vitro cytotoxicity of the studied ligand and its complexes were tested by the 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay against the human colorectal cancer cell lines HCT116 and HT29. The results suggested that the HCT116 cell line is highly sensitive to complex 1 with a half-maximal inhibitory concentration (IC50) of 45.6 μM, while both cell lines tolerated complexes 2 and 4 better in comparison with HL. In addition, complex 1 with significant anticancer activity was analyzed by molecular docking studies to explore its binding efficacy to the cyclin-dependent kinase 2 active site. [ABSTRACT FROM AUTHOR]

ParE, a subunit of topoisomerase IV, is involved in the management of DNA topology and validated to be an attractive target for the development of antibacterial agents. Availability of the crystal structure of Francisella tularensis in combination with one of the pyrrolo [2,3-d] pyrimidine-2-thiolinhibitor facilitated us to emphasize the combined computational approach for discovering the presumed binding mode of selected inhibitors into the binding pocket of ParE (pdb. 4HY1). In the current study, pharmacophore modelling and 3D-QSAR studies were performed using 33 reported F. tularensis ParE inhibitors having pKi ranging from 5.06 to 9.00. The developed five featured pharmacophore model, DHHRR_1 was statistically validated with different parameters like Q2 (0.66), R2 (0.99) and F value (682) at four-component partial least squares factor. Enrichment analysis was performed to validate the generated pharmacophore model. Extra-precision molecular docking, binding free energy calculation using PRIME MM-GBSA were performed for the selected inhibitors. Induced fit docking was performed for the highest active inhibitor 16. The highest-ranked induced fit docked complex 16/4HY1 was used to run a 50 ns molecular dynamic simulation to validate the stability. Further, in silico High Throughput Virtual Screening was performed using 22 lakhs chemical database molecules to identify the potential virtual hits and predicted activity was found for the virtual hits. These results provide promising strategies for the development of novel molecules with better inhibitory activity against F. tularensis ParE. [ABSTRACT FROM AUTHOR]

A novel zinc complex derived from a multidentate ligand, nitrilotris(ethane-2,1-diyl)tris(azanylylidene)tris(methanylylidene)tris(2-methoxyphenol), was designed and structurally investigated by elemental analyses, IR, NMR, ESI-MS, and UV–Vis studies. The density functional theory was also recorded to investigate the additional insights into the structural and electronic properties of the ligand and its complex. Both the ligand and its complex showed significant neurite outgrowth and viability in brain neuron at lower concentration when investigated for neurological properties. Thus, it can be suggested that the ligand and its complex may play a potential role in brain development, functioning as well as in the treatment of neurological disorders. [ABSTRACT FROM AUTHOR]

In the present work, a method based on solvent extraction and gas chromatography–mass spectrometry (GC-MS) has been validated for the determination of 1,4-dioxane in cosmetics. Various solvents including ethyl acetate, hexane, methanol, dichloromethane and acetone have been used for the extraction of 1,4-dioxane, among them the ethyl acetate was found to be the most efficient extracting solvent. This method has offered excellent quality parameters for instance linearity (R2 > 0.9991), limit of detection (LOD, 0.00065-0.00091 µg/mL), limit of quantification (LOQ, 0.00217–0.00304 µg/mL) and, precision intra-day (1.65–2.60%, n = 5) and inter-day (0.16–0.32%, n = 5) in terms of relative standard deviation (RSD%). A total of thirty-nine cosmetic samples of different brands and origin have been studied. Among them, the 1,4-dioxane was found in twenty-three samples (FB1-FB7, MC1-MC4, MC6-MC8, HS3, HS5, BL1-BL3, BL5 and PLD1-PLD3) at the levels between 0.15 µg/mL and 9.92 µg/mL, whereas in sixteen samples (MC5, HS1, HS2, SG1-SG5, BL4 and HP1- HP6) was found to be not detected. The recovery values were achieved between 93% and 99% in both low and high level of spiked samples. In comparison to the traditional analytical techniques, the proposed method was found to be very sensitive and cost-effective for the routine analysis of 1,4-dioxane at low concentration in cosmetics. [ABSTRACT FROM AUTHOR]

Background: This paper analyses acoustic response of thin plate with discrete patches with variable thickness in water medium. Method: Finite-element method and Rayleigh integral method are used for sound power calculation in water medium. Results: For low-frequency range up to 50 Hz, the peak sound power level (SPL) is achieved at higher taper ratio of 0.9 with parabolically increasing–decreasing thickness variation with one patch. In the frequency range of 70–180 Hz and 260–290 Hz, a taper ratio of 0.6 with four patches on the plate with parabolically increasing–decreasing variation is preferred for minimum SPL. Conclusions: It is observed that SPL is influenced by redistribution of patches, thickness variations, and taper ratios. [ABSTRACT FROM AUTHOR]

Elastic deformation of surfaces and piezo-viscous effect of lubricant make EHL a very complex lubrication regime. Elastohydrodynamic Lubrication becomes much more complex when conditions like rough surfaces, non-newtonian behavior of lubricant and temperature dependent flow are considered. The present paper takes the task of reviewing experimental methods applied till date for measuring film thickness and pressure. The paper has been divided into many sections and sub-sections to deal with these techniques in a lucid manner. Experimental methods have been categorized into Electrical, Optical and Acoustic methods. The difference of 8-10% between theoretical and experimental results are witnessed using Electrical methods. Whereas, this difference is less than 1% using Optical methods. Among all optical methods, Relative Optical Interference Intensity Technique is the most effective technique with an ability to measure the film thickness as small as 1 nm or less. The last section of the paper deals with the scope of improvement in measurement techniques in future to understand EHL in more detail. [ABSTRACT FROM AUTHOR]

Two new palladium complexes derived from the di(2-pyridinyl)methanone N-(2-pyridinyl)hydrazone (DPMNPH) ligand are reported. The compounds were characterized by elemental analysis, spectroscopic studies, and, for the DPMNPH ligand, single-crystal X-ray diffraction analysis. The DPMNPH ligand crystallized as orthorhombic with the space group P222. The H1 atom is intramolecularly bonded to the pyridinic N4 with N1-H1 = 0.92(3) Å, H1···N4 = 1.87(2) Å, N1···N4 = 2.615(2) Å, and N1-H1···N4 = 137(2)°. Both complexes were excellent catalysts in the Heck reaction in the presence of base. [ABSTRACT FROM AUTHOR]

Multiple members of the let-7 family of miRNAs are often repressed in human cancers, thereby promoting oncogenesis by derepressing targets such as HMGA2, K-Ras and c-Myc. However, the mechanism by which let-7 miRNAs are coordinately repressed is unclear. The RNA-binding proteins LIN28 and LIN28B block let-7 precursors from being processed to mature miRNAs, suggesting that their overexpression might promote malignancy through repression of let-7. Here we show that LIN28 and LIN28B are overexpressed in primary human tumors and human cancer cell lines (overall frequency ∼15%), and that overexpression is linked to repression of let-7 family miRNAs and derepression of let-7 targets. LIN28 and LIN28b facilitate cellular transformation in vitro, and overexpression is associated with advanced disease across multiple tumor types. Our work provides a mechanism for the coordinate repression of let-7 miRNAs observed in a subset of human cancers, and associates activation of LIN28 and LIN28B with poor clinical prognosis. [ABSTRACT FROM AUTHOR]

Protein kinases targeted by small-molecule inhibitors develop resistance through mutation of the 'gatekeeper' threonine residue of the active site. Here we show that the gatekeeper mutation in the cellular forms of c-ABL, c-SRC, platelet-derived growth factor receptor-α and -β, and epidermal growth factor receptor activates the kinase and promotes malignant transformation of BaF3 cells. Structural analysis reveals that a network of hydrophobic interactions—the hydrophobic spine—characteristic of the active kinase conformation is stabilized by the gatekeeper substitution. Substitution of glycine for the residues constituting the spine disrupts the hydrophobic connectivity and inactivates the kinase. Furthermore, a small-molecule inhibitor that maximizes complementarity with the dismantled spine (compound 14) inhibits the gatekeeper mutation of BCR-ABL-T315I. These results demonstrate that mutation of the gatekeeper threonine is a common mechanism of activation for tyrosine kinases and provide structural insights to guide the development of next-generation inhibitors. [ABSTRACT FROM AUTHOR]

The deregulated tyrosine kinase activity of BCR-ABL is necessary and sufficient to induce chronic myelogenous leukemia (CML). This observation has paved the way for the development of small-molecule inhibitors specifically targeting the kinase activity of the BCR-ABL protein. Indeed, the amazing success of imatinib has revolutionized the whole area of targeted cancer therapeutics. However, enthusiasm for the striking efficacy of imatinib has been tempered by the development of clinical resistance. In essentially all cases, resistance results from kinase domain mutations and/or overexpression of the BCR-ABL gene. To overcome resistance, several novel BCR-ABL inhibitors have been developed and are in clinical trials, though it is inevitable that resistance to second-generation inhibitors will occur as well. Nonetheless, kinases represent an attractive target for therapeutic intervention in several diseases and, at present, some 50 different kinase inhibitors are in clinical trials. We anticipate that resistance to these compounds will follow mechanisms similar to those observed with imatinib. Resistance mutations cause their effect either by direct steric hindrance to drug binding or by allosterically modulating kinase dynamics. This review highlights the principal mechanisms underlying point mutations from these two different classes to confer drug resistance. [ABSTRACT FROM AUTHOR]

Granulocyte colony stimulating factor receptor (G-CSFR) plays an important role in the production of neutrophil granulocytes. Mutated G-CSFRs have been directly associated with two distinct malignant phenotypes in patients, e.g. acute myeloid leukemia (AML) and chronic neutrophilic leukemia (CNL). However, the signaling mechanism of the mutated G-CSFRs is not well understood. Here, we present a comprehensive SILAC-based quantitative phosphoserine and phosphothreonine dataset of the normal and mutated G-CSFRs signaling using the BaF3 cell-line-based in vitro model system. High pH reversed phase concatenation and Titanium Dioxide Spin Tip column were utilized to increase the dynamic range and detection of the phosphoproteome of G-CSFRs. The dataset was further analyzed using several computational tools to validate the quality of the dataset. Overall, this dataset is the first global phosphoproteomics analysis of both normal and disease-associated-mutant G-CSFRs. We anticipate that this dataset will have a strong potential to decipher the phospho-signaling differences between the normal and malignant G-CSFR biology with therapeutic implications. The phosphoproteomic dataset is available via the PRIDE partner repository. Design Type(s) protein physical property analysis objective • replicate design • factorial design Measurement Type(s) protein expression profiling Technology Type(s) liquid chromatography-tandem mass spectrometry Factor Type(s) biological replicate • experimental condition Sample Characteristic(s) Mus musculus • BA/F3 cell Machine-accessible metadata file describing the reported data (ISA-Tab format) [ABSTRACT FROM AUTHOR]

Emergence of genetic resistance against kinase inhibitors poses a great challenge for durable therapeutic response. Here, we report a novel mechanism of JAK2 kinase inhibition by fedratinib (TG101348) that prevents emergence of genetic resistance. Using in vitro drug screening, we identified 211 amino-acid substitutions conferring resistance to ruxolitinib (INCB018424) and cross-resistance to the JAK2 inhibitors AZD1480, CYT-387 and lestaurtinib. In contrast, these resistant variants were fully sensitive to fedratinib. Structural modeling, coupled with mutagenesis and biochemical studies, revealed dual binding sites for fedratinib. In vitro binding assays using purified proteins showed strong affinity for the substrate-binding site (Kd = 20 nM) while affinity for the ATP site was poor (Kd = ~8 μM). Our studies demonstrate that mutations affecting the substrate-binding pocket encode a catalytically incompetent kinase, thereby preventing emergence of resistant variants. Most importantly, our data suggest that in order to develop resistance-free kinase inhibitors, the next-generation drug design should target the substrate-binding site. [ABSTRACT FROM AUTHOR]