Repurposing Old Drugs: Substituted Benzodiazepines as New Antibacterial Agents

This project aims to develop a greater understanding of how old drugs can be repurposed into new and exciting therapeutic areas. In particular, developing an understanding of the antibacterial mode of action exerted by modified benzodiazepines possessing unique fluoropyridines will be explored. The work described in this thesis was mainly focused on the synthesis of a library of substituted benzodiazepines containing the fluoropyridine moiety and the biological investigation of these compounds. We present an effective synthetic route to the core benzodiazepine framework which was later attached to fluoropyridines. The target benzodiazepines substituted by Cl, Br and F on the aryl rings were synthesized and isolated successfully. Except the N1 substituted benzodiazepine, other target compounds all show great activity to a host of bacteria

Healing effect of Terminalia chebula Retz extract on second-degree burns in rats

Purpose: To investigate the healing effect of Terminalia chebula Retz. Extract (TCRE) on seconddegree burns in rats.Methods: Male Sprague Dawley (SD) rats, weighing 200 – 220 g, were subjected to deep seconddegree skin burns by electrical scald instrument. The animals were divided into three groups as follows: (1) second-degree burns model (control) group, (2) burns model treated with 1 % silver sulfadiazine (SSD) group, and (3) burns model treated with 100 mg·mL-1 TCRE group. On days 3, 7 and 14 following the administration of the drug/extract, the wound area and histopathological changes in rat epidermis were evaluated for the various groups. The minimum inhibitory concentration (MIC) of TCRE on Staphyloccocus aureus, Pseudomonas aeruginosa and Escherichia coli were also assessed separately.Results: On day 14, the mean wound area of TCRE treatment group (0.25 ± 0.06 cm2) was significantly smaller than that of the control rats (2.71 ± 0.20 cm2, p < 0.01). The histological results indicate that the inflammatory cells disappeared and were replaced by new granulation tissue in the group treated with 100 mg·mL-1 TCRE by day 14. Compared with SSD group rats, the inflammatory cells and fibroblast and granulation tissues of burnt rats treated with 100 mg·mL-1 TCRE were same as those of rats that had no burns. The antibacterial results revealed that the MIC of TCRE on Staphyloccocus aureus, Pseudomonas aeruginosa and Escherichia coli was 3.13, 12.5 and 6.25 mg·mL-1, respectively.Conclusion: Terminalia chebula Retz. has potentials to be developed as an effective medicinal herb for the treatment of second-degree burns.Keywords: Terminalia chebula, Second-degree burns, Burn wound, Healing, Granulation tissues, Fibroblast, Antibacterial, Inflammatory cell

An Empirical Study of Untangling Patterns of Two-Class Dependency Cycles

Dependency cycles pose a significant challenge to software quality and maintainability. However, there is limited understanding of how practitioners resolve dependency cycles in real-world scenarios. This paper presents an empirical study investigating the recurring patterns employed by software developers to resolve dependency cycles between two classes in practice. We analyzed the data from 38 open-source projects across different domains and manually inspected hundreds of cycle untangling cases. Our findings reveal that developers tend to employ five recurring patterns to address dependency cycles. The chosen patterns are not only determined by dependency relations between cyclic classes, but also highly related to their design context, i.e., how cyclic classes depend on or are depended by their neighbor classes. Through this empirical study, we also discovered three common counterintuitive solutions developers usually adopted during cycles' handling. These recurring patterns and common counterintuitive solutions observed in dependency cycles' practice can serve as a taxonomy to improve developers' awareness and also be used as learning materials for students in software engineering and inexperienced developers. Our results also suggest that, in addition to considering the internal structure of dependency cycles, automatic tools need to consider the design context of cycles to provide better support for refactoring dependency cycles.Comment: Preprint accepted for publication in Empirical Software Engineering, 202

FINITE ELEMENT ANALYSIS OF MECHANICAL PROPERTIES OF SPECIMEN WITH UHPC AND STUD CONNECTOR

UHPC is different from ordinary concrete for mechanical properties. To study the stress state of stud connector when UHPC is used to strengthen RC beam and its influence on bearing capacity of the strengthened beam, in this paper, ABAQUS was adopted first to simulate the push-out test of  stud to verify  accuracy of the finite element model. The nonlinearity of materials and contact conditions was considered in the model, and then three parameters including concrete strength, stud length and stud diameter were studied. Results showed the finite element model established by surface to surface contact method was possible to simulate the force and failure of the stud connector. UHPC could improve the  bearing capacity of the stud specimens obviously, and the length of stud had little effect on bearing capacity of stud while failure of the stud may occur if length of the stud was too small. The increase of stud diameter could improve bearing capacity of elastic working stage

Thermodynamic Calculation of CO 2 Sequestration by Waste Slag from Steelmaking Plant

Abstract: Mineral carbonation is an effective way to store CO 2 . CO 2 fixation by steel slag carbonation is of great significance on CO 2 emissions and solid waste disposal in metallurgical plants. In this paper, the thermodynamics of CO 2 storage with ten major calcium and magnesium containing phases in steelmaking slag, such as C 2 S and C 3 S, by the dry and wet process were calculated. The results show that the direct dry carbonation reactions with steelmaking slag are exothermic in the temperature ranges of 273 K-1073 K. At atmospheric temperature and pressure, all the carbonate reactions by calcium and magnesium containing phases in the steelmaking slag, can be spontaneous. In addition, the direct hydro-carbonation reaction with the leaching agent of water is endothermic in the temperature ranges of 273 K-573 K. The carbonation reactions also occur spontaneously at atmospheric pressure. The indirect hydro-carbonation reaction with steelmaking slag using acetic acid as leaching agent are spontaneous, and the reaction is very complete when the reaction temperature is below 350 K. Keywords: steelmaking slag; carbonation; CO 2 ; thermodynamics E-mail address: [email protected]

Structural variability of 4f and 5f thiocyanate complexes and dissociation of uranium(III)–thiocyanate bonds with increased ionicity

A series of complexes [Et4N][Ln(NCS)4(H2O)4] (Ln = Pr, Tb, Dy, Ho, Yb) have been structurally characterized, all showing the same structure, namely a distorted square antiprismatic coordination geometry, and the Ln–O and Ln–N bond lengths following the expected lanthanide contraction. When the counterion is Cs+, a different structural motif is observed and the eight-coordinate complex Cs5[Nd(NCS)8] isolated. The thorium compounds [Me4N]4[Th(NCS)7(NO3)] and [Me4N]4[Th(NCS)6(NO3)2] have been characterized, and high coordination numbers are also observed. Finally, attempts to synthesize a U(III) thiocyanate compound has been unsuccessful; from the reaction mixture, a heterocycle formed by condensation of five MeCN solvent molecules, possibly promoted by U(III), was isolated and structurally characterized. To rationalize the inability to isolate U(III) thiocyanate compounds, thin-layer cyclic voltammetry and IR spectroelectrochemistry have been utilized to explore the cathodic behavior of [Et4N]4[U(NCS)8] and [Et4N][U(NCS)5(bipy)2] along with a related uranyl compound [Et4N]3[UO2(NCS)5]. In all examples, the reduction triggers a rapid dissociation of [NCS]− ions and decomposition. Interestingly, the oxidation chemistry of [Et4N]3[UO2(NCS)5] in the presence of bipy gives the U(IV) compound [Et4N]4[U(NCS)8], an unusual example of a ligand-based oxidation triggering a metal-based reduction. The experimental results have been augmented by a computational investigation, concluding that the U(III)–NCS bond is more ionic than the U(IV)–NCS bond

Clinical value of mean platelet volume in predicting and diagnosing pre-eclampsia: a systematic review and meta-analysis

BackgroundPre-eclampsia (PE) is a severe pregnancy complication. Thrombocytopenia and platelet dysfunction are common hematology disorders in PE. Previous studies considered mean platelet volume (MPV), a functional marker of platelets, as a potentially useful predictor for the diagnosis of PE.MethodsPubMed, China Biomedical Literature Database, Chinese National Knowledge Infrastructure, Embase, Wanfang, VIP, and Cochrane Library databases were searched to gather diagnostic trials evaluating the diagnosis of PE using MPV, from their inception to 13 March 2023. We also searched Google Scholar and Baidu.ResultsA total of 22 studies from 20 articles were found. The pooled diagnostic accuracy of the MPV for PE recognition was as follows: sensitivity (SEN) 0.676 [95% confidence interval (CI) (0.658–0.694)], specificity (SPE) 0.710 [95% CI (0.703–0.717)], and diagnostic odds ratio (DOR) 7.012 [95% CI (4.226–11.636)], and the SROC-AUC and Q* indices were 0.7889 and 0.7262, respectively. The pooled SEN, SPE, and DOR of the diagnostic accuracy of MPV for PE before 16 weeks of gestation were 0.707 [95% CI (0.670–0.743)], 0.639 [95% CI (0.611–0.667)], and 4.026 [95% CI (2.727–5.943)], and the SROC-AUC and Q* indices were 0.7278 and 0.6753, respectively. For the interval of truncation values between 9 and 10 fl, the SROC-AUC and Q* indices for MPV were 0.8856 and 0.8162, respectively.ConclusionsAvailable evidence suggests that MPV has a moderate predictive and diagnostic value for PE, particularly in diagnosing after 20 weeks of gestation. The diagnostic accuracy is higher when the MPV cut-off falls between 9 and 10 fl. The sensitivity of MPV alone in diagnosing PE is not high, and the combination of other markers for predictive diagnosis may better differentiate PE.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023425154, identifier: CRD42023425154

Extraction, structural characterization, and antioxidant activity of polysaccharides derived from Arctium lappa L.

IntroductionArctium lappa L. root has high nutritional and medicinal values and has been identified as a healthy food raw material by the Ministry of Health of the People's Republic of China.MethodsIn the present study, an aqueous two-phase system (ATPS) of polyethylene glycol (PEG)-(NH4)2SO4 was used to extract Arctium lappa L. polysaccharides (ALPs) from the Arctium lappa L. roots, the optimal extraction conditions of crude ALPs were optimized by using the single-factor experiment and response surface methodology. The structure and composition of ALPs were determined by fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), and high-performance liquid chromatography (HPLC). At the same time, the antioxidant activity of ALPs was investigated by in vitro antioxidant experiment.ResultsThe optimized extraction parameters for extraction ALPs were as follows: the PEG relative molecular weight of 6,000, a quality fraction of PEG 25%, a quality fraction of (NH4)2SO4 18%, and an extraction temperature of 80°C. Under these conditions, the extraction rate of ALPs could reach 28.83%. FTIR, SEM and HPLC results showed that ALPs were typical acidic heteropolysaccharides and had uneven particle size distribution, an irregular shape, and a rough surface. The ALPs were chiefly composed of glucose, rhamnose, arabinose, and galactose with a molar ratio of 70.19:10.95:11.16:6.90. In addition, the ALPs had intense antioxidant activity in vitro with IC50 values in the ·OH radical (1.732 mg/ml), DPPH radical (0.29 mg/ml), and superoxide anion (0.15 mg/ml) scavenging abilities.DiscussionThe results showed that ATPS was an efficient method to extract polysaccharides and could be used for the extraction of other polysaccharides. These results indicated that ALPs had great prospects as a functional food and could be exploited in multiple fields