bluuebunny/crossref_metadata_2025 huggingface dataset:
Punching Shear Behavior of Slabs Made from Different Types of Concrete Internally Reinforced with SHCC-Filled Steel Tubes
Authors: Elsamak Galal , Abdullah Ali , Salama Magdy I. , Hu Jong Wan , El-Mandouh Mahmoud A.
Published: December 2022

The punching shear failure of reinforced concrete (RC) flat slabs is an undesirable type of failure, as it is sudden and brittle. This paper presents an experimental and numerical study to explore the behavior of flat slabs made of different types of concrete under the influence of punching shear. Experimental tests were carried out on four groups of flat slabs, each group representing a different type of concrete: ordinary normal concrete (NC), high-strength concrete (HSC), strain-hardening cementitious composite concrete (SHCC), and ultra-high-performance fiber concrete (UHPFC). Each group consisted of six slabs, one representing an unreinforced control slab other than the reinforcement of the bottom mesh, and the others representing slabs internally reinforced with SHCC-filled steel tubes and high-strength bolts. An analytical equation was used to predict the punching shear capacity of slabs internally reinforced using steel assemblies. A numerical model was proposed using the ABAQUS program, and was validated by comparing its results with our experimental results. Finally, a case study was performed on large-scale slabs. The results showed that using steel assemblies inside NC slabs increased the slab’s punching shear capacity but does not completely prevent punching shear failure. Internally unreinforced slabs made of UHPFC and SHCC were able to avoid punching shear failure and collapse in a ductile bending pattern due to the high compressive and tensile strength of these types of concrete. The proposed analytical method succeeded in predicting the collapse load of slabs reinforced with steel assemblies with a difference not exceeding 9%.
Robust Stability Analysis of Filtered PI and PID Controllers for IPDT Processes
Authors: Huba Mikulas , Bistak Pavol , Vrancic Damir
Published: December 2022

The paper discusses the stability and robustness of the proportional-integral (PI), proportional-integral-derivative (PID), and proportional-integral-derivative-accelerative (PIDA) controller for the integral-plus-dead-time (IPDT) plants. To enable the implementation and measurement of noise attenuation, binomial low-pass filters are added to the traditional design of controllers with ideal transfer functions, and the impact of the low-pass filters on the robust stability of the circuit is studied in detail. The proposed controller tuning, which integrates the suboptimal controller and filter design, is based on explicit tuning formulas derived by using the multiple real dominant pole (MRDP) method. It is shown that by combining derivative actions with possibly higher-order low-pass filters, it is possible to either accelerate the transients or increase the closed loop robustness and that the problem of defining the robust stability area should be addressed at the stage of determining the process model. In addition, if wishing to maintain the closed loop robustness of unfiltered PI control, while increasing the degree of the derivative components, one needs to increase the filtering properties of the low-pass filter used accordingly. Simple analytical relations for setting filtered PI, PID, and PIDA controllers with equivalent robustness are derived.
Using a Modified Polysaccharide as a Hemostatic Agent Results in Less Reduction of the Ovarian Reserve after Laparoscopic Surgery of Ovarian Tumors—Prospective Study
Authors: Moszynski Rafal , Burchardt Bartosz , Sajdak Stefan , Moszynska Marta , Englert-Golon Monika , Olbromski Piotr
Published: December 2022

Background and Objectives: The study investigated whether the method of achieving hemostasis affects the ovarian reserve in patients undergoing laparoscopic surgery due to ovarian tumors or cysts. Materials and Methods: Patients with unilateral tumors or ovarian cysts, who qualified for laparoscopic tumor enucleation, were randomly selected to receive modified polysaccharides or bipolar coagulation. Ovarian reserve was analyzed by anti-Mullerian hormone (AMH) level. Results: The study included 38 patients: 19 patients in the modified polysaccharide group and 19 in the bipolar coagulation group. Patients after bipolar coagulation treatment had statistically significantly lower AMH 6 months after surgery compared to the group treated with modified starch. The levels of AMH in the study and control groups were 3.96 +/− 2.12 vs. 2.51 +/− 1.39 ng/mL, respectively; p = 0.018. A statistically significant decrease in AMH was also demonstrated in the bipolar coagulation group as compared to the preoperative assessment (p = 0.049). There was no statistically significant decrease in AMH in the group of patients treated with the modified starch. Conclusions: Using a modified polysaccharide during laparoscopic cystectomy is effective and has a positive effect on the ovarian reserve compared to the use of bipolar coagulation. Both the AMH level 6 months after surgery and the percentage decrease in AMH were more favorable in the group of patients treated with modified starch.
The Role of C-Reactive Protein and Neutrophil to Lymphocyte Ratio in Predicting the Severity of Odontogenic Infections in Adult Patients
Authors: Rosca Ovidiu , Bumbu Bogdan Andrei , Ancusa Oana , Talpos Serban , Urechescu Horatiu , Ursoniu Sorin , Bloanca Vlad , Pricop Marius
Published: December 2022

Background and Objectives: Odontogenic infections (OI) represent a frequent cause of dental and maxillo-facial interventions, mostly due to late presentations or misdiagnosed complications. It is believed that the intensity of the immunoinflammatory response in OI is the main prognostic factor. Therefore, in this research, it was pursued to determine if the combination of C-reactive protein (CRP) and Neutrophil to Lymphocyte Ratio (NLR) (CRP-NLR) may serve as potential severity predictors in patients with odontogenic infections. Materials and Methods: A retrospective analysis on 108 patients hospitalized for odontogenic infections was conducted at the Department of Maxillofacial Surgery. Depending on the symptom severity scale, patients hospitalized with OI were divided into two equal groups based on infection severity (SS). Results: Patients with severe OI from Group B were associated more frequently with diabetes mellitus and smoking more often than those with a lower severity from Group A. In Group A, abscesses of odontogenic origin accounted for 70.4% of hospitalizations, while in Group B, abscesses and cellulitis were associated in 55.6% of cases (p-value < 0.001). The disease outcomes were more severe in Group B patients, where 22.2% of them developed sepsis, compared to 7.4% of Group A patients (p-value = 0.030). However, there was no significant difference in mortality rates. The SS and systemic immune inflammation index (SII) scores of Group B patients were substantially higher than Group A patients (13.6 vs. 6.1 for the SS score, p-value < 0.001), respectively, 2312.4 vs. 696.3 for the SII score (p-value < 0.001). All biomarker scores, including the CRP-NLR relationship, were considerably higher in Group B patients, with a median score of 341.4 vs. 79.0 in Group B (p-value < 0.001). The CRP-NLR association determined a 7.28-fold increased risk of severe OI. The receiver operating curve (ROC) analysis of CRP-NLR yielded an area under curve (AUC) value of 0.889, with high sensitivity (79.6%) and high specificity (85.1%), for predicting a severe odontogenic infection using biomarkers measured at hospital admission (p-value < 0.001). Conclusions: Therefore, it can be concluded that CRP-NLR is a reliable and affordable biomarker for determining the severity of odontogenic infections that may be included in other prognostic models for dental infections.
The Effect of Cooling Rate on Microstructure and Mechanical Properties of the Zr-4Hf-3Nb (wt%) Alloy
Authors: Guo Shenglan , Wang Qi , Xing Xiangdong , Du Yueli , Zheng Jianlu , Wang Sunxuan , Shen Zhenghua
Published: December 2022

The mechanical properties of Zr-based alloys, such as strength and elongation, are heavily dependent on the cooling rate during heat treatment. Understanding the phase transformation and microstructural evolution in various cooling media can establish the connection between the cooling rate and mechanical properties. The effect of the cooling rate on the phase, microstructure, and tensile properties of Zr-4Hf-3Nb (wt%) alloy is studied in this paper. The results show that the phase composition of the samples transforms from α+β to α+β+ω, and, finally, to α+α’+ω, while the average grain size of α phase decreases from 3.73 μm to 1.96 μm, and the distribution varies from compact to scattering as the cooling rate increases. Hf tends to distribute in β phase, and the slower cooling rate is beneficial to the existence of Hf. The strength and microhardness enhances monotonously, while the elongation ascends first, then decreases as the cooling rate increases. The high strength of water-cooling samples is attributed to the reduction in average grain size and volume fraction of α phase, and the lath α’ martensite and granular ω phase. The fracture pattern of Zr-4Hf-3Nb (wt%) alloy is ductile fracture, and the plasticity gets better with decreasing cooling rate.
Functional Behaviour of Cold-Worked and Straight-Annealed NiTi Elements Processed with Ultrashort Laser Cutting
Authors: Biffi Carlo Alberto , Tuissi Ausonio
Published: December 2022

Among functional materials, quasiequiatomic NiTi alloys are one of the most promising and diffused for some sectors, from the biomedical to aerospace ones. Their peculiar performance, namely, shape memory effect and pseudoelasticity, is induced via a thermomechanical treatment called shape setting or with the heat treatment of annealing. This heat treatment is carried out in cold-worked conditions. The present work studies the effect of the material conditions of straight annealing and cold working on the functional performance of diamond-shaped NiTi microdevices realised through ultrashort laser cutting. In detail, experiments were carried out aimed at studying the effect of laser power, scanning speed, and number of passes on the kerf width with the focus on defining the most suitable process condition on both straight-annealed and cold-worked sheets of 100 µm in thickness. After the process parameters had been defined, the transformation temperatures and superelastic behaviour were analysed though differential scanning calorimetry and force–displacement testing. The femtosecond cutting of straight-annealed NiTi did not change the characteristic temperatures of the base material, while the same process induced a soft martensitic transformation with respect to the cold-worked material due to a heat accumulation effect.
Relieving Residual Stress of 316L Stainless Steel by Acoustic/Thermal Composite Treatment
Authors: Xiang Pengyu , Zhang Chenhao , Jin Junjun , Zhu Zhongyin , Gou Guoqing
Published: December 2022

The influence of temperature, vibration time, amplitude, and other factors on the residual stress release effect was studied using the method of low-temperature heating and high-frequency ultrasonic vibration, and excellent control parameters were obtained. In addition, the influence of cutting weld reinforcement on the residual stress release was also studied. The results demonstrate that the highest relative residual stress release rate was 280.29%, the average release was over 150 MPa, and the efficiency was higher than that of the general stress release methods. After cutting the reinforcement, only a small part of residual stress was released, influencing the overall residual stress distribution relatively little. The experimental material was a butt-welded 316L stainless steel plate μ-X360s diffractometer, and this was used for measuring the residual stress.
Effect of Alcohol on the Mechanical and Electrical Properties of Ultrasonic Spot Welded Cu/Cu Joints
Authors: Yang Jiajia , Ni Zenglei , Nazarov Ayrat A. , Ye Fuxing
Published: December 2022

In order to improve the Cu/Cu joint quality, the bottom Cu sheet surface to be welded was dampened by a drop of absolute ethyl alcohol before the welding. Then, the ultrasonic spot welding (USW) was utilized to join a 0.5 mm thick Cu sheet to a 1.0 mm thick Cu sheet. The results demonstrated that, due to the action of the alcohol, obvious changes of the welding interface temperature, effective thickness, bond density, interface microstructure, joint resistance, micro-hardness, lap shear strength and fracture mode occurred in comparison with the joint without alcohol. Discontinuous dynamic recrystallization took place at the welding interface and facilitated the migration of grain boundaries across the contact interface, leading to the formation of the metallurgical bonding between the two Cu sheets.
Evaluation of Zamia floridana A. DC. Leaves and Its Isolated Secondary Metabolites as Natural Anti-Toxoplasma and Anti-Cancer Agents Using In Vitro and In Silico Studies
Authors: El-Seadawy Hosam M. , Abo El-Seoud Kamilia A. , El-Aasr Mona , Tawfik Haytham O. , Eldehna Wagdy M. , Ragab Amany E.
Published: December 2022

Toxoplasmosis and cancer are life-threatening diseases with worldwide distribution. However, currently used chemosynthetic treatments are not devoid of their own intrinsic problems. Natural metabolites are gaining attention due to their lower side effects. In this study, we investigated for the first time Zamia floridana leaves extract and its different fractions for their toxoplasmocidal activity, using Virulent RH Toxoplasma gondii, and cytotoxic activity against MCF-7 and HCT-116 cancer cell lines using MTT assay. The n-butanol fraction was the most potent fraction against T. gondii with an EC50 of 7.16 ± 0.4 µg/mL compared to cotrimoxazole (4.18 ± 0.3 µg/mL). In addition, the n-BuOH fraction showed a significant cytotoxicity against MCF-7 and HCT-116 with IC50 of 12.33 ± 1.1 and 17.88 ± 1.4 µg/mL, respectively, compared to doxorubicin (4.17 ± 0.2 and 5.23 ± 0.3 µg/mL, respectively), with higher safety index against normal cell line (WISH). Therefore, the n-BuOH fraction was investigated for its phytochemicals using extensive chromatographic techniques, which led to the isolation of six compounds that were fully characterized using different spectroscopic techniques. Three biflavonoids (1, 2 and 4) in addition to two phenolic acid derivatives (3 and 5) and a flavonoid glycoside (6) were isolated. Compounds (1, 3, 5 and 6) were reported for the first time from Z. floridana. In silico docking studies for toxoplasmocidal and cytotoxic effects of these compounds revealed that compounds (1, 2, 4 and 6) have promising inhibition potential of either thymidylate synthase-dihydrofolate reductase (TS-DHFR) or cyclin dependent kinase 2 (CDK2) target proteins. This study is considered the first report of chemical and biological investigation of Z. floridana leaves.
Research on the Relationship between Multi-Component Complex Ore and Its Component Minerals’ Grinding Characteristics under Abrasion Force
Authors: Yang Jinlin , Zhu Pengyan , Li Hengjun , Li Zongyu , Huo Xingnan , Ma Shaojian
Published: December 2022

The relationship between the grinding characteristics of polymetallic complex ore and its component minerals, pyrrhotite, sphalerite, and quartz, under the action of abrasion was studied, based on batch grinding experiments and theoretical analysis methods of selective grinding. The results show that when the polymetallic complex ore was subjected to the action of abrasion, the crushing effect of ore was enhanced by the existence of sphalerite, that is, sphalerite plays a positive role in the crushing effect of ore. The crushing effect of ore was reduced by the existence of pyrrhotite and quartz, that is, pyrrhotite and quartz plays a negative role in the crushing effect of ore. In addition, the sphalerite had a more prominent effect on the grinding characteristics of the ore. The grinding speed of ore and its component minerals decreased exponentially with the grinding time, and the instantaneous grinding speed of 0 min was negatively correlated with the feed sizes. The rapidly decreasing trend of the grinding speed reached the threshold when the grinding time reached 4 min. The results can provide some theoretical guidance for the study of grinding characteristics of multi-component complex ores in subsequent grinding process.
Synthesis and Pesticidal Activity of New Niacinamide Derivatives Containing a Flexible, Chiral Chain
Authors: Wei Zhe-Cheng , Wang Qiao , Min Li-Jing , Bajsa-Hirschel Joanna , Cantrell Charles L. , Han Liang , Tan Cheng-Xia , Weng Jian-Quan , Li Yu-Xin , Sun Na-Bo , Duke Stephen O. , Liu Xing-Hai
Published: December 2022

Natural products are a source for pesticide or drug discovery. In order to discover lead compounds with high fungicidal or herbicidal activity, new niacinamide derivatives derived from the natural product niacinamide, containing chiral flexible chains, were designed and synthesized. Their structures were confirmed by 1H NMR, 13C NMR and HRMS analysis. The fungicidal and herbicidal activities of these compounds were tested. The fungicidal activity results demonstrated that the compound (S)-2-(2-chloronicotinamido)propyl-2-methylbenzoate (3i) exhibited good fungicidal activity (92.3% inhibition) against the plant pathogen Botryosphaeria berengriana at 50 μg/mL and with an EC50 of 6.68 ± 0.72 μg/mL, which is the same as the positive control (fluxapyroxad). Compound 3i was not phytotoxic and could therefore be used as a fungicide on crops. Structure-activity relationships (SAR) were studied by molecular docking simulations with the succinate dehydrogenase of the fungal mitochondrial respiratory chain.
Analysis of Chemical Constituents of Traditional Chinese Medicine Jianqu before and after Fermentation Based on LC-MS/MS
Authors: Wang Yishuo , Wang Ruisheng , Zhang Zhenling , Chen Yitian , Sun Mengmei , Qiao Jia , Du Ziwei
Published: December 2022

Objective: To detect the chemical constituents in Jianqu samples under different fermentated states by using UPLC-QTOF-MS/MS technology, to conduct preliminary analyses, and to establish an HPLC method for the simultaneous determination of hesperidin and naringenin in Jianqu, and the variation of the two components during fermentation were compared. Methods: Waters ACQUITYTM UPLC HSST3 column (2.1 mm × 100 mm, 1.8 μm) was used; the mobile phase was 0.1% formic acid aqueous solution (A)-0.1% formic acid acetonitrile (B); The flow rate was 0.4 mL·min−1 with gradient elution; the column temperature was 45 °C; injection volume was 5 μL. The mass spectra of the samples were collected by negative ion mode under the electrospray ion source, and the data were screened and matched by UNIFI software. Hypersil gold C18 column (100 mm × 2.1 mm, 1.9 μm) was used; the mobile phase was acetonitrile (A)-0.1% acetic acid (B);; the flow rate with gradient elution was 0.3 mL·min−1; the column temperature was 30 °C; the injection volume was 2 μL. The content changes of hesperetin and naringenin in Jianqu at different fermentation time were detected. Results: A total of 54 compounds were identified, including flavonoids, amino acids, organic acids, terpenoids, coumarins, lignans, and other compounds. Under the selected HPLC conditions, the linear relationship between hesperidin and naringenin was discovered (r2 = 0.9996). The content of hesperidin and naringenin changed significantly in the whole fermentation process. The highest concentration of content was observed at 36 h of fermentation and then decreased to varying degrees. Conclusion: This experiment can effectively identify various chemical components in Jianqu during different fermentation periods, and determine the content of the characteristic components, so as to provide a scientific basis for further study of Jianqu fermentation processing technology as well as a sound pharmacodynamic material basis.
Extracts from European Propolises as Potent Tyrosinase Inhibitors
Authors: Widelski Jarosław , Gaweł-Bęben Katarzyna , Czech Karolina , Paluch Emil , Bortkiewicz Olga , Kozachok Solomiia , Mroczek Tomasz , Okińczyc Piotr
Published: December 2022

Tyrosinase is a key enzyme in the melanogenesis pathway. Melanin, the product of this process, is the main pigment of the human skin and a major protection factor against harmful ultraviolet radiation (UVR). Increased melanin synthesis due to tyrosinase hyperactivity can cause hyperpigmentation disorders, which in consequence causes freckles, age spots, melasma, or postinflammatory hyperpigmentation. Tyrosinase overproduction and hyperactivity are triggered by the ageing processes and skin inflammation as a result of oxidative stress. Therefore, the control of tyrosinase activity is the main goal of the prevention and treatment of pigmentation disorders. Natural products, especially propolis, according to their phytochemical profile abundant in polyphenols, is a very rich resource of new potential tyrosinase inhibitors. Therefore, this study focused on the assessment of the tyrosinase inhibitory potential of six extracts obtained from the European propolis samples of various origins. The results showed the potent inhibitory activity of all tested propolis extracts towards commercially available mushroom tyrosinase. The four most active propolis extracts showed inhibitory activity in the range of 86.66–93.25%. Apart from the evaluation of the tyrosinase inhibition, the performed research included UHPLC–DAD–MS/MS (ultra high performance liquid chromatography coupled with diode array detection and tandem mass spectrometry) phytochemical profiling as well as antioxidant activity assessment using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) and the 2,2”-azino-bis(3-ethylbenzothiazoline-6-sulfuric acid (ABTS) radical scavenging tests. Moreover, statistical analysis was used to correlate the tyrosinase inhibitory and antioxidant activities of propolis extracts with their phytochemical composition. To summarise, the results of our research showed that tested propolis extracts could be used for skin cosmeceutical and medical applications.
Enhancement of the Functional Properties of Mead Aged with Oak (Quercus) Chips at Different Toasting Levels
Authors: Fortes Juciane Prois , Franco Fernanda Wouters , Baranzelli Julia , Ugalde Gustavo Andrade , Ballus Cristiano Augusto , Rodrigues Eliseu , Mazutti Márcio Antônio , Somacal Sabrina , Sautter Claudia Kaehler
Published: December 2022

Consumers increasingly prefer and seek functional beverages, which, given their characteristics, provide important bioactive compounds that help prevent and treat chronic diseases. Mead is a traditional fermented alcoholic beverage made from honey solution. The aging process of mead with oak chips is innovative and bestows functional characteristics to this beverage. Thus, in this study, we sought to develop and characterize a novel functional beverage by combining the health benefits of honey with the traditional aging process of alcoholic beverages in wood. Phenolic compounds, flavonoids, and antioxidant capacity were analyzed in mead using oak chips at different toasting levels and aged for 360 days. LC-ESI-QTOF-MS/MS was used to analyze the chemical profile of different meads. Over time, the aging process with oak chips showed a higher total phenolic and flavonoid content and antioxidant capacity. Eighteen compounds belonging to the classes of organic acids, phenolic acids, flavonoids, and tannins were identified in meads after 360 days. Our findings revealed that the addition of oak chips during aging contributed to p-coumaric, ellagic, abscisic, and chlorogenic acids, and naringenin, vanillin, and tiliroside significantly impacted the functional quality of mead.
A New Flavanone from Chromolaena tacotana (Klatt) R. M. King and H. Rob, Promotes Apoptosis in Human Breast Cancer Cells by Downregulating Antiapoptotic Proteins
Authors: Mendez-Callejas Gina , Torrenegra Ruben , Muñoz Diego , Celis Crispin , Roso Michael , Garzon Jojhan , Beltran Ferney , Cardenas Andres
Published: December 2022

Chromolaena tacotana is a source of flavonoids with antiproliferative properties in human breast cancer cells, the most common neoplasm diagnosed in patients worldwide. Until now, the mechanisms of cell death related to the antiproliferative activity of its flavonoids have not been elucidated. In this study, a novel flavanone (3′,4′-dihydroxy-5,7-dimethoxy-flavanone) was isolated from the plant leaves and identified by nuclear magnetic resonance (NMR) and mass spectrometry (MS). This molecule selectively inhibited cell proliferation of triple-negative human breast cancer cell lines MDA-MB-231 and MCF-7 whit IC50 values of 25.3 μg/mL and 20.8 μg/mL, respectively, determined by MTT assays with a selectivity index greater than 3. Early and late pro-apoptotic characteristics were observed by annexin-V/7-AAD detection, accompanied by a high percentage of the Bcl-2 anti-apoptotic protein inactivated and the activation of effector Caspase-3 and/or 7 in breast cancer cells. It was verified the decreasing of XIAP more than Bcl-2 anti-apoptotic proteins expression, as well as the XIAP/Caspase-7 and Bcl-2/Bax complexes dissociation after flavanone treatment. Docking and molecular modeling analysis between the flavanone and the antiapoptotic protein XIAP suggests that the natural compound inhibits XIAP by binding to the BIR3 domain of XIAP. In this case, we demonstrate that the new flavanone isolated from leaves of Chomolaena tacotana has a promising and selective anti-breast cancer potential that includes the induction of intrinsic apoptosis by downregulation of the anti-apoptotic proteins XIAP and Bcl-2. New studies should deepen these findings to demonstrate its potential as an anticancer agent.
Supramolecular Crystal Networks Constructed from Cucurbit[8]uril with Two Naphthyl Groups
Authors: Gao Zhong-Zheng , Shen Lei , Hu Yu-Lu , Sun Ji-Fu , Wei Gang , Zhao Hui
Published: December 2022

Naphthyl groups are widely used as building blocks for the self-assembly of supramolecular crystal networks. Host–guest complexation of cucurbit[8]uril (Q[8]) with two guests NapA and Nap1 in both aqueous solution and solid state has been fully investigated. Experimental data indicated that double guests resided within the cavity of Q[8], generating highly stable homoternary complexes NapA2@Q[8] and Nap12@Q[8]. Meanwhile, the strong hydrogen-bonding and π···π interaction play critical roles in the formation of 1D supramolecular chain, as well as 2D and 3D networks in solid state.
One-Pot Solvent-Involved Synthesis of 5-O-Substituted 5H-Chromeno[2,3-b]pyridines
Authors: Ryzhkova Yuliya E. , Ryzhkov Fedor V. , Elinson Michail N. , Maslov Oleg I. , Fakhrutdinov Artem N.
Published: December 2022

Chromeno[2,3-b]pyridines are substances demanded in medicinal and material chemistry. PASE (pot, atom, and step economy) and in particular one-pot approaches are key green chemistry techniques that are applied for the synthesis of heterocyclic compounds. In this case, the PASE approach was extended with ‘component economy’, as solvent was used also as reactant (solvent-involved reaction). This approach was adopted for the one-pot synthesis of previously unknown O-substituted 5-alkoxy-5H-chromeno[2,3-b]pyridines via two-step transformation, namely the reaction of salicylaldehydes and malononitrile dimer, with the subsequent addition of alcohol. The mechanistic studies revealed the possibility of concurrent reaction. The studies aided in optimizing the reaction conditions for the best yields (77–93%). Thus, the one-pot reaction proceeds efficient and quickly, and the work-up procedure (only simple filtering) is very convenient. The structure of synthesized chromeno[2,3-b]pyridines was confirmed by 2D NMR spectroscopy.
Quantum Mechanical Calculations of Redox Potentials of the Metal Clusters in Nitrogenase
Authors: Jiang Hao , Svensson Oskar K. G. , Ryde Ulf
Published: December 2022

We have calculated redox potentials of the two metal clusters in Mo-nitrogenase with quantum mechanical (QM) calculations. We employ an approach calibrated for iron–sulfur clusters with 1–4 Fe ions, involving QM-cluster calculations in continuum solvent and large QM systems (400–500 atoms), based on structures from combined QM and molecular mechanics (QM/MM) geometry optimisations. Calculations on the P-cluster show that we can reproduce the experimental redox potentials within 0.33 V. This is similar to the accuracy obtained for the smaller clusters, although two of the redox reactions involve also proton transfer. The calculated P1+/PN redox potential is nearly the same independently of whether P1+ is protonated or deprotonated, explaining why redox titrations do not show any pH dependence. For the FeMo cluster, the calculations clearly show that the formal oxidation state of the cluster in the resting E0 state is MoIIIFe3IIFe4III , in agreement with previous experimental studies and QM calculations. Moreover, the redox potentials of the first five E0–E4 states are nearly constant, as is expected if the electrons are delivered by the same site (the P-cluster). However, the redox potentials are insensitive to the formal oxidation states of the Fe ion (i.e., whether the added protons bind to sulfide or Fe ions). Finally, we show that the later (E4–E8) states of the reaction mechanism have redox potential that are more positive (i.e., more exothermic) than that of the E0/E1 couple.
Multifunctional Roles of Betulinic Acid in Cancer Chemoprevention: Spotlight on JAK/STAT, VEGF, EGF/EGFR, TRAIL/TRAIL-R, AKT/mTOR and Non-Coding RNAs in the Inhibition of Carcinogenesis and Metastasis
Authors: Farooqi Ammad Ahmad , Turgambayeva Assiya , Tashenova Gulnara , Tulebayeva Aigul , Bazarbayeva Aigul , Kapanova Gulnara , Abzaliyeva Symbat
Published: December 2022

The pursual of novel anticancer molecules from natural sources has gained worthwhile appreciation, and a significant fraction of conceptual knowledge has revolutionized our understanding about heterogeneous nature of cancer. Betulinic acid has fascinated interdisciplinary researchers due to its tremendous pharmacological properties. Ground-breaking discoveries have unraveled previously unprecedented empirical proof-of-concept about momentous chemopreventive role of betulinic acid against carcinogenesis and metastasis. Deregulation of cell signaling pathways has been reported to play a linchpin role in cancer progression and colonization of metastatically competent cancer cells to the distant organs for the development of secondary tumors. Importantly, betulinic acid has demonstrated unique properties to mechanistically modulate oncogenic transduction cascades. In this mini-review, we have attempted to provide a sophisticated compendium of regulatory role of betulinic acid in cancer chemoprevention. We have partitioned this multi-component review into different sections in which we summarized landmark research-works which highlighted betulinic acid mediated regulation of JAK/STAT, VEGF, EGF/EGFR, TRAIL/TRAIL-R, AKT/mTOR and ubiquitination pathways in the inhibition of cancer. In parallel, betulinic acid mediated regulation of signaling cascades and non-coding RNAs will be critically analyzed in cell culture and animal model studies. Better comprehension of the pharmaceutical features of betulinic acid and mapping of the existing knowledge gaps will be valuable in the translatability of preclinical studies into rationally designed clinical trials.
Investigating the Mechanisms of Bisdemethoxycurcumin in Ulcerative Colitis: Network Pharmacology and Experimental Verification
Authors: Wu Huihuan , Tu Sha , Zhuo Zewei , Jiang Rui , Zeng Ruijie , Yang Qi , Lian Qizhou , Sha Weihong , Chen Hao
Published: December 2022

Ulcerative colitis is a chronic inflammatory bowel disorder that is hard to cure once diagnosed. Bisdemethoxycurcumin has shown positive effects on inflammatory diseases. However, the underlying bioactive interaction between bisdemethoxycurcumin and ulcerative colitis is unclear. The objective of this study was to determine the core target and potential mechanism of action of bisdemethoxycurcumin as a therapy for ulcerative colitis. The public databases were used to identify potential targets for bisdemethoxycurcumin and ulcerative colitis. To investigate the potential mechanisms, the protein-protein interaction network, gene ontology analysis, and Kyoto encyclopedia of genes and genomes analysis have been carried out. Subsequently, experimental verification was conducted to confirm the findings. A total of 132 intersecting genes of bisdemethoxycurcumin, as well as ulcerative coli-tis-related targets, were obtained. SRC, EGFR, AKT1, and PIK3R1 were the targets of highest potential, and the PI3K/Akt and MAPK pathways may be essential for the treatment of ulcerative colitis by bisdemethoxycurcumin. Molecular docking demonstrated that bisdemethoxycurcumin combined well with SRC, EGFR, PIK3R1, and AKT1. Moreover, the in vitro experiments suggested that bisdemethoxycurcumin might reduce LPS-induced pro-inflammatory cytokines levels in RAW264.7 cells by suppressing PI3K/Akt and MAPK pathways. Our study provided a comprehensive overview of the potential targets and molecular mechanism of bisdemethoxycurcumin against ulcerative colitis. Furthermore, it also provided a theoretical basis for the clinical treatment of ulcerative colitis, as well as compelling evidence for further study on the mechanism of bisdemethoxycurcumin in the treatment of ulcerative colitis.
Biginelli Reaction Synthesis of Novel Multitarget-Directed Ligands with Ca2+ Channel Blocking Ability, Cholinesterase Inhibition, Antioxidant Capacity, and Nrf2 Activation
Authors: Malek Rim , Simakov Alexey , Davis Audrey , Maj Maciej , Bernard Paul J. , Wnorowski Artur , Martin Helene , Marco-Contelles José , Chabchoub Fakher , Dallemagne Patrick , Rochais Christophe , Jozwiak Krzysztof , Ismaili Lhassane
Published: December 2022

Novel multitarget-directed ligands BIGI 4a-d and BIGI 5a-d were designed and synthesized with a simple and cost-efficient procedure via a one-pot three-component Biginelli reaction targeting acetyl-/butyrylcholinesterases inhibition, calcium channel antagonism, and antioxidant ability. Among these multitarget-directed ligands, BIGI 4b, BIGI 4d, and BIGI 5b were identified as promising new hit compounds showing in vitro balanced activities toward the recognized AD targets. In addition, these compounds showed suitable physicochemical properties and a good druglikeness score predicted by Data Warrior software.
Remarkable Single Atom Catalyst of Transition Metal (Fe, Co & Ni) Doped on C2N Surface for Hydrogen Dissociation Reaction
Authors: Shah Ahmed Bilal , Sarfaraz Sehrish , Yar Muhammad , Sheikh Nadeem S. , Hammud Hassan H. , Ayub Khurshid
Published: December 2022

Currently, hydrogen is recognized as the best alternative for fossil fuels because of its sustainable nature and environmentally friendly processing. In this study, hydrogen dissociation reaction is studied theoretically on the transition metal doped carbon nitride (C2N) surface through single atom catalysis. Each TMs@C2N complex is evaluated to obtain the most stable spin state for catalytic reaction. In addition, electronic properties (natural bond orbital NBO & frontier molecular orbital FMO) of the most stable spin state complex are further explored. During dissociation, hydrogen is primarily adsorbed on metal doped C2N surface and then dissociated heterolytically between metal and nitrogen atom of C2N surface. Results revealed that theFe@C2N surface is the most suitable catalyst for H2 dissociation reaction with activation barrier of 0.36 eV compared with Ni@C2N (0.40 eV) and Co@C2N (0.45 eV) complexes. The activation barrier for H2 dissociation reaction is quite low in case of Fe@C2N surface, which is comparatively better than already reported noble metal catalysts.
Morphological Structures and Self-Cleaning Properties of Nano-TiO2 Coated Cotton Yarn at Different Washing Cycles
Authors: Sallehudin Mirra Edreena , Affandi Nor Dalila Nor , Harun Ahmad Mukifza , Alam Mohammad Khursheed , Indrie Liliana
Published: December 2022

Titanium dioxide (TiO2) has an extraordinary photocatalytic activity and it effectively provides self-cleaning properties for cotton products. With the presence of succinic acid, it helps the adherence of the TiO2 nanoparticles on cotton surfaces. However, the ability of succinic acid to keep the TiO2 adhered on cotton after washing is not yet fully understood. Therefore, this study aimed to investigate the effects of washing cycles on nano-TiO2 coated cotton yarn with the aid of succinic acid on the morphological structures and self-cleaning properties. In this study, the nano-TiO2 was synthesized using a hydrothermal method. The cotton yarn was coated with succinic acid and was later dipped in a nano-TiO2 nanoparticles suspension. The nano-TiO2 coated yarn samples then underwent the 5th, 10th, 15th, and 20th wash cycles and were tested for morphological structures and self-cleaning. The self-cleaning properties of the nano-TiO2 coated yarn were determined using the depth of colour stain. The depth of the colour stain was presented as K/S value, where K and S are corresponded to the absorption and scattering coefficients of the stained fabric, respectively. From the analysis, our synthesized nano-TiO2 had a size of 20–50 nm range with a band gap of 3.06 eV. After coating, the nano-TiO2 coated cotton yarn changed in its morphological structure at 5th, 10th, 15th, and 20th wash cycles, respectively. At the 20th wash cycle, the weight (%) of the Ti element continued to decrease up to 4.45%, reducing the photocatalytic activity with the K/S value close to the stained yarn, which was about 0.4. The 5th wash cycle maintained a good photocatalytic activity with the K/S value of 0.06 near to the K/S value of the unstained cotton yarn. The presence of succinic acid in the nano-TiO2 coated cotton yarn provided good self-cleaning properties up to the 15th wash cycle. By undertaking this study, an enhanced cotton property has been developed that will benefit the textile and clothing industry. This nano-TiO2 coated cotton the has potential to be used for daily apparel and sportwear.
Melaleuca armillaris Essential Oil as an Antibacterial Agent: The Use of Mesoporous Bioactive Glass Nanoparticles as Drug Carrier
Authors: Ballarre Josefina , Buldain Daniel , Unalan Irem , Pastore Juan I. , Mestorino Nora , Boccaccini Aldo R.
Published: December 2022

Bioactive glasses have been proposed for bone tissue engineering due to their excellent biocompatibility and osteo-inductive behaviour. The generation of mesoporous bioactive glass (nano) particles adds a high surface area for the dissolution and release of bioactive ions, and the possibility to load them with different drugs for antibacterial purposes. Essential oils (EO) are an interesting resource for alternative medical therapy, providing antimicrobial compounds that come from organic/natural resources like aromatic plants. Also, a biological polymer, such as chitosan, could be used to control the release of active agents from mesoporous bioactive glass (MBG) loaded particles. This work presents MBG particles with nominal composition (in mol) 60% SiO2, 30% CaO and 10% P2O5, loaded with essential oil of Melaleuca armillaris, which contains 1,8-cineol as the main active component, with an inhibitory in vitro activity against several bacterial species. Also, co-loading with a broad-spectrum antibiotic, namely gentamicin, was investigated. The MBG particles were found to be of around 300nm in diameter and to exhibit highly porous open structure. The release of EO from the particles reached 72% of the initial content after the first 24 h, and 80% at 48 h of immersion in phosphate buffered solution. Also, the MBG particles with EO and EO-gentamicin loading presented in vitro apatite formation after 7 days of immersion in simulated body fluid. The antibacterial tests indicated that the main effect, after 24 h of contact with the bacteria, was reached either for the MBG EO or MBG EO-gentamicin particles against E. coli, while the effect against S. aureus was less marked. The results indicate that MBG particles are highly bioactive with the tested composition and loaded with EO of Melaleuca armillaris. The EO, also combined with gentamicin, acts as an antibacterial agent but with different efficacy depending on the bacteria type.
Synthesis of cBN-hBN-SiCw Nanocomposite with Superior Hardness, Strength, and Toughness
Authors: Sun Lei , Zou Yitong , Ma Mengdong , Li Guangqian , Wang Xiaoyu , Zhang Xiang , Zhuge Zewen , Liu Bing , Wu Yingju , Li Baozhong , Zhao Zhisheng
Published: December 2022

Nanocomposites with one-dimensional (1D) and two-dimensional (2D) phases can demonstrate superior hardness, fracture toughness, and flexural strength. Cubic boron nitride-hexagonal boron nitride-silicon carbide whiskers (cBN-hBN-SiCw) nanocomposites with the simultaneous containing 1D SiCw and 2D hBN phases were successfully fabricated via the high-pressure sintering of a mixture of SiCw and cBN nanopowders. The hBN was generated in situ via the limited phase transition from cBN to hBN. Nanocomposites with 25 wt.% SiCw exhibited optimal comprehensive mechanical properties with Vickers hardness of 36.5 GPa, fracture toughness of 6.2 MPa·m1/2, and flexural strength of 687.4 MPa. Higher SiCw contents did not significantly affect the flexural strength but clearly decreased the hardness and toughness. The main toughening mechanism is believed to be a combination of hBN inter-layer sliding, SiCw pull-out, crack deflection, and crack bridging.
Efficacy and Safety of Monacolin K Combined with Coenzyme Q10, Grape Seed, and Olive Leaf Extracts in Improving Lipid Profile of Patients with Mild-to-Moderate Hypercholesterolemia: A Self-Control Study
Authors: Angelopoulos Nicholas , Paparodis Rodis D. , Androulakis Ioannis , Boniakos Anastasios , Anagnostis Panagiotis , Tsimihodimos Vasilis , Livadas Sarantis
Published: December 2022

The objective of the present study was to assess the lipid-lowering efficacy and safety of a novel dietary supplement containing monacolin K combined with the coenzyme Q10 and grape seed and olive tree leaf extracts (Arichol®®) on the lipid profile of adults with moderate cholesterol elevations and an absence of concomitant risk factors. We recruited patients from our Endocrinology Clinics in Greece who had low-density lipoprotein cholesterol (LDL-C) 140–180 mg/dL, were on no medications affecting serum lipid concentrations, and consented to participate in the present study. All subjects received 8-weeks supplementation with Arichol®® once daily. We measured total cholesterol (TC), high-density lipoprotein cholesterol (HDL), LDL-C, triglycerides (TG), and liver enzymes with enzymatic colorimetric assays at baseline and at the end of the study, and documented complaints potentially attributable to muscle injury. We recruited a total of 37 subjects, 33 females and 4 males (with a mean age of 55.89 ± 1.50 [mean ± standard error mean, SEM]). The treatment resulted in a statistically significant reduction in TC (from 258.9 ± 4.0 mg/dL to 212.7 ± 4.5 mg/dL, p < 0.001), LDL-C (from 173.8 ± 3.5 to 129.0 ± 4.5 mg/dL, p < 0.001), and TG (from 127.0 ± 12.2 to 117.0 ± 9.2, mg/dL, p = 0.012) concentrations, while HDL-C concentrations remained unchanged. There were no alterations in liver enzymes or symptoms of muscle pain in any subject. These promising results suggest that supplementation with this nutraceutical mixture favorably influences lipid concentrations during a short period of administration while exhibiting an excellent safety profile. Larger controlled studies are required to assess the potential for cardiovascular risk reduction with the above compound.
Itraconazole-Loaded Ufasomes: Evaluation, Characterization, and Anti-Fungal Activity against Candida albicans
Authors: Hashem Sara M. , Gad Mary K. , Anwar Hend M. , Saleh Neveen M. , Shamma Rehab N. , Elsherif Noha I.
Published: December 2022

Numerous obstacles challenge the treatment of fungal infections, including the uprising resistance and the low penetration of available drugs. One of the main active agents against fungal infections is itraconazole (ITZ), with activity against a broad spectrum of fungi while having few side effects. The aim of this study was to design ufasomes, oleic acid-based colloidal carriers, that could encapsulate ITZ to improve its penetration power. Employing a 2231 factorial design, the effect of three independent factors (oleic acid amount, cholesterol concentration, and ITZ amount) was investigated and evaluated for the percentage encapsulation efficiency (%EE), particle size (PS), and zeta potential (ZP). Optimization was performed using Design® expert software and the optimized ITZ-loaded ufasomes obtained had %EE of 99.4 ± 0.7%, PS of 190 ± 1 nm, and ZP of −81.6 ± 0.4 mV, with spherical unilamellar morphology and no aggregation. An in vitro microbiological study was conducted to identify the minimum inhibitory concentration of the selected formula against Candida albicans, which was found to be 0.0625 μg/mL. Moreover, the optimized formula reduced the expression of toll-like receptors-4 and pro-inflammatory cytokine IL-1β secretion in the C. albicans-infected fibroblasts, indicating that the proposed ITZ-loaded ufasomes are a promising drug delivery system for ITZ.
Exploring Key Aspects of an Integrated Sustainable Urban Development Strategy in Greece: The Case of Thessaloniki City
Authors: Chatzitheodoridis Fotios , Melfou Katerina , Kontogeorgos Achilleas , Kalogiannidis Stavros
Published: December 2022

Even though efforts have been made in recent decades to revive urban areas in the European Union (EU), the contemporary challenges that mostly large cities face require continuous support and adjustments in urban policies. Under the EU Cohesion Policy for the 2014–2020 programming period, the integrated territorial development of various specific areas is pursued by the Integrated Territorial Investments (ITI). In Greece, many of these programs concern Integrated Sustainable Urban Development Strategies (ISUDSs). One of these is the ISUDS of Thessaloniki, which is perhaps the most complex in terms of management and implementation in Greece, mainly due to the chosen managerial approach and the size of Thessaloniki, the second largest city in the country. Thessaloniki’s ISUDS is managed by the Urban Authority (UA), which has already evolved into a separate model of metropolitan governance administration. The aim of this paper is to identify the determinants in its design and implementation, as well as the effects of the strategy on urban development through the assessment of its strengths and weaknesses, as well as the opportunities and prospects of strategy through the Delphi approach.