Rational Design, Synthesis, and Computational Investigation of Dihydropyridine [2,3-d] Pyrimidines as Polyphenol Oxidase Inhibitors with Improved Potency

Polyphenol oxidase (PPO) is an industrially important enzyme associated with browning reactions. In the present study, a set of ten new dihydropyridine [2,3-d] pyrimidines (TD-Hid-1-10) were synthesized and was found to be proven characteristically by 1H NMR, 13C NMR, IR, elemental analysis, and assessed as possible PPO inhibitors. PPO was purified from banana using three-phase partitioning, achieving an 18.65-fold purification and 136.47% activity recovery. Enzyme kinetics revealed that the compounds TD-Hid-6 and TD-Hid-7 are to be the most potent inhibitors, exhibiting mixed-type inhibition profile with IC50 values of 1.14 mu M, 5.29 mu M respectively against purified PPO enzyme. Electronic structure calculations at the B3LYP/PBE0 level of theories using def-2 SVP, def2-TZVP basis sets with various molecular descriptors characterized the electronic behavior of studied derivatives TD-Hid-1-10. Molecular electrostatic potential (MEP) and reduced density gradient analyses of RDG-NCI provided insights into charge distributions and weak intermolecular interactions. Docking study simulations predicted binding poses within crucial amino acid sequence in the 2y9x enzyme's active site, which is typically similar in sequence to the PPO form is not allowed. Ligands were analysed in terms of binding energies, inhibitor concentrations (mM) and various molecular interactions such as H-bonds, H-carbon, pi-carbon, pi-sigma, pi-sigma, pi-pi T-shaped, pi-pi stacked, pi-alkyl, Van der Waals and Cu interactions. The lowest binding energy (-7.83 kcal/mol) and the highest inhibitory effect (1.83 mM) were shown by the ligand Td-Hid-6, which forms H-bonds with Met280 and Asn260, exhibits pi-sigma interactions with His61 and pi-alkyl interactions with Val283. Other ligands also showed different interactions with various amino acids; for example, the Td-Hid-1 ligand formed H-bonds with His244 and showed pi-sigma interactions with His244 and Val283.Sakarya University [2012-02-04-033/2016-50-02-002]This work was supported by the Research Fund of Sakarya University (2012-02-04-033/2016-50-02-002) and authors are thankful to Duezce University Scientific and Technological Research Laboratory for providing spectral data. DAS:No datasets were generated or analysed during the current study

The crime and punishment of non-Muslims for insulting the prophet

In recent years, there has been a systematic increase in the number of verbal and actual insults against the holy places of Muslims. It is seen that a significant portion of these insulting and humiliating activities are directed against the Prophet Muhammad. No one has the right to engage in verbal or actual acts that hurt the honor and dignity of another person. Words and behaviors that violate personal rights are considered as crimes by all legal systems and criminal sanctions are envisaged. Since the offense of insulting the Prophet is not only a violation of personal rights, but also against the sacred values of all Muslims, it is more appropriate to consider it as a qualified crime. Since the crime of insulting the Prophet by a Muslim person is considered within the scope of apostasy, which is a separate type of crime, the study is limited to the crime of insulting the Prophet by non -Muslims. In the Islamic legal literature, the crime of insulting the Prophet by a non -Muslim is mostly dealt with outside the heading of uk & umacr;b & amacr;t within the framework of the dhimma contract/citizenship law. Detached works have also been written on the subject. Although there are different opinions, there is a general opinion that the penalty for the crime of insulting the Prophet is death. In this context, Hanafis, unlike other schools of fiqh, express their opinion that the crime of a non -Muslim citizen in this context will not harm the dhimmah contract, which is an important breakthrough on the subject. This article focuses on the bases of the death penalty for the crime of insulting the Prophet. In addition, the issue is discussed in terms of crime -punishment compatibility and a new approach to the punishment for the crime of insulting the Prophet is presented. In this context, it is revealed that the death penalty envisaged within the scope of the crime in question is incompatible with the crime -punishment compatibility

Investigation of the effects of Toxoplasma gondii on behavioral and molecular mechanism in bradyzoite stage

Toxoplasma gondii is a single-celled parasite that causes a disease called toxoplasmosis. It can reach the central nervous system, but the mechanism of T. gondii disrupting the functioning of these brain regions occurs in bradyzoite stage of parasite, causing brain damage by forming tissue cysts in brain. In our study, the effects of T. gondii on locomotor activity, anxiety, learning and memory, and norepinephrine (NE), levodopa (L -DOPA), dopamine (DA) and 3,4-D-dihydroxyphenylacetic acid (DOPAC) catecholamines in amygdala, striatum, prefrontal cortex and hippocampus regions of the brain were investigated in bradyzoite stage. Twenty male Albino mice Mus musculus, 4-5 weeks old, weighing 20-25 g, were used. T. gondii inoculated to mice intraperitonealy with 48-50-hour passages of T. gondii RH Ankara strain. For intraperitoneal inoculation of mice 5x104 tachyzoites per mouse. No inoculation was made in control group (n: 20). Locomotor activity behavior in open field test (OFT), anxious behavior in elevated plus maze (EPM), and learning behavior in novel object recognition (NOR) tests were evaluated. NE, L -DOPA, DA and DOPAC were measured by HPLC in brain tissues of amygdala, striatum, prefrontal cortex and hippocampus. A decrease was observed in the locomotor activity, anxiety and learning values of the T. gondii group compared to the control group (p < 0.05). The heighten in NE and L -DOPA levels in amygdala tissue of T. gondii group compared to control group, an elevation in NE, L -DOPA, DA and DOPAC levels in striatum tissue, and an increase in levels of NE in prefrontal cortex tissue were detected in monoamine results. In hippocampus tissue, an increase was observed in DA levels, while a decrease was observed in NE, L -DOPA and DOPAC levels. In our study, it has been shown that T. gondii in bradyzoite stage reduces locomotor activity, causes learning and memory impairment, and has anxiogenic effects.Coordination Unit of Scientific Research Projects of Hitit University [TIP19001.21.007]Funding This work was supported by Coordination Unit of Scientific Research Projects of Hitit University (Project number: TIP19001.21.007)

Fe/PZT ve Co/PZT ince filmlerinin dielektrik özelliklerinin incelenmesi

Ferroelektrik özelliklere sahip PbZr0.5Ti0.5O3 seramik malzemesi elektriksel ve elektromekaniksel özelliklerinden dolayı araştırmacılar tarafından büyük ilgi görmektedir. Bu çalışmada, Ferroelektrik PbZr0.5Ti0.5O3 (PZT) seramik malzemesi üzerine vakum buharlaştırma tekniği ile ferromanyetik özelliklere sahip Fe ve Co malzemeleri ayrı ayrı kaplanmıştır. Hazırlanmış ince filmlerin dielektrik sabitinin reel ve sanal kısımları, kayıp tanjantı, cole-cole diyagram gibi dielektrik özelliklerin frekansla değişimi incelenmiştir. Saf PZT, Fe kaplı PZT ve Co kaplı PZT ince filmlerin dielektrik sabitinin reel ve sanal kısımları, kayıp tanjantı, cole-cole diyagramı oda sıcaklığında frekansın bir fonksiyonu olarak yüksek frekans (1 MHz – 3 GHz) aralığında empedans analizörü ile ölçülmüştür.PbZr0.5Ti0.5O3 ceramic material, which has ferroelectric properties, attracts great attention from researchers due to its electrical and electromechanical properties. In this study, Fe and Co materials with ferromagnetic properties were coated separately on the ferroelectric PbZr0.5Ti0.5O3 (PZT) ceramic material by vacuum evaporation technique. The variation of dielectric properties such as the real and imaginary parts of dielectric constant, loss tangent, cole-cole diagram of the prepared thin films with frequency was examined. The real and imaginary parts of dielectric constant, loss tangent, cole-cole diagram of pure PZT, Fe-coated PZT and Co-coated PZT thin films were measured with an impedance analyzer as a function of frequency in the range of high frequency (1 MHz – 3 GHz) at room temperature

Durability Ratings of Post-treated Wood-based Composites after 14 Years of Field Exposure

Several commercial wood -based composites (softwood plywood [SWP], hardwood plywood [HWP], medium -density fiberboard [MDF], oriented strand board [OSB], and particleboard) [PB]) were post -treated with alkaline copper quat and copper azole at two different retention levels. The treated specimens were installed on concrete blocks covered with 5 -sided PVC boxes simulating the crawl space conditions (protected aboveground) in Japanese houses in Southern Japan where decay and termite activity are high. The experimental variables are a comparison of treated versus untreated, preservative type and retention levels. During 14 years of exposure, the specimens were biannually visually rated. In general, termite damage became visible earlier and the harshness of attack was higher when compared to decay damage. The untreated and treated MDFs were the most resistant under the protected above ground conditions at the end of 14 years exposure. Particleboard durability performance followed the MDF rating during the same period. The untreated OSB, HWP, and SWP were the least resistant composite types. The treatments substantially increased the durability of the mentioned composite types by 317.6%, 80.5%, and 133% higher termite grading when correlated to their untreated controls, respectfully, yet they failed to maintain full protection. Based on statistical analysis, preservative types and retention levels did not significantly affect decay and termite ratings.RISH, Kyoto UniversityThe first author extends his appreciation to RISH, Kyoto University for support under the Visiting Professor program between 1St March 2023 to 31St August 2023, and to Mr. Akio Adachi and the Laboratory of Innovative Humano-habitability personnel who were involved in 14 years of data collection

A Case of Giant Retropharyngeal Lipoma Causing Airway Obstruction

[No abstract available

Application of Optimization Response Surface for the Adsorption of Methylene Blue Dye onto Zinc-coated Activated Carbon

The activated carbon was produced in the first phase of this investigation by chemically activating hazelnut shell waste with H3PO4. Composite materials were obtained by coating the activated carbon with zinc oxide, whose BET surface area was calculated as 1278 m2 g-1. ZnO-doped ZnO/AC composite was synthesized as an adsorbent for its possible application in the elimination of organic dyestuff MB, and its removal efficiency was investigated. Morphological properties of ZnO/AC were characterized using analytical methods such as XRD, SEM, and BET. The adsorption system and its parameters were investigated and modeled using the response surface method of batch adsorption experiments. The experimental design consisted of three levels of pH (3, 6.5, and 10), initial MB concentration (50, 100, and 150 mg L-1), dosage (0.1, 0.3, and 0.5 g 100 mL-1), and contact time (5, 50, and 95 min). The results from the RSM suggested that the MB removal efficiency was 98.7% under the optimum conditions of the experimental factors. The R2 value, which expresses the significance of the model, was determined as 99.05%. Adsorption studies showed that the equilibrium data fit well with the Langmuir isotherm model compared to Freundlich. The maximum adsorption capacity was calculated as 270.70 mg g-1.SUBU Research Scientific Research Projects Unit (SUBU BAP) [2021-27-05-037]This study was supported by the SUBU Research Scientific Research Projects Unit (SUBU BAP, Project No: 2021-27-05-03

Field Observations and Numerical Investigations on Seismic Damage Assessment of RC and Masonry Minarets During the February 6th, 2023, Kahramanmaraş (Mw 7.7 Pazarcık and Mw 7.6 Elbistan) Earthquakes in Türkiye

On February 6, 2023, two massive earthquakes struck the EasternAnatolian Fault Line (EAF) at 9-hour intervals. The Mw 7.7 and Mw 7.6 earthquakes were located in Pazarcik and Elbistan districts inKahramanmaras province. These earthquakes directly damaged 11 provinces in Eastern and Southeastern Anatolia (Kahramanmaras,Hatay, Adyaman, Osmaniye, Gaziantep, Sanlurfa, Malatya, Diyarbakir,Adana, Kilis, and Elazig), causing substantial loss of life and property. This study aims to present the field investigation of reinforced concrete (RC) and masonry minarets in 11 cities around the area after these earthquakes and the structural performance and collapse mechanism of two minarets selected as case studies. For this purpose, the damaged or collapsed minarets in the region affected by the earthquakes were determined and the reasons were explained. In addition, an RC and a masonry minaret in the Islahiye district were chosen as case studies, and finite element models (FEM) were created.The validity and correctness of the reasons for damages determined by field observations were further demonstrated by numerical findings.It was determined that nearly all of the damaged and collapsed minarets did not obtain proper engineering services. Additionally, it is believed that the lack of any norms or regulations for these unique constructions is a significant weakness that places engineers in a challenging situation throughout the design phaseScientific and Technological Research Council of Turkiye (TUEBITAK)The authors would like to acknowledge sincere thanks to The Scientific and Technological Research Council of Turkiye (TUBITAK), for supporting and funding the site investigations with 1002-C Natural Disasters - Focused Fieldwork Emergency Investigation program

The effect of resilience psychoeducation program based on positive psychotherapy on nurses' resi?li?ence and balanced life skills

Bu araştırma, Pozitif Psikoterapiye Dayalı Psikolojik Dayanıklılık Programının hemşirelerin psikolojik dayanıklılıklarına etkisini belirlemek amacıyla yapılmıştır. Araştırma, randomize kontrollü ve fenomolojik (olgu bilim) desende karma bir çalışma olarak yürütülmüştür. Araştırmada, ön test-son test–izlem yaklaşımı ile randomize kontrollü deneysel araştırma tasarımı, hemşirelerin yaşam enerjilerini dengeli kullanma durumlarını ve dengeli yaşam becerilerini belirlemek amacıyla niteliksel yöntemlerden "derinlemesine görüşme tekniği" kullanılmıştır. Araştırma Mayıs 2023-Aralık 2023 tarihleri arasında Düzce Üniversitesi Araştırma ve Uygulama Hastanesi'nde yapılmıştır. Araştırmanın örneklemini, yapılan güç analizi sonucunda çalışmaya katılmayı kabul eden ve örnekleme alınma kriterlerini taşıyan toplam 66 hemşire (müdahale grubu=31, kontrol grubu=35) oluşturmuştur. Araştırmanın nicel verileri "Kişisel Bilgi Formu" ve "Yetişkinler için Psikolojik Dayanıklılık Ölçeği" ile ön test-son test ve izlem testi şeklinde toplanmıştır. Nitel veriler programı tamamlayan 14 gönüllü hemşire ile derinlemesine görüşme tekniği kullanılarak toplanmıştır. Araştırmanın nicel verilerinin analizi SPSS (Statistical Package for Social Sciences) for Windows 25.0 programı paket programı üzerinden yapılmıştır. Yapılan analizler sonucunda, Yetişkinler için Psikolojik Dayanıklılık Ölçeği alt boyutlarında aile uyumu alt boyutunda deney grubunda; gruplar arası, zamana göre ve grup zaman etkileşimi yönünden anlamlı fark bulunmuştur. Gelecek algısı ve sosyal yeterlilik alt boyutlarında deney grubunda zamana göre ve grup zaman etkileşimi yönünden anlamlı sonuçlar ortaya çıkmıştır. Psikolojik dayanıklılık toplam puanında gruplar arası düşük, deney grubunda zamana göre yüksek düzeyde anlamlı fark tespit edilmiştir (p<0,05). Nitel verilerin analizinde katılımcıların ifadeleri hiç değiştirilmeden bilgisayar ortamında deşifre edilmiştir. Kodlar anlam bütünlüğüne göre gruplandırılmış ve bu kodları temsil edebilecek, ana tema ve alt temalar oluşturulmuştur. Yaşam dengesi, gerçek yetenekler, anahtar çatışma, zorlayıcı yaşam olayları, programın genel değerlendirilmesi ve 5 yıl sonra olarak toplam 6 ana temaya ulaşılmıştır. Bu sonuçlar doğrultusunda Pozitif Psikoterapiye Dayalı Psikolojik Dayanıklılık Programının hemşirelerin psikolojik dayanıklılık geliştirmesinde ve dengeli yaşam becerilerini öğrenme ve kullanma konusunda etkin olduğunu düşünülerek, programın hemşirelerin psikolojik dayanıklılığını arttırma ve dengeli yaşam becerileri öğrenebilmeleri için kullanılması önerilmektedir.This study was conducted to determine the effect of Positive Psychotherapy Based Resilience Program on the resilience of nurses. The research was designed as a mixed randomized controlled and phenomenological study. In the study, randomized controlled experimental research design with pretest-posttest-follow-up approach, "in-depth interview technique" from qualitative methods was employed to determine nurses' balanced utilization of life energies and balanced life skills. The research was conducted between May 2023 and December 2023 at Düzce University Research and Application Hospital. The sample of the study consisted of 66 nurses (intervention group=31, control group=35) who consented to participate in the study as a result of the power analysis and fulfilled the sampling criteria. The quantitative data of the study were collected through "Personal Information Form" and "Resilience Scale for Adults" as pre-test, post-test and follow-up test. Qualitative data were obtained through in-depth interviews with 14 volunteer nurses who completed the program. The quantitative data of the study were analyzed through SPSS (Statistical Package for Social Sciences) for Windows 25.0 software package. As a result of the analyses, in the sub-dimension measurements of the Resilience Scale for Adults, there was a significant difference in family harmony in the experimental group, between groups, in terms of time and group-time interaction. In the total score of resilience, there was a low significant difference between the groups and a high significant difference in the experimental group according to time (p<0.05). In the analysis of qualitative data, the statements of the participants were deciphered in the computer environment without any change. The codes were grouped according to the integrity of meaning and main themes and sub-themes were formed to represent these codes. A total of 6 main themes were reached: life balance, genuine abilities, key conflict, challenging life events, general evaluation of the program and 5 years later. In line with these results, it is believed that the Positive Psychotherapy-Based Resilience Program is effective in developing resilience of nurses and learning and utilizing balanced life skills, and it is recommended that the program should be implemented to increase the resilience of nurses and assist them to develop balanced life skills

Evidence-based herbal treatments in liver diseases

The liver is the main organ for metabolic and detoxification reactions in the body. Therefore, its diseases can be associated with both metabolic disorders, such as insulin resistance, obesity, diabetes, or dyslipidemia, and exogenous insults such as drugs, xenobiotics, or alcohol. Indeed, lifestyle changes are the primary approaches for the prevention and treatment of liver diseases. Since ancient times, herbals have also been used for preventive and therapeu-tic purposes, because of their anti-apoptotic, anti-inflammatory, and antioxi-dant effects. Here, the literature was reviewed for potential therapeutic effects of plants and their compounds by including in vitro and in vivo studies, as well as clinical trials. Although the available data imply some beneficial roles of herbals on the liver, the indications and posology of specific plants need to be clarified through multicenter, randomized clinical trials