Solid Phase Synthesis, DFT Calculations, Molecular Docking, and Biological Studies of Symmetrical N 2,N 4,N 6-Trisubstituted-1,3,5-triazines.

A diversity-oriented, multicomponent convergent synthesis of symmetrical triazines through a one-pot protocol is presented in this research project. The assembly of trisubstituted triazines was initially carried out using easily available reagents through three different protocols, i.e., conventional, MW-assisted synthesis, and solid-supported MW-assisted synthesis using organic and inorganic support to carry out a comparative analysis as to which procedure best corresponds to a greener synthesis protocol. The compounds formed were characterized for structure elucidation and subjected to in vitro anticancer and antibacterial screening. Additionally, computational studies, such as DFT calculations and molecular docking analyses, were conducted.

New Pyrimidinone Bearing Aminomethylenes and Schiff Bases as Potent Antioxidant, Antibacterial, SARS-CoV-2, and COVID-19 Main Protease MPro Inhibitors: Design, Synthesis, Bioactivities, and Computational Studies.

New 2-thioxopyrimidinone derivatives (A1-A10) were synthesized in 87-96% yields via a simple three-component condensation reaction. These compounds were screened extensively through in vitro assays for antioxidant and antibacterial investigations. The DPPH assays resulted in the excellent potency of A6-A10 as antioxidants with IC50 values of 0.83 ± 0.125, 0.90 ± 0.77, 0.36 ± 0.063, 1.4 ± 0.07, and 1.18 ± 0.06 mg/mL, which were much better than 1.79 ± 0.045 mg/mL for the reference ascorbic acid. These compounds exhibited better antibacterial potency against Klebsiella with IC50 values of 2 ± 7, 1.32 ± 8.9, 1.19 ± 11, 1.1 ± 12, and 1.16 ± 11 mg/mL for A6-A10. High-throughput screenings (HTS) of these motifs were carried out including investigation of drug-like behaviors, physiochemical property evaluation, and structure-related studies involving DFT and metabolic transformation trends. The radical scavenging ability of the synthesized motifs was validated through molecular docking studies through ligand-protein binding against human inducible nitric oxide synthase (HINOS) PDB ID: 4NOS, and the results were promising. Furthermore, the antiviral capability of the compounds was examined by in silico studies using two viral proteins PDB ID: 6Y84 and PDB ID: 6LU7. Binding poses of ligands were discussed, and amino acids in the protein binding pockets were investigated, where the tested compounds showed much better binding affinities than the standard inhibitors, proving to be suitable leads for antiviral drug discovery. The stabilities of the molecular docked complexes in real systems were validated by molecular dynamics simulations.

Pre- and postharvest chitosan coatings extend the physicochemical and bioactive qualities of minimally processed 'Crimson Seedless' grapes during cold storage.

BACKGROUND: Food marketers desire residue-free fresh grapes although grapes have a short postharvest life. This study was performed to determine the influences of pre- and/or postharvest chitosan (Ch) coatings on postharvest quality of minimally processed (stem-detached) organic 'Crimson Seedless' berries. Berries were sorted as: (a) control (untreated berries); (b) preharvest Ch (dipping the clusters on the vine into 1% Ch 10 days before harvest at 20% soluble solid content (SSC)); (c) postharvest Ch (dipping the stem-detached berries into 1% Ch); and (d) pre + postharvest Ch. Berries were stored in 12 × 15 cm rigid polypropylene cups for up to 42 days at 1.0 ± 0.5 °C. RESULTS: Pre- and/or postharvest Ch coating reduced weight loss during storage. Pre- + postharvest Ch was the best treatment for restricting polygalacturonase (PG) activity, extending the visual quality, color features (L*, C and h°), skin rupture force, biochemical (SSC, titratable acidity, maturity index and pH) and bioactive (total phenol content, antioxidant activity) features. Pre- or postharvest Ch was also significantly effective in maintaining many quality features. CONCLUSION: Pre- and/or postharvest 1% Ch coatings effectively maintained the quality of minimally processed grape berries of organically produced 'Crimson Seedless' grapes by delaying weight loss and PG activity and keeping the postharvest physical, biochemical and bioactive features for 42-day cold storage at 1.0 ± 0.5 °C. The combined use of pre- and postharvest Ch found to be more effective than single treatment. Thus, pre- + postharvest 1% Ch coating could be recommended as an ecofriendly sustainable methodology for extending the postharvest quality of minimally processed fresh grapes. © 2024 The Author(s). Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

2-Pyridone-Directed CuII-Catalyzed General Method of C(sp2)-H Activation for C-S, C-Se, and C-N Cross-Coupling: Easy Access to Aryl Thioethers, Selenide Ethers, and Sulfonamides and DFT Study.

We have demonstrated N-substituted 2-pyridones as an N,O-directing group for selective C(sp2)-H-activated thiolation, selenylation, and sulfonamidation of ortho C-H bonds of benzamides. This method utilizes a cost-effective Cu(II)-salt catalyst instead of precious metal catalysts, achieving high yields, including gram-scale synthesis and excellent functional group tolerance. We applied this protocol to access 30 different compounds with high yields, demonstrating thiolation of fluorine-substituted benzamides as well. Density functional theory (DFT) calculations support the mechanism, including acetate-supported concerted metalation deprotonation (CMD) steps and the unique role of dimethyl sulfoxide (DMSO) solvent. The facile synthesis of pharmaceutically important sulfonamides and other compounds highlights the method's potential in chemistry and medicinal chemistry.

Synthesis, X-ray crystallography, computational investigation on quinoxaline derivatives as potent against adenosine receptor A2AAR.

Quinoxaline represents one of the most important classes of heterocyclic compounds, which have exhibited a wide range of biological activities and industrial importance in many different fields. In this regard, we have synthetized two new quinoxaline derivatives. Their structures were confirmed by single-crystal X-ray analysis. The compounds show potent activity against adenosine receptors A2AAR based on structural activity relationship studies. Further molecular docking, molecular dynamics, ADMET analysis, and DFT (density functional theory) calculations were performed to understand the titled compound's future drug candidacy. DFT computations confirmed the good stability of the synthesized compounds, as evidenced by the optimized molecular geometry, HOMO-LUMO energy gap, and intermolecular interactions. NBO analysis confirmed intermolecular interactions mediated by lone pair, bonding, and anti-bonding orbitals. All DFT findings were consistent with experimental results, indicating that the synthesized molecules are highly stable. These findings suggest that the synthesized compounds are promising candidates for further development as drugs for the treatment of A2AAR-related diseases.Communicated by Ramaswamy H. Sarma.

Epidemiological and clinical characteristics of esophageal carcinoma: An experience from tertiary care hospital of Karachi, Pakistan.

Objectives: To describe current trends and characteristics of esophageal cancer (EC) over the past ten years largest tertiary care hospital of Karachi, Pakistan. Methods: This single center retrospective study was conducted at the Department of Gastroenterology and Oncology, Jinnah Postgraduate Medical Center, Karachi, Pakistan, between the period of ten years from 1st January 2010 to 31st December 2019. Patient data including epidemiological characteristics such as age, gender, education, residence, occupation, addictions, comorbidities, symptoms, location of EC, laboratory parameters and histopathological type were recorded. All patients with missing histological and radiological findings were excluded. Results: The mean age of all patients was 49.26±14.24 years and among them majority were females 566 (56.1%). Almost, 834 (82.7%) patients had SQC and 175 (17.3%) presented with ADS. Most common presenting symptom was dysphagia in both groups 327 (32.4%) followed by vomiting (22.8%) and weight loss 196 (19.4%). The Esophagogastroduodenoscopy (EGD) findings showed the distal esophagus involvement in most of the patients (36.3%) in both groups. CT scan findings showed that the lower region was the most involved region in 367 (36.4%) patients, followed by middle and upper in 227 (22.5%) and 156 (15.5%) patients respectively. The thickening of mass on CT- scan was circumferential in most of the patients (42.7%) in both groups. Conclusion: According to our findings, SQC is more prevalent than ADC. Female predominance especially at younger age was most common as compared to past studies. No significant association between a single risk factor has been found in our study however smoking and betel nut chewing were found as known putative risk factors.

Insight on the structural, electronic and optical properties of Zn, Ga-doped/dual-doped graphitic carbon nitride for visible-light applications.

The density functional theory (DFT) was applied for the first time to study the doping and co-doping of Ga and Zn metals on graphitic carbon nitride (g-C3N4). The doping of these metal impurities into g-C3N4 leads to a significant decrease in the bandgap energy. Moreover, the co-doping leads to even lower bandgap energy than either individual Zn or Ga-doped g-C3N4. The theoretical electronic and optical properties including the density of state (DOS), energy levels of the frontier orbital, excited state lifetime, and molecular electrostatic potential of the doped and co-doped g-C3N4 support their application in UV-visible light-based technologies. The quantum mechanical parameters (energy band gap, binding energy, exciton energy, softness, hardness) and dipole moment exhibit higher values (ranging from 1.36 to 4.94 D) compared to the bare g-C3N4 (0.29 D), indicating better solubility in the water solvent. The time-dependent DFT (TD-DFT) calculations showed absorption maxima in between the UV-Vis region (309-878 nm). Additionally, charge transfer characteristics, transition density matrix (TDM), excited state lifetime and light harvesting efficiency (LHE) were investigated. Overall, these theoretical studies suggest that doped and co-doped g-C3N4 are excellent candidates for electronic semiconductor devices, light-emitting diodes (LEDs), solar cells, and photodetectors.

Influence of COVID-19 vaccination on the dynamics of new infected cases in the world.

The initial COVID-19 vaccinations were created and distributed to the general population in 2020 thanks to emergency authorization and conditional approval. Consequently, numerous countries followed the process that is currently a global campaign. Taking into account the fact that people are being vaccinated, there are concerns about the effectiveness of that medical solution. Actually, this study is the first one focusing on how the number of vaccinated people might influence the spread of the pandemic in the world. From the Global Change Data Lab "Our World in Data", we were able to get data sets about the number of new cases and vaccinated people. This study is a longitudinal one from 14/12/2020 to 21/03/2021. In addition, we computed Generalized log-Linear Model on count time series (Negative Binomial distribution due to over dispersion in data) and implemented validation tests to confirm the robustness of our results. The findings revealed that when the number of vaccinated people increases by one new vaccination on a given day, the number of new cases decreases significantly two days after by one. The influence is not notable on the same day of vaccination. Authorities should increase the vaccination campaign to control well the pandemic. That solution has effectively started to reduce the spread of COVID-19 in the world.

Structure, functions, performance and gaps of event-based surveillance (EBS) in Sudan, 2021: a cross-sectional review.

BACKGROUND: Event-based surveillance (EBS) is an essential component of Early Warning Alert and Response (EWAR) as per the International Health Regulations (IHR), 2005. EBS was established in Sudan in 2016 as a complementary system for Indicator-based surveillance (IBS). This review will provide an overview of the current EBS structure, functions and performance in Sudan and identify the gaps and ways forward.  METHODS: The review followed the WHO/EMRO guidelines and tools. Structured discussions, observation and review of records and guidelines were done at national and state levels. Community volunteers were interviewed through phone calls. Directors of Health Emergency and Epidemic Control, surveillance officers and focal persons for EBS at the state level were also interviewed. SPSS software was used to perform descriptive statistical analysis for quantitative data, while qualitative data was analysed manually using thematic analysis, paying particular attention to the health system level allowing for an exploration of how and why experiences differ across levels. Written and verbal consents were obtained from all participants as appropriate. RESULTS: Sudan has a functioning EBS; however, there is an underestimation of its contribution and importance at the national and states levels. The link between the national level and states is ad hoc or is driven by the need for reports. While community event-based surveillance (CEBS) is functioning, EBS from health facilities and from non-health sectors is not currently active. The integration of EBS into overall surveillance was not addressed, and the pathway from detection to action is not clear. The use of electronic databases and platforms is generally limited. Factors that would improve performance include training, presence of a trained focal person at state level, and regular follow-up from the national level. Factors such as staff turnover, income in relation to expenses and not having a high academic qualification (Diploma or MSc) were noticed as inhibiting factors. CONCLUSION: The review recommended revisiting the surveillance structure at national and state levels to put EBS as an essential component and to update guidelines and standard operation procedures SOPs to foster the integration between EBS components and the overall surveillance system. The need for strengthening the link with states, capacity building and re-addressing the training modalities was highlighted.

Parameter Estimation in Step Stress Partially Accelerated Life Testing under Different Types of Censored Data.

A long testing period is usually required for the life testing of high-reliability products or materials. It is possible to shorten the testing process by using ALTs (accelerated life tests). Due to the fact that ALTs test products in harsher settings than are typical use conditions, the life expectancy of the objects they evaluate is reduced. Censored data in which the specific failure timings of all units assigned to test are not known, or all units assigned to test have not failed, may arise in ALTs for a variety of reasons, including operational failure, device malfunction, expense, and time restrictions. In this paper, we have considered the step stress partially accelerated life test (SSPALT) under two different censoring schemes, namely the type-I progressive hybrid censoring scheme (type-I PHCS) and the type-II progressive censorship scheme (type-II PCS). The failure times of the items are assumed to follow NH distribution, while the tampered random variable (TRV) model is used to explain the effect of stress change. In order to obtain the estimates of the unknown parameters, the maximum likelihood estimation (MLE) approach is adopted. Furthermore, based on the asymptotic theory of MLEs, the approximate confidence intervals (ACIs) are also constructed. The point estimates under two censoring schemes are compared in terms of root mean squared errors (RMSEs) and relative absolute biases (RABs), while ACIs are compared in terms of their lengths and coverage probabilities (CPs). The performance of the estimators has been evaluated and compared under two censoring schemes with various sample sizes through a simulation study. Simulation results show that estimates with type-I PHCS outperform estimates with type-II PCS in terms of RMSEs, RABs, lengths, and CPs. Finally, a real-world numerical example of insulating fluid failure times is presented to show how the approaches will work in reality.

Heat transfer analysis for EMHD peristalsis of ionic-nanofluids via curved channel with Joule dissipation and Hall effects.

The objective of this research is to study the combined influences of applied electric and magnetic fields on the two-phase peristaltic motion of nanofluid through a curved channel. A two-phase model of a nanofluid, Maxwell's model of thermal conductivity [1], and no-slip velocity and thermal boundary conditions have been used in this study. Hall effects, Joule heating (due to magnetic and electric fields), and viscous heating aspects are under consideration. Governing equations for the present flow configuration have been modeled and simplified by enforcing the lubrication scheme. Debye-Huckel approximation is used to obtain the analytical solution of the electric potential function (Poisson-Boltzmann equation). Resulting expressions are solved numerically through the NDSolve command in Mathematica and plotted in order to understand the effects of different dimensionless parameters on the temperature, stress, heat transmission rate, and fluid's velocity. Graphical results demonstrated that the thermal transmission rate is augmented by increasing the Hartmann number, Brinkman number, and Debye-Huckel parameter while decreases for zeta potential ratio, Joule dissipation parameter, and electro-osmotic velocity. A decrease in axial velocity is noted near the lower wall for higher values of [Formula: see text].

Retrospective study of frequency of ABO and Rhesus blood group among population of Safdarabad and Faisalabad cities of Pakistan.

OBJECTIVE: The current study aimed to investigate the ABO and rhesus (Rh) blood group frequency in the people of District Faisalabad and Sheikhupura, Punjab Province, Pakistan. The retrospective study was conducted on more than thirty thousand people including both male and female patients admitted to the Tehsil Headquarter Hospital, Safdarabad and The Best Hospital, Faisalabad. Blood samples were taken from each subject and subsequently ABO and Rh blood groups were evaluated separately. The antigen antibody agglutination slide test for blood grouping (ABO) and Rh were used to assess the blood group frequencies. RESULTS: The frequencies of ABO blood group distribution indicated that blood group B was predominant in the people of Safdarabad followed by O, A and AB respectively. While, among people of Faisalabad, blood group O was predominant followed B, A and AB respectively. Rh negative phenotype was found lesser distributed as compared to the positive Rh phenotype.

Efficient tuning of zinc phthalocyanine-based dyes for dye-sensitized solar cells: a detailed DFT study.

The growing energy demand speed up the designing of competent photovoltaic materials. Herein, five zinc phthalocyanine-based donor materials T1-T5 are designed by substituting various groups (isopropoxy, cyano, fluoro, methoxycarbonyl, and dicyanomethyl) around zinc phthalocyanine. B3LYP/6-31G (d,p) level density functional theory (DFT) was used to investigate the optoelectronic properties of five zinc phthalocyanine-based dyes T1-T5 for dye-sensitized solar cells. The designed molecule T1 shows maximum absorption wavelength (λ max) in the absorption spectrum at 708.89 and 751.88 nm both in gaseous state and in THF (tetrahydrofuran) solvent. The E g value of T1 (1.86 eV) is less than reference R, indicating a greater charge transfer rate for T1 among the molecules. The values of open-circuit voltages achieved with acceptor polymer PC71BM are higher than R except for T1 and are 0.69 V, 1.95 V, 1.20 V, 1.44 V, and 1.84 V for T1, T2, T3, T4, and T5, respectively. The lower the reorganization energy, the higher the charge transfer for T1 due to its lower hole mobility (0.06297 eV) than R. Thus, the designed T1-T5 molecules are expected to exhibit superior performance in dye-sensitized solar cells.

Patterns of Diabetes Care Among People with Type 1 Diabetes During Ramadan: An International Prospective Study (DAR-MENA T1DM).

INTRODUCTION: To describe the characteristics and care of participants with type 1 diabetes during Ramadan in the Middle East and North Africa. METHODS: The DAR-MENA (Diabetes and Ramadan-Middle East and North Africa) study was a prospective, observational study of adults with type 1 and type 2 diabetes who were Muslim and did/did not intend to fast during Ramadan 2016. Baseline data were collected 6 weeks prior to Ramadan, with a follow-up visit 1-2 months after Ramadan. This is the analysis of the population with type 1 diabetes. Measurements included proportion who fasted, reasons for fasting and not fasting, changes in diabetes treatment, hypoglycemic events, and proportion with access to diabetes education. RESULTS: Of 136 participants with type 1 diabetes, 76.9% (100/130) fasted for at least 1 day, 72.3% (94/130) fasted for at least 15 days, and 48.5% (63/130) fasted for 30 days. The majority (63.0%, 63/100) reported personal decision as a reason to fast. Fear of diabetic complications (58.6%, 17/29) and previous complications related to fasting (48.3%, 14/29) were the most common reasons for not fasting. Adjustment of diabetic medication regimen occurred for 84.6% (115/136) of participants, and 72.8% (99/136) changed their treatment dose. The incidence and number of adverse events for confirmed and severe hypoglycemia were similar before and during Ramadan. Almost half of participants had access to diabetes education (45.6%, 62/136). CONCLUSION: The DAR-MENA study showed that despite the risks associated with fasting for people with type 1 diabetes, almost half fasted for the full 30 days of Ramadan with no significant change in hypoglycemia events. Since the current International Diabetes Federation and Diabetes and Ramadan guidelines do not endorse fasting for people with type 1 diabetes, it is important that those who insist on fasting work closely with their healthcare practitioner to avoid any complications.

Novel approach in managing post-extraction alveolar bone dimensions.

This case report presents a novel approach towards the preservation of alveolar ridge dimensions following the extraction of an upper left lateral incisor. The extracted teeth of a 56-year old patient was ground with a diamond bur running under the normal saline spray. Sedimented fine tooth-powder was collected and mixed with 2.0 ml of patient's intravenous blood. The powdered paste pushed inside the tooth socket by means of plugger until the socket was filled, leaving a space of 3mm only. The socket was sutured with a non-resorbable silk material. After one week, the adjacent tooth were endodontically prepared and a fixed partial denture was placed on the prepared abutments. The results suggest therapeutic approach with no immune response, which can be implemented at chairside. A significant preservation of alveolar ridge can be maintained using this novel approach.

Macrophage Activation Syndrome Associated With Adult Onset Still's Disease.

Macrophage activation syndrome (MAS) is a potentially lethal complication of chronic rheumatological conditions like ankylosing spondylitis, rheumatoid arthritis, and adult-onset Still's disease (AOSD). It is a multisystem inflammatory syndrome caused by immense cytokine release from activated lymphocytes and macrophages. We give an account of the incidence of a twenty years old Asian girl suffering from non-remitting fever and an evanescent rash for last ten weeks. Physical examination and laboratory work-up suggested high grade fever, pancytopenia, hyperferritinemia, hypertriglyceridemia, hypofibrinogenemia and impaired liver function. Bone marrow biopsy was also done. It showed active hemophagocytosis. She was diagnosed as a case of Macrophage Activation Syndrome associated with Adult Onset Still's disease. She was treated with high dose steroids and cyclosporine and recovered completely.

Nonlinear thermal radiation and cubic autocatalysis chemical reaction effects on the flow of stretched nanofluid under rotational oscillations.

Combined effects of nonlinear thermal radiation and cubic autocatalysis chemical reaction on the three dimensional flow of stretched nanofluid along a rotating sheet have been investigated in this paper. The flow field is assumed to be suspended with magnetic iron oxide nanoparticles (IONPs). Hamilton-Crosser model is applied to measure effective thermal conductivity of nanofluid. Rosseland approximation is employed to obtain the nonlinear radiative heat flux. For novelty and practical point of view, influence of fluctuating surface velocity and periodic surface temperature constraints are incorporated into the governing equations which in turn are made dimension free by employing suitable transformations. For numerical solutions, an explicit finite difference scheme has been proposed under the restrictions of derived stability conditions.

Temperature and Concentration Stratification Effects in Mixed Convection Flow of an Oldroyd-B Fluid with Thermal Radiation and Chemical Reaction.

This research addresses the mixed convection flow of an Oldroyd-B fluid in a doubly stratified surface. Both temperature and concentration stratification effects are considered. Thermal radiation and chemical reaction effects are accounted. The governing nonlinear boundary layer equations are converted to coupled nonlinear ordinary differential equations using appropriate transformations. Resulting nonlinear systems are solved for the convergent series solutions. Graphs are plotted to examine the impacts of physical parameters on the non-dimensional temperature and concentration distributions. The local Nusselt number and the local Sherwood number are computed and analyzed numerically.

MHD mixed convective peristaltic motion of nanofluid with Joule heating and thermophoresis effects.

The primary objective of present investigation is to introduce the novel aspect of thermophoresis in the mixed convective peristaltic transport of viscous nanofluid. Viscous dissipation and Joule heating are also taken into account. Problem is modeled using the lubrication approach. Resulting system of equations is solved numerically. Effects of sundry parameters on the velocity, temperature, concentration of nanoparticles and heat and mass transfer rates at the wall are studied through graphs. It is noted that the concentration of nanoparticles near the boundaries is enhanced for larger thermophoresis parameter. However reverse situation is observed for an increase in the value of Brownian motion parameter. Further, the mass transfer rate at the wall significantly decreases when Brownian motion parameter is assigned higher values.