Pyrimidine-morpholine hybrids as potent druggable therapeutics for Alzheimer's disease: Synthesis, biochemical and in silico analyses.

The identification of effective and druggable cholinesterase inhibitors to treat progressive neurodegenerative Alzheimer's disorder remains a continuous drug discovery hunt. In this perspective, the present study investigates the design and discovery of pyrimidine-morpholine hybrids (5a-l) as potent cholinesterase inhibitors. Palladium-catalyzed Suzuki-Miyaura cross-coupling reaction was employed to introduce the structural diversity on the pyrimidine heterocyclic core. A range of commercially available boronic acids was successfully coupled showing a high functional group tolerance. In vitro cholinesterase inhibitory potential using Ellman's method revealed significantly strong potency. Compound 5h bearing a meta-tolyl substituent at 2-position of pyrimidine ring emerged as a lead candidate against AChE with an inhibitory potency of 0.43 ± 0.42 µM, ∼38-fold stronger value than neostigmine (IC50 = 16.3 ± 1.12 µM). Compound 5h also showed the lead inhibition against BuChE with an IC50 value of 2.5 ± 0.04 µM. The kinetics analysis of 5h revealed the non-competitive mode of inhibition against AChE whereas computational modelling results of potent leads depicted diverse contacts with the binding site amino acid residues. Molecular dynamics simulations revealed the stability of biomolecular system, while, ADME analysis demonstrated druglikeness behaviour of potent compounds. Overall, the investigated pyrimidine-morpholine scaffold presented a remarkable potential to be developed as efficacious anti-Alzheimer's drugs.

Toward QoS Monitoring in IoT Edge Devices Driven Healthcare-A Systematic Literature Review.

Smart healthcare is altering the delivery of healthcare by combining the benefits of IoT, mobile, and cloud computing. Cloud computing has tremendously helped the health industry connect healthcare facilities, caregivers, and patients for information sharing. The main drivers for implementing effective healthcare systems are low latency and faster response times. Thus, quick responses among healthcare organizations are important in general, but in an emergency, significant latency at different stakeholders might result in disastrous situations. Thus, cutting-edge approaches like edge computing and artificial intelligence (AI) can deal with such problems. A packet cannot be sent from one location to another unless the "quality of service" (QoS) specifications are met. The term QoS refers to how well a service works for users. QoS parameters like throughput, bandwidth, transmission delay, availability, jitter, latency, and packet loss are crucial in this regard. Our focus is on the individual devices present at different levels of the smart healthcare infrastructure and the QoS requirements of the healthcare system as a whole. The contribution of this paper is five-fold: first, a novel pre-SLR method for comprehensive keyword research on subject-related themes for mining pertinent research papers for quality SLR; second, SLR on QoS improvement in smart healthcare apps; third a review of several QoS techniques used in current smart healthcare apps; fourth, the examination of the most important QoS measures in contemporary smart healthcare apps; fifth, offering solutions to the problems encountered in delivering QoS in smart healthcare IoT applications to improve healthcare services.

Melatonin Role in Plant Growth and Physiology under Abiotic Stress.

Phyto-melatonin improves crop yield by mitigating the negative effects of abiotic stresses on plant growth. Numerous studies are currently being conducted to investigate the significant performance of melatonin in crops in regulating agricultural growth and productivity. However, a comprehensive review of the pivotal performance of phyto-melatonin in regulating plant morpho-physiological and biochemical activities under abiotic stresses needs to be clarified. This review focused on the research on morpho-physiological activities, plant growth regulation, redox status, and signal transduction in plants under abiotic stresses. Furthermore, it also highlighted the role of phyto-melatonin in plant defense systems and as biostimulants under abiotic stress conditions. The study revealed that phyto-melatonin enhances some leaf senescence proteins, and that protein further interacts with the plant's photosynthesis activity, macromolecules, and changes in redox and response to abiotic stress. Our goal is to thoroughly evaluate phyto-melatonin performance under abiotic stress, which will help us better understand the mechanism by which phyto-melatonin regulates crop growth and yield.

Identification of Elite R-Gene Combinations against Blast Disease in Geng Rice Varieties.

Rice blast, caused by the Magnaporthe oryzae fungus, is one of the most devastating rice diseases worldwide. Developing resistant varieties by pyramiding different blast resistance (R) genes is an effective approach to control the disease. However, due to complex interactions among R genes and crop genetic backgrounds, different R-gene combinations may have varying effects on resistance. Here, we report the identification of two core R-gene combinations that will benefit the improvement of Geng (Japonica) rice blast resistance. We first evaluated 68 Geng rice cultivars at seedling stage by challenging with 58 M. oryzae isolates. To evaluate panicle blast resistance, we inoculated 190 Geng rice cultivars at boosting stage with five groups of mixed conidial suspensions (MCSs), with each containing 5-6 isolates. More than 60% cultivars displayed moderate or lower levels of susceptibility to panicle blast against the five MCSs. Most cultivars contained two to six R genes detected by the functional markers corresponding to 18 known R genes. Through multinomial logistics regression analysis, we found that Pi-zt, Pita, Pi3/5/I, and Pikh loci contributed significantly to seedling blast resistance, and Pita, Pi3/5/i, Pia, and Pit contributed significantly to panicle blast resistance. For gene combinations, Pita+Pi3/5/i and Pita+Pia yielded more stable pyramiding effects on panicle blast resistance against all five MCSs and were designated as core R-gene combinations. Up to 51.6% Geng cultivars in the Jiangsu area contained Pita, but less than 30% harbored either Pia or Pi3/5/i, leading to less cultivars containing Pita+Pia (15.8%) or Pita+Pi3/5/i (5.8%). Only a few varieties simultaneously contained Pia and Pi3/5/i, implying the opportunity to use hybrid breeding procedures to efficiently generate varieties with either Pita+Pia or Pita+Pi3/5/i. This study provides valuable information for breeders to develop Geng rice cultivars with high resistance to blast, especially panicle blast.

Approaches to Reduce Rice Blast Disease Using Knowledge from Host Resistance and Pathogen Pathogenicity.

Rice is one of the staple foods for the majority of the global population that depends directly or indirectly on it. The yield of this important crop is constantly challenged by various biotic stresses. Rice blast, caused by Magnaporthe oryzae (M. oryzae), is a devastating rice disease causing severe yield losses annually and threatening rice production globally. The development of a resistant variety is one of the most effective and economical approaches to control rice blast. Researchers in the past few decades have witnessed the characterization of several qualitative resistance (R) and quantitative resistance (qR) genes to blast disease as well as several avirulence (Avr) genes from the pathogen. These provide great help for either breeders to develop a resistant variety or pathologists to monitor the dynamics of pathogenic isolates, and ultimately to control the disease. Here, we summarize the current status of the isolation of R, qR and Avr genes in the rice-M. oryzae interaction system, and review the progresses and problems of these genes utilized in practice for reducing rice blast disease. Research perspectives towards better managing blast disease by developing a broad-spectrum and durable blast resistance variety and new fungicides are also discussed.

Ultrasound-Assisted Synthesis of Piperidinyl-Quinoline Acylhydrazones as New Anti-Alzheimer's Agents: Assessment of Cholinesterase Inhibitory Profile, Molecular Docking Analysis, and Drug-like Properties.

Alzheimer's disease (AD) is one of the progressive neurological disorders and the main cause of dementia all over the world. The multifactorial nature of Alzheimer's disease is a reason for the lack of effective drugs as well as a basis for the development of new structural leads. In addition, the appalling side effects such as nausea, vomiting, loss of appetite, muscle cramps, and headaches associated with the marketed treatment modalities and many failed clinical trials significantly limit the use of drugs and alarm for a detailed understanding of disease heterogeneity and the development of preventive and multifaceted remedial approach desperately. With this motivation, we herein report a diverse series of piperidinyl-quinoline acylhydrazone therapeutics as selective as well as potent inhibitors of cholinesterase enzymes. Ultrasound-assisted conjugation of 6/8-methyl-2-(piperidin-1-yl)quinoline-3-carbaldehydes (4a,b) and (un)substituted aromatic acid hydrazides (7a-m) provided facile access to target compounds (8a-m and 9a-j) in 4-6 min in excellent yields. The structures were fully established using spectroscopic techniques such as FTIR, 1H- and 13C NMR, and purity was estimated using elemental analysis. The synthesized compounds were investigated for their cholinesterase inhibitory potential. In vitro enzymatic studies revealed potent and selective inhibitors of AChE and BuChE. Compound 8c showed remarkable results and emerged as a lead candidate for the inhibition of AChE with an IC50 value of 5.3 ± 0.51 µM. The inhibitory strength of the optimal compound was 3-fold higher compared to neostigmine (IC50 = 16.3 ± 1.12 µM). Compound 8g exhibited the highest potency and inhibited the BuChE selectively with an IC50 value of 1.31 ± 0.05 µM. Several compounds, such as 8a-c, also displayed dual inhibitory strength, and acquired data were superior to the standard drugs. In vitro results were further supported by molecular docking analysis, where potent compounds revealed various important interactions with the key amino acid residues in the active site of both enzymes. Molecular dynamics simulation data, as well as physicochemical properties of the lead compounds, supported the identified class of hybrid compounds as a promising avenue for the discovery and development of new molecules for multifactorial diseases, such as Alzheimer's disease (AD).

Assessment of heavy metals and associated oxidative stress in occupationally exposed workers from Bannu and Karak Districts in Pakistan.

Heavy metals (HMs) are extensively found in occupationally exposed miners and industrial workers, which may cause serious health-related problems to the large workforce. In order to evaluate the impact of these toxic pollutants, we have investigated the effect of cadmium (Cd), chromium (Cr), copper (Cu), and lead (Pb) concentration on exposed workers of mining, and woolen textile mill and compared the findings with unexposed individuals. From each category like exposed workers (mining, and woolen mill textile site) and unexposed individuals, 50 blood samples were taken. The occurrence of HMs in a sample was investigated through atomic absorption spectrometry while the oxidative stress marker malondialdehyde (MDA) and antioxidant enzyme statuses such as superoxide dismutase (SOD) and catalase (CAT) were analyzed in exposed and control samples. The results showed significant (p < 0.05) variation in Cd, Cr, Cu, and Pb levels in exposed and control samples. The concentration of Cd in the blood of WMWs, KMWs, and control group was 5.75, 3.89, and 0.42 µg/dL, respectively. On the other hand, the concentration of Pb in the blood of WMWs, MWs, and control was 32.34, 24.39, and 0.39 µg/dL while the concentrations of Cr and Cu in the blood of WMWs, MWs, and control group were 11.61 and 104.14 µg/dL, 4.21 and 113.21 µg/dL, 0.32 and 65.53 µg/dL, respectively. An increase in MDA was recorded in the exposed workers' group as compared to control subjects, whereas SOD and CAT activities decreased. Meanwhile, MDA was significantly and positively (p < 0.01) correlated with HMs, while negative significant correlations were found among HMs with SOD and CAT.

DOCUMENTATION OF TRYPANOSOMA EVANSI IN CAPTIVE TIGERS AND LIONS IN PUNJAB (2016-2018), PAKISTAN.

Trypanosoma evansi is an important hemoparasite of a variety of animal species worldwide. This parasite is a threat to the health of domestic animals as well as wild animals, particularly those managed in captivity. The current study investigated the presence of T. evansi in captive tigers (Panthera tigris tigris) and lions (Panthera leo) in Pakistan. In total, 24 blood samples from 11 tigers and 3 lions (n = 14) were collected during the course of roughly 3 yr (2016-2018). Eighteen samples were subjected to both microscopic and molecular evaluation for the presence of T. evansi; the remaining 6 samples were processed for PCR only. Of the 18 samples tested by both methods, 3 (16%) and 8 (44%) were positive by microscopy and PCR, respectively. This highlights the higher sensitivity of PCR over microscopy for detection of trypanosomes. Of the 24 total samples evaluated by PCR, 12 (50%) were positive. The three sequences obtained showed 99% identity with variant surface glycoprotein genes of the different isolates of T. evansi. The sensitivity, specificity, positive predictive value, and negative predictive value of microscopy in identifying T. evansi was 37.5, 100, 100, and 66.7%, respectively, considering PCR as the gold standard. We recommend rigorous monitoring of captive tigers and lions for hemoparasites, particularly in winter and early spring in areas with high infection rate of this parasite, preferably via PCR.

High Dielectric Transparent Film Tailored by Acceptor and Donor Codoping.

High dielectric constant materials are of particular current interests as indispensable components in transistors, capacitors, etc. In this context, there are emerging trends to exploit defect engineering in dielectric ceramics for enhancing the performance. However, demonstrations of similar high dielectric performance in integration-compatible crystalline films are rare. Herein, such a breakthrough via the functionalization of donor-acceptor dipoles by compositional tuning in GaCu codoped ZnO films is reported. The dielectric constant reaches ~200 at 1 kHz and the optical transmittance in visible light reaches ~80%. Importantly, by analyzing the impedance spectroscopy data, prominent relaxation mechanisms in correlation with the dipole properties, enabling consistent explanations of the dielectric constant as a function of frequency are discriminated. The atomistic nature of the dipoles is revealed by the systematic X-ray spectroscopy analysis. Spectacularly, similar trends for the dielectric properties are observed, while synthesizing samples by pulsed laser deposition and ion implantation, indicating the general character of the phenomena.

Molecular Characterization of Wild and Cultivated Strawberry (Fragaria × ananassa) through DNA Barcode Markers.

Background: DNA barcoding is a useful technique for the identification, conservation, and diversity estimation at the species level in plants. The current research work was carried out to characterize selected Fragaria species from northern Pakistan using DNA barcode markers. Methodology. Initially, the efficacy of eight DNA barcode markers was analyzed based on the amplification and sequencing of the genome of selected Fragaria species. The resultant sequences were analyzed using BLAST, MEGA 7.0, and Bio Edit software. The phylogenetic tree was constructed by using Fragaria current species sequences and reference sequences through the neighbor-joining method or maximum likelihood method. Results: Among eight DNA barcode markers, only two (ITS2 and rbclC) were amplified, and sequences were obtained. ITS2 sequence was BLAST in NCBI for related reference species which ranged from 89.79% to 90.05% along with Fragaria vesca (AF163517.1) which have 99.05% identity. Similarly, the rbclC sequence of Fragaria species was ranged from 96% to 99.58% along with Fragaria × ananassa (KY358226.1) which had 99.58% identity. Conclusion: It is recommended that DNA barcode markers are a useful tool to identify the genetic diversity of a species. Moreover, this study could be helpful for the identification of the Fragaria species cultivated in other regions of the world.

Catalytic potential of endophytes facilitates synthesis of biometallic zinc oxide nanoparticles for agricultural application.

Recent advances fascinated the use of biological resources in combination with metals to obtain high quality biometals and apply its advantages in different fields. Endophytic mediated Zinc oxide nanoparticles (ZnO-NPs) is an economical and ecofriendly way for farmers to avoid Zn deficiency in rice crop and obtain high yield. Here we synthesized ZnO-NPs utilizing endophytic bacterial strain of Enterobacter hormaechei (E. hormaechei). The physiochemical properties of the prepared NPs were determined through UV-Vis spectroscopy, XRD, FT-IR, SEM and TEM. The prepared NPs revealed surface plasmon resonance (SPR) at 320 nm (nm) and crystalline structure with 21 nm average crystalline size. FT-IR spectra showed the presence of carboxylic, alcohol and amine functional groups, which confirm the biometallic assembling of the ZnO and endophytic bacterial functional groups. SEM showed pyramidal symmetry whereas TEM revealed poly dispersed spherical shape with particle size distribution 18-48 nm. Our results showed that prepared NPs possess significant antifungal, antibacterial and antioxidant potential at 25, 50 and 100 µg/mL concentrations. Moreover, Cytotoxic and hemolytic assay showed significant results (less % viability and hemolysis activity) at 50 and 100 µg/mL (ZnO-NP's) concentrations as compared to control. The prepared ZnO-NPs were used as bio fertilizer in various concentrations as a foliar spray, which showed significant enhancement of the rice plant growth, along with chlorophyll, proteins and carotenoid contents. These results recommend that endophytic mediated ZnO-NPs are biocompatible and possess significant potential for agricultural applications.

Discovery of urease inhibitory effect of sulfamate derivatives: Biological and computational studies.

The discovery of life-changing medicines continues to be the driving force for the rapid exploration and expansion of chemical space, enabling access to innovative small molecules of medicinal importance. These small molecules remain the backbone for modern drug discovery. In this context, the treatment of ureolytic bacterial infections inspires the identification of potent and effective inhibitors of urease, a promising and highly needed target for H. pylori eradication. The present study explores the evaluation of sulfamate derivatives for the inhibition of urease enzyme. The tested compounds showed remarkable inhibitory effect and high level of potency. Compound 1q emerged as the lead inhibitor with an IC50 value of 0.062 ± 0.001 µM, ∼360-fold more potent than thiourea (IC50 = 22.31 ± 0.031 µM). The assessment of various contributing factors towards the inhibition profile allowed for the establishment of diverse structure-activity relationships. Kinetics studies revealed the competitive mode of inhibition of compound 1q while molecular modeling analysis identified various crucial binding interactions with ARG609, ARG439, HIS519, HIS492, HIS593, ALA440, and ALA636 in the active pocket of the enzyme. Finally, the calculated pharmacokinetic properties suggest a promising profile of our potent sulfamate-based urease inhibitors.

First report of perfluoroalkyl acids (PFAAs) in the Indus Drainage System: Occurrence, source and environmental risk.

Perfluoroalkyl acids (PFAAs) are of global interest due to their persistence in the aquatic environment. This study assessed the occurrence of PFAAs in the Indus Drainage System and discerned their potential sources and environmental risks for the first time in Pakistan. 13 perfluoroalkyl carboxylic acids (PFCAs) and 4 perfluoroalkyl sulfonates (PFSAs) were analyzed to verify the dominant prevalence of short-chain PFAAs in the environment since the phase-out of long-chain perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS). A significant variation (p ≤ 0.05) of individual PFAAs between the monitoring sites was confirmed by data normality tests Kolmogorov-Smirnov and Shapiro-Wilk, suggesting that different locations contribute differently to individual PFAAs concentrations. ΣPFAAs concentrations in riverine water and sediments ranged from 2.28 to 221.75 ng/L and 0.78-29.19 ng/g dw, respectively. PFBA, PFPeA, and PFHxA were the most abundant PFAAs, and on average accounted for 14.64, 13.75, and 12.97 ng/L of ∑PFAAs in riverine water and 0.34, 0.64, and 0.79 ng/g dw of ∑PFAAs in sediments. ΣPFAAs mean contamination in the drainage was significantly (p < 0.05) high in River Chenab followed by River Indus > Soan > Ravi > Kabul > Swat with more prevalence of short-chain (C4-C7) PFCAs followed by PFOA, PFBS, PFOS, PFNA, PFDA, PFHxS, PFUnDA, and PFDoDA. The correlation analysis determined the PFAAs' fate and distribution along the drainage, indicating that PFAAs with carbon chains C4-C12, except for PFSAs with carbon chains C6-C8, were most likely contaminated by the same source, the values of Kd and Koc increased linearly with the length of the perfluoroalkyl carbon chain, better understand the transport and partitioning of individual PFAAs between riverine water and sediments, where the HCA and PCA discerned industrial/municipal wastewater discharge, agricultural and surface runoff from nearby fields, and urban localities as potential sources of PFAAs contamination. The collective mass flux of short-chain (C4-C7) PFCAs was 5x higher than that of PFOS + PFOA, suggesting a continuous shift in the production and usage of fluorinated replacements for long-chain PFAAs with short-chain homologs. In terms of risk, individual PFAAs pollution in the drainage was within the world's risk thresholds for human health, with the exception of PFBA, PFPeA, PFHpA, PFHxA, PFOA, PFNA, and PFBS, whereas for ecology, the concentrations of individual PFAAs did not exceed the ecological risk thresholds of the United States of America, Canada, European Union (EU), Italy, Australia, and New Zealand, with the exception of PFSAs, whose detected individual concentrations were significantly higher than the EU, Australian and New Zealander PFSAs guidelines of 0.002 µg/L, 0.00047 µg/L, 0.00065 µg/L, 0.00013 µg/L, and 0.00023 µg/L, respectively, which may pose chronic risks to the regional ecosystem and population.

Characterization of Prochloraz Resistance in Fusarium fujikuroi from Heilongjiang Province in China.

Prochloraz is widely used to control rice bakanae disease caused by Fusarium fujikuroi. The current study was aimed at monitoring the development of F. fujikuroi resistance to prochloraz in the Heilongjiang Province and analyzing the fitness of F. fujikuroi strains with different resistance levels. The results indicated that most of the 89 F. fujikuroi strains collected from the Heilongjiang Province were resistant to prochloraz, with resistance frequency reaching 92.1%. To assess the field resistance risk of prochloraz, 21 F. fujikuroi strains with different resistance levels were selected to investigate their biological characteristics and assess their fitness. Mycelial growth, sporulation, and germination rates were significantly different among the tested strains. However, when grouped into two subpopulations, no significant difference was tested between prochloraz-resistant and prochloraz-sensitive strains. Pathogenicity assays revealed that the disease severity index of prochloraz-resistant strains was higher than that of prochloraz-sensitive strains. Cross-resistance assays showed no cross-resistance between prochloraz and five other fungicides, namely phenamacril, ipconazole, tebuconazole, carbendazim, and fluopyram. Ffcyp51A gene overexpression was observed in the prochloraz-resistant F. fujikuroi strains after exposure to prochloraz. Collectively, these results indicated that F. fujikuroi resistance against prochloraz was severe. Furthermore, prochloraz-resistant strains were highly fit and could potentially become a dominant population in rice fields, consequently resulting in yield loss.

Percutaneous closure of ventricular septal defect using LifeTechTM Konar-MF VSD Occluder: initial and short-term multi-institutional results.

BACKGROUND: Transcatheter ventricular septal defect closure remains a complex procedure with potential complications like complete heart block and aortic regurgitation. The ideal device design for such intervention is still evolving. AIM: To assess the safety, efficacy, and short-term outcome of ventricular septal defect closure using LifeTechTM multifunctional (KONAR-MFTM) VSD Occluder. PATIENTS AND METHODS: In a multicenre study, 44 patients with haemodynamically significant, restrictive ventricular septal defects underwent closure with the KONAR-MFTM device from April, 2019 to March, 2020. Clinical, echocardiographic, and angiographic data were collected and reviewed. Patients were followed up at 1, 3, 6, and 12 months. RESULTS: The median age and weight were 8 (1.7-36) years and 20 (11-79) kg. Of 44 patients, 8 (18%) had a high muscular and 36 (82%) had a perimembranous defect, of which 6 had mild prolapse of the right coronary cusp. The median ventricular septal defect size was 8.8 (3.9-13.4) mm. A retrograde approach was adopted in 39 (88.6%) patients. Nine patients (20.5%) had a small residual leak and there was a slight increase in aortic regurgitation in one patient. One device, which embolised to pulmonary artery was retrieved, and the defect was closed with a larger device. At a median follow-up of 13 (5-18) months, the residual leak persisted in 1 (2.3%) patient. Mild aortic regurgitation in one patient remained unchanged. There were no major complications. CONCLUSION: Percutaneous closure of ventricular septal defect using KONAR-MFTM device is safe and effective in short and midterm follow-up including selected patients with perimembranous defect and mild prolapse of the right coronary cusp.

Pivotal Role of Phytohormones and Their Responsive Genes in Plant Growth and Their Signaling and Transduction Pathway under Salt Stress in Cotton.

The presence of phyto-hormones in plants at relatively low concentrations plays an indispensable role in regulating crop growth and yield. Salt stress is one of the major abiotic stresses limiting cotton production. It has been reported that exogenous phyto-hormones are involved in various plant defense systems against salt stress. Recently, different studies revealed the pivotal performance of hormones in regulating cotton growth and yield. However, a comprehensive understanding of these exogenous hormones, which regulate cotton growth and yield under salt stress, is lacking. In this review, we focused on new advances in elucidating the roles of exogenous hormones (gibberellin (GA) and salicylic acid (SA)) and their signaling and transduction pathways and the cross-talk between GA and SA in regulating crop growth and development under salt stress. In this review, we not only focused on the role of phyto-hormones but also identified the roles of GA and SA responsive genes to salt stress. Our aim is to provide a comprehensive review of the performance of GA and SA and their responsive genes under salt stress, assisting in the further elucidation of the mechanism that plant hormones use to regulate growth and yield under salt stress.

Mentha: Nutritional and Health Attributes to Treat Various Ailments Including Cardiovascular Diseases.

A poor diet, resulting in malnutrition, is a critical challenge that leads to a variety of metabolic disorders, including obesity, diabetes, and cardiovascular diseases. Mentha species are famous as therapeutic herbs and have long served as herbal medicine. Recently, the demand for its products, such as herbal drugs, medicines, and natural herbal formulations, has increased significantly. However, the available literature lacks a thorough overview of Mentha phytochemicals' effects for reducing malnutritional risks against cardiovascular diseases. In this context, we aimed to review the recent advances of Mentha phytochemicals and future challenges for reducing malnutritional risks in cardiovascular patients. Current studies indicated that Mentha species phytochemicals possess unique antimicrobial, antidiabetic, cytotoxic, and antioxidant potential, which can be used as herbal medicine directly or indirectly (such as food ingredients) and are effective in controlling and curing cardiovascular diseases. The presence of aromatic and flavor compounds of Mentha species greatly enhance the nutritional values of the food. Further interdisciplinary investigations are pivotal to explore main volatile compounds, synergistic actions of phytochemicals, organoleptic effects, and stability of Mentha sp. phytochemicals.

Heavy metal pollution in the soil of a riverine basin: distribution, source, and potential hazards.

Soil pollution with heavy metals (HMs) has become a world environmental problem. This study focuses on surface soil contamination with Cr, Mn, Co, Ni, Cu, Zn, Cd, Hg, Pb, Fe, and Al, their sources, and potential hazards along the basin of River Swat, Pakistan. The average concentrations (mg/kg) of HMs were the most abundant for Al (24,730.19) followed by Fe (22,419.41) > Mn (386.78) > Zn (57.75) > Cr (38.07) > Ni (32.46) > Cu (23.43) > Pb (19.59) > Co (10.77) > Cd (3.18) > Hg (0.12). The concentrations of Cr and Mn in 5.45% each, Co in 10.90%, Zn in 27.27%, Cu in 36.36%, Ni in 41.81%, and Hg in 92.72% of the total soil samples exceeded their respective background values. The geostatistical approaches determined the distribution patterns of HM pollution along the basin, whereas the statistics of principal component analysis exposed the likely sources of HM contamination in the area. Pollution indices evaluated the overall HM distribution and pollution status in the area. Contamination factor showed a high degree of HM contamination in 82% of the total sampling sites, while the geo-accumulation index designated low to moderate contamination with Cr, Mn, Co, Ni, Cu, Zn, Hg, and Pb, and moderate to extreme contamination with Cd, Fe, and Al. The trend of ecological toxicity showed potential ups and downs along with the sites from low to considerable hazard (< 95 < PEHI < 190), whereas the human carcinogenic hazard was within the USEPA acceptable limits (1 × 10-7-1 × 10-4), but the non-carcinogenic hazard was higher than the threshold (HI > 1) for children because they are more exposed than adults.

Hybrid Quinoline-Thiosemicarbazone Therapeutics as a New Treatment Opportunity for Alzheimer's Disease‒Synthesis, In Vitro Cholinesterase Inhibitory Potential and Computational Modeling Analysis.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder and the leading cause of dementia worldwide. The limited pharmacological approaches based on cholinesterase inhibitors only provide symptomatic relief to AD patients. Moreover, the adverse side effects such as nausea, vomiting, loss of appetite, muscle cramps, and headaches associated with these drugs and numerous clinical trial failures present substantial limitations on the use of medications and call for a detailed insight of disease heterogeneity and development of preventive and multifactorial therapeutic strategies on urgent basis. In this context, we herein report a series of quinoline-thiosemicarbazone hybrid therapeutics as selective and potent inhibitors of cholinesterases. A facile multistep synthetic approach was utilized to generate target structures bearing multiple sites for chemical modifications and establishing drug-receptor interactions. The structures of all the synthesized compounds were fully established using readily available spectroscopic techniques (FTIR, 1H- and 13C-NMR). In vitro inhibitory results revealed compound 5b as a promising and lead inhibitor with an IC50 value of 0.12 ± 0.02 µM, a 5-fold higher potency than standard drug (galantamine; IC50 = 0.62 ± 0.01 µM). The synergistic effect of electron-rich (methoxy) group and ethylmorpholine moiety in quinoline-thiosemicarbazone conjugates contributes significantly in improving the inhibition level. Molecular docking analysis revealed various vital interactions of potent compounds with amino acid residues and reinforced the in vitro results. Kinetics experiments revealed the competitive mode of inhibition while ADME properties favored the translation of identified inhibitors into safe and promising drug candidates for pre-clinical testing. Collectively, inhibitory activity data and results from key physicochemical properties merit further research to ensure the design and development of safe and high-quality drug candidates for Alzheimer's disease.

Experience of transcatheter device closure of atrial septal defect in a tertiary care institute.

OBJECTIVE: To share institutional experience of transcatheter device closure of secundum atrial septal defect in children and adults. METHODS: The descriptive cross-sectional study was conducted at the Department of Paediatric Cardiology, Institute of Cardiology, Multan, Pakistan, from February 2011 to September 2019, and comprised patients with moderate to large secundum atrial septal defect without severe pulmonary hypertension. All procedures were performed under general anaesthesia and trans-oesophageal echo guidance. Success and safety of procedure were evaluated. Data was analysed using SPSS 16. RESULTS: Of the 75 patients, 26(34.6%) were males and 49(65.3%) were females. The overall mean age was 25±1.53 years (range: 4 -54 years). Mean defect was 20.38±0.58mm (range: 9-32mm). Large defects >25mm were 17(22.7%). Significant pulmonary stenosis was observed in 3(4%) patients and valvuloplasty was performed. Device size was selected on the basis of trans-oesophageal echo measurement +4-5mm. Balloon sizing was performed in only 3(4%) patients. Amplatzer septal occluder was used in 60(80%) patients. Balloon-assisted technique was used in 9(12%) patients. All the procedures were successful except 2(2.7%) where device was embolised and retrieved by surgery. Transient arrhythmias were observed in 6(8%) patients and small pericardial effusion in 1(1.3%) patient who was managed conservatively. There was no procedure-related mortality. CONCLUSION: Transcatheter closure of moderate to large secundum atrial septal defect in children and adults was found to be a safe procedure.