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The conventional approach of drug development, which focused on inhibiting a single target, has been superseded by a more advanced strategy known as multi-target design. In this study, we describe the synthesis of new N-adamantyl-2-(2-(phenyl)hydrazone)-3-oxobutanamide (6a-k). These compounds were designed with the intention of serving as prospective drug like candidates that can target both alpha glucosidase and urease enzymes. For this purpose, both in-vitro and in-silico investigations were performed after synthesis and characterization. The density functional theory calculations were employed to calculate optimized geometries, global reactivity descriptors and frontier molecular orbital (FMO) analysis. All compounds were found reactive and compounds 6b, 6c, 6d and 6e were found the most stable. The synthesized compounds were also tested for their ability to inhibit the enzyme activities of urease and α-glucosidase. The compound 6c exhibited strong inhibition of urease enzyme, with IC50 value of 13.10 ± 0.55 µM, in comparison to the IC50 value of the standard inhibitor thiourea i.e., 16.4 ± 1.02 µM. In addition to this, compounds 6d and 6e demonstrated a significant α-glucosidase inhibition with IC50 values of 17.16 ± 0.91 µM but found less potent as compared to the standard inhibitor Acarbose, i.e. 9.80 ± 0.20 μM. The structure–activity relationship (SAR) was established and the in-vitro results were further supported by the molecular docking investigations and molecular dynamic simulation studies. The in-vitro and in-silico results demonstrated a strong correlation in assessing the drug-like characteristics of all synthesized compounds (6a-k). The in silico investigation confirmed the findings in the search for inhibitors against the listed enzymes by elucidating the binding relationship between most of the active compounds and the active site of urease and α-glucosidase.

Abstract The China-Pakistan Economic Corridor (CPEC) is an ongoing mega-construction project in Pakistan that necessitates further exploration of new natural resources of aggregate to facilitate the extensive construction. Therefore, the Late Permian strata of Chhidru and Wargal Limestone for aggregates resources were envisaged to evaluate their optimal way of construction usage through detailed geotechnical, geochemical, and petrographic analyses. Geotechnical analysis was performed under BS and ASTM standards with the help of employing different laboratory tests. A simple regression analysis was employed to ascertain mutual correlations between physical parameters. Based on the petrographic analysis, the Wargal Limestone is classified into mudstones and wackestone, and Chhidru Formation is categorized into wackestone and floatstone microfacies, both containing primary constituents of calcite and bioclasts. The geochemical analysis revealed that the Wargal Limestone and Chhidru Formation encompass calcium oxide (CaO) as the dominant mineral content. These analyses also depicted that the Wargal Limestone aggregates bear no vulnerability to alkali-aggregate reactions (AAR), whereas the Chhidru Formation tends to be susceptible to AAR and deleterious. Moreover, the coefficient of determination and strength characteristics, for instance, unconfined compressive strength and point load test were found inversely associated with bioclast concentrations and directly linked to calcite contents. Based on the geotechnical, petrographic, and geochemical analyses, the Wargal Limestone proved to be a significant potential source for both small and large-scale construction projects, such as CPEC, but the Chhidru Formation aggregates should be used with extra caution due to high silica content.

Abstract The chronic nature of coronavirus disease (COVID-19) outbreak and lack of success in treatment and cure is creating an environment that is crucial for mental wellbeing. Presently, we extracted and classified sentiments and emotions from 141,208 headlines of global English news sources regarding the coronavirus disease (COVID-19). The headlines considered were those carrying keyword coronavirus between the time frame 15 Janaury, 2020 to 3 June, 2020 from top rated 25 English news sources. The headlines were classified into positive, negative and neutral sentiments after the calculation of text unbounded polarity at the sentence level score and incorporating the valence shifters. In addition, the National Research Council Canada (NRC) Word-Emotion Lexicon was used to calculate the presence of eight emotions at their emotional weight. The results reveal that the news headlines had high emotional scores with a negative polarity. More precisely, around 52% of the news headlines evoked negative sentiments and only 30% evoked positive sentiments while 18% were neutral. Fear, trust, anticipation, sadness, and anger were the main emotions evoked by the news headlines. Overall, the findings of this study can be weaved together into important implications for emotional wellbeing and economic perspective.

Pakistan’s largest city, Karachi, which is industrial centre and economic hub needs focus in research and development of every field of Engineering, Science and Technology. Urbanization and industrialization is resulting bad weather conditions which prolongs until a climate change. Since, Meteorology serves as interdisciplinary field of study, an analytical study of real and region-specific meteorological data is conducted which focuses on routine, extreme and engineering meteorology of metropolitan city Karachi. Results of study endorse the meteorological parameters relationship and establish the variability of those parameters for Karachi Coastal Area. The rise of temperature, decreasing trend of atmospheric pressure, increment in precipitation and fall in relative humidity depict the effects of urbanization and industrialization. The recorded extreme maximum temperature of 45.50C (on June 11, 1988) and the extreme minimum temperature of 4.5 0C(on January 1, 2007) is observed at Karachi south meteorological station. The estimated temperature rise in 32 years is 0.9 0C, which is crossing the Intergovernmental Panel on Climate Change (IPCC) predicted/estimated limit of 2oC rise per century. The maximum annual precipitation of 487.0mm appearing in 1994 and the minimum annual precipitation of 2.5mm appearing in 1987 is observed at same station which is representative meteorological station for Karachi Coast. Further Engineering meteorological parameters for heating ventilation air condition (HVAC) system design for industrial purpose are deduced as supporting data for coastal area site study for industrial as well as any follow-up engineering work in the specified region.

Abstract Sixteen parent PAHs and twelve nitro-PAHs were measured in PM2.5 samples collected over one year (2013–2014) at nine urban sites in China. During the sampling period, concentrations of individual nitro-PAHs were one or two orders of magnitude lower than their parent PAHs. Typical seasonal variations in parent PAH concentrations, which increased 10- to 80- fold in winter compared to summer, were observed in this study. Conversely, the mean atmospheric concentrations of nitro-PAHs were similar in all four seasons, with the exception of 9-nitroanthracene (9n-Ant). Compared to other nitro-PAHs which were secondary formation products, 9n-Ant had a higher concentration and made up a larger proportion of total nitro-PAHs. Positive matrix factorization results indicated that 9n-Ant sources included biomass burning (20%), vehicle exhaust emissions (43%), and secondary formation (30%). Overall, the elevated concentrations of parent PAHs observed in winter correlated with the contribution from coal combustion at all sites, especially in north China (>80%). The contribution of secondary formation products to total nitro-PAHs was measured during the summer, and was especially high in the larger cities such as Shanghai (84%), Beijing (76%), Guangzhou (60%), and Chengdu (64%), largely due to the summer concentrations of parent PAHs were markedly lower than in winter.

Abstract Previous studies reported that forest ecosystems can play a vital role in scavenging anthropogenic polycyclic aromatic hydrocarbons (PAHs) and act as primary reservoirs of these environmental pollutants. The present study aimed to investigate the occurrence, spatial pattern and source apportionment of PAHs across Chinese background forest soils (O- & A-horizons). The 143 soils collected from 30 mountains showed significantly (p

The present study used human lung fibroblast (HELF) cells as a test model to evaluate the role of oxidative stress (OS) and extracellular signal-regulated kinases 1/2 (ERK1/2) protein in HELF cell proliferation exposed to PCB118. Results from 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide demonstrated that PCB118 at lower concentrations stimulated proliferation of HELF cell and abrogate proliferative effect at higher dose concentrations and in a time-dependent manner. Moreover, reactive oxygen species, malondialdehyde (MDA), and superoxide dismutase showed a significant increase at higher concentrations of PCB118 than the lower concentrations with the passage of time. Antioxidant enzymes such as glutathione peroxidase exhibited decreasing trends in dose- and time-dependent manner. Lipid peroxidation assay resulted in a significant increase in MDA level in PCB118-treated HELF cells compared with controls, suggesting that OS plays a key role in PCB118-induced toxicity. Comet assay indicated a significant increase in genotoxicity at higher concentrations of PCB118 exposure than the lower concentrations. It was found that PCB118 showed expression of ERK1/2 protein after 4 hours, while after 48 hours, the protein expression was less, indicating PCB toxicity to MAPK protein of HELF cell. Oxidative stress, ERK1/2, and HELF cell proliferation exhibited correlation. The results will elaborate toxicological evaluation of PCB118 to HELF cells and will help to develop drug for PCB-induced diseases.

The current paper presents an innovative form of the cold‐formed U‐shape steel encasing concrete composite beam (CUCB). The suggested CUCB consists of a cold‐formed U‐shaped steel encasing plain concrete beam which are connected to each other using continuous transversal threaded stud bolts. The experimental program consisted of eight beam specimens tested in the four‐point bending set‐up. One of them was a normal reinforced concrete beam and considered as a reference specimen while the remaining specimens were CUCB specimens without ordinary flexural and shear reinforcement. Four parameters were studied in this paper: (i) the thickness of the U‐shaped steel, (ii) the spacing between the stud bolts, (iii) the arrangement of the bolts, and (iv) the number of the bolt's rows. Results indicated an overall improvement in the load‐carrying capacity and stiffness of most CUCB specimens in comparison with the reference specimen. It was found that the using of three rows of bolts can significantly improve the ductility and toughness of the CUCB specimen in comparison with two rows of bolts. On the contrary, an increase in the bolt spacing entails a decrease in the CUCB specimens' toughness. [ABSTRACT FROM AUTHOR]

Lacing reinforcement plays a critical role in the design and performance of reinforced concrete (RC) slabs by distributing the applied loads more evenly across the slab, ensuring that no specific area of the slab is overloaded. In this study, nine slabs, divided into three groups according to the investigated parameters, were meticulously designed and evaluated to study the interplay between the lacing reinforcement and other key parameters. Each slab was crafted for simple support and was subjected to both static and repeated two-point load tests. The lacing reinforcement had an angle of 45° with various tension and lacing steel. The repeated-tested specimens with lacing reinforcement experienced smaller ductility than those of similar static-tested specimens, where the reduction in ductility factor ranged between 8.4% and 22.3% for all specimens. Additionally, the tested slabs were analyzed numerically using the ABAQUS software package. The validated FE test program was used to study the effect of varying the lacing reinforcement ratio, the compressive strength of concrete, and the material types of the tension and lacing reinforcements. The lacing reinforcement becomes more effective in increasing the slab capacity when using the higher compressive strength of concrete. [ABSTRACT FROM AUTHOR]

Understanding the size distribution, variation patterns, and potential formation mechanisms of particulate organic nitrates (PONs) is crucial for assessing their influences on atmospheric chemistry, air quality, and the regional climate. This study investigates PONs in the coastal atmosphere of Qingdao, China by collecting size-resolved particulate matter samples and analyzing six types of organic nitrates, namely pinene keto nitrate (PKN229), monoterpene hydroxyl nitrate (MHN215), monoterpene dicarbonyl nitrate (MDCN247), oleic acid hydroxyl nitrate (OAHN361), oleic acid keto nitrate (OAKN359), and pinene sulfate organic nitrate (PSON295), using ultrahigh-performance liquid chromatography(mass spectrometry). The mean total concentration of organic nitrates in fine particles reaches 677 ng m−3. The predominant compound is MHN215, followed by PKN229 and MDCN247. All six organic nitrates exhibited distinct concentration peaks in the droplet mode, with MDCN247 and OAHN361 showing a minor peak in the condensation mode. In addition, an apparent concentration peak is observed in the coarse mode for OAKN359. Comparative analyses under various conditions highlight the significant influences of primary emissions and secondary formation processes on the abundance and size distribution of organic nitrates. For instance, both firework displays during festivals and high NOx emissions from fuel combustion significantly increase the concentrations of condensation-mode organic nitrates, whereas dust particles enhanced the heterogeneous formation of coarse-mode particles. Furthermore, the high humidity of the coastal area promotes aqueous formation in droplet-mode particles. [ABSTRACT FROM AUTHOR]