Screening of Multitarget Compounds against Acetaminophen Hepatic Toxicity Using In Silico, In Vitro, and In Vivo Approaches.

Combination therapy and multitarget drugs have recently attracted much attention as promising tools to fight against many challenging diseases and, thus, represent a new research focus area. The aim of the current project was to screen multitarget compounds and to study their individual and combined effects on acetaminophen-induced liver injury. In this study, 2 of the best hepatoprotective multitargeting compounds were selected from a pool of 40 major compounds present in Curcuma longa and Cinnamomum zeylanicum by using molecular docking, ADMET profiling, and Pfizer's rule of five. The two selected compounds, quercetin and curcumin, showed a high binding affinity for the CYP2E1 enzyme, MAPK, and TLR4 receptors that contribute to liver injury. The candidates caused the decreased viability of cancer cell lines (HepG2 and Huh7) but showed no effect on a normal cell line (Vero). Examination of biochemical parameters (ALT, AST, ALP, and bilirubin) showed the hepatoprotective effect of the candidate drugs in comparison with the control group, which was confirmed by histological findings. Taken together, quercetin and curcumin not only satisfied the drug-like assessment criterion and proved to be multitargeting by preventing liver damage but also showed anticancer activities.

A Novel Insight into the Identification of Potential SNP Markers for the Genomic Characterization of Buffalo Breeds in Pakistan.

Domestic buffaloes (Bubalus bubalis), known as water buffaloes, play a key role as versatile multipurpose agricultural animals in the Asiatic region. Pakistan, with the second-largest buffalo population in the world, holds a rich domestication history of buffaloes. The overall trends in buffalo production demand the genomic characterization of Pakistani buffalo breeds. To this end, the resequencing data of Pakistani breeds, along with buffalo breeds from 13 other countries, were retrieved from our previous study. This dataset, which contained 34,671,886 single-nucleotide polymorphisms (SNPs), was analyzed through a pipeline that was developed to compare possible allele differences among breeds at each SNP position. In contrast, other available tools only check for positional SNP differences for breed-specific markers. In total, 1918, 1549, 404, and 341 breed-specific markers were identified to characterize the Nili, Nili-Ravi, Azakheli, and Kundi breeds of Pakistani buffalo, respectively. Sufficient evidence in the form of phenotypic data, principal component analysis, admixture analysis, and linkage analysis showed that the Nili breed has maintained its distinct breed status despite sharing a close evolutionary relationship with the Nili-Ravi breed of buffalo. In this era of genome science, the conservation of these breeds and the further validation of the given selection markers in larger populations is a pressing need.

Nivolumab-induced exocrine pancreatic insufficiency.

Immune checkpoint inhibition is the standard-of-care for many advanced cancers. Side effects of therapy may prevent optimal treatment of the cancer. Management of side effects is dominated by recommendations derived from oncological, not gastroenterological practice. We report a patient who developed pancreatic insufficiency during checkpoint inhibitor therapy with a programmed cell death receptor 1 inhibitor, nivolumab, which if not diagnosed would have prevented ongoing treatment. This is a problem which affects approximately 1 in 100 patients treated with this agent but is rarely recognised. Gastroenterologists need to be aware of the spectrum of gastrointestinal disorders which occur after immunotherapy to treat cancer.

Wind-noise reduction for infrasonic measurements using adaptive line enhancement.

Measurement quality and analysis capability of infrasonic signals are both affected by background wind-noise. Physical filters, i.e., barriers and pipe arrays, are traditionally employed to reduce such noise. However, limited efficacy, site dependence, cost, requirement of space, non-portability, and frequent maintenance are some of their major drawbacks. This work proposes an adaptive filtering-based adaptive line enhancer (ALE) noise cancellation scheme as an alternative. Two infrasonic sensors (Chaparral Physics 50A), are adjacently deployed. One sensor is fitted with a conventional four-armed non-porous hose array (physical filter), while the ALE scheme is applied to the second sensor, sans physical filter. In high wind-noise conditions, the ALE scheme seems to behave as a lowpass filter (cutoff at 0.2 Hz), with a maximum attenuation of 26 dB at 8 Hz, while the physical filter provides significant attenuation only above 4 Hz with a maximum attenuation of 17 dB at 8 Hz. Generally, at other frequencies, the ALE scheme provides up to 20 dB superior noise attenuation as compared to the physical filter. The ALE also provides up to 6 dB gain in the signal-to-noise ratio as compared to the physical filter, due to non-attenuation of the infrasonic signal.

Host Defence Peptides: A Potent Alternative to Combat Antimicrobial Resistance in the Era of the COVID-19 Pandemic.

One of the greatest challenges facing the medical community today is the ever-increasing trajectory of antimicrobial resistance (AMR), which is being compounded by the decrease in our antimicrobial armamentarium. From their initial discovery to the current day, antibiotics have seen an exponential increase in their usage, from medical to agricultural use. Benefits aside, this has led to an exponential increase in AMR, with the fear that over 10 million lives are predicted to be lost by 2050, according to the World Health Organisation (WHO). As such, medical researchers are turning their focus to discovering novel alternatives to antimicrobials, one being Host Defence Peptides (HDPs). These small cationic peptides have shown great efficacy in being used as an antimicrobial therapy for currently resistant microbial variants. With the sudden emergence of the SARS-CoV-2 variant and the subsequent global pandemic, the great versatility and potential use of HDPs as an alternative to conventional antibiotics in treating as well as preventing the spread of COVID-19 has been reviewed. Thus, to allow the reader to have a full understanding of the multifaceted therapeutic use of HDPs, this literature review shall cover the association between COVID-19 and AMR whilst discussing and evaluating the use of HDPs as an answer to antimicrobial resistance (AMR).

Data set showing the development of a hyperspectral imaging technique using LA-ICP-MS to determine the spatial distribution of nutrients in soil cores.

This data in brief article represents the data set associated with a research article published in Geoderma [1]. The data set represents figures showing the spatial distribution of selected macro and micronutrients, and their quantification in different crop or nutrient management systems practiced in the boreal ecosystem. Spatial distribution of nutrients was measured by laser ablation inductively coupled plasma mass spectrometry (LA‒ICP‒MS), using the new techniques we developed to visualize nutrient distribution in intact soil cores representative of the root rhizosphere. This data article supports the findings published in the main article [1]. This work also demonstrates that LA-ICP-MS is a valuable technique to image the spatial distribution of macro and micronutrients in intact soil cores as affected by different crop management practices.

Heavy metals immobilization and improvement in maize (Zea mays L.) growth amended with biochar and compost.

Soil with heavy metals contamination, mainly lead (Pb), cadmium (Cd), and chromium (Cr) is a progressively worldwide alarming environmental problem. Recently, biochar has been used as a soil amendment to remediate contaminated soils, but little work has been done to compare with other organic amendments like compost. We investigated biochar and compost's comparative effect on Pb, Cd, and Cr immobilization in soil, photosynthesis, and growth of maize plants. Ten kg soil was placed in pots and were spiked with Pb, Cd, and Cr at concentrations 20, 10, 20 mg kg-1. The biochar and compost treatments included 0, 0.5, 1, 2, and 4% were separately applied to the soil. The crop from pots was harvested after 60 days. The results show that the highest reduction of AB-DTPA extractable Pb, Cd, and Cr in soil was 79%, 61% and 78% with 4% biochar, followed by 61%, 43% and 60% with 4% compost compared to the control, respectively. Similarly, the highest reduction in shoot Pb, Cd, and Cr concentration was 71%, 63% and 78%with 4% biochar, followed by 50%, 50% and 71% with 4% compost than the control, respectively. The maximum increase in shoot and dry root weight, total chlorophyll contents, and gas exchange characteristics were recorded with 4% biochar, followed by 4% compost than the control. The maximum increase in soil organic matter and total nitrogen (N) was recorded at 4% biochar application while available phosphorus and potassium in the soil at 4% compost application. It is concluded that both biochar and compost decreased heavy metals availability in the soil, reducing toxicity in the plant. However, biochar was most effective in reducing heavy metals content in soil and plant compared to compost. In the future, more low-cost, eco-friendly soil remediation methods should be developed for better soil health and plant productivity.

Development of a LAMP assay using a portable device for the real-time detection of cotton leaf curl disease in field conditions.

Cotton production is seriously affected by the prevalent cotton leaf curl disease (CLCuD) that originated from Nigeria (Africa) to various parts of Asia including Pakistan, India, China and Philippines. Due to CLCuD, Pakistan suffers heavy losses approximately 2 billion USD per annum. Numerous reports showed that CLCuD is associated with multiple species of begomoviruses, alphasatellites and a single species of betasatellite, that is 'Cotton leaf curl Multan betasatellite' (CLCuMuB). The most prevalent form of CLCuD is the combination of 'Cotton leaf curl Kokhran virus'-Burewala strain (CLCuKoV-Bur) and CLCuMuB. Thus, the availability of an in-field assay for the timely detection of CLCuD is important for the control and management of the disease. In this study, a robust method using the loop-mediated isothermal amplification (LAMP) assay was developed for the detection of CLCuD. Multiple sets of six primers were designed based on the conserved regions of CLCuKoV-Bur and CLCuMuB-ßC1 genes. The results showed that the primer set targeting the CLCuMuB-ßC1 gene performed best when the LAMP assay was performed at 58°C using 100 ng of total plant tissue DNA as a template in a 25 µl reaction volume. The limit of detection for the assay was as low as 22 copies of total purified DNA template per reaction. This assay was further adapted to perform as a colorimetric and real-time LAMP assay which proved to be advantageously applied for the rapid and early point-of-care detection of CLCuD in the field. Application of the assay could help to prevent the huge economic losses caused by the disease and contribute to the socio-economic development of underdeveloped countries.

Corn-Soybean Intercropping Improved the Nutritional Quality of Forage Cultivated on Podzols in Boreal Climate.

Intercropping systems could be a potential source of nutrient-rich forage production in cool climates on podzolic soils common in boreal ecosystems. In this study, we evaluated the effects of corn-soybean intercropping (IC) on the nutritional quality of forage. Two silage corn varieties were cultivated as monocropping (MC) or were intercropped with three forage soybean varieties using a randomized complete block design. IC significantly increased the crude protein (22%) and decreased the acid detergent (14%) and neutral detergent (6%) fibers. Forage net energy, total digestible nutrients, ash, dry matter intake, digestible dry matter and relative feed value were also significantly increased (p ≤ 0.05) in the IC treatments compared to corn MC. The macro and micro nutrients were higher in IC than corn MC. Intercropping increased the omega 3 fatty acid (FA) contents (67%) compared to corn MC. IC also increased the active microbial community in the plant root zone, which may contribute to the improvement in forage nutritional quality because the active soil microbial community composition showed significant correlations with soluble sugars, soluble proteins and potassium contents of the forage. These results demonstrate that corn-soybean IC could be a suitable cropping system to increase the nutritional quality of forage cultivated on podzols in boreal climates. The resultant forage has the potential to be a source of high-value animal feed for livestock production in cool climate regions of the world.

First record of Euphlyctis kalasgramensis (Anura: Dicroglossidae) from Punjab, Pakistan.

The present study documented the first record of Euphlyctis kalasgramensis from Punjab, Pakistan. The specimens were collected during field visits from June through August 2018. Various morphometric measurements of E. kalasgramensis were taken and compared with Euphlyctis cyanophlyctis. Snout-vent length (SVL) was 38.11 ± 0.87 mm (n = 5), snout length was 3% of SVL, foot length was 55% of SVL, head length was 32% of SVL and weight was 8.01 ± 0.12 g (n = 5). A few specimens (n = 2) were euthanized and preserved for molecular analysis through mitochondrial 16S rRNA gene sequences. The newly obtained DNA sequences of E. kalasgramensis were submitted to GenBank and accession numbers were obtained (MK881165.1 and MK920114.1). The Maximum likelihood and Neighbor-joining trees based on Kimura 2-parameter distance resulted in similar phylogenetic trees. Euphlyctis kalasgramensis was out group in both phylogenetic trees. The interspecific divergence of E. kalasgramensis and E. cyanophlyctis was high ranging from 4% to 6% as compared to low intraspecific divergence 0% and 1%. The diversity and distribution ranges of many amphibians species are not well known in Pakistan due to lack of taxonomic information. In our recommendation, a large scale DNA barcoding is required to report more cryptic or new species from Pakistan.

Growth Inhibition of Common Enteric Pathogens in the Intestine of Broilers by Microbially Produced Dextran and Levan Exopolysaccharides.

Antibiotics are generally applied for treatment or as subtherapeutic agents to overcome diseases caused by pathogenic bacteria including Escherichia coli, Salmonella and Enterococcus species in poultry. However, due to their possible adverse effects on animal health and to maintain food safety, probiotics, prebiotics, and synbiotics have been proposed as alternatives to antibiotic growth promoters (AGPs) in poultry production. In this study, the effects of prebiotics on the augmentation of broiler's indigenous gut microbiology were studied. Day old 180 broilers chicks were divided into four treatment groups: G, L, C1, and C2. The groups G and L were fed with basal diet containing 3% dextran and 3% levan, respectively. Control groups were fed with basal diets without antibiotic (C1) and with antibiotics (C2). The experimental groups showed decreased mortality as compared to control groups. After 35 days, the chickens were euthanized and intestinal fluid was analyzed for enteric pathogens on chromogenic agar plates and by 16S rRNA gene sequencing. Inhibition of the growth of E. coli and Enterococcus was observed in groups G and L, respectively, whereas Salmonella was only present in group C1. Also, high populations of lactic acid bacteria were detected in the intestine of prebiotic fed birds as compared to controls. These results depict that dextran and levan have the potential to replace the use of antibiotics in poultry feed for inhibiting the growth of common enteric pathogens. To the best of our knowledge, this is the first study where effects of dextran and levan on intestinal microbiota of broilers have been reported.

Biochar amendment mitigates greenhouse gases emission and global warming potential in dairy manure based silage corn in boreal climate.

About 11% of the global anthropogenic greenhouse gases (GHGs) emissions result from agricultural practices. Dairy manure (DM) application to soil is regarded as a best management practice due to C sequestration and improvement of soil physiochemical properties. However, GHGs emissions from the soil following the DM application could offset its advantages. Biochar (BC) is known to affect N transformation and GHGs emissions from soil. There had been considerably less focus on the BC amendment and its effects on GHGs emissions following DM application under field conditions. The objectives of this study were; i) to determine the temporal patterns and cumulative GHGs fluxes following DM and inorganic nitrogen (IN) application and, ii) to investigate BC amendment impact on DMY, GWP, direct N2O emission factor (EFd) and the response of CH4 emissions (RC) in DM based silage corn. To achieve these objectives a two-year field experiment was conducted with these treatments: 1) DM with high N conc. (DM1: 0.37% N); 2) DM with low N conc. (DM2: 0.13% N); 3) IN; 4) DM1+BC; 5) DM2+BC; 6) IN + BC; and 7) Control (N0); and were laid out in randomized complete block design with four replications. BC amendment to DM1, DM2 and IN significantly reduced cumulative CO2 emission by 16, 25.5 and 26.5%, CH4 emission by 184, 200 and 293% and N2O emission by 95, 86 and 93% respectively. It also reduced area-scaled and yield-scaled GWP, EFd, RC and enhanced DMY. Thus, BC application showed great potential to offset the negative effects of DM application i.e GHGs emissions from the silage corn cropping system. Further research is needed to evaluate soil organic carbon and nitrogen dynamics (substrates for GHG emissions) after DM and BC application on various soil types and cropping systems under field conditions.

Molecular identification of genus Duttaphrynus from Punjab, Pakistan.

The Indus valley toad and common Asian toad are widely distributed toads in Pakistan. There is doubt in the taxonomic position of species within the genus Duttaphrynus in Pakistan as most of the species identified on morphology. Previously, Bufo melanostictus hazarensis identified on morphology but during the present study, it is confirmed as Duttaphrynus melanostictus-based COI sequences (MK941836). The interspecific divergence between Duttaphrynus stomaticus and D. melanostictus was 16%. The intraspecific divergence of D. stomaticus (MK947909.1) was ranging from 0% to 1% while the intraspecific divergence of D. melanostictus (MK941836) was high ranging from 10% to 11%. Overall, genetic variation between the species of genus Duttaphrynus based on p-distance was 14%. In our recommendation, a large-scale molecular identification of amphibians should take into consideration for exact species identification to report any new species from Pakistan.

Does Absenteeism Affect Academic Performance Among Undergraduate Medical Students? Evidence From "Rashid Latif Medical College (RLMC)."

BACKGROUND: Despite the strictness in attendance policies, absenteeism is an important current issue among medical and health sciences that affects the performance of undergraduate students worldwide. Attending lectures is the key to reaping the rewards of academic achievements in undergraduate medical students. As attendance pattern and performance go hand in hand- the physical engagement of students in the classroom and practical teaching approach have a synergistic impact on the output of lower-performing students to do their best. METHODS: A total of 404 full-time undergraduate MBBS male and female students of Rashid Latif Medical College (RLMC) of age 18 or above were included in this study. The principal outcome variable, such as class grades or performance, is the dependent variable, while absenteeism is a unique independent variable. RESULTS: Our results capture the positive and significant impact of attendance coefficient in all proxy variables of regression models but exhibit significant decline from OLS3 to OLS4 when proxy variables for ability, effort, and motivation were included. However, we found the effect disappears, when we incorporate panel data fixed effect estimators to minimize the time-invariant student-specific unobservable traits on performance. CONCLUSION: Attendance of the student is only the mandatory variable that must be monitored and regulated by corrective actions to achieve the better academic performance of the students.

The effects of organic and inorganic phosphorus amendments on the biochemical attributes and active microbial population of agriculture podzols following silage corn cultivation in boreal climate.

Phosphorus (P) is the second most important macronutrient that limits the plant growth, development and productivity. Inorganic P fertilization in podzol soils predominantly bound with aluminum and iron, thereby reducing its availability to crop plants. Dairy manure (DM) amendment to agricultural soils can improve physiochemical properties, nutrient cycling through enhanced enzyme and soil microbial activities leading to improved P bioavailability to crops. We hypothesized that DM amendment in podzol soil will improve biochemical attributes and microbial community and abundance in silage corn cropping system under boreal climate. We evaluated the effects of organic and inorganic P amendments on soil biochemical attributes and abundance in podzol soil under boreal climate. Additionally, biochemical attributes and microbial population and abundance under short-term silage corn monocropping system was also investigated. Experimental treatments were [P0 (control); P1: DM with high P2O5; P2: DM with low P2O5; P3: inorganic P and five silage-corn genotypes (Fusion RR, Yukon R, A4177G3RIB, DKC 23-17RIB and DKC 26-28RIB) were laid out in a randomized complete block design in factorial settings with three replications. Results showed that P1 treatment increased acid phosphatase (AP-ase) activity (29% and 44%), and soil available P (SAP) (60% and 39%) compared to control treatment, during 2016 and 2017, respectively. Additionally, P1 treatments significantly increased total bacterial phospholipids fatty acids (ΣB-PLFA), total phospholipids fatty acids (ΣPLFA), fungi, and eukaryotes compared to control and inorganic P. Yukon R and DKC 26-28RIB genotypes exhibited higher total bacterial PLFA, fungi, and total PLFA in their rhizospheres compared to the other genotypes. Redundancy analyses showed promising association between P1 and P2 amendment, biochemical attributes and active microbial population and Yukon R and DKC 26-28RIB genotypes. Pearson correlation also demonstrated significant and positive correlation between AP-ase, SAP and gram negative bacteria (G-), fungi, ΣB-PLFA, and total PLFA. Study results demonstrated that P1 treatment enhanced biochemical attributes, active microbial community composition and abundance and forage production of silage corn. Results further demonstrated higher active microbial population and abundance in rhizosphere of Yukon R and DKC 26-28RIB genotypes. Therefore, we argue that dairy manure amendment with high P2O5 in podzol soils could be a sustainable nutrient source to enhance soil quality, health and forage production of silage corn. Yukon R and DKC 26-28RIB genotypes showed superior agronomic performance, therefore, could be good fit under boreal climatic conditions.

The potential of corn-soybean intercropping to improve the soil health status and biomass production in cool climate boreal ecosystems.

Intercropping (IC) is a promising approach used to improve soil health and sustainable crop production. However, it is unknown whether IC improve the soil health status and biomass productivity of crops cultivated in podzols under cool climate in boreal ecosystems. Two silage corn and three forage soybean genotypes were cultivated either as inter or monocrop (MC) treatments in a randomized complete block design. IC resulted in 28% increase in total forage production (FP). A reduction in rhizosphere soil pH (RS-pH) was observed in the IC treatments. Conversely, the rhizosphere soil acid phosphatase (RS-APase) activity was significantly higher (26-46%) in the IC treatments and occurred concomitant with a significant increase in available phosphorus (RS-Pavailable) (26-74%) in the rhizosphere. Furthermore, IC enhanced the active microbial composition and strong positive correlations were observed between RS-Pavailable, RS-APase, microbial biomass and FP; while RS-pH was negatively correlated with FP, RS-APase and RS-Pavailable. These findings suggested silage corn intercropped with forage soybean could be a viable approach to enhance FP through improved active microbial community structure, RS-APase activity and RS-Pavailable when cultivated on podzols in cool climate boreal ecosystem.

The soybean root membrane lipids and forage quality data in response to field cultivation on agricultural podzols in boreal climates.

The objective of this data in brief article is to represent the associated data set regarding our published paper in Plant Science Nadeem et al., 2019. Data set represent soil acid phosphatase activity, association of individual molecular species of four major lipid classes with soybean forage quality indices when cultivated in boreal podzolic soils under cool climatic conditions. Phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidic acid (PA) and acylated glucosyl betasitosterol ester (AGIcSiE) molecular species grouped the soybean forage quality indices in different quadrants on principal component analyses. Furthermore, the total lipid profile and correlation of major lipid species with forage quality indices are included in this data in brief article. This data set support the main findings described in Nadeem et al., 2019.

Adaptation strategies of forage soybeans cultivated on acidic soils under cool climate to produce high quality forage.

Boreal soils tend to be podzols characterized by acidic pH, which can further limit forage crop growth and production. It is unclear, how forage soybeans adopt to produce forage with high nutritional quality when cultivated on podzols in boreal climate. To answer this question, we cultivated forage soybeans on agricultural podzols at 3 farm sites with varied soil pH (6.8, 6.0 or 5.1), and assessed the root membrane lipidome remodeling response to such climatic conditions. Contrary to our expectations, significantly lower biomass was observed at pH 6.8 compared to 6.0 and 5.1. However, surprisingly the plants produced similar forage quality at 6.8 and 5.1 pH. Three major lipid classes including phospholipids, glycolipids and phytosterols were observed in roots irrespective of soil pH. Phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidic acid (PA), and acylated glucosyl betasitosterol ester (AGlcSiE) accounted for 95% of the root lipidome, and expressed significant changes in response to cultivation across the three soil pH levels. These lipids were also observed to have strong correlations with forage production, and forage quality. Therefore, soybean genotypes with higher abilities to remodel PC, PE, PA, and AGlcSiE could be better suited for producing higher quality forage in acid podzolic soils characteristics of boreal ecosystems.

A State Optimization Model Based on Kalman Filtering and Robust Estimation Theory for Fusion of Multi-Source Information in Highly Non-linear Systems.

Consistent state estimation is a vital requirement in numerous real life applications from localization to multi-source information fusion. The Kalman filter and its variants have been successfully used for solving state estimation problems. Kalman filtering-based estimators are dependent upon system model assumptions. A deviation from defined assumptions may lead to divergence or failure of the system. In this work, we propose a Kalman filtering-based robust state estimation model using statistical estimation theory. Its primary intention is for multiple source information fusion, although it is applicable to most non-linear systems. First, we propose a robust state prediction model to maintain state constancy over time. Secondly, we derive an error covariance estimation model to accept deviations in the system error assumptions. Afterward, an optimal state is attained in an iterative process using system observations. A modified robust MM estimation model is executed within every iteration to minimize the impact of outlying observation and approximation errors by reducing their weights. For systems having a large number of observations, a subsampling process is introduced to intensify the optimized solution redundancy. Performance is evaluated for numerical simulation and real multi sensor data. Results show high precision and robustness of proposed scheme in state estimation.