A nanoformulation of cisplatin with arabinoxylan having enhanced activity against hepatocellular carcinoma through upregulation of apoptotic and necroptotic pathways.

Cisplatin is a versatile drug used to treat various types of cancer, but it is associated with high toxicity and resistance problems. Several approaches, including nanotechnology, have been adopted to minimize the toxic effects and to overcome the resistance of cisplatin. Most of the nanoformulations involve the use of synthetic or semisynthetic polymers as drug carriers. In this study arabinoxylan nanoparticles have been investigated as drug reservoirs for intestinal drug delivery. The drug-loaded arabinoxylan nanoparticles (size: ∼1.8 nm, polydispersity index: 0.3 ± 0.04) were prepared and nanoformulation was characterized by various analytical techniques. The nanoformulation was found to be stable (zeta potential: 31.6 ± 1.1 mV). An in vitro cytotoxicity against HepG2 and HEK 293 cell lines was studied. The cell viability analysis showed greater efficacy than the standard cisplatin (IC50: cisplatin 2.4, arabinoxylan nanoformulation 1.3 µg mL-1). The expression profile of carcinogenic markers revealed a six-fold upregulation of MLKL and 0.9-fold down regulation of KRAS, suggesting the activation of the necroptotic pathway by the drug-loaded nanoparticles. The nanoformulation exhibited a sustained release of cisplatin with a cumulative release of ∼40 % (at pH 7.4) and ∼30 % (at pH 5.5) over a period of 12 h with very low initial burst. The study suggests that the use of the new nanoformulation can significantly reduce the required dose of cisplatin without compromising efficacy and more efficient release at basic pH.

Fingerprinting hyperglycemia using predictive modelling approach based on low-cost routine CBC and CRP diagnostics.

Hyperglycemia is an outcome of dysregulated glucose homeostasis in the human body and may induce chronic elevation of blood glucose levels. Lifestyle factors such as overnutrition, physical inactivity, and psychosocials coupled with systemic low-grade inflammation have a strong negative impact on glucose homeostasis, in particular, insulin sensitivity. Together, these factors contribute to the pathophysiology of diabetes (DM) and expanding landscape of its prevalence regionally and globally. The rapid rise in the prevalence of type 2 diabetes, therefore, underscores the need for its early diagnosis and treatment. In this work, we have evaluated the discriminatory capacity of different diagnostic markers including inflammatory biomolecules and RBC (Red Blood Cell) indices in predicting the risk of hyperglycemia and borderline hyperglycemia. For that, 208,137 clinical diagnostic entries obtained over five years from Chugtai Labs, Pakistan, were retrospectively evaluated. The dataset included HbA1c (n = 142,011), complete blood count (CBC, n = 84,263), fasting blood glucose (FBG, n = 35,363), and C-reactive protein (CRP, n = 9035) tests. Our results provide four glycemic predictive models for two cohorts HbA1c and FBG) each having an overall predictive accuracy of more than 80% (p-value < 0.0001). Next, multivariate analysis (MANOVA) followed by univariate analysis (ANOVA) was employed to identify predictors with significant discriminatory capacity for different levels of glycemia. We show that the interplay between inflammation, hyperglycemic-induced derangements in RBC indices, and altered glucose homeostasis could be employed for prognosticating hyperglycemic outcomes. Our results then conclude a glycemic predictor with high sensitivity and specificity, employing inflammatory markers coupled with RBC indices, to predict glycemic outcomes (ROC p-value < 0.0001). Taken together, this study outlines a predictor of glycemic outcomes which could assist as a prophylactic intervention in predicting the early onset of hyperglycemia and borderline hyperglycemia.

Virtual Clinical Trials Guided Design of an Age-Appropriate Formulation and Dosing Strategy of Nifedipine for Paediatric Use.

The rapid onset of action of nifedipine causes a precipitous reduction in blood pressure leading to adverse effects associated with reflex sympathetic nervous system (SNS) activation, including tachycardia and worsening myocardial and cerebrovascular ischemia. As a result, short acting nifedipine preparations are not recommended. However, importantly, there are no modified release preparations of nifedipine authorised for paediatric use, and hence a paucity of clinical studies reporting pharmacokinetics data in paediatrics. Pharmacokinetic parameters may differ significantly between children and adults due to anatomical and physiological differences, often resulting in sub therapeutic and/or toxic plasma concentrations of medication. However, in the field of paediatric pharmacokinetics, the use of pharmacokinetic modelling, particularly physiological-based pharmacokinetics (PBPK), has revolutionised the ability to extrapolate drug pharmacokinetics across age groups, allowing for pragmatic determination of paediatric plasma concentrations to support drug licensing and clinical dosing. In order to pragmatically assess the translation of resultant dissolution profiles to the paediatric populations, virtual clinical trials simulations were conducted. In the context of formulation development, the use of PBPK modelling allowed the determination of optimised formulations that achieved plasma concentrations within the target therapeutic window throughout the dosing strategy. A 5 mg sustained release mini-tablet was successfully developed with the duration of release extending over 24 h and an informed optimised dosing strategy of 450 µg/kg twice daily. The resulting formulation provides flexible dosing opportunities, improves patient adherence by reducing frequent administration burden and enhances patient safety profiles by maintaining efficacious levels of consistent drug plasma levels over a sustained period of time.

A comparative study of the policy response to COVID-19 in the ASEAN region: A dynamic simulated ARDL approach.

The COVID-19 epidemic is the most significant global health disaster of this century and the greatest challenge to humanity since World War II. One of the most important research issues is to determine the effectiveness of measures implemented worldwide to control the spread of the corona virus. A dynamic simulated Autoregressive-Distributed Lag (ARDL) approach was adopted to analyze the policy response to COVID-19 in the ASEAN region using data from February 1, 2020, to November 8, 2021. The results of unit root concluded that the dependent variable is integrated of order one while the independent variables are stationarized at the level or first difference, and the use of a dynamic simulated ARDL technique is appropriate for this paper. The outcomes of the dynamic simulated ARDL model explored that government economic support and debt/contract relief for poor families is substantially important in the fight against COVID-19. The study also explored that closing schools and workplaces, restrictions on gatherings, cancellation of public events, stay at home, closing public transport, restrictions on domestic and international travel are necessary to reduce the spread of COVID-19. Finally, this study explored that public awareness campaigns, testing policy and social distancing significantly decrease the spread of COVID-19. Policy implications such as economic support from the government to help poor families, closing schools and public gatherings during the pandemic, public awareness among the masses, and testing policies must be adopted to reduce the spread of COVID-19. Moreover, the reduction in mortality shows that immunization could be a possible new strategy to combat COVID-19, but the factors responsible for the acceptability of the vaccine must be addressed immediately through public health policies.

Activation of signaling pathways in models of t(6;9)-acute myeloid leukemia.

Patients within the WHO-subgroup of t(6;9)-positive acute myeloid leukemia (AML) differ from other AML subgroups as they are characterised by younger age and a grim prognosis. Leukemic transformation can often be attributed to single chromosomal aberrations encoding oncogenes, in the case of t(6;9)-AML to the fusion protein DEK-CAN (also called DEK-NUP214). As being a rare disease there is the urgent need for models of t(6;9)-AML. The only cell line derived from a t(6;9)-AML patient currently available is FKH1. By using phospho-proteomics on FKH1 cells, we found a strongly activated ABL1 kinase. Further investigation revealed the presence of ETV6-ABL1. This finding renders necessary to determine DEK-CAN- and ETV6-ABL1-related features when using FKH1. This can be done as ETV6-ABL1 activity in FKH1 is responsive to imatinib. Nevertheless, we provided evidence that both SFK and mTOR activation in FKH1 are DEK-CAN-related features as they were activated also in other t(6;9) and DEK-CAN-positive models. The activation of STAT5 previously shown to be strong in t(6;9)-AML and activated by DEK-CAN is regulated in FKH1 by both DEK-CAN and ETV6-ABL1. In conclusion, FKH1 cells still represent a model for t(6;9)-AML and could serve as model for ETV6-ABL1-positive AML if the presence of these leukemia-inducing oncogenes is adequately considered.Taken together, all our results provide clear evidence of novel and specific interdependencies between leukemia-inducing oncogenes and cancer signaling pathways which will influence the design of therapeutic strategies to better address the complexity of cancer signaling.

Assessing the asymmetric impact of physical infrastructure and trade openness on ecological footprint: An empirical evidence from Pakistan.

This study analyzed the asymmetric impact of the physical infrastructure and trade openness on Pakistan's ecological footprint over the period 1970-2019 using the non-linear autoregressive distributed lag model. The study results posit that positive and negative shocks to physical infrastructure increase and decrease the ecological footprint asymmetrically in the short-run and symmetrically in the long-run. Likewise, the positive and negative shocks to trade openness increase and decrease the ecological footprint asymmetrically, both in the short and in the long run. Furthermore, urbanization also positively and significantly increases Pakistan's ecological footprint in the short and long run. Moreover, a 1% increase in physical infrastructure increases the ecological footprint by 0.32%, while a 1% decrease in physical infrastructure decreases the ecological footprint by 0.33% in the long run. Similarly, a 1% increase in trade openness causes a 0.09% increase in the ecological footprint in the long term, while a 1% reduction in trade openness causes a 0.61% reduction in the ecological footprint. The results also conclude that urbanization is a major determinant of Pakistan's long-term ecological footprint. Thus, a 1% increase in urbanization causes a 1.31% increase in the ecological footprint in the long run. Finally, this study recommends that policies regarding physical infrastructure be formulated keeping in view its environmental impact. In addition, strict environmental policies should be implemented to reduce the environmental degradation effect of trade openness.

Transcriptome Profiling Reveals Role of MicroRNAs and Their Targeted Genes during Adventitious Root Formation in Dark-Pretreated Micro-Shoot Cuttings of Tetraploid Robinia pseudoacacia L.

Tetraploid Robinia pseudoacacia L. is a difficult-to-root species, and is vegetatively propagated through stem cuttings. Limited information is available regarding the adventitious root (AR) formation of dark-pretreated micro-shoot cuttings. Moreover, the role of specific miRNAs and their targeted genes during dark-pretreated AR formation under in vitro conditions has never been revealed. The dark pretreatment has successfully promoted and stimulated adventitious rooting signaling-related genes in tissue-cultured stem cuttings with the application of auxin (0.2 mg L-1 IBA). Histological analysis was performed for AR formation at 0, 12, 36, 48, and 72 h after excision (HAE) of the cuttings. The first histological events were observed at 36 HAE in the dark-pretreated cuttings; however, no cellular activities were observed in the control cuttings. In addition, the present study aimed to uncover the role of differentially expressed (DE) microRNAs (miRNAs) and their targeted genes during adventitious root formation using the lower portion (1-1.5 cm) of tetraploid R. pseudoacacia L. micro-shoot cuttings. The samples were analyzed using Illumina high-throughput sequencing technology for the identification of miRNAs at the mentioned time points. Seven DE miRNA libraries were constructed and sequenced. The DE number of 81, 162, 153, 154, 41, 9, and 77 miRNAs were upregulated, whereas 67, 98, 84, 116, 19, 16, and 93 miRNAs were downregulated in the following comparisons of the libraries: 0-vs-12, 0-vs-36, 0-vs-48, 0-vs-72, 12-vs-36, 36-vs-48, and 48-vs-72, respectively. Furthermore, we depicted an association between ten miRNAs (novel-m0778-3p, miR6135e.2-5p, miR477-3p, miR4416c-5p, miR946d, miR398b, miR389a-3p, novel m0068-5p, novel-m0650-3p, and novel-m0560-3p) and important target genes (auxin response factor-3, gretchen hagen-9, scarecrow-like-1, squamosa promoter-binding protein-like-12, small auxin upregulated RNA-70, binding protein-9, vacuolar invertase-1, starch synthase-3, sucrose synthase-3, probable starch synthase-3, cell wall invertase-4, and trehalose phosphatase synthase-5), all of which play a role in plant hormone signaling and starch and sucrose metabolism pathways. The quantitative polymerase chain reaction (qRT-PCR) was used to validate the relative expression of these miRNAs and their targeted genes. These results provide novel insights and a foundation for further studies to elucidate the molecular factors and processes controlling AR formation in woody plants.

WITHDRAWN: Original Antigenic Sin in COVID-19: Hoskins Effect and Vaccine

The article has been withdrawn at the request of the authors.Bentham Science apologizes to the readers of the journal for any inconvenience this may have caused.The Bentham Editorial Policy on Article Withdrawal can be found at https://benthamscience.com/editorial-policies-main.php. Bentham Science Disclaimer: It is a condition of publication that manuscripts submitted to this journal have not been published and will not be simultaneously submitted or published elsewhere. Furthermore, any data, illustration, structure or table that has been published elsewhere must be reported, and copyright permission for reproduction must be obtained. Plagiarism is strictly forbidden, and by submitting the article for publication the authors agree that the publishers have the legal right to take appropriate action against the authors, if plagiarism or fabricated information is discovered. By submitting a manuscript the authors agree that the copyright of their article is transferred to the publishers if and when the article is accepted for publication.

Silencing of Curlin Protein via M13 Phagemid-Mediated Synthetic sRNA Expression Reduces Virulence in the Avian Pathogenic E. coli (APEC).

Curli fimbriae, a virulent factor of the Avian Pathogenic Escherichia coli (APEC), is responsible for adhesion, biofilm formation, and colonization of pathogen. Major curli fimbriae protein is encoded by csgA gene. APEC is one of the leading causes of colibacillosis in poultry flocks and due to excessive use of antibiotics and vaccines in poultry, the emergence of various multi-drug resistant (MDR) bacterial strainsare is frequently reported. The growing concern of MDR bacterial strains necessitate novel antibacterial approaches to combat colibacillosis in poultry. RNA-based gene silencing is a very specific and robust strategy to target specific bacterial factors involved in pathogenicity and virulence. In this study, a phagemid-mediated sRNA expression system to target a vital gene, csgA, is employed. This comprises an M13 phagemid harboring a sRNA expression cassette and a pre-designed GUIDE sequences for the csgA target gene. To target the csgA gene at the mRNA level, a GUIDE sequence was computationally designed for pre-designed sRNA expression cassette. Online web tools were used to predict the binding energy, secondary structure, and off-target binding potential of the sRNA to optimize its expression. Results showed that the designed sRNA has a binding energy of - 29.60 kcal/mol with zero off-targets. After expression of the sRNA in the APEC cells, Ì´ 45% reduction in the csgA level was observed via RT-PCR in the CS-APEC-O1 strains compared to the wt-APEC-O1. Similarly, the biofilm forming ability decreased by 40% in the CS-APEC-O1 strains. The swarming motility and hemagglutination efficiency were not affected by the sRNA expression. Future studies investigating the in vivo efficiency of M13 phagemid delivery are required to evaluate its candidacy in phage therapy.

Nexus between export variety and carbon emissions in Pakistan: The role of FDI and technological development.

Carbon emissions constitute a large portion of greenhouse gases that are responsible for global warming and climate change. This study examines the impact of export variety on carbon emissions along with foreign direct investment (FDI) and technological development as determinants of environmental degradation in Pakistan. Moreover, this study is conducted in the context of the environmental Kuznets curve hypothesis (EKC). This study applies dynamic ordinary least squares and error correction models for long-term and short-term estimates, respectively. The results indicate that the EKC hypothesis is valid in the long term. This implies that Pakistan's economy reached the threshold level of income, after which an increase in income was not responsible for environmental degradation. Export variety restrains environmental degradation in the short term and is not a significant factor in the long term. Energy consumption has aggravated environmental degradation, while FDI and technological development are restraining environmental degradation. Policy measures are recommended to curb environmental degradation in Pakistan.

Paediatric specific dosage forms: Patient and formulation considerations.

The total number of paediatric formulations available only account for a small proportion of the full therapeutic plethora required to effectively treat paediatrics and, therefore, the availability of high quality medicines designed specifically for children remains an ongoing challenge. Currently, the World Health Organisation (WHO) report that around 50% of medication issued for long-term conditions are not taken as advised, whilst it has also been established that, in general practice, around one tenth of medicines prescribed for children are either off-label or unlicensed. Such off-label and unlicensed use is owing to the considerable anatomical and physiological differences observed between paediatric subsets. Identifying such differences, is essential for better informing paediatric drug development and assisting regulatory reviews, whilst ensuring safe and effective therapeutic concentrations of pharmacological substances. Points covered: The review discusses factors affecting the safety, toxicity and efficacy of paediatric drug delivery systems. The research highlights features of the gastrointestinal tract and reports anatomical and physiological differences between paediatrics and adults. Additionally, differences observed in paediatric pharmacokinetic profiles (absorption, distribution, metabolism and elimination) due to physiological differences are also discussed. Furthermore, this review considers the advantages and limitations of current paediatric specific dosage forms available and assesses the acceptability of innovative small flexible solid oral dosage forms. Lastly, this review highlights factors affecting paediatric medicine adherence and acceptability and discusses the techniques available to overcome barriers associated with non-adherence.

Fiscal policy and environment: a long-run multivariate empirical analysis of ecological footprint in Pakistan.

The ecological footprint attempts to quantify human impact on nature and its resources necessary to satisfy human needs. This research study explores the long-run implications of fiscal policy on the ecological footprint in Pakistan empirically, keeping different socio-economic factors into consideration. Per annum, time series data have been collected between 1976 and 2018, and the ARDL model is applied to investigate this long-run and short-run association. The conclusion of ARDL model shows that a 1% increase in public development expenditures, total population, GDP, and energy consumption increase 0.19, 2.17, 1.16, and 2.17% ecological footprint, respectively, in Pakistan between 1976 and 2018 vice versa. However, it is also derived that a 1% increase in public tax and non-tax revenue and current public expenditures (in health, education, and other social sectors) shrink 0.36 and 0.013% ecological footprint in the long run in Pakistan. For policy implications, these results focus on practical fiscal policy significance to achieve environmental targets in Pakistan, suggesting an increase in public current expenditures in public and social sectors and increasing public revenue by expanding the tax base, which will ultimately reduce ecological footprint in the long run in Pakistan.

A Short Review on Key Role of Plants and their Extracts in Boosting up Immune Response to Combat COVID-19.

In the wake of the recent global pandemic of COVID-19, there has been increasing concern among the general public to improve their immune system. The causative agent of COVID-19 is SARS CoV-2, similar to its relative viruses SARS Cov-1 and MERS. Although vaccines have been developed now and are in public use, still the role of a healthy immune system is crucial as new strains of the virus are being discovered and along with emergence of new strains, short and long term side effects of vaccine cannot be excluded. Plants have been used in herbal medicines and many chemicals since ancient times and extracts in them are found to boost the immune system. Therefore, a consciously maintained diet consisting of plant-based immunity boosters is the need of the hour. Plants are known to provide many chemicals, natural therapeutics and vitamins which naturally enhance our immune system. Recently, vaccination research is also being carried out in transgenic plants. In this review, main focus has been put on highlighting some of the key players within the Kingdom Plantae, which, when taken up in regular diet, can significantly boost our immune system capacity and thus helps the human body to combat this deadly virus more efficiently.

Development of an Age-Appropriate Mini Orally Disintegrating Carvedilol Tablet with Paediatric Biopharmaceutical Considerations.

Owing to considerable differences observed in anatomy and physiology between paediatric subsets, it has been well established that children respond to drugs differently compared to adults. Furthermore, from a formulation perspective, there is a distinct challenge to develop a dosage form that is capable of safely, accurately, and reliably delivering the dose across the whole paediatric population. Orally disintegrating mini-tablets (ODMT) have widely been considered as an age-appropriate formulation option that possess the ability for adequate dose flexibility, avoids swallowing difficulties, and exhibits superior stability due to its solid state. Within this study, two strengths (0.5 mg and 2 mg) of carvedilol ODMT formulations were developed using an excipient composition and load that is appropriate for paediatric use. The formulations demonstrated adequate mechanical strength (>20 N) and fast disintegration times (<30 s). Dissolution profiles observed were robust and comparable to the marketed conventional tablet formulation across various parts of the gastrointestinal (GI) tract in both the fed and fasted state, signifying appropriate efficacy, quality, and performance. As such, the formulations developed in this study show potential to address the need of an 'age-appropriate' formulation of carvedilol, as highlighted by the European Medicines Agency (EMA) Inventory of the Needs for Paediatric Medicine.

AXL receptor tyrosine kinase: a possible therapeutic target in acute promyelocytic leukemia.

BACKGROUND: Acute promyelocytic leukemia (APL) is a subset of acute myeloid leukemia (AML) which is characterized by the fusion of promyelocytic leukemia PML and retinoic acid receptor- alpha (RAR-alpha) genes. All-trans retinoic acid (ATRA) and/or arsenic trioxide (ATO) have resulted in durable cytogenetic and molecular remissions in most APL patients and have altered the natural history of the disease. Most APL patients treated with ATRA and/or ATO are now anticipated to have a nearly normal life expectancy. Unfortunately, relapse and resistance to the current treatment occur in APL patients and the outcome remains dismal in these refractory patients. AXL receptor tyrosine kinase (AXL-RTK) has been shown to increase tumour burden, provide resistance to therapy and is critical to maintain cancer stem cells (CSCs) in chronic myeloid leukemia (CML) by stabilizing ß-catenin in the Wnt/ß-catenin signalling pathway. However, the role of AXL-RTK has not been explored in PML/RARα-positive APL. This study aimed to explore the role of AXL-RTK receptor in PML/RARα-positive APL. METHODS AND RESULTS: By using biochemical and pharmacological approaches, here we report that targeting of AXL-RTK is related to the down-regulation of ß-catenin target genes including c-myc (p < 0.001), AXIN2 (p < 0.001), and HIF1α (p < 0.01) and induction of apoptosis in PML/RARα-positive APL cell line. Resistance to all-trans retinoic acid (ATRA) was also overcomed by targeting AXL-RTK with R428 in APL (p < 0.05). CONCLUSION: Our results provide clear evidence of the involvement of AXL-RTK in leukemogenic potential of PML/RARα-positive APL and suggest targeting of AXL-RTK in the treatment of therapy resistant APL patients.

Does the prevailing Indian agricultural ecosystem cause carbon dioxide emission? A consent towards risk reduction.

Recently, due to the increasing concentration of carbon dioxide emissions in the atmosphere, the global environment has changed dramatically. As a result, climate change, global warming, and environmental degradation-like issues have been raised. Presumably, human beings, as well as the agricultural ecosystem, become most vulnerable to these issues. In this context, the study focuses on the nexus between Indian's agricultural ecosystem and carbon dioxide emission. For the purpose of this study, annual time series data over the time span from 1990 to 2014 was used. The modern techniques, for instance, Johansen, ARDL, and Granger causality, were employed. The Johansen test and ARDL model suggest that carbon dioxide emissions and agricultural ecosystems are co-integrated. In the short run, the ARDL model suggests that a 1% increase in biomass-burned crop residues, total pesticides, and stock of livestock would increase carbon dioxide emissions by 0.26, 0.3, and 6.58% respectively. The residual diagnostics tests suggest that the ARDL model is stable, reliable, and credible in the present form. The results of the granger causality show that a unidirectional causality was found between carbon dioxide and total heads of livestock, all animal manure applied to the soil, agricultural technology, and total pesticide used in the agricultural sector. In contrast, bidirectional causality was found between the production of biomass-burned crop residues and carbon dioxide emission. Therefore, it is suggested that the government should take preemptive action to reduce the risk of environmental pollution and degradation through synchronized strategies particularly by reducing the amount of biomass-burned crop residues and usage of total pesticides in the country.

Pymetrozine inhibits reproductive behavior of brown planthopper Nilaparvata lugens and fruit fly Drosophila melanogaster.

Pymetrozine is a promising chemical used to control brown planthopper, which developed resistance to imidacloprid and buprofezin in the past decade. Field efficacy indicates that pymetrozine can reduce the number of offsprings of brown planthopper, but the specific physiological mechanism is unknown. In this study, we systematically described the mating process of brown planthopper including 8 steps (abdominal vibration, following, positioning, wing extension, attempted copulation, copulation, terminated copulation and leaving) and explored the optimal mating time after adult eclosion (3-5 days) and observation time (30 mins). Also, behavioral data showed that pymetrozine can affect the mating behavior and female fecundity of brown planthopper and fruit fly. As one of the target genes for pymetrozine, Nanchung (Nan), the nan36a mutant male courtship index, female receptivity and the number of offsprings were significantly decreased. Behavioral defects in nan36a mutant flies can be rescued by expressed NlNan. Our results indicated that Nan plays essential roles in the mating behavior and female fecundity. These findings provide useful information for demonstrating that pymetrozine effectively reduce the reproduction of brown planthopper and contribute to our understanding of reproductive strategies controlled by pymetrozine in insects.

Testing environmental Kuznets curve hypothesis in the presence of green revolution: a cointegration analysis for Pakistan.

Recently, it has been observed that ecological and environmental condition of Pakistan is going worse due to greenhouse gases emissions. Therefore, an immediate response is necessary to mitigate the high impact of these gases. We employed modern time series econometric models to examine the association between green revolution and carbon dioxide emission in Pakistan spanning the time period of 1972-2014. These modern econometrics techniques encompassing of Johansen cointegration, ARDL bounds testing approach and its diagnostics statistics. Evidence of the Johansen model shows significant long-run cointegration between the green revolution and carbon dioxide emission in Pakistan. Results of the ARDL model show that a 1% increase in area irrigated, agricultural tractors and fertilizer used will increase carbon dioxide emissions by 0.35, 0.33 and 0.32%, respectively. Moreover, an inverted U-shaped relation was found between crops production and carbon dioxide emission both in the short and long-run. This relationship indicates that environmental Kuznets curve hypothesis validation prevailed in the presence of green revolution. The ARDL model credibility, stability and reliability were found correct based on the diagnostic statistics. The findings of variance decomposition analysis revealed that the green revolution in Pakistan significantly causes carbon dioxide emissions.

Integrated control of dry root rot of chickpea caused by Rhizoctoniabataticola under the natural field condition.

The study investigated the effect of three fungicides Bavistin®, Aliette®, and Biomagic® at the rate of 2 g/L were tested In vitro and In vivo to control dry root rot and their impact on yield were evaluated at the rate of 4 g/L against R. bataticola while varieties used were Karak-1, Karak-2, Karak-3, and Sheenghar. Disease severity was recorded lowest (19 %) and highest yield (1467 Kg/ha), plant height (47.5 cm), number of pods/plant (15.0) and number of grain/pods (1.66) were recorded in cultivar Karak-1. Among the fungicides drugs, the Bavistin®, significantly reduced the disease severity (5 %) and Kg/ha), highest plant height (64.1 cm), highest grain yield (1488 Kg/ha), number of pods/plant (24.5) and number of grain/pods (2.25). It is concluded that the integrated use of Karak-1 and Bavistin®, fungicide drugs gave promising results for controlling dry root rot of chickpea, and increased plant height, number of pods/plant and number of grain/pods.

Testing the relationship between globalization and carbon dioxide emissions in Pakistan: does environmental Kuznets curve exist?

Over the last few decades, the atmospheric carbon dioxide emission has been amplified to a great extent in Pakistan. This amplification may cause global warming, climate change, and environmental degradation in Pakistan. Consequently, ecological condition and human life may suffer in the near future from these indicated threats. Therefore, an attempt was made to test the relationship between globalization and carbon dioxide emissions in case of Pakistan. The study covers the time series data over the period of 1975-2014. We employed modern econometric techniques such as Johansen co-integration, ARDL bound testing approach, and variance decomposition analysis. Results of the Johansen co-integration test show that there is a significant long-run relationship between carbon dioxide emissions and globalization. The long-run elasticities of the ARDL model show that a 1% increase in economic globalization, political globalization, and social globalization will increase carbon dioxide emissions by 0.38, 0.19, and 0.11%, respectively. Further, our findings reveal that the environmental Kuznets curve (EKC) hypothesis prevails an inverted U-shaped relationship between carbon dioxide emission and economic growth. Therefore, the EKC hypothesis is valid in the presence of globalization. The diagnostic test results show that the parameters of the ARDL model are credible, stable, and reliable in the current form. Finally, variance decomposition analysis displays that economic, political, and social globalization are contributing significantly to carbon dioxide emissions in Pakistan.