Structural, dynamic behaviour, in-vitro and computational investigations of Schiff's bases of 1,3-diphenyl urea derivatives against SARS-CoV-2 spike protein.

The COVID-19 has had a significant influence on people's lives across the world. The viral genome has undergone numerous unanticipated changes that have given rise to new varieties, raising alarm on a global scale. Bioactive phytochemicals derived from nature and synthetic sources possess lot of potential as pathogenic virus inhibitors. The goal of the recent study is to report new inhibitors of Schiff bases of 1,3-dipheny urea derivatives against SARS COV-2 spike protein through in-vitro and in-silico approach. Total 14 compounds were evaluated, surprisingly, all the compounds showed strong inhibition with inhibitory values between 79.60% and 96.00% inhibition. Here, compounds 3a (96.00%), 3d (89.60%), 3e (84.30%), 3f (86.20%), 3g (88.30%), 3h (86.80%), 3k (82.10%), 3l (90.10%), 3m (93.49%), 3n (85.64%), and 3o (81.79%) exhibited high inhibitory potential against SARS COV-2 spike protein. While 3c also showed significant inhibitory potential with 79.60% inhibition. The molecular docking of these compounds revealed excellent fitting of molecules in the spike protein receptor binding domain (RBD) with good interactions with the key residues of RBD and docking scores ranging from - 4.73 to - 5.60 kcal/mol. Furthermore, molecular dynamics simulation for 150 ns indicated a strong stability of a complex 3a:6MOJ. These findings obtained from the in-vitro and in-silico study reflect higher potency of the Schiff bases of 1,3-diphenyl urea derivatives. Furthermore, also highlight their medicinal importance for the treatment of SARS COV-2 infection. Therefore, these small molecules could be a possible drug candidate.

Revision Lumbar Spine Surgeries: An Early Career Neurosurgery Experience.

BACKGROUND: The aims and ambitions of a surgeon in the early years of his professional career are to make a good reputation by providing excellent patient outcomes and avoiding complex and difficult surgeries. Revision lumbar spine surgeries (RLSSs) pose a significant challenge in terms of surgical management, as the moribund anatomy increases the risk of complications, adding to an unlikely outcome. OBJECTIVE: We conducted this study to determine the clinical indications and outcomes of RLSSs performed by an early career neurosurgeon. MATERIALS AND METHODS: This cross-sectional study was conducted after approval from the hospital's ethical committee, and data was collected in late December of 2022 and early January 2023, from retrospective records for a single early career neurosurgeon. A form was filled with each patient's data, such as age, gender, time since surgery, indication for surgery, operative findings, types of surgery performed, etc. All variables were noted for the patient and were further categorized, based on the clinical records, into many sub-categories. RESULTS: Almost 400 lumbar spine surgeries were performed by the surgeon, and about 45 (11.25%) were revision surgeries, and the full record was available for 42 surgeries. These patients' ages ranged from 22 to 70 years, and the mean age was about 46.74±13.29 SD. The common symptoms leading to revision surgeries were numbness and pain in 17 (40.5%) patients each; common per-operative findings were recurrent disc in eight patients (19%), infection in nine patients (21.4%), and fibrosis/adhesions in 16 (38.1%); most common surgeries performed were diskectomy in 11 (26.2%) and diskectomy plus release of adhesions in 12 (28.6%); complications occurred in 14 (33%), and good to excellent outcomes was recorded in 29 (69%) cases.  Conclusion: RLSSs are difficult compared to first-time lumbar spine surgeries, and the moribund anatomy predisposes to complications, and better shall be dealt with great care and, at the minimum, shall be embarked upon as a team.

Identification of small molecular inhibitors of SIRT3 by computational and biochemical approaches a potential target of breast cancer.

Sirtuin 3 (SIRT3) belongs to the Sirtuin protein family, which consists of NAD+-dependent lysine deacylase, involved in the regulation of various cellular activities. Dysregulation of SIRT3 activity has been linked to several types of cancer, including breast cancer. Because of its ability to stimulate adaptive metabolic pathways, it can aid in the survival and proliferation of breast cancer cells. Finding new chemical compounds targeted towards SIRT3 was the primary goal of the current investigation. Virtual screening of ~ 800 compounds using molecular docking techniques yielded 8 active hits with favorable binding affinities and poses. Docking studies verified that the final eight compounds formed stable contacts with the catalytic domain of SIRT3. Those compounds have good pharmacokinetic/dynamic properties and gastrointestinal absorption. Based on excellent pharmacokinetic and pharmacodynamic properties, two compounds (MI-44 and MI-217) were subjected to MD simulation. Upon drug interaction, molecular dynamics simulations demonstrate mild alterations in the structure of proteins and stability. Binding free energy calculations revealed that compounds MI-44 (- 45.61 ± 0.064 kcal/mol) and MI-217 (- 41.65 ± 0.089 kcal/mol) showed the maximum energy, suggesting an intense preference for the SIRT3 catalytic site for attachment. The in-vitro MTT assay on breast cancer cell line (MDA-MB-231) and an apoptotic assay for these potential compounds (MI-44/MI-217) was also performed, with flow cytometry to determine the compound's ability to cause apoptosis in breast cancer cells. The percentage of apoptotic cells (including early and late apoptotic cells) increased from 1.94% in control to 79.37% for MI-44 and 85.37% for MI-217 at 15 µM. Apoptotic cell death was effectively induced by these two compounds in a flow cytometry assay indicating them as a good inhibitor of human SIRT3. Based on our findings, MI-44 and MI-217 merit additional investigation as possible breast cancer therapeutics.

Novel Natural Inhibitors for Glioblastoma by Targeting Epidermal Growth Factor Receptor and Phosphoinositide 3-kinase.

BACKGROUND/AIM: Glioblastoma is an extensively malignant neoplasm of the brain that predominantly impacts the human population. To address the challenge of glioblastoma, herein, we have searched for new drug-like candidates by extensive computational and biochemical investigations. METHOD: Approximately 950 compounds were virtually screened against the two most promising targets of glioblastoma, i.e., epidermal growth factor receptor (EGFR) and phosphoinositide 3-kinase (PI3K). Based on highly negative docking scores, excellent binding capabilities and good pharmacokinetic properties, eight and seven compounds were selected for EGFR and PI3K, respectively. RESULTS: Among those hits, four natural products (SBEH-40, QUER, QTME-12, and HCFR) exerted dual inhibitory effects on EGFR and PI3K in our in-silico analysis; therefore, their capacity to suppress the cell proliferation was assessed in U87 cell line (type of glioma cell line). The compounds SBEH-40, QUER, andQTME-12 exhibited significant anti-proliferative capability with IC50 values of 11.97 ± 0.73 µM, 28.27 ± 1.52 µM, and 22.93 ± 1.63 µM respectively, while HCFR displayed weak inhibitory potency (IC50 = 74.97 ± 2.30 µM). CONCLUSION: This study has identified novel natural products that inhibit the progression of glioblastoma; however, further examinations of these molecules are required in animal and tissue models to better understand their downstream targeting mechanisms.

Compromise optimum allocation in neutrosophic multi-character survey under stratified random sampling using neutrosophic fuzzy programming.

Survey sampling has wide range of applications in social and scientific investigation to draw inference about the unknown parameter of interest. In complex surveys, the sample information about the study variable cannot be expressed by a precise number under uncertain environment due fuzziness and indeterminacy. Therefore, this information is expressed by neutrosophic numbers rather than the classical numbers. The neutrosophic statistics, which is generalization of classical statistics, deals with the neutrosophic data that has some degree of indeterminacy and fuzziness. In this study, we investigate the compromise optimum allocation problem for estimating the population means of the neutrosophic study variables in a multi-character stratified random sampling under uncertain per unit measurement cost. We proposed the intuitionistic fuzzy cost function, modeling the fuzzy uncertainty in stratum per unit measurement cost. The compromise optimum allocation problem is formulated as a multi-objective intuitionistic fuzzy optimization problem. The solution methodology is suggested using neutrosophic fuzzy programming and intuitionistic fuzzy programming approaches. A numerical study includes the means estimation of atmospheric variables is presented to explore the real-life application, explain the mathematical formulation, and efficiency comparison with some existing methods. The results show that the suggested methods produce more precise estimates with less utilization of survey resources as compared to some existing methods. The Python is used for statistical analysis, graphical designing and numerical optimization problems are solved using GAMS.

Identification of new pharmacophore against SARS-CoV-2 spike protein by multi-fold computational and biochemical techniques.

COVID-19 appeared as a highly contagious disease after its outbreak in December 2019 by the virus, named SARS-CoV-2. The threat, which originated in Wuhan, China, swiftly became an international emergency. Among different genomic products, spike protein of virus plays a crucial role in the initiation of the infection by binding to the human lung cells, therefore, SARS-CoV-2's spike protein is a promising therapeutic target. Using a combination of a structure-based virtual screening and biochemical assay, this study seeks possible therapeutic candidates that specifically target the viral spike protein. A database of ~ 850 naturally derived compounds was screened against SARS-CoV-2 spike protein to find natural inhibitors. Using virtual screening and inhibitory experiments, we identified acetyl 11-keto-boswellic acid (AKBA) as a promising molecule for spike protein, which encouraged us to scan the rest of AKBA derivatives in our in-house database via 2D-similarity searching. Later 19 compounds with > 85% similarity with AKBA were selected and docked with receptor binding domain (RBD) of spike protein. Those hits declared significant interactions at the RBD interface, best possess and excellent drug-likeness and pharmacokinetics properties with high gastrointestinal absorption (GIA) without toxicity and allergenicity. Our in-silico observations were eventually validated by in vitro bioassay, interestingly, 10 compounds (A3, A4, C3, C6A, C6B, C6C, C6E, C6H, C6I, and C6J) displayed significant inhibitory ability with good percent inhibition (range: > 72-90). The compounds C3 (90.00%), C6E (91.00%), C6C (87.20%), and C6D (86.23%) demonstrated excellent anti-SARS CoV-2 spike protein activities. The docking interaction of high percent inhibition of inhibitor compounds C3 and C6E was confirmed by MD Simulation. In the molecular dynamics simulation, we observed the stable dynamics of spike protein inhibitor complexes and the influence of inhibitor binding on the protein's conformational arrangements. The binding free energy ΔGTOTAL of C3 (-38.0 ± 0.08 kcal/mol) and C6E (-41.98 ± 0.08 kcal/mol) respectively indicate a strong binding affinity to Spike protein active pocket. These findings demonstrate that these molecules particularly inhibit the function of spike protein and, therefore have the potential to be evaluated as drug candidates against SARS-CoV-2.

Revolutionizing Cardiac Care: A Comprehensive Narrative Review of Cardiac Rehabilitation and the Evolution of Cardiovascular Medicine.

Cardiovascular disease (CVD) stands as a global health crisis, with its complex web of conditions, including coronary artery disease, heart failure, hypertension, and stroke, continuing to exact a heavy toll on individuals and healthcare systems worldwide. Despite substantial advances in medical technology and pharmaceutical interventions, CVD remains a formidable adversary, necessitating innovative prevention, management, and rehabilitation approaches. In tracing the historical trajectory of CVD, the narrative reveals the antiquated practices of early 20th-century medicine, marked by extended bed rest as the primary modality for heart-related conditions. It underscores the critical juncture when exercise was first recognized as a therapeutic tool for cardiac health, setting the stage for the evolution of cardiac rehabilitation (CR). CR programs have transcended their initial focus on exercise, expanding to encompass dietary guidance, psychosocial support, and comprehensive risk factor modification. These holistic interventions enhance physical recovery and address the psychosocial and lifestyle aspects of CVD management, ultimately improving patients' overall well-being. CR programs increasingly leverage advanced technologies and personalized strategies to tailor interventions to individual patient needs, ultimately enhancing outcomes and reducing the burden of CVD. In conclusion, this narrative review illuminates the transformative journey of cardiac care, with a particular spotlight on the indispensable role of CR in reshaping the landscape of cardiovascular medicine. By evolving from historical practices to comprehensive, patient-centered interventions, CR has made significant strides in improving the prognosis, quality of life, and holistic well-being of individuals grappling with the complexities of CVD. Understanding this historical context and the contemporary advancements is paramount for healthcare professionals and policymakers as they navigate the intricate terrain of cardiovascular medicine and endeavor to mitigate the impact of this pervasive disease.

Integrative Medicine Approaches: Bridging the Gap Between Conventional and Renal Complementary Therapies.

The global incidence of renal disorders is on the rise, demanding the implementation of novel and comprehensive strategies for patient care. The present study demonstrates the significance of renal health, offering a comprehensive comprehension of renal physiology and the escalating load of renal illnesses. The relevance of controlling renal illnesses is underscored by a thorough examination of conventional treatments, which encompass pharmaceutical interventions, dialysis, and transplantation. Subsequently, the story redirects its attention towards complementary therapies, classifying them into several categories, such as herbal medicine, acupuncture, dietary supplements, and mind-body activities, among various others. This paper presents a comprehensive examination of the available information, providing a critical study of the effectiveness and safety of alternative therapies in renal care. This study focuses on the central idea of integrative medicine, distinguished by its patient-centered and holistic approach and its seamless integration of conventional and complementary therapies. This study examines several integrative care models, using case studies to illustrate successful integrative approaches that have enhanced patient outcomes. The review thoroughly examines the current body of literature on integrative renal care, including meta-analyses, systematic reviews, and notable research discoveries. This study highlights the need for further research to address knowledge gaps and explore areas that require additional examination. These findings emphasize the importance of future research endeavors in this crucial sector. In addition, the paper thoroughly examines the safety issues and regulatory factors pertaining to complementary therapies, underscoring the importance of making educated decisions and maintaining diligent monitoring to safeguard patients' well-being. Integrating patient perspectives, experiences, and shared decision-making is essential to the integrated healthcare process, promoting a collaborative and patient-centered approach. The study culminates by providing a concise overview of the primary discoveries and delineating the ramifications of implementing therapeutic procedures. This statement underscores the considerable potential of integrative medicine in augmenting renal care, ultimately leading to enhanced patient outcomes and an improved overall quality of life for persons with renal diseases. Also, this literature review provides a thorough and knowledgeable examination of the incorporation of conventional and complementary therapies in the context of renal health. It gives valuable perspectives for healthcare practitioners, researchers, and policymakers interested in enhancing care strategies for individuals with renal conditions.

Causality and interdependencies among sustainable development goals: assessing the nexus of agriculture, environment, and finance development.

This study examines the causal relationships and interdependencies among three dimensions of sustainable development goals (SDGs) in Africa: environmental factors, agricultural production (for societal aspects), and finance development (for economic aspects). The study focuses on three regions, the whole SSA (Sub-Saharan Africa, excluding the high-income countries), West-Central Africa (W-CA), and South and East Africa (S-EA), and uses data from 1970 to 2018. It uses vector error correction model (VECM), impulse response function (IRF), and analysis of causality direction methods. The findings indicate bidirectional causal effects among the three SDG dimensions in Africa. Finance development factors influence both environmental and agricultural factors, while agro-production factors significantly affect both finance development and environmental factors. This study concludes that bidirectional causal effects exist within these dimensions, confirming their interdependencies and emphasizing the need for integrating these dimensions into African sustainable development goals. Recommendations include incorporating green aspects in financing development plans and establishing regulatory authorities to effectively coordinate and control these sustainable dimensions at both the Sub-Saharan Africa and state levels, ensuring impactful greenhouse and sustainable agriculture development for sustainable food production.

Sirtuin 1 inhibition: a promising avenue to suppress cancer progression through small inhibitors design.

SIRT1 is a protein associated with vital cell functions such as gene regulation, metabolism, ageing, and cellular energy restoration. Its association with the tumor suppressor protein p53 is essential for controlling the growth of cells, apoptosis, and response to DNA damage. By raising p53 acetylation, encouraging apoptosis, and reducing cell proliferation, inhibiting SIRT1's catalytic domain, which interacts with p53, shows potential as a cancer treatment. The aim of the study is to find compounds that could inhibit SIRT1 and thus lower the proliferation of cancer cells. Employing molecular docking techniques, a virtual screening of ∼900 compounds (isolated from medicinal plants and derivatives) gave us 13 active compounds with good binding affinity. Additional evaluation of pharmacokinetic and pharmacodynamic properties led to the selection of eight compounds with desirable properties. Docking analysis confirmed stable interactions between the final eight compounds (C1-C8) and the SIRT1 catalytic domain. Molecular dynamics simulations show overall stability and moderate changes in protein structure upon compound binding. The compactness of the protein indicated the protein's tight packing upon the inhibitors binding. Binding free energy calculations revealed that compounds C2 (-49.96 ± 0.073 kcal/mol and C1 (-44.79 ± 0.077 kcal/mol) exhibited the highest energy, indicating strong binding affinity to the SIRT1 catalytic domain. These compounds, along with C8, C5, C6, C3, C4 and C7, showed promising potential as SIRT1 inhibitors. Based on their ability to reduce SIRT1 activity and increase apoptosis, the eight chemicals discovered in this work may be useful in treating cancer.Communicated by Ramaswamy H. Sarma.

A convenient method for the construction of triazole-bonded chalcone derivatives from acetophenone: Synthesis and free radical scavenging investigation.

The substituted 1,2,3-triazole core is prevalent in numerous commercially available drugs utilized for a wide range of clinical applications. Simultaneously, chalcone represents a privileged framework discovered in natural products exhibiting intriguing bioactivities. In this study, we synthesized triazole-bonded chalcone compounds (4ax-4by), starting from a simple aromatic ketone, acetophenone, which underwent aldol condensation to give hydroxychalcone intermediate. In the second step, the hydroxyl group of chalcone compound was adducted with propargyl moiety through propargylation reaction. Then, the propargylated products underwent smooth copper-mediated azide-alkyne cyclization to give the triazole-bonded chalcones as the final products. They were characterized by IR, NMR and HRMS, and evaluated their radical scavenging activity against 2,2-diphenyl-1-picrylhydrazyl (DPPH). Among the tested products, compound 4by was denoted as the most potent derivative which can inhibit DPPH radical in 91.62 ± 0.10% at 500 ppm.•Acetophenone as a simple ketone was modified to triazole-bonded chalcones.•Modification was performed through three steps reaction.•Final products exhibited free radical scavenging activity.

Bioinformatics and immunoinformatics approach to develop potent multi-peptide vaccine for coxsackievirus B3 capable of eliciting cellular and humoral immune response.

Coxsackievirus B3 (CVB3) is a viral pathogen of various human disorders with no effective preventative interventions. Herein, we aimed to design a chimeric vaccine construct for CVB3 using reverse vaccinology and immunoinformatics approaches by screening the whole viral polyprotein sequence. Firstly, screening and mapping of viral polyprotein to predict 21 immunodominant epitopes (B-cell, CD8+ and CD4+ T-cell epitopes), fused with an adjuvant (Resuscitation-promoting factor), appropriate linkers, HIV-TAT peptide, Pan DR epitope, and 6His-tag to assemble a multi-epitope vaccine construct. The chimeric construct is predicted as probable antigen, non-allergen, stable, possess encouraging physicochemical features, and indicates a broader population coverage (98 %). The tertiary structure of the constructed vaccine was predicted and refined, and its interaction with the Toll-like receptor 4 (TLR4) was investigated through molecular docking and dynamics simulation. Computational cloning of the construct was carried out in pET28a (+) plasmid to guarantee the higher expression of the vaccine protein. Lastly, in silico immune simulation foreseen that humoral and cellular immune responses would be elicited in response to the administration of such a potent chimeric construct. Thus, the design constructed could vaccinate against CVB3 infection and various CVB serotypes. However, further in vitro/in vivo research must assess its safety and effectiveness.

Heterogeneous role of energy utilization, financial development, and economic development in ecological footprint: How far away are developing economies from developed ones.

This research aims to investigate the impact of energy consumption, financial development, and economic development on the ecological footprint in a panel of 119 developed and developing countries between 2002 and 2018. The study employs panel unit root and autoregressive distributed lag (ARDL) model to achieve this goal. The ARDL results reveal that several factors such as energy consumption, financial development, urbanization, globalization, foreign direct investment, and population growth have a positive relationship with the ecological footprint in developed countries. On the other hand, the human development index and natural resources negatively affect the ecological footprint in developed countries. Moreover, the ARDL results indicate that energy consumption, financial development, urbanization, foreign direct investment, and population growth positively impact the ecological footprint in developing countries in the long run. In contrast, the human development index, natural resources, and globalization have a negative impact on the ecological footprint. These findings imply the need for different policy implications for both developed and developing countries to reduce their ecological footprint.

Multi-Fold Computational Analysis to Discover Novel Putative Inhibitors of Isethionate Sulfite-Lyase (Isla) from Bilophila wadsworthia: Combating Colorectal Cancer and Inflammatory Bowel Diseases.

A glycal radical enzyme called isethionate sulfite-lyase (Isla) breaks the C-S bond in isethionate to produce acetaldehyde and sulfite. This enzyme was found in the Gram-negative, colonial Bilophila wadsworthia bacteria. Sulfur dioxide, acetate, and ammonia are produced by the anaerobic respiration route from (sulfonate isethionate). Strong genotoxic H2S damages the colon's mucous lining, which aids in the development of colorectal cancer. H2S production also contributes to inflammatory bowel diseases such as colitis. Here, we describe the structure-based drug designing for the Isla using an in-house database of naturally isolated compounds and synthetic derivatives. In structure-based drug discovery, a combination of methods was used, including molecular docking, pharmacokinetics properties evaluation, binding free energy calculations by the molecular mechanics/generalized born surface area (MM/GBSA) method, and protein structure dynamics exploration via molecular dynamic simulations, to retrieve novel and putative inhibitors for the Isla protein. Based on the docking score, six compounds show significant binding interaction with the Isla active site crucial residues and exhibit drug-like features, good absorption, distribution, metabolism, and excretion profile with no toxicity. The binding free energy reveals that these compounds have a strong affinity with the Isla. In addition, the molecular dynamics simulations reveal that these compounds substantially affect the protein structure dynamics. As per our knowledge, this study is the first attempt to discover Isla potential inhibitors. The compounds proposed in the study using a multi-fold computational technique may be verified in vitro as possible inhibitors of Isla and possess the potential for the future development of new medications that target Isla.

Generalized ß-Hyers-Ulam-Rassias Stability of Impulsive Difference Equations.

This paper describes the existence and uniqueness of the solution, ß-Hyers-Ulam-Rassias stability and generalized ß-Hyers-Ulam-Rassias stability of an impulsive difference system on bounded and unbounded discrete intervals. At the end, an example is given to illustrate the theoretical result.

Impact of tourism on sustainable development in BRI countries: The moderating role of institutional quality.

This study investigated the influence of tourism on sustainable development while considering institutional quality as a moderating variable. Moreover, exchange rate, urbanization, household consumption, per capita income and renewable energy per capita were also essential factors in determining sustainable development. The sample consists of 64 Belt and Road Initiative (BRI) countries from 2003-2018. The outcomes of the two-step system GMM confirmed the statistically significant and positive dynamic nature of sustainable development and its relationship with tourism and other determinants at a significance level of 1% for BRI countries. Institutional quality enhanced the 4.693% sustainability path to achieve the sustainable development goals (SDGs) agenda with regionally interconnected countries at significance level of 1%. Renewable energy per-capita and income per-capita played a significant and positive role, while the exchange rate, household consumption, and urbanization negatively influenced by hurting thd path of sustainable development. The current research findings have valuable contributions to academics as it offers novel insights about the 0. 351% influence of tourism on sustainable development at significance level of 1%, and it proposes valued suggestions to policymakers concerning tourism development strategies.

Exploring the dynamic relationship between financial development, renewable energy, and carbon emissions: A new evidence from belt and road countries.

This empirical study examines the endogenous relationship between carbon emissions (CO2), financial development, renewable energy, globalization, and institutional quality in 64 belt and road initiative countries (BRI) using a two-step system generalized method of moments (GMM) approach with panel data over the period 2003 to 2018. Furthermore, this study used (Dumitrescu & Hurlin, 2012) causality test to estimate the variables' causal relationship. The results indicate that financial development significantly increases CO2 emissions and causes environmental degradation in BRI countries. However, renewable energy and globalization mitigate CO2 emissions and improve the quality of the environment. Institutional quality was positive in correlation with CO2 emission and indicates bad governance, corruption, weak bureaucracy, and improper implementation of environmental laws cause environmental degradation. Further, the study also reports a bidirectional relationship of financial development, renewable energy, and institutional quality with CO2 emissions and a unidirectional causality running from globalization to CO2 emissions in BRI countries. This study offers policymakers insight into restructuring the financial system, energy consumption pattern, and global integration and improving institutions' quality for a sustainable environment and the economy at the national and regional levels.

The dynamic impact of financial, technological, and natural resources on sustainable development in Belt and Road countries.

This study attempts to determine the untapped factors that affect sustainable development in 64 Belt and Road Initiative (BRI) countries from 2006 to 2019. The study employed the two-step system Generalized Method of Moments (GMM) validated through Two-stage Least Square (2SLS). The findings of system-GMM revealed a significant dynamic nature of the relationship between sustainable development and its determinants. Findings demonstrate that financial development, financial inclusion, energy efficiency ratio, per capita health expenditure, per capita income growth, governance, and integration of before and after BRI dummy show a significant positive impact by contributing to BRI countries' sustainable development path. However, e-government, natural resource rent, macroeconomic conditions, and government size have a significant but negative effect by hurting sustainable development. Integration of BRI further enhances and promotes a country and regional sustainable development path. Therefore, better regional policies for financial development, financial inclusion for poverty alleviation, and e-government development are required, boosting per-capita income and sustainable development in the coming years. The study concludes that BRI country's natural resources rent contributes to national saving but declines the natural resources. Also, it endorses the theory that a nation should adopt the "Hartwick rule" to reinvest rents from the depletion of the natural resources in reproducible capital forms to shift from a weak sustainable path. This study also proposes significant policy implications for balanced and sustainable growth in light of the current research findings.

COVID-19 pandemic control and administrative issues in Pakistan: How Pakistan mitigated both pandemic and administration issues?

COVID-19 is wreaking havoc all around the globe, and Pakistan bears no exception. This study explores Pakistan's response toward controlling COVID-19 Pandemic from the day the 1st case was reported, February 26, 2020, in Pakistan until August 31, 2020. It explores the administrative conflicts among federal and provincial governments and political behaviors of political parties toward the COVID-19 pandemic by referring Government Response Index. By applying the ARDL model approach, results show that since the administrative harmony had been implemented in Pakistan in July 2020, its positive impact on combating the COVID-19 situation in Pakistan and substantial improvement in recovered cases and a downward trend new confirmed and fatal cases has observed in Pakistan. The findings demonstrate that administrative efforts scattered due to internal conflicts from February to mid-July 2020 have ended, and collective aggressive policy enforcement has been mitigating the adverse impact of COVID-19 in Pakistan since July to date. However, sustainable measures and prudent policy implications are needed to combat the ongoing COVID-19 pandemic and future calamities.

Does regional integration matter for sustainable economic growth? Fostering the role of FDI, trade openness, IT exports, and capital formation in BRI countries.

IT exports, capital formation, FDI, and trade openness are the key elements to bring sustainable economic growth to any country, since these act as a lifeline to bring sustainability to countries. This study aims to estimate the impact of IT exports, gross capital formation, FDI, and trade openness on sustainable economic growth with regional integration of BRI countries using the annual panel data from 2013 to 2018. Moderating variable is regional integration, while the trade freedom index, investment freedom index, real interest rate, and inflation are control variables. The two-step system GMM technique is applied to the sample as the number of moment conditions is greater than the number of parameters. The results suggest that FDI and gross capital formation have a substantial positive impact on economic growth, whereas IT exports and trade openness have a negative, insignificant impact. The overall results suggest that China's outward FDI has boosted the economic growth in countries while trade openness has a negligible since most developing countries need to invest in industrialization and encourage exports based growth.