Fine particulate matter from brick kilns site and roadside in Lahore, Pakistan: Insight into chemical composition, oxidative potential, and health risk assessment.

Background: Human health is seriously threatened by particulate matter (PM) pollution, which is a major environmental problem. A better indicator of biological responses to PM exposure than its mass alone is the PM "oxidative potential (OP)," or ability to oxidize target molecules. When reactive oxygen species (ROS) are generated in the OP in excess of the antioxidant capacity of body due to PM components such metals and organic species, it causes inflammation, deoxyribonucleic acid (DNA), proteins, and lipids damage. Method: The samples of fine particulate matter (PM2.5) are collected from the brick kiln site and the roadside in Lahore, Pakistan. The organic carbon (OC) and elemental carbon (EC) were estimated by carbon analyzer (DRI 2001A) using the thermal/optical transmittance (TOT) protocol. The water-soluble organic carbon (WSOC) concentration was determined using a total organic carbon analyzer (Shimadzu TOC-L CPN). Ion chromatography (Dionex ICS-900) with a conductivity detector was used to analyze the water-soluble anions (Cl-, NO3-, and SO42-) and cations (NH4+, Na+, K+, Mg2+, and Ca2+). Inductively coupled plasma-mass spectrometry (iCAP TQ ICP-MS, Thermo Scientific) was used to determine the concentrations of metals in the solution. The dithiothreitol (DTT) consumption rate was calculated using a spectrophotometer at a wavelength of 412 nm. Results: The mean concentrations of PM2.5 at the brick kiln site and roadside reported are 509.3 ± 32.3 µg/m3 and 467.5 ± 24.9 µg/m3, and the average OC/EC ratio is 1.9 ± 0.4 and 2.1 ± 0.1. primary organic carbon (POC) contributed more to OC than secondary organic carbon (SOC), which indicated the dominance of primary combustion sources. The anion equivalent (AE) to cation equivalent (CE) ratio indicated that PM2.5 is acidic at both sites due to the dominance of NO3- and SO42-. The DTT consumption rate normalized by PM2.5 mass (DTTm) and DTT consumption rate normalized by air volume (DTTv) of PM2.5 at the roadside samples are higher than at the brick kiln site due to the higher contribution of ionic species to the mass of PM2.5. Carbonaceous species of PM2.5 at both sampling sites are significantly correlated with DTTv of PM2.5, while metallic species behaved differently. The incremental lifetime cancer risk (ILCR) values (lung cancer) of As and Cr at both sampling sites, while the ILCR value of Cd at the roadside samples is exceeding the permissible limits for adults and children. The lifetime average daily dose (LADD) value for adults is higher than that for children, indicating that children are less vulnerable to metals. Conclusion: The concentration of PM2.5 at both sampling sites were exceeding the permissible limits of Pakistan' National Environmental Quality Standard (NEQS) and posing risk to the health of the local population. The POC and SOC contribution to OC at the brick kiln site and roadside in Lahore were 84.6%, 15.4% and 84.4%, 15.6%. POC at both sampling sites were the dominant carbon species indicating the dominance of primary combustion sources. The residence of Lahore poses the lung cancer risk due to Cr, As, and Cd at both sampling sites. The results of this study provide important data and evidence for further evaluation of the potential health risks of PM2.5 from brick kiln site and road side in Pakistan and formulation of efficient air-pollution control measures.

Formation of morpholine-acetamide derivatives as potent anti-tumor drug candidates: Pharmacological evaluation and molecular docking studies.

Heterocyclic amines and acetamide derivatives are known for their chemotherapeutic potential. Hence, in the present study, morpholine was taken as a principal product and novel morpholine derivatives were designed, formulated, characterized, and screened for the mechanism of inhibition of carbonic anhydrase and their anticancer potential. In addition, in vitro inhibition of hypoxia-inducible factor-1 (HIF-1) protein was also investigated. Results revealed that compounds 1c, 1d, and 1h possessed significant inhibitory activities against carbonic anhydrase with IC50 of 8.80, 11.13, and 8.12 µM, respectively. Interestingly, the carbonic anhydrase inhibitory activity of compound 1h was comparable with that of standard acetazolamide (IC50 7.51 µM). The compounds 1h and 1i significantly inhibited the proliferation of ovarian cancer cell line ID8 with IC50 of 9.40, and 11.2 µM, respectively while the standard cisplatin exhibited an IC50 8.50 µM. In addition, compounds 1c, 1b, 1h and 1i also exhibited significant inhibitory effects on HIF-1α. In conclusion, we report first time the biological potential of morpholine based compounds against ovarian cancer and HIF-1α that may serve as lead molecules for drug discovery.

Geraniol Suppresses Oxidative Stress, Inflammation, and Interstitial Collagenase to Protect against Inflammatory Arthritis.

Geraniol (GER) is a plant-derived acyclic isoprenoid monoterpene that has displayed anti-inflammatory effects in numerous in vivo and in vitro models. This study was therefore designed to evaluate the antiarthritic potential of GER in complete Freund's adjuvant (CFA)-induced inflammatory arthritis (IA) model in rats. IA was induced by intraplantar injection of CFA (0.1 mL), and a week after CFA administration, rats were treated with various doses of methotrexate (MTX; 1 mg/kg) or GER (25, 50, and 100 mg/kg). Treatments were given on every alternate day, and animals were sacrificed on the 35th day. Paw volume, histopathological, hematological, radiographic, and qPCR analyses were performed to analyze the severity of the disease. GER significantly reduced paw edema after 35 days of treatment, and these results were comparable to the MTX-treated group. GER-treated animals displayed a perfect joint structure with minimal inflammation and no signs of cartilage or bone damage. Moreover, GER restored red blood cell and hemoglobin levels, normalized erythrocyte sedimentation rate, platelet, and c-reactive protein values, and also attenuated the levels of rheumatoid factor. RT-qPCR analysis demonstrated that GER decreased mRNA expression of pro-inflammatory cytokines like tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta. GER also down-regulated the transcript levels of cyclooxygenase-2 (COX-2), microsomal prostaglandin E synthase-1, prostaglandin D2 synthase, and interstitial collagenase (MMP-1). Molecular docking of GER with COX-2, TNF-α, and MMP-1 also revealed that the antiarthritic effects of GER could be due to its direct interactions with these mediators. Based on our findings, it is conceivable that the antiarthritic effects of GER could be attributed to downregulation of pro-inflammatory mediators and protease like MMP-1.

Long-term clinical efficacy and safety of thalidomide in patients with transfusion-dependent ß-thalassemia: results from Thal-Thalido study.

Regular blood transfusion is the mainstay of treatment in transfusion-dependent ß-thalassemia (TDT); however, transfusions culminate in an array of serious complications. Therefore, a single-arm, non-randomized clinical trial was conducted in hydroxyurea refractory TDT patients to explore the long-term safety and efficacy of thalidomide. The primary outcomes for efficacy were rise in hemoglobin (Hb) level and changes in transfusion frequency. Whereas, several clinical and laboratory parameters were assessed for safety of thalidomide. Secondary outcomes included changes in serum ferritin, serum lactate dehydrogenase (LDH), serum uric acid, red blood cell indices, and size of liver and spleen. A total of 532 patients were followed for a period of 30 months. Significant increase in mean Hb level was identified at 6 months (1.4 g/dL, p ≤ 0.001) and 30 months (2 g/dL, p ≤ 0.001) in comparison with baseline. A total of 408 (76.7%) patients responded to thalidomide therapy (excellent responders 25.8%, good responders 31%, and partial responders 19.9%) and attained transfusion independence within 6 months of therapy. A significant decline in mean ferritin, LDH level, liver size, and spleen size was observed. No unfavorable effects were observed on kidney and liver functions. Mild adverse events were reported in 48 (9%) patients and serious adverse events, including cerebral vascular accident and portal vein thrombosis were reported in two patients each. This study concludes that thalidomide is an effective and well-tolerated drug that can improve Hb levels and reduce transfusion burden in hydroxyurea refractory TDT patients.Trial registration: This trial is registered at http://www.clinicaltrial.gov as # NCT03651102.

Cardioprotective effect of 2-methoxy phenol derivatives against oxidative stress-induced vascular complications: An integrated in vitro, in silico, and in vivo investigation.

BACKGROUND: Oxidative stress and inflammation play crucial roles in macro/microvascular complications. Phenolic compounds and their derivatives show promise as therapeutic agents for diseases like cancer, metabolic disorders, and cardiovascular diseases. With their antioxidant and anti-inflammatory properties, these compounds hold potential for mitigating vascular complications and improving overall health. METHODOLOGY: This study aimed to assess the therapeutic potential of five 2-methoxy phenol derivatives (T2, T5, T6, T7, and T8) as antioxidants, anti-inflammatory agents, and vasorelaxants using in vitro, in silico, and in vivo approaches. RESULTS: Among all, T2 exhibited substantial antioxidant potential against 2, 2-diphenyl-1-picrylhydrazyl (DPPH) radicals with IC50 (27.97 µg/mL), nitric oxide (NO) radicals (IC50 = 34.36 µg/mL), hydroxyl (OH) radicals (IC50 = 34.83 µg/mL) and Iron chelation (IC50 = 24.32 µg/mL). Molecular docking analysis confirms that all derivatives, particularly T2, exhibit favorable binding energies with the target proteins, ACE (-7.7 Kcal/mol), ECE-1 (-7.9 Kcal/mol), and COX-1 (-7.8 Kcal/mol). All of the compounds demonstrated satisfactory physicochemical and pharmacokinetic characteristics, and showed minimal to no toxicity during in silico, in vitro, and in vivo assessments. In isolated aortic rings from Sprague Dawley rats, pre-contracted with high K+ (80 mM), T2 induced vasorelaxation in dose dependent manner and shifted calcium response curves to the right as compared to verapamil. T2 also showed substantial platelet aggregation inhibition in a dose dependent manner with IC50 21.29 µM. All derivatives except T7 exhibited significant conservation of endogenous antioxidants i.e. catalase (CAT), peroxidase (POD), superoxide dismutase (SOD) and reduced glutathione (GSH) and significantly suppressed serum levels of inflammatory markers i.e. nitric oxide (NO), peroxides (TBARS), interleukin-6 (IL-6) and cyclooxygenase-2 (COX-2). CONCLUSION: The study concludes that T2 has significant antioxidant potential and vasorelaxant effects with adequate pharmacokinetics, making it a promising lead compound for further molecular investigation in cardiovascular disorders.

Exploring the Students' Perceived Effectiveness of Online Education during the COVID-19 Pandemic: Empirical Analysis Using Structural Equation Modeling (SEM).

The world faced COVID-19, which was a threat to public health and disturbed the educational system and economic stability. Educational institutes were closed for a longer period, and students faced difficulty to complete their syllabus. The government adopted a policy of "suspending classes without stopping learning" to continue education activities. However, student satisfaction with online education is a growing concern. Satisfaction of students is an important indicator of academic quality. Therefore, this study attempts to investigate the influencing factors behind learning satisfaction using information from 335 students from various institutes in Pakistan. This research examined the impact of computer and internet knowledge, instructor and course material, and Learning Management Systems (LMS) on learning satisfaction. The path coefficients were obtained via Partial Least Square-Structural Equation Modeling (PLS-SEM). The LMS is a tool that facilitates the learning process with the provision of all types of educational material. The path coefficient was more in the case of LMS (0.489), which indicates its positive and significant role to attain learning satisfaction. The instructor and course material ordered second (0.261), which shows that the quality of an instructor and course material also plays a positive role to attain learning satisfaction. The computer and internet are essential ingredients of online education, showing a significant and positive path coefficient (0.123), implying that computer and internet knowledge could enhance learning satisfaction. The universities should develop their LMS to implement online education with quality course materials. It is also vital that the instructor should be up to date with modern learning techniques while ensuring internet connectivity, especially in rural areas. The government should provide an internet connection to students at discounted rates.

Aloe vera-Based Polymeric Network: A Promising Approach for Sustained Drug Delivery, Development, Characterization, and In Vitro Evaluation.

The present study was conducted to fabricate and characterize mucilage-based polymeric networks of Aloe vera for controlled drug release. Aloe vera mucilage was used to develop a polymeric network via the free-radical polymerization method using potassium persulphate as the initiator, N' N'-Methylene bisacrylamide as the crosslinker, and acrylamide as the monomer. Using varying concentrations of Aloe vera mucilage, crosslinker, and monomer, we developed different formulations. Swelling studies were conducted at pH 1.2 and 7.4. Concentrations of polymer, monomer, and crosslinker were optimized as a function of swelling. Porosity and gel content were calculated for all samples. FTIR, SEM, XRD, TGA, and DSC studies were conducted for the characterization of polymeric networks. Thiocolchicoside was used as a model drug to study the in vitro release in acidic and alkaline pH. Various kinetics models were applied by using a DD solver. Increasing content of monomer and crosslinker swelling, porosity, and drug release decreased while gel content increased. An increase in Aloe vera mucilage concentration promotes swelling, porosity, and drug release of the polymeric network but decreases gel content. The FTIR study confirmed the formation of crosslinked networks. SEM indicated that the polymeric network had a porous structure. DSC and XRD studies indicated the entrapment of drugs inside the polymeric networks in amorphous form. The analytical method was validated according to ICH guidelines in terms of linearity, range, LOD, LOQ, accuracy, precision, and robustness. Analysis of drug release mechanism revealed Fickian behavior of all formulations. All these results indicated that the M1 formulation was considered to be the best polymeric network formulation in terms of sustaining drug release patterns.

Antibacterial Potential of Novel Acetamide Derivatives of 2-Mercaptobenzothiazole: Synthesis and Docking Studies.

2-Mercaptobenzothiazole and its derivatives are widely known for their diverse biological activities, particularly antimicrobial and anticancer potential. In the present study, a series of new hybrid compounds consisting of 2-mercaptobenzothiazole and different aryl amines 2(a-j) were synthesized and characterized by Fourier transform infrared (FTIR), 1H NMR, and 13C NMR spectral data. The synthesized compounds were screened for in vitro antibacterial activities through agar well diffusion assay. Among the series, 2b, 2c, and 2i exhibited significant antibacterial activity comparable to the standard drug levofloxacin. Based on their antibacterial potential, these compounds were further tested for their antibiofilm activity. All of the three compounds showed promising antibiofilm potential, even better than the standard drug cefadroxil at 100 µg/100 µL concentration. Molecular docking studies were performed to explore the antibacterial mechanism of these compounds. Strikingly, the molecule 2i shared the same hydrophobic pockets as those of levofloxacin in case of bacterial kinases and DNA gyrases. In addition, 2i exhibited satisfactory antibiofilm activity in comparison to the standard. Our study therefore suggested that the synthetic compound 2i possesses remarkable antibacterial activity and may serve as a lead molecule for the discovery of potent antibacterial agents.

Do natural disasters affect economic growth? The role of human capital, foreign direct investment, and infrastructure dynamics.

Natural disasters do occur and have become a global problem due to increasing intensity. Developing countries are mostly affected due to natural disasters owing to a poor environment, feeble adaptation, impoverished socioeconomic conditions, poor infrastructure, limited resources, and unstable institutions. The SDG 11.5 target which highlights the mitigation of loss due to natural disasters--remains crucial to achieving sustainable cities and human settlements--but the literature is limited on this scope. Thus, this research contributes to the literature by incorporating an infrastructure index, foreign direct investment (FDI), human capital index, globalization, and capital formation into the disaster-growth debate across four-income groups in 98 countries from 1995 to 2019. We developed infrastructure and human capital indices using a standard procedure across all income groups. The two-step generalized method of moments employed herein confirmed the income reduction effect of natural disasters. While the economic cost of natural disasters is relatively high in low-income countries and mild in high- and upper-middle-income countries. Besides, infrastructural development, FDI, human capital, globalization, and gross fixed capital formation also affect economic growth across income groups. Thus, the enhancement of socio-economic policies could decline economic losses, especially in vulnerable and poor settlements in developing countries.

Personal protective equipment (PPE) disposal during COVID-19: An emerging source of microplastic and microfiber pollution in the environment.

Waste generated by healthcare facilities during the COVID-19 pandemic has become a new source of pollution, particularly with the widespread use of single-use personal protective equipment (PPE). Releasing microplastics (MPs) and microfibers (MFs) from discarded PPE becomes an emerging threat to environmental sustainability. MPs/MFs have recently been reported in a variety of aquatic and terrestrial ecosystems, including water, deep-sea sediments, air, and soil. As COVID-19 spreads, the use of plastic-made PPE in healthcare facilities has increased significantly worldwide, resulting in massive amounts of plastic waste entering the terrestrial and marine environments. High loads of MPs/MFs emitted into the environment due to excessive PPE consumption are easily consumed by aquatic organisms, disrupting the food chain, and potentially causing chronic health problems in humans. Thus, proper management of PPE waste is critical for ensuring a post-COVID sustainable environment, which has recently attracted the attention of the scientific community. The current study aims to review the global consumption and sustainable management of discarded PPE in the context of COVID-19. The severe impacts of PPE-emitted MPs/MFs on human health and other environmental segments are briefly addressed. Despite extensive research progress in the area, many questions about MP/MF contamination in the context of COVID-19 remain unanswered. Therefore, in response to the post-COVID environmental remediation concerns, future research directions and recommendations are highlighted considering the current MP/MF research progress from COVID-related PPE waste.

Exploring Therapeutic Potential of 1,3,4-Oxadiazole Nucleus as Anticancer Agents: A Mini-review.

Cancer is an uncontrolled, abnormal growth of cells and the second cause of death after cardiovascular disease. At present, chemotherapy and related drugs have three major categories. All three have characteristic action and toxicity levels of antitumor activity. Due to indications of unwanted side effects, the exploration of novel and selective anticancer agents is crucially required. Heterocyclic compounds have always played a major role in research for new drug discovery and development. 1,3,4-oxadiazole derivatives are heterocyclic isomers having pharmacological properties and play an important role as antiproliferative agents. The present review summarizes anticancer activities of 1,3,4-oxadiazole derivatives against different cell lines, such as HCT-116, MCF-7, HeLa, SMMC-7721, and A549. The results showed that 1,3,4-oxadiazole and its derivatives have the potential to play a major role as an anticancer agent with fewer side effects.

Estimation of economic, environmental, and social efficiency for sustainable development in G-8 and SAARC countries: a data envelopment analysis.

In the recent era, economic growth is not enough to represent sustainable development. Sustainable development has three dimensions (i.e., economic, social, and environment). This study estimated the economic, social, and environmental efficiency using data from 2000 to 2021. Input-oriented data envelopment analysis shows strong heterogeneity across developed (G-8) and developing countries (SAARC). There is a potential to increase economic and environmental efficiency in the G-8 and SAARC countries. The average economic efficiencies are 0.682 and 0.414, which implies the possibility of the same output (GDP/capita) by using 31.8% and 58.6% fewer inputs in G-8 and SAARC countries, respectively. The social efficiency score is more than 0.980 in both panels. The average environmental efficiencies are 0.712 and 0.724, which implies that selected countries can obtain the same output (CO2 emission reduction) by using 28.8% and 27.6% fewer inputs in G-8 and SAARC countries, respectively. The top three economically efficient countries are (a) the USA, the UK, and Japan in the G-8 panel and (b) Maldives, Sri Lanka, and Pakistan in the SAARC panel. The top three environmentally efficient countries are (a) France, the UK, and Italy in the G-8 panel and (b) Afghanistan, Nepal, and Bangladesh in the SAARC panel. It is recommended to adopt suitable policies to reduce emission, minimize waste, efficient utilization of resources, increase forest cover, and incentive for clean technologies. It is suggested to promote renewable energy through the provision of micro-credit to the poor, subsidizing renewable energy technologies, implementation of stringent environmental policies, and increasing awareness. It is essential to invest in eco-friendly and innovative technologies; thus, the government should encourage green practices in production. Human development is recommended to increase the living standard and healthy life. The government should invest in the health system and conduct seminars on general health awareness. Investment in basic infrastructure (drinking water, sanitation, and clean fuel) is essential to increase the living standard. The G-8 countries should provide financial and technological help to the SAARC countries.

Amino Acid Conjugates of 2-Mercaptobenzimidazole Ameliorates High-Fat Diet-Induced Hyperlipidemia in Rats via Attenuation of HMGCR, APOB, and PCSK9.

PURPOSE: This study was designed to explore the antihyperlipidemic effects of amino acid derivatives of 2-mercaptobenzimidazole (4J and 4K) in high-fat diet (HFD)-fed rats. METHODS: Male Sprague-Dawley rats were divided into nine groups which received either standard diet or HFD for 28 days. Blood samples were taken on 27th day from HFD-fed rats to ensure hyperlipidemia. HFD-induced hyperlipidemic rats later received daily dosing of either vehicle or simvastatin (SIM; 20 mg/kg) or 4J/4K compounds (10, 20, and 30 mg/kg) for 12 consecutive days. On 40th day, animals were sacrificed, and blood samples were collected for the determination of serum lipid profile and liver function parameters. Liver samples were harvested for histopathological, antioxidant, and qPCR analyses. Molecular docking of tested compounds with HMGCR was also performed to assess the binding affinities. RESULTS: 4J and 4K dose dependently decreased serum total cholesterol, triglycerides, low-density lipoprotein, very low-density lipoproteins, alanine transaminase (ALT), and aspartate aminotransferase (AST) levels while significantly alleviated high-density lipoproteins. However, SIM failed to reduce AST and ALT levels. Moreover, tested compounds displayed antioxidant effects by inducing superoxide dismutase and glutathione levels. Histopathology data also displayed protective effects of 4J and 4K against HFD-induced fatty changes and hepatic damage. In addition, 4J and 4K downregulated transcript levels of HMGCR, APOB, PCSK9, and VCAM1, and molecular docking analysis also supported the experimental data. CONCLUSION: It is conceivable from this study that 4J and 4K exert their antihyperlipidemic effects by modulating multiple targets regulating lipid levels.

Ajuga bracteosa Exerts Antihypertensive Activity in l-NAME-Induced Hypertension Possibly through Modulation of Oxidative Stress, Proinflammatory Cytokines, and the Nitric Oxide/Cyclic Guanosine Monophosphate Pathway.

Ajuga bracteosa has been used in traditional medicine to treat hypertension and other ailments. The present study has been designed to investigate the beneficial effects of A. bracteosa in l-nitro arginine methyl ester (l-NAME)-induced hypertensive rats. Hypertension was induced by intraperitoneal injection of l-NAME (185 µmol kg-1 i.p.). The aqueous methanol extract of A. bracteosa (AMEAB, 250 and 500 mg kg-1) and coumarin (30 and 70 mg kg-1) were administered orally from day 8 to day 35 of the study. In vivo antihypertensive activity was assessed by measuring the blood pressure using a PowerLab data system. The effects of the AMEAB and coumarin on nitric oxide (NO), cyclic guanosine monophosphate (cGMP), interleukin-6 (IL-6), the tumor necrosis factor (TNF-α), and oxidative stress markers were also assessed using kit methods. Phytochemical profiling of the AMEAB was carried out through high-performance liquid chromatography (HPLC) where quercetin, gallic acid, caffeic acid, vanillic acid, benzoic acid, syringic acid, p-coumaric acid, and ferulic acid were labeled as plant constituents including coumarin. The AMEAB and coumarin significantly reduced blood pressure at the tested doses of 500 and 70 mg kg-1, respectively. Serum levels of NO and cGMP were found to be significantly increased in AMEAB- and coumarin-treated groups when compared with only l-NAME-challenged rats. In addition, a marked decrease was noticed in the serum concentrations of proinflammatory cytokines (IL-6 and TNF-α) in AMEAB- and coumarin-treated rats. Moreover, in AMEAB- and coumarin-treated animals, a noticeable improvement was observed in the levels of antioxidant enzymes including catalase, superoxide dismutase, and malonaldehyde, and the total oxidant status when compared with those of only l-NAME-challenged rats. The data of real-time polymerase chain reaction (RT-PCR) experiments supported that the antihypertensive and anti-inflammatory activities of the AMEAB and coumarin are possibly mediated through modulation of endothelial nitric oxide synthase (eNOS), angiotensin-converting enzyme (ACE), nuclear factor (NF)-kB, and COX-2 gene expressions. This study concludes that A. bracteosa possesses an antihypertensive effect mediated through the modulation of the antioxidant, anti-inflammatory, and NO/cGMP pathways, thus providing a rationale to the antihypertensive use of A. bracteosa in traditional medicine.

Novel acetamide derivatives of 2-aminobenzimidazole prevent inflammatory arthritis in rats via suppression of pro-inflammatory mediators.

Benzimidazole ring system is an important pharmacophore with diverse pharmacological activities. In this study, we explored the anti-arthritic effects of newly synthesized acetamide derivatives of 2-aminobenzimidazole (N1 and N2) in rats. FTIR and NMR spectroscopies were used to characterize these compounds. Carrageenan (CRG) induced paw edema model was used to test the acute anti-inflammatory activity of various doses (10, 20 and 30 mg/kg) of N1 and N2 compounds. Based on acute anti-inflammatory effects, the most potent dose of each compound was selected and investigated in complete freund's adjuvant (CFA) induced inflammatory arthritis (RA) model (n = 4 in each group). Histopathological, hematological, radiographic, and RT-qPCR analyses were performed to assess the progression or resolution of inflammatory arthritis. The tested compounds produced a dose-dependent anti-inflammatory activity against CRG induced paw inflammation and similarly reduced edema in CFA induced inflammatory arthritis model. Histopathological and X-ray analyses of ankle joints revealed minimal inflammation and normal joint structures in N1 and N2 treated groups. The tested compounds also reduced the levels of autoantibodies and restored hematological parameters. Interestingly, the tested compounds did not elevate aspartate aminotransferase and alanine transaminase levels and displayed a better safety profile than methotrexate. N1 and N2 compounds also attenuated the transcript levels of IRAK1, NF-kB1, TNF-α, IL-1ß, IL17 and MMP1. In addition, N1 displayed a greater inhibition of mRNA levels of COX1, COX2, mPGES1 and PTGDS as compared to N2. Our findings demonstrate that N1 and N2 compounds possess strong anti-arthritic activity which can be attributed to the suppression of pro-inflammatory mediators.

The role of infrastructure, socio-economic development, and food security to mitigate the loss of natural disasters.

This study shows the impact of risk (hazard, exposure, and vulnerability) and resilience (infrastructure, information and communication technology, institutional quality, food security, women empowerment, economic performance, human capital, emergency workforce, and social capital) indicators on losses due to natural disasters in 24 high-income, 24 upper-middle-income, 30 lower-middle-income, and 12 low-income countries from 1995 to 2019. It develops a new disaster risk index and disaster resilience index using standard index-making procedure (indicators selection, winsorization, normalization, aggregation). The generalized additive modeling was used to explore the non-linear relationship between response and explanatory variables. There exists a positive link between damage due to natural disasters and hazard index (all panels) and exposure index in high-income countries. The decrease in damage due to natural disasters was observed due to an increase in infrastructure (upper-middle-, lower-middle-, and low-income countries), information and communication technology (high-income countries), institutional quality (high-income countries), food security (high- and upper-middle-income countries), women empowerment (lower-middle-income countries), economic performance (high- and low-income countries), human capital (low-income countries), and emergency workforce (upper-middle and lower-middle-income countries). The governments should enhance disaster resilience through Sendai Framework, having seven targets and four priority areas to increase disaster resilience.

Synthesis and evaluation of Ca-doped ferrihydrite as a novel adsorbent for the efficient removal of fluoride.

Ferric hydrate has been extensively applied for the removal of various types of pollutants from wastewater because of its low cost and high efficiency. However, its wide-scale application has been greatly restricted by high-dose and low-adsorption capacity. Therefore, a novel Ca-doped ferrihydrite adsorbent has been synthesized and used for the enhanced removal of fluoride from wastewater in the presence of other co-existing ions. At 5 mg/L initial fluoride concentration and pH 5, the removal efficiency of fluoride approached to 97.5% and remained stable. Similarly, with the increase of dose from 100 to 300 mg/L, the fluoride removal linearly increased to 98% and remained plateau at neutral pH. Also, the presence of co-existing ions such as NO3-, SO42-, Cl-, and natural organic matter has not significantly influenced the removal performance of the adsorbent. Fluoride removal best fit the pseudo-second-order reaction kinetics and Langmuir isotherm model. The prepared adsorbent exhibited a maximum adsorption capacity of 53.21 mg/g for fluoride uptake from water. The SEM-EDX confirmed the doping of Ca onto the ferrihydrite where the elemental peaks of Ca and Fe emerged at the energy value of about 3.6 Kev and 7.1 Kev respectively in EDX analysis. In addition, SEM results of Ca-doped ferrihydrite adsorbent illustrated that a large microplates type of products was acquired after synthesis. The regeneration results confirmed that adsorbent could retain their original adsorption capacity after five regeneration cycles. The current study suggested that Ca-doped ferrihydrite has the application potential for the enhanced adsorption of fluoride from the water phase.

Removal of pharmaceuticals from water using sewage sludge-derived biochar: A review.

In recent years, considerable attention has been paid to the beneficial utilization of sewage sludge to reduce the risks associated with sludge disposal. Besides other applications of sludge, biochar produced from sludge has also been employed for the elimination of various pollutants from water. This review critically evaluates the recent progress in applications of sludge-based biochar for the adsorption of pharmaceuticals from water. The synthesis techniques of biochar production from sludge and their effects on physicochemical characteristics of produced biochar are discussed. The removal of various pharmaceuticals by sludge-based biochar are described in detail, with the emphasis on the adsorption mechanism and their reusability potential. It is evident from the literature that sludge-based biochar has demonstrated excellent potential for the adsorption of numerous pharmaceuticals from the aqueous phase. The major hurdles and issues related to the synthesis of sludge-based biochar and applications are highlighted, with reference to the adsorption of pharmaceuticals. Finally, a roadmap is suggested along with future research directions to ensure the sustainable production of biochar from sludge and its applications in water treatment.

Ameliorative Effect of Structurally Divergent Oleanane Triterpenoid, 3-Epifriedelinol from Ipomoea batatas against BPA-Induced Gonadotoxicity by Targeting PARP and NF-κB Signaling in Rats.

The pentacyclic triterpenoids (PTs) of plant origin are reputed to restrain prostate cancer (PCa) cell proliferation. This study aims to assess 3-epifriedelinol (EFD) isolated from aerial part of Ipomoea batatas against PCa and its potential mechanism, in vitro and in vivo. Molecular docking affirms good binding affinity of the compound with target proteins exhibiting binding energy of −7.9 Kcal/mol with BAX, −8.1 Kcal/mol (BCL-2), −1.9 Kcal/mol (NF-κB) and −8.5 Kcal/mol with P53. In the MTT assay, EFD treatment (3−50 µM) showed a significant (p < 0.05 and p < 0.01) dose and time dependent drop in the proliferative graph of DU145 and PC3, and an upsurge in apoptotic cell population. EFD displayed substantial IC50 against DU145 (32.32 ± 3.72 µM) and PC3 (35.22 ± 3.47 µM). According to Western blots, EFD administration significantly enhanced the cleavage of caspases and PARP, elevated BAX and P53 and decreased BCL-2 and NF-κB expression, thereby triggering apoptosis in PCa cells. When male Sprague Dawley rats were intoxicated with Bisphenol A (BPA), an apparent increase in prostate mass (0.478 ± 0.08 g) in comparison to control (0.385 ± 0.03 g) indicates prostatitis. Multidose treatment of EFD (10 mg/kg) significantly reduced prostate size (0.404 ± 0.05 g). EFD exhibited substantial curative potential in vivo, as hematological, hormonal and histopathological parameters have been significantly improved. Reduced peroxidation (TBARS), and suppression of inflammatory markers i.e., NO, IL-6 and TNF-α, signposts substantial antiinflammatory potential of the compound. Overall, EFD has shown better binding affinity with target molecules, acceptable ADMET profile, potent antiproliferative and apoptotic nature and significant reduction in inflamed prostate mass of rats. The present study demonstrates acceptable physicochemical and pharmacokinetic properties of the compound with excellent drugable nature, hence EFD in the form of standardized formulation can be developed as primary or adjuvant therapy against PCa and toxins-induced gonadotoxicity.

Biallelic inheritance in a single Pakistani family with intellectual disability implicates new candidate gene RDH14.

In a multi-branch family from Pakistan, individuals presenting with palmoplantar keratoderma segregate in autosomal dominant fashion, and individuals with intellectual disability (ID) segregate in apparent autosomal recessive fashion. Initial attempts to identify the ID locus using homozygosity-by-descent (HBD) mapping were unsuccessful. However, following an assumption of locus heterogeneity, a reiterative HBD approach in concert with whole exome sequencing (WES) was employed. We identified a known disease-linked mutation in the polymicrogyria gene, ADGRG1, in two affected members. In the remaining two (living) affected members, HBD mapping cross-referenced with WES data identified a single biallelic frameshifting variant in the gene encoding retinol dehydrogenase 14 (RDH14). Transcription data indicate that RDH14 is expressed in brain, but not in retina. Magnetic resonance imaging for the individuals with this RDH14 mutation show no signs of polymicrogyria, however cerebellar atrophy was a notable feature. RDH14 in HEK293 cells localized mainly in the nucleoplasm. Co-immunoprecipitation studies confirmed binding to the proton-activated chloride channel 1 (PACC1/TMEM206), which is greatly diminished by the mutation. Our studies suggest RDH14 as a candidate for autosomal recessive ID and cerebellar atrophy, implicating either disrupted retinoic acid signaling, or, through PACC1, disrupted chloride ion homeostasis in the brain as a putative disease mechanism.