Live imaging of SARS-CoV-2 infection in mice reveals that neutralizing antibodies require Fc function for optimal efficacy.

Neutralizing antibodies (NAbs) are effective in treating COVID-19, but the mechanism of immune protection is not fully understood. Here, we applied live bioluminescence imaging (BLI) to monitor the real-time effects of NAb treatment during prophylaxis and therapy of K18-hACE2 mice intranasally infected with SARS-CoV-2-nanoluciferase. Real-time imaging revealed that the virus spread sequentially from the nasal cavity to the lungs in mice and thereafter systemically to various organs including the brain, culminating in death. Highly potent NAbs from a COVID-19 convalescent subject prevented, and also effectively resolved, established infection when administered within three days. In addition to direct neutralization, depletion studies indicated that Fc effector interactions of NAbs with monocytes, neutrophils, and natural killer cells were required to effectively dampen inflammatory responses and limit immunopathology. Our study highlights that both Fab and Fc effector functions of NAbs are essential for optimal in vivo efficacy against SARS-CoV-2.

Proof-of-concept studies with a computationally designed Mpro inhibitor as a synergistic combination regimen alternative to Paxlovid.

As the SARS-CoV-2 virus continues to spread and mutate, it remains important to focus not only on preventing spread through vaccination but also on treating infection with direct-acting antivirals (DAA). The approval of Paxlovid, a SARS-CoV-2 main protease (Mpro) DAA, has been significant for treatment of patients. A limitation of this DAA, however, is that the antiviral component, nirmatrelvir, is rapidly metabolized and requires inclusion of a CYP450 3A4 metabolic inhibitor, ritonavir, to boost levels of the active drug. Serious drug-drug interactions can occur with Paxlovid for patients who are also taking other medications metabolized by CYP4503A4, particularly transplant or otherwise immunocompromised patients who are most at risk for SARS-CoV-2 infection and the development of severe symptoms. Developing an alternative antiviral with improved pharmacological properties is critical for treatment of these patients. By using a computational and structure-guided approach, we were able to optimize a 100 to 250 µM screening hit to a potent nanomolar inhibitor and lead compound, Mpro61. In this study, we further evaluate Mpro61 as a lead compound, starting with examination of its mode of binding to SARS-CoV-2 Mpro. In vitro pharmacological profiling established a lack of off-target effects, particularly CYP450 3A4 inhibition, as well as potential for synergy with the currently approved alternate antiviral, molnupiravir. Development and subsequent testing of a capsule formulation for oral dosing of Mpro61 in B6-K18-hACE2 mice demonstrated favorable pharmacological properties, efficacy, and synergy with molnupiravir, and complete recovery from subsequent challenge by SARS-CoV-2, establishing Mpro61 as a promising potential preclinical candidate.

Biosynthesis of nonnutritive monosaccharide d-allulose by metabolically engineered Escherichia coli from nutritive disaccharide sucrose.

Sucrose is a commonly utilized nutritive sweetener in food and beverages due to its abundance in nature and low production costs. However, excessive intake of sucrose increases the risk of metabolic disorders, including diabetes and obesity. Therefore, there is a growing demand for the development of nonnutritive sweeteners with almost no calories. d-Allulose is an ultra-low-calorie, rare six-carbon monosaccharide with high sweetness, making it an ideal alternative to sucrose. In this study, we developed a cell factory for d-allulose production from sucrose using Escherichia coli JM109 (DE3) as a chassis host. The genes cscA, cscB, cscK, alsE, and a6PP were co-expressed for the construction of the synthesis pathway. Then, the introduction of ptsG-F and knockout of ptsG, fruA, ptsI, and ptsH to reprogram sugar transport pathways resulted in an improvement in substrate utilization. Next, the carbon fluxes of the Embden-Meyerhof-Parnas and the pentose phosphate pathways were regulated by the inactivation of pfkA and zwf, achieving an increase in d-allulose titer and yield of 154.2% and 161.1%, respectively. Finally, scaled-up fermentation was performed in a 5 L fermenter. The titer of d-allulose reached 11.15 g/L, with a yield of 0.208 g/g on sucrose.

Genetic heterogeneity in epilepsy and comorbidities: insights from Pakistani families.

BACKGROUND: Epilepsy, a challenging neurological condition, is often present with comorbidities that significantly impact diagnosis and management. In the Pakistani population, where financial limitations and geographical challenges hinder access to advanced diagnostic methods, understanding the genetic underpinnings of epilepsy and its associated conditions becomes crucial. METHODS: This study investigated four distinct Pakistani families, each presenting with epilepsy and a spectrum of comorbidities, using a combination of whole exome sequencing (WES) and Sanger sequencing. The epileptic patients were prescribed multiple antiseizure medications (ASMs), yet their seizures persist, indicating the challenging nature of ASM-resistant epilepsy. RESULTS: Identified genetic variants contributed to a diverse range of clinical phenotypes. In the family 1, which presented with epilepsy, developmental delay (DD), sleep disturbance, and aggressive behavior, a homozygous splice site variant, c.1339-6 C > T, in the COL18A1 gene was detected. The family 2 exhibited epilepsy, intellectual disability (ID), DD, and anxiety phenotypes, a homozygous missense variant, c.344T > A (p. Val115Glu), in the UFSP2 gene was identified. In family 3, which displayed epilepsy, ataxia, ID, DD, and speech impediment, a novel homozygous frameshift variant, c.1926_1941del (p. Tyr643MetfsX2), in the ZFYVE26 gene was found. Lastly, family 4 was presented with epilepsy, ID, DD, deafness, drooling, speech impediment, hypotonia, and a weak cry. A homozygous missense variant, c.1208 C > A (p. Ala403Glu), in the ATP13A2 gene was identified. CONCLUSION: This study highlights the genetic heterogeneity in ASM-resistant epilepsy and comorbidities among Pakistani families, emphasizing the importance of genotype-phenotype correlation and the necessity for expanded genetic testing in complex clinical cases.

Investigating the genetic basis of hereditary spastic paraplegia and cerebellar Ataxia in Pakistani families.

BACKGROUND: Hereditary Spastic Paraplegias (HSPs) and Hereditary Cerebellar Ataxias (HCAs) are progressive neurodegenerative disorders encompassing a spectrum of neurogenetic conditions with significant overlaps of clinical features. Spastic ataxias are a group of conditions that have features of both cerebellar ataxia and spasticity, and these conditions are frequently clinically challenging to distinguish. Accurate genetic diagnosis is crucial but challenging, particularly in resource-limited settings. This study aims to investigate the genetic basis of HSPs and HCAs in Pakistani families. METHODS: Families from Khyber Pakhtunkhwa with at least two members showing HSP or HCA phenotypes, and who had not previously been analyzed genetically, were included. Families were referred for genetic analysis by local neurologists based on the proband's clinical features and signs of a potential genetic neurodegenerative disorder. Whole Exome Sequencing (WES) and Sanger sequencing were then used to identify and validate genetic variants, and to analyze variant segregation within families to determine inheritance patterns. The mean age of onset and standard deviation were calculated to assess variability among affected individuals, and the success rate was compared with literature reports using differences in proportions and Cohen's h. RESULTS: Pathogenic variants associated with these conditions were identified in five of eight families, segregating according to autosomal recessive inheritance. These variants included previously reported SACS c.2182 C > T, p.(Arg728*), FA2H c.159_176del, p.(Arg53_Ile58del) and SPG11 c.2146 C > T, p.(Gln716*) variants, and two previously unreported variants in SACS c.2229del, p.(Phe743Leufs*8) and ZFYVE26 c.1926_1941del, p.(Tyr643Metfs*2). Additionally, FA2H and SPG11 variants were found to have recurrent occurrences, suggesting a potential founder effect within the Pakistani population. Onset age among affected individuals ranged from 1 to 14 years (M = 6.23, SD = 3.96). The diagnostic success rate was 62.5%, with moderate effect sizes compared to previous studies. CONCLUSIONS: The findings of this study expand the genotypic and phenotypic spectrum of HSPs and HCAs in Pakistan and emphasize the importance of utilizing exome/genome sequencing for accurate diagnosis or support accurate differential diagnosis. This approach can improve genetic counseling and clinical management, addressing the challenges of diagnosing neurodegenerative disorders in resource-limited settings.

Systemic Treatment with Fas-Blocking Peptide Attenuates Apoptosis in Brain Ischemia.

Apoptosis plays a crucial role in neuronal injury, with substantial evidence implicating Fas-mediated cell death as a key factor in ischemic strokes. To address this, inhibition of Fas-signaling has emerged as a promising strategy in preventing neuronal cell death and alleviating brain ischemia. However, the challenge of overcoming the blood-brain barrier (BBB) hampers the effective delivery of therapeutic drugs to the central nervous system (CNS). In this study, we employed a 30 amino acid-long leptin peptide to facilitate BBB penetration. By conjugating the leptin peptide with a Fas-blocking peptide (FBP) using polyethylene glycol (PEG), we achieved specific accumulation in the Fas-expressing infarction region of the brain following systemic administration. Notably, administration in leptin receptor-deficient db/db mice demonstrated that leptin facilitated the delivery of FBP peptide. We found that the systemic administration of leptin-PEG-FBP effectively inhibited Fas-mediated apoptosis in the ischemic region, resulting in a significant reduction of neuronal cell death, decreased infarct volumes, and accelerated recovery. Importantly, neither leptin nor PEG-FBP influenced apoptotic signaling in brain ischemia. Here, we demonstrate that the systemic delivery of leptin-PEG-FBP presents a promising and viable strategy for treating cerebral ischemic stroke. Our approach not only highlights the therapeutic potential but also emphasizes the importance of overcoming BBB challenges to advance treatments for neurological disorders.

Ethnobotanical, ecological and health risk assessment of some selected wild medicinal plants collected along mafic and Ultra Mafic rocks of Northwest Pakistan.

The current study investigated wild plant resources and health risk assessment along with northern Pakistan's mafic and ultramafic regions. Ethnobotanical data was collected through field visits and semi-structured questionnaire surveys conducted from local inhabitants and healers. Six potentially toxic elements (PTEs) such as lead (Pb), cadmium (Cd), nickel (Ni), chromium (Cr), manganese (Mn), and zinc (Zn) were extracted with acids and analyzed using atomic absorption spectrophotometer (AAS, Perkin Elmer-7000) in nine selected wild medicinal plants. Contamination factor (CF), pollution load index (PLI), estimated daily intake (EDI), target hazard quotient (THQ), and hazard index (HI) were used to determine the health risk assessment of the studied medicinal plants. The results showed that the selected medicinal plants were used for the treatments of cough, joint swelling, cardiovascular disorders, toothaches, diabetes, and skin pimples by the local inhabitants due to their low-cost and easy accessibility. The concentrations of Pb (3.4-53 mg kg-1), Cd (0.03-0.39 mg kg-1), Ni (17.5-82 mg kg-1), Cr (29-315 mg kg-1), Mn (20-142 mg kg-1), and Zn (7.4-64 mg kg-1) in the studied medicinal plants were found above the safe limits (except Zn) set by WHO/FAO/USEPA (1984/2010). The Pb contamination factor was significantly (p < 0.05) higher in A. modesta (7.84) and D. viscosa (6.81), and Cd contamination factor was significantly higher in C. officinalis (26.67), followed by A. modesta (8.0) mg kg-1. Based on PTE concentrations, the studied plants are considered not suitable for human consumption purposes. Pollution load index values for A. modesta, A. barbadensis, A. caudatus, A. indica, C. procera (2.93), D. viscosa (2.79), and C. officinalis (2.83), R. hastatus (3.12), and Z. armatum were observed as 1.00, 2.80, 2.29, 2.29, 2.93, 2.79, 2.83, 3.12 and 2.19, respectively. Hazard index values were in order of R. hastatus (1.32 × 10-1) ˃ C. procera (1.21 × 10-1) ˃ D. viscosa (1.10 × 10-1) ˃ A. caudatus (9.11 × 10-2) ˃ A. barbadensis (8.66 × 10-2) ˃ Z. armatum (7.99 × 10-2) ˃ A. indica (6.87 × 10-2) ˃ A. modesta (5.6 × 10-2) ˃ C. officinalis (5.42 × 10-2). The health risk index values suggested that consumption of these plants individually or in combination would cause severe health problems in the consumers. Pearson's correlation results showed a significant correlation (p ≤ 0.001) between Zn and Mn in the studied medicinal plants. The current study suggests that wild medicinal plants should be adequately addressed for PTEs and other carcinogenic pollutants before their uses in the study area. Open dumping of mining waste should be banned and eco-friendly technology like organic amendments application should be used to mitigate PTEs in the study area.

The brown algae: Sargassum binderi sonder shows a potential nephroprotective activity in in-vivo experimental model.

OBJECTIVES: This study aimed to investigate the protective activity of brown seaweed, the ethanolic and water extracts of Sargassum binderi (S. binderi) were examined. Anticancer drug, cisplatin is normally used for the treatment of solid tumors that cause acute kidney damage after assemblage in the renal tubules. MATERIAL AND METHODS: It was an acute nephrotoxicity study, animals were divided into several groups randomly, cisplatin (7mg/kg i.p.) and normal saline were used as positive and negative control respectively. The S. bindari ethanolic and water extract were given orally in a dose of 200mg/kg for 5days. Various biomarkers were assessed to observe the nephroprotective potential, while antioxidant activities were investigated using reduced glutathione, catalase and malondialdehyde as oxidative stress. GCMS was performed to validate the presence of important therapeutic moieties. RESULTS: The current result justified that pretreatment with S. binderi inhibited the elevation of antioxidant parameters and also showed protection against lipid peroxidation, induced by cisplatin challenge. The overall impact was the nephroprotection, which has been revealed from the results. GCMS evaluation of hexanes fraction revealed the presence of therapeutically important compounds including heptasiloxane, 3,7,11,15-tetramethyl-2-hexadecen-1-ol, hexadecamethyl, cyclooctasiloxane, and hexadecamethyl. These compounds have been reported for their antioxidant, antibacterial, anticancer, and antifungal activities. CONCLUSION: S. binderi showed reno-protective effect by checking their well-known biochemical parameters probably due to the antioxidant activity as confirmed by the presence of compounds.

A Low-Acidity Chloride Electrolyte Enables Exceptional Reversibility and Stability in Aqueous Tin Metal Batteries.

Tin (Sn) metal has emerged as a promising anode for aqueous batteries, due to its high capacity, non-toxicity, and cost-effectiveness. However, Sn metal has often been coupled with strong and corrosive sulfuric acids (2-3 M), leading to severe electrode corrosion and hydrogen evolution issues. Although high efficiency and long cycling were reported, the results were achieved using high currents to kinetically mask electrode-electrolyte side reactions. Herein, we introduce a low-acidity tin chloride electrolyte (pH=1.09) as a more viable option, which eliminates the need of strong acids and enables a reversible dendrite-free Sn plating chemistry. Remarkably, the plating efficiency approaches unity (99.97%) under standard testing conditions (1 mA cm-2 for 1 mAh cm-2), which maintains high at 99.23-99.93% across various aggressive conditions, including low current (0.1-0.25 mA cm-2), high capacity (5-10 mAh cm-2), and extended resting time (24-72 hours). The battery calendar life is further prolonged to 3064 hours, significantly surpassing literature reports. Additionally, we presented an effective method to mitigate the potential Sn2+ oxidization issue on the cathode, demonstrating long-cycling Sn||LiMn2O4 hybrid batteries. This work offers critical insights for developing highly reversible Sn metal batteries.

An Ultralow-concentration and Moisture-resistant Electrolyte of Lithium Difluoro(oxalato)borate in Carbonate Solvents for Stable Cycling in Practical Lithium-ion Batteries.

The electrolyte concentration not only impacts the battery performance but also affects the battery cost and manufacturing. Currently, most studies focus on high-concentration (>3 M) or localized high-concentration electrolytes (~1 M); however, the expensive lithium salt imposes a major concern. Most recently, ultralow concentration electrolytes (<0.3 M) have emerged as intriguing alternatives for battery applications, which feature low cost, low viscosity, and extreme-temperature operation. However, at such an early development stage, many works are urgently needed to further understand the electrolyte properties. Herein, we introduce an ultralow concentration electrolyte of 2 wt % (0.16 M) lithium difluoro(oxalato)borate (LiDFOB) in standard carbonate solvents. This electrolyte exhibits a record-low salt/solvent mass ratio reported to date, thus pointing to a superior low cost. Furthermore, this electrolyte is highly compatible with commercial Li-ion materials, forming stable and inorganic-rich interphases on the lithium cobalt oxide (LiCoO2) cathode and graphite anode. Consequently, the LiCoO2-graphite full cell demonstrates excellent cycling performance. Besides, this electrolyte is moisture-resistant and effectively suppresses the generation of hydrogen fluoride, which will markedly facilitate the battery assembly and recycling process under ambient conditions.

Nonsense variant in a consanguineous family expands the phenotype of KPTN gene-related syndrome to include hearing impairment.

A short report with two affected siblings from consanguineous family born with intellectual disability, motor disability, language deficit, and hearing impairment and found to carry biallelic nonsense variant in KPTN gene known to be associated with KPTN gene related syndrome.

Highly potent anti-inflammatory, analgesic and antioxidant activities of 3,5-disubstituted tetrahydro-2H-1,3,5-thiadiazine thiones.

Four series of tetrahydro-2H-1,3,5-thiadiazine-2-thiones (series A and B including two novel enantiopure isomers), tetrahydro-2H-1,3,5-thiadiazine-6-thiones (series C) and N-3 ester derivatives of tetrahydro-2H-1,3,5-thiadiazine-6-thiones (series D) were synthesized and evaluated for their anti-inflammatory, analgesic and anti-oxidant activities. These THTT analogues specially series D were first time examined for their in vitro anti-inflammatory, in vivo analgesic and anti-oxidant activities. Among them lipophilic compounds (series B and D) were found to be highly active for anti-inflammatory evaluation with IC50 values between 5.1-16.9 and 4.1-32.4 µM, respectively when compared with the standard drug ibuprofen IC50 = 11.2 µM. The structure-activity relationship exposed the importance of lipophilic substituents especially ester and n-propyl group for inhibition of inflammation. The molecular docking studies demonstrated that all the active analogues of THTT have notable binding relations with Arg120 of the active sites of COX-1 enzyme either through CS moiety of the THTT nucleus or with COO attached at N-3 of THTT nucleus. In vivo analgesic activity of the selected THTT compounds 14, 17, 18, 19 (series B) and 28 (series D) were also carried out by acetic acid-induced writhing procedure. The compound 28 showed significant anti-nociceptive/analgesic activity at the oral dose of 5 mg/kg body weight with the percent protection (32.05 %) when compared with standard indomethacin at 10 mg/kg (48.83 %). Additionally, these compounds demonstrated the moderate level of antioxidant potential with IC50 values in the range of 60.9 to 93.6 µM (standard butylated hyroxyanisole; IC50 = 44.2 µM). These results indicated that this class of heterocyclic compounds may be a template specially to design better anti-inflammatory and analgesic agents.

A phubbing scale tested in Bangladesh, Iran, and Pakistan: confirmatory factor, network, and Rasch analyses.

BACKGROUND: Phubbing, a phenomenon of ignoring others in face-to-face conversations due to mobile phone use, can be assessed using a Phubbing Scale (PS). Recently, the PS has been shortened into an eight-item version, the PS-8. However, psychometric properties of the PS-8 among Iranian, Bangladeshi and Pakistani individuals remain understudied, especially using advanced psychometric testing, such as Rasch and network analyses. METHODS: Participants residing in Iran, Bangladesh, and Pakistan (n = 1902; 50.4% females; mean age = 26.3 years) completed the PS-8 and the Internet Disorder Scale-Short Form (IDS9-SF) via an online survey. Network analysis was used to examine if PS-8 items were differentiated from IDS9-SF items; confirmatory factor analysis (CFA) was used to examine the factor structure and measurement invariance of the PS-8; Rasch modeling was used to examine the dimensionality of the PS-8 and differential item functioning (DIF). RESULTS: Network analysis showed that PS-8 items were clustered together with a distance to the IDS9-SF items. The CFA results supported a two-factor structure of the PS-8, and the two-factor structure was found to be invariant across countries and women and men. Rasch model results indicated that the two PS-8 subscales were both unidimensional and did not display DIF across countries and gender/sex. CONCLUSION: The PS-8 is a feasible and robust instrument for healthcare providers, especially mental health professionals, to quickly assess and evaluate individuals' phubbing behaviors.

Spatial spillover impact of determinants on child mortality in Pakistan: evidence from Spatial Durbin Model.

BACKGROUND: Child mortality is a major challenge to public health in Pakistan and other developing countries. Reduction of the child mortality rate would improve public health and enhance human well-being and prosperity. This study recognizes the spatial clusters of child mortality across districts of Pakistan and identifies the direct and spatial spillover effects of determinants on the Child Mortality Rate (CMR). METHOD: Data of the multiple indicators cluster survey (MICS) conducted by the United Nations International Children's Emergency Fund (UNICEF) was used to study the CMR. We used spatial univariate autocorrelation to test the spatial dependence between contiguous districts concerning CMR. We also applied the Spatial Durbin Model (SDM) to measure the spatial spillover effects of factors on CMR. RESULTS: The study results showed 31% significant spatial association across the districts and identified a cluster of hot spots characterized by the high-high CMR in the districts of Punjab province. The empirical analysis of the SDM confirmed that the direct and spatial spillover effect of the poorest wealth quintile and MPI vulnerability on CMR is positive whereas access to postnatal care to the newly born child and improved drinking water has negatively (directly and indirectly) determined the CMR in Pakistan. CONCLUSION: The instant results concluded that spatial dependence and significant spatial spillover effects concerning CMR exist across districts. Prioritization of the hot spot districts characterized by higher CMR can significantly reduce the CMR with improvement in financial statuses of households from the poorest quintile and MPI vulnerability as well as improvement in accessibility to postnatal care services and safe drinking water.

Norovirus outbreak amid COVID-19 in the United Kingdom; priorities for achieving control.

Norovirus, an enteric virus primarily responsible for gastroenteritis outbreaks worldwide, is currently causing outbreaks around the United Kingdom during the COVID-19 pandemic. With an already exhausted health care system, the significant burden norovirus can have on the National Health Service, including economic and social burdens, is immense and cannot be tolerated. Primary challenges and priorities to be focused on due to the increase in norovirus outbreaks include a further depletion of health care services, increase cases in schools, nurseries, and care facilities, underreporting of the cases, and no effective vaccine being available. Therefore, it is essential to increase awareness about norovirus and its transmission in public, take necessary precautions, and increase reporting of cases. This article discusses the impact norovirus has during the COVID-19 pandemic, and the challenges, and recommendations to achieve control before it reaches epidemic levels.

Intelligent self-control of carbon metabolic flux in SecY-engineered Escherichia coli for xylitol biosynthesis from xylose-glucose mixtures.

Xylitol is a salutary sugar substitute that has been widely used in the food, pharmaceutical, and chemical industries. Co-fermentation of xylose and glucose by metabolically engineered cell factories is a promising alternative to chemical hydrogenation of xylose for commercial production of xylitol. Here, we engineered a mutant of SecY protein-translocation channel (SecY [ΔP]) in xylitol-producing Escherichia coli JM109 (DE3) as a passageway for xylose uptake. It was found that SecY (ΔP) channel could rapidly transport xylose without being interfered by XylB-catalyzed synthesis of xylitol-phosphate, which is impossible for native XylFGH and XylE transporters. More importantly, with the coaction of SecY (ΔP) channel and carbon catabolite repression (CCR), the flux of xylose to the pentose phosphate (PP) pathway and the xylitol synthesis pathway in E. coli could be automatically controlled in response to glucose, thereby ensuring that the mutant cells were able to fully utilize sugars with high xylitol yields. The E. coli cell factory developed in this study has been proven to be applicable to a broad range of xylose-glucose mixtures, which is conducive to simplifying the mixed-sugar fermentation process for efficient and economical production of xylitol.

Covid-19 and dengue: Double punches for dengue-endemic countries in Asia.

The coronavirus disease 2019 (Covid-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is an international public health crisis with devastating effects. In particular, this pandemic has further exacerbated the burden in tropical and subtropical regions of the world, where dengue fever, caused by dengue virus (DENV), is already endemic to the population. The similar clinical manifestations shared by Covid-19 and dengue fever have raised concerns, especially in dengue-endemic countries with limited resources, leading to diagnostic challenges. In addition, cross-reactivity of the immune responses in these infections is an emerging concern, as pre-existing DENV-antibodies might potentially affect Covid-19 through antibody-dependent enhancement. In this review article, we aimed to raise the issue of Covid-19 and dengue fever misdiagnosis, not only in a clinical setting but also with regards to cross-reactivity between SARS-CoV-2 and DENV antibodies. We also have discussed the potential consequences of overlapping immunological cascades between dengue and Covid-19 on disease severity and vaccine development.

Protective effect of the solvent extracts of Portulacca oleracea against acidified ethanol induced gastric ulcer in rabbits.

Portulacca oleracea L. has been used for treatment of different ailments. The aim of this study was to investigate the effectiveness and possible mechanism of action involved in the anti gastric ulcerogenic effect of Portulacca oleracea. Methanolic extract & subsequent fractions (100, 200 and 400 mg/kg) of Portulacca oleracea (P. oleracea) were administered orally to experimental rabbits one hour before oral administration of HCl/ethanol (40:60). Anti gastric ulcerogenic potential of P. oleracea was evaluated by assessment of gastric pH, pepsin, free acidity, ulcer index, mucus content and total acidity. For the investigation of possible mechanism of action malondialdehyde (MDA), histamine, and H + K + ATPase content were determined in the stomach homogenate. Histopathological study of stomach tissue was carried out by H&E dye. Ethyl acetate fraction (EAF) of P. oleracea was the most potent fraction among all fractions that exhibited efficient protection against acidified ethanol mediated gastric-ulcer. The ethyl acetate fraction (EAF) significantly increased the pH of gastric juice, while pepsin and histamine was observed to decrease significantly in comparison to acidified ethanol group (***p ≤ 0.001). The EAF showed moderately H + K + ATPase inhibitory activity. Moreover, it was also observed that EAF decreased the malondialdehyde (MDA) level in the stomach tissue homogenate showing antioxidant effect. Histopathological studies showed that among the tested fractions, EAF significantly prevented acidified ethanol induced gastric mucosal damage. These results showed that mechanism of anti gastric ulcerogenic potential of P. oleracea could be associated with the reduction in histamine level, H + K + ATPase inhibition and reduced MDA level.

Does tourism increase CO2 emissions and health spending in Mexico? New evidence from nonlinear ARDL approach.

This study investigates the nexus between tourism, CO2 emissions and health spending in Mexico. We applied a nonlinear ARDL approach for the empirical analysis for the time period 1996-2018. Mexico receives a large number of tourists each year, tourism improves foreign exchange earnings and contributes positively to the economic growth. However, tourist activities impose a serious environmental cost in terms of CO2 emissions which increase health spending. The empirical findings suggest that tourism leads to CO2 emissions which resultantly causes a high level of health spending in Mexico. Both short-run and long-run findings reported a significant positive association between tourism, CO2 emissions, and health expenditures. Therefore, the government needs legislation to reduce CO2 emissions, besides the use of renewable energy could also help to reduce the CO2 emissions and health expenditures in society. This study does not support to reduce the health expenditure, rather it suggests optimal utilization of the funds allocated to the health sector.

Polio amidst COVID-19 in Pakistan: Ongoing efforts, challenges, and recommendations.

Poliomyelitis is a crippling viral disease caused by poliovirus, a positive-stranded RNA virus that is a serotype of Enterovirus C. Pakistan remains one of the countries in the world where poliomyelitis is still prevalent, posing an obstacle to global poliomyelitis eradication. With the commencement of the COVID-19 pandemic, polio eradication campaigns have proven less feasible, resulting in an increase in polio cases across the country. Pakistan's healthcare system and socio-economic framework are incapable of dealing with two deadly viruses at the same time. As a result, effective measures for combating the destruction caused by the spread of the poliovirus are required.