In Vitro and In Vivo Anti-Inflammatory Activity of a Combination of Extracts from Cinnamomum zeylanicum, Alpinia galanga, and Withania somnifera used in Unani Medicine.

Objectives: Continuous and excessive secretion of pro-inflammatory and anti-inflammatory chemicals and cytokines may further deteriorate inflammation. Anti-inflammatory drugs play an imperative role in inhibiting the evolution of inflammatory diseases. As per the Unani doctrine, a holistic treatment approach is used to treat illnesses. Therefore, drugs having different actions are used to achieve the synergic effect. Three drugs (Cinnamomum zeylanicum, Alpinia galanga, and Withania somnifera), which are frequently used in Unani medicine for joint disorders were selected to evaluate the anti-inflammatory activity of the extract derived from them. Methods: We used RAW 264.7 macrophage cells to see the expression of inflammatory markers IL-1ß, IL-6, and TNF-α. Cytotoxic activity was assessed with MTT assay and Nitric Oxide (NO) was evaluated using Griess reagent. Further, anti-inflammatory activity was evaluated in Wistar Albino rats using carrageenan-induced paw oedema and immunohistochemistry assays for Cyclooxygenase-2 (COX-2). All the data were analyzed using ANOVA and Dunnett t test for multiple comparisons. Results: This extract did not show any cytotoxic effect and the gene expression was significantly reduced for IL-1ß, IL-6, and TNF-α in a dose-dependent manner. Further, NO production was also significantly reduced in the test groups. Immunohistochemistry revealed that the test groups had less inflammation as compared to the control group. Conclusion: It may be inferred that the ethanolic extract of the three herbs has strong anti-inflammatory activity in the tested inflammatory models and the extract is safe as it did not show any cytotoxic effects in both in vitro and in vivo conditions.

Clinical and laboratory profile of Expanded Dengue Syndrome: experience of 2019 outbreak from Dhaka, Bangladesh.

BACKGROUND OBJECTIVES: Bangladesh is afflicted with periodic dengue outbreak every few years and one of the worst upsurges was recorded in 2019 during which there was an increasing trend of dengue with unusual symptoms which were not so common before. This study aims to describe the experience of three tertiary care centres of Dhaka regarding the clinical and laboratory, hospital outcome and management profile of the Expanded Dengue Syndrome (EDS) cases admitted from the 2019 outbreak. METHODS: The current work was a cross-sectional observational study which took place from August 1 to December 31 2019 at three major tertiary care centres in Dhaka, Bangladesh. Out of total 2017 screened dengue cases, 49 met the inclusion criteria and 39 were enrolled after taking informed written consent. Data was analysed using Microsoft Excel and Graph pad prism 9.3.1. A probability value of p<0.05 was considered statistically significant. RESULTS: Out of the 39 cases, majority were male (79.49%) with median (±IQR) age of 33(±9) years. Hypertension (4; 10.26%) was the most commonly associated co-morbidity. Among the systemic manifestations, most prevalent was hepatitis (38.49%) followed by encephalopathy (12.82%). Majority of the patients were suffering from primary infection (85%). Case fatality rate was 15.38%. Hepatitis and meningoencephalitis were the predominant cause of death. This study records the only known case report of Acute respiratory dress syndrome (ARDS) complicating dengue from Bangladesh. None of the patients from our cohort were managed by steroids. Only two (5.13%) out of 39 cases received antibiotics. INTERPRETATION CONCLUSION: In the year 2019, an unusual rise in EDS cases with about 15.4% fatalities were observed in this study. Hepatitis was the most common presentation and cause of death. Here, we report the first ARDS case encountered in Bangladesh. Despite the multifaceted presentation of EDS, indiscriminate use of antibiotics and steroid was minimal. Early recognition of multifarious features of EDS is important for choosing the targeted treatment option which can avert many deaths. The results of this study underline the necessity for more in-depth research into the risk factors that are contributing to mortality in EDS cases.

Waste natural fibers for polymer toughening and biodegradability of epoxy-based polymer composite through toughness and thermal analysis.

Polymeric materials are being increasingly used to replace many metallic components due to their beneficial properties such as higher strength-to-weight ratio and corrosion resistance. However, the widespread use of polymers poses a risk to the environment as they are not biodegradable. The addition of the waste jute fiber and sawdust fiber as reinforcement to the epoxy resin improved its toughness and induced the biodegradability of the polymer. To examine the effect of the jute fiber and sawdust fiber on biodegradability, the composites were then kept in the drainage system for one year, and the impact energy and fracture morphology of the as-cast and weathered samples were examined using a drop ball impact test and a Charpy impact test. During the weathering period, weight gain was initially observed due to the water absorption by the porous fibers, but after three months, the composites started to lose weight due to the degradation of the fiber by swelling and microbial attacks. Microorganisms in the drainage system used the fiber as their energy source, which resulted in the deterioration of the fiber and the production of CO2. The production of CO2 was identified by the FTIR analysis of the weathered composite samples. TGA analysis of the as-cast and weathered samples reveals the reduction of the onset thermal degradation temperature of the weathered composites due to the degradation of the composites. The fiber disintegrated through microbial attack and the fiber swelling caused by the absorption of water by jute fiber and sawdust fiber is identified through SEM imaging. The SEM image also reveals the formation of biofilms and the growth of microorganisms at the fibers. A higher growth rate of the microorganisms was observed in the jute fiber composite than in the sawdust fiber composite, as sawdust contains a high level of lignin that protects it from degradation. The results of this study suggest that both sawdust fiber and jute fiber composites induce biodegradability in the epoxy matrix, but jute fiber was more prominent in this regard. The discovery paves the way for using natural fibers in biodegradable polymer composites, reducing polymeric pollution in the environment.

Prevalence of unqualified sources of antimalarial drug prescription for children under the age of five: A study in 19 low- and middle-income countries.

BACKGROUND: Antimalarial drug resistance poses a severe danger to global health. In Low- and Middle-Income Countries (LMICs), there is a lack of reliable information on antimalarial prescriptions for recent malarial fever in children under five. Our study aims to determine the prevalence of unqualified sources of antimalarial drug prescription for children under the age of five in 19 low- and middle-income countries. METHODS: We performed a cross-sectional study of the Malaria Indicator Survey (MIS) datasets (n = 106265) across 19 LMICs. The recent MIS datasets were used, and the study only included children under five who had taken an antimalarial drug for a recent malarial fever. The outcome variable was classified into two distinct categories: those who had taken antimalarial drugs for malarial fever from qualified sources and those who did not. FINDINGS: Among LMICs, we found that 87.1% of children under five received an antimalarial prescription from unqualified sources who had recently experienced malarial fever. In several LMICs (Tanzania, Nigeria, and Ghana), a substantial portion of recent antimalarial prescriptions for malaria was taken from unqualified sources (about 60%). Some LMICs (Guinea (31.8%), Mali (31.3%), Nigeria (20.4%), Kenya (2.6%), and Senegal (2.7%)) had low rates of antimalarial drug consumption even though children under five received a high percentage of antimalarial prescriptions from qualified sources for a recent malarial fever. Living in rural areas, having mothers with higher education, and having parents with more wealth were frequently taken antimalarial from qualified sources for recent malarial fever in children under five across the LMICs. INTERPRETATION: The study draws attention to the importance of national and local level preventative strategies across the LMICs to restrict antimalarial drug consumption. This is because antimalarial prescriptions from unqualified sources for recent malarial fever in children under five were shockingly high in most LMICs and had high rates of unqualified prescriptions in certain other LMICs.

Cell-free DNA from nail clippings as source of normal control for genomic studies in hematologic malignancies.

Comprehensive genomic sequencing is becoming a critical component in the assessment of hematologic malignancies, with broad implications for patient management. In this context, unequivocally discriminating somatic from germline events is challenging but greatly facilitated by matched analysis of tumor:normal pairs. In contrast to solid tumors, conventional sources of normal control (peripheral blood, buccal swabs, saliva) could be highly involved by the neoplastic process, rendering them unsuitable. In this work we describe our real-world experience using cell free DNA (cfDNA) isolated from nail clippings as an alternate source of normal control, through the dedicated review of 2,610 tumor:nail pairs comprehensively sequenced by MSK-IMPACT-heme. Overall, we find nail cfDNA is a robust source of germline control for paired genomic studies. In a subset of patients, nail DNA may have tumor DNA contamination, reflecting unique attributes of the hematologic disease and transplant history. Contamination is generally low level, but significantly more common among patients with myeloid neoplasms (20.5%; 304/1482) compared to lymphoid diseases (5.4%; 61/1128) and particularly enriched in myeloproliferative neoplasms with marked myelofibrosis. When identified in patients with lymphoid and plasma-cell neoplasms, mutations commonly reflected a myeloid profile and correlated with a concurrent/evolving clonal myeloid neoplasm. For nails collected after allogeneic stem-cell transplantation, donor DNA was identified in 22% (11/50). In this cohort, an association with recent history of graft-vs-host disease was identified. These findings should be considered as a potential limitation for the use of nail as normal control but could also provide important diagnostic information regarding the disease process.

Uncovering the role of aquaporin and chromobox family members as potential biomarkers in head and neck squamous cell carcinoma via integrative multiomics and in silico approach.

Head and neck squamous cell carcinoma (HNSC) is a diverse group of tumors arising from oral cavity, oropharynx, larynx, and hypopharynx squamous epithelium, posing significant morbidity. Aquaporins (AQPs) are membrane proteins forming water channels, some associated with carcinomas. Chromobox (CBX) family is known to modulate physiological and oncological processes. In our study, we analyzed AQPs and CBXs having significant expression followed by their prognostic and mutational assessment. Next, we performed enrichment and tumor infiltration analysis followed by HPA validation. Lastly, we established a 3-node miRNA-TF-mRNA regulatory network and performed protein-protein docking of the highest-degree subnetwork motif between TF and mRNA. Significant upregulation of CBX3/2 and downregulation of AQP3/5/7 correlated with poor overall survival (OS) in HNSC patients. The most significant pathway, GO-BP, GO-MF, and GO-CC terms associated with AQP3 and CBX3 were passive transport by aquaporins, response to vitamin, glycerol channel activity, and condensed chromosome, centromeric region. AQP3 negatively correlated with [Formula: see text] T cells, positively with [Formula: see text] T cells and B cells, and negatively with tumor purity, whereas CBX3 positively correlated with [Formula: see text] T cells, negatively with [Formula: see text] T cells and B cells, and positively with tumor purity. Three-node miRNA-TF-mRNA regulatory network revealed a highest-degree subnetwork motif comprising one TF (SMAD3), one miRNA (miR-423-5p), and one mRNA (AQP3). Protein-protein interaction studies suggested a direct interaction between AQP3 and Smad3 proteins. We concluded that AQP3 and CBX3 hold potential as treatment strategies and individual prognostic biomarkers, while further protein-protein interaction studies of AQP3 could offer insights into its interactions with Smad3 proteins.

Synergistic effect of Mg addition on the enhancement of the mechanical properties and evaluation of corrosion behaviors in 3.5 wt % NaCl of aluminum alloys.

Aluminum alloys are highly preferred for their superior properties, including high corrosion resistance and lightweight in the automotive industry. To better understand how magnesium addition affects aluminum's corrosion and strengthening properties, three different percentages of magnesium-added aluminum alloys, as well as pure aluminum, were melted at a temperature of 800 ± 10 °C in a furnace and cast using the sand molding process. Subsequently, weight loss was used to conduct corrosion testing along with mechanical tests such as tensile, flexural, hardness, and impact tests. In-depth research revealed that the addition of magnesium at 3 wt %, 5 wt %, and 7 wt % strengthened the aluminum alloy. The addition of magnesium resulted in the formation of Al3Mg2, which restricted the movement of dislocation, induced grain refinement, and increased the strength of the alloy. However, it was observed that the addition of magnesium caused a decrease in the alloy's toughness and ductility, resulting in decreased impact energy and % elongation by 29.19 % and 34.87 % respectively by the addition of 5 wt% Mg compared to pure aluminum. Nevertheless, the optical microstructure and SEM image revealed refined grains and the formation of Al3Mg2, providing valuable insight into magnesium's strengthening behavior in aluminum. The study found that adding 7 wt % Mg to the aluminum alloy did not significantly improve its strength and hardness compared to adding 5 wt % Mg. This was because the 7 wt % Mg addition caused the grain size to increase, making it less effective at resisting dislocation movements. The grain coarsening of the 7 wt % Mg added alloy was also revealed in the optical microscope and the SEM images. The EDS analysis confirmed the presence of Al and Mg within the globular-shaped intermetallic particles, indicating the formation of the Al3Mg2 intermetallic phases. However, the highly reactive nature of magnesium results in a higher corrosion rate in terms of weight loss and corrosion current density, which causes the formation of pits and metal dissolution, leading to significant metal loss beneath the original surface when immersed in 3.5 wt % NaCl medium for a period of fifteen and thirty days. Localized corrosion was indicated by the SEM images, which showed concave and convex structures formed by the corrosion products on the alloys. The breakdown of the Al2O3 protective layer, which is the cause of the pits and cracks in the corrosion products, may be brought on by internal stress or the dehydration of hydroxides, which is known as Mg-induced stress corrosion cracking. However, more pits and cracks are found in the SEM image for the 7 wt % Mg addition as it was corroded more compared to the other alloys. The map analysis of the corroded alloy confirmed the corrosion behaviors of the Mg-added alloy by the presence of oxygen all over the surface. Because of the alloy's Al3Mg2 intermetallic compound's refinement and lower corrosion rate, 5 wt % of Mg was found to be the optimal amount for the addition of aluminum to increase strength and hardness without compromising the alloy's toughness and ductility.

Two rare flavonoid glycosides from Litsea glutinosa (Lour.) C. B. Rob.: experimental and computational approaches endorse antidiabetic potentiality.

BACKGROUND: Litsea glutinosa (Lour.) C. B. Rob. belongs to the Litsea genus and is categorized under the family of Lauraceae. The study aimed to investigate the phytoconstituents and pharmacological properties of methanol extract of leaves of Litsea glutinosa, focusing on antidiabetic activity via in vivo and in silico techniques. METHODS: Extensive chromatographic and spectroscopic techniques were applied to isolate and characterize the constituents from the L. glutinosa plant species. The antidiabetic activity was studied in streptozotocin-induced diabetes mice, and the computational study of the isolated compounds was carried out by utilizing AutoDock Vina programs. In addition, the pharmacokinetic properties in terms of absorption, distribution, metabolism and excretion (ADME) and toxicological profiles of the isolated compounds were examined via in silico techniques. RESULTS: In the present study, two flavonoid glycosides 4΄-O-methyl (2 ̋,4 ̋-di-E-p-coumaroyl) afzelin (1) and quercetin 3-O-(2 ̋,4 ̋-di-E-p-coumaroyl)-α-L-rhamnopyranoside (2) were isolated from the leaves of L. glutinosa and characterized by 1H and 13C NMR, COSY, HSQC, HMBC, and mass spectral data. Although compounds 1 and 2 have been reported twice from Machilis litseifolia and Lindera akoensis, and Machilis litseifolia and Mammea longifolia, respectively, this is the first report of this isolation from a Litsea species. Administering the methanolic extract of L. glutinosa at doses of 300 and 500 mg/kg/day to mice with diabetes induced by streptozotocin led to a significant decrease in fasting blood glucose levels (p < 0.05) starting from the 7th day of treatment. Besides, the computational study and PASS analysis endorsed the current in vivo findings that the both isolated compounds exerted higher binding affinities to human pancreatic α-amylase and aldose reductase than the conventional drugs. The in silico ADMET analysis revealed that the both isolated compounds have a favorable pharmacokinetic and safety profile suitable for human consumption. CONCLUSION: According to the current outcomes obtained from in vivo and in silico techniques, the leaf extract of L. glutinosa could be a natural remedy for treating diabetes, and the isolated phytoconstituents could be applied against various illnesses, mainly hyperglycemia. However, more investigations are required for extensive phytochemical isolation and pharmacological activities of these phytoconstituents against broader targets with exact mechanisms of action.

Antioxidant activity study and GC-MS profiling of Camellia sinensis Linn.

The antioxidant activity of tea leaves extract is a widely researched topic. Tea leaves, particularly those from the Camellia sinensis Linn plant, have garnered attention due to their potential health benefits attributed to their antioxidant properties. Antioxidants are compounds that can neutralize harmful free radicals in the body, which can damage cells and contribute to various health issues, including cancer, cardiovascular diseases, and aging. In this research, the matured tea leaves which has been considered as agricultural waste in Moulovibazar area of Bangladesh have been investigated as a potential source of antioxidant. Methanol was used as solvent for the extraction of antioxidant. DPPH (1,1-diphenyl-2-picryl hydrazyl) scavenging free radical assay method was used to assess the antioxidant activity of the extracts and ascorbic acid was used as positive control. Gas chromatography with mass spectrometric (GC-MS) analysis method was conducted on this extract to investigate the principal components. The half inhibitory concentration (IC50) values of methanol extract and ascorbic acid were found to be 69.51 µg/mL and 10.70 µg/mL, respectively. Caffeine is the main compound (74.47%) among the eight bioactive compounds was identify and quantified by GC-MS.

Data on growth performance of marine Chlorella sp. cultured in different cost-effective media.

This paper presents the data on growth performance of marine Chlorella sp. cultured in different cost-effective media including cow dung, cow urine, poultry litter, compost, NPK (nitrogen, phosphorus, and potassium), and UTR (Urea, TSP, and red potash). Growth curve of Chlorella sp. was determined at 5 mg of cow dung, poultry litter, compost, NPK, UTR and 5 µL of cow urine per 350 ml sea water (25 ppt) to identify the onset of stationary phase. Further four media among these were selected to continue the experiment at 8 mg and 11 mg of concentration. The higher cell densities were 4.21 × 106 and 4.18 × 106 cells/mL for NPK at 8 mg and 11 mg of concentration on 6th and 5th day, respectively. Cow dung with an 11 mg of concentration exhibited 2.67 × 106 cells/mL on the 3rd day, which is around 1.5 times greater than the highest growth in the same concentration of poultry litter. Chlorella sp. had a higher cell density in NPK media than in other media, however it was discarded since it is inorganic and costly. Due to the low cell density in cow urine media and the prolonged stationary phase in poultry litter media, the focus of the subsequent study was then placed on cow dung media. The data will contribute to the selection of locally available and cost-effective culture media by determining the stationary phases for specific microalgal species which will replace the costly and labor-intensive commercial media.

Nitric oxide as a double-edged sword in pulmonary viral infections: Mechanistic insights and potential therapeutic implications.

In the face of the global pandemic caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), researchers are tirelessly exploring novel therapeutic approaches to combat coronavirus disease 2019 (COVID-19) and its associated complications. Nitric oxide (NO) has appeared as a multifaceted signaling mediator with diverse and often contrasting biological activities. Its intricate biochemistry renders it a crucial regulator of cardiovascular and pulmonary functions, immunity, and neurotransmission. Perturbations in NO production, whether excessive or insufficient, contribute to the pathogenesis of various diseases, encompassing cardiovascular disease, pulmonary hypertension, asthma, diabetes, and cancer. Recent investigations have unveiled the potential of NO donors to impede SARS-CoV- 2 replication, while inhaled NO demonstrates promise as a therapeutic avenue for improving oxygenation in COVID-19-related hypoxic pulmonary conditions. Interestingly, NO's association with the inflammatory response in asthma suggests a potential protective role against SARS-CoV-2 infection. Furthermore, compelling evidence indicates the benefits of inhaled NO in optimizing ventilation-perfusion ratios and mitigating the need for mechanical ventilation in COVID-19 patients. In this review, we delve into the molecular targets of NO, its utility as a diagnostic marker, the mechanisms underlying its action in COVID-19, and the potential of inhaled NO as a therapeutic intervention against viral infections. The topmost significant pathway, gene ontology (GO)-biological process (BP), GO-molecular function (MF) and GO-cellular compartment (CC) terms associated with Nitric Oxide Synthase (NOS)1, NOS2, NOS3 were arginine biosynthesis (p-value = 1.15 x 10-9) regulation of guanylate cyclase activity (p-value = 7.5 x 10-12), arginine binding (p-value = 2.62 x 10-11), vesicle membrane (p-value = 3.93 x 10-8). Transcriptomics analysis further validates the significant presence of NOS1, NOS2, NOS3 in independent COVID-19 and pulmonary hypertension cohorts with respect to controls. This review investigates NO's molecular targets, diagnostic potentials, and therapeutic role in COVID-19, employing bioinformatics to identify key pathways and NOS isoforms' significance.

Hummingbirds use wing inertial effects to improve manoeuvrability.

Hummingbirds outperform other birds in terms of aerial agility at low flight speeds. To reveal the key mechanisms that enable such unparalleled agility, we reconstructed body and wing motion of hummingbird escape manoeuvres from high-speed videos; then, we performed computational fluid dynamics modelling and flight mechanics analysis, in which the time-dependent forces within each wingbeat were resolved. We found that the birds may use the inertia of their wings to achieve peak body rotational acceleration around wing reversal when the aerodynamic forces were small. The aerodynamic forces instead counteracted the reversed inertial forces at a different wingbeat phase, thereby stabilizing the body from inertial oscillations, or they could become dominant and provide additional rotational acceleration. Our results suggest such an inertial steering mechanism was present for all four hummingbird species considered, and it was used by the birds for both pitch-up and roll accelerations. The combined inertial steering and aerodynamic mechanisms made it possible for the hummingbirds to generate instantaneous body acceleration at any phase of a wingbeat, and this feature is probably the key to understanding the unique dexterity distinguishing hummingbirds from other small-size flyers that solely rely on aerodynamics for manoeuvering.

Enhanced clinical assessment of hematologic malignancies through routine paired tumor and normal sequencing.

Genomic profiling of hematologic malignancies has augmented our understanding of variants that contribute to disease pathogenesis and supported development of prognostic models that inform disease management in the clinic. Tumor only sequencing assays are limited in their ability to identify definitive somatic variants, which can lead to ambiguity in clinical reporting and patient management. Here, we describe the MSK-IMPACT Heme cohort, a comprehensive data set of somatic alterations from paired tumor and normal DNA using a hybridization capture-based next generation sequencing platform. We highlight patterns of mutations, copy number alterations, and mutation signatures in a broad set of myeloid and lymphoid neoplasms. We also demonstrate the power of appropriate matching to make definitive somatic calls, including in patients who have undergone allogeneic stem cell transplant. We expect that this resource will further spur research into the pathobiology and clinical utility of clinical sequencing for patients with hematologic neoplasms.

Sugar osmolyte inhibits and attenuates the fibrillogenesis in RNase A: An in vitro and in silico characterizations.

Mechanisms of protein aggregation are of immense interest in therapeutic biology and neurodegenerative medicine. Biochemical processes within the living cell occur in a highly crowded environment. The phenomenon of macromolecular crowding affects the diffusional and conformational dynamics of proteins and modulates their folding. Macromolecular crowding is reported to cause protein aggregation in some cases, so it is a cause of concern as it leads to a plethora of neurodegenerative disorders and systemic amyloidosis. To divulge the mechanism of aggregation, it is imperative to study aggregation in well-characterized model proteins in the presence of macromolecular crowder. One such protein is ribonuclease A (RNase A), which deciphers neurotoxic function in humans; therefore we decided to explore the amyloid fibrillogenesis of this thermodynamically stable protein. To elucidate the impact of crowder, dextran-70 and its monomer glucose on the aggregation profile of RNase-A various techniques such as Absorbance, Fluorescence, Fourier Transforms Infrared, Dynamic Light Scattering and circular Dichroism spectroscopies along with imaging techniques like Atomic Force Microscopy and Transmission Electron Microscopy were employed. Thermal aggregation and fibrillation were further promoted by dextran-70 while glucose counteracted the effect of the crowding agent in a concentration-dependent manner. This study shows that glucose provides stability to the protein and prevents fibrillation. Intending to combat aggregation, which is the hallmark of numerous late-onset neurological disorders and systemic amyloidosis, this investigation unveils that naturally occurring osmolytes or other co-solutes can be further exploited in novel drug design strategies.

Chemico-pharmacological and computational studies of Ophiorrhiza fasciculata D. Don and Psychotria silhetensis Hook. f. focusing cytotoxic, thrombolytic, anti-inflammatory, antioxidant, and antibacterial properties.

The current study sought to examine the pharmacological potentials of crude methanolic extracts of Ophiorrhiza fasciculata and Psychotria silhetensis, as well as their various solvent fractionates, with a focus on cytotoxic, thrombolytic, membrane stabilizing, antioxidant, and antibacterial activities via in vitro and in silico approaches. The extensive chromatographic and spectroscopic analyses confirmed and characterized two compounds as (±)-licarin B (1) and stigmasterol (2) from O. fasciculata and P. silhetensis, respectively. Petroleum ether soluble fraction of O. fasciculata and the aqueous soluble fraction of P. silhetensis showed the lowest 50% lethal concentrations (1.41 and 1.94 µg/mL, respectively) in brine shrimp bioassay. Likewise, petroleum ether soluble fraction of O. fasciculata and aqueous soluble fraction of P. silhetensis showed the highest thrombolytic activity with 46.66% and 50.10% lyses of the clot, respectively. The methanol and dichloromethane soluble fractions of O. fasciculata reduced erythrocyte hemolysis by 64.03% and 37.08%, respectively, under hypotonic and heat-induced conditions, compared to 81.97% and 42.12% for standard acetylsalicylic acid. In antioxidant activity test, aqueous soluble fraction O. fasciculata (IC50 = 7.22 µg/mL) revealed promising antioxidant potentialities in comparison to standard butylated hydroxytoluene (IC50 = 21.20 µg/mL). In antibacterial screening, chloroform, and dichloromethane soluble fractions of P. silhetensis showed a mild antibacterial activity compared with the standard drug ciprofloxacin. Additionally, the molecular docking study corroborated the current in vitro findings, and the isolated two constituents had higher binding affinities toward epidermal growth factor receptor, tissue plasminogen activator, vFLIP-IKK gamma stapled peptide dimer, glutathione reductase, and dihydrofolate reductase enzyme than their corresponding standard drugs. In addition, the both isolated compounds exerted favorable pharmacokinetics (absorption, distribution, metabolism, excretion) and toxicological profiles with drug-like qualities in computational-based ADMET and drug likeliness analyses. The current research suggests that both plants have potential as a natural treatment for treating thrombosis, inflammation, and oxidative stress. However, more thorough research is required to thoroughly screen for phytochemicals and pinpoint the precise mechanisms of action of the bioactive metabolites derived from these plants against a broad range of molecular targets.

Effect of oil price shocks on output and prices: evidence from Saudi Arabia.

The primary objective of this article is to estimate how the spike in oil prices has impacted Saudi Arabia's output and other macroeconomic indicators. To address this question, the study utilizes a simple VAR estimation and VAR estimation with sign restrictions, specifically an oil demand shock and an oil supply shock, to determine the influence of oil price shocks. The study's findings are consistent with conventional wisdom and current research from oil-exporting countries. Consistent with all model specifications for both periods (monthly 2010q1 to 2020q2 and quarterly 1996q1 to 2020q2), the study finds that an oil price shock benefits the Saudi Arabian economy. The results indicate that a 10% increase in oil prices leads to a 2% increase in output, a 0.15 percentage point increase in the consumer price index, a 6% increase in export value, and a 3% increase in import value. The study highlights the importance of considering both oil supply and demand shocks in analyzing the impact of oil price fluctuations and concludes that the demand shock is more influential than the supply shock.

The molecular mechanism of WRINKLED1 transcription factor regulating oil accumulation in developing seeds of castor bean.

The transcription factor WRINKLED1 (WRI1), a member of AP2 gene family that contain typical AP2 domains, has been considered as a master regulator regulating oil biosynthesis in oilseeds. However, the regulatory mechanism of RcWRI1 in regulating oil accumulation during seed development has not been clearly addressed. Castor bean (Ricinus communis) is one of the most important non-edible oil crops and its seed oils are rich in hydroxy fatty acids, widely applied in industry. In this study, based on castor bean reference genome, three RcWRIs genes (RcWRI1, RcWRI2 and RcWRI3) were identified and the expressed association of RcWRI1 with oil accumulation were determined. Heterologous transformation of RcWRI1 significantly increased oil content in tobacco leaf, confirming that RcWRI1 activate lipid biosynthesis pathway. Using DNA Affinity Purification sequencing (DAP-seq) technology, we confirmed RcWRI1 binding with Transcription Start Site of genes and identified 7961 WRI1-binding candidate genes. Functionally, these identified genes were mainly involved in diverse metabolism pathways (including lipid biosynthesis). Three cis-elements AW-box ([CnTnG](n)7[CG]) and AW-boxes like ([GnAnC](n)6[GC]/[GnAnC](n)7[G]) bound with RcWRI1 were identified. Co-expression network analysis of RcWRI1 further found that RcWRI1 might be widely involved in biosynthesis of storage materials during seed development. In particular, yeast one hybrid experiments found that both AP2 domains within RcWRI1 were required in binding targeted genes. These results not only provide new evidence to understand the regulatory mechanism of RcWRI1 in regulation of oil accumulation during castor bean seed development, but also give candidate gene resource for subsequent genetic improvement toward increasing oil content in oilseed crops.

Active wing-pitching mechanism in hummingbird escape maneuvers.

Previous studies suggested that wing pitching, i.e. the wing rotation around its long axis, of insects and hummingbirds is primarily driven by an inertial effect associated with stroke deceleration and acceleration of the wings and is thus passive. Here we considered the rapid escape maneuver of hummingbirds who were initially hovering but then startled by the frontal approach of a looming object. During the maneuver, the hummingbirds substantially changed their wingbeat frequency, wing trajectory, and other kinematic parameters. Using wing kinematics reconstructed from high-speed videos and computational fluid dynamics modeling, we found that although the same inertial effect drove the wing flipping at stroke reversal as in hovering, significant power input was required to pitch up the wings during downstroke to enhance aerodynamic force production; furthermore, the net power input could be positive for wing pitching in a complete wingbeat cycle. Therefore, our study suggests that an active mechanism was present during the maneuver to drive wing pitching. In addition to the powered pitching, wing deviation during upstroke required twice as much power as hovering to move the wings caudally when the birds redirected the aerodynamic force vector for escaping. These findings were consistent with our hypothesis that enhanced muscle recruitment is essential for hummingbirds' escape maneuvers.

Breast Cancer Prognostic Hub Genes Identified by Integrated Transcriptomic and Weighted Network Analysis: A Road Toward Personalized Medicine.

Breast cancer (BC) is the second-most common type and among the leading causes of worldwide cancer-related deaths. There is marked person-to-person variability in susceptibility to, and phenotypic expression and prognosis of BC, a predicament that calls for personalized medicine and individually tailored therapeutics. In this study, we report new observations on prognostic hub genes and key pathways involved in BC. We used the data set GSE109169, comprising 25 pairs of BC and adjacent normal tissues. Using a high-throughput transcriptomic approach, we selected data on 293 differentially expressed genes to establish a weighted gene coexpression network. We identified three age-linked modules where the light-gray module strongly correlated with BC. Based on the gene significance and module membership features, peptidase inhibitor 15 (PI15) and KRT5 were identified as our hub genes from the light-gray module. These genes were further verified at transcriptional and translational levels across 25 pairs of BC and adjacent normal tissues. Their promoter methylation profiles were assessed based on various clinical parameters. In addition, these hub genes were used for Kaplan-Meier survival analysis, and their correlation with tumor-infiltrating immune cells was investigated. We found that PI15 and KRT5 may be potential biomarkers and potential drug targets. These findings call for future research in a larger sample size, which could inform diagnosis and clinical management of BC, thus paving the way toward personalized medicine.

Continued fractions and the Thomson problem.

We introduce new analytical approximations of the minimum electrostatic energy configuration of n electrons, E(n), when they are constrained to be on the surface of a unit sphere. Using 453 putative optimal configurations, we searched for approximations of the form [Formula: see text] where g(n) was obtained via a memetic algorithm that searched for truncated analytic continued fractions finally obtaining one with Mean Squared Error equal to [Formula: see text] for the model of the normalized energy ([Formula: see text]). Using the Online Encyclopedia of Integer Sequences, we searched over 350,000 sequences and, for small values of n, we identified a strong correlation of the highest residual of our best approximations with the sequence of integers n defined by the condition that [Formula: see text] is a prime. We also observed an interesting correlation with the behavior of the smallest angle [Formula: see text], measured in radians, subtended by the vectors associated with the nearest pair of electrons in the optimal configuration. When using both [Formula: see text] and [Formula: see text] as variables a very simple approximation formula for [Formula: see text] was obtained with MSE= [Formula: see text] and MSE= 73.2349 for E(n). When expanded as a power series in infinity, we observe that an unknown constant of an expansion as a function of [Formula: see text] of E(n) first proposed by Glasser and Every in 1992 as [Formula: see text], and later refined by Morris, Deaven and Ho as [Formula: see text] in 1996, may actually be very close to -1.10462553440167 when the assumed optima for [Formula: see text] are used.