Identification of novel and potential inhibitors against the dengue virus NS2B/NS3 protease using virtual screening and biomolecular simulations.

Approximately 3.9 billion individuals are vulnerable to dengue infection, a prevalent cause of tropical diseases worldwide. Currently, no drugs are available for preventing or treating Flavivirus diseases, including Dengue, West Nile, and the more recent Zika virus. The highly conserved Flavivirus NS2B-NS3 protease, crucial for viral replication, is a promising therapeutic target. This study employed in-silico methodologies to identify novel and potentially effective anti-dengue small molecules. A pharmacophore model was constructed using an experimentally validated NS2B-NS3 inhibitor, with the Gunner Henry score confirming the model's validity. The Natural Product Activity and Species Source (NPASS) database was screened using the validated pharmacophore model, yielding a total of 60 hits against the NS2B-NS3 protease. Furthermore, the docking finding reveals that our newly identified compounds from the NPASS database have enhanced binding affinities and established significant interactions with allosteric residues of the target protein. MD simulation and post-MD analysis further validated this finding. The free binding energy was computed in terms of MM-GBSA analysis, with the total binding energy for compound 1 (-57.3 ± 2.8 and - 52.9 ± 1.9 replica 1 and 2) indicating a stronger binding affinity for the target protein. Overall, this computational study identified these compounds as potential hit molecules, and these findings can open up a new avenue to explore and develop inhibitors against Dengue virus infection.

Germination responses of Lens Culiunaris L. seeds to osmotic potentials at cardinal temperatures using hydrothermal time model.

BACKGROUND: Lentil is a significant legume that are consumed as a staple food and have a significant economic impact around the world. The purpose of the present research on lentil was to assess the hydrothermal time model's capacity to explain the dynamics of Lens culinaris L. var. Markaz-09 seed germination, as well as to ascertain the germination responses at various sub-optimal temperatures (T) and water potentials (Ψ). In order to study lentil seed germination (SG) behavior at variable water potentials (Ψs) and temperatures (Ts). A lab experiment employing the hydrothermal time model was created. Seeds were germinated at six distinct temperatures: 15 0С, 20 0С, 25 0С, 30 0С, 35 0С, and 40 0С, with five Ψs of 0, -0.3, -0.6, -0.9, and - 1.2 MPa in a PEG-6000 (Polyethylene glycol 6000) solution. RESULTS: The results indicated that the agronomic parameters like Germination index (GI), Germination energy (GE), Timson germination index (TGI), were maximum in 25 0C at (-0.9 MPa) and lowest at 40 0C in 0 MPa. On other hand, mean germination time (MGT) value was highest at 15 0C in -1.2 MPa and minimum at 40 0C in (-0.6 MPa) while Mean germination rate (MGR) was maximum at 40 0C in (0 MPa) and minimum at 15 0C in (-0.6 MPa). CONCLUSIONS: The HTT model eventually defined the germination response of Lens culinaris L. var. Markaz-09 (Lentil) for all Ts and Ψs, allowing it to be employed as a predictive tool in Lens culinaris L. var. Markaz-09 (Lentil) seed germination simulation models.

Effects of Proton Pump Inhibitors on Cardiovascular Events and Inflammatory Factors in Patients With Upper Gastrointestinal Bleeding Undergoing Dual Antiplatelet Therapy.

INTRODUCTION: Dual antiplatelet therapy (DAPT), vital post-percutaneous coronary intervention (PCI) to prevent cardiovascular events (CVEs) via aspirin and P2Y12 receptor antagonists, faces controversy when combined with proton pump inhibitors (PPIs) due to potential impacts on bleeding risk and antiplatelet efficacy, prompting the need for further research to determine optimal co-administration practices. This work evaluated the effects of PPIs on CVEs and inflammatory factors in patients with upper gastrointestinal bleeding (UGIB) undergoing DAPT after PCI. MATERIALS AND METHODS: The data of 166 patients who underwent PCI and developed UGIB while on DAPT from April 2021 to April 2023 were retrospectively analyzed. The patients were rolled into two groups: those who received PPI treatment and those who did not, namely, the PPI and non-PPI group, respectively. Clinical data from these patients was analyzed, intending to provide relevant theoretical evidence for clinical practice. Furthermore, the occurrence of CVEs and the levels of inflammatory factors of patients in all groups were statistically analyzed. RESULTS: Melena was the most common clinical symptom observed in all UGIB patients. The incidence of CVEs in the PPI group was not greatly different from that in the non-PPI group (P>0.05). The distribution of CVEs occurrence among different PPI drugs also exhibited no obvious difference (P>0.05). The PPI group exhibited greatly lower C-reactive protein (CRP) and tumor necrosis factor α (TNF-α) based on the non-PPI group (P<0.05). CONCLUSION: Melena was the most frequent clinical manifestation in UGIB patients. The use of PPIs did not increase the risk of CVEs, and different PPI drugs did not affect the occurrence of CVEs. Furthermore, PPIs lowered CRP and TNF-α levels in serum of these patients.

Ion-Exchange Resin/Carrageenan-Copper-Based Nanocomposite: Artificial Neural Network, Advanced Thermodynamic Profiling, and Anticoagulant Studies.

Carrageenan (CG) and ion exchange resins (IERs) are better metal chelators. Kappa (κ) CG and IERs were synthesized and subjected to copper ion (Cu2+) adsorption to obtain DMSCH/κ-Cu, DC20H/κ-Cu, and IRP69H/κ-Cu nanocomposites (NCs). The NCs were studied using statistical physics formalism (SPF) at 315-375 K and a multilayer perceptron with five input nodes. The percentage of Cu2+ uptake efficiency was used as an outcome variable. Via the grand canonical ensemble, SPF gives models for both monolayer and multilayer sorption layers. For in vitro anticoagulant activity (ACA), the activated partial thromboplastin time were calculated using 100 µL of rabbit plasma incubated at 37 °C. After 2 min, 100 L of 0.025 M CaCl2 was added, and the clotting time was recorded for each group (n = 6). The results demonstrated that the key covariables for the adsorption process were pH and concentration. The results of artificial neural network models were comparable with the experimental findings. The error rates varied between 4.3 and 1.0%. The prediction analysis results ranged from 43.6 to 89.2. The ΔG and ΔS values for IRP69H/κ-Cu obtained were -18.91 and -16.32 and 26.21 and 22.74 kJ/mol for the temperatures 315 and 345 K, respectively. Adsorbate species were perpendicular to the adsorbent surfaces, notwithstanding the apparent importance of macro- and micropore volumes. These adsorbents typically fluctuate with temperature changes and contain one or more layers of sorption. Negative and positive sorption energies correspond to endothermic and exothermic processes. The biosorption energy (E1 and E2) values in this experiment have a value of less than 23 kJ mol-1. Complex SPF models' energy distributions validate surface properties and interactions with adsorbates. At a concentration of 100 µg/mL, DC20H/κ-Cu2+ exhibited an ACA of only 8 s. These NCs demonstrated better greater ACA with the order DC20H/κ < DMSCH/κ < IRP69H/κ. More research is needed to rule out the chemical processes behind the ACA of CG/IER-Cu NCs.

Salicylic acid and Tocopherol improve wheat (Triticum aestivum L.) Physio-biochemical and agronomic features grown in deep sowing stress: a way forward towards sustainable production.

BACKGROUND: The rate of germination and other physiological characteristics of seeds that are germinating are impacted by deep sowing. Based on the results of earlier studies, conclusions were drawn that deep sowing altered the physio-biochemical and agronomic characteristics of wheat (Triticum aestivum L.). RESULTS: In this study, seeds of wheat were sown at 2 (control) and 6 cm depth and the impact of exogenously applied salicylic acid and tocopherol (Vitamin-E) on its physio-biochemical and agronomic features was assessed. As a result, seeds grown at 2 cm depth witnessed an increase in mean germination time, germination percentage, germination rate index, germination energy, and seed vigor index. In contrast, 6 cm deep sowing resulted in negatively affecting all the aforementioned agronomic characteristics. In addition, deep planting led to a rise in MDA, glutathione reductase, and antioxidants enzymes including APX, POD, and SOD concentration. Moreover, the concentration of chlorophyll a, b, carotenoids, proline, protein, sugar, hydrogen peroxide, and agronomic attributes was boosted significantly with exogenously applied salicylic acid and tocopherol under deep sowing stress. CONCLUSIONS: The results of the study showed that the depth of seed sowing has an impact on agronomic and physio-biochemical characteristics and that the negative effects of deep sowing stress can be reduced by applying salicylic acid and tocopherol to the leaves.

Reponses of morphological and biochemical traits of bamboo trees under elevated atmospheric O3 enrichment.

Dwarf bamboo (Indocalamus decorus) is an O3-tolerant plant species. To identify the possible mechanism and response of leaf morphological, antioxidant, and anatomical characteristics to elevated atmospheric O3 (EO3) concentrations, we exposed three-year-old I. decorus seedlings to three O3 levels (low O3-LO: ambient air; medium O3-MO: Ambient air+70 ppb high O3-HO: Ambient air+140 ppb O3) over a growing season using open-top chambers. Leaf shape and stomatal characteristics, and leaf microscopic structure of I. decorus were examined. The results indicated that 1) the stomata O3 flux (Fst) of HO decreased more rapidly under EO3 as the exposure time increased. The foliar O3 injury of HO and MO occurred when AOT40 was 26.62 ppm h and 33.20 ppm h, respectively, 2) under EO3, leaf number, leaf mass per area, leaf area, and stomata length/width all decreased, while leaf thickness, stomatal density, width, and area increased compared to the control, 3) MDA and total soluble protein contents all showed significantly increase under HO (36.57% and 32.77%) and MO(31.91% and 19.52%) while proline contents only increased under HO(33.27%). 4) MO and HO increased bulliform cells numbers in the leaves by 6.28% and 23.01%, respectively. HO reduced the transverse area of bulliform cells by 13.73%, while MO treatments had no effect, and 5) the number of fusoid cells interspace, the transverse area of fusoid cells interspace, and mesophyll thickness of HO significantly increased by 11.16%, 28.58%, and 13.42%, respectively. In conclusion, I. decorus exhibits strong O3 tolerance characteristics, which stem from adaptions in the leaf's morphological, structural, antioxidant, and anatomical features. One critical attribute was the enlargement of the bulliform cell transverse area and the transverse area of fusoid cells interspace that drove this resistance to O3. Local bamboo species with high resistance to O3 pollution thus need to be promoted for sustained productivity and ecosystem services in areas with high O3 pollution.

Assessment of body mass-related covariates for rifampicin pharmacokinetics in healthy Caucasian volunteers.

PURPOSE: Currently, body weight-based dosing of rifampicin is recommended. But lately, fat-free mass (FFM) was reported to be superior to body weight (BW). The present evaluation aimed to assess the influence of body mass-related covariates on rifampicin's pharmacokinetics (PK) parameters in more detail using non-linear mixed effects modeling (NLMEM). METHODS: Twenty-four healthy Caucasian volunteers were enrolled in a bioequivalence study, each receiving a test and a reference tablet of 600 mg of rifampicin separated by a wash-out period of at least 9 days. Monolix version 2023R1 was used for NLMEM. Monte Carlo simulations (MCS) were performed to visualize the relationship of body size descriptors to the exposure to rifampicin. RESULTS: A one-compartment model with nonlinear (Michaelis-Menten) elimination and zero-order absorption kinetics with a lag time best described the data. The covariate model including fat-free mass (FFM) on volume of distribution (V/F) and on maximum elimination rate (Vmax/F) lowered the objective function value (OFV) by 56.4. The second-best covariate model of sex on V/F and Vmax/F and BW on V/F reduced the OFV by 51.2. The decrease in unexplained inter-individual variability on Vmax/F in both covariate models was similar. For a given dose, MCS showed lower exposure to rifampicin with higher FFM and accordingly in males compared to females with the same BW and body height. CONCLUSION: Our results indicate that beyond BW, body composition as reflected by FFM could also be relevant for optimized dosing of rifampicin. This assumption needs to be studied further in patients treated with rifampicin.

Computing the effects of temperature and osmotic stress on the seed germination of Helianthus annuus L. by using a mathematical model.

An extremely important oil crop in the world, Helianthus annuus L. is one of the world's most significant members of the Asteraceae family. The rate and extent of seed germination and agronomic features are consistently affecting  by temperature (T) and changes in water potential (ψ). A broad hydrothermal time model with T and ψ components could explain sunflower responses over suboptimal T and ψ. A lab experiment was performed using the HTT model to discover both T and ψ and their interactive effects on sunflower germination and also to figure  out the cardinal Ts values. The sunflower seeds were germinated at temperatures (15 °C, 20 °C, 25 °C and 30 °C); each Ts had five constant ψs of 0, 0.3, 0.6, 0.9, and 1.2 MPa via PEG 6000 as osmotic stress inducer. The results revealed that highest germination index was found in seed grown at 20 °C in distilled water (0 MPa) and the lowest at 30 °C with osmotic stress of (- 1.2 MPa). The highest value of germination rate index was found in seed grown at 20 °C in distilled water (0 MPa) and the lowest at 15 °C with an osmotic stress of (- 1.2 MPa). In conclusion, water potential, temperature, and their interactions have a considerable impact on seed germination rate, and other metrics (GI, SVI-I, GRI, GE, SVI-II, and MGT). Seeds sown  at 20 °C with zero water potential showed high germination metrics such as GE, GP, GRI, and T50%. The maximum value to TTsub noted at 30 °C in - 0.9 MPa osmotic stress and the minimum value was calculated at 15 °C in - 1.2 MPa osmotic stress. The result of TTsupra recorded highest at 15 °C in  controlled group (0 MPa). Moreover, θH was  highest at 30 °C in controlled condition (0 MPa) and minimum value was observed at  20 °C under - 1.2 MPa osmotic stress. The value of θHTT were  maximum at  30 °C in controlled group (0 MPa) and minimum value was  recorded at 15 °C under - 1.2 MPa osmotic potential. The base, optimum and ceiling temperatures for sunflower germination metrics in this experiment were noted  6.8, 20 and 30 °C respectively.

Inorganic carbon is overlooked in global soil carbon research: A bibliometric analysis.

Soils are a major player in the global carbon (C) cycle and climate change by functioning as a sink or a source of atmospheric carbon dioxide (CO2). The largest terrestrial C reservoir in soils comprises two main pools: organic (SOC) and inorganic C (SIC), each having distinct fates and functions but with a large disparity in global research attention. This study quantified global soil C research trends and the proportional focus on SOC and SIC pools based on a bibliometric analysis and raise the importance of SIC pools fully underrepresented in research, applications, and modeling. Studies on soil C pools started in 1905 and has produced over 47,000 publications (>1.7 million citations). Although the global C stocks down to 2 m depth are nearly the same for SOC and SIC, the research has dominantly examined SOC (>96 % of publications and citations) with a minimal share on SIC (<4%). Approximately 40 % of the soil C research was related to climate change. Despite poor coverage and publications, the climate change-related research impact (citations per document) of SIC studies was higher than that of SOC. Mineral associated organic carbon, machine learning, soil health, and biochar were the recent top trend topics for SOC research (2020-2023), whereas digital soil mapping, soil properties, soil acidification, and calcite were recent top trend topics for SIC. SOC research was contributed by 151 countries compared to 88 for SIC. As assessed by publications, soil C research was mainly concentrated in a few countries, with only 9 countries accounting for 70 % of the research. China and the USA were the major producers (45 %), collaborators (37 %), and funders of soil C research. SIC is a long-lived soil C pool with a turnover rate (leaching and recrystallization) of more than 1000 years in natural ecosystems, but intensive agricultural practices have accelerated SIC losses, making SIC an important player in global C cycle and climate change. The lack of attention and investment towards SIC research could jeopardize the ongoing efforts to mitigate climate change impacts to meet the 1.5-2.0 °C targets under the Paris Climate Agreement of 2015. This bibliographic study calls to expand the research focus on SIC and including SIC fluxes in C budgets and models, without which the representation of the global C cycle is incomplete.

Recent Trends and Advances in Additive-Mediated Composting Technology for Agricultural Waste Resources: A Comprehensive Review.

Agriculture waste has increased annually due to the global food demand and intensive animal production. Preventing environmental degradation requires fast and effective agricultural waste treatment. Aerobic digestion or composting uses agricultural wastes to create a stabilized and sterilized organic fertilizer and reduces chemical fertilizer input. Indeed, conventional composting technology requires a large surface area, a long fermentation period, significant malodorous emissions, inferior product quality, and little demand for poor end results. Conventional composting loses a lot of organic nitrogen and carbon. Thus, this comprehensive research examined sustainable and adaptable methods for improving agricultural waste composting efficiency. This review summarizes composting processes and examines how compost additives affect organic solid waste composting and product quality. Our findings indicate that additives have an impact on the composting process by influencing variables including temperature, pH, and moisture. Compost additive amendment could dramatically reduce gas emissions and mineral ion mobility. Composting additives can (1) improve the physicochemical composition of the compost mixture, (2) accelerate organic material disintegration and increase microbial activity, (3) reduce greenhouse gas (GHG) and ammonia (NH3) emissions to reduce nitrogen (N) losses, and (4) retain compost nutrients to increase soil nutrient content, maturity, and phytotoxicity. This essay concluded with a brief summary of compost maturity, which is essential before using it as an organic fertilizer. This work will add to agricultural waste composting technology literature. To increase the sustainability of agricultural waste resource utilization, composting strategies must be locally optimized and involve the created amendments in a circular economy.

Assessment of ubiquitin specific Peptidase-18 gene in peripheral blood of chronic hepatitis C patients treated with direct-acting antiviral drugs.

Hepatitis C virus (HCV) infection remains one of the leading causes of liver complications globally. Ubiquitin Specific Peptidase-18 (USP18) is a ubiquitin-specific protease that cleaves interferon-stimulated gene 15 (ISG15) from ISGylated protein complexes and is involved in regulating interferon responsiveness. To study the effect of direct-acting antivirals (DAAs) on the USP18 gene using qPCR, 132 participants were recruited and classified into different groups based on treatment duration. USP18 expression was raised compared to rapid virologic response (RVR) and early virologic response (EVR) groups with P = 0.0026 and P = 0.0016, respectively. USP18 was found to be 7.36 folds higher in naïve patients than those with RVR and sustained viral response (SVR). In RVR and SVR groups where patients had cleared HCV RNA after treatment with direct-acting antiviral agents (DAA) therapy, the expression of USP18 was found to be low, with a fold change of 1.3 and 1.4 folds, respectively. Expression of USP18 was significantly higher in the non-RVR group than in the RVR group. In the No EVR group, gene expression was significantly higher than in the EVR group. It is concluded that targeting HCV proteins using DAAs can cause USP18 expression to be normalized more effectively. Moreover, USP18 is a vital marker indicating treatment resistance and distinguishing responders from non-responders during DAA therapy.

Mitigation effect of alpha-tocopherol and thermo-priming in Brassica napus L. under induced mercuric chloride stress.

Soil pollution with heavy metals has grown to be a big hassle, leading to the loss in farming production particularly in developing countries like Pakistan, where no proper channel is present for irrigation and extraction of these toxic heavy metals. The present study aims to ameliorate the damages caused by heavy metal ions (Hg-Mercury) on rapeseed (Brassica napus L.) via a growth regulator (α-tocopherol 150 mg/L) and thermopriming technique at 4 °C and 50 °C to maintain plant agronomical and physiological characteristics. In pot experiments, we designed total of 11 treatments viz.( T0 (control), T1 (Hg4ppm), T2 (Hg8ppm), T3 (Hg4ppm + 4 °C), T4 (Hg4ppm + 4 °C + tocopherol (150 m/L)), T5 (Hg4ppm + 50 °C), T6 (Hg4ppm + 50 °C + tocopherol (150 mg/L)), T7 (Hg8ppm + 4 °C), T8 (Hg8ppm + 4 °C + tocopherol (150 mg/L)), T9 (Hg8ppm + 50 °C), T10 (Hg8ppm + 50 °C + tocopherol (150 mg/L) the results revealed that chlorophyll content at p < 0.05 with growth regulator and antioxidant enzymes such as catalase, peroxidase, and malondialdehyde enhanced up to the maximum level at T5 = Hg4ppm + 50 °C (50 °C thermopriming under 4 ppm mercuric chloride stress), suggesting that high temperature initiate the antioxidant system to reduce photosystem damage. However, protein, proline, superoxide dismutase at p < 0.05, and carotenoid, soluble sugar, and ascorbate peroxidase were increased non-significantly (p > 0.05) 50 °C thermopriming under 8 ppm high mercuric chloride stress (T9 = Hg8ppm + 50 °C) representing the tolerance of selected specie by synthesizing osmolytes to resist oxidation mechanism. Furthermore, reduction in % MC (moisture content) is easily improved with foliar application of α-tocopherol and 50 °C thermopriming and 4 ppm heavy metal stress at T6 = Hg4ppm + 50 °C + α-tocopherol (150 mg/L), with a remarkable increase in plant vigor and germination energy. It has resulted that the inhibitory effect of only lower concentration (4 ppm) of heavy metal stress was ameliorated by exogenous application of α-tocopherol and thermopriming technique by synthesizing high levels of proline and antioxidant activities in maintaining seedling growth and development on heavy metal contaminated soil.

Evaluating forest depletion and structural change effects on environmental sustainability in Pakistan: Through the lens of the load capacity factor.

The pace of species extinction and deforestation has increased dramatically due to the substantial increase in global environmental degradation. This trend is approaching the crucial temperature threshold of 2 °C and calls for more attention. Although previous research has observed the individual impacts of forest depletion, structural change, economic growth, and urbanization on various sustainability outcomes, there has been no previous research into their interrelationships with an emphasis on the load capacity factor (LCF). Furthermore, no previous study has examined the environmental impacts of the abovementioned variables by contrasting the results of LCF and CO2 emissions in Pakistan. Therefore, this research suggests a theoretical framework that integrates these concepts, provides a roadmap for an effective and sustainable mitigation strategy for Pakistan and compares LCF results with CO2 emissions. Using the time-series data from 1970 to 2021, a unique and sophisticated dynamic Autoregressive Distributed Lag (DARDL) technique, the authors found that (i) a 1 % rise in forest depletion leads to a decline in load capacity factor by 0.026 %. (ii) A one per cent upsurge in structural change fosters environmental sustainability by raising the load capacity factor by 0.084 %. (iii) An increase of 1 % in economic growth dwindles the load capacity factor by 0.027 %. (iv) A one per cent surge in urbanization enhances the load capacity factor by 0.029 %. The findings suggest that Pakistan's Government should promote afforestation by emphasizing the constructive role of structural change in achieving environmental sustainability.

The germination response of Zea mays L. to osmotic potentials across optimal temperatures via halo-thermal time model.

The maize (Zea mays L.) is a monocot that is a member of the Poaceae family and a valuable feed for livestock, human food, and raw material for various industries. The halothermal time model determines how plants respond to salt (NaCl) stress under sub-optimal conditions. This model examines the relation between NaClb (g), GR, GP, salinity and temperature stress on germination of seeds dynamics in various crops. Five constant temperatures i.e. 20, 25, 30, 35, and 40 °C and five ψ levels (NaCl concentrations converted to ψ - 0, - 0.2, - 0.4, - 0.6, and - 0.8 MPa) were used in this experiment. In light of the results, the maximum halo-thermal time constant value was recorded at 35 °C temperature, while maximum germination percentage was detected at 30 °C in the controlled condition. Moreover, the lowermost value was recorded at 20 °C at - 0.8 MPa osmotic potential. The highest CAT, APX, and GPX activities were recorded at 15 °C at - 0.8 MPa, while the lowest values were observed for 0 MPa at 30 °C temperature. In conclusion, by employing the halo thermal time model, the germination of maize variety (var.30W52) was accurately predicted for the first time under varying levels of temperature and osmotic potentials.

Mitigation of sciatica injury-induced neuropathic pain through active metabolites derived from medicinal plants.

Sciatica characterized by irritation, inflammation, and compression of the lower back nerve, is considered one of the most common back ailments globally. Currently, the therapeutic regimens for sciatica are experiencing a paradigm shift from the conventional pharmacological approach toward exploring potent phytochemicals from medicinal plants. There is a dire need to identify novel phytochemicals with anti-neuropathic potential. This review aimed to identify the potent phytochemicals from diverse medicinal plants capable of alleviating neuropathic pain associated with sciatica. This review describes the pathophysiology of sciatic nerve pain, its cellular mechanisms, and the pharmacological potential of various plants and phytochemicals using animal-based models of sciatic nerve injury-induced pain. Extensive searches across databases such as Medline, PubMed, Web of Science, Scopus, ScienceDirect, and Google Scholar were conducted. The findings highlights 39 families including Lamiaceae, Asteraceae, Fabaceae, and Apocyanaceae and Cucurbitaceae, effectively treating sciatic nerve injury-induced pain. Flavonoids made up 53% constituents, phenols and terpenoids made up 15%, alkaloids made up 13%, and glycosides made up 6% to be used in neuorpathic pain. Phytochemicals derived from various medicinal plants can serve as potential therapeutic targets for both acute and chronic sciatic injury-induced neuropathic pain.

Infective endocarditis surgery timing.

BACKGROUND: The optimum timing of surgical intervention in complicated left-sided infective endocarditis is not well established. Guidelines from various professional societies are not consistent regarding this. Data concerning this remains limited with conflicting results. METHODS: The national inpatient database (NIS) was used to identify patients hospitalized from the year 2016 to 2020 for infective endocarditis and who underwent surgical intervention for complicated left-sided endocarditis. Primary and secondary outcomes were analyzed in patients who had surgical intervention within 7 days (early surgery group) and after 7 days (late surgery group) of the index hospitalization. RESULTS: Primary outcome [composite of all-cause death, acute cerebrovascular accident (CVA), peripheral septic emboli, intracranial or intraspinal abscess, and cardiac arrest] was better in the early surgery group compared to the late surgery group 32.6 % vs 45.1 % [adjusted Odds ratio (aOR) = 0.59, 95 % Confidence interval (CI) = 0.52-0.67, P value â‰ª 0.001]. This was mainly due to better incidence of acute CVA (15.7 %vs 24 %, aOR = 0.59, CI = 0.50-0.69, P value â‰ª 0.001), peripheral septic emboli (18.5 % vs 27.3 %, aOR = 0.60, CI = 0.52-0.70, P value â‰ª 0.001) and intracranial/intraspinal abscess (1.2 % vs 4.74 %, aOR = 0.24, CI = 0.14-0.38, P value â‰ª 0.001). There is no difference in the incidence of all-cause in-hospital death (7.57 % vs 7.75 % aOR = 0.97, CI = 0.77-1.23, P value = 0.82) or cardiac arrest (3.4 % vs 3.54 %, aOR = 0.96, CI = 0.68-1.35, P value = 0.80). CONCLUSION: Surgical intervention within 7 days of index hospitalization is associated with a better incidence of acute CVA, peripheral septic emboli, and intracranial or intraspinal abscess but not with a better incidence of all-cause in-hospital death.

Financial inclusion, environmental degradation, and the moderating role of ICT: a global perspective.

This study aims to investigate the global perspective on the relationship between financial inclusion and environmental degradation, taking into account the potential moderating role of information and communication technology (ICT). The research utilizes panel data from 131 countries, covering the period of 1995 to 2019. The findings show that financial inclusion has significant and positive impact on carbon emissions, implying that as financial inclusion increases, so do carbon emissions. Moreover, our findings reveal a significant negative moderating effect of the ICT on the relationship between financial inclusion and carbon emissions. This implies that the impact of financial inclusion on carbon emissions is contingent upon the level of ICT development. The robustness of these findings is confirmed through the use of alternative proxies for the explanatory and moderating variables, as well as alternative estimation methods. The outcomes of this study carry significant implications for both policy and practice.

Ligilactobacillus acidipiscis YJ5 modulates the gut microbiota and produces beneficial metabolites to relieve constipation by enhancing the mucosal barrier.

Constipation is a prevalent gastrointestinal (GI) problem affecting a large number of individuals. This study aimed to investigate peristalsis-promoting potential characteristics of Ligilactobacillus acidipiscis YJ5 and the underlying molecular mechanism. The study demonstrated the relieving effect of L. acidipiscis YJ5 on constipation in both zebrafish and mouse models. L. acidipiscis YJ5 intervention significantly increased intestinal peristalsis by reducing the peak time and increasing the fluorescence disappearance rate in the zebrafish model. In the mouse model, the symptoms of constipation relief induced by L. acidipiscis YJ5 included a shortened first black stool time, an increased number of defecation particles, an accelerated propulsion rate of the small intestine, and an increase in fecal water content. L. acidipiscis YJ5 was found to reduce the expression of colonic aquaporins to normalize the colonic water transport system of constipated mice. Additionally, L. acidipiscis YJ5 reversed loperamide-induced morphological damage in the ileum and colon and increased the colonic mucosal barrier. The results of the 16S rRNA gene analysis indicated that L. acidipiscis YJ5 could reverse the structure of gut microbiota to a near-normal group, including levels of ß-diversity, phylum, family, and genus. Furthermore, the fermentation supernatant of L. acidipiscis YJ5 was shown to relieve constipation, and metabolomics analysis revealed that these positive effects were related to its metabolites like malic acid and heliangin.