Assessing the antibacterial potential of 6-gingerol: Combined experimental and computational approaches.

The rise of antibiotic resistance in bacteria is becoming a global concern, particularly due to the dwindling supply of new antibiotics. This situation mandates the discovery of new antimicrobial candidates. Plant-derived natural compounds have historically played a crucial role in the development of antibiotics, serving as a rich source of substances possessing antimicrobial properties. Numerous studies have supported the reputation of 6-gingerol, a prominent compound found in the ginger family, for its antibacterial properties. In this study, the antibacterial activities of 6-gingerol were evaluated against Gram-negative bacteria, Acinetobacter baumannii and Klebsiella pneumoniae, with a particular focus on the clinically significant Gram-negative Pseudomonas aeruginosa and Gram-positive bacteria Staphylococcus aureus. Furthermore, the anti-virulence activities were assessed in vitro, in vivo, and in silico. The current findings showed that 6-gingerol's antibacterial activity is due to its significant effect on the disruption of the bacterial cell membrane and efflux pumps, as it significantly decreased the efflux and disrupted the cell membrane of S. aureus and P. aeruginosa. Furthermore, 6-gingerol significantly decreased the biofilm formation and production of virulence factors in S. aureus and P. aeruginosa in concentrations below MICs. The anti-virulence properties of 6-gingerol could be attributed to its capacity to disrupt bacterial virulence-regulating systems; quorum sensing (QS). 6-Gingerol was found to interact with QS receptors and downregulate the genes responsible for QS. In addition, molecular docking, and molecular dynamics (MD) simulation results indicated that 6-gingerol showed a comparable binding affinity to the co-crystalized ligands of different P. aeruginosa QS targets as well as stable interactions during 100 ns MD simulations. These findings suggest that 6-gingerol holds promise as an anti-virulence agent that can be combined with antibiotics for the treatment of severe infections.

Sense of Place and Perceived Impacts in the Rural Industrialized Nexus: Insights for Sustainability Pathways.

As representative of the water-energy-food nexus, fossil fuel development and industrial agriculture are rural industries that continue to expand and increasingly occur in the same areas. Being a top agricultural export county and the fossil fuel capital of California while ranking among the worst in the US for industrial pollution, Kern County is a poster child of rural nexus development and, thus, an essential place for initiating sustainability transitions. Such transitions rely on policy support and the adoption of methods by individuals and communities who may disagree with such changes. While sense of place and impact perceptions are recognized as playing critical roles in sustainability management, they have yet to be utilized in nexus research. A survey (N = 256) of the perceived impacts of nexus industries with place meaning and place attachment as possible drivers for perceptions was conducted in nexus industry pollution exposure risk zones. Factor analysis and bivariate correlations showed that place meaning and place attachment are drivers for perceptions while also being drivers for concern for changes in nexus industries. While perceptions of impacts indicated contested place meanings, participants strongly perceive the economy and environment as being in decline. To build support for sustainability policy, directing funds from Kern County's renewable energy industry to local sectors of society, implementation of regenerative agriculture, cooperative management, and nurturing place meaning as aligned with nature's restorative quality are important paths forward. These nexus management foci could strengthen place attachment, build trust in government, and repair environmental alienation.

Development of a New Bioequivalent Omeprazole Product.

Background and Objectives: The enteric form of omeprazole is one of the most commonly prescribed medications. Similarly to Europe, Kazakhstan relies on the localization of pharmaceutical drug production as one of its primary strategies to ensure that its population has access to affordable and good-quality medicines. This study comprehensively describes the technologically available development of bioequivalent delayed-release omeprazole. Materials and Methods: Various regimes and technological parameters were tested on laboratory- and production-scale equipment to establish a technical process where a functional and gastro-protective layer is essential. According to the ICH guidance on stability testing and Kazakhstan local rules, stability studies were conducted under conditions appropriate for climate zone II. The comparison of the rate and extent of absorption with subsequent assessment of the bioequivalence of the generic and reference drugs after a single dose of each drug at a dose of 40 mg was performed. Results: The quantitative and qualitative composition and technology of producing a new generic enteric form of omeprazole in capsules were developed and implemented at the manufacturing site of solid forms. Dissolution profiles in media with pH 1.2 and 6.8 were proven. During the accelerated six-month and long-term twelve-month studies, the developed formulation in both packaging materials at each control point passed the average weight and mass uniformity test, dissolution test, acid-resistance stage test, buffer stage test, impurity assay, and microbiological purity test and met all the specification criteria. A bioequivalence study in 24 healthy volunteers compared against the innovative drug showed the bioequivalency of the new generic system. The obtained values from the test and reference products were 1321 ± 249.0 ng/mL and 1274 ± 233 ng/mL for Cmax, 4521 ± 841 ng·h /mL and 4371 ± 695 ng·h /mL for AUC0-t, and 4636 ± 814 ng·h /mL and 4502 ± 640 ng·h /mL for AUC0-∞. Conclusions: Using affordable technologies, a bioequivalent generic delayed-release formulation of 20 and 40 mg omeprazole has been developed.

Modulation of the crosstalk between Keap1/Nrf2/HO-1 and NF-κB signaling pathways by Tomatidine protects against inflammation/oxidative stress-driven fulminant hepatic failure in mice.

Fulminant hepatic failure (FHF) is the terminal phase of acute liver injury, which is characterized by massive hepatocyte necrosis and rapid hepatic dysfunction in patients without preexisting liver disease. There are currently no therapeutic options for such a life-threatening hepatic failure except liver transplantation; therefore, the terminal phase of the underlying acute liver injury should be avoided. Tomatidine (TOM), asteroidal alkaloid, may have different biological activities, including antioxidant and anti-inflammatory effects. Herein, the lipopolysaccharide (LPS)/D-galactosamine (D-GalN)-induced FHF mouse model was established to explore the protective potential of TOM and the underlying mechanisms of action. TOM pretreatment significantly inhibited hepatocyte necrosis and decreased serum aminotransferase activities in LPS/D-GalN-stimulated mice. TOM further increased the level of different antioxidant enzymes while reducing lipid peroxidation biomarkers in the liver. These beneficial effects of TOM were shown to be associated with targeting of NF-κB signaling pathways, where TOM repressed NF-κB activation and decreased LPS/D-GalN-induced TNF-α, IL-6, IL-1ß, and iNOS production. Moreover, TOM prevented LPS/D-GalN-induced upregulation of Keap1 expression and downregulation of Nrf2 and HO-1 expression, leading to increased Nrf2-binding activity and HO-1 levels. Besides, TOM pretreatment repressed LPS/D-GalN-induced upregulation of proliferating cell nuclear antigen (PCNA) expression, which spared the hepatocytes from damage and subsequent repair following the LPS/D-GalN challenge. Collectively, our findings revealed that TOM has a protective effect on LPS/D-GalN-induced FHF in mice, showing powerful antioxidant and anti-inflammatory effects, primarily mediated via modulating Keap1/Nrf2/HO-1 and NF-κB/TNF-α/IL-6/IL-1ß/iNOS signaling pathways.

Structural and biofunctional diversity of sulfated polysaccharides from the genus Codium (Bryopsidales, Chlorophyta): A review.

It is believed that polysaccharides will become a focal point for future production of food, pharmaceuticals, and materials due to their ubiquitous and renewable nature, as well as their exceptional properties that have been extensively validated in the fields of nutrition, healthcare, and materials. Sulfated polysaccharides derived from seaweed sources have attracted considerable attention owing to their distinctive structures and properties. The genus Codium, represented by the species C. fragile, holds significance as a vital economic green seaweed and serves as a traditional Chinese medicinal herb. To date, the cell walls of the genus Codium have been found to contain at least four types of sulfated polysaccharides, specifically pyruvylated ß-d-galactan sulfates, sulfated arabinogalactans, sulfated ß-l-arabinans, and sulfated ß-d-mannans. These sulfated polysaccharides exhibit diverse biofunctions, including anticoagulant, immune-enhancing, anticancer, antioxidant activities, and drug-carrying capacity. This review explores the structural and biofunctional diversity of sulfated polysaccharides derived from the genus Codium. Additionally, in addressing the impending challenges within the industrialization of these polysaccharides, encompassing concerns regarding scale-up production and quality control, we outline potential strategies to address these challenges from the perspectives of raw materials, extraction processes, purification technologies, and methods for quality control.

Rise of inflation and formation of interest rate on loans in industrial sector: A VECM approach to assess the impact on total industrial production from evidence of Bangladesh.

Industrial development is the prerequisite for sustainable economic growth. This study has examined the impact of the interest rate imposed on advances in the small and medium enterprise (SME) industrial sector, the large industrial (LI) sector, and inflation on the total industrial development of Bangladesh. For this purpose, we have used monthly data from January 2015 to June 2021. The weighted average interest rate of advances (WAIRA) is used as a substitute for the interest rate imposed on advances that were sourced from Bangladesh Bank (BB). We have applied Johansen co integration and the VECM technique to investigate long- and short run relationships, and the results have revealed the existence of both. We have observed that, in the short run, only WAIRA on SME industries has a significant negative impact on total industrial development. In the long run, inflation and WAIRA on SME and large industry have a significant impact on industrial development. The long run relationships have indicated that, inflation and WAIRA in the SME sector have a negative influence on total industrial development, but WAIRA in the large industry (LI) sector has a positive influence. Finally, considering the entire situation of the economy of Bangladesh, especially the growing industrial sector, these findings are highly momentous for policy implications and achieving sustainable development in this sector.

Selective recovery of gold and silver from electronic wastes through a sequential process of Qalkari and room-temperature hydrometallurgy.

This work was focused on the selective recovery of gold and silver from electronic wastes using a sequential process of pyrometallurgy (Qalkari) and room-temperature hydrometallurgy. In the first step, electronic wastes underwent Qalkari recycling, yielding tablets containing precious elements (Qalkari furnace product) and melting slag (Qalkari furnace waste). In the subsequent hydrometallurgy phase, the nitric acid concentration and the input solid amount were optimized for the effective room-temperature recovery of gold. Due to the successful separation of precision elements and disturbing substances in Qalkari, the gold recovery efficiency of 99.99% was obtained at the acid concentration of 50% (v/v) and the solid input of 15% (w/v). Afterwards, HCl, NH4Cl, and NaCl were used for silver recovery from the Qalkari-processed gold-recovered leaching solution, leading to the efficiency of 99.99%. But NH4Cl was recognized as the most effective precipitant as it promises the most enhanced potential for the possible subsequent recovery of palladium. In conclusion, this study draws the effectiveness of Qalkari in recycling electronic wastes, with a significant impact on the efficiency of succeeding room-temperature hydrometallurgical processes for gold and silver recovery within a reasonable leaching time.

Decoupling livestock and poultry pollution emissions from industrial development: A step towards reducing environmental emissions.

China has implemented policies like Leading areas for Agricultural Green Development (LAGD) to mitigate livestock and poultry farming pollution while promoting industry growth. However, it remains uncertain whether LAGDs have successfully balanced emission reduction with stable development. This study examines 165 LAGDs to analyze changes in emissions, assess the decoupling of emission reduction from output value, and identify influencing factors. Findings reveal that emissions from livestock and poultry in LAGDs initially increased and then decreased between 2010 and 2019. Cattle were responsible for over 40% of fecal emissions, and pigs for more than 20%. Additionally, pigs contributed to over 61% of urine emissions. From 2010 to 2014, increases in chemical oxygen demand were mainly due to pigs and cattle. Total nitrogen levels were significantly impacted by cattle, while pigs were affected by total phosphorus. From 2014 to 2019, reductions in emissions were largely attributed to a decrease in pig-related pollutants. The decoupling status shifted from strong to weak and then back to strong between 2014 and 2019. Production efficiency played a crucial role in reducing emissions, while changes in industrial structure moved from supporting to hindering this reduction. Economic development was a primary factor in driving these changes. Standard emissions in Chinese regions showed a rising and then declining trend from 2010 to 2019. The Northeast and Northwest regions of China demonstrated emission trends that were in sync with the growth in rural income. This study offers insights into the successes and challenges of LAGDs in achieving a balance between reduced emissions and development, using quantitative analysis. The findings are instrumental in informing policies for a sustainable livestock and poultry industry. Recommendations include evaluating coordinated approaches to pollution reduction and industrial growth, setting decoupling goals, designing policies based on influential factors, conducting regional assessments of livestock and poultry demand, and implementing region-specific strategies.

Antimicrobial and anti-virulence activities of 4-shogaol from grains of paradise against gram-negative bacteria: Integration of experimental and computational methods.

ETHNOPHARMACOLOGICAL RELEVANCE: Bacterial resistance to antibiotics is a growing global concern, highlighting the urgent need for new antimicrobial candidates. Aframomum melegueta was traditionally used for combating urinary tract and soft tissue infections, which implies its potential as an antimicrobial agent. AIM OF STUDY: This study was designed to explore the antibacterial and anti-virulence capabilities of 4-shogaol isolated from A. melegueta seeds versus gram-negative bacteria: Serratia marcescens, Klebsiella pneumoniae, Acinetobacter baumannii, and the clinically important pathogen Pseudomonas aeruginosa. MATERIALS AND METHODS: 4-Shogeol was isolated from A. melegueta seeds and its MICs were determined for Acinetobacter baumannii (ATCC-17978), Pseudomonas aeruginosa (ATCC-27853), Klebsiella pneumoniae (ATCC-700603), and Serratia marcescens clinical isolate. The anti-efflux activity and effect on the bacterial cell membrane for the compound were evaluated. Furthermore, the anti-virulence activities of the compound were evaluated. The effects of 4-shogeol at sub-MIC on bacterial motility, biofilm formation, and production of virulent enzymes and pigments were assessed. The anti-quorum sensing activities of 4-shogeol were evaluated virtually and by quantification its effect on the expression of quorum sensing encoding genes. The in vivo protection assay was conducted to evaluate the effect of 4-shogaol on the P. aeruginosa capacity to induce pathogenesis in mice. Finally, the effect of shogaol-antibiotics combination was assessed. RESULTS: The research revealed that 4-shogaol's antibacterial action primarily involves disrupting the bacterial cell membrane and efflux pumps. It also exhibited significant anti-virulence effects by reducing biofilm development and repressing virulence factors production, effectively protecting mice against P. aeruginosa infection. Furthermore, when combined with antibiotics, 4-shogaol demonstrated synergistic effects, leading to reduced minimum inhibitory concentrations (MICs) against P. aeruginosa. Its anti-virulence properties were linked to its ability to disrupt bacterial quorum sensing (QS) mechanisms, as evidenced by its interaction with QS receptors and downregulation of QS-related genes. Notably, in silico analysis indicated that 4-shogaol exhibited strong binding affinity to different P. aeruginosa QS targets. CONCLUSION: These findings suggest that 4-shogaol holds promise as an effective anti-virulence agent that can be utilized in combination with antibiotics for treating severe infections caused by gram-positive bacteria.

Acetyl barlerin from Barleria trispinosa induces chemopreventive NQO1 and attenuates LPS-induced inflammation: in vitro and molecular dynamic studies.

Extraction and fractionation of Barleria trispinosa growing in Saudi Arabia yielded four iridoid compounds identified by spectroscopic techniques as acetylbarlerin (1), barlerin (2), shanzhiside methyl ester (3) and 6-⍺-L-rhamnopyranosyl-8-O-acetylshanzihiside methyl ester (4). Preliminary experiments confirmed that compound 1 acts as an inducer of chemopreventive NAD(P)H:Quinone oxidoreductase 1 (NQO1) enzymatic activity in a murine hepatoma (Hepa1c1c7) chemoprevention model. It also demonstrated the ability to inhibit the lipopolysaccharides (LPS)-induced nitric oxide (NO) production in the RAW264.7 macrophage model. Western blotting revealed the ability of compound 1 to up-regulate the protein expression of the NQO1 marker. Furthermore, compound 1 elicited NO suppression in RAW264.7 macrophages by inhibiting iNOS protein expression. Molecular docking and molecular simulation studies of 1 supported its experimental results as an inhibitor of the nuclear factor erythroid 2-Kelch-like ECH-associated protein 1 (Nrf2-KEAP1) complex, resulting in Nrf2-mediated induction of chemopreventive NQO1.Communicated by Ramaswamy H. Sarma.

Incorporation of Perillyl Alcohol into Lipid-Based Nanocarriers Enhances the Antiproliferative Activity in Malignant Glioma Cells.

Perillyl alcohol (PA), a naturally existing monocyclic terpene related to limonene, is characterized by its poor aqueous solubility and very limited bioavailability. Its potential anti-cancer activity against malignant glioma has been reported. The aim was to develop PA-loaded lipid-based nanocarriers (LNCs), and to investigate their anti-cancer activity against two different brain cell lines. Non-medicated and PA-loaded LNCs were prepared and characterized. The mechanism of cytotoxic activity of PA was conducted using a molecular docking technique. The cell viabilities against A172 and ANGM-CSS cells were evaluated. The results revealed that the average particle size of the prepared LNCs ranged from 248.67 ± 12.42 to 1124.21 ± 12.77 nm, the polydispersity index was 0.418 ± 0.043-0.509 ± 0.064, while the zeta potential ranged from -36.91 ± 1.31 to -15.20 ± 0.96 mV. The molecular docking studies demonstrated that the drug had binding activity to human farnesyltransferase. Following exposure of the two glioblastoma cell lines to the PA-loaded nanoformulations, MTS assays were carried out, and the data showed a far lower half-maximal inhibitory concentration in both cell lines when compared to pure drug and non-medicated nanocarriers. These results indicate the potential in vitro antiproliferative activity of PA-loaded LNCs. Therefore, the prepared PA-loaded nanocarriers could be used to enhance drug delivery across the blood-brain barrier (BBB) in order to treat brain cancer, especially when formulated in a suitable dosage form. The size, surface charge, and lipid composition of the LNCs make them promising for drug delivery across the BBB. Detailed pharmacokinetic and pharmacodynamic assessments, including the evaluation of BBB penetration, are necessary to better understand the compound's distribution and effects within the brain.

Exploring the impact of China-Europe Railway Express on the urban-rural income gap.

The China-Europe Railway Express (CRexpress) has established a new land transportation route between Asia and Europe as part of China's westward expansion. The resulting trade promotion effect has the potential to improve industrial development and factor flows, ultimately leading to a reduction in the income disparity between urban and rural areas in cities that use the CRexpress. The impact of the CRexpress on income disparities between urban and rural areas in cities that use the service is of particular interest, as the empirical evidence on the relationship between international trade and these disparities is inconsistent. Using a difference-in-differences model and macro panel data, this study found that the CRexpress significantly narrowed the urban-rural income gap in cities where it was operational, and that this effect had a spillover effect on nearby cities. However, the magnitude of this effect decreased with distance. The mechanism analysis indicated that the CRexpress narrowed the income gap by promoting secondary industry development, but this effect varied significantly by region, with pronounced effects in eastern coastal cities and less pronounced effects in inland cities in the central and western region. The study suggests that local governments in these regions should focus on improving the institutional environment and providing industrial support to promote industrial transfer in order to narrow the urban-rural income gap and promote overall economic development.

Neuroprotective and nephroprotective effects of Ircinia sponge in polycyclic aromatic hydrocarbons (PAHs) induced toxicity in animal model: a pharmacological and computational approach.

The present study investigated the neuroprotective and nephroprotective effects of the sponge Ircinia sp. ethyl acetate extract (ISPE) against persistent aromatic pollutants in vitro and in vivo. Different exponential experimental assays were applied to this study. An in vitro study to investigate the potential therapeutic effect of ISPE using antioxidants (for example, ABTS and DPPH) and anti-Alzheimer assays (inhibition of acetylcholinesterase); the in-vivo study was designed to evaluate the protective effect of ISPE as neuroprotective and nephroprotective against the destructive effect of PAH. Several assays included oxidative assays (LPO), antioxidant biomarkers (GSH, GST), and inflammatory and neurodegenerative biomarkers (PTK,SAA). Additionally, the results were confirmed using histopathological examination. The in silico screening study improved the in vitro and in vivo findings through interaction between the aryl hydrocarbon receptor (AHR) and the polyphenolic content of ISPE extract, which was determined using LCMSM. The results and discussion showed that ISPE exhibited a promising antioxidant and anti-acetylcholinesterase activity as evidenced by IC50 values of 49.74, 28.25, and 0.18 µg/mL in DPPH, ABTS, and acetylcholinesterase inhibition assays, respectively. In vivo, the study showed that animals receiving ISPE before poly aromatic hydrocarbons administration PAHs (Prot, ISPE) showed significant amelioration in kidney functions manifested by the reduction of serum urea, uric acid, and creatinine by 40.6%, 66.4%, and 134.8%, respectively, concerning PAH-injected mice (HAA). Prot, ISPE revealed a decline in malondialdehyde (MDA) and total proteins (TP) in kidney and brain tissues by 73.63% and 50.21%, respectively, for MDA and 59.82% and 80.41%, respectively, for TP with respect to HAA. Prot, ISPE showed significant elevation in reduced glutathione (GSH) and glutathione transferase (GST) in kidney and brain tissues and reduction in the inflammatory and pre-cancerous biomarkers, namely, serum protein tyrosine kinases (PTKs) and serum amyloid A (SAA). These findings were further supported by histopathological examination of kidney and brain tissues, which revealed normal structure approaching normal control. Metabolic profiling of ISPE using LC-MS-MS showed the presence of fourteen polyphenolic compounds belonging mainly to phenolic acids and flavonoids. In silico study revealed that all the tested compounds exerted certain binding with the aryl hydrocarbon receptor, where rutin showed the best fitting (ΔG = - 7.6 kcal/mol-1) with considerable pharmacokinetic and pharmacodynamic properties revealed from in silico ADME (Absorption, Distribution, Metabolism, and Excretion) study. Hence, it can be concluded that the Ircinia sponge showed a promising protective effect versus kidney and brain toxicity triggered by PAHs.

Calculation and influencing factors of the sustainable development of urban industries: a case study of China's state-level new districts.

China's state-level new districts (SNDs) have become the new growth poles for the economic development of the cities where they are located, and a reasonable industrial structure is crucial to industrial sustainable development of SNDs and urban economic growth. This study uses multi-dimensional indicators to measure the convergence level of industrial structure among SNDs and reveals its dynamic evolution trend and formation mechanism. In this context, this study uses dynamic panel model to test the effect of various factors on the convergence of industrial structure. The results are as follows: the advantageous industries in Pudong New District (PND) and Liangjiang New District (LND) are concentrated in capital-intensive and technology-intensive industries. The advantageous industries in Binhai New District (BND) are scattered, and its advantageous industries are distributed in resource-intensive, technology-intensive, and capital-intensive industries. There is an obvious convergence of industrial structure among SNDs, but the degree of convergence of industrial structure among SNDs is different. The result of the regression model shows that the convergence of industrial structure has a significant cumulative effect; investment scale (IS) and government intervention (GI) significantly increase the convergence level of industrial structure, while market demand (MD) and technology level (TL) significantly decrease it. Moreover, the effects of GI and MD on industrial structure convergence are stronger.

Incorporating valsartan in sesame oil enriched self-nanoemulsifying system-loaded liquisolid tablets to improve its bioavailability.

Valsartan (VST) is a poorly soluble antihypertensive drug characterized by its limited dissolution rate and low bioavailability. This study aims to improve VST solubility and dissolution rate via developing liquisolid tablets (LSTs) containing a self-nanoemulsifying drug delivery system (SNEDDS), which is expected to enhance VST bioavailability. This aim was achieved via two designs of experiment. The first was the simplex-lattice design to optimize VST-loaded-SNEDDS using sesame oil, Tween 80, and polyethylene glycol 400. The second was the 32-3-level factorial design to optimize the liquisolid system using the SNEDDS-loaded VST and Neusilin®US2 as a carrier and fumed silica as a coating material. Different excipient ratios (X1) and varioussuper-disintegrants (X2) were also used in developing the optimized VST-LSTs. Thein vitrodissolution of VST from LSTs was compared with the marketed product (Diovan®). Non-compartmental analysis of plasma data after extravascular input with the linear trapezoidal method was used to calculate thepharmacokinetic parameters of the optimized VST-LSTs compared with the marketed tablet in male Wistar rats. The optimized SNEDDS compromised 24.9% sesame oil, 33.3% surfactant, and 41.8% cosurfactant, giving 173.9 nm size and 63.9 mg/ml loading capacity. Also, the SNEDDS-loaded VST tablet revealed good quality attributes with the release of 75% of its content in 5 min and 100% within 15 min. On the other hand, the marketed product took 1 h for the entire drug to be released.Moreover, the maximum plasma concentration (Cmax) of the optimizedVST-LSTwas6585.33 ng/ml within 1 h (Tmax), compared to 2884.67 ng/ml within 2 h of the marketed tablet.The relative bioavailability of the SNEDDS-loaded VST tablet was 213.7% compared to that of the marketed tablet, indicating that this formulation approach could be applied for increasing solubility, dissolution behavior in GIT, and bioavailability of poorly water-soluble drugs.

[Application of "major scientific issues and engineering technology difficulties in traditional Chinese medicine(2019-2021)" in national science and t echnology layout].

In order to judge the future development trend of science and technology, plan ahead and lay out the frontier technology fields and directions, China Association of Chinese Medicine(CACM) has launched consultation projects for collecting "major scienti-fic issues and engineering technology difficulties in traditional Chinese medicine(TCM)" for the industry for three consecutive years since 2019. Up to now, 18 projects have been selected as major issues for research, and some experience and achievements have been made. These projects have been applied in important scientific and technological work such as scientific and technological planning and deployment at all levels of national, local, and scientific research institutions, the selection and cultivation of major national scientific and technological projects, and the construction of innovation bases, giving full play to the role of the think tank advisory committee of CACM. This study reviewed the selection of major issues for the first time, systematically combed its application in the national layout of science and technology, and put forward the existing problems and improvement suggestions, aiming to provide new ideas for further improving the selection of major issues and research direction, providing a theoretical basis and decision support for the national scientific and technological layout in the field of TCM, and promoting scientific and technological innovation to facilitate the high quality development of TCM.

An Underutilized Food "Miwu": Diet History, Nutritional Evaluations, and Countermeasures for Industrial Development.

About 10 major crops basically feed the world. In fact, there are still a large number of plants that have not been fully explored and utilized because they have been ignored by the market and research. The expansion of food sources in various countries plays an important role in maintaining food security and nutrition security in the world. Miwu is the aerial part of the medicinal plant Rhizoma Chuanxiong belonging to a traditional local characteristic food raw material. Its edible value is still little known. Through textual research, component determination, literature survey, field research, and SWOT analysis, this paper has a comprehensive understanding of Miwu's diet history, chemical components, safety risks, and industrial development status. It is found that Miwu has been eaten for 800 years, is rich in nutrients and active ingredients, and has no acute toxicity. In addition, the current industrial development of Miwu has significant advantages and many challenges. To sum up, Miwu is a potentially underutilized food raw material. This paper also provides countermeasures for the industrialized development of Miwu, which will provide a milestone reference for the future utilization and development of Miwu.

The digital economy and the green and high-quality development of the industry-a study on the mechanism of action and regional heterogeneity.

Consistently rising carbon emissions in the global economy make it more challenging to meet the goals of the Paris climate agreement. Knowing what factors play a role is essential to help shape strategies to reduce carbon emissions. While there is a wealth of material on how GDP expansion correlates with increases in carbon emissions, little is known about how democracy and renewable energy could improve environmental conditions in developing nations. The purpose of this article was to use fair data to assess the effect of renewable energy and green technology advances on carbon neutrality in 23 provinces across China from 2005 to 2020. The research used the dynamic ordinary least square, the fully modified ordinary least square, and the two-step GMM to determine that digitalization, industrial development, and health expenditures result in lower carbon emissions. Urbanization, tourism, and per capita income in certain Chinese provinces also drove carbon emissions. The study also showed that the impact of these factors on carbon emissions varies depending on the amount of economic growth. Environmental pollution is reduced due to the digitalization of tourist and healthcare costs, industrial development, and urbanization. According to the study's findings, we advise these nations to seek economic growth and invest in health care and renewable energy initiatives.

Incorporating sodium deoxycholate endorsed the buccal administration of avanafil to heighten the bioavailability and duration of action.

The highly effective phosphodiesterase type 5 inhibitor (avanafil; AVA) is routinely prescribed to treat erectile dysfunction. The drug has poor oral bioavailability and undergoes a significant first-pass metabolism. Therefore, altering AVA's solubility and choosing a different delivery method may boost its effectiveness. Nine different solid dispersion formulations utilizing polyvinylpyrrolidone (PVP) at three different ratios were prepared and characterized. The Box-Behnken design was employed to optimize AVA-buccal tablets. The pre-compression and post-compression characteristics of the tablets were assessed. The mucoadhesion strength of the optimized tablet was investigated using cow buccal mucosal tissue. In vivo performance of the optimized tablets was examined on human volunteers compared to the commercial tablets. PVP K90 at 2:1 drug to polymer ratio showed the highest solubilization capacity. The mucoadhesive polymer type and percentage and the mucopenetration enhancer percentage were significantly affect the mucoadhesion strength, tablet hardness, and the initial and cumulative AVA released from the prepared tablets. The optimized AVA-buccal tablet showed 4.96 folds increase in the mean residence time, higher plasma exposure, and an improvement in the relative bioavailability of AVA by 1076.27% compared with the commercial tablet. Therefore, a successful approach to deal with AVA first-pass metabolism and low bioavailability could be to employ buccal tablets containing a solubility-enhanced form of AVA.

Unveiling the Efficacy of Sesquiterpenes from Marine Sponge Dactylospongia elegans in Inhibiting Dihydrofolate Reductase Using Docking and Molecular Dynamic Studies.

Dihydrofolate reductase (DHFR) is a crucial enzyme that maintains the levels of 5,6,7,8-tetrahydrofolate (THF) required for the biological synthesis of the building blocks of DNA, RNA, and proteins. Over-activation of DHFR results in the progression of multiple pathological conditions such as cancer, bacterial infection, and inflammation. Therefore, DHFR inhibition plays a major role in treating these illnesses. Sesquiterpenes of various types are prime metabolites derived from the marine sponge Dactylospongia elegans and have demonstrated antitumor, anti-inflammation, and antibacterial capacities. Here, we investigated the in silico potential inhibitory effects of 87 D. elegans metabolites on DHFR and predicted their ADMET properties. Compounds were prepared computationally for molecular docking into the selected crystal structure of DHFR (PDB: 1KMV). The docking scores of metabolites 34, 28, and 44 were the highest among this series (gscore values of -12.431, -11.502, and -10.62 kcal/mol, respectively), even above the co-crystallized inhibitor SRI-9662 score (-10.432 kcal/mol). The binding affinity and protein stability of these top three scored compounds were further estimated using molecular dynamic simulation. Compounds 34, 28, and 44 revealed high binding affinity to the enzyme and could be possible leads for DHFR inhibitors; however, further in vitro and in vivo investigations are required to validate their potential.