Potential acetylcholinesterase inhibitors to treat Alzheimer's disease.

OBJECTIVE: Alzheimer's disease (AD) is identified by neuropathological symptoms, and there is now no effective treatment for the condition. A lack of the brain neurotransmitter acetylcholine has been related to the etiology of Alzheimer's disease. Acetylcholinesterase is an enzyme that breaks down acetylcholine to an inactive form and causes the death of cholinergic neurons. Conventional treatments were used but had less effectiveness. Therefore, there is a crucial need to identify alternative compounds with potential anti-cholinesterase agents and minimal undesirable effects. MATERIALS AND METHODS: Fluoroquinolones and benzimidazole-benzothiazole derivatives offer antimicrobial, anti-inflammatory, anti-oxidant, anti-diabetic, and anti-Alzheimer activities. To enhance the chemical portfolio of cholinesterase inhibitors, a variety of fluoroquinolones and benzimidazole-benzothiazole compounds were evaluated against acetylcholinesterase (AChE) butyrylcholinesterase (BChE) enzymes. For this purpose, molecular docking and adsorption, distribution, metabolism, excretion, and toxicology ADMET models were used for in-silico studies for both AChE and BChE enzymes to investigate possible binding mechanisms and drug-likeness of the compounds. The inhibitory effect of docked heterocyclic compounds was also verified in vitro against AChE and BChE enzymes. Fluoroquinolones (Z, Z3, Z4, Z6, Z8, Z12, Z15, and Z9) and benzimidazole-benzothiazole compounds (TBIS-16, TBAF-1 to 9) passed through the AChE inhibition assay and their IC50 values were calculated. RESULTS: The compound 1-ethyl-6-fluoro-7-(4-(2-(4-nitrophenylamino)-2-oxoethyl)piperazin-1-yl) -4-oxo-1,4 di-hydroquinoline-3-carboxylic acid and 2-((1H-benzo[d]imidazol-2-yl)methyl)-N'-(3-bromobenzyl)-4-hydroxy-2H-thiochromene-3-carbohydrazide 1,1-dioxide (Z-9 and TBAF-6) showed the lowest IC50 values against AChE/BChE (0.37±0.02/2.93±0.03 µM and 0.638±0.001/1.31±0.01 µM, respectively) than the standard drug, donepezil (3.9±0.01/4.9±0.05 µM). During the in-vivo investigation, behavioral trials were performed to analyze the neuroprotective impact of Z-9 and TBAF-6 compounds on AD mouse models. The groups treated with Z-9 and TBAF-6 compounds had better cognitive behavior than the standard drug. CONCLUSIONS: This study found that Z-9 (Fluoroquinolones) and TBAF-6 (benzimidazole-benzothiazole) compounds improve behavioral and biochemical parameters, thus treating neurodegenerative disorders effectively.

Machine learning in internet financial risk management: A systematic literature review.

Internet finance has permeated into myriad households, bringing about lifestyle convenience alongside potential risks. Presently, internet finance enterprises are progressively adopting machine learning and other artificial intelligence methods for risk alertness. What is the current status of the application of various machine learning models and algorithms across different institutions? Is there an optimal machine learning algorithm suited for the majority of internet finance platforms and application scenarios? Scholars have embarked on a series of studies addressing these questions; however, the focus predominantly lies in comparing different algorithms within specific platforms and contexts, lacking a comprehensive discourse and summary on the utilization of machine learning in this domain. Thus, based on the data from Web of Science and Scopus databases, this paper conducts a systematic literature review on all aspects of machine learning in internet finance risk in recent years, based on publications trends, geographical distribution, literature focus, machine learning models and algorithms, and evaluations. The research reveals that machine learning, as a nascent technology, whether through basic algorithms or intricate algorithmic combinations, has made significant strides compared to traditional credit scoring methods in predicting accuracy, time efficiency, and robustness in internet finance risk management. Nonetheless, there exist noticeable disparities among different algorithms, and factors such as model structure, sample data, and parameter settings also influence prediction accuracy, although generally, updated algorithms tend to achieve higher accuracy. Consequently, there is no one-size-fits-all approach applicable to all platforms; each platform should enhance its machine learning models and algorithms based on its unique characteristics, data, and the development of AI technology, starting from key evaluation indicators to mitigate internet finance risks.

Crisis and environmental governance decisions amidst the COVID-19 pandemic: Lessons from European countries.

This study investigates the influence of the COVID-19 pandemic crisis on environmental governance decisions within publicly listed European companies. It utilizes a comprehensive analysis of publicly available data regarding these firms and check the environmental governance practices during the pandemic, informed by risk society theory which describes modern societies marked by ongoing risks and uncertainties primarily stemming from technological and scientific advancements. The regression and robustness analysis has been performed on how companies have responded to the crisis, specifically in terms of their approaches to environmental sustainability and governance. Covid-19 has a significantly positive impact on environmental governance (EG), with a coefficient of 18.73 and a p-value of .000. Other variables like human development (HD), size, and free cash flow (FCF) positively affect EG, while corruption (Corrupt) and leverage (Lev) have a negative influence. Robust analysis confirms the negative impact of Covid-19 on EG, with a coefficient of 18.46 and a p-value below .01, consistent across different subsamples. However, it also underscores the challenges companies have encountered in upholding their sustainability efforts amid the crisis. In sum, this research offers valuable insights into how the COVID-19 pandemic has affected environmental governance decisions, with potential implications for policymakers, regulators, and business leaders striving to advance sustainability in the post-pandemic landscape.

Unravelling trends, patterns and intellectual structure of research on bankruptcy in SMEs: A bibliometric assessment and visualisation.

Despite the burgeoning interest among academics in investigating the factors contributing to the high business failure rate among SMEs (small and medium-sized enterprises), the systematic synthesis of the literature on bankruptcy in SMEs is restricted. This article aims to significantly advance the understanding of the causes and repercussions of bankruptcy in SMEs and the preventative actions that may be taken to avoid it. This review assesses 282 articles from 175 outlets employing quantitative and statistics-based bibliometric tools. This bibliometric assessment helped delineate the citation and publication trends and the top contributors to the domain. The underlying thematic clusters of research on bankruptcy in SMEs were also identified, deciphered and elaborated, along with charting the future research vistas through the lens of theory, context, and methods framework. The authors believe this bibliometric variant of systematic literature review makes a significant contribution to bankruptcy and SME research by highlighting the development of the literature and some of the most active research fronts in the domain by offering insights that were not clasped thoroughly or assessed by prior literature assessments.

Research trend in Sustainable Development Goals reporting: a systematic literature review.

This paper examines the common themes delivered in studies on corporate reporting in relation to Sustainable Development Goals (SDGs). Articles of the aforesaid studies were mostly acquired from Scopus and Web of Science (WoS) archives from year 2015 to 2022 in which the contents were carefully reviewed for selection. To systematise the literature, PRISMA 2020 statement is used. Descriptive analysis reveals an increase in publications on corporate SDG reporting, although most are focused on developed nations. The analysis also shows a scarcity of studies on the consumer goods, agricultural, fishery, and forestry sectors. Furthermore, current studies have yet to adopt a qualitative or mixed-method approach. There are fundamentally six themes that emerged from the review of literature-the degree of SDG engagement, the quality of SDG reporting, the determining factor in SDG reporting mechanism, the consequences of SDG reporting, the legitimisation approaches, as well as the institutional/stakeholder pressure. For determinants of SDG reporting, it is observed that environmental governance is not explored. This paper identifies the least addressed SDGs that businesses can focus on to accelerate their SDG contribution rate. This paper guides future research and informs decision-making by organisations and stakeholders interested in promoting sustainable development through SDG reporting.

ESG performance in the time of COVID-19 pandemic: cross-country evidence.

The purpose of this paper is to compare the performance of environmental, social, and governance (ESG) in developing and developed countries prior to and during the COVID-19 pandemic; the study also seeks to reveal the impact of the COVID-19 on the performance of ESG during the pandemic period. Based on a large international panel dataset of 12,325 company-year observations covering 2016-2021, panel regression analysis examined the study hypotheses and achieved the study objectives. The findings indicate that companies have taken precautions against the threats of the COVID-19 pandemic by ensuring compliance with ESG performance to prove their ethical behavior during a crisis. Our findings call into question the notion that companies in developed countries outperform companies in developing countries in terms of ESG performance. As a result, companies in emerging markets outperform companies in developed markets regarding environmental performance, while developed markets focus on social performance. Besides, the ESG performance is positively and significantly affected by the COVID-19, which indicates that during crises, it is important for companies to comply with ethical behavior and the most acceptable in societies. Also, the pandemic has a positive impact on both environmental and social performance, while it has a negative impact on governance performance alone. A considerable body of the literature has addressed the effect of the COVID-19 pandemic on various aspects of a company's financial and non-financial practices. However, limited effort was given to ESG performance. The current study fills this gap by evaluating the direct effect of the COVID-19 crisis on the ESG performance in developing and developed countries. It also provides insight into the ESG performance and corporate behavior and obligations.

Sustainability assurance practices: a systematic review and future research agenda.

Although firms increasingly publish sustainability reports, assuring such reports is relatively new. This study reviews the literature of sustainability assurance to evaluate the intellectual development of the field and provide recommendations for future studies. It also demonstrates the role of assurance to enhance the credibility of sustainability reports and corporate reputation. This paper systematically reviews 94 papers obtained from the Scopus database between 1993 and August 2021. Our study shows that there is an increase in the number of studies published in recent years. We also found that some countries have received limited attention, such as the USA. The scant literature examining sustainability assurance in private institutions and non-profit organisations should be reinforced. Likewise, the sustainability research also provides limited evidence on the governance debate. The vast majority of research is not based on theoretical grounds. The need for assurance of sustainability reports not only enhances the reputation but also adds more value to the organisation's planning, monitoring, and accountability. We highlight several new research suggestions that may enhance the understanding of sustainability assurance practices.

Effects of endothelial cells on human mesenchymal stem cell activity in a three-dimensional in vitro model.

An increasing body of data suggest that mesenchymal stem cells (MSCs) reside in a perivascular niche. To more closely mimic this in vivo microenvironment and for better understanding of its complexity, and the factors that regulate the MSC activity, human umbilical vein endothelial cells (HUVECs) were co-cultured with human bone marrow MSCs--using a novel three-dimensional (3D) spheroid co-culture system. Using confocal microscopy of fluorescently labelled cells, we observed HUVECs and MSCs to self-assemble and form organised structures with segregated cell-type partitioning. Under osteogenic conditions, the rate and extent of differentiation in MSC/HUVEC spheroids was significantly elevated compared to 3D co-cultures of MSCs and human dermal fibroblast controls as shown by alkaline phosphatase staining. Conversely, HUVECs inhibited adipogenic differentiation and the proliferation of MSCs in 3D co-cultures indicating that HUVECs suppressed MSC cycling and selectively promoted osteogenic differentiation in 3D. We have also shown that HUVECs enhanced activation of endogenous Wnt signalling and bone morphogenetic protein (BMP) signalling as shown by increased levels of active nuclear ß-catenin and pSmad 1/5/8 immunopositivity respectively. These data suggest strongly that endothelial cells regulate the MSC activity in simulated in vivo conditions, by maintaining quiescence and facilitating niche exit via osteogenic differentiation following appropriate cues. Our findings also underline the importance of 3D heterotypic cell-cell interactions in the regulation of MSC behaviour, suggesting that multicellular cocktails and/or 3D-based delivery strategies may be beneficial for bone repair.

Inhibitory effect of yoghurt and soya yoghurt containing bifidobacteria on the proliferation of Ehrlich ascites tumour cells in vitro and in vivo in a mouse tumour model.

The effect of yoghurt and soya yoghurt containing Bifidobacterium lactis Bb-12 or B. longum Bb-46 on Ehrlich ascites tumour cell proliferation was investigated in vitro and in vivo. Tumour cells were incubated with B. lactis Bb-12 or B. longum Bb-46 cultivated in de Mann Rogosa Sharpe (MRS) broth medium, or with their centrifuged supernatant fractions or sediments, for 2 h at 37 degrees C. Treatment resulted in the inhibition of tumour cell proliferation by 85.42 (SD 0.78) and 85.10 (SD 1.28) % by intact micro-organisms, 77.61 (SD 0.29) and 71.43 (SD 1.75) % by their supernatant fractions, but only 4.00 (SD 0.19) and 9.09 (SD 1.24) % by the two sedimented bacteria, respectively. The incubation of tumour cells with yoghurt and soya yoghurt containing Bb-12 for 2 h resulted in 83.01 (SD 0.11) and 88.23 (SD 0.06) % inhibition, respectively, while it was 83.82 (SD 0.24) and 86.36 (SD 0.06) %, respectively for the same products containing Bb-46. Corresponding values for plain yoghurt and soya milk (without bifidobacteria) were 32.81 (SD 0.14) and 5.55 (SD 0.12) %, respectively. The differences between yoghurt or soya yoghurt containing Bb-12 or Bb-46 and plain yoghurt, soya milk or control treatments were statistically significant (n 3; P<0.05). Female Swiss albino mice were injected intraperitoneally with the same tumour cells. The lifespan of mice fed diets supplemented with yoghurt or soya yoghurt containing Bb-12 or Bb-46 was prolonged by 16, 23, 34 and 39 %, respectively compared with that of the positive control group (n 6; P<0.05). The lifespan of groups fed plain yoghurt or soya milk was prolonged by 15 and 8 %, respectively. Prolongation of lifespan was positively correlated with faeces bifidobacterial count in the groups fed yoghurt or soya yoghurt containing bifidobacteria (r 0.917; P<0.05).

Inhibition of secretion of staphylococcal alpha toxin by cerulenin.

Secretion of alpha toxin by Staphylococcus aureus strain Wood 46 was preferentially inhibited by cerulenin, an antibiotic that stops fatty-acid synthesis by inhibiting beta-keto acyl acyl carrier-protein synthetase. At the concentrations used, cerulenin had a negligible effect on cell growth and total protein synthesis, but reduced lipid synthesis by 50%. Extracellular and membrane-associated alpha toxin was absent in cultures treated with cerulenin, but toxin formation was resumed after either removal of the antibiotic or addition of exogenous fatty acids. The apparent absence of toxin precursor in membranes of inhibited cells favours inhibition at an earlier stage in toxin synthesis.

Bacterial food-poisoning versus coliforms-faecal streptococci and gamma radiation survival/dose.

All the species tested were sensitive to gamma radiation treatment, even at a dose as low as 0.001 Mrad. The spore-former Bacillus cereus (PCJ 213) proved to be more resistant than the rest of the tested species, while the Gram-negative organisms were more susceptible to irradiation treatment. The tolerance among those organisms is depicted by the descending order: Proteus vulgaris, irregular VI, Escherichia coli I, E. coli III, and Salmonella typhi-murium. Yet all the tested faecal streptococci species, with the exception of Streptococcus bovis, may be regarded as holding an intermediate position between the more resistant B. cereus (PCJ 213) and the more sensitive Gram-negative organisms.

Bacteriophages recovery from raw sewage of different texture.

Bacteriophages recovery was enhanced by the addition of Mg2+ divalent cation or when the raw sewage filtrate was adjusted to pH 4.5. On the other hand, when Mg2+ or Ca2+ divalent cations were added to the acidified sewage filtrate, all sensitive phase species were found to be phage-resistant.

Bacteriological quality of Nile water before and after impoundment (1963--1973): a review.

The normal old picture of the river Nile during 1963 -- 1965 revealed that the rise and fall in bacterial counts followed the seasonal changes. Thus, the highest bacterial counts (10(7) -- 10(9)) 100 ml) were recorded during flood season. Otherwise, a phase of decline (10(5) -- 10(7)/100 ml) prevailed during the whole year. After complete storage, i.e., during (1970 -- 1973, the complete abolishment of seasonal fluctuation was recorded. Secondly, a drop in bacterial counts (10(5) -- 10(7) 100 ml) marked the impoundment water. Thirdly, a rise in coliform and faecal Streptococcus density was recorded in the river water. Moreover, a higher incidence of coliforms and faecal streptococci, untyped forms, marked the river water after full lake storage.

Faecal Streptococcus recovery and efficiency of selective media via surface plating technique.

The recovery rate of faecal streptococci from various vehicles was studied via different selective media and surface plating technique. With the exception of thallous acetate medium, the adopted media and method were only successful for examining the highly polluted materials. Medium bearing thallous acetate at concentrations up to 1 : 500 was selected as the better means for obtaining high yield and fair selectivity. Otherwise, the tellurite medium (1 : 4,000) was found to give low yield and fair selectivity, while medium bearing sodium azide (1 : 2,000) appeared to give low yield and high selectivity. Media bearing twin combinations second low yield and high selectivity, other than media bearing one concentrating agent. However, thallous-azide combination secured better conditions for faecal streptococci recovery than the tellurite-azide combination. Addition of selective agents to the examined liquid samples for 1 hr, singly or in combination before faecal streptococci recovery, exerted no marked effect on the cut down of contaminants.

On the transformation of coliform types, proper and irregular forms.

Physiological changes have been induced in strains of E. coli I and its irregular forms, using a basal synthetic medium and addition of sodium pyruvate, or glucose, or yeast extract, or peptone. Changes in biochemical patterns, using the IMViC reactions plus growth at 44.5 degrees C, were induced, thus brining transformations between the regular types and irregular forms. Ultra-violet irradiation of E. coli I for 90 seconds may turn it into a methyl-red negative strain, while education of E. coli III for producing acid and gas at 44.5 degrees C was possible. Thus, E. coli I could be transformed to give the same reactions as the untyped form 1 of Geldreich (1966) through U.V. irradiation, while E. coli III may give the biochemical reactions of E. coli I via heat-resistance and training in MacConkey broth. The relationship between regular and irregular coliforms was also verified by phage typing. The results obtained were discussed both qualitatively, using "lytic activity", and quantitatively in terms of "efficiency of plating", especially with sewage-derived phages and irregular coliforms.

Untyped forms of faecal streptococci in Egyptian sewage and Nile water.

When the thallous-azide agar medium was used a higher incidence of pure faecal streptococci recovery was recorded especially from slightly polluted vehicles such as river water than on the standard M-enterococcus agar medium. In addition, a thallous-azide combination at pH 6.5 was used successfully for the primary isolation of Str. faecalis and its two variants. Results of biochemical tests of 274 faecal streptococci isolates showed that 20% belonged to Str. faecalis and its two variants as well as Str. durans, Str. faecium and Str. equinus. Thirty-eight percent of the isolated strains were classified as atypical I, II, III, and V previously designated by COOPER and RAMADAN (1955) as well as the unclassified group of RAMADAN et al. (1972). While the remaining 42% were found to belong to seven different categories (SALEH 1976 and 1977). The correlation between four differential tests used for defining the source of faecal streptococci isolates was discussed.

Generation rates of faecal streptococci in various vehicles.

Potassium tellurite media gave the highest detrimental effects on the generation number of all tested faecal streptococci species. This applies to all investigated vehicles. However, drastic tellurite effects became more conspicuous with certain vehicles than with others. This is particularly true with acid and alkaline foods and water, especially with strains like Streptococcus bovis, Str. faecium, and Str. durans. Again, tellurite becomes more influencial with regard to old cells rather than young cells in the logarithmic phase. On the other hand, the use of thallous acetate as a concentration agent secured better results than either the tellurite or azide almost with all tested vehicles. Yet, sodium azide may be regarded as holding an intermediate position between tellurite and thallous acetate in terms of vehicles, Streptococcus species, and age of pollution. A lower number of generation resulted with all tested faecal streptococci species, using liquid media bearing more than one concentrating agent. This applied to water and milk examination.