Biosurfactants (BSs) are microbial compounds that have emerged as potential alternatives to chemical surfactants due to their multifunctional properties, sustainability, and biodegradability. Owing to their amphipathic nature and distinctive structural arrangement, biosurfactants exhibit a range of physicochemical properties, including excellent surface activity, efficient critical micelle concentration, humectant properties, foaming and cleaning abilities and the capacity to form microemulsions. Furthermore, numerous biosurfactants display additional biological characteristics, such as antibacterial, antifungal, and antiviral effects, antioxidant, anticancer, and immunomodulatory activities. Over the past two decades, numerous studies have explored their potential applications, including pharmaceuticals, cosmetics, antimicrobial and antibiofilm agents, wound healing, anticancer treatments, immune system modulators and drug/gene carriers. These applications are particularly important in addressing challenges such as antimicrobial resistance and biofilm formation in clinical, hygiene, and therapeutic settings. They can also serve as coating agents for surfaces, enabling antiadhesive, suppression, or eradication strategies. Not least importantly, biosurfactants have shown compatibility with various drug formulations, including nanoparticles, liposomes, micro and nanoemulsions, and hydrogels, improving drug solubility, stability, and bioavailability and enabling targeted and controlled drug release. These qualities make biosurfactants promising candidates for the development of next-generation antimicrobial, antibiofilm, anticancer, wound healing, immunomodulating, drug or gene delivery agents, as well as adjuvants to other antibiotics. Analyzing recent literature, this review aims to provide insights into the present understanding, highlight emerging trends, identify promising directions and advancements in the utilization of biosurfactants within the pharmaceutical and biomedical fields.

Knowledge is a property that measures the degree of awareness of an agent about a target in an environment. The goal in conventional intelligent and cognitive agent development is to build agents that can be trained to gain knowledge about a target. The definition and operations of this knowledge associated to the agent is not clear, whereas these are required for developing a reliable, scalable and flexible agent. In this paper, we provide a concise theoretical framework for the description and quantification of the knowledge property needed for an efficient design of cognitive and rational intelligent agents. We relate the quantification scheme to the epistemological description of knowledge and present many illustrative examples on the usefulness of the quantification scheme.

Despite the availability of therapeutic treatments, multiple myeloma is an incurable haematological disorder. In this study, we aimed to clarify the role of CXorf48 as a therapeutic target in multiple myeloma. Based on a previously identified HLA-A*24:02-restiricted epitope from this novel cancer/testis antigen, we characterized the activities of cytotoxic T lymphocytes (CTLs) specific to this antigen against myeloma cells and evaluated the effects of demethylating agents in increasing antigen expression and enhancing the cytotoxic activity of CTLs. CXorf48 expression was examined by RT-PCR using nine myeloma cell lines. Cell lines with low CXorf48 expression were treated by demethylating agents (DMAs), 5-azacytidine (5-aza), and 5-aza-2'-deoxycytidine (DAC) to evaluate gene expression using quantitative RT-PCR. Furthermore, CXorf48-specific CTLs were induced from peripheral blood mononuclear cells of HLA-A*24:02-positive healthy donors to evaluate antigen recognition using ELISpot and 51Cr cytotoxicity assays. CXorf48 was widely expressed in myeloma cells and gene expression was significantly increased by DMAs. Furthermore, CXorf48-specific CTLs recognized DMA-treated myeloma cells. These findings suggest that CXorf48 is a useful target for immunotherapy, such as vaccination, in combination with demethylating agents for the treatment of patients with myeloma.

This paper presents a multi-year research study conducted at the University of Toledo, aimed at improving human-machine teaming (HMT) methods and technologies. With the incorporation of artificial intelligence (AI) into 21st-century machines, collaboration between humans and machines has become highly complicated for real-time applications. The penetration of intelligent and synthetic assistants (IA/SA) in virtually every field has opened a path for the new area of HMT. When it comes to crucial tasks such as patient treatment and care, defense, and industrial production, the use of non-standardized HMT technologies may pose a risk to human lives as well as up to billions of taxpayer dollars. A thorough literature survey revealed that there are not many established standards or benchmarks for HMT. In this paper, we aim to address the lack of HMT design and development standards. We propose a method to design an HMT based on a generalized architecture. This design includes the development of an intelligent collaborative system and human team. Followed by processes and metrics to test and validate the proposed model, we present a novel human-in-the-loop (HIL) simulation method using two controlled HMT scenarios; first, emergency care provider (ECP) training, and second, patient treatment by an experienced medic. Both scenarios include humans processing visual data and performing actions that represent real-world applications while responding to a Voice-Based Synthetic Assistant (VBSA) as a collaborator that keeps track of actions. As part of these HMT simulation studies, the impact of each parameter related to machines, humans, and HMT (such as errors made by humans and by the VBSA) is presented from the perspective of performance, rules, roles, and operation limitations. In addition, based on the analysis of results from two case studies, we presented guidelines for designing future HMT. Our conclusions indicate that the proposed HIL can be used to perform standardization studies in the pursuit of developing techniques for benchmarking HMT that can be used in critical situations.

Products derived from Cannabis sativa have gained increased interest and popularity. As these products become common amongst the public, the heath and potential therapeutic values associated with hemp have become a premier focus of research. While the psychoactive and medicinal properties of Cannabis products have been extensively highlighted in literature, the antibacterial properties of CBD have not been explored in depth. This research serves to examine the antibacterial potential of CBD against Salmonella newington and Salmonella typhimurium. In this study we observed bacterial response to CBD exposure through biological assays, bacterial kinetics, and fluorescence microscopy. Additionally, comparative studies between CBD and ampicillin were conducted against Salmonella typhimurium and Salmonella newington to determine comparative efficacy. Furthermore, we observed potential resistance development of our Salmonella spp. against CBD treatment.

Abstract: Given the increasing resistance of some bacterial strains to many common antibiotics used in the local market, the current study aimed to produce nanoscale particles capable of combating pathogenic bacteria that have developed resistance to current antibiotics. In this research, an ex-perimental study was conducted to produce nanoscale particles using the single-celled blue-green algae Synechococcus sp., which was isolated from a local environment in the Arab Republic of Egypt, specifically from a soil sample in Beni-Suef City. The aim of the study was to generate silver NPs employing different biological approaches, encompassing the direct strain powder technique, ethanol extract pellet technique, and ethanol extract technique. These synthesized nanoparticles displayed different shapes, including cubic, spherical, pellet-like, and rod-shaped particles. They were characterized by bio-functional groups containing Ag+ ions, which were detected using FT-IR, Zeta sizer, and Zeta potential measurements. High-resolution SEM imaging unveiled the mor-phological features of Silver NPs with biologically formed protective layers, spanning sizes from 20 to 430 nm for individual particles. The study evaluated the antibacterial efficiency against both G+ve and G-ve bacteria. The ethanolic extract technique exhibited the largest inhibition zone (24 mm) against G+ve bacteria, particularly Staphy. aureus. Furthermore, it was observed that the larger particles produced using the powder and pellet techniques were less effective antibacterial agents. In conclusion, this investigation emphasizes the potential of cyanobacteria-based synthesis of silver nanoparticles as a promising approach for producing innovative antimicrobial agents.

Background: The clinical outcomes of antiretroviral drugs may be modified by drug interactions; thus, it is important to update the drug interactions in people living with HIV. Aim: To update clinically relevant drug interactions in people living with HIV on antiretroviral therapy. Methods: A systematic review in Medline/PubMed database from July 2017 to December 2022, using the Mesh terms: Anti-retroviral agents and drug interactions or herb-drug interactions or food-drug interactions. Publications with drug interactions in humans, in English or Spanish, and with full text were retrieved. The clinical relevance of drug interaction was grouped into 5 levels according to gravity and probability of occurrence. Results: 361 articles were identified and 148 were included, which allowed the identification of 894 drug interaction pairs. Among these 894 drug pairs, 355 have not been identified previously; and 89 (25.1%) and 72 (20.2%) were of levels 1 and 2, respectively. In addition, for 197 (55.5%) pairs the mechanism was pharmacokinetic. The non-nucleoside reverse transcriptase inhibitors (NNRTIs) and the protease inhibitors (PIs) with 91 (25.6%) and 76 (21.4%) pairs, respectively were more frequent. Conclusions: In people living with HIV on antiretroviral therapy, we identify 355 new drug interaction pairs, of them 161 (45.3%) are assessed as levels 1 and 2 and thus, clinically relevant; a figure that is lower compared to 2014-2107 update. The pharmacokinetic mechanism is the most frequently identified. The non-nucleoside reverse transcriptase inhibitors (NNRTIs) and the protease inhibitors (PIs) are the antiretroviral groups with the highest number of clinically relevant drug interactions.

In this review, we discuss novel natural products discovered within the last decade that are reported to have antifungal activity against pathogenic species. Nearly a hundred natural products were identified that originate from bacteria, alga, fungi, sponges and plants. Fungi were the most prolific source of antifungal compounds discovered during the period of review. The structural diversity of these antifungal leads encompasses all the major classes of natural products including polyketides, shikimate metabolites, terpenoids, alkaloids and peptides.

Background: Immunosuppressant blood levels should be measured at regular periods in order to keep them within the therapeutic index. Although LC-MS/MS is preferred as a reliable method, some molecules like radiopaque agents in blood matrix may lead to false results. The aim of this study is to investigate the effect of seven different radiopaque agents on immunosuppressant drugs. Methods: Seven different radiopaque agents were added into control materials containing tacrolimus, everolimus, sirolimus and cyclosporine A drugs. Measurements were performed by LC-MS/MS instrument. The amount of deviations from target values were calculated. Results: Immunosuppressant blood levels significantly changed after the administration of radiopaque agents. Seven different radiopaque products led to false negative results in tacrolimus and cyclosporine A levels at a rate of 19.77% to 44.45%. The smallest deviations were seen in everolimus levels with administration of RM6 (gadodiamide) and in sirolimus levels with RM1 (gadobutrol) at rates of 4.04% and 2.11%, respectively. The highest deviations were observed with RM3 (iohexol) administration in everolimus and sirolimus levels at rates of 153.72% and 171.41%, respectively. Conclusions: False immunosuppressant results associated with radiopaque agents may result in organ rejection. Preferring radiopaque agents that cause the least interference risk is important to reduce the organ rejection risk. However, the least risky method is to obtain samples for drug levels before contrast-enhanced imaging.

CLIPPERS which stand for Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids, is a chronic inflammatory disorder of the central nervous system. The aetiology of CLIPPERS remains unclear, although its pathogenesis shows immune-mediated processes. The diagnosis of CLIPPERS is challenging without a specific biomarker hence, it is important to consider if both the clinical and radiological features are consistent with the diagnosis, or rather any other disease that mimics CLIPPERS. The Authors present a case of a 40-year-old Female patient diagnosed with CLIPPERS syndrome in India. Differential diagnosis, clinical and MRI characteristics of CLIPPERS syndrome, and treatment approaches are discussed.

Phenacoccus manihoti (Hemiptera: Pseudococcidae), is an invasive pest that is very detrimental to cassava cultivation in Indonesia. Control efforts by utilizing natural enemies of the parasitoid have succeeded in overcoming the cassava mealybug in 25 countries such as in Africa and Thailand. The purpose of this study was to specifically evaluate the potential for parasitoid species associated with the mealybug P. manihoti by (1) determining the level of parasitization against mealybugs on various varieties of cassava, (2) determining parasitoid preference for P. manihoti instars, and (3) determining the type of parasitoid. This study was undertaken in the field to re-evaluate the kinds of parasitoids associated with cassava pests, and in the laboratory to assess the amount of parasitization, predilection, and functional response of parasitoids to P. manihoti population density. The findings revealed three of parasitoids linked with P. manihoti in the field: Anagyrus lopezi, Acerophagus sp., and Blepyrus sp. The parasitoid A. lopezi had the greatest parasitization rate in the field, which was 18.67 %. Furthermore, the parasitoids A. lopezi and Blepyrus sp. preferred 3rd instar nymphs, but Acerophagus sp. preferred 2nd instar nymphs. The parasitoid A. lopezi demonstrated a type-III functional response, while Acerophagus sp. and Blepyrus sp. demonstrated a type-II functional response. The handling capacity (Th) of A. lopezi is the shortest at 3.42 minutes. This work is a comprehensive study of the parasitoid A. lopezi's potential as a biological agent, highlighting how it effectively suppresses P. manihoti on various cassava varieties in Bali, providing an inexpensive, environmentally friendly, and applicable control in tropical countries.

Conversational spoken dialogue systems that interact with the user rather than merely reading text can be equipped with hesitations to manage the dialogue flow and the users' attention. Based on a series of empirical studies, we built an elaborated hesitation synthesis strategy for dialogue systems that inserts hesitations of scalable extent wherever needed in the ongoing utterance. So far, evaluations of hesitating systems have shown that synthesis quality is affected negatively by hesitations, but that there is improvement in interaction quality. We argue that due to its conversational nature, hesitation synthesis needs interactive evaluation rather than traditional MOS-based questionnaires. To prove this point, we dually evaluate our system’s speech synthesis component: on the one hand, linked to the dialogue system evaluation, on the other hand, in the traditional MOS way. This way we are able to analyze and discuss differences that arise due to the evaluation methodology. Our results suggest that MOS scales are not sufficient to assess speech synthesis quality, which has implications for future research that are discussed in this paper. Furthermore, our results indicate that hesitations work well to increase task performance and that an elaborated strategy is necessary to avoid likability issues.

Environmental contamination has exposed humans to various metal agents, including mercury. It has been determined that mercury is not only harmful to the health of vulnerable populations such as pregnant women and children, but is also toxic to ordinary adults in various ways. For many years, mercury was used in a wide variety of human activities. Nowadays, the exposure to this metal from both natural and artificial sources is significantly increasing. Recent studies suggest that chronic exposure, even to low concentration levels of mercury, can cause cardiovascular, reproductive and developmental toxicity, neurotoxicity, nephrotoxicity, immunotoxicity, and carcinogenicity. Possible biological effects of mercury, including the relationship between mercury toxicity and diseases of the cardiovascular system, such as hypertension, coronary heart disease and myocardial infarction, are being studied. As heart rhythm and function are under autonomic nervous system control, it has been hypothesized that the neurotoxic effects of mercury might also impact cardiac autonomic function. Mercury exposure could have a long-lasting effect on cardiac parasympathetic activity and some evidence show that mercury exposure might affect heart rate variability, particularly early exposures in children. The mechanism by which mercury produces toxic effects on the cardiovascular system is not fully elucidated, but this mechanism is believed to involve an increase in oxidative stress. The exposure to mercury increases the production of free radicals, potentially because of the role of mercury in the Fenton reaction and a reduction in the activity of antioxidant enzymes, such as glutathione peroxidase. In this review we report an overview on the toxicity of mercury and focus our attention on the toxic effects on the cardiovascular system.

Access to medical care is a global issue. Technology-aided approaches have been applied in addressing this. Interventions have however not focused on medical diagnosis as a fully automated procedure and available applications employ mainly text-based inputs rather than conversation in natural language. We explored the utility of ontology-based chatbot technology for the design of intelligent agents for medical diagnosis through a systematic review of the most recent related literature. English articles published in 2011-2016 returned 233 hits which yielded 11 relevant articles after a 3-stage screening. Findings showed that the creation of expert systems had been the focus of many the studies which utilize the physician-system-patient framework with system training based mostly on expert knowledge for designing web- or mobile phone-based applications that serve assistive purposes. Findings further indicated gaps in the design and evaluation of more effective systems deployable as standalone applications, for example, on an embodied robotic system. The need for technology supporting the physical examination part of diagnosis, connection to data sources on patients’ vitals and medical history are also indicated in addition to the need for more qualitative work on natural language-based interaction. The system should be one that is continuously learning. Future works should also be directed towards the building of more robust knowledge base as well as evaluation of theory-based diagnostic methodological options

52 years have passed since President Nixon launched the "War on Cancer". The goals outlined by the President were not achieved because cancer treatment applied such as chemotherapy, radiotherapy, and targeted therapy have not fully met expectations. We suggest a new chemotherapeutic strategy: disrupting the communication between cancer cells and their microenvironment by chemical means. Immunological synapses that form between cancer cells and immune or other stromal cells provide an attractive target for this approach. Synapses form ligand-receptor clusters within interface of the interacting cells. Despite their differences, synapses share common properties: intercellular protein clusters; the proximity of these proteins; and their cooperative interaction making a synapse an unified functional unit. Synapses provide the limited space for the focused intercellular exchange of signaling molecules and particles. Therefore, destruction of synapses is expected to cause collapse of various tumor types. Additionally, the clustered arrangement of synapse components offers opportunities to increase treatment safety by reducing the concentration of cell impermeable agents used, to enhance its specificity applying cross-linking reagents, thus restricting modifications of surface-exposed molecules. By attaching a cleavable cell permeable toxic agent to a crosslinker should further enhance a killing potential in treating cancer. The proposed approach promises to be simple, universal, and less expensive than existing cancer therapy methods.

Severe Acute Respiratory Disease Syndrome Coronavirus 2 has caused a global pandemic. Monoclonal antibodies, antiviral therapy (Remdesivir) and immunomodulatory agents represent one of the most promising therapies to prevent disease progression and reduce the relative risk of severe COVID-19. The aim of this study was to evaluate the impact on the disease progression of the main pharmacological options approved for the patients admitted in hospital with acute COVID-19 infection, according to their vaccination status.. We conducted a study including adult patients with confirmed COVID-19 admitted to the Infectious Diseases Unit of Alessandria’s Hospital in Italy, from October 2021 to March 2022. 102 patients were included in the analysis. The mean age was 69.2 ±15.4 years, 66.7% were males. According to the internal hospital’s guidelines, 47.06% patients with mild to moderate disease were treated with mAbs, 45.10% were treated with Remdesivir, of which 10.78% received combination therapy with mAbs. The most frequently complications were pneumonia (18.63%), respiratory failure (15.68%) and acute respiratory distress syndrome (13.72%). The mean length of hospitalization was 13.42 (±10.90) days and the mortality rate was 11.76%. The treatment with mAbs and immunomodulatory therapy for mild to moderate COVID-19 infection seem to be effective to improve the outcome reducing disease progression and mortality. C-reactive protein (CRP) and ferritin could be considered a good inflammatory marker of disease progression.

Saponins are a diverse group of naturally occurring plant secondary metabolites present in a wide range of foods ranging from grains, pulses, green leaves to sea creatures. They consist of a hydrophilic sugar moiety linked to a lipophilic aglycone, resulting in an amphiphilic nature and unique functional properties. The amphiphilic structures enable saponins to exhibit surface-active properties, forming stable foams and complexes with various molecules. In the context of food applications, saponins are utilized as natural emulsifiers, foaming agents, and stabilizers. They contribute to texture and stability in food products and have potential health benefits, including cholesterol-lowering and anticancer effects. Saponins possess additional bioactivities that make them valuable in the pharmaceutical industry as anti-inflammatory, antimicrobial, antiviral, and antiparasitic agents to name a few. Saponins can demonstrate cytotoxic activity against cancer cell lines and can also act as adjuvants, enhancing the immune response to vaccines. Their ability to form stable complexes with drugs further expands their potential in drug delivery systems. However, challenges such as bitterness, cytotoxicity, and instability under certain conditions need to be addressed for effective utilization of saponins in foods and related applications. In this paper, we have reviewed chemistry, functionality, and application aspects of saponins from various plant sources and have summarised the regulatory aspects of food application of Quillaja saponins. Further research to explore the full potential of saponins in improving food quality and human health has been suggested. It is expected that this article will be a useful resource for researchers in food, feed, pharmaceutical and material science.

With the evolution of toxic chemicals continuing to progress, developing methods for the destruction of chemical warfare agents (CWAs) has become an increasingly important research topic. Metal-organic frameworks (MOFs) are a class of porous crystalline solids that have sparked interest in this area. Due to their exceptional porosities and large surface areas, MOFs possess superior adsorption, reactivity, and catalytic abilities, making them structurally ideal candidates for the capture and decomposition of target species. Additionally, the tunable networks of MOFs allow their chemical functionalities to be customized for various applications and operating conditions, making them practicable in personal protective equipment and adjustable to dynamic environments. This paper reviews experimental and computational studies on CWA removal by MOFs, with a special emphasis on nerve agent (GB, GD, and VX) removal via hydrolysis and sulfur mustard (HD) removal via selective photooxidation. With extraordinary structural stability and reusability, zirconium-based MOFs are the most promising materials for hydrolytic and photooxidative degradation of CWAs and are thus the primary focus of this work. First-principles approximations of the intrinsic catalytic reaction mechanisms towards different agents in Zr-MOFs are summarized, and developments in the structure-property relationships governing Zr-MOF design rules for efficient degradation in the aqueous and solid phases are discussed. We also examine recent progress in tuning and functionalizing MOFs to promote practical CWA removal under realistic battlefield conditions.

Antibiotics have become a widely used drug classes worldwide. Its indiscriminate use in the clini-cal-hospital environment ended up causing antibiotic-resistance genes. Pharmaceutical technology is an essential ally for new formulation development in the antibacterial field. Cyclodextrins (CDs) are ap-proaches that can potentially improve the effectiveness of antibacterial drugs. Thus, this study aimed to review experimental models using CDs as inclusion complexes to improve antibacterial drugs’ physi-cochemical characteristics and biological activities. The review was carried out using the three online journals database PubMed, Scopus, and Embase, limited to Medical Subjects Headings Index. The search protocol was registered in the Open Science Framework database. The following terms and their com-binations were used: cyclodextrins and antibacterial agents in title or abstract, and a total of 1580 studies were identified in a period up to October 2022. Finally, 27 articles were selected for discussion in this review. The biological results reveal that the antibacterial effect of the compounds, complexed with CDs, was extensively improved when compared to the free drugs. CDs can improve the therapeutic effects of antibiotics, already existing on the market, natural products, and synthetic molecules. Therefore, these inclusion complexes using CDs increase the new pharmaceutical products development for clinical ap-plication.

Improvements in the treatment of childhood cancer have considerably enhanced survival rates over the last decades, to over 80% as per today. However, this great achievement has been accompanied by the occurrence of several early and long-term treatment-related complications major of which is the cardiotoxicity. The chemotherapeutic agents that have been implicated as a cause of cardiotoxicity, are mostly anthracyclines and mitoxantrone, alkylating agents, proteasome inhibitors and to a lesser extent anti-microtubule agents, cisplatin, monoclonal antibodies, small molecular tyrosine kinase inhibitors, and nucleotide synthesis inhibitors. Routine diagnosis and monitoring of cardiotoxicity rely on electrocardiography and echocardiography. For the early detection of cardiotoxicity, in recent years, major studies have been conducted using biomarkers such as troponin, N-terminal pro b-natriuretic peptide, etc. Despite refinements in diagnostics still severe limitations exist, due to the increase of the above-mentioned biomarkers, only after significant cardiac damage has occurred. Lately, research has been expanded by introducing new technologies and finding new markers by omics approach. These new markers could be used not only for early detection, but also for early prevention of cardiotoxicity. The omics science, which includes genomics, transcriptomics, proteomics, and metabolomics, offers new opportunities for biomarker discovery in cardiotoxicity and may provide understanding of mechanisms of cardiotoxicity, beyond traditional technologies. This article reviews the contemporary definition of cardiotoxicity, older and newer chemotherapeutic agents mainly involved in cardiotoxicity and the methods of early and preventive diagnosis, using omics technology.

Organophosphorus nerve agents are amongst the most toxic chemicals known to human beings. 9 They interfere with the central nervous system, resulting in continuous muscle contractions, 10 paralysis and even death. Prohibition by many countries around the world cannot disguise the 11 remaining presence of nerve agents in stockpile storage and governmental deployment, 12 highlighting the dire need for an efficient catalyst to degrade and detoxify nerve agents by 13 hydrolysis. Metal-organic frameworks (MOFs) have raised a few eyebrows for their permanent 14 porosity, precise tunability, and lasting stability. Modern Reticular Chemistry fosters the design and 15 synthesis of well-defined crystalline MOFs with open Lewis acidic metal sites that can catalytically 16 hydrolyze nerve agents both in aqueous solution and in solid state systems, unveiling unparalleled 17 potential for MOF-based personal protection gears. In this review, a summary of the representative 18 catalytically active MOFs in nerve agent hydrolysis is discussed. MOFs are categorized by their 19 reticular structure, emphasizing the capability and mechanistic insights of each single MOF in nerve 20 agent hydrolysis. The author’s perspective on the current challenges and future directions of MOF- 21 based catalysts in real-world protection applications is also provided, which hopefully could shed some 22 light on the future development of commercially available MOF protection suits.

Organically-coated nanomaterials are intensively studied and find numerous applications in a wide range of areas ranging from optics to biomedicine. One of the recent trends in material science is the application of bio-mimetic polydopamine coatings that can be produced on a variety of substrates in a cost-efficient way under mild conditions. Such coatings not only modify the biocompatibility of the material but also add functional amino groups to the surface that can be further modified by classic conjugation techniques. Here we show an alternative strategy of substrates modification using not dopamine but dopamine conjugates. Compared to the classic scheme the proposed strategy allows for separation of the "organic" and "colloidal" stages and simplifies identification and purification steps. Modification with pre-modified dopamine allowed to achieve high active components loading up to 10.5% wt. A series of organo-inorganic hybrids were synthesized and their bioactivity was analyzed.

While the COVID-19 pandemic advances, the scientific community struggles in the search for treatments. Several improvements have been made, including the discovery of clinical efficacy of chloroquine (CQ) in COVID-19 patients, but the effective treatment protocols are still missing. In order to find novel treatment options many scientists utilize the in silico approach to identify compounds that could interfere with the key molecules involved in entrance, replication, or dissemination of the SARS-CoV-2. However, most of the identified molecules are currently not available as pharmacological agents, and assessing their safety and efficacy could take many months. Here, we took a different approach based on the proposed pharmacodynamic model of CQ in COVID-19. The main mechanism of action responsible for the favourable outcome of COVID-19 patients treated with CQ seems to be related to pH modulation-mediated effect on the endolysosomal trafficking, a characteristic of chemical compounds often called lysosomotropic agents because of the physico-chemical properties that enable them to passively diffuse through the endosomal membrane and undergo protonation-based trapping in the lumen of the acidic vesicles. In this review, we discuss lysosomotropic and lysosome targeting drugs that are already in clinical use and are characterized by good safety profiles, low cost, and wide availability. We emphasize that some of these drugs, in particular azithromycin and other macrolide antibiotics, indomethacin and some other non-steroidal anti-inflammatory drugs, proton pump inhibitors, and fluoxetine could provide additional therapeutic benefits in addition to the potential antiviral effect that still has to be confirmed by well-controlled clinical trials. As some of these drugs, mostly antibiotics, were already empirically used in the treatment of COVID-19, we encourage our colleagues all over the world to publish patient data so potential efficacy of these agents can be evaluated in the clinical context and rapidly implemented in the therapeutic protocols if the beneficial effect on clinical outcome is observed.

What drives an individual police officer to activate his body-worn camera (BWC)? Some evidence suggests officer attitudes and resistance to the technology contributes to the equivocal results in studies testing for BWCs effect on use-of-force, complaints, and other outcomes of interest. Leveraging a novel survey and administrative dataset, we investigate the predictors of BWC activation among 147 police officers in a single agency. With a test of three nested models, we find job function covariates offer robust predictive power of how often an officer activates her or his BWC. Neither demographic nor attitudinal measures significantly predict BWC activations, except for a negative relationship with how officers perceive BWC impacts on professional discretion. The study furnishes empirical support for understanding officers as Principled Agents: job function, guided by administrative policy is the most explanatory and parsimonious, while models of attitudes and demographics fail to improve upon the job function model.

PZT-Poly(vinylidene fluoride) composites were prepared by hot-pressing method. Before addition, PZT particles were firstly modified with two different coupling agents. The micromorphology, microstructure, dielectric properties, and piezoelectric properties of the composites were characterized and investigated. Results indicated that PZT particles were homogeneously dispersed in the PVDF matrix by the addition of coupling agents. The electric properties of PZT-PVDF composites with NDZ-101 were the best. Especially when the volume ratio of the titanate coupling agent NDZ-101 was 1%, the piezoelectric strain constant d33 of PZT-PVDF composites reached maximum value 19.23pC/N; its relative dielectric constant εr was 67.45; at the same time its dielectric loss tanδ was 0.0766.

The present review focuses on recent clinical trials that analyze the efficacy of intravitreal therapeutic agents for the treatment of dry age-related macular degeneration (AMD), such as neuroprotective drugs, and complement inhibitors, also called immunomodulatory or anti-inflammatory. A systematic literature search was performed to identify randomized controlled trials published prior to January 2019. Patients affected by dry AMD treated with intravitreal therapeutic agents were included. The changes in the correct visual acuity and the reduction in geographic atrophy progression were evaluated. Several new drugs have shown some promising results, including those targeting the complement cascade and agents called neuroprotective. The action potential of the two groups of drugs is to block the complement cascade model for immunomodulating agents, and prevent the degeneration and apoptosis of ganglion cells for the neuroprotectors, respectively. To the best of knowledge, and after extensive studies on the matter, there are still many investigations to be carried out on dry AMD in collaboration between researchers. They will have to identify truly effective molecules, understand the practical potential of pluripotent stem cells, and refine gene therapies. Only in-depth clinical trials will be able to allow the most appropriate and personalized treatments for each dry AMD patient.

Chatbots are intelligent conversational computer systems designed to mimic human conversation to enable automated online guidance and support. The increased benefits of chatbots led to their wide adoption by many industries in order to provide virtual assistance to customers. Chatbots utilise methods and algorithms from two Artificial Intelligence domains: Natural Language Processing and Machine Learning. However, there are many challenges and limitations in their application. In this survey we review recent advances on chatbots, where Artificial Intelligence and Natural Language processing are used. We highlight the main challenges and limitations of current work and make recommendations for future research investigation

Antimicrobial Peptides (AMPs), as immune effectors synthesized by a variety of organisms, not only constitute a robust defense mechanism against a broad spectrum of pathogens in the host, but also show promising applications as effective antimicrobial agents. Notably, insects are significant reservoirs of natural AMPs. However, the complex array of variations in types, quantities, antimicrobial activities, production pathways of AMPs, and evolution of AMPs across insect species presents a significant challenge for immunity system understanding and AMP applications. This review covers insect AMP discoveries, classification, common properties, and mechanisms of action. Additionally, we summarize the types, quantities, and activities of im-mune-related AMPs in each model insect. We also conducted the first comprehensive investigation into the diversity, distribution, and evolution of 20 types of AMPs in model insects, employing phylogenetic analysis to describe their evolutionary relationships and shed light on conserved and distinctive AMP families. Furthermore, we summarize the regulatory pathways of AMP production through classical signaling pathways and additional pathways associated with Nitric Oxide, insulin-like signaling, and hormones. This review advances our understanding of AMP as guardians in insect immunity system and also unlocks a gateway to insect AMP resources, facilitating the use of AMPs to address food safety concerns.

The development of new and effective antimicrobial compounds is an urgent need with the emergence of resistant bacteria. Natural plant flavonoids are known to be effective molecules but their activity and selectivity have to be increased. Based on previous aurone potency, we designed new aurone derivatives bearing acetamido and amino groups at the position 5 of the A ring and managing various monosubstitutions at the B ring. A series of 31 new aurone derivatives were first evaluated for their antimicrobial activity with five derivatives being the most active (compounds 10, 12, 15, 16, and 20). The evaluation of their cytotoxicity on human cells and of their therapeutic index (TI) showed that compounds 10 and 20 have the highest TI. Finally, screening against a large panel of pathogens confirmed that compounds 10 and 20 possess a large spectrum antimicrobial activity, including on bioweapon BSL3 strains, with MIC values as low as 0.78 µM. These results demonstrate that 5-acetamidoaurones are far more active and safest compared with 5-aminoaurones, and that benzyloxy and isopropyl substitutions at the B ring are the most promising strategy in the exploration of new antimicrobial aurones.

The Distributed eLearning Center (DeLC) is a portal, providing extensive support in the day-to-day work when it comes to e-learning content – it helps students and teachers organize their learning materials, fill the gaps in knowledge (for students) and educational approaches (for teachers), organize and conduct exams, and overall, with providing proactive and personalized e-learning environment. The scope of DeLC as a project involves many extensions, covering the aspects of learning, teaching, exams, and collecting statistical information. Such extension is an agent-oriented environment, which enriches the functionalities with intelligent components, that are reactive and proactive, referred to as agents or assistants. This paper is focused on presenting the latest step in the evolution of FraudDetector software agent, which started with base functionality for fraud detection, and now it aims at usage of AI to accomplish its tasks, taking advantage not only from its knowledgebase, but from a much larger one, used by ChatGPT – through integration with it, which is the main contribution of this research, although the real results from production environment are still pending. In this process, agent’s architecture should stay open for collaboration with another external AI provider if necessary, trying to decouple the components, responsible for integration. As of now, the experiments show that involving ChatGPT in FraudDetector’s functionality enriches it and the agent’s precision could be improved this way.

Artificial intelligence (AI) agents are widely used in the retail and distribution industry, often in-corporating human-like elements such as possessing names and genders. This paper examines the influence of AI agent gender and brand concepts on trust and grounding within virtual brand spaces; exploring the correlation between user identification with AI agents and subsequent brand recommendations. The study revealed that in virtual brand spaces centered around a functional concept, male AI agents generated higher levels of trust than female AI agents, whereas, when focused on an experiential concept, female AI agents induced higher levels of grounding than male AI agents. Furthermore, this research indicates that the association between customers’ iden-tification with AI agents and recommendations for actual brand purchases is mediated by trust and grounding. These findings support the idea that users who strongly identify with AI agents are more inclined to recommend brand products after engaging in conversations within the virtu-al brand space.

Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by itching, impaired epidermal barrier function and unbalanced inflammatory response. The pathophysiology involves immune dysregulation, with a predominance of T-helper 2 cells. AD is triggered by many known and unknown factors, including oxidative stress. Reactive oxygen species (ROS) contribute to AD pathogenesis by causing cellular damage and inflammation. Moreover, increased oxidative stress in AD leads to hyperactivation of the MAP kinase pathway, extracellular signal-regulated kinase (ERK) and p38, with DNA damage and subsequent skin barrier dysfunction. This narrative review provides a comprehensive overview of the role of natural antioxidant compounds, highlighting their potential therapeutic value in AD management. They include vitamin D, vitamin E, pyridoxine (vitamin B6), Vitamin C, carotenoids and melatonin, in AD. Despite some studies have shown an association between vitamin D, vitamin E, vitamin C and carotenoids levels and AD course, conflicting results exist. Pyridoxine supplementation has shown mixed results, and melatonin has demonstrated antioxidant and anti-inflammatory properties in AD; in fact, melatonin treatment resulted in a decrease in symptoms in patients with AD, although no significant correlation with changes in sleep latency was reported. In addition, iron and zinc (Zn) supplementation can also improve AD symptoms. Further research is needed to elucidate the optimal use of these natural antioxidants in AD treatment

In large industrial plants, the trend is to move the position of the human to the area of service and diagnostics, in medium and smaller plants the trend is different and is mainly directed to the sphere of close cooperation between the human and the robotic system. This paper deals with the implementation of human-cooperating robots in manufacturing processes. The analytical part of the paper deals with theoretical knowledge, taking into account the latest trends in the subject area. To achieve a successful implementation of cobots based on the above-mentioned operating systems in manufacturing systems, it is necessary to pay attention specifically to the interfacing of the robotic operating system with the control systems of the manufacturing systems at the process level of the enterprise. Within the practical part, an algorithm with well-defined steps towards the successful implementation of cobots in holonic manufacturing processes is proposed. By setting up an experimental workstation in the laboratory, the proposed procedures are verified at the end of the paper. In the context of the implementation of collaborative robots in enterprises, the paper also discusses cloud computing. The creation of a design for the implementation of a collaborative robot with a human represents the missing link in the whole chain of commercial applications of the latest trends from the field of robotic systems in the industrial sphere.

New generation antibiotics are needed to combat the development of resistance to antimicrobials. One of the most promising new classes of antibiotics is cannabidiol (CBD). It is a non-toxic and low-resistance chemical that can be used to treat bacterial infections. The antibacterial activity of Cannabis sativa L. byproducts, specifically CBD, has been of growing interest in the field of novel therapeutics. As research continues to define and characterize the antibacterial activity that CBD possesses against a wide variety of bacterial species it is important to examine potential interaction between CBD and common therapeutics such as broad-spectrum antibiotics. Here, we show that CBD-antibiotic co-therapy can effectively fight S. typhimurium via membrane integrity disruption. This research serves to examine the potential synergy between CBD and three broad-spectrum antibiotics for potential antibiotic-CBD co-therapy. In this study, we reveal that Salmonella typhimurium (S. typhimurium) growth is inhibited at very low dosages of CBD-antibiotic. This interesting finding demonstrates that CBD and CBD-antibiotic co-therapies are viable novel alternatives to combating Salmonella typhimurium.

Lung cancer (LC) is one of the leading causes of cancer occurrence and mortality worldwide. Treatment of patients with advanced and metastatic LC presents a significant challenge as malignant cells use different mechanisms to resist chemotherapy. Drug resistance (DR) is a complex process that occurs due to a variety of genetic and acquired factors. Identifying the mechanisms underlying DR in LC patients and possible therapeutic alternatives for more efficient therapy is a central goal of LC research. Advances in nanotechnology resulted in the development of targeted and multifunctional nanoscale drug constructs. The possible modulation of the components of nanomedicine, their surface functionalization, and encapsulation of various active therapeutics provide promising tools to bypass crucial biological barriers. These attributes enhance the delivery of multiple therapeutic agents directly to the tumor microenvironment (TME), resulting in reversal of LC resistance to anticancer treatment. This review provides a broad framework for understanding the different molecular mechanisms of DR in lung cancer; presents novel nanomedicine therapeutics aimed to improve the efficacy of treatment of various forms of resistant LC; outlines current challenges in using nanotechnology for reversing DR; and discusses the future directions for clinical application of nanomedicine in management of LC resistance.

The treatment of benzylidenemalononitriles 3a-c with phenylhydrazines 4a-n in refluxing ethanol did not provide pyrazole derivatives but furnished hydrazones 1a-o. The structure of hydrazones was secured by X-Ray analysis. Newly synthesized hydrazones 1a-o were tested against 8 Candida spp. strains in a dose response assay to determine the minimum inhibitory concentration (MIC99). Five compounds 1c, 1d, 1i, 1k and 1l were identified as promising antifungal agents against Candida spp. (C. albicans SC5314, C. glabrata, C. tropicalis, C. parapsilosis and C. glabrata (R azoles)) with MIC99 values ranging from 16 to 32 µg/mL. To further evaluate the antifungal potential of the active compounds, they have been assayed against a mammalian cell line HEK293 to determine general cell toxicity and on NCI-60 cancer cell lines panel, demonstrating selectivity antifungal activity over cytotoxicity.

Presently, nano-crystallization is widely accepted for increasing the solubility and biological barrier permeability of poorly soluble drugs. It improves the bioavailability of therapeutic agents, increasing the effectiveness for treating diseased conditions, and could be safely administered by oral, parenteral, or transdermal routes. Drug nanocrystals are drug particles coated with a thin polymer layer to enhance their stability and could be decorated with ligands for active targeting. In addition, nanocrystals, due to their morphological properties, improve cell internalization. Therefore, passive targeting by high cellular uptake and retention in the mononuclear phagocyte system (MPS) may be expected. Drug nanocrystals are formulated by either top-down or bottom-up methods and could be scaled up for industrial manufacturing. In the past few decades, nanocrystal formulation has been increasingly studied to overcome the limitations of BCS Class II and IV chemotherapeutic agents. The study of cytotoxic effects of drug formulation on cell lines gives an insight for estimating its in-vivo biodistribution. This review highlights the role of morphology, stabilizer, and ligand conjugation on drug targeting and cellular uptake in cancer cells, as well as a brief discussion on nanocrystal production.

Influenza is a highly contagious, acute respiratory illness, which represents one of the main health issues worldwide. Even though some antivirals are available, the alarming increase of virus strains resistant to them highlights the need to find new drugs. Previously, Superti et al. have deeper investigated the mechanism of the anti-Influenza virus effect of bovine Lactoferrin (bLf) and the role of its tryptic fragments (the N and C-lobes) in the antiviral activity. Recently, through a truncation library, we identified the tetrapeptides, SKHS (1) and SLDC (2), derived from bLf C-lobe fragment 418-429, which were able to bind hemagglutinin (HA) and inhibit cell infection in a concentration range of femto- to picomolar. Starting from these results, in this work, we initiated a systematic SAR study on the peptides mentioned above, through an Alanine scanning approach. We carried out binding affinity measurements by microscale thermophoresis (MST) and Surface Plasmon Resonance (SPR), and hemagglutination inhibition (HI) and virus neutralization (NT) assays on synthesized peptides. Computational studies were performed to identify possible lig-and-HA interactions. Results obtained led to the identification of an interesting peptide endowed with broad anti-Influenza activity and able to inhibit viral infection to a greater extent of reference peptide.

This review revisits clinical use of antibiotics for most common acute oro-dental conditions; we aim to provide evidence governing antibiotics use when access to oral healthcare is not available, as during the ongoing outbreak of the severe acute respiratory syndrome coronavirus 2. In this rapid review, articles were retrieved after conducting a search on PubMed and Google Scholar. Relevant publications were selected and analyzed. Most recent systematic reviews with/without meta-analyses and societal guidelines were selected. Data were extracted, grouped, and synthesized according to the respective subtopic analysis. There were evidence supporting the use of antibiotics in common oro-dental conditions as temporary measure when immediate care is not accessible, such as in case of localized oral swellings as well as to prevent post-extraction complications. No sufficient evidence could be found in support of antibiotic use for pain resulting from pulpal origin. Consequently, antibiotic use may be justified to defer treatment temporarily or reduce risk of complications in case of localized infection and tooth extraction, when no access to immediate dental care is possible.

Japanese encephalitis is a zoonotic disease caused by Japanese encephalitis virus (JEV). It is mainly epidemic in Asia with an estimated 69,000 cases occurring per year. However, no approved agents are available for the treatment of JEV infection, and existing vaccines cannot resist various types of JEV strains. Drug repurposing is a new concept for finding new indication of existing drugs, and recently, it has been used to discover new antiviral agents. Identifying host proteins involved in the progress of JEV infection and using these proteins as targets are the center of drug repurposing for JEV infection. In this study, based on the gene expression data of JEV infection and the phenome-wide association study (PheWAS) data, we identified 286 genes participating in the progress of JEV infection using the systems biology methods. The enrichment analysis of these genes suggested that the genes identified by our methods were predominantly related to viral infection pathways and immune response-related pathways. We found that bortezomib which can target these genes may have potential effect on the treatment of JEV infection. Subsequently, we evaluated the antiviral activity of bortezomib using the JEV-infected mice model. The results showed that bortezomib can lower JEV-induced lethality in mice, alleviate suffering in JEV-infected mice and reduce the damage in brains caused by JEV infection. This work provides a new method for the development of antiviral agents.

Carbon nanotubes are hybridized with metal crystals to impart multifunctionality into the nanohybrids (NHs). Simple but effective synthesis techniques are desired to form both zero-valent and oxides of different metal species on carbon nanotube surfaces. Sol-gel technique brings in significant advantages and is a viable technique for such synthesis. This study probes the efficacy of sol-gel process and aims to identify underlying mechanisms of crystal formation. Standard electron potential (SEP) is used as a guiding parameter to choose the metal species; i.e., highly negative SEP (e.g., Zn) with oxide crystal tendency, highly positive SEP (e.g., Ag) with zero-valent crystal-tendency, and intermediate range SEP (e.g., Cu) to probe the oxidation tendency in crystal formation are chosen. Transmission electron microscopy and X-ray diffraction are used to evaluate the synthesized NHs. Results indicate that SEP can be a reliable guide for the resulting crystalline phase of a certain metal species, particularly when the magnitude of this parameter is relatively high. However, for intermediate range SEP-metals, mix phase crystals can be expected. For example, Cu will form Cu₂O and zero-valent Cu crystals, unless the synthesis is performed in a reducing environment.

Research on the chemical mechanism and reciprocal behavior of the coronavirus relate to living organisms, engaging in the give and take of electrochemical mediators, is a very important, controversial and vital issue. What we should accept is the chemical identity of this scenario, and not preferably a characteristic of a biological system. This chemical reaction should be familiar, referring to the theory of chemical pathways involved in DNA/proteins in the body against aggressive guests (such as viruses). From the point of view of a chemist, this simple reaction is nothing more than an oxidation-reduction reaction (redox-stress signaling) which conducted and carried out by coronavirus in a biointerface medium. Thereby, oxidizing as well as reducing reagents should be very constructive, promoting development in such chemical process. We understand redox reactions as switchable thiol/disulfide exchanges (formation and cleavage of inherent disulfide bonds), then, we can hugely profit from redox-responsive nano-surfaces equipped with multiple new ionic and covalent interactions. This game-changing idea can substantiate by surface modified-nanoparticles to play powerful roles in synthesis of nano oxidizers as well as reducing agents in nanomedicine. Chemists and pharmacists must then explore new thoughts and present modern experiences/approaches of preparation nanoparticles and nanocomposites to create novel vaccines as well as coronavirus drugs. In this regard, this experience can also be so helpful for HIV/AIDS, which is caused by viruses.

Hepatitis C virus (HCV) is an oncogenic virus that causes chronic liver disease in more than 80% of patients. During the last decade, efficient direct acting antivirals were introduced into clinical practice. However, clearance of the virus does not reduce risk of end-stage liver diseases to the level observed in patients that have never been infected. So, investigation of HCV pathogenesis is still warranted. Virus-induced changes in cell metabolism contribute to the development of HCV-associated liver pathologies. Here we studied the impact of the virus on the metabolism of polyamines and proline as well as on the urea cycle, which plays a crucial role in liver function. It was found that HCV strongly suppresses the expression of arginase, a key enzyme of the urea cycle, leading to accumulation of arginine and upregulates proline oxidase with a concomitant decrease in proline concentrations. Addition of exogenous proline moderately suppressed viral replication. HCV upregulated transcription but suppressed protein levels of polyamine-metabolizing enzymes. This resulted in a decrease in polyamine content in infected cells. Finally, compounds targeting polyamine metabolism demonstrated pronounced antiviral activity pointing to spermine and spermidine as compounds affecting HCV replication. These data expand our understanding of HCV’s imprint on cell metabolism.

This Systematic Review examines studies focusing on tooth bleaching and its effect on healthy enamel or incipient caries and bacterial adhesion. The aim is to explore the impact of different bleaching agents on incipient caries lesions and healthy enamel. Randomized controlled trials, clinical trials, observational studies, and in vitro studies that compared at least two groups were included. A comprehensive search strategy was used to select studies from Pubmed and Scopus databases. Two evaluators performed data extraction, screening, and quality assessment independently. Only studies written in English were included. From 968 initial records, 28 studies were selected for a full-text evaluation. 7 studies were classified as cluster 1 (bacterial adherence on teeth), 12 studies as cluster 2 (no bacteria involved), 4 studies as cluster 3 (no teeth deployment), and 5 clinical studies were cluster 4. Of the selected studies, 6 (21.43%) supported increased bacterial attachment capacity and cariogenic dynamics, 4 (14.29%) decreased adhesion and cariogenic activity, 7 (25%) no difference, and 11 (39.28%) followed a differentiated methodological approach and could not be categorized. Due to different methodology strategies used in the studies of all clusters, the risk of bias was high. Thus, we cannot reach a confident conclusion.

Four 1,10-phenanthroline derivatives (1-4) have been synthesized as potential telomeric DNA binders, three substituted in their chains with thiosemicarbazones (TSCs), the neutral compound (1) and two ionic derivatives (PF6¯ and BF4¯ salts, 2 and 3, respectively), and a fourth corresponding to a 4-phenylthiazole derivative (4). Quadruplex and dsDNA interactions have been preliminarily studied, especially for the neutral derivative 1, by FRET-based DNA melting assays, equilibrium dialysis (both competitive and non-competitive), circular dichroism and viscosity titrations. The TSC derivatives bind and stabilize the telomeric Tel22 quadruplex more efficiently than dsDNA, with an estimated 24-fold selectivity determined by equilibrium dialysis for compound 1. In addition, cytotoxic activity against different tumor cells (PC-3, DU145, HeLa, MCF-7 and HT29), and two non-tumor cell lines (HFF-1 and RWPE-1) has been evaluated. Except for the 4-phenylthiazole derivative, which was inactive, the compounds show moderate cytotoxic properties, with the salts displaying lower IC50 values, compared to the neutral TSC. However, the neutral derivative was the only compound that exhibited a modest selectivity in the case of prostate cells (tumor PC-3 versus healthy RWPE-1). Cell cycle analysis and Annexin V/PI assays revealed that the compounds can produce cell death by apoptosis, an effect that has proven similar to that demonstrated by other known 1,10-phenanthroline G4 ligands endowed with antitumor properties, such as PhenDC3 or PhenQE8.

Diarrhea-related mortality remains an important public health concern, particularly in developing countries, and has become difficult to treat because of antibacterial resistance. The development of synergistic antimicrobial agents appears to be a promising alternative treatment against diar-rheal infections. In this study, the combined effect of tetracycline together with either nitroxoline, sanguinarine, or zinc pyrithione (representing various classes of alkaloid-related compounds) was evaluated in vitro against selected diarrheagenic bacteria (Enterococcus faecalis, Escherichia coli, Listeria monocytogenes, Shigella flexneri, Vibrio parahaemolyticus, and Yersinia enterocolitica). The chequerboard method in 96-well microtiter plates was used to determine the sum of the fractional inhibitory concentration indices (FICIs). Three independent experiments were performed per combination, each in triplicate. It was observed that the combinations of tetracycline with either nitroxoline, sanguinarine, or zinc pyrithione produced synergistic effects against most of the pathogenic bacteria tested, with FICI values ranging from 0.086 to 0.5. Tetracycline-nitroxoline combinations produced the greatest synergistic action against S. flexneri at a FICI value of 0.086. Combinations of the agents tested in this study can thus be used for the development of new anti-diarrheal medications. However, studies focusing on their in vivo anti-diarrheal activity and safety are required before any consideration for utilization in human medicine.

Stevia rebaudiana (Bert.) is a natural sweetener with diterpenic glycosides, offering 300 times more sweetness than sucrose, and boasting low-calorie content, along with medicinal and therapeutic properties. To address a limited genetic diversity, a germplasm bank comprising 115 segregated lines of stevia was established in Colombia. Notwithstanding, the fungus Athelia rolfsii adversely impacted key stevia lines, leading to wilting and plant mortality. For this reason our study aimed to explore the biocontrol potential of native strains of Trichoderma spp., isolated from productive lots in Colombia's Cordoba department, as a solution to manage A. rolfsii. Soil samples underwent serial dilution technique (103 conidia.mL-1) to obtain Trichoderma spp. isolates, which were thoroughly morphologically and molecularly characterized. A total five native strains were identified through sequencing the PCR products using universal ITS primers, and comparisons with the GENBANK database confirmed their identity (OK310695.1, ON237703.1, ON238106.1, ON237737.1, and ON237923.1). Their biocontrol efficacy against A. rolfsii was evaluated using the dual culture technique. Remarkably, all strains exhibited significant biocontrol capacity against the A. rolfsii isolate INVEPAR-05 (OK271308.1), except for Trichoderma viride INVEPAR-T10 (ON237923.1). These findings suggest that Trichoderma spp. could be a potential option to manage the fungus in stevia.

Phytoalexins are naturally-occurring molecules with antimicrobial activity deriving from the secondary metabolism of plants, which are synthesized in response to physical agents or stresses, phytopathogenic agents (fungi, bacteria and viruses) as well as numerous chemical compounds and biological control agents. Among these, grapevine phytoalexins, which belong to the chem-ical group of stilbenes, exhibit biocidal activity against a large number and a variety of plant pathogens. An important issue in research on these compounds is to be able to stimulate their synthesis in planta and to determine whether the induction of their production can serve as a basis for protecting that plant against its pathogens. Quite a few chemical compounds, derivatives of phytohormones bio-elicitors as well as biocontrol agents have been used to induce the synthesis of stilbene phytoalexins with the aim of conferring protection to grapevine against its main dis-eases (gray mold, downy mildew, powdery mildew and esca). This article reviews the experi-ments that have been carried out in this direction during the last thirty years and shows that the observed protective effects towards pathogens are generally linked to induction and priming of the grapevine phytoalexin response, confirming the interest of using, in a more general way, stimulation of the production of phytoalexins in plants as a basis for crop protection.

As the COVID-19 pandemic progresses, new variants of SARS-CoV-2 continue to emerge. This underscores the need to develop optimized tools to study such variants, as well as new coronaviruses that may arise in the future, and to use them for antiviral drug development. Here we introduce microscale thermophoresis (MST) as a reliable and versatile tool for coronavirus research, which we demonstrate through three different applications described in this report: 1) binding of the SARS-CoV-2 spike receptor binding domain (RBD) to peptides as a strategy to prevent virus entry, 2) binding of the RBD to the viral receptor ACE2, and 3) binding of the RBD to ACE2 in complex with the amino acid transporter SLC6A20/SIT1 or its allelic variant rs61731475 (p.Ile529Val). Our results demonstrate that MST is a highly precise approach to study protein-protein and/or protein-ligand interactions in coronavirus research, making it an ideal tool for studying viral variants and developing antiviral agents. The ability to measure interactions with proteins in their near-native plasma membrane environment is a unique advantage of the MST assay over other available binding assays.

Hemorrhage is a detrimental event present in traumatic injury, surgery, and disorders of bleeding, that can become life-threatening if not properly managed. Moreover, uncontrolled bleeding can complicate surgical interventions, altering the outcome of surgical procedures. Therefore, to reduce the risk of complications and decrease the risk of morbidity and mortality associated with hemorrhage, it is necessary to use an effective hemostatic agent that ensures immediate control of bleeding. In recent years, there have been increasingly rapid advances in developing novel generation of biomaterials with hemostatic properties. Nowadays, a wide array of topical hemostatic agents is available, including chitosan-based biomaterials that have shown outstanding properties such as: antibacterial, antifungal, hemostatic, analgesic activity, in addition to their biocompatibility, biodegradability, and wound-healing effects. This review provides an analysis of chitosan-based hemostatic and discusses the progress made in their performance, mechanism of action, efficacy, cost, and safety in recent years.

Oligosaccharides derived from λ-carrageenan (λ-COs) are gaining interest in the cancer field. They have been recently reported to regulate heparanase (HPSE) activity, a protumor enzyme involved in cancer cell migration and invasion, making them very promising molecules for new therapeutic applications. However, one of the specific features of commercial λ-carrageenan (λ-CARs) is that they are in fact heterogeneous mixtures of different CARs families, and are named according to the thickening purpose of the product which does not reflect the real com-position. Consequently, this can limit their use in a clinical grade. To address this issue, six commercial λ-CARs were compared for which differences in their physiochemical properties were shown. Then, a H2O2-assissed radical depolymerization was applied to each commercial source and the number and weight averaged molar masses (Mn and Mw) and sulfation degree (DS) of the λ-COs produced over time were determined. By adjusting the depolymerization time for each product, almost comparable λ-CO formulations could be obtained in term of molar masses and DS, that ranged within previously reported values suitable for anti-tumor proper-ties. However, when the anti-HPSE activity of these new λ-COs was screened, small changes that could not be attributed only to their small length or DS changes between them were found, suggesting a role of other features such as differences in the initial mixture composition. Further structural MS and NMR analysis revealed indeed qualitative and semi-quantitative differences between the molecular species, especially in the proportion of the anti-HPSE λ-type, other CARs types and adjuvants, but also showed that H2O2-based hydrolysis induced sugar degradation. Finally, when the effects of λ-COs were assessed in an in vitro migration cell-based model, they seemed more related to the proportion of other CAR types in the formulation than to their λ-type-dependent anti-HPSE activity.

The emergence of drug resistant pathogenic bacteria is increasingly challenging conventional antibiotics. Plant derived flavonoids are considered as potential alternatives to antibiotics due to their antimicrobial properties. However, the mechanisms by which flavonoids modulate pathogenic microorganisms’ growth are not fully understood. In our previous studies we found that Rutin, a kind of flavonoids showed inhibition against Klebsiella pneumoniae strains. In order to better understand its inhibitory mechanism on strain growth, we used both Rutin and Luteolin as treatments to incubate K. pneumoniae ATCC700603 strain. After incubation for 4 hours, the homogenous and differential effects of two different flavonoids on the growth of K. pneumoniae were evaluated. The integrated metabolomic and transcriptomic analysis was performed. The expression levels of 5,483 genes and the contents of 882 metabolites were measured. The differentially expressed genes (DEGs) and metabolites (DEMs) were screened and analyzed. The correlation between DEGs and DEMs were also studied. Our results showed that Rutin could inhibit the strain growth by changing metabolic pathways and ABC transporters pathways. Our study also revealed FU841_RS17580 and FU841_RS19145 as functional genes that played vital roles in the strain growth.

Purpose: To assess the utility of measurement of the computed tomography (CT) attenuation value (CTav) in predicting tumor necrosis in hepatocellular carcinoma (HCC) patients who achieve a complete response (CR), defined using modified Response Evaluation Criteria in Solid Tumors (mRECIST), after lenvatinib treatment. Method: We compared CTav in arterial phase CT images with postoperative histopathology in four patients who underwent HCC resection after lenvatinib treatment, to determine CTav thresholds indicative of histological necrosis (N-CTav). Next, we confirmed the accuracy of the determined N-CTav in 15 cases with histopathologically proven necrosis in surgical specimens. Furthermore, the percentage of the tumor with N-CTav, i.e. the N-CTav occupancy rate, assessed using Image J software in 30 tumors in 12 patients with CR out of 571 HCC patients treated with lenvatinib, and its correlation with local recurrence following CR were examined. Results: Receiver operating characteristic (ROC) curve analysis revealed an optimal cut-off value of CTav of 30.2 HU, with 90.0% specificity and 65.0% sensitivity in discriminating between pathologically identified necrosis and degeneration, with a CTav of less than 30.2 HU indicating necrosis after lenvatinib treatment (N30-CTav). Furthermore, the optimal cut-off value of 30.6% for the N30-CTav occupancy rate by ROC analysis was a significant indicator of local recurrence following CR with 76.9% specificity and sensitivity (area under the ROC curve; 0.939), with the CR group with high N30-CTav occupancy (>30.6%) after lenvatinib treatment showing significantly lower local recurrence (8.3% at 1 year) compared with the low (<30.6%) N30-CTav group (P<0.001, 61.5% at 1 year). Conclusion: The cut-off value of 30.2 HU for CTav (N30-CTav) might be appropriate for identifying post-lenvatinib necrosis in HCC, and an N30-CTav occupancy rate of >30.6% might be a　predictor of maintenance of CR. Use of these indicators have the potential to impact systemic chemotherapy for HCC.

The morbidity and mortality caused by invasive fungal infections is increasing across the globe due to developments in transplant surgery, the use of immunosuppressive agents, and the emergence of drug-resistant fungal strains, which has led to a challenge in terms of treatment due to the limitations of three classes of drugs. Hence, it is imperative to establish effective strategies to identify and design new antifungal drugs. Drug repurposing is an effective way of expanding the application of existing drugs. In the last years, various existing drugs have been shown to be useful in the prevention and treatment of the invasive fungi. In this review, we summarize the currently used antifungal agents. In addition, the most up to date information on the effectiveness of existing drugs with antifungal activity is discussed. Moreover, the antifungal mechanisms of existing drugs are highlighted. These data will provide valuable knowledge to stimulate further investigation and clinical application in this field.

The search for new antibacterial agents that could decrease bacterial resistance is a subject that is continuously developing. The Gram-negative and Gram-positive bacteria have a metalloproteins group belonging to the M4 family. That is the main virulence factor of these bacteria. In this work, we have used a computational protocol based on the comprehensive analysis of the results of docking, molecular dynamics simulation, MM-PBSA, ligand efficiency, and ADME-Tox properties of ligand designed in silico in the previous manuscript using the Thermolysin from Bacillus thermoproteolyticus, a metalloprotein of the M4 family as a target. The principal results obtained were the designed ligands were adequately oriented in the thermolysin active center. The Lig783, Lig2177, and Lig3444 compounds were those with better dynamic behavior, however, when analyzing the results extracted from the ADME-Tox properties, only Lig783 was the best antibacterial agent candidate.

In this study, we examine the relationship of bank level lending and borrowing decisions and the risk preferences on the dynamics of the interbank lending We develop an agent-based model that incorporates individual bank decisions using the temporal difference reinforcement learning algorithm with empirical data of 6600 S. banks. The model can successfully replicate the key characteristics of interbank lending and borrowing relationships documented in the recent literatur A key finding of this study is that risk preferences at individual bank level can lead to unique interbank market structures which are suggestive of the capacity that the market responds to surprising

Biopolymers are of growing interest, but to improve some of their poor properties and performance, it is required the formulation of bio-based blends and/or adding of nanoparticles. For this purpose, in this work, two different metal oxides, such as zinc oxide (ZnO) and titanium dioxide (TiO2), at different concentrations (0.5, 1 and 2 %wt.) have been added in polylactic acid (PLA) and polylactic acid/polyamide 11 (PLA/PA11) blends to establish their effects on solid-state properties, morphology, melt behaviour, and photo-oxidation resistance. It seems that the addition of ZnO in PLA leads to a significant reduction of its rigidity probably due to an inefficient dispersion in the melt state, while the addition of TiO2 does not penalise PLA rigidity. Interestingly, the addition of both ZnO and TiO2 in PLA/PA11 blend has a positive effect on the rigidity because of blend morphology refinement and leads to a slight increase in film hydrophobicity. The photo-oxidation resistance of neat PLA and PLA/PA11 blend is significantly reduced due to the presence of both metal oxides, and this must be considered when designing the potential applications. The last results suggest that both metal oxides could be considered as photo-sensitive degradant agents for biopolymer and biopolymer blends.

Collaborative robotics is a major topic in current robotics research posing new challenges, especially in Human-Robot Interaction. The crucial aspect in this area of research focuses on understanding the behavior of robots when engaging with humans, where reinforcement learning is a key discipline that allows us to explore sophisticated emerging reactions. This review aims to delve into the relevance of different sensors and techniques, with special attention to EEG (electroencephalography data on brain activity) and its influence on the behavior of robots interacting with humans. In addition, mechanisms available to mitigate potential risks during the experimentation process such as virtual reality will also be addressed. In the final part of the paper, future lines of research combining the areas of collaborative robotics, reinforcement learning, virtual reality and human factors will be explored, as this last aspect is vital to ensure safe and effective Human-Robot Interactions.

A soluble biopolymer (SBP) was obtained by hydrolysis in pH 13 water at 60 °C. The dry product was re-dissolved in plain water at pH 10 and used as control against the same solution added with hydrogen peroxide at 0.1-3 H2O2 moles per SBP carbon mole. The control and test solutions were kept at room temperature, in the dark or in a climatic chamber under irradiation with simulated solar light, until the solutions pH remained constant. Afterwards, the solutions were processed to recover and analyze the crude soluble products. For the control solution, the results indicated significant production of CO2, production of organic carboxyl functional groups and de-polymerization of the pristine SBP organic matter. These findings demonstrate the oxidation of SBP by water, which could only occur through the production of O and OH radicals catalyzed by SBP. The present work reports the results obtained from the control solution and for the test solution treated in the presence and absence of H2O2, with and without pH control, in the dark and under irradiation with simulated solar light. The paper discusses the perspectives of further implementation of the autocatalytic properties of SBP for the realization of a municipal biowaste-based biorefinery producing value added bio-products for consumer’s use.

Tuberculosis (TB) is a leading infectious disease with serious antibiotic resistance. The benzothiazinone (BTZ) scaffold PBTZ169, an inhibitor of the decaprenylphosphoryl-β-D-ribose 2'-oxidase (DprE1) in Mycobacterium tuberculosis (Mtb), showed anti-TB potential in animal model and piloted clinical tests. Although highly potent, the BTZ type DprE1 inhibitors in general shows extremely low aqueous solubility, which adversely affect the drug like property. To improve the compounds physiochemical properties, we generated a series of BTZ analogues. Several optimized compounds had MIC values against Mtb in single digit nanomolar. The representative compound 37 displayed improved solubility and bioavailability compared to the lead compound. Additionally, compound 37 shows Mtb-killing ability in an acute infection mouse model.

Polymeric wet-strength agents are important additives used in the paper industry to improve the mechanical properties of paper products, especially when they come in contact with water. These agents play a crucial role in enhancing the durability, strength, and dimensional stability of paper products. The aim of this review is to provide an overview of the different types of wet-strength agents available and their mechanisms of action. We will also discuss the challenges associated with the use of wet-strength agents and the recent advances in the development of more sustainable and environmentally friendly agents. As the demand for more sustainable and durable paper products continues to grow, the use of wet strength agents is expected to increase in the coming years.

Since the onset of coronavirus disease 2019 (COVID-19) pandemic, the virus kept developing and mutating into different variants over time that also gained increased transmissibility and spread in populations at a higher pace, culminating in successive waves of COVID-19 cases. The scientific community has developed vaccines and antiviral agents against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease. Realizing that growing SARS-CoV-2 variations significantly impact the efficacy of antiviral therapies and vaccines, we have summarized the appearance and attributes of SARS-CoV-2 variants for future perspectives in drug design, bringing up-to-date hints for developing therapeutic agents targeting the variants. The Omicron variant is among the most mutated form; its strong transmissibility and immune resistance capacity have prompted international worry. Most mutation sites currently being studied are located in the BCOV_S1_CTD of the S protein. Despite this, several hurdles remain, such as developing vaccination and pharmacological treatment efficacies for emerging mutants of SARS-CoV-2 strains. In this review, we present an updated viewpoint on the current issues faced by the emergence of various SARS-CoV-2 variants. Furthermore, we discuss the clinical studies conducted to assist the development and dissemination of vaccines, small molecule therapeutics, and therapeutic antibodies having broad-spectrum action against SARS-CoV-2 strains.

Among bryophytes, the Plagiochila genus represents a large group of leafy liverworts, with over 500 species. Plagiochilins A-to-X are sesquiterpenoids isolated from Plagiochila species. The lead compound plagiochilin A (Plg-A), endowed with anticancer and anti-parasitic properties, has been characterized as a potent mitosis inhibitor, acting selectively at the late stage of cytokinesis termed abscission. The compound perturbs the dynamic of microtubules, blocking cell cycle progression and triggering the death of malignant cells. Based on the compound mechanism of action and the analogy with other natural products bearing a dihydro-pyrone moiety, we postulated that Plg-A could bind to the pironetin site of α-tubulin. A molecular docking analysis has been performed to compare binding of all 24 plagiochilins to α-tubulin and to establish structure-binding relationships. The identification of Plg-E and Plg-G as the best binders in the series pointed out to the importance of the C13-OH or C=O group for α-tubulin recognition. This observation led to the testing of the natural product ester plagiochilin A-15-yl n-octanoate and the corresponding alcohol (Plg-OH), both identified as robust α-tubulin binders. The study provides a rational to explain potentially the mechanism of action of Plg-A and to guide the design of new derivatives.

Small rodents and insectivores are potential reservoirs of many pathogens transmissible to humans such as bacteria, parasites and viruses responsible for epidemics in sub-Saharan Africa, particularly in West Africa. Few studies on small mammal species in the Kolikoro and Sikasso regions are available, hence the interest in investigating the different species of small rodents and insectivores, and their role in the transmission of pathogens to humans. The study aims to identify commensal small mammal species circulating in Faladjè and Bougouni areas, and likely to represent major risks of epidemic disease emergence. Sessions of trapping were carried out in December 2016 in Faladjè and Bougouni with wire mesh traps type “Besançon tous services” (BTS) baited with peanut butter and/or onion. All animals captured were identified morphologically. Out of 123 small rodents and insectivores captured in 674 trap nights, 75 (60.97%) were from Faladjè and 48 (39.02%) from Bougouni, Of these, six species of small rodents belong to the family Muridae (Mastomys erythroleucus, Mastomys natalensis, Rattus rattus, Praomys daltoni, Gerbilliscus gambianus, Taterillus gracilis) and two species of insectivores associated with the genus Crocidura spp. belong to the family Soricidae and Erinaceidae (Crocidura cf olivieri and Atelerix cf albiventris) respectively. There is low specific diversity within these two stands, but the variation in relative abundance is significant (binomial test, p = 0.018 ˂ 0.05) between the Faladjè and Bougouni stands of small mammals. Mastomys erythroleucus was the most dominant species (57.33%, 43/75) in the Faladjè settlement and R. rattus dominated (37.5%,18/48) that of Bougouni. These two species of small mammals are potentially involved in the transmission of bacteria, parasites and pathogenic viruses to humans.

In the recent years, biochar has emerged as a remarkable biosourced material for addressing global environmental, agricultural, biomedical, and energy challenges. However, the performances of biochar rest in part on finely tuning its surface chemical properties, intended to obtain specific functionalities. In this review, we tackle surface treatment of biochar with silane and other coupling agents such as diazonium salts, titatantes, ionic/non-ionic surfactants, as well as nitrogen-containing (macro)molecules. We summarize the recent progress achieved mostly in the last five years, and correlate the nature and extent of functionalization to eye catchy end applications of the surface engineered biochar.

Mucormycosis (previously called zygomycosis or phycomycosis), an aggressive, life-threatening infection is further aggravating the human health-impact of the devastating COVID-19 pandemic. Additionally, a great deal of mostly misleading discussion is focused also on the aggravation of the COVID-19 accrued impacts due to the white and yellow fungal diseases. In addition to the knowledge of important risk factors, modes of spread, pathogenesis and host defences, a critical discussion on the botanical insights into the main causative agents of mucormycosis in the current context is very imperative. Given above, in this paper: (i) general background of the mucormycosis and COVID-19 is briefly presented; (ii) overview of fungi is presented, the major beneficial and harmful fungi are highlighted; and also the major ways of fungal infections such as mycosis, mycotoxicosis, and mycetismus are enlightened; (iii) the major causative agents of mucormycosis are critically discussed; (iv) the systematic position, occurrence, structure, and the major modes of reproduction are summarized for Rhizopus sp. and Mucor sp., the major causative agents of mucormycosis; (v) the other causative agents of mucormycosis includes Cunninghamella bertholletiae, Apophysomyces elegans, Lichtheimia (Absidia), Saksenaea, and Rhizomucor pusillus are briefly introduced; (vi) facts related with the infection-misnomers based on fungi colour are also highlighted; and lastly, (vii) the major take-home message and clues for future research on the subject are listed.

Total 219 countries and territories globally suffering from the recent pandemic COVID-19 is now in its second wave with more brutality, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) . It has several symptoms like as persistent fever; respiratory illnesses; cough; fatigue; shortness of breath; loss of appetite; persistent pain or pressure in the chest; dysgeusia; acute respiratory distress syndrome (ARDS) etc., and here the things to worry about is the development of pulmonary fibrosis after COVID-19 in both peoples who had died of due to acute respiratory distress syndrome (ARDS) or those who survived. Due to COVID-19, dysregulated immune response and wound repair mainly in elderly patients causes this secondary pulmonary fibrosis. Thus using anti-fibrotic agents could be meaningful in these circumstances although their efficacy in treating COVID-19 is subject to more detailed laboratory research works. In this review article you will get to know about the lung fibrosis generation due to COVID-19 infection, about anti-fibrotic agents and the currents challenges of this field.

Recently, it was proposed that the thiophene ring is capable of promoting mitochondrial accumulation when linked to fluorescent markers. As a noncharged group, thiophene presents several advantages from a synthetic point of view, making it easier to incorporate such a side moiety into different molecules. Herein, we confirm the general applicability of thiophene group as mitochondrial carrier for drugs and fluorescent markers, based on a new concept of nonprotonable, noncharged transporters. We implemented this concept in a medicinal chemistry application by developing an anti-tumoral, metabolic chimeric drug, based on PDHK inhibitor dichloroacetate (DCA). The promising features of the thiophene moiety as a noncharged carrier for targeting mitochondria may represent a starting point for the design of new metabolism-aimed drugs.

Around the world, there is no population clear from urinary tract infection (UTI), particularly among women. UTI is considered the most predominant bacterial infection. This study aimed to detect the incidence of the most common major uropathogens in patients severe from urinary tract infection with antibiotic sensitivity tests that assist urologist doctors for appropriate antimicrobial empirical therapy.Methods: This study was carried in a private laboratory in Babil city, Iraq from May 2019 to May 2020. Totally 70 individuals suffering from clear symptoms of UTI, as well as, 20 healthy persons participated in this study as a control group. Then, the standard microbiological methods carried out to isolate and identify bacterial species. Antimicrobial susceptibility tests were performed using different antimicrobial discs by applying the Kirby–Bauer disc diffusion method.Results: Totally, 90 specimens were obtained from them 20 control group, 19 with no growth, and 51 patients with bacterial growth distributed as 43 (83%) females and 8 (17%) males. E. coli were the most common predominant organisms. All isolates were showed a high rate of resistance to evaluated cephalosporins 100% and 82% to cefotaxime and ceftriaxone respectively, while very low resistance recorded in Aminoglycosides 20% and 13% to Gentamicin and amikacin respectively. Most age group infected with UTI was 21-40 years old.Conclusion: The current study showed an increasing burden of urinary tract infection caused by various bacteria implicated in UTI that causes changeable sensitivity to various antimicrobial agents. Therefore, in clinical use appropriate medications should be selected based on the data obtained from antimicrobial susceptibility tests.

This research was conducted to manufacture thermally expandable microspheres (TEMs) for vehicles’ underbody coating and to apply them on an industrial scale. TEMs heat resistance was studied depending on the ratios of a cross-linking agent and an initiator. This research focused on the content of a cross-linking agent and how it affected the results. The TEMs’ outer shell was thickened to solve the problem of the foam expansion ratio’s reduction that occurred due to the shrinkage after the maximum expansion (Tmax) was reached. After foaming, the cross-sectional thickness and surface of the sample with thickened outer shell were observed. The TEMs with the thickened shell showed the least shrinkage, which indicated excellent shrinkage stability, even after prolonged exposure to heat.

AI is often looked at as a logical rational way to develop a games agent that methodically looks at options and delivers rational solutions. This paper is based on developing an AI agent that plays a game with a similar emotive content like a human. The purpose of the study was to see if the incorporation of this emotive content would influence the outcomes within the game Love Letter. In order to do this an AI agent with an emotive layer was developed to paly the game over a million times. A lower win/loss ratio demonstrates that to some extent this methodology was vindicated and a 100 per cent win for the AI agent did not happen. Machine learning techniques were modelled purposely so as to match extreme models of behavioural change. The results demonstrated a win/loss ration of 0.67 for the AI agent and in many ways reflectd the frustration that a normal player would exhibit during game play. As was hypothesised the final agent investment value was, on average, lower after matchplay than its initial value.

This paper argues that popular misrepresentation of the nature of AI has important consequences concerning how it should be regulated. Viewing AI as something that exists in itself, rather than as a set of cognitive technologies whose characteristics – physical, cognitive, and systemic – are quite different from ours (and at times from each other) leads to inefficient approaches to regulation. It limits our ability to anticipate the consequences of its foreseeable developments and social diffusion. It undermines attempts to protect ourselves from the social and political dangers it presents. After a short introduction, section 2 retraces rapidly the history of the idea that intelligence is essentially a quality, one that AI shares with human intelligence and that this resemblance trumps the differences that exist between artificial and natural cognitive systems. Section 3 reviews two approaches to the dangers of AI that reflect the illusion that AI exists in itself. Section 4 turns to the proper understanding of regulations and what is their main goal and purpose. Section 5 analyses three central characteristics of artificial cognitive systems which section six compares with corresponding characteristics of natural cognitive systems. Finally, section 7 draws some conclusions regarding how we should regulate artificial intelligence.

Photon-counting Computed Tomography (PCCT) is a promising cardiovascular-imaging technique. Using detectors that count the number and energy of photons in multiple bins, PCCT offers several advantages over conventional CT, including a higher image quality, reduced contrast agent volume, radiation doses, and artifacts. Although PCCT is well established for cardiac imaging in assessing coronary artery disease, its application in vascular imaging remains limited. This review summarizes the available literature and provides an overview of the current use of PCCT for the diagnosis of vascular conditions. Of the 13 records selected in the initial search, 7 articles were included in the present review: 6 cohort studies and 1 case report. This review synthesized the available literature on PCCT in vascular imaging, focusing mainly on endoleaks detection and characterization after endovascular aneurysm repair (EVAR), contrast dose volume, and radiation exposure reduction, particularly in patients with chronic kidney disease and in those requiring follow-up CT.

During meat processing, lactic acid bacteria (LAB) have to competitively adapt to the hostile en-vironment produced by curing additives (CA). The objective of this study was to investigate the ability of Latilactobacillus curvatus CRL 705, a bioprotective strain of meat origin, to adapt to CA. A physiological and proteomic approach was performed. CRL 705 was grown in a chemically de-fined medium (CDM) containing specific concentrations of CA (NaCl, nitrite, sucrose and ascor-bic acid). The results showed minor differences in growth kinetics in the presence of CA. Glucose consumption, present in CDM, and production of lactic acid and bacteriocins were not signifi-cantly affected. Proteomic analyses indicated that most of the identified proteins (36 out of 39) mainly related to carbohydrate metabolism (18%), posttranslational modifications (15.6%), energy production and conversion (11.1%), translation (11.1%) and nucleotide metabolism (8.9%), were under expressed. In response to the studied CA, CRL 705 slowed down its general metabolism, achieving slight changes in physiological and proteomic parameters. The observed performance is another characteristic that extends the well-known competitive profile of CRL 705 as a meat starter- and -bioprotective culture. This is the first report dealing with the impact of CA on LAB proteomics.

Apoptosis, also known as the programmed death of cells, is responsible for maintaining the homeostasis of tissues and this function is carried out by caspases. The process of apoptosis is carried out via two distinct pathways: the extrinsic pathway, which is governed by death receptors, and the intrinsic pathway, also known as the mitochondrial pathway. The BCL-2 protein family encoded by the BCL-2 gene, located at the 18q21.33 chromosomal location, is in charge of regulating the intrinsic pathway, which is responsible for inducing cell death via the permeabilization of the mitochondrial membrane and the release of apoptosis - inducing components. The BCL-2 homology (BH1, BH2, BH3, BH4) domains of this family proteins are crucial for their functioning and their common BH domains allow interactions between members of the same family and can also serve as indications of pro- or anti-apoptotic activity. A direct correlation may be shown between the overexpression of BCL-2 and the postponement of cell death. It has been determined that a change in the expression of BCL-2 is the root cause of a variety of malignancies, including lung, breast, melanoma, and chronic lymphocytic leukemia, Multiple Sclerosis, Diabetes. In this review, we discuss the therapeutic potential of regulating BCL-2 family connections and their relevance to health and disease.

Metformin, the treatment of first choice in type 2 diabetes (T2D), is known to mainly act by decreasing endogenous glucose production (EGP) in the liver. Paradoxically, in the last decade several reports documented increased EGP after metformin treatment. This increase, was often attributed to pronounced rises in glucagon, consistent with counter-regulatory response to the glucose lowering effect of metformin. However, considering that hyperglucagonemia, but not hypoinsulinemia, is a main driver of EGP in T2D, increased EGP should have been a common finding. This observation, together with the finding that metformin antagonizes glucagon effects on energy expenditure and protein synthesis, concurrently to its effects on EGP and the emerging evidences demonstrating increased branched chain and gluconeogenic amino acids in response to metformin treatment may points to a liver alpha-cell skeletal muscle cross talk similar to that observed in the liver-alpha cell axis. Here, we provide a mechanistic perspective to this latter possibility, based on mechanistic studies of metformin’s transcriptional targets; retaining thus its glucagon antagonistic and presumably anti-gluconeogenic effects on liver and attributing the increase in EGP to renal gluconeogenesis. We finally discuss how increased EGP might reflect an adverse response to metformin treatment, providing support from clinical and epidemiological data.

In recent years, new treatments have been studied for relapsed-refractory multiple myeloma (RRMM), including two CAR-T products and a variety of non CAR-T agents. Since direct comparisons between these innovative treatments are not available, indirect comparisons can be of interest. Reconstruction of individual patient data from Kaplan-Meier graphs (Shiny method) has been employed in numerous reports that have validated its performance. In the present review, we evaluated six treatments proposed for RRMM including two CAR-T products (ciltacabtagene autoleucel and idecabtagene vicleucel) and four treatments not based on a CAR-T (melflufen plus dexamethasone, isatuximab plus dexamethasone, selinexor, and belantamab). The end-point was overall survival (OS); the Shiny method was used to generate reconstructed survival curves. Our results showed statistically significant differences in OS across these treatments. Compared with pharmacological treatments, CAR-T products significantly prolonged OS with an improvement of remarkable clinical relevance. In particular, ciltacabtagene autoleucel showed better OS than idecabtagene vicleucel. As regards non CAR-T treatments, the ranking in OS was headed by isatuximab plus dexamethasone, followed by belantamab, selinexor, and melflufen plus dexamethasone. In conclusion, while the Shiny method has confirmed its validity in reconstructing individual patient data, our indirect comparisons have offered some original clues to better interpret the information on OS published in these studies.

Modern advances in molecular medicine have led to reframing osteoarthritis as a metabolically active, inflammatory disorder with local and systemic contributing factors. According to the ‘inflammatory theory’ of osteoarthritis, immune response to an initial damage is the key trigger that leads to progressive joint destruction. Several intertwined pathways are known to induce and govern articular inflammation, cartilage matrix degradation, and subchondral bone changes. Effective treatments capable of halting or delaying the progression of osteoarthritis remain elusive. As a result, supplements such as glucosamine and chondroitin sulphate are commonly used despite the lack of scientific consensus. A novel option for adjunctive therapy of osteoarthritis is LithoLexal®, a marine-derived, mineral-rich extract, that exhibited significant efficacy in clinical trials. LithoLexal® has a lattice microstructure containing a combination of bioactive rare minerals. Mechanistic research suggests that this novel treatment possesses various potential disease-modifying properties, such as suppression of nuclear factor kappa-B, interleukin 1β, tumour necrosis factor α, and cyclooxygenase-2. Accordingly, LithoLexal® can be considered a disease-modifying adjunctive therapy (DMAT). LithoLexal® monotherapy in patients with knee osteoarthritis has significantly improved symptoms and walking ability with higher efficacy than glucosamine. Preliminary evidence also suggests that LithoLexal® may allow clinicians to reduce the dose of nonsteroidal anti-inflammatory drugs in osteoarthritic patients by up to 50%. In conclusion, the multi-mineral complex, LithoLexal®, appears to be a promising candidate for DMAT of osteoarthritis, which may narrow the existing gap in clinical practice.

Composite materials are widely used in the dental field in clinics as biomaterials. For example, it has been used as a biomaterial to repair caries and restore masticatory function, and as a cement to adhere the restoration to the tooth substrate. In order to demonstrate its function, dental biomaterials are measured their mechanical strength. From such basic research, we explained the potential of dental biomaterials, especially flexural strength and modulus of elasticity. Mechanical properties of dental biomaterials similar to those of the tooth, thermal stimulation, and aesthetic elements in the oral cavity. In this part, we will introduce the commercialized products of composites suitable for the characteristics and tooth quality, and provide the reader with the characteristics from the flexural characteristics of the composite materials used in clinical dentistry. In clinical performance, it might be advisable to delay polishing when composite biomaterials are used for luting materials, filling materials and core build-up materials since improved the flexural strength and the flexural modulus of elasticity were displayed after 1-day storage. And it is thought that flexural strength or characteristics is a significant important mechanical property of oral biomaterials.

Global teacher shortage is a serious concern with grave implications for the future of education. This calls for novel ways of addressing teacher roles. The economic benefits of tireless labour inspires the need for teachers who are unlimited by natural human demands, highlighting consideration for the affordances of robotics and Artificial Intelligence in Education (AIED) as currently obtainable in other areas of human life. This however demands designing robotic personalities that can take on independent teacher roles despite strong opinions that robots will not be able to fully replace humans in the classroom of the future. In this paper, we argue for a future classroom with independent robot teachers, highlighting the minimum capabilities required of such personalities in terms of personality, instructional delivery, social interaction and affect. We describe our project on the design of a robot teacher based on these. Possible directions for future system development and studies are highlighted.

Rheumatoid arthritis (RA) is a well-known autoimmune inflammatory disease that affects the diarthrodial joints. Inflammation increases the production of reactive oxygen species (ROS), which may explain why RA is one of the diseases that induce oxidative stress. This study aimed to evaluate potential differences in biochemical, hematological and oxidative stress markers in early stages of RA and after different treatment regimens. The study involved 111 patients, 28 men and 83 women, aged 34 to 59 years who were divided based on their c-reactive protein (CRP) levels into inactive RA patients (IRA) with CRP < 1.3 (n = 57, 22 men and 35 women) and active RA patients (ARA) with CRP ≥ 1.3 (n = 54, 6 men and 48 women). The study participants were divided into two groups, A and B, based on their treatment regimen. Group A, which comprised 90% IRA, received methotrexate (MTX) monotherapy. Group B, which comprised 90% ARA, received a combination of leflunomide, a conventional disease-modifying antirheumatic drug (DMARD), and a biologic DMARD. Hematological, biochemical, oxidative stress and RA-specific biomarkers were measured twice in groups A and B, in the early stage in the disease, before and 3 months post-treatment, using conventional colorimetric, fluorometric and immunological assays. According to the results of our study, glutathione peroxidase (GPx), ROS, calcium (Ca) and phosphorus (P) ions, vitamin C and D, and lipid profile could serve as potential diagnostic markers in the early stages of the disease. Both treatment options were equally effective in improving the overall health of the patients. However, treatment resulted in a further increase in ROS levels and a decrease in antioxidant markers.

In the context of sustainable and eco-friendly agriculture, current scientific researches are focusing on plant-based bioproducts to remedy the toxicity caused by chemical fertilizers and pesticides. This study was conducted on cladodes of Opuntia ficus-indicato screen the bioactive molecules and to evaluate the activity againstfungal agentsisolated from tomato fruits. Quantitative analysis of the methanolic extractrevealed its richeness in total polyphenols (86.6 mg GAE/100 g FW), flavonoids (13.4 mg QE/100 g FW), condensed tannins (08.9 mg TAE/100 g FW), and carotenoids(0.9 mg β-CE/100 g FW). DPPH test revealed that the cladodes extract had a high antioxidant potential (0.6 mg/ml). On the other hand, 7 fungal agents were isolated from infected tomato fruits and identifyed asbelonging to the following genera: Rhizoctonia (EC2), Fusarium (EC1 and EC3), Alternaria (EC4), Mucor (EC5), Aspergillus (EC6) and Penicillium (EC7). At a concentration 0.02% of cladodehydro-ethanolic extract, results of the antifungal activity showed aninhibition of mycelial growth up to70% for the isolates ofAlternariaspEC4 (70.91%), Rhizoctonia solaniEC2 (58.49%), Fusarium oxysporiumEC3 (57.63%) and Fusarium solaniEC1 (53.13%). While,inhibitory activities lower than 50% were obtained for fungal isolates MucorspEC6 (31.08%), Aspergillus sp EC5 (35.14%) and Penicillium sp EC7 (28.38%).At 0.04%all thecladode hydro-ethanolic extractwere able to inhibit mycelium growth in more than 50%.Similarly, maximum spore inhibition development were obtained with 0.04 cladode hydro-ethanolicreaching more than 60%. Inhibition percentages of 83.02%, 85.96%, 87.76% and 90.20% were obtained for fungal isolates Fusarium oxysporium EC3, Fusarium solani EC1, Rhizoctonia solani EC2 and Alternaria sp EC4, respectively. All together, the results show that Opuntia ficus-indica extract has potential tobe used effectively as a biopesticide against fungal agents of tomato fruits.

Pathogens, especially invasive species, have caused significant global ecological, economic, and social losses in forests. Plant disease research has traditionally focused on direct interactions between plants and pathogens in an appropriate environment. However, recent research indicates that the microbiome can interact with the plant host and pathogens to modulate plant resistance or pathogen pathogenicity, thereby altering the outcome of plant–pathogen interactions. Thus, this presents new opportunities for studying the microbial management of forest diseases. Compared to parallel studies on human and crop microbiomes, research into the forest tree microbiome and its critical role in forest disease progression has lagged. The rapid development of microbiome sequencing and analysis technologies has resulted in the rapid accumulation of a large body of evidence regarding the association between forest microbiomes and diseases. These data will aid the development of innovative, effective, and environmentally sustainable methods for the microbial management of forest diseases. Herein, we summarize the most recent findings on the dynamic structure and composition of forest tree microbiomes in belowground and aboveground plant tissues (i.e., rhizosphere, endosphere, and phyllosphere), as well as their pleiotropic impact on plant immunity and pathogen pathogenicity, highlighting representative examples of biological control agents used to modulate relevant tree microbiomes. Lastly, we discuss the potential application of forest tree microbiomes in disease control as well as their future prospects and challenges.

In the food sector, packaging is one of the important steps that ensures the safe, unspoiled, min-imum cost of storing, transporting and delivering the food that goes into production to the con-sumer. Food spoilage caused by foodborne pathogens and microorganisms is a serious problem in the food chain, reducing the shelf life of foods. Therefore, consumers' demands for more natural, disposable, biodegradable and recyclable antibacterial food packaging materials have considera-bly increased. This review covers a comprehensive current literature review of antibacterial food packaging, which includes with titles antibacterial agents, organic acids and other compounds, enzymes, bacteriocins, natural extracts, essential oils, application of encapsulation and antimi-crobial packaging. Research findings on antimicrobial food packaging used to extend the shelf life of foods were collected from online databases such as PubMed/MedLine, Wiley Online Li-brary, Scopus, Web of Science, and Google Scholar. In this review, the activities of different bio-materials and compounds used to extend the shelf life of foods were compared

Background and Objectives: Treatment of visceral artery pseudoaneurysms (VAP) is always indicated regardless of their diameters, as their risk of rupture is significantly higher than that of visceral artery aneurysms. The invasiveness of surgery and its associated complications have led to a shift in favour of radiological interventions as the initial treatment of choice. However, there are still some unanswered questions on endovascular treatment of VAP regarding the optimal endovascular technique and the efficacy and safety outcomes. The purpose of this multicenter study was to retrospectively evaluate the effectiveness and safety of endovascular treatment of visceral pseudoaneurysms using Ethylene-Vinyl Alcohol (EVOH) Copolymer-Based Non-Adhesive Liquid Embolic Agents (NALEAs). Materials and Methods: Consecutive patients who underwent endovascular embolization with EVOH-based NALEAs for visceral artery pseudoaneurysms between January 2018 and June 2023 were retrospectively evaluated. Results: 38 embolizations were performed. Technical success was achieved in all patients. The clinical success rate was high (92.1% overall), with no significant differences between ruptured and unruptured VAPs (p=0.679). 7 patients (18.4%) experienced procedure-related complications, related to a case of non-target embolization, four splenic abscesses due to end-organ infarction and two femoral pseudoaneurysms. The rates of procedure-related complications, end-organ infarction, and vascular access-site complications did not significantly differ between ruptured and unruptured VAPs (p>0.05). Conclusions: Both ruptured and unruptured visceral pseudoaneurysms can be effectively and safely treated with NALEA-based endovascular embolization. We suggest considering the use of NALEAs, particularly in specific clinical cases that highlight their advantages, including patients with coagulopathy, fragile vessels, and embolization targets that are located at a considerable distance from the microcatheter tip and are otherwise difficult to reach.

Systemic lupus erythematosus (SLE), the prototype of systemic autoimmune diseases is characterized by extreme heterogeneity with a variable clinical course. Renal involvement may be observed and affects the outcome. Hydroxychloroquine is the cornerstone of lupus treatment. Conventional immunosuppressive therapy includes corticosteroids, methotrexate, azathioprine, cyclosporine and tacrolimus. Cyclophosphamide and mycophenolate mofetil may also be used. However, despite conventional immunosuppressive treatment flares occur and broad immunosuppression is accompanied by multiple side effects. Flare occurrence, target organ involvement, side effects of broad immunosuppression, increased knowledge of the pathogenetic mechanisms involved in SLE pathogenesis as well as the availability of biologic agents has led to the application of biologic agents in SLE management. Biologic agents targeting various pathogenetic paths have been applied. B cell targeting agents have been used successfully. Belimumab, a B cell targeting agent has been approved for the treatment of SLE. Rituximab, an anti-CD20 targeting agent is also used in SLE. Anifrolumab, an interferon I receptor targeting agent has beneficial effects on SLE. In conclusion, biologic treatment is applied in SLE and should be further evaluated with the aim of a good treatment response and a significant improvement in quality of life.

A review of influence of drag-reducing agents on curved pipe flows is presented in this work. In addition, this review outlined proposed mechanism, friction factor and fluid flux models for drag-reducing agents in curved pipe flows. Our finding reveals that drag reduction by additives in curved pipes is quite significant but generally lower than the corresponding drag reduction in straight pipes. It decreases with increase in curvature ratio and more pronounced in the transition and turbulent flow regimes. Drag reduction strongly depends on the polymers and surfactants’ concentrations as well as the bubble fraction of micro-bubbles. It is also reported that drag reduction in curved pipes depends on temperature and existence of dissolved salts in the fluids. Maximum drag reduction asymptote differed between straight and curved pipes and between polymer and surfactant. No definite conclusion could be drawn as regards drag reduction for two-phase flow in curved pipes due to the limited studies in this area. Many questions such as the mechanism of drag reduction in curved pipes and how drag-reducing agents interact with secondary flows still remained unanswered. Hence, some research gaps have been identified with recommendations for areas of future researches.

Abstract: This study reviewed aspects of the biology of two members of the glucosinolate family, namely sinigrin and glucoraphanin and their anti-tumour and anti-microbial properties. Sinigrin and glucoraphanin are converted by the β-sulphoglucosidase myrosinase or the gut microbiota into their bioactive forms, allyl isothiocyanate (AITC) and sulphoraphanin (SFN) which constitute part of a sophisticated defence system plants developed over several hundred million years of evolution to protect them from parasitic attack from aphids, ticks, bacteria or nematodes. Delivery of these components from consumption of cruciferous vegetables rich in the glucosinolates also delivers many other members of the glucosinolate family so the dietary AITCs and SFN do not act in isolation. In-vitro experiments with purified AITC and SFN have demonstrated their therapeutic utility as antimicrobials against a range of clinically important bacteria and fungi. AITC and SFN are as potent as Vancomycin in the treatment of bacteria listed by the World Health Organisation as antibiotic-resistant "priority pathogens" and also act as anti- cancer agents through the induction of phase II antioxidant enzymes which inactivate potential carcinogens. Glucosinolates may be useful in the treatment of biofilms formed on medical implants and catheters by problematic pathogenic bacteria such as Pseudomonas aeruginosa and Staphylococcus aureus and are potent antimicrobials against a range of clinically important bacteria and fungi. The glucosinolates have also been applied in the prevention of bacterial and fungal spoilage of food products in advanced atmospheric packaging technology which improves the shelf-life of these products.

DR2B and DR2C extracts, from peel of commercially and physiologically ripe eggplants, were studied for the antioxidative cytoprotective properties and anti-HSV-1 activity, in line with the evidence that several antioxidants can impair viral replication by maintaining reducing conditions into the host cells. The antioxidative cytoprotective effects against tBOOH-induced damage was assessed in Caco2 cells, while the antiviral activity was studied in Vero cells; phenolic and anthocyanin fingerprint was characterized by integrated phytochemical methods. Results highlighted different compositions of the extracts, with chlorogenic acid and delphinidin-3-rutinoside as the major constituents; other peculiar phytochemicals were also identified. DR2C resulted able to partly counteract the tBOOH-induced cytotoxicity, with a remarkable lowering of lactate metabolism under both normoxia and hypoxia. DR2B and DR2C reduced ROS production, possessed scavenging and chelating properties. Interestingly, DR2C increased intracellular GSH levels. Furthermore, DR2C inhibited the HSV-1 replication when added for 24 h after viral adsorption, as also confirmed by the reduction of many viral proteins expression. Since DR2C was able to reduce NOX4 expression during HSV-1 infection, its antiviral activity may be correlated to its antioxidant properties. Although further studies are needed to better characterize DR2C activity, the results suggest this extract as a promising new anti-HSV-1 agent.

The study aims to compare the efficacy and safety of bulking agents and single-incision slings in the treatment of urinary incontinence in 159 patients during a 29-month follow-up period. Of the 159 patients suffering from stress urinary incontinence, 64 were treated with bulking agents and 75 with a single incision sling. The ICIQ-UI-SF, PISQ-12, FSFI, FSDS, and PGI-I were used to assess efficiency and quality of life. In the 29-month follow-up, the bulking agents showed significantly increased efficacy and safety. Compared to the ones treated with a single-incision sling, the patients treated with bulking agents showed less and mild postoperative complications. Furthermore, at our follow-up there was no discernible difference in terms of effectiveness or quality of life between patients treated with bulking agents and those treated with single-incision slings

Based on the Flashing Ratchet Potential (FRP) and Electro-Spectroscopy detection techniques, a new detection method was experimentally examined. This method allows the detection of sub-micro particles in the human exhaled air such as viral particles and other biological agents. The detection signal created by this method is carried out by electron current buildup forming an Electric Current-Spectrum (ECS) distinguishing the contents of the exhaled air samples. The detection method was developed based on FRP and a beam of free charges passing through the electrodes of the FRP. The ECS is characterized by low-energy free charges interacting with the medium through which they pass, where numerous free charges are scattered (delayed) as a result of these interactions. The resulting ECS is characterized by FRP's capacity to drift back the delayed free charges to their original starting positions. By comparing the ECS of two exhale air samples, this new technology can be utilized to identify the presence of viral and microorganisms’ particles. The time-escalating ECS difference quickly indicates the presence of such particles. Moreover, the FRP's optimal operating settings was experimentally defined, in addition to the experimental evaluation of its functionality to confirm the FRP's promising sensing capabilities, which were statistically examined several times to ensure the reproducibility of the results.

With the current increase in the demand from animal and agricultural products, management of agrowaste has become critical to avoid greenhouse gas emissions. The present article investigates the applicability of ammonium bicarbonate synthesis via flash distillation to valorize and stabilize several types of anaerobic digestate produced from individual fermentations of amino acids. Prior to the development of the model in Aspen Plus v12, the description of the system aqua-ammonia-carbon dioxide provided by the electrolyte non-random two-liquid property method was validated with empirical data available in the literature. The content of CO₂ in the digestate was found to be responsible of the OH alkalinity (0.4 equivalents of acid/kg digestate), while the partial and total alkalinities (0.8 eq/kg digestate) were essentially derived from the content of NH₃. The most suitable conditions for the flash distillation were 95 ⁰C and 1 bar with the condensation occurring at 25 ⁰C. However, in order to attain the precipitation of NH₄HCO₃ in the distillate, it was necessary to consider digestates with a moisture content of 50 wt.%, since the minimum levels of inorganic nitrogen and inorganic carbon were not attained otherwise. Even under these conditions, few amino acids (i.e. arginine, glycine, and histidine) were able to provide an anaerobic digestate, upon fermentation, that would be suitable for NH₄HCO₃ stabilization. Despite alanine digestate and glutamine digestate presented sufficient concentrations of inorganic nitrogen and inorganic carbon, the NH₄HCO₃-stabilization was not feasible due to the limited volatilization of NH₃. The process of stabilization with a capacity of a tonne of digestate per hour was improved by adding hydrochloric acid or sodium hydroxide at rates 44 kg/h, leading to production of 34 kg NH₄HCO₃/h. The economic viability of this process needs to be investigated considering not only the market value of the isolated inorganic fertilizer but the carbon credits saved, resulting from handling a more stabilized organic manure. Furthermore, given the role of the volatile elements of the biogas as endogenous stripping agents, it is recommended to use a fresh and saturated digestate as feed for the flash distillation.

Bovine mastitis is the most impacting disease of dairy industry, and it is characterized by a complexity of causal agents, which have revealed a geographical variation among regions and countries. The mastitis-related pathogens have been traditionally classified as contagious or environmental, based on habits of the microorganisms and transmission routes. In addition, the severity of mammary infections has been associated with the virulence of the pathogens, and immune and nutritional status of the hosts. Considering this scenario, we investigated the etiological nature, clinical severity scores, and days in milk (DIM) data in 4,273 clinical cases of bovine mastitis among ten large-dairy farms located in the Southeast region of Brazil. Streptococcus dysgalactiae (283/4,273=6.6%), Escherichia coli (190/4,273=4.4%), Prototheca spp. (112/4,273=2.6%), and Streptococcus uberis (95/4,273=2.2%) were the predominant pathogens isolated, all from the environmental origin. Among 4,273 clinical cases, clinical gravity score was available in 43.8% (1,871/4,273) animals. From these, 69.8% (1,306/1,871), 27.3% (510/1,871) and 2.9% (55/1,871) were scored as mild, moderate, and severe, respectively. Most of isolation of pathogens were observed in the first 100 days in milk, and their clinical severity scored as mild (3,612/4,273=84.5%). Our results contribute to the etiological identification, clinical severity scoring, and milking aspects of bovine clinical mastitis in dairy farms with a history of clinical mammary infections.

Magnetic Resonance Imaging (MRI) is a powerful, non-invasive and nondestructive tool, capable of providing three-dimensional (3D) images of living organisms. The use of magnetic contrast agents has allowed clinical researchers and analysts to enormously increase the sensitivity and specificity of MRI since these substances change the intrinsic properties of the tissues within a living body, increasing the information present in the images. The advances in nanotechnology and materials science as well as the research of new magnetic effects have been the driving forces that propel the use of magnetic nanostructures as promising alternatives to the commercial contrast agents used in MRI. This review discusses the principles associated with the use of contrast agents in MRI as well as the most recent reports focused on nanostructured contrast agents. The potential applications of gadolinium (Gd) and manganese Mn-based nanomaterials and iron oxide nanoparticles in this imaging technique are discussed as well, from their magnetic behavior to the mainly used materials and nanoarchitectures. Then, it is also addressed the recent efforts made to develop new types of contrast agents based on synthetic antiferromagnetic and high-aspect ratio nanostructures. Furthermore, the application of these materials in theragnosis, either as contrast agents and controlled drug release, contrast agents and thermal therapy or contrast agents and radiosensitizers, is also presented.

In this study, ozone oxidation experiment was carried out for the removal of fluorescent whitening agent which is widely used in textile dyeing and paper industry. The stilbene fluorescent whitening agent has been industrialized since the earliest, and the amount of current production is the highest. Due to the characteristics of the fluorescent whitening agent that cannot be removed by conventional wastewater treatment methods, the fluorescent whitening agent in wastewater treatment has difficulty in using as recycled water in the process. Pre-treatment ozone oxidation experiment was conducted prior to the introduction of Membrane Bio Reactor (MBR) treatment process by converting biodegradable materials into biodegradable materials. The removal efficiencies of fluorescent whitening agents, a diaminostilbene disulfonic acid derivative by ozone oxidation were evaluated by UV254 Scan, COD, T-N and color using a synthetic wastewater sample (COD=433.0 mg/ℓ) and paper and paper mill wastewater (COD=157.2 mg/ℓ).

In this study, effluent water was produced through Submerged Membrane Bio-Reactor (SMBR) process, which is a simple system and decomposes organic matter contained in wastewater with biological treatment process and performs solid-liquid separation, Especially, ozone oxidation treatment process is applied to effluent water containing fluorescent whitening agent, which is a trace pollutant which is not removed by biological treatment, and influences the quality of reused water. The concentration of COD in the SMBR was 449.3 mg/ℓ-COD, and the concentration of permeate water was 100.3 mg/ℓ-COD. The removal efficiency was about 70.1%. The amount of ozone re- quired for the removal of the fluorescent whitening agent in the permeated water in SMBR was 6.67 g-O3/min, and the amount of ozone required to remove COD relative to the permeate water was calculated to remove 0.997 mg-COD for 1 mg of O3.

The temporary immersion system bioreactor named GreenTray®[2], [3]presents advantages over the existing ones. Firstly, there is no need to use forceps to move the shoots or plantlets in or out of the recipient, neither the use of scalpel to divide them. Secondly, the basis of the shoot can remain in the GreenTray® and can sprout again in several cycles of growth. These two characteristics reduce the costs in the process of micropropagation. Besides, shoots or plantlets development is enhanced by the aeration of the recipient, thus enriching with CO2 the recipient atmosphere. The chapter describes and provides images and values of interest in (1) the micropropagation process of some commercial Prunus or Pyrus rootstocks; (2) the plantlet growth under autotrophic conditions; and (2) the inoculation of plants with pathogens that reproduce in vitro the symptoms observed in vivo, using the GreenTray® bioreactor.

This paper examines the transformative journey of Artificial Intelligence (AI) agents from copilots to integral coworkers within diverse sectors. Beginning with a foundational overview, we delve into the historical evolution of AI agents, highlighting key technological milestones and the shift from simple automated tools to sophisticated decision-making systems capable of learning and adapting over time. We explore the capabilities of AI agents, including problem-solving, predictive analytics, and automation, and their applications across healthcare, business, and education, showcasing their role in diagnostics, customer service, and personalized learning, among other areas. We also address the integration of AI agents in the workplace, presenting strategies for collaboration between humans and AI, and outline the challenges and ethical considerations that accompany the development and deployment of AI technologies. A comprehensive tutorial provides insight into the development process of AI agents, emphasizing goal definition, data handling, algorithm selection, and ethical guidelines. We also consider the pathway towards Artificial General Intelligence (AGI) and the societal and ethical implications of widespread AI integration, proposing strategies for equitable and ethical AI use.

The strong couplings among ecological, economic, social and technological processes explains the complexification of human-made systems, and phenomena such as globalization, climate change, the increased urbanization and inequality of human societies, the power of information, and the COVID-19 syndemics. Among complexification’s essential features are non-decomposability, asynchronous behavior, components with many degrees of freedom, increased likelihood of catastrophic events, irreversibility, nonlinear phase spaces with immense combinatorial sizes, and the impossibility of long-term, detailed prediction. Sustainability for complex systems implies enough efficiency to explore and exploit their dynamic phase spaces and enough flexibility to coevolve with their environments. This in turn means solving intractable nonlinear semi-structured dynamic multi-objective optimization problems, with conflicting, incommensurable, non-cooperative objectives and purposes, under dynamic uncertainty, restricted access to materials, energy and information, and a given time horizon, aiming at enhancing the co-evolutionary power of the Biosphere and its human subsystems. Giving the high-stakes, the need for effective, efficient, diverse solutions, their local-global, present-future effects, and their unforeseen short, medium and long-term impacts, achieving sustainable complex systems implies the need for Sustainability-designed Universal Intelligent Agents, harnessing the strong functional coupling between human, artificial and nonhuman biological intelligence in a no-zero-sum game to achieve sustainability.

Nowadays, an increasing number of heterocyclic-based drugs found application in medicinal chemistry and, in particular, as anticancer agents. In this context, oxadiazoles, five-membered aromatic rings, emerged for their interesting biological properties. Modification of oxadiazole scaffolds represents a valid strategy to increase their anticancer activity, especially on 1,2,4 and 1,3,4 regioisomers. In the last years, an increasing number of oxadiazole derivatives, with remarkable cytotoxicity for several tumor lines, were identified. Structural modifications, that ensure higher cytotoxicity towards malignant cells, represent a solid starting point in the development of novel oxadiazoles-based drugs. To increase the specificity of this strategy, outstanding oxadiazole scaffolds have been designed to selectively interact with biological targets, including enzymes, globular proteins and nucleic acids, showing more promising antitumor effects. In the present work, we aim to provide a comprehensive overview of the anticancer activity of these heterocycles, describing their effect on different targets and highlighting how their structural versatility has been exploited to modulate their biological properties.