Current Knowledge Research Articles

Brain neurotrophic factor BDNF: new data, functions and questions

The brain-derived neurotrophic factor (BDNF) is a key modulator of neurogenesis, synaptogenesis, neuroregeneration, and cell differentiation in the nervous system. Impaired BDNF functioning is a characteristic of various neurological diseases, such as Alzheimer’s disease, multiple sclerosis, and depressive disorders. There is recent evidence that patients with COVID-19 have reduced BDNF levels in the blood plasma. Furthermore, exogenous BDNF and its mimetics have demonstrated therapeutic potential.
 In this review, we systematized data of the BDNF gene structure, epigenetic and microRNA-mediated regulation of its expression, transcriptional variants of BDNF, and the effects of BDNF on neuronal and oligodendroglial differentiation. Further, we point out the gaps in the current knowledge about BDNF and propose experiments that can expand such knowledge and the range of possibilities for using BDNF in biomedicine. These include determining the expression pattern of all BDNF gene transcripts at different stages of differentiation and in different cell subpopulations and studying the role of receptor-independent BDNF signaling, circadian fluctuations in BDNF levels, and their role in physiological and pathophysiological conditions. Finally, for translational medicine, evaluating the effect of BDNF mimetics (including those immobilized on three-dimensional scaffolds for tissue engineering) on neuronal and oligodendroglial differentiation of pluripotent and polypotent cells and identifying molecular regulators of BDNF transcription, including small molecules and microRNAs capable of regulating BDNF gene expression, are crucial.

The concept of "state fishes of India": Current status, knowledge gaps, and strategic plans for conservation and sustainable utilization.

The concept of "state fishes of India" highlights the importance and significance of the prioritized fish species distributed across various states within the country. This review article systematically documents the current status of state fishes from various perspectives, identifies the prevailing knowledge gaps, and also highlights the issues and strategic plans essential for the conservation and sustainable utilization of these valuable genetic resources. A total of 8357 publications were checked for the consolidated information on state fish species, and the appropriate items were selected under eight categories: biology, physiology and nutrition, aquaculture, habitat and environmental parameters, genetics and biotechnology, harvest and postharvest, fish health management, and others. The synthesized information was used to present the current status of research and development on state fish species. The knowledge gaps that are to be addressed are also depicted under the perspectives of fisheries management and conservation aquaculture. Based on the findings, strategic plans for the targeted conservation programmes are proposed and discussed under various in situ and ex situ conservation measures. Further, the departmental processes involved in the declaration, the importance of stakeholder involvement, namely, local communities and policymakers, in fostering effective conservation measures, and planning for utilization of these valuable fish genetic resources are also indicated.

Carbapenem-resistant Klebsiella pneumoniae in the Balkans: Clonal distribution and associated resistance determinants.

Carbapenems are considered to be among the last line antibiotics against extended-spectrum β-lactamase producing Enterobacterales. Carbapenem-resistant Klebsiella pneumoniae (CRKP) has been frequently reported and its spread in Europe is indisputable and poses an enormous threat to hospitalized patients which is of growing concern. This review aims to record prevalence of CRKP in the Balkan region and to review the current knowledge about this life-threatening pathogen. In this review, we summarize data about clinical isolates of carbapenem-resistant K. pneumoniae from Greece, Croatia, Romania, Bulgaria, Serbia, Slovenia, Montenegro, Bosnia-Herzegovina and Albania from published reports between 2000 and 2023. Among Balkan countries, Greece and Romania are the ones with the most reports about CRKP. Since 2007, KPCs are the dominant carbapenemases in both countries. KPC-2 and NDM-1-producing K. pneumoniae strains have been identified as the most frequent CRKP in Croatia, Bulgaria, Serbia, and Slovenia. OXA-48 enzyme has been identified in most Balkan countries. In addition, since 2018, CRKP sequence type 11 (ST11) seems to have replaced ST258 in Balkan Peninsula, while ST15 continues to thrive throughout the years. Not only efficacy of colistin against CRKP has decreased dramatically during the last ten years but colistin resistance mechanism is based on alterations of chromosomal mgrB gene, rather than the already known mcr genes.Moreover, ceftazidime-avibactam-resistant CRKP were detected mostly in Greece. Emergence of CRKP poses a severe threat to the Balkan countries. Due to the narrow therapeutic window, it is essential to prevent the spread of multiresistant K. pneumoniae strains.

Digestion and importance of starch in ruminants

Ruminants have a unique digestive physiology that heavily relies on microbial fermentation specifically in the rumen. This review explores the complex mechanisms of starch digestion in ruminants and highlights its crucial role in shaping their nutritional landscape. The rumen, a complex microbial ecosystem, is the primary site for starch digestion. Enzymatic hydrolysis and microbial fermentation of starch in this compartment produce important byproducts, such as volatile fatty acids (VFAs) and microbial proteins. These byproducts are crucial sources of energy and protein, which affect the overall metabolic dynamics of ruminants. It is essential to have a comprehensive understanding of the factors that influence starch digestion rates to optimize ruminant nutrition. This review examines the various factors involved in starch digestion, including feed composition, microbial populations, and enzymatic activity, and how they contribute to the digestive process. Additionally, identifying and characterizing starch fractions in concentrated feed sources is crucial for formulating well-balanced rations. In conclusion, this review synthesizes current knowledge on starch digestion in ruminants, offering insights into the complexities of the process. The collected information not only contributes to our academic understanding but also has practical implications for optimizing feeding strategies, enhancing nutrient utilization, and promoting the overall well-being of ruminants.

Free‐ranging cattle and the return of the wolf: behavioral responses and implications for conservation management

Over the last decades, wolves have considerably expanded their distribution in Europe. Their range expansion even led to recolonizing densely human‐populated countries such as Belgium and the Netherlands. The few available studies on the effects of returning wolves in these landscapes focus primarily on the behavioral responses of wild ungulates, such as deer. While livestock in intensive farming practices can be protected against wolves, free‐ranging cattle in nature areas often have to protect themselves. How these cattle respond to the returned wolves is thus far unclear, yet highly relevant for conservation management. There is very little information about how free‐ranging cattle respond to the re‐appearance of wolves in terms of anti‐predator behavior and ability to defend themselves. In June 2022, a newly established wolf pair was located in a natural area in Drenthe. This natural area is grazed year‐round by free‐ranging Galloway cattle, a small and hornless primitive breed commonly used in conservation management. Here, we reported on the behavioral responses of the herd following two wolf attacks that occurred at nighttime in April 2023, the first caught on wildlife cameras in the Netherlands. During these events, the Galloways showed a clear behavioral response: they became active, restless and vigilant, and showed grouping behavior, presumably to protect the calves. Chasing behavior towards the attacking wolf was even exhibited by some individuals. The reported attacks did not result in killed or injured cattle. These two well‐documented wolf–cattle interactions show promising information as they highlight anti‐predator behaviors from an unexperienced cattle breed, all within a year of the wolves' return. We broadly discuss the relevance of these findings for grazing management, including selection for breeds, anti‐predator behaviors, and impact of herd structure and size, and we provide avenues for future research to address current knowledge gaps.

Wellness Tourism Attributes and Tourist Outcomes: An Analysis of Configurational Effects

Prior studies have identified the complexity involved in explaining the relationship between wellness tourism attributes and tourist behavior. This study investigated the configurational effects of 10 constructs in predicting the ambiguous area between overall satisfaction and destination behavioral loyalty. To achieve this, the study used a fuzzy set qualitative comparative analysis (fsQCA) and necessary condition analysis (NCA). The results of the fsQCA generated a range of models that effectively predicted tourists’ high or low levels of overall satisfaction and behavioral loyalty. Furthermore, the NCA results identified perceived quality as an essential construct for achieving the combination of overall satisfaction and behavioral loyalty. The study enhances our current knowledge by broadening our comprehension of the intricate aspects of tourists’ decision-making processes and the formation of their behaviors. Additionally, it provides a roadmap for the industry to effectively address challenges in managing wellness tourism resources.

The Overlooked Potential of Sulfated Zirconia: Reexamining Solid Superacidity Toward the Controlled Depolymerization of Polyolefins.

Closed-loop recycling via an efficient chemical process can help alleviate the global plastic waste crisis. However, conventional depolymerization methods for polyolefins, which compose more than 50% of plastics, demand high temperatures and pressures, employ precious noble metals, and/or yield complex mixtures of products limited to single-use fuels or oils. Superacidic forms of sulfated zirconia (SZrO) with Hammet Acidity Functions (H0) ≤ - 12 (i.e., stronger than 100% H2SO4) are industrially deployed heterogeneous catalysts capable of activating hydrocarbons under mild conditions and are shown to decompose polyolefins at temperatures near 200 °C and ambient pressure. Additionally, confinement of active sites in porous supports is known to radically increase selectivity, coking and sintering resistance, and acid site activity, presenting a possible approach to low-energy polyolefin depolymerization. However, a critical examination of the literature on SZrO led us to a surprising conclusion: despite 40 years of catalytic study, engineering, and industrial use, the surface chemistry of SZrO is poorly understood. Ostensibly spurred by SZrO's impressive catalytic activity, the application-driven study of SZrO has resulted in deleterious ambiguity in requisite synthetic conditions for superacidity and insufficient characterization of acidity, porosity, and active site structure. This ambiguity has produced significant knowledge gaps surrounding the synthesis, structure, and mechanisms of hydrocarbon activation for optimized SZrO, stunting the potential of this catalyst in olefin cracking and other industrially relevant reactions, such as isomerization, esterification, and alkylation. Toward mitigating these long extant issues, we herein identify and highlight these current shortcomings and knowledge gaps, propose explicit guidelines for characterization of and reporting on characterization of solid acidity, and discuss the potential of pore-confined superacids in the efficient and selective depolymerization of polyolefins.

Direct visualization of stacking-selective self-intercalation in epitaxial Nb1+xSe2 films

Two-dimensional (2D) van der Waals (vdW) materials offer rich tuning opportunities generated by different stacking configurations or by introducing intercalants into the vdW gaps. Current knowledge of the interplay between stacking polytypes and intercalation often relies on macroscopically averaged probes, which fail to pinpoint the exact atomic position and chemical state of the intercalants in real space. Here, by using atomic-resolution electron energy-loss spectroscopy in a scanning transmission electron microscope, we visualize a stacking-selective self-intercalation phenomenon in thin films of the transition-metal dichalcogenide (TMDC) Nb1+xSe2. We observe robust contrasts between 180°-stacked layers with large amounts of Nb intercalants inside their vdW gaps and 0°-stacked layers with little detectable intercalants inside their vdW gaps, coexisting on the atomic scale. First-principles calculations suggest that the films lie at the boundary of a phase transition from 0° to 180° stacking when the intercalant concentration x exceeds ~0.25, which we could attain in our films due to specific kinetic pathways. Our results offer not only renewed mechanistic insights into stacking and intercalation, but also open up prospects for engineering the functionality of TMDCs via stacking-selective self-intercalation.

Apoptotic Effects of Adipose-Derived Stem Cell Secretome in Breast Cancer Stem Cells: A Literature Review

Adipose-derived stem cells (ASC) are cells from the core of fat tissue that secrete various cytokines, growth factors, proteins and extracellular vesicles that can be used in regenerative therapy, especially in the case of cancer. This ASC produces a secretome which is an exosome derived from ASC. In many studies it has been proven that the secretome has proangiogenic, neurotrophic and epithelialization activities and has the potential to be used for cardiovascular, respiratory, neurodegenerative, inflammatory and autoimmune diseases, as a wound healing treatment and as an immunomodulator in anticancer therapy through induction of apoptosis. Due to the limited use of stem cells in cell-based therapies, secretomes from ACS-derived exosomes may be a safer alternative treatment in the future with higher levels of effectiveness and lower side effects. Therefore in this review, we focus on the current knowledge about the ASC secretome that can induce breast cancer cell apoptosis.

State of the Art Review for Titanium Fluorine Glasses and Glass Ceramics.

Titanium (Ti) and fluorine (F) have the potential to provide a variety of desirable physical, chemical, mechanical, and biological properties applicable to a broad range of indications. Consequently, Ti- and F-containing glasses and glass ceramics are currently under investigation for use in nuclear, optical, electrochemical, dental, and industrial fields. Accordingly, significant interest exists with respect to understanding the individual and interaction effects that these elements have on material structure and properties to support the accelerated design, development, and deployment of these materials. This review aims to serve as a foundational reference across multiple disciplines, highlighting the fundamental properties and versatility of Ti- and F-containing glasses and glass ceramics. By consolidating our current knowledge of these materials, this broad overview will identify areas in which we can further our understanding to support the a priori prediction and effective design of these systems. Finally, this paper will introduce the potential to improve material design by integrating experimentation, modelling, and computational approaches in a manner commensurate with the principles of the Materials Genome Initiative.

Knowledge of vitamin D and practices of vitamin D supplementation in a Scottish adult population: A cross-sectional study.

Background: Vitamin D supplementation practices (dose and frequency) are relatively unknown in the Scottish population, with no recent up-to-date data available. Reassessing current knowledge, practices, and awareness of vitamin D supplementation following a national health campaign in 2020 by Food Standards Scotland on vitamin D is warranted. Aim: This article aims to present the knowledge and awareness of vitamin D, and current vitamin D supplementation practices in adults living in Scotland. Methods: A cross-sectional study was performed between June and July 2022 using an online survey adapted from previous work on assessing knowledge of vitamin D in adults. Participants aged 18+, living in Scotland for ≥6 months were eligible to participate. Scores for knowledge were calculated as a percentage. Univariate associations between demographic and supplement use were established by χ2-test and logistic regression performed to predict factors associated with daily vitamin D intake. Results: Four hundred and three participants (72.7% female), mean age 36.4 (±14.2 years), completed the study. Awareness of vitamin D was very high (99.5%) but the mean overall knowledge score was poor (31.4 ± 15.3%), with those with a university degree more likely to have knowledge scores at/above the mean compared with those with lower levels of education, χ2(1, N = 393) 10.7, p = 0.001, odds ratio (OR) = 2.1 (95% confidence interval (CI) 1.7-2.7). Finally, 64.3% took vitamin D supplements, of which 37.5% took them daily during winter months, with only 7.4% taking the recommended daily dose. Conclusion: The current study highlights the need to improve both knowledge of vitamin D and practices of vitamin D supplementation during the autumn and winter months in Scotland.

Robots and emotional intelligence: A thematic analysis

The research on emotional intelligence in social robots is growing. This paper provides a thematic analysis of the studies on robots and emotional intelligence, synthesising and evaluating current knowledge and research topics. In addition, based on the thematic analysis of the studies, it also provides a conceptual framework explaining the emotional intelligence of robots that includes both actors (human and robot) in a human-robot interaction setting. The findings are based on the analysis of 252 studies published until the end of 2022 and indexed in the Scopus database. The results unveiled two main themes (robot design-technical developments and characteristics and human-robot interaction), including sub-themes and topics that emerged in the literature. Finally, the themes and sub-themes were evaluated through a critical discussion to develop a conceptual framework for robots and emotional intelligence.

Noninvasive biomarkers for lupus nephritis.

Lupus nephritis (LN) is one of the most severe clinical manifestations of systemic lupus erythematosus (SLE). Notably, the clinical manifestations of LN are not always consistent with the histopathological findings. Therefore, the diagnosis and activity monitoring of this disease are challenging and largely depend on invasive renal biopsy. Renal biopsy has side effects and is associated with the risk of bleeding and infection. There is a growing interest in the development of novel noninvasive biomarkers for LN. In this review, we summarize most of the LN biomarkers discovered so far by correlating current knowledge with future perspectives. These biomarkers fundamentally reflect the biological processes of kidney damage and repair during disease. Furthermore, this review highlights the role of urinary cell phenotype detection in the diagnosis, monitoring, and treatment of LN and summarizes the limitations and countermeasures of this test.

Progress report: Peutz-Jeghers syndrome.

Peutz-Jeghers syndrome is a rare, autosomal dominant polyposis syndrome. Presenting with a remarkable phenotype including development of characteristic gastrointestinal polyps, mucocutaneous pigmentations, and an increased risk of cancer, the syndrome has been subject to many studies concerning the natural course of disease. In most patients, pathogenic germline variants are detected in the STK11 gene including cases of mosaicism and structural variants. Yet, studies assessing the effect of surveillance, understanding of cancer development, as well as clinical studies evaluating chemoprevention are lacking. In addition, the impact of Peutz-Jeghers syndrome on mental health, education, and family planning are insufficiently addressed. In this progress report, we describe current knowledge, clinical phenotype, surveillance strategies, and future areas of research.

The Current Understanding of Mechanistic Pathways in Zeolite Crystallization.

Zeolite catalysts and adsorbents have been an integral part of many commercial processes and are projected to play a significant role in emerging technologies to address the changing energy and environmental landscapes. The ability to rationally design zeolites with tailored properties relies on a fundamental understanding of crystallization pathways to strategically manipulate processes of nucleation and growth. The complexity of zeolite growth media engenders a diversity of crystallization mechanisms that can manifest at different synthesis stages. In this review, we discuss the current understanding of classical and nonclassical pathways associated with the formation of (alumino)silicate zeolites. We begin with a brief overview of zeolite history and seminal advancements, followed by a comprehensive discussion of different classes of zeolite precursors with respect to their methods of assembly and physicochemical properties. The following two sections provide detailed discussions of nucleation and growth pathways wherein we emphasize general trends and highlight specific observations for select zeolite framework types. We then close with conclusions and future outlook to summarize key hypotheses, current knowledge gaps, and potential opportunities to guide zeolite synthesis toward a more exact science.

Understanding CYP3A4 and P-gp mediated drug-drug interactions through PBPK modeling - Case example of pralsetinib.

Pralsetinib, a potent and selective inhibitor of oncogenic RET fusion and RET mutant proteins, is a substrate of the drug metabolizing enzyme CYP3A4 and a substrate of the efflux transporter P-gp based on invitro data. Therefore, its pharmacokinetics (PKs) may be affected by co-administration of potent CYP3A4 inhibitors and inducers, P-gp inhibitors, and combined CYP3A4 and P-gp inhibitors. With the frequent overlap between CYP3A4 and P-gp substrates/inhibitors, pralsetinib is a challenging and representative example of the need to more quantitatively characterize transporter-enzyme interplay. A physiologically-based PK (PBPK) model for pralsetinib was developed to understand the victim drug-drug interaction (DDI) risk for pralsetinib. The key parameters driving the magnitude of pralsetinib DDIs, the P-gp intrinsic clearance and the fraction metabolized by CYP3A4, were determined from PBPK simulations that best captured observed DDIs from three clinical studies. Sensitivity analyses and scenario simulations were also conducted to ensure these key parameters were determined with sound mechanistic rationale based on current knowledge, including the worst-case scenarios. The verified pralsetinib PBPK model was then applied to predict the effect of other inhibitors and inducers on the PKs of pralsetinib. This work highlights the challenges in understanding DDIs when enzyme-transporter interplay occurs, and demonstrates an important strategy for differentiating enzyme/transporter contributions to enable PBPK predictions for untested scenarios and to inform labeling.

Decreased oxytocin levels related to social cognition impairment in borderline personality disorder.

Dysfunctions in the oxytocin system have been reported in patients with borderline personality disorder (BPD). Deficits could be related to interpersonal hypersensitivity, which has been previously associated with failures in social cognition (SC) in this disorder, especially in Theory of Mind (ToM) skills. The aim of this work is to study the links between the oxytocin system and SC impairments in patients with BPD. Plasma oxytocin levels (OXT) and protein expression of oxytocin receptors in blood mononuclear cells (OXTR) were examined in 33 patients with a diagnosis of BPD (age: M 28.85, DT = 8.83). Social cognition was assessed using the Movie for the Assessment of Social Cognition (MASC). Statistical associations between biochemical factors and different response errors in MASC were analyzed through generalized linear regression controlling for relevant clinical factors. Generalized linear regression showed a significant relationship between lower OXTR and overmentalization in BPD patients (OR = 0.90). This work supports the relationship between alterations in the oxytocin system and ToM impairments observed in BPD patients, enhancing the search for endophenotypes related to the phenotypic features of the disorder to improve current clinical knowledge and address more specific therapeutic targets.

Testicular niche repair after gonadotoxic treatments: Current knowledge and future directions.

The testicular niche, which includes the germ cells, somatic cells, and extracellular matrix, plays a crucial role in maintaining the proper functions of the testis. Gonadotoxic treatments, such as chemotherapy and radiation therapy, have significantly improved the survival rates of cancer patients but have also been shown to have adverse effects on the testicular microenvironment. Therefore, repairing the testicular niche after gonadotoxic treatments is essential to restore its function. In recent years, several approaches, such as stem cell transplantation, gene therapy, growth factor therapy, and pharmacological interventions have been proposed as potential therapeutic strategies to repair the testicular niche. This comprehensive review aims to provide an overview of the current understanding of testis damage and repair mechanisms. We will cover a range of topics, including the mechanism of gonadotoxic action, repair mechanisms, and treatment approaches. Overall, this review highlights the importance of repairing the testicular niche after gonadotoxic treatments and identifies potential avenues for future research to improve the outcomes for cancer survivors.

Assessing Metal Toxicity on Crustaceans in Aquatic Ecosystems: A Comprehensive Review.

Residual concentrations of some trace elements and lightweight metals, including cadmium, copper, lead, mercury, silver, zinc, nickel, chromium, arsenic, gallium, indium, gold, cobalt, polonium, and thallium, are widely detected in aquatic ecosystems globally. Although their origin may be natural, human activities significantly elevate their environmental concentrations. Metals, renowned pollutants, threaten various organisms, particularly crustaceans. Due to their feeding habits and habitat, crustaceans are highly exposed to contaminants and are considered a crucial link in xenobiotic transfer through the food chain. Moreover, crustaceans absorb metals via their gills, crucial pathways for metal uptake in water. This review summarises the adverse effects of well-studied metals (Cd, Cu, Pb, Hg, Zn, Ni, Cr, As, Co) and synthesizes knowledge on the toxicity of less-studied metals (Ag, Ga, In, Au, Pl, Tl), their presence in waters, and impact on crustaceans. Bibliometric analysis underscores the significance of this topic. In general, the toxic effects of the examined metals can decrease survival rates by inducing oxidative stress, disrupting biochemical balance, causing histological damage, interfering with endocrine gland function, and inducing cytotoxicity. Metal exposure can also result in genotoxicity, reduced reproduction, and mortality. Despite current toxicity knowledge, there remains a research gap in this field, particularly concerning the toxicity of rare earth metals, presenting a potential future challenge.

Current and Developing Pharmacologic Agents for Improving Skeletal Health in Adults with Osteogenesis Imperfecta.

Osteogenesis imperfecta (OI) is a genetic disorder characterized by increased bone fragility largely caused by defects in structure, synthesis, or post-translational processing of type I collagen. Drugs currently used to improve skeletal health in OI were initially developed to treat osteoporosis and clinical trials are ongoing to study their effectiveness in OI adults. Additionally, novel bone-protective agents are in preclinical studies and various phases of OI clinical trials. This review summarizes current knowledge on available pharmacologic agents and current drug trials involving OI participants. A PubMed online database search of all study types published in the English language using the terms "osteogenesis imperfecta," "OI," and "brittle bone disease" was performed in August 2022. Articles screened were restricted to adults. A ClinicalTrials.gov database search of all studies involving "osteogenesis imperfecta" was performed in August 2023. Although clinical trial data are limited, bisphosphonates and teriparatide may be useful in improving bone mineral density. As of yet, no clinical trials are available that adequately evaluate the usefulness of current therapies in reducing fracture risk. Several therapeutics, including teriparatide, setrusumab, anti-TGF-β antibodies, and allogeneic stem cells, are being studied in clinical trials. Preclinical studies involving Dickkopf-1 antagonists present promising data in non-OI bone disease, and could be useful in OI. Research is ongoing to improve therapeutic options for adults with OI and clinical trials involving gene-editing may be possible in the coming decade.