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The article announces winners of the International Journal of Molecular Science Best Paper Award for 2018, including a research paper on development of amperometric biosensor, one on prostate cancer cells, and one on detection of Staphylococcus aureus.

The article discusses the advances in fractional-order neural networks and their applications in various fields such as biology, biochemistry, engineering, economics, and physics. Volume II of the Special Issue focuses on the synchronization of fractional-order neural networks, with four papers addressing this topic. Other papers explore variable-order fractionals, non-periodicity of complex maps, impulsive delayed reaction-diffusion gene regulatory networks, split-plot designs, consensus in multi-agent systems, and the mathematical theory of nabla tempered fractional calculus. The editors express their gratitude to the authors and reviewers for their contributions, and believe that the selected papers will enrich readers' knowledge in this field. [Extracted from the article]

Recent developments in microfluidic devices, nanoparticle chemistry, fluorescent microscopy, and biochemical techniques such as genetic identification and antibody capture have provided easier and more sensitive platforms for detecting and diagnosing diseases as well as providing new fundamental insight into disease progression. These advancements have led to the development of new technology and assays capable of easy and early detection of pathogenicity as well as the enhancement of the drug discovery and development pipeline. While some studies have focused on treatment, many of these technologies have found initial success in laboratories as a precursor for clinical applications. This review highlights the current and future progress of microfluidic techniques geared toward the timely and inexpensive diagnosis of disease including technologies aimed at high-throughput single cell analysis for drug development. It also summarizes novel microfluidic approaches to characterize fundamental cellular behavior and heterogeneity. [ABSTRACT FROM AUTHOR]

The ability to study chemical dynamics on ultrafast timescales has greatly advanced with the introduction of X-ray free electron lasers (XFELs) providing short pulses of intense X-rays tailored to probe atomic structure and electronic configuration. Fully exploiting the full potential of XFELs requires specialized experimental endstations along with the development of techniques and methods to successfully carry out experiments. The liquid jet endstation (LJE) at the Linac Coherent Light Source (LCLS) has been developed to study photochemistry and biochemistry in solution systems using a combination of X-ray solution scattering (XSS), X-ray absorption spectroscopy (XAS), and X-ray emission spectroscopy (XES). The pump–probe setup utilizes an optical laser to excite the sample, which is subsequently probed by a hard X-ray pulse to resolve structural and electronic dynamics at their intrinsic femtosecond timescales. The LJE ensures reliable sample delivery to the X-ray interaction point via various liquid jets, enabling rapid replenishment of thin samples with millimolar concentrations and low sample volumes at the 120 Hz repetition rate of the LCLS beam. This paper provides a detailed description of the LJE design and of the techniques it enables, with an emphasis on the diagnostics required for real-time monitoring of the liquid jet and on the spatiotemporal overlap methods used to optimize the signal. Additionally, various scientific examples are discussed, highlighting the versatility of the LJE. [ABSTRACT FROM AUTHOR]

In recent years, sphingolipids have attracted significant attention due to their pivotal role in cellular functions and physiological diseases. A valuable tool for investigating the characteristics of sphingolipids can be represented via FT-IR spectroscopy, generally recognized as a very powerful technique that provides detailed biochemical information on the examined sample with the unique properties of sensitivity and accuracy. In the present paper, some fundamental aspects of sphingolipid components of human cells are summarized, and the most relevant articles devoted to the FT-IR spectroscopic studies of sphingolipids are revised. A short description of different FT-IR experimental approaches adopted for investigating sphingolipids is also given, with details about the most commonly used data analysis procedures. The present overview of FT-IR investigations, although not exhaustive, attests to the relevant role this vibrational technique has played in giving significant insight into many aspects of this fascinating class of lipids. [ABSTRACT FROM AUTHOR]

Introduction: The Krebs cycle is an important set of reactions that synthesize different molecules and substances that affect various organs. The objective of this paper was to compare the effects of Krebs cycle intermediates on the endocrine system and the immune system. Methods and Materials: The articles used in this paper were obtained from a systematic search of PsycINFO, PubMed, Web of Science, CINAHL, and primary databases. The search terms were "Krebs cycle," "intermediates," "endocrine system," "tricarboxylic acid," "citric acid cycle," and "immune system," and Boolean operators (AND/OR) were used to combine terms. Results: A review of the selected studies showed that Krebs cycle intermediates influence how the endocrine system regulates and controls body processes, including energy uptake. Moreover, these intermediates have both direct and indirect effects on immune function, memory, and activation. Discussion: An understanding of the effects of Krebs cycle intermediates on endocrine and immune processes will provide valuable insights for the development of new therapies. Additionally, this knowledge is a basis for exploring the pathogenesis of the complications related to endocrine system function and for evaluating the immune system response to pathogens. Conclusions: The evidence gathered in this review shows that Krebs cycle intermediates have significant effects on immune and endocrine processes. However, further human and in vivo studies are required to generate additional evidence for the underlying pathways and to identify the potential strategies for targeting these mechanisms to manage specific disorders. [ABSTRACT FROM AUTHOR]

Neutral starch microspheres (NSMs) were synthesized by an inverse microemulsion technology with epichlorohydrin as a crosslinker and soluble starch as starting material. Anionic starch microspheres (ASMs) were prepared from NSMs by the secondary polymerization with chloroacetic acid as the anionic etherifying agent. Fourier transform infrared spectroscopy (FT-IR), scanning electron microscopy (SEM) and laser diffraction particle size analyzer were used to characterize the anionic starch microspheres. The results showed that structure of the microspheres was compact and the hardness of microspheres was great, and the average diameter of the product was about 75 μm. The anionic starch microspheres (ASMs) were used to adsorb methylene blue (MB) from aqueous solution. Effects of adsorption time, initial concentration of MB, and temperature on the adsorption of MB onto ASMs were studied, and the equilibrium and kinetics of the adsorption process were further investigated. It shows that ASMs can effectively remove MB from the solution. The adsorption equilibrium data correlates well with the Langmuir isotherm model compared with Frendlich isotherem model. The pseudo-first-order and pseudo-second-order kinetic models were applied to test the experimental data. The pseudo-second-order kinetic model provided a better correlation of the experimental data in comparison with the pseudo-first-order model. Temperature variations did not significantly affect the adsorption of MB onto ASMs. [ABSTRACT FROM AUTHOR]

Simple Summary: Penile cancer is a rare and aggressive disease. Current treatment options when the cancer is locally advanced are suboptimal and potentially mutilating. Insight into the immune dysregulation necessary for the emergence of penile cancer could suggest innovative ways to manipulate the immune system which have already demonstrated efficacy in other, more common malignancies. In this paper, we use multiplex immunofluorescence, a novel technology, to investigate the immune microenvironment of penile cancer for the first time. We describe a pattern of immune exhaustion as cancer becomes more advanced and identify tumor-associated macrophages as a potential key player in regulating this process. Penile squamous cell carcinoma (PSCC) is a rare and deadly malignancy. Therapeutic advances have been stifled by a poor understanding of disease biology. Specifically, the immune microenvironment is an underexplored component in PSCC and the activity of immune checkpoint inhibitors observed in a subset of patients suggests immune escape may play an important role in tumorigenesis. Herein, we explored for the first time the immune microenvironment of 57 men with PSCC and how it varies with the presence of human papillomavirus (HPV) infection and across tumor stages using multiplex immunofluorescence of key immune cell markers. We observed an increase in the density of immune effector cells in node-negative tumors and a progressive rise in inhibitory immune players such as type 2 macrophages and upregulation of the PD-L1 checkpoint in men with N1 and N2-3 disease. There were no differences in immune cell densities with HPV status. [ABSTRACT FROM AUTHOR]

Fetal alcohol spectrum disorder (FASD) is commonly misdiagnosed because of the complexity of presentation and multiple diagnostic criteria. FASD includes four categorical entities (fetal alcohol syndrome, partial fetal alcohol syndrome, alcohol related neurodevelopmental disorder, and alcohol related birth defects). The four FASD diagnostic criteria are facial dysmorphology, growth deficiency, central nervous system dysfunction, and prenatal alcohol exposure. Sensory processing disorders (SPDs) are common in FASD and are observed as inappropriate behavioral responses to environmental stimuli. These can be either a sensory-based motor disorder, sensory discrimination disorder, or sensory modulation disorder. A child with SPD may experience challenges with their fine motor coordination, gross motor coordination, organizational challenges, or behavioral regulation impairments. FASD requires a multidimensional approach to intervention. Although FASD cannot be cured, symptoms can be managed with sleep-based therapies, sensory integration, and cognitive therapies. This paper reviews SPDs in FASD and the interventions that can be used by practitioners to help improve their therapeutic management, although it is unlikely that any single intervention will be the right choice for all patients. [ABSTRACT FROM AUTHOR]

For the structure and functioning of bio-molecules, metals are important. The main focus of research remains the design and synthesis of novel metal-based complexes and metal ion binding to substances in search of novel medicines. Studies have established the well-defined geometry, thermodynamic stability and excellent coordination power of vanadium in different oxidation states. This paper summarizes the biological activities of vanadium complexes, particularly their anticancer activity. Future multidisciplinary research and analysis focused on comprehending the biochemistry of vanadium complexes with different ligands is required. [ABSTRACT FROM AUTHOR]

Metabolic pathway prediction and reconstruction play crucial roles in solving fundamental and applied biomedical problems. In the case of fundamental research, annotation of metabolic pathways allows one to study human health in normal, stressed, and diseased conditions. In applied research, it allows one to identify novel drugs and drug targets and to design mimetics (biomolecules with tailored properties), as well as contributes to the development of such disciplines as toxicology and nutrigenomics. It is important to understand the role of a metabolite as a substrate (the product or intermediate participant of an enzymatic reaction) in cellular signaling and phenotype implementation according to the pivotal paradigm of biology: "one gene–one protein–one function (one trait)". Due to the development of omics technologies, a vast body of data on the metabolome composition of living organisms has been accumulated over the past two decades. Systematization of the information on the roles played by metabolites in implementation of cellular signaling, as well as metabolic pathway reconstruction and refinement, have necessitated the development of bioinformatic tools for performing large-scale omics data mining. This paper reviews web-accessible databases relevant to metabolic pathways and considers the applications of the three types of bioinformatics methods for constructing metabolic networks (graphs for substrate–enzyme–product transformation; stoichiometric analysis of substrate–product transformation; and product retrosynthesis). It describes, step by step, a generalized algorithm for constructing biological pathway maps which explains to the researcher the workflow implemented in available bioinformatics tools and can be used to create new tools in projects requiring pathway reconstruction. [ABSTRACT FROM AUTHOR]

Simple Summary: Malignant melanoma is an aggressive cancer of the skin and the leading cause of death from skin cancer. One major risk factor linked to melanoma development is exposure to UV radiation. However, the sharp increase in melanoma cases cannot be explained only by more UV exposure. Identifying additional modifiable social-environmental risk factors for melanoma beyond UV exposure would greatly impact public health initiatives and the methods of patient outreach and education. Recent studies have shown the link between melanoma and alcohol consumption. This perspective review paper aims to understand the mechanisms underlying ethanol's ability to induce human cancers, including melanoma. Although cancer mortality has declined among the general population, the incidence of melanoma continues to rise. While identifying high-risk cohorts with genetic risk factors improves public health initiatives and clinical care management, recognizing modifiable risk factors such as social-environmental risk factors would also affect the methods of patient outreach and education. One major modifiable social-environmental risk factor associated with melanoma is ultraviolet (UV) radiation. However, not all forms of melanoma are correlated with sun exposure or occur in sun-exposed areas. Additionally, UV exposure is rarely associated with tumor progression. Another social-environmental factor, pregnancy, does not explain the sharply increased incidence of melanoma. Recent studies have demonstrated that alcohol consumption is positively linked with an increased risk of cancers, including melanoma. This perspective review paper summarizes epidemiological data correlating melanoma incidence with alcohol consumption, describes the biochemical mechanisms of ethanol metabolism, and discusses how ethanol and ethanol metabolites contribute to human cancer, including melanoma. [ABSTRACT FROM AUTHOR]

Simple Summary: Ceramide and associated enzymes play a substantial role in cell function such as in cell proliferation, differentiation, and apoptosis processes. Knowing the enzymatic pathway and targeting particular enzymes from that pathway can lead to a very successful therapeutic outcome. As such, this review is focused on the elaboration of the natural products and small inhibitor molecules that can target important enzymes such as ceramidase and ceramide synthase that participate in the central lipid ceramide pathway, as well as the outcome when those pathways are disturbed during disease progression. In addition, this paper also discusses cancer that is associated with the imbalance of ceramide enzymes. Molecular targeting strategies have been used for years in order to control cancer progression and are often based on targeting various enzymes involved in metabolic pathways. Keeping this in mind, it is essential to determine the role of each enzyme in a particular metabolic pathway. In this review, we provide in-depth information on various enzymes such as ceramidase, sphingosine kinase, sphingomyelin synthase, dihydroceramide desaturase, and ceramide synthase which are associated with various types of cancers. We also discuss the physicochemical properties of well-studied inhibitors with natural product origins and their related structures in terms of these enzymes. Targeting ceramide metabolism exhibited promising mono- and combination therapies at preclinical stages in preventing cancer progression and cemented the significance of sphingolipid metabolism in cancer treatments. Targeting ceramide-metabolizing enzymes will help medicinal chemists design potent and selective small molecules for treating cancer progression at various levels. [ABSTRACT FROM AUTHOR]

Base excision repair (BER) is a cellular process that removes damaged bases arising from exogenous and endogenous sources including reactive oxygen species, alkylation agents, and ionizing radiation. BER is mediated by the actions of multiple proteins which work in a highly concerted manner to resolve DNA damage efficiently to prevent toxic repair intermediates. During the initiation of BER, the damaged base is removed by one of 11 mammalian DNA glycosylases, resulting in abasic sites. Many DNA glycosylases are product-inhibited by binding to the abasic site more avidly than the damaged base. Traditionally, apurinic/apyrimidinic endonuclease 1, APE1, was believed to help turn over the glycosylases to undergo multiple rounds of damaged base removal. However, in a series of papers from our laboratory, we have demonstrated that UV-damaged DNA binding protein (UV-DDB) stimulates the glycosylase activities of human 8-oxoguanine glycosylase (OGG1), MUTY DNA glycosylase (MUTYH), alkyladenine glycosylase/N-methylpurine DNA glycosylase (AAG/MPG), and single-strand selective monofunctional glycosylase (SMUG1), between three- and five-fold. Moreover, we have shown that UV-DDB can assist chromatin decompaction, facilitating access of OGG1 to 8-oxoguanine damage in telomeres. This review summarizes the biochemistry, single-molecule, and cell biology approaches that our group used to directly demonstrate the essential role of UV-DDB in BER. [ABSTRACT FROM AUTHOR]

A protometabolic approach to the origins of life assumes that the conserved biochemistry of metabolism has direct continuity with prebiotic chemistry. One of the most important amino acids in modern biology is aspartic acid, serving as a nodal metabolite for the synthesis of many other essential biomolecules. Aspartate's prebiotic synthesis is complicated by the instability of its precursor, oxaloacetate. In this paper, we show that the use of the biologically relevant cofactor pyridoxamine, supported by metal ion catalysis, is sufficiently fast to offset oxaloacetate's degradation. Cu2+-catalysed transamination of oxaloacetate by pyridoxamine achieves around a 5% yield within 1 h, and can operate across a broad range of pH, temperature, and pressure. In addition, the synthesis of the downstream product β-alanine may also take place in the same reaction system at very low yields, directly mimicking an archaeal synthesis route. Amino group transfer supported by pyridoxal is shown to take place from aspartate to alanine, but the reverse reaction (alanine to aspartate) shows a poor yield. Overall, our results show that the nodal metabolite aspartate and related amino acids can indeed be synthesised via protometabolic pathways that foreshadow modern metabolism in the presence of the simple cofactor pyridoxamine and metal ions. [ABSTRACT FROM AUTHOR]

36430343 45 Geiger N., Diesendorf V., Roll V., König E.M., Obernolte H., Sewald K., Breidenbach J., Pillaiyar T., Gütschow M., Müller C.E. Cell Type-Specific Anti-Viral Effects of Novel SARS-CoV-2 Main Protease Inhibitors. 36430304 25 Angeli A., Petrou A., Kartsev V., Lichitsky B., Komogortsev A., Capasso C., Geronikaki A., Supuran C.T. Synthesis, Biological and In Silico Studies of Griseofulvin and Usnic Acid Sulfonamide Derivatives as Fungal, Bacterial and Human Carbonic Anhydrase Inhibitors. 10.3390/ijms23084342 29 Grossmannova K., Barathova M., Belvoncikova P., Lauko V., Csaderova L., Tomka J., Dulka T., Pastorek J., Madaric J. Hypoxia Marker Carbonic Anhydrase IX Is Present in Abdominal Aortic Aneurysm Tissue and Plasma. 10.3390/ijms232113082 49 Valdovino-Navarro B.J., Dueñas S., Flores-Acosta G.I., Gasperin-Bulbarela J., Bernaldez-Sarabia J., Cabanillas-Bernal O., Cervantes-Luevano K.E., Licea-Navarro A.F. Neutralizing Ability of a Single Domain VNAR Antibody: In Vitro Neutralization of SARS-CoV-2 Variants of Concern. [Extracted from the article]

Simple Summary: The compounds named PROTACs are formed by two fragments, which bring together a particular protein with a ubiquitinating enzyme. This allows ubiquitination and degradation of the targeted protein. Ubiquitination-mediated protein degradation is an important regulatory process to control the expression levels of proteins and maintain the homeostatic conditions in cells. Thus, by re-directing a mechanism that is normally used for cell regulation, PROTACs allow to remove specific proteins associated to particular diseases or pathological conditions. In this paper, we report a type of PROTAC that targets for degradation the protein named p38α, whose functions have been linked to cancer and other diseases. We show that these PROTACs effectively reduce p38α protein expression not only in several cancer cell lines but also in tumors generated in mice. These compounds may provide an attractive strategy to evaluate potential therapeutic applications for targeting p38α in the clinical context. We report a series of small molecule proteolysis-targeting chimeras (PROTACs) that target the protein kinase p38α for degradation. These PROTACs are based on a ligand of the VHL E3 ubiquitin ligase, which is linked to an ATP competitive inhibitor of p38α. We provide evidence that these compounds can induce the specific degradation of p38α, but not p38β and other related kinases, at nanomolar concentrations in several mammalian cell lines. We also show that the p38α-specific PROTACs are soluble in aqueous solutions and therefore suitable for their administration to mice. Systemic administration of the PROTACs induces p38α degradation only in the liver, probably due to the PROTAC becoming inactivated in that organ, but upon local administration the PROTACs induce p38α degradation in mammary tumors. Our compounds provide an alternative to traditional chemical inhibitors for targeting p38α signaling in cultured cells and in vivo. [ABSTRACT FROM AUTHOR]

Research on food-derived bioactive peptides is expanding and the need for a convenient online platform that combines a foolproof and intuitive user interface with a reliable database and tools for prediction and analysis is rising. In this regard, this paper presents an open-access web-based platform PepLab (Peptides Laboratory). The database contains 2764 peptide sequence entries, grouped into sixteen classes according to their biological activity and into seven classes according to the source from which they were derived. Moreover, it includes bioinformatic tools for their processing and analysis. The DMpep tool allows extracting information about a number of physicochemical characteristics of a peptide or a set of peptides, including those that are not recorded in the database. The main advantages of PepLab are a user-friendly interface, a responsive design, and optimized search engines for better visibility on the Internet. Prediction of non-reported activity is available based on amino acid sequence analysis. In addition, users can download data and results in a convenient format (text and/or graphic) that was limited in the existing platforms. In this way, the presented PepLab platform will be helpful for researchers from various fields—bioinformatics, pharmaceuticals, food sciences, dietetics, biotechnology, analytical chemistry, etc. [ABSTRACT FROM AUTHOR]

Charge transport across proteins can be surprisingly efficient over long distances—so-called long-range tunneling—but it is still unclear as to why and under which conditions (e.g., presence of co-factors, type of cargo) the long-range tunneling regime can be accessed. This paper describes molecular tunneling junctions based on an encapsulin (Enc), which is a large protein cage with a diameter of 24 nm that can be loaded with various types of (small) proteins, also referred to as "cargo". We demonstrate with dynamic light scattering, transmission electron microscopy, and atomic force microscopy that Enc, with and without cargo, can be made stable in solution and immobilized on metal electrodes without aggregation. We investigated the electronic properties of Enc in EGaIn-based tunnel junctions (EGaIn = eutectic alloy of Ga and In that is widely used to contact (bio)molecular monolayers) by measuring the current density for a large range of applied bias of ±2.5 V. The encapsulated cargo has an important effect on the electrical properties of the junctions. The measured current densities are higher for junctions with Enc loaded with redox-active cargo (ferritin-like protein) than those junctions without cargo or redox-inactive cargo (green fluorescent protein). These findings open the door to charge transport studies across complex biomolecular hierarchical structures. [ABSTRACT FROM AUTHOR]

Simple Summary: Prostate-specific membrane antigen positron emission tomography (PSMA PET) is a modern imaging modality used in the management of patients with prostate cancer with improved accuracy in detecting lymph nodes and distant disease spread. In this paper, we discuss how the increasing use of PSMA PET is changing clinical management in patients with prostate cancer, specifically those previously treated for localized disease and now presenting with recurrence or low-volume metastatic disease spread. We also discuss how PSMA PET is affecting clinical trial design and interpretation. More clinical trials are needed to investigate whether the use of PSMA PET translates into improved patient survival or quality of life. Prostate-specific membrane antigen (PSMA) positron emission tomography (PET) scans have higher sensitivity and specificity for detecting lymph nodes or metastatic disease relative to conventional imaging in prostate cancer staging. Since its FDA approval and incorporation into treatment guidelines, the use of PSMA PET has increased in patients undergoing initial staging, those with recurrence after initial definitive treatment, and patients with metastatic disease. Although the early detection of metastatic lesions is changing disease management, it is unclear whether this impact on management translates into clinical benefit. This review will summarize evidence pertaining to the change in patient management due to PSMA PET use and will discuss the implications of PSMA PET on treatment decisions in prostate cancer, particularly in the settings of biochemical recurrence and metachronous oligometastatic disease. [ABSTRACT FROM AUTHOR]

Simple Summary: Given that wild animal hospitalisations are increasing, veterinary knowledge of wildlife medicine needs to be improved along with more effective clinical and diagnostic procedures. A blood test can be a quick and minimally invasive way of gathering useful clinical information. This study evaluates the haematological and biochemical parameters in injured roe deer and discusses their values in relation to animal hospitalisation outcomes. The study was conducted on a cohort of 98 roe deer divided into groups based on age and hospitalisation outcome. A panel of haematological and biochemical parameters was performed for each animal. Significant differences were found within both the unweaned and weaned groups. Creatine kinase, creatinine, and bilirubin may be useful indicators to correlate with the severity of trauma. Veterinary facility admissions of wild animals are increasing alongside the interest in wildlife diseases. To improve animal welfare, it is therefore important to increase veterinarians' knowledge of wild animal medicine and to improve the clinical and diagnostic procedures, especially in the case of patients affected by trauma or multiple traumas. Blood analysis can be a quick and minimally invasive way of gathering useful clinical information for adequate treatment and management, and, together with a good clinical examination, to help predict hospitalisation outcomes. Few papers have reported reference ranges for the haematological and biochemical parameters of roe deer. This study evaluates the haematological and biochemical parameters in traumatised roe deer in relation to animal hospitalisation outcomes. The study was carried out on a cohort of 98 roe deer divided into groups according to their age and hospitalisation outcome. For each animal, a panel of haematological and biochemical parameters was performed. Significant differences were found between unweaned (<4 months old) groups in terms of MCV, MCH, CK, creatinine, total bilirubin, direct bilirubin, and indirect bilirubin, and between weaned (>4 months old) groups for total bilirubin. Creatine kinase, creatinine, and bilirubin may be useful indicators to correlate with the severity of trauma and help predict prognosis. [ABSTRACT FROM AUTHOR]

Simple Summary: We summarized and cataloged the E3 ligases involved in endometrial carcinoma (EC) and cervical cancer (CC). Finally, an overview of the current drugs that target the ubiquitination process to rescue patients with EC and CC is presented to provide researchers with important research ideas that can be applied to clinical treatment. Endometrial (EC) and cervical (CC) cancers are the most prevalent malignancies of the female reproductive system. There is a global trend towards increasing incidence and mortality, with a decreasing age trend. E3 ligases label substrates with ubiquitin to regulate their activity and stability and are involved in various cellular functions. Studies have confirmed abnormal expression or mutations of E3 ligases in EC and CC, indicating their vital roles in the occurrence and progression of EC and CC. This paper provides an overview of the E3 ligases implicated in EC and CC and discusses their underlying mechanism. In addition, this review provides research advances in the target of ubiquitination processes in EC and CC. [ABSTRACT FROM AUTHOR]

Cotinus coggygria Scop. as a precious landscape shrub and a good afforestation species that is used in the pharmaceutical industry. In this paper, TG-FTIR, TG-DTG, and Py-GC/MS were used to study the biomaterials of Cotinus coggygria used as biofuels and biochemicals under the catalysis of nano-Mo/Fe2O3. The wood powder was extracted using a methanol/benzene solution, and the extract was analyzed by FTIR and GC-MS. The results showed that the pyrolysis products of Cotinus coggygria wood were rich in phenols, alcohols, and biofuels. The metal nano-Mo powder played a catalytic role in the interpretation of the gas in the species, where it accelerates gas products. Metal nano-Fe2O3 has a certain flame-retardant effect on the burning process of Cotinus coggygria wood, and the residual amount of pyrolysis is greater. The contents of the extract Formamide, 1-Hexanol, Levodopa, and 9,12-Octadecadienoic acid (Z,Z)- are not only widely used industrially but also play an important role in medicine. Cotinus coggygria is therefore an excellent biomaterial for biofuels and biochemicals. [ABSTRACT FROM AUTHOR]

Simple Summary: In patients with acute myeloid leukemia (AML), genetic mutations can cause cells to evade regulated cell death (RCD), resulting in excessive cell proliferation. The best-known form of RCD is apoptosis, which prevents the emergence of cancer cells; disturbances in this process are an important factor in the development and progression of AML. Clearly, it is essential to understand the mechanisms of apoptosis to establish a personalized, patient-specific approach in AML therapy. Therefore, this paper comprehensively reviews the current range of AML treatment approaches related to apoptosis and highlights other promising concepts such as neddylation. More than 97% of patients with acute myeloid leukemia (AML) demonstrate genetic mutations leading to excessive proliferation combined with the evasion of regulated cell death (RCD). The most prominent and well-defined form of RCD is apoptosis, which serves as a defense mechanism against the emergence of cancer cells. Apoptosis is regulated in part by the BCL-2 family of pro- and anti-apoptotic proteins, whose balance can significantly determine cell survival. Apoptosis evasion plays a key role in tumorigenesis and drug resistance, and thus in the development and progression of AML. Research on the structural and biochemical aspects of apoptosis proteins and their regulators offers promise for new classes of targeted therapies and strategies for therapeutic intervention. This review provides a comprehensive overview of current AML treatment options related to the mechanism of apoptosis, particularly its mitochondrial pathway, and other promising concepts such as neddylation. It pays particular attention to clinically-relevant aspects of current and future AML treatment approaches, highlighting the molecular basis of individual therapies. [ABSTRACT FROM AUTHOR]

The quantitative analysis of cell surface antigens has attracted increasing attention due to the antigenic variation recognition that can facilitate early diagnoses. This paper presents a novel methodology based on the optical "cell-tearing" and the especially proposed "dilution regulations" to detect variations in cell surface antigens. The cell attaches to the corresponding antibody-coated slide surface. Then, the cell-binding firmness between a single cell and the functionalized surface is assayed by optically tearing using gradually reduced laser powers incorporated with serial antibody dilutions. Groups B and B3 of red blood cells (RBCs) were selected as the experiment subject. The results indicate that a higher dilution called for lower power to tear off the cell binding. According to the proposed relative-quantitative analysis theory, antigenic variation can be intuitively estimated by comparing the maximum allowable dilution folds. The estimation result shows good consistency with the finding in the literature. This study suggests a novel methodology for examining the variation in cell surface antigens, expected to be widely capable with potential sensor applications not only in biochemistry and biophysics, but also in the micro-/nano- engineering field. [ABSTRACT FROM AUTHOR]

The vitality demonstration refers to determining if an injury has been caused ante- or post-mortem, while wound age means to evaluate how long a subject has survived after the infliction of an injury. Histology alone is not enough to prove the vitality of a lesion. Recently, immunohistochemistry, biochemistry, and molecular biology have been introduced in the field of lesions vitality and age demonstration. The study was conducted according to the preferred reporting items for systematic review (PRISMA) protocol. The search terms were "wound", "lesion", "vitality", "evaluation", "immunohistochemistry", "proteins", "electrolytes", "mRNAs", and "miRNAs" in the title, abstract, and keywords. This evaluation left 137 scientific papers. This review aimed to collect all the knowledge on vital wound demonstration and provide a temporal distribution of the methods currently available, in order to determine the age of lesions, thus helping forensic pathologists in finding a way through the tangled jungle of wound vitality evaluation. [ABSTRACT FROM AUTHOR]

Quorum sensing (QS) regulates the expression of several genes including motility, biofilm development, virulence expression, population density detection and plasmid conjugation. It is based on "autoinducers", small molecules that microorganisms produce and release in the extracellular milieu. The biochemistry of quorum sensing is widely discussed and numerous papers are available to scientists. The main purpose of this research is to understand how knowledge about this mechanism can be exploited for the benefit of humans and the environment. Here, we report the most promising studies on QS and their resulting applications in different fields of global interest: food, agriculture and nanomedicine. [ABSTRACT FROM AUTHOR]

Despite the fact that breast cancer was detected in the early stages, the prognosis was not always favorable. In this paper, we examined the impact of clinical and pathological characteristics of patients and the composition of saliva before treatment on overall survival and the risk of recurrence of primary resectable breast cancer. The study included 355 patients of the Omsk Clinical Oncology Center with a diagnosis of primary resectable breast cancer (T1-3N0-1M0). Saliva was analyzed for 42 biochemical indicators before the start of treatment. We have identified two biochemical indicators of saliva that can act as prognostic markers: alkaline phosphatase (ALP) and diene conjugates (DC). Favorable prognostic factors were ALP activity above 71.7 U/L and DC level above 3.93 c.u. Additional accounting for aspartate aminotransferase (AST) activity allows for forming a group with a favorable prognosis, for which the relative risk is reduced by more than 11 times (HR = 11.49, 95% CI 1.43–88.99, p = 0.01591). Salivary AST activity has no independent prognostic value. Multivariate analysis showed that tumor size, lymph nodes metastasis status, malignancy grade, tumor HER2 status, and salivary ALP activity were independent predictors. It was shown that the risk of recurrence decreased with menopause and increased with an increase in the size of the primary tumor and lymph node involvement. Significant risk factors for recurrence were salivary ALP activity below 71.7 U/L and DC levels below 3.93 c.u. before treatment. Thus, the assessment of biochemical indicators of saliva before treatment can provide prognostic information comparable in importance to the clinicopathological characteristics of the tumor and can be used to identify a risk group for recurrence in primary resectable breast cancer. [ABSTRACT FROM AUTHOR]

Transglutaminases (TGases) are calcium-dependent enzymes that catalyse an acyl-transfer reaction between primary amino groups and protein-bound Gln residues. They are widely distributed in nature, being found in vertebrates, invertebrates, microorganisms, and plants. TGases and their functionality have been less studied in plants than humans and animals. TGases are distributed in all plant organs, such as leaves, tubers, roots, flowers, buds, pollen, and various cell compartments, including chloroplasts, the cytoplasm, and the cell wall. Recent molecular, physiological, and biochemical evidence pointing to the role of TGases in plant biology and the mechanisms in which they are involved allows us to consider their role in processes such as photosynthesis, plant fertilisation, responses to biotic and abiotic stresses, and leaf senescence. In the present paper, an in-depth description of the biochemical characteristics and a bioinformatics comparison of plant TGases is provided. We also present the phylogenetic relationship, gene structure, and sequence alignment of TGase proteins in various plant species, not described elsewhere. Currently, our knowledge of these proteins in plants is still insufficient. Further research with the aim of identifying and describing the regulatory components of these enzymes and the processes regulated by them is needed. [ABSTRACT FROM AUTHOR]

Simple Summary: Given the importance of the epithelial-to-mesenchymal transition in tumor progression and the pivotal role of ZEB1 as a transcriptional repressor during this process, the regulation of ZEB1-targeted gene expression is an active area of investigation. Diverse signaling pathways converge to induce ZEB1 activity, but few studies have focused on the enzyme-dependent modifications of ZEB1 that occur after its translation from mRNA (i.e., post-translational modifications, PTM). In addition to outlining the current knowledge in the field, we outline several questions regarding the PTM-mediated regulation of ZEB1 that remain unanswered. Thus, the areas of research covered in this review paper will provide a noteworthy conceptual advancement in our understanding of ZEB1′s biological function, as well as its post-transcriptional and post-translational regulation. Furthermore, the review will enhance the development of treatment strategies by identifying knowledge gaps in ZEB1′s regulatory mechanisms that could potentially be targeted to prevent and treat metastasis in cancer patients. Zinc finger E-box binding homeobox 1 (ZEB1) is a pleiotropic transcription factor frequently expressed in carcinomas. ZEB1 orchestrates the transcription of genes in the control of several key developmental processes and tumor metastasis via the epithelial-to-mesenchymal transition (EMT). The biological function of ZEB1 is regulated through pathways that influence its transcription and post-transcriptional mechanisms. Diverse signaling pathways converge to induce ZEB1 activity; however, only a few studies have focused on the molecular associations or functional changes of ZEB1 by post-translational modifications (PTMs). Due to the robust effect of ZEB1 as a transcription repressor of epithelial genes during EMT, the contribution of PTMs in the regulation of ZEB1-targeted gene expression is an active area of investigation. Herein, we review the pivotal roles that phosphorylation, acetylation, ubiquitination, sumoylation, and other modifications have in regulating the molecular associations and behavior of ZEB1. We also outline several questions regarding the PTM-mediated regulation of ZEB1 that remain unanswered. The areas of research covered in this review are contributing to new treatment strategies for cancer by improving our mechanistic understanding of ZEB1-mediated EMT. [ABSTRACT FROM AUTHOR]

This paper presents an ontology that involves using information from various sources from different disciplines and combining it in order to predict whether a given person is in a radicalization process. The purpose of the ontology is to improve the early detection of radicalization in persons, thereby contributing to increasing the extent to which the unwanted escalation of radicalization processes can be prevented. The ontology combines findings related to existential anxiety that are related to political radicalization with well-known criminal profiles or radicalization findings. The software Protégé, delivered by the technical field at Stanford University, including the SPARQL tab, is used to develop and test the ontology. The testing, which involved five models, showed that the ontology could detect individuals according to "risk profiles" for subjects based on existential anxiety. SPARQL queries showed an average detection probability of 5% including only a risk population and 2% on a whole test population. Testing by using machine learning algorithms proved that inclusion of less than four variables in each model produced unreliable results. This suggest that the Ontology Framework to Facilitate Early Detection of 'Radicalization' (OFEDR) ontology risk model should consist of at least four variables to reach a certain level of reliability. Analysis shows that use of a probability based on an estimated risk of terrorism may produce a gap between the number of subjects who actually have early signs of radicalization and those found by using probability estimates for extremely rare events. It is reasoned that an ontology exists as a world three object in the real world. [ABSTRACT FROM AUTHOR]

In the 1940-1950s, studies of algae stoichiometry - primarily nutrients (carbon, nitrogen, and phosphorus), as well as trace elements - formed the basis of production hydrobiology [[14]]. Algae play a key role in the biogeochemical fate of many chemical elements and in the regulation of their cycling in the aquatic ecosystems [[4]]. The term "algae" has no formal taxonomic position. Being able to concentrate various chemical elements from the environment, algae may serve as biological sorbents, promoting the development of biotechnologies for the removal of inorganic contaminants from industrial waters [[2], [22]]. [Extracted from the article]

Simple Summary: Epithelial-to-mesenchymal transition (EMT) plays a critical role in cancer progression, contributing to the invasive and migratory abilities of tumor cells. In this study, we show that FBXO11 promotes the degradation of ZEB1, a key EMT regulator, via ubiquitination. Loss of FBXO11 increases ZEB1 levels, enhancing the invasiveness of lung cancer cells, while its overexpression reduces ZEB1 and suppresses invasion. Importantly, higher FBXO11 expression is associated with better prognosis in non-small cell lung cancer (NSCLC), highlighting its potential role as a therapeutic target for controlling EMT and cancer metastasis. Epithelial-to-mesenchymal transition (EMT) affects the invasion and migration of cancer cells. Here, we show that FBXO11 recognizes and promotes ubiquitin-mediated degradation of ZEB1. There is a strong association between FBXO11 and ZEB1 in non-small cell lung cancer (NSLC) in a clinical database. FBXO11 interacts with ZEB1, a core inducer of EMT. FBXO11 leads to increased ubiquitination and proteasomal degradation of ZEB1. Depletion of endogenous FBXO11 causes ZEB1 protein accumulation and EMT in A549 and H1299 cells, while overexpression of FBXO11 reduces ZEB1 protein abundance and cellular invasiveness. Importantly, the depletion of ZEB1 suppresses the increased migration and invasion of A549 and H1299 cells promoted by the depletion of FBXO11. The same results are shown in xenograft tumors. High FBXO11 expression is associated with a favorable prognosis in NSLC. Collectively, our study demonstrates that FBXO11 modulates EMT by mediating the stability of ZEB1 in lung cancer cells. [ABSTRACT FROM AUTHOR]

The International Journal of Molecular Sciences has published a special issue titled "Rational Design and Synthesis of Bioactive Molecules." The issue covers various topics related to rational drug design and provides up-to-date information and recent advances in the field. The articles in the issue discuss the design and synthesis of bioactive molecules for different pharmacological systems and diseases, including cancer, viruses, immune response, and reactive oxygen radicals. The use of computational methods, such as molecular docking and molecular dynamics simulations, is highlighted as a valuable tool in drug development research. The issue also explores the design of new drug candidates with enhanced biological action, the antioxidant properties of flavonoids, the development of sustained-release drug delivery systems, the search for antiviral agents, the discovery of antibiotics with novel structures, and the biotransformation processes of 4'-hydroxychalcones. The special issue aims to provide valuable insights and inspire further research in the rational design of bioactive compounds. [Extracted from the article]

In exploring the male–female differentiation and differences in the seedling stage of the F1 generation of ginkgo hybrids, an early selection test for the cultivation and research of leafy or medicinal ginkgo industry was conducted, which may provide a basis for boosting the precision of the ginkgo industry. The hybrid F1 generation obtained from the cross-mating was used as material for the determination of growth and development, as well as of the physiology and biochemistry of the monocots, and the male and female differential genes were obtained based on the data of SNPs obtained from the GBS sequencing of the hybrid progeny. In the seedling stage of ginkgo hybrid offspring, male plants had a significantly higher nutrient growth capacity than female plants, while the total flavonoid and terpene lactone contents in female plants were higher than those of the male plants. This result can provide a corresponding theoretical basis for the use of ginkgo germplasm resources, which can make full use of the male and female differences in the seedling stage and maximize the benefits of early sex identification. [ABSTRACT FROM AUTHOR]

Metabolism is a network of chemical reactions that sustain cellular life. Parts of this metabolic network are defined as metabolic pathways containing specific biochemical reactions. Products and reactants of these reactions are called metabolites, which are associated with certain human-defined metabolic pathways. Metabolic knowledgebases, such as the Kyoto Encyclopedia of Gene and Genomes (KEGG) contain metabolites, reactions, and pathway annotations; however, such resources are incomplete due to current limits of metabolic knowledge. To fill in missing metabolite pathway annotations, past machine learning models showed some success at predicting the KEGG Level 2 pathway category involvement of metabolites based on their chemical structure. Here, we present the first machine learning model to predict metabolite association to more granular KEGG Level 3 metabolic pathways. We used a feature and dataset engineering approach to generate over one million metabolite-pathway entries in the dataset used to train a single binary classifier. This approach produced a mean Matthews correlation coefficient (MCC) of 0.806 ± 0.017 SD across 100 cross-validation iterations. The 172 Level 3 pathways were predicted with an overall MCC of 0.726. Moreover, metabolite association with the 12 Level 2 pathway categories was predicted with an overall MCC of 0.891, representing significant transfer learning from the Level 3 pathway entries. These are the best metabolite pathway prediction results published so far in the field. [ABSTRACT FROM AUTHOR]

Kynurenic acid (KYNA) is an antioxidant degradation product of tryptophan that has been shown to have a variety of cytoprotective, neuroprotective and neuronal signalling properties. However, mammalian transporters and receptors display micromolar binding constants; these are consistent with its typically micromolar tissue concentrations but far above its serum/plasma concentration (normally tens of nanomolar), suggesting large gaps in our knowledge of its transport and mechanisms of action, in that the main influx transporters characterized to date are equilibrative, not concentrative. In addition, it is a substrate of a known anion efflux pump (ABCC4), whose in vivo activity is largely unknown. Exogeneous addition of L-tryptophan or L-kynurenine leads to the production of KYNA but also to that of many other co-metabolites (including some such as 3-hydroxy-L-kynurenine and quinolinic acid that may be toxic). With the exception of chestnut honey, KYNA exists at relatively low levels in natural foodstuffs. However, its bioavailability is reasonable, and as the terminal element of an irreversible reaction of most tryptophan degradation pathways, it might be added exogenously without disturbing upstream metabolism significantly. Many examples, which we review, show that it has valuable bioactivity. Given the above, we review its potential utility as a nutraceutical, finding it significantly worthy of further study and development. [ABSTRACT FROM AUTHOR]

Werner syndrome (WS) is an autosomal recessive disease caused by loss of function of WRN. WS is a segmental progeroid disease and shows early onset or increased frequency of many characteristics of normal aging. WRN possesses helicase, annealing, strand exchange, and exonuclease activities and acts on a variety of DNA substrates, even complex replication and recombination intermediates. Here, we review the genetics, biochemistry, and probably physiological functions of the WRN protein. Although its precise role is unclear, evidence suggests WRN plays a role in pathways that respond to replication stress and maintain genome stability particularly in telomeric regions. [ABSTRACT FROM AUTHOR]

This document discusses the importance of conserving and managing marine benthic ecosystems, which provide essential resources and services. It emphasizes the need for ecosystem-based strategies in the face of challenges like global warming and invasive species. The document presents several studies that deepen our understanding of the ecology and biogeography of marine benthos, including investigations into specific regions and the effects of different factors on benthic communities. The document also highlights the importance of identifying species within these ecosystems and the use of DNA barcoding for ecological research and conservation efforts. The special issue includes a variety of research articles and reports that cover different marine ecosystems and utilize various research methods. The findings contribute to our understanding of marine ecology and biogeography, supporting conservation and management efforts. The summary also emphasizes the need for future studies to be more cost-effective and innovative in data collection and analysis. [Extracted from the article]

This document is an editorial from the journal Biomolecules, dedicated to the life and work of scientist Michael Breitenbach on the occasion of his 80th birthday. Michael Breitenbach is a pioneer in yeast research and has made significant contributions to biochemistry and molecular biology. The editorial highlights his diverse scientific interests and contributions, ranging from yeast sporulation to aging processes, allergens, and other fields. The Special Issue includes a collection of articles written by long-standing colleagues and collaborators, covering topics such as genomic stability, oxidative stress, hypoxia, signaling pathways, and more. The editors also acknowledge Michael's unique traits as a mentor and his broad knowledge in various disciplines. [Extracted from the article]

Social changes in higher education have led to a transformation in teaching innovation for developing a critical and creative mentality in students. To this end, video capsules have emerged as an optimal tool that allows combining the management of information and communication technologies and collaborative work. Video capsules were elaborated by groups of students for the virtualization of the laboratory practices of the subjects Environmental Microbiology and Biochemistry of the Degree in Environmental Sciences for two academic years (2022–2023 and 2023–2024), paying special attention to the principles of Universal Design of Learning. To assess the impact of this activity on the knowledge acquired by the students in the laboratory practices, the marks from these academic years were compared with the previous academic year (2021–2022) without the generation of video capsules. Moreover, an evaluation of the development and acquisition of cross-curricular competencies was carried out. The generation of video capsules by the students tended to increase the average grade obtained in the laboratory practices of both subjects. Furthermore, instrumental, interpersonal, and systemic competencies obtained by the students by performing the video capsules improved their transversal skills. The creation of video capsules during laboratory practices and the methodology used had a very positive direct influence on the academic outcomes of the subjects and facilitated the acquisition of transversal competencies for the students. [ABSTRACT FROM AUTHOR]

Many studies have consistently demonstrated that the near-surface phytoplankton chlorophyll (Chl) levels in anticyclonic eddies (AEs) are higher than in cyclonic eddies (CEs) in the South Pacific Ocean (SPO), using remote sensing data, which is attributed to higher phytoplankton biomass or physiological adjustments in AEs. However, the characteristics of the Chl profile induced by mesoscale eddies and their underlying dynamic mechanism have not been comprehensively studied by means of field measurement, and the influence mechanism of environmental factors at different depths on Chl has not been investigated. To fill this gap, we utilized Biogeochemical-Argo (BGC-Argo) data to investigate the relationships between Chl concentration and environmental factors at different water layers and the underlying dynamic mechanisms of mesoscale eddies in the SPO. Our findings indicate that the same environmental factor can have different effects on Chl at different depths. Within a mixed layer (ML), the elevated Chl levels in AEs result from both physiological adjustments and increased phytoplankton biomass, and the former plays a more dominant role, which is induced by enhanced nutrient availability and weakened light, due to the deepening ML in AEs. At depths ranging from 50 m to 110 m, and between 110 m and 150 m (near the depth of pycnocline or the bottom of the euphotic zone), the dominant factor contributing to higher Chl levels in CEs is phytoplankton physiological adaptation driven by reduced temperature and light. At depths exceeding 150 m (beyond the euphotic zone), higher Chl in AEs is primarily caused by high phytoplankton biomass as a result of downwelling by eddy pumping. This work should advance our comprehensive understanding of the physical–biological interactions of mesoscale eddies and their impacts on primary productivity throughout the water column, and it should provide some implications for understanding the biogeochemical processes. [ABSTRACT FROM AUTHOR]

Background: Significant improvement in neonatal care has enabled increasing survival of preterm infants. Metabolic bone disease of prematurity is often overlooked due to other comorbidities of preterm birth. The best approach is screening and prevention of the disease in high-risk infants such as preterm infants. Aim: We followed up the clinical, radiological, and serum biochemical markers of metabolic bone disease in extremely preterm infants (<28 weeks of gestation). The clinical applicability and validation of C-terminal telopeptide of type I collagen (CTX-I) as a novel bone turnover marker were assessed. Standard and novel biochemical bone turnover markers and quantitative ultrasound were compared. Method: Patients' data were collected from medical records. Assessments of calcium, phosphate, alkaline phosphatase, bone-alkaline phosphatase, CTX-I, and quantitative ultrasound were prospectively performed twice in 42 extremely preterm infants at postmenstrual ages of 30–32 weeks and 36–40 weeks. Bone mineral density was measured by quantitative ultrasound. Conclusion: Phosphate, alkaline phosphatase, bone alkaline phosphatase, calcium, or ionized calcium are not related to gestational age, but bone mineral density, measured by quantitative ultrasound, is related. There is no correlation between standard and novel biochemical markers and quantitative ultrasound for the identification of metabolic bone disease. [ABSTRACT FROM AUTHOR]

As one of the most influential environmental factors, drought stress greatly impacts the development and production of plants. Triploid-induced Passiflora edulis Sims 'Mantianxing' is an important new cultivar for multi-resistance variety selective breeding, which is one of the P. edulis breeding essential targets. However, the performance of triploid 'Mantianxing' under drought stress is unknown. In order to study the drought resistance of triploid 'Mantianxing', our study compared drought-related indicators in diploids and triploids under natural drought experiments, including morphological, physiological, and biochemical characteristics. Results showed that triploid P. edulis 'Mantianxing' showed variable responses to drought treatment. Compared with diploids, triploids showed higher photosynthesis and chlorophyll fluorescence, osmotic adjustment substances, and antioxidant enzyme activity under drought stress and faster chlorophyll biosynthesis and growth recovery after rewatering. Generally speaking, these results indicate that the drought resistance of triploid P. edulis is superior to diploid. This study provides scientific information for breeding stress tolerance variety of P. edulis 'Mantianxing' new cultivar. [ABSTRACT FROM AUTHOR]

Simple Summary: Since they have a unique phenotype, with an approximately 20% increase in muscle mass, we hypothesized that Belgian blue (BB) cows may have hematologic and biochemical characteristics that are significantly different from those of other cattle breeds. However, most available reference intervals in cattle are derived from dairy cows, mainly Holstein Friesian (HF) cows. Therefore, the aim of our study was to measure and compare biochemical and hematologic parameters in clinically healthy BB and HF cows. We studied 183 clinically healthy adult BB and HF cows. Our results confirmed that BB and HF represent different populations from a laboratory perspective. Therefore, we propose the first breed-specific reference intervals for BB, which are essential to improve the health management of this breed. Belgian blue (BB) cattle have an 11-bp deletion in myostatin that causes skeletal muscle hyperplasia and increased muscle mass, leading to a 'double-muscled' phenotype. Preliminary data suggest that this phenotype may be associated with breed-specific hematologic and biochemical values. Therefore, in this study, we sought to compare hematologic and serum biochemical parameters in healthy BB and Holstein Friesian (HF) cows and to propose breed-specific reference intervals for BB cows. Hematologic parameters, total protein, creatinine, creatine kinase (CK) and aspartate transaminase (AST) activities, albumin, and globulins were measured in 183 clinically healthy adult BB and HF cows. There were significant differences between BB and HF cows in 17 of 27 measured parameters. BB cows had significantly higher creatinine concentration and CK and AST activities (p < 0.001). RBCs, hemoglobin, hematocrit (p < 0.001), MCV and lymphocytes (p < 0.05) were also significantly higher in BB cows compared with HF cows. The average N/L ratio was greater than 1 in both breeds. These results suggest that BB and HF cows have significantly different clinically relevant hematologic and serum biochemical values, and, therefore, breed-specific reference intervals should be used. [ABSTRACT FROM AUTHOR]

Stress research in sports tends to focus on athletes, with sports officials typically being overlooked. In the current study, baseline, pre-game, and post-game cortisol levels among a sample of softball umpires were measured to assess the pattern of stress responses and determine if umpire performance (pass/fail) and position on the diamond (plate/field) could be predicted from cortisol levels. Nine male and four female participants aged 25–68 years (N = 13, M = 47.06 ± 15.65 years) each provided saliva samples on multiple occasions prior to and after officiating games at two Australian National Softball Championships. Data from 65 games were analysed. Performance was assessed using Softball Australia's official umpire assessment tool. Cortisol levels increased significantly from baseline to pre-game (p < 0.001, d = −0.69) and declined significantly from pre-game to post-game (p < 0.001, d = 0.47). Umpiring performances were correctly classified as pass or fail from baseline and pre-game cortisol levels in 61.5% of cases and umpire position on the diamond from pre-game cortisol in 63.1% of cases. Findings suggest that stress management strategies should be recommended to softball umpires for performance enhancement and to safeguard their mental health. [ABSTRACT FROM AUTHOR]

Simple Summary: Acute Promyelocytic Leukemia (APL) was the most aggressive form of leukemia, historically associated with massive and rapid mortality. However, empirical clinical advancements and in-depth mechanistic exploration have now transformed APL into the most curable form of leukemia, culminating with the ATRA/ATO combination, which cures up to 98% APL patients. This review recapitulates a three-decade journey which led to the development of this groundbreaking treatment, through several paradigm shifts to explain its scientific underpinnings. The story of acute promyelocytic leukemia (APL) discovery, physiopathology, and treatment is a unique journey, transforming the most aggressive form of leukemia to the most curable. It followed an empirical route fueled by clinical breakthroughs driving major advances in biochemistry and cell biology, including the discovery of PML nuclear bodies (PML NBs) and their central role in APL physiopathology. Beyond APL, PML NBs have emerged as key players in a wide variety of biological functions, including tumor-suppression and SUMO-initiated protein degradation, underscoring their broad importance. The APL story is an example of how clinical observations led to the incremental development of the first targeted leukemia therapy. The understanding of APL pathogenesis and the basis for cure now opens new insights in the treatment of other diseases, especially other acute myeloid leukemias. [ABSTRACT FROM AUTHOR]

Background: The prevalence of obesity has been increasing worldwide. It has been reported that physiological and environmental factors such as diet, culture, physical activity, and genetics are the principal factors related to obesity. The fat mass and obesity-associated (FTO) gen variant (rs9939609: T>A) has been associated with class III obesity. The A variant has been correlated with anthropometric and metabolic alterations. Therefore, the purpose of this study was to analyze the association of the FTO rs9939609: T>A variant and environmental factors with clinical, anthropometric, and biochemical variables in subjects with class III obesity. Results: The A variant frequency was higher in the class III obesity group compared with the normal weight group (44% vs. 25%, p < 0.001). Subjects with the AA genotype had a higher body mass index (BMI) than those with the AT genotype (35.46 kg/m2 (31–39.8) vs. 26.91 kg/m2 (23.7–30), p = 0.005). Women with the AA genotype showed higher waist circumferences than the AT group (101.07 cm (90.9–111.1) vs. 85.45 cm (77–93.8) p = 0.047). The FTO A variant increases the risk by 3.54 times and physical inactivity increases the risk by 6.37 times for class III obesity. Conclusions: Our results suggest that among the studied variables, those most related to class III obesity were the FTO risk genotype (A allele) and physical inactivity. [ABSTRACT FROM AUTHOR]

Xanthohumol (Xn), a prenylated chalcone found in Hop (Humulus lupulus L.), has been shown to have potent anti-aging, diabetes, inflammation, microbial infection, and cancer properties. Unfortunately, this molecule has undesirable characteristics such as inadequate intake, low aqueous solubility, and a short half-life. To address these drawbacks, researchers have made numerous attempts to improve its absorption, solubility, and bioavailability. Polymeric drug delivery systems (PDDSs) have experienced significant development over the last two decades. Polymeric drug delivery is defined as a formulation or device that allows the introduction of a therapeutic substance into the body. Biodegradable and bioreducible polymers are the ideal choice for a variety of new DDSs. Xn formulations based on biodegradable polymers and naturally derived compounds could solve some of the major drawbacks of Xn-based drug delivery. In this regard, the primary concern of this study is on presenting innovative formulations for Xn delivery, such as nanoparticles (NPs), nanomicelles, nanoliposomes, solid lipid nanoparticles (SLNs), and others, as well as the received in vitro and in vivo data. Furthermore, this work describes the chemistry and broad biological activity of Xn, which is particularly useful in modern drug technology as well as the cosmetics industry. It is also important to point out that the safety of using Xn, and its biotransformation, pharmacokinetics, and clinical applications, have been thoroughly explained in this review. [ABSTRACT FROM AUTHOR]

Reactive oxygen species (ROS) and free radicals work to maintain homeostasis in the body, but their excessive production causes damage to the organism. The human body is composed of a variety of cells totaling over 60 trillion cells. Each cell performs different functions and has a unique lifespan. The lifespan of cells is preprogrammed in their genes, and the death of cells that have reached the end of their lifespan is called apoptosis. This is contrary to necrosis, which is the premature death of cells brought about by physical or scientific forces. Each species has its own unique lifespan, which in humans is estimated to be up to 120 years. Elucidating the mechanism of the death of a single cell will lead to a better understanding of human death, and, conversely, the death of a single cell will lead to exploring the mechanisms of life. In this sense, research on active oxygen and free radicals, which are implicated in biological disorders and homeostasis, requires an understanding of both the physicochemical as well as the biochemical aspects. Based on the discussion above, it is clear to see that active oxygen and free radicals have dual functions of both injuring and facilitating homeostasis in living organisms. [ABSTRACT FROM AUTHOR]