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Copyright of Chinese Journal of Bioprocess Engineering is the property of Chinese Journal of Bioprocess Engineering Editorial Office and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

High‐resolution spatio‐temporal monitoring of the cell membrane lipid order provides visual insights into the complex and sophisticated systems that control cellular physiological functions. Solvatochromic fluorescent probes are highly promising noninvasive visualization tools for identifying the ordering of the microenvironment of plasma membrane microdomains. However, conventional probes, although capable of structural analysis, lack the necessary long‐term photostability required for live imaging at the cellular level. Here, an ultra‐high‐light‐resistant solvatochromic fluorescence probe, 2‐N,N‐diethylamino‐7‐(4‐methoxycarbonylphenyl)‐9,9‐dimethylfluorene (FπCM) is reported, which enables live lipid order imaging of cell division. This probe and its derivatives exhibit sufficient fluorescence wavelengths, brightness, polarity responsiveness, low phototoxicity, and remarkable photostability under physiological conditions compared to conventional solvatochromic probes. Therefore, these probes have the potential to overcome the limitations of fluorescence microscopy, particularly those associated with photobleaching. FπCM probes can serve as valuable tools for elucidating mechanisms of cellular processes at the bio‐membrane level. [ABSTRACT FROM AUTHOR]

Abstract High‐resolution spatio‐temporal monitoring of the cell membrane lipid order provides visual insights into the complex and sophisticated systems that control cellular physiological functions. Solvatochromic fluorescent probes are highly promising noninvasive visualization tools for identifying the ordering of the microenvironment of plasma membrane microdomains. However, conventional probes, although capable of structural analysis, lack the necessary long‐term photostability required for live imaging at the cellular level. Here, an ultra‐high‐light‐resistant solvatochromic fluorescence probe, 2‐N,N‐diethylamino‐7‐(4‐methoxycarbonylphenyl)‐9,9‐dimethylfluorene (FπCM) is reported, which enables live lipid order imaging of cell division. This probe and its derivatives exhibit sufficient fluorescence wavelengths, brightness, polarity responsiveness, low phototoxicity, and remarkable photostability under physiological conditions compared to conventional solvatochromic probes. Therefore, these probes have the potential to overcome the limitations of fluorescence microscopy, particularly those associated with photobleaching. FπCM probes can serve as valuable tools for elucidating mechanisms of cellular processes at the bio‐membrane level.

In 1974 the Nobel laureate Sir Robert Robinson OM PRS (1886–1975) was gathering information for the memoirs he was writing. As part of his research, he recorded a conversation with his former student, fellow Nobel laureate Professor Dorothy Hodgkin OM FRS (1910–1994), during which she outlined the key stages of her career. She explained the principles underlying crystallography and described her work on the structure of biological molecules including penicillin and vitamin B12—for which she received the Nobel Prize—and on insulin. This paper includes a verbatim transcript of the conversation, which reveals the key figures in Hodgkin's career and the technical breakthroughs which underlay the elucidation of the structure of very large complex molecules. The paper includes a commentary on the value of oral accounts and concludes on the issues raised and not raised during the conversation. Sir Robert was President of the Royal Society between 1945 and 1950 when women were first elected Fellows. Hodgkin was elected in 1947. However, no mention is made of the challenges facing women developing a scientific career in the first half of the twentieth century. [ABSTRACT FROM AUTHOR]

Damage from ultraviolet (UV) radiation was likely to be an important selection pressure during the origin of life. RNA is believed to have been central to the origin of life and might form the basis for simple synthetic cells. Although photodamage of DNA has been extensively studied, photodamage is highly dependent on local molecular context, and damage to functional RNAs has been relatively under-studied. We irradiated two fluorescent RNA aptamers and monitored the loss of activity, folding, and the kinetics of lesion accumulation. The loss of activity differed depending on the aptamer, with the Spinach2 aptamer retaining substantial activity after long exposure times. The binding pocket was particularly susceptible to damage, and melting of the duplex regions increased susceptibility; this is consistent with the view that duplex formation is protective. At the same time, susceptibility varied greatly depending on context, thus emphasizing the importance of studying many different RNAs to understand UV hardiness.

The knowledge of interactions between different molecules is undoubtedly the driving force of all contemporary biomedical and biological sciences. Chemical biology/biological chemistry has become an important multidisciplinary bridge connecting the perspectives of chemistry and biology to the study of small molecules/peptidomimetics and their interactions in biological systems. Advances in structural biology research, in particular linking atomic structure to molecular properties and cellular context, are essential for the sophisticated design of new medicines that exhibit a high degree of druggability and very importantly, druglikeness. The authors of this contribution are outstanding scientists in the field who provided a brief overview of their work, which is arranged from in silico investigation through the characterization of interactions of compounds with biomolecules to bioactive materials. [ABSTRACT FROM AUTHOR]

Copyright of Educación (18133363) is the property of Universidad Femenina del Sagrado Corazon and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

PULCON (Pulse Length-Based Concentration Determination) is a powerful, versatile, non-invasive, and accurate technique for measuring solution concentrations via routine NMR spectroscopy. It is particularly useful for preparing accurate solutions of compounds for biological assays, and avoids weight-based errors caused by contaminants (e.g. moisture). This article provides an introductory guide for biological and medicinal chemists, and highlights the diversity of applications. [ABSTRACT FROM AUTHOR]

The issue of cancer became a research topic for the humanities and social sciences. Its goal is primarily to establish an inventory of research on the cancer history. Far from confining reflection to the medical and biological realms, it includes the political, social and cultural dimensions. This collaboration made it possible to study cancer under very different aspects: representations of the disease from the mid-eighteenth century to the 1950s. The fight against cancer in Algeria is imperative with the same imperative need as in the Metropolis and the other French territories of North Africa. The ravages caused by cancer in Algeria are in fact of the same order as those of which it overwhelms the other Mediterranean countries.

The knowledge of interactions between different molecules is undoubtedly the driving force of all contemporary biomedical and biological sciences. Chemical biology/biological chemistry has become an important multidisciplinary bridge connecting the perspectives of chemistry and biology to the study of small molecules/peptidomimetics and their interactions in biological systems. Advances in structural biology research, in particular linking atomic structure to molecular properties and cellular context, are essential for the sophisticated design of new medicines that exhibit a high degree of druggability and very importantly, druglikeness. The authors of this contribution are outstanding scientists in the field who provided a brief overview of their work, which is arranged from in silico investigation through the characterization of interactions of compounds with biomolecules to bioactive materials.

The purpose of the research: study of the influence of increased doses of fenbendazole supramolecular complex (FSMC) on sheep’s organism. Materials and methods. The experiment was carried out at the Podolsk Department of All-Russian Scientific Research Institute of Fundamental and Applied Parasitology of Animals and Plants named after K. I. Skryabin on 20 manorial invasion-free sheep aged 2-3 years old. Animals were divided according to the principle of analogues into 4 groups, 5 heads in each group. Animals of the 1, 2 and 3 group were orally administered with FSMC given as a single dose of 2, 6, 10 mg/kg, respectively, according to the active substance, i.e in therapeutic and in a dose increased by 3 and 5 times. Sheep of the fourth group didn’t receive the drug and they were as control. Study of clinical, hematological and biochemical parameters of animals from all groups was conducted 1 day before and in 1, 3, 5 days after administration of the drug by means of standard methods. Results and discussion. FSMC in therapeutic dose as well as in a dose increased by 3 and 5 times doesn’t have negative influence on clinical, hematological and biochemical parameters of the sheep. State of the sheep, which received the drug in doses of 20, 60, 100 mg/kg, was within the physiologically normal state and didn’t differ from the state before administration of the drug and from the animals of the control group. Drug security index exceeds 5. Red blood cell count, white blood cell count, hemoglobin count, leukogram parameters as well as biochemical parameters of blood: activity of alkaline phosphatase and amylase, bilirubin, creatinine, urea and glucose counts were within normal limits and didn’t differ from the parameters of the control animals.

During the last decade, there has been a tremendous interest for developing non‐natural biocompatible transformations in biologically relevant media. Among the different encountered strategies, the use of transition metal complexes offers unique possibilities due to their high transformative power. However, translating the potential of metal catalysts to biological settings, including living cells or small‐animal models such as mice or zebrafish, poses numerous challenges associated to their biocompatibility, and their stability and reactivity in crowded aqueous environments. Herein, we describe the most relevant advances in this direction, with a particular emphasis on the systems' structure, their mode of action and the mechanistic bases of each transformation. Thus, the key challenges from an organometallic perspective might be more easily identified. [ABSTRACT FROM AUTHOR]

Metal‐mediated intracellular reactions are becoming invaluable tools in chemical and cell biology, and hold promise for strongly impacting the field of biomedicine. Most of the reactions reported so far involve either uncaging or redox processes. Demonstrated here for the first time is the viability of performing multicomponent alkyne cycloaromatizations inside live mammalian cells using ruthenium catalysts. Both fully intramolecular and intermolecular cycloadditions of diynes with alkynes are feasible, the latter providing an intracellular synthesis of appealing anthraquinones. The power of the approach is further demonstrated by generating anthraquinone AIEgens (AIE=aggregation induced emission) that otherwise do not go inside cells, and by modifying the intracellular distribution of the products by simply varying the type of ruthenium complex. [ABSTRACT FROM AUTHOR]

Формирование задания к ла- бораторного практикума с сочетанием перечнем лабораторных работ и их совершенствованием новых технологий. Методы исследования. В статье представлено, одна из форм учебного занятия, как лабораторный практикум, который является достаточно важным для студента-медика, так как, во время лабораторного експеримету улучшаются и углубляются знания студента из курс биоорганической и биологической химии, а самое главное приобретает практические навыки эксперимен- тальных исследований и с лабораторным оборудованием. Научная новизна. Впервые представлены основные рекоменда- ции для лабораторного практикума по медицинской дисциплины для студентов первого курса по биоорганической и биоло- гической химии с использованием современных методов и новейших технологиях. Выводы. Лабораторный практикум способствует повышению уровня знаний студентов по дисциплине биоорганической и биологической химии, так как сту- дент учится самостоятельно приобретать и применять свои знания в процессе выполнения лабораторных работ, а это соот- ветственно воспитывает у студента чувство ответственности и мотивирует к саморазвитию.The Formation of the task for a laboratory practice with a combination of a list of laboratory works and their improvement of new technologies. Research methods. The article presents one of the forms of classes as a laboratory practice, which is very important for a medical student, so how, during a laboratory experiment, students' knowledge of the theoretical material is improved and deepened, and what is the most important – he or she acquires practical skills from experimental research and laboratory equipment. The course of bioor- ganic and biological chemistry deepens and generalizes the fundamen- tal knowledge of the school curriculum of the basic laws of natural science, which provides the theoretical and practical training necessary for the understanding of various biochemical processes and the further study of special medical disciplines. Laboratory work has a great adva- ntage in mastering the course of bioorganic and biological chemistry, it helps to improve the understanding of theoretical material and solidifyit with the help of practice while a student acquires skills in experimental work in the laboratory. Scientific novelty. For the first time, the main recommendations for the laboratory workshop on medical discipline for the first year students in bioorganic and biological chemistry using modern methods and the latest technology are presented. Conclusions. One can confidently say that the laboratory practice contributes to raising the level of knowledge of the students in the discipline of bioor- ganic and biological chemistry, asthe students learn to independently acquire and apply their knowledge in the process of laboratory work, and this, accordingly, leads to the greater sense of responsibility and motivates self-development. The success during the laboratory- practical work, which is on the list of laboratory practice, depends on many components, in particular on theoreticalpart, practical part, as well as on the degree of the students’preparedness, their commitment in the class.

β‐Glucuronidase (GUS) enzymes in the gastrointestinal tract are involved in maintaining mammalian‐microbial symbiosis and can play key roles in drug efficacy and toxicity. Parabacteroides merdae GUS was identified as an abundant mini‐Loop 2 (mL2) type GUS enzyme in the Human Microbiome Project gut metagenomic database. Here, we report the crystal structure of P. merdae GUS and highlight the differences between this enzyme and extant structures of gut microbial GUS proteins. We find that P. merdae GUS exhibits a distinct tetrameric quaternary structure and that the mL2 motif traces a unique path within the active site, which also includes two arginines distinctive to this GUS. We observe two states of the P. merdae GUS active site; a loop repositions itself by more than 50 Å to place a functionally‐relevant residue into the enzyme's catalytic site. Finally, we find that P. merdae GUS is able to bind to homo and heteropolymers of the polysaccharide alginic acid. Together, these data broaden our understanding of the structural and functional diversity in the GUS family of enzymes present in the human gut microbiome and point to specialization as an important feature of microbial GUS orthologs. PDB Code(s): 6D7J, 6DXU [ABSTRACT FROM AUTHOR]

Undergraduate biochemistry students frequently find the quantitative treatment of weak acids and bases troublesome. Given the pKa of a weak acid HA, for instance, many students struggle to calculate the pH of a solution of the conjugate base A− at concentration C, pH(A−, C). The traditional method involves calculating the base dissociation constant Kb and the artificial quantity pOH before reaching pH, but these steps increase the risk of mistakes and provide little insight into acid–base equilibria. The alternative method presented here allows students to calculate the pH of a weak base solution from the pKa of its conjugate acid without calculating Kb and pOH, using a memorable relationship: pH(HA, C) + pH(A−, C) = pKa + 7. [ABSTRACT FROM AUTHOR]

Research into understanding the origins—and evolution—of life has long been dominated by the concept of taking clues from extant biology and extrapolating its molecules and pathways backwards in time. This approach has also guided the search for solutions to the problem of how contemporary biomolecules would have arisen directly from prebiotic chemistry on early earth. However, the continuing difficulties in finding universally convincing solutions in connecting prebiotic chemistry to biological chemistry should give us pause, and prompt us to rethink this concept of treating extant life's chemical processes as the sole end goal and, therefore, focusing only, and implicitly, on the respective extant chemical building blocks. Rather, it may be worthwhile "to set aside the goal" and begin with what would have been plausible prebiotic reaction mixtures (which may have no obvious or direct connection to life's chemical building blocks and processes) and allow their chemistries and interactions, under different geochemical constraints, to guide and illuminate as to what processes and systems can emerge. Such a conceptual approach gives rise to the prospect that chemistry of life‐as‐we‐know‐it is not the only result (not a "destiny"), but one that has emerged among many potential possibilities (a "destination"). This postulate, in turn, could impact the way we think about chemical signatures and criteria used in the search for alternative and extraterrestrial "life". As a bonus, we may discover the chemistries and pathways naturally that led to the emergence of life as we know it. All roads lead to life? The search for prebiotic and abiotic origin of biological chemistry continues to be guided largely by reliance on clues from extant life's processes. Here, it is suggested such an approach may be misleading, and that decoupling the emphasis on extant biology may actually be beneficial in finding unscripted solutions leading to the chemical origin(s) of life. [ABSTRACT FROM AUTHOR]

Abstract: Pulsed electron–electron double resonance spectroscopy (known as PELDOR or DEER) has recently become a very popular tool in structural biology. The technique can be used to accurately measure distance distributions within macromolecules or macromolecular complexes, and has become a standard method to validate structural models and to study the conformational flexibility of macromolecules. It can be applied in solution, in lipid environments or even in cells. Because most biological macromolecules are diamagnetic, they are normally invisible for PELDOR spectroscopy. To render a particular target molecule accessible for PELDOR, it can be engineered to contain only one or two surface‐exposed cysteine residues, which can be efficiently spin‐labelled using thiol‐reactive nitroxide compounds. This method has been coined “site‐directed spin labelling” (SDSL) and is normally straight‐forward. But, SDSL can be very challenging for proteins with many native cysteines, or even a single functionally or structurally important cysteine residue. For such cases, alternative spin labelling techniques are needed. Here we describe the concept of “inhibitor‐directed spin labelling” (IDSL) as an approach to spin label suitable cysteine‐rich proteins in a site‐directed and highly specific manner by employing bespoke spin‐labelled inhibitors. Advantages and disadvantages of IDSL are discussed. [ABSTRACT FROM AUTHOR]

Bacterial permeability‐increasing family member A1 (BPIFA1) is an innate immunity factor and one of the most abundantly secreted proteins in the upper airways. BPIFA1 is multifunctional, with antimicrobial, surfactant and lipopolysaccharide‐binding activities, as well as established roles in lung hydration. Here, the 2.5 Å resolution crystal structure of BPIFA1 from Mus musculus (mBPIFA1) is presented and compared with those of human BPIFA1 (hBPIFA1) and structural homologs. Structural distinctions between mBPIFA1 and hBPIFA1 suggest potential differences in biological function, including the regulation of a key pulmonary ion channel. [ABSTRACT FROM AUTHOR]

Abstract: Cysteine plays a crucial role in cellular functions and in human pathologies. However, the development of cysteine probes with extremely accurate detection is still a key challenge for the field. Herein, we have fully characterized and developed a novel selective fluorescent probe: red emission, aqueous detection and large Stokes’ shift for cysteine (Reals‐C). Key in the probe synthesis is a Michael addition onto an acroylate group and subsequent intramolecular cyclization. The probe exhibits analyte detection via an intricate role set up by the leaving groups so to discriminate and form the red‐emissive analyte sensing platform (λex=471 nm, λem=637 nm) through a chemical cascade pathway. Furthermore, the sensing ability of the probe was demonstrated by both in vitro and in vivo assays. This probe enables for successfully endogenous cysteine sensing in HaCaT human keratinocytes through comparison with a commercial thiol‐sensitive probe; Reals‐C shows excellent in vivo cysteine detection in a drug‐induced animal liver injury model. [ABSTRACT FROM AUTHOR]

Abstract: Cancer stem cells (CSCs) are associated with drug resistance, metastasis and recurrence of cancer. A synthetic binder of CSCs can provide a valuable tool to study the biology of CSCs and a lead to develop imaging, diagnostic and therapeutic agents targeting CSCs. Herein, a synthetic ligand (1) that specifically binds to CSCs over non‐CSCs of breast cancer cells was identified for the first time via a cell‐binding screening of a chemical library. The ligand 1 showed specific binding to CD24−/CD44+/ALDH+ CSC population of MCF‐7 and MDA‐MB‐231. We have demonstrated that 1‐immobilized beads can be used as matrices for affinity isolation of 1‐binding CSC population from breast cancer cells. The 1‐binding population showed significantly increased expressions of stemness‐associated transcription factors. Importantly, the 1‐binding population demonstrated accelerated tumor growth in vivo, and the resulting tumor displayed an increased migratory activity and high expressions of CSC markers. [ABSTRACT FROM AUTHOR]

Abstract: New 1,7‐closo‐carboranylanilinoquinazoline hybrids have been identified as EGFR inhibitors, one of them with higher affinity than the parent compound erlotinib. The comparative docking analysis with compounds bearing bioisoster‐substructures, demonstrated the relevance of the 3D aromatic‐boron‐rich moiety for interacting into the EGFR ATP binding region. The capability to accumulate in glioma cells, the ability to cross the blood–brain barrier and the stability on simulated biological conditions, render these molecules as lead compounds for further structural modifications to obtain dual action drugs to treat glioblastoma. [ABSTRACT FROM AUTHOR]

Abstract: The 8‐nitroguanine lesion in DNA is increasingly associated with inflammation‐related carcinogenesis, whereas the same modification on guanosine 3′,5′‐cyclic monophosphate generates a second messenger in NO‐mediated signal transduction. Very little is known about the chemistry of 8‐nitroguanine nucleotides, despite the fact that their biological effects are closely linked to their chemical properties. To this end, a selection of chemical reactions have been performed on 8‐nitroguanine nucleosides and oligodeoxynucleotides. Reactions with alkylating reagents reveal how the 8‐nitro substituent affects the reactivity of the purine ring, by significantly decreasing the reactivity of the N2 position, whilst the relative reactivity at N1 appears to be enhanced. Interestingly, the displacement of the nitro group with thiols results in an efficient and specific method of labelling this lesion and is demonstrated in oligodeoxynucleotides. Additionally, the repair of this lesion is also shown to be a chemically feasible reaction through a reductive denitration with a hydride source. [ABSTRACT FROM AUTHOR]

The reaction specificity of lipoxygenases is of physiological relevance since the various oxygenation products exhibit different biological activities. Among mammalian ALOX15 orthologs there are arachidonic acid 12- and 15- lipoxygenating enzymes and recent studies suggested an evolutionary switch in that reaction specificity during late primate development. Previous reports showed that 12-lipoxygenating ALOX15 orthologs can be converted to 15-lipoxygenating enzymes by site-directed mutagenesis of some sequence determinants. Unfortunately, the molecular basis for those alterations are not well understood. Here, the arachidonic acid 12-lipoxygenating N-terminal truncation variant of pig ALOX15, for which a crystal structure is available, was used to explore the catalytic mechanism of the specificity switch induced by mutagenesis of Val418 and Val419 sequence determinants. We found that Val418Ile+ Val419Met double mutant is dominantly 15-lipoxygenating. Docking and MD simulations, and quantum mechanics/molecular mechanics calculations indicated that the wildtype energy barrier for arachidonic acid 15-lipoxygenation is 3.4 kcalmol@1 higher than for 12-lipoxygenation. In contrast, for the Val418Ile+Val419Met double mutant the energy barrier for 12-lipoxygenation is 6.0 kcalmol@1 higher than for 15-lipoxygenation. Our data suggest that enzyme-substrate complex geometries determine the value of these energy barriers and, as a consequence, the reaction specificity of ALOX15 orthologs. [ABSTRACT FROM AUTHOR]

Abstract: The possible role of DNA i‐motif structures in telomere biology and in the transcriptional regulation of oncogene promoter regions is supported by several recent studies. Herein we investigate the effect of four cytidine nucleosides (and combinations thereof) on i‐motif structure and stability, namely 2′‐deoxycytidine (dC), 2′‐deoxy‐5‐methyl‐cytidine (5‐Me‐dC), 2′‐deoxy‐2′‐fluoro‐arabinocytidine (2′F‐araC), and 2′‐deoxy‐2′‐fluoro‐5‐methyl‐arabinocytidine (5‐Me‐2′F‐araC). The base pair 5‐Me‐2′F‐araC:2′F‐araC produced i‐motifs with a pH1/2 (“pKa”) value that closely matches physiological pH (7.34±0.3). NMR analysis of the most stable telomeric sequence (HJ‐2) at pH 7.0 indicated that the structure is stabilized by hybrid 5‐Me‐dC:2′F‐araC hemiprotonated base pairs and therefore highlights the significance of the interplay between base and sugar modifications on the stability of i‐motif structures. [ABSTRACT FROM AUTHOR]

Different tail-engineered resorcinarenes have been examined for insulin fibrillation by experimental and computational studies. The resorcinarene showed a promising effect on the inhibition of insulin fibrillation, studied using a ThT assay, circular dichroism spectroscopy, and atomic force microscopy. Both the ThT assay and computational results indicate the tail from the resorcinarene has an impact on insulin fibrillation by either inhibition or promotion because of the resident position on insulin. These observations have significant biological implications in the design of drug molecules as well as the development of potential therapeutic strategies. [ABSTRACT FROM AUTHOR]