Biological Importance Research Articles

Mosna reveals different types of cellular interactions predictive of response to immunotherapies and survival in cancer.

Spatially resolved omics enable the discovery of tissue organization of biological or clinical importance. Despite the existence of several methods, performing a rational analysis including multiple algorithms while integrating different conditions such as clinical data is still not trivial. To make such investigations more accessible, we developed mosna, a Python package to analyze spatial omics data with respect to clinical or biological data and to gain insight on cell interaction patterns or tissue architecture of biological relevance. mosna is compatible with all spatial omics methods, it leverages tysserand to build accurate spatial networks, and is compatible with Squidpy. It proposes an analysis pipeline, in which increasingly complex features computed at each step can be explored in integration with clinical data, either with easy-to-use descriptive statistics and data visualization, or by seamlessly training machine learning models and identifying variables with the most predictive power. mosna can take as input any dataset produced by spatial omics methods, including sub-cellular resolved transcriptomics (MERFISH, seqFISH) and proteomics (CODEX, MIBI-TOF, low-plex immuno-fluorescence), as well as spot-based spatial transcriptomics (10x Visium). Integration with experimental metadata or clinical data is adapted to binary conditions, such as biological treatments or response status of patients, and to survival data. We demonstrate the proposed analysis pipeline on two spatially resolved proteomic datasets containing either binary response to immunotherapy or survival data. mosna identifies features describing cellular composition and spatial distribution that can provide biological insight regarding factors that affect response to immunotherapies or survival.

Determination of selenium in polyheteroatomic organic compounds by microwave plasma atomic emission spectrometry

Currently, the problem of selenium determination in various objects attracts a large number of scientists. Interest in this area is attributed to the biological importance of selenium, since it is both an important nutrient and has a toxic effect on the body, depending on its amount and the properties of the compounds in which it is contained. Checking the purity of selenium-containing organic compounds (both determination of impurities and analysis of the basic composition), which is carried out by methods of elemental analysis, is an important task, however, in modern literature there is lack of information regarding this problem. The purpose of the presented study is to develop a method for the determination of selenium in the basic composition of synthetic polyheteroatomic organic compounds by microwave plasma atomic emission spectrometry. Various selenodiazole derivatives were mainly used for analysis. Optimal conditions for sample preparation and atomic emission determination of the selenium content were specified. To mineralize the substances under study, oxygen flask combustion was used with the addition of potassium nitrate, which improves combustion and prevents the formation of soot. Hydrochloric acid at a concentration of 0.1 M was used as an absorption solution. It is noted that before measurements it is necessary to purge the monochromator and optimize the pressure in the atomic emission spectrometer nebulizer and optimize pressure in the atomizer. In addition, the number of replicates and sampling time were increased to optimize selenium measurement. Under specified conditions, the metrological characteristics of the technique were determined: the detection limit and quantitation limit, intra-laboratory precision and accuracy. Selenium was determined in 11 synthetic organic compounds with selenium content ranged from 12 to 51%. The error of the analysis did not exceed 0.3%, which meets the requirements of organic elemental analysis.

Organic Transformations through Cooperative Bimetallic Catalysis: An Overview

Under the broad domain of multimetallic catalysis, the utilisation of two transition metals (either homometallic or heterometallic) as catalysts in a cooperative way to enhance reactivity and promote higher stereoselectivity and versatility has witnessed remarkable advancements in organic synthesis in the last two decades. This review attempts to provide an account of the development in the recent past to its progress now in this area, highlighting the importance of simultaneous catalytic cycles in the mechanistic pathway and optimal reaction conditions for organic transformations leading to building blocks of importance in biology and pharmaceutical applications. The reactions presented here include, among others, C-H activation, reductive crosscoupling, allenylation, tandem isomerisation-allylation, heteroarylation, and asymmetric synthesis.

Multicellular artificial neural network-type architectures demonstrate computational problem solving.

Here, we report a modular multicellular system created by mixing and matching discrete engineered bacterial cells. This system can be designed to solve multiple computational decision problems. The modular system is based on a set of engineered bacteria that are modeled as an 'artificial neurosynapse' that, in a coculture, formed a single-layer artificial neural network-type architecture that can perform computational tasks. As a demonstration, we constructed devices that function as a full subtractor and a full adder. The system is also capable of solving problems such as determining if a number between 0 and 9 is a prime number and if a letter between A and L is a vowel. Finally, we built a system that determines the maximum number of pieces of a pie that can be made for a given number of straight cuts. This work may have importance in biocomputer technology development and multicellular synthetic biology.

Pan-cancer analysis of m1A writer gene RRP8: implications for immune infiltration and prognosis in human cancers

BackgroundRibosomal RNA Processing 8 (RRP8) is a gene associated with RNA modification and has been implicated in the development of several types of tumors in recent research. Nevertheless, the biological importance of RRP8 in pan-cancer has not yet been thoroughly and comprehensively investigated.MethodsIn this study, we conducted an analysis of various public databases to investigate the biological functions of RRP8. Our analysis included examining its correlation with pan-cancer prognosis, heterogeneity, stemness, immune checkpoint genes, and immune cell infiltration. Furthermore, we utilized the GDSC and CTRP databases to assess the sensitivity of RRP8 to small molecule drugs.ResultsOur findings indicate that RRP8 exhibits differential expression between tumor and normal samples, particularly impacting the prognosis of various cancers such as Adrenocortical carcinoma (ACC) and Kidney Chromophobe (KICH). The expression of RRP8 is intricately linked to tumor heterogeneity and stemness markers. Additionally, RRP8 shows a positive correlation with the presence of tumor-infiltrating cells, with TP53 being the predominant mutated gene in these malignancies.ConclusionOur findings suggest that RRP8 may serve as a potential prognostic marker and therapeutic target in a variety of cancer types.

Nonadiabatic Hydrogen Tunneling Dynamics for Multiple Proton Transfer Processes with Generalized Nuclear-Electronic Orbital Multistate Density Functional Theory.

Proton transfer and hydrogen tunneling play key roles in many processes of chemical and biological importance. The generalized nuclear-electronic orbital multistate density functional theory (NEO-MSDFT) method was developed in order to capture hydrogen tunneling effects in systems involving the transfer and tunneling of one or more protons. The generalized NEO-MSDFT method treats the transferring protons quantum mechanically on the same level as the electrons and obtains the delocalized vibronic states associated with hydrogen tunneling by mixing localized NEO-DFT states in a nonorthogonal configuration interaction scheme. Herein, we present the derivation and implementation of analytical gradients for the generalized NEO-MSDFT vibronic state energies and the nonadiabatic coupling vectors between these vibronic states. We use this methodology to perform adiabatic and nonadiabatic dynamics simulations of the double proton transfer reactions in the formic acid dimer and the heterodimer of formamidine and formic acid. The generalized NEO-MSDFT method is shown to capture the strongly coupled synchronous or asynchronous tunneling of the two protons in these processes. Inclusion of vibronically nonadiabatic effects is found to significantly impact the double proton transfer dynamics. This work lays the foundation for a variety of nonadiabatic dynamics simulations of multiple proton transfer systems, such as proton relays and hydrogen-bonding networks.

Fine-tuning plant valuable secondary metabolite biosynthesis via small RNA manipulation: strategies and potential.

Plants produce secondary metabolites that serve various functions, including defense against biotic and abiotic stimuli. Many of these secondary metabolites possess valuable applications in diverse fields, including medicine, cosmetic, agriculture, and food and beverage industries, exhibiting their importance in both plant biology and various human needs. Small RNAs (sRNA), such as microRNA (miRNA) and small interfering RNA (siRNA), have been shown to play significant roles in regulating the metabolic pathways post-transcriptionally by targeting specific key genes and transcription factors, thus offering a promising tool for enhancing plant secondary metabolite biosynthesis. In this review, we summarize current approaches for manipulating sRNAs to regulate secondary metabolite biosynthesis in plants. We provide an overview of the latest research strategies for sRNA manipulation across diverse plant species, including the identification of potential sRNAs involved in secondary metabolite biosynthesis in non-model plants. We also highlight the potential future research directions, focusing on the manipulation of sRNAs to produce high-value compounds with applications in pharmaceuticals, nutraceuticals, agriculture, cosmetics, and other industries. By exploring these advanced techniques, we aim to unlock new potentials for biotechnological applications, contributing to the production of high-value plant-derived products.

A Modular Biosensor Design for Quantitative Measurement of Free Nedd8.

The objective of our study was to develop a genetically encoded biosensor for quantification of Nedd8, a post-translational modifier that regulates cellular signals through conjugation to other proteins. Perturbations in the balance of free (i.e., unconjugated) and conjugated Nedd8 caused by defects in Nedd8 enzymes or cellular stress are implicated in various diseases. Despite the biological and biomedical importance of Nedd8 dynamics, no method exists for direct quantification of free Nedd8, hindering the study of Nedd8 and activities of its associated enzymes. Genetically encoded biosensors are established as tools to study other dynamic systems, but limitations of current biosensor design methods make them poorly suited for free Nedd8 quantification. We have developed a modular method to design genetically encoded biosensors that employs a target binding domain and two reporter domains positioned on opposite sides of the target binding site. Target quantification is based on competition between target binding and the interaction of the reporter domains. We applied our design strategy to free Nedd8 quantification by developing a selective binder for free Nedd8 and combining it with fluorescent or split nanoluciferase reporters. Our sensors produced quantifiable and specific signals for free Nedd8 and enabled real-time monitoring of deneddylation by DEN1 with a physiological substrate. Our sensor design will be useful for high-throughput screening for deneddylation inhibitors, which have potential in treatment of cancers such as acute lymphoblastic leukemia. The modular design strategy can be extended to develop genetically encoded quantitative biosensors for other proteins of interest.

ATP-dependent remodeling of chromatin condensates uncovers distinct mesoscale effects of two remodelers.

ATP-dependent chromatin remodeling enzymes mobilize nucleosomes, but how such mobilization affects chromatin condensation is unclear. Here, we investigate effects of two major remodelers, ACF and RSC using chromatin condensates and single-molecule footprinting. We find that both remodelers inhibit the formation of condensed chromatin. However, the remodelers have distinct effects on pre-formed chromatin condensates. ACF spaces nucleosomes without de-condensing the chromatin, explaining how ACF maintains nucleosome organization in transcriptionally repressed genomic regions. In contrast, RSC catalyzes ATP-dependent de-condensation of chromatin. Surprisingly, RSC also drives micron-scale movements of entire condensates. These newly uncovered activities of RSC explain its central role in transcriptional activation. The biological importance of remodelers may thus reflect both their effects on nucleosome mobilization and the corresponding consequences on chromatin dynamics at the mesoscale.

Characteristics and transcriptional regulators of spontaneous epithelial–mesenchymal transition in genetically unperturbed patient-derived non-spindled breast carcinoma

BackgroundAlthough tumor cells undergoing epithelial–mesenchymal transition (EMT) typically exhibit spindle morphology in experimental models, such histomorphological evidence of EMT has predominantly been observed in rare primary spindle carcinomas. The characteristics and transcriptional regulators of spontaneous EMT in genetically unperturbed non-spindled carcinomas remain underexplored.MethodsWe used primary culture combined with RNA sequencing (RNA-seq), single-cell RNA-seq (scRNA-seq), and in situ RNA-seq to explore the characteristics and transcription factors (TFs) associated with potential spontaneous EMT in non-spindled breast carcinoma.ResultsOur primary culture revealed carcinoma cells expressing diverse epithelial–mesenchymal traits, consistent with epithelial–mesenchymal plasticity. Importantly, carcinoma cells undergoing spontaneous EMT did not necessarily exhibit spindle morphology, even when undergoing complete EMT. EMT was a favored process, whereas mesenchymal–epithelial transition appeared to be crucial for secondary tumor growth. Through scRNA-seq, we identified TFs that were sequentially and significantly upregulated as carcinoma cells progressed through the EMT process, which correlated with increasing VIM expression. Once upregulated, the TFs remained active throughout the EMT process. ZEB1 was a key initiator and sustainer of EMT, as indicated by its earliest significant upregulation in the EMT process, its exact correlation with VIM expression, and the reversal of EMT and downregulation of EMT-upregulated TFs upon ZEB1 knockdown. The correlation between ZEB1 and vimentin expression in triple-negative breast cancer and metaplastic breast carcinoma tumor cohorts further highlighted its role. The immediate upregulation of ZEB2 following that of ZEB1, along with the observation that the knockdown of ZEB1 or ZEB2 downregulates both ZEB1 and ZEB2 concomitant with the reversal of EMT, suggests their functional cooperation in EMT. This finding, together with that of a lack of correlation of SNAI1, SNAI2, and TWIST1 expression with the mesenchymal phenotype, indicated EMT-TFs have a context-dependent role in EMT. Upregulation of EMT-related gene signatures during EMT correlated with poor patient outcomes, highlighting the biological importance of the model. Elevated EMT gene signatures and increased ZEB1 and ZEB2 expression in vimentin-positive compared to vimentin-negative carcinoma cells within the corresponding primary tumor tissue confirmed ZEB1 and ZEB2 as intrinsic, instead of microenvironmentally-induced, EMT regulators, and vimentin as an in vivo indicator of EMT.ConclusionsOur findings provide insights into the characteristics and transcriptional regulators of spontaneous EMT in primary non-spindled carcinoma.

Dr. Vasant Ramji Khanolkar: A Revolutionary Pathologist in India.

Dr. Vasant Ramji Khanolkar is known as the Father of Pathology in India. His outstanding contributions include research on the epidemiology of cancer in India, leprosy, reproduction anatomy, and family planning practices in India. He had the lion's share in medical education in India and started the subjects of Biophysics and Applied Biology at Bombay University. He recognized the importance of basic science, experimental biology, biochemistry, biophysics, and numerology in medical education. He suggested many changes in the medical education curriculum of India and strengthened the research facilities in medical education. Dr. Vasant Ramji Khanolkar was honored with Padma Bhushan, a prestigious award by the Government of India.

Introducing Ion Mobility Mass Spectrometry in Brain Glycosaminoglycomics: Application to Chondroitin/Dermatan Sulfate Octasaccharide Domains.

Glycosaminoglycans (GAGs) are sulfated linear O-glycan chains abundantly expressed in the extracellular matrix (ECM). Among GAGs, chondroitin sulfate (CS) and dermatan sulfate (DS) play important roles at the brain level, where the distribution and location of the sulfates within the CS/DS chains are responsible for numerous biological events. The diversity of the neural hybrid CS/DS expressed in the brain and the need to elucidate their structure gave rise to considerable efforts toward the development of analytical methods able to discover novel regularly and irregularly sulfated domains. In this context, we report here the introduction of ion mobility separation (IMS) mass spectrometry (MS) in brain glycosaminoglycomics. Based on IMS MS and tandem MS (MS/MS) by collision-induced dissociation (CID), we have developed a powerful approach for the screening and structural analysis of neural CS/DS and optimized and validated the method for the structural analysis of octasaccharides that were released from brain proteoglycans by β-elimination and pooled after chain depolymerization using chondroitin AC lyase. The IMS MS data revealed the separation of CS/DS octamers into mobility families based on the amount of sulfation. Among the discovered oversulfated domains, of major biological importance is the pentasulfated-[4,5-Δ-GlcAGalNAc(IdoAGalNAc)3], for which the (-) nanoESI IMS CID MS/MS analysis disclosed through the presence of distinct drift times, the incidence of two isomers. Moreover, the generated fragment ions revealed an uncommon trisulfated motif and an uncommon pentasulfated motif. Hence, using IMS MS and CID MS/MS, novel brain-related CS/DS domains of atypical sulfation patterns were discovered and structurally characterized in detail.

A Versatile Method for Site-Specific Chemical Installation of Aromatic Posttranslational Modification Analogs into Proteins.

Posttranslational modifications (PTMs) of proteins play central roles in regulating the protein structure, interactome, and functions. A notable modification site is the aromatic side chain of Tyr, which undergoes modifications such as phosphorylation and nitration. Despite the biological and physiological importance of Tyr-PTMs, our current understanding of the mechanisms by which these modifications contribute to human health and disease remains incomplete. This knowledge gap arises from the absence of natural amino acids that can mimic these PTMs and the lack of synthetic tools for the site-specific introduction of aromatic PTMs into proteins. Herein, we describe a facile method for the site-specific chemical installation of aromatic PTMs into proteins through palladium-mediated S-C(sp2) bond formation under ambient conditions. We demonstrate the incorporation of novel PTMs such as Tyr-nitration and phosphorylation analogs to synthetic and recombinantly expressed Cys-containing peptides and proteins within minutes and in good yields. To demonstrate the versatility of our approach, we employed it to prepare 10 site-specifically modified proteins, including nitrated and phosphorylated analogs of Myc and Max proteins. Furthermore, we prepared a focused library of site-specifically nitrated and phosphorylated α-synuclein (α-Syn) protein, which enabled, for the first time, deciphering the role of these competing modifications in regulating α-Syn conformation aggregation in vitro. Our strategy offers advantages over synthetic or semisynthetic approaches, as it enables rapid and selective transfer of rarely explored aromatic PTMs into recombinant proteins, thus facilitating the generation of novel libraries of homogeneous posttranslationally modified proteins for biomarker discovery, mechanistic studies, and drug discovery.

Therapeutic Potential and Pharmacological Activities of Moscatilin in Medicine for the Treatment of Cancers and other Human Complication: A Review of the Active Components of Dendrobium Species

Background: Plant-derived byproducts have been used to treat numerous kinds of human complications in medicine since a very early age. Moscatilin is a bibenzyl compound found to be present in Dendrobium. Moscatilin, also called 4,4′-dihydroxyl-3,3′,5-trimethoxybibenzyl has potential benefits in medicine for the treatment of ovarian, lung, breast, esophageal, hepatic, colorectal, pancreatic and neck squamous cancer. Methods: The present work summarized the health-beneficial aspects of moscatilin for its effectiveness against numerous kinds of cancerous disorders in medicine. Pharmacological activities and analytical aspects of moscatilin have been analyzed in the present work through available scientific data on Google, Scopus, Science Direct, and PubMed. Results: Scientific data analysis of moscatilin signified their therapeutic effectiveness against ovarian cancer, lung cancer, breast cancer, esophageal cancer, hepatic cancer, colorectal cancer, pancreatic cancer, neck squamous cell cancer, apoptosis, and angiogenesis. Further, moscatilin has a significant effect on inflammation, Alzheimer's disease, diabetic neuropathy, and retinal ischemia. However, analytical data on moscatilin were also discussed in the present work in order to know the effective separation, isolation and identification of moscatilin. Conclusion: Scientific information on moscatilin presented in this work will be helpful to all scientific people to understand the biological importance and therapeutic potential of moscatilin in medicine.

MEN1 Deficiency-Driven Activation of the β-Catenin-MGMT Axis Promotes Pancreatic Neuroendocrine Tumor Growth and Confers Temozolomide Resistance.

O6-methylguanine DNA methyltransferase (MGMT) removes alkyl adducts from the guanine O6 position (O6-MG) and repairs DNA damage. High MGMT expression results in poor response to temozolomide (TMZ). However, the biological importance of MGMT and the mechanism underlying its high expression in pancreatic neuroendocrine tumors (PanNETs) remain elusive. Here, it is found that MGMT expression is highly elevated in PanNET tissues compared with paired normal tissues and negatively associated with progression-free survival (PFS) time in patients with PanNETs. Knocking out MGMT inhibits cancer cell growth in vitro and in vivo. Ectopic MEN1 expression suppresses MGMT transcription in a manner that depends on β-Catenin nuclear export and degradation. The Leucine 267 residue of MEN1 is crucial for regulating β-Catenin-MGMT axis activation and chemosensitivity to TMZ. Interference with β-Catenin re-sensitizes tumor cells to TMZ and significantly reduces the cytotoxic effects of high-dose TMZ treatment, and MGMT overexpression counteracts the effects of β-Catenin deficiency. This study reveals the biological importance of MGMT and a new mechanism by which MEN1 deficiency regulates its expression, thus providing a potential combinational strategy for treating patients with TMZ-resistant PanNETs.

Biological Activities and Importance of the Medicinal Plant, Commiphora gileadensis Collected from Makka Region, Saudi Arabia

Objective: This study aimed to discover safe antibacterial and antibiofilm agents from natural sources to control resistant bacteria. Methods: C. gileadensis leaves and stems were collected, identified, and extracted using different organic solvents, methanol, ethyl acetate, chloroform, and hot water. The tested bacteria were multidrug-resistant Escherichia coli, Acinetobacter baumannii, Listeria monocytogenes, Serratia marcescens, Klebsiella pneumonia, Staphylococcus aureus, Pseudomonas aeruginosa. Crystal violet method was used to detect biofilm formation while the phenol-sulphonic acid method to measure exopolysaccharide contents, which are an effective factor in biofilm formation. Results: No significant differences were noted in the biological activities between leave and stem. Ethyl acetate and chloroform extracts showed lower activities. Still, hot water extract showed the weakest activities.There is a synergistic effect between the Commiphora extract and some antibiotics, especially Amoxicillin, Polymixin B, and Tetracycline. The highest inhibition of biofilm was recorded against K. pneumonia which had the highest EPS content (0.29 ±0.04 μg/mg of cells), decreased after treatment with plant extract by 39%. Cytotoxicity studies using Artimia salina as a test organism were conducted for the methanolic extracts, which showed antitumor activity against two cell lines, MCF-7 (breast cancer) and HepG2 (hepatocellular carcinoma). Commiphora extract showed antioxidant activity using two different protocols. Conclusion, the methanolic extract of Commiphora singly or in combination with antibiotics inhibit many pathogenic bacteria that form biofilm and recorded antitumor and antioxidant activities.

Vasostatin-1 restores autistic disorders in an idiopathic autism model (BTBR T+ Itpr3tf/J mice) by decreasing hippocampal neuroinflammation

Chromogranin A (CgA), a ∼ 49 kDa acidic secretory protein, is ubiquitously distributed in endocrine and neuroendocrine cells and neurons. As a propeptide, CgA is proteolytically cleaved to generate several peptides of biological importance, including pancreastatin (PST: hCgA250–301), Vasostatin 1 (VS1: hCgA1–76), and catestatin (CST: CgA 352–372). VS1 represents the most conserved fragment of CgA. A 20 amino acid domain within VS1 (CgA 47–66) exhibits potent antimicrobial and anti-inflammatory activities. Autism is known to be associated with inflammation. Therefore, we seek to test the hypothesis that VS1 modulates autism behaviors by reducing inflammation in the hippocampus. Treatment of C57BL/6 (B6) and BTBR (a mouse model of idiopathic autism) mice with VS1 revealed the following: BTBR mice showed a significant decrease in chamber time in the presence of a stranger or a novel object. Treatment with VS1 significantly increased chamber time in both cases, underscoring a crucial role for VS1 in improving behavioral deficits in BTBR mice. In contrast to chamber time, sniffing time in BTBR mice in the presence of a stranger was less compared to B6 control mice. VS1 did not improve this latter parameter. Surprisingly, sniffing time in BTBR mice in the presence of a novel object was comparable with B6 mice. Proinflammatory cytokines such as IL-6 and IL-1b, as well as other inflammatory markers, were elevated in BTBR mice, which were dramatically reduced after supplementation with VS1. Interestingly, even Beclin-1/p62, pAKT/AKT, and p-p70-S6K/p70-S6K ratios were notably reduced by VS1. We conclude that VS1 plays a crucial role in restoring autistic spectrum disorders (ASD) plausibly by attenuating neuroinflammation.

Biological function of Aβ peptides revealed by analysis of membrane-association properties: Implications for Azheimer's disease pathogenesis

Proteolytic processing of amyloid precursor protein (APP) plays a critical role in the pathogenesis of Azheimer's disease (AD). Sequential cleavage of APP by β and γ secretases leads to generation of Aβ40 (non-amyloidogenic) and Aβ42 (amyloidogenic) peptides. Despite intense studies, the biological function of these peptides and the mechanism of Aβ42 toxicity is poorly understood. In the previous publications we proposed that association of Aβ peptides with the endosomal membranes may have important implications for pathogenesis of AD (Kim and Bezprozvanny, IJMS, 2021, vol 22, 13600; Kim and Bezprozvanny, IJMS, 2023, vol 24, 2092). To understand potential biological importance of such interaction, we focused on the region of Aβ peptides involved in peri-membrane association (E682 to N698). We discovered that association of this region with the membranes is reminiscent of several known anti-microbial peptides (AMP) such as PA13, Aurein1.2 and BP100. Our analysis further revealed that energy of peri-membrane association of Aβ40 is significantly weaker than for Aβ42 or AMP peptides, but it can be increased in the presence of non-amyloidogenic FAD mutations or in the presence of cholesterol in the membrane. Based on similarity with established mechanism of action of AMP peptides, we propose that Aβ peptides affect the curvature of endosomal membranes and shift the balance between endosomal recycling to plasma membrane and late endosomal/lysosomal pathway. We further propose that these effects are enhanced as a result of non-amyloidogenic FAD mutations in the sequence of Aβ peptides or in the presence of cholesterol in the membrane. The proposed model provides potential mechanistic explanation to synaptic defects induced by increased levels of Aβ42, by non-amyloidogenic FAD mutations in APP and by age-related increase in the levels of cholesterol in the brain.

3D-printed devices for optimized generation of cold atmospheric plasma to improve decontamination of surfaces from respiratory pathogens

Three-dimensional (3D)-printing technology is instrumental in creating devices for biological applications, including the exploitation of cold atmospheric plasma (CAP). CAP, a partially ionized gas that functions at ambient temperatures, serves as a safe, inexpensive, and effective tool for the inactivation of various pathogens on different surfaces. In this study, we compared three different 3D-printed devices with respect to their ability to provide optimized CAP compositions effective against select respiratory viruses (SARS-CoV-2, influenza virus, adenovirus, and rhinovirus) and the bacterium Pseudomonas aeruginosa, which is associated with serious lung diseases. The transmission of respiratory pathogens via surface contamination may pose a serious health threat, thus highlighting the biological importance of the current study. The properties of a prototype 3D-printed CAP-generating device and two optimized versions were characterized by detecting reactive oxygen and nitrogen species (RONS) in a gaseous environment via infrared spectroscopy and analyzing the composition of the reactive compounds. The virucidal effects of CAP were examined by determining virus infectivity and particle integrity. The bactericidal effect was documented by viability testing and visualization via transmission electron microscopy. The findings indicate that optimization of the 3D-printed devices for CAP production yielded an environment with relatively high amounts of RONS (O3, N2O, NO2, and H2O2), reducing the exposure time required for inactivation of respiratory pathogens by approximately 50%. In addition to reducing infectivity and viability, CAP treatment led to the destruction of viral nucleic acids and physical damage to bacterial cells. Owing to its flexibility and easy implementation, optimized CAP generated by 3D-printed devices provides an attractive inactivation method adaptable for different biological applications, including surface decontamination from viral and bacterial pathogens.   

Chemical Methods for the Construction of Spirocyclic β-Lactams and Their Biological Importance

AbstractSpirocyclic β-lactams are a family of natural and synthetic chemicals with different biological activities, including antibacterial properties, and interact with critical physiological targets such as T-type calcium channels and acetyl-CoA cholesterol acyltransferase. Their unique chemical structure, combining a spiro ring system with a β-lactam group, offers promising opportunities for the targeted discovery of medications in medicinal chemistry. Spirocyclic β-lactams have the potential to be adaptable frameworks for developing novel therapeutic medicines with particular three-dimensional pharmacophoric characteristics and increased biological efficacy. Numerous methods are employed for the synthesis of spirocyclic β-lactams, such as cyclization, functional group modifications, asymmetric synthesis utilizing chiral catalysts and biomimetic approaches. In this short review, two distinct approaches describing recent syntheses of spirocyclic β-lactams (from 2021 to 2024) are discussed. The first is based on constructing the β-lactam ring, while the other entails transforming monocyclic β-lactams into spirocyclic structures. These methods include detailed reaction processes and descriptions of the biological functions of the target spirocycles. The applications of spirocyclic β-lactams in medicinal chemistry highlight their role in the synthesis of structurally diverse compounds with significant therapeutic potential, demonstrating creative chemical methods for building complex molecular structures.1 Introduction2 β-Lactam Ring Synthesis3 Non-β-Lactam Ring Synthesis4 Miscellaneous Examples5 Conclusion and Outlook