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A substantial increase in colorectal cancer (CRC)–associated fatalities can be attributed to tumor recurrence and multidrug resistance. Traditional treatment options, including radio- and chemotherapy, also exhibit adverse side effects. Ancient treatment strategies that include phytochemicals like resveratrol are now widely encouraged as an alternative therapeutic option. Resveratrol is the natural polyphenolic stilbene in vegetables and fruits like grapes and apples. It inhibits CRC progression via targeting dysregulated cancer-promoting pathways, including PI3K/Akt/Kras, targeting transcription factors like NF-κB and STAT3, and an immunosuppressive tumor microenvironment. In addition, combination therapies for cancer include resveratrol as an adjuvant to decrease multidrug resistance that develops in CRC cells. The current review discusses the biology of resveratrol and explores different mechanisms of action of resveratrol in inhibiting CRC progression. Further, the detrimental role of resveratrol on the immunosuppressive tumor microenvironment of CRC has been discussed. This review illustrates clinical trials on resveratrol in different cancers, including resveratrol analogs, and their efficiency in promoting CRC inhibition. [ABSTRACT FROM AUTHOR]

Somatostatin is a peptide that plays a variety of roles such as neurotransmitter and endocrine regulator; its actions as a cell regulator in various tissues of the human body are represented mainly by inhibitory effects, and it shows potent activity despite its physiological low concentrations. Somatostatin binds to specific receptors, called somatostatin receptors (SSTRs), which have different tissue distributions and associated signaling pathways. The expression of SSTRs can be altered in various conditions, including tumors; therefore, they can be used as biomarkers for cancer cell susceptibility to certain pharmacological agents and can provide prognostic information regarding disease evolution. Moreover, based on the affinity of somatostatin analogs for the different types of SSTRs, the therapeutic range includes conditions such as tumors, acromegaly, post-prandial hypotension, hyperinsulinism, and many more. On the other hand, a number of somatostatin antagonists may prove useful in certain medical settings, based on their differential affinity for SSTRs. The aim of this review is to present in detail the principal characteristics of all five SSTRs and to provide an overview of the associated therapeutic potential in neoplasias.

Fecal Microbiota Transplantation (FMT) has shown to possess impressive potential benefit for a wide range of clinical indications. Due to its inherent safety issues and efficacy constraints, the use of personalized FMT analogs could be a promising avenue. The development of such analogs will require a detailed understanding of their functionality, encompassing not only microbe-host interactions of the microbial taxa that are involved, but also of the ecological dimensions of the analogs and an overview of the gastrointestinal sites where these relevant microbial interactions take place. Moreover, characterization of taxa that have been lost due to diminished exposure to beneficial microbes, as a consequence of Western lifestyle, may lead to creation of future FMT analogs with the capacity to restore functionalities that we have lost. [ABSTRACT FROM AUTHOR]

The collection, storage, and transport of samples prior to and during analysis is of utmost importance, especially for highly potent analogs that may not be present in high concentrations and are susceptible to pH or thermally mediated degradation. An accelerated stability study was performed on 17 fentanyl analogs (fentalogs) over a wide range of pH (2–10) and temperature (20–60°C) conditions over 24 h. Dilute aqueous systems were used to investigate temperature and pH‐dependent kinetics using liquid chromatography–tandem mass spectrometry (LC–MS/MS). Liquid chromatography‐quadrupole/time‐of‐flight‐mass spectrometry (LC‐Q/TOF–MS) was used for structural elucidation of degradants. With the exception of remifentanil, all fentalogs evaluated were stable at pH 6 or lower. Fentalogs were generally unstable in strongly alkaline environments and at elevated temperatures. Remifentanil was the least stable drug and N‐dealkylated fentalogs were the most stable. Fentanyl degraded to acetylfentanyl, norfentanyl, fentanyl N‐oxide, and 1‐phenethylpyridinium salt (1‐PEP). A total of 26 unique breakdown products were observed for 15 of the fentanyl derivatives studied. Common degradation pathways involved N‐dealkylation, oxidation of the piperidine nitrogen, and β‐elimination of N‐phenylpropanamide followed by oxidation/dehydration of the piperidine ring. Ester and amide hydrolysis, demethylation at the propanamide, and O‐demethylation were observed for selected fentalogs only. The potential for analyte loss should be considered during the pre‐analytical phase (i.e., shipping and transport) where environmental conditions may not be controlled, as well as during the analysis itself. [ABSTRACT FROM AUTHOR]

Boron, the neighbor element to carbon in the periodic table, is characterized by unique electron deficiency that fosters multicenter delocalized bonding, contributing to its diverse chemistry. Unlike carbon cages (fullerenes), which preserve their structural integrity under endohedral or exohedral doping, larger boron cages (borospherenes) exhibit diverse structural configurations. These configurations can differ from those of pure boron cages and are stabilized by various metals through unique metal–boron bonding, resulting in a variety of metalloborospherenes. Due to boron's electron deficiency, metalloborospherenes exhibit fascinating chemical bonding patterns that vary with cluster size and the type of metal dopants. This review paper highlights recent advancements in metalloborospherene research, drawing comparisons with metallofullerenes, and focuses on the use of transition metals, lanthanides, and actinides as dopants across various cage dimensions. [ABSTRACT FROM AUTHOR]

Fungal infections have become an increasing threat as a result of growing numbers of susceptible hosts and diminishing effectiveness of antifungal drugs due to multi-drug resistance. This reality underscores the need to develop novel drugs with unique mechanisms of action. We recently identified 5-(N,N-hexamethylene)amiloride (HMA), an inhibitor of human Na+/H+ exchanger isoform 1, as a promising scaffold for antifungal drug development. In this work, we carried out susceptibility testing of 45 6-substituted HMA and amiloride analogs against a panel of pathogenic fungi. A series of 6-(2-benzofuran)amiloride and HMA analogs that showed up to a 16-fold increase in activity against Cryptococcus neoformans were identified. Hits from these series showed broad-spectrum activity against both basidiomycete and ascomycete fungal pathogens, including multidrug-resistant clinical isolates.

The COVID-19 pandemic has been a major reason behind the increased research aimed at the identification of effective antiviral agents. Among these, Nucleoside analogs have shown a promising effect on the inhibition of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus replication, the pathogen of COVID-19. Nucleoside analogs are synthetic compounds designed to mimic natural nucleosides, the building blocks of RNA and DNA. This review provides a comprehensive examination of the pivotal role nucleoside analogs play in combating SARS-CoV-2 infections. These analogs function by incorporating into the viral RNA during replication, disrupting the synthesis process and preventing the virus from proliferating. Researchers have identified multiple nucleoside analogs exhibiting robust antiviral efficacy against SARS-CoV-2, including remdesivir, favipiravir, and molnupiravir. This review explores the mechanisms of action, pharmacokinetics, and safety profiles of these nucleoside analogs. Furthermore, it discusses the challenges and limitations associated with their use, including the emergence of resistant viral strains and potential side effects. Additionally, the review delves into ongoing research efforts to optimize nucleoside analogs for enhanced efficacy and reduced adverse effects. In summary, the article aims to enhance our overall understanding of nucleoside-based treatments by combining information about their chemistry, mechanisms of action, and activation pathways. The goal is to contribute to advancements in addressing emerging viral threats in the future. [ABSTRACT FROM AUTHOR]

Cecropin A (1–7) is a cationic antimicrobial peptide which contain lots of basic amino acids. To understand the effect of basic amino acids on cecropin A (1–7), analogues CA2, CA3 and CA4 which have more arginine or lysine at the N-terminal or C-terminal were designed and synthesized. The interaction of cecropin A (1–7) and its analogs with DNA was studied using ultraviolet–visible spectroscopy, fluorescence spectroscopy and circular dichroism spectroscopy. Multispectral analysis showed that basic amino acids improved the interaction between the analogues and DNA. The interaction between CA4 and DNA is most pronounced. Fluorescence spectrum indicated that Ksv value of CA4 is 1.19 × 105 L mol−1 compared to original peptide cecropin A (1–7) of 3.73 × 104 L mol−1. The results of antimicrobial experiments with cecropin A (1–7) and its analogues showed that basic amino acids enhanced the antimicrobial effect of the analogues. The antimicrobial activity of CA4 against E. coli was eightfold higher than that of cecropin A (1–7). The importance of basic amino acid in peptides is revealed and provides useful information for subsequent studies of antimicrobial peptides. [ABSTRACT FROM AUTHOR]

Fecal Microbiota Transplantation (FMT) has shown to possess impressive potential benefit for a wide range of clinical indications. Due to its inherent safety issues and efficacy constraints, the use of personalized FMT analogs could be a promising avenue. The development of such analogs will require a detailed understanding of their functionality, encompassing not only microbe-host interactions of the microbial taxa that are involved, but also of the ecological dimensions of the analogs and an overview of the gastrointestinal sites where these relevant microbial interactions take place. Moreover, characterization of taxa that have been lost due to diminished exposure to beneficial microbes, as a consequence of Western lifestyle, may lead to creation of future FMT analogs with the capacity to restore functionalities that we have lost.

Zika virus represents the primary cause of infection during pregnancy and can lead to various neurological disorders such as microcephaly and Guillain-Barré syndrome affecting both children and adults. This infection is also associated with urological and nephrological problems. So far, evidence of mosquito-borne Zika virus infection has been reported in a total of 89 countries and territories. However, surveillance efforts primarily concentrate on outbreaks that this virus can cause, yet the measures implemented are typically limited. Currently, there are no specific treatments or vaccines designed for the prevention or treatment of Zika virus infection or its associated disease. The development of effective therapeutic agents presents an urgent need. Importantly, an alternative for advancing the discovery of new molecules could be dermaseptins, a family of antimicrobial peptides known for their potential antiviral properties. In this study, we carried out the synthesis of dermaseptins and their analogs and subsequently assessed the bioactivity tests against Zika virus (ZIKV PF13) of dermaseptins B2 and S4 and their derivatives. The cytotoxicity of these peptides was investigated on HMC3 cell line and HeLa cells by CellTiter-Glo® Luminescent Cell Viability Assay. Thereafter, we evaluated the antiviral activity caused by the action of our dermaseptins on the viral envelope using the Fluorescence Activated Cell Sorting (FACS). The cytotoxicity of our molecules was concentration-dependent at microgram concentrations Expect for dermaseptin B2 and its derivative which present no toxicity against HeLa and HMC3 cell lines. It was observed that all tested analogs from S4 family exhibited antiviral activity with low concentrations ranging from 3 to 12.5 μg/ml , unlike the native B2 and its derivative which increased the infectivity. Pre-incubating of dermaseptins with ZIKV PF13 before infection revealed that these derivatives inhibit the initial stages of virus infection. In summary, these results suggest that dermaseptins could serve as novel lead structures for the development of potent antiviral agents against Zika virus infections.

The central nervous system (CNS) is the final frontier in drug delivery because of the blood–brain barrier (BBB), which poses significant barriers to the access of most drugs to their targets. Kynurenic acid (KYNA), a tryptophan (Trp) metabolite, plays an important role in behavioral functions, and abnormal KYNA levels have been observed in neuropsychiatric conditions. The current challenge lies in delivering KYNA to the CNS owing to its polar side chain. Recently, C-3 side chain-modified KYNA analogs have been shown to cross the BBB; however, it is unclear whether they retain the biological functions of the parent molecule. This study examined the impact of KYNA analogs, specifically, SZR-72, SZR-104, and the newly developed SZRG-21, on behavior. The analogs were administered intracerebroventricularly (i.c.v.), and their effects on the motor domain were compared with those of KYNA. Specifically, open-field (OF) and rotarod (RR) tests were employed to assess motor activity and skills. SZR-104 increased horizontal exploratory activity in the OF test at a dose of 0.04 μmol/4 μL, while SZR-72 decreased vertical activity at doses of 0.04 and 0.1 μmol/4 μL. In the RR test, however, neither KYNA nor its analogs showed any significant differences in motor skills at either dose. Side chain modification affects affective motor performance and exploratory behavior, as the results show for the first time. In this study, we showed that KYNA analogs alter emotional components such as motor-associated curiosity and emotions. Consequently, drug design necessitates the development of precise strategies to traverse the BBB while paying close attention to modifications in their effects on behavior. [ABSTRACT FROM AUTHOR]

Cyclic dinucleotides (CDNs) are cyclic molecules consisting of two nucleoside monophosphates linked by two phosphodiester bonds, which act as a second messenger and bind to the interferon gene stimulating factor (STING) to activate the downstream signaling pathway and ultimately induce interferon secretion, initiating an anti-infective immune response. Cyclic dinucleotides and their analogs are lead compounds in the immunotherapy of infectious diseases and tumors, as well as immune adjuvants with promising applications. Many agonists of pathogen recognition receptors have been developed as effective adjuvants to optimize vaccine immunogenicity and efficacy. In this work, the binding mechanism of human-derived interferon gene-stimulating protein and its isoforms with cyclic dinucleotides and their analogs was theoretically investigated using computer simulations and combined with experimental results in the hope of providing guidance for the subsequent synthesis of cyclic dinucleotide analogs. [ABSTRACT FROM AUTHOR]

The Iris mission is a student-led 3-U CubeSat comprised of a science payload of 20 geological samples placed in low-Earth orbit (LEO) to study the effects of space weathering (i.e., those aspects that can be investigated in LEO). This experiment is the first of its kind to take place in the vacuum of space. The science objective of the mission is to investigate how space weathering processes affect the surfaces of airless planetary bodies by monitoring the spectral reflectance properties of geological samples over time. Two three-color cameras acquire spectral reflectance data within the visible spectrum to measure any spectral and/or textural changes exhibited throughout the ∼1-year orbital mission. This mission will provide valuable data to help understand how the space environment may affect the surfaces of the Moon, Mercury, and main-belt and near-Earth asteroids. The acquired data will help constrain meteorite-asteroid links and provide insight into the spectroscopic analysis of samples returned from the Moon, and near-Earth asteroids Itokawa, Bennu, and Ryugu. The results of this mission will also complement the results of laboratory simulations of space weathering. All samples selected for flight on the CubeSat have undergone several tests to ensure suitability for launch and operations. This paper describes the payload subsystem, sample selection and preparation. • First-of-its-kind geological space weathering investigation of lunar and asteroid materials. • The Iris CubeSat geological samples will be directly exposed to the LEO environment. • This study will observe changes in the visible spectral range of the samples over short time scales. • The results of this mission will complement laboratory studies of space weathering. • The CubeSat mission is led by post-secondary students to gain hands-on experience. [ABSTRACT FROM AUTHOR]

Background: During the ongoing opioid epidemic, Cuyahoga County (second largest in Ohio) reported overdose mortality rates (54/per 100,000) higher than the national average. Prior research demonstrates that people who use drugs often use alone but there is minimal research on people who died of overdose while using alone. The objective of this study is to examine sociodemographic, toxicologic, and injury characteristics, and emergency medical response to overdose decedents who died using drugs alone. Method: Data from the Cuyahoga County Medical Examiner's Office (2016–2020, N = 2944) on unintentional overdose deaths in adults was tabulated including socio-demographic, toxicologic, and injury-related information. Decedents using drugs alone were identified and compared to those not using alone via Chi-square and Fisher's exact tests. We further fit a multivariate logistic regression model to evaluate socio-demographic, toxicologic, and injury-related factors associated with increased odds of using alone. All results are reported with 95% confidence intervals. Result: Among decedents, 75% (n = 2205) were using drugs alone. Decedents using alone were more likely to be using drugs at home (p = 0.001) or be found dead at the scene (p < 0.001) and less likely to receive naloxone (p < 0.001) have other person/bystander, not using, present (p = 0.002). Using drugs at home (aOR = 1.61[1.19–2.20]) was associated with higher odds of using alone; and being married (aOR = 0.57[0.38–0.86]), having history of illicit drug use (aOR = 0.25[0.08–0.81]) and other person present, who was not using (aOR = 0.58[0.42–0.79]) were associated with lower odds of using alone. Conclusion: New harm reduction approaches targeting people using drugs alone are needed to reduce overdose deaths. [ABSTRACT FROM AUTHOR]

Curcumin is found in the medicinal plant turmeric and has a wide range of pharmacological activities. To improve their low stability, poor solubility, and low bioavailability, their monocarbonyl derivatives (MACs) modification has received much attention from researchers. In this study, MACs (1a–1e) were investigated with the help of density functional theory (DFT). The equilibrium geometries were optimized and then the predictions of vibration frequencies, conceptual density functional indices, antioxidant activity, and aromaticity were carried out. The results showed that the hydroxyl substitution at o- and p-positions in MACs exhibited strong reactivity, especially the substitution at the p-position significantly improved the electrophilic and antioxidant activity of compounds. This work also found that aqueous solutions had a booster effect on the reactivity of MACs. In contrast, the effect of hydroxyl at the m-position on the structure and properties was not significant. Furthermore, the molecular docking results show that the presence of hydroxyl group in MACs facilitates the enhancement of the interaction between MACs and the receptor. Results of this work introduce new and important information that contributes to the understanding of the potential properties of MACs and provides references and directions for the design of this type of drugs. [ABSTRACT FROM AUTHOR]

Nosocomial infections represent one of the biggest health problems nowadays. Acinetobacter baumannii is known as an opportunistic pathogen in humans, affecting people with compromised immune systems, and is becoming increasingly important as a hospital-derived infection. It is known that in recent years, more and more bacteria have become multidrug-resistant (MDR) and, for this reason, the development of new drugs is a priority. However, these products must not affect the human body, and therefore, cytotoxicity studies are mandatory. In this context, antimicrobial peptides with potential antibacterial proprieties could be an alternative. In this research, we describe the synthesis and the bioactivity of dermaseptins and their derivatives against Acinetobacter baumannii. The cytotoxicity of these compounds was investigated on the HEp-2 cell line by MTT cell viability assay. Thereafter, we studied the morphological alterations caused by the action of one of the active peptides on the bacterial membrane using atomic force microscopy (AFM). The cytotoxicity of dermaseptins was concentration-dependent at microgram concentrations. It was observed that all tested analogs exhibited antibacterial activity with Minimum Inhibitory Concentrations (MICs) ranging from 3.125 to 12.5 μg/mL and Minimum Bactericidal Concentrations (MBCs) ranging from 6.25 to 25 μg/mL. Microscopic images obtained by AFM revealed morphological changes on the surface of the treated bacteria caused by K4S4(1-16), as well as significant surface alterations. Overall, these findings demonstrate that dermaseptins might constitute new lead structures for the development of potent antibacterial agents against Acinetobacter baumannii infections. [ABSTRACT FROM AUTHOR]

Boron, the neighbor element to carbon in the periodic table, is characterized by unique electron deficiency that fosters multicenter delocalized bonding, contributing to its diverse chemistry. Unlike carbon cages (fullerenes), which preserve their structural integrity under endohedral or exohedral doping, larger boron cages (borospherenes) exhibit diverse structural configurations. These configurations can differ from those of pure boron cages and are stabilized by various metals through unique metal–boron bonding, resulting in a variety of metalloborospherenes. Due to boron’s electron deficiency, metalloborospherenes exhibit fascinating chemical bonding patterns that vary with cluster size and the type of metal dopants. This review paper highlights recent advancements in metalloborospherene research, drawing comparisons with metallofullerenes, and focuses on the use of transition metals, lanthanides, and actinides as dopants across various cage dimensions.

In colorectal cancer (CRC), aberrations in KRAS are associated with aggressive tumorigenesis and an overall low survival rate because of chemoresistance and adverse effects. Ergo, complementary, and integrative medicines are being considered for CRC treatment. Among which is the use of natural chalcones that are known to exhibit anti-tumor activities in KRAS mutant CRC subtypes treatment regimens. Consequently, we examine the effect of two novel compounds (DK13 and DK14) having chalcones with nitrogen mustard moiety on CRC cell lines (HCT-116 and LoVo) with KRAS mutation. These compounds were synthesized in our lab and previously reported to exhibit potent activity against breast cancer cells. Our data revealed that DK13 and DK14 treatment suppress cell growth, disturb the progression of cell cycle, and trigger apoptosis in CRC cell lines. Besides, treatment with both compounds impedes cell invasion and colony formation in both cell lines as compared to 5-FU; this is accompanied by up and down regulations of E-cadherin and Vimentin, respectively. At the molecular level, both compounds deregulate the expression and phosphorylation of β-catenin, Akt and mTOR, which are the main likely molecular mechanisms underlying these biological occurrences. Our findings present DK13 and DK14 as novel chemotherapies against CRC, through β-catenin/Akt/mTOR signaling pathways.

The concept of torsion in geometry, although known for a long time, has not gained considerable attention from the physics community until relatively recently, due to its diverse and potentially important applications to a plethora of contexts of physical interest. These range from novel materials, such as graphene and graphene-like materials, to advanced theoretical ideas, such as string theory and supersymmetry/supergravity, and applications thereof in terms of understanding the dark sector of our Universe. This work reviews such applications of torsion at different physical scales. [ABSTRACT FROM AUTHOR]

BACKGROUND: This investigation provides an important insight into Eurasian consumers' food safety beliefs and trust issues influenced by the COVID‐19 pandemic. An online survey was conducted in 15 European and Asian countries involving more than 4000 consumers. RESULTS: It has confirmed that different socioeconomic characteristics, cultural aspects and education levels shape food safety perceptions within Eurasian countries. The COVID‐19 pandemic influenced their beliefs and trust in food safety, which is relatively low on average. However, it is significantly higher for European consumers (especially European Union ones) compared to their Asian counterparts. Both Asian and European respondents agreed that food fraud and climate changes represent a food safety issue. However, European consumers were less concerned regarding the food safety of genetically modified foods and meat and dairy analogs/hybrids. Asian consumers were, to a greater extent, worried about the risk of getting COVID‐19 from food, restaurants, food retail establishments and home food deliveries. CONCLUSION: Eurasian consumers have put their greatest extent of trust, when food safety assurance is concerned, into food scientists and food producers holding a food safety certificate. Broadly, they are uncertain to what extent their federal governments and food inspectors are competent, able and efficient in ensuring food safety. Higher education of Eurasian consumers was followed by increased food safety confidence in all parts of the food chain. © 2023 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

Chikungunya virus (CHIKV) belongs to the Alphavirus genus and is responsible for significant outbreaks worldwide. Currently, there is no approved antiviral therapy against CHIKV. Bioactive peptides have great potential for new drug development. Here, we evaluated the antiviral activity of the synthetic peptide GA-Hecate and its analogs PSSct1905 and PSSct1910 against CHIKV infection. Initial screening showed that all three peptides inhibited the CHIKV replication cycle in baby hamster kidney fibroblast cells (BHK-21) and human hepatocarcinoma epithelial cells (Huh-7). GA-Hecate and its analog PSSct1905 were the most active, demonstrating suppression of viral infection by more than 91%. The analog PSSct1905 exhibited a protective effect in cells against CHIKV infection. We also observed that the analogs PSSct1905 and PSSct1910 affected CHIKV entry into both cell lines, inhibiting viral attachment and internalization. Finally, all tested compounds presented antiviral activity on the post-entry steps of CHIKV infection in all cells evaluated. In conclusion, this study highlights the potential of the peptide GA-Hecate and its analogs as novel anti-CHIKV compounds targeting different stages of the viral replication cycle, warranting the development of GA-Hecate-based compounds with broad antiviral activity. [ABSTRACT FROM AUTHOR]

Copyright of Revista Ciencia y Poder Aéreo is the property of Escuela de Postgrados de la Fuerza Aerea Colombiana 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.)

Siderophores are small metal chelators synthesized by numerous organisms to access iron. These secondary metabolites are ubiquitously present on Earth, and because their production represents the main strategy to assimilate iron, they play an important role in both positive and negative interactions between organisms. In addition, siderophores are used in biotechnology for diverse applications in medicine, agriculture and the environment. The generation of non-natural siderophore analogs provides a new opportunity to create new-to-nature chelating biomolecules that can offer new properties to expand applications. This review summarizes the main strategies of combinatorial biosynthesis that have been used to generate siderophore analogs. We first provide a brief overview of siderophore biosynthesis, followed by a description of the strategies, namely, precursor-directed biosynthesis, the design of synthetic or heterologous pathways and enzyme engineering, used in siderophore biosynthetic pathways to create diversity. In addition, this review highlights the engineering strategies that have been used to improve the production of siderophores by cells to facilitate their downstream utilization. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Food Safety & Quality is the property of Journal of Food Safety & Quality Editorial Department 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.)

Marine products are among the most promising sources of biologically active molecules. Aplysinopsins, tryptophan-derived marine natural products, were isolated from different natural marine sources including sponges, stony corals (hard corals) especially genus scleractinian, as well as sea anemone, in addition to one nudibranch. Aplysinopsins were reported to be isolated from different marine organisms related to various geographic areas such as Pacific, Indonesia, Caribbean, and Mediterranean regions. This review gives an up-to-date overview of marine alkaloid aplysinopsins: their various sources, their synthesis, and the fact that many aplysinopsin derivatives are biologically active compounds. [ABSTRACT FROM AUTHOR]

The ensemble forecast dominates the computational cost of many data assimilation methods, especially for high‐resolution and coupled models. In situations where the cost is prohibitive, one can either use a lower‐cost model or a lower‐cost data assimilation method, or both. Ensemble optimal interpolation (EnOI) is a classical example of a lower‐cost ensemble data assimilation method that replaces the ensemble forecast with a single forecast and then constructs an ensemble about this single forecast by adding perturbations drawn from climatology. This research develops lower‐cost ensemble data assimilation methods that add perturbations to a single forecast, where the perturbations are obtained from analogs of the single model forecast. These analogs can either be found from a catalog of model states, constructed using linear combinations of model states from a catalog, or constructed using generative machine‐learning methods. Four analog ensemble data assimilation methods, including two new ones, are compared with EnOI in the context of a coupled model of intermediate complexity: Q‐GCM. Depending on the method and on the physical variable, analog methods can be up to 40% more accurate than EnOI. [ABSTRACT FROM AUTHOR]

Cyclic dinucleotides (CDNs) are cyclic molecules consisting of two nucleoside monophosphates linked by two phosphodiester bonds, which act as a second messenger and bind to the interferon gene stimulating factor (STING) to activate the downstream signaling pathway and ultimately induce interferon secretion, initiating an anti-infective immune response. Cyclic dinucleotides and their analogs are lead compounds in the immunotherapy of infectious diseases and tumors, as well as immune adjuvants with promising applications. Many agonists of pathogen recognition receptors have been developed as effective adjuvants to optimize vaccine immunogenicity and efficacy. In this work, the binding mechanism of human-derived interferon gene-stimulating protein and its isoforms with cyclic dinucleotides and their analogs was theoretically investigated using computer simulations and combined with experimental results in the hope of providing guidance for the subsequent synthesis of cyclic dinucleotide analogs.

Nosocomial infections represent one of the biggest health problems nowadays. Acinetobacter baumannii is known as an opportunistic pathogen in humans, affecting people with compromised immune systems, and is becoming increasingly important as a hospital-derived infection. It is known that in recent years, more and more bacteria have become multidrug-resistant (MDR) and, for this reason, the development of new drugs is a priority. However, these products must not affect the human body, and therefore, cytotoxicity studies are mandatory. In this context, antimicrobial peptides with potential antibacterial proprieties could be an alternative. In this research, we describe the synthesis and the bioactivity of dermaseptins and their derivatives against Acinetobacter baumannii. The cytotoxicity of these compounds was investigated on the HEp-2 cell line by MTT cell viability assay. Thereafter, we studied the morphological alterations caused by the action of one of the active peptides on the bacterial membrane using atomic force microscopy (AFM). The cytotoxicity of dermaseptins was concentration-dependent at microgram concentrations. It was observed that all tested analogs exhibited antibacterial activity with Minimum Inhibitory Concentrations (MICs) ranging from 3.125 to 12.5 μg/mL and Minimum Bactericidal Concentrations (MBCs) ranging from 6.25 to 25 μg/mL. Microscopic images obtained by AFM revealed morphological changes on the surface of the treated bacteria caused by K4S4(1-16), as well as significant surface alterations. Overall, these findings demonstrate that dermaseptins might constitute new lead structures for the development of potent antibacterial agents against Acinetobacter baumannii infections.

Dan Wang,1– 3 Xiaolong Wang1– 3 1Cardiovascular Research Institute of Traditional Chinese Medicine, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 2Cardiovascular Department of Traditional Chinese Medicine, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 3Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Branch of National Clinical Research Center for Chinese Medicine Cardiology, Shanghai, People’s Republic of ChinaCorrespondence: Xiaolong Wang, Tel +86 13501991450, Fax +86 21 51322445, Email wxlqy0214@163.comAbstract: Atherosclerosis is a chronic inflammatory disease of the artery wall associated with lipid metabolism imbalance and maladaptive immune response, which mediates most cardiovascular events. First-line drugs such as statins and antiplatelet drug aspirin have shown good effects against atherosclerosis but may lead to certain side effects. Thus, the development of new, safer, and less toxic agents for atherosclerosis is urgently needed. Diosgenin and its analogs have gained importance for their efficacy against life-threatening diseases, including cardiovascular, endocrine, nervous system diseases, and cancer. Diosgenin and its analogs are widely found in the rhizomes of Dioscore, Solanum, and other species and share similar chemical structures and pharmacological effects. Recent data suggested diosgenin plays an anti-atherosclerosis role through its anti-inflammatory, antioxidant, plasma cholesterol-lowering, anti-proliferation, and anti-thrombotic effects. However, a review of the effects of diosgenin and its natural structure analogs on AS is still lacking. This review summarizes the effects of diosgenin and its analogs on vascular endothelial dysfunction, vascular smooth muscle cell (VSMC) proliferation, migration and calcification, lipid metabolism, and inflammation, and provides a new overview of its anti-atherosclerosis mechanism. Besides, the structures, sources, safety, pharmacokinetic characteristics, and biological availability are introduced to reveal the limitations and challenges of current studies, hoping to provide a theoretical basis for the clinical application of diosgenin and its analogs and provide a new idea for developing new agents for atherosclerosis.Keywords: atherosclerosis, diosgenin, dioscin, analogs

Volcanic products are widely present on Mercury: they occur as low-viscosity lava flows, but traces of ash deriving from explosive volcanism are also observed. Silicate glasses represent a major component in volcanic products, and it is likely that the fine-powdered regolith on Mercury contains a non-negligible fraction of glassy material. In the laboratory, we have reproduced a Mercury-like silicate glass, from which we have obtained 14 powdered samples with different granulometric characteristics: 8 samples are extremely sorted with grain sizes ranging from 25 to 425 µm, and 6 samples consist of less sorted powders with normal distributions, varying mean values (30, 95, and 160 µm) and standard deviation (40 and 80 µm). The reflectance of samples was investigated in the mid-infrared (MIR) region: we observe how the reflectance intensity increases with grain size, and the presence of extremely fine material defines the emergence of the transparency feature (TF). We provide reference data with qualitative observations and quantitative parameterization of spectral characteristics; in particular, we observe how a small fraction of fine material can greatly influence the spectral response of coarser powders. Results of this work will be crucial for the interpretation of data collected by the BepiColombo mission, but need to be integrated with other possible Mercurian compositions. [ABSTRACT FROM AUTHOR]

The biological activity of natural products YM-254890 (YM) and FR900359 (FR) has led to significant interest in both their synthesis and the construction of more simplified analogs. While the simplified analogs lose much of the potency of the natural products, they are of interest in their own right, and their synthesis has revealed synthetic barriers to the family of molecules that need to be addressed if a scalable synthesis of YM and FR analogs is to be constructed. In the work described here, a synthetic route to simplified analogs of YM is examined and strategies for circumventing some of the challenges inherent to constructing the molecules are forwarded. [ABSTRACT FROM AUTHOR]

• Developed a fast UHPLC-MS/MS method for detecting etomidate and analogs in hair samples. • LOQs for etomidate, etomidate acid, metomidate, propoxate, and isopropoxate range from 5 to 20 pg/mg. • The method was validated and applied to hair samples, identifying 56 positive cases. The regulation of etomidate, a widely used drug for anesthesia induction and short surgical procedures, has led to the emergence of etomidate analogs such as metomidate, propoxate, and isopropoxate. This study introduces and validates a simple, rapid, and cost-effective ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method for the determination and quantification of etomidate, etomidate acid, metomidate, propoxate, and isopropoxate in human hair. Using a five-minute gradient elution on a Phenomenex Kinetex Biphenyl column, the method achieves low limits of quantification (LOQs), ranging from 5 to 20 pg/mg. Method validation confirms robust linear calibration curves for the target substances in hair samples within the range of LOQs to 1000 pg/mg, with average correlation coefficients (r) all exceeding 0.999. The method also achieves acceptable intra-day and inter-day precision (<15 %) and trueness(bias, −10.9 % to 14.4 %). The matrix effect ranges from 46.9 % to 94.2 %, and the extraction recovery rate ranges from 84.5 % to 105 %. When applied to authentic cases, this method successfully identified 56 positive samples. The concentrations of etomidate, etomidate acid, metomidate, propoxate, and isopropoxate in positive samples ranged from 27 to 1.5 × 105 pg/mg, 21 to 1.5 × 103 pg/mg, 18 to 8.7 × 104 pg/mg, 25 to 1.6 × 104 pg/mg, and 22 to 5.0 × 105 pg/mg, respectively. [ABSTRACT FROM AUTHOR]

• An LC-MS/MS assay was developed for the identification of 19 fentanyl analogs in urine. • Additional biomarkers of fentanyl use were qualitatively identified. • Two diastereomers of fentanyl N-oxide were qualitatively identified in human urine. • Both norfentanyl and fentanyl N-oxide had a 9 7% co-positivity with fentanyl. • Fentanyl N-oxides may be underutilized as biomarkers of fentalog use. Novel synthetic opioids are a class of drugs abused for their potent analgesic effect and are responsible for many fatal intoxications, particularly within the United States. A targeted assay was developed and validated using LC-MS/MS, capable of identifying nineteen fentalogs. Solid phase extraction was used to isolate analytes of interest from urine. Limits of detection ranged from 0.05 to 0.1 ng/mL and the limit of quantitation was 0.5 ng/mL. Extraction efficiencies using the optimized procedure were 77–88 % for all targeted species. Bias, precision, matrix effects and interferences were within acceptable thresholds for all analytes. The validated assay was used to identify analytes of interest from thirty-seven individuals that had used fentanyl and related substances. In addition to quantitative analyses, a non-targeted liquid chromatography quadrupole time-of-flight mass spectrometry (LC-Q/TOF-MS) assay was also used to identify additional substances and potential biomarkers. Additional N-oxide and N-dealkylated species were identified using this approach, and the potential for biomarker use is presented, given the stability of some analytes within this class. [ABSTRACT FROM AUTHOR]

The concept of torsion in geometry, although known for a long time, has not gained considerable attention from the physics community until relatively recently, due to its diverse and potentially important applications to a plethora of contexts of physical interest. These range from novel materials, such as graphene and graphene-like materials, to advanced theoretical ideas, such as string theory and supersymmetry/supergravity, and applications thereof in terms of understanding the dark sector of our Universe. This work reviews such applications of torsion at different physical scales.

Fungal infections have become an increasing threat as a result of growing numbers of susceptible hosts and diminishing effectiveness of antifungal drugs due to multi-drug resistance. This reality underscores the need to develop novel drugs with unique mechanisms of action. We recently identified 5-(N,N-hexamethylene)amiloride (HMA), an inhibitor of human Na+/H+ exchanger isoform 1, as a promising scaffold for antifungal drug development. In this work, we carried out susceptibility testing of 45 6-substituted HMA and amiloride analogs against a panel of pathogenic fungi. A series of 6-(2-benzofuran)amiloride and HMA analogs that showed up to a 16-fold increase in activity against Cryptococcus neoformans were identified. Hits from these series showed broad-spectrum activity against both basidiomycete and ascomycete fungal pathogens, including multidrug-resistant clinical isolates.

HIV latency in resting CD4+ T cell represents a key barrier preventing cure of the infection with antiretroviral drugs alone. Latency reversing agents (LRAs) can activate HIV expression in latently infected cells, potentially leading to their elimination through virus-mediated cytopathic effects, host immune responses, and/or therapeutic strategies targeting cells actively expressing virus. We have recently described several structurally simplified analogs of the PKC modulator LRA bryostatin (termed bryologs) designed to improve synthetic accessibility, tolerability in vivo, and efficacy in inducing HIV latency reversal. Here we report the comparative performance of lead bryologs, including their effects in reducing cell surface expression of HIV entry receptors, inducing proinflammatory cytokines, inhibiting short-term HIV replication, and synergizing with histone deacetylase inhibitors to reverse HIV latency. These data provide unique insights into structure-function relationships between A- and B-ring bryolog modifications and activities in primary cells, and suggest that bryologs represent promising leads for preclinical advancement.

Empirical statistical downscaling (ESD) under the perfect prognosis approach was carried out to simulate daily maximum (Tx) and minimum temperatures (Tn) in 101 meteorological stations over the different climatic regions of Argentina. To this end, three ESD families were evaluated: analogs (AN), generalized linear models (GLM) and artificial neural networks (ANN) considering a variety of predictor sets with multiple configurations driven by three different reanalyses (ERA, JRA, NCEP). ESD models were cross‐validated using folds of nonconsecutive years (1979–2014) and then evaluated in a warmer set of years (independent warm period, 2015–2018) to assess their extrapolation capability. Depending on the aspect analysed, AN, GLM or ANN models were more/less skilful, but no method fulfilled all the features of both predicand variables. In this sense, the predictor set and model configuration were key factors. For each ESD method, the different predictor structures (point‐wise, spatial‐wise and combinations of them) introduced the main differences, regardless of the predictand variable, region and reanalysis choice. However, some specific results could be highlighted. ERA (NCEP)‐driven ESD models were the most (least) skilful in representing Tx and Tn. In the case of Tn, models' skills considerably increased when humidity information was included in the predictor set. Our results showed that downscaling models were able to capture the general characteristics of Tx and Tn in all regions, with better performance in the latter variable. However, regions with complex topography (Argentinian Patagonia and the subtropical Andes) pose a further challenge for capturing the local variability of daily extreme temperatures. The performance of the ESD models in the atypical warm conditions was similar to the one during the cross‐validated period, showing some extrapolation skill. The results of this work set a reference for future ESD developments and comparisons in Argentina. [ABSTRACT FROM AUTHOR]

Since the discovery of vitamin D a century ago, a great number of metabolites, analogs, hybrids and nonsteroidal VDR ligands have been developed. An enormous effort has been made to synthesize compounds which present beneficial properties while attaining lower calcium serum levels than calcitriol. This structural review covers VDR ligands published to date. [ABSTRACT FROM AUTHOR]

Background: Potato (Solanum tuberosum L.) is a staple food crop globally, but its production is consistently threatened by diseases and arthropod pests like the potato tuber moth, Phthorimaea operculella Zeller (Lepidoptera: Gelechiidae). Phthorimaea operculella is often controlled by chemical applications. Sex pheromones have been used to detect, monitor, or control agricultural pests. Phthorimaea operculella sex pheromones mainly contain two chemical structures, 4E,7Z-trisadene-1-ol acetate and 4E,7Z,10Z-trisadene-1-ol acetate. However, the pheromone analogs are expected to act as mimics, synergists, antagonists, and inhibitors for pheromones and can be synthesized at a large scale., Result: In this study, a total of 11 sex pheromone analogs of P. operculella were designed and synthesized. Results showed that the antennae exhibited a concentration-dependent response to sex pheromones and their analogs. Different analogs and dosages had significant effects on the electrophysiological response of the antennae. In the field trials, when used alone, A 6 , B 3 and B 5 exhibited significant trapping effects in tobacco and potato fields. When used alternately with sex pheromone components, the analog B 3 had significantly higher trapping effects in both tobacco and potato fields compared to the control, while combinations containing fluorinated analogs showed lower trapping effects., Conclusion: In summary, the use of sex pheromone analogs holds great promise for integration into pest management programs. Further investigation to fine-tune dosage and duration for optimal use is still needed. © 2024 Society of Chemical Industry. Published by John Wiley & Sons Ltd., (© 2024 Society of Chemical Industry. Published by John Wiley & Sons Ltd.)

The synthesis of α-galactosylceramide (KRN7000) and its C-6 modified analogs remains a challenge due to the difficult α-1,2-cis-glycosidic bond. A non-participating benzyl (Bn) protecting group has been commonly used to favor the α-glycosylation product. Here, we report the α-selective glycosylation by using a bulky 4,6-O-di-tert-butylsilylene (DTBS) galactosyl donor, regardless of the 2-benzoyl (Bz) participating group. Compared with Bn, Bz groups can be selectively removed in basic conditions without impacting the C-6 azide modification. The azide has the potential for clicking with alkyne or being easily transformed to other functional groups.

Chikungunya virus (CHIKV) belongs to the Alphavirus genus and is responsible for significant outbreaks worldwide. Currently, there is no approved antiviral therapy against CHIKV. Bioactive peptides have great potential for new drug development. Here, we evaluated the antiviral activity of the synthetic peptide GA-Hecate and its analogs PSSct1905 and PSSct1910 against CHIKV infection. Initial screening showed that all three peptides inhibited the CHIKV replication cycle in baby hamster kidney fibroblast cells (BHK-21) and human hepatocarcinoma epithelial cells (Huh-7). GA-Hecate and its analog PSSct1905 were the most active, demonstrating suppression of viral infection by more than 91%. The analog PSSct1905 exhibited a protective effect in cells against CHIKV infection. We also observed that the analogs PSSct1905 and PSSct1910 affected CHIKV entry into both cell lines, inhibiting viral attachment and internalization. Finally, all tested compounds presented antiviral activity on the post-entry steps of CHIKV infection in all cells evaluated. In conclusion, this study highlights the potential of the peptide GA-Hecate and its analogs as novel anti-CHIKV compounds targeting different stages of the viral replication cycle, warranting the development of GA-Hecate-based compounds with broad antiviral activity.

A comprehensive strategy is required to mitigate risks to astronauts’ health, well-being, and performance. This strategy includes developing countermeasures to prevent or reduce adverse responses to the stressors astronauts encounter during spaceflight, such as weightlessness. Because artificial gravity (AG) by centrifugation simultaneously affects all physiological systems, AG could mitigate the effects of weightlessness in multiple systems. In 2019, NASA and the German Aerospace Center conducted a 60-days Artificial Gravity Bed Rest Study with the European Space Agency (AGBRESA). The objectives of this study were to 1) determine if 30 min of AG daily is protective during head down bed rest, and 2) compare the protective effects of a single daily bout (30 min) of AG versus multiple daily bouts (6 × 5 min) of AG (1 Gz at the center of mass) on physiological functions that are affected by weightlessness and by head-down tilt bed rest. The AGBRESA study involved a comprehensive suite of standard and innovative technologies to characterize changes in a broad spectrum of physiological systems. The current article is intended to provide a detailed overview of the methods used during AGBRESA. [ABSTRACT FROM AUTHOR]

In this review, we collect, for the first time, old and new research results, and present future perspectives on how hadron production, in high-energy scattering processes, can experimentally probe fundamental questions of quantum gravity. The key observations that ignited the link between the two arenas are the so-called "color-event horizon" of quantum chromodynamics, and the (de)accelerations involved in such scattering processes. Both phenomena point to the Unruh (and related Hawking)-type effects. After the first pioneering investigations, such research studies continued, including studies of the horizon entropy and other "black-hole thermodynamical" behaviors, which incidentally are also part of the frontier of the analog gravity research itself. It has been stressed that the trait d'union between the two phenomenologies is that in both hadron physics and black hole physics, "thermal" behaviors are more easily understood, not as due to real thermalization processes (sometimes just impossible, given the small number of particles involved), but rather to a stochastic/quantum entanglement nature of such temperatures. Finally, other aspects, such as the self-critical organizations of hadronic matter and of black holes, have been recently investigated. The results of those investigations are also summarized and commented upon here. As a general remark, this research line shows that we can probe quantum gravity theoretical constructions with analog systems that are not confined to only the condensed matter arena. [ABSTRACT FROM AUTHOR]

Analogs of fundamental physical phenomena can be used in two ways. One way consists in reproducing specific aspects of the classical or quantum gravity of quantum fields in curved space or of other high-energy scenarios on lower-energy corresponding systems. The "reverse way" consists in building fundamental physical theories, for instance, quantum gravity models, inspired by the lower-energy corresponding systems. Here, we present the case of graphene and other Dirac materials. [ABSTRACT FROM AUTHOR]

Neurological disorders remained the leading cause of long-term disability and the second leading cause of death in 2019, hence there is an urgent need for new neuropharmacological agents. P. ophthalmicus is a Philippine medicinal plant with reported antibacterial, antitubercular, and COX- 2 inhibitory activities which have recently been attributed to its alkaloids (+)-tetrandrine and limacusine. It also contains phaeantharine, phaeanthine, oxostephanine, and O-methyldauricine which are alkaloids with a benzylisoquinoline moiety also present in the known neuroactive drugs papaverine, morphine, and tubocurarine. As of this writing, there have been no investigations into the neuropharmacological uses of these alkaloids yet. Therefore, extensive molecular docking studies using Discovery Studio software were conducted. Our findings identified 4MF3 (Kainate 1), 5O8F and 6HUK (GABAA), and 6G79 (Serotonin 1B) as potential neuroreceptor targets, which are involved with pain, migraine, stroke, epilepsy, and anxiety, among other neurological disorders. Furthermore, 50 out of 232 generated analogs of the alkaloids displayed better docking scores, novelty, and predicted drug-likeness. It was observed that the replacement of the methoxy groups attached to the bisbenzylisoquinoline moiety generally resulted in better binding. Lastly, a particular corydaldine analog is considered a very promising oral neuropharmacological agent after displaying consistent top docking scores across all neuroreceptors, drug-likeness, and favorable pK profiles in silico. Therefore, synthesis of such analog and follow-up in vitro-in vivo studies are highly suggested by the researchers. [ABSTRACT FROM AUTHOR]