Class Of Products Research Articles

Integrating bacterial molecular genetics with chemical biology for renewed antibacterial drug discovery.

The application of dyes to understanding the aetiology of infection inspired antimicrobial chemotherapy and the first wave of antibacterial drugs. The second wave of antibacterial drug discovery was driven by rapid discovery of natural products, now making up 69% of current antibacterial drugs. But now with the most prevalent natural products already discovered, ∼107 new soil-dwelling bacterial species must be screened to discover one new class of natural product. Therefore, instead of a third wave of antibacterial drug discovery, there is now a discovery bottleneck. Unlike natural products which are curated by billions of years of microbial antagonism, the vast synthetic chemical space still requires artificial curation through the therapeutics science of antibacterial drugs - a systematic understanding of how small molecules interact with bacterial physiology, effect desired phenotypes, and benefit the host. Bacterial molecular genetics can elucidate pathogen biology relevant to therapeutics development, but it can also be applied directly to understanding mechanisms and liabilities of new chemical agents with new mechanisms of action. Therefore, the next phase of antibacterial drug discovery could be enabled by integrating chemical expertise with systematic dissection of bacterial infection biology. Facing the ambitious endeavour to find new molecules from nature or new-to-nature which cure bacterial infections, the capabilities furnished by modern chemical biology and molecular genetics can be applied to prospecting for chemical modulators of new targets which circumvent prevalent resistance mechanisms.

Bioinformatic prediction of the stereoselectivity of modular polyketide synthase: an update of the sequence motifs in ketoreductase domain.

Polyketides are a major class of natural products, including bioactive medicines such as erythromycin and rapamycin. They are often rich in stereocenters biosynthesized by the ketoreductase (KR) domain within the polyketide synthase (PKS) assembly line. Previous studies have identified conserved motifs in KR sequences that enable the bioinformatic prediction of product stereochemistry. However, the reliability and applicability of these prediction methods have not been thoroughly assessed. In this study, we conducted a comprehensive bioinformatic analysis of 1,762 KR sequences from cis-AT PKSs to reevaluate the residues involved in conferring stereoselectivity. Our findings indicate that the previously identified fingerprint motifs remain valid for KRs in β-modules from actinobacteria, but their reliability diminishes for KRs from other module types or taxonomic origins. Additionally, we have identified several new motifs that exhibit a strong correlation with the stereochemical outcomes of KRs. These updated fingerprint motifs for stereochemical prediction not only enhance our understanding of the enzymatic mechanisms governing stereocontrol but also facilitate accurate stereochemical prediction and genome mining of polyketides derived from modular cis-AT PKSs.

Heme-catalyzed degradation of linoleate 9-hydroperoxide (9-HPODE) forms two allylic epoxy-ketones via a proposed pseudo-symmetrical diepoxy radical intermediate

Heme-initiated decomposition of unsaturated fatty acid hydroperoxides creates alkoxyl radicals that propagate a complex series of reactions to hydroxy, keto, epoxy and aldehydic products. Herein, among the products from the hematin-catalyzed degradation of 9-hydroperoxy-linoleic acid (9-HPODE), we observed a double peak on normal-phase HPLC that resolved on RP-HPLC into equal proportions of two epoxy-allylic ketones with identical UV spectra. Their proton NMR spectra were also indistinguishable and consistent with 9,10-trans-epoxy-11E-13-keto- and 9-keto-10E-12,13-trans-epoxy-octadecenoic acids. Acid hydrolysis to the corresponding dihydroxy-ketones and GC-MS analysis identified the earlier eluting product on RP-HPLC as the 9,10-epoxy regio-isomer. Starting from the C9-hydroperoxide, recovery of the two epoxy-ketones in equal proportions suggests their formation from a common intermediate. Earlier work has proposed formation of a pseudo-symmetrical diepoxy radical (9,10-epoxy-11(•)-12,13-epoxy, derived from an epoxy allylic hydroperoxide precursor) in the carbon chain fragmentation leading to aldehydic products. This intermediate in pathways of alkoxyl radical reactions forms equal pairs of aldehydes, and now also a pair of epoxy-ketones, and based on mechanism the same products arise from either 9-HPODE or 13-HPODE. Our results point to the intermediacy of this diepoxy-carbinyl radical in the origin of at least two classes of linoleate peroxidation products, and it should be considered as a viable intermediate for homo-conjugated diene peroxidation in general. The reactions could contribute to the aldehydes and epoxy-ketones in tissues undergoing oxidative transformations of polyunsaturated fatty acids.

Mutagenic Azido Impurities in Drug Substances: A Perspective.

Contamination of drug products and substances containing impurities is a significant concern in the pharmaceutical industry because it may impact the quality and safety of medicinal products. Special attention is required when mutagenic impurities are present in pharmaceuticals, as they may pose a risk of carcinogenicity to humans. Therefore, controlling potential mutagenic impurities in active pharmaceutical ingredients to an acceptable safety limit is mandatory to ensure patient safety. As per the International Council for Harmonization (ICH) M7 (R2)3 Guideline, mutagenic impurities are those compounds or materials that induce point mutations. In 2018, the sartan class of drugs was recalled due to the presence of N-nitrosamine impurities, which are potential mutagens. In addition to the primary impurities being detected, this class of products, especially losartan, irbesartan and valsartan, have been identified as having organic azido contaminants, which are again highly reactive toward DNA, leading to an increased risk of cancer. These azido impurities form during the preparation of the tetrazole moiety via the reaction of a nitrile intermediate with sodium azide. Given that this is a newly raised issue in the pharmaceutical world, it should be noteworthy to review the related literature. Thus, this review article critically accounts for (i) the toxicity of azido impurities and the proposed mechanism of mutagenicity, (ii) the regulatory perspective, and (iii) the sources and control strategies used during the preparation of drug substances and (iv) future perspectives.

Incremental-based YoloV3 model with hyper-parameter optimization for product image classification in E-commerce sector

Over the past few years, the E-commerce industry has grown tremendously for selling products to consumers. Here, the consumer can easily purchase the products from their residing seats and gets the products at the door step. Also, the image quality is suggested and also the image classification is intruded to meet the consumer prerequisite. Most of the image classification models are developed by machine learning approaches to improve the reliability, scalability, and accuracy level. Due to the heterogeneous nature of images, it restricts the features and lengthy dimensions for datasets which it degrades the performance whereas the classification of products becomes a cumbersome situation. In order to resolve the problem raised by existing methods, a novel product image classification model is proposed for the fashion E-commerce sector. The prime aspect of the proposed model is to build an effective E-commerce sector for a layman, where every individual can purchase the products appropriately. Initially, the dataset is constructed with diverse product images that are obtained from different E-commerce fields with various classes. Consequently, a novel Incremental-based Improved YoloV3 with Hyper-parameter Optimization (II-Yolov3-HO) model is introduced to enhance the classification performance. In the proposed model, some of the hyper parameters like convolution and pooling layers are replaced with the Visual Geometry Group16 (VGG16) model, the remaining convolutional layers are enhanced by the atrous convolution operation, and pooling layers are modified with Atrous Spatial Pyramid Pooling (ASPP). In entire architecture, the weight factor is optimized using Predator-based Squirrel Search Algorithm (PDP-SSA) algorithm. Thus, the new E-commerce sector becomes free to categorize the products, and if it deals with a new product, it is declared as unknown data, which is then trained again in the proposed model. Hence, the concept of classification score matching with the threshold value is accomplished to deal the untrained product and the training weight is updated optimally using the proposed PDP-SSA. Finally, the enhanced model is compared over the state-of-the-art classification, provides the expected result for significantly classifying the multiple classes of products. The developed PDP-SSA-II-YoloV3-HO model is also able to perform recommendations in E-commerce sites even when the input is given as images other than text for searching the items. These uploaded images are analyzed in the developed II-Yolov3-HO model for providing the relevant items to the customer based on their features. The developed PDP-SSA-II-YoloV3-HO model achieves 99.46 % regarding accuracy. Throughout the validation, the developed model outperforms enhanced and reliable performance than the existing approaches.

Engineered skin microbiome reduces mosquito attraction to mice.

The skin microbiome plays a pivotal role in the production of attractive cues detected by mosquitoes. Here, we leveraged recent advances in genetic engineering to significantly reduce the production of L-(+)-lactic acid as a strategy to reduce mosquito attraction to the highly prominent skin commensals Staphylococcus epidermidis and Corynebacterium amycolatum. Engraftment of these engineered bacteria onto the skin of mice reduced mosquito attraction and feeding for up to 11 uninterrupted days, which is considerably longer than the several hours of protection conferred by the leading chemical repellent N,N-diethyl-meta-toluamide. Taken together, our findings demonstrate engineering the skin microbiome to reduce attractive volatiles represents an innovative untapped strategy to reduce vector attraction, preventing bites, and pathogen transmission. These findings set the stage for new classes of long-lasting microbiome-based repellent products.

Total Synthesis and Antibacterial Activity of Marine Tris-indole Alkaloid Tulongicin A.

Bis-indole alkaloids from marine sponges are an intriguing class of natural products with a variety of activities. However, only a preliminary biological study of tulongicin A (5), a related previously isolated marine tris-indole alkaloid, has been conducted. In this study, we accomplished the first asymmetric total synthesis of 5 via the construction of an imidazoline-linked bis-indolylmethane skeleton using a Friedel-Crafts-type reaction. Our synthesis enabled a detailed study of the antibacterial profile of 5. Compound 5 displayed bactericidal activity against Staphylococcus aureus, including methicillin-resistant S. aureus (MRSA) strains.

Prevention method preferences and factors influencing hypothetical choice among women in South Africa: a survey exploring opportunities for a multipurpose prevention technology implant.

South African women bear an intersecting burden of HIV, sexually transmitted infections (STIs) and unintended pregnancy. Multipurpose prevention technologies (MPTs) are a class of products that address multiple needs and have the potential to improve uptake and use of prevention products. Analysing survey data from 703 HIV-negative women 18-40 years in three provinces in South Africa, collected between July and November 2022, this study explores their preferences for prevention methods and factors influencing choice of hypothetical prevention methods, including MPTs. Descriptive statistics and multinomial regression analyses were conducted to determine prevention method preferences and factors associated with choosing a pill, injectable or MPT-implant type prevention method. Most women wanted to prevent HIV, STIs and pregnancy. The most important factors when choosing a prevention product were whether it provided dual and long-term protection and if side effects were manageable. If choosing only one method, half of women would choose any MPT-implant and a quarter each would choose a pill or an injectable method, with method choices differing by population group. Prevention method choices were influenced by sexual-behavioural factors and current and prior contraceptive method use. Providing a choice of prevention methods and a population specific approach to new method development and introduction with access to accurate information could enhance their ability to fill a gap in prevention needs.

Discovering type I cis-AT polyketides through computational mass spectrometry and genome mining with Seq2PKS

Type 1 polyketides are a major class of natural products used as antiviral, antibiotic, antifungal, antiparasitic, immunosuppressive, and antitumor drugs. Analysis of public microbial genomes leads to the discovery of over sixty thousand type 1 polyketide gene clusters. However, the molecular products of only about a hundred of these clusters are characterized, leaving most metabolites unknown. Characterizing polyketides relies on bioactivity-guided purification, which is expensive and time-consuming. To address this, we present Seq2PKS, a machine learning algorithm that predicts chemical structures derived from Type 1 polyketide synthases. Seq2PKS predicts numerous putative structures for each gene cluster to enhance accuracy. The correct structure is identified using a variable mass spectral database search. Benchmarks show that Seq2PKS outperforms existing methods. Applying Seq2PKS to Actinobacteria datasets, we discover biosynthetic gene clusters for monazomycin, oasomycin A, and 2-aminobenzamide-actiphenol.

Recent advances in lycopene and germacrene a biosynthesis and their role as antineoplastic drugs.

Sesquiterpenes and tetraterpenes are classes of plant-derived natural products with antineoplastic effects. While plant extraction of the sesquiterpene, germacrene A, and the tetraterpene, lycopene suffers supply chain deficits and poor yields, chemical synthesis has difficulties in separating stereoisomers. This review highlights cutting-edge developments in producing germacrene A and lycopene from microbial cell factories. We then summarize the antineoplastic properties of β-elemene (a thermal product from germacrene A), sesquiterpene lactones (metabolic products from germacrene A), and lycopene. We also elaborate on strategies to optimize microbial-based germacrene A and lycopene production.

A Gap Condition for the Zeros and Singularities of a Certain Class of Products

We carry out complete membership to Kaplan classes of functions given by formula {ζ∈C:|ζ|<1}∋z↦∏k=1n(1-ze-itk)pk,\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\begin{aligned} \\{\\zeta \\in {\\mathbb {C}}:|\\zeta |<1\\}\ i z\\mapsto \\prod \\limits _{k=1}^n (1-z\ extrm{e}^{-\ extrm{i}t_k})^{p_k}, \\end{aligned}$$\\end{document}where n∈N\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$n\\in \\mathbb N$$\\end{document}, tk∈[0;2π)\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$t_k\\in [0;2\\pi )$$\\end{document} and pk∈R\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$p_k\\in \\mathbb R$$\\end{document} for k∈N∩[1;n]\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$k\\in \\mathbb N\\cap [1;n]$$\\end{document}. In this way we extend Sheil-Small’s, Jahangiri’s and our previous results. Moreover, physical and geometric applications of the obtained gap condition are given. The first one is an interpretation in terms of mass and density. The second one is a visualization in terms of angular inequalities between vectors in R2\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\mathbb {R}^2$$\\end{document}.

Discovery and Biosynthesis of Streptolateritic Acids A-D: Acyclic Pentacarboxylic Acids from Streptomyces sp. FXJ1.172 with Promising Activity against Potato Common Scab.

Potato common scab (PCS) is a widespread plant disease that lacks effective control measures. Using a small molecule elicitor, we activate the production of a novel class of polyketide antibiotics, streptolateritic acids A-D, in Streptomyces sp. FXJ1.172. These compounds show a promising control efficacy against PCS and an unusual acyclic pentacarboxylic acid structure. A gene cluster encoding a type I modular polyketide synthase is identified to be responsible for the biosynthesis of these metabolites. A cytochrome P450 (CYP) and an aldehyde dehydrogenase (ADH) encoded by two genes in the cluster are proposed to catalyze iterative oxidation of the starter-unit-derived methyl group and three of six branching methyl groups to carboxylic acids during chain assembly. Our findings highlight how activation of silent biosynthetic gene clusters can be employed to discover completely new natural product classes able to combat PCS and new types of modular polyketide synthase-based biosynthetic machinery.

The Potential Impact of Oral Nicotine Pouches on Public Health: A Scoping Review.

Oral nicotine pouches (ONPs) are a new class of nicotine products. This scoping review summarizes evidence on ONPs and explores their potential public health impact. We conducted a structured literature search for empirical studies across three electronic databases through January 10, 2024. Outcomes included ONP product characteristics, use patterns, beliefs and perceptions, toxicity, and marketing and sales. Sixty-two studies were included, 17 were industry-funded. Most studies were from the United States. While large variations across studies were observed in ONP youth prevalence estimates, nationally representative U.S. studies find current use at 1.5% and lifetime use below 2.5% through 2023. Between 35% and 42% of U.S. adolescents and young adults have heard of ONPs, and 9-21% of tobacco-naïve youth were susceptible to trying them. U.S. adult-use estimates varied widely (0.8%-3% current; 3%-16% lifetime use) and were limited to populations with a history of tobacco use. The chemical composition of ONPs suggests fewer harmful/potentially harmful compounds at lower levels than cigarettes and smokeless tobacco (SLT), except formaldehyde. Industry-funded studies find substantially less cytotoxicity compared to cigarettes and suggest that higher nicotine-strength ONPs can deliver nicotine at levels comparable to or higher than SLT or cigarettes, although with slower nicotine release than cigarettes. Evidence on the cytotoxicity of ONPs relative to SLT is mixed. ONPs appear to be less toxic than cigarettes and deliver comparable nicotine, presenting an alternative for combustible product users, although key data are mainly available from industry-funded studies. Data from independent research is critically needed. Industry marketing of ONPs may encourage initiation in youth and situational and dual use in adults. The review provides an initial assessment of the potential role of ONPs in harm reduction and aims to determine unintended consequences of their use (youth uptake and dual-use) and identify populations that disproportionately use the product. This information is essential for tobacco regulatory bodies in determining the net public health impact of nicotine pouches.

Biochemical Characterization of a Marine Pseudoalteromonas citrea-Derived Fatty Acyl-AMP Ligase That Exhibits N-Acyl Amino Acid Synthetic Activity.

Activation of fatty acids as acyl-adenylates by fatty acid-AMP ligase (FAAL) is a well-established process contributing to the formation of various functional natural products. Enzymatic characterization of FAALs is pivotal for unraveling both the catalytic mechanism and its role in specific biosynthetic pathways. In this study, we recombinantly expressed and characterized a novel FAAL derived from marine Pseudoalteromonas citrea (PcFAAL). PcFAAL was a cold-adapted neutral enzyme, demonstrating optimal activity at 30°C and pH 7.5. Notably, its specific activity relied on the presence of Mg2+; however, higher concentrations exceeding 10mM resulted in inhibition of enzyme activity. Various organic solvents, especially water-immiscible organic solvents, demonstrated an activating effect on the activity of PcFAAL on various fatty acids. The specific activity exhibited a remarkable 50-fold increase under 4% (v/v) n-hexane compared to the aqueous system. PcFAAL displayed a broad spectrum of fatty acid substrate selectivity, with the highest specific activity for octanoic acid (C8:0), and the catalytic efficiency (kcat/Km) for octanoic acid was determined to be 1.8nM-1·min-1. Furthermore, the enzyme demonstrated biocatalytic promiscuity in producing a class of N-acyl amino acid natural products, as verified by LC-ESI MS. Results indicated that the PcFAAL exhibits promiscuity towards 10 different kinds of amino acids and further demonstrated their potential value in the biosynthesis of corresponding functional N-acyl amino acids.

Cytotoxic Pentaketide-Sesquiterpenes from the Marine-Derived Fungus Talaromyces variabilis M22734.

Talaromyces, a filamentous fungus widely distributed across terrestrial and marine environments, can produce a diverse array of natural products, including alkaloids, polyketones, and polyketide-terpenoids. Among these, chrodrimanins represented a typical class of natural products. In this study, we isolated three previously undescribed pentaketide-sesquiterpenes, 8,9-epi-chrodrimanins (1-3), along with eight known compounds (4-11). The structures of compounds 1-3 were elucidated using nuclear magnetic resonance (NMR) and mass spectrometry (MS), while their absolute configurations were determined through X-ray crystallography and electronic circular dichroism (ECD) computations. The biosynthetic pathways of compounds 1-3 initiate with 6-hydroxymellein and involve multiple stages of isoprenylation, cyclization, oxidation, and acetylation. We selected four strains of gastrointestinal cancer cells for activity evaluation. We found that compound 3 selectively inhibited MKN-45, whereas compounds 1 and 2 exhibited no significant inhibitory activity against the four cell lines. These findings suggested that 8,9-epi-chrodrimanins could serve as scaffold compounds for further structural modifications, potentially leading to the development of targeted therapies for gastric cancer.

Global outlook on affordability of biotherapeutic drugs.

Although biotherapeutic drugs have the potential of transforming the management of many life-threatening diseases, their affordability and accessibility remain an issue. This study offers an overview of the global affordability of biotherapeutic products. For this, prices for 10 representative biotherapeutic products were examined in 40 countries, including high-income countries (HICs), upper middle-income countries (UMICs), lower middle-income countries (LMICs), and low-income countries (LICs). The affordability of these biotherapeutics was calculated based on the World Health Organization/Health Action International (WHO/HAI) method. As expected, affordability was found to be better in HICs, followed by UMICs, LMICs, and finally, LICs. Furthermore, based on the trend of per capita income, we predict that in UMICs and LMICs, the affordability of high molecular weight biologics will worsen by 1.5× and 2× by 2030, respectively, and further by 4× and 6× by 2040. On the other hand, affordability will stay nearly the same for people living in HICs in the coming decades. Our analysis suggests that it is imperative that measures be taken to make this class of products more affordable and accessible. Governments can contribute by creating conducive policies. Global institutions like the WHO can play a significant role as well. Finally, manufacturers need to invest in and implement manufacturing innovations.

Incorporating new variables into a model of brand extension in fast fashion

This study tests a brand extension in fast fashion to explore the extension’s effect on the parent brand. It investigates whether extensions to varyingly distant product classes modify customers’ attitudes toward the parent brand. University students from the Technical University of Liberec, the Faculty of Economics (Czech Republic), aged 22-25 years, participated in an online survey for this study. The number of respondents was 310. The outcomes are relevant for this segment of customers. The model with classic brand extension factors (perceived fit (FIT), attitudes toward the brand extension (ATE), parent brand attitude change (PBCH)) was constructed. Factors of fashion leaders and emotional variables (e.g., trust and loyalty) were added to the model. The model was tested using structural equation modeling (SEM) in AMOS software and was statistically significant (Chi-squared value of 6.402, p = 0.171). A positive relationship was observed between FIT and ATE (β = 0.534, p-value = 0.000), the same as trust and ATE (β = 0.693, p-value = 0.000). Equally, ATE had a significant positive impact on PBCH (β = 0.722, p-value = 0.000) and trust and loyalty (β = 0.649, p-value = 0.000). Loyalty negatively affects ATE (β = -0.126, p-value = 0.010), indicating that these customers may have problems with brand extension, similar to a fashion leader (β = -0.126, p-value = 0.010). TRUST has a negative effect on the PBCH (β = -0.338, p-value = 0.000). Insights derived from this study hold substantial relevance for marketers in fast fashion aiming to prepare brand extensions effectively. AcknowledgmentThis work is supported by the Technical University of Liberec, Faculty of Economics – internal grant.

Mind the gap: National brands’ sensitivity to price and line-length differentials at hard discounters versus conventional retailers

Hard discounters are increasingly selling national brands that previously were only sold through conventional retailers. While this trend is gaining traction across various product categories and countries, the marketing literature has provided scant empirical evidence on the market-response effects of these brands at hard discounters, while conceptual perspectives remain conflicting.Using an empirics-first approach, the authors address this gap by offering a rich set of First Insights into the price and line-length elasticities of national brands at hard discounters, compared to conventional retailers. They analyze data from over 1,200 national-brand listings across eight European hard discounters and 84 product categories in six countries. They examine two primary differentials: the national brands’ price and line length relative to private labels within the same format (within-store gaps) and compared to their own offering in the other format (between-store gaps).Similar to conventional retailers, price adjustments at hard discounters have a much more pronounced impact on national-brand sales than changes in line length. However, other findings at hard discounters diverge markedly from those commonly observed at conventional retailers. At hard discounters, consumers exhibit similar responsiveness to changes in both within-store and between-store gaps, unlike in conventional retail settings where within-store reference points are typically more influential than their between-store counterparts. While national brands’ responsiveness to within-store gaps is roughly the same at hard discounters and conventional retailers, their responsiveness to between-store gaps is more than twice as pronounced at hard discounters. While these findings are consistent across four product classes, they show less stability across the six countries, highlighting the need for future research to explore country-specific boundary conditions.

Natural Products with Potential Effects on Hemorrhoids: A Review.

Hemorrhoid disease is a common anorectal disorder affecting populations worldwide, with high prevalence, treatment difficulties, and considerable treatment costs. Compared to other treatment options, medical therapy for hemorrhoids offers minimal harm, more dignity to patients, and is more economical. Unfortunately, there are few chemical hemorrhoid medications available clinically, which makes the search for efficacious, cost-effective, and environmentally friendly new medication classes a focal point of research. In this context, searching for available natural products to improve hemorrhoids exhibits tremendous potential. These products are derived from nature, predominantly from plants, with a minor portion coming from animals, fungi, and algae. They have excellent coagulation pathway regulation, anti-inflammatory, antibacterial, and tissue regeneration activities. Therefore, we take the view that they are a class of potential hemorrhoid drugs, prevention products, and medication add-on ingredients. This article first reviews the factors contributing to the development of hemorrhoids, types, primary symptoms, and the mechanisms of natural products for hemorrhoids. Building on this foundation, we screened natural products with potential hemorrhoid improvement activity, including polyphenols and flavonoids, terpenes, polysaccharides, and other types.

Copper-Initiated Regiodivergent Chloropentafluorosulfanylation of 1,3-Enynes under Substrate Control.

A copper-catalyzed regiodivergent chloropentafluorosulfanylation strategy for 1,3-enynes using SF5Cl has been developed. The regioselectivity is dictated by the structural and substitution patterns of 1,3-enynes, enabling facile access to three classes of SF5-containing products: propargylic chlorides, 1,3-dienes, and allenes. The reaction systems involve radical species, where the transfer of a chlorine atom from SF5Cl to a carbon radical is considered the predominant pathway. Diverse types of SF5- building blocks can be synthesized through simple functional group transformations.