Biofilm-associated infections remain a tremendous obstacle to the treatment of microbial infections globally. However, the poor penetrability to a dense extracellular polymeric substance matrix of traditional antibacterial agents limits their antibiofilm activity. Here, we show that nanoaggregates formed by self-assembly of amphiphilic borneol-guanidine-based cationic polymers (BGNx-n) possess strong antibacterial activity and can eliminate mature Staphylococcus aureus (S. aureus) biofilms. The introduction of the guanidine moiety improves the hydrophilicity and membrane penetrability of BGNx-n. The self-assembled nanoaggregates with highly localized positive charges are expected to enhance their interaction with negatively charged bacteria and biofilms. Furthermore, nanoaggregates dissociate on the surface of biofilms into smaller BGNx-n polymers, which enhances their ability to penetrate biofilms. BGNx-n nanoaggregates that exhibit superior antibacterial activity have the minimum inhibitory concentration (MIC) of 62.5 μg·mL-1 against S. aureus and eradicate mature biofilms at 4 × MIC with negligible hemolysis. Taken together, this size-variable self-assembly system offers a promising strategy for the development of effective antibiofilm agents.

Vanadium-dependent haloperoxidases (VHPOs) are a unique family of enzymes that utilize vanadate, an aqueous halide ion, and hydrogen peroxide to produce an electrophilic halogen species that can be incorporated into electron rich organic substrates. This halogen species can react with terpene substrates and trigger halonium-induced cyclization in a manner reminiscent of class II terpene synthases. While not all VHPOs act in this capacity, several notable examples from algal and actinobacterial species have been characterized to catalyze regio- and enantioselective reactions on terpene and meroterpenoid substrates, resulting in complex halogenated cyclic terpenes through the action of single enzyme. In this article, we describe the expression, purification, and chemical assays of NapH4, a difficult to express characterized VHPO that catalyzes the chloronium-induced cyclization of its meroterpenoid substrate.

Terpenes comprise the largest class of natural products and are used in applications spanning the areas of medicine, cosmetics, fuels, flavorings, and more. Copalyl diphosphate synthase from the Penicillium genus is the first bifunctional terpene synthase identified to have both prenyltransferase and class II cyclase activities within the same polypeptide chain. Prior studies of bifunctional terpene synthases reveal that these systems achieve greater catalytic efficiency by channeling geranylgeranyl diphosphate between the prenyltransferase and cyclase domains. A molecular-level understanding of substrate transit phenomena in these systems is highly desirable, but a long disordered polypeptide segment connecting the prenyltranferase and cyclase domains thwarts the crystallization of full-length enzymes. Accordingly, these systems are excellent candidates for structural analysis using cryo-electron microscopy (cryo-EM). Notably, these systems form hexameric or octameric oligomers, so the quaternary structure of the full-length enzyme may influence substrate transit between catalytic domains. Here, we describe methods for the preparation of bifunctional hexameric copalyl diphosphate synthase from Penicillium fellutanum (PfCPS). We also outline approaches for the preparation of cryo-EM grids, data collection, and data processing to yield two-dimensional and three-dimensional reconstructions.

Increasing evidence shows that microbial synthesis plays an important role in producing high value-added products. However, microbial monoculture generally hampers metabolites production and limits scalability due to the increased metabolic burden on the host strain. In contrast, co-culture is a more flexible approach to improve the environmental adaptability and reduce the overall metabolic burden. The well-defined co-culturing microbial consortia can tap their metabolic potential to obtain yet-to-be discovered and pre-existing metabolites. This review focuses on the use of a co-culture strategy and its underlying mechanisms to enhance the production of products. Notably, the significance of comprehending the microbial interactions, diverse communication modes, genetic information, and modular co-culture involved in co-culture systems were highlighted. Furthermore, it addresses the current challenges and outlines potential future directions for microbial co-culture. This review provides better understanding the diversity and complexity of the interesting interaction and communication to advance the development of co-culture techniques.

Aromatic amino acids (AAA) and derived compounds have enormous commercial value with extensive applications in the food, chemical and pharmaceutical fields. Microbial production of AAA and derived compounds is a promising prospect for its environmental friendliness and sustainability. However, low yield and production efficiency remain major challenges for realizing industrial production. With the advancement of synthetic biology, microbial production of AAA and derived compounds has been significantly facilitated. In this review, a comprehensive overview on the current progresses, challenges and corresponding solutions for AAA and derived compounds biosynthesis is provided. The most cutting-edge developments of synthetic biology technology in AAA and derived compounds biosynthesis, including CRISPR-based system, genetically encoded biosensors and synthetic genetic circuits, were highlighted. Finally, future prospects of modern strategies conducive to the biosynthesis of AAA and derived compounds are discussed. This review offers guidance on constructing microbial cell factory for aromatic compound using synthetic biology technology.

Rheumatoid arthritis (RA) is an immune-mediated disease that necessitates a thorough understanding of its intricate pathophysiological mechanism for precise and effective therapeutic targeting. The European League Against Rheumatism (EULAR) has established guidelines for RA treatment, endorsing monotherapy or combination therapy with corticosteroids and synthetic disease-modifying antirheumatic drugs (sDMARDs). This review delves into clinical trials and research outcomes related to combination drug delivery, with an emphasis on the role of natural products in combination with synthetic drugs. Given the significant adverse effects associated with systemic administration, topical delivery has emerged as an alternative avenue for effective management of RA.

More than 20 million people worldwide have Alzheimer\'s disease (AD), making it the most prevalent disease. Patients with AD may live for at least a decade after diagnosis, making it the most common cause of disability in the elderly. Each year, 1% to 4% of the population is affected by AD, with prevalence peaking between ages 65 and 70 and declining to 6% among those over 85. Researchers have accumulated evidence on medicinal herbs that may reverse the pathogenesis of Alzheimer\'s disease. Alzheimer\'s disease (AD) is associated with severe memory loss, which can negatively impact social and professional life. The first neurotransmitter linked to Alzheimer\'s was acetylcholine (ACh). There is no known cure, and the available treatments are ineffective. Multiple studies indicate that Ayurvedic restorative herbs and their constituents may be effective in treating Alzheimer\'s disease. This technique emphasizes the fact that delaying or preventing Alzheimer\'s disease with the help of natural bio-actives could reduce the number of cases over the next half-century. To provide detailed information, the pathology and pathophysiology of Alzheimer\'s Disease are discussed in the text of this review, along with an overview of the neurotransmitters involved in the progression of the disease. The importance of different natural bioactives for the treatment of Alzheimer\'s disease is also outlined in the paper. The information contained in this paper can serve as a template for future research expressing the more beneficial role of other bioactive in acting as an adjuvant in the prevention and treatment of this disease, facing certain challenges and gaps with conventional drugs used to treat Alzheimer\'s disease.

BACKGROUND: Prevention and management of nipple problems are crucial during the postpartum period for effective breastfeeding. Breastmilk is the most commonly recommended method for lactating women. However, insufficient studies have proven its superiority over other methods in the current literature. This study aims to determine the effects of natural products compared to breast milk in preventing and treating nipple trauma and pain in lactating women.
METHODS: In this review, we investigated studies from PubMed, Web of Science, Cochrane Library, MEDLINE, CINAHL, Scopus, and Google Scholar databases that met the inclusion criteria. We also assessed the studies\' methodological quality with the Cochrane and JBI checklists. This study was performed based on the Guidelines of Systematic Reporting of Examination presented in the PRISMA checklist. The search protocol has been registered at the PROSPERO International Prospective Register of Systematic Reviews.
RESULTS: A total of ten published studies, including 1139 lactating women, were included in this review. The meta-analysis results showed a significant effect of natural product intervention on nipple trauma (Hedge\'s g -0.702, Q = 81,154, I2 =91,374 %, p < 0.001), soreness (Hedge\'s g =-0.648, Q = 7,092, I2 =71,801 %, p < 0.001), and pain levels (Hedge\'s g =-0.613, Q = 25,058, I2 =76,056 %, p < 0.001) experienced by lactating women.
CONCLUSIONS: The findings showed that natural products have greater potential than breast milk in managing nipple pain, trauma, and soreness. However, the evidence for these interventions is low or very low quality. Further research is needed to determine the most effective treatment for nipple trauma in lactating women.

OBJECTIVE: Dermal papilla (DP) stem cells are known for their remarkable regenerative capacity, making them a valuable model for assessing the effects of natural products on cellular processes, including stemness, and autophagy.
METHODS: Autophagy and stemness characteristics were assessed using real-time RT-PCR to analyze mRNA levels, along with immunofluorescence and western blot techniques for protein level evaluation.
RESULTS: Butterfly Pea, Emblica Fruits, Kaffir Lime, and Thunbergia Laurifolia extracts induced autophagy in DP cells. Kaffir Lime-treated cells exhibited increase in the OCT4, NANOG, and SOX2 mRNA (6-, 5, and 5.5-fold, respectively), and protein levels (4-, 3-, and 1.5-fold, respectively). All extracts activated the survival protein kinase B (Akt) in DP cells.
CONCLUSIONS: Natural products are a promising source for promoting hair growth by rejuvenating hair stem cells.

A challenge remains in the development of anti-infectious coatings for the inert surfaces of biomedical devices that are prone to bacterial colonization and biofilm formation. Here, we developed a facile photocuring method to construct functionalized polymeric coatings on inert PDMS surfaces. Using ATRP initiator bearing thymol group, hydrophilic DMAEMA and benzophenone-containing monomers were copolymerized to form polymers with end functional groups. An end-functionalized biocidal coating was then constructed on the inert PDMS surface in one step using a photocuring reaction. The functionalized PDMS surfaces show excellent antibacterial and antifouling properties, are capable of completely eradiating MRSA within approximately 6 hours, and effectively inhibit the growth of biofilms. In addition, it has good stability and long-lasting antibacterial activity in body fluid environments such as 0.9% saline and urine. According to bladder model experiments, the catheter\'s lifespan can be extended from approximately 7 to 35 days by inhibiting the growth and migration of bacteria along its inner surface. The photocuring technique is therefore very promising in terms of surface functionalization of inert biomedical devices in order to minimize the spread of infection. This article is protected by copyright. All rights reserved.