Search

The photo-oxidation of amyloid-β (Aβ) protein catalyzed by Aβ-targeting photosensitizers shows high potential in treating Alzheimer's disease (AD). Herein, we report the first example of photosensitizers based on the rofecoxib scaffold, in which rational introduction of the electron-absorbing pyridinium/quinolinium moiety to the skeleton of rofecoxib could not only extend the absorption and emission wavelengths but also increase the efficiency of singlet oxygen ( 1 O 2 ) production. The emission wavelengths of R-S-MP , R-S-MC , and R-S-MQ are red-shifted to 860 nm, which might benefit the NIR imaging of Aβ aggregates with low photoscattering and autofluorescence. In addition, R-S-MP can identify Aβ plaques in brain sections of AD mice and detect abnormal viscosity environments, facilitating the pathological study of Alzheimer's disease. Most importantly, upon complexation with Aβ plaques, R-S-MP and R-S-MC could produce high singlet oxygen ( 1 O 2 ) under light irradiation, which can achieve the specific photo-oxidation of Aβ protein. Our optimized photosensitizers could change the conformation of β-rich Aβ protein and enhance its clearance through the lysosomal pathway, leading to the reduction of the Aβ-mediated neurotoxicity. All these excellent characteristics of our dual-functional photosensitizers for simultaneous imaging and photo-oxidation of Aβ aggregates suggest their promising prospects in pathological research in AD.

The paper reports new multifunctional plant biostimulant formulations obtained via in situ hydrogelation of chitosan with salicylaldehyde in the presence of a mimetic naphthalimide-based strigolactone, in specific conditions. Various analytical techniques (FTIR, 1 H NMR, SEM, POM, TGA, WRXD) were employed to understand the particularities of the hydrogelation mechanism and its consequences on the formulations' properties. Further, in order to evaluate their potential for the targeted application, the swelling in media of pH characteristic for different soils, water holding capacity, soil biodegradability, in vitro release of the strigolactone mimic and impact on tomatoes plant growth in laboratory conditions were investigated and discussed. It was found that the strigolactone mimic has the ability to bond to the chitosan matrix via physical forces, favoring a prolonged release. Moreover, the combination of chitosan with the strigolactone mimic in an optimal mass ratio triggered a synergistic effect on the plant growth, up to 4 times higher compared to the neat control soil., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

We synthesize four series of novel biodegradable poly(alkylene succinate- ran -caprolactone) random copolyesters using a two-step ring-opening/transesterification and polycondensation process with ε-caprolactone (PCL) as a common comonomer. The second comonomers are succinic acid derivatives, with variations in the number of methylene groups ( n CH2 ) in the glycol segment, n CH2 = 2, 4, 8, and 12. The obtained copolyesters were poly(ethylene succinate- ran -PCL) (ES x CL y ), poly(butylene succinate- ran -PCL) (BS x CL y ), poly(octamethylene succinate- ran -PCL) (OS x CL y ), and poly(dodecylene succinate- ran -PCL) (DS x CL y ). We discovered a new mixed isodimorphic/comonomer exclusion crystallization in ES x CL y copolymers. The BS x CL y , OS x CL y , and DS x CL y copolymers display isodimorphic behavior. Our findings revealed a significant variation in the pseudoeutectic point position, from mixed isodimorphism/comonomer exclusion crystallization to isodimorphism with pseudoeutectic point variation from 54% to up to 90%. Moreover, we established a link between the melting temperature depression slope variation and the comonomer inclusion/exclusion balance, providing valuable insights into the complex topic of isodimorphic random copolymers.

Conventional chemotherapy, especially with natural anticancer drugs, usually suffers from poor bioavailability and low tumor accumulation. To address these limitations, we developed a novel approach for modifying natural products in which amphiphilic hydroxamic acid hybrids based on a natural product: isoalantolactone (IAL) were rationally designed. Compound 18 is identified as a highly potent dual signal transducer and activator of transcription 3 (STAT3)/histone deacetylases (HDAC) inhibitor and induces autophagy and apoptosis. 18 exhibits higher antitumor potency than IAL and the hydroxamic acid SAHA in vitro and in vivo. Furthermore, 18 self-assembled in water to form nanoparticles (18 NPs), which facilitated the accumulation of drugs in tumor tissues and promoted their cellular uptake, resulting in superior anticancer efficacy compared to free 18. Compared to drug-drug conjugates, hydroxamic acid hybrids have a smaller molecular weight and can synergize with various anticancer drugs. Overall, these findings indicate that 18 utilizing nanomedicines and dual-target drugs provide an efficient strategy for the rational design of dual-target drugs and the modification of natural products., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

A stereoselective synthesis of fused tricyclic framework of epi-parvistemonine A from D-glucono-δ-lactone is described. The synthetic strategic is based on the stereoselective construction of the 7-membered cyclic skeleton via a cross-metathesis reaction followed by a Michael type cyclization promoted by Tf 2 O., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

This study investigated the effect of gellan gum (GG) and glucono-δ-lactone (GDL) on the acid-induced gel properties of pea protein isolate (PPI) pretreated with media milling. The inclusion of GG substantially enhanced the gel hardness of PPI gel from 18.69 g to 792.47 g though slightly reduced its water holding capacity (WHC). Rheological analysis showed that GG increased storage modulus (G') and decreased damping factor of gels in the small amplitude oscillatory shear region and transformed its strain thinning behavior into weak strain overshoot behavior in the large amplitude oscillatory shear region. SEM revealed that GG transformed the microstructure of gel from a uniform particle aggregate structure to a chain-like architecture composed of filaments with small protein particles attached. Turbidity and zeta potential analysis showed that GG promoted the transformation of PPI from a soluble polymer system to an insoluble coagulant during acidification. When GG content was relatively high (0.2 %-0.3 %), high GDL content increased the electrostatic interaction between PPI and GG molecules, causing their rapid aggregation into a dense irregular aggregate structure, further enhancing gel strength and WHC. Overall, GG and GDL can offer the opportunity to modulate the microstructure and gel properties of acid-induced PPI gels, presenting potential for diversifying food gel design strategies through PPI-GG hybrid systems., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

The Lamiaceae (mint family) is the largest known source of furanoclerodanes, a subset of clerodane diterpenoids with broad bioactivities including insect antifeedant properties. The Ajugoideae subfamily, in particular, accumulates significant numbers of structurally related furanoclerodanes. The biosynthetic capacity for formation of these diterpenoids is retained across most Lamiaceae subfamilies, including the early-diverging Callicarpoideae which forms a sister clade to the rest of Lamiaceae. VacCYP76BK1, a cytochrome P450 monooxygenase from Vitex agnus-castus, was previously found to catalyze the formation of the proposed precursor to furan and lactone-containing labdane diterpenoids. Through transcriptome-guided pathway exploration, we identified orthologs of VacCYP76BK1 in Ajuga reptans and Callicarpa americana. Functional characterization demonstrated that both could catalyze the oxidative cyclization of clerodane backbones to yield a furan ring. Subsequent investigation revealed a total of 10 CYP76BK1 orthologs across six Lamiaceae subfamilies. Through analysis of available chromosome-scale genomes, we identified four CYP76BK1 members as syntelogs within a conserved syntenic block across divergent subfamilies. This suggests an evolutionary lineage that predates the speciation of the Lamiaceae. Functional characterization of the CYP76BK1 orthologs affirmed conservation of function, as all catalyzed furan ring formation. Additionally, some orthologs yielded two novel lactone ring moieties. The presence of the CYP76BK1 orthologs across Lamiaceae subfamilies closely overlaps with the distribution of reported furanoclerodanes. Together, the activities and distribution of the CYP76BK1 orthologs identified here support their central role in furanoclerodane biosynthesis within the Lamiaceae family. Our findings lay the groundwork for biotechnological applications to harness the economic potential of this promising class of compounds., (© 2024 The Author(s). The Plant Journal published by Society for Experimental Biology and John Wiley & Sons Ltd.)

Autoinducer-2 can mediate inter- and intra-species communication signal between bacteria and these signals from AI-2 is noted from limited species of bacteria. In humans, S. pyogenes is a pathogen that causes a wide range of illnesses and can survive in the host system and transmit infection. The process by which S. pyogenes acquires the competence to live and disseminate infection remains unknown. We hypothesized that AI-2 and their receptors would play a significant role during infection, and for that present investigation provides the experimental and molecular insights. In the absence of details about the receptor LuxP and LuxQ, the screening approach provides supporting insights. The evolutionary relationship and similarities of the PBP domain (Spy 1535) and the signal transmission PDZ domain (Spy 1536) were studied in relation to their counterparts in other bacteria. Molecular docking and modeling confirmed the domain-enhanced specificity for AI-2 binding. In vitro studies showed that AI-2, which is present in the cell-free supernatant of S. pyogenes , regulates luminescence in P. luminous and biofilm development in E. coli using the LuxS reporter genes. Examination of S. pyogenes gene expression revealed modulation of virulence genes when the pathogen was exposed to V. harveyi HSL and AI-2. Therefore, S. pyogenes pathogenicity is sequentially regulated by AI-2 it acquires from other commensal bacteria. Overall, this study lays the groundwork for understanding the signalling mechanism from AI-2, which are critical to the pathogenic mechanism of S. pyogenes .Communicated by Ramaswamy H. Sarma.

Background: Mycotoxin contamination of food has been gaining increasing attention. Hidden mycotoxins that interact with biological macromolecules in food could make the detection of mycotoxins less accurate, potentially leading to the underestimation of the total exposure risk. Interactions of the mycotoxins alternariol (AOH) and alternariol monomethyl ether (AME) with high-molecular glutenin were explored in this study., Results: The recovery rates of AOH and AME (1, 2, and 10 μg kg -1 ) in three types of grains (rice, corn, and wheat) were relatively low. Molecular dynamics (MD) simulations indicated that AOH and AME bound to glutenin spontaneously. Hydrogen bonds and π-π stacking were the primary interaction forces at the binding sites. Alternariol with one additional hydroxyl group exhibited stronger binding affinity to glutenin than AME when analyzing average local ionization energy. The average interaction energy between AOH and glutenin was -80.68 KJ mol -1 , whereas that of AME was -67.11 KJ mol -1 ., Conclusion: This study revealed the mechanisms of the interactions between AOH (or AME) and high-molecular glutenin using MD and molecular docking. This could be useful in the development of effective methods to detect pollution levels. These results could also play an important role in the evaluation of the toxicological properties of bound altertoxins. © 2024 Society of Chemical Industry., (© 2024 Society of Chemical Industry.)

A new lactone, collectindolide ( 1 ), as well as three known compounds, ( S )-sydonic acid ( 2 ), ( S )-hidroxysydonic acid ( 3 ), and indole-3-aceticacid ( 4 ) were obtained from the liquid media of Colletotrichum gloeosporioides , which was obtained from Artocarpus heterophyllus . The chemical structures of 1-4 were established by spectroscopic analyses, including NMR experiments and by HR-ESI-TOF-MS mass spectroscopy. Compounds 1 - 4 were evaluated for their cytotoxicity against murine leukaemia P-388 cell lines by MTT assay. Antibacterial activity of compounds 1 - 4 was also assayed against four bacteria. Phytochemical investigation of the genus Colletotrichum derived from the plant genus Artocarpus is reported for the first time.

Phytochemical studies on the leaves and twigs of Garcinia oligantha Merr. led to the isolation of twelve previously undescribed depsidone derivatives (oliganthdepsidones A-L, 1-12). Their structures were elucidated by extensive spectroscopic analysis including 1 H and 13 C NMR, HSQC, HMBC and NOESY along with HRESIMS. The structures of oliganthdepsidones G and J were finally determined using DFT-NMR chemical shift calculations and DP4+ methods. Cytotoxicity test in four human cancer cell lines indicated that oliganthdepsidone F had relatively strong cytotoxic effect against A375 (melanoma), A549 (lung cancer), HepG2 (liver cancer), and MCF-7 (breast cancer) cell lines with IC 50 of 18.71, 15.44, 10.92, and 15.90 μM, respectively. The dose- and time-dependent antiproliferative effects of oliganthdepsidone F on these cell lines were also observed by CCK-8 test. As determined by fluorescent microscopy and flow cytometry in these cell lines, oliganthdepsidone F could promote cell apoptosis, leading to the inhibition of cell proliferation. The results of wound healing assay and transwell assay showed that oliganthdepsidone F could inhibit the migration and invasion of A549 and MCF-7 cell lines in a concentration-dependent manner., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Two monoterpenoid lactones, loliolide ( 1 ) and epi -loliolide ( 2 ), were isolated from the crude dichloromethane extract of a microalga, Thalassiosira sp.). The structures of loliolide ( 1 ) and epi -loliolide ( 2 ) were elucidated by 1D and 2D NMR analysis, as well as a comparison of their 1 H or/and 13 C NMR data with those reported in the literature. In the case of loliolide ( 1 ), the absolute configurations of its stereogenic carbons were confirmed by X-ray analysis, whereas those of epi -loliolide ( 2 ) were determined by NOESY correlations. Loliolide ( 1 ) and epi -loliolide ( 2 ) were tested for their growth inhibitory activity against two Gram-positive ( Staphylococcus aureus ATCC 29213, Enterococcus faecalis ATCC 29212) and two Gram-negative ( Escherichia coli ATCC 25922, Pseudomonas aeruginosa ATCC 27853) bacteria, as well as one clinical isolate ( E. coli SA/2, an extended-spectrum β-lactamase producer-ESBL) and two environmental isolates, S. aureus 74/24, a methicillin-resistant (MRSA), and E. faecalis B3/101, a vancomycin-resistant (VRE) isolates. The results showed that none of the tested compounds exhibited antibacterial activity at the highest concentrations tested (325 μM), and both revealed low antioxidant activity, with ORAC values of 2.786 ± 0.070 and 2.520 ± 0.319 µmol TE/100 mg for loliolide ( 1 ) and epi -loliolide ( 2 ), respectively.

Fungal infections pose a great threat to public health and there are only four main types of antifungal drugs, which are often limited with toxicity, drug-drug interactions and antibiotic resistance. Streptomyces is an important source of antibiotics, represented by the clinical drug amphotericin B. Here we report the discovery of alligamycin A (1) as an antifungal compound from the rapamycin-producer Streptomyces iranensis through genome-mining, genetics and natural product chemistry approaches. Alligamycin A harbors a unique chemical scaffold with 13 chiral centers, featuring a β-lactone moiety, a [6,6]-spiroketal ring, and an unreported 7-oxo-octylmalonyl-CoA extender unit incorporated by a potential crotonyl-CoA carboxylase/reductase. It is biosynthesized by a type I polyketide synthase which is confirmed through CRISPR-based gene editing. Alligamycin A displayed potent antifungal effects against numerous clinically relevant filamentous fungi, including resistant Aspergillus and Talaromyces species. β-Lactone ring is essential for the antifungal activity since alligamycin B (2) with disruption in the ring abolished the antifungal effect. Proteomics analysis revealed alligamycin A potentially disrupts the integrity of fungal cell walls and induces the expression of stress-response proteins in Aspergillus niger. Discovery of the potent antifungal candidate alligamycin A expands the limited antifungal chemical space., (© 2024. The Author(s).)

Ganoderma meroterpenoids are fungal derived hybrid natural product class containing a 1,2,4-trisubstituted benzene ring and a polycyclic terpenoid part. The representatives applanatumol E, H and I, lingzhilactone B, and meroapplanin B share the same bicyclic lactone moiety connected to the arene. Employing photo-Fries rearrangements as the key step enabled a general entry to these natural products. For the synthesis of the tetracyclic framework of lingzhiol, we made use of a powerful photoredox oxidative decarboxylation/Friedel-Crafts sequence.

Antimicrobial resistance (AMR) represents a critical global health crisis. An innovative strategy to deal with AMR is to interfere with biofilm formation and bacterial quorum sensing (QS). In this study, newly designed autoinducer-2 (AI-2)-inspired compounds in targeting biofilm-associated infections were evaluated for their ability to inhibit biofilm formation in Staphylococcus aureus and Pseudomonas aeruginosa . The most effective compounds, 5d , 5e , and 7b , exhibited potent antibiofilm activity with minimal inhibitory concentrations in the low microgram per mL range. Detailed biological assays confirmed that the antibiofilm activity was primarily driven through AI-2 QS inhibition rather than direct antimicrobial effects. The combination of different spectroscopic techniques, such as differential scanning fluorimetry, intrinsic tryptophan fluorescence, circular dichroism, and nuclear magnetic resonance, elucidated the binding between the compounds and the LsrK enzyme, a key player in AI-2 mediated QS. Our findings highlight the potential of these novel QS inhibitors as promising therapeutic agents against biofilm-associated infections.

(2 Z )- Lachnophyllum methyl ester and (4 Z )- Lachnophyllum lactone were recently identified as major components in essential oils and extracts of Conyza bonariensis from Togo. Extended biological evaluation of these acetylenic compounds was however hampered by the reduced amounts isolated. A synthetic route was designed providing access to larger quantities of these two natural products as well as to original non-natural analogs with the prospect of exploring for the first time the structure-activity relationships in this series. Using LC/MS analysis, synthetic samples allowed confirming the presence of the two previously isolated natural products in plant extracts obtained by the accelerated solvent extraction technique. The nematocidal activity of the synthesized compounds confirmed the potency of the natural products, which remain the most active among all analogs tested. The synthesized compounds were also assessed against Leishmania infantum axenic amastigotes and the Mycobacterium tuberculosis H 37 Rv pathogenic strain. (2 Z )- Lachnophyllum methyl ester, (4 Z )- Lachnophyllum lactone and lactone analogs exhibited the strongest antileishmanial potency. As expected, a longer alkyl chain was necessary to observe significant antimycobacterial activity. The lactone analog bearing a C10 lipophilic appendage displayed the highest antimycobacterial potency. The notable activities of lactones, naturally occurring or analogs, either nematicidal, antileishmanial or antimycobacterial, were compared to their cytotoxicity for mammalian cells and revealed moderate selectivity index values. In this regard, the innocuous (2 Z )- Lachnophyllum methyl ester and its analogs open up more promising perspectives for the discovery of bioactive agents to protect both agricultural crops and human health.

Background: Citrus products often suffer from delayed bitterness, which is generated from the conversion of non-bitter precursors (limonoate A-ring lactone, LARL) to limonin under the catalysis of limonin D-ring lactone hydrolase (LDLH). In this study, LDLH was isolated and purified from sweet orange seeds, and a rapid and accurate high-performance liquid chromatography method to quantify LARL was developed and applied to analyze the activity and enzymatic properties of purified LDLH., Results: Purified LDLH (25.22 U mg -1 ) showed bands of 245 kDa and 17.5 kDa molecular weights in native polyacrylamide gel electrophoresis (PAGE) and sodium dodecyl sulfate PAGE analysis respectively. After a 24 h incubation under strongly acidic (pH 3) or strongly alkaline (pH 9) conditions, LDLH still retained approximately 100% activity. Moreover, LDLH activity was not impaired by thermal treatment at 50 °C for 120 min. Enzyme inhibition assays showed that LDLH was inactivated only after ethylenediaminetetraacetic acid treatment, and other enzyme inhibitors showed no significant effect on its activity. In addition, the LDLH activity of calcium ion (Ca 2+ ) intervention was 108% of that in the blank group, and that of zinc ion (Zn 2+ ) intervention was 71%., Conclusion: LDLH purified in this study was a multimer containing 17.5 kDa monomer with a wide pH tolerance range (pH 3-9) and excellent thermal stability. Moreover, LDLH might be a metallopeptidase, and its activity was stimulated by Ca 2+ and significantly inhibited by Zn 2+ . These findings improve our understanding of LDLH and provide some important implications for reducing the bitterness in citrus products in the future. © 2024 Society of Chemical Industry., (© 2024 Society of Chemical Industry.)

STING agonists are potent enhancers of a pro-inflammatory response and, thus, potentially useful therapeutics. Unfortunately, many agonists developed to date require complex drug delivery formulations and often have poor water solubility, limiting their use for systemic administration. Here, we report the discovery and chemical characterization of lactones of MSA-2 as new STING prodrugs with enhanced properties. We show that these prodrugs form efficient inclusion complexes with tumor myeloid cell targeting cyclodextrin nanoparticles and propose a new mechanism of formation and hydrolysis., (© 2024 The Authors. ChemMedChem published by Wiley-VCH GmbH.)

Zearalenone (ZEN) is a fungal toxin produced by Fusarium exospore, which poses a significant threat to both animal and human health due to its reproductive toxicity. Removing ZEN through ZEN lactonase is currently the most effective method reported, however, all published ZEN lactonases suffer from the poor thermal stability, losing almost all activity after 10 min of treatment at 55℃. In this study, we heterologously expressed ZHD11A from Phialophora macrospora and engineered it via semi-rational design. A mutant I160Y-G242S that can retain about 40 % residual activity at 55℃ for 10 min was obtained, which is the most heat-tolerant ZEN hydrolase reported to date. Moreover, the specific activity of the I160Y-G242S was also elevated 2-fold compared to ZHD11A from 220 U/mg to 450 U/mg, which is one of the most active ZEN lactonses reported. Dynamics analysis revealed that the decreased flexibility of the main-chain carbons contributes to increased thermal stability and the improved substrate binding affinity and catalytic turnover contribute to enhanced activity of variant I160Y-G242S. In all, the mutant I160Y-G242S is an excellent candidate for the industrial application of ZEN degradation., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Eight previously undescribed sesquiterpene lactones (1-8), together with six known ones (9-14) were isolated from the aerial parts of Tithonia diversifolia (Hemsl.) A. Gray. The absolute configurations of these compounds were elucidated using HRMS, NMR spectroscopy, optical rotation measurements, X-ray crystallography, and ECD. Among them, sesquiterpene lactones 2-4 share a unique carbon skeleton with a rare C-3/C-4 ring-opened structure. Compounds 1 and 8 showed moderate inhibitory effects toward CT26 murine colon carcinoma cells by promoting lipid ROS production, highlighting their potential as ferroptosis inducers., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

In order to investigate the effect of glucono-δ-lactone (GDL) and different salt ions (Na + and Ca 2+ ) induction on the cold-set gels of bovine serum albumin (BSA)-arabinoxylan (AX), the gel properties and structure of BSA-AX cold-set gels were evaluated by analyzing the gel strength, water-holding capacity, thermal properties, and Fourier Transform Infrared (FTIR) spectra. It was shown that the best gel strength (109.15 g) was obtained when the ratio of BSA to AX was 15:1. The addition of 1 % GDL significantly improved the water-holding capacity, gel strength and thermal stability of the cold-set gels (p < 0.05), and the microstructure was smoother. Low concentrations of Na + (3 mM) and Ca 2+ (6 mM) significantly enhanced the hydrophobic interaction and hydrogen bonding between BSA and AX after acid induction, and the Na + -induced formation of a denser microstructure with a higher water-holding capacity (75.51 %). However, the excess salt ions disrupted the stable network structure of the cold-set gels and reduced their thermal stability and crystalline structure. The results of this study contribute to the understanding of the interactions between BSA and AX induced by GDL and salt ions, and provide a basis for designing hydrogels with different properties., Competing Interests: Declaration of competing interest The authors declare that they have no known financial interests or personal relationships that might influence the work reported here., (Copyright © 2024. Published by Elsevier B.V.)

Nature has evolved biosynthetic pathways to molecules possessing reactive warheads that inspired the development of many therapeutic agents, including penicillin antibiotics. Peptides armed with electrophilic warheads have proven to be particularly effective covalent inhibitors, providing essential antimicrobial, antiviral and anticancer agents. Here we provide a full characterization of the pathways that nature deploys to assemble peptides with β-lactone warheads, which are potent proteasome inhibitors with promising anticancer activity. Warhead assembly involves a three-step cryptic methylation sequence, which is likely required to reduce unfavorable electrostatic interactions during the sterically demanding β-lactonization. Amide-bond synthetase and adenosine triphosphate (ATP)-grasp enzymes couple amino acids to the β-lactone warhead, generating the bioactive peptide products. After reconstituting the entire pathway to β-lactone peptides in vitro, we go on to deliver a diverse range of analogs through enzymatic cascade reactions. Our approach is more efficient and cleaner than the synthetic methods currently used to produce clinically important warhead-containing peptides., (© 2024. The Author(s).)

Eight undescribed guaianolide sesquiterpene lactones cicholosumins A-H and twelve known ones were isolated from the aerial parts of Cichorium glandulosum Boiss et Huet. Their structures were established by 1D and 2D NMR spectroscopic data, electronic circular dichroism, quantum chemical calculations and single crystal X-ray diffraction analysis. Compounds 9α-hydroxy-3-deoxyzaluzanin C, epi-8α-angeloyloxycichoralexin, 8-O-methylsenecioylaustricin and lactucin showed strong anti-neuroinflammation activity with IC 50 values of 1.69 ± 0.11, 1.08 ± 0.23, 1.67 ± 0.28 and 1.82 ± 0.27 μM, respectively. The mechanism research indicated that epi-8α-angeloyloxycichoralexin inhibited neuroinflammation through the NF-κB and MAPK pathways., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

The incidence of Mycobacterium marinum infection is on the rise; however, the existing drug treatment cycle is lengthy and often requires multi-drug combination. Therefore, there is a need to develop new and effective anti- M. marinum drugs. Cochliomycin A, a 14-membered resorcylic acid lactone with an acetonide group at C-5' and C-6', exhibits a wide range of antimicrobial, antimalarial, and antifouling activities. To further explore the effect of this structural change at C-5' and C-6' on this compound's activity, we synthesized a series of compounds with a structure similar to that of cochliomycin A, bearing ketal groups at C-5' and C-6'. The R / S configuration of the diastereoisomer at C-13' was further determined through an NOE correlation analysis of CH 3 or CH 2 at the derivative C-13' position and the H-5' and H-6' by means of a 1D NOE experiment. Further comparative 1 H NMR analysis of diastereoisomers showed the difference in the chemical shift ( δ ) value of the diastereoisomers. The synthetic compounds were screened for their anti-microbial activities in vitro. Compounds 15 - 24 and 28 - 35 demonstrated promising activity against M. marinum , with MIC 90 values ranging from 70 to 90 μM, closely approaching the MIC 90 of isoniazid. The preliminary structure-activity relationships showed that the ketal groups with aromatic rings at C-5' and C-6' could enhance the inhibition of M. marinum . Further study demonstrated that compounds 23 , 24 , 29 , and 30 had significant inhibitory effects on M. marinum and addictive effects with isoniazid and rifampicin. Its effective properties make it an important clue for future drug development toward combatting M. marinum resistance.

Strigolactones (SLs), plant-derived apocarotenoids, serve dual roles as phytohormones and rhizosphere signaling molecules. While exogenous administration of SLs to plants aids in studying their functions, the metabolic destiny of these administered SLs remains poorly elucidated. Our previous research demonstrated that among synthetic SL GR24 stereoisomers administered to cowpea (Vigna unguiculata), 2'-epi-GR24 undergoes selective reduction at the C-3',4' double bond in its D-ring. In this investigation, we isolated proteins from cowpea roots based on SL reducing activity and identified 12-oxophytodienoate reductase 3 homologs (VuOPR3s) as contributors to this reduction. Enzymatic assays conducted with recombinant proteins revealed that VuOPR3s exhibited a preference for reducing activity toward 2'S-configured SLs, including 2'-epi-GR24. This specificity for 2'S-configured SLs was congruent with that observed for orobanchol produced by cowpea and its stereoisomers. These findings suggest that exogenously administered SLs undergo enzymatic stereoselective reduction, underscoring the importance of considering stereospecificity when interpreting data obtained from SL usage., (© The Author(s) 2024. Published by Oxford University Press on behalf of Japan Society for Bioscience, Biotechnology, and Agrochemistry.)

Ricinoleic acid (RA) from castor oil was employed in biotransformation of peach-flavoured γ-decalactone (GDL), using a Candida parapsilosis strain (MTCC13027) which was isolated from waste of pineapple crown base. Using four variables-pH, cell density, amount of RA, and temperature-the biotransformation parameters were optimized using RSM and BBD. Under optimized conditions (pH 6, 10 % of microbial cells, 10 g/L RA at 28°C), the conversion was maximum and resulted to 80 % (+)-GDL (4.4 g/L/120 h) yield in shake flask (500 mL). Furthermore, optimization was achieved by adjusting the aeration and agitation parameters in a 3 L bioreactor, which were then replicated in a 10 L bioreactor to accurately determine the amount of (+)-GDL. In bioreactor condition, 4.7 g/L (>85 %) of (+)-GDL is produced with 20 % and 40 % dissolved oxygen (1.0 vvm) at 150 rpm in 72 h and 66 h, respectively. Further, a new Al-Mg-Ca-Si composite column-chromatography method is developed to purify enantiospecific (+)-GDL (99.9 %). This (+)-GDL is 100 % nature-identical as validated through 14 C-radio-carbon dating. Thorough chemical investigation of enantiospecific (+)-GDL is authenticated for its use as flavour. This bioflavour has been developed through a cost-effective biotechnological process in response to the demand from the food industry on commercial scale., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Competing interests The authors declare no competing interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Zearalenone and radicicol are resorcylic acid lactones produced by numerous plant pathogenic fungi. Zearalenone is a non-steroidal estrogen mimic that can cause serious reproductive issues in livestock that consume contaminated feed. Radicicol is a potent inhibitor of the molecular chaperone Hsp90, which, in plants, has an important role in coordinating the host's immune response during infection. Here, we describe the identification and characterization of a soil-borne strain of the Gram-positive bacterium Aeromicrobium sp. capable of hydrolyzing the macrolide ring of resorcylic acid lactones, including zearalenone and radicicol. Proteomic analysis of biochemically enriched fractions from the isolated and cultured bacterium identified an α/β-hydrolase responsible for this activity. A recombinantly expressed and purified form of the hydrolase (termed RALH) was active against both zearalenone and radicicol. Interpretation of high-resolution mass spectrometry and NMR data confirmed the structures of the enzymatic products as the previously reported non-toxic metabolite hydrolyzed zearalenone and hydrolyzed radicicol. Hydrolyzed radicicol was demonstrated to no longer inhibit the ATPase activity of the Saccharomyces cerevisiae Hsp90 homolog in vitro. Enzymatic degradation of resorcylic acid lactones will enable insight into their biological functions.

Exploring and accurately detecting new adulteration markers in sesame oil is an important measure for sesame oil adulteration monitoring. In this study, two endogenous flavors sulfurol and γ-nonalactone which can be used as potential adulteration markers were first discovered in sesame oil and accurately quantified. First, the two endogenous flavors were discovered using gas chromatography-mass spectrometry (GC-MS), and their structures were confirmed by comparing the mass spectrograms with the NIST spectral library. Then the liquid chromatography-tandem mass spectrometry (LC-MS/MS) method using direct methanol extraction pretreatment and vanillin-D3 as an internal standard was developed for rapid quantitation and application. The method was successfully validated with recoveries ranging from 88.5% to 102.2% and relative standard deviations between 2.6% and 10.5% ( n = 6). The combined method of GC-MS and LC-MS/MS was indicated to be efficient and highly sensitive for detection of sulfurol and γ-nonalactone in edible oil. Subsequently, 31 sesame oils from the market were detected, revealing that 31 samples contained the identified flavors within a relatively consistent range. However, the concentration of these flavor substances in one sample was abnormally high, indicating that there was a potential risk of adulteration. Therefore, the developed method shows good potential for quality evaluation and adulteration screening of sesame oil.

Barrel aging is a crucial stage that influences the taste of wines and spirits, particularly increasing their sweetness and bitterness. This increase is caused by nonvolatile compounds released from oak wood. To search for such molecules, we performed a taste-guided inductive fractionation protocol using several analytical techniques. By using HRMS and NMR, two new galloylated derivatives were elucidated. Their enzymatic hydrolysis revealed the formation of β-methyl-γ-octalactone, indicating that they are potential precursors. The taste properties of these isomers revealed a sweet and bitter taste for P-WL-1 and P-WL-2, respectively. An LC-HRMS quantification method was performed to evaluate the influence of aging parameters such as botanical origin and toasting process on their concentrations. Several spirits were also analyzed to confirm their presence in this matrix. These results improve the understanding of the molecular markers responsible for the taste of beverages.

Parasitic weeds, such as Orobanche and Striga , threaten crops globally. Contiguous efforts on the discovery and development of structurally novel seed germination stimulants targeting HYPOSENSITIVE TO LIGHT/KARRIKIN INSENSITIVE 2 (HTL/KAI2) have been made with the goal of weed control. Here, we demonstrate that a natural compound dehydrocostus lactone (DCL) exhibits effective "suicide germination" activity against Orobanche cumana and covalently binds to OcKAI2d2 on two catalytic serine sites with the second modification dependent on the first one. The same interactions and covalent modifications of DCL are also confirmed in AtKAI2. Further in-depth evolution analysis indicates that the proposed two catalytic sites are present throughout the streptophyte algae, hornworts, lycophytes, and seed plants. This discovery is particularly noteworthy as it signifies the first confirmation of a plant endogenous molecule directly binding to KAI2, which is valuable for unraveling the elusive identity of the KAI2 ligand and for targeting KAI2 paralogues for the development of novel germination stimulants.

Wound healing is a dynamic process that requires an optimal extracellular environment, as well as an accurate synchronization between various cell types. Over the past few years, great efforts have been devoted to developing novel approaches for treating and managing burn injuries, sepsis, and chronic or accidental skin injuries. Multifunctional smart-polymer-based dressings represent a promising approach to support natural healing and address several problems plaguing partially healed injuries, including severe inflammation, scarring, and wound infection. Naturally derived compounds offer unique advantages such as minimal toxicity, cost-effectiveness, and outstanding biocompatibility along with potential anti-inflammatory and antimicrobial activity. Herein, the main driving idea of the work was the design and development of konjac glucomannan d-glucono-1,5-lactone (KG) films bioactivated by tannic acid and d-glucono-1,5-lactone (GL) addition. Our analysis, using attenuated total reflectance-Fourier transform infrared, atomic force microscopy, and surface energy measurements demonstrated that tannic acid (TA) clearly interacted with the KG matrix, acting as its cross-linker, whereas GL was embedded within the polymer structure. All developed films maintained a moist environment, which represents a pivotal property for wound dressing. Hemocompatibility experiments showed that all tested films exhibited no hemolytic impact on human erythrocytes. Moreover, the presence of TA and GL enhanced the metabolic and energetic activity in human dermal fibroblasts, as indicated by the MTT assay, showing results exceeding 150%. Finally, all films demonstrated high antibacterial properties as they significantly reduced the multiplication rate of both Staphylococcus aureus and Escherichia coli in bacterial broth and created the inhibition zones for S. aureus in agar plates. These remarkable outcomes make the KG/TA/GL film promising candidates for wound healing applications.

Strigolactones (SLs) are plant hormones that regulate shoot branching. In addition, SLs act as compounds that stimulate the germination of root parasitic weeds, such as Striga spp. and Orobanche spp., which cause significant damage to agriculture worldwide. Thus, SL agonists have the potential to induce suicidal germination, thereby reducing the seed banks of root parasitic weeds in the soil. Particularly, phenoxyfuranone-type SL agonists, known as debranones, exhibit SL-like activity in rice and Striga hermonthica . However, little is known about their effects on Orobanche spp. In this study, we evaluated the germination-inducing activity of debranones against Orobanche minor . Analysis of structure-activity relationships revealed that debranones with electron-withdrawing substituents at the 2,4- or 2,6-position strongly induced the germination of Orobanche minor . Lastly, biological assays indicated that 5-(2-fluoro-4-nitrophenoxy)-3-methylfuran-2(5 H )-one (test compound 61 ) induced germination to a comparable or even stronger extent than GR24, a well-known synthetic SL. Altogether, our data allowed us to infer that this enhanced activity was due to the recognition of compound 61 by the SLs receptor, KAI 2d, in Orobanche minor .

Cystargolides and belactosins are natural products with a distinct dipeptide structure and an electrophilic β-lactone warhead. They are known to inhibit proteases such as the proteasome or caseinolytic protease P, highlighting their potential in treating cancers and neurodegenerative diseases. Recent genetic analyses have shown homology between the biosynthetic pathways of the two inhibitors. Here, we characterize the O-methyltransferases BelI and CysG, which catalyze the initial step of β-lactone formation. Employing techniques such as crystallography, computational analysis, mutagenesis, and activity assays, we identified a His-His-Asp (HHD) motif in the active sites of the two enzymes, which is crucial for binding a catalytically active calcium ion. Our findings thus elucidate a conserved divalent metal-dependent mechanism in both biosynthetic pathways that distinguish BelI and CysG from previously characterized O-methyltransferases., Competing Interests: Conflict of interest The authors declare no conflicts of interest with the contents of the article., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

In the process of searching for anti-breast cancer agents, five sesquiterpene lactones (1-5), including two previously undescribed ones, yjaponica B-C (1-2), were isolated from the herb of Youngia japonica. Their structures were elucidated by spectroscopic data analyses and Marfey's method. Cytotoxic activities of all compounds against A549, U87, and 4T1 cell lines were tested using the CCK8 assay. The result showed that compound 3 possessed the highest cytotoxic activity against 4T1 cells with an IC 50 value of 10.60 μM. Furthermore, compound 3 distinctly induced apoptosis, inhibited immigration, and blocked the cell cycle of 4T1 cells. In addition, compound 3 induced the production of reactive oxygen species. Further anticancer mechanism studies showed that compound 3 significantly upregulated expression of the cleaved caspase 3 and PARP, whereas it downregulated the expression of Bcl-2, cyclin D1, cyclin A2, CDK4, and CDK2. Taken together, our results demonstrate that compound 3 has a high potential of being used as a leading compound for the discovery of new anti-breast cancer agent., (© 2024 Wiley-VHCA AG, Zurich, Switzerland.)

Background: Striga hermonthica, an obligate root parasitic weed, poses a significant threat to cereal production in sub-Saharan Africa. Lowering Striga seed bank in infested soils is a promising strategy to mitigate infestation levels. The dependency of Striga seed germination on strigolactones opens up the possibility of a 'suicidal germination' approach, where synthetic germination stimulants induce lethal germination in the absence of a host. Implementing this approach requires active germination stimulants with a suitable formulation for field application. Here, we describe the development of slow-releasing granular formulation of two potent germination stimulants 'Methyl Phenlactonoate 3' and 'Nijmegen-1' and the assessment of their activity under Laboratory, greenhouse, mini-field, and field conditions., Results: Under laboratory conditions, the granular formulation of either of the two germination stimulants (1.25 mg per plate, corresponding to 0.09 mg a.i.) induced Striga seed germination at a rate of up to 43%. With 10 mg granular product (0.75 mg a.i.) per pot, we observed 77-83% reduction in Striga emergence under greenhouse pot conditions. Application of the formulated stimulants under artificially or naturally infested fields resulted in approximately 56%, 60%, and 72% reduction in Striga emergence in maize, sorghum, and millet fields in Kenya and Burkina Faso, respectively., Conclusion: Our findings on the newly designed granular formulation of Methyl Phenlactonoate 3 and Nijmegen-1 reveal encouraging prospects for addressing the Striga problem in Africa. These findings underscore several significant advantages of the formulated stimulants, including suitability for the African agricultural context, and, most importantly, their effectiveness in reducing Striga infection. © 2024 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry., (© 2024 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.)

Three 12, 8-guaianolide sesquiterpene lactones, including a new compound intybusin F ( 1 ), and a new natural product cichoriolide I ( 2 ), along with six known 12, 6-guaianolide compounds ( 4 - 9 ) were isolated from the roots of Cichorium intybus L. Their structures were determined by extensive spectroscopic analysis. The absolute configurations of new compounds were elucidated based on analysis of the experimental and calculated electronic circular dichroism spectra. Compounds 1 , 2 , 4 , 7 , 8 showed significant effects on facilitating the glucose uptake in oleic acid plus high glucose-stimulated HepG2 cells at 50 μM. In addition, compounds 1 , 2 , 3 , 6 , 7 exhibited obvious inhibitory effects against NO production, of them, compounds 1 , 2 , 7 can significantly decrease the secretion of inflammatory cytokines (TNF-α, IL-6 and COX-2) levels in this hyperglycemic HepG2 cell model.

Ultrasound spectroscopy and confocal laser scanning microscopy (CLSM) methods were developed to visualize the interaction between sodium caseinate (SC) and whey protein isolate (WPI) with a mild preheat treatment (57°C, 10 min) followed by adding glucono-δ-lactone (GDL). Ultrasonic velocity changes during incubation at 25°C after adding GDL for four kinds of mixtures (no-treated SC plus no-treated WPI, preheated SC plus no-treated WPI, no-treated SC plus preheated WPI and preheated SC plus preheated WPI) were monitored. The results reveal that the mild preheating treatment of the proteins affected the timing of the increase in compressibility of each system. CLSM observation with individualized dyes which have different maxima of excitation and emission wavelengths, showed the preheated SC plus no-treated WPI mixture had a slightly coarse structure and the highest correlation coefficient, suggesting the highest colocalization of the SC and WPI among the four kinds of mixed-protein systems. Furthermore, the scanning electron microscopy (SEM) observation suggests that there are some differences among the gels, namely, preheated WPI leads to the formation of developed three-dimensional gel networks with filamentous structures, whereas SC promotes the formation of cluster-like crowded networks composed of more fine aggregated particles instead of developed filamentous structures. These results demonstrated that although SC is known as a heat-stable protein, pretreated SC could lead to an increase of the collaboration with WPI in the presence of GDL. This finding anticipated the possibility creating a food material with another texture using a milk-protein mixed system., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Citrus fruits are highly susceptible to pathogenic fungal infections after harvesting, which causes serious economic losses. Therefore, it's necessary to develop new antifungal packaging. In this study, gamma-Decanolactone (DL) was successfully encapsulated in a polycaprolactone (PCL)/β-cyclodextrin (β-CD) composite system using electrostatic spinning technology. PCL/β-CD was compounded in different ratios, the ratio was screened through other indicators such as fiber morphologies and mechanical properties. Then, antifungal mats were prepared by adding different concentrations of DL to the PCL/β-CD solution. The results showed that when the mixture ratio of PCL/β-CD was 6:1 and loaded with 6 % DL, the antifungal felt had strong mechanical, significantly inhibiting the growth of three citrus pathogens (P. digitatum, P. italicum and G. candidum), released DL for up to 204 h and effectively reduced the morbidity rate of citrus fruits. Therefore, the antifungal pad prepared in this study has great potential in the field of citrus disease control., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Euphohelinodes D-I (1-6), six previously unreported ent-abietane lactones, along with two known analogues (7 and 8), were isolated from the anti-inflammatory fraction extracted from E. helioscopia by a bioactivity-guided isolation. Their structures were characterized using a combination of spectroscopic data interpretation, single-crystal X-ray diffraction and ECD analysis. The anti-inflammatory activity of these compounds was evaluated by measuring their inhibitory effects on NO production in LPS-stimulated RAW264.7 macrophages. The most active candidate, euphohelinode H (5), had better inhibitory activity against NO production with an IC 50 value of 30.23 ± 2.33 μM. Further study revealed that 5 significantly suppressed the expressions of iNOS and COX-2 through the NF-κB signaling pathway., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

In case of organic frameworks (COFs) as adsorbents in the pretreatment of complex food matrices, challenges such as poor dispersion and non-specific adsorption of interfering macromolecules like proteins are often encountered. To address this issue, this work prepared a three-dimensional covalent organic framework (3D-COF) with a novel bcu topology based on polyhedral oligomeric silsesquioxane (POSS). Subsequently, gluconolactone (GDL) was modified onto the external surface of the material via the reaction with the exposed reactive residues. The resulting POSS-COF@GDL adsorbent has an enhanced hydrophilicity in the external surface, thereby significantly improves the dispersion of materials in aqueous solution and reduces the adsorption ability toward protein. Whereas, the inner of material retains hydrophobic pores that exhibit high adsorption efficiency to small hydrophobic molecules. Compared with the traditional pretreatment methods, POSS-COF@GDL can directly extract bisphenols (BPs) in milk samples without any additional treatment. The established sample pretreatment method is coupled with high-performance liquid chromatography-ultraviolet detection (HPLC-UV), resulting in recoveries of 71.8 to 93.6%, intra- and inter-day relative standard deviations (RSDs) of <8.3%, and limits of detection (LODs) of 0.042-0.16 ng∙mL -1 for four BPs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Breast cancer is the most common malignant tumor and a major cause of mortality among women worldwide. Atramacronoid A (AM-A) is a unique natural sesquiterpene lactone isolated from the rhizome of Atractylodes macrocephala Koidz (known as Baizhu in Chinese). Our study demonstrated that AM-A triggers a specific form of cell death resembling PANoptosis-like cell death. Further analysis indicated that AM-A-induced PANoptosis-like cell death is associated with the CASP-3/PARP-GSDMD-MLKL pathways, which are mediated by mitochondrial dysfunction. These results suggest the potential of AM-A as a lead compound and offer insights for the development of therapeutic agents for breast cancer from natural products.

The preliminary study revealed that the ethyl acetate eluate of Youngia japonica (YJ-E) could inhibit the expression of key proteins of p-p65, p-IκBα, p-IKKα/β, and p-AKT in LPS stimulated BV2 cell. Further phytochemical study led to the isolation of eight compounds from YJ-E, including one new sesquiterpene lactone. Their structures were elucidated by several spectroscopic data, and comparing the NMR data of known compound. In addition, all of the isolates were evaluated for the anti-inflammatory effect. As a result, compounds 3 and 4 distinctly attenuated the expressions of p-IκBα, p-p65, and p-AKT in LPS stimulated BV2 cell, respectively.

Three new eudesmane type rare sesquiterpene lactone galactosides, costunosides A-C ( 1-3) were isolated from the rhizomes of Aucklandia costus along with ten known compounds ( 4-13 ). Costunosides A-C ( 1-3) are the first example of naturally eudesmane glycosides containing a β -galactopyranoside moiety. The structure and relative configurations of these compounds were established by comprehensive analysis of MS and, in particular 1D/2D NMR spectroscopic data. The isolated compounds were tested against a panel of human cancer cell lines, where compounds 3, 6 and 7 have shown promising cytotoxic activity against PC-3, HCT-116 and A549 cell lines with IC 50 values in the range of 3.4 µM to 9.3 µM, respectively. Costunosides A-C ( 1-3) were also screened for inhibition assay of acetyl-cholinesterase (AChE), and butyrylcholinesterase (BChE) and found inactive at a concentration of 10 µM.

Natural products are important precursors for antibiotic drug design. These chemical scaffolds serve as synthetic inspiration for chemists who leverage their structures to develop novel antibacterials and chemical probes. We have previously studied carolacton, a natural product macrolactone from Sorangium cellulosum , and discovered a simplified derivative, A2 , that maintained apparent biofilm inhibitory activity, although the biological target was unknown. Herein, we utilize affinity-based protein profiling (AfBPP) in situ during biofilm formation to identify the protein target using a photoexcitable cross-linking derivative of A2 . From these studies, we identified glucan binding protein B (GbpB), a peptidoglycan hydrolase, as the primary target of A2 . Further characterization of the interaction between A2 and GbpB, as well as PcsB, a closely related homologue from the more pathogenic S. pneumoniae , revealed binding to the catalytic CHAP (cysteine, histidine, aminopeptidase) domain. To the best of our knowledge, this is the first report of a small-molecule binder of a conserved and essential bacterial CHAP hydrolase, revealing its potential as an antibiotic target. This work also highlights A2 as a useful tool compound for streptococci and as an initial scaffold for the design of more potent CHAP binders.

Competing Interests: Competing interests statement:The author declares no competing interest.

Zearalenone (ZEN) is an estrogenic mycotoxin causing reproductive toxicity in livestock. Currently, lactone hydrolases are used in the enzymatic degradation of ZEN. However, most lactone hydrolases suffer from low degradation efficiency and poor thermal stability. ZHD518, as a documented neutral enzyme for ZEN degradation, exhibits high enzymatic activity under neutral conditions. In this study, a multifunctional peptide S1v1-(AEAEAHAH) 2 was fused to the N-terminus of ZHD518. Compared with the wild-type enzyme, the peptide fusion significantly enhanced protein expression by 1.28 times, enzyme activity by 9.27 times, thermal stability by 37.08 times after incubation at 45 °C for 10 min and enzyme stability during long-term storage. Moreover, ZEN concentrations in corn bran, corn germ meal, and corn gluten powder decreased from 5.29 ± 0.04, 5.31 ± 0.03, and 5.30 ± 0.01 μg/g to 0.48 ± 0.05, 0.48 ± 0.06, and 0.21 ± 0.04 μg/g, respectively, following a 60 min treatment with S1v1-GS-ZHD518, resulting in degradation rates of 90.98, 91.00, and 95.32%, respectively. In conclusion, the properties of S1v1-GS-ZHD518, such as its efficient degradability, high temperature resistance and storage resistance, offer the possibility of its application in food or feed.

Alantolactone (ALT), a natural sesquiterpene lactone from Inula helenium L., demonstrates potent antitumor activity in various human cancers, notably non-small cell lung cancer (NSCLC). Despite its recognized efficacy, the precise mechanisms of action remain elusive. Our study aimed to elucidate ALT's impact on NSCLC. Our findings suggested that ALT triggered apoptosis both in vitro and in vivo, underscoring its anticancer potential. Interestingly, the ferroptosis inhibitor (Fer-1), rather than necrostatin-1 (Nec-1) or Z-VAD-FMK, rescued ALT-induced cell death, implicating ferroptosis as pivotal. Subsequent analyses revealed ferroptosis as the primary mechanism underlying ALT-induced NSCLC cell death, supported by markers including ROS accumulation, MDA elevation, GSH depletion, Fe 2+ generation, and GPX4 reduction. Through DARTS/MS proteomics, we identified FTH1 as the target of ALT-induced ferroptosis. Immunoblotting confirmed ALT's inhibition of FTH1 protein expression and accelerated its degradation in NSCLC cells. Immunoprecipitation assays demonstrated increased FTH1 ubiquitination induced by ALT. Additionally, ALT induced ferroptosis and facilitated Fe 2+ accumulation via FTH1 ubiquitination. Importantly, ALT displayed potent antitumor effects in a subcutaneous xenograft model in BALB/c-nu/nu nude mice by enhancing ferroptosis. In summary, ALT induced ferroptosis by promoting intracellular Fe 2+ accumulation through accelerated FTH1 degradation, highlighting its potential as an antitumor agent targeting ferroptosis., (© 2024 John Wiley & Sons Ltd.)

A new depsidone, parmoferone A ( 1 ), together with three known compounds, parmosidone K ( 2 ), albifolione ( 3 ), and 4-chloroorcinol ( 4 ) were isolated from the lichen Parmotrema cristiferum (Taylor) Hale (Parmeliaceae). The structures of isolated compounds were identified from its spectroscopic data and by comparison with the literature. Compounds 1-4 were evaluated for alpha-glucosidase inhibition. Compound 1 was determined to be a potent non-competitive inhibitor against alpha-glucosidase with an IC 50 value of 18.1 μM.

Oxygen vacancies (Ov) in metal oxides play a crucial role in modifying the electronic and acidic properties of catalysts, thereby influencing their catalytic activity. This study explores the impact of Ov in MnOx catalysts on their acidic and catalytic properties for the Meerwein-Ponndorf-Verley reduction of levulinic acid (LA) and levulinate to γ-valerolactone (GVL). Various characterization techniques demonstrate that surface Ov significantly modulate the acidic properties of MnOx catalysts, positively correlating with Lewis/Brønsted acid ratio and GVL yield. In situ DRIFTS and DFT calculations further unveil the reaction mechanism, revealing that Ov facilitate the activation and dehydrogenation of isopropanol and subsequent hydrogen transfer and hydrogenation of LA, leading to enhanced GVL production. These insights underscore the pivotal role of Ov in MnOx catalysts for the efficient conversion of LA to GVL, highlighting their importance in improving catalytic performance., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

A new 14-membered resorcylic acid lactone (RAL 14 ), chaetolactone A ( 1 ), along with three known ones ( 2 - 4 ), was obtained from the fermentation of the soil-derived fungus Chaetosphaeronema sp. SSJZ001. Their structures were established based on extensive spectroscopic data analyses (UV, IR, HRESIMS, 1D, and 2D NMR), 13 C NMR chemical shifts calculations coupled with the DP4 + probability method, theoretical calculations of ECD spectra, as well as X-ray diffraction analysis. All compounds were evaluated for their cytotoxic effects against A549, HO-8910, and MCF-7 cell lines.