Search Results (194)

Chemical analysis of the marine-derived Saccharopolyspora sp. PG10 led to the isolation of a novel macrolactam, cebulactam A₃ (1), along with four known congeners, cebulactams A₁ and A₂ (2 and 3) and shengliangmycins B and D (4 and 5). The structure of 1 was established by high-resolution mass spectrometry (HRMS) and comprehensive nuclear magnetic resonance (NMR) analyses, and its absolute configuration was determined using Mosher’s method. Genome analysis identified a putative biosynthetic gene cluster consistent with a hybrid polyketide pathway. Antimicrobial evaluation revealed that shengliangmycin B exhibited the strongest activity, whereas cebulactam analogs exhibited weaker effects. These findings expand the structural diversity of cebulactam-type macrolactams and provide insights into their stereochemical variation. Full article

Nine new mycophenolic acid derivatives, penicacids O–W (1–9), two first-time reported natural products (10, 11), and five known compounds (12–16), were isolated from a marine-derived fungus Penicillium senticosum RCDB005 found in a South China Sea sediment sample. Their structures were determined using NMR, HRESIMS, and optical rotatory dispersion (ORD) spectra, electronic circular dichroism (ECD) calculations, X-ray crystallography, and modified Mosher’s methods. Eight of these compounds were evaluated for anti-proliferative effects against nine human cancer cell lines and the IC₅₀ values ranged from nM to μM levels. Compounds 5, 7–9 showed potent inhibition activity against MOLM-13 acute myeloid leukemia cells with IC₅₀ values between 0.13 and 1.13 μM. Full article

Cordyceps cicadae, a medicinal and edible entomopathogenic fungus, has been widely used in traditional Chinese medicine for treating various ailments. This study aimed to validate its ethnopharmacological uses by investigating bioactive constituents and their antithrombotic and antioxidant activities. Through various chromatographic separations, one unreported flavonoid; quercetin-3-O-β-D-methylglucopyranoside (1); three known flavonoids (2–4); and one new dicarboxylic acid derivative, cicadae acid (5), were isolated from C. cicadae. Their chemical structures were elucidated by a comprehensive spectroscopic analysis (1D/2D NMR and HRESIMS), electronic circular dichroism (ECD) calculations, a DP4+ probability analysis, and the modified Mosher method. All compounds exhibited significant antithrombotic effects at a concentration of 20 μM in a zebrafish model. Compounds 1–4 exhibited potent antioxidant activity in the DPPH radical scavenging assay, with IC₅₀ values ranging from 12.81 ± 3.42 to 20.16 ± 2.64 μM. These findings provide scientific evidence supporting the traditional application of C. cicadae, identifying specific flavonoids and dicarboxylic acids as potential therapeutic agents for thrombosis and oxidative stress-related disorders. Full article

Two new cytochalasans (1–2), along with eight known ones (3–10) were isolated from sponge-derived Aspergillus sp. SCSIO 41044. The planar structures of 1–2 were elucidated through extensive spectroscopic analyses and their absolute configurations determined by modified Mosher’s methods. Biological evaluation revealed that 5, 7, and 8 showed potent cytotoxicity against small cell lung cancers H446 and H1048, with IC₅₀ values ranging from 0.0441 to 1.61 μM. Full article

Background/Objectives: To determine whether adolescent (T1) mental health, quality of life, and adjustment to celiac disease (CeD) are associated with college-age (T2) perceived physical and mental health and gluten-free diet (GFD) adherence. Methods: In 2015, adolescents with CeD (n = 101, T1) completed standardized surveys assessing mental health (CSI-4), quality of life (PedsQL), and adjustment to CeD (CDDUX). Five years later, participants ≥18 years self-reported GFD adherence and physical and mental health perception in college (n = 59, T2). Patients who were current or recent college students that provided complete data at both time points were analyzed (n = 43) using Kendall’s tau to test: concurrent associations among T2 perceived physical/mental health and GFD adherence; and prospective associations between T1 measures and T2 perceived outcomes. Results: Higher T1 CSI-4 and PedsQL scores were negatively correlated with T2 perceived physical health (τ = −0.31, p = 0.02 and τ = −0.28, p = 0.04, respectively). There was trending association between T1 PedsQL and T2 mental health perception (τ = −0.23, p = 0.06). T2 physical and mental health perception were positively correlated (τ = 0.41, p = 0.001). No significant associations emerged between T1 measures and T2 GFD adherence, nor between T2 health perception and GFD adherence, although T2 physical health perception positively trended with GFD adherence (p = 0.78). Conclusions: Adolescents with CeD reporting more depressive symptoms or lower quality of life feel less physically and mentally healthy when in college. In college, feeling physically healthy aligns with feeling mentally healthy, although neither clearly predicts GFD adherence. Early mental health screening in adolescents with CeD may support transitions to independent dietary management. Full article

Hollow heart, and other crop defects, can be devastating to farmers. Hollow heart is not a disease but a physiological disorder affected by temperature, soil moisture, plant density, and other factors. These defects can cause substantial annual losses for farmers. Currently, potatoes are shipped and inspected from producers to shipping points and markets. At these facilities, samples are inspected for defects. Detection of hollow heart consists of halving potatoes and visually inspecting for defects. The defect size is compared to USDA hollow heart classification charts for acceptance or rejection. An automatic, non-destructive system to identify hollow heart has the potential to improve quality. Two methods have been developed to collect data for such a system: acoustic signal capture and visual/vibration signal capture. Data is collected and stored for one potato at a time. The procedure includes the collection of weight, proportional size, and volume, as well as the generation of an acoustic sound signal through a drop test and a motion signal captured through a vision system. To simulate hollow heart, potatoes are cored and retested by producing a new set of data. Each potato is manually cut and inspected for true hollow heart. The generated data includes over 1000 samples, each comprising proportional volume, weight, proportional size, motion, and acoustic data. Such a dataset does not exist in the current literature and can serve for the development of machine learning algorithms to detect hollow heart nondestructively. In this paper, the data is also analyzed in terms of its statistical properties, as applied for possible feature engineering in machine learning. Full article

Objectives: The aim was to measure wait times for rheumatologist consultation and disease-modifying antirheumatic drug (DMARD) treatment and examine their association with travel time to primary care practitioners (PCP) and rheumatologists within a centralized intake system, respectively. Methods: Within a centralized intake system serving 4.2 million people, we measured wait time for rheumatologist consultations and DMARD treatment for an RA incidence cohort between 1 April 2015 and 31 March 2020. Wait times were reported as the median with the interquartile range (IQR). Using multivariate logistics regression models, we examined the impact of travel times to primary/rheumatology care on wait times for rheumatologist consultation (28-day benchmark) and DMARD treatment (14-day benchmark). Travel times were defined according to quantiles and pre-defined categories. Results: The median wait time was 47 days (IQR: 18–114) for rheumatologist consultations (36% meeting the benchmark) and 35 days (IQR: 1–132) for DMARD treatment (43% meeting the benchmark). Patients living >120 min away had lower odds of meeting the 28-day consultation benchmark compared with those within 30 min (OR 0.64; 95% CI: 0.42–0.97). Compared with patients driving ≤30 min, lower odds of meeting the 14-day benchmark for DMARD treatment were observed for those driving over 60 min to PCPs (OR 0.62; 95% CI: 0.39–0.99) and patients driving 30–60 min to rheumatologists (OR 0.68; 95% CI: 0.55–0.85). Conclusion: RA management was suboptimal due to low rates of meeting RA consultation and treatment benchmarks, which was significantly associated with long travel times to both primary and RA care within a centralized triage system. This highlights the need for complementary strategies (e.g., tele-rheumatology, travel support, or alternate care providers) to ensure timely RA care in rural and remote communities. Full article

The bis-thiourea chiral solvating agent (CSA) BTDA enables the NMR-based determination of absolute configuration in N-3,5-dinitrobenzoyl (DNB) amino acid derivatives without requiring covalent derivatization. A reliable trend of the sense of nonequivalence and absolute configuration is found in both ¹H and ¹³C NMR spectra. A dual-enantiomer approach, using (R,R)- and (S,S)-BTDA, generates diastereomeric complexes with the enantiopure substrate, and distinct spatial arrangements are reflected in consistent and interpretable Δδ values. The observed chemical shift differences correlate reliably with the stereochemistry of the chiral center and are further supported by ROESY (Rotating-frame Overhauser Enhancement SpectroscopY) experiments and binding constants’ measurements, confirming the formation of stereoselective non-covalent complexes. This methodology extends the logic of Mosher’s analysis to solvating agents and remains effective even in samples containing single pure enantiomers of the amino acid derivative. The BTDA-based dual-CSA system thus represents a robust, non-derivatizing strategy for stereochemical assignment by NMR, combining operational simplicity with broad applicability to DNB derivatives of amino acids with free carboxyl function. Full article

Obesity is a major risk factor for atrial fibrillation (AF), the most common serious cardiac arrhythmia, but the molecular mechanisms underlying obesity-induced AF remain unclear. In this study, we subjected mice to a chronic high-fat diet and acute sympathetic activation to investigate how obesity promotes AF. Surface electrocardiography revealed that obesity and sympathetic activation synergize during intracardiac tachypacing to induce AF. At the cellular level, this combination facilitated delayed afterdepolarizations in atrial myocytes, implicating altered Ca²⁺ dynamics. Interestingly, obesity did not affect the expression of key atrial Ca²⁺-handling proteins, including the cardiac sarcoplasmic reticulum Ca²⁺-ATPase (SERCA2a). However, obesity increases the proportion of inhibitory phospholamban (PLN) monomers and decreases PLN phosphorylation, suggesting reduced SERCA2a activity. Paradoxically, Ca²⁺ reuptake in atrial myocytes from obese mice was similar to that achieved by potent small-molecule SERCA2a activators. We found that adrenergic stimulation increased Ca²⁺ transient amplitude without altering Ca²⁺ reuptake in myocytes from obese mice. Transcriptomic analysis revealed that a high-fat diet upregulated neuronatin, a protein involved in obesity that enhances SERCA2-mediated Ca²⁺ reuptake in neurons. We propose that obesity enables SERCA2a activation independently of PLN regulation, while adrenergic stimulation triggers arrhythmogenic Ca²⁺-induced Ca²⁺ release, promoting AF. In conclusion, this study demonstrates that obesity causes a paradoxical dysregulation of SERCA2a in atrial myocytes, with increased activity despite higher levels of inhibitory PLN monomers and reduced PLN phosphorylation. These findings offer new insights into the cellular mechanisms of obesity-induced AF and suggest potential therapeutic targets. Full article

Seven new (1–7) and six known (8–13) statin derivatives were obtained from the deep-sea-derived fungus Penicillium viridicatum MCCC 3A00265. The structures assigned to the new compounds were based on a comprehensive analysis of the spectroscopic data, with absolute configurations established by Mosher analysis and biogenetic consideration. Most of the new compounds (1–5 and 7) share an octohydronaphthalene backbone, except that viridecalin F (6) possesses an uncommon naphthalene core. Viridecalins C (3) and F (6) and the two known compounds 9 and 11 exhibit considerable ability in reactivating mutant p53 protein at 10 μM, while viridecalin C showcases the most potent reactivation activity, indicating the potential of application in cancer therapy. Full article

The use of electrically driven drivetrains is increasing for passenger cars and light-, medium-, and heavy-duty trucks. Off-the-shelf automatic transmission fluids (ATFs) are still being used as electric drivetrain fluids (EDFs). EDFs are trending toward lower viscosity for better energy efficiency and better heat transfer capacity, while satisfying all the other challenging requirements, such as gear/bearing scuffing/wear protection, oxidative stability, copper corrosion, and coating/seal material compatibility. In this paper, we will highlight the importance of low foaming, low aeration, and low traction coefficient which are critical for the performance of the EDF during high-speed applications, measured using metrics such as energy efficiency, heat transfer capacity, and longer oil drain interval. Full article

Thiochroman derivatives are highly versatile molecules widely used for the synthesis of novel heterocycles and bioactive compounds. In our study, we conducted the biotransformation of thiochroman-4-ol (1) and 6-chlorothiochroman-4-ol (1a) using the marine-derived fungal strains Emericellopsis maritima BC17 and Purpureocillium lilacinum BC17-2. Biotransformations yielded ten known thiochroman derivatives along with the compound 1-(5-chloro-2-(methylthio)phenyl)propane-1,3-diol (6a), which was described for the first time. Moreover, we successfully characterized the stereoisomers of sulfoxides 3 and 3a. Their structures and absolute configurations were established though comprehensive analyses of NMR, HR ESI-MS, and ECD spectra, as well as by using Mosher’s method. Antimicrobial activity of the isolated metabolites was evaluated against bacterial and fungal human pathogens, specifically Staphylococcus aureus ATCC 29213, Escherichia coli ATCC25922, and Candida albicans HPM-1922816. Full article

Human lactate dehydrogenase A (hLDHA) is a homotetrameric isozyme involved in the conversion of glyoxylate into oxalate in the cytosol of liver cells (hepatocytes) and partially responsible for the overproduction of oxalate in patients with the rare disease called primary hyperoxaluria (PH). Recently, hLDHA inhibition has been validated as a safe therapeutic method to try to control the PH disease. Stiripentol (STP) is an approved drug used in the treatment of seizures associated with Dravet’s syndrome (a severe form of epilepsy in infancy) which, in addition, has been drawing interest in recent years also for potentially treating PH, due to its hLDHA inhibitory activity. In this work, several new STP-related compounds have been synthesized and their hLDHA inhibitory activity has been compared to that of STP. The synthesis of these analogues to STP was accomplished using crossed-aldol condensation guided by lithium enolate chemistry and a successive regioselective reduction of the resulting α,β-unsaturated ketones. The target molecules were obtained as racemates, which were separated into their enantiomers by chiral HPLC. The absolute configurations of pure enantiomers were determined by the modified Mosher’s method and electronic circular dichroism (ECD) spectroscopy. For the inhibitory effect over the hLDHA catalytic activity, a kinetic spectrofluorometric assay was used. All the new synthesized compounds turned out to be more active at 500 μM (46–72% of inhibition percentage) than STP (10%), which opens a new line of study on the possible capacity of these analogues to reduce urinary oxalate levels in vivo more efficiently. Full article

Two new harziane diterpenes (1–2), five undescribed cyclonerane sesquiterpenes (3–7), and three known compounds, 11-cycloneren-3, 7, 10-triol (8), harziandione (9), and dehydroacetic acid (10), were isolated from Trichoderma hamatum b-3. Their structures were elucidated via comprehensive inspection of spectral evidence in HRESIMS and 1D and 2D NMR, and the absolute configuration of 1–8 was confirmed by NMR, ECD calculation, as well as Mosher’s method. In vitro fungicidal activity showed that some compounds showed great inhibitory activity against pathogenic fungi, including Fusarium graminearum, Sclerotinia sclerotiorum, Botrytis cinerea, and Rhizoctonia solani, among which compound 10 showed 100% inhibition of S. sclerotiorum and B. cinerea. The in vivo activity test showed that compound 10 was 65.8% effective against B. cinerea and compound 10 can be used as a lead compound for the development of biopesticides that inhibit B. cinerea. This study elucidated the bioactivity of secondary metabolites of T. hamatum and indicated the direction for the subsequent development of the biological control activity of T. hamatum. Full article

Acyl-quinic acids (AQAs), present in various plants with many health benefits, are regarded as therapeutic agents in the prevention and treatment of chronic and cardiovascular diseases. The molecular network-guided identification of ten AQA compounds, two new (5 and 7) and eight known compounds, were isolated from V. rotundifolia L. f. by using a newly applied extraction method. Their structures were determined through spectroscopic means, reaction mixtures, and modified Mosher and PGME techniques. These compounds were assessed for their anti-inflammatory and antioxidant capabilities. Notably, compounds 1, 3, 4, 6, 8, and 9 exhibited notable DPPH radical scavenging activity. In LPS-induced HT-29 cells, compounds 2–7 significantly inhibited IL-8 production. Furthermore, compounds 3–5 and 7 markedly suppressed NO production, while compounds 1–10 effectively inhibited IL-6 production in LPS-induced RAW264.7 cells. Western blot analyses revealed that compounds 3–5, and 7 reduced iNOS and COX-2 expression, and compounds 2–5, 7, and 8 also diminished the expression levels of p38 MAPK phosphorylation. Docking studies demonstrated the active compounds’ binding affinity with the IL-8, iNOS, COX-2, and p38 MAPK proteins through interactions with essential amino acids within the binding pockets of complexes. The findings suggest that compounds 1, 3, 4, 6, 8, and 9, and compounds 3–5, and 7, hold promise as potential therapeutic agents for treating antioxidative and inflammatory diseases, respectively. Full article