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Chemical & Pharmaceutical Bulletin 2024We report the first total synthesis of silybin A (1). Key synthetic steps include the construction of the 1,4-benzodioxane neolignan skeleton, a modified Julia-Kocienski...
We report the first total synthesis of silybin A (1). Key synthetic steps include the construction of the 1,4-benzodioxane neolignan skeleton, a modified Julia-Kocienski olefination reaction between m-nitrophenyltetrazole sulfone (m-NPT sulfone) 10 and aldehyde 21, the formation of the flavanol lignan skeleton 28 via a quinomethide intermediate under acidic conditions, and stepwise oxidation of the benzylic position of flavanol 29.
Topics: Silybin; Stereoisomerism; Molecular Structure; Silymarin; Oxidation-Reduction
PubMed: 38910121
DOI: 10.1248/cpb.c24-00276 -
Journal of Dairy Science Jun 2024Infant formulas (IFs), the sole adequate substitute to human milk, undergo several thermal treatments during production that can damage milk proteins and promote the...
Infant formulas (IFs), the sole adequate substitute to human milk, undergo several thermal treatments during production that can damage milk proteins and promote the formation of Maillard reaction products, modifying nutritional and sensory properties. The aim of this study was to determine the impact of a minimally processing route based on membrane filtration associated with different levels of heat treatment, on the odor, taste, texture and color attributes of IFs, then to compare with those of commercial milks. Three experimental IFs (produced with membrane filtration associated with low - T, medium - T, or high thermal treatments - T) were evaluated. Triangular tests conducted with a panel of 50 adults highlighted clear disparities between all the IFs. The same panel applied the Check-All-That-Apply method to evaluate the IFs: the range of variability between T and T was similar to that between the 2 commercial IFs, and the sensory characteristics of the experimental IFs were not far from the commercial brands for flavor and texture attributes. Analysis performed on the citation frequencies for each descriptor differentiated T/T from T, but all the experimental IFs were described with positive sensory characteristics, unlike one commercial IF. Volatile organic compounds (VOCs) content of IFs with low and high thermal treatments were analyzed. Forty VOCs were identified by gas chromatography-mass spectrometry. T contained a higher quantity of VOCs than T, except for benzaldehyde (Maillard reaction product), and aldehydes (oxidation-related products) were the most represented compounds. In conclusion, the processing was associated with sensory differences among IFs, but no marked difference in flavors was found according to CATA and physicochemical analysis. Additionally, no unpleasant sensory descriptors were noted. This shows that the minimally processed route leads to IFs that could fit well within the market from a sensory point of view.
PubMed: 38908693
DOI: 10.3168/jds.2024-24937 -
Developmental Cell Jun 2024Sexually reproducing eukaryotes employ a developmentally regulated cell division program-meiosis-to generate haploid gametes from diploid germ cells. To understand how...
Sexually reproducing eukaryotes employ a developmentally regulated cell division program-meiosis-to generate haploid gametes from diploid germ cells. To understand how gametes arise, we generated a proteomic census encompassing the entire meiotic program of budding yeast. We found that concerted waves of protein expression and phosphorylation modify nearly all cellular pathways to support meiotic entry, meiotic progression, and gamete morphogenesis. Leveraging this comprehensive resource, we pinpointed dynamic changes in mitochondrial components and showed that phosphorylation of the FF-ATP synthase complex is required for efficient gametogenesis. Furthermore, using cryoET as an orthogonal approach to visualize mitochondria, we uncovered highly ordered filament arrays of Ald4, a conserved aldehyde dehydrogenase that is highly expressed and phosphorylated during meiosis. Notably, phosphorylation-resistant mutants failed to accumulate filaments, suggesting that phosphorylation regulates context-specific Ald4 polymerization. Overall, this proteomic census constitutes a broad resource to guide the exploration of the unique sequence of events underpinning gametogenesis.
PubMed: 38906138
DOI: 10.1016/j.devcel.2024.05.025 -
Cell Jun 2024Gamete formation and subsequent offspring development often involve extended phases of suspended cellular development or even dormancy. How cells adapt to recover and...
Gamete formation and subsequent offspring development often involve extended phases of suspended cellular development or even dormancy. How cells adapt to recover and resume growth remains poorly understood. Here, we visualized budding yeast cells undergoing meiosis by cryo-electron tomography (cryoET) and discovered elaborate filamentous assemblies decorating the nucleus, cytoplasm, and mitochondria. To determine filament composition, we developed a "filament identification" (FilamentID) workflow that combines multiscale cryoET/cryo-electron microscopy (cryoEM) analyses of partially lysed cells or organelles. FilamentID identified the mitochondrial filaments as being composed of the conserved aldehyde dehydrogenase Ald4 and the nucleoplasmic/cytoplasmic filaments as consisting of acetyl-coenzyme A (CoA) synthetase Acs1. Structural characterization further revealed the mechanism underlying polymerization and enabled us to genetically perturb filament formation. Acs1 polymerization facilitates the recovery of chronologically aged spores and, more generally, the cell cycle re-entry of starved cells. FilamentID is broadly applicable to characterize filaments of unknown identity in diverse cellular contexts.
Topics: Saccharomyces cerevisiae; Saccharomyces cerevisiae Proteins; Cryoelectron Microscopy; Mitochondria; Gametogenesis; Meiosis; Aldehyde Dehydrogenase; Electron Microscope Tomography; Coenzyme A Ligases; Spores, Fungal; Cytoplasm; Cell Nucleus
PubMed: 38906101
DOI: 10.1016/j.cell.2024.04.026 -
IScience Jun 2024Scent marking sites served as a primary means of chemical communication for giant pandas, enabling intraspecific communication. We integrated metabolomics and...
Scent marking sites served as a primary means of chemical communication for giant pandas, enabling intraspecific communication. We integrated metabolomics and high-throughput sequencing techniques to examine the non-targeted metabolome and microbial community structure of scent marking sites and feces in the field. Integrative analysis revealed a more comprehensive array of chemical compounds compared to previous investigations, including ketones, acids, heterocycles, alcohols, and aldehydes. Notably, specific compounds such as 2-decenal, (E)-, octanal, decanal, L-α-terpineol, vanillin, and nonanal emerged as potential key players in scent signaling. Intriguingly, our study of the microbial domain identified dominant bacterial species from the Actinobacteria, Bacteroidetes, and Proteobacteria phyla, likely orchestrating metabolic processes at scent marking sites. Comparative analyses showed, for the first time, that feces do not share the same functions as scent markers, indicating distinct functional roles. This research deepens scientific understanding of chemical communication in wild pandas.
PubMed: 38904067
DOI: 10.1016/j.isci.2024.110051 -
Journal of Physiological Investigation May 2024Inflammatory bowel disease (IBD) comprises a group of idiopathic intestinal disorders, including ulcerative colitis and Crohn's disease, significantly impacting the...
Cinnamaldehyde, A Bioactive Compound from the Leaves of Cinnamomum osmophloeum Kaneh, Ameliorates Dextran Sulfate Sodium-Induced Colitis in Mice by Inhibiting the NLRP3 Inflammasome.
Inflammatory bowel disease (IBD) comprises a group of idiopathic intestinal disorders, including ulcerative colitis and Crohn's disease, significantly impacting the quality of life for affected individuals. The effective management of these conditions remains a persistent challenge. The NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome, a complex molecular structure, regulates the production of pro-inflammatory cytokines such as interleukin-1β. Abnormal activation of the NLRP3 inflammasome plays a pivotal role in the development of IBD, making it a compelling target for therapeutic intervention. Our research revealed that cinnamaldehyde (CA), a major bioactive compound found in the leaves of Cinnamomum osmophloeum kaneh, demonstrated a remarkable ability to alleviate colitis induced by dextran sulfate sodium (DSS) in a mouse model. This effect was attributed to CA's ability to downregulate the activation of the NLRP3 inflammasome and reduce the expression of pro-inflammatory mediators in the colon. In the mechanism study, we observed that CA inhibited the NLRP3 inflammasome in macrophages, at least partially, by enhancing the autophagic response, without reducing mitochondrial damage. These findings collectively suggest that CA holds significant potential as a therapeutic agent for enhancing the management of IBD, offering a promising avenue for further research and development.
Topics: Animals; Dextran Sulfate; Acrolein; NLR Family, Pyrin Domain-Containing 3 Protein; Mice; Colitis; Cinnamomum; Inflammasomes; Mice, Inbred C57BL; Plant Leaves; Male
PubMed: 38902958
DOI: 10.4103/ejpi.EJPI-D-24-00017 -
BMC Veterinary Research Jun 2024Camels are bred for their milk, meat, wool and hair, transportation, and their excrement as fuel. The seasonal reproduction of camel bull is accompanied by changes in...
BACKGROUND
Camels are bred for their milk, meat, wool and hair, transportation, and their excrement as fuel. The seasonal reproduction of camel bull is accompanied by changes in sexual activity, the morphology, and function of the testes. This study aimed to evaluate the seasonal fluctuations in serum testosterone (T) levels as well as total antioxidant capacity (TAC) and malondialdehyde (MDA) levels in the testes of dromedary bulls (Camelus dromedarius) during the rutting and non-rutting seasons. Moreover, the impact of rutting season on the testicular size and histomorphology was also observed. Seventy mature dromedary bulls were divided into a rutting group (n = 35) and a non-rutting group (n = 35). From these bulls, blood samples and testes were collected during the rutting season (October to April) and non-rutting season (May to September) from a local slaughterhouse.
RESULTS
All parameters changed significantly during rutting and non-rutting periods in camel bulls. The levels of TAC in testes, and serum T were significantly (P < 0.05) higher in the rutting group than in the non-rutting group. However, testicular MDA was significantly (P < 0.05) lower in the rutting group than in the non-rutting group. TAC was negatively correlated with MDA (r = -0.59, p < 0.01). Moreover, in the rutting group and the non-rutting group, T was positively correlated with levels of TAC (r = 0.66, p < 0.0003). Additionally, testicular size (length, breadth, and thickness) was significantly greater in camels during the rutting season than in camels during the non-rutting season. Moreover, the number and diameter of seminiferous tubules, and spermatogenesis increased during the rutting season, whereas, the collagen content and apoptosis increased during the non-rutting season.
CONCLUSION
This study revealed that the rutting normal breeding season (NBS, rutting group) was associated with higher levels of total antioxidant capacity (TAC), T, and spermatogenic activity while the collagen content, concentrations of MDA (the oxidative stress factor) and apoptosis (an outcome of oxidative stress) were lower than those in the low breeding season (LBS, non-rutting group). In addition, the testicular size and seminiferous tubule diameter and number were higher during the NBS.
Topics: Animals; Male; Camelus; Testis; Seasons; Malondialdehyde; Testosterone; Antioxidants; Sexual Behavior, Animal
PubMed: 38902750
DOI: 10.1186/s12917-024-04108-6 -
BMC Veterinary Research Jun 2024Scale drop disease virus (SDDV) threatens Asian seabass (Lates calcarifer) aquaculture production by causing scale drop disease (SDD) in Asian seabass. Research on the...
Protective efficiency and immune responses to single and booster doses of formalin-inactivated scale drop disease virus (SDDV) vaccine in Asian seabass (Lates calcarifer).
BACKGROUND
Scale drop disease virus (SDDV) threatens Asian seabass (Lates calcarifer) aquaculture production by causing scale drop disease (SDD) in Asian seabass. Research on the development of SDDV vaccines is missing an in-depth examination of long-term immunity and the immune reactions it provokes. This study investigated the long-term immune protection and responses elicited by an SDDV vaccine. The research evaluated the effectiveness of a formalin-inactivated SDDV vaccine (SDDV-FIV) using both prime and prime-booster vaccination strategies in Asian seabass. Three groups were used: control (unvaccinated), single-vaccination (prime only), and booster (prime and booster). SDDV-FIV was administered via intraperitoneal route, with a booster dose given 28 days post-initial vaccination.
RESULTS
The immune responses in vaccinated fish (single and booster groups) showed that SDDV-FIV triggered both SDDV-specific IgM and total IgM production. SDDV-specific IgM levels were evident until 28 days post-vaccination (dpv) in the single vaccination group, while an elevated antibody response was maintained in the booster group until 70 dpv. The expression of immune-related genes (dcst, mhc2a1, cd4, ighm, cd8, il8, ifng, and mx) in the head kidney and peripheral blood lymphocytes (PBLs) of vaccinated and challenged fish were significantly upregulated within 1-3 dpv and post-SDDV challenge. Fish were challenged with SDDV at 42 dpv (challenge 1) and 70 dpv (challenge 2). In the first challenge, the group that received booster vaccinations demonstrated notably higher survival rates than the control group (60% versus 20%, P < 0.05). However, in the second challenge, while there was an observable trend towards improved survival rates for the booster group compared to controls (42% versus 25%), these differences did not reach statistical significance (P > 0.05). These findings suggest that the SDDV-FIV vaccine effectively stimulates both humoral and cellular immune responses against SDDV. Booster vaccination enhances this response and improves survival rates up to 42 dpv.
CONCLUSIONS
This research provides valuable insights into the development of efficient SDDV vaccines and aids in advancing strategies for immune modulation to enhance disease management in the aquaculture of Asian seabass.
Topics: Animals; Fish Diseases; Viral Vaccines; Vaccines, Inactivated; Immunization, Secondary; Iridoviridae; DNA Virus Infections; Formaldehyde; Antibodies, Viral; Vaccination; Immunoglobulin M; Perciformes; Bass
PubMed: 38902724
DOI: 10.1186/s12917-024-04132-6 -
BMC Plant Biology Jun 2024The Prunus sibirica seeds with rich oils has great utilization, but contain amygdalin that can be hydrolyzed to release toxic HCN. Thus, how to effectively reduce seed...
BACKGROUND
The Prunus sibirica seeds with rich oils has great utilization, but contain amygdalin that can be hydrolyzed to release toxic HCN. Thus, how to effectively reduce seed amygdalin content of P. sibirica is an interesting question. Mandelonitrile is known as one key intermediate of amygdalin metabolism, but which mandelonitrile lyase (MDL) family member essential for its dissociation destined to low amygdalin accumulation in P. sibirica seeds still remains enigmatic. An integration of our recent 454 RNA-seq data, amygdalin and mandelonitrile content detection, qRT-PCR analysis and function determination is described as a critical attempt to determine key MDL and to highlight its function in governing mandelonitrile catabolism with low amygdalin accumulation in Prunus sibirica seeds for better developing edible oil and biodiesel in China.
RESULTS
To identify key MDL and to unravel its function in governing seed mandelonitrile catabolism with low amygdalin accumulation in P. sibirica. Global identification of mandelonitrile catabolism-associated MDLs, integrated with the across-accessions/developing stages association of accumulative amount of amygdalin and mandelonitrile with transcriptional level of MDLs was performed on P. sibirica seeds of 5 accessions to determine crucial MDL2 for seed mandelonitrile catabolism of P. sibirica. MDL2 gene was cloned from the seeds of P. sibirica, and yeast eukaryotic expression revealed an ability of MDL2 to specifically catalyze the dissociation of mandelonitrile with the ideal values of K (0.22 mM) and V (178.57 U/mg). A combination of overexpression and mutation was conducted in Arabidopsis. Overexpression of PsMDL2 decreased seed mandelonitrile content with an increase of oil accumulation, upregulated transcript of mandelonitrile metabolic enzymes and oil synthesis enzymes (involving FA biosynthesis and TAG assembly), but exhibited an opposite situation in mdl2 mutant, revealing a role of PsMDL2-mediated regulation in seed amygdalin and oil biosynthesis. The PsMDL2 gene has shown as key molecular target for bioengineering high seed oil production with low amygdalin in oilseed plants.
CONCLUSIONS
This work presents the first integrated assay of genome-wide identification of mandelonitrile catabolism-related MDLs and the comparative association of transcriptional level of MDLs with accumulative amount of amygdalin and mandelonitrile in the seeds across different germplasms and developmental periods of P. sibirica to determine MDL2 for mandelonitrile dissociation, and an effective combination of PsMDL2 expression and mutation, oil and mandelonitrile content detection and qRT-PCR assay was performed to unravel a mechanism of PsMDL2 for controlling amygdalin and oil production in P. sibirica seeds. These findings could offer new bioengineering strategy for high oil production with low amygdalin in oil plants.
Topics: Amygdalin; Prunus; Seeds; Plant Proteins; Plant Oils; Aldehyde-Lyases; Gene Expression Regulation, Plant
PubMed: 38902595
DOI: 10.1186/s12870-024-05300-4 -
Scientific Reports Jun 2024Glutamatergic neurotransmission and oxidative stress are involved in the pathophysiology of seizures. Some anticonvulsants exert their effects through modulation of...
Glutamatergic neurotransmission and oxidative stress are involved in the pathophysiology of seizures. Some anticonvulsants exert their effects through modulation of these pathways. Trigonelline (TRG) has been shown to possess various pharmacological effects like neuroprotection. Therefore, this study was performed to determine TRG's anticonvulsant effects, focusing on its potential effects on N-methyl-D-aspartate (NMDA) receptors, a type of glutamate receptor, and oxidative stress state in the prefrontal cortex (PFC) in PTZ-induced seizure in mice. Seventy-two male mice were randomly divided into nine groups. The groups included mice that received normal saline, TRG at doses of 10, 50, and 100 mg/kg, diazepam, NMDA (an agonist), ketamine (an antagonist), the effective dose of TRG with NMDA, as well as sub-effective dose of TRG with ketamine, respectively. All agents were administrated intraperitoneally 60 min before induction of seizures by PTZ. Latency to seizure, total antioxidant capacity (TAC), and malondialdehyde (MDA) levels in serum and PFC were measured. Furthermore, the gene expression of NR2A and NR2B, subunits of NMDA receptors, was measured in the PFC. TRG administration increased the latency to seizure onset and enhanced TAC while reducing MDA levels in both the PFC and serum. TRG also decreased the gene expression of NR2B in the PFC. Unexpectedly, the findings revealed that the concurrent administration of ketamine amplified, whereas NMDA mitigated, the impact of TRG on latency to seizure. Furthermore, NMDA diminished the positive effects of TRG on antioxidant capacity and oxidative stress, while ketamine amplified these beneficial effects, indicating a complex interaction between TRG and NMDA receptor modulation. In the gene expression of NMDA receptors, results showed that ketamine significantly decreased the gene expression of NR2B when co-administrated with a sub-effective dose of TRG. It was found that, at least partially, the anticonvulsant effect of TRG in PTZ-induced seizures in male mice was mediated by the attenuation of glutamatergic neurotransmission as well as the reduction of oxidative stress.
Topics: Animals; Receptors, N-Methyl-D-Aspartate; Oxidative Stress; Anticonvulsants; Mice; Male; Alkaloids; Seizures; Prefrontal Cortex; Malondialdehyde; Ketamine; Pentylenetetrazole; Antioxidants
PubMed: 38902338
DOI: 10.1038/s41598-024-65301-z