ABSTRACT
BACKGROUND: Prostate cancer (PC) is driven by aberrant signaling of the androgen receptor (AR) or its ligands, and androgen deprivation therapies (ADT) are a cornerstone of treatment. ADT responsiveness may be associated with germline alterations in genes that regulate androgen production, uptake, and conversion (APUC). METHODS: We analyzed whole-exome sequencing (WES) and whole transcriptome sequencing (WTS) data from prostate tissues (SU2C/PCF, TCGA, GETx). We also interrogated the Caris POA DNA (592-gene/whole exome) and RNA (whole transcriptome) NGS databases. Algorithm for Linking Activity Networks (ALAN) was used to quantify all pairwise gene-to-gene associations. Real-world overall survival (OS) was determined from insurance claims data using Kaplan-Meier estimates. RESULTS: Six APUC genes (HSD3B1, HSD3B2, CYP3A43, CYP11A1, CYP11B1, CYP17A1) exhibited coalescent gene behavior in a cohort of metastatic tumors (n = 208). In the Caris POA dataset, the 6 APUC genes (APUC-6) exhibited robust clustering in primary prostate (n = 4,490) and metastatic (n = 2,593) biopsies. Surprisingly, tumors with elevated APUC-6 expression had statically lower expression of AR, AR-V7, and AR signaling scores suggesting ligand-driven disease biology. APUC-6 genes instead associated with the expression of alternative steroid hormone receptors, ESR1/2 and PGR. We used RNA expression of AR or APUC-6 genes to define two subgroups of tumors with differential association with hallmark pathways and cell surface targets. CONCLUSIONS: The APUC-6 high/AR-low tumors represented a subgroup of patients with good clinical outcomes in contrast to the AR-high or neuroendocrine prostate cancers. Altogether, measuring the aggregate expression of APUC-6 genes in current genomic tests identifies PCs that are ligand- (rather than AR-) driven and require distinct therapeutic strategies. FUNDING: NCI/NIH 1R37CA288972-01, NCI Cancer Center Support P30 CA077598, DOD W81XWH-22-2-0025, R01 CA249279.
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Escherichia coli (E. coli) is a prevalent pathogen that is frequently associated with the foodborne illness. It causes various infections and poses a significant threat to human health. A rapid and sensitive assay for detecting E. coli is essential for timely diagnosis. Herein, a simple and sensitive colorimetric analysis method for detecting E. coli was developed based on the formation of Au@Ag core-shell nanoparticles facilitated by p-benzoquinone (BQ). E. coli reduced p-benzoquinone to generate hydroquinone (HQ), which could reduce the added Tollens' reagent to silver elemental and grow on the surface of gold nanoparticles (AuNPs). As the E. coli concentration increased, the silver layer thickess on the AuNPs surface growed, resulting in a stronger silver absorption peak observed at 390 nm. The color of the solution changed from red to orange, which could be used to detect E. coli by the naked eye. As a result, E. coli was detected with a linear range from 1.0 × 101 to 1.0 × 107 CFU/mL based on the absorbance intensity. In addition, this method accurately detected E. coli in real milk sample, demonstrating promising applications in foodborne pathogen detection. With satisfactory accuracy, the proposed colorimetric method holds excellent prospects in detecting pathogens in actual food samples.
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An efficient rhodium-catalyzed asymmetric transfer hydrogenation of ß-cyano α-ketoesters via dynamic kinetic resolution has been developed. Despite the challenge posed by multiple functional groups, the reaction proceeded smoothly under mild conditions, generating versatile synthons with two adjacent stereocenters in high yields with excellent enantio- and diastereoselectivities. Furthermore, the power of this strategy is highlighted by the scale-up reaction and the follow-up synthesis of cytoxazone and paclitaxel intermediates.
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Chloroplast development underpins plant growth, by facilitating not only photosynthesis but also other essential biochemical processes. Nonetheless, the regulatory mechanisms and functional components of chloroplast development remain largely uncharacterized due to their complexity. In our study, we identified a plastid-targeted gene, ATYCO/RP8/CDB1, as a critical factor in early chloroplast development in Arabidopsis thaliana. YCO knock-out mutant (yco) exhibited a seedling-lethal, albino phenotype, resulting from dysfunctional chloroplasts lacking thylakoid membranes. Conversely, YCO knock-down mutants produced a chlorophyll-deficient cotyledon and normal leaves when supplemented with sucrose. Transcription analysis also revealed that YCO deficiency could be partially compensated by sucrose supplementation, and that YCO played different roles in the cotyledons and the true leaves. In YCO knock-down mutants, the transcript levels of plastid-encoded RNA polymerase (PEP)-dependent genes and nuclear-encoded photosynthetic genes, as well as the accumulation of photosynthetic proteins, were significantly reduced in the cotyledons. Moreover, the chlorophyll-deficient phenotype in YCO knock-down line can be effectively suppressed by inhibition of PSI cyclic electron transport activity, implying an interaction between YCO and PSI cyclic electron transport. Taken together, our findings de underscore the vital role of YCO in early chloroplast development and photosynthesis.
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IgG4-related tubulointerstitial nephritis (IgG4-related TIN) is the prevalent clinical manifestation of IgG4-related diseases (IgG4-RD). However, there are limited cases of IgG4-RD occurring with membranous nephropathy (MN) in the absence of phospholipase A2 receptor (PLA2R). There have been no indications of treatment using Tripterygium wilfordii. This study reported a rare case of IgG4-RD with PLA2R-associated MN without any of the distinct IgG4-related TIN. The patient was treated effectively with T. wilfordii. A 71-year-old patient was admitted to the medical facility after presenting with a 1 month history of edema and 8 months of albuminuria. The renal biopsy tissue examination confirmed the presence of MN (phase II) in the absence of pathological manifestations of IgG4-related TIN. Immunohistochemistry identified PLA2R++ (granular capillaries). The serum PLA2R antibody titer was 1:180 (1:20). The patient met the diagnosis with IgG4-RD. Over 8 years of follow-up, the patient was effectively treated with low-dose hormones and T. wilfordii, without any adverse effects. This MN is considered a unique form of IgG4-RD, regardless of whether PLA2R antibodies are present or not. Research suggests that T. wilfordii could be a promising option for elderly people with IgG4-related MN, as it has been found to have fewer adverse effects.
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Photosystem I (PSI) from Fittonia albivenis, an Acanthaceae ornamental plant, is notable among green plants for its red-shifted emission spectrum. Here, we solved the structure of a PSI-light harvesting complex I (LHCI) supercomplex from F. albivenis at 2.46-Å resolution using cryo-electron microscopy. The supercomplex contains a core complex of 14 subunits and an LHCI belt with four antenna subunits (Lhca1-4) similar to previously reported angiosperm PSI-LHCI structures; however, Lhca3 differs in three regions surrounding a dimer of low-energy chlorophylls (Chls) termed red Chls, which absorb far-red beyond visible light. The unique amino acid sequences within these regions are exclusively shared by plants with strongly red-shifted fluorescence emission, suggesting candidate structural elements for regulating the energy state of red Chls. These results provide a structural basis for unraveling the mechanisms of light harvest and transfer in PSI-LHCI of under canopy plants and for designing Lhc to harness longer-wavelength light in the far-red spectral range.
Subject(s)
Cryoelectron Microscopy , Light-Harvesting Protein Complexes , Photosystem I Protein Complex , Amino Acid Sequence , Chlorophyll/metabolism , Chlorophyll/chemistry , Light , Light-Harvesting Protein Complexes/chemistry , Light-Harvesting Protein Complexes/metabolism , Models, Molecular , Photosystem I Protein Complex/chemistry , Photosystem I Protein Complex/metabolism , Photosystem I Protein Complex/ultrastructure , Plant Proteins/metabolism , Plant Proteins/chemistry , AcanthaceaeABSTRACT
Catalytic asymmetric synthesis of polysubstituted chiral cyclopropane presents a significant challenge in organic synthesis due to the difficulty in enantioselective control. Here we report a rhodium-catalyzed highly chemo-, regio- and enantioselective hydroformylation of trisubstituted cyclopropenes affording chiral quaternary cyclopropanes. Importantly, the easy made sterically bulky ligand L1 can effectively suppress hydrogenation and decomposition reactions and give quaternary cyclopropanes with high regio- and enantioselectivities for both aryl and alkyl functionalized substrates. Control experiments and computational studies reveal the sterically hindered well-defined chiral pocket instead of the substrates bearing electron-withdrawing diester groups is important for controlling the enantioselectivity and regioselectivity. Scale-up reaction and follow-up diverse transformations are also presented. Density Functional theory (DFT) computations suggest that the regio- and enantio-selectivities originate from the cyclopropene insertion to the Rh-H bond. The high regioselectivity is found to benefit from the presence of more efficient noncovalent interactions (NCIs) manifesting in the form of C-H···Cl, C-H···N, and l.p(Cl)···π contacts.
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OBJECTIVE: To investigate the extent of knowledge about breastfeeding and attitudes towards infant feeding among spouses of puerperas at the time of discharge from hospital, and explore the factors influencing spousal attitudes toward breastfeeding. METHODS: We conducted a questionnaire survey among 204 spouses of puerperas who were admitted in the maternity wards at a tertiary hospital in Shaanxi Province between October 2021 and December 2021. Respondents who fulfilled the inclusion criteria were identified using convenient sampling. RESULTS: (1) The score of breastfeeding knowledge among spouses prior to discharge from the hospital was (10.56 ± 3.78), with an accuracy rate of 59.6%, and the lowest accuracy rate was for Item 1 "Newborns should be fed on time, not on demand" (42.6%) and Item 5 "Breastfeeding can prevent infant rickets" (49.5%). (2) The average score of spouses' infant feeding attitudes was (58.15 ± 5.55), and the lowest scoring was for Item 17 "Daily urine volume of infants is a reliable indicator to judge whether they get enough breast milk" (1.99 ± 1.14). (3) Generalized linear model analysis showed a more positive attitude (higher score) among spousal attitudes towards infant feeding in those who had received breastfeeding education [OR = 4.588, 95% CI (0.160 â¼ 3.598)] and those with a master's degree or above [OR = 18.278, 95% CI (3.471 â¼ 9.346)]. CONCLUSION: (1) Spouses that received breastfeeding education and those that had a Masters Degree and above had more positive attitude towards infant feeding. (2) Medical staff should focus on puerperas'spouses with degrees below master's level who had not received breastfeeding education. We recommend using a variety of education methods to enable them to acquire more knowledge on breastfeeding and develop a more positive attitude towards breastfeeding, which will further enhance spousal support for breastfeeding, thus positivizing postpartum co-parenting attitudes and improving the rate of exclusive breastfeeding.
Subject(s)
Breast Feeding , Health Knowledge, Attitudes, Practice , Spouses , Humans , Breast Feeding/psychology , Breast Feeding/statistics & numerical data , Spouses/psychology , Female , Adult , Male , Surveys and Questionnaires , Postpartum Period/psychology , China , Infant, NewbornABSTRACT
Azaphilones represent a particular group of fascinating pigments from fungal source, with easier industrialization and lower cost than the traditional plant-derived pigments, and they also display a wide range of pharmacological activities. Herein, 28 azaphilone analogs, including 12 new ones, were obtained from the fermentation culture of a marine fungus Penicillium sclerotium UJNMF 0503. Their structures were elucidated by MS, NMR and ECD analyses, together with NMR and ECD calculations and biogenetic considerations. Among them, compounds 1 and 2 feature an unusual natural benzo[d][1,3]dioxepine ring embedded with an orthoformate unit, while 3 and 4 represent the first azaphilone examples incorporating a novel rearranged 5/6 bicyclic core and a tetrahydropyran ring on the side chain, respectively. Our bioassays revealed that half of the isolates exhibited neuroprotective potential against H2O2-induced injury on RSC96 cells, while compound 13 displayed the best rescuing capacity toward the cell viability by blocking cellular apoptosis, which was likely achieved by upregulating the PI3K/Akt signaling pathway.
Subject(s)
Apoptosis , Benzopyrans , Dose-Response Relationship, Drug , Hydrogen Peroxide , Neuroprotective Agents , Penicillium , Phosphatidylinositol 3-Kinases , Pigments, Biological , Proto-Oncogene Proteins c-akt , Apoptosis/drug effects , Penicillium/chemistry , Neuroprotective Agents/pharmacology , Neuroprotective Agents/chemistry , Neuroprotective Agents/isolation & purification , Proto-Oncogene Proteins c-akt/metabolism , Proto-Oncogene Proteins c-akt/antagonists & inhibitors , Phosphatidylinositol 3-Kinases/metabolism , Pigments, Biological/pharmacology , Pigments, Biological/chemistry , Pigments, Biological/isolation & purification , Hydrogen Peroxide/pharmacology , Hydrogen Peroxide/antagonists & inhibitors , Molecular Structure , Benzopyrans/pharmacology , Benzopyrans/chemistry , Benzopyrans/isolation & purification , Structure-Activity Relationship , Animals , Cell Survival/drug effects , Rats , Signal Transduction/drug effectsABSTRACT
Zearalenone (ZEN) is widely found in foodstuffs and has serious harmful effects on female fertility, especially in pigs. Cyanidin-3-O-glucoside (C3G), a type of anthocyanin, exists in most dark fruits and vegetables; it has many positive dietary effects including as an antioxidant, anti-inflammatory, or anti-apoptotic agent. However, the beneficial effects of C3G alongside ZEN-induced damage in porcine oocytes and the underlying molecular mechanism have not been investigated. In this work, porcine cumulus-oocyte complexes (COCs) were divided into Control (Ctrl), ZEN, ZEN + C3G (Z + C), and C3G, and treated for 44-46 h in vitro. The results showed that C3G could alleviate ZEN-induced disorders of first polar body (PBI) extrusion, abnormalities of spindle assembly, cortical granule distribution, and mitochondrial distribution; these results were produced via restoring transzonal projections (TZPs), and inhibiting nicotinamide adenine dinucleotide phosphate oxidase (NOX4)-dependent oxidative stress and 'glucose regulatory protein 78/protein kinase-like endoplasmic reticulum kinase/α subunit of eukaryotic initiation factor 2α/activating transcription factor 4/C/EBP-homologous protein' (GRP78/PERK/eIF2α/ATF4/CHOP)-mediated endoplasmic reticulum stress (ERS) during oocyte maturation. Moreover, the over-expression of NOX4 in cumulus cells could result in a significant increase in ROS levels and ER fluorescence intensity in oocytes. In conclusion, C3G promoted in vitro maturation of porcine oocytes exposed to ZEN via mitigating NOX4-dependent oxidative stress and ERS in cumulus cells. These results contribute to our comprehension of the molecular mechanisms underlying the protective effects of C3G against ZEN toxicity in porcine oocytes, and they provide a novel theoretical foundation and strategy for future applications of C3G in the improvement of female reproduction.
Subject(s)
Anthocyanins , Cumulus Cells , Endoplasmic Reticulum Stress , Glucosides , NADPH Oxidase 4 , Oocytes , Oxidative Stress , Zearalenone , Animals , Cumulus Cells/drug effects , Swine , Endoplasmic Reticulum Stress/drug effects , Oocytes/drug effects , Oxidative Stress/drug effects , NADPH Oxidase 4/metabolism , Zearalenone/toxicity , Female , Anthocyanins/pharmacology , Glucosides/pharmacology , Reactive Oxygen Species/metabolism , Antioxidants/pharmacology , Antioxidants/metabolismABSTRACT
The construction of materials regulated by chemical reaction networks requires regulatory motifs that can be stacked together into systems with desired properties. Multiple autocatalytic reactions producing thiols are known. However, negative feedback loop motifs are unavailable for thiol chemistry. Here, we develop a negative feedback loop based on the selenocarbonates. In this system, thiols induce the release of aromatic selenols that catalyze the oxidation of thiols by organic peroxides. This negative feedback loop has two important features. First, catalytic oxidation of thiols follows Michaelis-Menten-like kinetics, thus increasing nonlinearity for the negative feedback. Second, the strength of the negative feedback can be tuned by varying substituents in selenocarbonates. When combined with the autocatalytic production of thiols in a flow reactor, this negative feedback loop induces sustained oscillations. The availability of this negative feedback motif enables the future construction of oscillatory, homeostatic, adaptive, and other regulatory circuits in life-inspired systems and materials.
ABSTRACT
Parasite-specific CD4+ Th1 cell responses are the predominant immune effector for controlling malaria infection; however, the underlying regulatory mechanisms remain largely unknown. This study demonstrated that ATG5 deficiency in myeloid cells can significantly inhibit the growth of rodent blood-stage malarial parasites by selectively enhancing parasite-specific CD4+ Th1 cell responses. This effect was independent of ATG5-mediated canonical and non-canonical autophagy. Mechanistically, ATG5 deficiency suppressed FAS-mediated apoptosis of LY6G- ITGAM/CD11b+ ADGRE1/F4/80- cells and subsequently increased CCL2/MCP-1 production in parasite-infected mice. LY6G- ITGAM+ ADGRE1- cell-derived CCL2 selectively interacted with CCR2 on CD4+ Th1 cells for their optimized responses through the JAK2-STAT4 pathway. The administration of recombinant CCL2 significantly promoted parasite-specific CD4+ Th1 responses and suppressed malaria infection. Conclusively, our study highlights the previously unrecognized role of ATG5 in modulating myeloid cells apoptosis and sequentially affecting CCL2 production, which selectively promotes CD4+ Th1 cell responses. Our findings provide new insights into the development of immune interventions and effective anti-malarial vaccines.Abbreviations: ATG5: autophagy related 5; CBA: cytometric bead array; CCL2/MCP-1: C-C motif chemokine ligand 2; IgG: immunoglobulin G; IL6: interleukin 6; IL10: interleukin 10; IL12: interleukin 12; MFI: mean fluorescence intensity; JAK2: Janus kinase 2; LAP: LC3-associated phagocytosis; MAP1LC3/LC3: microtubule-associated protein 1 light chain 3; pRBCs: parasitized red blood cells; RUBCN: RUN domain and cysteine-rich domain containing, Beclin 1-interacting protein; STAT4: signal transducer and activator of transcription 4; Th1: T helper 1 cell; Tfh: follicular helper cell; ULK1: unc-51 like kinase 1.
Subject(s)
Autophagy-Related Protein 5 , Chemokine CCL2 , Malaria , Myeloid Cells , Th1 Cells , Animals , Autophagy-Related Protein 5/metabolism , Chemokine CCL2/metabolism , Th1 Cells/immunology , Malaria/immunology , Malaria/parasitology , Mice , Myeloid Cells/metabolism , Autophagy/drug effects , Mice, Inbred C57BL , Apoptosis/drug effects , Signal Transduction/drug effects , CD4-Positive T-Lymphocytes/immunology , CD4-Positive T-Lymphocytes/metabolism , Plasmodium berghei/immunologyABSTRACT
BACKGROUND: Little is known about the long-term trends of preterm birth rates in China and their geographic variation by province. OBJECTIVES: To estimate the annual spatial-temporal distribution of preterm birth rates in China by province from 1990 to 2020. DATA SOURCES: We searched PubMed, EMBASE, Web of Science, CNKI, WANFANG and VIP from January 1990 to September 2023. STUDY SELECTION AND DATA EXTRACTION: Studies that provided data on preterm births in China after 1990 were included. Data were extracted following the Guidelines for Accurate and Transparent Health Estimates Reporting. SYNTHESIS: We assessed the quality of each survey using a 9-point checklist. We estimated the annual preterm birth risk by province using Bayesian multilevel logistic regression models considering potential socioeconomic, environmental, and sanitary predictors. RESULTS: Based on 634 survey data from 343 included studies, we found a gradual increase in the preterm birth risk in most provinces in China since 1990, with an average annual increase of 0.7% nationally. However, the preterm birth rates in Inner Mongolia, Hubei, and Fujian Province showed a decline, while those in Sichuan were quite stable since 1990. In 2020, the estimates of preterm birth rates ranged from 2.9% (95% Bayesian credible interval [BCI] 2.1, 3.8) in Inner Mongolia to 8.5% (95% BCI 6.6, 10.9) in Jiangxi, with the national estimate of 5.9% (95% BCI 4.3, 8.1). Specifically, some provinces were identified as high-risk provinces for either consistently high preterm birth rates (e.g. Jiangxi) or relatively large increases (e.g. Shanxi) since 1990. CONCLUSIONS: This study provides annual information on the preterm birth risk in China since 1990 and identifies high-risk provinces to assist in targeted control and intervention for this health issue.
Subject(s)
Premature Birth , Female , Infant, Newborn , Humans , Premature Birth/epidemiology , Bayes Theorem , China/epidemiology , Birth RateABSTRACT
BACKGROUND: Physical activity(PA) is associated with health-related quality of life (HRQoL) among older adults, and both are associated with mood, such as depression. However, the indirect effects of PA on HRQoL in older adults have not been clearly established. This study explained how different types and intensities of PA were associated with HRQoL while considering the effects of depression in older adults. METHODS: A cross-sectional study was conducted with 7,518 community-dwelling older adults aged 60 years and older. PA (leisure-time, household, and work-related), depression, and HRQoL were measured using the Physical Activity Scale for the Elderly (PASE), the 30-item Geriatric Depression Scale (GDS-30), and the 36-Item Short-Form Health Survey (SF-36), respectively. Information on age, gender, education, monthly income, activities of daily living, smoking, and alcohol drinking was also collected. Regression analysis was used to explore the relationship between PA, depression and HRQoL, and a mediation effect test process was used to verify the mediating mechanism of the depression on this relationship. RESULTS: The study showed that after adjusting for a set of covariates, SF-36 Physical Component Summary (PCS) scores were negatively associated with depression (B = -2.046, 95% CI [2.584, -1.509]) and positively with PA (p < 0.001). Similarly, SF-36 Mental Component Summary (MCS) scores were negatively associated with depression (B = -11.657, 95% CI [-12.190, -11.124]). In mediation analyses, we found that depression partially mediated the relationship between different types and intensities PA and PCS (moderate leisure-time PA: B = 0.223, 95%CI [0.153,0.293], P < 0.001; vigorous leisure-time PA: B = 0.323, 95%CI [0.232,0.413], P < 0.001; moderate household PA: B = 0.092, 95%CI [0.045,0.139], P < 0.001; vigorous household PA: B = 0.137, 95%CI [0.085,0.190], P < 0.001; work-related PA: B = 0.193, 95%CI [0.658,0.190], P < 0.001) and MCS (moderate leisure-time PA: B = 1.243, 95%CI [1.008,1.479], P < 0.001; vigorous leisure-time PA: B = 1.800, 95%CI [1.585,2.015], P < 0.001; moderate household PA: B = 0.496, 95%CI [0.274,0.718], P < 0.001; vigorous household PA: B = 0.742, 95%CI [0.521,0.963], P < 0.001; work-related PA: B = 1.026, 95%CI [0.819,1.234], P < 0.001). CONCLUSIONS: This study suggested that leisure-time, household, and work-related PA were negatively associated with depression, while positively affecting HRQoL in Chinese older adults. The relationships between different types and intensities of PA and HRQoL were mediated by depression. Interventions aimed at promoting purposeful exercise and different types of PA may have mental health benefits. It is recommended that geriatric health managers and healthcare planners prioritize interventions to help improve PA intensities, alleviate depressive symptoms to promote beneficial effects on HRQoL in older adults.
Subject(s)
Activities of Daily Living , Quality of Life , Aged , Humans , Middle Aged , Cross-Sectional Studies , Depression/diagnosis , Depression/epidemiology , ExerciseABSTRACT
Most fresh bananas belong to the Cavendish and Gros Michel subgroups. Here, we report chromosome-scale genome assemblies of Cavendish (1.48 Gb) and Gros Michel (1.33 Gb), defining three subgenomes, Ban, Dh and Ze, with Musa acuminata ssp. banksii, malaccensis and zebrina as their major ancestral contributors, respectively. The insertion of repeat sequences in the Fusarium oxysporum f. sp. cubense (Foc) tropical race 4 RGA2 (resistance gene analog 2) promoter was identified in most diploid and triploid bananas. We found that the receptor-like protein (RLP) locus, including Foc race 1-resistant genes, is absent in the Gros Michel Ze subgenome. We identified two NAP (NAC-like, activated by apetala3/pistillata) transcription factor homologs specifically and highly expressed in fruit that directly bind to the promoters of many fruit ripening genes and may be key regulators of fruit ripening. Our genome data should facilitate the breeding and super-domestication of bananas.
Subject(s)
Fusarium , Musa , Musa/genetics , Fusarium/genetics , Triploidy , Plant Breeding , Transcription Factors/genetics , Plant Diseases/geneticsABSTRACT
Zearalenone (ZEN) is well known as a kind of endocrine disruptor whose exposure is capable of causing reproductive toxicity in animals. Cyanidin-3-O-glucoside (C3G) is a derivative of cyanidin and owns multiple biofunctions, and prior efforts have suggested that C3G has therapeutic actions for reproductive diseases. In this article, a ZEN exposure model during primordial follicle assembly was constructed using the in vitro culture platform of neonatal mouse ovaries. We investigated the protective effect of C3G on ZEN-induced ovarian toxicity during primordial follicle assembly in mice, as well as its potential mechanism. Interestingly, we observed that C3G could effectively protect the ovary from ZEN damage, mainly by restoring primordial follicle assembly, which upregulated the expression of LHX8 and SOHLH1 proteins and relieved ZEN-induced DNA damage. Next, to explore the mechanism by which C3G rescued ZEN-induced injury, we performed RNA sequencing (RNA-seq). The bioinformatic analysis illustrated that the rescue pathway of C3G was associated with p53-Gadd45a signaling and cell cycle. Then, western blotting and flow cytometry results revealed that C3G restored the expression levels of cyclin-dependent kinase 6 (CDK6) and cyclin D2 (CCND2) and regulated the ovarian cell cycle to normal. In conclusion, our findings manifested that C3G could alleviate ZEN-induced primordial follicle assembly impairment by restoring the cell cycle involved in p53-GADD45a signaling.
Subject(s)
Ovary , Zearalenone , Female , Animals , Mice , Zearalenone/toxicity , Tumor Suppressor Protein p53 , Anthocyanins/pharmacology , Glucosides/pharmacologyABSTRACT
Background: Iron deficiency (ID) and iron deficiency anemia (IDA) during pregnancy are highly prevalent worldwide. Hepcidin is considered an important biomarker of iron status. Currently, few longitudinal cohort studies have assessed the potential causal relationship between hepcidin and ID/IDA. Therefore, we aimed to investigate the association of first-trimester maternal serum hepcidin with third-trimester ID/IDA risk in a prospective cohort. Methods: Total of 353 non-ID/IDA pregnant women at 11-13 weeks' gestation were enrolled in Southern China and followed up to 38 weeks of gestation. Data on demography and anthropometry were obtained from a structured questionnaire at enrollment. Iron biomarkers including hepcidin were measured at enrollment and follow-up. Regression models were used to evaluate the association of first-trimester hepcidin with third-trimester ID/IDA risk. Results: Serum hepcidin levels substantially decreased from 19.39 ng/mL in the first trimester to 1.32 ng/mL in the third trimester. Incidences of third-trimester ID and IDA were 46.2 and 11.4%, respectively. Moreover, moderate and high levels of first-trimester hepcidin were positively related to third-trimester hepcidin (log-transformed ß = 0.51; 95% CI = 0.01, 1.00 and log-transformed ß = 0.66; 95% CI = 0.15, 1.17). Importantly, elevated first-trimester hepcidin was significantly associated with reduced risk of third-trimester IDA (OR = 0.38; 95% CI = 0.15, 0.99), but not with ID after adjustment with potential confounders. Conclusion: First-trimester hepcidin was negatively associated with IDA risk in late pregnancy, indicating higher first-trimester hepcidin level may predict reduced risk for developing IDA. Nonetheless, given the limited sample size, larger studies are still needed.
ABSTRACT
Long non-coding RNA (lncRNA), a class of RNA molecules with transcripts longer than 200 nt, is crucial for maintaining animal reproductive function. Zearalenone (ZEN) damaged animal reproduction by targeting ovarian granulosa cells (GCs), especially in pigs. Nonetheless, it is not quite clear that whether Cyanidin-3-O-glucoside (C3G) exert effects on porcine GCs (pGCs) after ZEN exposure by altering lncRNA expression. Here, we sought to gain novel information regarding C3G protect against damages induced by ZEN in pGCs. The pGCs were divided into control (Ctrl), ZEN, ZEN + C3G (Z + C), and C3G groups. Results revealed that C3G effectively increased cell viability and suppressed ZEN-induced apoptosis in pGCs. 87 and 82 differentially expressed lncRNAs (DELs) were identified in ZEN vs. Ctrl and Z + C vs. ZEN group, respectively. Gene Ontology (GO) analysis observed that the DELs were related to cell metabolism and cell-matrix adhesion biological processes. The Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis found that the DELs were associated with the phosphatidylinositide 3-kinases (PI3K)-protein kinase B (AKT) signaling pathway. In brief, we demonstrated that C3G could shield apoptosis induced by ZEN, which may be connected with the changes of lncRNA expression profiles in pGCs. This study complemented our understanding of the genetic basis and molecular mechanisms by which C3G mitigated the toxicity of ZEN in pGCs.
Subject(s)
RNA, Long Noncoding , Zearalenone , Female , Swine , Animals , Zearalenone/toxicity , Zearalenone/metabolism , RNA, Long Noncoding/genetics , Glucosides/pharmacology , Glucosides/metabolism , Granulosa Cells/metabolismABSTRACT
A guest molecule containing a short alkyl spacer between the tetraphenylethylene group and the methylpyridinium group was designed and synthesized. After complexation with a water-soluble pillar[5]arene, the resulting host-guest complex can further self-assemble into fluorescence-emitting nanoparticles in water. By loading a commercially available dye Rhodamine 6G into the nanoparticles, an efficient artificial light-harvesting system with high donor/acceptor ratios (>400/1) was successfully constructed. The obtained systems show considerable antenna effects with values of more than 10â times. The system also exhibits tunable fluorescence emission behavior and can be used as a fluorescent ink for information encryption.