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1.
Dalton Trans ; 2024 May 07.
Article in English | MEDLINE | ID: mdl-38713392

ABSTRACT

Potassium borate glass has great potential as an ion transport material. The ion transport rate is closely related to the microstructure of the glass. However, the disorder and variations in boron and oxygen atom types in the glass structure pose challenges in the analysis of this complex glass structure. In this work, the structure of potassium borate glass was unveiled through the neutron diffraction method and ab initio molecular dynamics (AIMD) simulations. The B-O, K-O, and O-O atomic interactions, bond lengths, coordination numbers, cavity distribution, ring structure distributions and other detailed information in the microstructure of potassium borate glass were obtained. By comparing the structure and properties of potassium borate glass with those of crystals of similar components, it is found that the bond lengths of 3B-BO (BO, bridging oxygen), 4B-BO and 3B-NBO (NBO, non-bridging oxygen) are longer than those of corresponding crystals, so the structure of the boron-oxygen network is looser and the density is smaller than that of similar crystals. Moreover, we found a rule that in both borate glass and crystal, the increase of NBO shortened the length of the B-O bond, and the increase of 4B increased the length of the B-O bond. The key structures affecting the transport rate of K+ were NBO, chain structure units and cavities. This work will provide reference data for designing and developing electrically conductive amorphous materials with faster potassium-ion transport rates.

2.
Ultrason Sonochem ; 106: 106883, 2024 Apr 26.
Article in English | MEDLINE | ID: mdl-38703594

ABSTRACT

Ultrasound has been widely used in industry due to its high energy and efficiency. This study optimized the ultrasonic-assisted extraction (UAE) process of frosted figs pectin (FFP) using response surface methodology (RSM), and further investigated the effect of ultrasonic power on the structural characteristics and antioxidant activities of FFPs. The UAE method of FFP through RSM was optimized, and the optimal extraction process conditions, particle size of 100 mesh, pH value of 1.95, liquid-solid ratio of 47:1 (mL/g), extraction temperature of 50 °C and extraction time of 65 min, were obtained. The extraction rate of FFP under this condition was 37.97 ± 2.56 %. Then, the four FFPs modified by ultrasound were obtained by changing the ultrasonic power. Research had found that ultrasonic power had little effect on the monosaccharide composition, Zeta potential, as well as the thermal stability and appearance structure of the four FFPs. However, ultrasonic power had a significant impact on other properties of FFP: as the ultrasonic power increased, the DM% and particle size decreased continuously, while the total carbohydrate content increased. Meanwhile, ultrasonic power also had a significant impact on antioxidant activities of FFPs. From the research results, it could be seen that different ultrasonic power had certain changes in its spatial structure and properties, and the structural changes also affected the biological activity of FFP. The study of the effects of ultrasonic power on the physicochemical properties and biological activity of FFP lays the foundation for the development and application of FFP in food additives and natural drug carriers.

3.
Chem Soc Rev ; 53(8): 4020-4044, 2024 Apr 22.
Article in English | MEDLINE | ID: mdl-38444346

ABSTRACT

The process of coordinating between the same or multiple types of cells to jointly execute various instructions in a controlled and carefully regulated environment is a very appealing field. In order to provide clearer insight into the role of cell-cell interactions and the cellular communication of this process in their local communities, several interdisciplinary approaches have been employed to enhance the core understanding of this phenomenon. DNA nanostructures have emerged in recent years as one of the most promising tools in exploring cell-cell communication and interactions due to their programmability and addressability. Herein, this review is dedicated to offering a new perspective on using DNA nanostructures to explore the progress of cell-cell communication. After briefly outlining the anchoring strategy of DNA nanostructures on cell membranes and the subsequent dynamic regulation of DNA nanostructures, this paper highlights the significant contribution of DNA nanostructures in monitoring cell-cell communication and regulating its interactions. Finally, we provide a quick overview of the current challenges and potential directions for the application of DNA nanostructures in cellular communication and interactions.


Subject(s)
Cell Communication , DNA , Nanostructures , Nanostructures/chemistry , DNA/chemistry , Humans , Animals , Cell Membrane/chemistry , Cell Membrane/metabolism
4.
J Comput Chem ; 45(17): 1456-1469, 2024 Jun 30.
Article in English | MEDLINE | ID: mdl-38471809

ABSTRACT

B 6 O 7 OH 6 2 - is a highly polymerized borate anion of three six-membered rings. Limited research on the B 6 O 7 OH 6 2 - hydrolysis mechanism under neutral solution conditions exists. Calculations based on density functional theory show that B 6 O 7 OH 6 2 - undergoes five steps of hydrolysis to form H3BO3 and B OH 4 - . At the same time, there are a small number of borate ions with different degrees of polymerization during the hydrolysis process, such as triborate, tetraborate, and pentaborate anions. The structure of the borate anion and the coordination environment of the bridging oxygen atoms control the hydrolysis process. Finally, this work explains that in existing experimental studies, the reason for the low B 6 O 7 OH 6 2 - content in solution environments with low total boron concentrations is that it depolymerizes into other types of borate ions and clarifies the borate species. The conversion relationship provides a basis for identifying the possibility of various borate ions existing in the solution. This work also provides a certain degree of theoretical support for the cause of the "dilution to salt" phenomenon.

5.
Plant Biotechnol J ; 2024 Feb 28.
Article in English | MEDLINE | ID: mdl-38415985

ABSTRACT

Fruit firmness is an important trait in sweet cherry breeding because it directly positively influences fruit transportability, storage and shelf life. However, the underlying genes responsible and the molecular mechanisms that control fruit firmness remain unknown. In this study, we identified a candidate gene, PavSCPL, encoding a serine carboxypeptidase-like protein with natural allelic variation, that controls fruit firmness in sweet cherry using map-based cloning and functionally characterized PavSCPL during sweet cherry fruit softening. Genetic analysis revealed that fruit firmness in the 'Rainier' × 'Summit' F1 population was controlled by a single dominant gene. Bulked segregant analysis combined with fine mapping narrowed the candidate gene to a 473-kb region (7418778-7 891 914 bp) on chromosome 6 which included 72 genes. The candidate gene PavSCPL, and a null allele harbouring a 5244-bp insertion in the second exon that completely inactivated PavSCPL expression and resulted in the extra-hard-flesh phenotype, were identified by RNA-sequencing analysis and gene cloning. Quantitative RT-PCR analysis revealed that the PavSCPL expression level was increased with fruit softening. Virus-induced gene silencing of PavSCPL enhanced fruit firmness and suppressed the activities of certain pectin-degrading enzymes in the fruit. In addition, we developed functional molecular markers for PavSCPL and the Pavscpl5.2-k allele that co-segregated with the fruit firmness trait. Overall, this research identified a crucial functional gene for fruit firmness. The results provide insights into the genetic control and molecular mechanism of the fruit firmness trait and present useful molecular markers for molecular-assisted breeding for fruit firmness in sweet cherry.

6.
Org Biomol Chem ; 22(9): 1770-1774, 2024 Feb 28.
Article in English | MEDLINE | ID: mdl-38324332

ABSTRACT

A facile and efficient method for constructing 2,3-diacyl trisubstituted furans via a silver-mediated radical process of ß-keto sulfones is developed. The reaction mechanism has been carefully investigated, revealing that the transformation proceeds through a radical pathway, leading to moderate to good yields of desired products.

7.
Environ Sci Pollut Res Int ; 31(13): 19674-19686, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38363509

ABSTRACT

Evidence around the relationship between air pollution and the development of diabetes mellitus (DM) remains limited and inconsistent. To investigate the potential mediation effect of asprosin on the association between fine particulate matter (PM2.5), tropospheric ozone (O3) and blood glucose homeostasis. A case-control study was conducted on a total of 320 individuals aged over 60 years, including both diabetic and non-diabetic individuals, from six communities in Taiyuan, China, from July to September 2021. Generalized linear models (GLMs) suggested that short-term exposure to PM2.5 was associated with elevated fasting blood glucose (FBG), insulin resistance index (HOMA-IR), as well as reduced pancreatic ß-cell function index (HOMA-ß), and short-term exposure to O3 was associated with increased FBG and decreased HOMA-ß in the total population and elderly diabetic patients. Mediation analysis showed that asprosin played a mediating role in the relationship of PM2.5 and O3 with FBG, with mediating ratios of 10.2% and 18.4%, respectively. Our study provides emerging evidence supporting that asprosin mediates the short-term effects of exposure to PM2.5 and O3 on elevated FBG levels in an elderly population. Additionally, the elderly who are diabetic, over 70 years, and BMI over 24 kg/m2 are more vulnerable to air pollutants and need additional protection to reduce their exposure to air pollution.


Subject(s)
Air Pollutants , Air Pollution , Diabetes Mellitus , Fibrillin-1 , Aged , Humans , Middle Aged , Air Pollutants/adverse effects , Air Pollution/adverse effects , Blood Glucose/metabolism , Case-Control Studies , China/epidemiology , Diabetes Mellitus/metabolism , Environmental Exposure/analysis , Particulate Matter/analysis , Fibrillin-1/metabolism , Adipokines/metabolism
8.
Infancy ; 29(3): 302-326, 2024.
Article in English | MEDLINE | ID: mdl-38217508

ABSTRACT

The valid assessment of vocabulary development in dual-language-learning infants is critical to developmental science. We developed the Dual Language Learners English-Spanish (DLL-ES) Inventories to measure vocabularies of U.S. English-Spanish DLLs. The inventories provide translation equivalents for all Spanish and English items on Communicative Development Inventory (CDI) short forms; extended inventories based on CDI long forms; and Spanish language-variety options. Item-Response Theory analyses applied to Wordbank and Web-CDI data (n = 2603, 12-18 months; n = 6722, 16-36 months; half female; 1% Asian, 3% Black, 2% Hispanic, 30% White, 64% unknown) showed near-perfect associations between DLL-ES and CDI long-form scores. Interviews with 10 Hispanic mothers of 18- to 24-month-olds (2 White, 1 Black, 7 multi-racial; 6 female) provide a proof of concept for the value of the DLL-ES for assessing the vocabularies of DLLs.


Subject(s)
Citrus sinensis , Malus , Multilingualism , Child , Infant , Humans , Female , Vocabulary , Child Language , Language Tests , Language
9.
Int J Hyg Environ Health ; 256: 114324, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38271819

ABSTRACT

BACKGROUND: Women with multiple pregnancies are vulnerable to experience postpartum depression (PPD). Emerging evidence indicates an association between poly- and perfluoroalkyl substances (PFAS) exposure and PPD in women delivering singletons. The health risks of PFAS may also be present in women delivering twins. OBJECTIVE: To estimate the impacts of prenatal PFAS exposure on the risk of PPD in women with twin pregnancies. METHODS: Our study included 150 mothers who gave birth to twins and were enrolled in the Wuhan Twin Birth Cohort. The concentrations of maternal plasma PFAS were measured in each trimester and averaged. Eight individual PFAS were included in analyses. We used Edinburgh Postnatal Depression Scale to evaluate maternal depression at early pregnancy and 1 and 6 months after childbirth. The outcome was dichotomized using a cutoff value of ≥10 for main analyses. Associations were examined using multiple informant models and modified Poisson regressions. PFAS mixture effects were estimated using quantile g-computation. RESULTS: Using quantile g-computation models, a quartile increase in the PFAS mixture during the first, second, third, and average pregnancy was significantly associated with a relative risk (RR) of 1.73 (95% CI: 1.42, 2.12), 1.54 (95% CI: 1.27, 1.84), 1.75 (95% CI: 1.49, 2.08), and 1.63 (95% CI: 1.35, 1.97) for PPD at 6 months after childbirth, respectively. The results of the single-PFAS models also indicated significant positive associations between individual PFAS and PPD at both 1 and 6 months. CONCLUSIONS: The first study of women with twin pregnancies suggests that prenatal exposure to PFAS increases PPD risk up to 6 months postpartum. Twin pregnant women should receive long-term follow-up after delivery and extensive social support.


Subject(s)
Alkanesulfonic Acids , Depression, Postpartum , Environmental Pollutants , Fluorocarbons , Prenatal Exposure Delayed Effects , Humans , Pregnancy , Female , Pregnancy, Twin , Depression, Postpartum/epidemiology
10.
Physiol Plant ; 175(6): e14065, 2023.
Article in English | MEDLINE | ID: mdl-38148242

ABSTRACT

For sweet cherry, fruit size is one of the main targets in breeding programs owing to the high market value of larger fruits. KLUH/CYP78A5 is an important regulator of seed/fruit size in several plant species, but its molecular mechanism is largely unknown. In this study, we characterized the function of PavKLUH in the regulation of sweet cherry fruit size. The ectopic overexpression of PavKLUH in Arabidopsis increased the size of its siliques and seeds, whereas virus-induced gene silencing of PavKLUH in sweet cherry significantly decreased fruit size by restricting mesocarp cell expansion. We screened out an AP2/ERF transcription factor containing a B3-like domain, designated as PavRAV2, which was able to physically interact with PavKLUH promoter in a yeast one-hybrid (Y1H) system. In Y1H assays, electrophoretic mobility shift assays, and dual-luciferase reporter analyses, PavRAV2 directly bound to the promoter of PavKLUH in vitro and in vivo, and suppressed PavKLUH expression. Silencing of PavRAV2 resulted in enlarged fruit as a result of enhanced mesocarp cell expansion. Together, our results provide new insights into signaling pathways related to fruit size, and outline a possible mechanism for how the RAV transcription factor directly regulates CYP78A family members to influence fruit size and development.


Subject(s)
Prunus avium , Fruit/metabolism , Transcription Factors/genetics , Transcription Factors/metabolism , Promoter Regions, Genetic/genetics , Signal Transduction , Gene Expression Regulation, Plant/genetics , Plant Proteins/genetics , Plant Proteins/metabolism
11.
Environ Geochem Health ; 46(1): 10, 2023 Dec 23.
Article in English | MEDLINE | ID: mdl-38142250

ABSTRACT

This study aimed to assess the relationships between exposure to individual organochlorine pesticides (OCPs), polychlorinated biphenyls (PCBs), and their mixture and arterial stiffness and explore whether adherence to an ideal cardiovascular health (CVH) could mitigate these associations. The cross-sectional study enrolled 1437 Chinese adults between March and May 2019 in Wuhan, China. OCPs and PCBs concentrations were measured using solid phase extraction coupled with gas chromatography-tandem mass spectrometry. Arterial stiffness was evaluated by brachial-ankle pulse wave velocity (baPWV). CVH was determined by three behavioral and four biological metrics and categorized as ideal, intermediate, and poor CVH. We applied generalized linear model and weighted quantile sum (WQS) regression to evaluate the associations of exposure to individual OCPs or PCBs and their mixture with baPWV, respectively. We found that participants with detectable levels of heptachlor epoxide, PCB-153, and PCB-180 had higher baPWV (ß: 34.25, 95% CI 14.28-54.22; ß: 27.64, 95% CI 7.90-47.38; and ß: 30.51, 95% CI 10.68-50.35) than those with undetectable levels. In WQS regression, the mixture of OCPs and PCBs was related to a higher baPWV (ß: 24.93, 95% CI 2.70-47.15). Compared with participants with ideal CVH and undetectable OCPs or PCBs levels, those with poor CVH and detectable OCPs or PCBs levels had the highest increase in baPWV (heptachlor epoxide: ß: 147.94, 95% CI 112.52-183.55; PCB-153: ß: 150.22, 95% CI 115.40-185.04; PCB-180: ß: 147.02, 95% CI 111.66-182.38). Our findings suggested that individual OCPs, PCBs, and their mixture exposure were positively associated with arterial stiffness, and adherence to an ideal CVH may mitigate the adverse effect.


Subject(s)
Hydrocarbons, Chlorinated , Pesticides , Polychlorinated Biphenyls , Vascular Stiffness , Adult , Humans , Polychlorinated Biphenyls/analysis , Heptachlor Epoxide/analysis , Ankle Brachial Index , Cross-Sectional Studies , Environmental Monitoring/methods , Gas Chromatography-Mass Spectrometry , Pulse Wave Analysis , Hydrocarbons, Chlorinated/analysis , Pesticides/analysis
12.
Reprod Toxicol ; 122: 108495, 2023 12.
Article in English | MEDLINE | ID: mdl-37926172

ABSTRACT

Imbalance or deficiencies of essential metals can lead to oxidative stress, that can damage mitochondrial DNA (mtDNA) molecule. Knowledge on effects of exposure to essential metals and their mixture remains limited. We aimed to evaluate individual and joint associations of prenatal essential metals with neonatal mtDNA copy number. We recruited 746 mother-newborn pairs from a birth cohort study conducted in Wuhan City, China, and collected trimester-specific urine and cord blood samples. We measured the concentrations of seven urinary essential metals, include zinc (Zn), iron (Fe), selenium (Se), cobalt (Co), manganese (Mn), copper (Cu), and chromium (Cr), using inductively coupled plasma mass spectrometry, and measured cord blood mtDNA copy number using real-time quantitative polymerase chain reaction. We estimated the trimester-specific associations of individual essential metal concentrations with mtDNA copy number using a multiple informant model, and assessed their joint association using weighted quantile sum (WQS) regression. For individual essential metal, a doubling of maternal urinary Zn concentrations during the second trimester was associated with a 7.47% (95% CI: 1.17-14.17%) higher level of neonatal mtDNA copy number. For the essential metal mixture, one-unit increased in the WQS index of the essential metals mixture during the second trimester resulted in a 10.41% (95% CI: 3.04-18.30%) increase in neonatal mtDNA copy number. Our findings suggest that exposure to both Zn and essential metal mixture during the second trimester is associated with a higher neonatal mtDNA copy number. Further research should assess whether mtDNA copy number is associated with child health.


Subject(s)
DNA Copy Number Variations , DNA, Mitochondrial , Pregnancy , Infant, Newborn , Female , Child , Humans , DNA, Mitochondrial/genetics , Cohort Studies , Maternal Exposure/adverse effects , Metals/toxicity , Zinc
13.
Sci Rep ; 13(1): 15321, 2023 09 15.
Article in English | MEDLINE | ID: mdl-37714886

ABSTRACT

The relation between exposure to single metal/metalloid and the risk of chronic kidney disease (CKD) remains unclear. We aimed to determine the single and mixed associations of 21 heavy metals/metalloids exposure and the risk of CKD. We performed a cross-sectional study that recruited 4055 participants. Multivariate logistic regression, linear regression and weighted quantile sum (WQS) regression were conducted to explore the possible effects of single and mixed metals/metalloids exposure on the risk of CKD, the risk of albuminuria and changes in the estimated glomerular filtration rate (eGFR). In single-metal models, Cu, Fe, and Zn were positively associated with increased risks of CKD (P-trend < 0.05). Compared to the lowest level, the highest quartiles of Cu (OR = 2.94; 95% CI: 1.70, 5.11; P-trend < 0.05), Fe (OR = 2.39; 95% CI: 1.42, 4.02; P-trend < 0.05), and Zn (OR = 2.35; 95% CI: 1.31, 4.24; P-trend < 0.05) were associated with an increased risk of CKD. After multi-metal adjustment, the association with the risk of CKD remained robust for Cu (P < 0.05). Weighted quantile sum regression revealed a positive association between mixed metals/metalloids and the risk of CKD, and the association was largely driven by Cu (43.7%). Specifically, the mixture of urinary metals/metalloids was positively associated with the risk of albuminuria and negatively associated with eGFR.


Subject(s)
Metalloids , Renal Insufficiency, Chronic , Humans , Adult , Albuminuria/epidemiology , Cross-Sectional Studies , Metals , China/epidemiology , Renal Insufficiency, Chronic/epidemiology , Renal Insufficiency, Chronic/etiology
14.
Environ Sci Pollut Res Int ; 30(48): 106562-106570, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37726631

ABSTRACT

Recent research has reported positive associations of exposure to polychlorinated biphenyls (PCBs) and organochlorine pesticides (OCPs) with hyperuricemia. However, most of these studies have primarily focused on the individual effects of PCB/OCP exposure. We aimed to explore the associations of both individual and combined PCB/OCP exposure with hyperuricemia and examine whether such associations could be modified by lifestyle factors. The cross-sectional study recruited 2032 adults between March and May 2019 in Wuhan, China. Logistic regression and weighted quantile sum (WQS) regression were applied to explore the relationship of individual and combined PCB/OCP exposure with hyperuricemia, while considering the modified effects of lifestyle factors. Of the 2032 participants, 522 (25.7%) had hyperuricemia. Compared with the non-detected group, the detected groups of PCB153 and PCB180 exhibited a positive association with hyperuricemia, with OR (95% CIs) of 1.52 (1.22, 1.91) and 1.51 (1.20, 1.90), respectively. WQS regression showed that PCB/OCP mixture was positively associated with hyperuricemia (OR: 1.31, 95% CI: 1.08, 1.58). PCB153/PCB180 exposure, combined with an unhealthy lifestyle, has a significant additive effect on hyperuricemia. Overall, PCB/OCP mixture and individual PCB153/PCB180 exposure were positively associated with hyperuricemia. Adherence to a healthy lifestyle may modify the potential negative impact of PCBs/OCPs on hyperuricemia.


Subject(s)
Environmental Pollutants , Hydrocarbons, Chlorinated , Hyperuricemia , Pesticides , Polychlorinated Biphenyls , Adult , Humans , Polychlorinated Biphenyls/analysis , Hyperuricemia/epidemiology , Cross-Sectional Studies , Hydrocarbons, Chlorinated/analysis , Pesticides/analysis , Life Style
15.
Hum Reprod ; 38(11): 2239-2246, 2023 11 02.
Article in English | MEDLINE | ID: mdl-37671590

ABSTRACT

STUDY QUESTION: What are the associations between female-specific reproductive factors and leukocyte telomere length (LTL)? SUMMARY ANSWER: Early menarche, early menopause, short reproductive lifespan, early age at first birth, multiparity, and use of oral contraceptives (OCs) and hormone replacement therapy (HRT) were associated with shorter LTL. WHAT IS KNOWN ALREADY: Reproductive factors have been associated with age-related diseases, but their associations with cellular aging, as indicated by LTL, are unclear. STUDY DESIGN, SIZE, DURATION: This population-based study included 224 965 women aged 40-69 years from the UK Biobank between 2006 and 2010. PARTICIPANTS/MATERIALS, SETTING, METHODS: Women aged 40-69 were included. Female-specific reproductive factors, including age at menarche, age at natural menopause, reproductive lifespan, number of live births, age at first live birth, history of stillbirth, history of miscarriage, and use of OCs and HRT were self-reported. LTL was measured using a validated polymerase chain reaction method. Multiple linear regression and restricted cubic spline models were applied to explore the association between each reproductive factor and LTL. MAIN RESULTS AND THE ROLE OF CHANCE: After adjustment for potential confounders, early menarche (<12 years; percent change, per unit change in LTL Z score: -1.29%, 95% CI: -2.32%, -0.26%), early menopause (<45 years; percent change: -7.18%, 95% CI: -8.87%, -5.45%), short reproductive lifespan (<30 years; percent change: -6.10%, 95% CI: -8.14%, -4.01%), multiparity (percent change: -3.38%, 95% CI: -4.38%, -2.37%), early age at first live birth (<20 years; percent change: -4.46%, 95% CI: -6.00%, -2.90%), and use of OCs (percent change: -1.10%, 95% CI: -2.18%, -0.02%) and HRT (percent change: -3.72%, 95% CI: -4.63%, -2.80%) were all significantly associated with shorter LTL. However, no significant association was found for history of miscarriage and stillbirth. We observed nonlinear relationships of age at menarche, age at natural menopause, reproductive lifespan, and age at first live birth with LTL (Pnonlinear < 0.05). LIMITATIONS, REASONS FOR CAUTION: Considering that the participants were predominantly of European ethnicity, the findings may not be generalizable to women of other ethnic backgrounds. WIDER IMPLICATIONS OF THE FINDINGS: Our findings suggest that early menarche, early menopause, short reproductive lifespan, early age at first birth, multiparity, and use of OCs and HRT were associated with shorter LTL, which has been linked to various chronic diseases. The accelerated shortening of telomeres may potentially contribute to the development of chronic diseases related to reproductive factors. STUDY FUNDING/COMPETING INTEREST(S): This study was funded by the National Natural Science Foundation of China (82003479, 82073660), Hubei Provincial Natural Science Foundation of China (2023AFB663), and the China Postdoctoral Science Foundation (2019M662646, 2020T130220). The authors have no competing interests to disclose. TRIAL REGISTRATION NUMBER: N/A.


Subject(s)
Abortion, Spontaneous , Menopause, Premature , Pregnancy , Female , Humans , Stillbirth , Leukocytes , Live Birth , Contraceptives, Oral , Menstruation Disturbances , Telomere , Chronic Disease
16.
Molecules ; 28(16)2023 Aug 10.
Article in English | MEDLINE | ID: mdl-37630253

ABSTRACT

Almond expeller is an undeveloped reservoir of bioactive peptides. In the current study, a zinc ion ligand Arg-Pro-Pro-Ser-Glu-Asp-Glu-Asp-Gln-Glu (RPPSEDEDQE) offering a noncompetitive inhibitory effect on ACE (IC50: 205.50 µmol·L-1) was identified from almond albumin hydrolysates via papain and thermolysin hydrolysis, subsequent chromatographic separation, and UPLC-Q-TOF-MS/MS analysis. Molecular docking simulated the binding modes of RPPSEDEDQE to ACE and showed the formation of hydrogen bonds between RPPSEDEDQE and seven active residues of ACE. Moreover, RPPSEDEDQE could bind to fifteen active sites of ACE by hydrophobic interactions, and link with the His387 and zinc ions of the zinc tetrahedral coordination. Ultraviolet wavelength scanning and Fourier-transformed infrared spectroscopy analysis revealed that RPPSEDEDQE can provide multiple binding sites for zinc ions. However, RPPSEDEDQE cannot bind with any central pocket of ACE, which was evidenced by an inhibition kinetics experiment. Additionally, the zinc-chelating capacity and inhibiting ability against ACE of RPPSEDEDQE were both not significantly reduced by the hydrolysis of gastrointestinal enzymes. A moderate to high dose of RPPSEDEDQE (100-150 mg·kg bw-1) significantly reduced the systolic and diastolic blood pressure of spontaneous hypertensive rats, but chelation with zinc ions decreased its antihypertensive efficiency. These results indicate that bitter almond albumin peptides may be used for lowering blood pressure.


Subject(s)
Antihypertensive Agents , Prunus dulcis , Animals , Rats , Antihypertensive Agents/pharmacology , Molecular Docking Simulation , Tandem Mass Spectrometry , Peptides/pharmacology , Albumins
17.
J Med Chem ; 66(16): 11187-11200, 2023 08 24.
Article in English | MEDLINE | ID: mdl-37480587

ABSTRACT

The combination of library-based screening and artificial intelligence (AI) has been accelerating the discovery and optimization of hit ligands. However, the potential of AI to assist in de novo macrocyclic peptide ligand discovery has yet to be fully explored. In this study, an integrated AI framework called PepScaf was developed to extract the critical scaffold relative to bioactivity based on a vast dataset from an initial in vitro selection campaign against a model protein target, interleukin-17C (IL-17C). Taking the generated scaffold, a focused macrocyclic peptide library was rationally constructed to target IL-17C, yielding over 20 potent peptides that effectively inhibited IL-17C/IL-17RE interaction. Notably, the top two peptides displayed exceptional potency with IC50 values of 1.4 nM. This approach presents a viable methodology for more efficient macrocyclic peptide discovery, offering potential time and cost savings. Additionally, this is also the first report regarding the discovery of macrocyclic peptides against IL-17C/IL-17RE interaction.


Subject(s)
Artificial Intelligence , Interleukin-17 , Machine Learning , Peptides , Peptide Library
18.
Biomacromolecules ; 24(7): 3228-3236, 2023 07 10.
Article in English | MEDLINE | ID: mdl-37319440

ABSTRACT

Receptor dimerization is an essential mechanism for the activation of most receptor tyrosine kinases by ligands. Thus, regulating the nanoscale spatial distribution of cell surface receptors is significant for studying both intracellular signaling pathways and cellular behavior. However, there are currently very limited methods for exploring the effects of modulating the spatial distribution of receptors on their function by using simple tools. Herein, we developed an aptamer-based double-stranded DNA bridge acting as "DNA nanobridge", which regulates receptor dimerization by changing the number of bases. On this basis, we confirmed that the different nanoscale arrangements of the receptor can influence receptor function and its downstream signals. Among them, the effect gradually changed from helping to activate to inhibiting as the length of DNA nanobridge increased. Hence, it can not only effectively inhibit receptor function and thus affect cellular behavior but also serve as a fine-tuning tool to get the desired signal activity. Our strategy is promising to provide insight into the action of receptors in cell biology from the perspective of spatial distribution.


Subject(s)
Receptors, Cell Surface , Signal Transduction , Dimerization , Receptors, Cell Surface/metabolism , Ligands , DNA/genetics , DNA/metabolism
19.
Sleep Health ; 9(4): 475-481, 2023 08.
Article in English | MEDLINE | ID: mdl-37230863

ABSTRACT

BACKGROUND: Telomere length (TL) at birth is considered a potential biomarker for lifelong health. Although maternal sleep disturbance has been linked to a series of adverse pregnancy outcomes, evidence on the effect of maternal sleep on newborn TL remains scarce. Therefore, we aim to investigate the association of maternal sleep duration and sleep quality with newborn TL. METHODS: A total of 742 mother-newborn pairs were recruited from Wuhan Children's Hospital between November 2013 and March 2015. Cord blood TL was measured using real-time quantitative polymerase chain reaction. Maternal sleep duration and quality during late pregnancy were obtained via questionnaires. Multivariate linear regression models were used to estimate the effects of maternal sleep duration and sleep quality on newborn TL. RESULTS: A total of 742 maternal-newborn pairs were included in the analyses. Mothers sleeping ≥10 hours had a 9.30% (95% CI: 2.09%, 15.99%) shorter newborn TL than those sleeping 7-<9 hours. However, the association in mothers with short sleep duration (<7 hours) did not reach statistical significance. Compared to mothers with good sleep quality, those with poor sleep quality had a 9.91% (95% CI: 4.06%, 15.40%) shorter newborn TL. We observed a joint effect of sleep duration and sleep quality on newborn telomere shortening. Women with sleep duration ≥10 hours and poor sleep quality were most likely to have newborns with short TL (percent change:-19.66%, 95% CI: -28.42, -9.84%). CONCLUSIONS: Long sleep duration and poor sleep quality during late pregnancy were associated with shorter newborn TL.


Subject(s)
Fetal Blood , Fetus , Pregnancy , Prenatal Exposure Delayed Effects , Self Report , Sleep Duration , Sleep Quality , Telomere , Female , Humans , Infant, Newborn , Pregnancy/physiology , Fetal Blood/metabolism , Telomere/metabolism , Cohort Studies , China , Fetus/metabolism , Prenatal Exposure Delayed Effects/genetics , Maternal Age , Gestational Age , Adult , Male
20.
World J Diabetes ; 14(3): 279-289, 2023 Mar 15.
Article in English | MEDLINE | ID: mdl-37035218

ABSTRACT

BACKGROUND: Microalbuminuria is an early and informative marker of diabetic nephropathy. Our study found that microalbuminuria developed in patients with newly diagnosed type 2 diabetes mellitus (T2DM). AIM: To investigate the association between glucagon-like peptide 1 (GLP-1) and microalbuminuria in newly diagnosed T2DM patients. METHODS: In total, 760 patients were recruited for this cross-sectional study. The GLP-1 levels during a standard meal test and urinary albumin-creatinine ratio (UACR) were determined. RESULTS: Patients with microalbuminuria exhibited lower GLP-1 levels at 30 min and 120 min during a standard meal test than patients with normal albuminuria (30 min GLP-1, 16.7 ± 13.3 pmol vs 19.9 ± 15.6 pmol, P = 0.007; 120 min GLP-1, 16.0 ± 14.1 pmol vs 18.4 ± 13.8 pmol, P = 0.037). The corresponding area under the curve for active GLP-1 (AUCGLP-1) was also lower in microalbuminuria patients (2257, 1585 to 3506 vs 2896, 1763 to 4726, pmol × min, P = 0.003). Postprandial GLP-1 levels at 30 min and 120 min and AUCGLP-1 were negatively correlated with the UACR (r = 0.159, r = 0.132, r = 0.206, respectively, P < 0.001). The prevalence of microalbuminuria in patients with newly diagnosed T2DM was 21.7%, which decreased with increasing quartiles of AUCGLP-1 levels (27.4%, 25.3%, 18.9% and 15.8%). After logistic regression analysis adjusted for sex, age, hemoglobin A1c, body mass index, systolic blood pressure, estimated glomerular filtration rate, homeostasis model assessment of insulin resistance, AUCglucose and AUCglucagon, patients in quartile 4 of the AUCGLP-1 presented a lower risk of microalbuminuria compared with the patients in quartile 1 (odds ratio = 0.547, 95% confidence interval: 0.325-0.920, P = 0.01). A consistent association was also found between 30 min GLP-1 or 120 min GLP-1 and microalbuminuria. CONCLUSION: Postprandial GLP-1 levels were independently associated with microalbuminuria in newly diagnosed Chinese T2DM patients.

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