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1.
Anal Chem ; 2024 May 19.
Article En | MEDLINE | ID: mdl-38764163

Gold nanorods (AuNRs) have been considered highly compelling materials for early cancer diagnosis and have aroused a burgeoning fascination among the biomedical sectors. By leveraging the versatile tunable optical properties of AuNRs, herein, we have developed a novel tumor-targeted dual-modal nanoprobe (FFA) that exhibits excellent bioluminescence and photoacoustic imaging performance for early tumor diagnosis. FFA has been synthesized by anchoring the recombinant bioluminescent firefly luciferase protein (Fluc) on the folate-conjugated AuNRs via the PEG linker. TEM images and UV-vis studies confirm the nanorod morphology and successful conjugation of the biomolecules to AuNRs. The nanoprobe FFA relies on the ability of the folate module to target the folate receptor-positive tumor cells actively, and simultaneously, the Fluc module facilitates excellent bioluminescent properties in physiological conditions. The success of chemical engineering in the present study enables stronger bioluminescent signals in the folate receptor-positive cells (Skov3, Hela, and MCF-7) than in folate receptor-negative cells (A549, 293T, MCF-10A, and HepG2). Additionally, the AuNRs induced strong photoacoustic conversion performance, enhancing the resolution of tumor imaging. No apparent toxicity was detected at the cellular and mouse tissue levels, manifesting the biocompatibility nature of the nanoprobe. Prompted by the positive merits of FFA, the in vivo animal studies were performed, and a notable enhancement was observed in the bioluminescent/photoacoustic intensity of the nanoprobe in the tumor region compared to that in the folate-blocking region. Therefore, this synergistic dual-modal bioluminescent and photoacoustic imaging platform holds great potential as a tumor-targeted contrast agent for early tumor diagnosis with high-performance imaging information.

2.
J Pharm Biomed Anal ; 246: 116208, 2024 May 08.
Article En | MEDLINE | ID: mdl-38735210

Amomum tsaoko (AT) is commonly used in clinical practice to treat abdominal distension and pain. It is also a seasoning for cooking, with the functions of appetizing, invigorating the spleen, and being digestive-promoting. Amomum tsaoko (AT) has three adulterants, Amomum paratsaoko (AP), Amomum koenigii (AK), and Alpinia katsumadai Hayata, because of the confusion in historical classics regarding recorded sources as well as the near geographic distribution and fruit morphological similarities. In this study, we established a functional dyspepsia (FD) rat model and then treated it with the corresponding medicinal solutions AT, AP, AK, and AKH. The gastric emptying rate, intestinal propulsion rate, serum biochemical indicators, histopathological changes, and fecal metabolism were measured. The efficacy and mechanism of AT, AP, AK, and AKH in the treatment of FD were compared. Fecal metabolomics revealed that 20 potential biomarkers were involved in seven significant metabolic pathways in FD rats. These pathways include ubiquinone and other terpenoid-quinone biosynthesis, glycerophospholipid metabolism, tyrosine metabolism, primary bile acid biosynthesis, purine metabolism, folate biosynthesis, and amino sugar and nucleotide sugar metabolism. AP regulates 6 metabolic pathways, 5 metabolic pathways affected by AT, 4 metabolic pathways affected by AK, and 2 metabolic pathways affected by AKH.The above results suggest that the different effects of AT, AP, AK, and AKH on FD rats may be due to their different regulatory effects on the metabolome.

3.
Biochim Biophys Acta Mol Basis Dis ; 1870(5): 167208, 2024 Jun.
Article En | MEDLINE | ID: mdl-38701956

OBJECTIVE: This study aims to investigate the cardiac protective effects and molecular mechanisms of electroacupuncture (EA) pre-treatment in lipopolysaccharide (LPS)-Induced Cardiomyopathy. METHODS AND RESULTS: Pre-treatment with EA was performed 30 min before intraperitoneal injection of LPS. Cardiac function changes in mice of the EA + LPS group were observed using electrocardiography, echocardiography, and enzyme linked immunosorbent assay (ELISA) and compared with the LPS group. The results demonstrated that EA pre-treatment significantly improved the survival rate of septic mice, alleviated the severity of endotoxemia, and exhibited notable cardiac protective effects. These effects were characterized by a reduction in ST-segment elevation on electrocardiography, an increase in ejection fraction (EF) and fraction shortening (FS) on echocardiography and a decrease in the expression of serum cardiac troponin I (cTn-I) levels. Serum exosomes obtained after EA pre-treatment were extracted and administered to septic mice, revealing significant cardiac protective effects of EA-derived exosomes. Furthermore, the antagonism of circulating exosomes in mice markedly suppressed the cardiac protective effects conferred by EA pre-treatment. Analysis of serum exosomes using quantitative reverse transcription-polymerase chain reaction (qRT-PCR) revealed a significant upregulation of miR-381 expression after EA pre-treatment. Inhibition or overexpression of miR-381 through serotype 9 adeno-associated virus (AAV9)-mediated gene delivery demonstrated that overexpression of miR-381 exerted a cardiac protective effect, while inhibition of miR-381 significantly attenuated the cardiac protective effects conferred by EA pre-treatment. CONCLUSIONS: Our research findings have revealed a novel endogenous cardiac protection mechanism, wherein circulating exosomes derived from EA pre-treatment mitigate LPS-induced cardiac dysfunction via miR-381.


Cardiomyopathies , Electroacupuncture , Exosomes , Lipopolysaccharides , MicroRNAs , Animals , MicroRNAs/genetics , MicroRNAs/metabolism , Exosomes/metabolism , Exosomes/genetics , Electroacupuncture/methods , Mice , Cardiomyopathies/chemically induced , Cardiomyopathies/metabolism , Cardiomyopathies/therapy , Cardiomyopathies/pathology , Cardiomyopathies/genetics , Cardiomyopathies/prevention & control , Lipopolysaccharides/toxicity , Male , Mice, Inbred C57BL , Disease Models, Animal
4.
J Magn Reson Imaging ; 2024 May 06.
Article En | MEDLINE | ID: mdl-38708838

BACKGROUND: Chronic kidney disease (CKD) is associated with increased, and early cardiovascular disease risk. Changes in hemodynamics within the left ventricle (LV) respond to cardiac remodeling. The LV hemodynamics in nondialysis CKD patients are not clearly understood. PURPOSE: To use four-dimensional blood flow MRI (4D flow MRI) to explore changes in LV kinetic energy (KE) and the relationship between LV KE and LV remodeling in CKD patients. STUDY TYPE: Retrospective. POPULATION: 98 predialysis CKD patients (Stage 3: n = 21, stage 4: n = 21, and stage 5: n = 56) and 16 age- and sex-matched healthy controls. FIELD STRENGTH/SEQUENCE: 3.0 T/balanced steady-state free precession (SSFP) cine sequence, 4D flow MRI with a fast field echo sequence, T1 mapping with a modified Look-Locker SSFP sequence, and T2 mapping with a gradient recalled and spin echo sequence. ASSESSMENT: Demographic characteristics (age, sex, height, weight, blood pressure, heart rate, aortic regurgitation, and mitral regurgitation) and laboratory data (eGFR, Creatinine, hemoglobin, ferritin, transferrin saturation, potassium, and carbon dioxide bonding capacity) were extracted from patient records. Myocardial T1, T2, LV ejection fraction, end diastolic volume (EDV), end systolic volume, LV flow components (direct flow, delayed ejection, retained inflow, and residual volume) and KE parameters (peak systolic, systolic, diastolic, peak E-wave, peak A-wave, E/A ratio, and global) were assessed. The KE parameters were normalized to EDV (KEiEDV). Parameters were compared between disease stage in CKD patients, and between CKD patients and healthy controls. STATISTICAL TESTS: Differences in clinical and imaging parameters between groups were compared using one-way ANOVA, Kruskal Walls and Mann-Whitney U tests, chi-square test, and Fisher's exact test. Pearson or Spearman's correlation coefficients and multiple linear regression analysis were used to compare the correlation between LV KE and other clinical and functional parameters. A P-value of <0.05 was considered significant. RESULTS: Compared with healthy controls, peak systolic (24.76 ± 5.40 µJ/mL vs. 31.86 ± 13.18 µJ/mL), systolic (11.62 ± 2.29 µJ/mL vs. 15.27 ± 5.10 µJ/mL), diastolic (7.95 ± 1.92 µJ/mL vs. 13.33 ± 5.15 µJ/mL), peak A-wave (15.95 ± 4.86 µJ/mL vs. 31.98 ± 14.51 µJ/mL), and global KEiEDV (9.40 ± 1.64 µJ/mL vs. 14.02 ± 4.14 µJ/mL) were significantly increased and the KEiEDV E/A ratio (1.16 ± 0.67 vs. 0.69 ± 0.53) was significantly decreased in CKD patients. As the CKD stage progressed, both diastolic KEiEDV (10.45 ± 4.30 µJ/mL vs. 12.28 ± 4.85 µJ/mL vs. 14.80 ± 5.06 µJ/mL) and peak E-wave KEiEDV (15.30 ± 7.06 µJ/mL vs. 14.69 ± 8.20 µJ/mL vs. 19.33 ± 8.29 µJ/mL) increased significantly. In multiple regression analysis, global KEiEDV (ß* = 0.505; ß* = 0.328), and proportion of direct flow (ß* = -0.376; ß* = -0.410) demonstrated an independent association with T1 and T2 times. DATA CONCLUSION: 4D flow MRI-derived LV KE parameters show altered LV adaptations in CKD patients and correlate independently with T1 and T2 mapping that may represent myocardial fibrosis and edema. TECHNICAL EFFICACY: Stage 3.

5.
Front Psychiatry ; 15: 1391653, 2024.
Article En | MEDLINE | ID: mdl-38699445

Background: Childhood trauma exerts enduring impacts on the physical and psychological well-being of individuals in adulthood, influencing their daily functioning. This study aims to investigate the impact of childhood trauma on stress recovery in adults, concentrating on heart rate variations during acute stress exposure. Methods: A cohort of 126 participants completed the Childhood Trauma Questionnaire (CTQ) and underwent the Trier Social Stress Test (TSST) to elicit acute stress, with continuous heart rate (HR) monitoring for stress recovery assessment. Results: The results revealed a negative correlation between childhood trauma and stress recovery, prominently observed in instances of emotional neglect and abuse. Individuals with heightened childhood trauma exhibited protracted stress recovery following acute stress exposure. Conclusion: Childhood traumatic experiences were associated with the recovery from acute stress, as indicated by heart rate indices. These findings contribute to the foundational framework for psychological interventions tailored to individuals with a history of childhood trauma.

6.
Research (Wash D C) ; 7: 0357, 2024.
Article En | MEDLINE | ID: mdl-38716472

Soft crawling robots have been widely studied and applied because of their excellent environmental adaptability and flexible movement. However, most existing soft crawling robots typically exhibit a single-motion mode and lack diverse capabilities. Inspired by Drosophila larvae, this paper proposes a compact soft crawling robot (weight, 13 g; length, 165 mm; diameter, 35 mm) with multimodal locomotion (forward, turning, rolling, and twisting). Each robot module uses 4 sets of high-power-density shape memory alloy actuators, endowing it with 4 degrees of motion freedom. We analyze the mechanical characteristics of the robot modules through experiments and simulation analysis. The plug-and-play modules can be quickly assembled to meet different motion and task requirements. The soft crawling robot can be remotely operated with an external controller, showcasing multimodal motion on various material surfaces. In a narrow maze, the robot demonstrates agile movement and effective maneuvering around obstacles. In addition, leveraging the inherent bistable characteristics of the robot modules, we used the robot modules as anchoring units and installed a microcamera on the robot's head for pipeline detection. The robot completed the inspection in horizontal, vertical, curved, and branched pipelines, adjusted the camera view, and twisted a valve in the pipeline for the first time. Our research highlights the robot's superior locomotion and application capabilities, providing an innovative strategy for the development of lightweight, compact, and multifunctional soft crawling robots.

7.
Org Lett ; 2024 May 10.
Article En | MEDLINE | ID: mdl-38726872

Ortho-selective C-H borylation of aromatic ketones has not been extensively explored. Herein, we report the iridium-catalyzed ortho-selective C-H borylation of aromatic ketones using in situ-formed imine as the ligand. Good compatibility is observed for various substituted acetophenones and other aromatic ketones, and corresponding products are obtained with medium to excellent yields.

8.
RSC Adv ; 14(20): 14202-14213, 2024 Apr 25.
Article En | MEDLINE | ID: mdl-38690107

In the search for pharmaceutically active compounds from natural products, it is crucial and challenging to develop separation methods that target not only structurally similar compounds but also a class of compounds with desired pharmaceutical functions. To achieve both structure-oriented and function-oriented selectivity, the choice of functional monomers with broad interactions or even biomimetic roles towards targeted compounds is essential. In this work, an imidazole (IM)-functionalized paper membrane was synthesized to realize selectivity. The IM was selected based on its capability to provide multiple interactions, participation in several bioprocesses, and experimental verification of adsorption performance. Using gallic acid as a representative component of Pomegranate Peel, the preparation conditions and extraction parameters were systematically investigated. The optimal membrane solid-phase extraction (MSPE) method allowed for enrichment of gallic acid from the complex matrix of Pomegranate Peel, enabling facile quantitative analysis with a limit of detection (LOD) of 0.1 ng mL-1. Furthermore, with the aid of cheminformatics, the extracted compounds were found to be similar in both their structures and pharmaceutical functions. This work offers a novel approach to preparing a readily synthesized extraction membrane capable of isolating compounds with similar structures and pharmaceutical effects, and provides an MSPE-based analytical method for natural products.

9.
BMC Bioinformatics ; 25(1): 196, 2024 May 20.
Article En | MEDLINE | ID: mdl-38769492

BACKGROUND: The identification of drug side effects plays a critical role in drug repositioning and drug screening. While clinical experiments yield accurate and reliable information about drug-related side effects, they are costly and time-consuming. Computational models have emerged as a promising alternative to predict the frequency of drug-side effects. However, earlier research has primarily centered on extracting and utilizing representations of drugs, like molecular structure or interaction graphs, often neglecting the inherent biomedical semantics of drugs and side effects. RESULTS: To address the previously mentioned issue, we introduce a hybrid multi-modal fusion framework (HMMF) for predicting drug side effect frequencies. Considering the wealth of biological and chemical semantic information related to drugs and side effects, incorporating multi-modal information offers additional, complementary semantics. HMMF utilizes various encoders to understand molecular structures, biomedical textual representations, and attribute similarities of both drugs and side effects. It then models drug-side effect interactions using both coarse and fine-grained fusion strategies, effectively integrating these multi-modal features. CONCLUSIONS: HMMF exhibits the ability to successfully detect previously unrecognized potential side effects, demonstrating superior performance over existing state-of-the-art methods across various evaluation metrics, including root mean squared error and area under receiver operating characteristic curve, and shows remarkable performance in cold-start scenarios.


Drug-Related Side Effects and Adverse Reactions , Computational Biology/methods , Humans , Algorithms
10.
Article En | MEDLINE | ID: mdl-38752269

The Gt(ROSA)26Sor ( ROSA26) and H11 loci are commonly used as safe harbors for the construction of targeted transgenic mice. However, it remains unclear whether these two loci have distinct effects on transgene expression. In this study, we insert three differently colored fluorescent protein expression cassettes (EGFP, tdTomato and mTagBFP2) driven by the CAG promoter into the ROSA26 and H11 loci. We generate five single-transgenic mouse models and a triple-transgenic mouse model expressing three distinct fluorescent proteins simultaneously. Our results reveal that the efficiency of transgene expression is greater at the ROSA26 locus with a reverse orientation relative to the transcription of the ROSA26 gene. In most tissues examined, the efficiency of transgene expression at the ROSA26 locus exceeds that at the H11 locus. Moreover, the expression profiles of identical transgenes display discrepancies across various tissues, and notably, substantial heterogeneity in transgene expression is discernible within cells of the same tissue. Our findings offer a valuable reference for the selection of safe harbors and strategies for the construction of transgenic mouse models.

11.
Mil Med Res ; 11(1): 20, 2024 Mar 31.
Article En | MEDLINE | ID: mdl-38556884

BACKGROUND: Neutrophils are traditionally viewed as first responders but have a short onset of action in response to traumatic brain injury (TBI). However, the heterogeneity, multifunctionality, and time-dependent modulation of brain damage and outcome mediated by neutrophils after TBI remain poorly understood. METHODS: Using the combined single-cell transcriptomics, metabolomics, and proteomics analysis from TBI patients and the TBI mouse model, we investigate a novel neutrophil phenotype and its associated effects on TBI outcome by neurological deficit scoring and behavioral tests. We also characterized the underlying mechanisms both in vitro and in vivo through molecular simulations, signaling detections, gene expression regulation assessments [including dual-luciferase reporter and chromatin immunoprecipitation (ChIP) assays], primary cultures or co-cultures of neutrophils and oligodendrocytes, intracellular iron, and lipid hydroperoxide concentration measurements, as well as forkhead box protein O1 (FOXO1) conditional knockout mice. RESULTS: We identified that high expression of the FOXO1 protein was induced in neutrophils after TBI both in TBI patients and the TBI mouse model. Infiltration of these FOXO1high neutrophils in the brain was detected not only in the acute phase but also in the chronic phase post-TBI, aggravating acute brain inflammatory damage and promoting late TBI-induced depression. In the acute stage, FOXO1 upregulated cytoplasmic Versican (VCAN) to interact with the apoptosis regulator B-cell lymphoma-2 (BCL-2)-associated X protein (BAX), suppressing the mitochondrial translocation of BAX, which mediated the antiapoptotic effect companied with enhancing interleukin-6 (IL-6) production of FOXO1high neutrophils. In the chronic stage, the "FOXO1-transferrin receptor (TFRC)" mechanism contributes to FOXO1high neutrophil ferroptosis, disturbing the iron homeostasis of oligodendrocytes and inducing a reduction in myelin basic protein, which contributes to the progression of late depression after TBI. CONCLUSIONS: FOXO1high neutrophils represent a novel neutrophil phenotype that emerges in response to acute and chronic TBI, which provides insight into the heterogeneity, reprogramming activity, and versatility of neutrophils in TBI.


Brain Injuries, Traumatic , Neutrophils , Animals , Humans , Mice , bcl-2-Associated X Protein/metabolism , Brain , Brain Injuries, Traumatic/complications , Depression , Forkhead Box Protein O1/metabolism , Iron
12.
J Inflamm Res ; 17: 2009-2021, 2024.
Article En | MEDLINE | ID: mdl-38566981

Purpose: This study aimed to investigate the relationship between peripheral blood indices and the efficacy and prognosis of advanced esophageal squamous cell carcinoma (ESCC) patients treated with camrelizumab. Patients and Methods: We retrospectively analyzed 64 patients who received camrelizumab for advanced ESCC at the Second People's Hospital of Lianyungang City between July 2020 and June 2022. The study included examination of the neutrophil-to-lymphocyte ratio (NLR), the platelet-to-lymphocyte ratio (PLR), the systemic inflammation index (SII), the lymph-to-monocytes ratio (LMR), the absolute lymphocyte count (ALC), and lactate dehydrogenase (LDH). We used multivariate logistic regression analysis to explore the link existing between peripheral blood and the efficacy of treatment. Determination of potential prognostic factors for Progression-free survival (PFS) and Overall survival (OS) using Cox regression analysis. The nomogram model was developed based on the results of the Cox multivariate analysis. Patients were divided into three groups according to the reduction in LDH and LDL levels before treatment, and the Kaplan-Meier survival curves for the three groups were compared and ROC curves for LDH combined with PLR were plotted. Results: Lower LDH (OR=6.237, 95% CI: 1.625-23.944) were independently associated with disease control rates(DCR). LDH was independently correlated with PFS (HR: 0.227 95% CI: 0.099-0.517). LDH and PLR were independently linked to OS. The C index of the nomogram model is 0.819, indicating good predictive performance. Kaplan-Meier Survival Curve suggested better OS in patients with reduced pretreatment LDH and PLR. The area under the ROC curve showed that the LDH index combined with the PLR index predicts patient survival better than the index alone. Conclusion: LDH combined with PLR predicted prognosis in patients with ESCC treated with camrelizumab.

13.
Acta Diabetol ; 2024 Apr 16.
Article En | MEDLINE | ID: mdl-38625392

AIMS: To identify correlations between omega-3 intake and incidence of diabetic retinopathy (DR). METHODS: This was a cross-sectional study using data from participants over age 40 in the National Health and Nutrition Examination Survey (NHANES) 2005-2008. Metrics included participants' intake of omega-3 fatty acids, specifically three types of representative polyunsaturated fatty acids, DR prevalence, and demographic characteristics. Multiple logistic regression models were used to assess the relationship between omega-3 intake and DR. RESULTS: Of the 1243 participants included in this study, omega-3 intake was lower in patients with DR relative to those without DR. Of the three polyunsaturated fatty acids within the omega-3 fatty acid family that we focused on, participants without DR consumed more docosapentaenoic acid (DPA) and docosahexaenoic acid (DHA) than those with DR. In contrast, there was no significant difference in the intake of eicosapentaenoic acid (EPA). Higher omega-3 intake was associated with a decreased risk of DR. In a crude model, the odds ratio (OR) was 0.548 (95% CI 0.315, 0.951; p = 0.033). In the fully adjusted model of omega-3 (model II), the adjusted OR was 0.525 (95% CI 0.306, 0.901; p = 0.021). DPA and DHA were also associated with a decreased risk of DR. In the full adjustment model (model II) of DPA and DHA, the adjusted ORs were 0.0002 (95% CI 0.000, 0.166; p = 0.014) and 0.293 (95% CI 0.105, 0.819; p = 0.020). Subgroup analysis showed that the protective effect of omega-3 against DR was more significant in younger patients (p value = 0.015). CONCLUSIONS: In this cross-sectional study of the U.S. general population, we found that increased intake of omega-3 and its components, specifically DPA and DHA were negatively associated with DR incidence. This suggests that omega-3 may be a potential protective factor for DR and may help to prevent or delay the onset and progression of DR.

14.
J Phys Chem Lett ; 15(15): 4088-4095, 2024 Apr 18.
Article En | MEDLINE | ID: mdl-38587462

Although it is generally acknowledged that transition metals at high oxidation states represent superior oxygen evolution reaction (OER) activity, the preparation and stability of such a high-valence state are still a challenge, which requires relatively harsh reaction conditions and is unstable under ambient conditions. Herein, we report the formation of trivalent nickel (Ni3+) in laser-fabricated nickel oxides induced by polyaniline (PANI) under electrochemical activation via a significant charge transfer between Ni and N, as confirmed by X-ray photoelectron spectroscopy and density functional theory calculations. Thereafter, the presence of Ni3+ and the improved conductivity by PANI effectively increase the electrochemical OER activity of the samples together with excellent long-term stability. This work provides new insights for the rational manufacture of high-valence metal for electrochemical reactions.

15.
Immunol Invest ; : 1-13, 2024 Apr 23.
Article En | MEDLINE | ID: mdl-38651786

BACKGROUND: Sterile alpha and TIR motif-containing 1 (Sarm1) is known as a negative regulator of inflammatory responses. However, its role in inflammatory bowel disease (IBD) is still unclear. OBJECTIVE: This study aimed to explore the function of Sarm1 in IBD and its underlying mechanisms. Sarm1 and tumor necrosis factor (TNF) receptor associated factor 3 (TRAF3) knockout (KO) micewere established. METHODS: The colitis was induced using dextran sulfate sodium (DSS). Bone marrow-derived macrophages (BMDMs) were isolated and stimulated with lipopolysaccharides (LPS) or cytidine phosphate guanosine(CpG). Inflammatory cytokines were measured viaELISA. qPCR and Western blotting were used to determine the levels of the mRNA and protein expression, respectively. RESULTS: It was demonstrated that reduced expression of Sarm1 was correlated with the severity of IBD in ulcerative colitis patients, and also with the reduction of pro-inflammatory cytokines in the mouse model induced by DSS. It was further observed that Sarm1 KO enhanced the induction of pro-inflammatory cytokines in both animal and in vitro cell models. Sarm1 deficiency in macrophages increased the severity of colitis in the mouse model induced by DSS. Moreover, Sarm1 regulatedTRAF3 recruitment to myeloid differentiation primary response protein 88 (MyD88), which in turn controlled the MYD88-mediated inflammatory responses. CONCLUSIONS: In summary, our data suggest that Sarm1 controls the MYD88-mediated inflammatory responses in IBD via its regulation of TRAF3 recruitment.


1. Sarm1 KO enhances the induction of pro-inflammatory cytokines in both animal and in vitro cell models.2. Sarm1 deficiency in macrophages increases the severity of colitis in the mouse model.3. Sarm1 regulates TRAF3 recruitment to MyD88.

17.
Redox Biol ; 72: 103147, 2024 Jun.
Article En | MEDLINE | ID: mdl-38593632

Adaptive response to physiological oxygen levels (physO2; 5% O2) enables embryonic survival in a low-oxygen developmental environment. However, the mechanism underlying the role of physO2 in supporting preimplantation development, remains elusive. Here, we systematically studied oxygen responses of hallmark events in preimplantation development. Focusing on impeded transcriptional upregulation under atmospheric oxygen levels (atmosO2; 20% O2) during the 2-cell stage, we functionally identified a novel role of HIF-1α in promoting major zygotic genome activation by serving as an oxygen-sensitive transcription factor. Moreover, during blastocyst formation, atmosO2 impeded H3K4me3 and H3K27me3 deposition by deregulating histone-lysine methyltransferases, thus impairing X-chromosome inactivation in blastocysts. In addition, we found atmosO2 impedes metabolic shift to glycolysis before blastocyst formation, thus resulting a low-level histone lactylation deposition. Notably, we also reported an increased sex-dimorphic oxygen response of embryos upon preimplantation development. Together, focusing on genetic and epigenetic events that are essential for embryonic survival and development, the present study advances current knowledge of embryonic adaptive responses to physO2, and provides novel insight into mechanism underlying irreversibly impaired developmental potential due to a short-term atmosO2 exposure.


Embryonic Development , Gene Expression Regulation, Developmental , Hypoxia-Inducible Factor 1, alpha Subunit , Oxygen , Transcriptome , Zygote , Animals , Oxygen/metabolism , Embryonic Development/genetics , Hypoxia-Inducible Factor 1, alpha Subunit/metabolism , Hypoxia-Inducible Factor 1, alpha Subunit/genetics , Mice , Zygote/metabolism , Female , Histones/metabolism , Blastocyst/metabolism , Male
18.
J Safety Res ; 88: 261-274, 2024 Feb.
Article En | MEDLINE | ID: mdl-38485368

INTRODUCTION: Young children cannot effectively adapt their behaviors to vehicles at varied distances and speeds, which is a critical cause of road accidents. However, the impact of this crucial ability on children's street-crossing decision-making and the age at which they acquire it remain unclear. METHOD: This study examined the crossing decision-making behavior of children at 6, 8, and 11 years of age in facing 51 different videotaped traffic scenarios with varying vehicle distances and speeds. Sixty Chinese elementary school students, with 20 children evenly distributed into each of the three age groups (6 years, 8 years, and 11 years old), participated in a simulated street-crossing task using video projections. Hierarchical logistic regression models were used to analyze how age moderated the effects of vehicular motion factors (vehicle-pedestrian distance, vehicle speed) on children's crossing safety, including dangerous crossing and crossing decision-making. RESULTS: The results showed that when either vehicle-pedestrian distance decreased or vehicle speed increased all age groups tended to cross less frequently but probability of dangerous crossing increased. Compared to 8-year-old and 11-year-old children, 6-year-old children showed a less pronounced tendency toward both of these crossing decision-making behaviors, and had more dangerous crossing outcomes. CONCLUSIONS: These findings suggest that inadequate adaptation to vehicle-pedestrian distance and vehicle speed may partly contribute to the inferior safety of street-crossing behavior in 6-year-olds compared to 8-year-olds. No significant differences were observed between 8- and 11-year-old children, suggesting the turning point for this ability might occur between 6 and 8 years of age. PRACTICAL APPLICATIONS: Preventive measures aimed to reduce crossing risks for children should consider children's developmental stages.


Accidents, Traffic , Pedestrians , Child , Humans , Child, Preschool , Safety , Accidents, Traffic/prevention & control , Walking , Logistic Models
19.
Molecules ; 29(5)2024 Feb 26.
Article En | MEDLINE | ID: mdl-38474526

Organic afterglow is a fascinating phenomenon with exceptional applications. However, it encounters challenges such as low intensity and efficiency, and typically requires UV-light excitation and facile intersystem crossing (ISC) due to its spin-forbidden nature. Here, we develop a novel strategy that bypasses the conventional ISC pathway by promoting singlet-triplet transition through the synergistic effects of the intra/intermolecular heavy-atom effect in aromatic crystals, enabling the direct population of triplet excited states from the ground state. The resulting materials exhibit a bright organic afterglow with a remarkably enhanced quantum efficiency of up to 5.81%, and a significantly increased organic afterglow lifetime of up to 157 microseconds under visible light. Moreover, given the high-efficiency visible-light excitable organic afterglow emission, the potential application is demonstrated in lifetime-resolved, color-encoded, and excitation wavelength-dependent pattern encryption. This work demonstrates the importance of the direct population method in enhancing the organic afterglow performance and red-shifting the excitation wavelength, and provides crucial insights for advancing organic optoelectronic technologies that involve triplet states.

20.
Molecules ; 29(5)2024 Feb 28.
Article En | MEDLINE | ID: mdl-38474558

The Hibiscus manihot L. (HML) Medic, an edible hibiscus of the Malvaceae family, is abundant with flavonoids. The study investigated how Rhizopus-arrhizus-31-assisted pretreatment affects the extraction and bioactivity of flavonoids from HML. The fiber structure of the fermented flavonoid sample (RFF) appears looser, more porous, and more disordered than the unfermented flavonoid sample (RUF). RFF demonstrates milder conditions and yields higher extraction rates. According to the Box-Behnken response surface optimization experiment, the optimal conditions for RFF include a material-liquid ratio of 1:41 g/mL, a 2 h extraction time, a 57% ethanol concentration, and an extraction temperature of 800 °C, resulting in a 3.69% extraction yield, which is 39.25% higher than that of RUF. Additionally, RFF exhibits greater activity than RUF in the radical-scavenging system. The IC50 values for DPPH, OH, and ABTS radicals are 83.43 µg/mL and 82.62 µg/mL, 208.38 µg/mL and 175.99 µg/mL, and 108.59 µg/mL and 75.39 µg/mL for RUF and RFF, respectively. UPLC-QTOF-MS analysis of the active components in the HML flavonoid sample revealed significant differences in the chromatograms of RUF and RFF, indicating that biofermentation led to substantial changes in composition and content from HML.


Hibiscus , Manihot , Flavonoids/chemistry , Antioxidants/chemistry , Hibiscus/chemistry , Plant Extracts/chemistry , Rhizopus
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