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1.
Food Chem ; 462: 141002, 2025 Jan 01.
Article in English | MEDLINE | ID: mdl-39216371

ABSTRACT

Making health-enhancing tea from Forsythia suspensa leaves has been a tradition of Chinese folk culture for centuries. However, these leaves were not officially recognized as a new food source until 2017 by the Chinese government. In this study, ethyl acetate fractions from Forsythia suspensa fruit and leaves exhibited excellent antioxidant activity in vitro antioxidant assays and in vivo D-galactose-induced aging mice model. The antioxidant activity of the leaves was higher than that of fruit both in vitro and in vivo. The chemical constituents present in these ethyl acetate fractions were comprehensively analyzed using UHPLC-Q-Exactive-Orbitrap/MS. A total of 20 compounds were identified, among which forsythoside E, (+)-epipinoresinol, dihydromyricetin, chlorogenic acid, and ursolic acid were exclusively detected in the ethyl acetate fraction of Forsythia suspensa leaves, but absent in the ethyl acetate fraction derived from its fruit. This study provides theoretical support for the utilization of Forsythia suspensa fruit and leaves.


Subject(s)
Aging , Antioxidants , Forsythia , Fruit , Galactose , Plant Extracts , Plant Leaves , Animals , Forsythia/chemistry , Plant Leaves/chemistry , Mice , Fruit/chemistry , Plant Extracts/chemistry , Chromatography, High Pressure Liquid , Antioxidants/chemistry , Antioxidants/pharmacology , Aging/drug effects , Male , Humans , Mass Spectrometry
2.
Mol Pharm ; 2024 Oct 01.
Article in English | MEDLINE | ID: mdl-39351992

ABSTRACT

Intracellular copper ion homeostasis has become an attractive target for cancer therapy. Herein, we report a 2,2'-dipicolylamine (DPA) functionalized polyglutamate derivative (PDHB) which is capable of rapidly forming PDHB-copper complex (PDHB@Cu) due to the strong coordination ability of pendant DPA with Cu2+. High drug loading content of doxorubicin (DOX) (>30 wt %) is realized due to the strong affinity of Cu2+ to DOX, while that is about 10 wt % for PDHB without Cu2+. The obtained PDHB@Cu-DOX can respond to specific endogenous stimuli (pH and glutathione (GSH)), releasing Cu2+ and DOX. The released DOX directly damages the DNA of tumor cells to cause apoptosis, while Cu2+ depletes intracellular GSH and is reduced to Cu+ simultaneously, which reacts with local H2O2 to produce highly toxic ·OH via a Fenton-like reaction, thus realizing synergistic chemodynamics and chemotherapy. This report provides an interesting polymeric ionophore strategy to deliver enough copper ions into cancer cells, which can also easily extend to other metal ions by replacing the ionophore components, thus having a wide application in nanomedicine.

3.
Article in English | MEDLINE | ID: mdl-39352683

ABSTRACT

The disruption of lipid droplet function is associated with the pathogenesis of various diseases. Clarifying the response behavior of lipid droplets to the microenvironment at the cellular level is of great significance. Plant lipids not only exist in phospholipids in cell membranes, but also in aromatic essential oils. Monitoring the level of lipid droplets in plant cells using fluorescent probes provides a simple method for screening lipid-rich varieties. We synthesized a polarity-viscosity responsive coumarin fluorescent probe, Cou-CN, which achieved sensitive detection of polarity and viscosity in dilute solution environments by constructing this simple probe with ICT and TICT properties and verifying it using Gaussian computational simulation. Cou-CN exhibited good lipid droplet illumination effects in HepG2 cells with a correlation coefficient of 0.92 compared to the commercial lipid droplet dye BODIPY. Additionally, co-staining the probe with the lipophilic commercial dye Nile Red in tobacco root stem seedling cells resulted in a high correlation coefficient of 0.9.

4.
Nano Lett ; 2024 Oct 01.
Article in English | MEDLINE | ID: mdl-39352718

ABSTRACT

The design and synthesis of nanomedicines capable of regulating programmed cell death patterns to enhance antitumor efficacy remain significant challenges in cancer therapy. In this study, we developed intelligent DNA nanospheres (NS) capable of distinguishing tiny pH changes between different endosomal compartments to regulate pyroptosis or apoptosis. These NS are self-assembled from two multifunctional DNA modules, enabling tumor targeting, acid-responsive disassembly, and photodynamic therapy (PDT) activation. By modifying the embedded i-motif sequence, the NS can be activated in early endosomes (EE) or lysosomes (Ly), producing singlet oxygen (1O2) at specific locations under laser irradiation. Our results demonstrate that EE-activated PDT induces gasdermin-E-mediated pyroptosis in tumor cells, enhancing antitumor efficacy and reducing systemic toxicity compared to Ly-activated apoptosis. This study offers new insights into the design of endosome-activated nanomedicines, advancing the biomedical applications of targeted cancer therapy.

5.
Front Pharmacol ; 15: 1430469, 2024.
Article in English | MEDLINE | ID: mdl-39380912

ABSTRACT

Cisplatin is widely used to treat various solid tumors. However, its toxicity to normal tissues limits its clinical application, particularly due to its ototoxic effects, which can result in hearing loss in patients undergoing chemotherapy. While significant progress has been made in preclinical studies to elucidate the cellular and molecular mechanisms underlying cisplatin-induced ototoxicity (CIO), the precise mechanisms remain unclear. Moreover, the optimal protective agent for preventing or mitigating cisplatin-induced ototoxicity has yet to be identified. This review summarizes the current understanding of the roles of apoptosis, autophagy, ferroptosis, pyroptosis, and protective agents in cisplatin-induced ototoxicity. A deeper understanding of these cell death mechanisms in the inner ear, along with the protective agents, could facilitate the translation of these agents into clinical therapeutics, help identify new therapeutic targets, and provide novel strategies for cisplatin-based cancer treatment.

6.
Int J Biol Macromol ; : 135871, 2024 Sep 30.
Article in English | MEDLINE | ID: mdl-39357718

ABSTRACT

Histone modifications (HMs) play various roles in growth, development, and resistance to abiotic stress. However, HMs have been systematically identified in a few plants, and identification of HMs in medicinal plants is very rare. Aquilaria sinensis is a typical stress-induced medicinal plant, in which HMs remain unexplored. We conducted a comprehensive study to identify HMs and obtained 123 HMs. To conduct evolutionary analysis, we constructed phylogenetic trees and analyzed gene structures. To conduct functional analysis, we performed promoter, GO, and KEGG analyses and ortholog analyses against AtHMs. Based on the expression profiles of different tissues and different layers of Agar-Wit, some HMs of A. sinensis (AsHMs) were predicted to be involved in the formation of agarwood, and their response to MeJA and NaCl stress was tested by qRT-PCR analysis. By analyzing the enrichment of H3K4me3, H3K27me3, and H4K5ac in the promoter regions of two key sesquiterpene synthase genes, AsTPS13/18, we hypothesized that AsHMs play important roles in the synthesis of agarwood sesquiterpenes. We confirmed this hypothesis by conducting RNAi transgenic interference experiments. This study provided valuable information and important biological theories for studying epigenetic regulation in the formation of agarwood. It also provided a framework for conducting further studies on the biological functions of HMs.

7.
Nat Commun ; 15(1): 8601, 2024 Oct 04.
Article in English | MEDLINE | ID: mdl-39366932

ABSTRACT

Over the past decade, there has been a growing interest in ferritin-based vaccines due to their enhanced antigen immunogenicity and favorable safety profiles, with several vaccine candidates targeting various pathogens advancing to phase I clinical trials. Nevertheless, challenges associated with particle heterogeneity, improper assembly and unanticipated immunogenicity due to the bulky protein adaptor have impeded further advancement. To overcome these challenges, we devise a universal ferritin-adaptor delivery platform based on structural insights derived from the natural ferritinophagy complex of the human ferritin heavy chain (FTH1) and the nuclear receptor coactivator 4 (NCOA4). The engineered ferritinophagy (Fagy)-tag peptide demonstrate significantly enhanced binding affinity to the 24-mer ferritin nanoparticle, enabling efficient antigen presentation. Subsequently, we construct a self-assembling rabies virus (RABV) vaccine candidate by noncovalently conjugating the Fagy-tagged glycoprotein domain III (GDIII) of RABV to the ferritin nanoparticle, maintaining superior homogeneity, stability and immunogenicity. This vaccine candidate induces potent, rapid, and durable immune responses, and protects female mice against the authentic RABV challenge after single-dose administration. Furthermore, this universal, ferritin-based antigen conjugating strategy offers significant potential for developing vaccine against diverse pathogens and diseases.


Subject(s)
Apoferritins , Ferritins , Nanoparticles , Rabies Vaccines , Rabies virus , Rabies , Animals , Nanoparticles/chemistry , Rabies virus/immunology , Rabies virus/genetics , Mice , Humans , Female , Rabies/prevention & control , Rabies/immunology , Apoferritins/chemistry , Apoferritins/immunology , Apoferritins/genetics , Rabies Vaccines/immunology , Rabies Vaccines/administration & dosage , Rabies Vaccines/genetics , Rabies Vaccines/chemistry , Ferritins/immunology , Ferritins/chemistry , Ferritins/metabolism , Antibodies, Viral/immunology , Mice, Inbred BALB C , Antigens, Viral/immunology , Antigens, Viral/chemistry , Antigens, Viral/genetics , Oxidoreductases
8.
Aging Dis ; 2024 Aug 30.
Article in English | MEDLINE | ID: mdl-39226169

ABSTRACT

Age-related hearing loss (ARHL) is a disease that impacts human quality of life and contributes to the progression of other neuronal problems. Various stressors induce an increase in free radicals, destroy mitochondria to further contribute to cellular malfunction, and compromise cell viability, ultimately leading to functional decline. Cisd2, a master gene for Marfan syndrome, plays an essential role in maintaining mitochondrial integrity and functions. As shown by our data, specific deletion of Cisd2 in the cochlea exacerbated the hearing impairment of ARHL in C57BL/6 mice. Increased defects in mitochondrial function, potassium homeostasis and synapse activity were observed in the Cisd2-deleted mouse models. These mechanistic phenotypes combined with oxidative stress contribute to cell death in the whole cochlea. Human patients with obviously deteriorated ARHL had low Cisd2 expression; therefore, Cisd2 may be a potential target for designing therapeutic methods to attenuate the disease progression of ARHL.

9.
Carbohydr Polym ; 345: 122581, 2024 Dec 01.
Article in English | MEDLINE | ID: mdl-39227110

ABSTRACT

High methyl-esterified citrus pectin (HMCP) is often used as a thickness in food products and is considered a poor emulsifier, especially in neutral pH solutions. Our previous findings show that the emulsifying capacity of HMCP could be significantly enhanced by calcium cations. Besides, the pH of the solution decreased in the presence of calcium cations. However, the impact of solution pH on HMCP emulsifying capacity in the presence of calcium cations is unclear. In this study, the pH of the HMCP solution was adjusted from 3.00 to 8.00 before adding calcium cations. The solution properties and emulsifying properties were analyzed in light of the existence of calcium cations. The results showed that the pH of the HMCP solutions decreased after bringing calcium cations into them. Calcium cations could change the solution rheological properties, particle size distributions and morphologies, and the particle microenvironmental hydrophobic areas in HMCP solutions while increasing the pH of HMCP solutions, contributing to improving the emulsifying capacity of HMCP. HMCP had the best emulsifying ability when the pH of the HMCP solutions was kept at a neutral level. This research gives us new ideas to adjust the emulsifying property of HMCP.


Subject(s)
Calcium , Emulsifying Agents , Pectins , Pectins/chemistry , Hydrogen-Ion Concentration , Calcium/chemistry , Emulsifying Agents/chemistry , Rheology , Emulsions/chemistry , Particle Size , Cations/chemistry , Hydrophobic and Hydrophilic Interactions , Esterification , Citrus/chemistry
10.
J Blood Med ; 15: 407-419, 2024.
Article in English | MEDLINE | ID: mdl-39279878

ABSTRACT

Background: The application of rituximab has significantly enhanced the overall survival rates in patients with diffuse large B-cell lymphoma (DLBCL). Regrettably, a significant number of patients still progress to relapse/refractory DLBCL (rrDLBCL). Methods: Herein, we employed targeted sequencing of 55 genes to investigate if gene mutations could predict the progression to rrDLBCL. Additionally, we compared the mutation profiles at the time of DLBCL diagnosis with those found in rrDLBCL cases. Results: Our findings highlighted significantly elevated mutation frequencies of TP53, MEF2B and CD58 in diagnostic biopsies from patients who progressed to relapse or refractory disease, with CD58 mutations exclusively observed in the rrDLBCL group. In assessing the predictive power of mutation profiles for treatment responses in primary DLBCL patients, we found that the frequency of CARD11 mutations was substantially higher in non-response group as compared with those who responded to immunochemotherapy. In addition, we revealed mutations in HIST2H2AB, BCL2, NRXN3, FOXO1, HIST1H1C, LYN and TBL1XR1 genes were only detected in initial diagnostic biopsies, mutations in the EBF1 gene were solely detected in the rrDLBCL patients. Conclusion: Collectively, this study elucidates some of the genetic mechanisms contributing to the progression of rrDLBCL and suggests that the presence of CD58 mutations might serve as a powerful predictive marker for relapse/refractory outcomes in primary DLBCL patients.

11.
Article in English | MEDLINE | ID: mdl-39292583

ABSTRACT

Tracking and reconstructing deformable objects with little texture is challenging due to the lack of features. Here we introduce "invisible markers" for accurate and robust correspondence matching and tracking. Our markers are visible only under ultraviolet (UV) light. We build a novel imaging system for capturing videos of deformed objects under their original untouched appearance (which may have little texture) and, simultaneously, with our markers. We develop an algorithm that first establishes accurate correspondences using video frames with markers, and then transfers them to the untouched views as ground-truth labels. In this way, we are able to generate high-quality labeled data for training learning-based algorithms. We contribute a large real-world dataset, DOT, for tracking deformable objects with little or no texture. Our dataset has about one million video frames of various types of deformable objects. We provide ground truth tracked correspondences in both 2D and 3D. We benchmark state-of-the-art methods on optical flow and deformable object reconstruction using our dataset, which poses great challenges. By training on DOT, their performance significantly improves, not only on our dataset, but also on other unseen data.

12.
Aging Cell ; : e14271, 2024 Sep 19.
Article in English | MEDLINE | ID: mdl-39300745

ABSTRACT

The causative mechanisms underlying the genetic relationships of neurodegenerative diseases with epigenetic aging and human longevity remain obscure. We aimed to detect causal associations and shared genetic etiology of neurodegenerative diseases with epigenetic aging and human longevity. We obtained large-scale genome-wide association study summary statistics data for four measures of epigenetic age (GrimAge, PhenoAge, IEAA, and HannumAge) (N = 34,710), multivariate longevity (healthspan, lifespan, and exceptional longevity) (N = 1,349,462), and for multiple neurodegenerative diseases (N = 6618-482,730), including Lewy body dementia, Alzheimer's disease (AD), Parkinson's disease, amyotrophic lateral sclerosis, and multiple sclerosis. Main analyses were conducted using multiplicative random effects inverse-variance weighted Mendelian randomization (MR), and conditional/conjunctional false discovery rate (cond/conjFDR) approach. Shared genomic loci were functionally characterized to gain biological understanding. Evidence showed that AD patients had 0.309 year less in exceptional longevity (IVW beta = -0.309, 95% CI: -0.38 to -0.24, p = 1.51E-19). We also observed suggestively significant causal evidence between AD and GrimAge age acceleration (IVW beta = -0.10, 95% CI: -0.188 to -0.013, p = 0.02). Following the discovery of polygenic overlap, we identified rs78143120 as shared genomic locus between AD and GrimAge age acceleration, and rs12691088 between AD and exceptional longevity. Among these loci, rs78143120 was novel for AD. In conclusion, we observed that only AD had causal effects on epigenetic aging and human longevity, while other neurodegenerative diseases did not. The genetic overlap between them, with mixed effect directions, suggested complex shared genetic etiology and molecular mechanisms.

13.
Anal Methods ; 2024 Sep 12.
Article in English | MEDLINE | ID: mdl-39264253

ABSTRACT

Bimetallic nanomaterial-based systems have been widely utilized across various fields due to their remarkable expandability and flexibility, including nanomedicine, diagnostics, and molecular information technology. Here, we constructed an electrochemical immunosensor using bimetallic gold/silver functionalized carbon spheres (AuAg@CSs) and mesoporous silica nanoparticles (MSNs) for the sensitive determination of cytokeratin 19 fragment antigen 21-1 (CYFRA 21-1) and ensuring information protection for textual data. The AuAg@CSs demonstrated exceptional catalytic activity towards hydrogen peroxide, generating a significant current signal. The introduction of CYFRA 21-1 facilitated the binding of MSNs, thereby forming a sandwich-type electrochemical immunosensor that resulted in a notable decrease in current. Notably, the detection limit for CYFRA 21-1 was determined to be 31 fg mL-1, accompanied by high selectivity. Furthermore, extensive textual information can be encrypted and concealed within the current responses of the electrochemical nanosensing system. By establishing a threshold, these current signals can be represented as a series of binary strings, which can subsequently be segmented into shorter strings. Through information coding methods, these shorter binary strings can be assembled and decrypted, ultimately merging into meaningful textual content. This study promotes the synthesis and multifunctional application of bimetallic nanomaterials, providing innovative solutions to enhance the sensing sensitivity of electrochemical immunosensors and paving the way for advancements in molecular digitization.

14.
Ecotoxicol Environ Saf ; 283: 116980, 2024 Sep 15.
Article in English | MEDLINE | ID: mdl-39226632

ABSTRACT

OBJECTIVE: Acetaminophen (APAP), an antipyretic and analgesic commonly used during pregnancy, has been recognized as a novel environmental contaminant. Preliminary evidence suggests that prenatal acetaminophen exposure (PAcE) could adversely affect offspring's gonadal and neurologic development, but there is no systematic investigation on the characteristics of APAP's fetal developmental toxicity. METHODS: Pregnant mice were treated with 100 or 400 mg/kg∙d APAP in the second-trimester, or 400 mg/kg∙d APAP in the second- or third-trimester, or different courses (single or multiple) of APAP, based on clinical regimen. The effects of PAcE on pregnancy outcomes, maternal/fetal blood phenotypes, and multi-organ morphological and functional development of fetal mice were analyzed. RESULTS: PAcE increased the incidence of adverse pregnancy outcomes and altered blood phenotypes including aminotransferases, lipids, and sex hormones in dams and fetuses. The expression of key functional genes in fetal organs indicated that PAcE inhibited hippocampal synaptic development, sex hormone synthesis, and osteogenic and chondrogenic development, but enhanced hepatic lipid synthesis and uptake, renal inflammatory hyperplasia, and adrenal steroid hormone synthesis. PAcE also induced marked pathological alterations in the fetal hippocampus, bone, kidney, and cartilage. The sensitivity rankings of fetal organs to PAcE might be hippocampus/bone > kidney > cartilage > liver > gonad > adrenal gland. Notably, PAcE-induced multi-organ developmental toxicity was more considerable under high-dose, second-trimester, and multi-course exposure and in male fetuses. CONCLUSION: This study confirmed PAcE-induced alterations in multi-organ development and function in fetal mice and elucidated its characteristics, which deepens the comprehensive understanding of APAP's developmental toxicity.


Subject(s)
Acetaminophen , Animals , Acetaminophen/toxicity , Female , Pregnancy , Mice , Male , Fetal Development/drug effects , Analgesics, Non-Narcotic/toxicity , Maternal Exposure , Prenatal Exposure Delayed Effects/chemically induced , Fetus/drug effects , Pregnancy Outcome
15.
Microsyst Nanoeng ; 10(1): 124, 2024 Sep 05.
Article in English | MEDLINE | ID: mdl-39237536

ABSTRACT

The demand for high-performance electromechanical resonators is ever-growing across diverse applications, ranging from sensing and time-keeping to advanced communication devices. Among the electromechanical materials being explored, thin-film lithium niobate stands out due to its strong piezoelectric properties and low acoustic loss. However, in nearly all existing lithium niobate electromechanical devices, the configuration is such that the electrodes are in direct contact with the mechanical resonator. This configuration introduces an undesirable mass-loading effect, producing spurious modes and additional damping. Here, we present an electromechanical platform that mitigates this challenge by leveraging a flip-chip bonding technique to separate the electrodes from the mechanical resonator. By offloading the electrodes from the resonator, our approach yields a substantial increase in the quality factor of these resonators, paving the way for enhanced performance and reliability for their device applications.

16.
Chem Commun (Camb) ; 60(77): 10732-10735, 2024 Sep 24.
Article in English | MEDLINE | ID: mdl-39246019

ABSTRACT

A molten-salt-induced structural heterogeneity strategy was developed to construct molecular heterostructured carbon nitride with intimately connected heptazine and triazine units, which effectively accelerate charge transport and suppress carrier recombination. Consequently, the prepared CN-2 exhibits significantly enhanced photocatalytic H2O2 production, about 143 times that of traditional carbon nitride.

17.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 41(9): 1084-1089, 2024 Sep 10.
Article in Chinese | MEDLINE | ID: mdl-39217487

ABSTRACT

OBJECTIVE: To explore the genetic etiology of a Chinese pedigree affected with Branchio-oculo-facial syndrome (BOFS) and summarize the prenatal phenotype of BOFS patients. METHODS: A pedigree with BOFS which had presented at the Genetics and Prenatal Diagnosis Center of the First Affiliated Hospital of Zhengzhou University in December 2021 was selected as the study subject. Clinical data of the pedigree was collected. The fetus was subjected to routine prenatal ultrasound scan. Trio-whole exome sequencing (trio-WES) was carried out for the fetus and its parents, and candidate variant was verified by Sanger sequencing. Relevant literature was searched from the database to summarize the prenatal phenotype of BOFS patients. RESULTS: Ultrasound exam suggested the fetus had cleft lip and palate. Its father had presented with high palatal arch, prematurely grayed hair, occult cleft lip, congenital preauricular fistula, red-green color blindness and unilateral renal agenesis. Its grandfather also had high palatal arch, prematurely gray hair, protruding ears, congenital preauricular fistula and hearing disorders. Trio-WES revealed that the fetus and its father had both harbored a heterozygous c.890-1G>A variant of the TFAP2A gene. The same variant was not found in its mother. Sanger sequencing confirmed that its grandfather had also harbored the same variant. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was rated as likely pathogenic (PVS1+PM2_Supporting). Combined with 36 similar cases retrieved from the literature, the prenatal phenotypes of BOFS patients had included growth restriction (25/37), renal abnormalities (10/37), cleft lip and palate (5/37) and oligohydramnios (5/37). CONCLUSION: The c.890-1G>A variant of the TFAP2A gene probably underlay the pathogenesis of BOFS in this pedigree. Discovery of the novel variant has enriched the mutational spectrum of the TFAP2A gene. The common prenatal phenotypes of BOFS have included growth restriction, renal abnormalities, cleft lip and palate and oligohydramnios. Delineation of the intrauterine phenotype of BOFS may facilitate its prenatal diagnosis, clinical diagnosis, treatment and genetic counseling.


Subject(s)
Branchio-Oto-Renal Syndrome , Transcription Factor AP-2 , Adult , Female , Humans , Male , Pregnancy , Branchio-Oto-Renal Syndrome/genetics , China , East Asian People/genetics , Exome Sequencing , Genetic Testing , Mutation , Pedigree , Phenotype , Prenatal Diagnosis , Transcription Factor AP-2/genetics
18.
Heliyon ; 10(18): e38062, 2024 Sep 30.
Article in English | MEDLINE | ID: mdl-39347396

ABSTRACT

Purpose: To identify brain regions affected by Hypoxic-Ischemic Encephalopathy (HIE) in neonates using Amide Proton Transfer (APT) imaging and Apparent Diffusion Coefficient (ADC). Materials and methods: Twenty neonates were divided into HIE and control groups. All neonates were undergoing MRI, including APT and DWI. Imaging analysis was performed using SPM12. The independent-samples t-test was used to analyze the difference in APTw values and ADC values between the mild HIE neonates and the control group. The receiver operating characteristic (ROC) curves were established to assess the diagnostic values of APTw and ADC values in different brain regions for HIE. Pearson's correlation analysis was used to analyze the correlation between APTw values and ADC values for each region. Results: APTw values were significantly higher in 26 regions of the HIE group. ADC values were lower in the right anterior temporal lobe and higher in bilateral Subthalamic nucleus in HIE. The APTw values of 22 regions showed very high area under the curve (AUC), whereas the AUC of ADC values in right anterior temporal lobe and right subthalamic nucleus were both 0.802. Notably, the right anterior temporal lobe exhibited significant differences in both APTw and ADC values between the HIE and control groups, additionally, APTw value was significant positive correlated with ADC values in right anterior temporal lobe. Conclusion: APTw and ADC are effective in detecting HIE, with APTw being more sensitive. The right anterior temporal lobe is particularly affected by HIE, with significant changes in APTw and ADC values and a positive correlation between them. This suggests that temporal lobe damage may be critical in the long-term neurological consequences of HIE.

19.
Front Neurosci ; 18: 1437464, 2024.
Article in English | MEDLINE | ID: mdl-39347533

ABSTRACT

Objectives: The study of autonomic responses to cardiac arrest (CA) resuscitation deserves attention due to the impact of autonomic function on survival and arousal. Orexins are known to modulate autonomic function, but the role of endogenous orexin in hyperacute recovery of autonomic function post-resuscitation is not well understood. We hypothesized that endogenous orexin facilitates hyperacute cardiovascular sympathetic activity post-resuscitation, and this response could be attenuated by suvorexant, a dual orexin receptor antagonist. Methods: A well-established 7-min asphyxial CA rat model was studied. Heart rate (HR) and blood pressure were monitored from baseline to 90-min post-resuscitation. Autonomic function was evaluated by spectral analysis of HR variability, whereby the ratio of low- and high-frequency components (LF/HF ratio) represents the balance between sympathetic/parasympathetic activities. Plasma orexin-A levels and orexin receptors immunoreactivity in the rostral ventrolateral medulla (RVLM), the key central region for regulating sympathetic output, were measured post-resuscitation. Neurological outcome was assessed via neurologic-deficit score at 4-h post-resuscitation. Key results: A significant increase in HR was found over 25-40 min post-resuscitation (p < 0.01 vs. baseline), which was attenuated by suvorexant significantly (p < 0.05). Increased HR (from 15-to 25-min post-resuscitation) was correlated with better neurological outcomes (rs = 0.827, p = 0.005). There was no evident increase in mean arterial pressure over 25-40 min post-resuscitation, while systolic pressure was reduced greatly by suvorexant (p < 0.05). The LF/HF ratio was higher in animals with favorable outcomes than in animals injected with suvorexant over 30-40 min post-resuscitation (p < 0.05). Plasma orexin-A levels elevated at 15-min and peaked at 30-min post-resuscitation (p < 0.01 vs. baseline). Activated orexin receptors-immunoreactive neurons were found co-stained with tyrosine hydroxylase-immunopositive cells in the RVLM at 2-h post-resuscitation. Conclusion: Together, increased HR and elevated LF/HF ratio indicative of sympathetic arousal during a critical window (25-40 min) post-resuscitation are observed in animals with favorable outcomes. The orexin system appears to facilitate this hyperacute autonomic response post-CA.

20.
Anal Methods ; 2024 Sep 30.
Article in English | MEDLINE | ID: mdl-39344492

ABSTRACT

Lipid droplets (LDs) and lysosomes were dynamic organelles present in most eukaryotic cells that were interconnected and worked closely together to ensure the smooth physiological activities of organisms. The interaction between lipid droplets and lysosomes was thought to play a role in the development of certain diseases. In this paper we designed and synthesised a lipid droplet lysosomal probe. The Nap-Lyso-Ph-OH probe was constructed according to the ICT mechanism and exhibited sensitivity to both polarity and viscosity. The probe exhibited low cytotoxicity, a large Stokes shift, excellent selectivity and photostability. The probe was successfully used for labelling and imaging of lipid droplets and lysosomes in cells and zebrafish. Interestingly, we used tobacco seedling cells to explore the ability of Nap-Lyso-Ph-OH for imaging lipid droplet labelling in plant cells.

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