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1.
Brain ; 2024 Oct 07.
Article in English | MEDLINE | ID: mdl-39375207

ABSTRACT

Post-mortem studies have shown that patients dying from severe acute respiratory syndrome coronavirus (SARS-CoV-2) infection frequently have pathological changes in their CNS, particularly in the brainstem. Many of these changes are proposed to result from para-infectious and/or post-infection immune responses. Clinical symptoms such as fatigue, breathlessness, and chest pain are frequently reported in post-hospitalized coronavirus disease 2019 (COVID-19) patients. We propose that these symptoms are in part due to damage to key neuromodulatory brainstem nuclei. While brainstem involvement has been demonstrated in the acute phase of the illness, the evidence of long-term brainstem change on MRI is inconclusive. We therefore used ultra-high field (7 T) quantitative susceptibility mapping (QSM) to test the hypothesis that brainstem abnormalities persist in post-COVID patients and that these are associated with persistence of key symptoms. We used 7 T QSM data from 30 patients, scanned 93-548 days after hospital admission for COVID-19 and compared them to 51 age-matched controls without prior history of COVID-19 infection. We correlated the patients' QSM signals with disease severity (duration of hospital admission and COVID-19 severity scale), inflammatory response during the acute illness (C-reactive protein, D-dimer and platelet levels), functional recovery (modified Rankin scale), depression (Patient Health Questionnaire-9) and anxiety (Generalized Anxiety Disorder-7). In COVID-19 survivors, the MR susceptibility increased in the medulla, pons and midbrain regions of the brainstem. Specifically, there was increased susceptibility in the inferior medullary reticular formation and the raphe pallidus and obscurus. In these regions, patients with higher tissue susceptibility had worse acute disease severity, higher acute inflammatory markers, and significantly worse functional recovery. This study contributes to understanding the long-term effects of COVID-19 and recovery. Using non-invasive ultra-high field 7 T MRI, we show evidence of brainstem pathophysiological changes associated with inflammatory processes in post-hospitalized COVID-19 survivors.

2.
Br J Pharmacol ; 2024 Oct 04.
Article in English | MEDLINE | ID: mdl-39367653

ABSTRACT

BACKGROUND AND PURPOSE: DT-678 is a novel antiplatelet prodrug, capable of releasing the antiplatelet active metabolite of clopidogrel (AM) upon exposure to glutathione. In this study, we investigated factors responsible for clopidogrel high on-treatment platelet reactivity (HTPR) in acute coronary syndrome (ACS) patients and evaluated the capacity of DT-678 to overcome HTPR. EXPERIMENTAL APPROACH: A total of 300 consecutive ACS patients naive to P2Y12 receptor inhibitors were recruited and genotyped for CYP2C19 alleles. Blood samples were drawn before and after administration of 600-mg clopidogrel. Platelet reactivity index (PRI) and plasma AM concentrations were determined and grouped according to their CYP2C19 genotypes. DT-678 was applied ex vivo to whole blood samples to examine its inhibitory effects. To further examine the antiplatelet effectiveness of DT-678 in vivo, 20 healthy human subjects were recruited in a Phase I clinical trial, and each received a single dose of either 3-mg DT-678 or 75-mg clopidogrel. The pharmacokinetics and pharmacodynamics in different CYP2C19 genotype groups were compared. KEY RESULTS: Statistical analyses revealed that CYP2C19 genotype, body mass index, hyperuricaemia, and baseline PRI were significantly associated with a higher risk of clopidogrel HTPR in ACS patients. The addition of DT-678 ex vivo decreased baseline PRI regardless of CYP2C19 genotypes, overcoming clopidogrel HTPR. This observation was further confirmed in healthy volunteers receiving 3 mg of DT-678. CONCLUSION AND IMPLICATIONS: These results suggest that DT-678 effectively overcomes clopidogrel HTPR resulting from genetic and/or clinical factors in Chinese ACS patients, demonstrating its potential to improve antiplatelet therapy.

3.
Angew Chem Int Ed Engl ; : e202417902, 2024 Oct 09.
Article in English | MEDLINE | ID: mdl-39383300

ABSTRACT

Single- and few-layer graphene-based thermal interface materials (TIMs) with extraordinary high-temperature resistance and ultra-high thermal conductivity are very essential to develop the next-generation integrated circuits. However, the function of the as-prepared graphene-based TIMs would undergo severe degradation when being transferred to chips, as the interface between the TIMs and chips possesses a very small interfacial thermal conductance. Here, a "2.5D" all-carbon interface containing rich covalent bonding, namely a sp2/sp3 hybrid interfaces is designed and realized by a plasma-assisted chemical vapor deposition with a function of ultra-rapid quenching. The interfacial thermal conductance of the 2.5D interface is excitingly very high, up to 110-117 MWm-2K-1 at graphene thickness of 12-25 nm, which is even more than 30% higher than various metal/diamond contacts, and orders of magnitude higher than the existing all-carbon contacts. Atomic-level simulation confirm the key role of the efficient heat conduction via covalent C-C bonds, and reveal that the covalent-based heat transport could contribute 85% to the total interfacial conduction at a hybridization degree of 22 at%. This study provides an efficient strategy to design and construct 2.5D all-carbon interfaces, which can be used to develop high performance all-carbon devices and circuits.

5.
Front Mol Biosci ; 11: 1471100, 2024.
Article in English | MEDLINE | ID: mdl-39398277

ABSTRACT

Melanoma is a highly malignant tumor, that stands as the most lethal form of skin cancer and is characterized by notable phenotypic plasticity and intratumoral heterogeneity. Melanoma plasticity is involved in tumor growth, metastasis and therapy resistance. Long non-coding RNAs (lncRNAs) could influence plasticity due to their regulatory function. However, their role and mode of action are poorly studied. Here, we show a relevance of lncRNA GRASLND in melanoma differentiation and IFNγ signaling. GRASLND knockdown revealed switching of differentiated, melanocytic melanoma cells towards a dedifferentiated, slow-proliferating and highly-invasive cell state. Interestingly, GRASLND is overexpressed in differentiated melanomas and associated with poor prognosis. Accordingly, we found GRASLND expressed in immunological "cold" tumors and it negatively correlates with gene signatures of immune response activation. In line, silencing of GRASLND under IFNγ enhanced the expression of IFNγ-stimulated genes, including HLA-I antigen presentation, demonstrating suppressive activity of GRASLND on IFNγ signaling. Our findings demonstrate that in differentiated melanomas elevated expression of GRASLND interferes with anti-tumor effects of IFNγ, suggesting a role of GRASLND in tumor immune evasion.

6.
Cleft Palate Craniofac J ; : 10556656241286314, 2024 Sep 24.
Article in English | MEDLINE | ID: mdl-39314083

ABSTRACT

OBJECTIVE: The aetiology of CL/P is complicated, with both genetic and environmental factors. This study aimed to investigate the association between TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin) exposure and changes in the expression of miR-214-3p in the context of cleft palate. DESIGN: In this study, we established a fetal mouse cleft palate model using TCDD and differentially expressed miRNAs were analysed by microarray analysis and verified by qRT-PCR. Finally, we demonstrated the effects of TCDD and microRNAs on the proliferation and migration of mesenchymal cells by using CCK8, EDU, Transwell, and wound-healing assays. RESULTS: Our findings revealed significant upregulation of miRNAs such as miR-214-3p, miR-296-5p, and miR-33-5p in the TCDD intervention group, while miRNAs like miR-92a-3p, miR-126a-3p, and miR-411-5p were significantly downregulated. Notably, qRT-PCR testing confirmed a significant difference in miR-214-3P expression. Further investigations involved the overexpression of miR-214-3p, reducing cell proliferation and migration in primary mouse embryonic palatal mesenchymal (MEPM) cells. CONCLUSIONS: These results are consistent with the finding that TCDD suppresses palatal mesenchymal cell proliferation and migration through miR-214-3p. In conclusion, miR-214-3p probably plays a role in TCDD-induced cleft palates in mice.

7.
J Econ Entomol ; 2024 Sep 20.
Article in English | MEDLINE | ID: mdl-39302975

ABSTRACT

Sogatella furcifera (Horváth) (Hemiptera: Delphacidae), a serious rice pest, has developed significant resistance to a wide range of pesticides. Neonicotinoid insecticides are currently the primary choice for controlling S. furcifera, yet their impact on the species remains poorly understood. In this study, we investigated the binding sites of a conventional insecticide (dinotefuran) and a novel insecticide (flupyrimin), and evaluated their sublethal effects on S. furcifera. Our results revealed that the LC50 of dinotefuran and flupyrimin were 2.51 mg/L and 2.80 mg/L in third-instar S. furcifera, respectively. RNA interference (RNAi) knockdown of S. furcifera nicotinic acetylcholine receptor (nAChR) alpha2 subunit (Sfα2) and S. furcifera nAChR beta1 subunit (Sfß1) significantly reduced the susceptibility to dinotefuran by 18.7% and 16.8%, respectively, but had no effect on flupyrimin. Reproduction of the F0 and F1 generations was significantly inhibited by the LC25 of both dinotefuran and flupyrimin. In the dinotefuran treatment at LC25, the intrinsic growth rate (r) and finite growth rate (λ) were reduced to 0.15 and 0.16 days, respectively; the mean generation time (T) increased to 27.77 days, and the relative fitness was only 0.76 compared to the control. Additionally, the relative fitness (Rf) of the flupyrimin-treated group was reduced to 0.93 and 0.86 times that of the control group. The population dynamics of S. furcifera are significantly affected by both dinotefuran and flupyrimin, making these insecticides valuable tools for integrated pest management and the rational use of insecticides.

8.
Water Environ Res ; 96(9): e11132, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39285708

ABSTRACT

In this study, the siphon-type composite vertical flow constructed wetland (Sc-VSsFCW) was constructed with anthracite and shale ceramsite chosen as the substrate bed materials. During the 90-day experiment, typical pollutant removal effects of wastewater and extracellular polymeric substance (EPS) accumulation were investigated. Meanwhile, X-ray diffraction and scanning electron microscopy were used to examine the phase composition and surface morphology to analyze adsorptive property. Additionally, we evaluated the impact of siphon effluent on clogging and depolymerization by measuring the EPS components' evolution within the system. The findings reveal that both the anthracite and shale ceramsite systems exhibit impressive removal efficiencies for total phosphorus (TP), total dissolved phosphorus (TDP), soluble reactive phosphorus (SRP), chemical oxygen demand (COD), ammonium nitrogen (NH4 +-N), and nitrate nitrogen (NO3 --N). However, as the experiment progressed, TP removal rates in both systems gradually declined because of the saturation of adsorption sites on the substrate surfaces. Although the dissolved oxygen (DO) levels remained relatively stable throughout the experiment, pH exhibited distinct patterns, suggesting that the anthracite system relies primarily on chemical adsorption, whereas the shale ceramsite system predominantly utilizes physical adsorption. After an initial period of fluctuation, the permeability coefficient and porosity of the system gradually stabilized, and the protein and polysaccharide contents in both systems exhibited a downward trend. The study underscores that anthracite and shale ceramsite have good effectiveness in pollutant removal as substrate materials. Overall, the hydraulic conditions of the double repeated oxygen coupling siphon in the Sc-VSsFCW system contribute to enhanced re-oxygenation capacity and permeability coefficient during operation. The changes in EPS content indicate that the siphon effluent exerts a certain depolymerization effect on the EPS within the system, thereby mitigating the risk of biological clogging to a certain extent. PRACTITIONER POINTS: The system can still maintain good pollutant treatment effect in long-term operation. The re-oxygenation method of the system can achieve efficient and long-term re-oxygenation effect. The siphon effluent has a certain improvement effect on the permeability coefficient and porosity, but it cannot effectively inhibit the occurrence of clogging. The EPS content did not change significantly during the operation of the system, and there was a risk of biological clogging.


Subject(s)
Extracellular Polymeric Substance Matrix , Waste Disposal, Fluid , Wastewater , Wetlands , Wastewater/chemistry , Waste Disposal, Fluid/methods , Extracellular Polymeric Substance Matrix/chemistry , Phosphorus/chemistry , Water Pollutants, Chemical/chemistry , Water Purification/methods
9.
J Int Med Res ; 52(9): 3000605241277740, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39324181

ABSTRACT

OBJECTIVE: To investigate the signature genes of fatty acid metabolism and their association with immune cells in pulmonary arterial hypertension (PAH). METHODS: Fatty acid metabolism-related genes were obtained from the GeneCards database. In this retrospective study, a PAH-related dataset was downloaded from the Gene Expression Omnibus database and analyzed to identify differentially expressed genes (DEGs). Weighted gene co-expression network analysis (WGCNA) and machine learning algorithms, including least absolute shrinkage and selection operator (LASSO) and random forest, were used to identify the signature genes. Diagnostic efficiency was assessed by receiver operating characteristic (ROC) curve analysis and a nomogram. Immune cell infiltration was subsequently classified using CIBERSORT. RESULTS: In total, 817 DEGs were screened from the GSE33463 dataset. The data were clustered into six modules via WGCNA, and the MEdarkred module was significantly related to PAH. The LASSO and random forest algorithms identified five signature genes: ARV1, KCNJ2, PEX11B, PITPNC1, and SCO1. The areas under the ROC curves of these signature genes were 0.917, 0.934, 0.947, 0.963, and 0.940, respectively. CIBERSORT suggested these signature genes may participate in immune cell infiltration. CONCLUSIONS: ARV1, KCNJ2, PEX11B, PITPNC1, and SCO1 show remarkable diagnostic performance in PAH and are involved in immune cell infiltration.


Subject(s)
Fatty Acids , Gene Expression Profiling , Machine Learning , Pulmonary Arterial Hypertension , ROC Curve , Humans , Fatty Acids/metabolism , Gene Expression Profiling/methods , Pulmonary Arterial Hypertension/genetics , Gene Regulatory Networks , Retrospective Studies , Databases, Genetic , Transcriptome , Male , Female , Algorithms , Computational Biology/methods , Hypertension, Pulmonary/genetics
10.
Neural Netw ; 180: 106756, 2024 Sep 22.
Article in English | MEDLINE | ID: mdl-39332210

ABSTRACT

This study introduces an innovative neural network framework named spectral integrated neural networks (SINNs) to address both forward and inverse dynamic problems in three-dimensional space. In the SINNs, the spectral integration technique is utilized for temporal discretization, followed by the application of a fully connected neural network to solve the resulting partial differential equations in the spatial domain. Furthermore, the polynomial basis functions are employed to expand the unknown function, with the goal of improving the performance of SINNs in tackling inverse problems. The performance of the developed framework is evaluated through several dynamic benchmark examples encompassing linear and nonlinear heat conduction problems, linear and nonlinear wave propagation problems, inverse problem of heat conduction, and long-time heat conduction problem. The numerical results demonstrate that the SINNs can effectively and accurately solve forward and inverse problems involving heat conduction and wave propagation. Additionally, the SINNs provide precise and stable solutions for dynamic problems with extended time durations. Compared to commonly used physics-informed neural networks, the SINNs exhibit superior performance with enhanced convergence speed, computational accuracy, and efficiency.

11.
J Hand Surg Eur Vol ; : 17531934241275462, 2024 Sep 14.
Article in English | MEDLINE | ID: mdl-39276382

ABSTRACT

We report our experience with correction of radially deviated Wassel type III thumb polydactyly. After comprehensive assessments from preoperative radiographs, physical examinations and intraoperative reports, we corrected the metacarpophalangeal joint in 34 cases of radially deviated Wassel type III thumb polydactyly. Opening-wedge osteotomies combining bone graft and soft tissue reconstruction were used in 28 cases and soft tissue reconstruction only in six cases. Absorbable sutures were used instead of traditional Kirschner (K)-wires to fix the bone grafts. Patients were followed up for 12-78 months (mean 47 months). According to the Tada scoring system, 25 patients achieved good results, seven fair results and two poor results. Our modified technique for correcting radially deviated Wassel type III thumb polydactyly yielded satisfactory results. Continued follow-up and further studies will contribute to a better understanding of the long-term efficacy and potential refinements of this technique.Level of evidence: IV.

12.
Neurotoxicology ; 105: 96-110, 2024 Sep 12.
Article in English | MEDLINE | ID: mdl-39276873

ABSTRACT

Human brain development is a complex, multi-stage, and sensitive process, especially during the fetal stage. Animal studies over the last two decades have highlighted the potential risks of anesthetics to the developing brain, impacting its structure and function. This has raised concerns regarding the safety of anesthesia during pregnancy and its influence on fetal brain development, garnering significant attention from the anesthesiology community. Although preclinical studies predominantly indicate the neurotoxic effects of prenatal anesthesia, these findings cannot be directly extrapolated to humans due to interspecies variations. Clinical research, constrained by ethical and technical hurdles in accessing human prenatal brain tissues, often yields conflicting results compared to preclinical data. The emergence of brain organoids as a cutting-edge research tool shows promise in modeling human brain development. When integrated with single-cell sequencing, these organoids offer insights into potential neurotoxic mechanisms triggered by prenatal anesthesia. Despite several retrospective and cohort studies exploring the clinical impact of anesthesia on brain development, many findings remain inconclusive. As such, this review synthesizes preclinical and clinical evidence on the effects of prenatal anesthesia on fetal brain development and suggests areas for future research advancement.

13.
Int J Biol Macromol ; 277(Pt 3): 134427, 2024 Oct.
Article in English | MEDLINE | ID: mdl-39097050

ABSTRACT

Salivary glands are the principal organs responsible for secreting saliva in the oral cavity. Tumors, trauma, inflammation, and other factors can cause functional or structural damage to the glands, leading to reduced saliva secretion. In this study, we innovatively prepared a acinar-mimetic silk fibroin-collagen-astragalus polysaccharide (SCA) scaffold using low-temperature three-dimensional (3D) printing and freeze-drying techniques. We evaluated the material properties and cell compatibility of the scaffold in vitro and implanted it into the damaged parotid glands (PG) of rats to assess its efficacy in tissue reconstruction and functional repair. The results demonstrated that the SCA scaffold featured a porous structure resembling natural acini, providing an environment conducive to cell growth and orderly aggregation. It exhibited excellent porosity, water absorption, mechanical properties, and biocompatibility, fulfilling the requirements for tissue engineering scaffolds. In vitro, the scaffold facilitated adhesion, proliferation, orderly polarization, and spherical aggregation of PG cells. In vivo, the SCA scaffold effectively recruited GECs locally, forming gland-like acinar structures that matured gradually, promoting the regeneration of damaged PGs. The SCA scaffold developed in this study supports tissue reconstruction and functional repair of damaged PGs, making it a promising implant material for salivary gland regeneration.


Subject(s)
Collagen , Fibroins , Parotid Gland , Polysaccharides , Printing, Three-Dimensional , Tissue Engineering , Tissue Scaffolds , Fibroins/chemistry , Fibroins/pharmacology , Tissue Scaffolds/chemistry , Animals , Parotid Gland/chemistry , Rats , Collagen/chemistry , Tissue Engineering/methods , Polysaccharides/chemistry , Polysaccharides/pharmacology , Porosity , Regeneration/drug effects , Rats, Sprague-Dawley , Acinar Cells/drug effects , Biocompatible Materials/chemistry , Biocompatible Materials/pharmacology , Cell Proliferation/drug effects , Male
14.
Talanta ; 279: 126682, 2024 Nov 01.
Article in English | MEDLINE | ID: mdl-39116734

ABSTRACT

Fabricating covalent organic frameworks with different morphologies based on the same structural motifs is both interesting and challenging. Here, a TTA-TFP-COF was synthesized by both solvothermal and room temperature methods, with 2,4,6-Tris(4-aminophenyl)-1,3,5-triazine (TTA) and 1,3,5-tris(4-formylphenyl)-benzene (TFP) as raw material. Using different synthesis conditions and adding aniline and benzaldehyde as regulators in the synthesis process, we found that these processes could slow down the reaction speed, increase the exchange and metathesis reactions of dynamic reversible reactions, and improve the reversibility of the reaction system. Thus, controllable synthesis of TTA-TFP-COF with different morphologies, including micro-particles, hollow tubes with controllable diameters, and micro-flowers was achieved. Our further study found that metal ions, Fe3+ and Cr3+ ions, could coordinate with N and O in TTA-TFP-COF and partially destroy the structure of TTA-TFP-COF. The particle size of the TTA-TFP-COF became smaller, thus resulting in the decrease of the light scattering intensity of the COF. An excellent linear relationship exists between the light scattering changes (ΔI) and metal ions concentration (c) from 2.0 to 350.0 µM for Fe3+ and 40.0-800.0 µM for Cr3+, respectively. Thus, rapid and selective analytical methods for detecting metal ions were developed by TTA-TFP-COF here.

15.
Zhongguo Zhong Yao Za Zhi ; 49(13): 3441-3451, 2024 Jul.
Article in Chinese | MEDLINE | ID: mdl-39041116

ABSTRACT

Type 2 diabetes(T2DM) is a metabolic disorder marked by glucose toxicity, lipotoxicity, insulin resistance, and other pathological manifestations, representing a pressing global health concern. Obesity stands out as a pivotal risk factor for T2DM development. When combined with T2DM, obesity exacerbates insulin resistance and metabolic abnormalities. The disturbance in the inflammatory microenvironmental balance between adipose and pancreatic islet tissue emerges as a significant contributor to obese with T2DM development. Macrophages play a crucial role in maintaining immune homeostasis and responding to inflammation in adipose and pancreatic islet tissue. Individuals with obese with T2DM exhibit an imbalanced M1/M2 macrophage polarization, contributing to the progression of glycolipid metabolism abnormalities. Hence, restoring the equilibrium of macrophage polarization becomes imperative for obese with T2DM treatment. Scientific researchers have demonstrated that traditional Chinese medicine(TCM) therapies can effectively modulate macrophage polarization, offering a viable approach for treating obese with T2DM. In light of the existing evidence, this study systematically reviewed the research progress of TCM targeting the balance of M1/M2 macrophage polarization to ameliorate obese with T2DM, so as to furnish evidence supporting the clinical diagnosis and treatment of obese with T2DM with TCM while also contributing to the exploration of the biological basis of obese with T2DM.


Subject(s)
Diabetes Mellitus, Type 2 , Drugs, Chinese Herbal , Macrophages , Obesity , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/immunology , Diabetes Mellitus, Type 2/complications , Obesity/drug therapy , Obesity/immunology , Obesity/metabolism , Obesity/complications , Humans , Macrophages/drug effects , Macrophages/immunology , Drugs, Chinese Herbal/pharmacology , Drugs, Chinese Herbal/administration & dosage , Animals , Medicine, Chinese Traditional
16.
Int J Pharm X ; 8: 100268, 2024 Dec.
Article in English | MEDLINE | ID: mdl-39070171

ABSTRACT

In assisted reproduction techniques, oocytes encounter elevated levels of reactive oxygen species (ROS) during in vitro maturation (IVM). Oxidative stress adversely affects oocyte quality, hampering their maturation, growth, and subsequent development. Thus, mitigating excessive ROS to safeguard less viable oocytes during IVM stands as a viable strategy. Numerous antioxidants have been explored for oocyte IVM, yielding considerable effects; however, several aspects, including solubility, stability, and safety, demand attention and resolution. In this study, we developed nanoparticles by self-assembling endogenous bilirubin and melatonin hormone coated with bilirubin-conjugated glycol chitosan (MB@GBn) to alleviate oxidative stress and enhance oocyte maturation. The optimized MB@GBn exhibited a uniform spherical shape, measuring 128 nm in particle size, with a PDI value of 0.1807 and a surface potential of +11.35 mV. The positively charged potential facilitated nanoparticle adherence to the oocyte surface through electrostatic interaction, allowing for functional action. In vitro studies demonstrated that MB@GB significantly enhanced the maturation of compromised oocytes. Further investigation revealed MB@GB's effectiveness in scavenging ROS, reducing intracellular calcium levels, and suppressing mitochondrial polarization. This study not only offers a novel perspective on nano drug delivery systems for biomedical applications but also presents an innovative strategy for enhancing oocyte IVM.

17.
Biomed Pharmacother ; 177: 117029, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38991305

ABSTRACT

Amifostine (AMF) as the first-line radiation protection drug, usually suffered from low compliance and short half-life upon clinical applications. The development of oral drug delivery system (DDS) for AMF is a promising solution. However, the inherent shortages of AMF present significant challenges in the design of suitable oral DDS. Here in this study, we utilized the ability of calcium ions to bind with AMF and prepared AMF loaded calcium carbonate (CC) core, CC/AMF, using phase transferred coprecipitation method. We further modified the CC/AMF using phospholipids to prepare AMF loaded lipid-calcium carbonate (LCC) hybrid nanoparticles (LCC/AMF) via a thin-film dispersion method. LCC/AMF combines the oral advantages of lipid nanoparticles with the drug-loading capabilities of CC, which was shown as uniform nano-sized formulation with decent stability in aqueous solution. With favorable intestinal transport and absorption effects, it effectively enhances the in vivo radiation protection efficacy of AMF through oral administration. More importantly, we further investigated the cellular accumulation profile and intracellular transport mechanism of LCC/AMF using MDCK and Caco-2 cell lines as models. This research not only alters the current administration method of AMF to enhance its convenience and compliance, but also provides insights and guidance for the development of more suitable oral DDS for AMF in the future.


Subject(s)
Amifostine , Calcium Carbonate , Nanoparticles , Radiation-Protective Agents , Calcium Carbonate/chemistry , Administration, Oral , Animals , Humans , Caco-2 Cells , Radiation-Protective Agents/administration & dosage , Radiation-Protective Agents/chemistry , Radiation-Protective Agents/pharmacology , Radiation-Protective Agents/pharmacokinetics , Nanoparticles/chemistry , Amifostine/administration & dosage , Amifostine/pharmacology , Dogs , Lipids/chemistry , Madin Darby Canine Kidney Cells , Drug Delivery Systems/methods , Radiation Protection/methods , Drug Carriers/chemistry
18.
Mol Biol Rep ; 51(1): 843, 2024 Jul 23.
Article in English | MEDLINE | ID: mdl-39042338

ABSTRACT

BACKGROUND: Energy homeostasis is vital for insects to survive food shortages. This study investigated the starvation tolerance of Spodoptera frugiperda, which invaded China in 2019, focusing on its storage protein family, crucial for energy balance. 10 storage protein family members were identified and their expression patterns at different development stages and under different starvation stress were analyzed. METHODS AND RESULTS: We used qPCR to evaluate the expression levels of storage protein family members under various larval instars and starvation conditions. We discovered that, among above 10 members, only 2 storage proteins, SfSP8 and SfSP7 showed significant upregulation in response to starvation stress. Notably, SfSP8 upregulated markedly after 24 h of fasting, whereas SfSP7 exhibited a delayed response, with significant upregulation observed only after 72 h of starvation. Then we significantly reduced the starvation tolerance of larvae through RNAi-mediated knockdown of SfSP8 and also altered the starvation response of SfSP7 from a late to an early activation pattern. Finally, we constructed transgenic Drosophila melanogaster with heterologous overexpressing SfSP8 revealed that the starvation tolerance of the transgenic line was significantly stronger than that of wild-type lines. CONCLUSIONS: SfSP8 was the core storage protein member that mediated the starvation tolerance of larvae of S. frugiperda. Our study on the novel function of storage proteins in mediating larval starvation tolerance of S. frugiperda is conducive to understanding the strong colonization of this terrible invasive pest.


Subject(s)
Insect Proteins , Larva , Spodoptera , Starvation , Animals , Spodoptera/genetics , Larva/genetics , Larva/metabolism , Starvation/genetics , Insect Proteins/genetics , Insect Proteins/metabolism , Drosophila melanogaster/genetics , Drosophila melanogaster/metabolism , Animals, Genetically Modified , Stress, Physiological/genetics
19.
Mol Biol Rep ; 51(1): 878, 2024 Jul 31.
Article in English | MEDLINE | ID: mdl-39083078

ABSTRACT

BACKGROUND: Saccharosydne procerus serves as a significant alternative host for parasitoids of the important rice pest, rice planthoppers. Rearing S. procerus on the water bamboo plants near rice field can provide a parasitic site for parasitic wasps during the idle period of rice fields, thereby stabilizing the number of parasitoids and suppressing the number of rice planthoppers in the field. However, limited understanding of genetic diversity of S. procerus restricts its application. Therefore, this study aims to analyze the genetic diversity of S. procerus in Hunan region. METHODS: In this study, 16 geographical populations of the S. procerus from the Hunan region were used. After screening, ISSR primers were employed for polymorphism detection. POPGENE32 software was used for genetic diversity analysis, and UPGMA clustering was applied for statistical analysis of different geographical populations to generate an evolutionary tree. RESULTS: Eleven ISSR primers were screened, resulting in the detection of 194 amplification locus, of which 126 were polymorphic. The average percentage of polymorphic locus was 64.95%. The mean Nei's gene diversity (H) was 0.2475, the mean Shannon's Information index (I) was 0.3708, and the Genetic diversity index among populations (Gst) was 0.3800. Cluster analysis identified three groups, with most populations concentrated in the second group, indicating no clear genetic structure. This suggests that the 16 populations of S. procerus exhibit high levels of genetic diversity.


Subject(s)
Genetic Variation , Phylogeny , China , Genetic Variation/genetics , Animals , Polymorphism, Genetic , Microsatellite Repeats/genetics , Hemiptera/genetics , Oryza/genetics , Oryza/parasitology , Genetics, Population/methods
20.
J Cardiothorac Surg ; 19(1): 312, 2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38824570

ABSTRACT

OBJECTIVE: About 10% of patients after cardiopulmonary bypass (CPB) would undergo acute liver injury, which aggravated the mortality of patients. Ac2-26 has been demonstrated to ameliorate organic injury by inhibiting inflammation. The present study aims to evaluate the effect and mechanism of Ac2-26 on acute liver injury after CPB. METHODS: A total of 32 SD rats were randomized into sham, CPB, Ac, and Ac/AKT1 groups. The rats only received anesthesia, and rats in other groups received CPB. The rats in Ac/AKT1 were pre-injected with the shRNA to interfere with the expression of AKT1. The rats in CPB were injected with saline, and rats in Ac and Ac/AKT1 groups were injected with Ac2-26. After 12 h of CPB, all the rats were sacrificed and the peripheral blood and liver samples were collected to analyze. The inflammatory factors in serum and liver were detected. The liver function was tested, and the pathological injury of liver tissue was evaluated. RESULTS: Compared with the sham group, the inflammatory factors, liver function, and pathological injury were worsened after CPB. Compared with the CPB group, the Ac2-26 significantly decreased the pro-inflammatory factors and increased the anti-inflammatory factor, improved liver function, and ameliorated the pathological injury. All the therapeutic effects of Ac2-26 were notably attenuated by the shRNA of AKT1. The Ac2-26 increased the GSK3ß and eNOS, and this promotion was inhibited by the shRNA. CONCLUSION: The Ac2-26 significantly treated the liver injury, inhibited inflammation, and improved liver function. The effect of Ac2-26 on liver injury induced by CPB was partly associated with the promotion of AKT1/GSK3ß/eNOS.


Subject(s)
Cardiopulmonary Bypass , Glycogen Synthase Kinase 3 beta , Nitric Oxide Synthase Type III , Proto-Oncogene Proteins c-akt , Rats, Sprague-Dawley , Animals , Cardiopulmonary Bypass/adverse effects , Proto-Oncogene Proteins c-akt/metabolism , Glycogen Synthase Kinase 3 beta/metabolism , Rats , Nitric Oxide Synthase Type III/metabolism , Male , Disease Models, Animal , Liver/pathology , Signal Transduction
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