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1.
Hepatol Int ; 2024 Jun 03.
Article in English | MEDLINE | ID: mdl-38829576

ABSTRACT

BACKGROUND: The role of neutrophils in hepatitis B virus (HBV) infection has been a subject of debate due to their involvement in antiviral responses and immune regulation. This study aimed to elucidate the neutrophil characteristics in patients with chronic hepatitis B (CHB). METHODS: Through flow cytometry and ribonucleic acid-sequencing analysis, the phenotypes and counts of neutrophils were analyzed in patients with CHB. Moreover, the effects of HBeAg on neutrophils and the corresponding pattern recognition receptors were identified. Simultaneously, the cross-talk between neutrophils and natural killer (NK) cells was investigated. RESULTS: Neutrophils were activated in patients with CHB, characterized by higher expression levels of programmed death-ligand 1 (PD-L1), cluster of differentiation 86, and interleukin-8, and lower levels of CXC motif chemokine receptor (CXCR) 1 and CXCR2. Hepatitis B e antigen (HBeAg) partially induces neutrophil activation through the Toll-like receptor 2 (TLR2). A consistent upregulation of the TLR2 and HBeAg expression was observed in patients with CHB. Notably, the genes encoding molecules pivotal for NK-cell function upon NK receptor engagement enriched in neutrophils after HBeAg activation. The HBeAg-activated neutrophils demonstrated the ability to decrease the production of interferon-gamma (IFN-γ) and tumor necrosis factor-alpha (TNF-α) in NK cells, while the PD-1 and PD-L1 pathways partially mediated the immunosuppression. CONCLUSIONS: The immunosuppression of neutrophils induced by HBeAg suggests a novel pathogenic mechanism contributing to immune tolerance in patients with CHB.

2.
Food Chem ; 455: 139679, 2024 May 18.
Article in English | MEDLINE | ID: mdl-38823125

ABSTRACT

This study involved the preparation of nanoparticles by combining oxidized starch (OS) with xanthan gum (XG), and emulsions were prepared from this nanoparticle. The physical and chemical characteristics, as well as the emulsification properties of oxidized starch-xanthan gum composite nanoparticles (OGNP), were analyzed. The findings revealed that the OGNP retained spherical shape after the addition of XG, although their diameter increased from approximately 50-150 to 200-400 nm. Zeta potential decreased with XG content. Moreover, emulsions prepared from OGNP exhibited outstanding thermal stability, also showing enhanced storage stability. In addition, emulsions had different rheological properties at different pH values. The apparent viscosity and shear stress of emulsions under alkaline conditions were lower than that of neutral conditions. NaCl increased the apparent viscosity of OGNP-stabilized emulsions while reducing their thermal stability. The nanoparticles prepared in this study have efficient emulsification properties and can extend the application of OS.

3.
iScience ; 27(6): 109827, 2024 Jun 21.
Article in English | MEDLINE | ID: mdl-38827395

ABSTRACT

Hepatocellular carcinoma (HCC) is a major global cause of death, with epithelial-mesenchymal transition (EMT) and cancer stem cell (CSC)-like properties contributing to its metastasis. DEAD box helicase 56 (DDX56) is involved in carcinogenesis, but its role in EMT induction and stem phenotype maintenance is unclear. This study assessed the impact of DDX56 absence on HCC cell stemness and EMT. DDX56 was found to be overexpressed in HCC tissues, correlating with disease stage and prognosis. In vitro, DDX56 stimulated tumor cell proliferation, migration, invasion, EMT, and stemness. It also enhanced maternal embryonic leucine-zipper kinase (MELK)-mediated forkhead box protein M1 (FOXM1) expression, regulating cancer stemness and malignant traits. In vivo, DDX56 knockdown in tumor-bearing mice reduced tumorigenicity and lung metastasis by modulating the MELK-FOXM1 signaling pathway. Collectively, DDX56 initiates stem cell-like traits in HCC and promotes EMT via MELK-FOXM1 activation, shedding light on HCC pathogenesis and suggesting a potential anti-cancer therapeutic target.

4.
Bioresour Technol ; : 130917, 2024 May 31.
Article in English | MEDLINE | ID: mdl-38824969

ABSTRACT

Electro-fermentation (EF) was combined with anaerobic fermentation (AF) to promote medium-chain fatty acid (MCFA) from sewage sludge. Results showed that EF at acidification process significantly increased short-chain fatty acid (SCFA) production of by 0.5 times (82.4 mmol C/L). AF facilitated the chain elongation (CE) process by enhancing the SCFA conversion. Combined EF at acidification and AF at CE (EF-AF) achieved the highest MCFA production of 27.9 mmol C/L, which was 20 %-866 % higher than the other groups. Electrochemical analyses showed that enhanced SCFA and MCFA production was accompanied with good electrochemical performance at acidification and CE. Microbial analyses showed that EF-AF promoted MCFA production by enriching electrochemically active bacteria (EAB, Bacillus sp.). Enzyme analyses indicated that EF-AF promoted MCFA production by enriching the functional enzymes involved in Acetyl-CoA formation and the fatty acid biosynthesis (FAB) pathway. This study provided new insights into the production of MCFA from enhanced sewage sludge.

5.
Gut Microbes ; 16(1): 2356278, 2024.
Article in English | MEDLINE | ID: mdl-38825779

ABSTRACT

The gut microbiota has been shown to be associated with a range of illnesses and disorders, including hypertension, which is recognized as the primary factor contributing to the development of serious cardiovascular diseases. In this review, we conducted a comprehensive analysis of the progression of the research domain pertaining to gut microbiota and hypertension. Our primary emphasis was on the interplay between gut microbiota and blood pressure that are mediated by host and gut microbiota-derived metabolites. Additionally, we elaborate the reciprocal communication between gut microbiota and antihypertensive drugs, and its influence on the blood pressure of the host. The field of computer science has seen rapid progress with its great potential in the application in biomedical sciences, we prompt an exploration of the use of microbiome databases and artificial intelligence in the realm of high blood pressure prediction and prevention. We propose the use of gut microbiota as potential biomarkers in the context of hypertension prevention and therapy.


Subject(s)
Antihypertensive Agents , Blood Pressure , Gastrointestinal Microbiome , Hypertension , Gastrointestinal Microbiome/physiology , Humans , Hypertension/microbiology , Antihypertensive Agents/therapeutic use , Animals , Bacteria/classification , Bacteria/metabolism , Bacteria/genetics , Bacteria/isolation & purification
6.
Materials (Basel) ; 17(10)2024 May 15.
Article in English | MEDLINE | ID: mdl-38793444

ABSTRACT

Developing an inexpensive and efficient catalyst for a hydrogen evolution reaction (HER) is an effective measure to alleviate the energy crisis. Single-atom catalysts (SACs) based on Janus materials demonstrated promising prospects for the HER. Herein, density functional theory calculations were conducted to systematically investigate the performance of SACs based on the BiTeBr monolayer. Among the one hundred and forty models that were constructed, fourteen SACs with potential HER activity were selected. Significantly, the SAC, in which a single Ru atom is anchored on a BiTeBr monolayer with a Bi vacancy (RuS2/VBi-BiTeBr), exhibits excellent HER activity with an ultra-low |ΔGH*| value. A further investigation revealed that RuS2/VBi-BiTeBr tends to react through the Volmer-Heyrovsky mechanism. An electronic structure analysis provided deeper insights into this phenomenon. This is because the Tafel pathway requires overcoming steric hindrance and disrupting stable electron filling states, making it challenging to proceed. This study finally employed constant potential calculations, which approximate experimental situations. The results indicated that the ΔGH* value at pH = 0 is 0.056 eV for RuS2/VBi-BiTeBr, validating the rationality of the traditional Computational Hydrogen Electrode (CHE) method for performance evaluation in this system. This work provides a reference for the research of new HER catalysts.

7.
Sensors (Basel) ; 24(10)2024 May 10.
Article in English | MEDLINE | ID: mdl-38793894

ABSTRACT

Hydrogel flexible strain sensors, renowned for their high stretchability, flexibility, and wearable comfort, have been employed in various applications in the field of human motion monitoring. However, the predominant method for fabricating hydrogels is the template method, which is particularly inefficient and costly for hydrogels with complex structural requirements, thereby limiting the development of flexible hydrogel electronic devices. Herein, we propose a novel method that involves using microgels to modify a hydrogel solution, printing the hydrogel ink using an electrohydrodynamic printing device, and subsequently forming the hydrogel under UV illumination. The resulting hydrogel exhibited a high tensile ratio (639.73%), high tensile strength (0.4243 MPa), and an ionic conductivity of 0.2256 S/m, along with excellent electrochemical properties. Moreover, its high linearity and sensitivity enabled the monitoring of a wide range of subtle changes in human movement. This novel approach offers a promising pathway for the development of high-performance, complexly structured hydrogel flexible sensors.

8.
J Stroke Cerebrovasc Dis ; : 107782, 2024 May 20.
Article in English | MEDLINE | ID: mdl-38777218

ABSTRACT

BACKGROUND AND PURPOSE: Atherosclerotic burden increases the risk of both extracranial internal carotid artery stenosis (ICS) and intracranial large artery disease (ICAD). However, the differences in risk profiles have not been thoroughly investigated. METHODS: Participants were recruited from the Nagahama study cohort in Japan. Individuals over 60 years old who underwent 1.5-T head and neck magnetic resonance angiography (MRA) between July 2013 and February 2017 were included. ICAD was defined as WASID ≥ 50%, and ICS was defined as NSCET ≥ 30%. The prevalence and association of risk factors, including proatherogenic and proinflammatory factors, and the p.R4810K variant in the RNF213 gene, were investigated. Multivariable logistic regression analyses were performed. RESULTS: A total of 3089 individuals participated in the study, with a mean age of 68.1 ± 5.3 years, and 36.0% were males. Among them, 52 (1.7%) had ICS, 119 (3.8%) had ICAD, and 15 (0.49%) had both conditions. Alopecia areata was an independent predictor for both ICS (Odds ratio [OR] 3.5; 95% CI 1.3-8.3) and ICAD (OR 2.1; 95% CI 1.0-3.9). Diabetes (OR 3.7; 95% CI 2.0-7.0) and older age (OR 2.4; 95% CI 1.2-4.5) were associated only with ICS, while the RNF213 variant was associated with only ICAD (OR 5.7; 95% CI 1.6-16.0). ICS and ICAD were also independently associated with each other. CONCLUSIONS: In this MRA-based large scale study, alopecia areata, known as a systemic inflammatory disease, was shown to be a common risk factor for ICS and ICAD. While conventional atherosclerotic factors were associated with ICS, non-atherosclerotic factors appear to contribute to ICAD in Japan.

10.
IEEE Trans Biomed Eng ; PP2024 May 24.
Article in English | MEDLINE | ID: mdl-38787675

ABSTRACT

OBJECTIVE: As biological wide-field visual neurons in locusts, lobula giant motion detectors (LGMDs) can effectively predict collisions and trigger avoidance before the collision occurs. This capability has extensive potential applications in autonomous driving, unmanned aerial vehicles, and more. Currently, describing the LGMD characteristics is divided into two viewpoints, one emphasizing the presynaptic visual pathway and the other emphasizing the postsynaptic LGMDs neuron. Indeed, both have their research support leading to the emergence of two computational models, but both lack a biophysical description of the behavior in the individual LGMD neuron. This paper aims to mimic and explain LGMD's behavior based on fractional spiking neurons and construct a biomimetic visual model for the LGMD compatible with these two characteristics. METHODS: We implement the visual model in the form of spikes by choosing an event camera rather than a conventional CMOS camera to simulate the photoreceptors and follow the topology of the ON/OFF visual pathway, enabling it to incorporate the lateral inhibition to mimic the LGMD's system from the bottom up. Second, most computational models of motion perception use only the dendrites within the LGMD neurons as the ideal pathway for linear summation, ignoring dendritic effects inducing neuronal properties. Thus, we introduced fractional spiking neuron (FSN) circuits into the model by altering dendritic morphological parameters to simulate multi-scale spike frequency adaptation (SFA) observed in LGMDs. In addition, we have attempted to add one more circuit of dendritic trees into fractional spiking neurons to be compatible with the postsynaptic FFI in LGMDs and provide a novel explanatory approach and a predictive model for studying LGMD neurons. RESULTS: Finally, we test that the event-driven biomimetic visual model can achieve collision detection and looming selection in different complex scenes, especially fast-moving objects.

11.
Am J Clin Nutr ; 2024 May 08.
Article in English | MEDLINE | ID: mdl-38729573

ABSTRACT

BACKGROUND: Long-chain free fatty acids (FFAs) are associated with risk of incident diabetes. However, a comprehensive assessment of the associations in normoglycemic populations is lacking. OBJECTIVES: Our study aimed to comprehensively investigate the prospective associations and patterns of FFA profiles with diabetes risk among normoglycemic Chinese adults. METHODS: This is a prospective nested case-control study from the China Cardiometabolic Disease and Cancer Cohort (4C) study. We quantitatively measured 53 serum FFAs using a targeted metabolomics approach in 1707 incident diabetes subjects and 1707 propensity score-matched normoglycemic controls. Conditional logistic regression models were employed to estimate odds ratios (ORs) for associations. Least Absolute Shrinkage and Selection Operator (LASSO) penalty regression and quantile g-computation (qg-comp) analyses were implemented to estimate the association between multi-FFA exposures and incident diabetes. RESULTS: The majority of odd-chain FFAs exhibited an inverse association with incident diabetes, wherein the ORs per SD increment of all 7 saturated fatty acids (SFAs), monounsaturated fatty acid (MUFA) 15:1, and polyunsaturated fatty acid (PUFA) 25:2 were ranging from 0.79 to 0.88 (95% CIs ranging between 0.71 and 0.97). Even-chain FFAs comprised 99.3% of total FFAs and displayed heterogeneity with incident diabetes. SFAs with 18-26 carbon atoms are inversely linked to incident diabetes, with ORs ranging from 0.81 to 0.86 (95% CIs ranging between 0.73 and 0.94). MUFAs 26:1 (OR: 0.85; 95% CI: 0.76, 0.94), PUFAs 20:4 (OR: 0.84; 95% CI: 0.75, 0.94), and 24:2 (OR: 0.87; 95% CI: 0.78, 0.97) demonstrated significant associations. In multi-FFA exposure model, 24 FFAs were significantly associated with incident diabetes, most of which were consistent with univariate results. The mixture OR was 0.78 (95% CI: 0.61, 0.99; P = 0.04159). Differential correlation network analysis revealed pre-existing perturbations in intraclass and interclass FFA coregulation before diabetes onset. CONCLUSIONS: These findings underscore the variations in diabetes risk associated with FFAs across chain length and unsaturation degree, highlighting the importance of recognizing FFA subtypes in the pathogenesis of diabetes.

12.
Water Res ; 257: 121699, 2024 Jun 15.
Article in English | MEDLINE | ID: mdl-38713937

ABSTRACT

The effective activation of natural chalcopyrite (CuFeS2) on peracetic acid (PAA) to remove organic micropollutants was studied under visible light irradiation. Results showed than an effective sulfamethoxazole (SMX) degradation (95.0 %) was achieved under visible light irradiation for 30 min at pH 7.0. Quenching experiments, electron spin resonance analysis, and LC/MS spectrum demonstrated that HO• and CH3C(O)OO• were the main reactive species for SMX degradation, accounting for 43.3 % and 56.7 % of the contributions, respectively. Combined with X-ray photoelectron spectroscopy analysis, the photoelectrons generated on CuFeS2 activated by visible light enhanced the Fe3+/Fe2+ and Cu2+/Cu+ cycles on the surface, thereby activating PAA to generate HO•/CH3C(O)OO•. The removal rate of SMX decreased with the increase in wavelengths, due to the formation of low energy photons at longer wavelengths. Besides, the optimal pH for degradation of SMX by CuFeS2/PAA/Vis-LED process was neutral, which was attributed to the increasing easily activated anionic form of PAA during the increase in pH and the depletion of Fe species at alkaline conditions. Cl-, HCO3-, and HA slightly inhibited SMX degradation because of reactive species being quenched and/or shielding effect. Furthermore, the degradation efficiency of different pollutants by CuFeS2/PAA/Vis-LED was also measured, and the removal efficiency was different owing to the selectivity of CH3C(O)OO•. Finally, the process exhibited good applicability in real waters. Overall, this study provides new insight into visible light-catalyzed activation of PAA and suggests on further exploration of the intrinsic activation mechanism of PAA.


Subject(s)
Copper , Peracetic Acid , Water Pollutants, Chemical , Water Pollutants, Chemical/chemistry , Copper/chemistry , Peracetic Acid/chemistry , Light , Hydrogen-Ion Concentration , Sulfamethoxazole/chemistry
13.
J Hematol Oncol ; 17(1): 27, 2024 May 01.
Article in English | MEDLINE | ID: mdl-38693553

ABSTRACT

The rapid advancements in large language models (LLMs) such as ChatGPT have raised concerns about their potential impact on academic integrity. While initial concerns focused on ChatGPT's writing capabilities, recent updates have integrated DALL-E 3's image generation features, extending the risks to visual evidence in biomedical research. Our tests revealed ChatGPT's nearly barrier-free image generation feature can be used to generate experimental result images, such as blood smears, Western Blot, immunofluorescence and so on. Although the current ability of ChatGPT to generate experimental images is limited, the risk of misuse is evident. This development underscores the need for immediate action. We suggest that AI providers restrict the generation of experimental image, develop tools to detect AI-generated images, and consider adding "invisible watermarks" to the generated images. By implementing these measures, we can better ensure the responsible use of AI technology in academic research and maintain the integrity of scientific evidence.


Subject(s)
Biomedical Research , Humans , Biomedical Research/methods , Image Processing, Computer-Assisted/methods , Artificial Intelligence , Software
14.
Eur J Med Res ; 29(1): 278, 2024 May 09.
Article in English | MEDLINE | ID: mdl-38725036

ABSTRACT

BACKGROUND: Sarcopenia is a progressive age-related disease that can cause a range of adverse health outcomes in older adults, and older adults with severe sarcopenia are also at increased short-term mortality risk. The aim of this study was to construct and validate a risk prediction model for sarcopenia in Chinese older adults. METHODS: This study used data from the 2015 China Health and Retirement Longitudinal Study (CHARLS), a high-quality micro-level data representative of households and individuals aged 45 years and older adults in China. The study analyzed 65 indicators, including sociodemographic indicators, health-related indicators, and biochemical indicators. RESULTS: 3454 older adults enrolled in the CHARLS database in 2015 were included in the final analysis. A total of 997 (28.8%) had phenotypes of sarcopenia. Multivariate logistic regression analysis showed that sex, Body Mass Index (BMI), Mean Systolic Blood Pressure (MSBP), Mean Diastolic Blood Pressure (MDBP) and pain were predictive factors for sarcopenia in older adults. These factors were used to construct a nomogram model, which showed good consistency and accuracy. The AUC value of the prediction model in the training set was 0.77 (95% CI = 0.75-0.79); the AUC value in the validation set was 0.76 (95% CI = 0.73-0.79). Hosmer-Lemeshow test values were P = 0.5041 and P = 0.2668 (both P > 0.05). Calibration curves showed significant agreement between the nomogram model and actual observations. ROC and DCA showed that the nomograms had good predictive properties. CONCLUSIONS: The constructed sarcopenia risk prediction model, incorporating factors such as sex, BMI, MSBP, MDBP, and pain, demonstrates promising predictive capabilities. This model offers valuable insights for clinical practitioners, aiding in early screening and targeted interventions for sarcopenia in Chinese older adults.


Subject(s)
Sarcopenia , Humans , Sarcopenia/epidemiology , Sarcopenia/diagnosis , Male , Female , Aged , China/epidemiology , Middle Aged , Risk Factors , Aged, 80 and over , Longitudinal Studies , Body Mass Index , Risk Assessment/methods , Nomograms
15.
Org Biomol Chem ; 2024 May 29.
Article in English | MEDLINE | ID: mdl-38809155

ABSTRACT

We report herein a synthesis of allylic phosphoramidates from alkenes by selenium-catalyzed allylic C-H derivatization. This method features mild conditions, broad substrate scope, and high functional group tolerance, enabling late-stage modification of a number of complex substrates. In addition, this protocol was applied to modify caryophyllene and produced a photoaffinity probe capable of proteomic target labeling in live HeLa cells.

16.
Nanoscale ; 16(21): 10318-10324, 2024 May 30.
Article in English | MEDLINE | ID: mdl-38738311

ABSTRACT

The study of structural isomerism in copper nanoclusters has been relatively limited compared to that in gold and silver nanoclusters. In this work, we present the controlled synthesis and structures of two isomeric copper nanoclusters, denoted as Cu22-1 and Cu22-2, whose compositions were determined to be Cu22(SePh)10(Se)6(P(Ph-4F)3)8 through single-crystal X-ray diffraction (SCXRD). The structural isomerism of Cu22-1 and Cu22-2 arises from the different arrangements of a few Cu(SeR)(PR3) motifs on the surface structure. These subtle changes in the surface structure also influence the distortion of the core and the spatial arrangement of the clusters, and affect the electronic structure. Furthermore, due to their distinct structures, Cu22-1 and Cu22-2 exhibit different catalytic properties in the copper-catalyzed [3 + 2] azide-alkyne cycloaddition (CuAAC). Notably, Cu22-1 demonstrates efficient catalytic activity for photoinduced AAC, achieving a yield of 90% within 1 hour. This research contributes to the understanding of structural isomerism in copper nanoclusters and offers insights into the structure-function relationship in these systems.

17.
J Hazard Mater ; 472: 134492, 2024 Jul 05.
Article in English | MEDLINE | ID: mdl-38703687

ABSTRACT

Nitrite plays a critical role in a variety of nitrification and denitrification processes in the nitrogen cycle. Due to the high surface energy, tendency to aggregate, and poor conductivity, current nitrite ZnS-based sensing platform could not meet the need of on-site nitrite detection in smart agriculture. In order to address these issues, the carboxylated carbon nanotube (CNT) was introduced to reduce the surface energy and prevented aggregation of ZnS, while ZnS-carboxylated CNT (ZnS-CNT) composite also provided excellent electrochemical conductivity. Furthermore, the introduction of phase transition BSA (PTB) created a three-dimensional porous conductive matrix without interfering with the mass transfer process of nitrite. The resulting sensing platform exhibited a linear detection range of 10 nM to 0.4 mM for nitrite, with a detection limit of 0.73 nM. And this sensing platform had the excellent antifouling ability to direct detection nitrite in real soil suspension. In addition, the sensing platform demonstrated remarkable resistance to interferences from pH variations, microbial presence, and organic pollutants that usually present in soil environment. Therefore, on-site detection of nitrite ions in soil environment was realized no needing complex pretreatments.

18.
Nat Plants ; 10(5): 815-827, 2024 May.
Article in English | MEDLINE | ID: mdl-38745100

ABSTRACT

A comprehensive understanding of inflorescence development is crucial for crop genetic improvement, as inflorescence meristems give rise to reproductive organs and determine grain yield. However, dissecting inflorescence development at the cellular level has been challenging owing to a lack of specific marker genes to distinguish among cell types, particularly in different types of meristems that are vital for organ formation. In this study, we used spatial enhanced resolution omics-sequencing (Stereo-seq) to construct a precise spatial transcriptome map of the developing maize ear primordium, identifying 12 cell types, including 4 newly defined cell types found mainly in the inflorescence meristem. By extracting the meristem components for detailed clustering, we identified three subtypes of meristem and validated two MADS-box genes that were specifically expressed at the apex of determinate meristems and involved in stem cell determinacy. Furthermore, by integrating single-cell RNA transcriptomes, we identified a series of spatially specific networks and hub genes that may provide new insights into the formation of different tissues. In summary, this study provides a valuable resource for research on cereal inflorescence development, offering new clues for yield improvement.


Subject(s)
Inflorescence , Meristem , Transcriptome , Zea mays , Zea mays/genetics , Zea mays/growth & development , Zea mays/metabolism , Inflorescence/genetics , Inflorescence/growth & development , Meristem/genetics , Meristem/growth & development , Meristem/metabolism , Gene Expression Regulation, Plant , Gene Expression Profiling
19.
J Chem Phys ; 160(18)2024 May 14.
Article in English | MEDLINE | ID: mdl-38726934

ABSTRACT

Fullerene-assembled low-dimensional materials have been experimentally realized in polymorphic forms and have attracted significant interest very recently. Here, we predict a two-dimensional (2D) honeycomb lattice material TM2(C60)3 (TM = Cr, Mo, and W) assembled from exohedral metallofullerene clusters TM(C60)3 that could exhibit planar triangular geometries. According to first-principles calculations combined with Monte Carlo simulations, we suggest that these 2D assembled materials exhibit various exotic physical properties, including ferromagnetism, ferroelectricity, and quantum anomalous Hall effect. Interestingly, mechanical strains could effectively tune their magnetic moments and switch the conducting spin channel of the Dirac bands at the Fermi level. Our work provides a new cluster-assembly design strategy toward cluster-assembled 2D materials based on fullerene characters.

20.
Stem Cell Res Ther ; 15(1): 143, 2024 May 20.
Article in English | MEDLINE | ID: mdl-38764049

ABSTRACT

BACKGROUND: Spinal cord injury (SCI) is a debilitating illness in humans that causes permanent loss of movement or sensation. To treat SCI, exosomes, with their unique benefits, can circumvent limitations through direct stem cell transplantation. Therefore, we utilized Gelfoam encapsulated with exosomes derived from human umbilical cord mesenchymal stem cells (HucMSC-EX) in a rat SCI model. METHODS: SCI model was established through hemisection surgery in T9 spinal cord of female Sprague-Dawley rats. Exosome-loaded Gelfoam was implanted into the lesion site. An in vivo uptake assay using labeled exosomes was conducted on day 3 post-implantation. Locomotor functions and gait analyses were assessed using Basso-Beattie-Bresnahan (BBB) locomotor rating scale and DigiGait Imaging System from weeks 1 to 8. Nociceptive responses were evaluated through von Frey filament and noxious radiant heat tests. The therapeutic effects and potential mechanisms were analyzed using Western blotting and immunofluorescence staining at week 8 post-SCI. RESULTS: For the in vivo exosome uptake assay, we observed the uptake of labeled exosomes by NeuN+, Iba1+, GFAP+, and OLIG2+ cells around the injured area. Exosome treatment consistently increased the BBB score from 1 to 8 weeks compared with the Gelfoam-saline and SCI control groups. Additionally, exosome treatment significantly improved gait abnormalities including right-to-left hind paw contact area ratio, stance/stride, stride length, stride frequency, and swing duration, validating motor function recovery. Immunostaining and Western blotting revealed high expression of NF200, MBP, GAP43, synaptophysin, and PSD95 in exosome treatment group, indicating the promotion of nerve regeneration, remyelination, and synapse formation. Interestingly, exosome treatment reduced SCI-induced upregulation of GFAP and CSPG. Furthermore, levels of Bax, p75NTR, Iba1, and iNOS were reduced around the injured area, suggesting anti-inflammatory and anti-apoptotic effects. Moreover, exosome treatment alleviated SCI-induced pain behaviors and reduced pain-associated proteins (BDNF, TRPV1, and Cav3.2). Exosomal miRNA analysis revealed several promising therapeutic miRNAs. The cell culture study also confirmed the neurotrophic effect of HucMSCs-EX. CONCLUSION: Implantation of HucMSCs-EX-encapsulated Gelfoam improves SCI-induced motor dysfunction and neuropathic pain, possibly through its capabilities in nerve regeneration, remyelination, anti-inflammation, and anti-apoptosis. Overall, exosomes could serve as a promising therapeutic alternative for SCI treatment.


Subject(s)
Disease Models, Animal , Exosomes , Mesenchymal Stem Cells , Neuralgia , Rats, Sprague-Dawley , Spinal Cord Injuries , Animals , Spinal Cord Injuries/therapy , Exosomes/metabolism , Neuralgia/therapy , Neuralgia/metabolism , Rats , Female , Humans , Mesenchymal Stem Cells/metabolism , Mesenchymal Stem Cells/cytology , Locomotion , Gelatin Sponge, Absorbable , Umbilical Cord/cytology
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