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Psychrophilic bacteria, the dominant spoilage organisms in raw milk, secrete heat-stable extracellular proteases and lipases that lead to the decomposition of milk and dairy products. In this study, we investigated psychrophilic bacteria in 165 raw milk samples collected across four seasons and six regions in China using shotgun metagenomic sequencing and traditional culture methods. The isolated psychrophilic bacteria were classified into 40 genera and 185 species. Pseudomonas was the most prevalent, accounting for 51.13â¯% of the genera, while Lactococcus and Chryseobacterium were also notably abundant (> 6.0â¯%). Metagenomic sequencing revealed that Pseudomonas (47.9â¯%), Stenotrophomonas (9.75â¯%), Sphingomonas (6.73â¯%), Latilactobacillus (6.38â¯%) and Lactococcus (5.16â¯%) were the dominant genera in the raw milk samples. The diversity of psychrophilic bacteria in raw milk was strongly influenced by seasonal variations, with the sampling region being a less significant factor. KEGG annotation indicated that carbohydrate and amino acid metabolism were the primary metabolic pathways in these bacteria. Metagenomic sequencing not only accurately identifies species but also provides functional insights into psychrophilic bacteria in raw milk, aiding in understanding their activities, promoting their control on farms, and ultimately improving raw milk quality.
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An approach for continuous tuning of on-chip optical delay with a microring resonator is proposed and demonstrated. By introducing an electro-optically tunable waveguide coupler, the bus waveguide to the resonance coupling can be effectively tuned from the under-coupling regime to the over-coupling regime. The optical delay is experimentally characterized by measuring the relative phase shift between lasers and shows a large dynamic range of delay from -600 to 600 ps and an efficient tuning of delay from -430 to -180 ps and from 40 to 240 ps by only a 5 V voltage.
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BACKGROUND: Systolic blood pressure (SBP) was a predictor of early neurological deterioration (END) in stroke. We performed a secondary analysis of ARAMIS trial to investigate whether baseline SBP affects the effect of dual antiplatelet versus intravenous alteplase on END. METHODS: This post hoc analysis included patients in the as-treated analysis set. According to SBP at admission, patients were divided into SBP ≥140 mmHg and SBP <140 mmHg subgroups. In each subgroup, patients were further classified into dual antiplatelet and intravenous alteplase treatment groups based on study drug actually received. Primary outcome was END, defined as an increase of ≥2 in the NIHSS score from baseline within 24 h. We investigated effect of dual antiplatelet vs intravenous alteplase on END in SBP subgroups and their interaction effect with subgroups. RESULTS: A total of 723 patients from as-treated analysis set were included: 344 were assigned into dual antiplatelet group and 379 into intravenous alteplase group. For primary outcome, there was more treatment effect of dual antiplatelet in SBP ≥140 mmHg subgroup (adjusted RD, -5.2%; 95% CI, -8.2% to -2.3%; p < 0.001) and no effect in SBP <140 mmHg subgroup (adjusted RD, -0.1%; 95% CI, -8.0% to 7.7%; p = 0.97), but no significant interaction between subgroups was found (adjusted p = 0.20). CONCLUSIONS: Among patients with minor nondisabling acute ischemic stroke, dual antiplatelet may be better than alteplase with respect to preventing END within 24 h when baseline SBP ≥140 mmHg.
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Presión Sanguínea , Fibrinolíticos , Inhibidores de Agregación Plaquetaria , Accidente Cerebrovascular , Activador de Tejido Plasminógeno , Humanos , Masculino , Femenino , Presión Sanguínea/efectos de los fármacos , Presión Sanguínea/fisiología , Anciano , Activador de Tejido Plasminógeno/uso terapéutico , Activador de Tejido Plasminógeno/administración & dosificación , Persona de Mediana Edad , Inhibidores de Agregación Plaquetaria/uso terapéutico , Fibrinolíticos/uso terapéutico , Fibrinolíticos/administración & dosificación , Accidente Cerebrovascular/tratamiento farmacológico , Accidente Cerebrovascular/complicaciones , Anciano de 80 o más Años , Método Doble Ciego , Accidente Cerebrovascular Isquémico/tratamiento farmacológicoRESUMEN
The Ag cluster-POM assemblies have been shown to possess interesting and potentially useful properties. However, there is no precedent example of atomically precise Ag cluster-POM assemblies showing heterojunction effects in photocatalysis. Herein, the synthesis and total structure determination of the periodically distributed molecular heterojunction [Ag12(SCy)6(CH3CN)12(PW12O40)]n (Ag12-PW12) are reported. The assembly of Ag/W clusters into 3D network can endow the resulting binary structure with an aesthetic topology and unique physicochemical properties. More remarkably, the incorporation of Ag12 cluster with PW12 can efficiently facilitate the separation of photogenerated electrons and holes, thus significantly promoting the catalytic efficiency in selective oxidation of sulfides. The Ag12-PW12 heterojunction can be recovered and reused five times with no drastic change in the catalytic performance. This research is expected to assist in the rational design of cluster-based heterojunction catalysts. The increase of catalytic activity of the Ag12-PW12 assembly in comparison with the unassembled Ag12 and PW12 clusters is attributed to the synergistic effect of Ag12 and PW12 clusters, offering the splendid opportunity for deciphering structure-reactivity relationship of heterostructure-coupled photosystem.
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Steamed ginseng water (SGW) is a by-product of the repeated thermal processing of red ginseng, which is characterized by a high bioactive content, better skin care activity, and a large output. However, its value has been ignored, resulting in environmental pollution and resource waste. In this study, UHPLC-Q-Exactive-MS/MS liquid chromatography-mass spectrometry and multivariate statistical analysis were conducted to characterize the compositional features of the repeated thermal-treated SGW. The antioxidant activity (DPPH, ABTS, FRAP, and OH) and chemical composition (total sugars, total saponins, and reducing and non-reducing sugars) were comprehensively evaluated based on the entropy weighting method. Four comparison groups (groups 1 and 3, groups 1 and 5, groups 1 and 7, and groups 1 and 9) were screened for 37 important common difference markers using OPLS-DA analysis. The entropy weight method was used to analyze the weights of the indicators; the seventh SGW sample was reported to have a significant weight. The results of this study suggest that heat treatment time and frequency can be an important indicator value for the quality control of SGW cycling operations, which have great potential in antioxidant products.
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Antioxidantes , Panax , Espectrometría de Masas en Tándem , Panax/química , Antioxidantes/química , Antioxidantes/análisis , Cromatografía Líquida de Alta Presión , Espectrometría de Masas en Tándem/métodos , Calor , Saponinas/química , Saponinas/análisis , Extractos Vegetales/químicaRESUMEN
The strategy of in vivo self-assembly has been developed for improved enrichment and long-term retention of anticancer drug in tumor tissues. However, most self-assemblies with non-covalent bonding interactions are susceptible to complex physiological environments, leading to weak stability and loss of biological function. Here, we develop a coupling-induced assembly (CIA) strategy to generate covalently crosslinked nanofibers, which is applied for in situ constructing artificial shell on mitochondria. The oxidation-responsive peptide-porphyrin conjugate P1 is synthesized, which self-assemble into nanoparticles. Under the oxidative microenvironment of mitochondria, the coupling of thiols in P1 causes the formation of dimers, which is further ordered and stacked into crosslinked nanofibers. As a result, the artificial shell is constructed on the mitochondria efficiently through multivalent cooperative interactions due to the increased binding sites. Under ultrasound (US) irradiation, the porphyrin molecules in the shell produce a large amount of reactive oxygen species (ROS) that act on the adjacent mitochondrial membrane, exhibiting ~2-fold higher antitumor activity than nanoparticles in vitro and in vivo. Therefore, the mitochondria-targeted CIA strategy provides a novel perspective on improved sonodynamic therapy (SDT) and shows potential applications in antitumor therapies.
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The application of acupuncture and moxibustion in alleviating the adverse effects of chemotherapy drugs has been widely recognized at home and abroad, but the studies have been rarely summarized for the enhanced anti-tumor effect and its mechanism of acupuncture and moxibustion to synergize the chemotherapy drugs. This paper reviewed the clinical and basic studies on the synergism of chemotherapy with acupuncture and moxibustion in recent years. It was found that chemotherapy synergized with acupuncture and moxibustion can suppress cancer to a certain extent and improve the quality of life in patients. The effect mechanism of acupuncture and moxibustion combined with chemotherapy drugs is related to promoting tumor cell apoptosis, improving the immune and vascular microenvironment, and advancing chemotherapy drug enrichment on the affected area. It provides the evidences and ideas for enhancing the effect of chemotherapy by delivering acupuncture and moxibustion as an adjuvant therapy.
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Terapia por Acupuntura , Antineoplásicos , Moxibustión , Neoplasias , Humanos , Neoplasias/terapia , Neoplasias/tratamiento farmacológico , Animales , Terapia CombinadaRESUMEN
Aï¬atoxin B1 (AFB1), a common mycotoxin, can occur in agricultural products. As a metabolite of AFB1, aï¬atoxin M1 (AFM1) mainly exist in dairy products. These two mycotoxins threaten human health, although it is unclear how they affect the function of the intestinal barrier. In this study, mice were exposed to AFB1 (0.3â¯mg/kg body b.w.) and AFM1(3.0â¯mg/kg b.w.) either individually or in combination for 28 days to explore the main differentially expressed proteins (DEPs) and the associated enriched pathways. These findings were preliminarily verified by the transcriptomic and proteomic analyses in differentiated Caco-2 cells. The results revealed that AFB1 and AFM1 exposure in mice disrupted the function of the intestinal barrier, and the combined toxicity was greater than that of each toxin alone. Further proteomic analysis in mice demonstrated that the mechanisms underlying these differences could be explained as follows: (i) lipid metabolism was enriched by AFB1-induced DEPs. (ii) protein export pathway was stimulated by AFM1-induced DEPs. (iii) cell metabolic ability was inhibited (as evidenced by changes in UDP-GT1, UDP-GT2, and Gatm6), apoptosis was induced (MAP4K3), and epithelial cell integrity was disrupted (Claudin7 and IQGAP2), resulting in more extensive intestinal damage after combined treatment. In conclusion, the hazardous impact of co-exposure to AFB1 and AFM1 from proteomic perspectives was demonstrated in the present study.
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Aflatoxina B1 , Aflatoxina M1 , Proteómica , Aflatoxina M1/toxicidad , Aflatoxina B1/toxicidad , Animales , Ratones , Células CACO-2 , Humanos , Masculino , Intestinos/efectos de los fármacos , Intestinos/patología , Mucosa Intestinal/efectos de los fármacos , Mucosa Intestinal/metabolismoRESUMEN
OBJECTIVE: The aim of this study was to design a novel lumbar cortical bone trajectory (CBT) penetrating the anterior, middle, and posterior vertebral area using imaging; measure the relevant parameters to find theoretical parameters and screw placement possibilities; and investigate the optimal implantation trajectory of the CBT in patients with osteoporosis. METHODS: Three types of CBTs with appropriate lengths were selected to simulate screw placement using Mimics software. These CBTs were classified as the leading tip of the trajectory pointing to the posterior quarter area (original CBT [CBT-O]) and middle (novel CBT A [CBT-A]) and anterior quarter (novel CBT B [CBT-B]) of the superior endplate. The authors then measured the maximum screw diameter (MSD) and length (MSL), cephalad (CA) and lateral (LA) angles, and bone mineral density (Hounsfield unit [HU] values) of the planned novel 3-column CBT screw placements. The differences in the parameters of the novel CBTs, the percentages of successfully planned CBT screws, and the factors that influenced the successful planning of 3-column CBT screws were analyzed. RESULTS: Three-column CBT screws were successfully designed in all segments of the lumbar spine. The success rate of the 3-column CBT planned screws was 72.25% (83.25% for CBT-A and 61.25% for CBT-B). From the CBT-O type, to the CBT-A type, to the CBT-B type, the LA, CA, and MSD of the novel CBT screws decreased with increasing trajectory length. The HU values of the three types of trajectories were all significantly higher than that of the traditional pedicle screw trajectory (p < 0.001). The main factor affecting successful planning of the 3-column CBT screw was pedicle width. CONCLUSIONS: Moderating adjustment of the original screw parameters by reducing LAs and CAs to penetrate the anterior, middle, and posterior columns of the vertebral body using the 3-column CBT screw is feasible, especially in the lower lumbar spine.
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Hueso Cortical , Vértebras Lumbares , Humanos , Vértebras Lumbares/cirugía , Vértebras Lumbares/diagnóstico por imagen , Hueso Cortical/cirugía , Hueso Cortical/diagnóstico por imagen , Anciano , Femenino , Masculino , Persona de Mediana Edad , Osteoporosis/cirugía , Osteoporosis/diagnóstico por imagen , Densidad Ósea/fisiología , Tornillos Óseos , Tomografía Computarizada por Rayos X , Fusión Vertebral/métodos , Fusión Vertebral/instrumentaciónRESUMEN
Immune checkpoint blockade therapy represented by programmed cell death ligand 1 (PD-L1) inhibitor for advanced renal carcinoma with an objective response rate (ORR) in patients is less than 20%. It is attributed to abundant tumoral vasculature with abnormal structure limiting effector T cell infiltration and drug penetration. We propose a bispecific fibrous glue (BFG) to regulate tumor immune and vascular microenvironments simultaneously. The bispecific precursor glue peptide-1 (pre-GP1) can penetrate tumor tissue deeply and self-assemble into BFG in the presence of neuropilin-1 (NRP-1) and PD-L1. The resultant fibrous glue is capable of normalizing tumoral vasculature as well as restricting immune escape. The pre-GP1 retains a 6-fold higher penetration depth than that of antibody in the multicellular spheroids (MCSs) model. It also shows remarkable tumor growth inhibition (TGI) from 19% to 61% in a murine advanced large tumor model compared to the clinical combination therapy. In addition, in the orthotopic renal tumor preclinical model, the lung metastatic nodules are reduced by 64% compared to the clinically used combination. This pre-GP1 provides a promising strategy to control the progression and metastasis of advanced renal carcinoma.
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Carcinoma de Células Renales , Neoplasias Renales , Animales , Neoplasias Renales/patología , Neoplasias Renales/tratamiento farmacológico , Neoplasias Renales/terapia , Neoplasias Renales/inmunología , Humanos , Ratones , Carcinoma de Células Renales/patología , Carcinoma de Células Renales/inmunología , Carcinoma de Células Renales/terapia , Carcinoma de Células Renales/tratamiento farmacológico , Línea Celular Tumoral , Microambiente Tumoral/efectos de los fármacos , Ratones Endogámicos BALB C , Femenino , Antígeno B7-H1/antagonistas & inhibidores , Antígeno B7-H1/metabolismoRESUMEN
On-chip acousto-optic modulators that operate at an optical wavelength of 780 nm and a microwave frequency of 6.835 GHz are proposed. The modulators are based on a lithium-niobate-on-sapphire platform and efficiently excite surface acoustic waves and exhibit strong interactions with tightly confined optical modes in waveguides. In particular, a high-efficiency phase modulator and single-sideband mode converter are designed. We found that for both microwave and optical wavelengths below 1 µm, the interactions at the cross-sections of photonic waveguides are sensitive to the waveguide width and are significantly different from those in previous studies. Our designed devices have small footprints and high efficiencies, making them suitable for controlling rubidium atoms and realizing hybrid photonic-atomic chips. Furthermore, our devices have the potential to extend the acousto-optic modulators to other visible wavelengths for other atom transitions and for visible light applications, including imaging and sensing.
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We investigated the changes of soil nutrients and plant communities in the artificial sand fixation forests of Caragana korshinskii with different ages. The results showed that soil organic carbon and soil total nitrogen contents increased with the stand ages, and were significantly higher in 40 and 50 year-old than other ages. Soil organic carbon and total nitrogen contents recovered much faster in the surface layer (0-10 cm) than in others. Soil nutrient stoichiometric ratios (C:P, N:P) in the 0-10 cm soil layer differed significantly among different stand ages. With the increases of stand age, C and N contents in C. korshinskii leaves increased significantly, and reached the maximum at 50 year-old. Leaf P content increased first and then decreased, being maximum at 18 year-old. Leaf C:N first increased and then decreased, being maximum at 12 year-old. The contents of photosynthetic pigments and leaf C:P and N:P decreased first and then increased, being minimum at 18 year-old. C. korshinskii was mainly influenced by N availability before 40 year-old, but mainly limited by P after. The species number, density, and vegetation cover of annual and perennial herbaceous plants increased with stand ages, and the community shifted from a simple shrub plant community to a complex shrub-herb community. The biomass of C. korshinskii and herbaceous plants increased significantly with stand age, and had a significant positive correlation with the contents of soil organic carbon, total nitrogen and N:P.
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Caragana , Suelo , Arena , Carbono/análisis , China , NitrógenoRESUMEN
BACKGROUND: Bone metastases are rare in oral squamous cell carcinoma (OSCC). It has not been defined on the risk and prognosis of OSCC patients with bone metastases. The purpose of this study was to assess the factors associated with the development and prognosis of bone metastases among OSCC patients. METHODS: Demographic and clinicopathological characteristics of OSCC patients diagnosed between 2010 and 2019 was retrieved from the Surveillance, Epidemiology, and End Results (SEER) database. To explore risk factors for developing bone metastases and prognosis, the univariate and multivariate logistic and Cox regression analysis were performed, further the predictive nomogram models were constructed. RESULTS: The incidence rate of bone metastases in newly diagnosed OSCC patients was 0.91 % (95 %CI 0.81% -1.02 %). Ultimately, 137 OSCC patients with bone metastases and 19,469 OSCC patients without bone metastases were included in the present study. Pathological grade, primary site, T/N stage and distant organ metastases (liver/lung/brain) were independently associated with the risk of developing bone metastases among OSCC patients. The C-index of a constructed risk-predicting nomogram was 0.86 (95 %CI 0.83-0.89). Multivariate Cox regression analysis indicated that lung metastases, the use of surgery as well as chemotherapy were three independent prognostic factors. The C-indexes of constructed risk-predicting nomograms were 0.70 (95 %CI 0.65-0.75), 0.68 (95 %CI 0.63-0.73) for OS and CSS, respectively. Calibration plots demonstrated an agreementbetween the established nomogram's predicted survival and actual survival. In addition, decision curve analysis (DCA) indicated these established nomograms had considerable net benefits and clinical utilities. CONCLUSION: This study defined the risk and prognostic factors for bone metastases among OSCC patients and the established nomograms were well calibrated for discrimination to predict bone metastasis development and prognosis.
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Neoplasias Óseas , Carcinoma de Células Escamosas , Neoplasias de la Boca , Nomogramas , Programa de VERF , Humanos , Masculino , Neoplasias Óseas/secundario , Neoplasias Óseas/epidemiología , Neoplasias Óseas/diagnóstico , Femenino , Estudios Retrospectivos , Programa de VERF/estadística & datos numéricos , Persona de Mediana Edad , Neoplasias de la Boca/patología , Neoplasias de la Boca/epidemiología , Neoplasias de la Boca/diagnóstico , Factores de Riesgo , Pronóstico , Anciano , Carcinoma de Células Escamosas/epidemiología , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/secundario , Carcinoma de Células Escamosas/diagnóstico , Adulto , Incidencia , Estadificación de NeoplasiasRESUMEN
BACKGROUND: Fetoscopic endoluminal tracheal occlusion (FETO) improves the survival rate in fetuses with severe congenital diaphragmatic hernia (CDH). We hypothesize that prenatal therapies into the trachea during FETO can further improve outcomes. Here, we present an ex vivo microinjection technique with rat lung explants to study prenatal therapy with nanoparticles. METHODS: We used microsurgery to isolate lungs from rats on embryonic day 18. We injected chitosan nanoparticles loaded with fluorescein (FITC) into the trachea of the lung explants. We compared the difference in biodistribution of two types of nanoparticles, functionalized IgG-conjugated nanoparticles (IgG-nanoparticles) and bare nanoparticles after 24 h culture with immunofluorescence (IF). We used IF to mark lung epithelial cells with E-cadherin and to investigate an apoptosis (Active-caspase 3) and inflammatory marker (Interleukin, IL-6) and compared its abundance between the two experimental groups and control lung explants. RESULTS: We detected the presence of nanoparticles in the lung explants, and the relative number of nanoparticles to cells was 2.49 fold higher in IgG-nanoparticles than bare nanoparticles (p < 0.001). Active caspase-3 protein abundance was similar in the control, bare nanoparticles (1.20 fold higher), and IgG-nanoparticles (1.34 fold higher) groups (p = 0.34). Similarly, IL-6 protein abundance was not different in the control, bare nanoparticles (1.13 fold higher), and IgG-nanoparticles (1.12 fold higher) groups (p = 0.33). CONCLUSIONS: Functionalized nanoparticles had a higher presence in lung cells and this did not result in more apoptosis or inflammation. Our proof-of-principle study will guide future research with therapies to improve lung development prenatally. LEVELS OF EVIDENCE: N/A TYPE OF STUDY: Animal and laboratory study.
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Hernias Diafragmáticas Congénitas , Embarazo , Femenino , Animales , Ratas , Hernias Diafragmáticas Congénitas/cirugía , Hernias Diafragmáticas Congénitas/metabolismo , Proyectos Piloto , Interleucina-6/metabolismo , Microinyecciones , Distribución Tisular , Pulmón/anomalías , Fetoscopía/métodos , Tráquea/cirugía , Inmunoglobulina G/metabolismoRESUMEN
Multiple sclerosis (MS) is a leading cause of chronic neurological dysfunction in young to middle-aged adults, affecting approximately 2.5 million people worldwide. It is characterized by inflammation, multifocal demyelination, axonal loss, and white and gray matter gliosis. Autophagy is a highly conserved protein degradation pathway. Polymorphisms in autophagy-related genes have been implicated in a variety of autoimmune diseases, including systemic lupus erythematosus, rheumatoid arthritis, psoriasis and MS. However, the significance of autophagy in MS remains to be elucidated. This paper aims to explore the potential role of autophagy-related genes in MS diseases by using bioinformatics combined with machine learning methods. Finally, we obtained 9 autophagy genes with the highest correlation with MS, and further changes in these autophagy genes were verified in the experimental autoimmune encephalomyelitis (EAE) model and oligodendrocyte precursor cells (OPCs) engulfed myelin debris (MD). Combined with bioinformatic analysis and experimental data, Becn1 showed obvious expression abnormalities suggesting that this gene has vital functions in autophagy and MD engulfed by OPCs. This work will be of great significance for the further exploration of autophagy-related genes in demyelinating diseases.
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Autofagia , Encefalomielitis Autoinmune Experimental , Esclerosis Múltiple , Células Precursoras de Oligodendrocitos , Fagocitosis , Autofagia/fisiología , Esclerosis Múltiple/patología , Esclerosis Múltiple/genética , Animales , Encefalomielitis Autoinmune Experimental/patología , Encefalomielitis Autoinmune Experimental/genética , Células Precursoras de Oligodendrocitos/patología , Células Precursoras de Oligodendrocitos/metabolismo , Humanos , Ratones Endogámicos C57BL , Vaina de Mielina/metabolismo , Vaina de Mielina/patología , Femenino , Beclina-1/metabolismo , Beclina-1/genéticaRESUMEN
Demyelination and failure of remyelination in the central nervous system (CNS) characterize a number of neurological disorders. Spontaneous remyelination in demyelinating diseases is limited, as oligodendrocyte precursor cells (OPCs), which are often present in demyelinated lesions in abundance, mostly fail to differentiate into oligodendrocytes, the myelinating cells in the CNS. In addition to OPCs, the lesions are assembled numbers of activated resident microglia/infiltrated macrophages; however, the mechanisms and potential role of interactions between the microglia/macrophages and OPCs are poorly understood. Here, we generated a transcriptional profile of exosomes from activated microglia, and found that miR-615-5p was elevated. miR-615-5p bound to 3'UTR of myelin regulator factor (MYRF), a crucial myelination transcription factor expressed in oligodendrocyte lineage cells. Mechanistically, exosomes from activated microglia transferred miR-615-5p to OPCs, which directly bound to MYRF and inhibited OPC maturation. Furthermore, an effect of AAV expressing miR-615-5p sponge in microglia was tested in experimental autoimmune encephalomyelitis (EAE) and cuprizone (CPZ)-induced demyelination model, the classical mouse models of multiple sclerosis. miR-615-5p sponge effectively alleviated disease progression and promoted remyelination. This study identifies miR-615-5p/MYRF as a new target for the therapy of demyelinating diseases.
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Encefalomielitis Autoinmune Experimental , Exosomas , MicroARNs , Vaina de Mielina , Animales , Ratones , Exosomas/metabolismo , Microglía/metabolismo , MicroARNs/genéticaRESUMEN
Demyelination is a pathological feature commonly observed in various central nervous system diseases. It is characterized by the aggregation of oligodendrocyte progenitor cells (OPCs) in the lesion area, which face difficulties in differentiating into mature oligodendrocytes (OLGs). The differentiation of OPCs requires the presence of Sox10, but its expression decreases under pathological conditions. Therefore, we propose a therapeutic strategy to regulate OPCs differentiation and achieve myelin repair by endogenously loading Sox10 into exosomes. To accomplish this, we generated a lentivirus-armed Sox10 that could anchor to the inner surface of the exosome membrane. We then infected HEK293 cells to obtain exosomes with high expression of Sox10 (exosomes-Sox10, ExoSs). In vitro, experiments confirmed that both Exos and ExoSs can be uptaken by OPCs, but only ExoSs exhibit a pro-differentiation effect on OPCs. In vivo, we administered PBS, Exos, and ExoSs to cuprizone-induced demyelinating mice. The results demonstrated that ExoSs can regulate the differentiation of PDGFRα+ OPCs into APC+ OLGs and reduce myelin damage in the corpus callosum region of the mouse brain compared to other groups. Further testing suggests that Sox10 may have a reparative effect on the myelin sheath by enhancing the expression of MBP, possibly facilitated by the exosome delivery of the protein into the lesion. This endogenously loaded technology holds promise as a strategy for protein-based drugs in the treatment of demyelinating diseases.
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Enfermedades Desmielinizantes , Exosomas , Ratones , Humanos , Animales , Cuprizona , Enfermedades Desmielinizantes/inducido químicamente , Exosomas/metabolismo , Células HEK293 , Vaina de Mielina/metabolismo , Diferenciación Celular , Ratones Endogámicos C57BL , Modelos Animales de Enfermedad , Factores de Transcripción SOXE/metabolismoRESUMEN
BACKGROUND: Anterior column realignment (ACR) is a novel surgical method for correcting spinal sagittal balance. meanwhile, oblique lumbar interbody fusion (OLIF) and anterior lumbar interbody fusion (ALIF) are considered minimally invasive surgical methods through natural anatomical space. This study aimed to explore the corrective effects and clinical outcomes of OLIF or ALIF combined with ACR technology in patients with adult spinal deformity (ASD). METHODS: We retrospectively analyzed patients with sagittal imbalance who received OLIF and/or ALIF and ACR treatment from 2018 to 2021. Surgical time and intraoperative bleeding volume are recorded, the corrective effect is determined by the intervertebral space angle (IVA), lumbar lordosis (LL), the sagittal vertical axis (SVA), clinical outcome is evaluated by preoperative and final follow-up visual analog pain score (VAS), Japanese orthopedic association scores (JOA) and complications. RESULTS: Sixty-four patients were enrolled in the study, average age of 65.1(range, 47-82) years. All patients completed 173 fusion segments, for 150 segments of ACR surgery. The operation time of ALIF-ACR was 50.4 ± 22.1 min; The intraoperative bleeding volume was 50.2 ± 23.6 ml. The operation time and intraoperative bleeding volume of single-segment OLIF-ACR was 66.2 ± 19.4 min and 70.2 ± 31.6 ml. At the follow-up of 6 months after surgery, the intervertebral space angle correction for OLIF-ACR and ALIF-ACR is 9.2° and 12.2°, the preoperative and postoperative lumbar lordosis were 16.7° ± 6.4°and 47.1° ± 3.6° (p < 0.001), VAS and JOA scores were improved from 6.8 to 1.8 and 7.8 to 22.1 respectively, statistically significant differences were observed in these parameters. The incidence of surgical related complications is 29.69%, but without serious complications. CONCLUSION: ACR via a minimally invasive hybrid approach for ASD has significant advantages in restoring local intervertebral space angulation and correcting the overall sagittal balance. Simultaneously, it can achieve good clinical outcomes and fewer surgical complications.
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Lordosis , Fusión Vertebral , Adulto , Humanos , Anciano , Lordosis/diagnóstico por imagen , Lordosis/cirugía , Estudios Retrospectivos , Resultado del Tratamiento , Vértebras Lumbares/diagnóstico por imagen , Vértebras Lumbares/cirugía , Fusión Vertebral/métodos , Procedimientos Quirúrgicos Mínimamente Invasivos/métodosRESUMEN
OBJECTIVE: Hounsfield units (HU), vertebral bone quality (VBQ), and bone mineral density (BMD) can all serve as predictive indicators for thoracolumbar fragility fractures. This study aims to explore which indicator provides better risk prediction for thoracolumbar fragility fractures. METHODS: Patients who have received medical attention from The First Affiliated Hospital of Anhui Medical University for thoracolumbar fragility fractures were selected. A total of 78 patients with thoracolumbar fragility fractures were included in the study. To establish a control group, 78 patients with degenerative spinal diseases were matched to the fracture group on the basis of gender, age, and body mass index. The lumbar vertebral HU, the VBQ, and the BMD were obtained for all the 156 patients through computed tomography, magnetic resonance imaging, and dual-energy x-ray absorptiometry (DEXA). The correlations among these parameters were analyzed. The area under curve (AUC) analysis was employed to assess the predictive efficacy and thresholds of lumbar vertebral HU, VBQ, and BMD in relation to the risk of thoracolumbar fragility fractures. RESULTS: Among the cohort of 156 patients, lumbar vertebral HU exhibited a positive correlation with BMD (p < 0.01). Conversely, VBQ showed a negative correlation with HU, BMD (p < 0.05). HU and BMD displayed a favorable predictive efficacy for thoracolumbar fragility fractures (p < 0.01), with HU (AUC = 0.863) showcasing the highest predictive efficacy, followed by the DEXA-measured BMD (AUC = 0.813). VBQ (AUC = 0.602) ranked lowest among the 3 indicators. The thresholds for predicting thoracolumbar fragility fractures were as follows: HU (88),VBQ (3.37), and BMD (0.81). CONCLUSION: All 3 of these indicators, HU, VBQ, and BMD, can predict thoracolumbar fragility fractures. Notably, lumbar vertebral HU exhibits the highest predictive efficacy, followed by the BMD obtained through DEXA scanning, with VBQ demonstrating the lowest predictive efficacy.