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1.
Geroscience ; 2024 Sep 12.
Artículo en Inglés | MEDLINE | ID: mdl-39264406

RESUMEN

The EAT-Lancet Commission has proposed a reference diet aiming to promote human health and environmental sustainability. Socioeconomic disadvantage and poor diet are well-known risk factors for dementia; however, whether the effect of this reference diet on dementia varies by socioeconomic status has not been investigated. The dietary habits of 190,893 participants from UK-Biobank were assessed; the association of EAT-Lancet diet with incident dementia across socioeconomic status was determined by Cox models. One thousand seven hundred twenty-eight dementia cases were identified during a median of 12.24 years follow-up. An inverse association between adherence to EAT-Lancet diet and all-cause dementia (high vs. low; hazard ratio [HR], 95% confidence interval [CI]: 0.82, 0.72-0.94) or late-onset dementia (high vs. low; HR, 95% CI: 0.78, 0.68-0.91) was observed only in individuals with high socioeconomic status. On the contrary, no protective effects of EAT-Lancet diet on early-onset dementia were observed, regardless of the socioeconomic status. Our findings indicated that adherence to an environment-friendly diet helps attenuate risk of dementia only in individuals with high socioeconomic level.

2.
J Biol Chem ; : 107765, 2024 Sep 12.
Artículo en Inglés | MEDLINE | ID: mdl-39276936

RESUMEN

Loss of terminal differentiation is a hallmark of cancer and offers a potential mechanism for differentiation therapy. Polycomb Repressive Complex 2 (PRC2) serves as the methyltransferase for K27 of histone H3 that is crucial in development. While PRC2 inhibitors show promise in treating various cancers, the underlying mechanisms remain incompletely understood. Here, we demonstrated that the inhibition or depletion of PRC2 enhanced adipocyte differentiation in malignant rhabdoid tumors (MRTs) and mesenchymal stem cells (MSCs), through upregulation of PPARG and CEBPA. Mechanistically, PRC2 directly represses their transcription through H3K27 methylation, as both genes exhibit a bivalent state in MSCs. Knockout of PPARG compromised C/EBPα expression and impeded the PRC2 inhibitor-induced differentiation into adipocytes. Furthermore, the combination of the PPARγ agonist rosiglitazone and the PRC2 inhibitor MAK683 exhibited a higher inhibition on Ki67 positivity in tumor xenograft compared to MAK683 alone. High CEBPA, PLIN1 and FABP4 levels positively correlated with favorable prognosis in sarcoma patients in TCGA cohort. Together, these findings unveil an epigenetic regulatory mechanism for PPARG and highlight the essential role of PPARγ and C/EBPα in the adipocyte differentiation of MRTs and sarcomas with a potential clinical implication.

3.
N Engl J Med ; 391(9): 821-831, 2024 Sep 05.
Artículo en Inglés | MEDLINE | ID: mdl-39231344

RESUMEN

BACKGROUND: In June 2019, a patient presented with persistent fever and multiple organ dysfunction after a tick bite at a wetland park in Inner Mongolia. Next-generation sequencing in this patient revealed an infection with a previously unknown orthonairovirus, which we designated Wetland virus (WELV). METHODS: We conducted active hospital-based surveillance to determine the prevalence of WELV infection among febrile patients with a history of tick bites. Epidemiologic investigation was performed. The virus was isolated, and its infectivity and pathogenicity were investigated in animal models. RESULTS: WELV is a member of the orthonairovirus genus in the Nairoviridae family and is most closely related to the tickborne Hazara orthonairovirus genogroup. Acute WELV infection was identified in 17 patients from Inner Mongolia, Heilongjiang, Jilin, and Liaoning, China, by means of reverse-transcriptase-polymerase-chain-reaction assay. These patients presented with nonspecific symptoms, including fever, dizziness, headache, malaise, myalgia, arthritis, and back pain and less frequently with petechiae and localized lymphadenopathy. One patient had neurologic symptoms. Common laboratory findings were leukopenia, thrombocytopenia, and elevated d-dimer and lactate dehydrogenase levels. Serologic assessment of convalescent-stage samples obtained from 8 patients showed WELV-specific antibody titers that were 4 times as high as those in acute-phase samples. WELV RNA was detected in five tick species and in sheep, horses, pigs, and Transbaikal zokors (Myospalax psilurus) sampled in northeastern China. The virus that was isolated from the index patient and ticks showed cytopathic effects in human umbilical-vein endothelial cells. Intraperitoneal injection of the virus resulted in lethal infections in BALB/c, C57BL/6, and Kunming mice. The Haemaphysalis concinna tick is a possible vector that can transovarially transmit WELV. CONCLUSIONS: A newly discovered orthonairovirus was identified and shown to be associated with human febrile illnesses in northeastern China. (Funded by the National Natural Science Foundation of China and the Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences.).


Asunto(s)
Fiebre , Nairovirus , Mordeduras de Garrapatas , Adulto , Anciano , Animales , Femenino , Humanos , Masculino , Ratones , Persona de Mediana Edad , Adulto Joven , Anticuerpos Antivirales/sangre , China/epidemiología , Fiebre/diagnóstico , Fiebre/epidemiología , Fiebre/virología , Nairovirus/genética , Nairovirus/aislamiento & purificación , Nairovirus/patogenicidad , Filogenia , Mordeduras de Garrapatas/complicaciones , Mordeduras de Garrapatas/virología , Prevalencia , Modelos Animales de Enfermedad , Ovinos , Caballos , Porcinos , Lactante , Preescolar , Niño , Adolescente , Anciano de 80 o más Años
4.
ChemSusChem ; : e202400451, 2024 Aug 21.
Artículo en Inglés | MEDLINE | ID: mdl-39167363

RESUMEN

The sluggish transition and shuttle of polysulfides (LiPS) significantly hinder the application and commercialization of Li-S batteries. Herein, carbon nanotubes (CNTs) supported 10 nm sized iron Hexadecafluorophthalocyanine (FePcF16/CNTs) are prepared using a solid synthesis approach. The well-exposed FePcF16 molecular improve the LiPS capture efficiency and redox kinetics by its central Fe-N4 units and F functional groups. The strong electron withdraw F groups significantly promote the conjugate effect and decrease the steric hindrance during mass migration procedure. Distribution of relaxation time (DRT) analysis shows that the Fe-N4 units exhibit strong affinity towards LiPS and the F groups further improve the Li+ diffusion rate in Li2S nucleation and oxidation procedure, accomplishing a porous surface on cathode. As a result, the FePcF16/CNTs separator exhibits a high initial capacity of 1136.2 mAh g-1 at 0.2 C, outstanding rate capacity of 624.9 mAh g-1 at 5 C and superior long-term stability at 2 C surviving 300 cycles with a low capacity decay of 0.43‰ per cycle.

5.
Nanomaterials (Basel) ; 14(15)2024 Jul 24.
Artículo en Inglés | MEDLINE | ID: mdl-39120345

RESUMEN

Water pollution seriously affects the development of society and human life. There are various kinds of pollutants, including soluble pollutants and insoluble floaters on the water surface. Herein, the photocatalyst semiconductor BiOCl and superhydrophobic functional particles Mg(OH)2 were deposited on the surfaces of canvas and polyester felt to construct superhydrophobic canvas and polyester felt. The contact angles of the synthetic superhydrophobic canvas and polyester felt were measured as 152° and 155.3°, respectively. The selective adsorption of hexadecane was achieved using the wetting difference between the surface of water and pollutants floating on the surface. For dissolved pollutants, the surface wettability needed to be changed with the help of ethanol. The degradation efficiencies were all greater than 90%, demonstrating the versatility of the synthetic superhydrophobic canvas and polyester felt.

6.
ACS Nano ; 18(33): 22334-22343, 2024 Aug 20.
Artículo en Inglés | MEDLINE | ID: mdl-39120711

RESUMEN

This work reports the synthesis of chiral perovskite heterostructure films by combining a two-dimensional (2D) chiral (R-/S-MBA)2PbI4 perovskite with CsPbBr3 quantum dots (QDs). The as-synthesized chiral heterostructure films exhibit obvious circularly polarized luminescence (CPL) properties, even though pure 2D chiral perovskite cannot present photoluminescence. It indicates that the chirality of the excited state of the QDs originates from the 2D chiral perovskite. The circular polarization-resolved transient absorption (TA) spectra further demonstrate that the CPL response of heterostructure films originates from the energy transfer between the chiral perovskite layer and QDs layer and the suppression of spin relaxation, which induces the imbalance of the spin population of excited states in QDs layer. In addition, the photoluminescence (PL), circular dichroism (CD), and CPL spectra of these heterostructure films can be controlled by varying the thickness and component of the chiral perovskite layer, which demonstrates that the anion exchange between chiral perovskite and CsPbBr3 QDs can tune the chemical composition and optoelectronic properties due to the low bonding energy difference between them and decrease the strain within the QDs layer to reduce the radiative recombination lifetime. This work provides guidance for the synthesis of chiral perovskites with a strong CPL response and further provides insight into the origination of CPL.

7.
J Nanobiotechnology ; 22(1): 520, 2024 Aug 30.
Artículo en Inglés | MEDLINE | ID: mdl-39210430

RESUMEN

The two-dimensional nanomaterials are characterized by their ultra-thin structure, diverse chemical functional groups, and remarkable anisotropic properties. Since its discovery in 2004, graphene has attracted significant scientific interest due to its potential applications in various fields, including electronics, energy systems, and biomedicine. In medicine, graphene is used for designing smart drug delivery systems, especially for antibiotics, and biosensing. Skin trauma is a prevalent dermatological condition that increasingly contributes to morbidities and mortalities, thus representing a significant health burden. During tissue damage, rapid skin repair is crucial to prevent blood loss and infection. Therefore, drugs used for skin trauma must possess antimicrobial and anti-inflammatory properties. Two-dimensional (2D) nanomaterials possess remarkable physical, chemical, optical, and biological characteristics due to their uniform shape, increased surface area, and surface charge. Graphene and its derivatives, transition-metal dichalcogenides (TMDs), black phosphorous (BP), hexagonal boron nitride (h-BN), MXene, and metal-organic frameworks (MOFs) are among the commonly used 2D nanomaterials. Moreover, they exhibit antibacterial and anti-inflammatory properties. This review presents a comprehensive discussion of the clinical approaches employed for wound healing treatment and explores the applications of commonly used 2D nanomaterials to enhance wound healing outcomes.


Asunto(s)
Grafito , Nanoestructuras , Piel , Cicatrización de Heridas , Cicatrización de Heridas/efectos de los fármacos , Nanoestructuras/química , Humanos , Grafito/química , Animales , Piel/efectos de los fármacos , Antibacterianos/farmacología , Antibacterianos/química , Sistemas de Liberación de Medicamentos/métodos , Antiinflamatorios/farmacología , Antiinflamatorios/química , Estructuras Metalorgánicas/química , Estructuras Metalorgánicas/farmacología
8.
Can J Cardiol ; 2024 Aug 29.
Artículo en Inglés | MEDLINE | ID: mdl-39216657

RESUMEN

BACKGROUND: Depression is an increasing illness worldwide that severely diminishes the quality of life. The study sought to elucidate the association of the American Heart Association's Life's Essential 8 (LE8) metrics with the incidence of cardiovascular disease (CVD) among depression participants and further quantify the related theoretical reduction of long-term CVD burden. METHODS: 20,832 participants with depression from UK-Biobank were included. LE8, including diet quality, physical activity, nicotine exposure, sleep duration, body mass index, lipids, glucose, and blood pressure, was calculated at baseline and categorized into low, medium, and high levels. Hazard ratios (HR) and 95% confidence interval (95%CI) for major cardiovascular events (MACE) was calculated using Cox models. We further quantified population attributable fractions (PAF) for CVD. RESULTS: During a median follow-up of 12.0 years, 658 MACE were recorded. After multi-variable adjustment, compared with participants with low LE8, people with high LE8 had a decreased risk of MACE (HR, 95%CI: 0.32, 0.22-0.47), non-fatal MACE (0.39, 0.26-0.61), myocardial infarction (0.23, 0.12-0.44), and ischaemic stroke (0.52, 0.27-0.99). Overall, 50.7% (95%CI: 34.5-66.9%) of MACE and 48.0% (95%CI: 29.5-66.4%) of non-fatal MACE were attributable to the low and medium adherence to LE8 at the 5-year follow-up, respectively. Sub-optimal control of blood pressure ranked as the top contributor to all types of CVD in individuals with depression. CONCLUSIONS: Optimal adherence to LE8 was associated with lower burden of CVD in depression. Adopting a comprehensive lifestyle intervention might help further reduce CVD burden in mental disorders.

9.
Entropy (Basel) ; 26(8)2024 Aug 22.
Artículo en Inglés | MEDLINE | ID: mdl-39202185

RESUMEN

The design of transportation networks is generally performed on the basis of the division of a metropolitan region into communities. With the combination of the scale, population density, and travel characteristics of each community, the transportation routes and stations can be more precisely determined to meet the travel demand of residents within each of the communities as well as the transportation links among communities. To accurately divide urban communities, the original word vector sampling method is improved on the classic Deepwalk model, proposing a Random Walk (RW) algorithm in which the sampling is modified with the generalized travel cost and improved logit model. Urban spatial community detection is realized with the K-means algorithm, building the F-Deepwalk model. Using the basic road network as an example, the experimental results show that the Deepwalk model, which considers the generalized travel cost of residents, has a higher profile coefficient, and the performance of the model improves with the reduction of random walk length. At the same time, taking the Shijiazhuang urban rail transit network as an example, the accuracy of the model is further verified.

10.
Circ Res ; 135(5): 596-613, 2024 Aug 16.
Artículo en Inglés | MEDLINE | ID: mdl-39056179

RESUMEN

BACKGROUND: Macrophages are key players in obesity-associated cardiovascular diseases, which are marked by inflammatory and immune alterations. However, the pathophysiological mechanisms underlying macrophage's role in obesity-induced cardiac inflammation are incompletely understood. Our study aimed to identify the key macrophage population involved in obesity-induced cardiac dysfunction and investigate the molecular mechanism that contributes to the inflammatory response. METHODS: In this study, we used single-cell RNA-sequencing analysis of Cd45+CD11b+F4/80+ cardiac macrophages to explore the heterogeneity of cardiac macrophages. The CCR2+ (C-C chemokine receptor 2) macrophages were specifically removed by a dual recombinase approach, and the macrophage CCR2 was deleted to investigate their functions. We also performed cleavage under target and tagmentation analysis, chromatin immunoprecipitation-polymerase chain reaction, luciferase assay, and macrophage-specific lentivirus transfection to define the impact of lysozyme C in macrophages on obesity-induced inflammation. RESULTS: We find that the Ccr2 cluster undergoes a functional transition from homeostatic maintenance to proinflammation. Our data highlight specific changes in macrophage behavior during cardiac dysfunction under metabolic challenge. Consistently, inducible ablation of CCR2+CX3CR1+ macrophages or selective deletion of macrophage CCR2 prevents obesity-induced cardiac dysfunction. At the mechanistic level, we demonstrate that the obesity-induced functional shift of CCR2-expressing macrophages is mediated by the CCR2/activating transcription factor 3/lysozyme 1/NF-κB (nuclear factor kappa B) signaling. Finally, we uncover a noncanonical role for lysozyme 1 as a transcription activator, binding to the RelA promoter, driving NF-κB signaling, and strongly promoting inflammation and cardiac dysfunction in obesity. CONCLUSIONS: Our findings suggest that lysozyme 1 may represent a potential target for the diagnosis of obesity-induced inflammation and the treatment of obesity-induced heart disease.


Asunto(s)
Macrófagos , Muramidasa , Obesidad , Receptores CCR2 , Animales , Obesidad/complicaciones , Obesidad/metabolismo , Macrófagos/metabolismo , Receptores CCR2/metabolismo , Receptores CCR2/genética , Ratones , Muramidasa/metabolismo , Muramidasa/genética , Ratones Endogámicos C57BL , Masculino , Ratones Noqueados , Transducción de Señal , Inflamación/metabolismo , Inflamación/genética , Cardiopatías/etiología , Cardiopatías/metabolismo , Cardiopatías/genética
11.
Front Microbiol ; 15: 1409593, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39027101

RESUMEN

Neoehrlichia mikurensis (N. mikurensis) is an emerging tick-borne pathogen that can cause neoehrlichiosis. Rodents are considered the major host for N. mikurensis. Currently, N. mikurensis has been detected in rodents in several studies from China and other countries. However, no research on N. mikurensis infection in rodents has been reported in the Liupan mountain region. The region of Liupan Mountain, located in northwestern China, is the center of the triangle formed by the cities of Xi'an, Yinchuan, and Lanzhou, with multiple tourist sites in the region. To survey whether there is N. mikurensis in hosts, rodents were captured in this region in September 2020. A nested polymerase chain reaction was used to detect the DNA of N. mikurensis, followed by nucleotide sequencing and phylogenetic analysis. In the region, among 88 rodents, 3 rodents were detected positive for N. mikurensis, a detection rate of 3.4%. Based on phylogenetic analysis of the partial groEL gene sequences, N. mikurensis from rodents in Liupan Mountain clustered in the same evolutionary branch with those found in rodents from Japan, Russia, and northeastern China, and also in ticks and clinical cases from Heilongjiang Province in northeastern China.

12.
Environ Sci Pollut Res Int ; 31(33): 45793-45807, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38977548

RESUMEN

Melting is an efficient method to turn municipal solid waste incineration (MSWI) fly ash (FA) into non-hazardous material. Coal fly ash (CFA) was selected as the silica-alumina source to carry out co-melting research with MSWI FA in this work. The effects of the temperature and the CFA content on mineral transformation and the migration characteristics of heavy metals were analyzed. The results showed that the mixtures of MSWI FA and CFA reacted at high temperatures to mainly generate Ca2Al2SiO7, Ca2SiO4, and CaAl2Si2O8 primarily and then melted and formed the amorphous-phase vitreous body when the CFA content was more than 40% and the temperature was higher than 1300 °C. During the melting process, Cd and Pb were almost volatilized, while Cr, Mn, and Ni were almost retained. Besides, the volatilization rates of Cu and Zn fluctuated with the temperature and the CFA content. Suitable treatment temperature and CFA content were conducive to the transformation of the heavy metals in the FA into stable forms, and the melting products were no longer hazardous wastes because the vitreous body could effectively encapsulate heavy metals. This study aims to help reuse the FA and CFA collaboratively and be more environmentally friendly.


Asunto(s)
Ceniza del Carbón , Incineración , Metales Pesados , Minerales , Residuos Sólidos , Ceniza del Carbón/química , Minerales/química
13.
Molecules ; 29(13)2024 Jul 04.
Artículo en Inglés | MEDLINE | ID: mdl-38999139

RESUMEN

With the intensification of the energy crisis, it is urgent to vigorously develop new environment-friendly energy storage materials. In this work, coexisting ferroelectric and relaxor-ferroelectric phases at a nanoscale were constructed in Sr(Zn1/3Nb2/3)O3 (SZN)-modified (Bi0.5Na0.5)0.94Ba0.06TiO3 (BNBT) ceramics, simultaneously contributing to large polarization and breakdown electric field and giving rise to a superior energy storage performance. Herein, a high recoverable energy density (Wrec) of 5.0 J/cm3 with a conversion efficiency of 82% at 370 kV/cm, a practical discharged energy density (Wd) of 1.74 J/cm3 at 230 kV/cm, a large power density (PD) of 157.84 MW/cm3, and an ultrafast discharge speed (t0.9) of 40 ns were achieved in the 0.85BNBT-0.15SZN ceramics characterized by the coexistence of a rhombohedral-tetragonal phase (ferroelectric state) and a pseudo-cubic phase (relaxor-ferroelectric state). Furthermore, the 0.85BNBT-0.15SZN ceramics also exhibited excellent temperature stability (25-120 °C) and cycling stability (104 cycles) of their energy storage properties. These results demonstrate the great application potential of 0.85BNBT-0.15SZN ceramics in capacitive pulse energy storage devices.

14.
Zookeys ; 1204: 105-133, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38873219

RESUMEN

Three new species of the genus Stenohya Beier, 1967 from China are described: Stenohyagibba sp. nov. and S.papillata sp. nov. from Hunan Province, and S.guangmingensis sp. nov. from Jiangxi Province. In addition to their sexually dimorphic pedipalp, these three new species also have a uniquely sexual dimorphic leg I, which has not been reported in other Stenohya species. Additionally, an updated key to the Chinese Stenohya species is provided.

15.
Opt Express ; 32(11): 19105-19116, 2024 May 20.
Artículo en Inglés | MEDLINE | ID: mdl-38859053

RESUMEN

The practical application of integrated gyroscopes in engineering has not yet been fully realized due to the linear correlation between the Sagnac effect and dimensions. In recent demonstrations, gyroscopes operating near exceptional points (EPs) under parity-time (PT) symmetry have shown significant potential in enhancing their response to rotational rates. However, constructing higher-order EPs with refined physical properties poses a considerable challenge. Additionally, current methods for constructing higher-order EPs with robustness primarily rely on passive cavities, with almost no reports on constructing robust EPs using PT-symmetric systems that encompass both gain and loss. Here, we propose a robust design for a scalable fabrication of higher-order EP gyroscopes with PT-symmetric structure. We investigate the influence of perturbations on the frequency splitting of the higher-order EP gyroscope and demonstrate that it is possible to achieve a resonance splitting eight orders of magnitude higher than that obtained through the classical Sagnac effect. In comparison to the previously proposed PT-symmetric gyroscope, our solution allows a tunable frequency splitting by adjusting the phase shift, making it more measurable at the output power spectrum.

16.
Biochem Biophys Res Commun ; 725: 150248, 2024 Sep 17.
Artículo en Inglés | MEDLINE | ID: mdl-38870847

RESUMEN

The excessive migration and proliferation of vascular smooth muscle cells (VSMCs) plays a vital role in vascular intimal hyperplasia. CIRBP is involved in the proliferation of various cancer cells. This study was aimed to explore the role of CIRBP in the proliferation and migration of VSMCs. Adenovirus was used to interfere with cold-inducible RNA-binding protein (CIRBP) expression, while lentivirus was used to overexpress Ras homolog enriched in brain (Rheb). Western blotting and qRT-PCR were used to evaluate the expression of CIRBP, Rheb, and mechanistic target of rapamycin complex 1 (mTORC1) activity. The cell proliferation was determined by Ki67 immunofluorescence staining and CCK-8 assay. The wound healing assay was performed to assess cell migration. Additionally, immunohistochemistry was conducted to explore the role of CIRBP in intimal hyperplasia after vascular injury. We found that silencing CIRBP inhibited the proliferation and migration of VSMCs, decreased the expression of Rheb and mTORC1 activity. Restoration of mTORC1 activity via insulin or overexpression of Rheb via lentiviral transfection both attenuated the inhibitory effects of silencing CIRBP on the proliferation and migration of VSMCs. Moreover, Rheb overexpression abolished the inhibitory effect of silencing CIRBP on mTORC1 activity in VSMCs. CIRBP was upregulated in the injured carotid artery. Silencing CIRBP ameliorated intimal hyperplasia after vascular injury. In the summary, silencing CIRBP attenuates mTORC1 activity via reducing Rheb expression, thereby supressing the proliferation and migration of VSMCs and intimal hyperplasia after vascular injury.


Asunto(s)
Movimiento Celular , Proliferación Celular , Diana Mecanicista del Complejo 1 de la Rapamicina , Músculo Liso Vascular , Miocitos del Músculo Liso , Proteínas de Unión al ARN , Proteína Homóloga de Ras Enriquecida en el Cerebro , Diana Mecanicista del Complejo 1 de la Rapamicina/metabolismo , Proteína Homóloga de Ras Enriquecida en el Cerebro/metabolismo , Proteína Homóloga de Ras Enriquecida en el Cerebro/genética , Músculo Liso Vascular/metabolismo , Músculo Liso Vascular/citología , Músculo Liso Vascular/patología , Animales , Proteínas de Unión al ARN/metabolismo , Proteínas de Unión al ARN/genética , Miocitos del Músculo Liso/metabolismo , Miocitos del Músculo Liso/patología , Miocitos del Músculo Liso/citología , Células Cultivadas , Transducción de Señal , Masculino , Ratas , Ratas Sprague-Dawley , Humanos
17.
Oncol Lett ; 28(1): 320, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38807668

RESUMEN

Gliomas are highly malignant and invasive tumors lacking clear boundaries. Previous bioinformatics and experimental analyses have indicated that F-box and leucine-rich repeat protein 6 (FBXL6), a protein crucial for the cell cycle and tumorigenesis, is highly expressed in certain types of tumors. The high expression level of FBXL6 is reported to promote tumor growth and adversely affect patient survival. However, the molecular mechanism, prognostic value and drug sensitivity of FBXL6 in glioma remain unclear. To address this, the present study analyzed FBXL6 expression in gliomas, utilizing data from The Cancer Genome Atlas and Chinese Glioma Genome Atlas databases. Analysis of FBXL6 mRNA expression levels, combined with patient factors such as age, sex and tumor grade using Kaplan-Meier plots and nomograms, demonstrated a strong correlation between FBXL6 expression and glioma progression. Co-expression networks provided further insights into the biological function of FBXL6. Additionally, using CIBERSORT and TISDB tools, the correlation between FBXL6 expression correlation tumor-infiltrating immune cells and immune genes was demonstrated to be statistically significant. These findings were validated by examining FBXL6 mRNA and protein levels in glioma tissues using various techniques, including western blot, reverse transcription-quantitative PCR and immunohistochemistry. These assays demonstrated the role of FBXL6 in glioma progression. Furthermore, drug sensitivity analysis demonstrated a strong correlation between FBXL6 expression and various drugs, which indicated that FBXL6 may potentially act as a future promising therapeutic target in glioma treatment. Therefore, the present study identified FBXL6 as a diagnostic and prognostic marker in patients with gliomas and highlighted its potential role in glioma progression.

18.
Exp Biol Med (Maywood) ; 249: 10112, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38715976

RESUMEN

Chronic inflammation is a key element in the progression of essential hypertension (EH). Calcium plays a key role in inflammation, so its receptor, the calcium-sensing receptor (CaSR), is an essential mediator of the inflammatory process. Compelling evidence suggests that CaSR mediates inflammation in tissues and immune cells, where it mediates their activity and chemotaxis. Macrophages (Mφs) play a major role in the inflammatory response process. This study provided convincing evidence that R568, a positive regulator of CaSR, was effective in lowering blood pressure in spontaneously hypertensive rats (SHRs), improving cardiac function by alleviating cardiac hypertrophy and fibrosis. R568 can increase the content of CaSR and M2 macrophages (M2Mφs, exert an anti-inflammatory effect) in myocardial tissue, reduce M1 macrophages (M1Mφs), which have a pro-inflammatory effect in this process. In contrast, NPS2143, a negative state regulator of CaSR, exerted the opposite effect in all of the above experiments. Following this study, R568 increased CaSR content in SHR myocardial tissue, lowered blood pressure, promoted macrophages to M2Mφs and improved myocardial fibrosis, but interestingly, both M1Mφs and M2Mφs were increased in the peritoneal cavity of SHRs, the number of M2Mφs remained lower than M1Mφs. In vitro, R568 increased CaSR content in RAW264.7 cells (a macrophage cell line), regulating intracellular Ca2+ ([Ca2+]i) inhibited NOD-like receptor family protein 3 (NLRP3) inflammasome activation and ultimately prevented its conversion to M1Mφs. The results showed that a decrease in CaSR in hypertensive rats causes further development of hypertension and cardiac damage. EH myocardial remodeling can be improved by CaSR overexpression by suppressing NLRP3 inflammasome activation and macrophage polarization toward M1Mφs and increasing M2Mφs.


Asunto(s)
Macrófagos , Receptores Sensibles al Calcio , Remodelación Ventricular , Animales , Masculino , Ratones , Ratas , Presión Sanguínea , Fibrosis/metabolismo , Hipertensión/metabolismo , Hipertensión/patología , Macrófagos/metabolismo , Miocardio/patología , Miocardio/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Ratas Endogámicas SHR , Receptores Sensibles al Calcio/metabolismo , Remodelación Ventricular/fisiología
19.
Indian J Orthop ; 58(5): 587-597, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38694692

RESUMEN

Background: Lumbar disc herniation is a common degenerative lumbar disease with an increasing incidence. Percutaneous endoscopic lumbar discectomy can treat lumbar disc herniation safely and effectively with a minimally invasive procedure. However, the learning curve of this technology is steep, which means that initial learners are often not sufficiently proficient in endoscopic operations, which can easily lead to iatrogenic damage. At present, the application of computer deep learning technology to clinical diagnosis, treatment, and surgical navigation has achieved satisfactory results. Purpose: The objective of our team is to develop a multi-element identification system for the visual field of endoscopic spine surgery using deep learning algorithms and to evaluate the feasibility of this system. Method: We established an image database by collecting surgical videos of 48 patients diagnosed with lumbar disc herniation, which was labeled by two spinal surgeons. We selected 6000 images of the visual field of percutaneous endoscopic spine surgery (including various tissue structures and surgical instruments), divided into the training data, validation data, and test data according to 2:1:2. We developed convolutional neural network models based on instance segmentation-Solov2, CondInst, Mask R-CNN and Yolact, and set the four network model backbone as ResNet101 and ResNet50 respectively. Mean average precision (mAP) and frames per second (FPS) were used to measure the performance of each model for classification, localization and recognition in real time, and AP (average) is used to evaluate how easily an element is detected by neural networks based on computer deep learning. Result: Comprehensively comparing mAP and FSP of each model for bounding box test and segmentation task for the test set of images, we found that Solov2 (ResNet101) (mAP = 73.5%, FPS = 28.9), Mask R-CNN (ResNet101) (mAP = 72.8%, FPS = 28.5) models are the most stable, with higher precision and faster image processing speed. Combining the average precision of the elements in the bounding box test and segmentation tasks in each network, the AP(average) was highest for tool 3 (bbox-0.85, segm-0.89) and lowest for tool 5 (bbox-0.63, segm-0.72) in the instrumentation, whereas in the anatomical tissue elements, the fibrosus annulus (bbox-0.68, segm-0.69) and ligamentum flavum (bbox-0.65, segm-0.62) had higher AP(average),while extra-dural fat (bbox-0.42, segm-0.44) was lowest. Conclusion: Our team has developed a multi-element identification system for the visual field of percutaneous endoscopic spine surgery adapted to the interlaminar and foraminal approaches, which can identify and track anatomical tissue (nerve, ligamentum flavum, nucleus pulposus, etc.) and surgical instruments (endoscopic forceps, an high-speed diamond burr, etc.), which can be used in the future as a virtual educational tool or applied to the intraoperative real-time assistance system for spinal endoscopic operation.

20.
Int J Nanomedicine ; 19: 4121-4136, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38736655

RESUMEN

Purpose: This study aims to broaden the application of nano-contrast agents (NCAs) within the realm of the musculoskeletal system. It aims to introduce novel methods, strategies, and insights for the clinical management of ischemic muscle disorders, encompassing diagnosis, monitoring, evaluation, and therapeutic intervention. Methods: We developed a composite encapsulation technique employing O-carboxymethyl chitosan (OCMC) and liposome to encapsulate NCA-containing gold nanorods (GNRs) and perfluoropentane (PFP). This nanoscale contrast agent was thoroughly characterized for its basic physicochemical properties and performance. Its capabilities for in vivo and in vitro ultrasound imaging and photothermal imaging were authenticated, alongside a comprehensive biocompatibility assessment to ascertain its effects on microcirculatory perfusion in skeletal muscle using a murine model of hindlimb ischemia, and its potential to augment blood flow and facilitate recovery. Results: The engineered GNR@OCMC-liposome/PFP nanostructure exhibited an average size of 203.18±1.49 nm, characterized by size uniformity, regular morphology, and a good biocompatibility profile. In vitro assessments revealed NCA's potent photothermal response and its transformation into microbubbles (MBs) under near-infrared (NIR) irradiation, thereby enhancing ultrasonographic visibility. Animal studies demonstrated the nanostructure's efficacy in photothermal imaging at ischemic loci in mouse hindlimbs, where NIR irradiation induced rapid temperature increases and significantly increased blood circulation. Conclusion: The dual-modal ultrasound/photothermal NCA, encapsulating GNR and PFP within a composite shell-core architecture, was synthesized successfully. It demonstrated exceptional stability, biocompatibility, and phase transition efficiency. Importantly, it facilitates the encapsulation of PFP, enabling both enhanced ultrasound imaging and photothermal imaging following NIR light exposure. This advancement provides a critical step towards the integrated diagnosis and treatment of ischemic muscle diseases, signifying a pivotal development in nanomedicine for musculoskeletal therapeutics.


Asunto(s)
Medios de Contraste , Oro , Isquemia , Músculo Esquelético , Nanotubos , Ultrasonografía , Animales , Oro/química , Nanotubos/química , Medios de Contraste/química , Medios de Contraste/farmacología , Ratones , Isquemia/diagnóstico por imagen , Isquemia/terapia , Músculo Esquelético/diagnóstico por imagen , Ultrasonografía/métodos , Miembro Posterior/irrigación sanguínea , Fluorocarburos/química , Fluorocarburos/farmacología , Liposomas/química , Quitosano/química , Quitosano/farmacología , Enfermedades Musculares/diagnóstico por imagen , Enfermedades Musculares/terapia , Terapia Fototérmica/métodos , Modelos Animales de Enfermedad , Humanos , Pentanos
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