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1.
Osteoporos Int ; 35(4): 613-623, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38062161

RESUMEN

An independent correlation between pre-RDW and 1-year mortality after surgery in elderly hip fracture can be used to predict mortality in elderly hip fracture patients and has predictive significance in anemia patients. With further research, a treatment algorithm can be developed to potentially identify patients at high risk of preoperative mortality. INTRODUCTION: Red blood cell distribution width (RDW) is an independent predictor of various disease states in elderly individuals, but its association with the prognosis of elderly hip fracture patients is controversial. This study aimed to evaluate the prognostic value of RDW in such patients, construct a prediction model containing RDW using random survival forest (RSF) and Cox regression analysis, and compare RDW in patients with and without anemia. METHODS: We retrospectively analyzed the data of elderly patients who underwent hip fracture surgery, selected the best variables using RSF, stratified the independent variables by Cox regression analysis, constructed a 1-year mortality prediction model of elderly hip fracture with RDW, and conducted internal validation and external validation. RESULTS: Two thousand one hundred six patients were included in this study. The RSF algorithm selects 12 important influencing factors, and Cox regression analysis showed that eight variables including preoperative RDW (pre-RDW) were independent risk factors for death within 1-year after hip fracture surgery in elderly patients. Stratified analysis showed that pre-RDW was still independently associated with 1-year mortality in the non-anemia group and not in the anemia group. The nomogram prediction model had high differentiation and fit, and the prediction model constructed by the total cohort of patients was also used for validation of patients in the anemia patients and obtained good clinical benefits. CONCLUSION: An independent correlation between pre-RDW and 1-year mortality after surgery in elderly hip fracture can be used to predict mortality in elderly hip fracture patients and has predictive significance in anemia patients.


Asunto(s)
Anemia , Fracturas de Cadera , Humanos , Anciano , Índices de Eritrocitos , Estudios Retrospectivos , Oportunidad Relativa , Anemia/complicaciones , Pronóstico
2.
Inorg Chem ; 62(41): 17012-17021, 2023 Oct 16.
Artículo en Inglés | MEDLINE | ID: mdl-37791743

RESUMEN

Efficient and low-cost electrocatalysts for the hydrogen evolution reaction (HER) are required for producing hydrogen energy through water splitting. Carbon materials as HER catalyst supports are explored widely since the strong metal-support interactions are generally believed to be active and stable toward HER. Herein, we report N-doped porous carbon materials as novel substrates to stabilize the cluster metal sites through the Ru(III) polyamine complexes, which play an important role not only in efficient electron transfer but also in the increasing utilization of metallic active sites. Meanwhile, due to the strong metal-support interactions driven by Ru(III) polyamine complexes, the obtained Ru cluster with a mass loading of 3% on N-doped porous carbon nanoplates (Ru cluster@NCs) exhibits robust stability for HER at a constant voltage, proving to be a promising candidate catalyst for HER. Density functional theory calculations further indicate that the Gibbs free energy (ΔG) of adsorbed H* of Ru cluster@NCs is much closer to zero compared to Ru@(10%)NCs and Pt/C(20%), thus Ru cluster@NCs facilitate the HER process.

3.
J Nanobiotechnology ; 21(1): 194, 2023 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-37322478

RESUMEN

BACKGROUND: Polarization of microglia, the resident retinal immune cells, plays important roles in mediating both injury and repair responses post-retinal ischemia-reperfusion (I/R) injury, which is one of the main pathological mechanisms behind ganglion cell apoptosis. Aging could perturb microglial balances, resulting in lowered post-I/R retinal repair. Young bone marrow (BM) stem cell antigen 1-positive (Sca-1+) cells have been demonstrated to have higher reparative capabilities post-I/R retinal injury when transplanted into old mice, where they were able to home and differentiate into retinal microglia. METHODS: Exosomes were enriched from young Sca-1+ or Sca-1- cells, and injected into the vitreous humor of old mice post-retinal I/R. Bioinformatics analyses, including miRNA sequencing, was used to analyze exosome contents, which was confirmed by RT-qPCR. Western blot was then performed to examine expression levels of inflammatory factors and underlying signaling pathway proteins, while immunofluorescence staining was used to examine the extent of pro-inflammatory M1 microglial polarization. Fluoro-Gold labelling was then utilized to identify viable ganglion cells, while H&E staining was used to examine retinal morphology post-I/R and exosome treatment. RESULTS: Sca-1+ exosome-injected mice yielded better visual functional preservation and lowered inflammatory factors, compared to Sca-1-, at days 1, 3, and 7 days post-I/R. miRNA sequencing found that Sca-1+ exosomes had higher miR-150-5p levels, compared to Sca-1- exosomes, which was confirmed by RT-qPCR. Mechanistic analysis found that miR-150-5p from Sca-1+ exosomes repressed the mitogen-activated protein kinase kinase kinase 3 (MEKK3)/JNK/c-Jun axis, leading to IL-6 and TNF-α downregulation, and subsequently reduced microglial polarization, all of which contributes to reduced ganglion cell apoptosis and preservation of proper retinal morphology. CONCLUSION: This study elucidates a potential new therapeutic approach for neuroprotection against I/R injury, via delivering miR-150-5p-enriched Sca-1+ exosomes, which targets the miR-150-5p/MEKK3/JNK/c-Jun axis, thereby serving as a cell-free remedy for treating retinal I/R injury and preserving visual functioning.


Asunto(s)
Exosomas , MicroARNs , Daño por Reperfusión , Ratones , Animales , Microglía/metabolismo , MicroARNs/metabolismo , Exosomas/metabolismo , Daño por Reperfusión/metabolismo , Células de la Médula Ósea/metabolismo
4.
J Environ Manage ; 328: 116894, 2023 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-36527804

RESUMEN

Combing the assisted dispersion strategy of support with the wet chemical reduction method, a novel nano-zero valent iron/microsilica (nZVI/M) composite was successfully fabricated, where the 2D nZVI nanosheets were uniformly anchored and covered on the surface of microsilica. The introduction of microsilica notably relieved the agglomeration effect of nZVI nanosheets, which induced the improvement of specific surface area (45.68 m2/g) and pore volume (0.172 cm3/g), and thereby exposing more active sites for bisphenol A (BPA) removal. The optimized nZVI/M-0.6 displayed the superior catalytic performance in the presence of peroxymonosulfate (PMS) with the degradation rate of BPA reached above 97% within 3 min and a higher constant rate of 0.659 min-1, which was approximately 3.9 times as high as that of nZVI/PMS system. The homogeneously dispersion of nZVI nanosheets on microsilica benefited for the assembly of the pollutants and boosting the kinetics of the catalytic degradation process. As a highly efficient PMS activator, it could well maintain the catalytic activity in different real water samples. The quenching experiments verified that SO4•- played the dominate role for BPA removal. This work offered novel insights for designing and preparing iron-based persulfate activator for wastewater treatment.


Asunto(s)
Hierro , Contaminantes Químicos del Agua , Hierro/química , Contaminantes Químicos del Agua/química , Fenoles
5.
Small ; 18(52): e2204793, 2022 12.
Artículo en Inglés | MEDLINE | ID: mdl-36344427

RESUMEN

Single-atom catalysts (SACs) feature maximum atomic utilization efficiency; however, the loading amount, dispersibility, synthesis cost, and regulation of the electronic structure are factors that need to be considered in water treatment. In this study, kaolinite, a natural layered clay mineral, is applied as the support for g-C3 N4 and single Fe atoms (FeSA-NGK). The FeSA-NGK composite exhibits an impressive degradation performance toward the target pollutant (>98% degradation rate in 10 min), and catalytic stability across consecutive runs (90% reactivity maintained after three runs in a fluidized-bed catalytic unit) under peroxymonosulfate (PMS)/visible light (Vis) synergetic system. The introduction of kaolinite promotes the loading amount of single Fe atoms (2.57 wt.%), which is a 14.2% increase compared to using a bare catalyst without kaolinite, and improved the concentration of N vacancies, thereby optimizing the regulation of the electronic structure of the single Fe atoms. It is discovered that the single Fe atoms successfully occupied five coordinated N atoms and combined with a neighboring N vacancy. Consequently, this regulated the local electronic structure of single Fe atoms, which drives the electrons of N atoms to accumulate on the Fe centers. This study opens an avenue for the design of clay-based SACs for water purification.


Asunto(s)
Hierro , Caolín , Hierro/química , Arcilla , Oxidación-Reducción
6.
Opt Express ; 30(4): 5879-5895, 2022 Feb 14.
Artículo en Inglés | MEDLINE | ID: mdl-35209541

RESUMEN

Plasmonic sensing that enables the detection of minute events, when the incident light field interacts with the nanostructure interface, has been widely applied to optical and biological detection. Implementation of the controllable plasmonic double Fano resonances (DFRs) offers a flexible and efficient way for plasmonic sensing. However, plasmonic sensing and digital metasurface induced by tailorable plasmonic DFRs require further study. In this work, we numerically and theoretically investigate the near-infrared plasmonic DFRs for plasmonic sensing and digital metasurface in a hybrid metasurface with concentric ϕ-shaped-hole and circular-ring-aperture unit cells. We show that a plasmonic Fano resonance, resulting from the interaction between a narrow and a wide effective dipolar modes, can be realized in the ϕ-shaped hybrid metasurface. In particular, we demonstrate that the tailoring plasmonic DFRs with distinct mechanisms of actions can be accomplished in three different ϕ-shaped hybrid metasurfaces. Moreover, the resonance mode-broadening and mode-shifting plasmonic sensing can be fulfilled by modulating the polarization orientation and the related geometric parameters of the unit cells in the near-infrared waveband, respectively. In addition, the plasmonic switch with a high ON/OFF ratio can not only be achieved but also be exploited to establish a single-bit digital metasurface, even empower to implement two- and three-bit digital metasurface characterized by the plasmonic DFRs in the telecom L-band. Our results offer a new perspective toward realizing polarization-sensitive optical sensing, passive optical switches, and programmable metasurface devices, which also broaden the landscape of subwavelength nanostructures for biosensors and optical communications.

7.
BMC Neurol ; 22(1): 445, 2022 Nov 29.
Artículo en Inglés | MEDLINE | ID: mdl-36447170

RESUMEN

BACKGROUND: The neutrophil-to-lymphocyte ratio (NLR) is positively associated with unfavorable outcomes in patients with cerebral infarction. This study aimed to investigate the relationship between the NLR and the short-term clinical outcome of acute pontine infarction. METHODS: Patients with acute pontine infarction were consecutively included. Clinical and laboratory data were collected. All patients were followed up at 3 months using modified Rankin Scale (mRS) scores. An unfavorable outcome was defined as an mRS score ≥ 3. Receiver operating characteristic (ROC) curve analysis was used to calculate the optimal cutoff values for patients with acute pontine infarction. risk factors can be predictive factors for an unfavorable outcome after acute pontine infarction. RESULTS: Two hundred fifty-six patients with acute pontine infarction were included in this study. The NLR was significantly higher in the unfavorable outcome group than in the favorable outcome group (P < 0.05). Additionally, the infarct size was significantly higher in the high NLR tertile group than in the low NLR tertile group (P < 0.05). Multivariate logistic regression analysis revealed that the baseline National Institutes of Health Stroke Scale (NIHSS) score, NLR, platelet count, and fasting blood glucose (FBG) level were significantly associated with unfavorable outcomes 3 months after acute pontine infarction. The optimal cutoff value of the NLR for predicting the 3-month outcome of acute pontine infarction was 3.055. The negative and positive predictive values of NLR were 85.7% and 61.3%, respectively, and the sensitivity and specificity of NLR were 69.2% and 80.9%. CONCLUSIONS: We found that the NLR may be an independent predictive factor for the outcome of acute pontine infarction.


Asunto(s)
Linfocitos , Neutrófilos , Estados Unidos , Humanos , Recuento de Plaquetas , Infarto Cerebral , Curva ROC
8.
Toxicol Appl Pharmacol ; 406: 115211, 2020 11 01.
Artículo en Inglés | MEDLINE | ID: mdl-32853627

RESUMEN

Liver X receptor (LXR) activation can achieve satisfactory anti-atherosclerotic activity, but can also lead to the development of fatty liver and hypertriglyceridemia. In contrast, Notch inhibition can suppress both atherosclerosis and the hepatic accumulation of lipids. In the present study, we sought to assess whether combining LXR ligand agonists (T317) with Notch receptor inhibitors (DAPT) would lead to enhanced anti-atherosclerotic activity while overcoming the adverse events associated with LXR ligand agonist therapy. The impact of the combined T317 + DAPT therapeutic regimen on atherosclerosis, fatty liver development, and hypertriglyceridemia was assessed using ApoE deficient (ApoE-/-) mice. The results of this analysis suggested that DAPT was able to improve the anti-atherosclerotic activity of T317 without reducing the stability of lesion plaques while simultaneously reducing blood lipids in treated ApoE-/- mice. This combination T317 + DAPT treatment was also linked with a significant upregulation of ABCA1 and the stimulation of reverse cholesterol transport (RCT), as well as with decreases in the levels of intercellular cell adhesion molecule-1 (ICAM-1) and p-p65, and with altered M1/M2 macrophage proportions within atherosclerotic plaques. Importantly, DAPT was also able to reduce T317-mediated lipid accumulation within the liver owing to its ability to reduce SREBP-1 expression while simultaneously increasing that of Pi-AMPKα and PPARα. Together, our results suggest that administering Notch receptor inhibitors to ApoE-/- mice may be an effective means of enhancing the anti-atherosclerotic activity of LXR ligand agonists while simultaneously limiting associated fatty liver and hypertriglyceridemia development in these animals.


Asunto(s)
Aterosclerosis/tratamiento farmacológico , Diaminas/uso terapéutico , Hígado Graso/tratamiento farmacológico , Hidrocarburos Fluorados/uso terapéutico , Hipertrigliceridemia/tratamiento farmacológico , Receptores X del Hígado/agonistas , Sulfonamidas/uso terapéutico , Tiazoles/uso terapéutico , Proteínas Quinasas Activadas por AMP/metabolismo , Animales , Aorta/efectos de los fármacos , Aorta/patología , Aterosclerosis/metabolismo , Aterosclerosis/patología , Diaminas/farmacología , Hígado Graso/metabolismo , Hígado Graso/patología , Femenino , Hidrocarburos Fluorados/farmacología , Hipertrigliceridemia/metabolismo , Hipertrigliceridemia/patología , Masculino , Ratones Endogámicos C57BL , Ratones Noqueados para ApoE , PPAR alfa/metabolismo , Receptores Notch/antagonistas & inhibidores , Proteína 1 de Unión a los Elementos Reguladores de Esteroles/metabolismo , Sulfonamidas/farmacología , Tiazoles/farmacología
9.
Opt Express ; 26(13): 16535-16546, 2018 Jun 25.
Artículo en Inglés | MEDLINE | ID: mdl-30119482

RESUMEN

We demonstrate that the optical event horizon can provide an effective technique to actively control the propagation properties of a dark soliton with another weak probe wave. Careful power adjustment of the probe wave enables the black soliton converted into a gray one with varying grayness through the nonlinear interaction, corresponding to a nearly adiabatic variation of the soliton's speed. The sign of the phase angle for the newly formed gray soliton at optical event horizon is significantly dependent on the frequency of the launched probe wave. Linear-stability analysis of dark solitons under the perturbation of a weak probe wave is performed to clarify the intrinsic mechanism of the nonlinear interaction. The probe wave manipulated collisional dynamics between both dark solitons are investigated as an analogue of the combined white-hole and black-hole horizons which provides some insights into exploring the transition between integrable and non-integrable systems.

12.
Phys Chem Chem Phys ; 16(38): 20755-62, 2014 Oct 14.
Artículo en Inglés | MEDLINE | ID: mdl-25163761

RESUMEN

We theoretically investigated Autler-Townes (AT) splitting in the photoelectron spectra of a four-level ladder K2 molecule driven by pump1-pump2-probe pulses by employing the time-dependent wave packet approach. The effect of pump-2 laser intensity and wavelength on AT splitting was studied for the first time. Triple splitting with asymmetric profiles arises because of the non-resonant excitation. The triple splitting transforms to double splitting when pump-2 detuning approaches ±1/2 times of pump-1 Rabi frequency. The splitting between two side band peaks in the triplet or doublet does not change with the pump-2 laser wavelength. The three peaks shift to a lower energy with a different shift as pump-2 wavelength increases. The magnitude of AT splitting increases with increasing pump-2 laser intensity. The asymptotic behavior of AT splitting with the pump-2 laser intensity are interesting at the threshold point of the near resonant region and far-off resonant region.

13.
Biochim Biophys Acta Mol Basis Dis ; 1870(5): 167137, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38527593

RESUMEN

BACKGROUND: Postoperative Cognitive Dysfunction (POCD) has attracted increased attention, but its precise mechanism remains to be explored. This study aimed to figure out whether HDAC6 could regulate NLRP3-induced pyroptosis by modulating the functions of HSP70 and HSP90 in microglia to participate in postoperative cognitive dysfunction in aged mice. METHODS: Animal models of postoperative cognitive dysfunction in aged mice were established by splenectomy under sevoflurane anesthesia. Morris water maze was used to examine the cognitive function and motor ability. Sixteen-months-old C57BL/6 male mice were randomly divided into six groups: control group (C group), sham surgery group (SA group), splenectomy group (S group), splenectomy + HDAC6 inhibitor ACY-1215 group (ACY group), splenectomy + HDAC6 inhibitor ACY-1215 + HSP70 inhibitor Apoptozole group (AP group), splenectomy + solvent control group (SC group). The serum and hippocampus of mice were taken after mice were executed. The protein levels of HDAC6, HSP90, HSP70, NLRP3, GSDMD-N, cleaved-Caspase-1 (P20), IL-1ß were detected by western blotting. Serum IL-1ß, IL-6 and S100ß were measured using ELISA assay, and cell localization of HDAC6 was detected by immunofluorescence. In vitro experiments, BV2 cells were used to validate whether this mechanism worked in microglia. The protein levels of HDAC6, HSP90, HSP70, NLRP3, GSDMD-N, P20, IL-1ß were detected by western blotting and the content of IL-1ß in the supernatant was measured using ELISA assay. The degree of acetylation of HSP90, the interaction of HSP70, HSP90 and NLRP3 were analyzed by coimmunoprecipitation assay. RESULTS: Splenectomy under sevoflurane anesthesia in aged mice could prolong the escape latency, reduce the number of crossing platforms, increase the expression of HDAC6 and activate the NLRP3 inflammasome to induce pyroptosis in hippocampus microglia. Using ACY-1215 could reduce the activation of NLRP3 inflammasome, the pyroptosis of microglia and the degree of spatial memory impairment. Apoptozole could inhibit the binding of HSP70 to NLRP3, reduce the degradation of NLRP3 and reverse the protective effect of HDAC6 inhibitors. The results acquired in vitro experiments closely resembled those in vivo, LPS stimulation led to the pyroptosis of BV2 microglia cells and the release of IL-1ß due to the activation of the NLRP3 inflammasome, ACY-1215 showed the anti-inflammatory effect and Apoptozole exerted the opposite effect. CONCLUSIONS: Our findings suggest that hippocampal HDAC6 promotes POCD by regulating NLRP3-induced microglia pyroptosis via HSP90/HSP70 in aged mice.


Asunto(s)
Proteínas HSP70 de Choque Térmico , Proteínas HSP90 de Choque Térmico , Hipocampo , Histona Desacetilasa 6 , Ratones Endogámicos C57BL , Microglía , Proteína con Dominio Pirina 3 de la Familia NLR , Piroptosis , Animales , Piroptosis/efectos de los fármacos , Histona Desacetilasa 6/metabolismo , Histona Desacetilasa 6/antagonistas & inhibidores , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Microglía/metabolismo , Microglía/patología , Microglía/efectos de los fármacos , Ratones , Masculino , Proteínas HSP90 de Choque Térmico/metabolismo , Hipocampo/metabolismo , Hipocampo/patología , Proteínas HSP70 de Choque Térmico/metabolismo , Complicaciones Cognitivas Postoperatorias/metabolismo , Complicaciones Cognitivas Postoperatorias/patología , Ácidos Hidroxámicos/farmacología , Envejecimiento/metabolismo , Envejecimiento/patología , Modelos Animales de Enfermedad
14.
Exp Neurol ; : 114922, 2024 Aug 12.
Artículo en Inglés | MEDLINE | ID: mdl-39142371

RESUMEN

OBJECTIVE: Multiple factors contribute to the development of perioperative neurocognitive disorders (PND). This study was designed to investigate whether Histone Deacetylase 6 (HDAC6) was involved in the formation of postoperative cognitive dysfunction in elderly mice by regulating the degree of acetylation of heat shock protein (HSP90) and related protein functions and quantities. METHODS: C57BL/6 J male mice were randomly divided into six groups: control naive (group Control), anesthesia (group Anesthesia), splenectomy surgery (group Surgery), splenectomy surgery plus dissolvent (group Vehicles), splenectomy surgery plus the inhibitor ACY-1215 (group Ricolinostat), and splenectomy surgery plus the inhibitor RU-486(group Mifepristone). After the mice were trained for Morris Water Maze (MWM) test for five days, anesthesia and operational surgery were carried out the following day. Cognitive function was assessed on the 1st, 3rd and 7th days post-surgery. The hippocampi were harvested on days 1, 3, and 7 post-surgeries for Western blots and ELISA assays. RESULTS: Mice with the splenectomy surgery displayed the activation of the hypothalamic-pituitary-adrenal axis (HPA-axis), marked an increase in adrenocorticotropic hormone (ACTH), glucocorticoid, mineralocorticoid at the molecular level and impaired spatial memory in the MWM test. The hippocampus of surgical groups showed a decrease in acetylated HSP90, a rise in glucocorticoid receptor (GR)-HSP90 association, and an increase in GR phosphorylation and translocation. HDAC6 was increased after the surgical treated. Using two specific inhibitors, HDAC6 inhibitor Ricolinostat (ACY-1215) and GR inhibitor Mifepristone (RU-486), can partially mitigate the effects caused by surgical operation. CONCLUSIONS: Abdominal surgery may impair hippocampal spatial memory, possibly through the HDAC6-triggered increase in the function of HSP90, consequently strengthening the negative role of steroids in cognitive function. Targeting HDAC6- HSP90/GR signaling may provide a potential avenue for the treatment of the impairment of cognitive function after surgery.

15.
Artículo en Inglés | MEDLINE | ID: mdl-39145598

RESUMEN

Facilitating the selective electrochemical oxidation of methanol into value-added formate is essential for electrochemical refining. Here we propose a high-dimensional Nb2O5 on Ni foam (Nb2O5-HD@NF) composite as anode for methanol oxidation reaction (MOR) for efficient production of formate. In an electrolyte containing 3 M methanol aqueous solution, the Nb2O5-HD@NF anode requires only 240 mV overpotential to deliver an industrial-level current density of 100 mA cm-2 with a formate Faraday efficiency of 100%. In situ Raman and electrochemical kinetic analyses reveal that the origin of the excellent activity in 3 M methanol electrolyte can be ascribed to the NbO6 octahedra as active sites and the Lewis acid sites on the surface of Nb2O5-HD. This work may pave a way for the design of non-noble metal electrocatalysts with surface acidity engineering for the effective electrocatalytic upgrading of biomass molecules.

16.
Adv Sci (Weinh) ; 11(29): e2304551, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38810137

RESUMEN

Mammalian cochlear hair cells (HCs) are essential for hearing, and damage to HCs results in severe hearing impairment. Damaged HCs can be regenerated by neighboring supporting cells (SCs), thus the functional regeneration of HCs is the main goal for the restoration of auditory function in vivo. Here, cochlear SC trans-differentiation into outer and inner HC by the induced expression of the key transcription factors Atoh1 and its co-regulators Gfi1, Pou4f3, and Six1 (GPAS), which are necessary for SCs that are destined for HC development and maturation via the AAV-ie targeting the inner ear stem cells are successfully achieved. Single-cell nuclear sequencing and lineaging tracing results showed that the majority of new Atoh1-derived HCs are in a state of initiating differentiation, while GP (Gfi1, Pou4f3) and GPS (Gfi1, Pou4f3, and Six1) enhanced the Atoh1-induced new HCs into inner and outer HCs. Moreover, the patch-clamp analysis indicated that newborn inner HCs induced by GPAS forced expression have similar electrophysiological characteristics to those of native inner HCs. Also, GPAS can induce HC regeneration in the HC-damaged mice model. In summary, the study demonstrates that AAV-mediated co-regulation of multiple genes, such as GPAS, is an effective means to achieve functional HC regeneration in the mouse cochlea.


Asunto(s)
Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico , Reprogramación Celular , Dependovirus , Células Ciliadas Auditivas , Regeneración , Animales , Ratones , Dependovirus/genética , Reprogramación Celular/genética , Regeneración/genética , Regeneración/fisiología , Células Ciliadas Auditivas/metabolismo , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/genética , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/metabolismo , Factor de Transcripción Brn-3C/genética , Factor de Transcripción Brn-3C/metabolismo , Diferenciación Celular/genética , Vectores Genéticos/genética , Proteínas de Unión al ADN , Factores de Transcripción , Proteínas de Homeodominio
17.
Sci China Life Sci ; 2024 Jul 29.
Artículo en Inglés | MEDLINE | ID: mdl-39083201

RESUMEN

Mammalian hair cells (HCs) are arranged spirally along the cochlear axis and correspond to different frequency ranges. Serving as primary sound detectors, HCs spatially segregate component frequencies into a topographical map. HCs display significant diversity in anatomical and physiological characteristics, yet little is known about the organization of the cochleotopic map of HCs or the molecules involved in this process. Using single-cell RNA sequencing, we determined the distinct molecular profiles of inner hair cells and outer hair cells, and we identified numerous position-dependent genes that were expressed as gradients. Newly identified genes such as Ptn, Rxra, and Nfe2l2 were found to be associated with tonotopy. We employed the SCENIC algorithm to predict the transcription factors that potentially shape these tonotopic gradients. Furthermore, we confirmed that Nfe2l2, a tonotopy-related transcription factor, is critical in mice for sensing low-to-medium sound frequencies in vivo. the analysis of cell-cell communication revealed potential receptor-ligand networks linking inner hair cells to spiral ganglion neurons, including pathways such as BDNF-Ntrk and PTN-Scd4, which likely play essential roles in tonotopic maintenance. Overall, these findings suggest that molecular gradients serve as the organizing principle for maintaining the selection of sound frequencies by HCs.

18.
Front Oncol ; 14: 1327691, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38444686

RESUMEN

Background: Baseline serological biomarkers have the potential to predict the benefits of adjuvant chemotherapy in patients with gastric cancer. However, the fluctuating nature of postoperative recurrence risk makes precise treatment challenging. We aimed to develop a risk score in real-time predicting outcomes for postoperative GC patients using blood chemistry tests. Materials and methods: This was a retrospective, multicentre, longitudinal cohort study from three cancer centres in China, with a total of 2737 GC patients in the pTNM stage Ib to III. Among them, 1651 patients with at least two serological records were assigned to the training cohort. Model validation was carried out using separate testing data with area under curve (AUC). The least absolute shrinkage and selection operator (LASSO) and random forest-recursive feature elimination (RF-RFE) algorithm were used to select the parameters. Results: The Cox regression model derived six risk factors to construct a composite score (low-risk: 0-2 score; high risk: 3-6 score), including CEA, CA125, CA199, haemoglobin, albumin, and neutrophil to lymphocyte ratio. The risk score accurately predicted mortality in 1000-time bootstrap (AUROCs:0.658; 95% CI: 0.645, 0.670), with the highest AUROC (0.767; 95% CI: 0.743, 0.791) after 1 year since the gastrectomy. In validation dataset, the risk score had an AUROC of 0.586 (95% CI 0.544, 0.628). Furthermore, patients with high risk at 1 month derived significant clinical benefits from adjuvant chemotherapy (P for interaction <0.0001). Compared with the low-low-low risk group, the low-low-high risk group of the long-term state chain (risk state at baseline, 6 months, 1 year) had the worse OS (HR, 6.91; 95%CI: 4.27, 11.19) and DFS (HR, 7.27; 95%CI: 4.55, 11.63). Conclusion: The dynamic risk score is an accurate and user-friendly serological risk assessment tool for predicting outcomes and assisting clinical decisions after gastrectomy.

19.
J Nanosci Nanotechnol ; 13(2): 1339-42, 2013 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-23646632

RESUMEN

Nitrile-butadiene-rubber composites, filled with super conducting carbon black, are successfully prepared with low percolation threshold, high conductivity and electromagnetic shielding effectiveness. Percolation theory is used to represent the system's conductivity, and the corresponding result is close to the experimental value. The fitting curve also gives the weight fraction threshold and conductivity exponent of the conducting polymer. The percolation threshold of the composite is 9.2 phr, which is much smaller than previous homologous findings and lower than the value of short carbon fiber counterparts reported. The volume resistivity becomes 3.17 omega x cm for the 20 phr sample and decreases to 0.66 omega x cm for the 40 phr sample. At 1.8 GHz for 40 phr sample, the shielding effectiveness is -43 dB.

20.
Am J Transl Res ; 15(8): 5276-5283, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37692929

RESUMEN

OBJECTIVE: To examine the efficacy of immune checkpoint inhibitors along with chemotherapy in non-small cell lung cancer (NSCLC) and the effect on adverse reactions and serum tumor markers. METHODS: Data of 112 NSCLC patients admitted to Geriatric respiratory department, Xi'an International Medical Center Hospital from February 2018 to March 2021 were analyzed retrospectively. Among them, 54 patients treated with concurrent chemotherapy were labeled as the control group (CG), and 58 patients treated with PD-1/PD-L1 inhibitors in addition to chemotherapy were the observation group (OG). The two groups were compared in terms of immune function indexes, therapeutic efficacy, incidence of adverse reactions, 1-year survival rate, serum tumor markers before and after treatment, and independent risk factors affecting patients' prognosis. RESULTS: Compared to the CG, the OG exhibited significantly better therapeutic efficacy. The levels of IgG, IgA and IgM 6 months after treatment were significantly higher in both groups than those before treatment, and the elevations in the OG were more evident than those in the CG, and the OG demonstrated markedly lower Recombinant Cytokeratin Fragment Antigen 21-1 (CYFRA21-1), Carcinoembryonic antigen (CEA) and Carbohydrate antigen 125 (CA125) levels after treatment than the CG did. Between the two groups, there was no significant difference identified in the incidence of adverse reactions, but the OG was observed to have much higher 1-year survival rate. The pathological stage, differentiation and treatment regimen were independent risk factors affecting patients' prognosis. CONCLUSION: For NSCLC patients, the adoption of PD-1/PD-L1 inhibitors following chemoradiotherapy shows potential in enhancing clinical efficacy, boosting patients' immune function, and improving long-term survival rates, with premising safety profile.

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