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Background: Mild cognitive impairment (MCI) is a critical transitional phase from healthy cognitive aging to dementia, offering a unique opportunity for early intervention. However, few studies focus on the correlation of brain structure and functional activity in patients with MCI due to Alzheimer's disease (AD). Elucidating the complex interactions between structural-functional (SC-FC) brain connectivity and glymphatic system function is crucial for understanding this condition. Method: The aims of this study were to explore the relationship among SC-FC coupling values, glymphatic system function and cognitive function. 23 MCI patients and 18 healthy controls (HC) underwent diffusion tensor imaging (DTI) and resting-state functional MRI (fMRI). DTI analysis along the perivascular space (DTI-ALPS) index and SC-FC coupling values were calculated using DTI and fMRI. Correlation analysis was conducted to assess the relationship between Mini-Mental State Examination (MMSE) scores, DTI-ALPS index, and coupling values. Receiver operating characteristic (ROC) curves was conducted on the SC-FC coupling between the whole brain and subnetworks. The correlation of coupling values with MMSE scores was also analyzed. Result: MCI patients (67.74 ± 6.99 years of age) exhibited significantly lower coupling in the whole-brain network and subnetworks, such as the somatomotor network (SMN) and ventral attention network (VAN), than HCs (63.44 ± 6.92 years of age). Whole-brain network coupling was positively correlated with dorsal attention network (DAN), SMN, and visual network (VN) coupling. MMSE scores were significantly positively correlated with whole-brain coupling and SMN coupling. In MCI, whole-brain network demonstrated the highest performance, followed by the SMN and VAN, with the VN, DAN, limbic network (LN), frontoparietal network (FPN), and default mode network (DMN). Compared to HCs, lower DTI-ALPS index was observed in individuals with MCI. Additionally, the left DTI-ALPS index showed a significant positive correlation with MMSE scores and coupling values in the whole-brain network and SMN. Conclusion: These findings reveal the critical role of SC-FC coupling values and the ALPS index in cognitive function of MCI. The positive correlations observed in the left DTI-ALPS and whole-brain and SMN coupling values provide a new insight for investigating the asymmetrical nature of cognitive impairments.
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BACKGROUND: NF2-schwannomatosis (NF2) is an autosomal dominant disorder prone to hearing loss. Auditory brainstem implants (ABIs) offer a promising solution for hearing rehabilitation in NF2. OBJECTIVE: To synthesize existing literature on ABI implantation in NF2, focusing on audiological outcomes and ABI-related complications. METHODS: The systematic review followed PRISMA guidelines and was registered in the PROSPERO database (CRD42022362155). Relevant studies were identified by searching PubMed, EMBASE, CENTRAL, CMB, and CNKI from inception to August 2023. Data on environmental sound discrimination, open-set discrimination, closed-set discrimination, and ABI-related complications were extracted and subjected to meta-analysis. Publication bias was evaluated using funnel plots and Egger's test. RESULTS: Thirty-three studies were included. The pooled estimate was 58% (95% CI 49-66%) for environmental sound discrimination and 55% (95% CI 40-69%) for closed-set discrimination. Regarding open-set discrimination, the pooled estimates were 30% (95% CI 19-42%) for sound only, 46% (95% CI 37-54%) for lip-reading only, and 63% (95% CI 55-70%) for sound plus lip-reading. The pooled occurrence of ABI-related complications was 33% (95% CI 15-52%). CONCLUSION: This meta-analysis underscores the effectiveness and safety of ABIs in NF2, providing valuable insights for evidence-based decision-making and hearing rehabilitation strategies.
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Implantación Auditiva en el Tronco Encefálico , Implantes Auditivos de Tronco Encefálico , Neurilemoma , Neurofibromatosis , Neurofibromatosis 2 , Neoplasias Cutáneas , Humanos , Neurofibromatosis 2/complicaciones , Neurofibromatosis 2/cirugía , Resultado del Tratamiento , Audición , Estudios RetrospectivosRESUMEN
OBJECTIVE: To investigate the visual outcomes and optimal timing for repeat surgery in cases of postoperative hematoma following transsphenoidal surgery for pituitary neuroendocrine tumors (PitNETs). METHODS: A retrospective study was conducted on 28 patients who developed evident postoperative hematoma out of a total of 9,010 patients. The hematomas were classified into three types based on their CT appearance. Type 1a - mild high density with no tension, Type 1b - thin-layer high density; Type 2a - solid high density with large empty cavities, Type 2b - solid high density with small empty cavities; Type 3 -solid high density with no cavity showing high tension. Patient data were collected for analysis. RESULTS: The study cohort comprised 10 female and 18 male patients, with a mean age of 51.5±11.9 years. Most patients presented with large adenomas (median diameter 36mm). Postoperative visual sight improved in 12 patients, remained stable in 11 patients, and worsened in 5 patients. Notably, no patients experienced worsened visual sight beyond twenty-four hours after the operation. Among the five patients with visual deterioration, four had CT type 3 hematoma (4/6, 66.7%), and one had CT type 2b hematoma (1/9, 11.1%). Patients in the type 3 CT group were significantly more prone to experience visual deterioration compared to those in the type 2 group (odds ratio [OR] 2.154 [95% CI 1.858-611.014], P=.027). Four patients underwent repeat surgery after visual deterioration, resulting in visual improvement following a prolonged recovery period. Postoperative hematoma had limited impact on pituitary dysfunction and hyponatremia. CONCLUSION: Our study reveals a significant association between postoperative hematoma CT types and visual deterioration. For patients with stable visual sight and type 1 or 2a hematoma, conservative strategies may be considered. Conversely, type 2b and 3 patients are at higher risk of visual deterioration, especially within the first 24 hours after the operation. Consequently, early reoperation before vision worsens may be a prudent approach to reduce risks and improve visual outcomes, particularly in type 3 patients.
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Adenoma , Tumores Neuroendocrinos , Neoplasias Hipofisarias , Humanos , Masculino , Femenino , Adulto , Persona de Mediana Edad , Reoperación , Estudios Retrospectivos , Tumores Neuroendocrinos/cirugía , Neoplasias Hipofisarias/cirugía , Neoplasias Hipofisarias/patología , Adenoma/cirugía , Adenoma/patología , Hematoma/diagnóstico por imagen , Hematoma/etiología , Hematoma/cirugía , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/cirugía , Resultado del TratamientoRESUMEN
This study used simulation software and experiments to analyze the microstructure and texture of FH36 ship plate steel at different thicknesses and temperatures. The austenite phase transformed into ferrite phase at 830 °C and MC and M7C3 phases precipitated at 1150 °C and 543 °C, respectively. At room temperature, the microstructure at the surface and 1/4 thickness consisted of polygonal ferrite, acicular ferrite and granular bainite, while the 1/2 thickness had less acicular ferrite and granular bainite. The texture components were mainly {111}<110> and {111}<112> at all thicknesses, but {001}<110> was stronger at 1/2 thickness. The grain size decreased gradually from 1/2 thickness to the surface, and the proportion of high-angle grain boundaries was significantly lower at the surface than at 1/4 and 1/2 thickness.
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The application of carbon-fiber-reinforced thermoplastic (CFRTP)/metal hybrid structures is a vital step for realizing the lightweight design concepts in aerospace. However, the CFRTP/metal hybrid structures are usually not reliable enough in practical applications due to the high differences in chemical and physical properties between these two materials. The current work provides a bottom-up strategy of introducing heteroatoms into CFRTP/metal interfaces to reconstruct the interfacial chemical structures and thus manufacture high-reliability hybrid structures. Based on the principle of utmost using reaction sites at metal surfaces, the heteroatoms of oxygen and hydrogen are specially designed and introduced to the CFRTP/A6061-T6 (6061) interfaces by simple and green plasma polymerization. The introduced oxygen and hydrogen heteroatoms react with the aluminum and oxygen of the oxidation film at 6061 surfaces to produce great interfacial Al-O covalencies and hydrogen bonds. The reconstructing interfacial chemical structures strengthen the joint strength of CFRTP/6061 hybrid structures from 8.82 to 23.97 MPa. Our heteroatom introduction strategy is expected to get a fresh insight into the interfacial design concept and has several important implications for the future application of high-reliability CFRTP/metal hybrid structures.
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Dysregulation of bone homeostasis is closely related to the pathogenesis of osteoporosis. Suppressing bone resorption by osteoclasts to attenuate bone loss has been widely investigated, but far less effort has been poured toward promoting bone formation by osteoblasts. Here, we aimed to explore magnesium ascorbyl phosphate (MAP), a hydrophilic and stable ascorbic acid derivative, as a potential treatment option for bone loss disorder by boosting osteoblastogenesis and bone formation. We found that MAP could promote the proliferation and osteoblastic differentiation of human skeletal stem and progenitor cells (SSPCs) in vitro. Moreover, MAP supplementation by gavage could alleviate bone loss and accelerate bone defect healing through promoting bone formation. Mechanistically, we identified calcium/calmodulin-dependent serine/threonine kinase IIα (CaMKIIα) as the target of MAP, which was found to be directly bound and activated by MAP, then with a concomitant activation in the phosphorylation of ERK1/2 (extracellular regulated kinase 1/2) and CREB (cAMP-response element binding protein) as well as an elevation of C-FOS expression. Further, blocking CaMKII signaling notably abolished these effects of MAP on SSPCs and bone remodeling. Taken together, our data indicated that MAP played an important role in enhancing bone formation through the activation of CaMKII/ERK1/2/CREB/C-FOS signaling pathway and may be used as a novel therapeutic option for bone loss disorders such as osteoporosis. © 2023 American Society for Bone and Mineral Research (ASBMR).
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Proteína Quinasa Tipo 2 Dependiente de Calcio Calmodulina , Osteoporosis , Humanos , Proteína Quinasa Tipo 2 Dependiente de Calcio Calmodulina/metabolismo , Proteína Quinasa Tipo 2 Dependiente de Calcio Calmodulina/farmacología , Proteína Quinasa Tipo 2 Dependiente de Calcio Calmodulina/uso terapéutico , Osteogénesis , Transducción de Señal , Diferenciación Celular , Sistema de Señalización de MAP Quinasas , Osteoblastos/metabolismo , Osteoporosis/metabolismoRESUMEN
Purpose: To evaluate the correlation between microvascular density (MVD) and intravoxel incoherent motion (IVIM) magnetic resonance imaging (MRI) parameters and the effect of glycolytic flux after transarterial chemoembolization (TACE) in a rabbit VX2 liver tumor. Materials and methods: VX2 liver tumor allografts in 15 New Zealand white rabbits were treated with sterile saline (control group, n = 5) or lipiodol-doxorubicin emulsion (experimental group, n = 10). MRI was performed 2 weeks after the procedure to evaluate IVIM parameters, including apparent diffusion coefficient (ADC), pure diffusion coefficient (D), pseudodiffusion coefficient (D*), and perfusion fraction (PF). All animal samples were taken of the tumor and surrounding liver. Immunostaining for CD31, CD34, CD105, and VEGF was used to evaluate MVD. The protein expression of Glut4, HK2, PKM2, LDHA, and MCT1 was determined using western blotting. Pearson correlation tests were used to analyze the relationship between MVD and IVIM parameters. Results: D* value in the peritumoral region was negatively correlated with CD34 (r = -0.71, P = 0.01). PF value positively correlated with CD34 (r = 0.68, P = 0.015), CD105 (r = 0.76, P = 0.004) and VEGF (r = 0.72, P = 0.008) in the peritumoral region. Glut4, HK2, PKM2, and MCT1 in the peritumoral regions were higher in the experimental group than in the control group (all P < 0.05). Conclusion: IVIM parameters were correlated with MVD in the intratumoral and peritumoral regions after TACE in a rabbit liver tumor model. The angiogenesis reflected by MVD may be related to changes of glycolytic flux.
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BACKGROUND: Adult posterior fossa ependymomas (PF-EPN) with preoperative cerebrospinal metastases are extremely rare. Only 3 cases have been reported in previous literature. CASE PRESENTATION: A case of a 32-year-old male patient complained of headaches for three months. Pure tone audiometry showed a slight decrease in bilateral hearing. Auditory evoked potential indicated that the hearing on the left was slightly weaker than that on the right. Magnetic resonance imaging (MRI) revealed a primary tumor arising within the fourth ventricle and metastasizing to bilateral cerebellopontine angle (CPA), the third ventricle, the left lateral ventricle, T1, L1-2 and L5. A gross total resection (GTR) was performed on the lesion located in the left CPA. The histological examination showed a papillary ependymoma (WHO grade II). Immunohistochemical staining for H3K27me3 showed that nuclear positivity in more than 80% of cells. No NF2 mutation was observed. No progression was found during a 24-month follow-up. CONCLUSIONS: Our data indicate that preoperative multiple metastases in adult PF-EPN are extremely rare. This kind of disease usually has a low WHO grade and a favorable prognosis. GTR should be achieved when feasible and patients need a long-term follow-up with MRI.
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Ependimoma , Tercer Ventrículo , Masculino , Adulto , Humanos , Pronóstico , Ependimoma/cirugía , Ependimoma/patología , Imagen por Resonancia Magnética , Cuarto VentrículoRESUMEN
BACKGROUND: Vascular calcification is a major cause of the high morbidity and mortality of cardiovascular diseases and is closely associated with the intestinal microbiota. Short-chain fatty acids (SCFAs) are derived from the intestinal microbiota and can also regulate intestinal microbiota homeostasis. However, it remains unclear whether exogenous supplementation with propionate, a SCFA, can ameliorate vascular calcification by regulating the intestinal microbiota. This study was conducted to explore the roles of propionate and the intestinal microbiota in the process of vascular calcification. METHODS: In total, 92 patients were enrolled consecutively as the observational cohort to analyse the relationship between SCFAs and vascular calcification in both blood and faecal samples. A rat model of vascular calcification was induced by vitamin D3 and nicotine (VDN) to validate the effect of propionate. Differences in the intestinal microbiota were analysed by 16S ribosomal RNA gene sequencing. Faecal microbiota transplantation and Akkermansia muciniphila transplantation experiments were performed to evaluate the functions of the intestinal microbiota. RESULTS: The results of the observational cohort study revealed that the levels of SCFAs (particularly propionate) in both blood and faecal samples independently correlated negatively with calcification scores (P < 0.01). To verify the activities of propionate, it was provided to VDN-treated rats, and oral or rectal propionate delivery reshaped the intestinal microbiota, resulted in elevated SCFA production, improved intestinal barrier function and alleviated inflammation, ultimately ameliorating vascular calcification. Furthermore, we demonstrated that transplantation of the propionate-modulated intestinal microbiota induced beneficial outcomes similar to those with oral or rectal propionate administration. Interestingly, linear discriminant analysis (LDA) effect size (LEfSe) revealed that oral or rectal propionate administration and propionate-modulated intestinal microbiota transplantation both enriched primarily Akkermansia. Subsequently, we demonstrated that Akkermansia supplementation could ameliorate VDN-induced vascular calcification in rats. CONCLUSIONS: Propionate can significantly ameliorate vascular calcification in VDN-treated rats, and this effect is mediated by intestinal microbiota remodelling. The findings in our study indicate that the intestinal tract-vessel axis is a promising target for alleviating vascular calcification. Video Abstract.
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Microbioma Gastrointestinal , Calcificación Vascular , Ratas , Animales , Microbioma Gastrointestinal/fisiología , Propionatos , Ácidos Grasos Volátiles , Verrucomicrobia , Calcificación Vascular/tratamiento farmacológicoRESUMEN
Metal-thermoplastic hybrid structures have proven their effectiveness to achieve lightweight design concepts in both primary and secondary structural components of advanced aircraft. However, the drastic differences in physical and chemical properties between metal and thermoplastic make it challenging to fabricate high-reliability hybrid structures. Here, a simple and universal strategy to obtain strong hybrid structures thermoplastics is reported by regulating the bonding behavior at metal/thermoplastic interfaces. To achieve such, we first researched and uncovered the bonding mechanism at metal/thermoplastic interfaces by experimental methods and density functional theory (DFT) calculations. The results suggest that the interfacial covalency, which is formed due to the interfacial reaction between high-electronegativity elements of thermoplastics and metallic elements at metal surfaces, dominates the interfacial bonding interaction of metal-thermoplastic hybrid structures. The differences in electronegativity and atomic size between bonding atoms influence the covalent-bond strength and finally control the interfacial reliability of hybrid structures. Based on our covalent-bonding mechanism, the carboxyl functional group (COOH) is specifically grafted on polyetheretherketone (PEEK) by plasma polymerization to increase the density and strength of interfacial covalency and thus fabricate high-reliability hybrid structures between PEEK and A6061-T6 aluminum alloy. Current work provides an in-depth understanding of the bonding mechanism at metal-thermoplastics interfaces, which opens a fascinating direction toward high-reliability metal-thermoplastic hybrid structures.
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Postmenopausal osteoporosis is a common bone metabolic disorder characterized by deterioration of the bone microarchitecture, leading to an increased risk of fractures. Recently, circular RNAs (circRNAs) have been demonstrated to play pivotal roles in regulating bone metabolism. However, the underlying functions of circRNAs in bone metabolism in postmenopausal osteoporosis remain obscure. Here, we report that circStag1 is a critical osteoporosis-related circRNA that shows significantly downregulated expression in osteoporotic bone marrow mesenchymal stem cells (BMSCs) and clinical bone tissue samples from patients with osteoporosis. Overexpression of circStag1 significantly promoted the osteogenic capability of BMSCs. Mechanistically, we found that circStag1 interacts with human antigen R (HuR), an RNA-binding protein, and promotes the translocation of HuR into the cytoplasm. A high cytoplasmic level of HuR led to the activation of the Wnt signaling pathway by stabilizing and enhancing low-density lipoprotein receptor-related protein 5/6 (Lrp5/6) and ß-catenin expression, thereby stimulating the osteogenic differentiation of BMSCs. Furthermore, overexpression of circStag1 in vivo by circStag1-loaded adeno-associated virus (circStag1-AAV) promoted new bone formation, thereby preventing bone loss in ovariectomized rats. Collectively, we show that circStag1 plays a pivotal role in promoting the regeneration of bone tissue via HuR/Wnt signaling, which may provide new strategies to prevent bone metabolic disorders such as postmenopausal osteoporosis.
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We previously showed that wound-induced hypoxia is related to keratinocyte migration. The ability of keratinocytes within wound healing to undergo epithelial to mesenchymal transition (EMT) contributes significantly to the acquisition of migratory properties. However, the effect of hypoxia on keratinocyte EMT on wound healing and the potential mechanism are poorly documented. This study first demonstrated that reactive oxygen species (ROS) appear to be an essential signalling mediator in keratinocytes with increased EMT and migration subjected to hypoxic conditions. Next, we showed that the expression of sex-determining region Y-box 2 (SOX2), a stemness-associated molecule, is ROS-dependent under hypoxia and that SOX2 inhibition in keratinocytes dramatically prevented hypoxia-induced EMT and migration. In addition, ß-catenin was found to be a potential molecular target of SOX2, and the activation of Wnt/ß-catenin was required for hypoxia-induced EMT and migration. Using an in vitro skin culture model and an in vivo skin wound model, our study further reinforced the critical role of ROS in inducing EMT through SOX2 expression and subsequent activation of Wnt/ß-catenin, allowing for rapid reepithelialization of the wound area. Taken together, our findings reveal a previously unknown mechanism by which hypoxia promotes wound healing by promoting reepithelialization through the production of ROS, inducing keratinocyte EMT and migration via the enhancement of SOX2 and activation of Wnt/ß-catenin.
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Queratinocitos/metabolismo , Factores de Transcripción SOXB1/metabolismo , beta Catenina/metabolismo , Animales , Hipoxia de la Célula , Transición Epitelial-Mesenquimal , Femenino , Humanos , Masculino , Ratones , Especies Reactivas de Oxígeno , TransfecciónRESUMEN
Bone remodeling is a dynamic process between bone formation mediated by osteoblasts and bone resorption mediated by osteoclasts. Disrupted bone remodeling is a key factor in postmenopausal osteoporosis, a metabolic disorder characterized by deteriorated bone microarchitecture and increased risk of fracture. Recent studies have shown that piwi-binding RNA (piRNA) is involved in the pathogenesis of certain diseases at the post-transcriptional level. Here, we analyzed piRNA-63049 (piR-63049), which may play an essential role in bone remodeling. The expression of piR-63049 significantly increased in both bone tissues and plasma of osteoporotic rats and postmenopausal osteoporotic patients. Overexpressing piR-63049 could inhibit the osteoblastogenesis of bone marrow stromal cells (BMSCs) while knocking down piR-63049 could promote the osteoblastogenesis of BMSCs through the Wnt2b/ß-catenin signaling pathway. Moreover, knocking-down piR-63049 (piR-63049-antagonist) in vivo could attenuate the bone loss in ovariectomized rats by promoting bone formation. Taken together, the current study shows that piR-63049 inhibits bone formation through the Wnt2b/ß-catenin signaling pathway. This novel piRNA may be a potential target to increase bone formation in bone loss disorders such as postmenopausal osteoporosis.
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Desarrollo Óseo/fisiología , Glicoproteínas/metabolismo , Proteínas Wnt/metabolismo , beta Catenina/metabolismo , Anciano , Animales , Densidad Ósea , Desarrollo Óseo/genética , Células de la Médula Ósea , Femenino , Regulación de la Expresión Génica/fisiología , Glicoproteínas/genética , Humanos , Persona de Mediana Edad , Osteogénesis , Osteoporosis , Ovariectomía , ARN Mensajero , ARN Interferente Pequeño , Ratas , Células Madre , Proteínas Wnt/genética , beta Catenina/genéticaRESUMEN
Scaffolds functionalized with bone morphogenetic protein-2 (BMP-2) have shown great potential for bone regeneration. However, structural instability and the necessity for supra-physiological dose have thus far limited practical applications for BMP-2. Protein modification and site-specific covalent immobilization of BMP-2 to carrier materials might be optimal strategies to overcome these problems. Here, we report a broadly applicable strategy where the polyhistidine tag-T4 Lysozyme (His6-T4L) was genetically fused at the N-terminus of BMP-2 and used as a protein spacer, which on one hand enhanced protein solubility and stability, and on the other hand mediated site-specific covalent anchoring of BMP-2 upon binding to nickel-chelated nitrilotriacetic acid (Ni-NTA) microparticles (denoted as MPs-His6-T4L-BMP2) to further maximize its rescued activity. We also constructed a novel gelatin-based hydrogel that was crosslinked by transglutaminase (TG) and tannic acid (TA). This hydrogel, when incorporated with MPs-His6-T4L-BMP2, displayed excellent in-situ injectability, thermosensitivity, adhesiveness and improved mechanical properties. The effective loading mode led to a controlled and long-term sustained release of His6-T4L-BMP2, thereby resulting in enhancement of bone regeneration in a critical-sized bone defect. We believe that the protein modification strategy proposed here opens up new route not only for BMP-2 applications, but can be used to inform novel uses for other macromolecules.
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Proteína Morfogenética Ósea 2 , Hidrogeles , Proteína Morfogenética Ósea 2/genética , Regeneración Ósea , GelatinaRESUMEN
Interfacial structures govern the reliability of metal-thermoplastic hybrid joints used in the aerospace industry. The current work demonstrated by experimental methods and density functional theory (DFT) calculations that introduction of carbon fibers (CFs) enhanced the mechanical properties and weakened the corrosion resistance of polyamide 6 (PA6)/A6061-T6 (6061) joints. The bonding strength of typical PA6/6061 joints was increased by 33.70% with the introduction of CF. However, the differences in intrinsic work functions of the CF and various phases within 6061 led to the formation of serious cracks at CFRPA6/6061 interfaces and heavy corrosion on 6061 surfaces, corresponding to the decreased corrosion resistance of PA6/6061 joints. Herein, we present a potential solution to adjust the welding heat input to enhance metal/thermoplastic interfacial reliability. With a rotation speed of 400 mm/min during friction lap joining (FLJ), the fabricated CFRPA6/6061 joint could achieve a strong interface with high strength (bonding strength = 1.730 kN) and relative corrosion resistance (corrosion rate < 0.1 mm/a). The results provide a reliable explanation for the effect of CF on mechanical properties and corrosion resistance of CFRPA6/6061 joints. Furthermore, the knowledge gained in this work will benefit future research in the optimization of processes to improve the reliability of metal-thermoplastic hybrid structures.
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The development of recombinant protein cross-linked injectable hydrogels with good mechanical strength and effective drug loading capacity for bone regeneration is extremely attractive and rarely reported. Here, we report the fabrication of a smart hydrogel delivery system by incorporating a rationally designed T4 lysozyme mutant (T4M) to mediate the localized delivery and synergistic release of Mg2+ and Zn2+ for bone repair. Apart from its intrinsic antibacterial properties, T4M bears abundant free amine groups on its surface to function as effective covalent crosslinkers to strengthen the hydrogel network as well as exhibits specific binding affinity to multivalent cations such as Zn2+. Moreover, the integrin receptor-binding Arg-Gly-Asp (RGD) sequence was introduced onto the C-terminus of T4 lysozyme to improve its cellular affinity and further facilitate rapid tissue regeneration. The final composite hydrogel displays excellent injectability, improved mechanical properties, antibacterial activity, and unique bioactivities. The effective loading of Mg2+/Zn2+ in the hydrogels could mediate the sequential and sustained release of Mg2+ and Zn2+, thereby resulting in synergistic enhancement on bone regeneration through modulation of the MAPK signaling pathway. We believe that the strategy proposed in this paper opens up a new route for developing protein cross-linked smart delivery systems for tissue regeneration.
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Hidrogeles , Magnesio , Regeneración Ósea , Iones , ZincRESUMEN
OBJECTIVE: Although bilateral vestibular schwannomas (VSs) in individual NF2 patients have the same NF2 gene mutation, they often show different growth patterns. We attempted to identify factors associated with this growth pattern inconsistency. PATIENTS AND METHODS: Cranial MR images of 120 untreated VSs in 60 NF2 patients were carefully reviewed for their growth rates. Growth pattern analysis was performed on 68 VSs in 34 NF2 patients followed up for more than three years with at least three cranial MR scans. RESULTS: Patient age and tumor volume were significantly associated with NF2 VS absolute growth rates (pâ¯<â¯0.05). Bilateral VS growth patterns in individual NF2 patients were the same in 18 (52.9 %) and different in 16 (47.1 %) patients. Patients with consistent bilateral growth patterns were significantly younger than the inconsistent patients (21.8⯱â¯5.8 years vs. 30.8⯱â¯13.1 years, pâ¯=â¯0.014). The bilateral VS volume consistency rates were significantly higher in patients with consistent growth patterns than in patients with inconsistent growth patterns (10/18 vs. 3/16, pâ¯=â¯0.028). CONCLUSIONS: Patient age and volume consistency are the clinical risk factors for bilateral NF2 VS growth pattern inconsistencies. Bilateral VSs in young NF2 patients tend to have the same growth patterns. These findings may help us to predict the future clinical behavior of small NF2 VSs based on the past clinical history of the large ones.
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Neurofibromina 2/genética , Neuroma Acústico/diagnóstico por imagen , Neuroma Acústico/genética , Carga Tumoral/genética , Adolescente , Adulto , Niño , Análisis Factorial , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Riesgo , Adulto JovenRESUMEN
BACKGROUND: Gastric cancer (GC) is the most commonly diagnosed malignancy worldwide. Increasing evidence suggests that it is necessary to further explore genetic and immunological characteristics of GC. AIM: To construct an immune-related gene (IRG) signature for accurately predicting the prognosis of patients with GC. METHODS: Differentially expressed genes (DEGs) between 375 gastric cancer tissues and 32 normal adjacent tissues were obtained from The Cancer Genome Atlas (TCGA) GDC data portal. Then, differentially expressed IRGs from the ImmPort database were identified for GC. Cox univariate survival analysis was used to screen survival-related IRGs. Differentially expressed survival-related IRGs were considered as hub IRGs. Genetic mutations of hub IRGs were analyzed. Then, hub IRGs were selected to conduct a prognostic signature. Receiver operating characteristic (ROC) curve analysis was used to evaluate the prognostic performance of the signature. The correlation of the signature with clinical features and tumor-infiltrating immune cells was analyzed. RESULTS: Among all DEGs, 70 hub IRGs were obtained for GC. The deletions and amplifications were the two most common types of genetic mutations of hub IRGs. A prognostic signature was identified, consisting of ten hub IRGs (including S100A12, DEFB126, KAL1, APOH, CGB5, GRP, GLP2R, LGR6, PTGER3, and CTLA4). This prognostic signature could accurately distinguish patients into high- and low- risk groups, and overall survival analysis showed that high risk patients had shortened survival time than low risk patients (P < 0.0001). The area under curve of the ROC of the signature was 0.761, suggesting that the prognostic signature had a high sensitivity and accuracy. Multivariate regression analysis demonstrated that the prognostic signature could become an independent prognostic predictor for GC after adjustment for other clinical features. Furthermore, we found that the prognostic signature was significantly correlated with macrophage infiltration. CONCLUSION: Our study proposed an immune-related prognostic signature for GC, which could help develop treatment strategies for patients with GC in the future.
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OBJECTIVE: NF2 patients can develop new meningiomas throughout their lifetime. Little is known about the clinical features of newly developed NF2 meningiomas. In this study, we analyzed newly developed NF2 meningiomas in a large patient population. PATIENTS AND METHODS: Among 452 NF2 patients, the location patterns of 81 pediatric and 939 adult NF2 meningiomas were compared to find the predominant locations of newly developed meningiomas in adulthood. The clinical features of 39 newly developed meningiomas in 24 NF2 patients were summarized. Clinical risk factors of NF2 meningioma growth rates were analyzed. RESULTS: Pediatric patients had significantly more intracranial meningiomas than adult patients at the skull base (except for the petrosal region) (pâ¯<â¯0.0063). Adult patients had significantly more cranial meningiomas than pediatric patients at the parasagittal, parafalcine (middle & posterior), and frontal/parietal/cerebellar convex surfaces (pâ¯<â¯0.0063). Newly developed NF2 meningiomas in adults tended to occur at different locations than the locations of NF2 meningiomas in pediatric patients. New meningiomas could develop at various ages. Ninety-five NF2 patients were imaged and followed up for at least one year. Twenty-four patients (25.3 %) developed 39 new meningiomas during the follow-up period. They usually had initial meningiomas when new meningiomas occurred. The number of newly developed meningiomas per patient and the petrosal location were significantly associated with both the absolute and relative annual growth rates (pâ¯<â¯0.05). CONCLUSIONS: The number of newly developed NF2 meningiomas seems to be a clinical marker of NF2 disease severity. In adults, new NF2 meningiomas tend to occur in patients with initial meningiomas. The predominant locations of newly developed NF2 meningiomas seem to be the parasagittal, parafalcine (middle/posterior), and frontal/parietal/cerebellar convex surfaces.