Visual outcomes and optimal timing for repeat surgery in cases of postoperative hematoma following transsphenoidal surgery for pituitary neuroendocrine tumors: A retrospective cohort study.

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.

Posterior fossa ependymoma with preoperative cerebrospinal metastases: a case report with literature review.

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.

miR-3188 (rs7247237-C>T) Single-Nucleotide Polymorphism Is Associated With the Incidence of Vascular Complications in Chinese Patients With Type 2 Diabetes.

miR-3188, one of the earliest discovered microRNAs, is involved in regulating the mTOR-p-PI3K/AKT pathway, thus affecting the progression of diabetic complications. In this study, we observed that the miR-3188 (rs7247237-C>T) polymorphism not only affected the production of nitric oxide (NO) production in endothelial cells, but also significantly associated with the incidence of vascular complications in Chinese patients with type 2 diabetes. Mechanistic analyses indicate that miR-3188 (rs7247237-T) polymorphism inhibited its own expression and upregulated the expression of gstm1 and trib3, which impairs NO production in human endothelial cells through inactivating AKT/eNOS signal transduction pathway. In addition, our clinical retrospective study indicated that, compared with patients with the CC genotype (n = 351), patients with rs7247237 TT + CT genotypes (n = 580) exhibited an increased risk of major vascular events during intensive glucose control treatment (hazard ratio = 1.560; 95% CI: 1.055-2.307, P = 0.025). Simultaneously, the risk of major vascular events was marginally decreased in patients with the CC genotype during intensive glucose control treatment compared with standard treatment (hazard ratio = 0.666; 95% CI: 0.433-1.016, P = 0.053). Our findings indicate that the miR-3188 (rs7247237-C>T) polymorphism is associated with the incidence of vascular complications in Chinese patients with type 2 diabetes, likely due to its remarkable effect on miR-3188 expression.

Down-regulation of FOXR2 inhibits non-small cell lung cancer cell proliferation and invasion through the Wnt/ß-catenin signaling pathway.

Forkhead box R2 (FOXR2), a new member of the FOX family, is an important player in a wide range of cellular processes such as proliferation, migration, differentiation and apoptosis. Recently, FOXR2 has been reported to be implicated in cancer development. However, the biological functions of FOXR2 in non-small cell lung cancer (NSCLC) remain unclear. In this study, we investigated the specific role of FOXR2 in NSCLC. The results showed that down-regulation of FOXR2 significantly inhibited NSCLC cell proliferation and invasion in vitro and suppressed NSCLC cell growth and metastasis in vivo. In addition, the decrease in FOXR2 expression markedly reduced the protein levels of ß-catenin, cyclinD1 and c-Myc and hence inactivated the Wnt/ß-catenin pathway in NSCLC cells. Taken together, we concluded that FOXR2 might be considered as a promising therapeutic target for NSCLC treatment.

A New Polar Transfer Alignment Algorithm with the Aid of a Star Sensor and Based on an Adaptive Unscented Kalman Filter.

Because of the harsh polar environment, the master strapdown inertial navigation system (SINS) has low accuracy and the system model information becomes abnormal. In this case, existing polar transfer alignment (TA) algorithms which use the measurement information provided by master SINS would lose their effectiveness. In this paper, a new polar TA algorithm with the aid of a star sensor and based on an adaptive unscented Kalman filter (AUKF) is proposed to deal with the problems. Since the measurement information provided by master SINS is inaccurate, the accurate information provided by the star sensor is chosen as the measurement. With the compensation of lever-arm effect and the model of star sensor, the nonlinear navigation equations are derived. Combined with the attitude matching method, the filter models for polar TA are designed. An AUKF is introduced to solve the abnormal information of system model. Then, the AUKF is used to estimate the states of TA. Results have demonstrated that the performance of the new polar TA algorithm is better than the state-of-the-art polar TA algorithms. Therefore, the new polar TA algorithm proposed in this paper is effectively to ensure and improve the accuracy of TA in the harsh polar environment.

The effects of rabeprazole on metformin pharmacokinetics and pharmacodynamics in Chinese healthy volunteers.

The aim was to investigate the role of rabeprazole on the pharmacokinetics (PK) and pharmacodynamics (PD) of metformin. The in vitro inhibition assays on metformin transport were carried out and showed that the half maximal inhibitory concentration (IC50) of rabeprazole on OCT2-mediated metformin transport was 26.0 µM, whereas the IC50 on MATE1-mediated metformin transport inhibition was 4.6 µM. Fifteen healthy Chinese male volunteers were enrolled and given two different doses of metformin plus the co-administration of placebo or rabeprazole. Plasma concentrations of metformin were measured up to 12 h after the second dose. The glucose-lowering effects and the variation of insulin concentrations were evaluated during the oral glucose tolerance test (OGTT). The AUC0-12 of metformin plus rabeprazole were 28,276 ± 5187 ng/ml·h, which was significantly higher than AUC0-12 of metformin plus placebo (24,691 ± 3129 ng/ml·h). Thus, rabeprazole can modestly influence the PK of metformin, suggesting the precaution of using the two drugs together. In OGTTs, rabeprazole decreased the values of AUCinsulin and the maximum insulin concentration. Although rabeprazole showed inhibition effect on OCT2-mediated metformin transport, the glucose-lowering effect of metformin remained the same regardless of its PK changes. Further studies are needed to warrant the effect of rabeprazole on metformin.

Clinical features of clear cell meningioma: a retrospective study of 36 cases among 10,529 patients in a single institution.

BACKGROUND: Clear cell meningioma (CCM) is a rare subtype of meningioma. We present the largest series of 36 CCMs and evaluate several prognostic factors of patient's clinical outcome. METHODS: Thirty-six patients with pathologically confirmed CCM among a total of 10,529 meningioma patients were retrospectively reviewed. RESULTS: CCM constituted 0.3 % of the intracranial meningiomas and 1.4 % of the intraspinal meningiomas. The male-to-female ratio (36 vs 64 %) for CCMs was similar to that for total meningiomas (28 vs 72 %) patients (chi-squared test, p = 0.3). The mean age at diagnosis of CCM patients (29.3 ± 18.4 years) was significantly younger than that of total meningiomas (49.8 ± 11.9 years) patients (t-test, p = 0). During the follow-up, 15 patients (42 %) suffered from tumor recurrence. The recurrence time ranged from 10 months to 12 years, with a median time of 29 months. Kaplan-Meier survival analysis showed that patients after total resection (Simpson grades I and II) had significantly longer progression-free survival (PFS) time than those after subtotal resection (Simpson grades III and IV) (log-rank test, p = 0.006). However, age (≤20 years or >20 years, p = 0.9), gender (p = 0.3), postoperative radiotherapy (p = 0.4), progesterone receptor staining (positivity or negativity, p = 0.2), and Ki-67 index (≤5 % or >5 %, p = 0.4) did not have significant effects on patients' PFS time. CONCLUSIONS: The proportion of CCM in spinal meningiomas is likely to be much larger than that in intracranial meningiomas. CCMs should be resected totally when possible to decrease the risk of recurrence or prolong patient's PFS time.

Granular cell tumors in the central nervous system: a report on eight cases and a literature review.

OBJECTIVE: Granular cell tumors (GCTs) in the central nervous system (CNS) are extremely rare. We report here a series of eight GCTs at various locations in the CNS and provide a full review of the published literature. METHODS: Eight patients with pathologically confirmed GCT in the CNS were retrospectively reviewed. The patients were followed up via telephone interview or an outpatient department. RESULTS: Five patients were female, and three were male. Of the eight tumors, three were located at the sellar region, two were located in the spinal canal, one was located at the cerebral hemisphere, one was parasellar-nasal communicating, and one was combined with an enterogenous cyst at the ventral aspect of the medulla oblongata. Six patients were symptomatic, and two patients were found incidentally. Most GCTs tended to be homogeneous and well defined on radiological images. The parasellar-nasal communicating GCT showed destruction of the skull base and an evident cystic component in the sphenoid sinus. The various GCTs had similar histological features, and they tended to be histologically benign. Most tumors did not recur after the operation. After subtotal resection, one residual spinal GCT regrew during the follow-up period. The patient with the parasellar-nasal communicating GCT developed progressive visual loss in the right eye after the operation; and she received adjuvant radiation therapy. CONCLUSION: GCTs at different locations in the CNS can have significantly different clinical features and should be considered distinct entities. Except for the granular cell astrocytoma (GCA), most GCTs in the CNS tended to be benign. Malignant GCTs are rare and difficult to treat.

[Endovascular treatment of ruptured aneurysms located at anterior communicating artery complex: a sixty-six cases report].

OBJECTIVE: To investigate the endovascular treatments for the ruptured aneurysms located at anterior communicating artery complex (ACoAC). METHODS: The data of patients with ruptured ACoAC aneurysms treated in Department of Neurosurgery, First Affiliated Hospital to Fourth Military Medical University from May 2013 to December 2014 was retrospectively analyzed. Sixty-six cases were recruited including 50 male and 16 female patients. The patients aged from 31 to 69 years old, averaging (51±8) years. The Hunt-Hess grade at admission were 13 cases with grade Ⅰ, 36 cases with grade Ⅱ, 11 cases with grade Ⅲ, and 6 cases with grade Ⅳ. The most diameter of aneurysms sac: 14 cases less than or equal to 3 mm, 36 cases more than 3 mm but less than or equal to 7 mm, and 16 cases more than 7 mm. The height diameter/neck width ratio: 8 cases with absolute wide neck, 50 cases with relatively wide neck, and 8 cases with narrow neck. There were 28 cases underwent single micro-catheter embolization, 18 cases underwent double micro-catheters embolization, 14 cases underwent stent-assisted embolization and 6 cases underwent balloon-assisted embolization. The patients were followed up for 6 to 12 months and evaluated by modified Rankin score (mRS) and digital subtraction angiography (DSA). The ratio of total embolization, recurrence rate, and time from operation to reexamination of four groups managed by different endovascular treatment were compared by χ(2) test or F test. RESULTS: Sixty cases were totally embolized, 3 cases subtotally embolized, 3 cases incompletely embolized. Mild hemiparalysis and aphasia occurred in 2 cases, and 1 case died of infarction induced by subarachnoid haemorrhage. The mRS at six months after operation were 0 in 31 cases, 1 in 22 cases, 2 in 8 cases, 3 in 2 cases, 4 in 2 cases, 6 in 1 case. All the included cases reexamined the DSA at averaging (7.5±1.0) month post-operatively and 4 cases recurred. There were not significant differences of the ratio of total embolization, recurrence rate, time from operation to reexamination among four groups (all P>0.05). CONCLUSION: The endovascular treatment maybe an ideal management for ruptured ACoAC aneurysms.

Mining and identification of polyunsaturated fatty acid synthesis genes active during camelina seed development using 454 pyrosequencing.

BACKGROUND: Camelina (Camelina sativa L.) is well known for its high unsaturated fatty acid content and great resistance to environmental stress. However, little is known about the molecular mechanisms of unsaturated fatty acid biosynthesis in this annual oilseed crop. To gain greater insight into this mechanism, the transcriptome profiles of seeds at different developmental stages were analyzed by 454 pyrosequencing. RESULTS: Sequencing of two normalized 454 libraries produced 831,632 clean reads. A total of 32,759 unigenes with an average length of 642 bp were obtained by de novo assembly, and 12,476 up-regulated and 12,390 down-regulated unigenes were identified in the 20 DAF (days after flowering) library compared with the 10 DAF library. Functional annotations showed that 220 genes annotated as fatty acid biosynthesis genes were up-regulated in 20 DAF sample. Among them, 47 candidate unigenes were characterized as responsible for polyunsaturated fatty acid synthesis. To verify unigene expression levels calculated from the transcriptome analysis results, quantitative real-time PCR was performed on 11 randomly selected genes from the 220 up-regulated genes; 10 showed consistency between qRT-PCR and 454 pyrosequencing results. CONCLUSIONS: Investigation of gene expression levels revealed 32,759 genes involved in seed development, many of which showed significant changes in the 20 DAF sample compared with the 10 DAF sample. Our 454 pyrosequencing data for the camelina transcriptome provide an insight into the molecular mechanisms and regulatory pathways of polyunsaturated fatty acid biosynthesis in camelina. The genes characterized in our research will provide candidate genes for the genetic modification of crops.

Exogenous bFGF or TGFß1 accelerates healing of reconstructed dura by CO2 laser soldering in minipigs.

This study aims to explore the probable mechanism of better result of dural reconstruction by CO2 laser soldering and the effect of exogenous basic fibroblast growth factor (bFGF) or transforming growth factor-beta1(TGFß1) on wound healing. In part I of the study, ten minipigs were randomized into two equal groups, and the dural defects were reconstructed by conventional fibrin glue (FG) bonding (group I a) or by CO2 laser soldering (group Ib). In part II, 36 minipigs were randomized into three equal groups, and the dural defect was reconstructed by CO2 laser soldering; then exogenous bFGF or TGFß1 was administered in group IIb and group IIc, respectively, while group IIa served as control group. The dural specimens were harvested at 1st week postoperatively in part I; and at 1st, 2nd, 3rd, and 4th week postoperatively in part II, they were examined for healing condition and subjected to hematoxylin-eosin (HE) staining and immunohistochemical (IHC) staining with antibodies against bFGF and TGFß1. In part I, group Ib showed higher fibroblast cell density than group Ia (P < 0.05). The optical density (OD) for IHC staining with antibodies against bFGF of group Ib was significantly higher than that of group Ia (P < 0.05), and for IHC staining with antibodies against TGFß1, group Ib showed positive staining while group Ia was negative. In part II, administering exogenous bFGF or TGFß1 made a left shift of fibroblast cell number-time curve compared with control group. For specimens' IHC staining with antibodies against bFGF, the OD of group IIb was higher than that of group IIa in the corresponding time. For specimens' IHC staining with antibodies against TGFß1, the OD of groups IIb and IIc was both higher than that of group IIa (P < 0.05 and P < 0.01, respectively). In conclusion, CO2 laser may trigger fibroblast proliferation through stimulating the secretion of bFGF and TGFß1. Topically administering exogenous bFGF or TGFß1 could accelerate the healing of the reconstructed dura by enhancing secretion of bFGF and/or TGFß1 and promoting the process of fibroblast gathering-degrading.

[Analysis of pathologic characteristics and prognosis in different subtypes of adult medulloblastoma].

OBJECTIVE: To study the pathologic characteristics and prognosis in different subtypes of adult medulloblastoma (MB). METHODS: The clinical information, imaging findings and pathologic characteristics of 151 cases of adult medulloblastomas were retrospectively reviewed and analyzed by chi-square test. The survival data were assessed using the Kaplan-Meier method. RESULTS: Amongst the 151 MB cases studied, there were 73 cases of classic MB, 36 cases of desmoplastic/nodular MB, 39 cases of anaplastic MB and 3 cases of large cell MB. The primary tumors were more frequently located in cerebral hemisphere in desmoplastic/nodular MB than in other subtypes (P=0.000).On the other hand, large cell/anaplastic MB were associated with more frequently local recurrence and distant metastasis (P=0.003). The post-operative overall survival time ranged from 6 to 150 months, with median survival being (103.3±5.7) months (95%CI, 92.52 to 115.09). The median survival of classic MB, desmoplastic/nodular MB and large cell/anaplastic MB was (110.7±7.8) months, (125.5±7.6) months and (57.6±7.6) months, respectively. The differences were statistically significant (P=0.000). CONCLUSIONS: The three variants of MB show different biologic behavior. Large cell/anaplastic MB represents an independent poor prognostic indicator in adults.

Auditory brainstem implants for hearing rehabilitation in NF2-schwannomatosis: A systematic review and single-arm meta-analysis.

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.

Heteroatom Introduction to Reconstruct Interfacial Chemical Structures for High-Reliability CFRTP/A6061-T6 Hybrid Structures.

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.

Studying on Alloying Elements, Phases, Microstructure and Texture in FH36 Ship Plate Steel.

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.

Intravoxel incoherent motion imaging used to assess tumor microvascular changes after transarterial chemoembolization in a rabbit VX2 liver tumor model.

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.

Magnesium Ascorbyl Phosphate Promotes Bone Formation Via CaMKII Signaling.

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).

ROS Promote Hypoxia-Induced Keratinocyte Epithelial-Mesenchymal Transition by Inducing SOX2 Expression and Subsequent Activation of Wnt/ß-Catenin.

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.

A Conceptual Strategy toward High-Reliability Metal-Thermoplastic Hybrid Structures Based on a Covalent-Bonding Mechanism.

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.

Circular RNA circStag1 promotes bone regeneration by interacting with HuR.

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.