Aquaporin 4 Mediates the Effect of Iron Overload on Hydrocephalus After Intraventricular Hemorrhage.

BACKGROUND: Iron overload plays an important role in hydrocephalus development following intraventricular hemorrhage (IVH). Aquaporin 4 (AQP4) participates in the balance of cerebrospinal fluid secretion and absorption. The current study investigated the role of AQP4 in the formation of hydrocephalus caused by iron overload after IVH. METHODS: There were three parts to this study. First, Sprague-Dawley rats received an intraventricular injection of 100 µl autologous blood or saline control. Second, rats had IVH and were treated with deferoxamine (DFX), an iron chelator, or vehicle. Third, rats had IVH and were treated with 2-(nicotinamide)-1,3,4-thiadiazole (TGN-020), a specific AQP4 inhibitor, or vehicle. Rats underwent T2-weighted and T2* gradient-echo magnetic resonance imaging to assess lateral ventricular volume and intraventricular iron deposition at 7, 14, and 28 days after intraventricular injection and were then euthanized. Real-time quantitative polymerase chain reaction, western blot analysis, and immunofluorescence analyses were conducted on the rat brains to evaluate the expression of AQP4 at different time points. Hematoxylin and eosin-stained brain sections were obtained to assess the ventricular wall damage on day 28. RESULTS: Intraventricular injection of autologous blood caused a significant ventricular dilatation, iron deposition, and ventricular wall damage. There was increased AQP4 mRNA and protein expression in the periventricular tissue in IVH rats through day 7 to day 28. The DFX treatment group had a lower lateral ventricular volume and less intraventricular iron deposition and ventricular wall damage than the vehicle-treated group after IVH. The expression of AQP4 protein in periventricular tissue was also inhibited by DFX on days 14 and 28 after IVH. The use of TGN-020 attenuated hydrocephalus development after IVH and inhibited the expression of AQP4 protein in the periventricular tissue between day 14 and day 28 without a significant effect on intraventricular iron deposition or ventricular wall damage. CONCLUSIONS: AQP4 located in the periventricular area mediated the effect of iron overload on hydrocephalus after IVH.

An Anthocyanin-Based Eco-Friendly Triboelectric Nanogenerator for pH Monitoring and Energy Harvesting.

In recent years, renewable and sustainable triboelectric nanogenerators have attracted attention due to their high energy conversion rate, and enhancing their functionality further contributes to their applicability across various fields. A pH-sensitive triboelectric nanogenerator (pH-TENG) has been prepared by electrostatic spinning technology, with anthocyanin as the pH indicator and environmentally friendly polyvinyl alcohol (PVA) as the substrate. Among many friction-negative materials, the pH-TENG exhibits the best combination with fluorinated ethylene propylene (FEP) and yields an open-circuit voltage of 62 V, a short-circuit current of 370 nA, and a transferred charge of 21.8 nC. At a frequency of 3 Hz, it can charge a 4.7 µF capacitor to 2 V within 45 s, effectively powering a thermometer. Furthermore, the presence of anthocyanin does not affect the pH-TENG's power generation performance and enables the monitoring of a wide range of environmental pH changes, with an ΔE change of 28.8 ± 7.6. Therefore, pH-TENG prepared with environmentally friendly materials can bring new available materials to the biological and medical fields.

Microcirculation No-Reflow Phenomenon after Acute Ischemic Stroke.

BACKGROUND: The no-reflow phenomenon refers to a failure to restore normal cerebral microcirculation despite brain large artery recanalization after acute ischemic stroke, which was observed over 50 years ago. SUMMARY: Different mechanisms contributing to no-reflow extend across the endovascular, vascular wall, and extravascular factors. There are some clinical tools to evaluate cerebral microvascular hemodynamics and represent biomarkers of the no-reflow phenomenon. As substantial experimental and clinical data showed that clinical outcome was better correlated with reperfusion status rather than recanalization in patients with ischemic stroke, how to address the no-reflow phenomenon is critical. But effective treatments for restoring cerebral microcirculation have not been well established until now, so there is an urgent need for novel therapeutic perspectives to improve outcomes after recanalization therapies. CONCLUSION: Here, we review the occurrence of the no-reflow phenomenon after ischemic stroke and discuss its impact, detection method, and therapeutic strategies on the course of ischemic stroke, from basic science to clinical findings.

Proteomic and bioinformatic analysis of human endometrium from polycystic ovarian syndrome with and without insulin resistance.

Objective: The aim of this study was to investigate the endometrial proteomic profiles of patients with polycystic ovary syndrome (PCOS) with and without insulin resistance (IR). Method of Study: We collected 40 endometrial samples, including PCOS-IR (n = 21), PCOS-non-IR (n = 12), and control (n = 7). Data-independent acquisition (DIA)-based proteomics method is used to identify the expressed proteins among the three groups. The correlation between pregnancy outcomes and identified proteins was analyzed by Lasso regression. Results: A total of 5331 proteins were identified, while 275 proteins were differentially expressed in the PCOS vs. control group and 215 proteins were differentially expressed in the PCOS-IR vs. PCOS-non-IR group. Platelet degranulation, neutrophil degranulation, and very long-chain fatty acid catabolic processes have been found to play important roles in the endometrium of patients with PCOS-IR. Lasso regression analysis found that ACTR1A, TSC22D2, CKB, ABRAXAS2, and TAGLN2 were associated with miscarriage in patients with PCOS. ACTR1A and CKB were higher in the PCOS-IR group and were positively correlated with HOMA-IR (p < .05). Conclusion: In this study, a panel of proteins was found to be differently expressed in the endometrium. ACTR1A and CKB may be considered as PCOS-IR candidate biomarkers.

Effect of ß2-microglobulin in evaluating the severity and prognosis of brain injury: a clinical study.

BACKGROUND: ß2-microglobulin has been showing to be vital that associated with brain function and neurological diseases. This study aimed to explore the expressions of ß2-microglobulin in blood and urine of the patients with brain injury, and the effect of hyperbaric oxygen therapy on the content of ß2-microglobulin. METHODS: This prospective study included 54 patients with brain injury and 11 healthy controls. The patients were further assigned to two groups: the conscious disturbance group (n = 32) and the non-conscious disturbance group (n = 22) depending on the Glasgow Coma Scale (GCS). The patients received routine treatment and two courses of hyperbaric oxygen therapy (2.0ATA, 60 min, once a day, 10 days for a course). In the brain injury group, blood ß2-microglobulin (ß2MG) and urine ß2-microglobulin (ß2MU) were detected respectively before and after hyperbaric oxygen therapy (HBOT). Consciousness and cognitive scores were performed, correspondingly. RESULTS: Compared with those of the control group, levels of ß2MG and ß2MU in the brain injury group were significantly increased before HBOT (P < 0.05). Whether it was before or after HBOT, ß2MG's content in the conscious disturbance group was higher than that in the non-conscious disturbance group, while ß2MU's content was obviously higher than that of the non-conscious disturbance group only before HBOT (P < 0.05). Besides, the ß2MU's content in the conscious disturbance group was negatively correlated with GCS score (R = -0.351, P < 0.05) and ß2MG's content in the non-conscious disturbance group was positively correlated with the MMSE score grade (R = 0.598, P < 0.05). The ROC curve was used to assess the evaluation of ß2MG and ß2MU for patients with impaired consciousness with the area under the curve (AUC) of ß2MG and ß2MU were 0.775 and 0.796, respectively. CONCLUSION: The concentrations of blood ß2-microglobulin and urinary ß2-microglobulin were significantly increased in patients with brain injury. The concentrations of ß2-microglobulin were correlated with the degree of consciousness and cognitive function. The changes tendency of ß2-microglobulin may be considered as clinical monitoring index to evaluate the patient's disturbance of consciousness and cognitive degree, and provide a basis for early assessment of prognosis.

Exploring the impact of urban form on urban land use efficiency under low-carbon emission constraints: A case study in China's Yellow River Basin.

In the Urban Anthropocene, how to meet the demands of growing urban populations on limited urban land is a key global challenge. Unreasonable urban planning and land use has brought about undesirable consequences including huge carbon emissions. However, research on the spatial impact of urban form on urban land use efficiency (ULUE) under low-carbon emission constraints is limited. This study analyzes 91 cities located in China's Yellow River Basin (YRB). First, we define a new comprehensive indicator system to measure ULUE under low-carbon constraints using the SBM-UN model. We then select nine landscape indicators to quantify the sprawl, complexity, and aggregation of urban form. Finally, we use Spatial Durbin Model to reveal the relationship between urban form and ULUE. We find that carbon emissions in the YRB increased steadily during the study period. The average value of ULUE increased from 0.469 in 1994 to 0.772 in 2018. Efficiency improved most in the provinces of Shaanxi, Henan, Ningxia, and Shandong, with growth rates of 234.15%, 102.40%, 93.09%, and 66.24%, respectively. Positive global Moran's I indices suggest that the spatial distribution of ULUE is positively correlated at basin level. Moreover, urban form metrics in the YRB demonstrated significant regional differences from 1994 to 2018. The regression results showed irregular urban form can negatively impact ULUE while compact and aggregated urban forms can improve ULUE under low carbon constrains. In addition, there are both positive and negative correlations between urban sprawl and ULUE in different regions. Today's choices on urban form can restrict the development pattern of cities and lock in pathways of carbon emissions in the future. Based on the findings in this study, the government should pursue optimal city sizes, avoid scattered patterns and aim for compact urban form.

New insights into targeting mitochondria in ischemic injury.

Stroke is the leading cause of adult disability and death worldwide. Mitochondrial dysfunction has been recognized as a marker of neuronal death during ischemic stroke. Maintaining the function of mitochondria is important for improving the survival of neurons and maintaining neuronal function. Damaged mitochondria induce neuronal cell apoptosis by releasing reactive oxygen species (ROS) and pro-apoptotic factors. Mitochondrial fission and fusion processes and mitophagy are of great importance to mitochondrial quality control. This paper reviews the dynamic changes in mitochondria, the roles of mitochondria in different cell types, and related signaling pathways in ischemic stroke. This review describes in detail the role of mitochondria in the process of neuronal injury and protection in cerebral ischemia, and integrates neuroprotective drugs targeting mitochondria in recent years, which may provide a theoretical basis for the progress of treatment of ischemic stroke. The potential of mitochondrial-targeted therapy is also emphasized, which provides valuable insights for clinical research.

A novel SPAST gene mutation identified in a Chinese family with hereditary spastic paraplegia.

BACKGROUND: Hereditary spastic paraplegia is a heterogeneous group of clinically and genetically neurodegenerative diseases characterized by progressive gait disorder. Hereditary spastic paraplegia can be inherited in various ways, and all modes of inheritance are associated with multiple genes or loci. At present, more than 76 disease-causing loci have been identified in hereditary spastic paraplegia patients. Here, we report a novel mutation in SPAST gene associated with hereditary spastic paraplegia in a Chinese family, further enriching the hereditary spastic paraplegia spectrum. METHODS: Whole genomic DNA was extracted from peripheral blood of the 15 subjects from a Chinese family using DNA Isolation Kit. The Whole Exome Sequencing of the proband was analyzed and the result was identified in the rest individuals. RaptorX prediction tool and Protein Variation Effect Analyzer were used to predict the effects of the mutation on protein tertiary structure and function. RESULTS: Spastic paraplegia has been inherited across at least four generations in this family, during which only four HSP patients were alive. The results obtained by analyzing the Whole Exome Sequencing of the proband exhibited a novel disease-associated in-frame deletion in the SPAST gene, and this mutation also existed in the rest three HSP patients in this family. This in-frame deletion consists of three nucleotides deletion (c.1710_1712delGAA) within the exon 16, resulting in lysine deficiency at the position 570 of the protein (p.K570del). This novel mutation was also predicted to result in the synthesis of misfolded SPAST protein and have the deleterious effect on the function of SPAST protein. CONCLUSION: In this case, we reported a novel mutation in the known SPAST gene that segregated with HSP disease, which can be inherited in each generation. Simultaneously, this novel discovery significantly enriches the mutation spectrum, which provides an opportunity for further investigation of genetic pathogenesis of HSP.

Myriocin and d-PDMP ameliorate atherosclerosis in ApoE-/- mice via reducing lipid uptake and vascular inflammation.

Sphingolipids have been implicated in the etiology of atherosclerosis. The commonly used sphingolipid inhibitors, myriocin (a ceramide inhibitor) and d-PDMP (d-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol, a glycosphingolipid inhibitor), have shown therapeutic potential but their efficacy and their underlying mechanisms remain unclear. Here, apolipoprotein E-deficient (apoE-/-) mice were fed a high-fat diet (HFD) and treated with a control, myriocin, d-PDMP, or atorvastatin for 12 weeks. We analyzed the effects of these drugs on the size and detailed composition of atherosclerotic plaques. Molecular biological approaches were used to explore how the inhibitors affect lipid metabolism and foam-cell formation. Treatment with myriocin or d-PDMP led to smaller and less vulnerable atherosclerotic lesions and was almost as effective as atorvastatin. Sphingolipid inhibitors down-regulated the expression of monocyte chemotactic protein 1 (MCP-1) and its receptor chemoattractant cytokine receptor 2 (CCR2), which play a key role in monocyte recruitment. They also decreased pro-inflammatory Ly-6chigh monocytes and influenced the uptake of modified LDL by down-regulating the expression of cluster of differentiation 36 (CD36) and lectin-like oxidized LDL (ox-LDL) receptor-1 (LOX-1). The inhibitors exhibited the advantage of maintaining normal glucose homeostasis compared with atorvastatin. These findings reveal for the first time that the modulation of sphingolipid synthesis can effectively alleviate atherosclerosis progression by preventing lipid uptake and reducing inflammatory responses in the arterial walls.

Cilostazol ameliorates ischemia/reperfusion-induced tight junction disruption in brain endothelial cells by inhibiting endoplasmic reticulum stress.

Endoplasmic reticulum (ER) stress is essential for brain ischemia/reperfusion (I/R) injury. However, whether it contributes to I/R-induced blood-brain barrier (BBB) injury remains unclear. cilostazol exerts protective effects toward I/R-induced BBB injury, with unclear mechanisms. This study explored the potential role of ER stress in I/R-induced endothelial cell damage and determined whether the therapeutic potential of cilostazol, with respect to I/R-induced endothelial cell damage, is related to inhibition of ER stress. We found that exposing brain endothelial cells (bEnd.3) to oxygen-glucose deprivation/reoxygenation (OGD/R) significantly activated ER stress and diminished the barrier function of cell monolayers; treatment with the ER stress inhibitor 4-phenylbutyric acid (4-PBA) or cilostazol prevented OGD/R-induced ER stress and preserved barrier function. Furthermore, OGD/R induced the expression and secretion of matrix metalloproteinase-9 and nuclear translocation of phosphorylated NF-κB. These changes were partially reversed by 4-PBA or cilostazol treatment. In vivo, 4-PBA or cilostazol significantly attenuated I/R-induced ER stress and ameliorated Evans blue leakage and tight junction loss. These results demonstrate that I/R-induced ER stress participates in BBB disruption. Targeting ER stress could be a useful strategy to protect the BBB from ischemic stroke, and cilostazol is a promising therapeutic agent for this process.-Nan, D., Jin, H., Deng, J., Yu, W., Liu, R., Sun, W., Huang, Y. Cilostazol ameliorates ischemia/reperfusion-induced tight junction disruption in brain endothelial cells by inhibiting endoplasmic reticulum stress.

Prevalence and risk factors of intracranial and extracranial artery stenosis in asymptomatic rural residents of 13 villages in China.

BACKGROUND: The present study aimed to investigate the prevalence and risk factors for extracranial carotid artery stenosis (ECAS) and intracranial carotid artery stenosis (ICAS) simultaneously in asymptomatic Chinese pure rural population. METHODS: We analyzed 2589 asymptomatic subjects aged over 30 yr. by ultrasonography and transcranial Doppler simultaneously in 13 isolated villages by door-to-door investigation. Both ECAS and ICAS were defined as more than 50% stenosis. Demographics, medical history documentation, and investigation of biochemical results were performed for each subject. Univariate and multivariate logistic regression analyses were employed to assess the risk factors associated with ECAS and ICAS, respectively. RESULTS: One hundred twenty-two (4.7%) residents with ICAS and 56 (2.2%) with ECAS were found in 2589 subjects. Three factors emerged as independent risk factors for ICAS: age (95% confidence interval [CI] = 1.01-1.04, odds ratio [OR] = 1.07), hypertension (95% CI = 1.98-4.37, OR = 2.94), and diabetes mellitus (95% CI = 1.72-4.38, OR = 2.75). As for ECAS, five factors presented as independent risk factors: age (95% CI = 1.09-1.11, OR = 1.10), male sex (95% CI = 1.01-1.02, OR = 1.01), diabetes mellitus (95% CI = 1.10-2.12, OR = 1.53), systolic blood pressure (95% CI = 1.95-2.88, OR = 2.37), and total cholesterol (95% CI = 1.00-1.13, OR = 1.06). CONCLUSIONS: ICAS and ECAS were relatively common among asymptomatic rural Chinese subjects. Although they shared similar risk factors, differences still existed between them.

Modeled microgravity suppressed invasion and migration of human glioblastoma U87 cells through downregulating store-operated calcium entry.

Glioblastoma is the most common brain tumor and is characterized with robust invasion and migration potential resulting in poor prognosis. Previous investigations have demonstrated that modeled microgravity (MMG) could decline the cell proliferation and attenuate the metastasis potential in several cell lines. In this study, we studied the effects of MMG on the invasion and migration potentials of glioblastoma in human glioblastoma U87 cells. We found that MMG stimulation significantly attenuated the invasion and migration potentials, decreased thapsigargin (TG) induced store-operated calcium entry (SOCE) and downregulated the expression of Orai1 in U87 cells. Inhibition of SOCE by 2-APB or stromal interaction molecule 1 (STIM1) downregulation both mimicked the effects of MMG on the invasion and migration potentials in U87 cells. Furthermore, upregulation of Orai1 significantly weakened the effects of MMG on the invasion and migration potentials in U87 cells. Therefore, these findings indicated that MMG stimulation inhibited the invasion and migration potentials of U87 cells by downregulating the expression of Orai1 and sequentially decreasing the SOCE, suggesting that MMG might be a new potential therapeutic strategy in glioblastoma treatment in the future.

The influence of proximity and knowledge base on recombination innovation in R&D collaboration.

Recombination innovation invented during organizations' research and development (R&D) collaborations is a vital mechanism for creating new technological knowledge for organizations. This study aims to reveal the contribution mechanism of different dimensions of proximity to the recombination innovation at the collaborative dyad level and how this mechanism depends on the characteristics of organizations' knowledge base structuration. We conceptualize that the interdependence among knowledge elements in the knowledge base forms the knowledge space of the organization and build a theoretical framework to explain the interactive effect of proximity and organizations' knowledge base characteristics on collaborative recombination innovation. We validated the theoretical hypotheses using Logit regression models based on the longitudinal data of 150 organizations in the global nanotechnology industry. As demonstrated by our findings, technological proximity exerts a negative effect, while geographic proximity exerts an inverted U-shaped effect on collaborative organizations' joint recombination innovation. Organizations' knowledge base decomposability plays a negative role in moderating the effect of technological proximity and plays a positive role in regulating the effect of geographic proximity. In contrast, the degree centrality of the knowledge elements positively moderates the effect of both technological and geographic proximity.

A noval transparent triboelectric nanogenerator as electronic skin for real-time breath monitoring.

Against the backdrop of advancements in modern multifunctional wearable electronics, there is a growing demand for simple, sustainable, and portable electronic skin (e-skin), posing significant challenges. This study aims to delineate the development of a straightforward, transparent, highly sensitive, and high power-density electronic skin based on a triboelectric nanogenerator(S-TENG), designed for harvesting human body energy and real-time monitoring of the physiological motion status. Our e-skin incorporates thermally treated polyvinylidene fluoride (PVDF) fiber membranes as the contact layer and a film of silver nanowires as the conductive electrodes. The resulting contact-separation type e-skin exhibits an impressive transparency of 80 %, along with a nice sensitivity value, capable of detecting a light touch from a 0.13 g sponge and demonstrating good working stability and breathability. Leveraging the triboelectric effect, our e-skin generates an open-circuit voltage of 301 V and a short-circuit current of 2.7 µA under an extrinsic force of 8 N over an interaction area of 4 × 4 cm2, achieving a power density up to 306 mW/m2. With its signal processing circuitry, the integrated S-TENG showcases nice energy harvesting and signal transmission capabilities. Accordingly, we contend that S-TENG has potential applications in energy capture and real-time human motion state monitoring. This research is anticipated to blaze a novel and practical trail for self-powered wearable devices and personalized health rehabilitation training regimens.

A Study on the Mechanisms and Performance of a Polyvinyl Alcohol-Based Nanogenerator Based on the Triboelectric Effect.

Polyvinyl alcohol (PVA), a versatile polymer, is extensively used across many industries, such as chemicals, food, healthcare, textiles, and packaging. However, research on applying PVA to triboelectric nanogenerators (TENGs) remains limited. Consequently, we chose PVA as the primary material to explore its contact electrification mechanisms at the molecular level, alongside materials like Polyethylene (PE), Polyvinylidene fluoride (PVDF), and Polytetrafluoroethylene (PTFE). Our findings show that PVA has the highest band gap, with the smallest band gap occurring between the HOMO of PVA and the LUMO of PTFE. During molecular contact, electron transfer primarily occurs in the outermost layers of the molecules, influenced by the functional groups of the polymers. The presence of fluorine atoms enhances the electron transfer between PVA and PTFE to maximum levels. Experimental validation confirmed that PVA and PTFE contact yields the highest triboelectric performance: VOC of 128 V, ISC of 2.83 µA, QSC of 82 nC, and an output power of 384 µW. Moreover, P-TENG, made of PVA and PTFE, was successfully applied in self-powered smart devices and monitored human respiration and bodily movements effectively. These findings offer valuable insights into using PVA in triboelectric nanogenerator technologies.

Amino-Modified Graphene Oxide from Kish Graphite for Enhancing Corrosion Resistance of Waterborne Epoxy Coatings.

Waterborne epoxy (WEP) coatings with enhanced corrosion resistance were prepared using graphene oxide (GO) that was obtained from kish graphite, and amino-functionalized graphene oxide (AGO) was modified by 2-aminomalonamide. The structural characteristics of the GO and AGO were analyzed using X-ray diffraction (XRD), Raman spectroscopy, Fourier transform infrared spectroscopy (FT-IR), scanning electron microscopy (SEM), and transmission electron microscopy (TEM). And the anti-corrosive performance of waterborne epoxy-cased composite coatings with different addition amounts of AGO was investigated using electrochemical measurements, pull-off adhesion tests, and salt spray tests. The results indicate that AGO15/WEP with 0.15 wt.% of AGO has the best anti-corrosive performance, and the lowest frequency impedance modulus increased from 1.03 × 108 to 1.63 × 1010 ohm·cm-2 compared to that of WEP. Furthermore, AGO15/WEP also demonstrates the minimal corrosion products or bubbles in the salt spray test for 200 h, affirming its exceptional long-term corrosion protection capability.

In-situ amino-functionalized and reduced graphene oxide/polyimide composite films for high-performance triboelectric nanogenerator.

As a promising sustainable power source in intelligent electronics, Triboelectric Nanogenerators (TENGs) have garnered widespread interest, with various strategies explored to enhance their output performance. However, most optimization methods for triboelectric materials have focused solely on tuning chemical compositions or fabricating surface microstructures. Here, we have prepared amino-functionalized reduced graphene oxide (FRGO)/polyimide (PI) composite films (PI-FRGO) via in-situ polymerization, aimed at enhancing PI materials' nanotribological power generation performance. By varying the doping levels of amino groups and controlling the FRGO proportion during synthesis, we can explore the optimal FRGO/PI composite film ratio. At a p-Phenylenediamine: reduced Graphene Oxide (PPDA: RGO) ratio of 1:1 and an FRGO addition of 0.1 %, the output electrical performance peaks with a voltage of 58 V, a charge of 33 nC and a current of 12 µA, nearly 2 times that of a pure PI film. We have fabricated a TENG with an optimally formulated PI-FRGO composite to explore its application potential. Under a 10 MΩ external load resistance, the TENG can deliver a power density of 3.5 mW/m2 and can be powering small devices. This work presents new effective strategies to significantly enhance TENG output performance and promote their widespread application.

Annexin A2 combined with TTK accelerates esophageal cancer progression via the Akt/mTOR signaling pathway.

Annexin A2 (ANXA2) is a widely reported oncogene. However, the mechanism of ANXA2 in esophageal cancer is not fully understood. In this study, we provided evidence that ANXA2 promotes the progression of esophageal squamous cell carcinoma (ESCC) through the downstream target threonine tyrosine kinase (TTK). These results are consistent with the up-regulation of ANXA2 and TTK in ESCC. In vitro experiments by knockdown and overexpression of ANXA2 revealed that ANXA2 promotes the progression of ESCC by enhancing cancer cell proliferation, migration, and invasion. Subsequently, animal models also confirmed the role of ANXA2 in promoting the proliferation and metastasis of ESCC. Mechanistically, the ANXA2/TTK complex activates the Akt/mTOR signaling pathway and accelerates epithelial-mesenchymal transition (EMT), thereby promoting the invasion and metastasis of ESCC. Furthermore, we identified that TTK overexpression can reverse the inhibition of ESCC invasion after ANXA2 knockdown. Overall, these data indicate that the combination of ANXA2 and TTK regulates the activation of the Akt/mTOR pathway and accelerates the progression of ESCC. Therefore, the ANXA2/TTK/Akt/mTOR axis is a potential therapeutic target for ESCC.

The relationship between ischemic penumbra progression and the oxygen content of cortex microcirculation in acute ischemic stroke.

The precise oxygen content thresholds of ischemic deep parenchymal (OCIDP) and that in cortical microcirculation (OCCM), which leads to ischemic penumbra converting into the infarcted core, remain uncertain. This study employed an invasive fiber-optic oxygen meter and a newly developed oxygen-responsive probe called RuA3-Cy5-rtPA (RC-rtPA) based on recombinant tissue-type plasminogen activator (rtPA) to examine the oxygen content thresholds. A mouse model of middle cerebral artery occlusion was generated and animals were randomly divided into a sham, 24-h reperfusion after 3-h ischemia (IR 3-h), and IR 6-h groups, all of which were sacrificed following reperfusion. Stroke severity was evaluated based on the infarction area, neurological symptoms, microcirculation perfusion, and microemboli in microcirculation. OCIDP was characterized based on its extent and distribution, whereas OCCM was measured using RC-rtPA. During ischemia, stroke severity escalation manifested as increasing infarction area, severe neurologic symptoms, and poorer microcirculation perfusion with more microthrombi depositions. OCIDP presented rapid decline following artery occlusion along with a gradual increase in the hypoxic area. Within 3 â€‹h following ischemia induction, the ischemic tissue that experienced hypoxia could be rescued, and this reversibility would disappear after 6 â€‹h. Within 6 â€‹h, OCCM continued to decrease. A significant decrease in oxygen content in cortical venules and cortical parenchyma was observed. These findings assist in establishing the extent of the ischemic penumbra at the microcirculation level and offer a foundation for assessing the ischemic penumbra that could respond positively to reperfusion therapy beyond the typical time window.

Role of Non-Receptor-Type Tyrosine Phosphatases in Brain-Related Diseases.

The non-receptor protein tyrosine phosphatase is a class of enzymes that catalyze the dephosphorylation of phosphotyrosines in protein molecules. They are involved in cellular signaling by regulating the phosphorylation status of a variety of receptors and signaling molecules within the cell, thereby influencing cellular physiological and pathological processes. In this article, we detail multiple non-receptor tyrosine phosphatase and non-receptor tyrosine phosphatase genes involved in the pathological process of brain disease. These include PTPN6, PTPN11, and PTPN13, which are involved in glioma signaling; PTPN1, PTPN5, and PTPN13, which are involved in the pathogenesis of Alzheimer's disease Tau protein lesions, PTPN23, which may be involved in the pathogenesis of Epilepsy and PTPN1, which is involved in the pathogenesis of Parkinson's disease. The role of mitochondrial tyrosine phosphatase in brain diseases was also discussed. Non-receptor tyrosine phosphatases have great potential for targeted therapies in brain diseases and are highly promising research areas.