Association of plasma sphingosine-1-phosphate levels with disease severity and prognosis after intracerebral hemorrhage.

Purpose: Sphingosine-1-phosphate (S1P) is a signaling lipid involved in many biological processes, including inflammatory and immune regulatory responses. The study aimed to determine whether admission S1P levels are associated with disease severity and prognosis after spontaneous intracerebral hemorrhage (ICH). Methods: Data of 134 patients with spontaneous ICH and 120 healthy controls were obtained from Biological Resource Sample Database of Intracerebral Hemorrhage at the First Affiliated Hospital of Zhengzhou University. Plasma S1P levels were measured. Regression analyses were used to analyze the association between S1P levels and admission and 90-day modified Rankin scale (mRS) scores. Receiver operating characteristic (ROC) curves assessed the predictive value of S1P levels for ICH severity and prognosis. Results: Patients with ICH exhibited elevated plasma S1P levels compared to the control group (median 286.95 vs. 239.80 ng/mL, p < 0.001). When divided patients into mild-to-moderate and severe groups according to their mRS scores both at admission and discharge, S1P levels were significantly elevated in the severe group compared to the mild-to-moderate group (admission 259.30 vs. 300.54, p < 0.001; 90-day 275.24 vs. 303.25, p < 0.001). The patients were divided into three groups with different concentration gradients, which showed significant statistical differences in admission mRS scores (3 vs. 4 vs. 5, p < 0.001), 90-day mRS scores (2.5 vs. 3 vs. 4, p < 0.001), consciousness disorders (45.5% vs. 68.2% vs. 69.6%, p = 0.033), ICU admission (29.5% vs. 59.1% vs. 89.1%, p < 0.001), surgery (15.9% vs. 47.7% vs. 82.6%, p < 0.001), intraventricular hemorrhages (27.3% vs. 61.4% vs. 65.2%, p < 0.001) and pulmonary infection (25% vs. 47.7% vs. 84.8%, p < 0.001). Multivariate analysis displayed that S1P level was an independent risk factor for disease severity (OR = 1.037, 95% CI = 1.020-1.054, p < 0.001) and prognosis (OR = 1.018, 95% CI = 1.006-1.030, p = 0.003). ROC curves revealed a predictive value of S1P levels with an area under the curve of 0.7952 (95% CI = 0.7144-0.8759, p < 0.001) for disease severity and 0.7105 (95% CI = 0.6227-0.7983, p < 0.001) for prognosis. Conclusion: Higher admission S1P is associated with worse initial disease severity and 90-day functional outcomes in intracerebral hemorrhage.

Multiscale Regulation of Ordered PtCu Intermetallic Electrocatalyst for Highly Durable Oxygen Reduction Reaction.

Transforming the Pt-M alloy into an ordered intermetallic is an effective strategy to improve the electrocatalytic activity and stability toward the oxygen reduction reaction (ORR). However, the synthesis of nanosized intermetallics remains challenging. Herein, we report an efficient ORR electrocatalyst, consisting of a monodisperse nanosized PtCu intermetallic on hollow mesoporous carbon spheres (HMCS). As predicted by theoretical calculations, PtCu intermetallics exhibit beneficial electronic structure, with a low theoretical overpotential of 0.33 V and enhanced Cu stability. Resulting from the multiscale modulation of catalyst structure, the O-PtCu/HMCS catalyst delivers a high mass activity of 2.73 A cm-2Pt at 0.9 V and remarkable stability. Identical location transmission electron microscopy (IL-TEM) investigations demonstrate that the rate of carbon corrosion is alleviated on HMCS, which contributes to the long-term durability. This work provides a promising design strategy for an ORR electrocatalyst, and the IL-TEM investigations offer new perspectives for the performance enhancement mechanism.

Hypochlorous acid derived from microglial myeloperoxidase could mediate high-mobility group box 1 release from neurons to amplify brain damage in cerebral ischemia-reperfusion injury.

Myeloperoxidase (MPO) plays critical role in the pathology of cerebral ischemia-reperfusion (I/R) injury via producing hypochlorous acid (HOCl) and inducing oxidative modification of proteins. High-mobility group box 1 (HMGB1) oxidation, particularly disulfide HMGB1 formation, facilitates the secretion and release of HMGB1 and activates neuroinflammation, aggravating cerebral I/R injury. However, the cellular sources of MPO/HOCl in ischemic brain injury are unclear yet. Whether HOCl could promote HMGB1 secretion and release remains unknown. In the present study, we investigated the roles of microglia-derived MPO/HOCl in mediating HMGB1 translocation and secretion, and aggravating the brain damage and blood-brain barrier (BBB) disruption in cerebral I/R injury. In vitro, under the co-culture conditions with microglia BV cells but not the single culture conditions, oxygen-glucose deprivation/reoxygenation (OGD/R) significantly increased MPO/HOCl expression in PC12 cells. After the cells were exposed to OGD/R, MPO-containing exosomes derived from BV2 cells were released and transferred to PC12 cells, increasing MPO/HOCl in the PC12 cells. The HOCl promoted disulfide HMGB1 translocation and secretion and aggravated OGD/R-induced apoptosis. In vivo, SD rats were subjected to 2 h of middle cerebral artery occlusion (MCAO) plus different periods of reperfusion. Increased MPO/HOCl production was observed at the reperfusion stage, accomplished with enlarged infarct volume, aggravated BBB disruption and neurological dysfunctions. Treatment of MPO inhibitor 4-aminobenzoic acid hydrazide (4-ABAH) and HOCl scavenger taurine reversed those changes. HOCl was colocalized with cytoplasm transferred HMGB1, which was blocked by taurine in rat I/R-injured brain. We finally performed a clinical investigation and found that plasma HOCl concentration was positively correlated with infarct volume and neurological deficit scores in ischemic stroke patients. Taken together, we conclude that ischemia/hypoxia could activate microglia to release MPO-containing exosomes that transfer MPO to adjacent cells for HOCl production; Subsequently, the production of HOCl could mediate the translocation and secretion of disulfide HMGB1 that aggravates cerebral I/R injury. Furthermore, plasma HOCl level could be a novel biomarker for indexing brain damage in ischemic stroke patients.

Enhanced Reactivities of Iron(IV)-Oxo Porphyrin Species in Oxidation Reactions Promoted by Intramolecular Hydrogen-Bonding.

High-valent iron-oxo species are one of the common intermediates in both biological and biomimetic catalytic oxidation reactions. Recently, hydrogen-bonding (H-bonding) has been proved to be critical in determining the selectivity and reactivity. However, few examples have been established for mechanistic insights into the H-bonding effect. Moreover, intramolecular H-bonding effect on both C-H activation and oxygen atom transfer (OAT) reactions in synthetic porphyrin model system has not been investigated yet. In this study, a series of heme-containing iron(IV)-oxo porphyrin species with or without intramolecular H-bonding are synthesized and characterized. Kinetic studies revealed that intramolecular H-bonding can significantly enhance the reactivity of iron(IV)-oxo species in OAT, C-H activation, and electron-transfer reactions. This unprecedented unified H-bonding effect is elucidated by theoretical calculations, which showed that intramolecular H-bonding interactions lower the energy of the anti-bonding orbital of iron(IV)-oxo porphyrin species, resulting in the enhanced reactivities in oxidation reactions irrespective of the reaction type. To the best of the knowledge, this is the first extensive investigation on the intramolecular H-bonding effect in heme system. The results show that H-bonding interactions have a unified effect with iron(IV)-oxo porphyrin species in all three investigated reactions.

Blocking cerebral lymphatic system reduces central and peripheral inflammatory response in ischemic stroke.

Reduced blood supply to the brain activates the intracranial inflammatory response, a key contributor to secondary brain damage in ischemic stroke. Post-stroke, activation of peripheral immune cells leads to systemic inflammatory responses. Usingin vivo approaches, we investigated meningeal lymphatics' role in central immune cell infiltration and peripheral immune cell activation. The bilateral deep cervical lymph nodes (dCLNs) were removed 7 days before right middle cerebral artery occlusion in Sprague Dawley (SD) rats. At 3, 24, and 72 h post-intervention, brain immune cell infiltration and microglial and astrocyte activation were measured, while immune cells were classified in the spleen and blood. Inflammatory factor levels in peripheral blood were analyzed. Simultaneously, reverse verification was conducted by injecting AAV-vascular endothelial growth factor C (AAV-VEGFC) adenovirus into the lateral ventricle 14 days before middle cerebral artery occlusion (MCAO) induction to enhance meningeal lymph function. Blocking meningeal LVs in MCAO rats significantly reduced infarct area and infiltration, and inhibited microglia and pro-inflammatory astrocytes activation. After removing dCLNs, CD4+ T lymphocytes, CD8+ T lymphocytes, B lymphocytes, macrophages, and neutrophils in the spleen and blood of MCAO rats decreased significantly at different time points. The levels of inflammatory factors IL-6, IL-10, IL-1ß, and TNF-α in plasma decreased significantly. Tests confirmed the results, and AAV-VEGFC-induced MCAO rats provided reverse validation.

Amyloid and Tau as cerebrospinal fluid biomarkers in anti-N-Methyl-D-aspartate receptor encephalitis.

INTRODUCTION: Neuroinfection is associated with the deposition of amyloid-beta (Aß) peptides, and subsequent decrease in cerebrospinal fluid (CSF) amyloid levels. However, whether autoimmune encephalitis involves extracellular deposition of Aß peptides in the brain is unreported. METHODS: We examined CSF amyloid and tau values in adults with anti-N-methyl-D-aspartate receptor encephalitis (NMDAR-E). Forty-two patients with NMDAR-E, 35 patients with viral and bacterial neuroinfections, and 16 controls were included. We measured CSF Aß1-42 (cAß1-42), Aß1-40 (cAß1-40), t-Tau (ct-Tau), and p-Tau181 (cp-Tau181) levels and assessed their efficacies regarding differential diagnosis and predicting prognosis. RESULTS: NMDAR-E patients had lower cAß1-42 levels; however, they were higher than those of patients with bacterial meningitis. ct-Tau levels in NMDAR-E patients were lower than those in patients with neuroinfections. No changes were observed in controls. cAß1-42 and ct-Tau were combined as an excellent marker to distinguish NMDAR-E from neuroinfections. cAß1-42 levels in NMDAR-E patients were positively correlated with Montreal Cognitive Assessment scores. We observed an inverse relationship between cAß1-42 levels and modified Rankin Scale scores. Patients with poor outcomes exhibited low cAß1-42 levels and high levels of several blood parameters. cAß1-42 was the highest quality biomarker for assessing NMDAR-E prognosis. Correlations were found between cAß1-42 and some inflammatory indicators. CONCLUSION: cAß1-42 was decreased in NMDAR-E patients. cAß1-42 levels indicated NMDAR-E severity and acted as a biomarker for its prognosis. Combining cAß1-42 and ct-Tau levels could serve as a novel differential diagnostic marker for NMDAR-E.

A liquid biopsy signature of circulating extracellular vesicles-derived RNAs predicts response to first line chemotherapy in patients with metastatic colorectal cancer.

BACKGROUND: Colorectal cancer (CRC) is one of the most threatening tumors in the world, and chemotherapy remains dominant in the treatment of metastatic CRC (mCRC) patients. The purpose of this study was to develop a biomarker panel to predict the response of the first line chemotherapy in mCRC patients. METHODS: Totally 190 mCRC patients treated with FOLFOX or XEOLX chemotherapy in 3 different institutions were included. We extracted the plasma extracellular vesicle (EV) RNA, performed RNA sequencing, constructed a model and generated a signature through shrinking the number of variables by the random forest algorithm and the least absolute shrinkage and selection operator (LASSO) algorithm in the training cohort (n = 80). We validated it in an internal validation cohort (n = 62) and a prospective external validation cohort (n = 48). RESULTS: We established a signature consisted of 22 EV RNAs which could identify responders, and the area under the receiver operating characteristic curve (AUC) values was 0.986, 0.821, and 0.816 in the training, internal validation, and external validation cohort respectively. The signature could also identify the progression-free survival (PFS) and overall survival (OS). Besides, we constructed a 7-gene signature which could predict tumor response to first-line oxaliplatin-containing chemotherapy and simultaneously resistance to second-line irinotecan-containing chemotherapy. CONCLUSIONS: The study was first to develop a signature of EV-derived RNAs to predict the response of the first line chemotherapy in mCRC with high accuracy using a non-invasive approach, indicating that the signature could help to select the optimal regimen for mCRC patients.

CircRREB1 mediates lipid metabolism related senescent phenotypes in chondrocytes through FASN post-translational modifications.

Osteoarthritis is a prevalent age-related disease characterized by dysregulation of extracellular matrix metabolism, lipid metabolism, and upregulation of senescence-associated secretory phenotypes. Herein, we clarify that CircRREB1 is highly expressed in secondary generation chondrocytes and its deficiency can alleviate FASN related senescent phenotypes and osteoarthritis progression. CircRREB1 impedes proteasome-mediated degradation of FASN by inhibiting acetylation-mediated ubiquitination. Meanwhile, CircRREB1 induces RanBP2-mediated SUMOylation of FASN and enhances its protein stability. CircRREB1-FASN axis inhibits FGF18 and FGFR3 mediated PI3K-AKT signal transduction, then increased p21 expression. Intra-articular injection of adenovirus-CircRreb1 reverses the protective effects in CircRreb1 deficiency mice. Further therapeutic interventions could have beneficial effects in identifying CircRREB1 as a potential prognostic and therapeutic target for age-related OA.

Printing 3D mesh-like grooves on zinc surface to enhance the stability of aqueous zinc ion batteries.

Aqueous zinc ion batteries (AZIBs) are receiving broad attention owing to their high safety and low cost. However, the high mechanical strength and irreversible growth of zinc dendrites limit the practical application of AZIBs. Herein, regular mesh-like gullies are built on the surface of zinc foil (M150 Zn) by using simple model pressing method and stainless steel mesh as a mold. Due to the charge-enrichment effect, zinc ion deposition and stripping will be preferentially carried out in the grooves to keep the outer surface flat. In addition, zinc is exposed to 002 crystal surface in the gully after being pressed, and the deposited zinc is more inclined to grow at a small angle, so that it has a sedimentary morphology parallel to the basement. Consequently, at a current density of 0.5 mA cm-2, the M150 zinc anode has a voltage hysteresis of only 35 mV and a cycle life of up to 400 h (relative to a zinc foil of 96 mV and 160 h). Even more imposing is that the full cell has a capacity retention of approximately 100% after 1000 cycles at 2 A g-1 and a specific capacity of almost 60 mAh g-1 when activated carbon is used as the cathode. It is a promising method to improve the stable cycle performance of AZIBs by using a simple method to realize the non-prominent dendrites on the surface of zinc electrode.

Trust game, survey trust, are they correlated? Evidence from China.

Trust Game and survey trust are the two most popular measurements in the field of trust research, but most studies conducted in developing countries have found low or even insignificant correlations between them, we therefore validated this phenomenon in the cultural context of the largest developing country, China. Within-country differences can be of the same magnitude as the between country differences, especially in a culturally diverse China. Thus, we focus on comparing the characteristics of trust in the South and North regions of China. Through zero-order correlation and hierarchical regression analysis, our findings are consistent with those of numerous developing countries: Trust Game is lowly correlated with in-group trust survey and not with out-group trust survey. On the other hand, we found that Chinese individuals exhibit a distinct pattern of in-group trust, and there is no fundamental difference in the characteristics of trust between the South and the North.

Boosting Magnesium Ion Storage Behavior via Heteroelement Doping in a Porous Tunnel Framework Cathode for Aqueous Mg-Ion Batteries.

To relieve the overwhelming pressure on fossil energy, aqueous magnesium ion batteries attracted tremendous attention owing to their low cost and high safety. However, the cathode materials are apt to occur lattice distortion because of the electrostatic interaction between magnesium ions and crystal. The 2×2 manganese octahedral molecular sieve with potassium ions and water located in the tunnels (K-OMS-2), utilized as a cathode material for chargeable magnesium ions batteries, is exposed to irreversible Mg2+ intercalation/deintercalation due to lattice distortion, which heavily damages the electrochemical properties and declines the capacity. Herein, we carry out an ion doping strategy to overcome the above issues, leading to an enhanced Mg Mg2+ storage behavior. The Nb or V cation is successfully doped into K-OMS-2 by a facile reflux method under room temperature. The specific surface area is enlarged by the addition of cations, which promise a large electrode-electrolyte contact area. The Nb and V doped K-OMS-2 present a capacity of 252.6 and 265.9 mAh/g at 20 mA/g, respectively. This work demonstrates an ion doping approach toward exploiting the stable and high-capacity Mg-ion battery cathode and provides potential cathode materials for a large-scale aqueous Mg-ion-based energy storage system.

Nitrogen-rich Graphite Flake from Hemp as Anode Material for High Performance Lithium-ion Batteries.

Biomass-derived carbon (BC) has attracted extensive attention as anode material for lithium ion batteries (LiBs) due to its natural hierarchical porous structure and rich heteroatoms that can adsorb Li+ . However, the specific surface area of pure biomass carbon is generally small, so we can help NH3 and inorganic acid produced by urea decomposition to strip biomass, improve its specific surface area and enrich nitrogen elements. The nitrogen-rich graphite flake obtained by the above treatment of hemp is named NGF. The product that has a high nitrogen content of 10.12% has a high specific surface area of 1151.1 m2 g-1 . In the lithium ion battery test, the capacity of NGF is 806.6 mAh g-1 at 30 mA g-1 , which is twice than that of BC. NGF also showed excellent performance that is 429.2 mAh g-1 under high current testing at 2000 mA g-1 . The reaction process kinetics is analyzed and we found that the outstanding rate performance is attributed to the large-scale capacitance control. In addition, the results of the constant current intermittent titration test indicate that the diffusion coefficient of NGF is greater than that of BC. This work proposes a simple method of nitrogen-rich activated carbon, which has a significantly commercial prospect.

Bioactive mineralized small intestinal submucosa acellular matrix/PMMA bone cement for vertebral bone regeneration.

Polymethylmethacrylate (PMMA) bone cement extensively utilized for the treatment of osteoporotic vertebral compression fractures due to its exceptional handleability and mechanical properties. Nevertheless, the clinical application of PMMA bone cement is restricted by its poor bioactivity and excessively high modulus of elasticity. Herein, mineralized small intestinal submucosa (mSIS) was incorporated into PMMA to prepare a partially degradable bone cement (mSIS-PMMA) that provided suitable compressive strength and reduced elastic modulus compared to pure PMMA. The ability of mSIS-PMMA bone cement to promote the attachment, proliferation and osteogenic differentiation of bone marrow mesenchymal stem cells was shown through cellular experiments carried out in vitro, and an animal osteoporosis model validated its potential to improve osseointegration. Considering these benefits, mSIS-PMMA bone cement shows promising potential as an injectable biomaterial for orthopedic procedures that require bone augmentation.

Positive Feedback Regulation of Circular RNA Hsa_circ_0000566 and HIF-1α promotes Osteosarcoma Progression and Glycolysis Metabolism.

Hypoxia is an indispensable factor for cancer progression and is closely associated with the Warburg effect. Circular RNAs (CircRNA) have garnered considerable attention in molecular malignancy therapy as they are potentially important modulators. However, the roles of circRNAs and hypoxia in osteosarcoma (OS) progression have not yet been elucidated. This study reveals the hypoxia-sensitive circRNA, Hsa_circ_0000566, that plays a crucial role in OS progression and energy metabolism under hypoxic stress. Hsa_circ_0000566 is regulated by hypoxia-inducible factor-1α (HIF-1α) and directly binds to it as well as to the Von Hippel-Lindau (VHL) E3 ubiquitin ligase protein. Consequentially, binding between VHL and HIF-1α is impeded. Furthermore, Hsa_circ_0000566 contributes to OS progression by binding to HIF-1α (while competing with VHL) and by confers protection against HIF-1α against VHL-mediated ubiquitin degradation. These findings demonstrate the existence of a positive feedback loop formed by HIF-1α and Hsa_circ_0000566 and the key role they play in OS glycolysis. Taken together, these data indicate the significance of Hsa_circ_0000566 in the Warburg effect and suggest that Hsa_circ_0000566 could be a potential therapeutic target to combat OS progression.

Exosomes from bone marrow mesenchymal stem cells are a potential treatment for ischemic stroke.

Exosomes derived from human bone marrow mesenchymal stem cells (MSC-Exo) are characterized by easy expansion and storage, low risk of tumor formation, low immunogenicity, and anti-inflammatory effects. The therapeutic effects of MSC-Exo on ischemic stroke have been widely explored. However, the underlying mechanism remains unclear. In this study, we established a mouse model of ischemic brain injury induced by occlusion of the middle cerebral artery using the thread bolt method and injected MSC-Exo into the tail vein. We found that administration of MSC-Exo reduced the volume of cerebral infarction in the ischemic brain injury mouse model, increased the levels of interleukin-33 (IL-33) and suppression of tumorigenicity 2 receptor (ST2) in the penumbra of cerebral infarction, and improved neurological function. In vitro results showed that astrocyte-conditioned medium of cells deprived of both oxygen and glucose, to simulate ischemia conditions, combined with MSC-Exo increased the survival rate of primary cortical neurons. However, after transfection by IL-33 siRNA or ST2 siRNA, the survival rate of primary cortical neurons was markedly decreased. These results indicated that MSC-Exo inhibited neuronal death induced by oxygen and glucose deprivation through the IL-33/ST2 signaling pathway in astrocytes. These findings suggest that MSC-Exo may reduce ischemia-induced brain injury through regulating the IL-33/ST2 signaling pathway. Therefore, MSC-Exo may be a potential therapeutic method for ischemic stroke.

Phases of surface-confined trivalent colloidal particles.

Patchy colloids promise the design and modelling of complex materials, but the realization of equilibrium patchy particle structures remains challenging. Here, we assemble pseudo-trivalent particles and elucidate their phase behaviour when confined to a plane. We observe the honeycomb phase, as well as more complex amorphous network and triangular phases. Structural analysis performed on the three condensed phases reveals their shared structural motifs. Using a combined experimental and simulation approach, we elucidate the energetics of these phases and construct the phase diagram of this system, using order parameters to determine the phase coexistence lines. Our results reveal the rich phase behaviour that a relatively simple patchy particle system can display, and open the door to a larger joined simulation and experimental exploration of the full patchy-particle phase space.

Visualizing defect dynamics by assembling the colloidal graphene lattice.

Graphene has been under intense scientific interest because of its remarkable optical, mechanical and electronic properties. Its honeycomb structure makes it an archetypical two-dimensional material exhibiting a photonic and phononic band gap with topologically protected states. Here, we assemble colloidal graphene, the analogue of atomic graphene using pseudo-trivalent patchy particles, allowing particle-scale insight into crystal growth and defect dynamics. We directly observe the formation and healing of common defects, like grain boundaries and vacancies using confocal microscopy. We identify a pentagonal defect motif that is kinetically favoured in the early stages of growth, and acts as seed for more extended defects in the later stages. We determine the conformational energy of the crystal from the bond saturation and bond angle distortions, and follow its evolution through the energy landscape upon defect rearrangement and healing. These direct observations reveal that the origins of the most common defects lie in the early stages of graphene assembly, where pentagons are kinetically favoured over the equilibrium hexagons of the honeycomb lattice, subsequently stabilized during further growth. Our results open the door to the assembly of complex 2D colloidal materials and investigation of their dynamical, mechanical and optical properties.

Fibrinogen-to-albumin ratio percentage: An independent predictor of disease severity and prognosis in anti-N-methyl-D-aspartate receptor encephalitis.

Purpose: This retrospective study aimed to investigate the relationship between fibrinogen-to-albumin ratio percentage (FARP) and disease severity and prognosis in patients with anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis. Methods: Medical records and clinical characteristics from 181 patients with anti-NMDAR encephalitis were included. The modified Rankin Scale (mRS) was used to analyze disease severity and prognosis at admission and discharge, and correlations between FARP, disease severity, and prognosis were analyzed. Receiver operating characteristic (ROC) curves were used to evaluate the efficiency of FARP in assessing disease severity and prognosis. Results: Compared to the control group, patients with anti-NMDAR encephalitis had higher fibrinogen (Fib) levels (P < 0.001), neutrophil counts (P < 0.001), and FARP levels (P < 0.001) but had lower albumin levels (P = 0.003). The enrolled patients were divided into mild-to-moderate and severe groups according to their mRS scores both at admission and discharge. FARP levels were significantly elevated in the severe group compared to the mild-to-moderate group among patients with anti-NMDAR encephalitis both at admission and discharge (admission 6.0 vs. 7.40, P < 0.001; discharge 6.43 vs. 8.18, P<0.001). Indeed, the mRS scores at admission (56 vs. 26%, P < 0.001) and discharge (26 vs. 11%, P = 0.006) in the high FARP group were significantly higher than those in the low FARP group. Furthermore, FARP was positively correlated with the mRS scores at admission (r = 0.383, P < 0.001) and discharge (r =0.312, P < 0.001). In the multivariate analysis, FARP was significantly associated with disease severity (odds ratio [OR] = 1.416, 95% confidence interval [CI] = 1.117-1.795, P = 0.004) and prognosis (OR = 1.252, 95% CI = 1.010-1.552, P = 0.040). FARP-based ROC curves predicted disease severity, with a sensitivity of 0.756, a specificity of 0.626, and an area under the ROC curve of 0.722 (95% CI = 0.648-0.796, P < 0.001*). The ROC curve predicted the disease prognosis with a sensitivity of 0.703, a specificity of 0.667, and an area under the ROC curve of 0.723 (95% CI = 0.629-0.817, P < 0.001*). Conclusion: Our results indicate that FARP is a novel predictive marker for disease severity and prognosis of anti-NMDAR encephalitis.

A novel circular RNA circRBMS3 regulates proliferation and metastasis of osteosarcoma by targeting miR-424-eIF4B/YRDC axis.

Circular RNAs (circRNAs) have been demonstrated to have critical regulatory roles in tumorigenesis. However, the contribution of circRNAs to OS (osteosarcoma) remains largely unknown. circRNA deep sequencing was performed to the expression of circRNAs between OS and chondroma tissues. The regulatory and functional role of circRBMS3 (a circRNA derived from exons 7 to 10 of the RBMS3 gene, hsa_circ_0064644) upregulation was examined in OS and was validated in vitro and in vivo, upstream regulator and downstream target of circRBMS3 were both explored. RNA pull down, a luciferase reporter assay, biotin-coupled microRNA capture and fluorescence in situ hybridization were used to evaluate the interaction between circRBMS3 and micro (mi)-R-424-5p. For in vivo tumorigenesis experiments, Subcutaneous and Orthotopic xenograft OS mouse models were built. Expression of circRBMS3 was higher in OS tissues due to the regulation of adenosine deaminase 1-acting on RNA (ADAR1), an abundant RNA editing enzyme. Our in vitro data indicated that ShcircRBMS3 inhibits the proliferation and migration of osteosarcoma cells. Mechanistically, we showed that circRBMS3 could regulate eIF4B and YRDC, through 'sponging' miR-424-5p. Furthermore, knockdown of circRBMS3 inhibited malignant phenotypes and bone destruction of OS in vivo. Our results reveal an important role for a novel circRBMS3 in the growth and metastasis of malignant tumor cells and offer a fresh perspective on circRNAs in OS progression.

LncRNA LINC01094 Promotes Cells Proliferation and Metastasis through the PTEN/AKT Pathway by Targeting AZGP1 in Gastric Cancer.

Long noncoding RNAs (lncRNAs) were recently reported to play an essential role in multiple cancer types. Herein, through next-generation sequencing, we screened metastasis-driving molecules by using tissues from early-stage gastric cancer (GC) patients with lymph node metastasis, and we identified a lncRNA LINC01094, which was associated with the metastasis of GC. According to the clinical data from the TCGA, GSE15459, and GSE62254 cohorts, the high expression of LINC01094 was associated with an unfavorable prognosis. Moreover, 106 clinical GC and paired normal samples were collected, and the qRT-PCR results showed that the high expression of LINC01094 was associated with high T and N stages and a poor prognosis. We found that LINC01094 promotes the proliferation and metastasis of GC in vitro and in vivo. AZGP1 was found as the protein-binding partner of LINC01094 by using RNA pulldown and RNA-binding protein immunoprecipitation (RIP) assays. LINC01094 antagonizes the function of AZGP1, downregulates the expression of PTEN, and further upregulates the AKT pathway. Collectively, our results suggested that LINC01094 might predict the prognosis of GC patients and become the therapy target for GC.