Quantifying perceived risk in driving: A Monte Carlo approach for obstacle avoidance.

OBJECTIVE: This study aims to develop a model for quantifying perceived risk in obstacle avoidance, emphasizing how drivers' perceived risk characteristics influence their driving decisions. The research addresses the lack of attention given to modeling risk from the perspective of drivers' risk perceptions. METHODS: Monte Carlo methods are employed to account for the uncertainties and complexities of driving behavior, restoring the probabilistic nature of risk. The proposed method quantifies perceived risk by incorporating drivers' fuzzy perceptions, enabling a quantitative evaluation during obstacle avoidance. A logit model is used to link perceived risk with driving decisions, identifying key factors influencing driver behavior in obstacle avoidance scenarios. RESULTS: Experimental data revealed significant variations in vehicle trajectories and speed distributions due to differences in drivers' experience and proficiency. The perceived risk indicator (PRI) values for leftward bypasses were higher compared to rightward bypasses, and the receiver operating characteristic (ROC) curve confirmed the PRI's strong predictive ability with an area under the curve (AUC) of 0.820. The logit model showed that both PRI and speed significantly influenced the probability of choosing a rightward bypass, achieving 90% accuracy. Building on the model, the study predicted and visualized the probability of vehicles turning right to avoid obstacles at different positions and speeds within 200 m of the obstacle. CONCLUSIONS: The research offers a framework for traffic professionals to understand driver-perceived risk and decision-making mechanisms. This understanding is beneficial for improving traffic safety and highlights the importance of considering drivers' risk perceptions in modeling driving behavior.

Long-lived topological time-crystalline order on a quantum processor.

Topologically ordered phases of matter elude Landau's symmetry-breaking theory, featuring a variety of intriguing properties such as long-range entanglement and intrinsic robustness against local perturbations. Their extension to periodically driven systems gives rise to exotic new phenomena that are forbidden in thermal equilibrium. Here, we report the observation of signatures of such a phenomenon-a prethermal topologically ordered time crystal-with programmable superconducting qubits arranged on a square lattice. By periodically driving the superconducting qubits with a surface code Hamiltonian, we observe discrete time-translation symmetry breaking dynamics that is only manifested in the subharmonic temporal response of nonlocal logical operators. We further connect the observed dynamics to the underlying topological order by measuring a nonzero topological entanglement entropy and studying its subsequent dynamics. Our results demonstrate the potential to explore exotic topologically ordered nonequilibrium phases of matter with noisy intermediate-scale quantum processors.

The Application Value of Using Semiquantitative and Quantitative Parameters in Multimodal Ultrasound to Distinguish Between Benign and Malignant BI-RADS 4 Lesions.

ABSTRACT: This study aims to explore the value of real-time strain elastography (RTE) and contrast-enhanced ultrasonography (CEUS) in the diagnosis of breast BI-RADS 4 lesions. It collected 85 cases (totaling 85 lesions) diagnosed with breast BI-RADS 4 through routine ultrasound from October 2020 to December 2022 in Huangshan City People's Hospital. All lesions underwent RTE and CEUS examination before surgery, and the ImageJ software was used to measure the periphery of lesion images in the enhancement peak mode and grayscale mode to calculate the contrast-enhanced ultrasound area ratio. The diagnostic capabilities of single-modal and multimodal ultrasound examination for the malignancy of breast BI-RADS 4 lesions were compared using the receiver operating characteristic curve; the Spearman correlation analysis was adopted to evaluate the correlation between multimodal ultrasound and CEUS area ratio. As a result, among the 85 lesions, 51 were benign, and 34 were malignant. The areas under the curve (AUCs) of routine ultrasound (US), US + RTE, US + CEUS, and US + RTE + CEUS were 0.816, 0.928, 0.953, and 0.967, respectively, with the combined method showing a higher AUC than the single application. The AUC of the CEUS area ratio diagnosing breast lesions was 0.888. There was a strong positive correlation (r = 0.819, P < 0.001) between the diagnostic performance of US + RTE + CEUS and the CEUS area ratio. In conclusion, based on routine ultrasound, the combination of RTE and CEUS can further improve the differential diagnosis of benign and malignant lesions in breast BI-RADS 4.

Long-Term Alcohol Exposure Aggravates Ischemic Stroke-Induced Damage by Promoting Pericyte NLRP3 Inflammasome Activation via Pre-Activating the TLR4/NF-κB Pathway in Rats.

Background: Ischemic stroke (IS) is one of the leading causes of death and disability in the world, and alcohol consumption has been gaining attention as an independent risk factor for IS. Blood-brain barrier (BBB) dysfunction and neuroinflammation are the core of cerebral ischemia/reperfusion (I/R) injury, and pericytes play a crucial role in the structure and function. This study is to explore the effects of long-term alcohol consumption on IS and the potential mechanisms of pericytes. Methods: Rat models of long-term alcohol intake followed by transient middle cerebral artery occlusion stroke (EtOH+tMCAO) and cell models of oxygen-glucose deprivation/reoxygenation (OGD/R) with alcohol pre-treatment were constructed. Results: Worsened infarct volume, neurological scores, and BBB disruption were observed in the EtOH+tMCAO group compared with the tMCAO group, and immunofluorescence staining showed increased pericytes NLPR3 inflammasome activation at the ischemic penumbra. In vitro, pericyte mortality and LDH release elevated pre-treated by alcohol after OGD/R, and amplified expression of NLRP3 inflammasome was detected by Western blotting and qPCR. Alcohol pre-treatment activated the TLR4/NF-κB pathway, and transfecting pericytes with TLR4-small interfering RNA (siRNA) to block TLR4 signaling markedly restrained NLRP3 inflammasome over-activation. Injecting TAK-242 in rats alleviated neurological impairment caused by alcohol. Conclusion: Long-term alcohol pre-treatment aggravated ischemic stroke-induced brain damage by activating NLRP3 inflammasome via TLR4/NF-κB signaling pathway in the pericytes.

A Brief Overview of the Development and Significance of Modern Scientific Medicine in China: Take Chinese Academy of Medical Science and Peking Union Medical College as an Example.

Since the early 20th century, China has gradually established a clinical, educational, and research system centered around modern scientific medicine, which has now become the dominant force in China's medical and health system and services, with the construction and development of the Chinese Academy of Medical Sciences and Peking Union Medical College as the most prominent symbol. The scientific medicine in the new era requires close cooperation across multiple disciplines and fields to build a high-quality and efficient medical and health service system. It also involves combining the excellent traditional Chinese culture with Western medicine to explore a unique path of modern scientific medicine with Chinese characteristics.

The ubiquitin-like protein UBTD1 promotes colorectal cancer progression by stabilizing c-Myc to upregulate glycolysis.

Dysfunction of the ubiquitin-proteasome system (UPS) is involved in the pathogenesis of various malignancies including colorectal cancer (CRC). Ubiquitin domain containing 1 (UBTD1), a ubiquitin-like protein, regulates UPS-mediated protein degradation and tumor progression in some cancer types. However, the biological function and mechanism of UBTD1 are far from being well elucidated, and its role in CRC has not been explored yet. In our study, we analyzed CRC patients' clinical information and UBTD1 expression data, and found that the expression of UBTD1 in cancer tissue was significantly higher than that in adjacent normal tissue. Higher UBTD1 expression was significantly associated with poorer survival and more lymph node metastasis. Overexpression of UBTD1 could facilitate, while knockdown could inhibit CRC cell proliferation and migration, respectively. RNA-seq and proteomics indicated that c-Myc is an important downstream target of UBTD1. Metabolomics showed the products of the glycolysis pathway were significantly increased in UBTD1 overexpression cells. In vitro, we verified UBTD1 upregulating c-Myc protein and promoting CRC cell proliferation and migration via regulating c-Myc. UBTD1 promoted CRC cells' glycolysis, evidenced by the increased lactate production and glucose uptake following UBTD1 overexpression. Mechanistically, UBTD1 prolonged the half-life of the c-Myc protein by binding to E3 ligase ß-transducin repeat-containing protein (ß-TrCP), thereby upregulated the expression of glycolysis rate-limiting enzyme hexokinase II (HK2), and enhanced glycolysis and promoted CRC progression. In conclusion, our study revealed that UBTD1 promotes CRC progression by upregulating glycolysis via the ß-TrCP/c-Myc/HK2 pathway, suggesting its potential as a prognostic biomarker and therapeutic target in CRC.

Magnetic fibrin nanofiber hydrogel delivering iron oxide magnetic nanoparticles promotes peripheral nerve regeneration.

Peripheral nerve injury is a debilitating condition that have a profound impact on the overall quality of an individual's life. The repair of peripheral nerve defects continues to present significant challenges in the field. Iron oxide magnetic nanoparticles (IONPs) have been recognized as potent nanotools for promoting the regeneration of peripheral nerves due to their capability as biological carriers and their ability to template the hydrogel structure under an external magnetic field. This research used a fibrin nanofiber hydrogel loaded with IONPs (IONPs/fibrin) to promote the regeneration of peripheral nerves in rats. In vitro examination of PC12 cells on various concentrations of IONPs/fibrin hydrogels revealed a remarkable increase in NGF and VEGF expression at 2% IONPs concentration. The biocompatibility and degradation of 2% IONPs/fibrin hydrogel were assessed using the in vivo imaging system, demonstrating subcutaneous degradation within a week without immediate inflammation. Bridging a 10-mm sciatic nerve gap in Sprague Dawley rats with 2% IONPs/fibrin hydrogel led to satisfactory morphological recovery of myelinated nerve fibers. And motor functional recovery in the 2% IONPs/fibrin group was comparable to autografts at 6, 9 and 12 weeks postoperatively. Hence, the composite fibrin hydrogel incorporating 2% IONPs exhibits potential for peripheral nerve regeneration.

Associations between sarcopenia and circulating branched-chain amino acids: a cross-sectional study over 100,000 participants.

BACKGROUND: Emerging evidence suggests that alterations in BCAA metabolism may contribute to the pathogenesis of sarcopenia. However, the relationship between branched-chain amino acids (BCAAs) and sarcopenia is incompletely understood, and existing literature presents conflicting results. In this study, we conducted a community-based study involving > 100,000 United Kingdom adults to comprehensively explore the association between BCAAs and sarcopenia, and assess the potential role of muscle mass in mediating the relationship between BCAAs and muscle strength. METHODS: Multivariable linear regression analysis examined the relationship between circulating BCAAs and muscle mass/strength. Logistic regression analysis assessed the impact of circulating BCAAs and quartiles of BCAAs on sarcopenia risk. Subgroup analyses explored the variations in associations across age, and gender. Mediation analysis investigated the potential mediating effect of muscle mass on the BCAA-muscle strength relationship. RESULTS: Among 108,017 participants (mean age: 56.40 ± 8.09 years; 46.23% men), positive associations were observed between total BCAA, isoleucine, leucine, valine, and muscle mass (beta, 0.56-2.53; p < 0.05) and between total BCAA, leucine, valine, and muscle strength (beta, 0.91-3.44; p < 0.05). Logistic regression analysis revealed that increased circulating valine was associated with a 47% reduced sarcopenia risk (odds ratio = 0.53; 95% confidence interval = 0.3-0.94; p = 0.029). Subgroup analyses demonstrated strong associations between circulating BCAAs and muscle mass/strength in men and individuals aged ≥ 60 years. Mediation analysis suggested that muscle mass completely mediated the relationship between total BCAA, and valine levels and muscle strength, partially mediated the relationship between leucine levels and muscle strength, obscuring the true effect of isoleucine on muscle strength. CONCLUSION: This study suggested the potential benefits of BCAAs in preserving muscle mass/strength and highlighted muscle mass might be mediator of BCAA-muscle strength association. Our findings contribute new evidence for the clinical prevention and treatment of sarcopenia and related conditions involving muscle mass/strength loss.

Polyoxometalate solution passivation enabling dendrite-free and high-performance zinc anodes in aqueous zinc-ion batteries.

Zinc metal anodes in aqueous electrolytes commonly face challenges such as dendrite growth and undesirable side reactions, limiting their application in the field of aqueous zinc-ion batteries (AZIBs) for energy storage. Drawing inspiration from industrial practices involving molybdenum salt solutions for metal modification, a polyoxometalate solution was formulated as a passivation solution for zinc anodes (referred to as MO solution). The formed passivation layer, referred to as the MO layer, exhibited a uniform and protective nature with a thickness of approximately 10 µm. The experimental results demonstrated that this passivation layer effectively suppressed side reactions at the zinc anode interface, as evidenced by lower corrosion current density for MO-Zn anodes. Additionally, the newly plated Zn was uniformly deposited atop the MO layer, ensuring coating integrity and inhibiting dendrite growth. As a result, under more demanding conditions such as a larger current of 8 mA cm-2, the MO-Zn anode displayed an extended cycle life exceeding 420 h in a symmetric battery, with an overpotential as low as 98 mV. This performance significantly outperformed that of commercially available pure Zn foils (with a cycle life of 60 h and an overpotential of 192 mV). Notably, a self-made Na-doped V2O5 served as the cathode (referred to as NaVO), forming the MO-Zn//NaVO full battery. Even under high current test conditions of 2 A/g, the specific capacity of the MO-Zn//NaVO full battery remained substantial at 152.83 mAh/g after 1000 cycles. Furthermore, pouch batteries assembled with NaVO//MO-Zn successfully illuminated small bulbs. This study offers a viable optimization strategy for AZIB anodes and demonstrates the potential of using polyoxometalate solution for etching zinc anodes to inhibit dendrite growth and interfacial corrosion of zinc metal anodes.

Oxidized mitochondrial DNA activates the cGAS-STING pathway in the neuronal intrinsic immune system after brain ischemia-reperfusion injury.

In the context of stroke and revascularization therapy, brain ischemia-reperfusion injury is a significant challenge that leads to oxidative stress and inflammation. Central to the cell's intrinsic immunity is the cGAS-STING pathway, which is typically activated by unusual DNA structures. The involvement of oxidized mitochondrial DNA (ox-mtDNA)-an oxidative stress byproduct-in this type of neurological damage has not been fully explored. This study is among the first to examine the effect of ox-mtDNA on the innate immunity of neurons following ischemia-reperfusion injury. Using a rat model of transient middle cerebral artery occlusion and a cellular model of oxygen-glucose deprivation/reoxygenation, we have discovered that ox-mtDNA activates the cGAS-STING pathway in neurons. Importantly, pharmacologically limiting the release of ox-mtDNA into the cytoplasm reduces inflammation and improves neurological functions. Our findings suggest that targeting ox-mtDNA release may be a valuable strategy to attenuate brain ischemia-reperfusion injury following revascularization therapy for acute ischemic stroke.

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.

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.

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.

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.

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.

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.