Side-Opened Hollow Fiber-Based SPR Sensor for High Refractive Index Detection.

To facilitate the sensor fabrication and sensing operation in microstructured optical fiber-based surface plasmon resonance (SPR) sensors for high refractive index (RI) detection, we propose a special hollow fiber-based SPR sensor that comprises an opening on its body side and a thin gold layer coated on its outer surface. The analyte is able to flow into the hollow core through the side-opening to form new fiber core, with the Gaussian-like mode propagating in it. We investigate the sensing performance of the proposed sensor in a higher RI range of 1.48 to 1.54 at two feasible schemes: one is to only fill the fiber core with analyte (Scheme A), and the other is to directly immerse the sensor in the analyte (Scheme B). The results demonstrate that our sensor exhibits higher wavelength sensitivity at Scheme A with a maximum wavelength sensitivity of 12,320 nm/RIU, while a greater amplitude sensitivity was found at Scheme B with a maximum amplitude sensitivity of 1146 RIU-1. Our proposed sensor features the advantages of simple fabrication, flexible operation, easy analyte filling and replacing, enhanced real-time detection capabilities, high RI detection, and very high wavelength sensitivity and amplitude sensitivity, which makes it more competitive in SPR sensing applications.

Dysfunctional astrocyte glutamate uptake in the hypothalamic paraventricular nucleus contributes to visceral pain and anxiety-like behavior in mice with chronic pancreatitis.

Abdominal visceral pain is a predominant symptom in patients with chronic pancreatitis (CP); however, the underlying mechanism of pain in CP remains elusive. We hypothesized that astrocytes in the hypothalamic paraventricular nucleus (PVH) contribute to CP pain pathogenesis. A mouse model of CP was established by repeated intraperitoneal administration of caerulein to induce abdominal visceral pain. Abdominal mechanical stimulation, open field and elevated plus maze tests were performed to assess visceral pain and anxiety-like behavior. Fiber photometry, brain slice Ca2+ imaging, electrophysiology, and immunohistochemistry were used to investigate the underlying mechanisms. Mice with CP displayed long-term abdominal mechanical allodynia and comorbid anxiety, which was accompanied by astrocyte glial fibrillary acidic protein reactivity, elevated Ca2+ signaling, and astroglial glutamate transporter-1 (GLT-1) deficits in the PVH. Specifically, reducing astrocyte Ca2+ signaling in the PVH via chemogenetics significantly rescued GLT-1 deficits and alleviated mechanical allodynia and anxiety in mice with CP. Furthermore, we found that GLT-1 deficits directly contributed to the hyperexcitability of VGLUT2PVH neurons in mice with CP, and that pharmacological activation of GLT-1 alleviated the hyperexcitability of VGLUT2PVH neurons, abdominal visceral pain, and anxiety in these mice. Taken together, our data suggest that dysfunctional astrocyte glutamate uptake in the PVH contributes to visceral pain and anxiety in mice with CP, highlighting GLT-1 as a potential therapeutic target for chronic pain in patients experiencing CP.

Cholesterol 25-hydroxylase prevents type 2 diabetes mellitus induced cardiomyopathy by alleviating cardiac lipotoxicity.

OBJECTIVES: Diabetic cardiomyopathy (DCM) is the leading cause of mortality in type 2 diabetes mellitus (T2DM) patients, with its underlying mechanisms still elusive. This study aims to investigate the role of cholesterol-25-monooxygenase (CH25H) in T2DM induced cardiomyopathy. METHODS: High fat diet combined with streptozotocin (HFD/STZ) were used to establish a T2DM model. CH25H and its product 25-hydroxycholesterol (25HC) were detected in the hearts of T2DM model. Gain- or loss-of-function of CH25H were performed by receiving AAV9-cTNT-CH25H or CH25H knockout (CH25H-/-) mice with HFD/STZ treatment. Cardiac function was evaluated using echocardiography, and cardiac tissues were collected for immunoblot analysis, histological assessment and quantitative polymerase chain reaction (qPCR). Mitochondrial morphology and function were evaluated using transmission electron microscopy (TEM) and Seahorse XF Cell Mito Stress Test Kit. RNA-sequence analysis was performed to determine the molecular changes associated with CH25H deletion. RESULTS: CH25H and 25HC were significantly decreased in the hearts of T2DM mice. CH25H-/- mice treated with HFD/STZ exhibited impaired mitochondrial function and structure, increased lipid accumulation, and aggregated cardiac dysfunction. Conversely, T2DM mice receiving AAV9-CH25H displayed cardioprotective effects. Mechanistically, RNA sequencing and qPCR analysis revealed that CH25H deficiency decreased peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) and its target gene expression. Additionally, administration of ZLN005, a potent PGC-1α activator, partially protected against high glucose and palmitic acid induced mitochondria dysfunction and lipid accumulation in vitro. CONCLUSION: Our study provides compelling evidence supporting the protective role of CH25H in T2DM-induced cardiomyopathy. Furthermore, the regulation of PGC-1α may be intricately involved in this cardioprotective process.

Dual regulation effect and mechanism of human myeloid-derived suppressor cells on anticolorectal cancer cells activity of Vγ9Vδ2 T cells.

Myeloid-derived suppressor cells (MDSC) are a group of immature inhibitory cells of bone marrow origin. Human γδ T cells (mainly Vγ9Vδ2 T cells) have emerged as dominant candidates for cancer immunotherapy because of their unique recognition pattern and broad killing activity against tumor cells. Intestinal mucosal intraepithelial lymphocytes are almost exclusively γδ T cells, so it plays an important role in inhibiting the development of colorectal cancer. In this study, we investigated the effects and molecular mechanism of human MDSC on anticolorectal cancer cells activity of Vγ9Vδ2 T cells. Our results suggested that MDSC can reduce the NKG2D expression of Vγ9Vδ2 T cells through direct cell-cell contact, which is associated with membrane-type transforming growth factor-ß. In contrast, MDSC can increase Vγ9Vδ2 T cells activation and production of IFN-γ, perforin, Granzyme B through direct cell-cell contact. This may be related to the upregulation of T-bet in Vγ9Vδ2 T cells by MDSC. However, MDSC had a dominant negative regulatory effect on the anticolorectal cancer cells activity of Vγ9Vδ2 T cells. Our study provides a theoretical basis for the immune regulatory function of human MDSC on γδ T cells. This will be conducive to the clinical development of a new antitumor therapy strategy.

GeoExplainer: A Visual Analytics Framework for Spatial Modeling Contextualization and Report Generation.

Geographic regression models of various descriptions are often applied to identify patterns and anomalies in the determinants of spatially distributed observations. These types of analyses focus on answering why questions about underlying spatial phenomena, e.g., why is crime higher in this locale, why do children in one school district outperform those in another, etc.? Answers to these questions require explanations of the model structure, the choice of parameters, and contextualization of the findings with respect to their geographic context. This is particularly true for local forms of regression models which are focused on the role of locational context in determining human behavior. In this paper, we present GeoExplainer, a visual analytics framework designed to support analysts in creating explanative documentation that summarizes and contextualizes their spatial analyses. As analysts create their spatial models, our framework flags potential issues with model parameter selections, utilizes template-based text generation to summarize model outputs, and links with external knowledge repositories to provide annotations that help to explain the model results. As analysts explore the model results, all visualizations and annotations can be captured in an interactive report generation widget. We demonstrate our framework using a case study modeling the determinants of voting in the 2016 US Presidential Election.

GeoLinter: A Linting Framework for Choropleth Maps.

Visualization linting is a proven effective tool in assisting users to follow established visualization guidelines. Despite its success, visualization linting for choropleth maps, one of the most popular visualizations on the internet, has yet to be investigated. In this paper, we present GeoLinter, a linting framework for choropleth maps that assists in creating accurate and robust maps. Based on a set of design guidelines and metrics drawing upon a collection of best practices from the cartographic literature, GeoLinter detects potentially suboptimal design decisions and provides further recommendations on design improvement with explanations at each step of the design process. We perform a validation study to evaluate the proposed framework's functionality with respect to identifying and fixing errors and apply its results to improve the robustness of GeoLinter. Finally, we demonstrate the effectiveness of the GeoLinter - validated through empirical studies - by applying it to a series of case studies using real-world datasets.

Visualization and Characterization of the Brain Regional Heterogeneity of Astrocyte-Astrocyte Structural Interactions by Using Improved Iontophoresis with Dual-Fluorescent Dyes.

Astrocytes are morphologically intricate cells and actively modulate the function of the brain. Through numerous fine processes, astrocytes come into contact with neurons, blood vessels, and other glia cells. Emerging evidence has shown that astrocytes exhibit brain regional diversity in their morphology, transcriptome, calcium signaling, and functions. However, little is known about the brain regional heterogeneity of astrocyte-astrocyte structural interaction. So far, the visualization and characterization of the morphological features of adjacent astrocytes have been difficult, and as a result, it is still well-accepted that astrocytes in the adult brain share non-overlapped territory. In contrast, employing an approach that combines viral labeling with dual-fluorescent dyes iontophoresis under brightfield and imaging using confocal microscopy allows for the efficient and specific labeling of adjacent astrocytes, enabling a comprehensive visualization of their fine processes and the degree of their territorial overlap. Our study in the hypothalamic regions of the brain revealed a marked spatial overlap among adjacent astrocytes, which differs from the conventional understanding based on more extensively studied regions, like the hippocampus. Additionally, we revealed the heterogeneity of the astrocyte-neuron ratio across brain regions and conducted an assessment of the photostability and labeling efficiency of fluorescent dyes used for labeling adjacent astrocytes. Our study provides new insights for studying the morphological heterogeneity of astrocytes across the central nervous system.

Retrospective Analysis of Death Cases of Oral Diphenidol Hydrochloride Poisoning.

OBJECTIVES: To explore the characteristics of postmortem examination, chemical examination and scene investigation of deaths caused by oral diphenidol hydrochloride poisoning, and so as to provide a reference for proper settlement and prevention of such deaths. METHODS: The data of 22 deaths caused by oral diphenidol hydrochloride poisoning in a city from January 2018 to August 2020 were collected, including case details, scene investigations, autopsies, chemical examinations and digital evidence. Thirty-one cases of deaths caused by oral diphenidol hydrochloride poisoning reported in previous literature were also collected. RESULTS: In the 53 oral diphenidol hydrochloride poisoning death cases, 50 cases were suicide, 2 cases were accidental, while 1 case was undetermined. Fifty-two cases were found in the medical records or crime scene investigation reports with doses ranging from 775 mg to 12 500 mg, and 23 deceased were detected with postmortem blood concentrations ranging from 2.71 mg/L to 83.1 mg/L. Clinical symptoms were recorded in 6 patients, including conscious disturbance and convulsion. Among the 45 cases which were performed with external examination, 23 cases autopsied. CONCLUSIONS: Most of the deceased of oral diphenidol hydrochloride poisoning were suicide. No significant correlation was found between dose and blood concentration through the retrospective analysis of cases.

Analytical Ultracentrifugation-Calibrated Anion-Exchange Chromatography for Sensitive and Intact Determination of Osteopontin in Infant Formula and Dairy Products.

Osteopontin is a crucial protein ingredient that has been applied in fortified dairy products and infant formula. It has great significance to infant gut health and brain development. However, current techniques including enzyme-linked immunosorbent assay and liquid chromatography coupled with mass spectrometry are still facing the bottleneck of low sensitivity and indirect quantification. Moreover, the unavailable certified commercial OPN standard hinders its accurate quantification. Herein, a novel method of anion-exchange chromatography was established to determine OPN concentration in several dairy matrices. The polarity-reversed capillary isoelectric focusing was utilized to measure the exact isoelectric point (pI) to support method development for OPN separation. Analytical ultracentrifugation was used to calibrate the purity of intact OPN to develop an in-house reference standard. The method showed the merits of limits of detection to 0.04 mg/100 g, relative standard deviation of reproducibility <5% for 13 out of 14 tested matrices, and an average recovery rate of 101.3%. This method has shown the potential to be adopted as an international standard method for the quantification of intact OPN in infant formula and dairy products.

Mediation of endoplasmic reticulum stress and NF-κB signaling pathway in DINP-exacerbated allergic asthma: A toxicological study with Balb/c mice.

Epidemiological evidence indicates a significant relationship between exposure to diisononyl phthalate and allergic asthma. Despite this, the mechanism underlying this association remains unclear. Previous toxicological researches have suggested that the development of allergic asthma may involve the activation of endoplasmic reticulum stress (ERS) and the nuclear factor κ-B (NF-κB) pathways. Nevertheless, it is currently unknown whether these specific signaling pathways are implicated in diisononyl phthalate (DINP)-induced allergic asthma. The objective of this research was to understand how DINP exacerbates allergic asthma in Balb/c mice through ERS and NF-κB pathways. To systematically examine the aggravated effects of DINP in Balb/c mice, we measured airway hyperresponsiveness (AHR), lung tissue pathology, cytokines, and ERS and NF-κB pathway biomarkers. Additionally, we applied the ERS antagonist phenylbutyric acid (4-PBA) or the NF-κB antagonist pyrrolidine dithiocarbamate (PDTC) to verify the mediating effects of ERS and NF-κB on DINP-exacerbated allergic asthma. The results of our experiment show that oral DINP exposure may exacerbate airway hyperresponsiveness and airway remodeling. This deterioration is accompanied by an imbalance in immunoglobulin levels, Th17/Treg cells, ERS, and NF-κB biomarkers, leading to the activation of pro-inflammatory pathways. Furthermore, our study found that the blocking effect of 4-PBA or PDTC can inhibit the Th17/Treg imbalance and effectively alleviate symptoms resembling allergic asthma. In conclusion, ERS and NF-κB signaling pathways play an important role in regulating DINP-induced allergic asthma exacerbations.

Ligand-installed polymeric nanocarriers for combination chemotherapy of EGFR-positive ovarian cancer.

Combination chemotherapeutic drugs administered via a single nanocarrier for cancer treatment provides benefits in reducing dose-limiting toxicities, improving the pharmacokinetic properties of the cargo and achieving spatial-temporal synchronization of drug exposure for maximized synergistic therapeutic effects. In an attempt to develop such a multi-drug carrier, our work focuses on functional multimodal polypeptide-based polymeric nanogels (NGs). Diblock copolymers poly (ethylene glycol)-b-poly (glutamic acid) (PEG-b-PGlu) modified with phenylalanine (Phe) were successfully synthesized and characterized. Self-assembly behavior of the resulting polymers was utilized for the synthesis of NGs with hydrophobic domains in cross-linked polyion cores coated with inert PEG chains. The resulting NGs were small (ca. 70 nm in diameter) and were able to encapsulate the combination of drugs with different physicochemical properties such as cisplatin and neratinib. Drug combination-loaded NGs exerted a selective synergistic cytotoxicity towards EGFR overexpressing ovarian cancer cells. Moreover, we developed ligand-installed EGFR-targeted NGs and tested them as an EGFR-overexpressing tumor-specific delivery system. Both in vitro and in vivo, ligand-installed NGs displayed preferential associations with EGFR (+) tumor cells. Ligand-installed NGs carrying cisplatin and neratinib significantly improved the treatment response of ovarian cancer xenografts. We also confirmed the importance of simultaneous administration of the dual drug combination via a single NG system which provides more therapeutic benefit than individual drug-loaded NGs administered at equivalent doses. This work illustrates the potential of our carrier system to mediate efficient delivery of a drug combination to treat EGFR overexpressing cancers.

Novel Effect of p-Coumaric Acid on Hepatic Lipolysis: Inhibition of Hepatic Lipid-Droplets.

p-coumaric acid (p-CA), a common plant phenolic acid with multiple bioactivities, has a lipid-lowering effect. As a dietary polyphenol, its low toxicity, with the advantages of prophylactic and long-term administration, makes it a potential drug for prophylaxis and the treatment of nonalcoholic fatty liver disease (NAFLD). However, the mechanism by which it regulates lipid metabolism is still unclear. In this study, we studied the effect of p-CA on the down-regulation of accumulated lipids in vivo and in vitro. p-CA increased a number of lipase expressions, including hormone-sensitive lipase (HSL), monoacylglycerol lipase (MGL) and hepatic triglyceride lipase (HTGL), as well as the expression of genes related to fatty acid oxidation, including long-chain fatty acyl-CoA synthetase 1 (ACSL1), carnitine palmitoyltransferase-1 (CPT1), by activating peroxisome proliferator-activated receptor α, and γ (PPARα and γ). Furthermore, p-CA promoted adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) phosphorylation and enhanced the expression of the mammalian suppressor of Sec4 (MSS4), a critical protein that can inhibit lipid droplet growth. Thus, p-CA can decrease lipid accumulation and inhibit lipid droplet fusion, which are correlated with the enhancement of liver lipases and genes related to fatty acid oxidation as an activator of PPARs. Therefore, p-CA is capable of regulating lipid metabolism and is a potential therapeutic drug or health care product for hyperlipidemia and fatty liver.

Plant-on-chip: Core morphogenesis processes in the tiny plant Wolffia australiana.

A plant can be thought of as a colony comprising numerous growth buds, each developing to its own rhythm. Such lack of synchrony impedes efforts to describe core principles of plant morphogenesis, dissect the underlying mechanisms, and identify regulators. Here, we use the minimalist known angiosperm to overcome this challenge and provide a model system for plant morphogenesis. We present a detailed morphological description of the monocot Wolffia australiana, as well as high-quality genome information. Further, we developed the plant-on-chip culture system and demonstrate the application of advanced technologies such as single-nucleus RNA-sequencing, protein structure prediction, and gene editing. We provide proof-of-concept examples that illustrate how W. australiana can decipher the core regulatory mechanisms of plant morphogenesis.

TODIM-VIKOR method based on hybrid weighted distance under probabilistic uncertain linguistic information and its application in medical logistics center site selection.

At a time of global epidemic control, the location of the medical logistics distribution center (MLDC) has an important impact on the operation of the entire logistics system to reduce the operating costs of the company, enhance the service quality and effectively control the COVID-19 on the premise of increasing the company's profits. Thus, the research on the location of MLDC has important theoretical and practical application significance separately. Recently, the TODIM and VIKOR method has been used to solve multiple-attribute group decision-making (MAGDM) issues. The probabilistic uncertain linguistic term sets (PULTSs) are used as a tool for characterizing uncertain information. In this paper, we design the TODIM-VIKOR model to solve the MAGDM in PULT condition. Firstly, some basic concept of PULTSs is reviewed, and TODIM and VIKOR method are introduced. The extended TODIM-VIKOR model is proposed to tackle MAGDM problems under the PULTSs. At last, a numerical case study for medical logistics center site selection (MLCSS) is given to validate the proposed method.

Impacts of additional cycles of neoadjuvant immunotherapy on surgery in non-small-cell lung cancer.

OBJECTIVE: Whether cycle number influences the subsequent pathological or surgical outcomes remained unclear. This study aimed to assess the efficacy and surgical safety of neoadjuvant immunochemotherapy-based treatment in the real-world setting. METHODS: Clinical data of patients who received neoadjuvant immunochemotherapy for non-small-cell lung cancer between 2018 and 2021 were collected. Oncological outcomes such as objective response rate (ORR), major pathological response (MPR), and pathological complete response (pCR), and surgical outcomes including operating time, intraoperative bleeding, postoperative drainage, and hospital stay were analyzed. RESULTS: In total, 176 patients were included, among whom 102 cases were lung squamous carcinoma (LUSQ). After immunochemotherapy, 98 (56%) of patients achieved ORR. Notably, the ORR (63% vs. 46%, p = 0.039) and pCR (45% vs. 27%, p = 0.022) were significantly higher in patients with LUSQ. For patients who received two, three, four, and five or more cycles, the ORRs were 52%, 67%, 53%, and 50% (p = 0.36). In post hoc analysis, cycle numbers showed no significant association with MPR or pCR (p = 0.14 and p = 0.073). Treatment cycles showed no influence on operating time, postoperative drainage, and hospital stay (p = 0.79, 0.37, and 0.22). Notably, the blood loss index of patients who received more than four cycles was higher than those receiving four or fewer cycles (mean blood loss: two or fewer cycles 153.1, three cycles 113.8, four cycles 137.6, and five or more cycles 293.3, respectively). CONCLUSIONS: This study indicated that cycles of neoadjuvant immunochemotherapy had no significant effect on the feasibility and safety of surgery. Although not statistically significant, patients who received five or more cycles of treatment experienced higher intraoperative blood loss.

The Relationship of Internet Gaming Addiction and Suicidal Ideation among Adolescents: The Mediating Role of Negative Emotion and the Moderating Role of Hope.

Recently, internet gaming addiction and suicide have been global public health issues among adolescents. This study used convenience sampling and surveyed 1906 Chinese adolescents to investigate the relationship between internet gaming addiction and suicidal ideation and the role of negative emotion and hope in the relationship between the two. The results showed that the detection rate of internet gaming addiction among adolescents was 17.16% and the detection rate of suicidal ideation was 16.37%. Moreover, there was a significant positive correlation between internet gaming addiction and suicidal ideation. Negative emotion partially mediated the relationship between internet gaming addiction and suicidal ideation. In addition, hope moderated the relationship between negative emotion and suicidal ideation. The effect of negative emotion on suicidal ideation decreased as hope increased. These findings suggest that the role of emotion and hope in coping with adolescent internet gaming addiction and suicidal ideation should be emphasized.

Apparent Deterioration Law and Shear Failure Mode of Rock-Mortar Interface Based on Topography-Sensing Technology.

As an advanced spatial technology, topography-sensing technology is comprehensive, macroscopic, and intuitive. It shows unique advantages for rock structure interpretation and has important guiding significance for the research of the shear performances of rock-mortar interface under cyclic load in rock mass engineering. In this paper, cyclic shearing tests combined with the shear surface topography-sensing technology are employed to investigate the evolution characteristics of the interface morphology and the strength deterioration of the rock-mortar interface. Primarily, mortar and three types of rocks are used to prepare different rock-mortar interfaces, which are then applied to cyclic shear loading under two constant normal stresses. Subsequently, the shear strength degradation and dilatancy characteristics of rock-mortar interfaces with varying shear times are discussed. In addition, on the basis of the non-contact three-dimensional topography-sensing technology, the apparent three-dimensional point-cloud coordinate information of rock-mortar interface before and after each shear loading is obtained, and the apparent three-dimensional topography parameters of rock-mortar interface are calculated, according to which the influences of normal stress and lithology on the topography of interface subjected to cyclic shearing loading are analyzed.

Preparation and Performance Characterization of Exploding Foil Initiator Based on ODPA-ODA Polyimide Flyer.

The exploding foil initiator (EFI) system has been extensively used in ignition and detonation sequences and proved to be of high safety and reliability. Polyimide is considered the ideal flyer material for EFI due to its excellent performance, including thermal stability, outstanding mechanical properties, high radiation resistance, and excellent dielectric properties. In this study, we prepared the EFI based on a polyimide (ODPA-ODA) flyer, which is spin-coated and solidified on patterned copper film in situ. The electric explosion test shows that the prepared EFI has good working performance, and the 4000 V working voltage drove the flyer to reach a maximum velocity of 5096 m/s. The polyimide morphology and chemical structure after the electric explosion was observed by microscope, SEM, XPS, and FTIR, which showed that the polyimide flyer underwent thermal deformation and complex chemical reactions during an electric explosion. A large number of polyimide bonds broke to form new carbonyl compounds, and the opening of aromatic rings was accompanied by the formation of aliphatic hydrocarbon chains. The morphology and chemical structure analysis after the electric explosion test will lay a foundation for us to further understand the working principle and evolution process of polyimide (ODPA-ODA) flyer.

Knockdown of CBX7 inhibits ferroptosis in rats with cerebral ischemia and improves cognitive dysfunction by activating the Nrf2/HO-1 pathway.

Iron-dependent lipid peroxidation-induced ferroptosis has been implicated in the pathogenesis of cerebral ischemia. Ischemia-reperfusion (I/R) contributes to cognitive dysfunction. Chromobox7 (CBX7) was upregulated in neural progenitor cells, followed by hypoxia and ischemia, and the suppression of CBX7 protected against renal and cerebral I/R injuries. However, the role of CBX7 in ferroptosis and cognitive dysfunction in rats with cerebral ischemia has not yet been reported. In our study, first, rats with cerebral I/R were established through middle cerebral artery occlusion (MCAO). Intracerebroventricular injection of shRNA targeting CBX7 (sh-CBX7) enhanced brain water content, and reduced neurological deficit scores and infarct size in rats post MCAO. Second, rats were subjected to 4 trials per day for 4 consecutive days in a Morris water maze. The time to find the platform in with 1 min was recorded as escape latency. On day 5, the platform was removed to conduct a spatial probe test. Rats were given 1 min to find the position of the platform, and the times for crossing the target within 1 min were recorded. Crossing the platform time is the time spent in each quadrant. Data from the Morris water maze showed that cognitive dysfunction in ischemic rats was ameliorated by the injection of sh-CBX7, which decreased the swimming distance and escape latency of ischemic rats, increased the times for crossing the target and platform in the maze. Moreover, injection of sh-CBX7 down-regulated levels of MDA and ROS, while it up-regulated SOD and GSH-Px to repress the oxidative stress. Third, knockdown of CBX7 in ischemic rats decreased the concentration of the ferric ions and the protein expression of transferrin receptor 1 (TFR1), but enhanced the solute carrier family 7 member 11 (SLC7A11) and glutathione peroxidase 4 (GPX4), resulting in the inhibition of ferroptosis. Lastly, expressions of Nrf2, HO-1 and NAD(P)H:quinone oxidoreductase 1 (NQO1) were up-regulated in ischemic rats post sh-CBX7 injection. In conclusion, suppression of CBX7 attenuated I/R injury, improved cognitive dysfunction and inhibited ferroptosis through the activation of the Nrf2/HO-1 signaling pathway.

[Comparative proteomic profiling of hippocampi in mice treated with Jingui Shenqi Pills and Liuwei Dihuang Pills].

The effects of Jingui Shenqi Pills(Jingui) and Liuwei Dihuang Pills(Liuwei) which respectively tonify kidney Yang and kidney Yin on brain function have attracted great attention, while the differences of protein expression regulated by Jingui and Liuwei remain to be studied. This study explored the difference of protein expression profiles in the hippocampi of mice orally administrated with the two drugs for 7 days. The protein expression was quantified using LC-MS/MS. The results showed that among the 5 860 proteins tested, 151, 282 and 75 proteins responded to Jingui alone, Liuwei alone, and both drugs, respectively. The ratio of up-regulated proteins to down-regulated proteins was 1.627 in Jingui group while only 0.56 in Liuwei group. The proteins up-regulated by Jingui were mainly involved in membrane transport, synaptic vesicle cycle, serotonergic synapse, dopaminergic synapse and so on, suggesting that Jingui may play a role in promoting the transport of neurotransmitter in the nervous system. The proteins down-regulated by Liuwei were mainly involved in membrane transport, synapse, ion transport(potassium and sodium transport), neurotransmitter transport, innate and acquired immune responses, complement activation, inflammatory response, etc. In particular, Liuwei showed obvious down-regulation effect on the members of solute carrier(SLC) superfamily, which suggested that Liuwei had potential inhibitory effect on membrane excitation and transport. Finally, consistent results were obtained in the normal mouse and the mouse model with corticosterone-induced depressive-like behavior. This study provides an experimental basis for understanding the effect of Jingui and Liuwei on brain function from protein network.