miR-196b-5p Affects Macrophage Polarization and Inflammation in Endometriosis.

Background: miR-196b-5p was found to be significantly reduced in endometriosis, but its function and the mechanisms involved remained unclear. Objective: To explore the effect of miR-196b-5p on manipulating macrophage phenotype and the underlying mechanisms in endometriosis. Methods: The endometriosis mice and End1/E6E7 cells were used for in vivo and in vitro experiments, respectively. QRT-PCR was used to detect miR-196b-5p, suppressor of cytokine signaling 1 (SOCS1), high mobility group AT-Hook 1 (HMGA1), and CCL2 expressions. Western blot was used to detect SOCS1 and HMGA1 protein levels while luciferase reporter assay was performed to determine the interaction between miR-196b-5p and SOCS1/ HMGA1. ELISA was used to measure CCL2, IL-10, and IL-6 levels and immunohistochemical staining and flow cytometry were used to examine CD86 and CD206 expressions. Results: Significantly reduced levels of miR-196b-5p, and increased levels of SOCS1, HMGA1, and CCL2 were observed in the ectopic endometrium of mice with endometriosis. The miR-196b-5p mimic significantly reduced the lesion size, increased M1 macrophages, and decreased M2 macrophages in the ectopic endometrium of mice with endometriosis. End1/E6E7 cells transfected with miR196b-5p mimic significantly increased M1 macrophages, decreased M2 macrophages and reduced the migration in PMA-treated THP1 cells. Conversely, transfection with a miR-196b-5p inhibitor led to the opposite outcomes. miR-196b-5p targeted SOCS1/HMGA1, and miR-196b-5p inhibitor significantly up-regulated CCL2 and IL-10, and down-regulated IL-6 levels in End1/E6E7 cells. These effects were markedly reversed by si-SOCS1/si-HMGA1. Conclusion: miR-196b-5p elevates M1 macrophages and decreases M2 macrophages in endometriosis, possibly by targeting SOCS1/ HMGA1. This research may provide a novel insight into the pathological mechanisms of endometriosis.

The Transtemporal Isthmus Approach for Insular Glioma Surgery.

BACKGROUND AND OBJECTIVES: Maximal and safe removal of insular gliomas by a transinsular cortex approach is challenging. In this article, a new transtemporal isthmus approach to resect insular gliomas is presented. METHODS: We retrospectively examined 53 patients with insular glioma who underwent resection through the temporal isthmus approach using magnetic resonance imaging and functional neuronavigation guidance and intraoperative electrophysiological monitoring. Extent of resection was determined using intraoperative magnetic resonance imaging. RESULTS: Fifty-three patients were included for analysis, 30 men and 23 women. The median (range) age was 45 (26-70) years. Tumor laterality was left in 22 patients and right in 31. All tumors involved at least zone III or IV (Berger-Sanai classification system), including zones I-IV were involved in 29 (54.7%) and zones III and IV in 17 (32.0%). Among the 37 low-grade gliomas, preoperative median (IQR) volume was 45.7 (31.8, 60.3) cm3, and gross total resection was achieved in 24 (64.9%). Among the 16 high-grade gliomas, preoperative median (IQR) volume was 45.3 (40.1, 54.0) cm3, and gross total resection was achieved in 14 (87.5%). The median (IQR) extent of resection of the whole group was 100% (89%-100%). The median (IQR) postoperative Karnofsky performance score 3 months after surgery was 90 (80-90). Mean temporal isthmus width was significantly higher in the affected side (involving tumor) than the contralateral one (21.6 vs 11.3 mm; 95% CI: 9.3 to 11.3, P < .01). Muscle strength was grade 4 or higher, and speech was nearly normal in all patients 3 months after surgery. CONCLUSION: Insular glioma surgery using the transtemporal isthmus approach can achieve safe and maximum resection. A widened temporal isthmus provides a surgical pathway for transisthmic resection of insular tumor.

[Sensitivity Analysis of Atmospheric Ozone and Source Apportionment of Volatile Organic Compounds in Yinchuan City].

Based on the observation data of O3 concentration in Yinchuan in 2022, the monthly variation characteristics of O3 concentrations were analyzed. Further, based on the observation data of meteorological elements, conventional pollutants, and volatile organic compounds （VOCs） concentrations at an urban site in Yinchuan from May to July, the difference in meteorological elements and precursor concentrations between the polluted days and the non-polluted days were compared. Then, the O3 sensitivity and the VOCs sources were discussed using the Framework for 0-D Atmospheric Modeling （F0AM） and positive matrix factorization （PMF） model, respectively. The results showed that： ① The O3 pollution occurred from May to July in 2022, and the concentrations of O3-8h-90per were 156 µg·m-3, 170 µg·m-3, and 174 µg·m-3, respectively, with exceeding standard rates of 9.7%, 26.7%, and 29.0%, respectively. ② Compared with those on the non-polluted days, the hourly mean values of temperature, total solar radiation, and concentrations of various precursors on the O3-polluted days increased, including the volume concentrations of propane, isobutane, ethane, n-butane, and dichloromethane, which increased significantly by 33.1%, 29.1%, 25.0%, 22.7%, and 21.3%, respectively. The results showed that the combined increase in pollutant emissions and adverse meteorological conditions contributed to the formation of O3. ③ From May to July 2022, the top five VOCs species in terms of ozone formation potential （OFP） value on whole, non-polluted, and polluted days were the same. They were acetaldehyde, m/p-xylene, ethylene, isoprene, and toluene, mainly from solvent use sources, natural sources, and chemical industry emissions. ④ The local O3 production was mostly controlled by VOCs, and the relative incremental reactivity （RIR） results revealed that O3 production showed strong positive sensitivity to alkene and aromatic hydrocarbon but showed negative sensitivity to NOx on both polluted and non-polluted days. The relative contributions of active species such as acetone, ethylene, and isobutane to O3 production were high, and the implementation of an emission reduction scheme with the ratio of VOCs to NOx emission reduction much greater than 1 could effectively reduce the local O3 concentration. ⑤ The main sources of atmospheric VOCs in Yinchuan were motor vehicle emission sources （32.3%）, process sources （20.7%）, combustion sources （19.2%）, solvent use sources （12.7%）, gasoline volatile sources （9.1%）, and natural sources （6%）, and the contribution rate of motor vehicle emission sources on polluted days increased by 4.6% compared with that on non-polluted days, indicating that the motor vehicle emission source was an important object of summer VOCs control in Yinchuan.

Unraveling the activity trends of T-C2N based Single-Atom catalysts for electrocatalytic nitrate reduction via high-throughput screening.

Electrochemical nitrate reduction reaction (NO3RR) offers a cost-effective and environmentally friendly method to simultaneously yield valuable NH3and alleviate NO3-pollution under mild operating conditions.However, this complicated eight-electron reaction suffers from low selectivity and Faradaic efficiency, which highlight the importance of developing efficient catalysts, but still a critical challenge. Here, a theoretical screening is performed on transition metal-tetragonal carbon nitride (TM@T-C2N) as active and selective electrocatalysts for NO3RR, where detailed reaction mechanisms and activity origins are explored. In addition, five-step screening criteria and volcano plots enable fast prescreening among numerous candidates.We identify that V@T-C2N and Cr@T-C2N are promising candidates with low overpotentials and high selectivity and stability. In particular, a significant negative correlation between the adsorption strength ofnitrate and the Gibbs free energy for the last proton-electron coupling step (*NH2→*NH3) was existed, which is considerably advantaged to track the activity trend and reveal the origin of activity. This work provides theoretical insights into the rational design of TM-N4/C catalysts for NO3RR andpaves a valuable electrochemical screening framework for other multi-step reactions.

Semimetallic state transition in Two-Dimensional carbon nitride covalent networks and enhanced electrocatalytic activity for nitrate to ammonia conversion.

Single-atom catalysts (SACs), due to their maximum atomic utilization rate, show tremendous potential for application in the electrocatalytic synthesis of ammonia from nitrate. Yet, the development of superior supports that preserve the high selectivity, activity, and stability of SACs remains an imperative challenge. In this work, based on first-principles calculations and tight-binding (TB) model analysis, a new two-dimensional (2D) carbon nitride monolayer, C7N6, is proposed. The C7N6 structure exhibits a strong covalent network, with dynamical, thermal, and mechanical stability. Surprisingly, the structural transition from C9N4 to C7N6 corresponds to a semimetallic state transition. Further symmetry analysis unveils that the Dirac states in C7N6 are protected by space-time inversion symmetry, and the physical origin of the Dirac cone was confirmed using the TB model. Additionally, a non-zero Z2 invariant and significant topological edge states demonstrate its topologically nontrivial nature. Considering the excellent structural and topological properties of C7N6, a three-step screening strategy is designed to identify eligible SACs for electrochemical nitrate reduction reaction (NO3RR), and Ti@C7N6 is identified as possessing the best activity, with the last proton-electron coupling step *NH2→*NH3 being the potential-determining step (PDS), for which the limiting potential is 0.48 V. Moreover, a free energy diagram shows that the *NOH reaction pathway is energetically preferred on Ti@C7N6, and ab initio molecular dynamics (AIMD) calculations at 500 K confirm its good thermal stability. Our study not only provides excellent CN-based support material but also offers theoretical guidance for constructing highly active and selective SACs for nitrate reduction.

Xiaoyao Pills, a Chinese patent medicine, treats mild and moderate depression: A randomized clinical trial combined with DNA methylation analysis.

BACKGROUND: Xiaoyao pills (XYP) is a commercial Chinese patent medicine used in the treatment of depression. However, the mechanisms underlying its therapeutic effects, as well as the patients who can benefit from XYP, have not been evaluated so far. OBJECTIVES: To this end, we conducted a double-blinded, random, and placebo-controlled clinical trial of orally administered XYP in patients with depression. METHODS: The 17-item Hamilton Depression Rating Scale (HAMD-17) scores were recorded at baseline, and every 2 weeks after the start of treatment. To further elucidate the epigenetic mechanism of XYP, we performed mRNA sequencing and genome-wide DNA methylation sequencing using peripheral blood leukocytes of patients and healthy. RESULTS: XYP effectively alleviated the symptoms in patients with mild or moderate depressive disorders, particularly that of psychomotor retardation. XYP restored aberrant gene expression and DNA methylation patterns associated with depression, and the normalization of DNA methylation correlated with downregulation of several genes. In addition, altered DNA methylation levels in the XYP-treated samples were attributed to increased expression of the DNA methyltransferase DNMT1. CONCLUSIONS: Our study provides new insights into the epigenetic mechanism underlying depression and the therapeutic effects of XYP, along with an experimental basis for using XYP in the treatment of depression. TRIAL REGISTRATION INFORMATION: The name of the registry and number: U.S. CLINICAL TRIALS REGISTRY: The link to the registration: ClinicalTrials.gov ISRCTN12746343 (https://www.isrctn.com/ISRCTN12746343). The name of the trial register is "Efficacy and safety of the Xiaoyao pill for improving the clinical symptoms of stagnation of liver qi (chi) and spleen deficiency". The clinical trial registration number is ISRCTN12746343.

Designing asymmetrical TMN4 sites via phosphorus or sulfur dual coordination as high-performance electrocatalysts for oxygen evolution reaction.

The development ofhighly efficient oxygen evolution reaction (OER) catalysts based on more cost-effective and earth-abundant elements is of great significance and still faces a huge challenge. In this work, a series of transition metal (TM)embedding a newly-defined monolayer carbon nitride phase is theoretically profiled and constructed as a catalytic platform for OER studies. Typically, a four-step screening strategy was proposed to rapidly identified high performance candidates and the coordination structure and catalytic performance relationship was thoroughly analyzed. Moreover, the eliminating criterion was established to condenses valid range based on the Gibbs free energy of OH*. Our results reveal that the as-constructed 2FeCN/P exhibits superior activity toward OER with an ultralow overpotential of 0.25 V, at the same time, the established 3FeCN/S configuration performed well as abifunctional OER/ORR electrocatalysis with extremely low overpotential ηOER/ηORR of 0.26/0.48 V. Overall, this work provides an effective framework for screening advanced OER catalysts, which can also be extended to other complex multistep catalytic reactions.

Gene expression insights: Chronic stress and bipolar disorder: A bioinformatics investigation.

Bipolar disorder (BD) is a psychiatric disorder that affects an increasing number of people worldwide. The mechanisms of BD are unclear, but some studies have suggested that it may be related to genetic factors with high heritability. Moreover, research has shown that chronic stress can contribute to the development of major illnesses. In this paper, we used bioinformatics methods to analyze the possible mechanisms of chronic stress affecting BD through various aspects. We obtained gene expression data from postmortem brains of BD patients and healthy controls in datasets GSE12649 and GSE53987, and we identified 11 chronic stress-related genes (CSRGs) that were differentially expressed in BD. Then, we screened five biomarkers (IGFBP6, ALOX5AP, MAOA, AIF1 and TRPM3) using machine learning models. We further validated the expression and diagnostic value of the biomarkers in other datasets (GSE5388 and GSE78936) and performed functional enrichment analysis, regulatory network analysis and drug prediction based on the biomarkers. Our bioinformatics analysis revealed that chronic stress can affect the occurrence and development of BD through many aspects, including monoamine oxidase production and decomposition, neuroinflammation, ion permeability, pain perception and others. In this paper, we confirm the importance of studying the genetic influences of chronic stress on BD and other psychiatric disorders and suggested that biomarkers related to chronic stress may be potential diagnostic tools and therapeutic targets for BD.

The surgical strategy and technical nuances of in situ side-to-side bypass for the management of complex intracranial aneurysms.

Background: Despite continuous advances in microsurgical and endovascular techniques, the treatment of complex aneurysms remains challenging. Aneurysms that are dilemmatic for conventional clipping or endovascular coiling often require bypass as part of a strategy to reduce the risk of ischemic complications. In anatomically favorable sites, the intracranial-intracranial in situ bypass may be an appealing choice. This article details the surgical strategies, operative nuances, and clinical outcomes of this technique with a consecutive series in our department. Methods: A retrospective review of a prospectively maintained neurosurgical patient database was performed to identify all patients treated with side-to-side in situ bypass from January 2016 to June 2022. In total, 12 consecutive patients, including 12 aneurysms, were identified and included in the series. The medical records, surgical videos, neuroimaging studies, and follow-up clinic notes were reviewed for every patient. Results: Of the 12 aneurysms, there were 5 middle cerebral artery aneurysms, 4 anterior cerebral artery aneurysms, and 3 posterior inferior cerebellar artery aneurysms. The morphology of the aneurysms was fusiform in 8 patients and saccular in the remaining 4 patients. There were 3 patients presented with subarachnoid hemorrhage. The treatment modality was simple in situ bypass in 8 cases and in situ bypass combined with other modalities in 4 cases. Bypass patency was confirmed in all cases by intraoperative micro-doppler probe and (or) infrared indocyanine green (ICG) video angiography intraoperatively and with digital subtraction angiography (DSA) or computed tomography angiography (CTA) postoperatively. None of the patients developed a clinically manifested stroke due to the procedure though a callosomarginal artery was intentionally removed in one patient. The median follow-up period was 16.2 months (6-36). All patients had achieved improved or unchanged modified Rankin scale scores at the final follow-ups. Conclusion: Cerebral revascularization technique remains an essential skill for the treatment of complex aneurysms. The in situ bypass is one of the most effective techniques to revascularize efferent territory when vital artery sacrifice or occlusion is unavoidable. The configuration of in situ bypass should be carefully tailored to each case, with consideration of variations in anatomy and pathology of the complex aneurysms.

A novel tetragonal T-C2N supported transition metal atoms as superior bifunctional catalysts for OER/ORR: From coordination environment to rational design.

Single-atom catalysts with particular electronic structures and precisely regulated coordination environments delivering excellent activity for oxygen-evolution reaction (OER) and oxygen-reduction reaction (ORR) are highly desirable for renewable energy applications. In this work, a novel tetragonal carbon nitride T-C2N monolayer with remarkable stability was predicted by using the RG2 method. Inspired by the well-defined atomic structures and just right N4 aperture of T-C2N substrate, the electrocatalytic performance of a series of transition metal single-atoms anchored on porous T-C2N matrix (TM@C2N) have been systematically investigated. In addition, machine learning (ML) method was employed with the gradient boosting regression GBR model to deeply explore the complex controlling factors and offer direct guidance for rational discovery of desirable catalysts. On this basis, the coordination environment of the central TM active sites has been tailored by incorporating heteroatoms. Impressively, the Co@C2N/B-C, Rh@C2N/SC and Rh@C2N/SN exhibit significantly enhanced OER/ORR activity with notably low ηOER/ηORR of 0.39/0.32, 0.26/0.35 and 0.37/0.27 V, respectively. Our work provides insights into the rational design, data-driven, performance regulation, mechanism analysis and practical application of TMNC catalysts. Such a systematic theoretical framework can also be expanded to many other kinds of catalysts for energy storage and conversion.

Screening quality markers (Q-markers) of Xiaoer Chaige Tuire Oral Liquid by in vitro sequential metabolism and in vivo biopharmaceutical analysis.

BACKGROUND: Xiaoer Chaige Tuire Oral Liquid (XCT) is a preparation composed of 7 traditional Chinese medicines including Bupleuri Radix, Puerariae Lobatae Radix, Scutellariae Radix, Gypsum Fibrosum, Artemisiae Annuae Herba, Paeoniae Radix Alba and Glycyrrhizae Radix Et Rhizoma Praeparata Cum Melle in proportion. According to traditional Chinese medicine theory, it has the function of dispelling wind evil and relieving exterior syndrome, clearing summer heat and dampness, and reducing internal heat. So, it is indicated for pediatric upper respiratory tract infection caused by exogenous wind-heat. Modern pharmacological studies have indicated that XCT has a variety of activities such as anti-inflammation and antivirus. PURPOSE: To screen potential quality markers (Q-markers) of XCT by tracking in vivo bioactive compounds concomitantly using in vitro sequential metabolism and in vivo biopharmaceutical analysis. METHODS: In vitro metabolic models including artificial gastric juice, intestinal juice, intestinal microbiota, Caco-2 cell monolayer and liver S9 were employed to simulate metabolism of main compounds of XCT in the body. High performance liquid chromatography with diode-array detection (HPLC-DAD) was used to quantitatively determine main components of XCT preparation and its sequential metabolism samples. Ultra performance liquid chromatography with QExactive Orbitrap tandem mass spectrometry (UPLC-QExactive-HF-x-Orbitrap-MS) was used to qualitatively determine in vivo components of XCT preparation in rat plasma and metabolites obtained with liver S9 fraction of rats. RESULTS: Twenty-five compounds were identified from the preparation of XCT. Sequential in vitro metabolism studies indicated that most of these compounds except baicalin and baicalein were stable in artificial gastric juice, albiflorin, glycyrrhizic acid, gallic acid and baicalein were unstable in artificial intestinal juice, daidzin, liquiritin and genistin were hydrolyzed into their aglycones daidzein, liquiritigenin and genistein by intestinal microbiota, and 7 compounds thereout including benzoic acid, puerarin, 3'-methoxypuerarin, paeoniflorin, scopoletin, daidzein and liquiritigenin were shown to be well absorbed with Caco-2 cell monolayer model. These 7 compounds were demonstrated to be metabolized via hydroxylation and glycosylation by liver S9 system. Ten components of XCT preparation including puerarin, baicalin, wogonoside, benzoic acid, daidzein, baicalein, wogonin, oroxylin A, isoscopoletin and isoliquiritigenin were identified from rat plasma by in vivo biopharmaceutical analysis. Most of the compounds screened with both in vitro and in vivo metabolic studies were shown to be active against inflammation and influenza virus. CONCLUSIONS: A screening strategy for potential quality markers (Q-markers) of XCT preparation based on tracking in vivo bioactive compounds using the combination of in vitro sequential metabolism and in vivo biopharmaceutical analysis was established. With this strategy, a total of 12 compounds including puerarin, daidzein, benzoic acid, baicalin, baicalein, wogonoside, wogonin, oroxylin A, 3'-methoxypuerarin, paeoniflorin, scopoletin and liquiritigenin were screened to be potential Q-markers of XCT, which provides a material basis for quality control and development of XCT.

[Characteristics of O3 Production in the Western Suburb of Hefei in Summer Based on the Observation of Total Peroxy Radical].

In August 2020, the observations of total peroxy radical concentrations were carried out in the western suburb site of Hefei using a peroxy radical chemical amplifier (PERCA) instrument. The ozone production and its sensitivity were characterized with the measured O3 and its precursors. The results showed that the daily variation in total peroxy radical concentrations exhibited an obvious convex tend, with the highest value at approximately 12:00; the average peak peroxy radical concentration was 43.8×10-12; and the concentrations of the peroxy radical and ozone were driven by strong solar radiation and high temperature. The photochemical ozone production rate could be determined with peroxy radical and NO concentration. The average ozone peak production rate in summer was 10.6×10-9 h-1, which was more sensitive to NO concentration. Based on the ratio of the radical loss rate due to reactions with NOx to the radical loss rate (Ln/Q), the characteristics of O3 production in the western suburb of Hefei in summer were analyzed. The results showed that O3 production sensitivity varied greatly during the day. The summer O3 production regime shifted from the VOC-sensitive chemistry in the early morning to NOx-sensitive chemistry in the afternoon, and this regime transition typically occurred in the morning.

Pentagram-type Ln15 (Ln = Dy, Tb, Eu, Sm, Ho) clusters with different anion templates: magnetic and luminescence properties.

Five 15-nuclearity lanthanide clusters were obtained under solvothermal conditions based on N-tris(hydroxymethyl)methylglycine (H5thmmg) with molecular formulas Ln15(OH)20(H4thmmg)10(H2O)10·xCl·(15 - x)NO3 (Ln = Dy, x = 15 (1); Ln = Tb, x = 11 (2); Ln = Eu, x = 13 (3); Ln = Sm, x = 15 (4); and Ln = Ho, x = 15 (5)). They have the same pentagram-type metal cores made up of five cubane-like [Ln4(µ3-OH)4] units by sharing vertical Ln3+ ions and their peripheries are all protected by ten H4thmmg- ligands and ten coordinated H2O. Such structural Sm15 and Ho15 clusters are reported for the first time. For 1, 4 and 5, these metal-hydroxide cores are further stabilized only by free Cl- ions, whereas NO3- and Cl- ions both operate as anionic templates for 2 and 3 to balance the positive charge and to promote lanthanide metal ion aggregation. These are the first reported Ln15 clusters self-assembled by NO3- and Cl- anion templates. The luminescence behaviors of 2 and 3 show the characteristic emissions of the corresponding Ln3+ (Ln = Tb, Eu) ions. The temperature-dependent luminescence of 2 and 3 reveals that their emission intensities increase as the temperature drops, and good linear relationships exist in the 120-300 K range, so 2 and 3 are potential luminescent molecular thermometers. Moreover, 2 and 3 exhibit high quantum yields (QYs) (58.05% for 2 and 17.34% for 3) and long luminescence lifetimes (τ = 934 µs for 2, τ = 242 µs for 3). In addition, 1 displays slow magnetic relaxation behavior.

Fabrication of a boron-doped nanocrystalline diamond grown on an WC-Co electrode for degradation of phenol.

Cemented carbide (WC-Co) is applied as the substrate instead of conventional ones such as Si, Ti, and Nb, on which nanocrystalline BDD films are deposited by hot filament chemical vapor deposition. Then the WC-Co/BDD electrodes are investigated by Field Emission Scanning Electron Microscopy (FE-SEM), Micro-Raman Spectroscopy, X-ray photoelectron spectroscopy (XPS), a four-point probe method, accelerated life test (ALT), and electrochemical analysis. According to the results, the BDD films deposited on the WC-Co substrate are highly uniform and pinhole-free with a grain size of 100 nm and a low compressive stress. The WC-Co/BDD electrode has a wide potential window of 3.8 V and low background currents in 0.5 mol L-1 H2SO4 electrolytes and shows a quasi-reversible behavior in the K3[Fe(CN)6] redox system. The electrode has a service life of more than 400 h in the ALT with 3 mol L-1 H2SO4 electrolytes at a constant current density of 1 A cm-2. These electrochemical performances of BDD films on the WC-Co substrate is similar to or even slightly better than that on the commonly used substrates. Finally, phenol is used as a pollutant to test the activity of the WC-Co/BDD electrode. The results of replicated experiments show that the average COD reduces from the initial 5795 to 85 mg L-1, and the average current efficiency is about 46%. This suggests that the WC-Co/BDD electrode has a good mineralization capacity in phenol with a high concentration.

The imaging features and prognosis of gliomas involving the subventricular zone: An MRI study.

RATIONALE AND OBJECTIVES: As the largest concentrated region of neural stem cells in the adult brain, the subventricular zone (SVZ) is considered to have a close relationship with the origin of gliomas. An in-depth study of the characteristic manifestations associated with SVZ involvement in glioma may provide new ideas for individualized diagnosis and treatment of this fatal disease. MATERIALS AND METHODS: All 279 patients with glioma who underwent surgical treatment in our department from January 2016 to December 2021 were included. Clinical and imaging data were collected, and telephonic follow-up was conducted to analyze the overall survival and progression-free survival. Prognostic factors including SVZ involvement on glioblastoma patients' survival were analyzed. Next, the relationship between SVZ involvement, a set of unique imaging features and gene status were determined respectively. The chi-squared test, logistics regression, and Cox regression were used for statistical analysis. RESULTS: The patients were divided into the SVZ involvement group (n = 198, 70.97 %) and SVZ non-involvement group (n = 81, 29.03 %). The median overall survival and progression-free survival were 13 months and 7 months for the SVZ involvement group, but 25 months and 17 months for the SVZ non-involvement group, respectively. In multivariate Cox survival analysis, MRI SVZ involvement proved an independent risk factor for the survival of patients with glioblastoma. The patients with SVZ involvement sign had a lower rate of cystic lesion (32.32 % vs. 48.48 %, p = 0.029), and a larger mean maximum diameter (5.88 ± 1.28 vs. 3.28 ± 1.65 cm). Compared with high grade gliomas (HGG), T1 enhancement (25.25 % vs. 10.42 %, p = 0.041) and homogeneous signal on T2WI (14.14 % vs. 43.75 %, p = 0.025) were independently associated with SVZ involvement in WHO grade 2 gliomas(LGG). In the gene status analysis, the SVZ involvement group showed the lower rate of MGMT promoter methylation (57.58 % vs. 79.17 %, p = 0.017). CONCLUSION: SVZ involvement in MRI at diagnosis is an independent negative prognostic indicator for the survival of glioblastoma patients. Some image signs are associated with SVZ involvement in HGG and LGG respectively. The unique imaging and gene features of gliomas with SVZ involvement indicate that this kind of tumor maybe a unique subgroup of gliomas.

Integrating Metabolomics and Network Analysis for Exploring the Mechanism Underlying the Antidepressant Activity of Paeoniflorin in Rats With CUMS-Induced Depression.

Background: Paeoniflorin (PF) represents the major bioactive constituent of the traditional Chinese medicine plant Paeonia suffruticosa (Ranunculaceae), which has a long history as a folk medicine in Asian. Paeoniflorin, a bitter pinene monoterpene glycoside, has antidepressant effects, but its potential therapeutic mechanism has not been thoroughly explored. Methods: Experimental depression in rats was established by the chronic unpredictable mild stress (CUMS) combined with orphan method, and the efficacy of paeoniflorin on depression was evaluated by the sucrose preference test and open field test. The antidepressant mechanism of paeoniflorin was investigated by metabolomic and network pharmacology. The relevant pathways of biomarkers highlighted in metabolomics were explored, and the possible targets of paeoniflorin in the treatment of depression were further revealed through network analysis. The binding activity of paeoniflorin to key targets was verified by molecular docking. Results: Metabolomics showed that rats with CUMS-induced depression had urine metabolic disorders, which were reversed by paeoniflorin through the regulation of metabolic pathways. Metabolites that play a key role in the function of paeoniflorin include citric acid, thiamine monophosphate, gluconolactone, 5-hydroxyindoleacetic acid and stachyose. Key predicted targets are SLC6A4, TNF, IL6 and SLC6A3. An important metabolic pathway is the Citrate cycle (TCA cycle). Conclusion: Network integrative analysis in this study showed that paeoniflorin could improve depressive-like symptoms in model rats with CUMS-induced depression and overall correct the disordered metabolic profile through multiple metabolic pathways.

Saikosaponin D exerts antidepressant effect by regulating Homer1-mGluR5 and mTOR signaling in a rat model of chronic unpredictable mild stress.

BACKGROUND: Many studies about depression have focused on the dysfunctional synaptic signaling in the hippocampus that drives the pathophysiology of depression. Radix Bupleuri has been used in China for over 2000 years to regulate liver-qi. Extracted from Radix Bupleuri, Saikosaponin D (SSD) is a pharmacologically active substance that has antidepressant effects. However, its underlying mechanism remains unknown. MATERIALS AND METHODS: A chronic unpredictable mild stress (CUMS) paradigm was used as a rat model of depression. SD rats were randomly assigned to a normal control (NC) group or one exposed to a CUMS paradigm. Of the latter group, rats were assigned to four subgroups: no treatment (CUMS), fluoxetine-treated (FLU), high-dose and low-dose SSD-treated (SSDH and SSDL). SSD was orally administrated of 1.50 mg/kg and 0.75 mg/kg/days for three weeks in the SSDH and SSDL groups, respectively. Fluoxetine was administrated at a dose of 2.0 mg/kg/days. SSD's antidepressant effects were assessed using the open field test, forced swim test, and sucrose preference test. Glutamate levels were quantified by ELISA. Western blot and immunochemical analyses were conducted to quantify proteins in the Homer protein homolog 1 (Homer1)-metabotropic glutamate receptor 5 (mGluR5) and mammalian target of rapamycin (mTOR) pathways in the hippocampal CA1 region. To measure related gene expression, RT-qPCR was employed. RESULTS: CUMS-exposed rats treated with SSD exhibited increases in food intake, body weight, and improvements in the time spent in the central are and total distance traveled in the OFT, and less pronounced pleasure-deprivation behaviors. SSD also decreased glutamate levels in CA1. In CA1 region of CUMS-exposed rats, SSD treatment increased mGluR5 expression while decreasing Homer1 expression. SSD also increased expressions of postsynaptic density protein 95 (PSD95) and synapsin I (SYP), and the ratios of p-mTOR/mTOR, p-p70S6k/p70S6k, and p-4E-BP1/4E-BP1 in the CA1 region in CUMS-exposed rats. CONCLUSIONS: SSD treatment reduces glutamate levels in the CA1 region and promotes the expression of the synaptic proteins PSD-95 and SYP via the regulation of the Homer1-mGluR5 and downstream mTOR signaling pathways. These findings suggest that SSD could act as a natural neuroprotective agent in the prevention of depression.

Extracellular Vesicles: Emerging Roles in Developing Therapeutic Approach and Delivery Tool of Chinese Herbal Medicine for the Treatment of Depressive Disorder.

Extracellular vesicles (EVs) are lipid bilayer-delimited particles released by cells, which play an essential role in intercellular communication by delivering cellular components including DNA, RNA, lipids, metabolites, cytoplasm, and cell surface proteins into recipient cells. EVs play a vital role in the pathogenesis of depression by transporting miRNA and effector molecules such as BDNF, IL34. Considering that some herbal therapies exhibit antidepressant effects, EVs might be a practical delivery approach for herbal medicine. Since EVs can cross the blood-brain barrier (BBB), one of the advantages of EV-mediated herbal drug delivery for treating depression with Chinese herbal medicine (CHM) is that EVs can transfer herbal medicine into the brain cells. This review focuses on discussing the roles of EVs in the pathophysiology of depression and outlines the emerging application of EVs in delivering CHM for the treatment of depression.

Visualization and Analysis of the Mapping Knowledge Domain of Acupuncture and Central Nervous System Cell Apoptosis.

Chinese acupuncture therapy has demonstrated good clinical effects on neurological diseases and is widely used internationally. In the past 20 years, an increasing number of researchers around the world have devoted themselves to the study of the effect and mechanism of acupuncture for the treatment of central nervous system cell apoptosis. To discover the current research status of acupuncture-induced antiapoptosis in the central nervous system, we used the method of scientometric research and data visualization software to visually analyse 155 articles. The findings are as follows. First, the antiapoptosis effects of acupuncture in the central nervous system have received increasing attention overseas and domestically. China and the United States have leading positions in this research field. Second, 5 stable and high-yielding research teams have been formed in the field of acupuncture-induced antiapoptosis. The main research directions of these teams are electroacupuncture (EA) pretreatment for the central nervous system cell apoptosis, acupuncture for antineuronal apoptosis in vascular dementia, EA regulation of related signalling pathways, EA regulation of nerve cell apoptosis and autophagy after stroke, and EA regulation of the MAPK signalling pathway. Researchers on teams with more extensive cooperation have more research results and better research continuity. Third, there are diversified research hotspots. The original research hotspots are still receiving attention, and new hotspots have emerged in recent years.