Fast inflows as the adjacent fuel of supermassive black hole accretion disks in quasars.

Quasars, which are exceptionally bright objects at the centres (or nuclei) of galaxies, are thought to be produced through the accretion of gas into disks surrounding supermassive black holes1-3. There is observational evidence at galactic and circumnuclear scales4 that gas flows inwards towards accretion disks around black holes, and such an inflow has been measured at the scale of the dusty torus that surrounds the central accretion disk5. At even smaller scales, inflows close to an accretion disk have been suggested to explain the results of recent modelling of the response of gaseous broad emission lines to continuum variations6,7. However, unambiguous observations of inflows that actually reach accretion disks have been elusive. Here we report the detection of redshifted broad absorption lines of hydrogen and helium atoms in a sample of quasars. The lines show broad ranges of Doppler velocities that extend continuously from zero to redshifts as high as about 5,000 kilometres per second. We interpret this as the inward motion of gases at velocities comparable to freefall speeds close to the black hole, constraining the fastest infalling gas to within 10,000 gravitational radii of the black hole (the gravitational radius being the gravitational constant multiplied by the object mass, divided by the speed of light squared). Extensive photoionization modelling yields a characteristic radial distance of the inflow of approximately 1,000 gravitational radii, possibly overlapping with the outer accretion disk.

Recent advances in the involvement of epigenetics in the pathogenesis of systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is a typical systemic autoimmune disease that manifests as skin rash, arthritis, lymphadenopathy, and multiple organ lesions. Epigenetics, including DNA methylation, histone modification, and non-coding RNA regulation, mainly affect the function and characteristics of cells through the regulation of gene transcription or translation. Increasing evidence indicates that there are a variety of complex epigenetic effects in patients with SLE, which interfere with the differentiation and function of T, and B lymphocytes, monocytes, and neutrophils, and enhance the expression of SLE-associated pathogenic genes. This paper summarizes our currently knowledge regarding pathogenesis of SLE, and introduces current advances in the epigenetic regulation of SLE from three aspects: immune function, inflammatory response, and lupus complications. We propose that epigenetic changes could be used as potential biomarkers and therapeutic targets of SLE.

CYP2E1 deficit mediates cholic acid-induced malignant growth in hepatocellular carcinoma cells.

BACKGROUND: Increased level of serum cholic acid (CA) is often accompanied with decreased CYP2E1 expression in hepatocellular carcinoma (HCC) patients. However, the roles of CA and CYP2E1 in hepatocarcinogenesis have not been elucidated. This study aimed to investigate the roles and the underlying mechanisms of CYP2E1 and CA in HCC cell growth. METHODS: The proteomic analysis of liver tumors from DEN-induced male SD rats with CA administration was used to reveal the changes of protein expression in the CA treated group. The growth of CA-treated HCC cells was examined by colony formation assays. Autophagic flux was assessed with immunofluorescence and confocal microscopy. Western blot analysis was used to examine the expression of CYP2E1, mTOR, AKT, p62, and LC3II/I. A xenograft tumor model in nude mice was used to examine the role of CYP2E1 in CA-induced hepatocellular carcinogenesis. The samples from HCC patients were used to evaluate the clinical value of CYP2E1 expression. RESULTS: CA treatment significantly increased the growth of HCC cells and promoted xenograft tumors accompanied by a decrease of CYP2E1 expression. Further studies revealed that both in vitro and in vivo, upregulated CYP2E1 expression inhibited the growth of HCC cells, blocked autophagic flux, decreased AKT phosphorylation, and increased mTOR phosphorylation. CYP2E1 was involved in CA-activated autophagy through the AKT/mTOR signaling. Finally, decreased CYP2E1 expression was observed in the tumor tissues of HCC patients and its expression level in tumors was negatively correlated with the serum level of total bile acids (TBA) and gamma-glutamyltransferase (GGT). CONCLUSIONS: CYP2E1 downregulation contributes to CA-induced HCC development presumably through autophagy regulation. Thus, CYP2E1 may serve as a potential target for HCC drug development.

A Novel Hydrated Iron Vanadate Cathode Material for Advanced Aqueous Nickel-Ion Batteries.

Aqueous nickel-ion batteries (ANIBs) as an emerging energy storage device attracted much attention owing to their multielectron redox reaction and dendrite-free Ni anode, yet their development is hindered by the divalent properties of Ni2+ and the lack of suitable cathode materials. Herein, a hydrated iron vanadate (Fe2V3O10.5∙1.5H2O, FOH) with a preferred orientation along the (200) plane is innovatively proposed and used as cathode material for ANIBs. The FOH cathode exhibits a remarkable capacity of 129.3 mAh g-1 at 50 mA g-1 and a super-high capacity retention of 95% at 500 mA g-1 after 700 cycles. The desirable Ni2+ storage capacity of FOH can be attributed to the preferentially oriented and tunnel structures, which offer abundant reaction active planes and a broad Ni2+ diffusion path, the abundant vacancies and high specific surface area further increase ion storage sites and accelerate ion diffusion in the FOH lattice. Furthermore, the Ni2+ storage mechanism and structural evolution in the FOH cathode are explored through ex situ XRD, ex situ Raman, ex situ XPS and other ex situ characteristics. This work opens a new way for designing novel cathode materials to promote the development of ANIBs.

The Impact of Health Education Based on the Pender Health Promotion Model on Patients with Deep Vein Thrombosis of the Lower Limbs Treated with Rivaroxaban.

Objective: To evaluate the impact of Pender-based health education on outcomes in rivaroxaban-treated lower limb DVT patients. Methods: 103 patients with DVT of the lower limbs treated with rivaroxaban admitted to The First Affiliated Hospital of Xi'an Jiaotong University from January 2022 to January 2023 were included in the study and were randomly divided into the conventional group (n=52, receiving routine care with medication instruction, exercise instruction, and psychological care as the main components) and the Pender group (n=51, giving health education based on the Pender health promotion model in addition to conventional care) to compare the recurrence rate of DVT of the lower limbs, DVT of the lower limbs clinical condition, complication rate, quality of life score, coagulation index and nursing satisfaction rate in the two groups. Primary results: The recurrence rate of lower limb DVT, circumference of the affected limb, time to get out of bed, and time to reduce swelling in the Pender group were lower (shorter) than those in the conventional group (P < .05); after the intervention, all quality of life scores in the Pender group were higher than those in the conventional group (P < .05). Secondary results: The complication rate, fibrinogen (FIB) and D-dimer (D-D) levels were lower (shorter) in the Pender group than in the conventional group (P < .05). After the intervention, the levels of activated partial thromboplastin time (APTT), prothrombin time (PT), and thrombin time (TT) were higher in the Pender group than in the conventional group (P < .05). Conclusion: The health education based on the Pender health promotion model is effective in patients with lower limb DVT treated with rivaroxaban, which can effectively reduce recurrence and complications, optimize coagulation indexes, and improve the quality of life and nursing care satisfaction by improving the patients' health cognition and health behaviors, which is of great value in clinical application and promotion.

Protocatechuic acid prevents isoproterenol-induced heart failure in mice by downregulating kynurenine-3-monooxygenase.

Protocatechuic acid (3,4-dihydroxybenzoic acid) prevents oxidative stress, inflammation and cardiac hypertrophy. This study aimed to investigate the therapeutic effects of protocatechuic acid in an isoproterenol-induced heart failure mouse model and to identify the underlying mechanisms. To establish the heart failure model, C57BL/6NTac mice were given high-dose isoproterenol (80 mg/kg body weight) for 14 days. Echocardiography revealed that protocatechuic acid reversed the isoproterenol-induced downregulation of fractional shortening and ejection fraction. Protocatechuic acid attenuated cardiac hypertrophy as evidenced by the decreased heart-weight-to-body-weight ratio and the expression of Nppb. RNA sequencing analysis identified kynurenine-3-monooxygenase (Kmo) as a potential target of protocatechuic acid. Protocatechuic acid treatment or transfection with short-interfering RNA against Kmo ameliorated transforming growth factor ß1-induced upregulation of Kmo, Col1a1, Col1a2 and Fn1 in vivo or in neonatal rat cardiac fibroblasts. Kmo knockdown attenuated the isoproterenol-induced increase in cardiomyocyte size, as well as Nppb and Col1a1 expression in H9c2 cells or primary neonatal rat cardiomyocytes. Moreover, protocatechuic acid attenuated Kmo overexpression-induced increases in Nppb mRNA levels. Protocatechuic acid or Kmo knockdown decreased isoproterenol-induced ROS generation in vivo and in vitro. Thus, protocatechuic acid prevents heart failure by downregulating Kmo. Therefore, protocatechuic acid and Kmo constitute a potential novel therapeutic agent and target, respectively, against heart failure.

BACE1 SUMOylation deregulates phosphorylation and ubiquitination in Alzheimer's disease pathology.

BACE1 is essential for the generation of amyloid-ß (Aß) that likely initiates the toxicity in Alzheimer's disease (AD). BACE1 activity is mainly regulated by post-translational modifications, but the relationship between these modifications is not fully characterized. Here, we studied the effects of BACE1 SUMOylation on its phosphorylation and ubiquitination. We demonstrate that SUMOylation of BACE1 inhibits its phosphorylation at S498 and its ubiquitination in vitro. Conversely, BACE1 phosphorylation at S498 suppresses its SUMOylation, which results in promoting BACE1 degradation in vitro. Furthermore, an increase in BACE1 SUMOylation is associated with the progression of AD pathology, while its phosphorylation and ubiquitination are decreased in an AD mouse model. Our findings suggest that BACE1 SUMOylation reciprocally influences its phosphorylation and competes against its ubiquitination, which might provide a new insight into the regulations of BACE1 activity and Aß accumulation.

Integrated metabolomics and transcriptomics analyses reveal the key genes regulating differential metabolites of longissimus dorsi muscle in castrated South Sichuan black goats (Capra hircus).

The main aim of the current work was to explore the differential metabolites and differentially expressed genes of longissimus dorsi muscle (LDM) between castrated and uncastrated fattening male South Sichuan black goats (Capra hircus). Then, the key genes regulating important differential metabolites (DMs) in castrated male goats were observed by integrated metabolomics and transcriptomics analyses. In addition, we evaluated the effects of castration on blood constituents, dressing percentage, and water holding capacity of LDM in male black goats. The results showed that the concentrations of alkaline phosphatase (ALP), total cholesterol (TC), triglyceride (TG), and low-density lipoprotein cholesterol (LDL-C) were significantly increased and testosterone was significantly decreased in castrated male goats compared with the uncastrated male goats, while dressing percentage of black goats and water holding capacity of longissimus dorsi muscle were not significant differences. Through metabolomics and transcriptomics analyses, 23 important KEGG pathways, 13 important DMs, 32 important differentially expressed genes (DEGs), and 13 key genes related to the "Metabolism" and "Organismal systems" pathways were screened. Lipid accumulation may be elevated in the blood of fattening South Sichuan black goats after castration. Castration might play a positive role in energy provision, intercellular signaling, muscle function, softening of meat, disease reduction, and anti-oxidation of LDM. P4HA2, AKR1B1, GPT2, L2HGDH, ENSCHIG00000021660, ENSCHIG00000023861, DGAT2, ULK1, SLC38A3, PLA2G4A, SLC6A1, ENSCHIG00000026624, and ND2 might be the key genes regulating important DMs in the KEGG pathways related to "Metabolism" and "Organismal systems" of castrated male goats compared with the uncastrated male goats.

Autophagy blockage and lysosomal dysfunction are involved in diallyl sulfide-induced inhibition of malignant growth in hepatocellular carcinoma cells.

Diallyl sulfide (DAS), as a major component of garlic extracts, has been shown to inhibit growth of hepatocellular carcinoma cells (HCC), but the underlying mechanism is still elusive. In this study, we aimed to explore the involvement of autophagy in DAS-induced growth inhibition of HepG2 and Huh7 hepatocellular carcinoma cells. We studied growth of DAS-treated HepG2 and Huh7 cells using the MTS and clonogenic assays. Autophagic flux was examined by immunofluorescence and confocal microscopy. The expression levels of autophagy-related proteins AMPK, mTOR, p62, LC3-II, LAMP1, and cathepsin D in the HepG2 and Huh7 cells treated with DAS as well as the tumors formed by HepG2 cells in the nude mice in the presence or absence of DAS were examined using western blotting and immunohistochemistry analysis. We found that DAS treatment induced activation of AMPK/mTOR, and accumulation of LC3-II and p62 both in vivo and in vitro. DAS inhibited autophagic flux through blocking the fusion of autophagosomes with lysosomes. Furthermore, DAS induced an increase in lysosomal pH and inhibition of Cathepsin D maturation. Co-treatment with an autophagy inhibitor (Chloroquine, CQ) further enhanced the growth inhibitory activity of DAS in HCC cells. Thus, our findings indicate that autophagy is involved in DAS-mediated growth inhibition of HCC cells both in vitro and in vivo.

[Comparison of alkaloids in Aconiti Kusnezoffii Radix, Aconiti Radix, and Aconiti Lateralis Radix Praeparata based on UHPLC-Q-Exactive Orbitrap MS/MS].

UHPLC-Q-Exactive Orbitrap MS/MS was used to systematically analyze and compare the alkaloids in Aconiti Kusnezoffii Radix, Aconiti Radix, and Aconiti Lateralis Radix Praeparata. After the samples were pretreated in the solid-phase extraction cartridges, 0.1% ammonium hydroxide(A)-acetonitrile(B) was used for gradient elution. The LC-MS method for characterization of alkaloids in the three herbal medicines was established in ESI positive ion mode to collect high resolution MS data of reference substances and samples. On the basis of the information of reference substance cracking behavior, retention time, accurate molecular mass, and related literature, a total of 155 alkaloids were identified in Aconiti Kusnezoffii Radix, Aconiti Radix, and Aconiti Lateralis Radix Prae-parata. Specifically, 130, 127, and 92 alkaloids were identified in Aconiti Kusnezoffii Radix, Aconiti Radix, and Aconiti Lateralis Radix Praeparata, respectively. Monoester alkaloids and amino-alcohol alkaloids were dominant in the three herbal medicines, and the alkaloids in Aconiti Kusnezoffii Radix and Aconiti Radix were similar. This paper can provide a reference for elucidating the pharmacological effects and clinical application differences of the three herbal medicines produced from plants of Aconitum.

Quantitative Susceptibility Mapping of Brain Iron Relating to Cognitive Impairment in Hypertension.

BACKGROUND: Hypertension (HTN) might impair cognition. Brain iron deposition correlates with cognitive impairment. The relationship between brain iron and cognition in HTN patients is less clear. PURPOSE: To measure brain susceptibility in HTN patients using quantitative susceptibility mapping (QSM) and to explore the relationship between brain iron and cognition. STUDY TYPE: Retrospective cross-sectional study. SUBJECTS: Sixty HTN patients (35 with mild cognitive impairment [MCI] and 25 without MCI) and 24 age, gender, and education matched controls. FIELD STRENGTH/SEQUENCE: 3 T; strategically acquired gradient echo (STAGE) imaging protocol for QSM analysis. ASSESSMENT: All subjects underwent Montreal Cognitive Assessment (MoCA) scoring of visuospatial/executive, naming, attention, abstraction, language, delayed memory, and orientation functions. HTN patients were divided into two groups (with and without MCI) depending on the MoCA score. Regions of interest (ROIs) were manually demarcated on the STAGE images by three independent radiologists and susceptibility were determined for bilateral frontal white matter, parietal white matter, occipital white matter, caudate nucleus (CN), putamen (PU), globus pallidus (GP), thalamus (TH), red nucleus (RN), substantia nigra (SN), and dentate nucleus (DN). STATISTICAL TESTS: Analysis of variance with post-hoc least significant difference (LSD) tests and Pearson correlation coefficients (r). A P-value <0.05 was considered to be statistically significant. RESULTS: The susceptibility was significantly different in CN, PU, and DN among the three groups. The susceptibility of right CN and left PU were correlated with MoCA scores (r = -0.429 and r = -0.389, respectively). The susceptibility of left PU was also correlated with delayed memory scores (r = -0.664). The susceptibility of left and right GP were correlated with naming scores (r = -0.494 and r = -0.446, respectively) and the susceptibility of left DN were correlated with visuospatial/executive scores (r = 0.479). DATA CONCLUSION: QSM measured brain iron was significantly higher in CN, PU, and DN in HTN patients. Cognitive impairment was correlated with regional brain iron deposition. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 3.

N,N-Diisopropylethylamine-Mediated Electrochemical Reduction of Azobenzenes in Dichloromethane.

We report a cathodic reduction-dominated electrochemical approach for the hydrogenation of azobenzenes in dichloromethane. With cheap and readily available N,N-diisopropylethylamine as a catalytic mediator, the reaction proceeded smoothly in a simple undivided cell under constant-current electrolysis. A series of azobenzenes were successfully reduced to the corresponding hydrazobenzenes in moderate to high yields at room temperature. Preliminarily mechanistic studies indicate that solvent dichloromethane acts as a hydrogen source. The use of a common solvent as a hydrogen source, no need for stoichiometric mediators or metallic reductants, and mild conditions make this work a more straightforward and sustainable protocol for hydrogenation of azobenzenes.

Quantitative assessment of normal hip cartilage in children under 9 years old by T2 mapping.

OBJECTIVE: To investigate the variation in T2 at different zones of normal hip cartilage in children and the relationship between T2 value and age. MATERIALS AND METHODS: Nineteen children with 30 normal hip joints were evaluated with a coronal T2 mapping sequence at a 3-Tesla MRI system. The femoral cartilage and acetabular cartilage were firstly segmented by mask-based interactive method and then equally divided into eight and six radial sections, respectively. Moreover, each radial section was further divided into two layers referring to the superficial and deep halves of the corresponding cartilage. Cartilage T2 of these sections and layers were measured and subsequently analyzed. RESULTS: There was a negative correlation between the T2 values in the hip cartilage and the age of children (rs < - 0.6, P1 < 0.05). Articular cartilage T2 increased at angles close to the magic angle (54.7°). Femoral cartilage and acetabular cartilage had a relatively shorter T2 in the radial sections near the vertex of the femoral head. The T2 values in superficial layers of both cartilages were significantly higher than those in deep layers (P < 0.05). CONCLUSION: The T2 value decreases as the cartilage developing into a more mature state. Cartilage T2 values in the weight-bearing areas are relatively low due to an increase of collagen density and the loss of interstitial water. The restriction of the water molecules by solid components in the deeper layer of cartilage may decrease the T2 values.

Prevalence of preoperative Deep Venous Thrombosis (DVT) following elderly intertrochanteric fractures and development of a risk prediction model.

BACKGROUND: This study aimed to investigate the prevalence of preoperative deep venous thrombosis (DVT) following intertrochanteric fractures in the elderly and identify the associated factors, based on which a risk prediction model was developed. METHOD: This was a retrospective single-center study of elderly patients presenting with intertrochanteric fractures between our institution between January 2017 and December 2020. Patients' duplex ultrasound (DUS) or venography results were retrieved to evaluate whether they had a preoperative deep venous thrombosis (DVT) of bilateral extremities, whereby patients were dichotomized. Various variables of interest on demographics, comorbidities, injury and biomarkers were extracted and their relationship between DVT were investigated. Statistically significant variables tested in multivariate logistics regression analyses were used to develop a risk prediction model. RESULTS: There were 855 patients eligible to be included in this study, and 105 were found to have preoperative DVT, with a prevalence rate of 12.3%. Ten factors were tested as significantly different and 2 marginally significant between DVT and non-DVT groups in the univariate analyses, but only 6 demonstrated the independent effect on DVT occurrence, including history of a VTE event (OR, 4.43; 95%CI, 2.04 to 9.62), time from injury to DVT screening (OR, 1.19; 95%CI, 1.13 to 1.25), BMI (OR, 1.11; 95%CI, 1.04-1.18), peripheral vascular disease (OR, 2.66; 95%CI, 1.10 to 6.40), reduced albumin (2.35; 95%CI, 1.48 to 3.71) and D-Dimer > 1.0 mg/L(OR, 1.90; 95%CI, 1.13 to 3.20). The DVT risk model showed an AUC of 0.780 (95%CI, 0.731 to 0.829), with a sensitivity of 0.667 and a specificity of 0.777. CONCLUSION: Despite without a so high prevalence rate of DVT in a general population with intertrochanteric fracture, particular attention should be paid to those involved in the associated risk factors above. The risk prediction model exhibited the improved specificity, but its validity required further studies to verify.

Initial experiences of transapical beating-heart mitral valve repair with a novel artificial chordal implantation device.

BACKGROUND: Severe mitral regurgitation (MR) is associated with progressive heart failure and impairment of survival. Degenerative MR accounts for most MV repair surgeries. Conventional mitral valve repair surgery requires cardiopulmonary bypass and is associated with significant morbidity and risks. Transapical beating-heart mitral valve repair by artificial chordae implantation with transesophageal echocardiography (TEE) guidance has the potential to significantly reduce surgical morbidity. We report the first-in-human experience of degenerative MR repair using a novel artificial chordae implantation device (MitralstitchTM system). METHODS: Ten patients with severe MR underwent transapical artificial chordae implantation using MitralstitchTM system. The procedure was performed through a small left thoracotomy under general anesthesia and TEE guidance. Patients underwent transthoracic echocardiography and other assessments during the follow-up. RESULTS: All 10 patients with an average age of 63.7 ± 9.6 years successfully received transapical artificial chordae implantation. Their MR reduced from severe to none or trace in five patients, mild in five patients before discharge. Five patients received one artificial chordal implantation, four patients received two, and one patient received three and edge-to-edge repair by locking two of them. The safety and efficacy endpoint were achieved in all patients at 1-month follow-up. At 1-year follow-up, six patients had mild MR, three patients had moderate MR, one patient had recurrence of severe MR and underwent surgical repair. CONCLUSIONS: The results of this first-in-human study show safety and feasibility of transapical mitral valve repair using MitralStitch system. Patient selection and technical refinement are crucial to improve the outcomes.

Estrogen receptor-α36 is involved in diallyl sulfide-induced inhibition of malignant growth of HepG2 and Huh7 hepatocellular carcinoma cells.

Hepatocellular carcinoma (HCC) is a highly malignant disease that currently lacks effective treatment. Epidemiological studies have suggested the preventive role of raw garlic intake in different tumors, such as HCC. Although diallyl sulfide (DAS), the main component of garlic extracts, has been reported to inhibit the growth of HCC cells, the underlying mechanism remains elusive. This study aimed to investigate the inhibitory effect of DAS on the growth of HepG2 and Huh7 hepatocellular carcinoma cells and its underlying mechanism. HepG2 and Huh7 cells were treated with DAS and nude mice were intrahepatically injected with human HCC HepG2 cells and maintained with or without DAS administration for 28 days. MTS and clonogenic assays revealed that DAS inhibited the growth and clonogenicity of HepG2 and Huh7 hepatocellular carcinoma cells. Furthermore, DAS inhibited the growth of xenograft tumors accompanied by a decreased rate of pathological karyomitosis as observed by H&E staining. The expression levels of estrogen receptor-α36 (ER-α36) and epidermal growth factor receptor (EGFR) in HepG2 and Huh7 cells and in xenograft tumors derived from HepG2 cells after DAS treatment were detected by immunohistochemistry and western blotting. We found that DAS disrupted the positive regulatory loop between ER-α36 and EGFR, and decreased the phosphorylation of AKT at Ser 473 both in vivo and in vitro. DAS also induced cell apoptosis, as evidenced by Hoechst and TUNEL staining. Western blotting revealed activation of caspase3, increased BAX and decreased Bcl-2 expression. However, the ER-α36 expression knockdown attenuated DAS-induced ERK and AKT phosphorylation in HCC cells. DAS was also able to inhibit ER-α36-mediated activation of the MAPK/ERK signaling induced by estrogen. Thus, our results indicate that ER-α36 signaling is involved in DAS-induced inhibition of HCC cell growth both in vitro and in vivo.

[Identification of metabolites of imperatorin in rats: based on UHPLC-Q-Exactive Orbitrap MS].

This study aims to identify and analyze the metabolites of imperatorin in rats by UHPLC-Q-Exactive Orbitrap MS. Specifically, after rats were treated(ig) with imperatorin, the plasma, urine, and feces were collected, and the samples were processed by solid phase extraction. Then, UHPLC-Q-Exactive Orbitrap MS was performed. In MS, 0.1% formic acid water(A)-acetonitrile(B) was applied as mobile phase for gradient elution and the data of MS in both positive and negative ion modes were collected. The metabolites of imperatorin in blood, urine, and feces of rats were analyzed to explore the metabolic pathways of imperatorin in rats. According to accurate molecular weight, multistage MS data, MS fragmentation rule of the standard substance, and previous reports, a total of 51 metabolites were identified, with 35, 40, and 16 from plasma, urine, and feces, separately. The main metabolic pathways were oxidization, glucuronidation, isopentenyl removal, sulphation, carboxylation, among others. The conclusion in this study is expected to serve as a reference for the further development and the further pharmacodynamics study of imperatorin.

Neuroprotective effects of four different fluids on cerebral ischaemia/reperfusion injury in rats through stabilization of the blood-brain barrier.

Protecting the blood-brain barrier (BBB) is a potential strategy to treat cerebral ischaemic injury. We previously reported that hypertonic sodium chloride hydroxyethyl starch 40 (HSH) treatment alleviates brain injury induced by transient middle cerebral artery occlusion (tMCAO). However, other fluids, including 20% mannitol (MN), 3% hypertonic sodium chloride (HTS) and hydroxyethyl starch 130/0.4 solution (HES), have the same effect as HSH in cerebral ischaemia/reperfusion injury (CI/RI) remains unclear. The present study evaluated the protective effects of these four fluids on the BBB in tMCAO rats. Sprague-Dawley (SD) rats were randomly assigned to six groups. A CI/RI rat model was established by tMCAO for 120 min followed by 24 h of reperfusion. The sham and tMCAO groups were treated with normal saline (NS), whereas the other four groups were treated with the four fluids. After 24 h of reperfusion, neurological function, brain oedema, brain infarction volume, permeability of the BBB, cortical neuron loss and protein and mRNA expression were assessed. The four fluids (especially HSH) alleviated neurological deficits and decreased the infarction volume, brain oedema, BBB permeability and cortical neuron loss induced by tMCAO. The expression levels of GFAP, IL-1ß, TNF-α, MMP-9, MMP-3, AQP4, MMP-9, PDGFR-ß and RGS5 were decreased, whereas the expression levels of laminin and claudin-5 were increased. These data suggested that small-volume reperfusion using HSH, HES, MN and HTS ameliorated CI/RI, probably by attenuating BBB disruption and postischaemic inflammation, with HSH exerting the strongest neuroprotective effect.

SubMito-XGBoost: predicting protein submitochondrial localization by fusing multiple feature information and eXtreme gradient boosting.

MOTIVATION: Mitochondria are an essential organelle in most eukaryotes. They not only play an important role in energy metabolism but also take part in many critical cytopathological processes. Abnormal mitochondria can trigger a series of human diseases, such as Parkinson's disease, multifactor disorder and Type-II diabetes. Protein submitochondrial localization enables the understanding of protein function in studying disease pathogenesis and drug design. RESULTS: We proposed a new method, SubMito-XGBoost, for protein submitochondrial localization prediction. Three steps are included: (i) the g-gap dipeptide composition (g-gap DC), pseudo-amino acid composition (PseAAC), auto-correlation function (ACF) and Bi-gram position-specific scoring matrix (Bi-gram PSSM) are employed to extract protein sequence features, (ii) Synthetic Minority Oversampling Technique (SMOTE) is used to balance samples, and the ReliefF algorithm is applied for feature selection and (iii) the obtained feature vectors are fed into XGBoost to predict protein submitochondrial locations. SubMito-XGBoost has obtained satisfactory prediction results by the leave-one-out-cross-validation (LOOCV) compared with existing methods. The prediction accuracies of the SubMito-XGBoost method on the two training datasets M317 and M983 were 97.7% and 98.9%, which are 2.8-12.5% and 3.8-9.9% higher than other methods, respectively. The prediction accuracy of the independent test set M495 was 94.8%, which is significantly better than the existing studies. The proposed method also achieves satisfactory predictive performance on plant and non-plant protein submitochondrial datasets. SubMito-XGBoost also plays an important role in new drug design for the treatment of related diseases. AVAILABILITY AND IMPLEMENTATION: The source codes and data are publicly available at https://github.com/QUST-AIBBDRC/SubMito-XGBoost/. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Immunoadsorption with staphylococcal protein A column in autoimmune encephalitis.

BACKGROUND: Early treatment has a positive effect on autoimmune encephalitis. However, different treatments have individual differences and corresponding contraindications in the clinical. Few reports have described the application of immunoadsorption with Staphylococcal Protein A Column (SPA-IA) in neuroimmune diseases. We aimed to observe the safety and efficiency of SPA-IA in autoimmune encephalitis. PATIENTS AND METHODS: We retrospectively analyzed three cases of autoimmune encephalitis wherein the first-line treatment was ineffective or contraindicated. The clinical features and prognosis during and after SPA-IA are described in detail. RESULTS: All patients were definitely diagnosed with autoimmune encephalitis. After treated with SPA-IA, all antibody titers, except for the serum antibody titer in Patient 2, were markedly decreased in both the cerebral spinal fluid and serum. The mean fibrinogen levels before and after SPA-IA were stable, and there were no clinical bleeding events. The modified Rankin Scale scores and their symptoms improved significantly after the last SPA-IA session or 3 months later. CONCLUSIONS: SPA-IA may be a viable, efficacious, and safe treatment alternative for autoimmune encephalitis with contraindications to traditional treatment or poor response.