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Abstract Based on our previous findings that salicylic acid and jasmonic acid increased Nostoc flagelliforme polysaccharide yield by regulating intracellular nitric oxide (NO) levels, the mechanism through which NO affects polysaccharide biosynthesis in Nostoc flagelliforme was explored from the perspective of S-nitrosylation (SNO). The addition of NO donor and scavenger showed that intracellular NO had a significant positive effect on the polysaccharide yield of N. flagelliforme. To explore the mechanism, we investigated the relationship between NO levels and the activity of several key enzymes involved in polysaccharide biosynthesis, including fructose 1,6-bisphosphate aldolase (FBA), glucokinase (GK), glucose 6-phosphate dehydrogenase (G6PDH), mitochondrial isocitrate dehydrogenase (ICDH), and UDP-glucose dehydrogenase (UGDH). The enzymatic activities of G6PDH, ICDH, and UGDH were shown to be significantly correlated with the shifts in intracellular NO levels. For further validation, G6PDH, ICDH, and UGDH were heterologously expressed in Escherichia coli and purified via Ni+-NAT affinity chromatography, and subjected to a biotin switch assay and western blot analysis, which revealed that UGDH and G6PDH were susceptible to SNO. Furthermore, mass spectrometry analysis of proteins treated with S-nitrosoglutathione (GSNO) identified the SNO modification sites for UGDH and G6PDH as cysteine 423 and cysteine 249, respectively. These findings suggest that NO modulates polysaccharide biosynthesis in N. flagelliforme through SNO of UGDH and G6PDH. This reveals a potential mechanism through which NO promotes polysaccharide synthesis in N. flagelliforme, while also providing a new strategy for improving the industrial production of polysaccharides.

Background and objectives: Studies on the effects of airborne particulates of diameter ≤ 1 µm (PM1), airborne particulates of diameter ≤ 2.5 µm (PM2.5) and airborne particulates of diameter ranges from 1 to 2.5 µm (PM1–2.5) on incidence of hyperuricemia are limited. We aimed to investigate the associations between PM1, PM2.5, and PM1–2.5 and hyperuricemia among male traffic officers. Methods: We conducted a prospective cohort study of 1460 traffic officers without hyperuricemia in Guangzhou, China from 2009 to 2016. Exposures of PM1 and PM2.5 were estimated with a spatiotemporal model. PM1–2.5 concentrations were calculated by subtracting PM1 from PM2.5 concentrations. Cox's proportional hazards regressions models were used to examine the association between PM1, PM2.5, and PM1–2.5 and hyperuricemia, adjusted for potential confounders. Associations between PM1, PM2.5, and PM1–2.5 and serum uric acid (SUA) levels were evaluated with multiple linear regression models. Results: Hazard ratios (HRs) and 95% confidence intervals (CIs) of hyperuricemia associated with 10 μg/m3 increment in PM1, PM2.5, and PM1–2.5 were 1.67 (95% CI:1.30–2.36), 1.49 (95% CI: 1.27–1.75), and 2.18 (95% CI: 1.58–3.02), respectively. The SUA concentrations increased by 12.23 μmol/L (95% CI: 5.91–18.56), 6.93 μmol/L (95% CI: 3.02–10.84), and 8.72 μmol/L (95% CI: 0.76–16.68) per 10 μg/m3 increase in PM1, PM2.5, and PM1–2.5, respectively. Stratified analyses indicated the positive associations of PM2.5 and PM1–2.5 with SUA levels were stronger in non-smokers, and PM1, PM2.5, and PM1–2.5 with SUA levels were stronger in non-drinkers. Conclusion: Long-term PM1, PM2.5, and PM1–2.5 exposures may increase the risk of hyperuricemia and elevate SUA levels among male traffic officers, especially in non-smokers and non-drinkers.

Taxol is a precious and effective anticancer drug. Cerium and methyl jasmonate (MJ) have been shown to increase the yield of taxol in taxus cells. However, the mechanisms of cerium-mediated and MJ-mediated taxol biosynthesis remain unknown. RNA-Seq was applied to study the overall regulation mechanism of cerium and MJ on taxol biosynthesis and analyze the differences among T. mairei cells elicited by Ce3+, Ce4+ and MJ on transcriptional level . Using sequence homology, 179 unigenes were identified as taxol synthesis genes. Under the condition of 100 μM MJ, taxol synthesis genes were up-regulated. Notably, taxol synthesis genes were down-regulated expression at 1 mM Ce3+ and 1 mM Ce4+. Differential expression genes involved in some related functions were analyzed, such as MAPK signaling pathway and plant-pathogen interaction. Sequence alignment and phylogenetic analysis of nine differentially expressed WRKYs in our data were carried out.

Objective To evaluate the clinical value of bedside ultrasound measurement of optic nervesheath diameter (ONSD) in the prognosis of severe traumatic brainin jury (sTBI). Methods Atotal of 78 sTBI patients admitted to Department of Neurosurgery ICU of He'nan Provincial People's Hospital from April 2017 to April 2019 were enrolled. Intracranial pressure (ICP) monitoring probe was placed when the patient was admitted, and bedside ultrasound was used to detect the ONSD. The values of ONSD in supine position and 30° head⁃up position, 30min before and after ventilation, and 30min before and after mannitol treatment were observed and analyzed. Receiver operating characteristic curve (ROC) was used to analyze the predictive value of ONSD for unfavourable prognosis of sTBI patients. Results The mean ICP in unfavourable prognosis group [Glasgow Outcome Scale (GOS) score 1-3] was higher than that in favourable prognosis group (GOS score 4-5; t=2.111, P=0.038). After 30° head⁃up position, 30 min after ventilation and mannitol treatment, the values of ONSD were lower than supine position (F=6.644, P= 0.012),and30 min befor eventilation (F=4.492, P=0.037) and mannitol treatment (F=5.552, P=0.021), and ONSD in unfavourable prognosis group were higher than those in favourable prognosis group (posture change: F=16.751, P=0.000; ventilation treatment: F=29.776, P=0.000; application of mannitol: F= 12.465, P=0.002). There was a positive correlation between ONSD and ICP (r=0.691, P=0.000). ONSD at 5.53 mm was the optimal threshold for unfavourable prognosis, the area under the curve (AUC) was 0.776 (95%CI: 0.826-0.978, P =0.000). The sensitivity was 91.52% and the specificity was 87.14%. Conclusions Dynamic detection of ONSD by bedside ultrasound is helpful to evaluate the prognosis of sTBI, and guide the precise treatment of severe ICP. DOI：10.3969/j.issn.1672⁃6731.2020.08.006

Exogenous toxicants (e.g. arsenic, cigarette smoke), trigger oxidative stress, and initiate the pathogenesis of many human diseases. Induction of nuclear factor E2-related factor 2 (Nrf2) counteracts exogenous toxicant-induced oxidative insults. Using a high-throughput screen, we firstly identified a citrus polymethoxyflavone, (2S)-5,6,7,3′,4′-pentamethoxyflavanone (PMF), to be an Nrf2 activator, and an investigation targeting Nrf2 pathway was performed. Our study indicated that: (i) PMF activated Nrf2 and its downstream genes, NQO1 and γ-GCS, and enhanced the stabilization of Nrf2 through inhibiting Nrf2 ubiquitination. (ii) Inhibition of PI3K, p38 MAPK, PKC and PERK by specific kinase inhibitors suppressed PMF-induced activation of Nrf2. (iii) PMF conferred Nrf2-dependent protection against sodium arsenite- and cigarette smoke extract- induced cytotoxicity in lung epithelial cells. Collectively, our data demonstrate that PMF is a novel Nrf2 activator with potential prevention against oxidative insults. The diverse pharmacological functions of citrus polymethoxyflavone might be related to their ability of activating Nrf2 pathway.

AIM: To observe the changes of intraocular pressure and choroidal thickness after hemodialysis in patients with chronic renal failure, and to explore the impact of hemodialysis on blood supply. METHODS: Totally 55 patients(110 eyes)with chronic renal failure who had been treated for a long time in our hospital were selected to test plasma osmotic pressure. Before and after hemodialysis 5min, hemodialysis venous blood was collected, and plasma osmotic pressure was measured. Before hemodialysis 1h and after hemodialysis 1h, intraocular pressure was measured; intraocular pressure and choroidal thickness were compared before and after hemodialysis measured by enhanced depth imaging technique of optical coherence tomography(OCT). RESULTS: After hemodialysis plasma osmotic pressure reduced, and the difference was statistically significant(t=12.73, Pt=2.07, PPCONCLUSION: After hemodialysis ocular pressure increased and the choroid thickness became thinner in chronic renal failure patients, which might affect the ocular blood flow state. It is suggested that the osmotic pressure gradient should be adjusted in hemodialysis patients and eye test and treatment must be given in necessity.

Human lung tissue, directly exposed to the environmental oxidants and toxicants, is apt to be harmed to bring about acute or chronic oxidative insults. The nuclear factor erythroid 2-related factor 2 (Nrf2) represents a central cellular defense mechanism, and is a target for developing agents against oxidative insult-induced human lung diseases. Our previous study found that the EtOH extract of Cinnamomum chartophyllum protected human bronchial epithelial cells against oxidative insults via Nrf2 activation. In this study, a systemic phytochemical investigation of the aerial parts of C. chartophyllum led to the isolation of thirty chemical constituents, which were further evaluated for their Nrf2 inducing potential using NAD(P)H: quinone reductase (QR) assay. Among these purified constituents, a sesquiterpenoid bearing α, β-unsaturated ketone group, 3S-(+)-9-oxonerolidol (NLD), and a diphenyl sharing phenolic groups, 3, 3â², 4, 4â²-tetrahydroxydiphenyl (THD) significantly activated Nrf2 and its downstream genes, NAD(P)H quinone oxidoreductase 1 (NQO-1), and γ-glutamyl cysteine synthetase (γ-GCS), and enhanced the nuclear translocation and stabilization of Nrf2 in human lung epithelial cells. Importantly, NLD and THD had no toxicities under the Nrf2 inducing doses. THD also demonstrated a potential of interrupting Nrf2-Keap1 proteinâprotein interaction (PPI). Furthermore, NLD and THD protected human lung epithelial cells against sodium arsenite [As(III)]-induced cytotoxicity. Taken together, we conclude that NLD and THD are two novel Nrf2 activators with potential application of preventing acute and chronic oxidative insults in human lung tissue. Keywords: Cinnamomum chartophyllum, Nrf2 activator, Arsenic, Oxidative insult

AIM:To investigate the prevalence and distribution of cataract among adults aged 50 or older in Foshan area.METHODS:Cluster sampling method was used in 4 539 inhabitants aged 50 or older in urban and rural of Foshan city from January 2014 to June 2015.All individuals were received visual acuity and eye examination, including slit lamp examination, fundus examination, automatic optometry and intraocular pressure examination. RESULTS:There were 641 patients with cataract among the 4 539 adults and the prevalence of cataract was 14.12%. The prevalence of cataract grew as the adults became older(PPP>0.05). CONCLUSION: Cataract is the most common eye disease that leads to blindness and severe visual impairment among adults aged 50 or older in the area.

Background: Obstructive sleep apnea is strongly associated with obesity, particularly abdominal obesity common in centrally obese males. Previous studies have demonstrated that intra-abdominal pressure (IAP) is increased in morbid obesity, and tracheal traction forces may influence pharyngeal airway collapsibility. This study aimed to investigate that whether IAP plays a role in the mechanism of upper airway (UA) collapsibility via IAP-related caudal tracheal traction. Methods: An abdominal wall lifting (AWL) system and graded CO2pneumoperitoneum pressure was applied to four supine, anesthetized Guizhou miniature pigs and its effects on tracheal displacement (TD) and airflow dynamics of UA were studied. Individual run data in 3 min obtained before and after AWL and obtained before and after graded pneumoperitoneum pressure were analyzed. Differences between baseline and AWL/graded pneumoperitoneum pressure data of each pig were examined using a Student's t-test or analysis of variance. Results: Application of AWL resulted in decreased IAP and significant caudal TD. The average displacement amplitude was 0.44 mm (P < 0.001). There were three subjects showed increased tidal volume (TV) (P < 0.01) and peak inspiratory airflow (P < 0.01); however, the change of flow limitation inspiratory UA resistance (Rua) was not significant. Experimental increased IAP by pneumoperitoneum resulted in significant cranial TD. The average displacement amplitude was 1.07 mm (P < 0.001) when IAP was 25 cmH2O compared to baseline. There were three subjects showed reduced Rua while the TV increased (P < 0.01). There was one subject had decreased TV and elevated Rua (P < 0.001). Conclusions: Decreased IAP significantly increased caudal TD, and elevated IAP significantly increased cranial TD. However, the mechanism of UA collapsibility appears primarily mediated by changes in lung volume rather than tracheal traction effect. TV plays an independent role in the mechanism of UA collapsibility.

Abstract Background This study aims to report the phenomenon of Myelin oligodendrocyte glycoprotein antibody-associated encephalitis induced by Mycoplasma pneumoniae infections and promote the potential benefits of combining early immunotherapy and anti-M—pneumoniae therapy for these patients. Methods Three children with MOG-IgG-associated encephalitis due to M. pneumoniae infections who were treated at our hospital from September to November 2023 were included in the study. We investigated and analyzed the background and clinical features of these patients. Results Three patients developed headaches, seizures, and/or other neurological manifestations, elevated mononuclear cells in cerebrospinal fluid, intracranial lesions on cranial magnetic resonance imaging (MRI), and positive MOG-IgG in serum, within 10–14 days. They were diagnosed with MOG-IgG-associated encephalitis due to M. pneumoniae infections, the treatment consisted of intravenous immunoglobulin, glucocorticoid, and erythromycin, then they were completely recovered. Conclusion Mycoplasma pneumoniae (M. pneumoniae) infections can cause oligodendrocyte glycoprotein (MOG) antibody-associated encephalitis. The recognition of this condition will promote the potential benefits of combining early immunotherapy and anti-M. pneumoniae therapy for patients with MOG-IgG-associated encephalitis.

Taxol is a precious and effective anticancer drug. Cerium and methyl jasmonate (MJ) have been shown to increase the yield of taxol in taxus cells. However, the mechanisms of cerium-mediated and MJ-mediated taxol biosynthesis remain unknown. RNA-Seq was applied to study the overall regulation mechanism of cerium and MJ on taxol biosynthesis and analyze the differences among T. mairei cells elicited by Ce3+, Ce4+ and MJ on transcriptional level. Using sequence homology, 179 unigenes were identified as taxol synthesis genes. Under the condition of 100 mM MJ, taxol synthesis genes were up-regulated. Notably, taxol synthesis genes were down-regulated expression at 1 mM Ce3+ and 1 mM Ce4+. Differential expression genes involved in some related functions were analyzed, such as MAPK signaling pathway and plantpathogen interaction. Sequence alignment and phylogenetic analysis of nine differentially expressed WRKYs in our data were carried out. [ABSTRACT FROM AUTHOR]

Abstract A long-standing and critical issue in the field of irradiated structural materials is that void swelling is significantly higher in face-centered cubic-structured (fcc) materials (1% dpa−1) as compared to that of body-centered cubic-structured (bcc) materials (0.2% dpa−1). Despite extensive research in this area, the underlying mechanism of the difference in swelling resistance between these two types of materials is not yet fully understood. Here, by combining atomistic simulations and STEM imaging, we find stacking fault tetrahedra (SFTs) are the primary cause of the high swelling rate in pure fcc copper. We reveal that SFTs in fcc copper are not neutral sinks, different from the conventional knowledge. On the contrary, they are highly biased compared to other types of sinks because of the SFT-point defect interaction mechanism. SFTs show strong absorption of mobile self-interstitial atoms (SIAs) from the faces and vertices, and weak absorption of mobile vacancies from the edges. We compare the predicted swelling rates with experimental findings under varying conditions, demonstrating the distinct contributions of each type of sink. These findings will contribute to understanding the swelling of irradiated structural materials, which may facilitate the design of materials with high swelling resistance.

Microtubule-severing proteins (MTSPs), are a family of proteins which use adenosine triphosphate to sever microtubules. MTSPs have been shown to play an important role in multiple microtubule-involved cellular processes. One member of this family, fidgetin (FIGN), is also involved in male fertility; however, no studies have explored its roles in female fertility. In this study, we found mouse fidgetin is rich within oocyte zona pellucida (ZP) and is the only MTSP member to do so. Fidgetin also appears to interact with all three ZP proteins. These findings prompted us to propose that fidgetin might prevent polyspermy. Results from in vitro maturation oocytes analysis showed that fidgetin knockdown did cause polyspermy. We then deleted all three fidgetin isoforms with CRISPR/Cas9 technologies; however, female mice remained healthy and with normal fertility. Of all mouse MTSPs, only the mRNA level of fidgetin-like 1 (FIGNL1) significantly increased. Therefore, we assert that fidgetin-like 1 compensates fidgetin's roles in fidgetin knockout female mice. [ABSTRACT FROM AUTHOR]

Abstract Background Fushenmu (Pini Radix in Poria, FSM) is a folk parasitic herb that has been mainly used for palpitation and amnesiain in traditional Chinese medicine (TCM). Recently, as an individual herb or a component of formulations, Fushenmu exhibits therapeutic potential for the treatment of cardiac arrhythmias. Yet, how specific targets or pathways of Fushenmu inhibit arrhythmia has not yet been reported. Methods Here, based on clinical functional genomics, metabolomics and molecular biologic technologies, a network construction strategy was adopted to identify FSM therapeutic targets and biomarkers that might explore its functions. Results In this study, it was found that FSM recovered arrhythmia-associated heart failure in barium chloride (BaCl2) induced arrhythmic zebrafish embryos, as was evidenced by the shortened cardiac sinus venosus—bulbus arteriosus (SV-BA) distance, smaller cardiovascular bleeding areas, and reduced cardiomyocyte apoptosis. Moreover, analysis via ultra-high-performance liquid chromatography–tandem mass spectrometry (UPLC-QTOF-ESI-MS/MS) components identification and network pharmacology prediction showed that 11 main active components of FSM acted on 33 candidate therapeutic targets. Metabolomic analysis also suggested that FSM could rescue 242 abnormal metabolites from arrhythmic zebrafish embryos. Further analysis based on the combination of target prediction and metabolomic results illustrated that FSM down-regulated Ryanodine Receptor 2 (RyR2) expressions, inhibited adrenaline and 3',5'-Cyclic AMP (cAMP) levels in a dose-dependent manner, which was confirmed by metabolites quantification and quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) assay. Conclusion In summary, this study revealed that FSM mitigated BaCl2 induced cardiac damage caused by arrhythmia by suppressing RyR2 expressions, decreasing adrenaline and cAMP through the adrenergic signalling pathway.

Background/purpose: The signaling mechanisms for Porphyromonas gingivalis lipopolysaccharide (PgLPS)-induced inflammation in human dental pulp cells are not fully clarified. This in vitro study aimed to evaluate the involvement of phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) pathway in PgLPS-induced pulpal inflammation. Methods: Human dental pulp cells (HDPCs) were challenged with PgLPS with or without pretreatment and coincubation with a PI3K/Akt inhibitor (LY294002). The gene or protein levels of PI3K, Akt, interleukin (IL)-6, IL-8, alkaline phosphatase (ALP), osteocalcin and osteonectin were analyzed by reverse transcription polymerase chain reaction (PCR), real-time PCR, western blotting, and immunofluorescent staining. In addition, an enzyme-linked immunosorbent assay was used to analyze IL-6 and IL-8 levels in culture medium. Results: In response to 5 μg/ml PgLPS, IL-6, IL-8, and PI3K, but not Akt mRNA expression of HDPCs, was upregulated. IL-6, IL-8, PI3K, and p-Akt protein levels were stimulated by 10–50 μg/ml of PgLPS in HDPCs. PgLPS also induced IL-6 and IL-8 secretion at concentrations higher than 5 μg/ml. Pretreatment and co-incubation by LY294002 attenuated PgLPS-induced IL-6 and IL-8 mRNA expression in HDPCs. The mRNA expression of ALP, but not osteocalcin and osteonectin, was inhibited by higher concentrations of PgLPS in HDPCs. Conclusion: P. gingivalis contributes to pulpal inflammation in HDPCs by dysregulating PI3K/Akt signaling pathway to stimulate IL-6 and IL-8 mRNA/protein expression and secretion. These results are useful for understanding the pulpal inflammation and possible biomarkers of inflamed pulp diagnosis and treatment.

Motion of point defects is a fundamental process that governs microstructure and properties of materials. Here, we examine the near-surface and grain boundary cavity swelling depth profiles in neutron- and ion-irradiated simple metals (Cu, Ni, and Fe-Cr) and investigate diffusional broadening of implanted Ni ions in Fe-Cr alloys. Vacancy migration energies and radiation-enhanced diffusion were experimentally estimated. Cavity denuded zone widths near planar sinks are shown to be dependent on temperature, damage rate, balance of point defects and sinks, and vacancy migration energies. An enhanced cavity swelling zone adjacent to the void-denuded zone was observed in specimens with low to moderate sink strength and interpreted as evidence of 1D gliding interstitial clusters. Radiation-enhanced diffusional broadening of implanted Ni ions (at 400–550 °C) in Fe and Fe-Cr was up to 250 nm toward the surface, which leads to a much broader near-peak-damage region where cavity swelling is suppressed. Diffusional broadening of implanted ions is calculated to be similarly pronounced for self-ion irradiations, particularly near the peak and higher swelling temperature regimes. Adequately high ion energies (∼8–15 MeV) are recommended for ion-irradiation studies to provide a sufficiently broad midrange safe analysis region with minimized surface and injected ion effects.

The level of chromium plays an essential role in irradiation tolerance of Fe-Cr ferritic alloys. However, conflicting results have been reported regarding the dependence of cavity swelling under irradiation on Cr level and temperature. Here, we have performed a comprehensive set of simultaneous dual-ion (Ni + He) irradiations to high dose (∼30 displacements per atom, dpa) at 400–550 °C on a series of ultra-high purity Fe and Fe-Cr binary alloys (3–14 wt.%Cr). Helium co-implantation rates of 0.1 and 10 appm He/dpa were selected to examine He synergistic effects relevant for fission and fusion reactor conditions, respectively. Cavities were observed in all irradiated samples by transmission electron microscopy. The results show that higher He implantation rate causes a shift in the swelling peak to higher temperatures in both Fe and Fe-Cr alloys. When assuming smaller cavities as biased sinks, the non-monotonic nature of the cavity swelling behavior is related to the ratio of biased to unbiased point defect sink strengths. Cr-enriched precipitates were observed in Fe-14Cr irradiated at 400 °C by atom probe tomography. Our analysis suggests the formation of Cr-enriched precipitates could suppress cavity swelling for Fe-Cr alloys with Cr content above 10 wt%.

In this paper, we report the synthesis of spirocyclopropane-containing 4H-pyrazolo[1,5-a]indoles 6a–e via alkylative dearomatization and intramolecular N-imination of indole–O-(methylsulfonyl)oxime 11. Starting materials tryptophol (7) and 2-bromocyclopetanone (8) were reacted in the presence of HBF4·OEt2, providing 1,2,3,5,6,11-hexahydrocyclopenta[2,3]oxepino[4,5-b]indole (9) in a 63% yield. Compound 9 was reacted with hydroxylamine hydrochloride to afford oxime 10 (65% yield), which was subsequently bis-methanesulfonated to form 11 in a 85% yield. Heating 11 with various alcohols in the presence of N,N-diisopropylethylamine (DIPEA) triggered the alkylative dearomatization and intramolecular N-imination, forming the spirocyclopropane and 4H-pyrazolo[1,5-a]indole structures in the targets 6a–e with 67–84% yields.

Apical Lesions, one of the most common oral diseases, can be effectively detected in daily dental examinations by a periapical radiograph (PA). In the current popular endodontic treatment, most dentists spend a lot of time manually marking the lesion area. In order to reduce the burden on dentists, this paper proposes a convolutional neural network (CNN)-based regional analysis model for spical lesions for periapical radiographs. In this study, the database was provided by dentists with more than three years of practical experience, meeting the criteria for clinical practical application. The contributions of this work are (1) an advanced adaptive threshold preprocessing technique for image segmentation, which can achieve an accuracy rate of more than 96%; (2) a better and more intuitive apical lesions symptom enhancement technique; and (3) a model for apical lesions detection with an accuracy as high as 96.21%. Compared with existing state-of-the-art technology, the proposed model has improved the accuracy by more than 5%. The proposed model has successfully improved the automatic diagnosis of apical lesions. With the help of automation, dentists can focus more on technical and medical diagnoses, such as treatment, tooth cleaning, or medical communication. This proposal has been certified by the Institutional Review Board (IRB) with the certification number 202002030B0.

The traditional Chinese medicine Poria cum Radix Pini (PRP) is a fungal medicinal material that has been proven to play an important role in the treatment of arrhythmia. However, the mechanism of its effect on arrhythmia is still unclear. In this study, network pharmacology and metabolomics correlation analysis methods were used to determine the key targets, metabolites and potential pathways involved in the effects of PRP on arrhythmia. The results showed that PRP can significantly improve cardiac congestion, shorten the SV-BA interval and reduce the apoptosis of myocardial cells induced by barium chloride in zebrafish. By upregulating the expression of the ADORA1 protein and the levels of adenosine and cGMP metabolites in the cGMP-PKG signalling pathway, PRP can participate in ameliorating arrhythmia. Therefore, we believe that PRP shows great potential for the treatment of arrhythmia.

Menopause and associated renal complications are linked to systemic redox stress, and the causal factors remain unclear. As the role of Hypericum perforatum L. (HPL) in menopause-induced kidney disease therapy is still ambiguous, we aim to explore the effects of HPL on systemic redox stress under ovariectomy (OVX)-induced kidney dysfunction conditions. Here, using combined proteomic and metabolomic approaches, we constructed a multi-scaled “HPL-disease-gene-metabolite” network to generate a therapeutic “big picture” that indicated an important link between glutathione redox stress and kidney impairment. HPL exhibited the potential to maintain cellular redox homeostasis by inhibiting gamma-glutamyltransferase 1 (Ggt1) overexpression, along with promoting the efflux of accumulated toxic amino acids and their metabolites. Moreover, HPL restored alanyl-aminopeptidase (Anpep) expression and metabolite shifts, promoting antioxidative metabolite processing, and recovery. These findings provide a comprehensive description of OVX-induced glutathione redox stress at multiple levels and support HPL therapy as an effective modulator in renal tissues to locally influence the glutathione metabolism pathway and subsequent redox homeostasis.

Objectives: To investigate the feasibility of pulse transit time (PTT) as a quantitative measure of inspiratory effort in patients with obstructive sleep apnea (OSA). Methods: Nineteen moderate to severe OSA patients were included to undergo overnight polysomnography simultaneously with esophageal pressure (Pes) and PTT. The quantitative relationships between the size of Pes variations (ΔPes) and PTT variations (ΔPTT) on a breath-by-breath basis in obstructive apneas were assessed. Results: A total of 19,833 breaths from 6,087 obstructive apneas were analyzed. There were good correlations with r = 0.779 ± 0.095 (mean ± SD) between ΔPes and ΔPTT based on overnight sleep. The correlation coefficients for supine and lateral position were of the approximated magnitude (r = 0.783 ± 0.060 and 0.757 ± 0.106, respectively), whereas they were lower in rapid eye movement (REM) sleep (r = 0.564 ± 0.140) compared with non-rapid eye movement (NREM) sleep (r = 0.787 ± 0.071). In NREM sleep, the regression lines of ΔPTT against ΔPes were plotted with intercepts (5.1 ± 2.1 ms) and slopes (0.35 ± 0.08 ms·cm H2O-1). Conclusions: PTT showed good ability in detecting changes of inspiratory effort in overnight sleep and was proved to be a clinically useful method in quantifying increases in inspiratory effort in NREM sleep. Hence, PTT has prospects to become an alternative to Pes in respiratory sleep studies. Copyright © 2011 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Abstract Background Olfactory ensheathing cells (OEC), specialized glia that ensheathe bundles of olfactory nerves, have been reported as a favorable substrate for axonal regeneration. Grafting OEC to injured spinal cord appears to facilitate axonal regeneration although the functional recovery is limited. In an attempt to improve the growth-promoting properties of OEC, we transduced prostacyclin synthase (PGIS) to OEC via adenoviral (Ad) gene transfer and examined the effect of OEC with enhanced prostacyclin synthesis in co-culture and in vivo. Prostacyclin is a vasodilator, platelet anti-aggregatory and cytoprotective agent. Results Cultured OEC expressed high level of cyclooxygneases, but not PGIS. Infection of AdPGIS to OEC could selectively augument prostacyclin synthesis. When cocultured with either OEC or AdPGIS-OEC, neuronal cells were resistant to OGD-induced damage. The resulted OEC were further transplanted to the transected cavity of thoracic spinal cord injured (SCI) rats. By 6 weeks post-surgery, significant functional recovery in hind limbs occurred in OEC or AdPGIS-OEC transplanted SCI rats compared with nontreated SCI rats. At 10–12 weeks postgraft, AdPGIS-OEC transplanted SCI rats showed significantly better motor restoration than OEC transplanted SCI rats. Futhermore, regenerating fiber tracts in the distal spinal cord stump were found in 40–60% of AdPGIS-OEC transplanted SCI rats. Conclusions Enhanced synthesis of prostacyclin in grafted OEC improved fiber tract regeneration and functional restoration in spinal cord injured rats. These results suggest an important potential of prostacyclin in stimulating OEC therapeutic properties that are relevant for neural transplant therapies.

Hypericum perforatum L., which includes a wide range of bioactive substances and is sold as a functional food formulation, has been used as an alternative to estrogen replacement treatment to relieve menopausal syndromes. However, methods to track HPL mechanisms and link them to metabolism disorder regulation during menopause periods have been lacking. To investigate HPL function in endocrine-related metabolic recognition, we applied both global and targeted metabolomic methods on ovariectomised rat serum and urine metabolites for treatment-specific metabolic profiling and to explore biomarkers and deduce their mechanisms via 1H-NMR and HPLC–MS/MS techniques. Results from the comparison of metabolite levels of rats that underwent an ovariectomy (OVX) before and after the administration of different doses of HPL showed that HPL can reverse the disordered changes induced in multiple biomarkers by menopausal syndromes. Through screening, identification, and quantification of the differential regulatory metabolites, 23 metabolites involved in 4 major metabolic pathways, including the arginine, taurine, pyruvate and tryptophan metabolic pathways, were highlighted as important for explaining the mechanisms of HPL. These pathways may be applicable for explanations of other menopausal syndrome symptoms, such as depression and hot flashes, and the effects of other herbs rich in flavonoids with menopause remission potential.

The title compound, [Cu(C16H11BrN2)(C18H15P)2]BF4, is composed of one CuI atom, one 6-(4-bromophenyl)-2,2′-bipyridine (L) ligand, two triphenylphosphane molecules and one tetrafluoridoborate anion. The CuI ion is four-coordinated in a distorted tetrahedral configuration by two N atoms from L and two P atoms from triphenylphosphane ligands. In the L ligand, the two pyridine rings are not coplanar; the mean planes making a dihedral angle of 15.3 (5)°. In the crystal, the ions are linked by weak C—H...F interactions.