Tough Self-Healing Materials via In Situ Growth of Zeolitic Imidazolate Framework-8 Nanocrystals in Polymers.

Construction of self-healing materials with improved mechanical performance is a great challenge. A strong and tough self-healing composite is fabricated via in situ growth of zeolitic imidazole framework-8 (ZIF-8) nanocrystals in imidazole-containing polymer networks. By adjusting the stoichiometric ratio of the zinc salt to 2-methylimidazole, composites with various mechanical performances are obtained. The existence of ZIF-8 nanocrystals via in situ growth in the polymer networks is confirmed by X-ray diffraction (XRD), transmission electron microscopy (TEM), and atomic force microscopy (AFM). The zinc-imidazole interactions between the ZIF-8 nanocrystals and the polymer are confirmed by attenuated total reflection Fourier transform infrared (ATR-FTIR) spectroscopy. The composites can repair themselves under mild conditions owing to dynamic zinc-imidazole interactions. The self-healing efficiency of composites can reach up to 91% under the condition of 60 °C for 48 h. In contrast to the pure zinc cation crosslinking system, the composite containing ZIF-8 nanocrystals prepared via in situ growth exhibited enhanced tensile strength and toughness by 43% and 100%, respectively. This study proves that incorporating the metal-organic frameworks (MOFs) materials into a self-healing system via an in situ growth strategy is highly promising for designing self-healing materials with improved mechanical performance.

Investigations on the defect structures for Mn2+ in CdSe nanocrystals and bulk materials and the criterion of occupation for Mn2+ in CdX (X = S, Se, Te) nanocrystals.

The spin Hamiltonian parameters and defect structures are theoretically studied for the substitutional Mn2+ at the core of CdSe nanocrystals and in the bulk materials from the perturbation calculations of spin Hamiltonian parameters for trigonal tetrahedral 3d5 clusters. Both the crystal-field and charge transfer contributions are taken into account in the calculations from the cluster approach. The impurity-ligand bond angles are found to be about 1.84° larger and 0.10° smaller in the CdSe:Mn2+ nanocrystals and bulk materials, respectively, than those (≈109.37°) of the host Cd2+ sites. The quantitative criterion of occupation (at the core or surface) for Mn2+ in CdX (X = S, Se, Te) nanocrystals is presented for the first time based on the inequations of hyperfine structure constants (HSCs). This criterion is well supported by the experimental HSCs data of Mn2+ in CdX nanocrystals. The previous assignments of signals SI as Mn2+ at the core of CdS nanocrystals are renewed as Mn2+ at the surface based on the above criterion. The present studies would be helpful to achieve convenient determination of occupation for Mn2+ impurities in CdX semiconductor nanocrystals by means of spectral (e.g., HSCs) analysis.

TMEM151A variants associated with paroxysmal kinesigenic dyskinesia.

TMEM151A, located at 11q13.2 and encoding transmembrane protein 151A, was recently reported as causative for autosomal dominant paroxysmal kinesigenic dyskinesia (PKD). Here, through comprehensive analysis of sporadic and familial cases, we expand the clinical and mutation spectrum of PKD. In doing so, we clarify the clinical and genetic features of Chinese PKD patients harboring TMEM151A variants and further explore the relationship between TMEM151A mutations and PKD. Whole exome sequencing was performed on 26 sporadic PKD patients and nine familial PKD pedigrees without PRRT2 variants. Quantitative real-time PCR was used to assess the gene expression of frameshift mutant TMEM151A in a PKD patient. TMEM151A variants reported to date were reviewed. Four TMEM151A variants were detected in four unrelated families with 12 individuals, including a frameshift mutation [c.606_607insA (p.Val203fs)], two missense mutations [c.166G > A (p.Gly56Arg) and c.791T > C (p.Val264Ala)], and a non-pathogenic variant [c.994G > A (p.Gly332Arg)]. The monoallelic frameshift mutation [c.606_607insA (p.Val203fs)] may cause TMEM151A mRNA decay, suggesting a potential pathogenic mechanism of haploinsufficiency. Patients with TMEM151A variants had short-duration attacks and presented with dystonia. Our study provides a detailed clinical description of PKD patients with TMEM151A mutations and reports a new disease-causing mutation, expanding the known phenotypes caused by TMEM151A mutations and providing further detail about the pathoetiology of PKD.

Genome-wide association analysis for grain moisture content and dehydration rate on maize hybrids.

For mechanized maize production, a low grain water content (GWC) at harvest is necessary. However, as a complex quantitative trait, understand the genetic mechanism of GWC remains a large gap, especially in hybrids. In this study, a hybrid population through two environments including 442 F1 was used for genome-wide association analysis of GWC and the grain dehydration rate (GDR), using the area under the dry down curve (AUDDC) as the index. Then, we identified 19 and 17 associated SNPs for GWC and AUDDC, including 10 co-localized SNPs, along with 64 and 77 pairs of epistatic SNPs for GWC and AUDDC, respectively. These loci could explain 11.39-68.2% of the total phenotypic variation for GWC and 41.07-67.02% for AUDDC at different stages, whose major effect was the additive and epistatic effect. By exploring the candidate genes around the significant sites, a total of 398 and 457 possible protein-coding genes were screened, including autophagy pathway and auxin regulation-related genes, and five inbred lines with the potential to reduce GWC in the combined F1 hybrid were identified. Our research not only provides a certain reference for the genetic mechanism analysis of GWC in hybrids but also provides an added reference for breeding low-GWC materials. Supplementary Information: The online version contains supplementary material available at 10.1007/s11032-022-01349-x.

The Influence of Altitude on Erythropoietin Resistance Index in Maintenance Hemodialysis Patients: Data from Tibetan Plateau.

BACKGROUND: It is known that hypoxia influences many of the biologic processes involved in erythropoiesis; therefore, the high-altitude hypoxia may affect erythropoietin (EPO) responsiveness in maintenance hemodialysis (MHD) patients. This study aimed to evaluate the impact of altitude on EPO responsiveness in MHD patients. METHODS: In this retrospective study, MHD patients from Tibet Autonomous Region People's Hospital (3,650 m above sea level) and Peking University People's Hospital (43.5 m above sea level) were recruited between May 2016 and December 2018. Patients were divided into 2 groups according to altitude. Variables including age, sex, dialysis vintage, dialysis modality, duration of EPO use, EPO doses, and laboratory tests were collected and analyzed. EPO responsiveness was measured in terms of the EPO resistance index (ERI). ERI was defined as the weekly weight-adjusted dose of EPO (IU/kg/week) divided by hemoglobin concentration (g/dL). The association between ERI and altitude was estimated using a multivariable linear regression model. RESULTS: Sixty-two patients from Tibet Autonomous Region People's Hospital (high-altitude [HA] group) and 102 patients from Peking University People's Hospital (low-altitude [LA] group) were recruited. The ERI for HA group and LA group was 6.9 ± 5.1 IU w-1 kg-1 (g/dL)-1 and 11.5 ± 6.4 IU w-1 kg-1 (g/dL)-1, respectively. After adjusting for covariates by multivariable regression, altitude was independently associated with ERI (R2 = 0.245, p < 0.001). CONCLUSION: Altitude had an independent negative correlation with ERI. This result supported the hypothesis that altitude-associated hypoxia improved EPO responsiveness in MHD patients.

Long noncoding RNA SYISL regulates myogenesis by interacting with polycomb repressive complex 2.

Although many long noncoding RNAs (lncRNAs) have been identified in muscle, their physiological function and regulatory mechanisms remain largely unexplored. In this study, we systematically characterized the expression profiles of lncRNAs during C2C12 myoblast differentiation and identified an intronic lncRNA, SYISL (SYNPO2 intron sense-overlapping lncRNA), that is highly expressed in muscle. Functionally, SYISL promotes myoblast proliferation and fusion but inhibits myogenic differentiation. SYISL knockout in mice results in significantly increased muscle fiber density and muscle mass. Mechanistically, SYISL recruits the enhancer of zeste homolog 2 (EZH2) protein, the core component of polycomb repressive complex 2 (PRC2), to the promoters of the cell-cycle inhibitor gene p21 and muscle-specific genes such as myogenin (MyoG), muscle creatine kinase (MCK), and myosin heavy chain 4 (Myh4), leading to H3K27 trimethylation and epigenetic silencing of target genes. Taken together, our results reveal that SYISL is a repressor of muscle development and plays a vital role in PRC2-mediated myogenesis.

Clinical study of a 125I particle-integrated esophageal covered stent and hyperbaric oxygen in the treatment of advanced esophageal cancer.

OBJECTIVE: this study aimed to investigate the clinical efficacy and feasibility of the treatment of advanced esophageal cancer with a combination of a 125I particle-integrated esophageal covered stent and hyperbaric oxygen. METHODS: forty-five patients with advanced esophageal cancer were enrolled and were randomly divided into two groups: a treatment group and a control group. Patients in the treatment group were treated with a 125I particle-integrated esophageal covered stent and hyperbaric oxygen, while patients in the control group were treated with a 125I particle-integrated esophageal covered stent. The clinical effects and long-term survival time of the two groups were observed. RESULTS: in the treatment group, the complete remission (CR) rate and partial remission (PR) rate of local lesions were 19.2 % and 61.5 %, respectively, and the total effective rate was 80.7 %. In the control group, the CR rate and PR rate of local lesions were 10.5 % and 52.6 %, respectively, and the total effective rate was 63.1 %. The total effective rate was higher in the treatment group than in the control group, which was statistically significant (p < 0.05). CONCLUSION: the combination of a 125I particle-integrated esophageal covered stent and hyperbaric oxygen shows a good short- and long-term efficacy in the treatment of advanced esophageal cancer.

Research progress of CTCF in mediating 3D genome formation and regulating gene expression.

In interphase eukaryotic nuclei, chromatin is folded to form a higher-order topological structure. The spatial organization of such chromatin domain has an important impact on the regulation of gene expression. As a key architectural structural protein, CTCF (CCCTC-binding factor) plays an important role in the formation of chromatin three-dimensional chromatin structure. CTCF can also bind to many insulator elements in the genome and insulate enhancers from activating target genes via modulating remote chromatin interactions. A recent study by Dr. Chunliang Li and his team at St. Jude Children's Research Hospital in the United States showed that when CTCF was acutely degraded, significant changes were found in the three-dimensional structure of chromatin. The mechanism by which CTCF binding sites function as insulator elements was investigated by Prof. Qiang Wu's team at Institute of Systems Biomedicine and Shanghai Jiao Tong University in China and Prof. Bing Ren's team at Ludwig Institute for Cancer Research in the United States. Here we mainly review and discuss some of these latest progresses.

Heat-response patterns of the heat shock transcription factor family in advanced development stages of wheat (Triticum aestivum L.) and thermotolerance-regulation by TaHsfA2-10.

BACKGROUND: Heat shock transcription factors (Hsfs) are present in majority of plants and play central roles in thermotolerance, transgenerational thermomemory, and many other stress responses. Our previous paper identified at least 82 Hsf members in a genome-wide study on wheat (Triticum aestivum L.). In this study, we analyzed the Hsf expression profiles in the advanced development stages of wheat, isolated the markedly heat-responsive gene TaHsfA2-10 (GenBank accession number MK922287), and characterized this gene and its role in thermotolerance regulation in seedlings of Arabidopsis thaliana (L. Heynh.). RESULTS: In the advanced development stages, wheat Hsf family transcription profiles exhibit different expression patterns and varying heat-responses in leaves and roots, and Hsfs are constitutively expressed to different degrees under the normal growth conditions. Overall, the majority of group A and B Hsfs are expressed in leaves while group C Hsfs are expressed at higher levels in roots. The expression of a few Hsf genes could not be detected. Heat shock (HS) caused upregulation about a quarter of genes in leaves and roots, while a number of genes were downregulated in response to HS. The highly heat-responsive gene TaHsfA2-10 was isolated through homeologous cloning. qRT-PCR revealed that TaHsfA2-10 is expressed in a wide range of tissues and organs of different development stages of wheat under the normal growth conditions. Compared to non-stress treatment, TaHsfA2-10 was highly upregulated in response to HS, H2O2, and salicylic acid (SA), and was downregulated by abscisic acid (ABA) treatment in two-leaf-old seedlings. Transient transfection of tobacco epidermal cells revealed subcellular localization of TaHsfA2-10 in the nucleus under the normal growth conditions. Phenotypic observation indicated that TaHsfA2-10 could improve both basal thermotolerance and acquired thermotolerance of transgenic Arabidopsis thaliana seedlings and rescue the thermotolerance defect of the T-DNA insertion mutant athsfa2 during HS. Compared to wild type (WT) seedlings, the TaHsfA2-10-overexpressing lines displayed both higher chlorophyll contents and higher survival rates. Yeast one-hybrid assay results revealed that TaHsfA2-10 had transactivation activity. The expression levels of thermotolerance-related AtHsps in the TaHsfA2-10 transgeinc Arabidopsis thaliana were higher than those in WT after HS. CONCLUSIONS: Wheat Hsf family members exhibit diversification and specificity of transcription expression patterns in advanced development stages under the normal conditions and after HS. As a markedly responsive transcriptional factor to HS, SA and H2O2, TaHsfA2-10 involves in thermotolerance regulation of plants through binding to the HS responsive element in promoter domain of relative Hsps and upregulating the expression of Hsp genes.

Mineral and bone disorder in hemodialysis patients in the Tibetan Plateau: a multicenter cross-sectional study.

Background: Mineral and bone disorder (MBD) in hemodialysis patients is associated with increased morbidity and mortality. Studies on the MBD status of hemodialysis patients at high altitudes are extremely limited. Methods: A total of 146 hemodialysis patients from 5 local hospitals across all districts with hemodialysis centers in the Tibetan Plateau were enrolled in this cross-sectional study. Parameters related to MBD, including serum phosphorus (P), calcium (Ca), and intact parathyroid hormone (iPTH) levels, were measured. The achievement of MBD goals was compared with the achievement in the Dialysis Outcomes and Practice Study (DOPPS) 3, DOPPS 4 and a multicenter study of MBD in China. Factors associated with hyperphosphatemia were examined. Results: Altogether, 146 hemodialysis patients were recruited from the Tibetan Plateau. According to the K/DIGO guidelines, there were low achievement rates for serum Ca (40.4%), P (29.7%), and iPTH (47.1%). As for the (KDOQI) guidelines, the rates of achievement of defined targets were 38.4%, 33.7% and 16.4% for serum Ca, P and iPTH, respectively. The percentages of patients reaching the KDOQI targets for corrected Ca, P, and iPTH were significantly lower for Tibetan patients than the percentages found in DOPPS 3 (38.4% vs. 50.4%, 33.7% vs. 49.8%, and 16.4% vs. 31.4%, respectively, all p < .001) and DOPPS 4 (38.4% vs. 56.0%, 33.7% vs. 54.5%, and 16.4% vs. 35.3%, respectively, all p < .001). The percentage of patients reaching the KDOQI targets for iPTH was significantly lower in Tibet than in the plain areas of China (16.4% vs. 26.5%, p < .001). The proportion of patients with hypocalcemia was higher in Tibet than in the plain areas (44.5% vs. 19.4%, p < .001). The percentage of local patients with optimal P was significantly higher for patients with an activated vitamin D prescription than for patients without an activated vitamin D prescription (45.3% vs. 19.3%, p < .001). Age and the activated vitamin D prescription were independently associated with hyperphosphatemia. Conclusion: The MBD status of hemodialysis patients in Tibet is far from the ideal level. High altitude is one of the possible causes of the differences found, but not the principal one. It is necessary for medical staff in Tibet to improve the detection and treatment of MBD.

[Epigenetics in the genesis and development of cancers].

Cancer is a complex disease caused by the malignant cellular proliferation and metastasis. Elucidating its pathogenic mechanism is one of the major challenges that we face currently. Epigenetic mechanisms are essential for maintaining specific patterns of gene expression and normal development and growth of living individuals. Disorders of epigenetic markers, such as histone modification, DNA/RNA methylation, and changes in the three-dimensional conformation of chromatin, can interfere with gene expression to some extent, and result in cancers. This review provides a brief overview of epigenetics, focusing on their association with the genesis of cancers, and we look forward to the application of epigenetics in cancer clinical diagnosis and treatment.

Association of white matter hyperintensities with migraine features and prognosis.

BACKGROUND: White matter hyperintensities (WMHs) are frequently detected in migraine patients. However, their significance and correlation to migraine disease burden remain unclear. This study aims to examine the correlation of WMHs with migraine features and explore the relationship between WMHs and migraine prognosis. METHODS: A total of 69 migraineurs underwent MRI scans to evaluate WMHs. Migraine features were compared between patients with and without WMHs. After an average follow-up period of 3 years, these patients were divided into two groups, according to the reduction of headache frequency: improved and non-improved groups. The percentage and degree of WMHs were compared between these two groups. RESULTS: A total of 24 patients (34.8%) had WMHs. Patients with WMHs were significantly older (39.0 ± 7.9 vs. 30.6 ± 10.4 years, P < 0.001) and had a longer disease duration (median: 180.0 vs. 84.0 months, P = 0.013). Furthermore, 33 patients completed the follow up period (15 patients improved and 18 patients did not improve). Patients in the non-improved group had a higher frequency of WMHs (55.6% vs. 13.3%, P = 0.027) and median WMHs score (1.0 vs. 0.0, P = 0.030). CONCLUSIONS: WMHs can predict unfavorable migraine prognosis. Furthermore, WMHs may have a closer association with age than migraine features.

Successful treatment of reflex epilepsy with praxis induction by stimulus avoidance only.

PURPOSE: Reflex epilepsy is a type of epilepsy with seizures that are consistently triggered by a specific stimulus. Zipai is a Chinese ancient card game which has been popular in Southern China for hundreds of years. We sought to report and characterize clinical features of patients with reflex epilepsy evoked by playing Zipai. METHODS: We collected and analyzed clinical data of patients with Zipai-induced epilepsy. Patients were regarded as having Zipai-induced epilepsy if they suffered at least two seizure attack during the course of playing Zipai. Prolonged electroencephalography (EEG) and brain magnetic resonance imaging (MRI) were applied to all patients. All patients were advised to avoid watching and playing Zipai games in daily life, instead of using antiepileptic drugs. The seizure outcome was assessed during outpatient visits and by telephone contact. RESULTS: Five patients were included in this study. No spontaneous seizures occurred in all five patients. No patients had experienced myoclonic and coexistent absences with generalized tonic-clonic seizures (GTCS). All patients had normal MRI and prolonged EEG findings. All patients were advised to avoid the Zipai game, and became seizure-free without medication during the follow-up period (mean 5.4 years, range 3.5-7 years). CONCLUSION: Zipai-induced epilepsy may be an unreported subtype form of reflex epilepsy with praxis induction. Nonpharmacological conservative treatment plays a significant role in the treatment of reflex epilepsy.

Value of a novel 16-lead High-Definition ECG machine to detect conduction abnormalities in structural heart disease.

BACKGROUND: Depolarization abnormalities are hardly detectable by standard 12-lead electrocardiogram (ECG) in some patients. OBJECTIVE: To evaluate the value of the 16-lead High-Definition (HD)-ECG machine to record conduction abnormalities including Epsilon waves in patients with structural heart disease. METHODS: Tracings with 12-lead ECG, 16-lead HD-ECG, and signal-averaged ECG were studied. RESULTS: (1) Case of severe coronary artery disease (CAD): On 16-lead HD-ECG, a tiny intra-QRS signal was noted in lead III, a prolonged P wave in lead II, and fragmentation on top of lead aVL and lead aVF. Proper automatic measurement of the prolonged P wave measuring 190 ms was noted. Signal-averaging by 16-lead HD-ECG in lead III showed the intra-QRS fragmentation and P wave prolongation of 180 ms. (2) First patient with arrhythmogenic right ventricular dysplasia (ARVD): Standard 12-lead ECG indicated Epsilon waves in lead III, V2, V3, and inverted T waves in V1-V3. 16-lead HD-ECG indicated QRS prolongation in lead II, III, aVL, aVF, V2, V3 as opposed to V6, and low amplitudes of QRS complexes in V4R and V3R as a new possible sign of ARVD. Notches in lead V2, widening of QRS complexes in all precordial leads, but shorter QRS in V8-V9 are also considered as a potential new diagnostic sign of ARVD. (3) Second ARVD patient: Notches at the end of the QRS in lead III and a negative initial deflection of the QRS in V1 and V2 were detected by standard 12-lead ECG. On 16-lead HD-ECG, a more pronounced QRS fragmentation was visible. CONCLUSION: 16-lead HD-ECG in both CAD and ARVD seems to be more sensitive than 12-lead ECG to record electrocardiographic abnormalities.

Epsilon waves: Milestones in the discovery and progress.

The Epsilon wave was first identified in 1977. Four decades of progress help people to better understand its pathological electrogenesis and diagnostic value. Currently, the Epsilon wave is on the list of the 2010 Task Force recommendations for the diagnosis of arrhythmogenic right ventricular dysplasia (ARVD). In this review, we provide the history of the first recording of the Epsilon wave in coronary artery disease and Uhl's anomaly, subsequently leading to the signal averaging technique to record late potentials. Based on our experience, we discuss some existing controversies. When we look back at the decades of progress of the Epsilon wave, we conclude that the Epsilon wave is only the tip of the iceberg of ECG abnormalities in ARVD.

Towards Dynamic but Supertough Healable Polymers through Biomimetic Hierarchical Hydrogen-Bonding Interactions.

A biomimetic (titin protein molecular structure) strategy is reported for preparing transparent and healable elastomers featuring supertoughness (345 MJ m-3 ) and high tensile strength (44 MPa) after self-healing enabled by hierarchical (single, double, and quadruple) hydrogen-bonding moieties in the polymer backbone. The rigid domain containing hierarchical H-bonds formed with urethane, urea, and 2-ureido-4[1H]-pyrimidinone groups leads to a durable network structure that has enhanced mechanical properties and is also dynamic for rapid self-healing. Healable polymers with hierarchical hydrogen-bonding interactions show excellent recoverability and high energy dissipation owing to the durable interaction between polymer chains. This biomimetic strategy of using hierarchical hydrogen bonds as building blocks is an alternative approach for obtaining dynamic, strong, yet smart self-healing polymers for heavy-duty protection materials and wearable electronics.

Optimal targeting of sympathetic chain levels for treatment of palmar hyperhidrosis: an updated systematic review.

BACKGROUND: Palmar hyperhidrosis involves excessive sweating of the palms, with no known etiology. Endoscopic thoracic sympathectomy (ETS) is a safe and effective treatment for palmar hyperhidrosis, but compensatory hyperhidrosis is a common complication after ETS, leading to reduced patient satisfaction and postoperative quality of life. However, the appropriate level of the sympathetic chain to target with ETS to achieve maximum efficacy and reduce the risk of compensatory hyperhidrosis (CH) is controversial. In this systemic review, we investigated the appropriate level of sympathectomy for palmar hyperhidrosis. METHODS: PRISMA guidelines were implemented to complete a systematic review. We performed a computerized systematic literature search using PubMed and EMBASE from January 1990 to July 2016. We chose the Cochrane Collaboration's tool and the methodological index for non-randomized studies tool for examining study bias. RESULTS: A total of 4075 citations were identified, of which 91 were eligible for inclusion, including 68 observational studies and 23 comparative trials. In observational studies, sympathectomies showed similar efficacies for curing PH at different levels. However, T2-free groups (i.e., at levels T3, T4, or T3-T4 combined) could render a lower risk of Horner's syndrome (0 vs. 1.21 ± 0.49%, p = 0.036) and CH (28.75 ± 7.25 vs. 57.46 ± 3.86, p = 0.002) compared with T2 involved. In comparative trials, there were 12 studies describing the comparison between T2-free ETS and T2 involved, and 9 of 12 (75%) showed T2-free ETS could reduce the incidence of CH. Overall, lowering the level and limiting the extent of sympathectomy could reduce the incidence of complications. CONCLUSIONS: Cumulative data from more than 13,000 patients suggest that ETS is a safe, effective, and reproducible procedure with a high degree of patient satisfaction. Currently available evidence suggests that T2-free ETS may reduce the incidence of compensatory hyperhidrosis without compromising success rates and safety.

Sterols from the Green Alga Ulva australis.

Three new sterols, (24R)-5,28-stigmastadiene-3ß,24-diol-7-one (1), (24S)-5,28-stigmastadiene-3ß,24-diol-7-one (2), and 24R and 24S-vinylcholesta-3ß,5α,6ß,24-tetraol (3), together with three known sterols (4-6) were isolated from the green alga Ulva australis. The structures of the new compounds (1-3) were elucidated through 1D and 2D nuclear magnetic resonance spectroscopy as well as mass spectrometry. Compounds 4-6 were identified as isofucoterol (4), 24R,28S and 24S,28R-epoxy-24-ethylcholesterol (5), and (24S)-stigmastadiene-3ß,24-diol (6) on the basis of spectroscopic data analyses and comparison with those reported in the literature. Compounds 4-6 were isolated from U. australis for the first time. These compounds, together with the previously isolated secondary metabolites of this alga, were investigated for their inhibitory effects on human recombinant aldose reductase in vitro. Of the compounds, 24R,28S and 24S,28R-epoxy-24-ethylcholesterol (5), 1-O-palmitoyl-3-O-(6'-sulfo-α-d-quinovopyranosyl) glycerol, (2S)-1-O-palmitoyl-3-O-[α-d-galactopyranosyl(1→2)ß-d-galactopyranosyl] glycerol, 4-hydroxybenzoic acid, 4-hydroxyphenylacetic acid, and 8-hydroxy-(6E)-octenoic acid weakly inhibited the enzyme, while the three new sterols, 1-3, were almost inactive.

[Changes in the expression of EphA5/ephrinA5 in the CA3 region of the hippocampus in rats with epilepsy and their role in the pathogenesis of temporal lobe epilepsy].

OBJECTIVE: To investigate the changes in the expression of EphA5 and its ligand ephrinA5 in the hippocampus of rats with epilepsy and their role in the pathogenesis of temporal lobe epilepsy (TLE). METHODS: A total of 240 Sprague-Dawley rats were randomly divided into control group and TLE group, with 120 rats in each group. A rat model of lithium-pilocarpine TLE was established, and then the rats were divided into subgroups at 12 and 24 hours and 7, 15, 30, and 60 days after epilepsy was induced. In-situ hybridization was used to measure the mRNA expression of ephrinA5 in the CA3 region and the dentate gyrus of the hippocampus in 9 rats; immunohistochemistry was used to measure the protein expression of EphA5 in the CA3 region and the dentate gyrus of the hippocampus in 9 rats; Neo-Timm silver staining was used to observe mossy fiber sprouting in the CA3 region of the hippocampus in 2 rats. RESULTS: In-situ hybridization showed mRNA expression of ephrinA5 in the CA3 region of the hippocampus, but this was not found in the dentate gyrus. Compared with the control group at the same time point, the TLE group had a significant reduction in the mRNA expression of ephrinA5 in the CA3 region of the hippocampus at 7 and 15 days after epilepsy was induced (P<0.05); at 30 and 60 days after epilepsy was induced, the TLE group had a gradual increase in the mRNA expression of ephrinA5 in the CA3 region of the hippocampus, and there was no significant difference between the TLE and control groups (P>0.05). Immunohistochemistry showed that EphA5 protein was expressed in the CA3 region and the dentate gyrus of the hippocampus and had a similar trend of change as ephrinA5 mRNA. Neo-Timm silver staining showed that the TLE group developed marked mossy fiber sprouting in the CA3 region of the hippocampus at 7 and 15 days after epilepsy was induced. CONCLUSIONS: Downregulation of ephrinA5 and EphA5 in the CA3 region of the hippocampus may participate in the mechanism of mossy fiber sprouting and is closely associated with the development and progression of epilepsy.

Differential Expression of Adenosine P1 Receptor ADORA1 and ADORA2A Associated with Glioma Development and Tumor-Associated Epilepsy.

Level of adenosine, an endogenous astrocyte-based neuromodulator, is primarily regulated by adenosine P1 receptors. This study assessed expression of adenosine P1 receptors, ADORA1 (adenosine A1 receptor) and ADORA2A (adenosine A2a receptor) and their association with glioma development and epilepsy in glioma patients. Expression of ADORA1/ADORA2A was assessed immunohistochemically in 65 surgically removed glioma tissue and 21 peri-tumor tissues and 8 cases of normal brain tissues obtained from hematoma patients with cerebral trauma. Immunofluorescence, Western blot, and qRT-PCR were also used to verify immunohistochemical data. Adenosine P1 receptor ADORA1 and ADORA2A proteins were localized in the cell membrane and cytoplasm and ADORA1/ADORA2A immunoreactivity was significantly stronger in glioma and peri-tumor tissues that contained infiltrating tumor cells than in normal brain tissues (p < 0.05). The World Health Organization (WHO) grade III gliomas expressed even higher level of ADORA1 and ADORA2A. Western blot and qRT-PCR confirmed immunohistochemical data. Moreover, higher levels of ADORA1 and ADORA2A expression occurred in high-grade gliomas, in which incidence of epilepsy were lower (p < 0.05). In contrast, a lower level of ADORA1/ADORA2A expression was found in peri-tumor tissues with tumor cell presence from patients with epilepsy compared to patients without epilepsy (p < 0.05). The data from the current study indicates that dysregulation in ADORA1/ADORA2A expression was associated with glioma development, whereas low level of ADORA1/ADORA2A expression could increase susceptibility of tumor-associated epilepsy.