Neuronal MeCP2 in the dentate gyrus regulates mossy fiber sprouting of mice with temporal lobe epilepsy.

Sprouting of mossy fibers, one of the most consistent findings in tissue from patients with mesial temporal lobe epilepsy, exhibits several uncommon axonal growth features and has been considered a paradigmatic example of circuit plasticity that occurs in the adult brain. Clarifying the mechanisms responsible may provide new insight into epileptogenesis as well as axon misguidance in the central nervous system. Methyl-CpG-binding protein 2 (MeCP2) binds to methylated genomic DNA to regulate a range of physiological functions implicated in neuronal development and adult synaptic plasticity. However, exploring the potential role of MeCP2 in the documented misguidance of axons in the dentate gyrus has not yet been attempted. In this study, a status epilepticus-induced decrease of neuronal MeCP2 was observed in the dentate gyrus (DG). An essential regulatory role of MeCP2 in the development of functional mossy fiber sprouting (MFS) was confirmed through stereotaxic injection of a recombinant adeno-associated virus (AAV) to up- or down-regulate MeCP2 in the dentate neurons. Chromatin immunoprecipitation sequencing (ChIP-seq) was performed to identify the binding profile of native MeCP2 using micro-dissected dentate tissues. In both dentate tissues and HT22 cell lines, we demonstrated that MeCP2 could act as a transcription repressor on miR-682 with the involvement of the DNA methylation mechanism. Further, we found that miR-682 could bind to mRNA of phosphatase and tensin homolog (PTEN) in a sequence specific manner, thus leading to the suppression of PTEN and excessive activation of mTOR. This study therefore presents a novel epigenetic mechanism by identifying MeCP2/miR-682/PTEN/mTOR as an essential signal pathway in regulating the formation of MFS in the temporal lobe epileptic (TLE) mice. SIGNIFICANCE STATEMENT: Understanding the mechanisms that regulate axon guidance is important for a better comprehension of neural disorders. Sprouting of mossy fibers, one of the most consistent findings in patients with mesial temporal lobe epilepsy, has been considered a paradigmatic example of circuit plasticity in the adult brain. Although abnormal regulation of DNA methylation has been observed in both experimental rodents and humans with epilepsy, the potential role of DNA methylation in this well-documented example of sprouting of dentate axon remains elusive. This study demonstrates an essential role of methyl-CpG-binding protein 2 in the formation of mossy fiber sprouting. The underlying signal pathway has been also identified. The data hence provide new insight into epileptogenesis as well as axon misguidance in the central nervous system.

Ultrasensitive quantitation of Paraquat based on a small molecule-induced dual-cycle amplification strategy.

Paraquat (PQ) is a typical biotoxic small molecule. Knowledge of how to directly introduce it into cyclic amplification rather than transform it into a secondary target is lacking in current analytical methods. Considering the urgent need for trace pesticide residue detection and the inherent defects of small molecule analysis, a CRISPR/Cas12a-driven small molecule-induced dual-cycle strategy was developed based on the immune competition method. The key to signal amplification is the mutual activation and acceleration between Cycle 1 triggered by the small molecule and Cycle 2 driven by CRISPR/Cas12a. Impressively, small molecules have been successfully incorporated into the dual-cycle strategy, which achieves a low detection limit (3.1 pg/mL) and a wide linear range (from 10 pg/mL to 50 µg/mL). Moreover, the designed biosensor was successfully employed to evaluate the PQ residual level in real samples and showed effective implementation for the bioanalysis of small molecule targets and pesticide residue-related food safety.

Isoflurane-induced reduction in neurogenesis derived from the tertiary dentate matrix.

Anesthetics-induced disruption of dentate neurogenesis in the young brain is strongly suggested to contribute to delayed neurocognitive deficit. In postnatal rodents, the neurogenesis of the dentate gyrus (DG) is sequentially derived from the secondary dentate matrix, tertiary dentate matrix and subgranular zone (SGZ). However, the effects of anesthetics on the dentate neurogenesis derived from specific sites are poorly understood. To trace the new cells generated from the postnatal secondary dentate matrix, peak stage of the tertiary dentate matrix and early stage of the SGZ after isoflurane exposure, mice at postnatal day 1 (P1), P7 and P31 were injected with BrdU at 12 h before the exposure. We found that isoflurane exposure significantly reduced the numbers of proliferating cells (1 day old), immature granule cells (21 days old) or mature granule cells (42 days old) derived from the peak stage of the tertiary dentate matrix and postnatal secondary dentate matrix, but not from the SGZ. Quantitative assessment of BrdU-/BrdU+NeuN-positive cells and cleaved caspase-3 level in the DG indicated that the reduction was correlated with cell loss rather than neuronal differentiation. Mechanistically, we demonstrated that the PI3K/Akt/GSK-3ß pathway enriched by mRNA-sequencing is a requirement for the isoflurane-induced loss of 1-day-old proliferating cells generated from the tertiary dentate matrix. In addition, this study demonstrated that P1 and P7 mice, but not P31 mice exposure to isoflurane resulted in subsequent deficits in performance of the tasks of the Morris Water Maze.

Altered fear engram encoding underlying conditioned versus unconditioned stimulus-initiated memory updating.

It is known that post-retrieval extinction but not extinction alone could erase fear memory. However, whether the coding pattern of original fear engrams is remodeled or inhibited remains largely unclear. We found increased reactivation of engram cells in the prelimbic cortex and basolateral amygdala during memory updating. Moreover, conditioned stimulus- and unconditioned stimulus-initiated memory updating depends on the engram cell reactivation in the prelimbic cortex and basolateral amygdala, respectively. Last, we found that memory updating causes increased overlapping between fear and extinction cells, and the original fear engram encoding was altered during memory updating. Our data provide the first evidence to show the overlapping ensembles between fear and extinction cells and the functional reorganization of original engrams underlying conditioned stimulus- and unconditioned stimulus-initiated memory updating.

Evolution and triggers of defibrillator shocks in patients with arrhythmogenic right ventricular cardiomyopathy.

INTRODUCTION: Implantable cardioverter-defibrillators (ICDs) can prevent sudden cardiac death due to ventricular arrhythmias in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC). The aim of our study was to assess the cumulative burden, evolution and potential triggers of appropriate ICD shocks during long-term follow-up, which may help to reduce and further refine individual arrhythmic risk in this challenging disease. METHODS: This retrospective cohort study included 53 patients with definite ARVC according to the 2010 Task Force Criteria from the multicentre Swiss ARVC Registry with an implanted ICD for primary or secondary prevention. Follow-up was conducted by assessing all available patient records from patient visits, hospitalisations, blood samples, genetic analysis, as well as device interrogation and tracings. RESULTS: Fifty-three patients (male 71.7%, mean age 43±2.2 years, genotype positive 58.5%) were analysed during a median follow-up of 7.9 (IQR 10) years. In 29 (54.7%) patients, 177 appropriate ICD shocks associated with 71 shock episodes occurred. Median time to first appropriate ICD shock was 2.8 (IQR 3.6) years. Long-term risk of shocks remained high throughout long-term follow-up. Shock episodes occurred mainly during daytime (91.5%, n=65) and without seasonal preference. We identified potentially reversible triggers in 56 of 71 (78.9%) appropriate shock episodes, the main triggers representing physical activity, inflammation and hypokalaemia. CONCLUSION: The long-term risk of appropriate ICD shocks in patients with ARVC remains high during long-term follow-up. Ventricular arrhythmias occur more often during daytime, without seasonal preference. Reversible triggers are frequent with the most common triggers for appropriate ICD shocks being physical activity, inflammation and hypokalaemia in this patient population.

Efficacy comparison of acupuncture and balanced acupuncture combined with TongduZhengji manipulation in the treatment of acute lumbar sprain.

OBJECTIVE: To compare the curative effect of balanced acupuncture combined with TongduZhengji manipulation vs acupuncture in the treatment of acute lumbar sprain. METHODS: Clinical data of 71 patients with acute lumbar sprains in our hospital from January 2020 to December 2020 were retrospectively analyzed. Patients were divided into single group (n=35) and combined group (n=36) based on treatment methods. The single group received only acupuncture treatment, while the combined group received balanced acupuncture combined with TongduZhengji manipulation. The treatment efficacy, pain level, lumbar function and motion of the lumbar spine were compared between the two groups. RESULTS: The Visual Analogue Scale (VAS) scores of the combined group were lower than those of the single group after 3, 4, and 5 days of treatment (P<0.05). There was no significant difference in VAS scores between the two groups after 1 and 2 days of treatment (P>0.05). The Roland-Morris Disability Questionnaire (RMDQ) score of the combined group showed no significant difference compared with that of the single group after 1 and 2 days of treatment (P>0.05), and were lower than those of the single group after 3, 4, and 5 days of treatment (P<0.05). The Japanese Orthopedic Association (JOA) score of the combined group after 1, 2, and 3 days of treatment showed no significant difference compared with the single group (P>0.05), and was higher than that of the single group after 4 and 5 days of treatment (P<0.05). The Range of Motion (ROM) score of the combined group showed no significant difference compared with the single group after 1 and 2 days of treatment (P>0.05), and was lower than that of the single group after 3, 4, and 5 days of treatment (P<0.05). The total effective rate of treatment in the combined group was significantly higher than that in the single group (91.67% vs. 71.43%) (P<0.05). CONCLUSION: Compared with acupuncture alone, balanced acupuncture combined with TongduZhengji manipulation can significantly reduce the pain level and improve lumbar spine mobility as well as lumbar spine function, exhibiting better curative effect than acupuncture only.

Behavioural regulator and molecular reception of a double-edge-sword hunter beetle.

BACKGROUND: The black carabid beetle Calosoma maximoviczi is a successful predator that serves as both a beneficial insect and a severe threat to economic herbivores. Its hunting technique relies heavily on olfaction, but the underlying mechanism has not been studied. Here, we report the electrophysiological, ecological and molecular traits of bioactive components identified from a comprehensive panel of natural odorants in the beetle-prey-plant system. The aim of this work was to investigate olfactory perceptions and their influence on the behaviours of C. maximoviczi. RESULTS: Among the 200 identified volatiles, 18 were concentrated in beetle and prey samples, and 14 were concentrated in plants. Insect feeding damage to plants led to a shift in the emission fingerprint. Twelve volatiles were selected using successive electrophysiological tests. Field trials showed that significant sex differences existed when trapping with a single chemical or chemical mixture. Expression profiles indicated that sex-biased catches were related to the expression of 15 annotated CmaxOBPs and 40 CmaxORs across 12 chemosensory organs. In silico evaluations were conducted with 16 CmaxORs using modelling and docking. Better recognition was predicted for the pairs CmaxOR5-(Z)-3-hexenyl acetate, CmaxOR6-ß-caryophyllene, CmaxOR18-(E)-ß-ocimene and CmaxOR18-tetradecane, with higher binding affinity and a suitable binding pocket. Lastly, 168Y in CmaxOR6 and 142Y in CmaxOR18 were predicted as key amino acid residues for binding ß-caryophyllene and tetradecane, respectively. CONCLUSION: This work provides an example pipeline for de novo investigation in C. maximoviczi baits and the underlying olfactory perceptions. The results will benefit the future development of trapping-based integrated pest management strategies and the deorphanization of odorant receptors in ground beetles. © 2022 Society of Chemical Industry.

Changes in Exercise Capacity and Ventricular Function in Arrhythmogenic Right Ventricular Cardiomyopathy: The Impact of Sports Restriction during Follow-Up.

(1) Background: Physical exercise has been suggested to promote disease progression in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC). We aimed to investigate the exercise performance and ventricular function of ARVC patients during follow-up, while taking into account their adherence to exercise restriction recommendations. (2) Methods: This retrospective study included 49 patients (33 male, 67%) who had an exercise test at baseline and after 4.2 ± 1.6 years. Of the 49 ARVC patients, 27 (55%) were athletes, while 22 (45%) were non-athletes. Of the athletes, 12 (44%) continued intensive sports activity (non-adherent), while 15 (56%) stopped intensive physical activity upon recommendation (adherent). The maximum workload in Watts (W), percentage of the target workload (W%), and double product (DP) factor were measured for all patients. (3) Results: The non-adherent cohort had a significant decrease in physical performance (W at baseline vs. follow-up, p = 0.012; W% at baseline vs. follow-up, p = 0.025; DP-factor at baseline vs. follow-up, p = 0.012) over time. Left ventricular (LV) function (LV ejection fraction at baseline vs. follow-up, p = 0.082) showed a decreasing trend in the non-adherent cohort, while the performance of the adherent cohort remained at a similar level. (4) Conclusions: If intensive sports activities are not discontinued, exercise capacity and left ventricular function of athletes with ARVC deteriorates during follow-up. All patients with ARVC need to strictly adhere to the recommendation to cease intense sports activity in order to halt disease progression.

Risk factors of prehypertension and hypertension among workers at public elderly welfare facilities in Taiwan: A cross-sectional survey.

ABSTRACT: The prevalence and factors that influence prehypertension and hypertension in workers at elderly welfare facilities remain unknown. This study investigated prehypertension and hypertension as well as the relevant factors affecting the development of these conditions in workers at elderly welfare facilities.A cross-sectional survey was conducted among 242 workers at 3 elderly welfare facilities in northern Taiwan. A structured questionnaire survey comprising demographic characteristics, job characteristics, burnout inventory, and health information was employed for data collection. Chi-Squared tests and multinomial logistic regression were adopted to analyze the correlation between research variables and blood pressures as well as relevant factors influencing prehypertension and hypertension.The results indicated that sex, age, education level, type of work shift, work-related burnout, and body mass index of the research participants were significantly correlated with prehypertension and hypertension. The results of multinominal logistic regression demonstrated that being male, being older, being a nonnurse assistant, being obese, working in shifts, and having moderate or severe work-related burnout were associated with higher risks of prehypertension and hypertension. The interaction between age and being a nonnurse assistant was statistically significant. Compared with nonnurse assistants, nurse assistants aged ≥55 years had a relatively low risk of prehypertension and hypertension.Age, job characteristics, work-related burnout, and obesity of workers in elderly welfare facilities were the major risk factors for prehypertension and hypertension.

Alanine aminotransferase is more sensitive to the decrease in hepatitis B virus-DNA load than other liver markers in chronic hepatitis B patients.

BACKGROUND: A direct correlation between hepatitis B virus DNA (HBV-DNA) and liver markers has not been identified in chronic hepatitis B (CHB) patients. However, the effect of HBV-DNA changes on liver markers remains unclear. We explored the association between decreased HBV-DNA and liver makers in CHB patients. METHODS: Chronic hepatitis B patients who visited Jinhua Central Hospital twice were selected for analysis. Finally, 171 participants with a 1-log reduction in HBV-DNA between the two visits were enrolled as the case group, and 158 participants with no significant changes in HBV-DNA were enrolled as the control group. RESULTS: There was no significant correlation between HBV-DNA and liver markers (P>.05). However, in longitudinal analysis, alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma-glutamyl transpeptidase (GGT) were significantly different between the two tests (P<.05) in the case group. Conversely, there was no significant difference in the control group. When HBV-DNA decreased >26 times, ALT was reduced by half or more. A similar trend was observed with a decrease of >63 times for AST and a decrease of >76 times for GGT. CONCLUSIONS: A large change in HBV-DNA can lead to a significant variation in liver markers. In particular, ALT was more sensitive than other liver markers to a reduction in HBV-DNA.

Bigelovii E,a triterpenoid compound of Salicornia bigelovii,induced apoptosis of breast cancer MCF-7 cells via inhibiting mTOR / P70S6K / 4-EBP signaling / 中国药理学通报

Aim To demonstrate that bigelovii E,one of the triterpenoid compounds isolated from Salicornia bigelovii Torr. ,induced apoptosis and inhibited prolif-eration of human breast cancer cells MCF-7. Methods MTT and Clonogenic were used to detect the anti-proliferative effect of bigelovii E on human tumor cells. Hoechst 33258 staining was used to observe the chan-ges of cell morphology in the treatment with bigelovii E. The effect of bigelovii E on cell apoptosis,cell mi-tochondrial membrane potential and the ROS level was analyzed by flow cytometry. The expression of mito-chondrial apoptotic pathway and its regulated proteins were analyzed by Western blot. Results Bigelovii E was most sensitive to MCF-7;bigelovii E had lower toxicity to normal cells HLF1;bigelovii E inhibited the colony formation of breast cancer MCF-7;the apoptosis pattern induced by bigelovii E was detected by Hoechst 33258;Western blot showed that bigelovii E could down-regulate the phosphorylation of mTOR,p70S6K and 4-EBP,up-regulate the expression of Bcl-xl and Mcl-1 proteins,promote the mitochondrial apoptosis pathway,reduce the mitochondrial membrane poten-tial,and induce ROS,leading to mitochondrial func-tion damage,and ultimately inducing apoptosis. Con-clusion Bigelovii E regulates mitochondrial apoptosis pathway through mTOR pathway,induces apoptosis and has a good anti-tumor effect.

Use of OTSC in Treatment of Gastrointestinal Bleeding / 胃肠病学

Gastrointestinal bleeding is a common complication of gastrointestinal diseases and gastrointestinal surgery, which may lead to hemorrhagic shock or cause death if not treated properly and promptly.Currently, endoscopic treatment for gastrointestinal bleeding includes clip closure, endoscopical injection of saline/adrenaline, argon plasma coagulation (APC), electrocoagulation and heater probe coagulation etc..Endoscopic clip closure mainly includes traditional closure through-the-scope clip (TTSC) and more novel closure over-the-scope clip (OTSC).This article reviewed the use of OTSC in the treatment of gastrointestinal bleeding.

Progress on Post Traumatic Epilepsy and Its Forensic Evaluation / 法医学杂志

Post traumatic epilepsy （PTE） refers to the epileptic seizures after traumatic brain injury. Organic damage can be found by imaging examination, and abnormal electroencephalogram can be detected via electroencephalogram examination which has the similar location of the brain injury. PTE has the characteristics of low incidence, absence of case reports, and easy to exaggerate the state of illness, which add difficulties to the forensic identification. This paper reviews the status of epidemiology, pathogenesis, clinical treatment and forensic identification for PTE.

Association of Rs11615 (C>T) in the excision repair cross-complementing group 1 gene with ovarian but not gynecological cancer susceptibility: a meta-analysis.

BACKGROUND: Evidence suggests that the rs11615 (C>T) polymorphism in the ERCC1 gene may be a risk factor for gynecological tumors. However, results have not been consistent. Therefore we performed this meta- analysis. METHODS: Eligible studies were identified by search of PubMed, MEDLINE and Chinese National Knowledge Infrastructure (CNKI). Odds ratios (ORs) and 95% confidence intervals (CIs) were applied to assess associations between rs11615 (C>T) and gynecological tumor risk. Heterogeneity among studies was tested and sensitivity analysis was applied. RESULTS: A total of 6 studies were identified, with 1,766 cases and 2,073 controls. No significant association was found overall between the rs11615 (C>T) polymorphism and gynecological tumor susceptibility in any genetic model. In further analysis stratified by cancer type, significantly elevated ovarian cancer risk was observed in the homozygote and recessive model comparison (TT vs CC: OR=1.69, 95% CI=1.03-2.77, heterogeneity=0.876; TT vs CT/CC: OR=1.72, 95% CI=1.07-2.77, heterogeneity=0.995). CONCLUSION: The results of the present meta-analysis suggest that there is no significant association between the rs11615 (C>T) polymorphism and gynecological tumor risk, but it had a increased risk in ovarian cancer.

Molecular cloning, sequence analysis and expression of a GHF 43 xylanase from Aspergillus niger in Escherichia coli.

A new xylanase gene (xyn43A) from Aspergillus niger XZ-3S was cloned and expressed in Escherichia coli BL21-CodonPlus (DE3)-RIL. The coding region of the gene was separated by only one intron 86 bp in length. It encoded 318 amino acid residues of a protein with a calculated molecular weight (MW) of 33.47 kDa plus a signal peptide of 19 amino acids. The amino acid sequence of the xyn43A gene showed 77.56% amino acid identity to A. nidulans xylanase, and the phylogenetic tree analysis revealed that xyn43A had close relationships with those of family 43 of glycosyl hydrolases reported from other microorganisms. Three-dimensional structure modeling showed that Xyn43A had a typical five-blade ß-propeller fold. The mature peptide encoding cDNA was subcloned into pET-28a (+) expression vector. The resultant recombinant plasmid pET-28a-xyn43A was transformed into Escherichia coli BL21-CodonPlus (DE3)-RIL, and xylanase activity was measured. A maximum activity of 61.43 U/mg was obtained from the cellular extract of E. coli BL21-CodonPlus (DE3)-RIL harboring pET-28a-xyn43A. The recombinant xylanase had optimal activity at pH5.0 and 45°C. Fe(3+), Cu(2+) and EDTA had an obvious active effect on the enzyme.

Correlation of daily living activities with location and severity of traumatic brain injury / 法医学杂志

OBJECTIVE@#To study the correlation of daily living activities with location and severity of trau- matic brain injury (TBI) and to provide a theoretical basis for improving the accuracy of expert opinion.@*METHODS@#Five hundred and one cases of patients with TBI were selected. Detailed records included following: pre-injury situation, location and severity of injury, treatment and education. Daily living activi- ties scale (Barthel index) was applied to test the subjects' daily living activities. The relevance among location and severity of TBI and Barthel index was statistically analyzed.@*RESULTS@#In mild TBI group, there was no significant difference in Barthel index among each location (P>0.05). In moderate TBI group, there were significant differences in Barthel index between subarachnoid hemorrhage and cerebral lobe injury, also between parietal, occipital lobes injury and frontal lobe injury, parietal, occipital lobes injury and temporal lobe (P<0.05), respectively, whereas no significant difference in Barthel index between frontal lobe injury and temporal lobe injury (P>0.05). In severe TBI, there were significant differences in Barthel index between every two different locations (P<0.05).@*CONCLUSION@#There is some correlation between the location of TBI and Barthel index, which provides an important reference value for analyzing and determining daily living activities after TBI.

Prognostic value by combination of angiographic and clinical characteristics in stenting patients with unprotected left main coronary artery lesion / 中华老年医学杂志

Objective To compare the predicting values for Prognosis among Global Risk Classification (GRS),Synergy Between Percutaneous Coronary Intervention With TAXUS and Cardiac Surgery (SYNTAX) score,the European System for Cardiac Operative Risk Evaluation (EuroSCORE) in patients who received stenting because of unprotected left main coronary artery (ULMCA) lesion.Methods Totally 105 successive elderly patients with ULMCA lesion who received stenting were divided into 2 groups:with and without main adverse cardiac events (MACE).The clinical and angiographic characteristics were analyzed and then compared among GRC,SYNTAX score and EuroSCORE.Results As compared with none MACE group,MACE group had higher EuroSCORE score (2.0±2.3 vs.6.5±2.9,t=8.18,P=0.002),and more trivessel disease and left main bifurcation lesion (x2 =8.96,6.96,P =0.011,P =0.008).High risk GRC showed more MACE than medium or low risk GRC [55.9％ (19/34) vs.20.5％(9/44),7.4％ (2/27),x2 =19.77,P=0.001].AUC(95％CI )of GRC,SYNTAX score and EuroSCORE were [0.821 (0.730-0.912),0.586(0.462-0.709) and 0.631 (0506-0.757)],respectively.Compared with SYNTAX score and EuroSCORE,GRC was superior in the MACE predicting value (Z=3.29,2.63,P＜0.01 or P＜0.05).