RyR2 Stabilizer Attenuates Cardiac Hypertrophy by Downregulating TNF-α/NF-κB/NLRP3 Signaling Pathway through Inhibiting Calcineurin.

The effect of Ryanodine receptor2 (RyR2) and its stabilizer on cardiac hypertrophy is not well known. C57/BL6 mice underwent transverse aortic contraction (TAC) or sham surgery were administered dantrolene, the RyR2 stabilizer, or control drug. Dantrolene significantly alleviated TAC-induced cardiac hypertrophy in mice, and RNA sequencing was performed implying calcineurin/NFAT3 and TNF-α/NF-κB/NLRP3 as critical signaling pathways. Further expression analysis and Western blot with heart tissue as well as neonatal rat cardiomyocyte (NRCM) model confirmed dantrolene decreases the activation of calcineurin/NFAT3 signaling pathway and TNF-α/NF-κB/NLRP3 signaling pathway, which was similar to FK506 and might be attenuated by calcineurin overexpression. The present study shows for the first time that RyR2 stabilizer dantrolene attenuates cardiac hypertrophy by inhibiting the calcineurin, therefore downregulating the TNF-α/NF-κB/NLRP3 pathway.

Structural insights into branch site proofreading by human spliceosome.

Selection of the pre-mRNA branch site (BS) by the U2 small nuclear ribonucleoprotein (snRNP) is crucial to prespliceosome (A complex) assembly. The RNA helicase PRP5 proofreads BS selection but the underlying mechanism remains unclear. Here we report the atomic structures of two sequential complexes leading to prespliceosome assembly: human 17S U2 snRNP and a cross-exon pre-A complex. PRP5 is anchored on 17S U2 snRNP mainly through occupation of the RNA path of SF3B1 by an acidic loop of PRP5; the helicase domain of PRP5 associates with U2 snRNA; the BS-interacting stem-loop (BSL) of U2 snRNA is shielded by TAT-SF1, unable to engage the BS. In the pre-A complex, an initial U2-BS duplex is formed; the translocated helicase domain of PRP5 stays with U2 snRNA and the acidic loop still occupies the RNA path. The pre-A conformation is specifically stabilized by the splicing factors SF1, DNAJC8 and SF3A2. Cancer-derived mutations in SF3B1 damage its association with PRP5, compromising BS proofreading. Together, these findings reveal key insights into prespliceosome assembly and BS selection or proofreading by PRP5.

An unexpected hydratase synthesizes the green light-absorbing pigment fucoxanthin.

The ketocarotenoid fucoxanthin and its derivatives can absorb blue-green light enriched in marine environments. Fucoxanthin is widely adopted by phytoplankton species as a main light-harvesting pigment, in contrast to land plants that primarily employ chlorophylls. Despite its supreme abundance in the oceans, the last steps of fucoxanthin biosynthesis have remained elusive. Here, we identified the carotenoid isomerase-like protein CRTISO5 as the diatom fucoxanthin synthase that is related to the carotenoid cis-trans isomerase CRTISO from land plants but harbors unexpected enzymatic activity. A crtiso5 knockout mutant in the model diatom Phaeodactylum tricornutum completely lacked fucoxanthin and accumulated the acetylenic carotenoid phaneroxanthin. Recombinant CRTISO5 converted phaneroxanthin into fucoxanthin in vitro by hydrating its carbon-carbon triple bond, instead of functioning as an isomerase. Molecular docking and mutational analyses revealed residues essential for this activity. Furthermore, a photophysiological characterization of the crtiso5 mutant revealed a major structural and functional role of fucoxanthin in photosynthetic pigment-protein complexes of diatoms. As CRTISO5 hydrates an internal alkyne physiologically, the enzyme has unique potential for biocatalytic applications. The discovery of CRTISO5 illustrates how neofunctionalization leads to major diversification events in evolution of photosynthetic mechanisms and the prominent brown coloration of most marine photosynthetic eukaryotes.

Structural basis of pre-tRNA intron removal by human tRNA splicing endonuclease.

Removal of the intron from precursor-tRNA (pre-tRNA) is essential in all three kingdoms of life. In humans, this process is mediated by the tRNA splicing endonuclease (TSEN) comprising four subunits: TSEN2, TSEN15, TSEN34, and TSEN54. Here, we report the cryo-EM structures of human TSEN bound to full-length pre-tRNA in the pre-catalytic and post-catalytic states at average resolutions of 2.94 and 2.88 Å, respectively. Human TSEN features an extended surface groove that holds the L-shaped pre-tRNA. The mature domain of pre-tRNA is recognized by conserved structural elements of TSEN34, TSEN54, and TSEN2. Such recognition orients the anticodon stem of pre-tRNA and places the 3'-splice site and 5'-splice site into the catalytic centers of TSEN34 and TSEN2, respectively. The bulk of the intron sequences makes no direct interaction with TSEN, explaining why pre-tRNAs of varying introns can be accommodated and cleaved. Our structures reveal the molecular ruler mechanism of pre-tRNA cleavage by TSEN.

Effects of Workplace Ostracism on Burnout among Nursing Staff during the COVID-19 Pandemic, Mediated by Emotional Labor.

This study investigated the effects of workplace ostracism on emotional labor and burnout among current nursing staff during the COVID-19 pandemic, as well as the relationship between the surface acting and deep acting of emotional labor as the mediators of workplace ostracism and burnout. The sample for this study consisted of 250 nursing staff recruited from Taiwanese medical institutions, and the questionnaire was divided into two stages. The first stage included questions about ostracism and personal data, and then two months later the same respondents completed part two of the questionnaire regarding emotional labor and burnout, which solved the problem of common-method variance (CMV). The results of this study indicate that ostracism had a positive and significant effect on burnout and surface acting, but its negative effect on deep acting was not supported. While surface acting showed partial mediation between ostracism and burnout, deep acting did not have a significant mediating effect between ostracism and burnout. These results can provide a reference for practice and researchers.

Mechanisms of the RNA helicases DDX42 and DDX46 in human U2 snRNP assembly.

Three RNA helicases - DDX42, DDX46 and DHX15 - are found to be associated with human U2 snRNP, but their roles and mechanisms in U2 snRNP and spliceosome assembly are insufficiently understood. Here we report the cryo-electron microscopy (cryo-EM) structures of the DDX42-SF3b complex and a putative assembly precursor of 17S U2 snRNP that contains DDX42 (DDX42-U2 complex). DDX42 is anchored on SF3B1 through N-terminal sequences, with its N-plug occupying the RNA path of SF3B1. The binding mode of DDX42 to SF3B1 is in striking analogy to that of DDX46. In the DDX42-U2 complex, the N-terminus of DDX42 remains anchored on SF3B1, but the helicase domain has been displaced by U2 snRNA and TAT-SF1. Through in vitro assays, we show DDX42 and DDX46 are mutually exclusive in terms of binding to SF3b. Cancer-driving mutations of SF3B1 target the residues in the RNA path that directly interact with DDX42 and DDX46. These findings reveal the distinct roles of DDX42 and DDX46 in assembly of 17S U2 snRNP and provide insights into the mechanisms of SF3B1 cancer mutations.

Temperature-dependent Functional Response of the Arboreal Rove Beetle, Oligota flavicornis (Coleoptera: Staphylinidae), a Voracious Predator of Tetranychus urticae (Acarina: Tetranychidae).

The functional responses of Oligota flavicornis (Boisduval & Lacordaire) (Coleoptera: Staphylinidae) preying on the eggs of Tetranychus urticae Koch (Acarina: Tetranychidae) were examined at seven constant temperature settings (12, 15, 18, 22, 25, 30, and 32°C) to elucidate the predator-prey interactions between them. Logistic regression showed that O. flavicornis exhibited type II functional responses to T. urticae eggs at different temperatures. The reciprocal of handling time declined exponentially with warming, and the search rate presented a single hump-shaped relationship with temperature. For the search rate, the lower temperature thresholds were 9.1°C (linear) and 8.7°C (Briere). The optimal temperature and upper temperature threshold were 29.1 and 37.8°C for Logan and 29.7 and 35.8°C for Briere, respectively. The predation threshold window of O. flavicornis reached 27.1°C with a range of 8.7-35.8°C. The predator could consume 244.7-388.4 T. urticae eggs in a day in the optimal temperature range (18-32°C). The voracious predatory behavior of O. flavicornis against T. urticae eggs over a broad temperature range indicates that the predator shows promise as a potential biological control agent and that temperature-dependent predation could be a basis for formulating strategies to control tetranychid mites.

METTL14 promotes doxorubicin-induced cardiomyocyte ferroptosis by regulating the KCNQ1OT1-miR-7-5p-TFRC axis.

Doxorubicin (DOX) has toxic effects on the heart, causing cardiomyopathy and heart injury, but the underlying mechanisms of these effects require further investigation. This study investigated the role of DOX in promoting ferroptosis to induce myocardial injury. AC16 cardiomyocyte and neonatal rat ventricle cardiomyocytes were used as an in vitro model to study the molecules involved in myocardial injury using gene silencing, ectopic expression, and RNA immunoprecipitation. Messenger RNA and protein level analyses showed that DOX treatment resulted in the upregulation of methyltransferase-like 14 (METTL14), which catalyzes the m6A modification of the long non-coding RNA KCNQ1OT1, a miR-7-5p sponge. The RNA-binding protein IGF2BP1 is associated with KCNQ1OT1 to increase its stability and robustly inhibit miR-7-5p activity. Furthermore, a lack of miR-7-5p expression led to increased levels of transferrin receptor, promoting the uptake of iron and production of lipid reactive oxygen species and demonstrating that DOX-induced ferroptosis occurs in AC16 cells. Additionally, we found that miR-7-5p targets METTL14 in AC16 cells. Meanwhile, the role of METTL14/KCNQ1OT1/miR-7-5p axis in regulating ferroptosis in neonatal rat ventricle cardiomyocytes was also confirmed. Our results indicate that selectively inhibiting ferroptosis mediated by a METTL14/KCNQ1OT1/miR-7-5p positive feedback loop in cardiomyocytes could provide a new therapeutic approach to control DOX-induced cardiac injury.

Are virtual anime endorsers a new type of endorser? Examining product involvement as a moderating role.

Virtual anime endorsement has been prevalent as an advertising strategy, and many companies invest massive amounts of money into virtual endorsements. While previous studies have found that endorser-product congruence is related to consumer brand attitude and purchase intention, it is not known whether moderate incongruence between a virtual anime endorser and a product has a positive influence on brand attitude and purchase intention. This study developed a 1 × 2 experiment to investigate the influences of virtual anime endorser-product congruence and moderate the endorser-product incongruence on consumer brand attitude and purchase intention. Product involvement played a key moderating role in the relationships of virtual anime endorser-product congruence and the endorser-product incongruence with consumer attitudes. A total of 919 participants were recruited from animation-related venues and stores in Taiwan. The findings of this study validated the interaction effects of virtual anime endorser-product congruence and incongruence on these two consumer responses, i.e., brand attitude and purchase intention. This study further investigated the moderating effect of product involvement in the relationships of virtual anime endorser-product congruence and moderate the endorser-product incongruence with consumer responses. The findings of this study provide a valuable reference regarding endorsers and product patterns through which enterprises can maximize their value.

Green diatom mutants reveal an intricate biosynthetic pathway of fucoxanthin.

Fucoxanthin is a major light-harvesting pigment in ecologically important algae such as diatoms, haptophytes, and brown algae (Phaeophyceae). Therefore, it is a major driver of global primary productivity. Species of these algal groups are brown colored because the high amounts of fucoxanthin bound to the proteins of their photosynthetic machineries enable efficient absorption of green light. While the structure of these fucoxanthin-chlorophyll proteins has recently been resolved, the biosynthetic pathway of fucoxanthin is still unknown. Here, we identified two enzymes central to this pathway by generating corresponding knockout mutants of the diatom Phaeodactylum tricornutum that are green due to the lack of fucoxanthin. Complementation of the mutants with the native genes or orthologs from haptophytes restored fucoxanthin biosynthesis. We propose a complete biosynthetic path to fucoxanthin in diatoms and haptophytes based on the carotenoid intermediates identified in the mutants and in vitro biochemical assays. It is substantially more complex than anticipated and reveals diadinoxanthin metabolism as the central regulatory hub connecting the photoprotective xanthophyll cycle and the formation of fucoxanthin. Moreover, our data show that the pathway evolved by repeated duplication and neofunctionalization of genes for the xanthophyll cycle enzymes violaxanthin de-epoxidase and zeaxanthin epoxidase. Brown algae lack diadinoxanthin and the genes described here and instead use an alternative pathway predicted to involve fewer enzymes. Our work represents a major step forward in elucidating the biosynthesis of fucoxanthin and understanding the evolution, biogenesis, and regulation of the photosynthetic machinery in algae.

Investigating the Pathogenesis of MYH7 Mutation Gly823Glu in Familial Hypertrophic Cardiomyopathy using a Mouse Model.

Familial hypertrophic cardiomyopathy (HCM, OMIM: 613690) is the most common cardiomyopathy in China. However, the underlying genetic etiology of HCM remains elusive. We previously identified a myosin heavy chain 7 (MYH7) gene heterozygous variant, NM_000257.4: c.G2468A (p.G823E), in a large Chinese Han family with HCM. In this family, variant G823E cosegregates with an autosomal dominant disorder. This variant is located in the lever arm domain of the neck region of the MYH7 protein and is highly conserved among homologous myosins and species. To verify the pathogenicity of the G823E variant, we produced a C57BL/6N mouse model with a point mutation (G823E) at the mouse MYH7 locus with CRISPR/Cas9-mediated genome engineering. We designed gRNA targeting vectors and donor oligonucleotides (with targeting sequences flanked by 134 bp of homology). The p.G823E (GGG to GAG) site in the donor oligonucleotide was introduced into exon 23 of MYH7 by homology-directed repair. A silenced p.R819 (AGG to CGA) was also inserted to prevent gRNA binding and re-cleavage of the sequence after homology-directed repair. Echocardiography revealed left ventricular posterior wall (LVPW) hypertrophy with systole in MYH7 G823E/- mice at 2 months of age. These results were likewise validated by histological analysis (Figure 3). These results demonstrate that the G823E variant plays an important role in the pathogenesis of HCM. Our findings enrich the spectrum of MYH7 variants linked to familial HCM and may provide guidance for genetic counseling and prenatal diagnosis in this Chinese family.

Examine the relationships between health-related quality of life, achievement motivation and job performance: the case of Taiwan hospitality industry.

BACKGROUND: Employees are considered as one of the most important assets in many organizations, and their health well-being is critical to help achieve a sustainable and motivated workforce that is committed to delivering quality hospitality services through enhanced performance and productivity. Given the extent of the challenges and impact presented by the COVID-19 pandemic to the hospitality industry, it is timely to gain further insights on employees' health well-being. The key purpose of this study is to examine the relationships between health-related quality of life, achievement motivation and job performance in the Taiwan hospitality industry, to acquire a better understanding of their relationships through the job performance pathway models. METHODS: This study has used a purposeful sampling technique to select the 10 highest-earning hospitality companies in Taiwan. A total of 292 questionnaires were collected from the employees of these hospitality companies. Based on the multi-dimensional concept of health-related quality of life (HRQoL), the relationships between the five key dimensions (i.e. psychological health, physical health, social health, achievement motivation, and job performance) were examined. To measure these dimensions, the survey questions were adapted from previous research such as the World Health Organization's WHOQOL-BREF scale, Minnesota Satisfaction Questionnaire. Partial least squares - Structural Equation Modeling method was used to explore these dimensions, and two job performance pathway models (for manager and staff) were subsequently developed. RESULTS AND CONCLUSIONS: Findings showed that psychological health directly affected the manager's job performance and physical health had a similar effect through social health. While psychological health had not affected the staff's job performance, but it could affect achievement motivation through both direct and indirect effects of social health. The pathway models that were developed indicated that the manager's job performance was mainly affected by psychological health and social health, whereas the key dimension that had affected the staff's job performance was achievement motivation.

Profilin 2 and Endothelial Exosomal Profilin 2 Promote Angiogenesis and Myocardial Infarction Repair in Mice.

Cardiovascular diseases (CVD) are the leading cause of death worldwide, wherein myocardial infarction (MI) is the most dangerous one. Promoting angiogenesis is a prospective strategy to alleviate MI. Our previous study indicated that profilin 2 (PFN2) may be a novel target associated with angiogenesis. Further results showed higher levels of serum PFN2 and exosomal PFN2 in patients, mice, and pigs with MI. In this study, we explored whether PFN2 and endothelial cell (EC)-derived exosomal PFN2 could increase angiogenesis and be beneficial for the treatment of MI. Serum PFN2, exosomes, and exosomal PFN2 were elevated in rats with MI. PFN2 and exosomes from PFN2-overexpressing ECs (OE-exo) enhanced EC proliferation, migration, and tube formation ability. OE-exo also significantly increased the vessel number in zebrafish and protected the ECs from inflammatory injury. Moreover, OE-exo-treated mice with MI showed improvement in motor ability, ejection fraction, left ventricular shortening fraction, and left ventricular mass, as well as increased vessel numbers in the MI location, and decreased infarction volume. Mechanistically, PI3K might be the upstream regulator of PFN2, while ERK might be the downstream regulator in the PI3K-PFN2-ERK axis. Taken together, our findings demonstrate that PFN2 and exosomal PFN2 promote EC proliferation, migration, and tube formation through the PI3K-PFN2-ERK axis. Exosomal PFN2 may be a valuable target in the repair of MI injury via angiogenesis.

Temperature-Dependent Demography of Thrips hawaiiensis (Thysanoptera: Thripidae): Implications for Prevention and Control.

The Hawaiian flower thrips, Thrips hawaiiensis (Morgan), a common flower-inhabiting thrip, is now a potential pest globally. Effective control of T. hawaiiensis requires information about the effects of temperature on its ontogeny and population growth. In this study, the life history characteristics and demography of T. hawaiiensis were defined at eight temperatures (9-35°C). Additionally, the thermal constant and temperature threshold were estimated by regression analysis. The developmental duration and longevity of T. hawaiiensis decreased with an increase in temperature between 16°C and 32°C; females survived for longer than males at all temperatures. The lower temperature threshold and thermal constant of preadult T. hawaiiensis were 10.5°C and 132.5 degree-days, respectively. The oviposition days of the females gradually decreased from 16°C to 32°C, and net maternity was higher at 20°C than at 16°C, even though the same number of eggs were laid at both temperatures. The mean longevities of the populations were greatest at 20°C; the life expectancy and reproductive value decreased with temperature. The intrinsic rate of increase and finite rate of increase were significantly highest at 20°C, 25°C, and 30°C. Population growth was triggered at 12.3°C, and reached a peak at approximately 27°C when it proliferated to the largest population size. Therefore, the results suggest that although the population of T. hawaiiensis starts to grow at lower temperatures, it adapts to a wide range of temperatures, and these findings facilitate prediction of different stages of damage, population size, and seasonal occurrence of T. hawaiiensis.

Compatibility of six reduced-risk insecticides with Orius strigicollis (Heteroptera: Anthocoridae) predators for controlling Thrips hawaiiensis (Thysanoptera: Thripidae) pests.

Contact toxicity assessments of six reduced risk insecticides were carried out to compare their selectivity and sensitivity toward the minute pirate bug Orius strigicollis and its prey Thrips hawaiiensis. Additionally, and their potential exposure risk were evaluated for O. strigicollis. The LR50 value of acetamiprid, emamectin benzoate, cyetpyrafen, and indoxacarb to T. hawaiiensis were 0.126, 2.093, 7.486, and 2.264 g a.i. ha-1, respectively, far less than the maximum field recommended rate (MFRR) for each. These four insecticides showed higher selectivity for predator and prey with selectivity ratio values of 37.3, 14.8, 22.1, and 119.3, respectively. However, the LR50 value of acetamiprid and emamectin benzoate were lower than MFRR, and unacceptable (approximately unacceptable for emamectin benzoate) risk to O. strigicollis in in-field, and the opposite results were shown in cyetpyrafen and indoxacarb. Although T. hawaiiensis was more sensitive to abamectin than O. strigicollis, the insecticide had poor selectivity for both test insects. The LR50 value of spirotetramat was more than 3 fold MFRR for T. hawaiiensis and O. strigicollis, showing extremely low contact toxicity and selectivity. In general, acetamiprid, emamectin benzoate, cyetpyrafen, and indoxacarb showed high bioactivity against T. hawaiiensis, but only cyetpyrafen and indoxacarb could be well compatible with O. strigicollis, the combination of two insecticides with O. strigicollis indicated a potential strategy for the efficient and safe control of T. hawaiiensis.

Advanced machine learning application for odor and corrosion control at a water resource recovery facility.

The objective of this study was to develop a machine learning (ML) application to determine the optimal dosage of sodium hypochlorite (NaOCl) to curtail corrosion and odor by H2 S in the headworks of a water resource recovery facility (WRRF) without overly consuming volatile fatty acids (VFAs) that are essential for the enhanced biological phosphorus removal. Given the highly diverse datasets available, three subproblems were formulated, and three cascaded ML modules were developed accordingly. The final ML models, chosen based on performance, were able to predict various targeted variables. More specifically, in Module 1, a recurrent neural network (RNN) was designed to predict wastewater characteristics. In Module 2, a random forest (RF) classifier and a support vector machine (SVM) classifier were built with the information from Module 1 along with other datasets to predict the concentrations of VFAs and H2 S, respectively. Finally, in Module 3, with the information obtained from Module 2, another RF classifier was developed to predict NaOCl dosage to reduce H2 S but keeping VFAs within the target range. These efforts are relevant and informative for WRRFs that are considering developing Intelligent Water Systems to predict the wastewater characteristics to make operational improvements. PRACTITIONER POINTS: A recurrent neural network (RNN) using long short-term memory (LSTM) successfully predicted influent wastewater parameters. A support vector machine classifier predicted hydrogen sulfide (H2 S) with 97.6% accuracy. The concentration of VFAs, an important parameter in EBPR, was predicted using a random forest classifier with 93.4% accuracy. The optimal NaOCl dosage for H2 S control can be predicted with a random forest classifier using H2 S, VFAs, and flow.

SYVN1/GPX5 axis affects ischemia/reperfusion induced apoptosis of AC16 cells by regulating ROS generation.

Ischemia/reperfusion (I/R) induced injury is a major cause of coronary heart disease (CHD). Increased production of reactive oxygen species (ROS) can lead to an I/R injury in CHD, and the ROS level can be regulated by Glutathione peroxidase (GPX) enzyme family. In this study, we investigated the role and underlying molecular mechanism of GPX5 in I/R-induced AC16 cells. We found that the serum level of GPX5 was down-regulated in patients with CHD and I/R-induced AC16 cells. Overexpression of GPX5 inhibited I/R-induced apoptosis by suppressing the production of ROS. On the other hand, knock-down of GPX5 promoted apoptosis in AC16 cells by up-regulating the level of ROS. Furthermore, we found that GPX5 was regulated by synovial apoptosis inhibitor 1 (SYVN1)-mediated ubiquitination in AC16 cells. In I/R-induced AC16 cells, the expression of SYVN1 was up-regulated, and SYVN1 knock-down decreased the ROS levels and apoptotic rate but increased GPX5 levels. Moreover, GPX5 knockdown promoted ROS production and apoptosis, while its effects were attenuated by SYVN1 knockdown. Furthermore, SYVN1 was up-regulated while GPX5 was down-regulated in the myocardial tissue of I/R-injured rats. Taken together, our data demonstrate that GPX5 inhibits I/R-induced apoptosis of AC16 cells by down-regulating ROS level, and its stabilization is regulated by SYVN1-mediated ubiquitination.

Case Report: A Case of Eyelid Myoclonic Status With Tonic-Clonic Seizure and Literature Review.

Eyelid myoclonus with or without absence epilepsy is a rare and usually misdiagnosed disease in the neurology department. It is an idiopathic general epileptic syndrome, the onset period is 6-8 years, and is more common in girls. It is characterized by rapid abnormal eye blinking, accompanied by upward rolling of the eye and slight backward movement of the head, with eye closure sensitivity and photosensitivity. The seizure is frequent and short, dozens or even hundreds of times a day; a small number of patients may have eyelid myoclonus status. We report a patient who visits the hospital for the first time with eyelid myoclonic problem; the patient continued to wink the eyes, eye rolled up, and backward movement of the head, accompanied by impairment of consciousness. Video electroencephalography (VEEG) suggests continued spike slow-wave, polyspike slow-wave. After the patient had 2, 4, 6, 8, 10, 12, and 14 Hz of intermittent photic stimulation (IPS), her seizures and epileptic discharges reduced or stopped. Seven min after giving stimulation at 20 Hz, the child developed an occipital-initiated tonic-clonic seizure, which demonstrated that after sufficient IPS stimulation, the occiput cortex became excited and initiated a brain network, leading to diffuse brain discharge and tonic-clonic seizures. At 1 h after onset, the child developed a nonconvulsive state, with impairment of consciousness despite no eyelid myoclonic movements, and VEEG suggested a large number of epileptic discharges. After 10 min of administrating midazolam, the patient's EEG immediately became normal, and the patient regained consciousness. Therefore, this paper presents an eyelid myoclonus status patient with occipital origin seizure, we recorded the whole course of the disease and the treatment effect, and reviewed the literature accordingly.

WTAP promotes myocardial ischemia/reperfusion injury by increasing endoplasmic reticulum stress via regulating m6A modification of ATF4 mRNA.

Myocardial infarction (MI) is one of the leading causes of death. Wilms' tumor 1-associating protein (WTAP), one of the components of the m6A methyltransferase complex, has been shown to affect gene expression via regulating mRNA modification. Although WTAP has been implicated in various diseases, its role in MI is unclear. In this study, we found that hypoxia/reoxygenation (H/R) time-dependently increased WTAP expression, which in turn promoted endoplasmic reticulum (ER) stress and apoptosis, in human cardiomyocytes (AC16). H/R effects on ER stress and apoptosis were all blocked by silencing of WTAP, promoted by WTAP overexpression, and ameliorated by administration of ER stress inhibitor, 4-PBA. We then investigated the underlying molecular mechanism and found that WTAP affected m6A methylation of ATF4 mRNA to regulate its expression, and that the inhibitory effects of WTAP on ER stress and apoptosis were ATF4 dependent. Finally, WTAP's effects on myocardial I/R injury were confirmed in vivo. WTAP promoted myocardial I/R injury through promoting ER stress and cell apoptosis by regulating m6A modification of ATF4 mRNA. These findings highlight the importance of WTAP in I/R injury and provide new insights into therapeutic strategies for MI.

CB2R induces a protective response against epileptic seizures through ERK and p38 signaling pathways.

BACKGROUND AND PURPOSE: Epilepsy is a pivotal neurological disorder characterized by the synchronous discharging of neurons to induce momentary brain dysfunction. Temporal lobe epilepsy is the most common type of epilepsy, with seizures originating from the mesial temporal lobe. The hippocampus forms part of the mesial temporal lobe and plays a significant role in epileptogenesis; it also has a vital influence on the mental development of children. In this study, we aimed to explore the effects of CB2 receptor (CB2R) activation on ERK and p38 signaling in nerve cells of a rat epilepsy model. MATERIALS AND METHODS: We treated Sprague-Dawley rats with pilocarpine to induce an epilepsy model and treated such animals with a CB2R agonist (JWH133) alone or with a CB2R antagonist (AM630). Nissl's stain showed the neuron conditon in different groups. Western blot analyzed the level of p-ERK and p-p38. RESULTS: JWH133 can increase the latent period of first seizure attack and decrease the Grades IV-V magnitude ratio after the termination of SE. Nissl's stain showed JWH133 protected neurons in the hippocampus while AM630 inhibited the functioning of CB2R in neurons. Western blot analysis showed that JWH133 decreased levels of p-ERK and p-p38, which is found at increased levels in the hippocampus of our epilepsy model. In contrast, AM630 inhibited the protective function of JWH133 and also enhanced levels of p-ERK and p-p38. CONCLUSIONS: CB2R activation can induce neurons proliferation and survival through activation of ERK and p38 signaling pathways.