Novel mutation in EFEMP1 identified from two Chinese POAG families differentially activated endoplasmic reticulum stress markers and induced glaucoma in mouse.

Primary open-angle glaucoma (POAG) is the most common type of glaucoma. Using whole-exome sequencing, we identified two independent families diagnosed as POAG from the China with a novel EFEMP1 variant (Exon3, c.175A>C p.Met59Leu); Three previously reported variants c.1160G>A p.R387Q, c.1189T>C p.Y397H, and c.1429C>T p.R477C in EFEPM1 from 55 sporadic POAG individuals were also identified. The variant c.175A>C p.Met59Leu co-segregated with the disease phenotype within the families. Immunoprecipitation and western blot assays showed that all three EFEMP1 mutants (p.Met59Leu, pArg140Trp, pArg345Trp) increased intracellular protein aggregations, and pMet59Leu and pArg140Arg also enhanced their extracellular proteins secretion, compared to WT in HEK293T. The differential regulations to endoplasmic reticulum (ER) stress markers ATF4, GPR78/94, and CHOP, and differential phosphorylation activations to CREB at Ser133, AKT at Ser473, p44/42 at Thr202/Tyr204, and STAT3 at Tyr705, were also detected among the mutants and WT. Finally, we revealed a significant increment of intraocular pressure and obvious reduction of RGC cells at the sixth week following intravitreal injection of adenovirus 5 (Ad5) expressing in pMet59Leu compared to WT and GFP controls. Together, variant c.175A>C p.Met59Leu in EFEMP1 is pathogenic and different mutants in EFEMP1 triggered distinct signaling pathways, explaining the reason of mutation-dependent disease phenotypes of EFEMP1.

Oxygen-enriched pitch-derived hierarchically porous carbon toward boosted zinc-ion storage performance.

The lack of cathode materials with satisfactory Zn2+ storage capability substantially hinders the realization of high-performance aqueous zinc-ion hybrid capacitors (ZHCs). Herein, we propose a facile KMnO4 template-assisted KOH activation strategy to prepare a novel oxygen-enriched hierarchically porous carbon (HPC-1-4). This strategy efficiently converts coal tar pitch (CTP) into a well-tuned carbon material with a large specific surface area of 3019 m2 g-1 and a high oxygen content of 9.20 at%, which is conducive to providing rich active sites, rapid charge transport, and appreciable pseudocapacitance for Zn-ion storage. Thus, the as-fabricated HPC-1-4-based aqueous ZHC exhibits prominent performance, including a high gravimetric capacity (206.7 mAh g-1 at 0.25 A g-1), a remarkable energy density (153.4 Wh kg-1 at 184.2 W kg-1), and an impressive power output (15240 W kg-1 at 63.5 Wh kg-1). In-depth ex-situ characterizations indicate that the excellent electrochemical properties of ZHCs are due to the synergistic effect of the Zn2+ adsorption mechanism and reversible chemisorption. In addition, the assembled quasi-solid-state device demonstrates excellent electrochemical stability of up to 100% capacity retention over 50000 cycles, accompanied with a desirable energy density of 115.6 Wh kg-1. The facile preparation method of converting CTP into carbonaceous functional materials has advanced the development of efficient and eco-friendly energy storage technologies.

Recyclable gold(I)-catalyzed heterocyclization of ynamides with benzyl or indolyl azides towards 2-aminoindoles or 3-amino-ß-carbolines.

A highly efficient heterogeneous gold(I)-catalyzed heterocyclization of ynamides with benzyl or indolyl azides has been achieved in 1,2-dichloroethane under mild conditions via a heterogenized α-imino gold carbene intermediate using 5 mol% of SBA-15-anchored strongly hindered NHC-gold(I) complex [IPr-SBA-15-AuNTf2] as the catalyst, delivering a wide range of valuable 2-aminoindoles or 3-amino-ß-carbolines in mostly good to excellent yields with high regioselectivity. Furthermore, the new heterogenized NHC-gold(I) complex displays the same catalytic activity as IPrAuNTf2 and is facile to recover by centrifugation of the reaction mixture and can be reused at least seven times without any appreciable drop in its catalytic activity.

MiR-122 knockdown regulates vascular smooth muscle cells phenotypic switching through enhanced FOXO3 expression.

Vascular smooth muscle cells (VSMCs) phenotypic switching is identified as enhanced dedifferentiation, proliferation, and migration ability of VSMCs, in which microRNAs have been identified as important regulators of the process. The present study is aimed to explore the pathophysiological effect of miR-122 on VSMC phenotypic modulation. Here, the result showed that the decreased miR-122 expression was found in VSMCs subjected to platelet-derived growth factor-BB (PDGF-BB) treatment. Next, we investigated the response of miR-122 knockdown in VSMCs with PDGF-BB stimulation. MiR-122 silencing showed increased proliferation and migration capability, whereas attenuated the differentiation markers expression. The above results were reversed by miR-122 overexpression. Finally, we further demonstrated that FOXO3 was an important target for miR-122. Collectively, we demonstrated that miR-122 silencing promoted VSMC phenotypic modulation partially through upregulated FOXO3 expression that indicated miR-122 may be a novel therapeutic target for neointimal formation.

Identification of two variants in PAX3 and FBN1 in a Chinese family with Waardenburg and Marfan syndrome via whole exome sequencing.

Both Warrensburg (WS) and Marfan syndrome (MFS) can impair the vision. Here, we recruited a Chinese family consisting of two WS affected individuals (II:1 and III:3) and five MFS affected individuals( I:1, II:2, III:1, III:2, and III:5) as well as one suspected MFS individual (II:4). Using whole exome sequencing (WES) and subsequent PCR-Sanger sequencing, we identified one novel heterozygous variant NM_000438 (PAX3) c.208 T > C, (p.Cys70Arg) from individuals with WS and one previous reported variant NM_000138 (FBN1) c.2740 T > A, (p.Cys914Ser) from individuals with MFS and co-segregated with the diseases. Real-time PCR and Western blot assay showed that, compared to their wild-type, both mRNAs and proteins of  PAX3 and FBN1 mutants reduced in HKE293T cells. Together, our study identified two disease-causing variants in a same Chinese family with WS and MFS, and confirmed their damaged effects on their genes' expression. Therefore, those findings expand the mutation spectrum of PAX3 and provide a new perspective for the potential therapy.

Circadian aspects of mortality in hospitalized patients: A retrospective observation from a large cohort.

AIM: This study aimed to describe the circadian characteristics of hospitalized mortality in order to provide nursing guidance for preventing in-hospital mortality. DESIGN: A retrospective analysis on inpatient information was implemented. METHODS: Harmonic Analysis of Time Series was applied to quantify the periodic structure of the frequency of the occurrence of death. RESULTS: A total of 3300 cases were included in the present study (male, 63.4% and median age 73 years), including 1540 (46.7%) ICU patients. Incidence of overall hospitalized death exhibited a circadian pattern, presenting peaks from 07:00 to 12:00 and 15:00 to 20:00 P.M., with 21.5% and 13.1% increase above the average at those peak points, respectively. Similarly, the incidence of sudden cardiac death (SCD) showed peaks between 06:00-12:00 and 15:00-20:00, with a 34.7% and 28.0% increase above the average at peak time, respectively. The distribution of death incidence revealed no statistical difference between SCD and non-SCD (p = 0.525).

Comorbidity among inpatients with dementia: a preliminary cross-sectional study in West China.

OBJECTIVE: To investigate comorbidities among hospitalized patients with dementia. METHOD: Data were extracted from the discharge records in our hospital. Comorbidities based on ICD-10 were selected from the Charlson Comorbidity Index (CCI) and Elixhauser Comorbidity Index (ECI). The distributions of these comorbidities were described in dementia inpatients and age- and sex-matched nondementia controls, as well as in inpatients with Alzheimer's disease and vascular dementia. A logistic regression model was applied to identify dementia-specific morbid conditions. RESULTS: A total of 3355 patients with dementia were included, with a majority of 1503 (44.8%) having Alzheimer's disease, 395 (11.8%) with vascular dementia, and 441 (13.1%) with mixed dementia. The mean number of comorbidities was 3.8 in dementia patients (vs. 2.9 in controls). The most prevalent comorbidities in inpatients with dementia compared with those without dementia were cerebral vascular disease (73.0% vs. 35.9%), hypertension (62.8% vs. 56.2%), and peripheral vascular disease (53.7% vs. 31.2%). Comorbidities associated with dementia included epilepsy (OR 4.8, 95% CI 3.5-6.8), cerebral vascular disease (OR 4.1, 95% CI 3.7-4.5), depression (OR 4.0, 95% CI 3.2-5.0), uncomplicated diabetes (OR 1.5, 95% CI 1.4-1.7), peripheral vascular disease (OR 1.8, 95% CI 1.6-2.0), rheumatoid arthritis collagen vascular disease (OR 1.7, 95% CI 1.3-2.3), and anemia (OR 1.2, 95% CI 1.04-1.3). Some comorbidities suggested a protective effect against dementia. They were hypertension (OR 0.8, 95% CI 0.7-0.9), COPD (OR 0.6, 95% CI 0.5-0.6), and solid tumor without metastasis (OR 0.4, 95% CI 0.3-0.4). Vascular dementia has more cardiovascular and cerebrovascular comorbidities than Alzheimer's disease. CONCLUSION: Patients with dementia coexisted with more comorbidities than those without dementia. Comorbidities (esp. cardio-cerebral vascular risks) in patients with vascular dementia were more than those in patients with AD. Specifically, vascular and circulatory diseases, epilepsy, diabetes and depression increased the risk of dementia.

Anti-contactin-associated protein-like 2 antibody autoimmune encephalitis with rapidly progressive parkinsonism: a case report and literature review.

OBJECTIVE: Anti-contactin-associated protein-like 2 (CASPR2) antibody encephalitis is a rare autoimmune encephalitis (AE) that often presents with epilepsy, cognitive dysfunction, peripheral neuropathy, autonomic nerve damage, and ataxia. Parkinsonism is often observed in neurodegenerative diseases but progresses slowly, and rapidly progressive parkinsonism is rare. Given that it is a curable parkinsonism, identifying and providing early immunotherapy is crucial. METHODS: We reported a patient initially presenting with anxiety and depression, whose symptoms were relieved following mood regulation treatment. After discontinuation of the mood-regulating drugs, mood disorders recurred, accompanied by parkinsonism. The onset of parkinsonism was subacute (< 3-month disease course), and progression was rapid. After immunotherapy, all symptoms disappeared completely. We reviewed all relevant literature on anti-CASPR2 antibody encephalitis with parkinsonism. RESULTS: Our literature review revealed three cases (including our patient): two male and one female, ranging in age from 48 to 72 years. All patients had parkinsonism, generalized tonic-clonic seizures, and hyponatremia. Three patients had anti-CASPR2 antibody positivity in the serum, and one patient had anti-CASPR2 antibody positivity in the CSF. All three patients were treated with anti-epileptic drugs and intravenous steroid pulse therapy, followed by oral steroid therapy, symptoms improved. CONCLUSION: Parkinsonism can be easily misdiagnosed as a neurodegenerative disease, especially during the early stages. In patients with parkinsonism, treatable diseases should be considered in addition to neurodegenerative diseases. In clinical practice, anti-CASPR2 antibody encephalitis should be considered if rapidly progressing parkinsonism is encountered after ruling out common etiologies.

PRPF31 interacts with PRPH2 confirmed by co-immunoprecipitation and co-localization.

Both PRPF31 and PRPH2 are the causative genes for retinitis pigmentosa. And both of them are associated with the balance of rhodopsin. In this study, we aim to investigate the co-expression and interaction of PRPF31 and PRPH2. We used PRPF31-eGFP, PRPF31-3xFlag and PRPH2-mCherry vectors were transfected into HEK293T and APRE-19 cells. Immunoblotting and co-immunoprecipitation (Co-IP) were used for gene expression validation and protein interaction. Immunofluorescence staining assay was used to test the co-localization analysis of PRPF31 and PRPH2. Co-IP experiments showed that PRPF31 could be pulled down with an anti-PRPH2 antibody. There was co-localization between PRPF31 and PRPH2 in HEK293T, APRE-19 and mouse retina. The Co-IP and co-localization experiments suggest that PRPF31 interacted with PRPH2.

Autoimmune Encephalitis With Psychotic Manifestations and Cognitive Impairment Presenting as Schizophrenia: Case Report and Literature Review.

Autoimmune encephalitis is characterized by mental and behavioral symptoms, seizures, and cognitive impairment. The presence of schizophrenia needs to be distinguished from that of autoimmune encephalitis. Herein, we describe the case of a woman who exhibited abnormal mental behavior and cognitive impairment. The patient had experienced similar symptoms more than 20 years previously and had been diagnosed with schizophrenia. The patient's psychotic symptoms improved after treatment with antipsychotic drugs; however, cognitive impairment persisted. She was diagnosed with anti-N-methyl-D-aspartate (NMDA)-receptor concurrent with anti-α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-receptor encephalitis. She showed improvement after treatment with steroids and intravenous immunoglobulins (IVIgs). Furthermore, we reviewed the literature and found that, including the present case, 10 patients have been diagnosed with anti-NMDA concurrent with anti-AMPA-receptor encephalitis. Three of these patients were men and seven were women, and their ages ranged from 21 to 71 years. Moreover, seven (70%) patients had a history of tumors. Symptoms of these patients included psychotic symptoms, varying degrees of consciousness disturbance, seizures, dyskinesia, dystonia, autonomic dysfunction, agitation, and verbal reduction. Brain magnetic resonance imaging findings showed scattered fluid-attenuated inversion recovery hyperintensity in subcortical white matter and/or medial temporal lobe in seven (70%) patients. After combination treatment, including tumor removal and administration of steroids, IVIg, plasma exchange, or immunity inhibitors, the symptoms improved in part of the patients. It is necessary to exclude autoimmune encephalitis for patients with psychiatric manifestations and cognitive impairment. Timely combination therapy is important in anti-NMDA-receptor concurrent with anti-AMPA-receptor encephalitis.

RIP2 Knockdown Attenuates Vascular Smooth Muscle Cells Activation via Negative Regulating Myocardin Expression.

BACKGROUND: RIP2 is an adaptor protein contributing to the activation of nuclear factor-κB induced by TNF receptor-associated factor (TRAF) and nucleotide oligomerization domain (NOD)-dependent signaling implicated in innate and adaptive immune response. Beyond regulation of immunity, we aimed to elucidate the role of RIP2 in vascular smooth muscle cell (VSMC) phenotypic modulation. METHODS AND RESULTS: In the current study, we observed that RIP2 showed an increased expression in VSMCs with PDGF-BB stimulation in a dose-dependent manner. Knockdown of RIP2 expression mediated by adenovirus dramatically accelerated the expression of VSMC-specific differentiation genes induced by PDGF-BB. Silencing of RIP2 inhibited proliferative and migratory ability of VSMCs. Additionally, we demonstrated that RIP2 knockdown can promoted myocardin expression. Furthermore, RIP2 inhibition also can attenuate the formation of intimal hyperplasia. CONCLUSIONS: These findings suggested that RIP2 played an important role in regulation of VSMCs differentiation, migration, and proliferation that may due to affect myocardin expression. Our results indicated that RIP2 may be a novel therapeutic target for intimal hyperplasia.

MicroRNA-183 as a Novel Regulator Protects Against Cardiomyocytes Hypertrophy via Targeting TIAM1.

BACKGROUND: MicroRNAs serve as important regulators of the pathogenesis of cardiac hypertrophy. Among them, miR-183 is well documented as a novel tumor suppressor in previous studies, whereas it exhibits a downregulated expression in cardiac hypertrophy recently. The present study was aimed to examine the effect of miR-183 on cardiomyocytes hypertrophy. METHODS: Angiotensin II (Ang II) was used for establishment of cardiac hypertrophy model in vitro. Neonatal rat ventricular cardiomyocytes transfected with miR-183 mimic or negative control were further utilized for the phenotype analysis. Moreover, the bioinformatics analysis and luciferase reporter assays were used for exploring the potential target of miR-183 in cardiomyocytes. RESULTS: We observed a significant decreased expression of miR-183 in hypertrophic cardiomyocytes. Overexpression of miR-183 significantly attenuated the cardiomyocytes size morphologically and prohypertrophic genes expression. Moreover, we demonstrated that TIAM1 was a direct target gene of miR-183 verified by bioinformatics analysis and luciferase reporter assays, which showed a decreased mRNA and protein expression in the cardiomyocytes transfected with miR-183 upon Ang II stimulation. Additionally, the downregulated TIAM1 expression was required for the attenuated effect of miR-183 on cardiomyocytes hypertrophy. CONCLUSIONS: Taken together, these evidences indicated that miR-183 acted as a cardioprotective regulator for the development of cardiomyocytes hypertrophy via directly regulation of TIAM1.

The willingness of Chinese adults to receive the COVID-19 vaccine and its associated factors at the early stage of the vaccination programme: a network analysis.

BACKGROUND: The coronavirus disease (COVID-19) pandemic has been a continuous global threat since the first identification of the disease in December 2019. COVID-19 vaccination is a crucial preventive approach that can halt this pandemic. However, many factors affect the willingness of the public to be vaccinated against COVID-19 at the early stage of the vaccination programme. We used network analysis to investigate the interrelation of vaccination willingness and its associated factors. METHODS: A population-representative sample of 539 Chinese adults completed a battery of online self-assessments, including those on vaccination willingness, health status, attitude towards vaccines, COVID-19-related psychological elements and other variables. Network analysis was performed using the R qgraph package. RESULTS: In total, 445 (82.6%) participants scored high on their willingness to vaccinate. Attitude towards vaccines, the influence of people around an individual and health status were directly significantly related to vaccination willingness. The betweenness of age was the highest and, the emotional states had the strongest centrality. LIMITATIONS: Network analysis is not sufficient to determine the causal relationships of the links between nodes. In addition, there are other latent essential elements that were not evaluated. Finally, the sample size was relatively small. CONCLUSION: Network analysis showed that attitude toward vaccines and emotional states are the most critical factors affecting vaccination willingness, which indicates that we should pay attention to the impact of the dissemination of Internet information on vaccination willingness and public emotional states during a pandemic which is very important for promoting vaccination programs.

Recyclable Gold Catalyst for the Stereoselective Thioallylation of Alkynes.

The heterogeneous gold(I)-catalyzed stereoselective thioallylation of electron-deficient alkynes with allyl sulfides has been achieved by using an MCM-41-immobilized sterically demanding NHC-gold(I) complex [MCM-41-IPrAuNTf2] as the catalyst under mild conditions, delivering a wide variety of stereodefined tri- and tetrasubstituted functionalized vinyl sulfides in good to excellent yields. The new heterogeneous MCM-41-IPrAuNTf2 catalyst exhibits an activity comparable to a homogeneous IPrAuNTf2 complex and can be recovered via a simple filtration process and reused for at least seven consecutive cycles without any apparent loss of its catalytic activity and selectivity.

Attenuated macrophage activation mediated by microRNA-183 knockdown through targeting NR4A2.

Atherosclerosis is considered a chronic inflammatory disease, and macrophages function as important mediators in the development of atherogenesis. MicroRNA (miR)-183 is a small non-coding RNA that acts as a novel tumor suppressor and has recently been proposed to affect cardiac hypertrophy. However, the exact role and underlying mechanism of miR-183 in macrophage activation remain unknown. In the present study, miR-183 showed upregulated expression in atheromatous plaques and in bone marrow-derived macrophages (BMDMs) subjected to stimulation with oxidized low-density lipoproteins. Using a miR-183 loss-of-function strategy, it was demonstrated that miR-183 knockdown significantly increased resolving M2 macrophage marker expression but decreased proinflammatory M1 macrophage marker expression, as well as attenuated NF-κB activation. Moreover, decreased foam-cell formation accompanied by upregulation of genes involved in cholesterol efflux and downregulation of genes implicated in cholesterol influx was found in BMDMs transfected with a miR-183 inhibitor. Mechanistically, macrophage activation mediated by miR-183 silencing was partially attributed to direct upregulation of NR4A2 expression in BMDMs. Thus, the present study suggests that neutralizing miR-183 may be a potential therapeutic strategy for the treatment of atherosclerosis.

Sodium Butyrate Inhibits Neovascularization Partially via TNXIP/VEGFR2 Pathway.

Control of neovascularization with small molecules is a promising tactics. Here, we tested the roles of sodium butyrate (NaBu) on the neovascularization and primary explained its underlining molecular links. We used models including cell and ex vivo culture of choroid and mouse, as well as the biochemical and cellular techniques, to confirm our hypothesis. We found that treating HUVEC cells with NaBu (both 2.5 mM and 5 mM) significantly inhibited its ability in tube formation and proliferation. This inhibitory effect was also observed in choroid sprouting experiments, compared to the control. Interestingly, the choroid sprouting suppressed by NaBu can proliferate again after removing it, indicating that the cell cycle progression might be arrested. The laser-induced choroid neovascularization (CNV) was significantly alleviated by assessing the CNV size (decreased to 0.73 fold) in contrast with the vehicle control group after 2.5 mM NaBu injection for 7 days. Mechanistically, we found an enhanced TXNIP expression in response to NaBu treatment in all the three models. Overexpressing TXNIP in HUVEC cells blocked its tube formation and inhibited its proliferation; on the other hand, knocking down its expression with shRNA reversed those phenotypes in context of NaBu treatment. Further investigation showed the expression of VEGF receptor 2 (VEGFR2) in HUVEC cells was regulated by TXNIP undergoing NaBu treatment. We therefore argued that NaBu inhibited neovascularization partially through TXNIP-regulated VEGFR2 signal pathway.

Clinical profile of aetiological and risk factors of young adults with ischemic stroke in West China.

OBJECTIVE: Our study aimed to present the clinical characteristics of aetiological and risk factors of ischemic stroke (IS) in young adults in order to provide reference to the early prevention and management. PATIENTS AND METHODS: Data of young IS patients aged 18-50 years who were admitted to our tertiary stroke center were retrospectively reviewed. Demographic and clinical characteristics, and risk factors/aetiologies were assessed. Differences of clinical characteristics between the young (18-34 years) and old (35-50 years) age groups were investigated. RESULTS: 343 consecutive inpatients were recruited (mean age 43.8 years). 40 patients (11.7 %) were in the young age group. The prevalence of smoking, diabetes and hypertension accounted for 49.0 %, 24.8 % and 36.2 % respectively, with higher rates in old age group (all p < 0.05). Hyperlipidemia and drinking took up 34.4 % and 45.2 %, with no statistical difference between age groups. 56 patients (16.3 %) were in the "large-artery atherosclerosis" category, and higher percentage of patients was in the old age group (17.8 % vs 5.0 %, p < 0.05). 9.9 % of the patients were classified as the "cardioembolism'' category, and higher percentage of patients was in the young age group (20.0 % vs 8.6 %, p < 0.05). 46 patients (13.4 %) were diagnosed as small vessel occlusion, with similar prevalence in the young and old age group. 15 patients (4.6 %) had other determined causes and 192 patients (56.0 %) were due to undetermined cause. CONCLUSION: the traditional vascular risk factors are frequent and increases with age in young stroke. Further investigation on the 'rare' risk factor and etiology would beneficial.

Effect of intensive self-management education on seizure frequency and quality of life in epilepsy patients with prodromes or precipitating factors.

PURPOSE: To explore the impact of an intensive self-management education strategy on seizure frequency and quality of life in patients with epileptic seizures with prodromes or precipitating factors. The intensive self-management education included monthly education sessions on prodromes and precipitating factors aiming to help patients to adopt self-management strategies. METHODS: Adult patients with epilepsy (PWE) able to identify prodromes or precipitating factors of their seizures were randomly assigned to an intensive education group (IEG) (n = 45) or a regular education group(REG) (n = 47). All patients received a single face-to-face self-management education session at the time of enrollment. Both groups of patients received monthly telephone follow-up for 1 year. PWE in the IEG received intensive education during each follow-up call. Primary outcomes were seizure frequency, quality of life(Quality of life in epilepsy-31 inventory scores, QOLIE 31), and drug adherence(Morisky medication adherence scale,MMAS). RESULTS: At the end of the 1-year follow-up period, seizure frequency in the IEG was significantly lower than at baseline (p < 0.001), but not in the REG(p = 0.085). Quality of life had improved significantly in the IEG (p < 0.001), but not in the REG (p = 0.073). Drug adherence was better in the IEG than in the REG (p = 0.003), and there were fewer accidental injuries in the IEG than the REG (p = 0.031). CONCLUSIONS: In PWE aware of seizure prodromes or precipitating factors, intensive self-management education may reduce seizure frequency, improve quality of life, increase adherence with antiepileptic medication and reduce accidental injuries caused by seizures.

ROBO4 deletion ameliorates PAF-mediated skin inflammation via regulating the mRNA translation efficiency of LPCAT1/LPCAT2 and the expression of PAF receptor.

The diminished level of platelet-activating factor acetylhydrolase (PAFAH) in milk causes an enhanced level of platelet activating factor (PAF) in the skin, leading to a severe hair loss phenotype during neonatal pup's lactation. The deletion of very-low-density-lipoprotein receptor (VLDLR) prevents the expression and secretion of PAFAH. Here we revealed that deletion of Roundabout 4 (ROBO4) in mice ameliorated hair loss phenotype via reducing PAF concentration in skin. As a consequence, the neonatal pups with ROBO4 deletion lactated by mother with VLDLR deletion showed normal hair phenotype during lactation. In details,ROBO4 deletion reduced the protein but not mRNA expression of two PAF synthetic enzymes LPCAT1/LPCAT2 in macrophage as well as the expression of PAF receptor in both macrophage and ocular tissue, but increased PAFAH protein in serum. On the other hand, RNA expression profile analysis in macrophages revealed that the genes involving in oxidative phosphorylation and ribosome obviously decreased their expression in response to ROBO4 deletion. Moreover, through High Performance Liquid Chromatography (HPLC) analysis, we found that ATP concentration also reduced in ROBO4 deletion macrophages. Because ribosome and energy are very important factors for the mRNA translation, we then tested whether ROBO4 deletion affects LPCAT1/LPCAT2 mRNA translation using polyribosome assay. As expected, the mRNA level of LPCAT1/LPCAT2 significantly decreased in polyribosome in ROBO4 deletion macrophage comparing to that of wild type. Additionally, mice with ROBO4 deletion suppressed LPS-induced IL-6 expression as well as the phosphorylation of p44/42 and p65, but enhanced the AKT phosphorylation. Collectively, ROBO4 deletion alleviates PAF- and LPS-mediated inflammation. And above results also indicate PAF signal might be a crosstalk point of ROBO4- and VLDLR-activated pathways.

Optimising epilepsy management with a smartphone application: a randomised controlled trial.

OBJECTIVE: To assess whether a practical intervention based upon a smartphone application (app) would improve self-management and seizure control in adults with epilepsy. DESIGN, SETTING: Randomised, controlled trial in western China, December 2017 to August 2018. PARTICIPANTS: 380 eligible people with epilepsy were recruited; 327 completed the 6-month follow-up (176 in the app group, 151 in the control group). MAIN OUTCOME MEASURES: Self-management of epilepsy (measured with the validated Chinese Epilepsy Self-Management Scale, C-ESMS) and self-reported seizure frequency. RESULTS: In the intention-to-treat analysis, the mean C-ESMS score increased significantly in the app group between baseline and the 6-month evaluation (from 121.7 [SD, 12.1] to 144.4 [SD, 10.0]; P < 0.001); improvements on the information management, medication management, and safety management subscales were also statistically significant. At 6 months, the mean overall C-ESMS score for the app group was significantly higher than that for the control group (125.4 [SD, 1.5];  P < 0.001). The proportion of patients who were seizure-free at the 6-month follow-up was larger for the app than the control group (54 of 190, 28% v 22 of 190, 12%), as was the proportion with reductions in frequency of between 75 and 100% (22 of 190, 12% v 8 of 190, 4%). Changes in C-ESMS score were not statistically associated with seizure frequency. CONCLUSIONS: Using a smartphone app improved epilepsy self-management scores in people in western China. It should be further tested in larger populations in other areas. Our preliminary investigation of building digital communities for people with epilepsy should encourage similar approaches to managing other chronic diseases. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR1900026864, 24 October 2019.