Potato E3 ubiquitin ligase StRFP1 positively regulates late blight resistance by degrading sugar transporters StSWEET10c and StSWEET11.

Potato (Solanum tuberosum) is the fourth largest food crop in the world. Late blight, caused by oomycete Phytophthora infestans, is the most devastating disease threatening potato production. Previous research has shown that StRFP1, a potato Arabidopsis Tóxicos en Levadura (ATL) family protein, positively regulates late blight resistance via its E3 ligase activity. However, the underlying mechanism is unknown. Here, we reveal that StRFP1 is associated with the plasma membrane (PM) and undergoes constitutive endocytic trafficking. Its PM localization is essential for inhibiting P. infestans colonization. Through in vivo and in vitro assays, we investigated that StRFP1 interacts with two sugar transporters StSWEET10c and StSWEET11 at the PM. Overexpression (OE) of StSWEET10c or StSWEET11 enhances P. infestans colonization. Both StSWEET10c and StSWEET11 exhibit sucrose transport ability in yeast, and OE of StSWEET10c leads to an increased sucrose content in the apoplastic fluid of potato leaves. StRFP1 ubiquitinates StSWEET10c and StSWEET11 to promote their degradation. We illustrate a novel mechanism by which a potato ATL protein enhances disease resistance by degrading susceptibility (S) factors, such as Sugars Will Eventually be Exported Transporters (SWEETs). This offers a potential strategy for improving disease resistance by utilizing host positive immune regulators to neutralize S factors.

Neurological complications during the Omicron COVID-19 wave in China: A cohort study.

BACKGROUND AND PURPOSE: The aim was to investigate the neurological complications associated with coronavirus disease 19 (COVID-19) during the 2022 Omicron wave. METHODS AND ANALYSIS: The medical records of a cohort of people admitted to neurological wards of three participating tertiary centres in Sichuan from 12 December 2022 to 12 January 2023 were reviewed. Demographics and clinical data were obtained and analysed with an interest in COVID-19-related new-onset or worse neurological symptoms. The current data were also compared in two centres with similar data from the same period 12 months earlier. RESULTS: In all, 790 people were enrolled, of whom 436 were positive for COVID-19. Ninety-nine had new onset COVID-related neurological problems, or their known neurological condition deteriorated during the wave. There was a significant difference in demographics from the findings amongst admissions 12 months earlier as there was an increase in the average age, the incidence of encephalitis and encephalopathy, and mortality rates. One hundred and one received COVID-specific antivirals, intravenous glucocorticoids and intravenous immunoglobulin therapy. No differences were seen between these and those who did not use them. CONCLUSION: New-onset neurological conditions, particularly encephalitis and encephalopathy, increased significantly during this period. Deterioration of existing neurological conditions, such as seizure exacerbation, was also observed. A large-scale treatment trial of people with COVID-19 infection presenting with neurological disorders is still needed.

Hepatic arterial infusion therapy for advanced hepatocellular carcinoma after systemic treatment failure: Multicenter, real-world study.

AIM: The study was conducted to evaluate the feasibility and safety profile of hepatic arterial infusion chemotherapy with oxaliplatin, 5-fluorouracil, and leucovorin (HAIC-FOLFOX) as an alternative therapeutic choice for patients with advanced hepatocellular carcinoma (HCC) that is refractory to systemic treatment including immune checkpoint blockades or molecular targeting agents. METHODS: Two hundred and forty five consecutive patients with advanced HCC who received HAIC-FOLFOX treatment after systemic treatment failure were retrospectively reviewed in six institutions and their survival, tumor response, and tolerance were assessed. RESULTS: The median overall survival (OS) and progression-free survival of the 209 included participants were 10.5 months (95% confidence interval [CI], 8.1-12.9) and 6.0 months (95% CI, 5.1-6.9), respectively. According to Response Evaluation Criteria in Solid Tumors 1.1 criteria, the objective response rate was 21.1%, and the disease control rate was 64.6%. Multivariate analysis of risk factors of OS were albumin-bilirubin grade (2 and 3 vs. 1, hazard ratio [HR] 1.57; 95% CI, 1.05-2.34; p = 0.028), tumor number (>3 vs. 1-3, HR 2.18; 95% CI, 1.10-4.34; p = 0.026), extrahepatic spread (present vs. absent, HR 1.61, 95% CI, 1.06-2.45; p = 0.027), synchronous systemic treatment (present vs. absent, HR 0.55, 95% CI, 0.37-0.83; p = 0.004) and treatment response (responder vs. nonresponder, HR 0.30, 95% CI, 0.17-0.53; p < 0.001). Grade 3-4 adverse events (AEs) occurred in 59 (28.2%) HCC patients. All AEs were manageable, and deaths related to hepatic artery infusion chemotherapy treatment were not observed. CONCLUSIONS: Our findings support the effectiveness and safety of HAIC-FOLFOX treatment for patients with advanced HCC who have failed systemic treatment.

A review on the antibiotic florfenicol: Occurrence, environmental fate, effects, and health risks.

Florfenicol, as a replacement for chloramphenicol, can tightly bind to the A site of the 23S rRNA in the 50S subunit of the 70S ribosome, thereby inhibiting protein synthesis and bacterial proliferation. Due to the widespread use in aquaculture and veterinary medicine, florfenicol has been detected in the aquatic environment worldwide. Concerns over the effects and health risks of florfenicol on target and non-target organisms have been raised in recent years. Although the ecotoxicity of florfenicol has been widely reported in different species, no attempt has been made to review the current research progress of florfenicol toxicity, hormesis, and its health risks posed to biota. In this study, a comprehensive literature review was conducted to summarize the effects of florfenicol on various organisms including bacteria, algae, invertebrates, fishes, birds, and mammals. The generation of antibiotic resistant bacteria and spread antibiotic resistant genes, closely associated with hormesis, are pressing environmental health issues stemming from overuse or misuse of antibiotics including florfenicol. Exposure to florfenicol at µg/L-mg/L induced hormetic effects in several algal species, and chromoplasts might serve as a target for florfenicol-induced effects; however, the underlying molecular mechanisms are completely lacking. Exposure to high levels (mg/L) of florfenicol modified the xenobiotic metabolism, antioxidant systems, and energy metabolism, resulting in hepatotoxicity, renal toxicity, immunotoxicity, developmental toxicity, reproductive toxicity, obesogenic effects, and hormesis in different animal species. Mitochondria and the associated energy metabolism are suggested to be the primary targets for florfenicol toxicity in animals, albeit further in-depth investigations are warranted for revealing the long-term effects (e.g., whole-life-cycle impacts, multigenerational effects) of florfenicol, especially at environmental levels, and the underlying mechanisms. This will facilitate the evaluation of potential hormetic effects and construction of adverse outcome pathways for environmental risk assessment and regulation of florfenicol.

Progressive structural damage in sleep-related hypermotor epilepsy.

This study aimed to explore the alterations in gray matter volume (GMV) based on high-resolution structural data and the temporal precedence of structural alterations in patients with sleep-related hypermotor epilepsy (SHE). After preprocessing of T1 structural images, the voxel-based morphometry and source-based morphometry (SBM) methods were applied in 60 SHE patients and 56 healthy controls to analyze the gray matter volumetric alterations. Furthermore, a causal network of structural covariance (CaSCN) was constructed using Granger causality analysis based on structural data of illness duration ordering to assess the causal impact of structural changes in abnormal gray matter regions. The GMVs of SHE patients were widely reduced, mainly in the bilateral cerebellums, fusiform gyri, the right angular gyrus, the right postcentral gyrus, and the left parahippocampal gyrus. In addition to those regions, the results of the SBM analysis also found decreased GMV in the bilateral frontal lobes, precuneus, and supramarginal gyri. The analysis of CaSCN showed that along with disease progression, the cerebellum was the prominent node that tended to affect other brain regions in SHE patients, while the frontal lobe was the transition node and the supramarginal gyrus was the prominent node that may be easily affected by other brain regions. Our study found widely affected regions of decreased GMVs in SHE patients; these regions underlie the morphological basis of epileptic networks, and there is a temporal precedence relationship between them.

Cells respond to space microgravity through cytoskeleton reorganization.

Decades of spaceflight studies have provided abundant evidence that individual cells in vitro are capable of sensing space microgravity and responding with cellular changes both structurally and functionally. However, how microgravity is perceived, transmitted, and converted to biochemical signals by single cells remains unrevealed. Here in this review, over 40 cellular biology studies of real space fights were summarized. Studies on cells of the musculoskeletal system, cardiovascular system, and immune system were covered. Among all the reported cellular changes in response to space microgravity, cytoskeleton (CSK) reorganization emerges as a key indicator. Based on the evidence of CSK reorganization from space flight research, a possible mechanism from the standpoint of "cellular mechanical equilibrium" is proposed for the explanation of cellular response to space microgravity. Cytoskeletal equilibrium is broken by the gravitational change from ground to space and is followed by cellular morphological changes, cell mechanical properties changes, extracellular matrix reorganization, as well as signaling pathway activation/inactivation, all of which ultimately lead to the cell functional changes in space microgravity.

Mechanistic insights into hormesis induced by erythromycin in the marine alga Thalassiosira weissflogii.

Erythromycin (ERY) is a typical macrolide antibiotic with large production and extensive use on a global scale. Detection of ERY in both freshwaters and coaster seawaters, as well as relatively high ecotoxicity of ERY have been documented. Notably, hormesis has been reported on several freshwater algae under ERY stress, where growth was promoted at relatively lower exposures but inhibited at higher treatment levels. On the contrary, there is limited information of ERY toxicity in marine algae, hampering the risk assessment on ERY in the coaster waters. The presence of hormesis may challenge the current concept of dose-response adopted in chemical risk assessment. Whether and how exposure to ERY can induce dose-dependent toxicity in marine algae remain virtually unknown, especially at environmentally relevant concentrations. The present study used a model marine diatom Thalassiosira weissflogii (T. weissflogii) to reveal its toxicological responses to ERY at different biological levels and decipher the underlying mechanisms. Assessment of multiple apical endpoints shows an evident growth promotion following ERY exposure at an environmentally relevant concentration (1 µg/L), associated with increased contents reactive oxygen species (ROS) and chlorophyll-a (Chl-a), activated signaling pathways related to ribosome biosynthesis and translation, and production of total soluble protein. By contrast, growth inhibition in the 750 and 2500 µg/L treatments was attributed to reduced viability, increased ROS formation, reduced content of total soluble protein, inhibited photosynthesis, and perturbed signaling pathways involved in xenobiotic metabolism, ribosome, metabolism of amino acid, and nitrogen metabolism. Measurements of multiple apical endpoints coupled with de novo transcriptomics analysis applied in the present study, a systems biology approach, can generate detailed mechanistic information of chemical toxicity including dose-response and species sensitivity difference used in environmental risk assessment.

Preventing Disused Bone Loss through Inhibition of Advanced Glycation End Products.

Bone loss occurs in astronauts during long-term space flight, but the mechanisms are still unclear. We previously showed that advanced glycation end products (AGEs) were involved in microgravity-induced osteoporosis. Here, we investigated the improvement effects of blocking AGEs formation on microgravity-induced bone loss by using the AGEs formation inhibitor, irbesartan. To achieve this objective, we used a tail-suspended (TS) rat model to simulate microgravity and treated the TS rats with 50 mg/kg/day irbesartan, as well as the fluorochrome biomarkers injected into rats to label dynamic bone formation. To assess the accumulation of AGEs, pentosidine (PEN), non-enzymatic cross-links (NE-xLR), and fluorescent AGEs (fAGEs) were identified in the bone; 8-hydroxydeoxyguanosine (8-OHdG) was analyzed for the reactive oxygen species (ROS) level in the bone. Meanwhile, bone mechanical properties, bone microstructure, and dynamic bone histomorphometry were tested for bone quality assessment, and Osterix and TRAP were immunofluorescences stained for the activities of osteoblastic and osteoclastic cells. Results showed AGEs increased significantly and 8-OHdG expression in bone showed an upward trend in TS rat hindlimbs. The bone quality (bone microstructure and mechanical properties) and bone formation process (dynamic bone formation and osteoblastic cells activities) were inhibited after tail-suspension, and showed a correlation with AGEs, suggesting the elevated AGEs contributed to the disused bone loss. After being treated with irbesartan, the increased AGEs and 8-OHdG expression were significantly inhibited, suggesting irbesartan may reduce ROS to inhibit dicarbonyl compounds, thus suppressing AGEs production after tail-suspension. The inhibition of AGEs can partially alter the bone remodeling process and improve bone quality. Both AGEs accumulation and bone alterations almost occurred in trabecular bone but not in cortical bone, suggesting AGEs effects on bone remodeling under microgravity are dependent on the biological milieu.

Complementary and alternative medicine for treating epilepsy in China: A systematic review.

There are about 10 million people with epilepsy (PWE) in China. In addition to therapies approved by the National Medical Products Administration, the use of complementary and alternative medicine (CAM) is prevalent in Chines PWE. These CAM therapies mainly comprise traditional Chinese medicine herbs (TCMHs), acupuncture, and music. A retrospective literature search was performed to summarize the updates of CAM in China in the past ten years, and sixty-two papers were finally included. In this following review, we listed the animal and clinical studies to summarize the antiepileptic mechanisms and clinical efficacy of CAM in Chines PWE. The main mechanisms of TCMHs and acupuncture included regulation of neurotransmitters and receptors, voltage-gated ion channels modulation, expression of apoptosis-related genes, antioxidant response, and anti-inflammation. Although there were enormous clinical studies on them, the current available clinical trials were small, short-term, heterogeneous, and had a high risk of bias. With regard to music, a few studies conducted by Chinese scholars suggested that it was beneficial for PWE as an add-on therapy, which was consistent with the results of foreign studies. Further randomized clinical trials in large populations are required to prove the effectiveness and safety of CAM.

Mitochonic Acid 5 Improves Duchenne Muscular Dystrophy and Parkinson's Disease Model of Caenorhabditis elegans.

Mitochonic Acid 5 (MA-5) enhances mitochondrial ATP production, restores fibroblasts from mitochondrial disease patients and extends the lifespan of the disease model "Mitomouse". Additionally, MA-5 interacts with mitofilin and modulates the mitochondrial inner membrane organizing system (MINOS) in mammalian cultured cells. Here, we used the nematode Caenorhabditis elegans to investigate whether MA-5 improves the Duchenne muscular dystrophy (DMD) model. Firstly, we confirmed the efficient penetration of MA-5 in the mitochondria of C. elegans. MA-5 also alleviated symptoms such as movement decline, muscular tone, mitochondrial fragmentation and Ca2+ accumulation of the DMD model. To assess the effect of MA-5 on mitochondria perturbation, we employed a low concentration of rotenone with or without MA-5. MA-5 significantly suppressed rotenone-induced mitochondria reactive oxygen species (ROS) increase, mitochondrial network fragmentation and nuclear destruction in body wall muscles as well as endogenous ATP levels decline. In addition, MA-5 suppressed rotenone-induced degeneration of dopaminergic cephalic (CEP) neurons seen in the Parkinson's disease (PD) model. Furthermore, the application of MA-5 reduced mitochondrial swelling due to the immt-1 null mutation. These results indicate that MA-5 has broad mitochondrial homing and MINOS stabilizing activity in metazoans and may be a therapeutic agent for these by ameliorating mitochondrial dysfunction in DMD and PD.

Effects of advanced glycation end products on osteocytes mechanosensitivity.

Osteocytes are extremely sensitive to mechanical loading and govern bone remodeling process. Advanced glycation end products (AGEs) have the capacity to induce osteocyte apoptosis. In order to investigate the effects of AGEs on the mechanosensitivity of osteocytes, the osteocytic-like cells (MLO-Y4) were treated with low (50 µg/ml) and high (400 µg/ml) concentrations of AGEs for 1day and exposed to 15 dyne/cm2 of fluid shear stress. Then the F-actin cytoskeleton, prostaglandin E2(PGE2), Nitric oxide (NO), the Wnt/ß-catenin signaling pathway activity mRNA expressions were detected for osteocytes mechanical response changes; osteocalcin (OCN) and receptor activator of nuclear factor-kappa B ligand (RANKL)/osteoprotegerin (OPG) were detected for the regulation on bone remodeling function of osteocytes. The results showed that AGEs accumulation inhibited the sense of osteocytes to external mechincal loading, promoted shear-induced NO and PGE2 release, suppressed the mechanosensitivity of Wnt/ß-catenin signaling pathway, and furthermore promoted OCN and RANKL/OPG mRNA expressions. These indicated AGEs had an adverse impact on the mechanosensitivity of osteocytes, and led to a negative effect on their regulation of bone remodeling process under mechanical stimulation. This work provides a new perspective to interpret the alteration mechanism of osteocytes mechanosensitivity and provides a novel clue for exploring the mechanism of osteoporosis.

Phytophthora infestans RXLR effector Pi04089 perturbs diverse defense-related genes to suppress host immunity.

BACKGROUND: The oomycete pathogen secretes many effectors into host cells to manipulate host defenses. For the majority of effectors, the mechanisms related to how they alter the expression of host genes and reprogram defenses are not well understood. In order to investigate the molecular mechanisms governing the influence that the Phytophthora infestans RXLR effector Pi04089 has on host immunity, a comparative transcriptome analysis was conducted on Pi04089 stable transgenic and wild-type potato plants. RESULTS: Potato plants stably expressing Pi04089 were more susceptible to P. infestans. RNA-seq analysis revealed that 658 upregulated genes and 722 downregulated genes were characterized in Pi04089 transgenic lines. A large number of genes involved in the biological process, including many defense-related genes and certain genes that respond to salicylic acid, were suppressed. Moreover, the comparative transcriptome analysis revealed that Pi04089 significantly inhibited the expression of many flg22 (a microbe-associated molecular pattern, PAMP)-inducible genes, including various Avr9/Cf-9 rapidly elicited (ACRE) genes. Four selected differentially expressed genes (StWAT1, StCEVI57, StKTI1, and StP450) were confirmed to be involved in host resistance against P. infestans when they were transiently expressed in Nicotiana benthamiana. CONCLUSION: The P. infestans effector Pi04089 was shown to suppress the expression of many resistance-related genes in potato plants. Moreover, Pi04089 was found to significantly suppress flg22-triggered defense signaling in potato plants. This research provides new insights into how an oomycete effector perturbs host immune responses at the transcriptome level.

Metabolic alterations of the dorsolateral prefrontal cortex in sleep-related hypermotor epilepsy: A proton magnetic resonance spectroscopy study.

Sleep-related hypermotor epilepsy (SHE) is a focal epilepsy whose neurobiological underpinnings remain poorly understood. The present study aimed to identify possible neurochemical alterations in the dorsolateral prefrontal cortex (DLPFC) in participants with SHE using proton magnetic resonance spectroscopy (1 H MRS). Thirty-nine participants with SHE (mean age, 30.7 years ± 11.3 [standard deviation], 24 men) and 59 controls (mean age, 29.4 years ± 10.4, 29 men) were consecutively and prospectively recruited and underwent brain magnetic resonance imaging and 1 H MRS in the bilateral DLPFCs. Brain concentrations of metabolites, including N-acetyl aspartate (NAA), myo-inositol (mI), choline, creatine, the sum of glutamate and glutamine, glutathione (GSH) and γ-aminobutyric acid, were estimated with LCModel and corrected for the partial volume effect of cerebrospinal fluid using tissue segmentation. ANCOVA analyses revealed lower concentration of NAA in the left DLPFC in participants with SHE compared with controls. A significant difference of NAA concentration between DLPFC in the two hemispheres (left > right) was observed only in the control group. We further confirmed a higher GSH concentration in men than in women in SHE participants, which probably indicates that men are more susceptible to this disease. The mI concentration in the right DLPFC was negatively correlated with epilepsy duration. This study demonstrates that DLPFC is an important brain region involved in the pathophysiology of SHE, in which both neurons and astrocytes appear impaired, and the elevated GSH level may suggest an abnormality related to oxidative stress.

Association between hyperpyrexia and poststroke outcomes in patients with recanalization after mechanical thrombectomy: a retrospective cohort study.

BACKGROUND: Limited data are available for evaluating the relationship between the prognosis and body temperature (BT) in patients treated with mechanical thrombectomy (MT), especially in those with successful recanalization. We aimed to explore the prognostic value of BT in predicting outcomes of stroke recovery at 3 months poststroke. METHODS: We retrospectively analyzed the relationship among BT levels as a continuous variable, with fever (BT ≥ 37.5℃) as a binary variable, and obtained several outcomes of interest. Subjects were stratified according to successful recanalization (thrombolysis in cerebral infarction scores of 2b-3) following MT. Functional independence was defined as a modified Rankin scale (mRS) score of 0-2. RESULTS: In total, 258 patients were included. The proportion of patients with functional independence was significantly lower among patients with BT ≥ 37.5℃ than among those with BT < 37.5 °C (45.3 % versus 23.0 %; P < 0.001). In the multivariate analysis, hyperpyrexia (especially BT ≥ 38 °C) was significantly associated with poor 3-month outcomes in patients treated with MT. Subgroup analysis was conducted by comparing the successful recanalization group with the non-recanalization group, showing that BT ≥ 37.5 °C was associated with a significantly lower proportion of functional independence in the recanalized patients. Besides, the Kaplan-Meier model showed that the fever group had significantly lower survival rates than the non-fever group during the 3-month follow-up. CONCLUSIONS: In patients treated with MT, hyperpyrexia is an independent predictor of poststroke outcomes at 3 months, particularly in those with successful recanalization.

Abnormal blood oxygen level-dependent fluctuations and remote connectivity in sleep-related hypermotor epilepsy.

OBJECTIVE: Sleep-related hypermotor epilepsy (SHE) is a form of the epileptic syndrome that involves stereotyped hypermotor seizures and presents as asymmetric tonic or dystonic posturing events. We aimed to investigate the brain activities of SHE patients using structural and functional magnetic resonance imaging (fMRI). METHODS: A total of 41 patients with SHE and 41 age- and sex-matched healthy controls (HCs) were prospectively enrolled and assessed using fMRI. The two groups were compared in amplitude of low-frequency fluctuations (ALFF) and regional homogeneity (ReHo), and potential correlations between these measures and clinical features were also examined. The involvement of functional network integration was explored by analyzing seed-based functional connectivity. RESULTS: In SHE patients, ALFF in the right precentral gyrus was significantly higher than in HCs, and ReHo in the left postcentral and right precentral gyrus was higher. None of the brain regions had lower ALFF or ReHo compared to HCs. ReHo in the left postcentral gyrus and ALFF in the right precentral gyrus were both negatively correlated with epilepsy duration. Patients with SHE had higher functional connectivity mainly in the precuneus, postcentral gyrus, and supplementary motor area. However, none of the brain regions in SHE group presented lower functional connectivity than in HCs. SHE is associated with disrupted regional and interregional functional activities. CONCLUSIONS: The patients showed abnormalities within the sensorimotor gyrus and supplementary motor area, suggesting spontaneous fluctuations correlated with remote functional brain network. These results at the whole-brain level argue for further investigation into connectivity disturbance in SHE.

The microgravity induces the ciliary shortening and an increased ratio of anterograde/retrograde intraflagellar transport of osteocytes.

It is hard to explain the decrease in mechanosensitivity of osteocytes under microgravity. Primary cilia are essential mechanosensor for osteocytes. The cilia become shorter under the simulated microgravity (SMG) environment. The cilia change may be the reason for the mechanosensitivity decrease of osteocytes under SMG. To reveal the role of primary cilia in weightless-induced osteocyte dysfunction, we investigate intraflagellar transport (IFT) to understand the mechanism of the decreased cilia length of osteocytes when subjected to SMG. We measure the number of anterograde IFT particles with GFP::IFT88 and retrograde IFT particles with OFP::IFT43 that occur at a particular transverse plane of the cilia. We also measure the expression of IFT88 and IFT43 and the size of IFT particles under SMG. Herein, the ratio of anterograde/retrograde particle number and the ratio of protein expression of IFT88/IFT43 increase under SMG. The size of anterograde IFT particles with GFP::IFT88 gets a significant decrease under SMG. Fundamentally, SMG has broken the balanced operating state of IFT and makes the IFT particles smaller. The phenomenon under SMG is intriguing.

Pharmacological Regulation of Primary Cilium Formation Affects the Mechanosensitivity of Osteocytes.

Primary cilia are responsible for sensing mechanical loading in osteocytes. However, the underlying working mechanism of cilia remains elusive. An osteocyte model is necessary to reveal the role of cilia. Furthermore, the osteocyte model should be with upregulated or downregulated primary cilium expression. Herein, we used a pharmacological method to regulate the cilium formation of osteocytes. After screening, some pharmacological agents can regulate the cilium formation of osteocytes. We performed a CCK-8 assay to analyze the optimal working conditions of the drugs for MLO-Y4 cells. The agents include chloral hydrate (CH), Gd3+, Li+, and rapamycin. The expression of cilia affects the cellular functions, including mechanosensitivity, of osteocytes. Results showed that CH downregulated the cilium formation and ciliogenesis of osteocytes. In addition, Gd3+, Li+, and rapamycin upregulated the cilium expression of osteocytes. Moreover, the cilium expression positively correlated with the mechanosensitivity of osteocytes. This work reveals the role of primary cilia in the mechanosensing of osteocytes.

Magnetoencephalography for epileptic focus localization in a series of 1000 cases.

The aim of epilepsy surgery in patients with focal, pharmacoresistant epilepsies is to remove the complete epileptogenic zone to achieve long-term seizure freedom. In addition to a spectrum of diagnostic methods, magnetoencephalography focus localization is used for planning of epilepsy surgery. We present results from a retrospective observational cohort study of 1000 patients, evaluated using magnetoencephalography at the University Hospital Erlangen over the time span of 28 years. One thousand consecutive cases were included in the study, evaluated at the University Hospital Erlangen between 1990 and 2018. All patients underwent magnetoencephalography as part of clinical workup for epilepsy surgery. Of these, 405 underwent epilepsy surgery after magnetoencephalography, with postsurgical follow-ups of up to 20 years. Sensitivity for interictal epileptic activity was evaluated, in addition to concordance of localization with the consensus of presurgical workup on a lobar level. We evaluate magnetoencephalography characteristics of patients who underwent epilepsy surgery versus patients who did not proceed to surgery. In operated patients, resection of magnetoencephalography localizations were related to postsurgical seizure outcomes, including long-term results after several years. In comparison, association of lesionectomy with seizure outcomes was analysed. Measures of diagnostic accuracy were calculated for magnetoencephalography resection and lesionectomy. Sensitivity for interictal epileptic activity was 72% with significant differences between temporal and extra-temporal lobe epilepsy. Magnetoencephalography was concordant with the presurgical consensus in 51% and showed additional or more focal involvement in an additional 32%. Patients who proceeded to surgery showed a significantly higher percentage of monofocal magnetoencephalography results. Complete magnetoencephalography resection was associated with significantly higher chances to achieve seizure freedom in the short and long-term. Diagnostic accuracy was significant in temporal and extra-temporal lobe cases, but was significantly higher in extra-temporal lobe epilepsy (diagnostic odds ratios of 4.4 and 41.6). Odds ratios were also higher in non-lesional versus lesional cases (42.0 versus 6.2). The results show that magnetoencephalography provides non-redundant information, which significantly contributes to patient selection, focus localization and ultimately long-term seizure freedom after epilepsy surgery. Specifically in extra-temporal lobe epilepsy and non-lesional cases, magnetoencephalography provides excellent accuracy.

Visfatin regulates the production of lipopolysaccharide-induced inflammatory cytokines through p38 signaling in murine macrophages.

Visfatin plays an important role in regulation of inflammatory cytokines. However, the role of visfatin under bacterial stress condition is not fully explored yet. Therefore, the present study was conducted for the better understanding of the regulation mechanism of visfatin on the production of inflammatory cytokines under lipopolysaccharide (LPS) stress in RAW264.7 murine macrophages. Enzyme Linked Immuno-sorbent Assay (ELISA) results showed that, as compared to the control group, visfatin significantly up-regulated the levels of interleukin (IL)-1ß, IL-6, IL-10, tumor necrosis factor (TNF)-α (P < 0.05). Compared to the LPS group, the levels of IL-1ß, IL-10, TNF-α was down-regulated in visfatin + LPS group (P < 0.05). After adding p38 inhibitor, SB203580 to culture, the production of IL-1ß, IL-6, IL-10, TNF-α was significantly reduced as compared to visfatin only (P < 0.01). The results showed that visfatin may regulate the production of IL-1ß, IL-6, IL-10, TNF-α through the p38 signaling pathway. As compared to the PBS group, phosphorylayed p38 (P-p38) level in visfatin group was significantly decreased (P < 0.05). Compared with LPS group, P-p38 level was significantly decreased in visfatin + LPS group (P < 0.05). Hence, it is concluded that visfatin can significantly increase the levels of IL-1ß, IL-10 and TNF-α in normal conditions, while their levels significantly decrease during inflammation. Moreover, visfatin participates in the inflammatory response through the p38 mitogen-activated protein kinase (MAPK) signal pathway by the up-regulation of p38 and down-regulation of P-p38 levels.

Quantitative MR spectroscopy reveals metabolic changes in the dorsolateral prefrontal cortex of patients with temporal lobe epilepsy.

OBJECTIVE: To characterize possible metabolic changes of the dorsolateral prefrontal cortex (DLPFC) in patients with temporal lobe epilepsy (TLE). METHODS: Quantitative proton magnetic resonance spectroscopy (1H-MRS) studies were performed on 24 TLE patients and 22 healthy controls. Metabolite concentrations were calculated using a linear combination model (LCModel) and corrected for cerebrospinal fluid contamination. Comparisons were performed between the TLE patients and the controls and between the left DLPFC and right DLPFC in each group. Pearson correlation coefficients were calculated between the metabolite concentrations and epilepsy duration and between the metabolite concentrations and voxel tissue composition: [gray matter (GM)/(GM+white matter (WM))]. RESULTS: Metabolic asymmetry was found in controls between the left and right DLPFC, i.e., the NAA concentration of the left DLPFC was significantly higher than that of the right. However, such metabolic asymmetry was not observed in TLE patients. Compared with the controls, TLE patients showed significantly decreased NAA and Ins, and the reductions were greater in the left DLPFC. No significant correlation was found between the metabolite concentrations and epilepsy duration or between the metabolite concentrations and voxel tissue composition [GM/(GM+WM)]. CONCLUSIONS: This study suggests that TLE can produce metabolic changes to DLPFC that is remote from the seizure focus. KEY POINTS: • Magnetic resonance spectroscopy probes the brain metabolism noninvasively. • Dorsolateral prefrontal reductions in NAA (a neuronal marker) and Ins are observed in TLE. • Temporal lobe epilepsy can result in metabolic changes remote from the seizure focus.