Untargeted metabolomics study of mature human milk from women with and without gestational diabetes mellitus.

Gestational diabetes mellitus (GDM) is a prevalent metabolic disorder during pregnancy that alters the metabolites in human milk. Integrated Gas Chromatography-Mass Spectrometry (GC-MS) and Liquid Chromatography-Mass Spectrometry (LC-MS) were employed for comprehensive identification and comparison of metabolites in mature human milk (MHM) from women with and without GDM. A total of 268 differentially expressed metabolites (DEMs) were identified. Among these, linoleic acid, arachidonic acid, 9R-HODE and L-glutamic acid were significantly elevated and 12,13-DHOME was significantly decreased in MHM of women with GDM. These metabolites are significantly enriched in linoleic acid metabolism, fatty acid biosynthesis, galactose metabolism and ABC transporters pathways. Disorders in these metabolic pathways are associated with insulin resistance and poor glucose metabolism indicating these conditions may persist postpartum.

[Fasudil improves cognitive function in APP/PS1 transgenic mice by promoting mitophagy and inhibiting NLRP3 inflammasome activation].

Objective To explore the mechanism of fasudil improving cognitive dysfunction in amyloid precursor protein/presenilin-1 (APP/PS1) transgenic mice based on mitophagy and nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome pathway. Methods APP/PS1 mice were divided into model group and treatment group, and C57BL/6 mice were used as control group. The treatment group was given intraperitoneal injection of Fasudil (25 mg/kg) once daily for 2 months, while the control group and the model group were injected with the same volume of normal saline. The behavior of mice was detected by water maze and Y maze test; Nissl staining and neuron-specific nuclear antigen (NeuN) immunofluorescence histochemical staining were used to evaluate the number and morphology of neurons. Terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assay (TUNEL) staining was used to detect neuronal apoptosis; The expression of P62 and NLRP3 was detected by immunofluorescence histochemical staining; Real time fluorescence quantitative PCR was used to detect the mRNA expression levels of phosphatase and tensin homolog deleted on chromosome ten (PTEN) -induced putative kinase 1 (PINK1), Parkin and NLRP3; Western blot analysis was used to detect the expression of PINK1, Parkin, P62, microtubule-associated protein 1 light chain 3 (LC3), NLRP3, adapter protein apoptosis-associated speck-like protein (ASC) and interleukin-18 (IL-18). Results The results of the water maze and Y maze showed that the cognitive behavior of mice in treatment group was significantly improved, and their spatial memory and exploration abilities were significantly enhanced; The results of Nissl staining and NeuN immunofluorescence histochemical staining showed that the number of neurons and Nissl bodies were lower in the model group than that in the control group, while the morphology and number of neurons were improved after fasudil treatment. The results of TUNEL staining also showed that the number of apoptotic cells in the brain tissue of APP/PS1 mice were decreased after fasudil treatment; Compared with the control group, the expression of PINK1 and Parkin in the model group decreased, while the expression of P62, LC3, NLRP3, ASC and IL-18 increased. After treatment with fasudil, the expression of PINK1, Parkin, and LC3 increased, while the expression of P62, NLRP3, ASC, and IL-18 decreased. Conclusions Fasudil can improve the cognitive function and neuronal damage in APP/PS1 mice, and its mechanism may be related to promoting mitochondrial autophagy and inhibiting the activation of NLRP3 inflammasomes.

Biocontrol of plant parasitic nematodes by bacteria and fungi: a multi-omics approach for the exploration of novel nematicides in sustainable agriculture.

Plant parasitic nematodes (PPNs) pose a significant threat to global crop productivity, causing an estimated annual loss of US $157 billion in the agriculture industry. While synthetic chemical nematicides can effectively control PPNs, their overuse has detrimental effects on human health and the environment. Biocontrol agents (BCAs), such as bacteria and fungi in the rhizosphere, are safe and promising alternatives for PPNs control. These BCAs interact with plant roots and produce extracellular enzymes, secondary metabolites, toxins, and volatile organic compounds (VOCs) to suppress nematodes. Plant root exudates also play a crucial role in attracting beneficial microbes toward infested roots. The complex interaction between plants and microbes in the rhizosphere against PPNs is mostly untapped which opens new avenues for discovering novel nematicides through multi-omics techniques. Advanced omics approaches, including metagenomics, transcriptomics, proteomics, and metabolomics, have led to the discovery of nematicidal compounds. This review summarizes the status of bacterial and fungal biocontrol strategies and their mechanisms for PPNs control. The importance of omics-based approaches for the exploration of novel nematicides and future directions in the biocontrol of PPNs are also addressed. The review highlighted the potential significance of multi-omics techniques in biocontrol of PPNs to ensure sustainable agriculture.

Synergistic and Antagonistic Activity of Selected Dietary Phytochemicals against Oxidative Stress-Induced Injury in Cardiac H9c2 Cells via the Nrf2 Signaling Pathway.

The antioxidant activities of lycopene (LY), lutein (LU), chlorogenic acid (CA), and delphinidin (DP) were tested in vitro on H9c2 cell-based models. Some indicators, such as the generation of reactive oxygen (ROS), the quantification of cell antioxidant activity (CAA), and the expressions of SOD, GSH-Px, and CAT, were calculated to examine their antioxidant interactions. From our results, the phytochemical mixtures (M1: CA-LU: F3/10, M2: DP-CA: F7/10, M3: DP-LY: F5/10) displayed strong synergistic effects based on the generation of ROS and the quantification of CAA. However, great antagonistic bioactivities were seen in the combinations of LY-LU: F5/10 (M4), CA-LU: F9/10 (M5), and DP-LY: F7/10 (M6). Western blotting analysis indicated that the possible mechanism underlying the synergistic antioxidant interactions among phytochemical combinations was to enhance the accumulation of Nrf2 in the nucleus and the expression of its downstream antioxidant enzymes, HO-1 and GCLC. The combinations (M1-M3 groups) showed significant protection against the loss of mitochondrial membrane potential than individual groups to avoid excessive ROS production. The M4-M6 groups exerted antagonistic protective effects compared with the individual groups. In addition, lutein and lycopene absorption was improved more because of the presence of chlorogenic acid and delphinidin in the M1 and M3 groups, respectively. However, delphinidin significantly reduced the cellular uptake of lycopene in the M6 group. It appeared that antioxidant interactions of phytochemical combinations may contribute to the restoration of cellular redox homeostasis and lead to an improvement in diet quality and collocation.

Deliberation concerning the role of M1-type macrophage subset in oral carcinogenesis.

Over the last decade, accumulating evidence has suggested that tumor-associated macrophages (TAMs) play a significant role in the tumor development. This commentary wishes to highlight the findings by You, et al. that M1-like TAMs could cascade a mesenchymal/stem-like phenotype of oral squamous cell carcinoma (OSCC) via the IL6/Stat3/THBS1 feedback loop. These unprecedented findings identified M1-like TAMs-regulated processes as potentially tumor-promotion in the context of OSCC immunomicroenvironment.

Shear-strained Pd Single-atom Electrocatalysts for Nitrate Reduction to Ammonia.

Electrochemical nitrate reduction method (NitRR) is a low-carbon, environmentally friendly, and efficient method for synthesizing ammonia, which has received widespread attention in recent years. Copper-based catalysts have a leading edge in nitrate reduction due to their good adsorption of *NO3. However, the formation of active hydrogen (*H) on Cu surfaces is difficult and insufficient, resulting in a large amount of the by-product NO2-. In this work, Pd single atoms suspended on the interlayer unsaturated bonds of CuO atoms formed due to dislocations (Pd-CuO) were prepared by low temperature treatment, and the Pd single atoms located on the dislocations were subjected to shear stress and the dynamic effect of support formation to promote the conversion of nitrate into ammonia. The catalysis had an ammonia yield of 4.2 mol.gcat-1. h-1, and a Faraday efficiency of 90% for ammonia production at -0.5 V vs. RHE. Electrochemical in-situ characterization and theoretical calculations indicate that the dynamic effects of Pd single atoms and carriers under shear stress obviously promote the production of active hydrogen, reduce the reaction energy barrier of the decision-making step for nitrate conversion to ammonia, further promote ammonia generation.

Advances of E3 ligases in lung cancer.

Lung cancer is a leading cause of cancer-related death, and the most common type of lung cancer is non-small cell lung cancer, which accounts for approximately 85 % of lung cancer diagnoses. Recent studies have revealed that ubiquitination acts as a crucial part of the development and progression of lung cancer. The E1-E2-E3 three-enzyme cascade has a core function in ubiquitination, so targeted adjustments of E3 ligases could be used in lung cancer treatment. Hence, we elucidate research advances in lung cancer-related E3 ligases by briefly describing the structure and categorization of E3 ligases. Here, we provide a detailed review of the mechanisms by which lung cancer-related E3 ligases modify substrate proteins and regulate signaling pathways to facilitate or suppress cancer progression. We hope to show a new perspective on targeted precision therapy for lung cancer.

Porous gradient hydrogel promotes skin regeneration by angiogenesis.

The skin has a multilayered structure, and deep-seated injuries are exposed to external microbial invasion and in vivo microenvironmental destabilization. Here, a bilayer bionic skin scaffold (Bilayer SF) was developed based on methacrylated sericin protein to mimic the skin's multilayered structure and corresponding functions. The outer layer (SF@TA), which mimics the epidermal layer, was endowed with the function of resisting external bacterial and microbial invasion using a small pore structure and bio-crosslinking with tannic acid (TA). The inner layer (SF@DA@Gel), which mimics the dermal layer, was used to promote cellular growth using a large pore structure and introducing dopamine (DA) to regulate the wound microenvironment. This Bilayer SF showed good mechanical properties and structural stability, satisfactory antioxidant and promote cell proliferation and migration abilities. In vitro studies confirmed the antimicrobial properties of the outer layer and the pro-angiogenic ability of the inner layer. In vivo animal studies demonstrated that the bilayer scaffolds promoted collagen deposition, neovascularization, and marginal hair follicle formation, which might be a promising new bionic skin scaffold.

Undergoing Lung Surgery (PSA-Lung) was appropriate for symptom assessment after discharge.

PURPOSE: To examine whether a 7-day or 24-h recall period of Perioperative Symptom Assessment for Patients Undergoing Lung Surgery (PSA-Lung) was appropriate for symptom assessment after discharge. METHODS: A total of 377 patients were recruited in a cohort study of patients who underwent lung surgery. We measured patient symptoms daily and weekly using the two recall period versions of the PSA-Lung scale, respectively. The psychometric properties of both versions were calculated. Spearman rank correlation coefficients and kappa (k) coefficients were used to measure the association between items score measured by the two version scales each week. Cohen's d effect size and mixed linear model were used to measure responsiveness to change over time. RESULTS: Spearman rank correlation coefficients between the symptom scores generated by the 7-day and 24-h versions (range 0.48-0.77; all P < 0.05). The correlations increased in patients in stable condition (weekly symptom change < 2). Cronbach's α coefficients for both ratings were > 0.87 and both had good test-retest reliability. The longitudinal analysis and Cohen's d effect sizes showed that both ratings had good ability to detect changes in all items. CONCLUSION: The 7-day retrospective scale was as effective as the 24-h retrospective scale in terms of psychometric performance. In the stage where the patient's symptoms change rapidly, it is recommended to use the 24-h retrospective scale for symptom monitoring. On the contrary, in a stable state, it can be considered to use the 7-day retrospective scale for monitoring to reduce the patient's burden.

Achieving NPVR ≥ 80% as technical success of high-intensity focused ultrasound ablation for uterine fibroids: a cohort study.

OBJECTIVE: To report the long-term re-intervention of patients with uterine fibroids after ultrasound-guided high-intensity focused ultrasound (USgHIFU) ablation and to analyse the influencing factors of re-intervention in patients in the NPVR ≥ 80% group. MATERIALS AND METHODS: Patients with a single uterine fibroid who underwent USgHIFU at our hospital from January 2012 to December 2019 were enrolled. The patients were divided into four groups according to different nonperfusion volume ratio (NPVR). Kaplan-Meier survival curve was used to analyse long-term re-intervention in different NPVR groups, and Cox regression was used to analyse the influencing factors of re-intervention in the NPVR ≥ 80% group. MAIN RESULTS: A total of 1,257 patients were enrolled, of whom 920 were successfully followed up. The median follow-up time was 88 months, and the median NPVR was 85.0%. The cumulative re-intervention rates at 1, 3, 5, 8 and 10 years after USgHIFU were 3.4%, 11.8%, 16.8%, 22.6% and 24.1%, respectively. The 10-year cumulative re-intervention rate was 37.3% in the NPVR < 70% group, 31.0% in the NPVR 70-79% group, 18.2% in the NPVR 80-89% group and 17.8% in the NPVR ≥ 90% group (P < 0.05). However, no difference was found between the group of NPVR 80-89% and the group of NPVR ≥ 90% (P = 0.499). Age of patients and signal intensity on T2-weighted imaging (T2WI) of tumours were found to be independent risk factors for long-term re-intervention in the NPVR ≥ 80% group. A younger age and greater signal intensity on T2W images corresponded to a greater risk of re-intervention. CONCLUSION: USgHIFU, an alternative treatment for uterine fibroids, has reliable long-term efficacy. NPVR ≥ 80% can be used as a sign of technical success, which can reduce re-intervention rates. However, an important step is to communicate with patients in combination with the age of patients and the signal intensity on T2WI of fibroids. TRIAL REGISTRATION: This retrospective study was approved by the ethics committee at our institution (Registration No. HF2023001; Date: 06/04/2023). The Chinese Clinical Trial Registry provided full approval for the study protocol (Registration No. CHiCTR2300074797; Date: 16/08/2023).

Adaptive Expectation-Maximization-Based Kalman Filter/Finite Impulse Response Filter for MEMS-INS-Based Posture Capture of Human Upper Limbs.

To obtain precise positional information, in this study, we propose an adaptive expectation-maximization (EM)-based Kalman filter (KF)/finite impulse response (FIR) integrated filter for inertial navigation system (INS)-based posture capture of human upper limbs. Initially, a data fusion model for wrist and elbow position is developed. Subsequently, the Mahalanobis distance is utilized to evaluate the performance of the filter. The integrated filter employs the EM-based KF to enhance noise estimation accuracy when the performance of KF declines. Conversely, upon deterioration in the performance of the EM-based KF, which is evaluated using the Mahalanobis distance, the FIR filter is employed to maintain the effectiveness of the data fusion filter. This research utilizes the proposed EM-based KF/FIR integrated filter to ascertain wrist and elbow positions. The empirical results demonstrate the proficiency of the proposed approach in estimating these positions, thereby overcoming the challenge and highlighting its inherent effectiveness.

Circulating microRNA-33b levels are associated with the presence and severity of coronary heart disease.

MicroRNA-33b (miR-33b) affected various biological pathways in regulating cholesterol homeostasis which may link to the pathogenesis of atherosclerotic lesions. However, whether this marker is associated with the presence and severity of coronary heart disease (CHD) is undetermined. We aim to explore the diagnostic value of circulating miR-33b level in the presence and severity of CHD. Altogether 320 patients were enrolled, including 240 patients diagnosed with CHD while 80 were classified as controls after CAG examination. Circulating miR-33b level was analyzed in all subjects, the Gensini score was calculated to assess the severity of stenotic lesions. The association between miR-33b and the presence and severity of CHD was analyzed, and the diagnostic potential of miR-33b of CHD was performed by the receiver operating characteristic (ROC) analysis. The CHD group had higher miR-33b levels (p < 0.001), and the miR-33b content significantly elevated following an increasing Gensini score (p for trend < 0.001). After adjustments for potential risk factors, such as several blood lipid markers, miR-33b remained a significant determinant for CHD (p < 0.001). ROC analysis disclosed that the AUC was 0.931. The optimal cutoff value of miR-33b was with a sensitivity of 81.3% and a specificity of 98.7% in differentiating CHD. It can prognosticate that the higher level of miR-33b was linked to increased severity of disease in CHD patients. Thus, the application of this marker might assist in the diagnosis and classification of CHD patients. Nevertheless, additional studies with larger sample sizes will be required to verify these results.

Association of DOK3 and infiltrated tumor-associated macrophages with risk for the prognosis of Porphyromonas gingivalis-infected oral cancer: a 12-year data analysis of 200 patients from a tertiary teaching hospital, Urumqi, China.

BACKGROUND: While there is an understanding of the association between the expression of Porphyromonas gingivalis (P. gingivalis) and prognosis of oral squamous cell carcinoma (OSCC), significance specially to address the relevance between different immunohistochemical intensities of P. gingivalis and tumor-associated macrophages (TAMs) in OSCC tissue and related clinicopathologic characteristics has not been well investigated. The present study aimed to investigate the pathological features related to M2-TAM in P. gingivalis-infected OSCC and ascertain its clinical relevance with patients' prognosis. METHODS: A prospective cohort study was designed to comparatively analyze 200 patients from June 2008 to June 2020. Bioinformatics analyses were implemented to identify DOK3 as a key molecule and to appraise immunocyte infiltration using Gene Expression Omnibus and The Cancer Genome Atlas databases. Immunohistochemical evaluation was performed to analyze the association between the expression levels of P. gingivalis, DOK3, and M2-TAM and clinicopathological variables using Fisher's exact test or Pearson's chi-square test. Cox analysis was used to calculate hazard ratios (HR) with corresponding 95% confidence interval (CI) for various clinicopathological features. The Kaplan-Meier approach and log-rank test were used to plot the survival curves. RESULTS: The expression level of P. gingivalis was positively associated with DOK3 and M2-TAMs expression level (P < 0.001). Parameters, including body mass index, clinical stage, recurrence, tumor differentiation, and P. gingivalis, DOK3, and M2-TAM immunoexpression levels, affected the prognosis of patients with OSCC (all P < 0.05). In addition, P. gingivalis (HR = 1.674, 95%CI 1.216-4.142, P = 0.012), DOK3 (HR = 1.881, 95%CI 1.433-3.457, P = 0.042), and M2-TAM (HR = 1.649, 95%CI 0.824-3.082, P = 0.034) were significantly associated with the 10-year cumulative survival rate. CONCLUSIONS: Elevated expression of P. gingivalis and DOK3 indicates M2-TAM infiltration and unfavorable prognosis of OSCC, and could be considered as three novel independent risk factors for predicting the prognosis of OSCC.

Case report: A rare combination of aldosterone-secreting adrenocortical carcinoma and papillary thyroid carcinoma with Graves' disease.

Adrenocortical carcinoma (ACC) is a rare malignancy originating in the adrenal glands, aldosterone-producing ACC, even rarer. Papillary thyroid carcinoma (PTC), by contrast, accounts for the majority of thyroid carcinomas. We herein describe the first reported case of a female with comorbidities of aldosterone-producing ACC, PTC, and Graves' Disease(GD). The patient achieved transient clinical remission following adrenalectomy. However, three months later, aldosterone-producing ACC lung metastases emerged. Subsequently, within another three-month interval, she developed thyroid eye disease(TED). The patient died roughly one year after the adrenal operation. Exome sequencing did not reveal associations between aldosterone-producing ACC, PTC, and GD, and the underlying concurrence mechanism has yet to be elucidated. Further research of similar cases are needed to confirm potential links between the three pathologies.

Impact of Immune Cells on Stroke Limited to Specific Subtypes: Evidence from Mendelian Randomization Study.

INTRODUCTION: Stroke is one of the common diseases that pose a severe threat to human health, with immune cells playing a crucial role in its onset and recovery. However, the specific mechanisms and causal relationships of different immune cell groups in various clinical stroke subtypes are unclear. This study explored the causal relationship between immune cells and stroke and its subtypes using Mendelian randomization (MR) analysis. METHODS: Data from genome-wide association studies were analyzed using inverse-variance weighted (IVW), MR-Egger, and weighted median methods for MR analysis, along with heterogeneity tests, sensitivity analysis, and pleiotropy analysis. RESULTS: CD45RA+CD28-CD8+ T cell %T cell (OR 1.002, 95% CI 1.001-1.003; PFDR = 0.02), CD27 on CD24+CD27+ B cell (OR 1.127, 95% CI 1.061-1.198; PFDR = 0.04), CD27 on IgD-CD38dim B cell (OR 1.138, 95% CI 1.076-1.203; PFDR = 0.005), and CD27 on switched memory B cell (OR 1.144, 95% CI 1.076-1.216; PFDR = 0.01) were found to increase the risk of large artery stroke. Switched memory B cell %lymphocyte (OR 1.206, 95% CI 1.103-1.318; PFDR = 0.02) increased the risk of small vessel stroke. Reverse MR analysis did not reveal any reverse causal associations. Furthermore, by substituting the outcome data, a secondary MR analysis was conducted to validate the primary findings. CONCLUSION: Our study reveals several causal links between immune phenotypes and stroke and its different subtypes, highlighting the complex interactions between the immune system and stroke. These findings provide new directions for further uncovering the biological basis of stroke and assist in advancing research on early interventions and treatment strategies.

[Triptolide reduces neuronal damage in cerebral ischemia-reperfusion rats by promoting microglial M2 polarization].

Objective To investigate the effects of triptolide (TP) on microglial M1/M2 polarization after cerebral ischemia-reperfusion (I/R) injury in rats and the underlying molecular mechanism. Methods A rat model of middle cerebral artery occlusion (MCAO) was established. TP was administered to rats at doses of 0.1 and 0.2 mg/kg, with a sham surgery group as the control group. Longa scoring was performed to grade neurological deficits in rats; HE staining was used to observe the morphology of neurons in ischemic brain tissues; neuron-specific nuclear protein (NeuN) immunofluorescence staining was used to measure the number of neurons; and Western blot analysis was used to measure the expression levels of ionised calcium-binding adaptor molecule-1 (Iba1), inducible nitric oxide synthase (iNOS), arginase 1 (Arg1), Toll-like receptor 4 (TLR4), nuclear factor κB (NF-κB), NeuN and caspase-3 in ischemic-brain tissues. The protein levels of interleukin 1ß (IL-1ß) and IL-10 were measured by ELISA. Immunofluorescence double labelling was performed to detect the expression of Arg1 and TLR4 in microglia. Results Compared with the model group, the neurological score of the TP treatment group was significantly reduced and the neuronal damage was significantly alleviated. IL-1ß levels decreased while IL-10 levels increased. The expression levels of iNOS, TLR4, NF-κB and caspase-3 decreased, while the expression levels of Arg1 and NeuN increased. Conclusion TP treatment ameliorates cerebral I/R injury in rats, which may be attributed to the promotion of microglial M2 polarization, thereby reducing the release of inflammatory factors and inhibiting apoptosis.

Proteomic analysis of milk fat globule membrane proteins in mature human milk of women with and without gestational diabetes mellitus.

Milk fat globule membrane proteins (MFGMP) in human milks have positive effects on infant's health. As gestational diabetes mellitus (GDM) causes variations in MFGMP, it is essential to understand the effects of GDMon MFGMP. This study aims to investigate and compare the MFGMP (>3 months postpartum) of GDM and non-GDM (NGDM) women using four-dimensional-data-independent-acquisition proteomics technology. Principal component analysis shows significant differences in the MFGMP of GDM and NGDM women. A total of 4747 MFGMP were identified in maturehuman milk of GDM and NGDM women. Among these proteins, 174 differentially expressed proteins (DEPs) were identified in MFGM of GDM and NGDM women. Albumin (FC = 7.96) and transthyretin (FC = 2.57) which are related to insulin resistance and involved in thyroid hormone synthesis, are significantly up-regulated in MFGMP of GDM mothers indicating insulin resistance, imbalance of glucose homeostasis and poor glucose metabolism might persist in postpartum period.

Triptolide promotes nerve repair after cerebral ischemia reperfusion injury by regulating the NogoA/NgR/ROCK pathway.

Activation of the NogoA/NgR/ROCK pathway limits nerve repair after brain ischemia-reperfusion (I/R) injury. Triptolide displays anti-inflammatory, anti-oxidant, and immunosuppressive effects and is derived from the traditional Chinese medicine Tripterygium wilfordii Hook F. This agent can also penetrate the blood-brain barrier, where it has a neuroprotective effect and ameliorates cerebral I/R injury via an as yet unknown mechanism(s). Here, an animal model of middle cerebral artery occlusion and reperfusion (MCAO/R) was employed to assess triptolide's therapeutic impact on brain I/R injury and the possible mechanism of action. The results indicate that triptolide treatment can decrease cerebral infarction and nerve injury after cerebral I/R injury. Importantly, in vivo and in vitro experiments revealed that treatment with triptolide decreased NogoA, NgR, p75NTR and ROCK2 expression, and upregulated the expression of GAP43 and PSD-95, thus suggesting improved synaptic function. These results indicate that triptolide can promote nerve repair following brain I/R injury by inhibiting NogoA/NgR/ROCK signalling.