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Centrosome amplification (CA) refers to a numerical increase in centrosomes resulting in cells with more than two centrosomes. CA has been shown to initiate tumorigenesis and increase the invasive potential of cancer cells in genetically modified experimental models. Hexavalent chromium is a recognized carcinogen that causes CA and tumorigenesis as well as promotes cancer metastasis. Thus, CA appears to be a biological link between chromium and cancer. In the present study, we investigated how chromium triggers CA. Our results showed that a subtoxic concentration of chromium‐induced CA in HCT116 colon cancer cells, resulted in the production of reactive oxygen species (ROS), activated ATF6 without causing endoplasmic reticulum stress, and upregulated the protein level of PLK4. Inhibition of ROS production, ATF6 activation, or PLK4 upregulation attenuated CA. Inhibition of ROS using N‐acetyl‐l‐cysteine (NAC) inhibited chromium‐induced activation of ATF6 and upregulation of PLK4. ATF6‐specific siRNA knocked down the protein level and activation of ATF6, and upregulated PLK4, with no effect on ROS production. Knockdown of PLK4 protein had no effect on chromium‐induced ROS production or activation of ATF6. In conclusion, our results suggest that hexavalent chromium induces CA via the ROS‐ATF6‐PLK4 pathway and provides molecular targets for inhibiting chromium‐mediated CA, which may be useful for the assessment of CA in chromium‐promoted tumorigenesis and cancer cell metastasis. [ABSTRACT FROM AUTHOR]

Diabetes not only increases the risk for cancer but also promotes cancer metastasis. Centrosome amplification (CA) is sufficient to initiate tumorigenesis and can enhance the invasion potential of cancer cells. We have reported that diabetes can induce CA, with diabetic pathophysiological factors as the triggers, which involves the signaling of nucleophosmin (NPM). Thus, CA can serve as a candidate biological link between diabetes and cancer. In the present study, we attempted to identify the NPM binding partners and investigated whether the binding between NPM and its partner mediated the CA. We confirmed that high glucose, insulin, and palmitic acid cancer could elicit CA in the HCT16 colon cancer cells and found that the experimental treatment increased the binding between NPM and H2B, but not between p‐NPM and H2B. The molecular docking analysis supported the fact that NPM and H2B could bind to each other through various amino acid residues. The treatment also increased the colocalization of NPM and H2B in the cytosol. Importantly, disruption of the NPM1–H2B complex by individual knockdown of the protein level of NPM or H2B led to the inhibition of the treatment‐evoked CA. In conclusion, our results suggest that the binding between NPM and H2B proteins signals for the CA by high glucose, insulin, and palmitic acid. Significance statement: Diabetes is increasingly recognized as a significant risk factor for cancer initiation and progression. Amplification of the centrosome is sufficient to induce carcinogenesis and can increase cancer cell invasion potential. Previous research has demonstrated that diabetic pathophysiological factors can cause centrosome amplification (CA) in both noncancerous and malignant colon cells. As a result, we suspect CA is a molecular relationship between diabetes and cancer. However, the mechanism behind this association between diabetes and cancer remains unknown. In the current study, we discovered that the interaction between nucleophosmin (NPM) and H2B caused diabetes‐associated CA, providing a target for decreasing diabetes‐associated CA and allowing us to investigate its functions in carcinogenesis and cancer cell metastasis. Our findings also show that H2B has a biological purpose other than nucleosome construction and gene transcription control in the nucleus, which is signaling for CA in the cytoplasm. Furthermore, the identification of the binding between NPM and H2B, but not phosphorylated NPM and H2B, as a signal for CA adds a new piece of information in the regulation of centrosome homeostasis, which could lead to a new method of cancer treatment by targeting CA. [ABSTRACT FROM AUTHOR]

Some subduction zones in nature show mainly overriding plate (OP) extension and low topography, and others show mainly shortening and elevated topography. Here we investigate how end‐member subduction modes (trench retreat with slab rollback and trench advance with slab rollover) affect overriding plate deformation (OPD), topography, and mantle flow with time‐evolving three‐dimensional fully‐dynamic analog models using particle image velocimetry. We conduct two sets of experiments, one of which is characterized by trench retreat, and the other characterized by trench advance. Experiments showing continuous trench retreat experience overall OP extension, while experiments dominated by trench advance experience overall shortening. Both subduction modes present fore‐arc shortening and intra‐arc extension. Our experiments indicate that the overall OPD is mainly driven by the horizontal mantle flow at the base of the OP inducing a viscous drag force (FD), and is determined by the horizontal gradient of the horizontal mantle shear rate dγ˙/dx $d\dot{\gamma }/dx$, which controls the horizontal trench‐normal gradient in FD. Furthermore, a large‐scale trenchward OP tilting and overall subsidence are observed in the experiments showing continuous trench retreat, while a landward OP tilting and an overall uplift are observed during long‐term trench advance. The two types of topography during the two different subduction modes can be ascribed to the downward component of the large‐scale trenchward mantle flow and the upward component of the landward mantle flow, respectively, and thus represent forms of dynamic topography. Our models showing trench advance provide a possible mechanism for OPD and topography at the Makran subduction zone. Key Points: 4D dynamic analog subduction models investigate how end‐member subduction modes affect the overriding plate deformation and topographyContinuous trench retreat produces overall overriding plate extension, while long term trench advance promotes overall shorteningContinuous trench retreat facilitates trenchward overriding plate tilting, while long term trench advance promotes landward tilting [ABSTRACT FROM AUTHOR]

Subduction style is controlled by a variety of physical parameters. Here we investigate the effect of subducting plate length on subduction style using laboratory experiments of time‐evolving buoyancy‐driven subduction in 3‐D space. The investigation includes two experimental sets, one with a lower (~740) and one with a higher (~1,680) subducting plate‐to‐mantle viscosity ratio (ηSP/ηM). Each set involves five models with a free‐trailing‐edge subducting plate and variable plate length (20–60 cm, scaling to 1,600–4,800 km), and one model with a fixed‐trailing‐edge subducting plate representing an infinitely long plate. Through determining the contact area between subducting plate and underlying mantle, plate length affects the resistance to trenchward motion of the subducting plate and thus controls the partitioning of the subduction velocity (vS) into the subducting plate velocity (vSP) and trench velocity (vT). This subduction partitioning thereby determines the subduction style by controlling the dip angle of the slab tip once it first touches the 660 km discontinuity. The low ηSP/ηM models display two subduction styles. Short plates (≤40 cm) induce a higher subduction partitioning ratio (vSP/vS), promoting trench advance and slab rollover geometries, whereas longer plates (≥50 cm) lead to a lower vSP/vS, producing continuous trench retreat and backward slab draping geometries. In contrast, the high ηSP/ηM models exclusively show trench retreat with draping geometries, as the high ηSP/ηM enables less slab bending before its tip touches the 660 km discontinuity. Our study indicates that future modeling work should consider the effects of plate length on the style and evolution of subduction. Key Points: Three‐dimensional dynamic analog subduction models investigate the effect of subducting plate length on subduction kinematics and slab geometrySubducting plate length affects the style of subduction by controlling the subduction partitioning between plate and trench motionPlate length shows a positive correlation with the slab bending radius and basal drag and a negative correlation with slab tip dip angle [ABSTRACT FROM AUTHOR]

In this work, the ultrafine grained (UFG) tungsten has been fabricated via high pressure torsion (HPT) of various turning numbers at a temperature of 823 K and a pressure of 1.5 GPa. The microstructure characteristics and mechanical properties of initial and high pressure torsion processed tungsten have been comparatively investigated by means of x‐ray diffraction (XRD), electron backscatter diffraction (EBSD), transmission electron microscope (TEM) and microhardness tests. It is shown that high pressure torsion leads to microstructure refinement with an average grain size of ∼0.92 μm and the fraction of high angle grain boundaries (HAGB) increasing to 62.9 %. Moreover, the dislocation density increases from initial 1.17×1014 m−2 to 3.89×1014 m−2. The microhardness tests revealed that hardness increased gradually and its distribution became more homogeneous with torsion strain increasing. The strengthening model was established considering the grain boundary strengthening and dislocation strengthening mechanisms. Resultantly, deviation of Hall‐Petch slope was found from the classic values, which is attributed to the easy movement of the extrinsic dislocations in the high angle grain boundaries with high distortion energy and high density of defects. [ABSTRACT FROM AUTHOR]

Abstract: High pressure torsion of powder mixture is a novel strategy for manufacturing high‐quality aluminum‐based silicon carbide composite SiCp/Al billet used in electronic packaging, however, the correlation between thermal properties and the high pressure torsion process and the related mechanisms are still unclear. To this end, the variation rules of thermal expansion coefficient and thermal conductivity with high pressure torsion turns are studied and the corresponding microstructure morphology and dislocation patterns are observed by optical and transmission electron microscopes. The results show that thermal expansion coefficient decreases monotonically but thermal conductivity first increases then decreases with the increase of high pressure torsion turns. Moreover, the results of differential scanning calorimetry experiments indicate the decrease of recrystallization temperature with turns of high pressure torsion. The non‐monotonic variation of thermal conductivity is attributed to the combined effect of the improved relative mass density brought by the consolidation effect and the dislocation tanglement and pattern transformation (formation of in‐situ sub‐grains) during high pressure torsion process. [ABSTRACT FROM AUTHOR]

Adequate sperm motility is requisite for human fertilization, whereas the underlying causes or mechanisms of impaired sperm motility, asthenozoospermia, still remain largely unknown. RNASET2 (Ribonuclease T2) may be one of the effectors modulating human sperm motility. We determined if there is a correlation between RNASET2 expression levels in human semen from asthenozoospermia and fertile individuals. Thus, RNASET2 expression levels in spermatozoa and seminal plasma of healthy and asthenozoospermia individuals were evaluated using Western blot, laser scanning confocal microscope analysis, ELISA and flow cytometry. The results revealed that RNASET2 expression was identified in both human spermatozoa and seminal plasma. In spermatozoa from fertile individuals, it was localized to the acrosome, neck and the middle piece of tail regions. However, in spermatozoa from asthenozoospermia individuals (n = 67), RNASET2 staining was especially more frequent and evident in the neck and middle piece than that in fertile individuals (n = 59, p < 0.01). Similarly, higher RNASET2 expression was also apparent in seminal plasma from asthenozoospermia than in fertile individuals (p < 0.01). Moreover, purified RNASET2 had an inhibitory effect on sperm motility, especially on progressive motility (n = 23, p < 0.05). In conclusion, higher expression of RNASET2 in the semen of asthenozoospermia individuals may contribute to sperm motility impairment. [ABSTRACT FROM AUTHOR]

Aim: To explore the trajectory of self-management behaviour and its influencing factors in patients with knee osteoarthritis., Design: This is a prospective, longitudinal observational study., Methods: From January 2024 to April 2024, 126 patients with knee osteoarthritis who were hospitalized in two tertiary-level hospitals in Hunan Province were selected to be surveyed on the day of discharge, 1 month after discharge and 3 months after discharge using the Chinese version of the Chronic Disease Self-Management Research Measurement Scale. The trajectories of self-management behaviours were performed using latent category growth analysis. The influencing factors were performed using Lasso regression., Results: Two classes were identified, including 'slow decline class' (37.1%) and 'significant decline class' (62.9%). Age, education, history of knee surgery and number of other chronic diseases combined were significant factors. Finally, older patients were more likely to be in the 'significant decline group' and patients with a history of knee surgery were more likely to be in the 'slow decline group'., Conclusion: We reported the existence of heterogeneity in self-management trajectories in patients with KOA and found that younger age and history of knee surgery were significantly associated with slow decline class trajectories. Further studies are needed to test the generalizability of these identified self-management trajectories in patients with KOA and their association with psychosocial aspects., Implications for the Profession and Patient Care: To identify the trajectory of self-management behaviours of patients with KOA and explore their influencing factors, to provide reference for healthcare professionals to formulate targeted intervention programmes, so as to prevent the recurrence of knee osteoarthritis and delay the course of the disease., Reporting Method: STROBE checklist was followed., Patient or Public Contribution: The authors would specially thank all the participants in this study., (© 2025 John Wiley & Sons Ltd.)

Objective: The E3 ubiquitin ligase is well recognized as a significant contributor to glioblastoma (GBM) progression and has promise as a prospective therapeutic target. This study explores the contribution of E3 ubiquitin ligase RNF122 in the GBM progression and the related molecular mechanisms., Methods: RNF122 expression levels were evaluated using qRT-PCR, WB, and IHC, while functional assays besides animal experiments were used to assess RNF122's effect on GBM progression. We also tested the RNF122 impact on JAK2/STAT3/c-Myc signaling using WB., Results: RNF122 was upregulated in GBM and correlated to the advanced stage and poor clinical outcomes, representing an independent prognostic factor. Based on functional assays, RNF122 promotes GBM growth and cell cycle, which was validated further in subsequent analyses by JAK2/STAT3/c-Myc pathway activation. Moreover, JAK2/STAT3 signaling pathway inhibitor WP1066 can weaken the effect of overexpression RNF122 on promoting GBM progression., Conclusion: Our results revealed that RNF122 caused an aggressive phenotype to GBM and was a poor prognosticator; thus, targeting RNF122 may be effectual in GBM treatment., (© 2024 The Author(s). CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.)

Aims: Schizophrenia is characterized by alterations in resting-state spontaneous brain activity; however, it remains uncertain whether variations at diverse spatial scales are capable of effectively distinguishing patients from healthy controls. Additionally, the genetic underpinnings of these alterations remain poorly elucidated. We aimed to address these questions in this study to gain better understanding of brain alterations and their underlying genetic factors in schizophrenia., Methods: A cohort of 103 individuals with diagnosed schizophrenia and 110 healthy controls underwent resting-state functional MRI scans. Spontaneous brain activity was assessed using the regional homogeneity (ReHo) metric at four spatial scales: voxel-level (Scale 1) and regional-level (Scales 2-4: 272, 53, 17 regions, respectively). For each spatial scale, multivariate pattern analysis was performed to classify schizophrenia patients from healthy controls, and a transcriptome-neuroimaging association analysis was performed to establish connections between gene expression data and ReHo alterations in schizophrenia., Results: The ReHo metrics at all spatial scales effectively discriminated schizophrenia from healthy controls. Scale 2 showed the highest classification accuracy at 84.6%, followed by Scale 1 (83.1%) and Scale 3 (78.5%), while Scale 4 exhibited the lowest accuracy (74.2%). Furthermore, the transcriptome-neuroimaging association analysis showed that there were not only shared but also unique enriched biological processes across the four spatial scales. These related biological processes were mainly linked to immune responses, inflammation, synaptic signaling, ion channels, cellular development, myelination, and transporter activity., Conclusions: This study highlights the potential of multi-scale ReHo as a valuable neuroimaging biomarker in the diagnosis of schizophrenia. By elucidating the complex molecular basis underlying the ReHo alterations of this disorder, this study not only enhances our understanding of its pathophysiology, but also pave the way for future advancements in genetic diagnosis and treatment of schizophrenia., (© 2024 The Author(s). CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.)

Although MRPS16 is involved in cancer development, its mechanisms in developing LAUD remain unclear. Herein, qRT-PCR, WB and IHC were utilized for evaluating MRPS16 expression levels, while functional assays besides animal experiments were performed to measure MRPS16 effect on LAUD progression. Using WB, the MRPS16 effect on PI3K/AKT/Frataxin signalling pathway was tested. According to our study, MRPS16 was upregulated in LAUD and was correlated to the advanced TNM stage as well as poor clinical outcomes, which represent an independent prognostic factor. Based on functional assays, MRPS16 is involved in promoting LAUD growth, migration and invasion, which was validated further in subsequent analyses through PI3K/AKT/Frataxin pathway activation. Moreover, MRPS16-knockdown-mediated Frataxin overexpression was shown to restore the reduction in tumour cells proliferation, migration and invasion. Our results revealed that MRPS16 caused an aggressive phenotype to LAUD and was a poor prognosticator; thus, targeting MRPS16 may be effectual in LAUD treatment., (© 2024 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

The role of KIAA0040 role in glioma development is not yet understood despite its connection to nervous system diseases. In this study, KIAA0040 expression levels were evaluated using qRT-PCR, WB and IHC, and functional assays were conducted to assess its impact on glioma progression, along with animal experiments. Moreover, WB was used to examine the impact of KIAA0040 on the JAK2/STAT3 signalling pathway. Our study found that KIAA0040 was increased in glioma and linked to tumour grade and poor clinical outcomes, serving as an independent prognostic factor. Functional assays showed that KIAA0040 enhances glioma growth, migration and invasion by activating the JAK2/STAT3 pathway. Of course, KIAA0040 enhances glioma growth by preventing tumour cell death and promoting cell cycle advancement. Our findings suggest that targeting KIAA0040 could be an effective treatment for glioma due to its role in promoting aggressive tumour behaviour and poor prognosis., (© 2024 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

Aims: Previous studies have indicated that smoking is linked to an increased risk of developing schizophrenia, and that individuals with schizophrenia are more prone to engaging in antisocial behavior. However, the causal effects of smoking behaviors on antisocial behavior and the potential mediating role of schizophrenia remains largely unclear., Methods: In the present study, using the summary data from genome wide association studies of smoking phenotypes (N = 323,386-805,431), schizophrenia (Ncases = 53,386, Ncontrols = 77,258), and antisocial behavior (N = 85,359), we assessed bidirectional causality between smoking phenotypes and schizophrenia by the Mendelian randomization (MR) approach. Using a two-step MR approach, we further examined whether causal effects of smoking phenotypes/schizophrenia on antisocial behavior were mediated by schizophrenia/smoking phenotypes., Results: The results showed that smoking initiation (SmkInit) and age of smoking initiation (AgeSmk) causally increase the risk of schizophrenia (SmkInit: OR = 2.06, 95% CI = 1.77-2.39, p = 4.36 × 10 -21 ; AgeSmk: OR = 0.32, 95% CI = 0.16-0.62, p = 8.11 × 10 -4 , Bonferroni corrected). However, there was no causal effect that liability to schizophrenia leads to smoking phenotypes. MR evidence also revealed causal influences of SmkInit and the amount smoked (CigDay) on antisocial behavior (SmkInit: OR = 1.28, 95% CI = 1.17-1.41, p = 2.53 × 10 -7 ; CigDay: OR = 1.16, 95% CI = 1.06-1.27, p = 1.60 × 10 -3 , Bonferroni corrected). Furthermore, the mediation analysis indicated that the relationship between SmkInit and antisocial behavior was partly mediated by schizophrenia (mediated proportion = 6.92%, 95% CI = 0.004-0.03, p = 9.66 × 10 -3 )., Conclusions: These results provide compelling evidence for taking smoking interventions as a prevention strategy for schizophrenia and its related antisocial behavior., (© 2023 The Authors. CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.)

Aim: Aberrations in brain connections are implicated in the pathogenesis of Parkinson's disease (PD). We previously demonstrated that Glial cell-derived neurotrophic factor (GDNF) reduction is associated with cognition decline. Nonetheless, it is elusive if the pattern of brain topological connectivity differed across PD with divergent serum GDNF levels, and the accompanying profile of cognitive deficits has yet to be determined., Methods: We collected data on the participants' cognition, demographics, and serum GDNF levels. Participants underwent 3.0T magnetic resonance imaging, and we assessed the degree centrality, brain network topology, and cortical thickness of the healthy control (HC) (n = 25), PD-high-GDNF (n = 19), and PD-low-GDNF (n = 19) groups using graph-theoretic measures of resting-state functional MRI to reveal how much brain connectivity varies and its clinical correlates, as well as to determine factors predicting the cognitive status in PD., Results: The results show different network properties between groups. Degree centrality abnormalities were found in the right inferior frontal gyrus and right parietal lobe postcentral gyrus, linked with cognition scores. The two aberrant clusters serve as a potentially powerful signal for determining whether a patient has PD and the patient's cognition level after integrating with GDNF, duration, and dopamine dosage. Moreover, we found a significant positive relationship between the thickness of the left caudal middle frontal lobe and a plethora of cognitive domains. Further discriminant analysis revealed that the cortical thickness of this region could distinguish PD patients from healthy controls. The mental state evaluation will also be more precise when paired with GDNF and duration., Conclusion: Our findings reveal that the topological features of brain networks and cortical thickness are altered in PD patients with cognitive deficits. The above change, accompanied by the serum GDNF, may have merit as a diagnosis marker for PD and, arguably, cognition status., (© 2023 The Authors. CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.)

Aims: The human brain is an extremely complex system in which neurons, clusters of neurons, or regions are connected to form a complex network. With the development of neuroimaging techniques, magnetic resonance imaging (MRI)-based brain networks play a key role in our understanding of the intricate architecture of human brain. Among them, the structural MRI-based brain morphological network approach has attracted increasing attention due to the advantages in data acquisition, image quality, and in revealing the structural organizing principles intrinsic to the brain. This review is to summarize the methodology and related applications of individual-level morphological networks., Background: There have been a growing number of studies related to brain morphological similarity networks. Conventional morphological networks are intersubject covariance networks constructed using a certain morphological indicator of a group of subjects; individual-level morphological networks, on the other hand, measure the morphological similarity between brain regions for individual brains and can reflect the morphological information of single subjects. In recent years, individual morphological networks have demonstrated significant worth in exploring the topological changes of the human brain under both normal and disease conditions. Such studies provided novel perspectives for understanding human brain development and exploring the pathological mechanisms of neuropsychiatric disorders., Conclusion: This paper mainly focuses on the studies of brain morphological networks at the individual level, introduces several ways for network construction, reviews representative work in this field, and finally points out current problems and future directions., (© 2023 The Authors. CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.)

Aims: The amplitude of low-frequency fluctuations (ALFF) of resting-state functional MRI signals is a reliable neuroimaging measure of spontaneous brain activity. Inconsistent ALFF alterations have been reported in major depressive disorder (MDD) possibly due to clinical heterogeneity. This study was designed to investigate clinically sensitive and insensitive genes associated with ALFF alterations in MDD and the potential mechanisms., Methods: Transcription-neuroimaging association analyses of case-control ALFF differences from two independent neuroimaging datasets with gene expression data from Allen Human Brain Atlas were performed to identify the two gene sets. Various enrichment analyses were conducted to characterize their preference in biological functions, cell types, temporal stages, and shared effects with other psychiatric disorders., Results: Compared with controls, first-episode and drug-naïve patients showed more extensive ALFF alterations than patients with varied clinical features. We identified 903 clinically sensitive genes and 633 clinically insensitive genes, and the former was enriched for genes with down-regulated expression in the cerebral cortex of MDD patients. Despite shared functions of cell communication, signaling, and transport, clinically sensitive genes were enriched for cell differentiation and development whereas clinically insensitive genes were for ion transport and synaptic signaling. Clinically sensitive genes showed enrichment for microglia and macrophage from childhood to young adulthood in contrast to clinically insensitive genes for neurons before early infancy. Clinically sensitive genes (15.2%) were less likely correlated with ALFF alterations in schizophrenia than clinically insensitive genes (66.8%), and both were not relevant to bipolar disorder and adult attention deficit and hyperactivity disorder based on a third independent neuroimaging dataset., Conclusions: Present results provide novel insights into the molecular mechanisms of spontaneous brain activity changes in clinically different patients with MDD., (© 2023 The Authors. CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.)

Aims: Complex cellular communications between glial cells and neurons are critical for brain normal function and disorders, and single-cell level RNA-sequencing datasets display more advantages for analyzing cell communications. Therefore, it is necessary to systematically explore brain cell communications when considering factors such as sex and brain region., Methods: We extracted a total of 1,039,459 cells derived from 28 brain single-cell RNA-sequencing (scRNA-seq) or single-nucleus RNA-sequencing (snRNA-seq) datasets from the GEO database, including 12 human and 16 mouse datasets. These datasets were further divided into 71 new sub-datasets when considering disease, sex, and region conditions. In the meanwhile, we integrated four methods to evaluate ligand-receptor interaction score among six major brain cell types (microglia, neuron, astrocyte, oligodendrocyte, OPC, and endothelial cell)., Results: For Alzheimer's disease (AD), disease-specific ligand-receptor pairs when compared with normal sub-datasets, such as SEMA4A-NRP1, were identified. Furthermore, we explored the sex- and region-specific cell communications and identified that WNT5A-ROR1 among microglia cells displayed close communications in male, and SPP1-ITGAV displayed close communications in the meninges region from microglia to neurons. Furthermore, based on the AD-specific cell communications, we constructed a model for AD early prediction and confirmed the predictive performance using multiple independent datasets. Finally, we developed an online platform for researchers to explore brain condition-specific cell communications., Conclusion: This research provided a comprehensive study to explore brain cell communications, which could reveal novel biological mechanisms involved in normal brain function and neurodegenerative diseases such as AD., (© 2023 The Authors. CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.)

As the main loading-bearing tissue of eye, sclera exerts an important role in the pathophysiology of glaucoma. Intraocular pressure (IOP) generates mechanical strain on sclera. Recent studies have demonstrated that sclera, especially the peripapillary sclera, undergoes complicated remodelling under the mechanical strain. However, the mechanisms of the hypertensive scleral remodelling in human eyes remained uncertain. In this study, peripapillary human scleral fibroblasts (ppHSFs) were applied cyclic mechanical strain by Flexcell-5000™ tension system. We found that CXC- ligands and CXCR2 were differentially expressed after strain. Increased cell proliferation and inhibited cell motility were observed when CXCR2 was upregulated under the strain, whereas cell proliferation and motility did not have a significant change when CXCR2 was knocked down. CXCR2 could facilitate cell proliferation ability, modulate the mRNA and protein expressions of type I collagen and matrix metalloproteinase 2 via JAK1/2-STAT3 signalling pathway. In addition, CXCR2 might inhibit cell migration via FAK/MLC 2 pathway. Taken together, CXCR2 regulated protein production and affected cell behaviours of ppHSFs. It might be a potential therapeutic target for the hypertensive scleral remodelling., (© 2022 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

Evidence of the impact of exposure to multiple mycotoxins and environment enteric dysfunction (EED) on child growth is limited. Using data from a birth cohort study, the objectives of this study were to (a) quantify exposure to multiple mycotoxins (serum aflatoxin [AFB 1 ] and ochratoxin A [OTA], urinary fumonisin [UFB 1 ] and deoxynivalenol [DON]), as well EED (lactulose:mannitol [L:M] ratio); (b) examine the potential combined effects of multiple mycotoxin exposure and EED on growth. Multivariate regressions were used to identify associations between growth measurements (length, weight, anthropometric z-scores, stunting and underweight) at 24-26 months of age and exposure to mycotoxins and EED at 18-22 months (n = 699). Prevalence of AFB 1 , DON, OTA and UFB 1 exposure ranged from 85% to 100%; average L:M ratio was 0.29 ± 0.53. In individual mycotoxin models, AFB 1 exposure was negatively associated with weight, WAZ, increased odds of stunting (odds ratio [OR]: 1.28, 95% confidence interval [CI]: 1.08, 1.52; p = 0.004) and underweight (OR: 1.18, 95% CI: 1.00, 1.38; p = 0.046). Irrespective of other mycotoxin exposure and presence of EED, AFB 1 was negatively associated with length, weight, head circumference, LAZ and WAZ, and with increased odds of stunting and underweight, UFB 1 was associated with increased odds of underweight, and DON was negatively associated with head circumference. EED was associated with the impaired length and weight. These findings suggest that certain mycotoxins and EED may have independent impacts on different facets of growth and that aflatoxin dominates such impacts. Thus, programs reducing exposure to mycotoxin and EED through multi-sectoral nutrition-sensitive interventions have the potential to improve child growth., (© 2021 The Authors. Maternal & Child Nutrition published by John Wiley & Sons Ltd.)

Purpose: To report the use of flying baby spectral domain optical coherence tomography (SD-OCT) on infants with advanced retinopathy of prematurity (ROP), where clinical findings alone failed to differentiate between retinoschisis and retinal detachment., Methods: Prospective, non-interventional case-series study of three premature infants with advanced ROP of clinically uncertain stage, after examination by indirect ophthalmoscopy. To confirm the diagnosis, table-mounted SD-OCT retinal imaging was performed with the infant held in the flying baby position under topical ocular anaesthesia only. Spectral domain optical coherence tomography (SD-OCT) findings were correlated with clinical examination and ultra-widefield scanning laser ophthalmoscopy to determine disease stage and appropriate management., Results: The flying baby position was well tolerated, and SD-OCT images of central and peripheral retina were successfully obtained in all three cases. Additional information provided by the SD-OCT changed the ROP staging from 3 to 4 in one case, which subsequently required surgical treatment. In two other cases, clinical suspicion of stage 4 ROP was overruled as SD-OCT revealed tractional retinoschisis rather than full-thickness retinal detachment, thereby avoiding the need for immediate surgical intervention., Conclusions: In this case-series study, flying baby SD-OCT provided a rapid and widely accessible imaging approach that overruled clinical findings and altered classification and management of infants with advanced ROP. The methodology was suitable for outpatient settings with no risks associated with systemic anaesthesia. The increased use of OCT imaging will make apparent how structural information is useful in management of ROP and may influence future classification of the disease., (© 2020 The Authors. Acta Ophthalmologica published by John Wiley & Sons Ltd on behalf of Acta Ophthalmologica Scandinavica Foundation.)

Ageing and hyperhomocysteinemia (HHcy) are important risk factors for cardiovascular diseases (CVDs). HHcy affects the occurrence of vascular diseases in the elderly. So far, the mechanism of HHcy-induced vascular ageing remains largely unknown. Autophagy level is significantly reduced in the ageing process, and restoring impaired autophagy to a normal state may be one of the possible ways to extend the expected longevity and lifespan in the future. In this study, we established the HHcy rat model by feeding a 2.5% methionine diet. Small animal ultrasound and the tail-cuff method indicated that the vascular pulse wave velocity (PWV) and pulse pressure (PP) of HHcy rats were increased significantly compared with the control group. Vascular morphology and structure have been changed in HHcy rats, including lumen dilation, increased collagen fibre deposition and increased p53/p21/p16 expression. In vitro, under the stimulation of homocysteine (500 μmol/L, 24 hours), the rat vascular smooth muscle cells (VSMCs) presented senescence, which was characterized by the increased expression of ageing-related markers, such as p16, p21 and p53 as well as increased senescence-associated beta-galactosidase (SA-β-gal) activity. Meanwhile, the autophagy level was decreased both in vivo and in vitro, shown as the increased level of autophagy substrate p62 and the reduced level of autophagy marker LC3 II/I in the thoracic aorta of HHcy rats and in Hcy-treated VSMCs, respectively. The senescence phenotype of VSMCs was reversed by increased autophagy levels induced by rapamycin. Our findings indicate that decreased autophagy of VSMCs is involved in hyperhomocysteinemia-induced vascular ageing., (© 2020 John Wiley & Sons Australia, Ltd.)

Purpose: To report the highest attained visual acuity with an electronic retinal implant for the treatment of advanced retinal degeneration following a novel intensive period of visual training., Methods: A case study as part of the prospective, international, multi-centre, interventional clinical trial (ClinicalTrials.gov NCT02720640 and NCT01024803) of patients with the Retina Implant Alpha AMS (Retina Implant AG, Reutlingen, Germany) for advanced retinal degeneration. A patient with subretinal device implanted into worse-seeing eye with no useful perception of light vision secondary to USH2A retinal degeneration underwent intensive period of visual training., Results: The device remains functional with no safety concerns at 3 years postsurgical implantation, and following visual training, the patient achieved the highest visual acuity so far with an electronic retinal device, with real, digitally unenhanced, reading vision of 0.04 decimal (equivalent to 1.39 LogMAR and 20/500 or 6/150 Snellen). In addition, perception as well as partial identification of obstacles and evaluation of distances was possible in both daylight and night-time settings., Conclusions: Retinal implants are currently the only available therapy option for advanced retinal degeneration. Visual rehabilitation postimplantation has potential to maximize visual percepts. The novel concept of intensive visual training presented herein shows what is achievable with electronic retinal implants and has implications for other therapeutic options, such as optogenetics, that aim to stimulate remaining inner retinal cells in advanced retinal degeneration., (© 2020 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Choroideremia is an X-linked recessive retinal degeneration predominantly affecting hemizygous males. It is caused by mutations in the CHM gene that encodes the Rab escort protein-1. Characteristic features include early nyctalopia followed by progressive constriction of peripheral visual fields and sparing of the central vision until late in life with a distinct fundoscopic appearance. We present the case of a 17-year-old male with a c.282delT in exon 4 of CHM that has not previously been reported. Phenotypically this patient presented with an atypical choroideremia phenotype of early central macular degeneration in addition to the classic peripheral fundus characteristic findings., (© 2019 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Transforming growth factor beta (TGFβ) plays a crucial role in tissue fibrosis. A number of studies have shown that TGFβ3 significantly attenuated tissue fibrosis. However, the mechanism involved in this effect is poorly understood. In this study we found that the expression level of TGFβ3 was higher in human myocardial infarction (MI) tissues than in normal tissues, and interestingly, it increased with the development of fibrosis post-myocardial infarction (post-MI). In vitro, human cardiac fibroblasts (CFs) were incubated with angiotensin II (Ang II) to mimic the ischaemic myocardium microenvironment and used to investigate the anti-fibrotic mechanism of TGFβ3. Then, fibrosis-related proteins were detected by Western blot. It was revealed that TGFβ3 up-regulation attenuated the proliferation, migration of human CFs and the expression of collagens, which are the main contributors to fibrosis, promoted the phenotype shift and the cross-linking of collagens. Importantly, the expression of collagens was higher in the si-smad7 groups than in the control groups, while silencing smad7 increased the phosphorylation level of the TGFβ/smad signalling pathway. Collectively, these results indicated that TGFβ3 inhibited fibrosis via the TGFβ/smad signalling pathway, possibly attributable to the regulation of smad7, and that TGFβ3 might serve as a potential therapeutic target for myocardial fibrosis post-MI., (© 2019 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.)

Purpose: Choroideremia is a currently incurable X-linked recessive retinal degeneration that leads to blindness. Gene therapy approaches to date target the outer retinal layers. However, the choroideremia (CHM) gene is expressed in all retinal layers, and a previous study on a small cohort of choroideremia patients suggested possible thinning of the retinal nerve fibre layer (RNFL). The purpose of the study was to examine the RNFL in detail using advanced imaging techniques in a larger cohort of choroideremia patients., Methods: Spectral domain optical coherence tomography of the peripapillary RNFL acquired with the Heidelberg Spectralis HRA circular scan mode were analysed retrospectively in 41 eyes of 21 choroideremia patients aged 39.6 years (±3.7 SEM). As age-matched controls, 20 eyes from 10 patients with retinitis pigmentosa and 56 eyes from 28 healthy individuals were also assessed. Automated RNFL segmentation was adjusted manually to precisely delineate the RNFL. The data were also compared against an external normative database., Results: Mean peripapillary RNFL thickness in choroideremia was 130 ± 3 μm in the right eye (OD) and 133 ± 3 μm in the left eye (OS). This was 24% and 27% thicker than RNFL thickness in the controls (p < 0.001 for both). Patients with retinitis pigmentosa also showed an increase in RNFL thickness, which was no different to the choroideremia cohort (p > 0.05). Compared with manual analysis, the automated function of the inbuilt software was consistently inaccurate in segmenting the RNFL in choroideremia., Conclusion: The RNFL is significantly thicker in choroideremia compared with age-matched normal controls, which was similar to what was seen in retinitis pigmentosa., (© 2018 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)