Fine-Regional Role of the Claustrum in Anxiety and Higher Sensitivity to Cocaine in Adolescent Cocaine-Exposed Male Mice during Adulthood.

Adolescent cocaine exposure (ACE) induces anxiety and higher sensitivity to substances abuse during adulthood. Here, we show that the claustrum is crucial for controlling these psychiatric problems in male mice. In anxiety-like behavioral tests, the CaMKII-positive neurons in the median portion of the claustrum (MClaustrum) were triggered, and local suppression of these neurons reduced the anxiety-like behavior in ACE mice during adulthood. In contrast, the CaMKII-positive neurons in the anterior portion of the claustrum (AClaustrum) were more activated in response to subthreshold dose of cocaine induced conditioned place preference (CPP), and local suppression of these neurons blocked the acquisition of cocaine CPP in ACE mice during adulthood. Our findings for the first time identified the fine-regional role of the claustrum in regulating the anxiety and susceptibility to cocaine in ACE mice during adulthood, extending our understanding of the claustrum in substance use disorder.

Lactobacillus reuteri inhibits Staphylococcus aureus-induced mastitis by regulating oxytocin releasing and gut microbiota in mice.

Mastitis is the most frequent disease of cows and has well-recognized detrimental effects on animal wellbeing and dairy farm profitability. With the advent of the postantibiotic era, alternative antibiotic agents, especially probiotics, have received increasing attention in the treatment of mastitis. Based on research showing that Lactobacillus reuteri (L. reuteri) has anti-inflammatory effects, this study explored the protective effects and mechanisms of L. reuteri against mastitis induced by Staphylococcus aureus (S. aureus) in mice. First, mice with S. aureus-induced mastitis were orally administered L. reuteri, and the inflammatory response in the mammary gland was observed. The results showed that L. reuteri significantly inhibited S. aureus-induced mastitis. Moreover, the concentration of oxytocin (OT) and protein expression of oxytocin receptor (OTR) were measured, and inhibition of OTR or vagotomy reversed the protective effect of L. reuteri or its culture supernatant (LCS) on S. aureus-induced mastitis. In addition, in mouse mammary epithelial cells (MMECs), OT inhibited the inflammation induced by S. aureus by inhibiting the protein expression of OTR. It was suggested that L. reuteri protected against S. aureus-induced mastitis by releasing OT. Furthermore, microbiological analysis showed that the composition of the microbiota was altered, and the relative abundance of Lactobacillus was significantly increased in gut and mammary gland after treatment with L. reuteri or LCS. In conclusion, our study found the L. reuteri inhibited the mastitis-induced by S. aureus via promoting the release of OT, and treatment with L. reuteri increased the abundance of Lactobacillus in both gut and mammary gland.

Oriented Alignment of CsPbBr3 Single-Crystal Arrays for Flexible X-ray Imaging.

The utilization of perovskite materials in flexible optoelectronics is experiencing distinct diversification including X-ray detection applications. Here, we report the oriented alignment of cesium lead bromide (CsPbBr3) single-crystal arrays on flexible polydimethylsiloxane (PDMS) substrates. By precisely confining the crystallization process within spatially delimited precursor droplets, we achieve a well-oriented crystal alignment through the spontaneous rotation of the CsPbBr3 microcuboids. This approach allows for precise control over the microcuboid morphologies by varying the growth temperature. We design flexible X-ray detector arrays by seamlessly integrating CsPbBr3 microcuboids with electrode arrays. The flexible X-ray detector can output a high sensitivity of 1.97 × 105 µC·Gyair-1·cm-2 and a low detection limit of 89 nGyair·s-1 after the surface passivation process. The excellent mechanical properties, outstanding X-ray detection capabilities, and high pixel uniformity are also demonstrated in conformal X-ray imaging of curved surfaces.

Microbiota-gut-brain axis in health and neurological disease: Interactions between gut microbiota and the nervous system.

Along with mounting evidence that gut microbiota and their metabolites migrate endogenously to distal organs, the 'gut-lung axis,' 'gut-brain axis,' 'gut-liver axis' and 'gut-renal axis' have been established. Multiple animal recent studies have demonstrated gut microbiota may also be a key susceptibility factor for neurological disorders such as Alzheimer's disease, Parkinson's disease and autism. The gastrointestinal tract is innervated by the extrinsic sympathetic and vagal nerves and the intrinsic enteric nervous system, and the gut microbiota interacts with the nervous system to maintain homeostatic balance in the host gut. A total of 1507 publications on the interactions between the gut microbiota, the gut-brain axis and neurological disorders are retrieved from the Web of Science to investigate the interactions between the gut microbiota and the nervous system and the underlying mechanisms involved in normal and disease states. We provide a comprehensive overview of the effects of the gut microbiota and its metabolites on nervous system function and neurotransmitter secretion, as well as alterations in the gut microbiota in neurological disorders, to provide a basis for the possibility of targeting the gut microbiota as a therapeutic agent for neurological disorders.

Water-Stable and Sensitive X-ray Detectors by Supramolecular Interaction-Enhanced Polyoxometalates.

Polyoxometalates (POMs) have shown prominence in the field of semiconductive materials in recent years. However, electronic applications based on these emerging materials are still in their early stages. Here, a sensitive and water-stable F-PEA-ZnW12 X-ray detector has been designed and constructed for hard X-ray detection and imaging. Supramolecular interactions of H···O bonding, electrostatic, and anion-π interactions not only enable FPEA-ZnW12 excellent water stability but also shorten the distance between [ZnW12O40]6- clusters, which reduces ion migration and dark current simultaneously, resulting in the conductivity of 3.2 × 10-11 S cm-1. Furthermore, the heteropoly blue formed on the surface of the O-FPEA-ZnW12 wafer device promotes the effective separation and extraction of X-ray-induced carriers, enhancing the sensitivity for X-ray detection. The R/O-FEPA-ZnW12 wafer device yields a high sensitivity of 3.1 × 104 µC Gyair-1 cm-2 with the lowest detectable dose rate of 69 nGyair s-1 under 120 kV hard X-ray irradiation. In addition, the O-FPEA-ZnW12 wafer detector exhibits the potential for X-ray detection in water with a sensitivity of 1.0 × 104 µC Gyair-1 cm-2. Moreover, the fabricated POM X-ray detector shows excellent X-ray imaging capability and long-term operational stability without any attenuation of 1 year exposure to air without any encapsulation.

Constructing and validating pan-apoptosis-related features for predicting prognosis and immunotherapy response in hepatocellular carcinoma.

The study aimed to develop a prognostic model for Hepatocellular Carcinoma (HCC) based on pan-apoptosis-related genes, a novel inflammatory programmed cell death form intricately linked to HCC progression. Utilizing transcriptome sequencing and clinical data from the TCGA database, we identified six crucial pan-apoptosis-related genes through statistical analyses. These genes were then employed to construct a prognostic model that accurately predicts overall survival rates in HCC patients. Our findings revealed a strong correlation between the model's risk scores and tumor microenvironment (TME) status, immune cell infiltration, and immune checkpoint expression. Furthermore, we screened for drugs with potential therapeutic efficacy in high- and low-risk HCC groups. Notably, PPP2R5B gene knockdown was found to inhibit HCC cell proliferation and clonogenic capacity, suggesting its role in HCC progression. In conclusion, this study presents a novel pan-apoptosis gene-based prognostic risk model for HCC, providing valuable insights into patient TME status and guiding the selection of targeted therapies and immunotherapies.

The effects of BMP2 and the mechanisms involved in the invasion and angiogenesis of IDH1 mutant glioma cells.

PURPOSE: This study investigated the effect of an isocitrate dehydrogenase 1 (IDH1) mutation (mutIDH1) on the invasion and angiogenesis of human glioma cells. METHODS: Doxycycline was used to induce the expression of mutIDH1 in glioma cells. Transwell and wound healing assays were conducted to assess glioma cell migration and invasion. Western blotting and cell immunofluorescence were used to measure the expression levels of various proteins. The influence of bone morphogenetic protein 2 (BMP2) on invasion, angiogenesis-related factors, BMP2-related receptor expression, and changes in Smad signaling pathway-related proteins were evaluated after treatment with BMP2. Differential gene expression and reference transcription analysis were performed. RESULTS: Successful infection with recombinant lentivirus expressing mutIDH1 was demonstrated. The IDH1 mutation promoted glioma cell migration and invasion while positively regulating the expression of vascularization-related factors and BMP2-related receptors. BMP2 exhibited a positive regulatory effect on the migration, invasion, and angiogenesis of mutIDH1-glioma cells, possibly mediated by BMP2-induced alterations in Smad signaling pathway-related factors.After BMP2 treatment, the differential genes of MutIDH1-glioma cells are closely related to the regulation of cell migration and cell adhesion, especially the regulation of Smad-related proteins. KEGG analysis confirmed that it was related to BMP signaling pathway and TGF-ß signaling pathway and cell adhesion. Enrichment analysis of gene ontology and genome encyclopedia further confirmed the correlation of these pathways. CONCLUSION: Mutation of isocitrate dehydrogenase 1 promotes the migration, invasion, and angiogenesis of glioma cells, through its effects on the BMP2-driven Smad signaling pathway. In addition, BMP2 altered the transcriptional patterns of mutIDH1 glioma cells, enriching different gene loci in pathways associated with invasion, migration, and angiogenesis.

Isolated optic neuritis with positive glial fibrillary acidic protein antibody.

BACKGROUND AND OBJECTIVES: Autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy (GFAP-A) has been reported as a spectrum of autoimmune, inflammatory central nervous system disorders. Linear perivascular radial gadolinium enhancement patterns on brain magnetic resonance imaging (MRI) are a hallmark of these disorders. GFAP-A is associated with cerebrospinal fluid (CSF) GFAP antibody (GFAP-Ab), while the association with serum GFAP-Ab is less clear. This study aimed to observe the clinical characteristic and MRI changes of GFAP-Ab-positive optic neuritis (ON). METHODS: We performed a retrospective, observational case study at the department of neurology, Beijing Tongren Hospital, from December 2020 to December 2021. The serum of 43 patients and CSF samples of 38 patients with ON were tested for GFAP-Ab by cell-based indirect immune-fluorescence test. RESULTS: Four patients (9.3%) were detected GFAP-Ab positive, and in three out of the four patients, GFAP-Abs were detected only in serum. All of them demonstrated unilateral optic neuritis. Three patients (1, 2, and 4) experienced severe visual loss (best corrected visual acuity ≤ 0.1). Two patients (2 and 4) had experienced more than one episode of ON at the time of sampling. MRI showed optic nerve hyperintensity on T2 FLAIR images in all GFAP-Ab positive patients, and orbital section involvement was the most common. During follow-up (mean 4.5 ± 1 months), only Patient 1 had a recurrent ON, and no patient developed new other neurological events or systemic symptoms. CONCLUSION: GFAP-Ab is rare in patients with ON and may manifest as isolated, relapsing ON. This supports the notion that the GFAP-A spectrum should comprise isolated ON.

ZEA mediates autophagy through the ROS-AMPK-m-TOR pathway to enhance the susceptibility of mastitis induced by Staphylococcus aureus in mice.

Mastitis is an inflammatory response of the mammary tissue caused by pathogenic bacterial infections, especially Staphylococcus aureus (S. aureus). Zearalenone (ZEA) is one of the common mycotoxins in moldy feed, which usually affects the cow's resistance to pathogenic microorganisms. However, it is not well understood whether ZEA affects the development of mastitis. Therefore, this study aimed to investigate the role of ZEA in the development of S. aureus-induced mastitis in mice. The results showed that administered daily by gavage for one week of ZEA (40 mg/kg) aggravated the severity of mastitis induced by S. aureus. Furthermore, we found that ZEA promotes the adhesion and invasion of S. aureus into mouse mammary epithelial cells (MMEC) by activating autophagy, and the activation of autophagy mediated by ROS-AMPK-m-TOR pathway. Taken together, the results showed that ZEA enhances S. aureus-induced mastitis susceptibility through activating autophagy mediated by ROS-AMPK-mTOR signaling pathway.

Organic Amine-Bridged Quasi-2D Perovskite/PbS Colloidal Quantum Dots Composites for High-Gain Near-Infrared Photodetectors.

Near-infrared (NIR) II detection at weak flux intensity is required in medical imaging and is especially urgent in light of the low quantum efficiency of NIR-II dyes. The low responsivity of traditional photodetectors in this region limits image quality. Here, we report a NIR-II photodetector with high gain based on perovskite coupled PbS colloidal quantum dots (CQDs). Tailoring the trap density of CQDs by designing surface ligands with dual functionality contributed to control over trap-induced charge-injection upon light illumination. As a result, a detector with high gain is realized, showing external quantum efficiency of 1260% at 1200 nm and achieving the lowest detectable light intensity, that is, as low as 0.67 pW cm-2 with a linear dynamic range of 200 dB. Devices maintain over 90% of responsivity after 150 days of storage. We acquired images of a butterfly wing, showing the skeleton texture with a maximum spatial resolution of 3.9 lp/mm.

Impact of COVID-19 Restrictions on the Urban Thermal Environment of Edmonton, Canada.

The effects of the COVID-19 pandemic on urban environments are addressed in many recent studies. However, limited research has been conducted to examine the impact of the pandemic on anthropogenic emissions over urban land use types, and their relation to socioeconomic characteristics. Anthropogenic heat, as the main contributor to the urban temperature, is changed by the sudden halt imposed by COVID-19 lockdowns. This study thus focuses on previously under-explored urban thermal environments by quantifying the impact of COVID-19 on urban thermal environments across different land-use types and related socioeconomic drivers in Edmonton, Canada. Using Landsat images, we quantified and mapped the spatial pattern of land surface temperature (LST) for business, industrial, and residential land use areas during both the pandemic lockdown and pre-pandemic periods in the study area. Results show that temperature declined in business and industrial areas and increased in residential areas during the pandemic lockdown. Canadian census and housing price data were then used to identify the potential drivers behind the LST anomaly of residential land use. The most important variables that affected LST during the lockdown were found to be median housing price, visible minority population, postsecondary degree, and median income. This study adds to the expanding body of literature about the impact of the COVID-19 pandemic by providing unique insights into the effect of lockdown on a city's thermal environments across different land use types and highlights critical issues of socioeconomic inequalities, which is useful for future heat mitigating and health equity-informed responses.

Low Bandgap 2D Perovskite Single Crystal with Anomalous-large Charges/ions Collection Ratio for Ultra-sensitive and Stable X-ray Detectors.

The low-dimensional halide perovskites have attracted increasing attention due to their improved moisture stability, reduced defects, and suppressed ions migration in many optoelectronic devices such as solar cells, light-emitting diodes, X-ray detectors, and so on. However, they are still limited by their large band gap and short charge carriers' diffusion length. Here, we demonstrate that the introduction of metal ions into organic interlayers of two-dimensional (2D) perovskite by cross-linking the copper paddle-wheel cluster-based lead bromide ([Cu(O2 C-(CH2 )3 -NH3 )2 ]PbBr4 ) perovskite single crystals with coordination bonds can not only significantly reduce the perovskite band gap to 0.96 eV to boost the X-ray induced charge carriers, but can also selectively improve the charge carriers' transport along the out-of-plane direction and blocking the ions motion paths. The [Cu(O2 C-(CH2 )3 -NH3 )2 ]PbBr4 single-crystal device can reach a record charges/ions collection ratio of 1.69×1018 ±4.7 % µGyair -1 s, and exhibit a large sensitivity of 1.14×105 ±7% µC Gyair -1 cm-2 with the lowest detectable dose rate of 56 nGyair s-1 under 120 keV X-rays irradiation. In addition, [Cu(O2 C-(CH2 )3 -NH3 )2 ]PbBr4 single-crystal detector exposed to the air without any encapsulation shows excellent X-ray imaging capability with long-term operational stability without any attenuation of 120 days.

Perovskite Dimensional Evolution Through Cations Engineering to Tailor the Detection Limit in Hard X-ray Response.

Halide perovskites with various compositions are potential candidates in low-dosage X-ray detection due to their large sensitivity and tunable optoelectronic properties. Here, cations engineering induced dimensional evolution of halide perovskites between 0D, 2D, and 3D is reported. Centimeter-sized 2D lead-free perovskite single-crystal of 4-fluorophenethylammonium antimony iodide (FPEA3 SbI6 ) is synthesized. In contrast to the 0D phenethylammonium antimony iodide (PEA3 Sb2 I9 ), face-shared [Sb2 I9 ]3- of the bi-octahedral structure of PEA3 Sb2 I9 is split into corner-shared [SbI6 ]3- by intermolecular interactions and steric hindrance of FPEA+ ions in 2D FPEA3 SbI6 . Two Sb3+ ions share three octahedral [SbI6 ]3- , leaving one-third of Sb3+ vacancies in the framework of FPEA3 SbI6 . Furthermore, Sn2+ ions can be filled into the vacancies to form continuous 2D frameworks to tune the anisotropic conductivity and device sensitivity to hard X-rays. The dimensional evolution of perovskite single-crystals from 3D to 2D or 0D to 2D maximizes the signal/noise ratio to facilize the adjustability of detection limit in hard X-ray detection, which is determined by both device sensitivity and device noise current. A record low detection limit coefficient of 0.65 is achieved in the 2D FPEA3 SbSn0.5 I7 single-crystal sample, which results from selective charges collection over mobile ions/noise current in the 2D perovskite structure.

In vitro induction and intraocular application in oxygen-induced retinopathy of adipose-derived mesenchymal stem cells.

Purpose: We designed a study to find theoretical evidence for the induction, movement, fusion, proliferation, and safety of human adipose mesenchymal stem cells (hADSCs) in intraocular application. Methods: HADSCs were induced to confirm that they can express the characteristics of endothelial cells (ECs) in vitro. HADSCs were intraocularly injected into oxygen-induced retinopathy (OIR) mice to check the movement, fusion, proliferation, and prognosis in vivo. Electron microscopy was used to check retinal changes to confirm the safety of hADSCs in intraocular application. Results: After induction, hADSCs expressed von Willebrand Factor (vWF), the cell marker of ECs. The hADSCs were distributed above the retina after an intravitreal injection in the OIR mice. The injected cells did not fuse with the retina and gathered in the central and peripheral areas, which is the lesion area of the OIR model. Five days after the hADSC intravitreal injection, the area of ​neovascularization was reduced by 94.83% compared with that of the OIR group. Hematologic staining and electron microscopy did not show noticeable proliferation and degeneration of the retina. Conclusions: This study provides evidence for the intraocular application of hADSCs.

Cadmium induces liver dysfunction and ferroptosis through the endoplasmic stress-ferritinophagy axis.

Cadmium (Cd) is a type of high-risk heavy metal that can damage organs such as the liver, but its mechanism is not yet clear. Ferroptosis is a newly discovered mode of regulatory cell death. We explored whether ferroptosis is involved in Cd-induced liver damage and the underlying mechanism. Our research showed that Cd induced liver damage by inducing ferroptosis, and the use of ferroptosis inhibitors reduced the degree of liver damage. Moreover, the occurrence of ferroptosis was accompanied by the activation of the PERK-eIF2α-ATF4-CHOP signaling pathway, and inhibiting endoplasmic reticulum (ER) stress reduced ferroptosis demonstrating that ferroptosis induced by Cd is dependent on ER stress. In addition, chloroquine, a common autophagy inhibitor, mitigated ferroptosis caused by Cd exposure. Then, the iron chelator deferoxamine reduced Cd-induced lipid peroxidation and cell death, demonstrating that the iron regulation disorder caused by ferritin phagocytosis contributes to the Cd-induced ferroptosis. In conclusion, our results show that Cd-induced liver toxicity is accompanied by ferroptosis, which contributes to Cd inducing oxidative stress to trigger autophagy and ER stress to promote the process of ferroptosis.

Preliminary study on impacts of polystyrene microplastics on the hematological system and gene expression in bone marrow cells of mice.

Microplastics (MPs) are currently a global environmental pollutants and health hazards that caused by MPs cannot be ignored. However, studies on MP toxicity in mammals are scare. Here, we investigated the effects of two doses (0.1 mg and 0.5 mg) of 5 µm polystyrene microplastic (PS-MP) particles on the hematological system of mice through traditional toxicology experiments and assessed the related potential biological mechanisms using transcriptome sequencing analysis. The toxicological examinations showed that the 0.5 mg dose significantly decreased white blood cell count, increased Pit count, and inhibited the growth of colony-forming unit CFU-G, CFU-M and CFU-GM. Compared with the control group, there were 41 differentially expressed genes (DEGs) in the 0.1 mg-treated group and 32 significantly changed genes in 0.5 mg-treated group. Of note, eight genes were found to be significantly altered in both the PS-MP-treated groups. Gene ontology analysis showed that DEGs were mainly involved in T cell homeostasis, response to osmotic stress, extracellular matrix and structure organization, and metabolic process of NADP and nucleotides. In addition, pathway analysis revealed that the Jak/Stat pathway, pentose and glucuronate interconversions, nicotinate and nicotinamide metabolism, biosynthesis of unsaturated fatty acids, and the pentose phosphate pathway were involved in PS-MP-induced toxicity in mice. These results indicated that PS-MP exposure can cause hematotoxicity to some extent, impact gene expression, and disturb related molecular and biological pathways in mouse bone marrow cells. Our study provides fundamental data on the hematotoxicity of PS-MPs in terrestrial mammals that will help to further assess the corresponding health risks in these mammals.

Interconnection of Key Microbial Functional Genes for Enhanced Benzo[a]pyrene Biodegradation in Sediments by Microbial Electrochemistry.

Sediment microbial fuel cells (SMFCs) can stimulate the degradation of polycyclic aromatic hydrocarbons in sediments, but the mechanism of this process is poorly understood at the microbial functional gene level. Here, the use of SMFC resulted in 92% benzo[a]pyrene (BaP) removal over 970 days relative to 54% in the controls. Sediment functions, microbial community structure, and network interactions were dramatically altered by the SMFC employment. Functional gene analysis showed that c-type cytochrome genes for electron transfer, aromatic degradation genes, and extracellular ligninolytic enzymes involved in lignin degradation were significantly enriched in bulk sediments during SMFC operation. Correspondingly, chemical analysis of the system showed that these genetic changes resulted in increases in the levels of easily oxidizable organic carbon and humic acids which may have resulted in increased BaP bioavailability and increased degradation rates. Tracking microbial functional genes and corresponding organic matter responses should aid mechanistic understanding of BaP enhanced biodegradation by microbial electrochemistry and development of sustainable bioremediation strategies.

Persistent androgen receptor-mediated transcription in castration-resistant prostate cancer under androgen-deprived conditions.

The androgen receptor (AR) is a ligand-inducible transcription factor that mediates androgen action in target tissues. Upon ligand binding, the AR binds to thousands of genomic loci and activates a cell-type specific gene program. Prostate cancer growth and progression depend on androgen-induced AR signaling. Treatment of advanced prostate cancer through medical or surgical castration leads to initial response and durable remission, but resistance inevitably develops. In castration-resistant prostate cancer (CRPC), AR activity remains critical for tumor growth despite androgen deprivation. Although previous studies have focused on ligand-dependent AR signaling, in this study we explore AR function under the androgen-deprived conditions characteristic of CRPC. Our data demonstrate that AR persistently occupies a distinct set of genomic loci after androgen deprivation in CRPC. These androgen-independent AR occupied regions have constitutively open chromatin structures that lack the canonical androgen response element and are independent of FoxA1, a transcription factor involved in ligand-dependent AR targeting. Many AR binding events occur at proximal promoters, which can act as enhancers to augment transcriptional activities of other promoters through DNA looping. We further show that androgen-independent AR binding directs a gene expression program in CRPC, which is necessary for the growth of CRPC after androgen withdrawal.

Exome sequencing-aided precise diagnosis of four families with type I Stickler syndrome.

BACKGROUND: Stickler syndrome is a multisystemic disorder characterized by ophthalmological and non-ophthalmological abnormalities, frequently misdiagnosed due to high clinical heterogeneity. Stickler syndrome type I (STL1) is predominantly caused by mutations in the COL2A1 gene. METHODS: Exome sequencing and co-segregation analysis were utilized to scrutinize 35 families with high myopia, and pathogenic mutations were identified. Mutant COL2A1 was overexpressed in cells for mechanistic study. A retrospective genotype-phenotype correlation analysis was further conducted. RESULTS: Two novel pathogenic mutations (c.2895+1G>C and c.3505G>A (p.Val1169Ile)) and two reported mutations (c.1597C>T (p.Arg533*) and c.1693C>T (p.Arg565Cys)) in COL2A1 were identified causing STL1. These mutations are all in the G-X-Y triplet, and c.2895+1G>C contributed to aberrant RNA splicing. COL2A1 mutants tended to form large aggregates in the endoplasmic reticulum (ER) and elevated ER stress. Additionally, mutations c.550G>A (p.Ala184Thr) and c.2806G>A (p.Gly936Ser) in COL2A1 were found in high myopia families, but were likely benign, although c.2806G>A (p.Gly936Ser) is on G-X-Y triplet. Moreover, genotype-phenotype correlation analysis revealed that mutations in exon 2 mainly contribute to retinal detachment, whereas mutations in the collagen alpha-1 chain region of COL2A1 tend to cause non-ophthalmologic symptoms. CONCLUSION: This study broadens the COL2A1 gene mutation spectrum, provides evidence for ER stress caused by pathogenic COL2A1 mutations and highlights the importance of non-ophthalmological examination in clinical diagnosis of high myopia.

Characteristics of Inflammatory and Normal Endothelial Exosomes on Endothelial Function and the Development of Hypertension.

Endothelial dysfunction is associated with the development of hypertension. We hypothesize that inflammatory and normal endothelial exosomes play their roles by mediating endothelial function, and they induce endothelial angiogenesis through different signaling pathways. Endothelial cell-derived exosomes were isolated from the human umbilical vein endothelial cells (HUVECs) treated with (TExo) or without (CExo) tumor necrosis factor (TNF)-α. We monitored dermal microcirculation profiles in spontaneously hypertensive rats (SHRs) and WKY rats using a laser Doppler imager and a laser Doppler perfusion and temperature monitor. Tube formation, levels of angiogenesis-related proteins in HUVEC-conditioned media, and reactive oxygen species (ROS) levels were assessed following TNF-α, CExo, or TExo treatments. Western blot analysis was conducted to examine signaling proteins associated with inflammation and ROS. The results showed increased blood perfusion and the mean amplitude of endothelial oscillator in SHRs following CExo administration. TNF-α, CExo, and TExo treatments promoted endothelial tube formation and elevated levels of angiogenic factors and ROS. TExo significantly increased phosphorylation levels of STAT3, p38, and level of NF-κB, while decreasing phosphorylation levels of JNK and Erk (P < 0.01 or P < 0.05). CExo significantly increased STAT3 phosphorylation and reduced JNK and Erk phosphorylation (all P < 0.01). In conclusion, TNF-α and TExo induce inflammatory and pathological angiogenesis via the NF-κB pathway, while CExo exhibits a physiologically pro-angiogenic effect on endothelial cells. Increased ROS, interplaying with inflammatory signals, contribute to exosome-mediated alterations of endothelial function, thereby playing a role in the development of hypertension.