[Clinicopathological characteristics of the CD8+ T lymphocytes infiltration and its mechanism in distinct molecular subtype of medulloblastoma].

OBJECTIVE: To investigate the characteristics of the CD8+ T cells infiltration from the 4 subtypes in medulloblastoma (MB), to analyze the relationship between CD8+ T cells infiltration and prognosis, to study the function of C-X-C motif chemokine ligand 11 (CXCL11) and its receptor in CD8+ T cells infiltration into tumors and to explore the potential mechanism, and to provide the necessary clinicopathological basis for exploring the immunotherapy of MB. METHODS: In the study, 48 clinical MB samples (12 cases in each of 4 subtypes) were selected from the multiple medical center from 2012 to 2019. The transcriptomics analysis for the tumor of 48 clinical samples was conducted on the NanoString PanCancer IO360TM Panel (NanoString Technologies). Immunohistochemistry (IHC) staining of formalin-fixed, paraffin-embedded sections from MB was carried out using CD8 primary antibody to analyze diffe-rential quantities of CD8+ T cells in the MB four subtypes. Through bioinformatics analysis, the relationship between CD8+T cells infiltration and prognosis of the patients and the expression differences of various chemokines in the different subtypes of MB were investigated. The expression of CXCR3 receptor on the surface of CD8+T cells in MB was verified by double immunofluorescence staining, and the underlying molecular mechanism of CD8+T cells infiltration into the tumor was explored. RESULTS: The characteristic index of CD8+T cells in the WNT subtype of MB was relatively high, suggesting that the number of CD8+T cells in the WNT subtype was significantly higher than that in the other three subtypes, which was confirmed by CD8 immunohistochemical staining and Gene Expression Omnibus (GEO) database analysis by using R2 online data analysis platform. And the increase of CD8+T cells infiltration was positively correlated with the patient survival. The expression level of CXCL11 in the WNT subtype MB was significantly higher than that of the other three subtypes. Immunofluorescence staining showed the presence of CXCL11 receptor, CXCR3, on the surface of CD8+T cells, suggesting that the CD8+T cells might be attracted to the MB microenvironment by CXCL11 through CXCR3. CONCLUSION: The CD8+T cells infiltrate more in the WNT subtype MB than other subtypes. The mechanism may be related to the activation of CXCL11-CXCR3 chemokine system, and the patients with more infiltration of CD8+T cells in tumor have better prognosis. This finding may provide the necessary clinicopathological basis for the regulatory mechanism of CD8+T cells infiltration in MB, and give a new potential therapeutic target for the future immunotherapy of MB.

Evaluating the microcirculation of the dome-shaped macula and its complications in adults with highly myopic eyes by swept-source optical coherence tomography angiography.

PURPOSE: The aim of this study was to investigate the microcirculatory characteristics of the dome-shaped macula (DSM), its complications in highly myopic eyes and to explore the factors associated with a DSM. METHODS: This cross-sectional case-control study included a total of 98 subjects (98 eyes): 49 eyes with DSM and 49 eyes without DSM. The axial length (AL) of the myopic eyes was matched 1:1 to eliminate the effect of AL differences on the results. Choroidal (CT) and scleral thickness (ST) and other structural parameters were assessed by swept-source optical coherence tomography (SS-OCT). OCT angiography was used to measure microcirculatory parameters in highly myopic eyes. RESULTS: Subjects with DSM had thinner subfoveal choroidal thickness (46.01 ± 13.25 vs. 81.62 ± 48.26 µm; p < 0.001), thicker subfoveal scleral thickness (SFST; 331.93 ± 79.87 vs. 238.74 ± 70.96 µm; p < 0.001) and thinner foveal CT (66.86 ± 24.65 vs. 107.85 ± 52.65 µm; p < 0.001) compared to subjects without DSM. The foveal choroidal perfusion area (0.72 ± 0.04 vs. 0.76 ± 0.04 mm2; p < 0.001) and foveal choroidal vascularity index (0.15 ± 0.04 vs. 0.33 ± 0.14; p < 0.001) were significantly lower in eyes with DSM. Retinoschisis (81.6% vs. 38.8%; p < 0.001) was more common in eyes with DSM. Eyes with horizontal DSM had worse best-corrected logMAR visual acuity than eyes with round DSM (0.34 ± 0.22 vs. 0.23 ± 0.22; p = 0.03). DSM height (98.95 ± 65.17 vs. 104.63 ± 44.62 µm; p = 0.05) was lower in the horizontal DSM. SFST (OR = 1.06, p = 0.04) and foveal choroidal vascularity index (OR = 0.711, p = 0.02) were significantly associated with DSM. DSM width (p < 0.001), foveal choroidal perfusion area (p = 0.01), foveal choriocapillaris perfusion area (p = 0.02) and parafoveal choroidal vascularity index (p = 0.03) were the most significantly associated factors with DSM height. CONCLUSIONS: The microcirculatory characteristics of eyes with DSM differed from those without DSM. Microcirculatory abnormalities were significantly associated with a DSM. The height of the DSM was associated with decreased blood perfusion.

INOS ablation promotes corneal wound healing via activation of Akt signaling.

Corneal injury leads to impaired normal structure of the cornea. Improving the wound healing process in epithelial cells significantly contributes to ocular damage treatments. Here, we aimed to investigate the potential mechanisms of nitric oxide (NO) and its mediator, inducible nitric oxide synthase (iNOS), in the process of corneal wound healing. We established a corneal injury model of iNOS-/- mice, and treated human corneal epithelial cell lines (HCE-2) with the iNOS inhibitor L-INL, with or without NO replenishment by supplying sodium nitroferricyanide dihydrate (SNP). Our findings showed that inhibition of NO/iNOS accelerated corneal repair, enhanced uPAR (a receptor protein indicating the migration ability), and improved epithelial cell migration. Furthermore, NO/iNOS ablation activated Akt phosphorylation, reduced neutrophil marker protein MPO expression, and downregulated the transcription of inflammation cytokines CXCL-1, CXCL-2, IL-1ß, IL-6, and TNF-α. However, the protective effects of NO/iNOS inhibition are significantly reduced by NO replenishment when treated with SNP. Therefore, we confirmed that inhibiting NO/iNOS improved the corneal wound healing by facilitating epithelial cell migration and reducing inflammatory reactions, which might be related to the activation of the Akt signaling pathway.

Single-Nuclei Characterization of Lacrimal Gland in Scopolamine-Induced Dry Eye Disease.

Purpose: The lacrimal gland (LG) is the main organ responsible for tear secretion and an important pathogenic site for dry eye disease (DED). This study aimed to comprehensively characterize LG cellular heterogeneity under normal and DED conditions using single-nucleus RNA sequencing (snRNA-seq). Methods: Single LG nuclei isolated from mice with or without DED induced by scopolamine (SCOP)/desiccating stress (DS) were subjected to snRNA-seq using the 10x Genomics platform. These cells were clustered and annotated using the t-distributed stochastic neighbor embedding (t-SNE) method and unbiased computational informatic analysis. Cluster identification and functional analysis were performed based on marker gene expression and bioinformatic data mining. Results: The snRNA-seq analysis of 30,351 nuclei identified eight major cell types, with acinar cells (∼72.6%) being the most abundant cell type in the LG. Subclustering analysis revealed that the LG mainly contained two acinar cell subtypes, two ductal cell subclusters, three myoepithelial cell (MECs) subtypes, and four immunocyte subclusters. In the SCOP-induced DED model, three major LG parenchymal cell types were significantly altered, characterized by a reduced proportion of acinar cells with a lowered secretion potential and an augmented proportion of ductal cells and MECs. LG immunocytes in DED scenarios showed an intensified inflammatory response and dysregulated intercellular communication with three major LG parenchymal cells. Conclusions: Overall, this study offers a systemic single-nucleus transcriptomic profile of LGs in both normal and DED conditions and an atlas of the complicated interactions of immunocytes with major LG parenchymal cells. The findings also facilitate understanding the pathogenesis of DED.

Morphological characteristics of the foveal avascular zone in pathological myopia and its relationship with macular structure and microcirculation.

PURPOSE: To explore the characteristics of macular structure, microcirculation, and foveal avascular zone (FAZ) morphology in pathological myopia and to research the associations between these factors and pathological myopia. METHODS: This is a cross-sectional study. The study included 103 eyes with non-high myopia and 206 eyes with high myopia (139 with simple high myopia and 67 with pathological myopia). Macular structural and microcirculation parameters were determined using optical coherence tomography angiography (OCTA). The FAZ morphological parameters were measured manually using Image J software. Correlations between pathological myopia and various factors were analyzed. RESULTS: Patients with pathological myopia had a thinner retinal thickness (RT) and choroidal thickness (CT) and a lower retinal superficial vascular density (SVD), retinal deep vascular complex density (DVD), choriocapillaris perfusion area (CCPA), and choroidal vascularity index (CVI) (all P < 0.05). Patients with pathological myopia had a larger FAZ area, perimeter, major axis, minor axis, acircularity index (AI), and lower circularity index (CI) (all P < 0.01). The axial length (AL), the major axis of the superficial FAZ, CI, and AI were significantly correlated with myopia severity (all P < 0.05). CONCLUSIONS: Patients with pathological myopia exhibited worse macular microcirculation and thinner macular retina and choroid. The FAZ in pathological myopia was larger and more irregular. The AL, CI, and AI were significantly associated with myopia severity. Thus, CI and AI might serve as new indicators for monitoring the progression of myopia. Further investigations should be performed. TRIAL REGISTRATION: Clinical Trials.gov Identifier: ChiCTR2100046590.

The Effects of Repeated Low-Level Red-Light Therapy on the Structure and Vasculature of the Choroid and Retina in Children with Premyopia.

INTRODUCTION: The purpose of this study was to explore the effects of repeated low-level red-light (RLRL) therapy on the structure and vasculature of the choroid and retina in Chinese children with premyopia. METHODS: This study was a single-center randomized clinical trial. A total of 94 children with premyopia (- 0.50 D < spherical equivalent [SE] ≤ + 0.75 D) were randomly assigned to either the RLRL therapy or control group. Follow-up visits were planned at 1, 3, 6, 9, and 12 months. Optical coherence biometry was used to measure axial length (AL) and anterior segment parameters. Choroidal thickness (CT), retinal thickness (RT), superficial retinal vascular density (SRVD), deep retinal vascular density (DRVD), choriocapillaris perfusion area (CCPA), and choroidal vessel volume (CVV) were measured by optical coherence tomography angiography, centered on the foveal, parafoveal (ParaF), and perifoveal (PeriF) regions. RESULTS: The thickening of the choroid was observed across the entire macular region at different time points in the RLRL therapy group. Relative to the baseline measurement, foveal CT significantly increased at the 1-month follow-up with RLRL therapy, with a mean (± standard deviation [SD]) adjusted change of 16.96 ± 19.87 µm. The greatest magnitude of foveal CT changes was observed at the 3-month visit (an increase of 19.58 ± 20.59 µm), with a slight reduction in the extent of foveal CT increase at the 6-month visit (an increase of 15.85 ± 23.77 µm). The second greatest CT increase was observed at the 9-month visit (an increase of 19.57 ± 35.51 µm), after which the extent of CT increase gradually decreased until the end of the study at the 12-month visit (an increase of 11.99 ± 32.66 µm). We also observed a significant increase in CT in the ParaF and PeriF areas in the RLRL group over 12 months. In contrast, CT across the entire macular region in the control group significantly decreased throughout the follow-up visits (all P < 0.05). Regarding the vascular parameters of the choroid, significant increases in CVV were observed primarily in the ParaF and PeriF regions of the choroid in the RLRL group. In comparison, the control group exhibited decreases in CVV throughout the entire area. Furthermore, notable elevations in CCPA were detected in the PeriF area of the choroid in the RLRL group during the 1-month (an increase of 0.40 mm2), 3-month (an increase of 0.25 mm2), and 12-month visits (an increase of 0.42 mm2) (all P < 0.05). In addition, no notable differences were observed between the groups regarding foveal RT and retinal vascular parameters throughout the 12 months (P > 0.05). Notably, RLRL therapy achieved a notable reduction in SE shift by 73.8%, a substantial decrease in AL change by 67.9%, and a significant reduction in myopia incidence by 45.1% within 1 year. CONCLUSION: Our study demonstrated a significant increase in CT and flow in the RLRL-treated eyes throughout the 12-months of the study. Combined with its reduction in spherical equivalent progression and axial elongation, RLRL could be used as an effective therapy for preventing progression in premyopes. TRIAL REGISTRATION: ChiCTR2200062028.

Tumor-associated astrocytes promote tumor progression of Sonic Hedgehog medulloblastoma by secreting lipocalin-2.

Sonic Hedgehog (SHH) subgroup of medulloblastoma (MB) accounts for about 25% of all subgroups of MB. Tumor microenvironment (TME) may play a key role in the tumor progression and therapeutic resistance. Tumor-associated astrocytes (TAAs) are reshaped to drive tumor progression through multiple paracrine signals. However, the mechanism by which TAAs modulate MB cells remains elusive. Here, we illuminated that TAAs showed a specific and dynamic pattern during SHH-MB development. Most TAAs gathered to the tumor margin during the tumor progression, rather than evenly distributed in the early-stage tumors. We further demonstrated that lipocalin-2 (LCN2) secreted by TAAs could promote the tumor growth and was correlated with the poor prognosis of MB patients. Knocking down LCN2 in TAAs in vitro impeded the proliferation and migration abilities of MB cells. In addition, we identified that TAAs accelerated the tumor growth by secreting LCN2 via STAT3 signaling pathway. Accordingly, blockade of STAT3 signaling by its inhibitor WP1066 and AAV-Lcn2 shRNA, respectively, in TAAs abrogated the effects of LCN2 on tumor progression in vitro and in vivo. In summary, we for the first time clarified that LCN2, secreted by TAAs, could promote MB tumor progression via STAT3 pathway and has potential prognostic value. Our findings unveiled a new sight in reprogramming the TME of SHH-MB and provided a potential therapeutic strategy targeting TAAs.

Comparison of two different orthokeratology lenses and defocus incorporated soft contact (DISC) lens in controlling myopia progression.

BACKGROUND: To compare axial elongation in 8-11-year-old myopes wearing orthokeratology (OK) lenses with different back optic zone diameters (BOZD), defocus incorporated soft contact (DISC) lenses, and single-vision soft contact lenses (SCLs). METHODS: A total of 122 children (aged 8-11 years) with spherical equivalent refraction (SER) between - 1.00 D and - 4.00 D were enrolled in this prospective study and randomly assigned to four groups: 5.0 mm-BOZD OK, 6.2 mm-BOZD OK, DISC, and single-vision SCLs. Children in each group were further divided into subgroups stratified by the average baseline SER: low myopic eyes (SER: - 1.00 D to - 2.50 D) and moderate myopic eyes (SER: - 2.50 D and over). Axial length (AL) was measured at baseline and after one year. RESULTS: The 5.0 mm-BOZD OK, 6.2 mm-BOZD OK, and DISC groups exhibited significantly slower AL elongation than the SCL group. The proportion of slow progressors (AL elongation ≤ 0.18 mm/year) in the first three groups was 42%, 23%, and 29%, respectively. Furthermore, one-year AL elongation was significantly smaller in the 5.0 mm-BOZD OK group compared with the 6.2 mm-BOZD OK group. Regardless of SER, children in the 5.0 mm-BOZD OK and DISC groups showed comparably slower AL elongation than those in the SCL group. However, fitting with 6.2 mm-BOZD OK lenses significantly retarded AL elongation in moderate myopic eyes, but not in low myopic eyes. CONCLUSIONS: Overall, 5.0 mm-BOZD OK lenses, 6.2 mm-BOZD OK lenses, and DISC lenses were effective in retarding AL elongation in 8-11-year-old myopes compared with single-vision SCLs, but for children with SER less than - 2.50 D, fitting with 5.0 mm-BOZD OK lenses and DISC lenses yielded better myopia control efficacy compared to wearing single-vision SCLs or 6.2 mm-BOZD OK lenses.

Analysis of the relationship between axial length, optic disc morphology, and regional variations in retinal vessel density in young adults with healthy eyes.

Purpose: To investigate the relationship between optic disc morphology, axial length, and regional distribution of retinal vessels in healthy eyes of young adults. Methods: Nine hundred and two healthy eyes were enrolled in this university-based, cross-sectional study. Spectral-domain optical coherence tomography angiography was used to measure the parapapillary retinal vessel density. We automated the process of calculating optic disc tilt and rotation by using a program written in Python. Relationships between optic disc rotation, optic disc tilt, parapapillary vessel density, and other ocular parameters were analyzed using regression models. Results: As axial length increased, optic disc morphology became more tilted and rotated inferiorly. The superficial vessel density (SVD) and radial peripapillary capillary density (RPCD) gradually decreased in all regions except for the temporal quadrant. Increased temporal SVD (OR [95% CI] = 1.081 [1.039, 1.124], p < 0.001), reduced nasal SVD (OR [95% CI] = 0.898 [0.861, 0.937], p < 0.01), and short relative lens position (OR [95% CI] = 0.126 [0.032, 0.495], p = 0.003) were significantly associated with the presence of a tilted optic disc. Inferior disc rotation was associated with decreased superior deep vessel density (DVD) and increased inferior DVD and temporal DVD after adjusting for sex and axial length. Conclusion: The tilted and rotated optic discs were associated with the distribution of SVD and DVD, respectively. We should fully consider the influence of optic disc morphology on parapapillary vessel density in eyes with myopia.

Compact cities and the Covid-19 pandemic: Systematic review of the associations between transmission of Covid-19 or other respiratory viruses and population density or other features of neighbourhood design.

Living in compact neighbourhoods that are walkable, well connected, with accessible green space can benefit physical and mental health. However, the pandemic raises concern up to what extent features of compact neighbourhood design affect transmission of viral respiratory infections. We conducted a systematic review to identify, appraise and synthesise evidence reporting associations between transmission of respiratory viruses, including Covid-19, and dwelling or population density or other features of neighbourhood design. Twenty-one studies met our inclusion criteria. These studies used different measures of neighbourhood design, contributing to inconsistent findings. Whereas no convincing conclusion can be drawn here, the outcome of this review indicates that robust, global evidence is warranted to inform future policies and legislation concerned with compact neighbourhood design and transmission of respiratory and viral infection.

Use of Urban Residential Community Parks for Stress Management During the COVID-19 Lockdown Period in China.

During the pandemic lockdown period, residents had to stay at home and increased stress and other mental health problems have been associated with the lockdown period. Since most public parks were closed, community parks within gated residential areas became the most important green space in Chinese cities, and the use of such space might help to reduce the residents' stress levels. This study aimed to investigate to what extent urban residents in China used community parks, engaged in outdoor activity during the lockdown period (23 January-8 April 2020) and if the use of such spaces helped to reduce their stress levels. An online questionnaire survey (n = 1342) was carried out from 23 March to 23 April 2020. Ordinary Least Squares regression was used to analyse the association between community park use, outdoor activity, willingness to engage in outdoor activity, and stress level. All results have been further analysed by two-sampled t-test to explore the difference between young and old age groups. We found that the overall self-reported stress level of the respondents was relatively moderate during the lockdown period. Respondents had generally reduced their use of community parks and engagement in outdoor activity. There was no significant association between stress level and the use of community parks or the engagement in outdoor activities. However, we found that older people showed much lower stress levels, used community parks more frequently, and engaged in more outdoor activities than younger adults. The findings suggest that outdoor activities and spatial characteristics in urban China differ from Western studies and advance the need to integrate the stress management role of community parks with urban green space policy to optimise the use of community parks blended in with everyday life, particularly during the lockdown period.

Circulating Metabolomic Signature in Generalized Pustular Psoriasis Blunts Monocyte Hyperinflammation by Triggering Amino Acid Response.

Generalized pustular psoriasis (GPP), the most grievous variant of psoriasis, is featured by dysregulated systemic inflammatory response. The cellular and molecular basis of GPP is poorly understood. Blood monocytes are key players of host defense and producers of inflammatory cytokines including IL-1ß. How the immune response of monocytes is affected by metabolic internal environment in GPP remains unclear. Here, we performed a metabolomic and functional investigation of GPP serum and monocytes. We demonstrated a significant increase in IL-1ß production from GPP monocytes. In GPP circulation, serum amyloid A (SAA), an acute-phase reactant, was dramatically increased, which induced the release of IL-1ß from monocytes in a NLRP3-dependent manner. Using metabolomic analysis, we showed that GPP serum exhibited an amino acid starvation signature, with glycine, histidine, asparagine, methionine, threonine, lysine, valine, isoleucine, tryptophan, tyrosine, alanine, proline, taurine and cystathionine being markedly downregulated. In functional assay, under amino acid starvation condition, SAA-stimulated mature IL-1ß secretion was suppressed. Mechanistically, at post-transcriptional level, amino acid starvation inhibited the SAA-mediated reactive oxygen species (ROS) formation and NLRP3 inflammasome activation. Moreover, the immune-modulatory effect of amino acid starvation was blocked by silencing general control nonderepressible 2 kinase (GCN2), suggesting the involvement of amino acid response (AAR) pathway. Collectively, our results suggested that decreased serum amino acids in GPP blunted the innate immune response in blood monocytes through AAR pathway, serving as a feedback mechanism preventing excessive inflammation in GPP.

A case of tripterygium glycosides-associated AGEP-like drug reaction combined with bullous pemphigoid.

Acute generalized exanthematous pustulosis (AGEP) is a severe cutaneous drug reaction. Bullous pemphigoid (BP) is an acquired autoimmune disease that might be associated with drugs. There is currently no report of tripterygium glycosides (TG)-induced AGEP-like lesions combined with BP. A 66-year-old male with a 20-year history of psoriasis was prescribed oral TG at 1 mg/kg, three times a day, due to aggravated psoriasis. Seven days later, erythemas, and blisters appeared. After another 3 days, there were two types of blisters: (1) numerous small tension blisters with a lot of neutrophils on the top similar to AGEP combined with BP; (2) a BP. After intravenous injection of methylprednisolone and gamma globulin, the lesions were controlled. This patient developed two types of lesions, including one similar to AGEP combined BP (AGEP-like) and a BP. It is a rare drug reaction induced by TG.

Time Distances to Residential Food Amenities and Daily Walking Duration: A Cross-Sectional Study in Two Low Tier Chinese Cities.

Recent studies indicate the accepted concept of using land-use mix (LUM) to promote physical activity is ineffective and even counteractive in the Chinese context. Before considering LUM as a whole, different amenity types need to be respectively analyzed in relation to various functions and demands. This study aims to examine the specific associations between food-related amenities and perceived daily walking duration (WD) in small Chinese cities. Two interviewer-administered questionnaire surveys (n = 354) were conducted in Yuncheng and Suihua between 2017 and 2018. Logistic regression models were used to examine the associations of WD with seven different categories of food outlet at three levels of walking distance. The associations were further explored by food environment diversity and through two age groups. With the exception of café/tea house, the other six food outlets were positively associated with WD. After adjusting for socioeconomic variables, the associations of grocery store and supermarket weakened. Higher levels of food environment diversity were associated with a longer WD. Among the age groups, food outlets were more associated with older adults' WD. This novel quantitative study suggests that increasing the number and heterogeneity of food-related amenities (including mobile street vendors) within a neighborhood can enhance physical activity in small Chinese cities.

Physical activity and COVID-19: an observational and Mendelian randomisation study.

BACKGROUND: Physical activity (PA) is known to be a protective lifestyle factor against several non-communicable diseases while its impact on infectious diseases, including Coronavirus Disease 2019 (COVID-19) is not as clear. METHODS: We performed univariate and multivariate logistic regression to identify associations between both objectively and subjectively measured PA collected prospectively and COVID-19 related outcomes (overall COVID-19, inpatient COVID-19, outpatient COVID-19, and COVID-19 death) in the UK Biobank cohort. Subsequently, we tested causality by using Mendelian randomisation (MR) analyses. RESULTS: In the multivariable model, the increased acceleration vector magnitude PA (AMPA) is associated with a decreased probability of overall and outpatient COVID-19 with an odds ratio (OR) and 95% confidence interval (CI) of 0.80 (0.69, 0.93) and 0.74 (0.58, 0.95), respectively. No association is found between self-reported moderate-to-vigorous PA (MVPA) and COVID-19 related outcomes. No association is found by MR analyses. CONCLUSIONS: Our results indicate a protective effect of objectively measured PA and COVID-19 outcomes (outpatient COVID-19 and overall COVID-19) independent of age, sex, measures of obesity, and smoking status. Although the MR analyses do not support a causal association, that may be due to limited power. We conclude that policies to encourage and facilitate exercise at a population level during the pandemic should be considered.

Monoamine Oxidase A is a Major Mediator of Mitochondrial Homeostasis and Glycolysis in Gastric Cancer Progression.

OBJECTIVE: Monoamine oxidase A (MAO-A) is a mitochondrial protein involved in tumourigenesis in different types of cancer. However, the biological function of MAO-A in gastric cancer development remains unknown. METHODS: We examined MAO-A expression in gastric cancer tissues and in gastric cancer cell lines by immunohistochemistry and Western blot analyses. CCK8, FACS and bromodeoxyuridine incorporation assays were performed to assess the effects of MAO-A on gastric cancer cell proliferation. The role of MAO-A in mitochondrial function was determined through MitoSOX Red staining, ATP generation and glycolysis assays. RESULTS: In the present study, we observed that MAO-A was significantly upregulated in gastric cancer tissues and in AGS and MGC803 cells. The observed MAO-A inhibition indicated decreased cell cycle progression and proliferation. Silencing MAO-A expression was associated with suppressed migration and invasion of gastric cancer cells in vitro. Moreover, alleviated mitochondrial damage in these cells was demonstrated by decreased levels of mitochondrial reactive oxygen species and increased ATP generation. MAO-A knockdown also regulated the expression of the glycolysis rate-limiting enzymes hexokinase 2 and pyruvate dehydrogenase. Finally, we observed that the glycolysis-mediated effect was weakened in AGS and MGC803 cells when MAO-A was blocked. CONCLUSION: The findings of the present study indicate that MAO-A is responsible for mitochondrial dysfunction and aerobic glycolysis, which in turn leads to the proliferation and metastasis of human gastric tumour cells.

Effects of aerosol pollution on PM2.5-associated bacteria in typical inland and coastal cities of northern China during the winter heating season.

Frequent heavy aerosol pollution occurs during the winter heating season in northern China. Here, we characterized the airborne bacterial community structure and concentration, during typical pollution episodes that occurred during the winter heating season of 2017-2018 in Jinan and Weihai. During this heating season, five and four heavy pollution episodes were observed in Jinan and Weihai, respectively. Compared with December and January, pollution episodes in March were significantly affected by sand dust events. Higher Bacillales were identified in the March samples from Jinan, indicating that sand dust influences bacterial communities. During similar pollution episodes, air pollution in the coastal city of Weihai was lower than the inland city of Jinan. The predominant bacteria included Staphylococcus, Cyanobacteria, Lactobacillus, Deinococcus, Enbydrobacter, Ralstonia, Bacillus, Comamonas, and Sphingomonas. These predominant bacteria are mainly from Proteobacteria, Firmicutes, Cyanobacteria, Actinobacteria, and Bacteroidetes phyla. Bacterial concentration showed significant variation with increased airborne pollutants. The highest concentration appeared during moderate pollution (up to 106 cells/m3), whereas bacterial concentration decreased during heavy and severe pollution (105 cells/m3), which may be related to toxic effects of high pollutant concentrations during heavy or severe pollution. Community structure variation indicated that Cyanobacterial genera were dominant in clean or slight pollution. With increased PM2.5, Staphylococcus increased and became the most abundant bacteria in moderate pollution (up to 40%). During heavy or severe pollution, bacteria that are adaptable to harsh or extreme environments predominate, such as Deinococcus and Bacillus. In the assessment of health risks from air pollution, the bioaerosols risks must consider. Additionally, although most microbial genera are similar between the two cities, there are important differences associated with pollution level. During air pollution regulation in different regions with varied geographical and climatic conditions, bioaerosol pollution difference is an unignored factor.

MiR-5692a promotes proliferation and inhibits apoptosis by targeting HOXD8 in hepatocellular carcinoma.

PURPOSE: Hepatocellular carcinoma (HCC) is a member of the most frequent malignancies in the world and the poor prognosis of HCC is mainly due to lack of early detection and treatment. The purpose of this study was to investigate the role of microRNA (miR)-5692a in the progression of HCC and its underlying mechanism. METHODS: The relative expression of miR-5692a in HCC tissues and cell lines was evaluated by quantitative real-time polymerase chain reaction (qRT-PCR) assay. Cell counting kit-8 assay and colony formation assay were used to determine cell proliferation. Flow cytometric analysis was carried out to determine cell cycle distribution and apoptotic cells. Bioinformatics analysis and dual luciferase reporter assay were employed to predict and verify the potential targets of miR-5692a. Protein expression level of HOXD8 was assessed by western blotting normalized by GAPDH in transfected cells. RESULTS: The relative expression level of miR-5692a was increased in both HCC tissues and cell lines. According to CCK8 assay and colony formation assay, miR-5692a was considered to promote proliferation in HCC. The consequence of flow cytometric analysis showed that overexpressed miR-5692a accelerated cell cycle and inhibited cell apoptosis. We verified that HOXD8 was a target of miR-5692a via online prediction database and dual luciferase reporter assay. The rescue assay we carried out subsequently validated that miR-5692a functioned as an oncogene by regulating HOXD8 in HCC. CONCLUSIONS: This study revealed that miR-5692a had an oncogenic role in HCC by targeting HOXD8 which might bring a novel insight into new therapeutic targets and biomarkers in HCC.

Exploring the Associations of Walking Behavior with Neighborhood Environments by Different Life Stages: A Cross-Sectional Study in a Smaller Chinese City.

Because of high population density and rapid urbanization, different human life stages have distinct growth experiences, leading to different lifestyles and age-spatial separation in the same neighborhood environment, particularly in smaller Chinese cities. The relationship of environment to physical activity may differ from western or larger Chinese cities. This study examined the associations of walking duration to the neighborhood environment and other factors, and explored the nuances of walking behavior for different life stages of adults in a smaller Chinese city, Yuncheng. An interviewer-administered questionnaire survey (n = 173) and face-to-face interviews (n = 19) were conducted in August 2017. Descriptive analysis and multiple linear regression were performed to describe walking motivations, sociodemographic characteristics, neighborhood environments, and their impacts on walking duration across three life stages. The quantitative findings were followed by interviews to validate and interpret them. Our results showed no positive associations of land-use mix (LUM) and residential density on walking duration, and even inverse associations of LUM-recreation and LUM-education for specific life stages were identified. Younger people's walking behavior was more related to consumption amenities distinct from those of older people. Our findings suggest that using walkable neighborhood policies (e.g., high residential density and land-use mix) to increase physical activity might be ineffective in smaller Chinese cities.

Serum Squamous Cell Carcinoma Antigen in Psoriasis: A Potential Quantitative Biomarker for Disease Severity.

BACKGROUND: An objective and quantitative method to evaluate psoriasis severity is important for practice and research in the precision care of psoriasis. OBJECTIVES: We aimed to explore serum biomarkers quantitatively in association with disease severity and treatment response in psoriasis patients, with serum squamous cell carcinoma antigen (SCCA) evaluated in this pilot study. METHODS: 15 psoriasis patients were treated with adalimumab. At different visits before and after treatment, quantitative body surface area (qBSA) was obtained from standardized digital body images of the patients, and the psoriasis area severity index (PASI) was also monitored. SCCA were detected by using microparticle enzyme immunoassay. The serum biomarkers were also tested in healthy volunteers as normal controls. Receiver-operating characteristic (ROC) curve analysis was used to explore the optimal cutoff point of SCCA to differentiate mild and moderate-to-severe psoriasis. RESULTS: The serum SCCA level in the psoriasis group was significantly higher (p < 0.05) than in the normal control group. After treatment, the serum SCCA levels were significantly decreased (p < 0.05). The SCCA level was well correlated with PASI and qBSA. In ROC analysis, when taking PASI = 10 or qBSA = 10% as the threshold, an optimal cutoff point of SCCA was found at 2.0 ng/mL with the highest Youden index. CONCLUSION: Serum SCCA might be a useful quantitative biomarker for psoriasis disease severity.