H2 supplied via ammonia borane stimulates lateral root branching via phytomelatonin signaling.

A reliable and stable hydrogen gas (H2) supply will benefit agricultural laboratory and field trials. Here, we assessed ammonia borane (AB), an efficient hydrogen storage material used in the energy industry, and determined its effect on plant physiology and the corresponding mechanism. Through hydroponics and pot experiments, we discovered that AB increases tomato (Solanum lycopersicum) lateral root (LR) branching and this function depended on the increased endogenous H2 level caused by the sustainable H2 supply. In particular, AB might trigger LR primordia initiation. Transgenic tomato and Arabidopsis (Arabidopsis thaliana) expressing hydrogenase1 (CrHYD1) from Chlamydomonas reinhardtii not only accumulated higher endogenous H2 and phytomelatonin levels but also displayed pronounced LR branching. These endogenous H2 responses achieved by AB or genetic manipulation were sensitive to the pharmacological removal of phytomelatonin, indicating the downstream role of phytomelatonin in endogenous H2 control of LR formation. Consistently, extra H2 supply failed to influence the LR defective phenotypes in phytomelatonin synthetic mutants. Molecular evidence showed that the phytomelatonin-regulated auxin signaling network and cell-cycle regulation were associated with the AB/H2 control of LR branching. Also, AB and melatonin had little effect on LR branching in the presence of auxin synthetic inhibitors. Collectively, our integrated approaches show that supplying H2 via AB increases LR branching via phytomelatonin signaling. This finding might open the way for applying hydrogen storage materials to horticultural production.

Mitochondria transplantation alleviates cardiomyocytes apoptosis through inhibiting AMPKα-mTOR mediated excessive autophagy.

The disruption of mitochondria homeostasis can impair the contractile function of cardiomyocytes, leading to cardiac dysfunction and an increased risk of heart failure. This study introduces a pioneering therapeutic strategy employing mitochondria derived from human umbilical cord mesenchymal stem cells (hu-MSC) (MSC-Mito) for heart failure treatment. Initially, we isolated MSC-Mito, confirming their functionality. Subsequently, we monitored the process of single mitochondria transplantation into recipient cells and observed a time-dependent uptake of mitochondria in vivo. Evidence of human-specific mitochondrial DNA (mtDNA) in murine cardiomyocytes was observed after MSC-Mito transplantation. Employing a doxorubicin (DOX)-induced heart failure model, we demonstrated that MSC-Mito transplantation could safeguard cardiac function and avert cardiomyocyte apoptosis, indicating metabolic compatibility between hu-MSC-derived mitochondria and recipient mitochondria. Finally, through RNA sequencing and validation experiments, we discovered that MSC-Mito transplantation potentially exerted cardioprotection by reinstating ATP production and curtailing AMPKα-mTOR-mediated excessive autophagy.

Membrane P-glycoprotein expression in lymphocytes from adult patients with refractory glomerulonephritis.

OBJECTIVES: To investigate the expression of P-glycoprotein in T-cell subpopulations of lymphocytes from adult patients with refractory glomerulonephritis (GN). MATERIALS AND METHODS: Flow cytometry was used to analyze the T-cell subpopulations of lymphocytes from adult patients with refractory GN and healthy individuals. The CD243 antibody marked the membrane P-glycoprotein of immune cells. RESULTS: The mean ± standard deviation (SD) values of percentages of CD3+, CD3+CD4+, CD3+CD8+ cells in lymphocytes from patients with refractory GN were 63.94 ± 26.98, 55.16 ± 4.78, and 37.79 ± 6.01%, respectively. These values in healthy individuals were 74.88 ± 3.75, 56.60 ± 9.22, and 34.20 ± 5.21%, respectively. No significant differences were observed between the patients with refractory GN and healthy individuals. The mean ± SD values of percentages of CD3+CD4+CD243+ and CD3+CD8+CD243+ cells in the lymphocytes of patients with refractory GN were 0.14 ± 0.11 and 0.11 ± 0.07%, respectively. These values in healthy individuals were 0.05 ± 0.02 and 0.04 ± 0.02%, respectively. The difference in CD3+CD8+CD243+ percentage between patients with refractory GN and healthy individuals was significant (p = 0.0216). CONCLUSION: These findings suggest that P-glycoprotein expression on CD3+CD8+ T cells is a promising marker and a suitable target of drug resistance in patients with refractory GN.

The Impact of Parental Myopia and High Myopia on the Hyperopia Reserve of Preschool Children.

INTRODUCTION: The aim of this study was to explore the association between parental myopia and high myopia with children's refraction and ocular biometry in large-scale Chinese preschool children from the Beijing Hyperopia Reserve Study. SUBJECTS/METHODS: This cross-sectional kindergarten-based study enrolled children aged 3-6 years. Cycloplegic refraction, axial length (AL), and corneal radius (CR) were measured for all children. Parents were asked to complete a questionnaire about refractive status (no myopia, mild myopia <-3 D, moderate myopia ≥-3 D and ≤-6, and high myopia >-6 D). RESULTS: The study enrolled 2,053 children (1,069 boys and 984 girls), with a mean age of 4.26 ± 0.96 years and mean spherical equivalent refraction (SER) of 1.11 ± 0.97 diopter. Of the children, 90.7% had at least one myopic parent, and 511 children (24.9%) had at least one highly myopic parent. SER decreased significantly with increasing severity of parental myopia (p < 0.001). Preschool children's myopia was independently associated with parental myopia (OR, 10.4 and 11.5 for one and two highly myopic parent[s]). Age (OR = 1.1), gender (OR = 1.7; girls as references), near work time (OR = 1.2), and both maternal (OR, 1.4 and 2.0 for moderate and high myopia) and paternal myopia (OR, 1.6 and 1.9 for moderate and high myopia) were independent risk factors for lacking hyperopia reserve. CONCLUSION: Severe parental myopia was associated with a lower SER, longer AL, and higher AL/CR ratio in preschool children. Parental myopia and near work may predispose children to faster elimination of hyperopia reserves before exposure to higher educational stress.

miR-34b-3p-mediated regulation of STC2 and FN1 enhances chemosensitivity and inhibits proliferation in cervical cancer.

Dysregulation of microRNA (miRNA) expression in cancer is a significant factor contributing to the progression of chemoresistance. The objective of this study is to explore the underlying mechanisms by which miR-34b-3p regulates chemoresistance in cervical cancer (CC). Previous findings have demonstrated low expression levels of miR-34b-3p in both CC chemoresistant cells and tissues. In this study, we initially characterize the behavior of SiHa/DDP cells which are CC cells resistant to the chemotherapeutic drug cisplatin (DDP). Subsequently, miR-34b-3p mimics are transfected into SiHa/DDP cells. It is observed that overexpression of miR-34b-3p substantially inhibits the proliferation, migration, and invasion abilities of SiHa/DDP cells and also enhances their sensitivity to DDP-induced cell death. Quantitative RT-PCR and western blot analysis further reveal elevated expression levels of STC2 and FN1 in SiHa/DDP cells, contrary to the expression pattern of miR-34b-3p. Moreover, STC2 and FN1 contribute to DDP resistance, proliferation, migration, invasion, and decreased apoptosis in CC cells. Through dual-luciferase assay analysis, we confirm that STC2 and FN1 are direct targets of miR-34b-3p in CC. Finally, rescue experiments demonstrate that overexpression of either STC2 or FN1 can partially reverse the inhibitory effects of miR-34b-3p overexpression on chemoresistance, proliferation, migration and invasion in CC cells. In conclusion, our findings support the role of miR-34b-3p as a tumor suppressor in CC. This study indicates that targeting the miR-34b-3p/STC2 or FN1 axis has potential therapeutic implications for overcoming chemoresistance in CC patients.

Melatonin alleviates valproic acid-induced neural tube defects by modulating Src/PI3K/ERK signaling and oxidative stress.

Neural tube defects (NTDs) represent a developmental disorder of the nervous system that can lead to significant disability in children and impose substantial social burdens. Valproic acid (VPA), a widely prescribed first-line antiepileptic drug for epilepsy and various neurological conditions, has been associated with a 4-fold increase in the risk of NTDs when used during pregnancy. Consequently, urgent efforts are required to identify innovative prevention and treatment approaches for VPA-induced NTDs. Studies have demonstrated that the disruption in the delicate balance between cell proliferation and apoptosis is a crucial factor contributing to NTDs induced by VPA. Encouragingly, our current data reveal that melatonin (MT) significantly inhibits apoptosis while promoting the restoration of neuroepithelial cell proliferation impaired by VPA. Moreover, further investigations demonstrate that MT substantially reduces the incidence of neural tube malformations resulted from VPA exposure, primarily by suppressing apoptosis through the modulation of intracellular reactive oxygen species levels. In addition, the Src/PI3K/ERK signaling pathway appears to play a pivotal role in VPA-induced NTDs, with significant inhibition observed in the affected samples. Notably, MT treatment successfully reinstates Src/PI3K/ERK signaling, thereby offering a potential underlying mechanism for the protective effects of MT against VPA-induced NTDs. In summary, our current study substantiates the considerable protective potential of MT in mitigating VPA-triggered NTDs, thereby offering valuable strategies for the clinical management of VPA-related birth defects.

First Detection of blaNDM-1-Haboring IncHI2 Plasmid in Escherichia coli Strain Isolated from Goose in China.

Carbapenem-resistant Enterobacteriaceae infections are among the most serious threats to human and animal health worldwide. Of the 1013 strains of Escherichia coli isolated and identified in 14 regions of China from 2007 to 2018, seven strains were resistant to meropenem and all were positive for blaNDM. The seven New Delhi metallo-ß-lactamase (NDM)-positive strains belonged to five different sequence types, indicating that most of the NDM-positive strains were nonclonal. An IncHI2 plasmid carrying the blaNDM-1 element was identified in the C1147 strain from a goose source and reported for the first time, showing a specific structure. Conjugation experiments revealed that the IncHI2 plasmid was conjugatable, and the horizontal propagation of the plasmid led to the rapid propagation of NDM in the same and different strains. This study revealed that waterfowl, as a potential transmission factor for carbapenem-resistant blaNDM-1, poses a threat to human health.

Cold-adaptive mechanism of psychrophilic bacteria in food and its application.

Psychrophilic bacteria are a type of microorganisms that normally grow in low-temperature environments. They are usually found in extremely cold environments. However, as people's demand for low-temperature storage of food becomes higher, psychrophilic bacteria have also begun to appear in cold storage and refrigerators, which has become a food safety hazard. In this paper, the optimal cooling strategies of psychrophilic bacteria are reviewed from the aspects of the cell membrane, psychrophilic enzymes, antifreeze proteins, cold shock proteins, gene regulation, metabolic levels and antifreeze agents, and the principle of psychrophilic mechanism is briefly described. The application of thermophilic bacteria and its products adapted to cold environments in food fields are analyzed. The purpose of this paper is to provide ideas for future research on psychrophilic bacteria based on the mechanism and application of psychrophilic bacteria.

The heat-labile toxin B subunit of E. coli fused with VP6 from GCRV (Grass carp reovirus) was expressed and folded into an active protein in rice calli.

Grass carp reovirus (GCRV) is one of the most serious pathogens threatening grass carp (Ctenopharyngon idellus) production in China. VP6 could be suitable for developing vaccine for the control of GCRV. Transgenic plants are an attractive bioreactor for their safety and ability to make economical vaccines. The B subunit of Escherichia coli heat-labile enterotoxin (LTB) fused to VP6 (LTB-VP6) was transformed into rice calli by Agrobacterium tumefaciens-mediated gene transformation. Transgenic rice calli was confirmed by PCR analysis separately. The copy numbers of LTB-VP6 inserted into the rice genome are between 1 and 2. The expression level of LTB-VP6 in rice calli was 0.0005-0.0019%, an average of 0.0011% of the TSP(total soluble proteins). LTB-VP6 was folded and assembled into a pentameric form of approximately 305 kDa capable of binding monosialoganglioside (GM1). The suitable concentration of LTB-VP6 in TSP was 0.4 µg/µl. LTB-VP6 is stable and highly active at room temperature. LTB-VP6 binding to GM1 is affected with different affinities under different temperatures. LTB-VP6 had a strong binding affinity at 25 °C and pH 8.4. Our results showed that LTB-VP6 is capable of forming an active pentameric form protein. It provides an ideal alternative to plant-based vaccines against GCRV in aquaculture.

Biodistribution and Non-linear Gene Expression of mRNA LNPs Affected by Delivery Route and Particle Size.

PURPOSE: Lipid nanoparticles (LNPs) are widely utilized as means to deliver mRNA molecules. However, metric connections between biodistribution and pharmacokinetics (PK) of the nanoparticle carrier and transgene expression dynamics remain largely unknown. METHODS: LNPs containing mRNAs encoding the firefly luciferase gene were prepared with varying sizes. Biodistributions of injected LNPs in mice were measured by fluorescence bioimaging or liquid chromatography with tandem mass spectrometry. In addition, luciferase expression levels were determined by bioluminescence imaging and enzyme activity assays. RESULTS: Some intramuscularly injected LNPs were found circulating in the system, resulting in accumulation in the liver and spleen, especially when the LNP sizes were relatively small. Bigger LNPs were more likely to remain at the injection site. Transgene expression in the liver was found most prominent compared with other organs and tissues. CONCLUSIONS: Biomolecules such as mRNAs encapsulated in locally injected LNPs can reach other organs and tissues via systemic circulation. Gene expression levels are affected by the LNP biodistribution and pharmacokinetics (PK), which are further influenced by the particle size and injection route. As transfection efficiency varies in different organs, the LNP exposure and mRNA expression are not linearly correlated.

Early identification and severity prediction of acute respiratory infection (ESAR): a study protocol for a randomized controlled trial.

BACKGROUND: The outbreak of SARS-CoV-2 at the end of 2019 sounded the alarm for early inspection on acute respiratory infection (ARI). However, diagnosis pathway of ARI has still not reached a consensus and its impact on prognosis needs to be further explored. METHODS: ESAR is a multicenter, open-label, randomized controlled, non-inferiority clinical trial on evaluating the diagnosis performance and its impact on prognosis of ARI between mNGS and multiplex PCR. Enrolled patients will be divided into two groups with a ratio of 1:1. Group I will be directly tested by mNGS. Group II will firstly receive multiplex PCR, then mNGS in patients with severe infection if multiplex PCR is negative or inconsistent with clinical manifestations. All patients will be followed up every 7 days for 28 days. The primary endpoint is time to initiate targeted treatment. Secondary endpoints include incidence of significant events (oxygen inhalation, mechanical ventilation, etc.), clinical remission rate, and hospitalization length. A total of 440 participants will be enrolled in both groups. DISCUSSION: ESAR compares the efficacy of different diagnostic strategies and their impact on treatment outcomes in ARI, which is of great significance to make precise diagnosis, balance clinical resources and demands, and ultimately optimize clinical diagnosis pathways and treatment strategies. Trial registration Clinicaltrial.gov, NCT04955756, Registered on July 9th 2021.

Analyzing the whole-transcriptome profiles of ncRNAs and predicting the competing endogenous RNA networks in cervical cancer cell lines with cisplatin resistance.

BACKGROUND: Cervical cancer (CC) is one of the most common malignant tumors in women. In order to identify the functional roles and the interaction between mRNA and non-coding RNA (ncRNA, including lncRNA, circRNA and miRNA) in CC cisplatin (DDP) resistance, the transcription profile analysis was performed and a RNA regulatory model of CC DDP resistance was proposed. METHODS: In this study, whole-transcriptome sequencing analysis was conducted to study the ncRNA and mRNA profiles of parental SiHa cells and DDP resistant SiHa/DDP cells. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were performed for pathway analysis based on the selected genes with significant differences in expression. Subsequently, ceRNA network analyses were conducted using the drug resistance-related genes and signal-transduction pathways by Cytoscape software. Furthermore, a ceRNA regulatory pathway, namely lncRNA-AC010198.2/hsa-miR-34b-3p/STC2, was selected by RT-qPCR validation and literature searching. Further validation was done by both dual-luciferase reporter gene assays and RNA pull-down assays. Besides that, the changes in gene expression and biological function were further studied by performing si-AC010198.2 transfection and DDP resistance analyses in the SiHa and SiHa/DDP cells, respectively. RESULTS: Using bioinformatics and dual-luciferase reporter gene analyses, we found that AC010198.2/miR-34b-3p/STC2 may be a key pathway for DDP resistance in CC cells. Significant differences in both downstream gene expression and the biological function assays including colony formation, migration efficiency and cell apoptosis were identified in AC010198.2 knockdown cells. CONCLUSIONS: Our study will not only provide new markers and potential mechanism models for CC DDP resistance, but also discover novel targets for attenuating it.

The association of dietary flavonoids, magnesium and their interactions with the metabolic syndrome in Chinese adults: a prospective cohort study.

The aim was to systematically analyse the association of the specific flavonoids, Mg and their interactions from different food sources with the metabolic syndrome (MetS) and its components in a cohort study. A total of 6417 participants aged 20 to 74 years from the Harbin Cohort Study on Diet, Nutrition and Chronic Non-communicable Diseases were included. Multivariate logistic regression analyses, forest plot and restricted cubic spline were performed in the study. After a 5·3-year follow-up, 1283 incident cases of the MetS were reported. Those with a higher total flavonoid intake had a lower risk of the MetS (fourth v. first quartile, relative risk (RR) 0·58; 95 % CI 0·37, 0·93; P = 0·024) and central obesity (RR 0·56; 95 % CI 0·33, 0·95; P = 0·032). Further analysis showed that the specific flavonoids quercetin, kaempferol, isorhamnetin, luteolin, and flavonoids from fruits, potatoes and legumes had the similar associations with risk of the MetS and central obesity (P < 0·05 for all). A higher intake of total flavonoids, quercetin and luteolin combined with a high level of Mg was more strongly associated with a lower risk of the MetS (RR 0·60; 95 % CI 0·45, 0·81 for total; RR 0·61; 95 % CI 0·45, 0·82 for quercetin; RR 0·52; 95 % CI 0·38, 0·71 for luteolin; all Pfor interaction < 0·01). Dose-response effects showed an L-shaped curve between the total intake of five flavonoids and the risk of the MetS. A higher flavonoid intake is associated with a lower risk of the MetS and central obesity; their combination with Mg helps to strengthen their negative association with the MetS.

Implantable collamer lens versus small incision lenticule extraction for high myopia correction: A systematic review and meta-analysis.

PURPOSE: To compare the efficacy, safety, predictability and visual quality between implantable collamer lens (ICL) implantation and small incision lenticule extraction (SMILE) for high myopia correction in adults. METHODS: A systematic review and meta-analysis was conducted. A comprehensive literature search was done based on databases including PubMed, Science Direct, Embase, and the Cochrane Central Register of Controlled Trials. The efficacy index, safety index, changes in Snellen lines of corrected distance visual acuity (CDVA), predictability (difference between post-operative and attempted spherical equivalent error, SER), incidence of halos, and change in higher-order aberrations (HOAs) were compared. Mean difference (MD) and 95% confidence interval (CI) was used to estimate continuous outcomes, risk ratio (RR) and 95%CI was used to estimate categorical outcomes. RESULTS: Five observational studies involving 555 eyes were included in this review. Studies' sample sizes (eyes) ranged from 76 to 197. Subjects' refraction ranged from -6 diopter (D) to -12D. Study duration of most researches were 6 months or 12 months. Compared to SMILE, ICL implantation showed better efficacy index (MD=0.09, 95%CI:0.01 to 0.16) and better safety index (MD=0.08, 95%CI: 0.00 to 0.16). Compared with SMILE, more ICL-treated eyes gained one or more Snellen lines of CDVA (RR=1.54, 95%CI:1.28 to 1.86), more gained two or more lines (RR=2.09, 95%CI:1.40 to 3.13), less lost one or more lines (RR=0.17, 95%CI:0.05 to 0.63). There was no difference in predictability between two treatments, RRs of predictability of within ±0.5D and ±1D were 1.13 (95%CI: 0.94 to 1.36) and 1.00 (95%CI: 0.98 to 1.02). Compared with SMILE, ICL implantation came with a higher risk of halos [RR=1.79, 95%CI: 1.48 to 2.16] and less increase in total HOAs (MD=-0.23, 95%CI: -0.42 to -0.03). CONCLUSION: Compared with SMILE, ICL implantation showed a higher risk of halos, but equal performance on SER control, and better performance on efficacy index, safety index, CDVA improvement and HOAs control. Overall, ICL implantation might be a better choice for high myopia correction in adults.

Advisability of primary intraocular lens implantation for infants under 2: A systematic review and meta-analysis.

PURPOSES: The present meta-analysis compared the postoperative visual performance of primary intraocular lens (IOL) implantation and primary aphakia in cataract infants. METHODS: PubMed, Embase, Science Direct and Cochrane Library were searched, and postoperative visual acuity (VA) and complications were extracted and pooled. RESULTS: Three randomised controlled trails (RCTs) and five retrospective studies were included. The postoperative VA of children younger than 4.5 years in primary IOL group was better than that in primary aphakia group [MD = -0.14, 95% CI: (-0.23, -0.06), P = .90]. The subgroup analysis based on RCTs and on unilateral cataract surgery revealed the same result. There was no significant difference in the incidence of glaucoma, strabismus, retinal detachment and nystagmus between primary IOL group and primary aphakia group [OR = 1.02, 95% CI: (0.62, 1.68), P = .48 for glaucoma; OR = 0.76, 95% CI: (0.30, 1.90), P = .05 for strabismus; OR = 0.49, 95% CI: (0.07, 3.30), P = .34 for retinal detachment; OR = 1.26, 95% CI: (0.68, 2.36), P = .92 for nystagmus]. The proportion of patients requiring postoperative visual axis opacification (VAO) clearing was higher in primary IOL group than that in primary aphakia group [OR = 9.22, 95% CI: (4.74, 17.96), P = .16]. CONCLUSION: For infants under 2 years of age, primary IOL implantation would provide more visual benefits compared with primary aphakia did, though the benefits would taper off with the age reaching 4.5 years. Moreover, the current study revealed a higher VAO incidence r in primary IOL implantation group.

1-Nitropyrene exposure impairs embryo implantation through disrupting endometrial receptivity genes expression and producing excessive ROS.

Haze problem is an important factor threatening human health. PM2.5 is the main culprit haze. 1-Nitropyrene (1-NP) is the main nitrated polycyclic aromatic hydrocarbon, the toxic component of PM2.5 particles. The effects of 1-NP on various organs and reproductive health have been extensively and deeply studied, but the effects of 1-NP on embryo implantation and endometrial receptivity remain to be determined. The purpose of this study was to investigate the adverse effects of 1-NP on mouse embryo implantation and human endometrial receptivity. In early pregnancy, CD1 mice were given 2 mg/kg 1-NP by oral gavage, which resulted in a decreased embryo implantation number on day 5, inhibited leukemic inhibitory factor (LIF)/STAT3 pathway, decreased expression of estrogen receptor and progesterone receptor, and disrupted regulation of uterine cell proliferation. In addition, in a human in vitro implantation model, 1-NP was found to significantly inhibit the adhesion rate between trophoblast spheroids and endometrial epithelial cells, possibly by inhibiting the expression of receptivity molecules in Ishikawa cells. Promoting reactive oxygen species (ROS) production may be an additional mechanism by which it inhibits trophoblast spheroid adhesion. In this study, we used an in vivo mouse pregnancy model and an in vitro human embryo implantation model to demonstrate that 1-NP can impair endometrial receptivity and compromise embryo implantation.

RNA m6 A methylation regulates uveal melanoma cell proliferation, migration, and invasion by targeting c-Met.

N6 -methyladenosine (m6 A) is a novel epitranscriptomic marker that contributes to regulating diverse biological processes through controlling messenger RNA metabolism. However, it is unknown if m6 A RNA methylation affects uveal melanoma (UM) development. To address this question, we probed its function and molecular mechanism in UM. Initially, we demonstrated that global RNA m6 A methylation levels were dramatically elevated in both UM cell lines and clinical specimens. Meanwhile, we found that METTL3, a main m6 A regulatory enzyme, was significantly increased in UM cells and specimens. Subsequently, cycloleucine (Cyc) or METTL3 targeted small interfering RNA was used to block m6 A methylation in UM cells. We found that Cyc or silencing METTL3 significantly suppressed UM cell proliferation and colony formation through cell cycle G1 arrest, as well as migration and invasion by functional analysis. On the other hand, overexpression of METTL3 had the opposite effects. Furthermore, bioinformatics and methylated RNA immunoprecipitation-quantitative polymerase chain reaction identified c-Met as a direct target of m6 A methylation in UM cells. In addition, western blot analysis showed that Cyc or knockdown of METTL3 downregulated c-Met, p-Akt, and cell cycle-related protein levels in UM cells. Taken together, our results demonstrate that METTL3-mediated m6 A RNA methylation modulates UM cell proliferation, migration, and invasion by targeting c-Met. Such a modification acts as a critical oncogenic regulator in UM development.

Progranulin inhibits LPS-induced macrophage M1 polarization via NF-кB and MAPK pathways.

BACKGROUND: Macrophage M1 polarization plays a pivotal role in inflammatory diseases. Progranulin (PGRN) has potential anti-inflammation action, however, the effect of PGRN on macrophage M1 polarization has been poorly studied. Our study aimed to investigate the effect of PGRN on lipopolysaccharide (LPS)-induced macrophage M1 polarization and clarify the underlying mechanisms. METHODS: RAW264.7 cells were polarized to M1 macrophage by LPS with or without recombinant PGRN (rPGRN) and tumor necrosis factor alpha antibody (anti-TNF-α). A cell counting kit-8 assay (CCK-8), flow cytometry, Quantitative Real-Time PCR assay (q-PCR), Western blot assay and enzyme-linked immunosorbent assay (ELISA) were used to determine the effect of different treatments on cell proliferation, expression of surface phenotype marker and expressions and secretion of inflammatory cytokines. The activation of NF-κB/mitogen-activated protein kinase (MAPK) pathways and the nuclear translocation of NF-κB p65 were detected by Western blot and immunofluorescence respectively. THP-1 and primary bone marrow-derived monocytes (BMDMs) were also used to demonstrate effect of PGRN on expressions and secretion of inflammatory cytokines induced by LPS. RESULTS: In RAW264.7 cells, rPGRN at concentrations below 80 ng/ml significantly promoted cell proliferation in dose dependent fashion. rPGRN significantly inhibited LPS-induced change of phenotype (CD86/CD206 ratio) and function (tumor necrosis factor (TNF-α) and inducible nitric oxide synthase (iNOS) expressions). LPS-stimulated secretion of TNF-α and activated phosphorylation of IKKα/ß, IкBα, p65, JNK and p38 and the nucleus translocation of NF-кB p65 were also significantly downregulated by rPGRN. In addition, recombinant TNF-α (rTNF-α) significantly boosted TNF-α and iNOS expression vs the control group. Moreover, anti-TNF-α significantly inhibited LPS-induced TNF-α and iNOS expression. In THP-1 and BMDM cells, reversing effect of rPGRN on LPS-enhanced expressions of TNF-α and iNOS and secretion of TNF-α was further demonstrated. CONCLUSIONS: PGRN down-regulates LPS-induced macrophage M1 polarization in phenotype and function via NF-κB/MAPK signaling pathways.

The effectiveness and safety of posterior scleral reinforcement with vitrectomy for myopic foveoschisis treatment: a systematic review and meta-analysis.

PURPOSE: To investigate the effectiveness and safety of posterior scleral reinforcement (PSR) combined with vitrectomy for myopic foveoschisis (MF) treatment. METHODS: We conducted a systematic review and meta-analysis. We evaluated the improvement of best-corrected visual acuity (BCVA) in logMAR unit, the percentage of patients with improved or stabled BCVA, benefit on axial length (AL), the retinal reattachment rate, the macular hole (MH) closure rate, as well as the complication rate. RESULTS: Fourteen studies (311 eyes) were included. Overall, patients' BCVA improved - 0.46 (95% confidence interval [CI] - 0.52, - 0.40) logMAR unit, with 80% (95%CI 74%, 85%) benefiting from BCVA improvement and 6% (95%CI 3%, 10%) suffering from BCVA loss. Patients' AL was shortened by - 1.74 (95%CI - 2.92, - 0.57) mm, and for patients whose AL was ≥ 30 mm, the average benefit reached - 3.68 (95%CI - 4.59, - 2.77) mm. Ninety-three percent (95%CI 89%, 96%) of the patients achieved retinal reattachment, and 65% (95%CI 47%, 80%) of the MH was closed. Patients' central foveal thickness decreased; the MD was - 187.32 (95%CI - 206.25, - 168.40) mm. The pooled complication rate was 9% (95%CI 8%, 19%), with extrusion, choroidal atrophy, and choroidal neovascularization being the most common complications. Subgroup analysis indicated no statistical difference in BCVA improvement, AL change, retinal reattachment rate, and complication rate between patients with or without MH. Subgroup analysis indicated no statistical difference in the above four outcomes between the primary and the recurrent patients either. There was no statistical difference in the above four outcomes no matter ILM peeling was combined or not. CONCLUSION: PSR combined with vitrectomy helps improve 80% MF patients' BCVA; the average benefit on BCVA is - 0.46 logMAR unit. The average change in AL is - 1.74 mm; patients with AL ≥ 30 mm benefit much more than the patients with AL < 30 mm. The retinal reattachment rate is up to 93%; the MH closure rate is 65%. About 9% patients will suffer from extrusion, choroidal atrophy, choroidal neovascularization, and other complications. The outcomes were not influenced by presence of MH, disease recurrence, or ILM peeling.

Association of serum 25-Hydroxyvitamin D with Vitamin D intervention and outdoor activity among children in North China: an observational study.

BACKGROUND: Living at high latitudes is one of the risk factors for vitamin D deficiency in children. However, evidence on vitamin D improvement for this pediatric population to date is limited. This study aims at evaluating the association of different vitamin D intervention methods and outdoor activity on the vitamin D status of children in North China. METHODS: In this observational study, a total of 55,925 children aged 1 month to 18 years old were recruited from pediatric outpatient departments from July 2016 to June 2017. Data on demographics, anthropometric measurements, vitamin D intervention (either prescribed by physicians or given by parents) and outdoor activity were recorded. The serum levels of 25-hydroxycholecalciferol (25(OH)D) were determined by high performance liquid chromatography tandem-mass spectrometry. Logistic regression analysis was performed to assess the association of vitamin D intervention or outdoor activity with blood vitamin D status, adjusted for age, gender, BMI for age, and seasons. RESULTS: The overall rate of hypovitaminosis D was 65.60%. Of the children's outdoor activity, 35.63, 31.95, and 32.42% were below 30 min/d, 30-60 min/d and over 60 min/d, respectively. Furthermore, the proportion of therapeutic intervention, supplementation intervention and no vitamin D intervention among the children was 16.48, 32.87, and 50.65%, respectively. After adjusted for confounding factors, vitamin D intervention was associated with a lower risk of hypovitaminosis D, with OR (95% CI) of 0.191 (0.180, 0.202) in children with therapeutic doses and 0.423 (0.404, 0.443) in those with supplementation doses, compared with children without vitamin D intervention. In addition, longer outdoor time was associated with a lower risk of hypovitaminosis D [0.479 (0.456, 0.504) for 60 min/d, 0.737 (0.701, 0.776) for 30-60 min/d], independent of vitamin D intervention. CONCLUSIONS: High prevalence of vitamin D deficiency was found in children living at high latitudes. Vitamin D intervention and outdoor activity are all negatively associated with children's vitamin D deficiency. Routine vitamin D intervention combined with increased outdoor time might be an effective approach to prevent hypovitaminosis D among children, especially those at school, living at high latitudes.