Reciprocal conversion between annual and polycarpic perennial flowering behavior in the Brassicaceae.

The development of perennial crops holds great promise for sustainable agriculture and food security. However, the evolution of the transition between perenniality and annuality is poorly understood. Here, using two Brassicaceae species, Crucihimalaya himalaica and Erysimum nevadense, as polycarpic perennial models, we reveal that the transition from polycarpic perennial to biennial and annual flowering behavior is a continuum determined by the dosage of three closely related MADS-box genes. Diversification of the expression patterns, functional strengths, and combinations of these genes endows species with the potential to adopt various life-history strategies. Remarkably, we find that a single gene among these three is sufficient to convert winter-annual or annual Brassicaceae plants into polycarpic perennial flowering plants. Our work delineates a genetic basis for the evolution of diverse life-history strategies in plants and lays the groundwork for the generation of diverse perennial Brassicaceae crops in the future.

AGK2 pre-treatment protects against thioacetamide-induced acute liver failure via regulating the MFN2-PERK axis and ferroptosis signaling pathway.

BACKGROUND: Acute liver failure (ALF) is an unpredictable and life-threatening critical illness. The pathological characteristic of ALF is massive necrosis of hepatocytes and lots of inflammatory cells infiltration which may lead to multiple organ failure. METHODS: Animals were divided into 3 groups, normal, thioacetamide (TAA, ALF model) and TAA + AGK2. Cultured L02 cells were divided into 5 groups, normal, TAA, TAA + mitofusin 2 (MFN2)-siRNA, TAA + AGK2, and TAA + AGK2 + MFN2-siRNA groups. The liver histology was evaluated with hematoxylin and eosin staining, inositol-requiring enzyme 1 (IRE1), activating transcription factor 6ß (ATF6ß), protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK) and phosphorylated-PERK (p-PERK). C/EBP homologous protein (CHOP), reactive oxygen species (ROS), MFN2 and glutathione peroxidase 4 (GPX4) were measured with Western blotting, and cell viability and liver chemistry were also measured. Mitochondria-associated endoplasmic reticulum membranes (MAMs) were measured by immunofluorescence. RESULTS: The liver tissue in the ALF group had massive inflammatory cell infiltration and hepatocytes necrosis, which were reduced by AGK2 pre-treatment. In comparison to the normal group, apoptosis rate and levels of IRE1, ATF6ß, p-PERK, CHOP, ROS and Fe2+ in the TAA-induced ALF model group were significantly increased, which were decreased by AGK2 pre-treatment. The levels of MFN2 and GPX4 were decreased in TAA-induced mice compared with the normal group, which were enhanced by AGK2 pre-treatment. Compared with the TAA-induced L02 cell, apoptosis rate and levels of IRE1, ATF6ß, p-PERK, CHOP, ROS and Fe2+ were further increased and levels of MFN2 and GPX4 were decreased in the MFN2-siRNA group. AGK2 pre-treatment decreased the apoptosis rate and levels of IRE1, ATF6ß, p-PERK, CHOP, ROS and Fe2+ and enhanced the protein expression of MFN2 and GPX4 in MFN2-siRNA treated L02 cell. Immunofluorescence observation showed that level of MAMs was promoted in the AGK2 pre-treatment group when compared with the TAA-induced group in both mice and L02 cells. CONCLUSIONS: The data suggested that AGK2 pre-treatment had hepatoprotective role in TAA-induced ALF via upregulating the expression of MFN2 and then inhibiting PERK and ferroptosis pathway in ALF.

Novel biallelic mutations in TMEM126B cause splicing defects and lead to Leigh-like syndrome with severe complex I deficiency.

Leigh syndrome (LS)/Leigh-like syndrome (LLS) is one of the most common mitochondrial disease subtypes, caused by mutations in either the nuclear or mitochondrial genomes. Here, we identified a novel intronic mutation (c.82-2 A > G) and a novel exonic insertion mutation (c.290dupT) in TMEM126B from a Chinese patient with clinical manifestations of LLS. In silico predictions, minigene splicing assays and patients' RNA analyses determined that the c.82-2 A > G mutation resulted in complete exon 2 skipping, and the c.290dupT mutation provoked partial and complete exon 3 skipping, leading to translational frameshifts and premature termination. Functional analysis revealed the impaired mitochondrial function in patient-derived lymphocytes due to severe complex I content and assembly defect. Altogether, this is the first report of LLS in a patient carrying mutations in TMEM126B. Our data uncovers the functional effect and the molecular mechanism of the pathogenic variants c.82-2 A > G and c.290dupT, which expands the gene mutation spectrum of LLS and clinical spectrum caused by TMEM126B mutations, and thus help to clinical diagnosis of TMEM126B mutation-related mitochondrial diseases.

Peripheral Blood-Derived CircVPS35L as a Potential Diagnostic Biomarker for Non-Small Cell Lung Cancer.

INTRODUCTION: Circular RNAs (circRNAs) are dysregulated in cancers and are stably expressed in body fluids such as blood. We therefore identified and evaluated the clinical value of a newly found circRNA VPS35L (circVPS35L) as a biomarker for the diagnosis of non-small cell lung cancer (NSCLC). METHODS: Reverse-transcription quantitative PCR (RT-qPCR) was used to determine the expression levels of circVPS35L in tissues, whole blood, and cell lines. The actinomycin D assay and RNase R treatment were utilized to determine the stability of circVPS35L. Receiver operating characteristic (ROC) curve analysis was conducted to predict the diagnostic value of blood-derived circVPS35L in NSCLC. RESULTS: CircVPS35L was found to be downregulated in NSCLC tissues and cell lines. Interestingly, circVPS35L expression was significantly correlated with tumor size (p = 0.0269), histology type (p < 0.0001), and TNM stage (p = 0.0437). Importantly, circVPS35L was poorly expressed in peripheral blood of NSCLC patients when compared with healthy controls and patients with benign lung disease. ROC analysis revealed a higher diagnostic value of circVPS35L than the three conventional tumor markers (CYFR21-1, NSE, and CEA) in patients with NSCLC. Moreover, circVPS35L was highly stable in peripheral blood when exposed to undesirable conditions. CONCLUSION: These findings demonstrate that circVPS35L has great potential as a novel biomarker for the diagnosis of NSCLC and can be used to distinguish NSCLC from benign lung disease.

Association between atmospheric pollutant levels and oxidative stress in pregnant women and newborns in Urumqi.

BACKGROUND: Frequent heavy air pollution occurred during the winter heating season of northern China. Particulate air pollution is a serious concern in Urumqi during heating season. Exposure to air pollution is known to increase adverse health outcomes, particularly oxidative damage. This study aimed to evaluate the impact of air pollution on oxidative damage around pregnant women and newborns in Urumqi. METHODS: This prospective observational study enrolled pregnant women in the Fifth Affiliated Hospital of Xinjiang Medical University between January 2019 and October 2019. Pregnant women and newborns were allocated into a heating season group (January - end of April 2019, October 2019) or non-heating season group (June 2019 - end of September) according to the specific delivery time. Venous blood, urine from the women and cord blood from their newborns were collected to measure the levels of PAHs and 8-deoxyguanosine (8-OHdG), a measure of oxidative stress. RESULTS: A total of 200 pregnant women and newborns were enrolled, with 100 pregnant women and newborns in the heating season group. Compared to the non-heating season group, the total contents of 8-OHdG in maternal urine, PAHs and 8-OHdG in maternal plasma and neonatal cord blood were higher in the heating season group (all P < 0.001). The average values for AQI, PM2.5, PM10, SO2, NO2, and CO were higher in the heating season group (all P < 0.001). Maternal and neonatal PAHs were correlated with 8-OHdG measurements in maternal urine (r = 0.288, P < 0.001 and r = 0.336, P < 0.001) and neonatal umbilical cord blood (r = 0.296, P < 0.001 and r = 0.252, P < 0.001). There was also a positive relationship between PAHs, 8-OHdG levels in pregnant women and their newborns and proximate air pollutant concentrations (all P < 0.05). Based on the results of multiple linear regression analysis, it was found that air pollutants(PM10, 03) had a great influence on the level of 8-OHdG in neonatal cord blood, and the contribution rate was high(R2 = 0.320). Based on the epidemiological questionnaire, a multiple linear regression model was established(R2 = 0.496). We found that 8-OHdG levels in neonatal umbilical cord blood were mainly affected by two aspects: (1) Biological samples collected during heating had higher levels of 8-OHdG in neonatal umbilical cord blood. (2) Study may suggest that in neonates, males are more sensitive to oxidative damage. CONCLUSION: Particulate air pollution may increase PAHs exposure and oxidative DNA damage in pregnant women and newborns.

Isolation of Bacillus siamensis B-612, a Strain That Is Resistant to Rice Blast Disease and an Investigation of the Mechanisms Responsible for Suppressing Rice Blast Fungus.

Rice yield can be significantly impacted by rice blast disease. In this investigation, an endophytic strain of Bacillus siamensis that exhibited a potent inhibitory effect on the growth of rice blast was isolated from healthy cauliflower leaves. 16S rDNA gene sequence analysis showed that it belongs to the genus Bacillus siamensis. Using the rice OsActin gene as an internal control, we analyzed the expression levels of genes related to the defense response of rice. Analysis showed that the expression levels of genes related to the defense response in rice were significantly upregulated 48 h after treatment. In addition, peroxidase (POD) activity gradually increased after treatment with B-612 fermentation solution and peaked 48 h after inoculation. These findings clearly demonstrated that the 1-butanol crude extract of B-612 retarded and inhibited conidial germination as well as the development of appressorium. The results of field experiments showed that treatment with B-612 fermentation solution and B-612 bacterial solution significantly reduced the severity of the disease before the seedling stage of Lijiangxintuan (LTH) was infected with rice blast. Future studies will focus on exploring whether Bacillus siamensis B-612 produces new lipopeptides and will apply proteomic and transcriptomic approaches to investigate the signaling pathways involved in its antimicrobial effects.

NOD2-mediated HDAC6/NF-κb signalling pathway regulates ferroptosis induced by extracellular histone H3 in acute liver failure.

Acute liver failure (ALF) is life-threatening and often associated with high mortality rates. The aim of the present study was to investigate whether extracellular histone H3 could induce ferroptosis in hepatic macrophages in ALF and explore its potential mechanism. RAW264.7 macrophages and C57BL/6 mice were used in this study. LPS, D-galactosamine (D-Gal), histone H3, histone H3 antibody, NOD2 agonist Muramyl Dipeptide (MDP) and HDAC6-siRNA were administered in this study. The key molecules of ferroptosis, NOD2, HDAC6 and the NF-κb pathway, were detected. In vitro, histone H3 was released into the extracellular environment from cell nucleus after LPS exposure. In addition, histone H3 could induce ferroptosis in RAW264.7 macrophages with increased level of Fe2+ and ROS and decreased levels of GPX4 and GSH. MDP further aggravated ferroptosis in RAW264.7 macrophages stimulated by histone H3, which was accompanied by elevated NOD2, HDAC6, p-P65 and IκBα. HDAC6-siRNA ameliorated ferroptosis in RAW264.7 macrophages induced by histone H3, which was accompanied by decreased levels of HDAC6, p-P65 and IκBα. However, HDAC6-siRNA did not alter NOD2 levels in RAW264.7 macrophages administered histone H3. In vivo, the levels of NOD2, HDAC6 the NF-κb pathway and ferroptosis were increased in ALF mice, which were downregulated by histone H3 antibody and upregulated by histone H3. Extracellular histone H3 could induce ferroptosis in hepatic macrophages in ALF by regulating theNOD2-mediated HDAC6/NF-κb signalling pathway.

Changes of flavin-containing monooxygenases and trimethylamine-N-oxide may be involved in the promotion of non-alcoholic fatty liver disease by intestinal microbiota metabolite trimethylamine.

Evidence shows that trimethylamine (TMA)/trimethylamine-N-oxide (TMAO) is closely related to non-alcoholic fatty liver disease (NAFLD). The conversion of TMA to TMAO is mainly catalyzed by flavin-containing monooxygenases 3 (FMO3) and FMO1. In this study, we explored the role of TMA in the process of NAFLD. The human NAFLD liver puncture data set GSE89632 and rat TMAO gene chip GSE135856 was downloaded for gene differential expression analysis. Besides, oleic acid (OA) combined with palmitate were used to establish high-fat cell model. TMA, TMAO and FMO1-siRNA were used to stimulate L02 cells. Contents of free fatty acid (FFA), triglyceride (TG), TMAO, FMO1 and unfolded protein response (UPR) related proteins GRP78, XBP1, Derlin-1 were detected. Our results showed that FMO1 and PEG10 were important in the progression of NAFLD. Immunohistochemistry showed that FMO1 in NAFLD liver was increased. In addition, the contents of FFA, TG, FMO1 expression, and TMAO were significantly increased after OA + palmitate and TMA stimulation. However, after silencing FMO1 with siRNA, the expressions of these molecules were decreased. Besides, the protein levels of GRP78, XBP1, Derlin-1 were increased after TMAO treatment (all P < 0.05). In Conclusion, high fat and TMA could induce the expression of FMO1 and its metabolite TMAO. When FMO1 is silenced, the effects of high fat and TMA on TMAO are blocked. And the role of TMAO in NAFLD may be through the activation of UPR.

The ADCY9 genetic variants are associated with glioma susceptibility and patient prognosis.

PURPOSE: Genetic factor is a risk factor in glioma occurrence. This study was designed to detect the effect of ADCY9 polymorphisms on glioma risk and prognosis. METHODS: We performed a case-control study of 1080 participants (584 cases and 496 controls) to assess the relationship of ADCY9 polymorphisms with the risk and prognosis of glioma among the Chinses Han population. Odds ratios (ORs) and 95% confidence intervals (CIs) were computed to evaluate the relationship between ADCY9 variants and glioma risk. The correlation of SNPs with survival was analyzed by the Cox regression model. RESULTS: Our study showed that rs2230742 and rs2531992 polymorphisms played protective roles in glioma susceptibility (OR 0.65, p = 0.001; OR 0.73, p = 0.038, respectively). While rs2230742 significantly increased the susceptibility of III-V grade glioma patients (OR 1.50, p = 0.036). Haplotype analysis revealed that Crs879620Ars2230742Ars2230741 haplotype was related to a significantly decreased glioma risk (OR 0.65, p = 0.002). Notably, rs2531995 and rs879620 polymorphisms significantly enhanced death risk in high-grade glioma patients (hazard ratio [HR] 1.36, p = 0.041; HR 1.37, p = 0.042; respectively). For rs2230742 and rs2531992 SNPs, glioma patients had a worse prognosis (HR 2.30, p = 0.021; HR 2.30, p = 0.021; respectively). We further observed that age, chemotherapy, and surgical scope can affect the glioma prognosis. CONCLUSION: We firstly studied the association of ADCY9 variants with glioma risk and prognosis, which might give scientific evidence for exploring the molecular mechanism of glioma.

Comparative efficacy evaluation of inverted internal limiting membrane flap technique and internal limiting membrane peeling in large macular holes: a systematic review and meta-analysis.

BACKGROUND: The purpose of this study was to compare the anatomical and visual outcomes of inverted internal limiting membrane (ILM) flap technique and internal limiting membrane peeling in large macular holes (MH). METHODS: Related studies were reviewed by searching electronic databases of Pubmed, Embase, Cochrane Library. We searched for articles that compared inverted ILM flap technique with ILM peeling for large MH (> 400 µm). Double-arm meta-analysis was performed for the primary end point that was the rate of MH closure, and the secondary end point was postoperative visual acuity (VA). Heterogeneity, publication bias, sensitivity analysis and subgroup analysis were conducted to guarantee the statistical power. RESULTS: This review included eight studies involving 593 eyes, 4 randomized control trials and 4 retrospective studies. After sensitivity analysis for eliminating the heterogeneity of primary outcome, the pooled data showed the rate of MH closure with inverted ILM flap technique group was statistically significantly higher than ILM peeling group (odds ratio (OR) = 3.95, 95% confidence interval (CI) = 1.89 to 8.27; P = 0.0003). At the follow-up duration of 3 months, postoperative VA was significantly better in the group of inverted ILM flap than ILM peeling (mean difference (MD) = - 0.16, 95% CI = - 0.23 to 0.09; P < 0.00001). However, there was no difference in visual outcomes between the two groups of different surgical treatments at relatively long-term follow-up over 6 months (MD = 0.01, 95% CI = - 0.12 to 0.15; P = 0.86). CONCLUSION: Vitrectomy with inverted ILM flap technique had a better anatomical outcome than ILM peeling. Flap technique also had a signifcant visual gain in the short term, but the limitations in visual recovery at a longer follow-up was found.

Are parents' education levels associated with either their oral health knowledge or their children's oral health behaviors? A survey of 8446 families in Wuhan.

BACKGROUND: Children aged 6-7 years are in the early mixed dentition, which is a period of high prevalence of dental caries and other dental diseases and a critical period for the formation of oral health behaviors. Therefore, good oral hygiene habits of children and oral health knowledge of parents are very important. This study sought to explore the relationship between children's oral health behaviors, parental oral health knowledge, parental choices of pit and fissure sealants, and parents' education levels based on a large-scale sample size for the first time, and to compare the influences of parental education levels between parents. METHODS: Families of the first and second graders of primary schools in Wuhan Hongshan District were included in this study. A total of 8446 questionnaires were collected to obtain comprehensive information on children's oral health behaviors, parents' oral health knowledge and parents' pit and fissure sealants-related choices. The relationship between these outcome variables and parents' education levels were studied using logistic regression analysis and chi-square test. RESULTS: Parents who reported good educational background had more favorable oral health knowledge than those of other parents, and their children had better oral hygiene behaviors. Four indicators of five measures to children's oral health behaviors were significantly associated with mother's education level (P < 0.05), and three of them were related to father's education level (P ≤ 0.01). Moreover, seven indicators of eight measures to parents' oral health knowledge were significantly related to mother's education level (P < 0.05) and four of them were affected by the father's (P < 0.05). In addition, parents with higher educational attainments paid more attention to the completeness of medical facilities, the environment of dental practice, the distance to treatment sites, and took less concern of children's willingness when choosing the pit and fissure sealants sites. CONCLUSIONS: In families with children at the early mixed dentition stage, parents with higher education levels tend to have better oral health knowledge and more oral health care needs, such as pit and fissure sealants. In addition, children of parents who have better educated parents tend to perform better oral hygiene practices.

Transdifferentiation effects and related mechanisms of nerve growth factor and internal limiting membrane on Müller cells.

In this study, we investigated the pro-proliferative, pro-transdifferentiation effects and mechanisms of nerve growth factor (NGF), internal limiting membrane (ILM), and NGF+ILM on Müller cells. The Müller cells cultured with NGF, ILM or both were mediated with tyrosine kinase A (TrkA) (a high affinity receptor for NGF) inhibitor, phosphatidylinositol 3 kinase (PI3K)/protein kinase B (Akt) (an intracellular signaling pathway important in regulating the cell cycle) inhibitor, or LIN28 (a RNA-binding protein and a posttranscriptional regulator of genes involved in developmental timing and self-renewal in embryonic stem cells) siRNA. Immunofluorescence (IF), western blotting (WB) and quantitative real-time polymerase chain reaction (qRT-PCR) were performed to detect the expression of related genes. As a result, NGF, ILM and NGF+ILM promoted cell proliferation, increased the ratio of 5-bromo-2-deoxyuridine (BrdU)-positive cells, and were correlated with TrkA and PI3K/Akt signaling. NGF alone promoted cell dedifferentiation and redifferentiation mainly towards neurons rather than towards glial cells, related to TrkA and PI3K/Akt signals. The expression of p-Akt and cyclinD1 was increased by the intervention of NGF, ILM or NGF+ILM via TrkA and PI3K/Akt signals. NGF alone promoted the expression of paired box 6 (PAX6) (a transcription factor present during embryonic development), sex-determining region Y-box 2 (SOX2) (a transcription factor essential for the self-renewal, or pluripotency, of undifferentiated embryonic stem cells) and LIN28, and inhibited the expression of lethal-7 (Let-7b), Let-7d, Let-7i and miR-98 (microRNAs, key developmental regulators). The expression of Achaete-scute homolog 1 (Ascl1, also called MASH1) (a neurodevelopmental gene) and endogenous NGF (closely related to neurogenesis) was also promoted by exogenous NGF and related to TrkA and PI3K/Akt signaling. The down-regulation of LIN28 significantly antagonized the effects of NGF on the transdifferentiation of Müller cells. Over all, our results showed that NGF promoted the proliferation and transdifferentiation of Müller cells towards photoreceptor neurons--not towards glial cells, which was related to the LIN28/Let-7 pathway through TrkA and PI3K/Akt signals. Additionally, ILM promoted Müller cells to enter the cell cycle and enhanced cell proliferation, since NGF+ILM promoted the proliferation of Müller cell more significantly than NGF alone.

Internal limiting membrane insertion technique combined with nerve growth factor injection for large macular hole.

BACKGROUND: The study was proposed to determine whether nerve growth factor (NGF) combined with an internal limiting membrane (ILM) insertion was effective in the large idiopathic full-thickness macular hole (iFTMH) therapy. METHODS: A subset of 18 eyes (July 2015-October 2017) diagnosed as the large iFTMH were enrolled in this study. The subjects were treated using ILM insertion technique alone (ILM group) or ILM combined with NGF injection (NGF group) and the follow-up period was 6 months. Macular hole closure rates, best-corrected visual acuity (BCVA, improvements using ETDRS), and optical coherence tomography (OCT) findings were analyzed at 1st, 3rd, and 6th months postoperatively. RESULTS: We found that macular holes in both groups fully closed. In comparison to ILM insertion group, the NGF group had better BCVA at the 3rd month (48.00 ± 2.392 vs 58.22 ± 2.957, 95% confidence interval (CI): 2.159 to 18.29). The mean external limiting membrane (ELM, 422.2 ± 96 vs 674.9 ± 103.6, 95% CI: - 47.26 to 552.8) and ellipsoid zone (EZ, 496.7 ± 101.6 vs 766.7 ± 111.8, 95% CI: - 50.29 to 590.4) defects were significantly smaller in the NGF group at the 6th month in the follow-up examination. Complete recovery of ELM and EZ was observed in the NGF group in one eye of a patient and two eyes of two patients, respectively. In comparison, one eye's ELM and another eye's EZ were completely recovered in the ILM insertion group. CONCLUSION: Our results indicated that ILM insertion with NGF injection might be an effective technique for the initial surgical treatment of eyes with large MHs. The proposed approach yielded better recovery of the photoreceptor layers and consequently might have superior postoperative visual acuity. TRIAL REGISTRATION: chiCTR1900021711. Retrospectively registered 5 March 2019.

Nerve growth factor promotes the proliferation of Müller cells co-cultured with internal limiting membrane by regulating cell cycle via Trk-A/PI3K/Akt pathway.

BACKGROUND: Nerve growth factor (NGF), produced by Müller cells, and internal limiting membrane (ILM) have fundamental roles in the development of full-thickness macular hole (FTMH). However, the potential crosstalk between NGF and ILM in FTMH is unclear. This study aimed to explore the mechanism and effects of NGF on the proliferation of Müller cells co-cultured with ILM. METHODS: Primary Müller cells and ILM from New Zealand rabbits were extracted and authenticated with specific staining. Müller cells co-cultured with or without ILM were exposed to NGF and then analysed. Müller cell viability was estimated using cell counting kit-8. Cell cycle analysis was performed by flow cytometry. The levels of cell cycle-related gene were detected using qRT-PCR. The TrK-A/Akt signal axis and downstream signaling cascades such as p21, CyclinE, CDK2, CyclinD1, and CDK4 were investigated by western blotting. RESULTS: ILM treatment alone induced the proliferation of Müller cells following the promotion of phosphorylated Akt, while growth of Müller cells was enhanced by activation of the Trk-A/Akt pathway under the stimulation of NGF or NGF + ILM. Additionally, the ratio of S-phase cells was increased, while G2-phase cells decreased upon the treatment with either ILM or NGF alone, or with NGF + ILM co-treatment. Cell cycle-related genes such as CyclinD1, CyclinE, CDK2, and CDK4 were all upregulated, but p21 expression was downregulated in the presence of NGF, ILM, or NGF + ILM. There was an additive effect on cell proliferation and cell cycle in the group of Müller cells exposed to NGF co-cultured with ILM compared with either NGF or ILM treatment alone. However, both K252ɑ (inhibitors of Trk-A) and LY294002 (inhibitor for Akt) counteracted the effect of NGF or NGF + ILM on the protein levels of Trk-A, Akt, CyclinD1, CyclinE, CDK2, and p21. CONCLUSIONS: Müller cells co-cultured with ILM or NGF promoted cell proliferation by regulating cell cycle-correlated proteins via the PI3K/Akt pathway. ILM + NGF further amplified the PI3K/Akt signaling pathway by binding to Trk-A, leading to more cell growth. This study provides new insight into the potential mechanism of NGF-mediated proliferation of Müller cells co-cultured with or without ILM, which may have considerable impact on therapies for FTMH.

Riboflavin and ultraviolet A irradiation for the prevention of progressive myopia in a guinea pig model.

In this study, we evaluated the effect of oral administration of riboflavin combined with whole-body ultraviolet A (UVA) irradiation on the biochemical and biomechanical properties of sclera in a guinea pig model to control the progression of myopia. Experimental groups were administered 0.1% riboflavin solution with or without vitamin C by gavage from 3 days before myopic modeling and during the modeling process. Guinea pigs underwent 30 min of whole-body UVA irradiation after each gavage for 2 weeks. For control groups, guinea pigs were administered vitamin C and underwent either whole-body UVA irradiation without 0.1% riboflavin solution or whole-body fluorescent lamp irradiation with or without 0.1% riboflavin solution. Resultantly, myopia models were established with an increased axial length and myopic diopter. Compared with myopic eyes in the control groups, the net increase in axial length, diopter and strain assessment decreased significantly, and the net decrease in sclera thickness, ultimate load, and stress assessment decreased significantly in experimental groups. MMP-2 expression showed a lower net increase, while TIMP-2 expression showed a lower net decrease. In addition, hyperplasia of scleral fibroblasts was more active in myopic eyes of experimental groups. Overall, our results showed that oral administration of riboflavin with whole-body UVA irradiation could increase the strength and stiffness of sclera by altering the biochemical and biomechanical properties, and decreases in axial elongation and myopic diopter are greater in the guinea pig myopic model.

Biogas properties and enzymatic analysis during anaerobic fermentation of Phragmites australis straw and cow dung: influence of nickel chloride supplement.

The importance of nickel (added as NiCl2) on mesophilic anaerobic fermentation of Phragmites australis straw and cow dung was demonstrated by investigating the biogas properties, pH values, organic matter degradation [chemical oxygen demand (COD)] and enzyme activities (cellulase, protease and dehydrogenase) during the fermentation process. The results showed that Ni2+ addition increased the cumulative biogas yields by >18 % by improving the efficiency of first peak stage and bringing forward the second peak stage. The pH values were not significantly influenced by Ni2+ addition (p > 0.05). Biogas yields were associated with variations in COD concentrations rather than momentary concentrations. At the start-up stage of fermentation (4th day), the biogas yields increased gradually together with the increase of dehydrogenase activities at elevated Ni2+ concentrations when cellulase and protease activities were similar in all test groups. It is suggested that Ni2+ addition was mainly dependent on the methanogenic stage. After the start-up stage, the impact of Ni2+ addition on biogas production was mainly dependent on its effect on cellulase activities, rather than protease or dehydrogenase activities.

Human adipose-derived mesenchymal progenitor cells engraft into rabbit articular cartilage.

Mesenchymal stem cells (MSCs) are known to have the potential for articular cartilage regeneration, and are suggested for the treatment of osteoarthritis (OA). Here, we investigated whether intra-articular injection of xenogeneic human adipose-derived mesenchymal progenitor cells (haMPCs) promoted articular cartilage repair in rabbit OA model and engrafted into rabbit articular cartilage. The haMPCs were cultured in vitro, and phenotypes and differentiation characteristics of cells were evaluated. OA was induced surgically by anterior cruciate ligament transection (ACLT) and medical meniscectomy of knee joints. At six weeks following surgery, hyaluronic acid (HA) or haMPCs was injected into the knee joints, the contralateral knee served as normal control. All animals were sacrificed at the 16th week post-surgery. Assessments were carried out by macroscopic examination, hematoxylin/eosin (HE) and Safranin-O/Fast green stainings and immunohistochemistry. The data showed that haMPC treatment promoted cartilage repair. Signals of human mitochondrial can be directly detected in haMPC treated cartilage. The haMPCs expressed human leukocyte antigen I (HLA-I) but not HLA-II-DR in vivo. These results suggest that intra-articular injection of haMPCs promotes regeneration of articular cartilage in rabbit OA model, and support the notion that MPCs are transplantable between HLA-incompatible individuals.

[The risk factors of posterior capsule rupture in phacoemulsification of cataract].

OBJECTIVE: To demonstrate the incidence of posterior capsule rupture during the phacoemulsification of cataract and the risk factors of the complication and to find ways to reduce the rate of the complication. METHODS: This retrospective chart review comprised cataract phacoemulsification performed from January 1, 2009 to December 31, 2009 with a total of 3,004 cases (3,186 eyes). The incidence of posterior capsule rupture and the risk factors were the main outcomes. The variables of patient age and gender; laterality of surgical eye; pre-operative visual acuity and intraocular pressure; post-operative visual acuity; the nuclear stages, presence of diabetes mellitus, glaucoma, hypertension and other diseases; history of vitrectomy the surgeons were collected and analyzed. RESULTS: Male (χ2=7.82, P<0.01), pre-operative visual acuity less than 20/200 (HR=2.3, P=0.01), and the nuclear stage higher than IV (χ2=18.01, P<0.01) all statistically significantly increased in the posterior capsule rupture group (χ2=14.13, P<0.01). The post-operative visual acuity increased in both groups (2.1±1.0) LogMAR to (1.2±0.8) LogMAR, t=7.71×10(-11), P<0.01 vs (1.5±0.8) LogMAR to (0.7±0.7) LogMAR, t=1.27×10(-42), P<0.01). CONCLUSIONS: Gender, pre-operative visual acuity, the nuclear stages are all significantly affect the incidence of the posterior capsule rupture. Improving training of surgeons should further reduce the frequency.

A rare case of primary central nervous system histiocytic sarcoma harboring a novel ARHGAP45::BRAF fusion: a case report and literature review.

INTRODUCTION: Patients with histiocytic sarcoma occurring in the central nervous system (CNS) are rare and have a very poor prognosis. The increased use of molecular diagnostic approaches in solid tumors has brought more opportunities for the diagnosis and treatment of central nervous system histiocytic sarcoma (CNSHS). CASE DESCRIPTION: A 9-year-old girl was admitted to the hospital with pain in her head and neck, as well as vomiting. Imaging scans showed a prominent abnormality in the anterior falciform region, and histopathology revealed the presence of CD68 (+) and CD163 (+) cells, leading to a preliminary diagnosis of primary intracerebral CNSHS. Molecular profiling tests identified a new variant of ARHGAP45::BRAF fusion in this case, which has not been reported in any other tumor. The patient underwent surgical removal of the tumor and will require long-term monitoring. CONCLUSION: The presence of the BRAF point mutation, predominantly BRAF p.V600E, has been documented in prior literature of CNSHS. This is the first case of pediatric histiocytic sarcoma in the anterior falciform region who has a unique ARHGAP45::BRAF fusion. The findings of our study indicate that a broader range of molecular assays should be employed in the diagnosis of CNSHS and opens up new possibilities for the treatment of the patient.

Adherence to Screening Tests for Gynaecological and Colorectal Cancer in Patients with Diabetes in Spain: A Population-Based Study (2014-2020).

Objectives: Both diabetes mellitus (DM) and gynaecological and colorectal cancers are highly prevalent diseases. Furthermore, the presence of DM constitutes a risk factor and poor prognostic indicator for these types of cancer. This study is based on the European Health Interview Surveys in Spain (EHISS) of 2014 and 2020. It aimed to determine the trends in adherence to screening tests for gynaecological cancers (breast and cervical) and colorectal cancer, compare adherence levels between populations with and without diabetes, and identify predictors of adherence in the population with diabetes. Methods: An epidemiological case-control study based on the EHISS data of 2014 and 2020 was conducted. The characteristics of participants who underwent screening tests were analysed based on the presence or absence of DM, and predictors of adherence to these preventive activities were identified. Results: A total of 1852 participants with reported DM and 1852 controls without DM, adjusted for age and sex, were included. A higher adherence to mammography was observed in women without diabetes compared to those with diabetes, although statistical significance was not reached (72.9% vs. 68.6%, p = 0.068). Similarly, higher Pap smear adherence was observed in the population without diabetes in the age group between 60 and 69 years compared to the population with diabetes (54.0% vs. 45.8%, p = 0.016). Pap smear adherence among women with diabetes was significantly higher in the EHISS of 2020 (52.0% in 2014 vs. 61.0% in 2020, p = 0.010), as was the case for faecal occult blood testing (13.8% in 2014 vs. 33.8% in 2020, p < 0.001), but it was not significant for mammography (70.4% in 2014 vs. 66.8% in 2020, p = 0.301). Overall, the predictors of adherence to screening tests were older age, history of cancer and higher education level. Conclusions: Adherence levels to cancer screening tests were lower in the population with diabetes compared to those without diabetes, although an improvement in Pap smear and faecal occult blood test adherence was observed in 2020 compared to 2014. Understanding predictors is important to improve adherence rates in the population with diabetes.