Mifepristone protects acetaminophen induced liver injury through NRF2/GSH/GST mediated ferroptosis suppression.

Ferroptosis is a form of iron-dependent cell death that has attracted significant attention for its potential role in numerous diseases. Targeted inhibition of ferroptosis could be of potential use in treating diseases: such as drug induced liver injury (DILI). Ferroptosis can be antagonized by the xCT/GSH/GPX4, FSP1/CoQ10, DHODH/CoQ10, GCH1/BH4, and NRF2 pathways. Identifying novel anti-ferroptosis pathways will further promote our understanding of the biological nature of ferroptosis and help discover new drugs targeting ferroptosis related human diseases. In this study, we identified the clinically used drug mifepristone (RU486) as a novel ferroptosis inhibitor. Mechanistically, RU486 inhibits ferroptosis by inducing GSH synthesis pathway, which supplies GSH for glutathione-S-transferase (GST) mediated 4-HNE detoxification. Furthermore, RU486 induced RLIP76 and MRP1 export 4-HNE conjugate contributes to its anti-ferroptosis activity. Interestingly, RU486 induced GSH/GSTs/RLIP76&MRP1 anti-ferroptosis pathway acts independent of classic anti-ferroptosis systems: including xCT/GSH/GPX4, FSP1, DHODH, GCH1, SCD1 and FTH1. Moreover, NRF2 was identified to be important for RU486's anti-ferroptosis activity by inducing downstream gene expression. Importantly, in mouse model, RU486 showed strong protection effect on acetaminophen (APAP)-induced acute liver injury, evidenced by decreased ALT, AST level and histological recovery after APAP treatment. Interestingly, RU486 also decreased oxidative markers, including 4-HNE and MDA, and induced NRF2 activation as well as GSTs, MRP1 expression. Together, these data suggest NRF2/GSH/GST/RLIP76&MRP1 mediated detoxification pathway as an important independent anti-ferroptosis pathway act both in vitro and in vivo.

O-RADS combined with contrast-enhanced ultrasound in risk stratification of adnexal masses.

BACKGROUND: Ovarian-Adnexal Reporting and Data System (O-RADS) for ultrasound is a lexicon and risk stratification system that includes all risk categories and relevant management recommendation. It has high sensitivity in diagnosing malignant adnexal tumors, but the specificity is lower. OBJECTIVE: To explore the value of O-RADS combined with contrast-enhanced ultrasound (CEUS) in risk stratification of adnexal masses. METHODS: A retrospective study was performed on 85 patients with 100 adnexal masses that preoperatively underwent conventional ultrasound as well as CEUS examination and obtained the postoperative pathological results. The masses were classified into O-RADS2, 3, 4, and 5 by conventional ultrasound. After contrast enhancement, the classification of O-RADS was adjusted according to CEUS imaging features. The O-RADS 2 and 3 lesions with suspected malignant features like irregular blood vessels or internal inhomogeneous hyperenhancement were upgraded to O-RADS 4, and the O-RADS 4 lesions with the above features were upgraded to O-RADS 5. The O-RADS 4 lesions with suspicious benign angiographic features like a regular vessel, interior hypoenhancement or non-enhancement were downgraded to O-RADS 3; the O-RADS 5 lesions with rim ring-enhancement and interior non-enhancement were downgraded to O-RADS 3. The sensitivity, specificity, accuracy, PPV, NPV, and AUC of the two methods were compared, taking pathological results as the gold standard. RESULTS: The sensitivity, specificity, accuracy, PPV, NPV, and AUC of O-RADS and O-RADS combined with CEUS in the diagnosis of malignant adnexal tumors were 96.6%, 66.2%, 75.0%, 53.8%, 97.9%, 0.910 and 96.6%, 91.5%, 93.0%, 82.4%, 98.5%, 0.962, respectively. The specificity, accuracy, PPV, and AUC of O-RADS combined with CEUS were considerably higher than those of O-RADS (P < 0.01). Furthermore, both methods had excellent sensitivity and NPV but there were no significant differences between them(P > 0.05). CONCLUSION: Combination of O-RADS and CEUS can significantly improve the specificity and PPV in diagnosing malignant adnexal tumors. It seems promising in the clinical application of risk stratification of adnexal masses.

Comparative study of Curcumin and Lucentis on retinal neovascularization.

Introduction To investigate the effect of Curcumin on retinal neovascularization in mice with oxygen-induced lesions. Methods 7-day-old (P7) C57/BL6J mice were randomly divided into control group, OIR group, DMSO group, 100 mg/kg, 50 mg/kg and 25 mg/kg curcumin group and Lucentis group (15 mice per group). Mice in the experimental group were fed for 5 days in high oxygen partial pressure environment, and then in normal oxygen air environment for another 5 days. Corresponding interventions were given at 12-16 days of age (P12-16). At 17 days of age (P17), the eyeball was removed and the retina was paved with Isolectin GS-IB4 fluorescence staining. Real-time PCR was used to detect VEGF mRNA levels in tissues and cells. The protein expression level of VEGF was detected by Western blot. Results Immunofluorescence showed that curcumin injection could significantly reduce the formation of retinal neovascularization and astrocyte injury in OIR, and 100 mg/kg curcumin group had the best effect. Compared with the control group, mRNA and protein expression of VEGF in retina of mice in OIR and DMSO groups were significantly up-regulated (P<0.05); Compared with OIR group, curcumin group and Lucentis group were down-regulated (P<0.05). The protein expression and mRNA level of VEGF in HRCECs of curcumin group decreased with the increase of curcumin concentration, and the effect of curcumin group at 80µmol/L was similar to that of Lucentis group. In the HRCECs cultured with the same concentration of curcumin, the protein expression and mRNA level of VEGF decreased with the prolongation of drug intervention time. Conclusion Curcumin can down-regulate the expression of VEGF in retinal tissues and cells, thereby inhibiting retinal neovascularization and HRCECs cell proliferation.

Adherence, Efficacy, and Safety of Wearable Technology-Assisted Combined Home-Based Exercise in Chinese Patients With Ankylosing Spondylitis: Randomized Pilot Controlled Clinical Trial.

BACKGROUND: Clinical practice guidelines recommend that exercise is essential in the self-management of ankylosing spondylitis (AS). Attending supervised interventions requiring periodic medical center visits can be difficult and patients may decline participation, whereas effective home-based exercise interventions that do not require regular medical center visits are likely to be more accessible for AS patients. OBJECTIVE: The goal of the research was to investigate the adherence, efficacy, and safety of a wearable technology-assisted combined home-based exercise program in AS. METHODS: This was a 16-week investigator-initiated, assessor-blinded, randomized, pilot controlled trial conducted at Chinese People's Liberation Army General Hospital. We enrolled patients with AS who had no regular exercise habits and had been stable in drug treatment for the preceding month. Patients were randomly assigned (1:1) using a computer algorithm. An exercise program consisting of moderate-intensity aerobic exercise and functional exercise was given to the patients in the intervention group. The exercise intensity was controlled by a Mio FUSE Heart Rate Monitor wristband, which uses photoplethysmography to measure heart rate. Patients in the control group received usual care. The primary outcome was the difference in the Ankylosing Spondylitis Disease Activity Score (ASDAS). The secondary outcomes were patient global assessment (PGA), physician global assessment (PhGA), total pain, nocturnal pain, Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), BAS Functional Index (BASFI), BAS Metrology Index (BASMI), Spondyloarthritis International Society Health Index (ASAS HI), 36-item Short Form Survey (SF-36), maximal oxygen uptake (VO2) max, body composition, range of motion of joints, and muscle endurance tests. Retention rate, adherence rate, barriers to being active, and adverse events were also assessed. RESULTS: A total of 77 patients were screened, of whom 55 (71%) patients were enrolled; 2% (1/55) withdrew without treatment after randomization. Patients were assigned to the intervention (n=26) or control group (n=28). The median adherence rate of the prescribed exercise protocol was 84.2% (IQR 48.7%-97.9%). For the primary outcome, between-group difference of ASDAS was significant, favoring the intervention (-0.2, 95% CI -0.4 to 0.02, P=.03). For the secondary outcomes, significant between-group differences at 16 weeks were detected in PGA, PhGA, total pain, BASDAI, BASDAI-fatigue, BASDAI-spinal pain, BASDAI-morning stiffness intensity, BASFI, and BASMI. Moreover, the frequency of difficulty in ASAS HI-motivation at 16 weeks was less in the intervention group (P=.03). Between-group difference for change from baseline were also detected in VO2 max, SF-36, back extensor endurance test, and the range of motion of cervical lateral flexion at 16 weeks. Lack of time, energy, and willpower were the most distinct barriers to being active. Incidences of adverse events were similar between groups (P=.11). CONCLUSIONS: Our pilot study suggests that this technology-assisted combined home-based exercise program can improve the clinical outcomes of patients with AS who have no exercise habit, with good adherence and safety profile. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR1900024244; http://www.chictr.org.cn/showproj.aspx?proj=40176.

Different patterns and origins between northwestern and southeastern Tibetan ice core glaciochemical records over the past century.

Atmospheric circulation systems differ between the northern and southern Tibetan Plateau (TP) and are characterized by prevailing westerly winds and the Indian monsoon, respectively. This leads to spatial differences between glaciochemical records in the northwestern and southeastern TP. We compared the spatial differences in major soluble ion concentrations (Ca2+, SO42-, NO3-, NH4+, Cl-, Na+, K+, and Mg2+) during the last century in the Aru (northwestern TP) and East Rongbuk (ER; southeastern TP) ice cores. Ca2+ exhibited the largest difference between the ice cores (2371 ppb in the Aru ice core and 65 ppb in the ER ice core), indicating that crustal processes were more dominant in the Aru ice core. NH4+ accounted for 17% of the total ion concentration in the ER ice core but only 3% in the Aru ice core, which may be related to the Indian monsoon traveling over NH3 emission zones in southern Asia. The major soluble ion concentrations exhibited decreasing trends in the Aru ice core but increasing trends in the ER ice core (P < 0.01). Empirical orthogonal function and backward trajectory analyses indicated that the major soluble ions in the Aru ice core originated from crustal sources in central Asia; those in the ER ice core had crustal, anthropogenic, and oceanic sources from southern Asia. The results from the Aru ice core suggest that dust events and enhanced prevailing westerly winds promoted the deposition of dust aerosols from the Taklamakan Desert and arid and semi-arid regions of central Asia. Contrastingly, the results from the ER ice core suggest that the Indian monsoon transported crustal and anthropogenic sources from southern Asia and oceanic sources from the Bay of Bengal and Arabian Sea. This study contributes to the comprehensive understanding of the differences in glaciochemical records and their causes between the northwestern and southeastern TP.

The sex-specific influence of FTO genotype on exercise intervention for weight loss in adult with obesity.

The impact of exercise on weight loss varies significantly among individuals, and genes play a critical role. This study aims to explore whether the FTO gene variant (rs8050136) affects the influence of exercise on weight. The study initially recruited 240 Han Chinese adults with obesity, and 178 of them (101 men, 77 women, aged from 21 to 60) completed a 12-week moderate aerobic exercise programme. The participants were genotyped and obesity-related data were collected before and after the intervention. The intensity and the amount of exercise were precisely monitored. After the intervention, most obesity-related parameters of the participants showed a significant decrease. For muscle and lean body mass, significant change was only observed in males (P < 0.001) but not females (P = 0.205, P = 0.200 respectively). Importantly, for weight and BMI loss, we observed a genotype-by-gender interaction (P = 0.041, P = 0.042 respectively, adjusted for age, exercise time and baseline value). In the further analysis, after stratified for gender, the exercise-induced weight loss (P = 0.008), BMI loss (P = 0.010), muscle mass loss (P = 0.005) and lean body mass loss (P = 0.004) showed greater decrease in male subjects carrying at least one A allele compared to non-carriers. In conclusion, our study suggests that in Han Chinese population with obesity, carrying "obese risk gene" FTO (rs8050136) does not lead to the resistance to weight management intervention. More importantly, in male subjects, carrying FTO risk allele would even lose more weight than non-carriers after exercise intervention.HighlightsFor Han Chinese adults with obesity, carrying "obese risk gene" FTO could still achieve weight loss through exercise.Males carrying FTO risk allele would lose more weight than non-carriers after a 12-weeks exercise programme.

Intraoperative intravitreal triamcinolone acetonide injection for prevention of postoperative inflammation and complications after phacoemulsification in patients with uveitic cataract.

BACKGROUND: We aimed to evaluate the efficacy and safety of phacoemulsification with intravitreal 3 mg triamcinolone acetonide injection in preventing postoperative inflammation and complications in patients with non-infectious anterior uveitis and panuveitis complicated cataract. METHOD: In this retrospective cohort study, 140 uveitic cataract patients who received phacoemulsification and intraocular lens implantation in Shanxi Eye hospital from January 2018 to January 2020 were reviewed. The IVTA group (51 eyes of 41 patients) received intravitreal injection of 3 mg triamcinolone acetonide (TA) at the end of surgery, and the control group (51 eyes of 41 patients) without injection matched by propensity score matching were enrolled. Outcome measures were best corrected visual acuity (BCVA), anterior chamber inflammation, intraocular pressure, corneal endothelial cell density, central macular thickness and complications within 3 months follow-up. RESULTS: The degree of postoperative anterior chamber inflammation in the IVTA group was lighter than that in the control group (P < 0.05). The postoperative logMAR BCVA of anterior uveitis was better and improved more quickly in the IVTA group(P < 0.05). Postoperative time of using corticosteroids was shorter in the IVTA group as compared to the control group (P < 0.05). The central macular thickness at postoperative month 1 was statistically significantly lower in the IVTA group (P < 0.05). There were no statistically significant differences between the two groups in postoperative corneal endothelial cell density and intraocular pressure (P > 0.05). Two of 51 eyes (3.9%) in the IVTA group and 8 of 51 eyes (15.7%) in the control group had recurrence of uveitis; 6 of 45 eyes (13.3%) in the control group developed cystoid macular edema but none in the IVTA group; 11 of 51 eyes (21.6%) in the IVTA group and 22 of 51 eyes (43.1%) in the control group developed posterior synechiae postoperatively. CONCLUSIONS: Intraoperative Intravitreal injection of 3 mg TA is an effective and safe adjunctive therapy for preventing postoperative inflammation and complications to promote early recovery for anterior uveitis or panuveitis complicated cataract patients following phacoemulsification. TRIAL REGISTRATION: This retrospective cohort study was in accordance with the tenets of the Helsinki Declaration and was approved by the Shanxi Eye Hospital Ethics Committee. Written informed consent was obtained from all participants for their clinical records to be used in this study.

Development and Evaluation of Diagnostic Criteria for Vogt-Koyanagi-Harada Disease.

Importance: To our knowledge, a set of well-defined diagnostic criteria is not yet developed for the diagnosis of Vogt-Koyanagi-Harada (VKH) disease. Objective: To develop and evaluate a set of diagnostic criteria for VKH disease using data from Chinese patients. Design, Setting, and Participants: This case-control study reviewed medical records of patients from a tertiary referral center between October 2011 and October 2016. Data from 634 patients with VKH disease and 623 patients with non-VKH uveitis from southern China were used to develop the Diagnostic Criteria for VKH Disease (DCV). Data from an additional group of 537 patients with a definite VKH disease diagnosis and 525 patients with non-VKH uveitis from northern China were used to evaluate the diagnostic criteria. Main Outcomes and Measures: Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and receiver operating characteristic. Results: Of the 1257 patients used to construct the DCV, 665 (52.9%) were male, and the mean (SD) age at disease onset was 38.6 (13.6) years. The 3-class model and 21 clinical findings were selected by latent class analysis. Variables with a high positive rate in the early-phase or late-phase VKH group or high specificity constituted essential parameters. Constellations of these essential parameters constructed the DCV. The sensitivity and NPV of the DCV were higher than those of the Revised Diagnostic Criteria for VKH Disease (RDC) (sensitivity: 94.6% vs 71.9%; difference, 22.7%; 95% CI, 18.5-27.0; NPV: 94.3% vs 76.6%; difference, 17.7%; 95% CI, 13.9-21.5). The specificity and PPV of the DCV were not different from that of the RDC (specificity: 92.2% vs 93.9%; difference, 1.7%; 95% CI, -1.4 to 4.8; PPV: 89.3% vs 92.3%; difference, 3.0%; 95% CI, -1.4 to 4.8). The area under the receiver operating characteristic curve of the DCV and the RDC were 0.934 (95% CI, 0.917-0.951) and 0.829 (95% CI, 0.803-0.855), respectively. Conclusions and Relevance: The DCV were developed and evaluated using data from Chinese patients with VKH disease and showed a high sensitivity, NPV, and area under the receiver operating characteristic curve in comparison with the RDC. However, they were developed using a retrospective analysis and should be evaluated in prospective studies in other racial/ethnic populations.

[Isolation and Identification of Petroleum Degradation Bacteria and Interspecific Interactions Among Four Bacillus Strains].

Six petroleum-degrading strains were isolated from oil-contaminated soil at Dagang oil field and oil sewage on Bohai offshore drilling platform in Tianjin using enrichment culture and isolation method. The physiological biochemical test together with 16S rDNA sequencing analysis indicated that they belonged to Bacillus (S1, S2, S3, S4), Pseudomonas (W1) and Ochrobactrum (W2), respectively. The strain S3 had the maximum degradation rate of alkane (41.3%) and aromatic hydrocarbon (30.9%) among all isolated strains showing the better degradation efficiency by endogenous bacteria when compared to that by the exogenous bacteria. The four Bacillus strains were used to construct microbiome, thereafter subjected to petroleum degradation efficiency test and analyzed. The results showed that microbiome F3 consisting of S1 and S4 had the maximum degradation rates of alkane (50.5%) and aromatic hydrocarbon (54.0%), which were 69.9% and 156.1% higher than those by single bacterium, respectively. Furthermore, they were 22.1% and 74.6% respectively higher than those by the most optimal degradation bacterium S3. Microbiome F4 consisting of S2 and S3 had the minimum degradation rates of alkane (18.5%) and aromatic hydrocarbon (18.9%) which were 55.3% and 39.0% lower than the degradation rates of single bacterium, respectively. The results also demonstrated that there were both microbial synergy promotion and antagonism inhibition among bacteria of the same genus in the petroleum degradation period. Bacteria with close affinity in Bacillus genus displayed mainly promoted petroleum degradation effect.

A Gibberellin-Mediated DELLA-NAC Signaling Cascade Regulates Cellulose Synthesis in Rice.

Cellulose, which can be converted into numerous industrial products, has important impacts on the global economy. It has long been known that cellulose synthesis in plants is tightly regulated by various phytohormones. However, the underlying mechanism of cellulose synthesis regulation remains elusive. Here, we show that in rice (Oryza sativa), gibberellin (GA) signals promote cellulose synthesis by relieving the interaction between SLENDER RICE1 (SLR1), a DELLA repressor of GA signaling, and NACs, the top-layer transcription factors for secondary wall formation. Mutations in GA-related genes and physiological treatments altered the transcription of CELLULOSE SYNTHASE genes (CESAs) and the cellulose level. Multiple experiments demonstrated that transcription factors NAC29/31 and MYB61 are CESA regulators in rice; NAC29/31 directly regulates MYB61, which in turn activates CESA expression. This hierarchical regulation pathway is blocked by SLR1-NAC29/31 interactions. Based on the results of anatomical analysis and GA content examination in developing rice internodes, this signaling cascade was found to be modulated by varied endogenous GA levels and to be required for internode development. Genetic and gene expression analyses were further performed in Arabidopsis thaliana GA-related mutants. Altogether, our findings reveal a conserved mechanism by which GA regulates secondary wall cellulose synthesis in land plants and provide a strategy for manipulating cellulose production and plant growth.

Protective immunity against Eimeria tenella infection in chickens following oral immunization with Bacillus subtilis expressing Eimeria tenella 3-1E protein.

The current experiment was conducted to construct recombinant Bacillus subtilis WB600 expressing Eimeria tenella 3-1E protein to investigate the oral immunization protective effects against E. tenella. The merozoite surface antigen 3-1E gene of E. tenella was introduced into the pBS-H1 expression vector with a novel signal peptide sequence. After the electro-transformation, the expression of objective protein in B. subtilis WB600 was detected by Western blot. The results showed that the recombinant B. subtilis strain with the ability of high-level secretion of 3-1E was constructed successfully. Seven-day-old broiler chickens were orally vaccinated with B. subtilis WB600 harboring 3-1E (B.S-pBS-H1-3-1E) or B. subtilis WB600 with empty plasmid (B.S-pBS-H1) 10 days prior to challenge with sporulated E. tenella oocysts. The results showed the recombinant B. subtilis strain with the ability of high-level secretion of 3-1E was constructed successfully. Vaccination with B.S-pBS-H1-3-1E strain significantly increased the anti-coccidial index and reduced cecal lesion scores compared with the positive control group (chickens were challenged with sporulated E. tenella oocysts without oral administration of B.S-pBS-H1-3-1E strain) and B.S-pBS-H1 group. Ceca mucosal sIgA, secretion, and IL-2, IL-12, IFN-γ, and IL-10 level after challenge were greater in the B.S-pBS-H1-3-1E group than in the positive control group. Taken together, these results indicated that B. subtilis WB600 harboring 3-1E protein induces protective immunity against E. tenella.

Association of a TNIP1 polymorphism with Vogt-Koyanagi-Harada syndrome but not with ocular Behcet's disease in Han Chinese.

OBJECTIVES: The aim of the study was to investigate the association of TNFα-induced protein 3 interacting with protein 1 (TNIP1) gene polymorphisms with Vogt-Koyanagi-Harada (VKH) syndrome and Behcet's disease (BD) in a Han Chinese population. METHODS: A total of 656 BD patients, 961 VKH syndrome patients and 1534 healthy controls were included in this two-stage case control study. Seven SNPs, including rs17728338, rs7708392, rs10036748, rs3762999, rs999556, rs4958881 and rs3792783, belonging to TNIP1 were genotyped and analyzed by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. The data were analyzed by using the χ2 or Fisher's exact test and corrected for multiple comparisons by the Bonferroni method. RESULTS: A significantly increased frequency of the GG genotype and a decreased frequency of the AG genotype of rs17728338 were found in VKH patients (Pc = 0.038 OR = 1.934, 95% CI  = 1.438 ∼ 2.601). No significant difference was noted in allele or genotype frequencies of rs7708392, rs10036748, rs3762999, rs999556, rs4958881 and rs3792783, between VKH patients and healthy controls (Pc>0.05). No significant difference was noted in allele or genotype frequencies of the tested 7 SNPs between BD patients and healthy controls. Analysis of extraocular clinical findings, did not reveal an association of the TNIP1 gene polymorphisms with BD or VKH syndrome subgroups. CONCLUSION: A TNIP1 polymorphism may be a risk factor for VKH syndrome in Han Chinese.

Retention of OsNMD3 in the cytoplasm disturbs protein synthesis efficiency and affects plant development in rice.

The ribosome is the basic machinery for translation, and biogenesis of ribosomes involves many coordinated events. However, knowledge about ribosomal dynamics in higher plants is very limited. This study chose a highly conserved trans-factor, the 60S ribosomal subunit nuclear export adaptor NMD3, to characterize the mechanism of ribosome biogenesis in the monocot plant Oryza sativa (rice). O. sativa NMD3 (OsNMD3) shares all the common motifs and shuttles between the nucleus and cytoplasm via CRM1/XPO1. A dominant negative form of OsNMD3 with a truncated nuclear localization sequence (OsNMD3(ΔNLS)) was retained in the cytoplasm, consequently interfering with the release of OsNMD3 from pre-60S particles and disturbing the assembly of ribosome subunits. Analyses of the transactivation activity and cellulose biosynthesis level revealed low protein synthesis efficiency in the transgenic plants compared with the wild-type plants. Pharmaceutical treatments demonstrated structural alterations in ribosomes in the transgenic plants. Moreover, global expression profiles of the wild-type and transgenic plants were investigated using the Illumina RNA sequencing approach. These expression profiles suggested that overexpression of OsNMD3(ΔNLS) affected ribosome biogenesis and certain basic pathways, leading to pleiotropic abnormalities in plant growth. Taken together, these results strongly suggest that OsNMD3 is important for ribosome assembly and the maintenance of normal protein synthesis efficiency.

Polymorphisms in genetics of vitamin D metabolism confer susceptibility to ocular Behçet disease in a Chinese Han population.

PURPOSE: To test whether single nucleotide polymorphisms (SNPs) of the 4 vitamin D family genes (DHCR7, CYP2R1, CYP27B1, and CYP24A1) previously associated with several autoimmune diseases are associated with ocular Behçet disease, Vogt-Koyanagi-Harada (VKH) syndrome, acute anterior uveitis (AAU) with ankylosing spondylitis, or pediatric uveitis in the Chinese Han population. DESIGN: Prospective case-control study. METHODS: Genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism, and the genotypes were verified with direct sequencing. The first-stage study comprised 400 ocular Behçet disease patients, 400 VKH syndrome patients, 218 AAU with ankylosing spondylitis patients, 400 pediatric uveitis patients, and 600 healthy subjects from Chinese Han populations. The second stage included 427 ocular Behçet disease patients and 1000 healthy Chinese Han subjects. Allele and genotype frequencies were compared between patients and controls using the χ(2) test. RESULTS: In the first-stage study, only the frequencies of the rs12785878 DHCR7 genotype TT and T allele were significantly higher in ocular Behçet disease patients (P = .036 and P = .008 with Bonferroni correction, respectively) compared with controls among 6 SNPs. No associations could be detected for VKH, AAU with ankylosing spondylitis, or pediatric uveitis. A second stage and combined study confirmed the association of rs12785878 DHCR7 TT genotype and T allele with ocular Behçet disease (P = 3.28E-04 with Bonferroni correction; odds ratio, 1.506; 95% confidence interval, 1.248 to 1.818; and P = 2.82E-05 with Bonferroni correction; odds ratio, 1.339; 95% confidence interval, 1.188 to 1.508, respectively). CONCLUSIONS: This study provides evidence that the DHCR7 gene is involved in the susceptibility to ocular Behçet disease.

Brittle Culm1, a COBRA-like protein, functions in cellulose assembly through binding cellulose microfibrils.

Cellulose represents the most abundant biopolymer in nature and has great economic importance. Cellulose chains pack laterally into crystalline forms, stacking into a complicated crystallographic structure. However, the mechanism of cellulose crystallization is poorly understood. Here, via functional characterization, we report that Brittle Culm1 (BC1), a COBRA-like protein in rice, modifies cellulose crystallinity. BC1 was demonstrated to be a glycosylphosphatidylinositol (GPI) anchored protein and can be released into cell walls by removal of the GPI anchor. BC1 possesses a carbohydrate-binding module (CBM) at its N-terminus. In vitro binding assays showed that this CBM interacts specifically with crystalline cellulose, and several aromatic residues in this domain are essential for binding. It was further demonstrated that cell wall-localized BC1 via the CBM and GPI anchor is one functional form of BC1. X-ray diffraction (XRD) assays revealed that mutations in BC1 and knockdown of BC1 expression decrease the crystallite width of cellulose; overexpression of BC1 and the CBM-mutated BC1s caused varied crystallinity with results that were consistent with the in vitro binding assay. Moreover, interaction between the CBM and cellulose microfibrils was largely repressed when the cell wall residues were pre-stained with two cellulose dyes. Treating wild-type and bc1 seedlings with the dyes resulted in insensitive root growth responses in bc1 plants. Combined with the evidence that BC1 and three secondary wall cellulose synthases (CESAs) function in different steps of cellulose production as revealed by genetic analysis, we conclude that BC1 modulates cellulose assembly by interacting with cellulose and affecting microfibril crystallinity.

Functional and morphologic benefits in early detection of neovascular age-related macular degeneration using the preferential hyperacuity perimeter.

PURPOSE: To estimate the usefulness of preferential hyperacuity perimetry (PHP) in detecting conversion of early to late age-related macular degeneration in the Carotenoids and co-antioxidants in patients with Age-Related Maculopathy, a multicenter randomized controlled clinical trial. METHODS: This was a nested case control study within the Carotenoids and co-antioxidants in patients with Age-Related Maculopathy (CARMA) clinical trial and included all participants enrolled in a single center (n = 200). Data are from participants who progressed to neovascular age-related macular degeneration (nvAMD) during time on study, Group 1 (n = 10) before the use of PHP and Group 2 (n = 10) during use of PHP. We also randomly selected 21 other participants (Group 3) who did not progress to nvAMD during time on study as a control group. Change in best-corrected visual acuity and contrast sensitivity and size of neovascular lesion at detection of conversion to nvAMD in Groups 1 and 2. RESULTS: At detection of nvAMD, mean best-corrected visual acuity in Group 1 was 57.5 letters versus 67.4 in Group 2. In Group 1, the change in best-corrected visual acuity from baseline to detection of nvAMD was twice that of Group 2 (21.6 ± 9.0 versus 11.9 ± 10.7) with a mean difference of 9.7 letters (95% confidence interval, 0.41 to 19.0, P = 0.04, independent-samples t-test). The size of the neovascular lesion at detection was 3.06 mm in Group 1 versus 0.89 mm in Group 2 (P = 0.02). Two thirds of the participants in Group 2 were asymptomatic at detection of nvAMD compared with one fifth in Group 1. Preferential hyperacuity perimetry distortion maps were abnormal in 9 of 10 eyes in Group 2, which were confirmed by optical coherence tomography. Of the 21 eyes in Group 3, PHP maps were normal in 18 and abnormal in 3. CONCLUSION: Preferential hyperacuity perimetry detected abnormalities in central visual function with high reliability. Eyes with nvAMD lesions detected by PHP had smaller lesions and better function when compared with the group before the introduction of PHP. The false-negative rate was <10% on PHP. The PHP distortion map was helpful in alerting clinicians to the presence of subclinical nvAMD.

Fabrication and repair of cartilage defects with a novel acellular cartilage matrix scaffold.

The objectives of this study were to develop a three-dimensional acellular cartilage matrix (ACM) and investigate its possibility for use as a scaffold in cartilage tissue engineering. Bovine articular cartilage was decellularized sequentially with trypsin, nuclease solution, hypotonic buffer, and Triton x 100 solution; molded with freeze-drying process; and cross-linked by ultraviolet irradiation. Histological and biochemical analysis showed that the ACM was devoid of cells and still maintained the collagen and glycosaminoglycan components of cartilage. Scanning electronic microscopy and mercury intrusion porosimetry showed that the ACM had a sponge-like structure of high porosity. The ACM scaffold had good biocompatibility with cultured rabbit bone marrow mesenchymal stem cells with no indication of cytotoxicity both in contact and in extraction assays. The cartilage defects repair in rabbit knees with the mesenchymal stem cell-ACM constructs had a significant improvement of histological scores when compared to the control groups at 6 and 12 weeks. In summary, the ACM possessed the characteristics that afford it as a potential scaffold for cartilage tissue engineering.

Distortion maps from preferential hyperacuity perimetry are helpful in monitoring functional response to Lucentis therapy.

PURPOSE: To use preferential hyperacuity perimetry to obtain a quantitative measure of central visual field distortion that would aid in the monitoring of functional responsiveness to ranibizumab treatment. METHODS: This study is a retrospective analysis of data from patients with neovascular age-related macular degeneration treated with ranibizumab. Preferential hyperacuity perimetry (PHP) were performed before and within 10 days of treatment. Pre- and posttreatment PHP metamorphopsia maps of contours showing 6 levels of metamorphopsia severity (S1 through S6; least to most distortion) were analyzed. Optical coherence tomography (OCT) outputs were subjected to standardized grading to generate metrics on subretinal fluid height, maximum retinal thickness, outer high-reflectivity band thickness, and height of pigment epithelial detachment (OCT metrics). RESULTS: Complete data were available from 17 patients. Statistically significant reductions were seen between baseline and posttreatment in PHP contour areas and OCT metrics, except for maximum retinal thickness. Mean best-corrected visual acuity improved by two letters, but this was not statistically significant. Change in PHP parameters correlated strongly with change in subretinal fluid height, with P values of <0.01 for most comparisons. Change in best-corrected visual acuity did not correlate with change in any of the OCT metrics or PHP distortion map areas. CONCLUSION: The reduction in the contour map area seen on PHP outputs occurs rapidly and correlates with the resolution of subretinal fluid, suggesting that this parameter may be used to monitor response to therapy.