Correlation of TBX21 gene polymorphisms with ankylosing spondylitis in a Chinese population.

Genome-wide association studies analysis has revealed associations between ankylosing spondylitis (AS) and loci on the TBX21 gene across various populations. This study aimed to investigate if there is a connection between a higher risk of AS in a Chinese population and two polymorphism loci on the TBX21 gene. To achieve this, we performed a case-control investigation involving 363 patients with AS and 907 healthy individuals. Genotyping was carried out using the iPLEX Gold genotyping assay. The analysis of genotypes and haplotypes was performed using SPSS 23.0 and SHEsis software. The results revealed no statistically significant correlation between the two specified single-nucleotide polymorphisms of TBX21 (rs11657479 C/T and rs4794067 C/T) and susceptibility to AS. However, upon conducting stratification analysis, our findings demonstrated a significant association between rs11657479 and susceptibility to human leucocyte antigen (HLA)-B27+ AS in allelic (C vs. T: odds ratio [OR] = 1.52, 95%CI = 1.09-2.11, corrected p [pc] = .028), heterozygous (CT vs. TT: OR = 1.63, 95%CI = 1.13-2.34, pc = .016) and dominant (CT + CC vs. TT: OR = 1.60, 95%CI = 1.12-2.28, pc = .018) models. Furthermore, the haplotype rs4794067/C-rs11657479/C of TBX21 was found to increase the risk of HLA-B27+ AS cases. In conclusion, our findings indicate a correlation between TBX21 gene polymorphism and HLA-B27+ AS patients within the Chinese population.

Reduced production of Ethyl Carbamate in wine by regulating the accumulation of arginine in Saccharomyces cerevisiae.

Ethyl carbamate (EC), a multisite carcinogenic compound, is naturally produced from urea and ethanol in alcoholic beverages. In order to reduce the content of EC in wine, the accumulation of arginine in Saccharomyces cerevisiae was regulated by genetic modifying genes involved in arginine transport and synthesis pathways to reduce the production of urea. Knockout of genes encoding arginine permease (Can1p) and amino acid permease (Gap1p) on the cell membrane as well as argininosuccinate synthase (Arg1) respectively resulted in a maximum reduction of 66.88% (9.40 µg/L) in EC, while overexpressing the gene encoding amino acid transporter (Vba2) reduced EC by 52.94% (24.13 µg/L). Simultaneously overexpressing Vba2 and deleting Arg1 showed the lowest EC production with a decrease of 68% (7.72 µg/L). The yield of total higher alcohols of the mutants all decreased compared with that of the original strain. Comprehensive consideration of flavor compound contents and sensory evaluation results indicated that mutant YG21 obtained by deleting two allele coding Gap1p performed best in must fermentation of Cabernet Sauvignon with the EC content low to 9.40 µg/L and the contents of total higher alcohols and esters of 245.61 mg/L and 41.71 mg/L respectively. This study has provided an effective strategy for reducing the EC in wine.

A 2D carbon nitride-based electrochemical aptasensor with reverse amplification for highly sensitive detection of okadaic acid in shellfish.

Okadaic acid (OA) is one of the main virulence factors of diarrheal shellfish toxins (DSP). It is of great significance to detect OA with an accurate, specific and cost-effective technique in the fields of seafood safety and water quality control. In this work, an electrochemical aptasensor with reverse amplification was developed for the sensitive detection of OA. A two-dimensional graphite-phase nanomaterial (carbon nitride) modified with an anti-OA aptamer and thionine (Th) was immobilized onto the surface of the electrochemical electrode as the sensitive element to capture target OA molecules. ssDNA-modified carbon nitride was used as the reverse amplification element by hybridizing with non-OA linked aptamers. The preparation of the electrochemical aptasensor was well characterized by Scanning Electron Microscopy (SEM), zeta potential detection, UV-Vis absorption, Brunner-Emmet-Teller (BET) measurements, and electrochemical measurements. The quantitative assessment of OA was achieved by differential pulse voltammetry (DPV). Experimental results indicated that this aptasensor showed a concentration-dependent response to OA with a good detection performance including in terms of selectivity, repeatability, reproducibility, and stability. It exhibited 100-fold selectivity between OA and other toxins including dinophysistoxins (DTX), pectenotoxins (PTX), and yessotoxins (YTX). In addition, it showed a much wider quantification range, which is 10-13 M-10-10 M (0.080-80.50 pg mL-1). The detection limit was as low as 10-13 M (0.080 pg mL-1). The aptasensor also successfully achieved significant practicality on real shellfish samples contaminated by OA. All these results demonstrated that the reverse amplification strategy for marine toxin detection may provide a label-free and rapid detection approach for portable applications in the fields of environmental monitoring and food security.

Associations of IL6R and IL10 Gene Polymorphisms with Susceptibility to Ankylosing Spondylitis with or without Acute Anterior Uveitis.

BACKGROUND: This research aims to explore the associations between ten candidate single nucleotide polymorphisms (SNPs) on Interleukin-6 receptor (IL6R) and Interleukin-10 (IL10) genes and ankylosing spondylitis (AS) patients with or without acute anterior uveitis (AAU). METHODS: This study involved a case-control approach that examined 354 cases with AS and AAU, 377 AS cases without AAU, and 918 healthy controls. Genotyping of ten SNPs of IL10 and IL6R genes was performed using iPLEX Gold genotyping method. The allele and genotype frequencies of cases and healthy individuals were contrasted using the chi-square test. The IL10 mRNA level in various IL10 genotypes was tested using real-time PCR. RESULTS: Two loci associated with AS with AAU were identified: IL10//rs3790622 (OR = 0.664; 95%CI = 0.503-0.878; Pc = 0.038); IL10//rs3021094 (OR = 1.365; 95%CI = 1.110-1.679; Pc = 0.032). The other eight loci located on IL10 and IL6R did not show significant associations with the diseases. Additionally, as shown by functional experiments, there was no correlation between the mRNA expression of IL10 and various genotypes. CONCLUSION: Our study suggests that the IL10 gene contributes to the susceptibility of the Chinese population to AS with AAU.

Chronic Central Serous Chorioretinopathy in Elderly Subjects: Structure and Blood Flow Characteristics of Retina and Choroid.

INTRODUCTION: With advancements in imaging technology, researchers have been able to identify more distinctive imaging features of central serous chorioretinopathy (CSC). However, existing research primarily concentrates on young patients aged 50 years and below, leaving a dearth of studies on elderly CSC patients. Previous studies indicate that elderly CSC patients may exhibit unique imaging characteristics and have a clinical prognosis that significantly differs from younger patients. This study aimed to evaluate the characteristics of retina, choroid structure, and blood flow in elderly patients with chronic CSC (cCSC) examined multimode imaging and try to find new pathogenesis information of it. METHODS: Using a cut-off age of 50 years, patients with chronic central serous chorioretinopathy were divided into two groups: older and younger. The control group consisted of 40 healthy individuals, with their right eyes assigned. Various clinical features were recorded, including the incidence of ellipsoid zone rupture (EZ-), fibrin in the subretinal fluid (SRF), pachydrusen, subretinal drusenoid deposits (SDD), pigment epithelial detachment (PED), double-layer sign (DLS), and choroidal lipid globule cavern. Measurements were taken for the thickness of the outer nuclear layer (ONL), the length of the extended outer photoreceptor segment (POS), the height and width of SRF, the vascular density of each layer of the retinal capillary plexus, the central macular thickness (CMT), and the subfoveal choroidal thickness (SFCT). RESULTS: The proportion of females in the elderly group (43.75%) was significantly higher than that in the youth group (22.41%) (p = 0.034). The degree of hyperopia in the elderly group (1.03 ± 0.73) was higher than that in the youth group (0.26 ± 1.06), with a significant difference in BCVA (p = 0.05). The thickness of SFCT, CMT, ONL in the elderly group, and the length of photoreceptor outer segment in the elderly group were thinner than those in the youth group (p < 0.05). Choroidal capillary perfusion area (CCPA), macular area, and paramacular area were lower in the elderly group than those in the youth group in the full scan range (p < 0.05). The blood flow densities of deep capillary plexus (DCP), intermediate capillary plexus (ICP), and superficial capillary plexus (SCP) in the whole scan range, macular area, and paramacular area were lower in the elderly group than in the youth group, but the differences were not statistically significant. CONCLUSIONS: In conclusion, our data suggest that elderly patients with cCSC may experience different disease outcomes. Elderly cCSC patients exhibit less gender bias, poorer vision, more severe structural damage and ischemia in the choroid and retina, and have a higher risk of developing choroidal neovascularization.

Longitudinal Assessment of Pancreas Volume by MRI Predicts Progression to Stage 3 Type 1 Diabetes.

OBJECTIVE: This multicenter prospective cohort study compared pancreas volume as assessed by MRI, metabolic scores derived from oral glucose tolerance testing (OGTT), and a combination of pancreas volume and metabolic scores for predicting progression to stage 3 type 1 diabetes (T1D) in individuals with multiple diabetes-related autoantibodies. RESEARCH DESIGN AND METHODS: Pancreas MRI was performed in 65 multiple autoantibody-positive participants enrolled in the Type 1 Diabetes TrialNet Pathway to Prevention study. Prediction of progression to stage 3 T1D was assessed using pancreas volume index (PVI), OGTT-derived Index60 score and Diabetes Prevention Trial-Type 1 Risk Score (DPTRS), and a combination of PVI and DPTRS. RESULTS: PVI, Index60, and DPTRS were all significantly different at study entry in 11 individuals who subsequently experienced progression to stage 3 T1D compared with 54 participants who did not experience progression (P < 0.005). PVI did not correlate with metabolic testing across individual study participants. PVI declined longitudinally in the 11 individuals diagnosed with stage 3 T1D, whereas Index60 and DPTRS increased. The area under the receiver operating characteristic curve for predicting progression to stage 3 from measurements at study entry was 0.76 for PVI, 0.79 for Index60, 0.79 for DPTRS, and 0.91 for PVI plus DPTRS. CONCLUSIONS: These findings suggest that measures of pancreas volume and metabolism reflect distinct components of risk for developing stage 3 type 1 diabetes and that a combination of these measures may provide superior prediction than either alone.

Fe-curcumin nanozyme-mediated immunosuppression and anti-inflammation in experimental autoimmune uveitis.

BACKGROUND: EAU is an inflammatory disease usually characterized by autoinflammation and autoimmunity and is aggravated by excessive generation of ROS. Conventional hormone therapy often has more adverse effects. It is urgent to find a therapeutic drug with higher efficiency and fewer adverse effects. METHODS: We developed an Fe-curcumin nanozyme in which natural antioxidants coordinate with Fe3+ to form nanoparticles with excellent solubility for directing anti-inflammatory and ROS scavenging effects to treat EAU. Several experiments were used to detect the characteristics of nanozymes. EAU model rats were used to detect the abilities of decreasing autoinflammation and autoimmunity. PBMCs were used to detect the ability to inhibit cell proliferation. RESULTS: Free radical scavenging experiments showed that nanozymes decreased the level of free radicals at low concentrations. In vitro and in vivo experiments revealed that the group treated with Fe-curcumin nanozymes had lower inflammatory reactions and ROS levels than the control group, as reflected by the downregulated levels of several critical inflammatory cytokines, such as IFN-γ, IL-17, and TNF-α; decreased H2O2 release; inhibited proliferation of Th1 and Th17 cells; and alleviated pathological changes in the eye. Importantly, the Fe-curcumin nanozyme was detected in the retina using Prussian blue staining. Additionally, Fe-curcumin nanozyme is noncytotoxic when directing these biological activities. CONCLUSION: This study has demonstrated the feasibility of using the Fe-curcumin nanozyme as a nanodrug to inhibit inflammatory reactions and scavenge ROS in the treatment of EAU, indicating that it may serve as a promising therapeutic agent in clinical treatment.

Label-Free Detection of CA19-9 Using a BSA/Graphene-Based Antifouling Electrochemical Immunosensor.

Evaluating the levels of the biomarker carbohydrate antigen 19-9 (CA19-9) is crucial in early cancer diagnosis and prognosis assessment. In this study, an antifouling electrochemical immunosensor was developed for the label-free detection of CA19-9, in which bovine serum albumin (BSA) and graphene were cross-linked with the aid of glutaraldehyde to form a 3D conductive porous network on the surface of an electrode. The electrochemical immunosensor was characterized through the use of transmission electron microscopy (TEM), scanning electron microscopy (SEM), atomic force microscope (AFM), UV spectroscopy, and electrochemical methods. The level of CA19-9 was determined through the use of label-free electrochemical impedance spectroscopy (EIS) measurements. The electron transfer at the interface of the electrode was well preserved in human serum samples, demonstrating that this electrochemical immunosensor has excellent antifouling performance. CA19-9 could be detected in a wide range from 13.5 U/mL to 1000 U/mL, with a detection limit of 13.5 U/mL in human serum samples. This immunosensor also exhibited good selectivity and stability. The detection results of this immunosensor were further validated and compared using an enzyme-linked immunosorbent assay (ELISA). All the results confirmed that this immunosensor has a good sensing performance in terms of CA19-9, suggesting its promising application prospects in clinical applications.

Relationship between Uveitis and the Differential Reactivity of Retinal Microglia.

Uveitis, a complicated group of ocular inflammatory diseases, can be affected by massive pathogenic contributors such as infection, autoimmunity, and genetics. Although it is well known that many pathological changes, including disorders of the immune system and disruption of the blood-retinal barrier, count much in the onset and progression of uveitis, there is a paucity of safe and effective treatments, which has exceedingly hindered the appropriate treatment of uveitis. As innate immune cells in the retina, microglia occupy a salient position in retinal homeostasis. Many studies have reported the activation of microglia in uveitis and the mitigation of uveitis by interfering with microglial reactivity, which strongly implicates microglia as a therapeutic target. However, it has been increasingly recognized that microglia are a nonhomogeneous population under different physiological and pathological conditions, which makes it essential to thoroughly have knowledge of their specific characteristics. The paper outlines the various properties of activated microglia in uveitis, summarizes the connections between their polarization patterns and the manifestations of uveitis, and ultimately is intended to enhance the understanding of microglial versatility and expedite the exploration of promising strategies for visual protection.

Effect of Previous Transarterial Chemoembolization on Survival and Toxicity after Yttrium-90 Transarterial Radioembolization of Hepatocellular Carcinoma in the Radiation-Emitting SIR-Spheres in Nonresectable Liver Tumor Registry.

PURPOSE: To determine overall survival (OS), best response, and toxicities in patients with hepatocellular carcinoma (HCC) previously treated with chemoembolization (TACE+) or yttrium-90 resin transarterial radioembolization (TARE) compared with those of TACE-naïve (T-N) participants. MATERIALS AND METHODS: In this prospective, observational study, 262 adult participants with HCC were divided into TACE+ (n = 93, 35%) or T-N (n = 169, 65%) groups, included from 36 centers in the United States. Overall survival (OS) was assessed using Kaplan-Meier analysis from the date of TARE. Best response at 6 months was evaluated using modified Response Evaluation Criteria in Solid Tumors. Six-month toxicities were reported using Common Terminology Criteria for Adverse Events, version 5. RESULTS: Median OS for patients in the TACE+ and T-N groups was 22.3 months (95% CI: 17.2 to not reachable) and 21.5 months (95% confidence interval [CI]: 14.9-29.9), respectively (P = .6). Imaging at 6 months ± 2 weeks was available in 156 of 262 (60%) participants. Partial or complete response was seen in 27 of 55 patients (49%) in the TACE+ group and 65 of 101 patients (64%) in the T-N group (P = .2). Six-month toxicities were available in 69 of 93 patients (74%) in the TACE+ group and 135 of 167 patients (81%) in the T-N group. Attributable Grade 3 or greater liver function toxicities were similar between the study groups (all P > .05). CONCLUSIONS: OS and imaging response at 6 months in the TACE+ group was similar to that in the T-N group with similar toxicities. Radioembolization is an acceptable treatment option for patients with HCC previously treated with TACE.

Epigenome-wide association study identifies Vogt-Koyanagi-Harada disease-associated DNA methylation loci in Chinese.

DNA methylation is one of the important epigenetic mechanisms for modulating gene expression. By performing a genome-wide methylation association analysis of whole peripheral blood from 60 Vogt-Koyanagi-Harada disease (VKH) patients and 60 healthy controls, we depicted the global DNA methylation status of VKH disease. Further pyrosequencing validation in 160 patients and 159 controls identified 3 aberrant CpG sites in HLA gene regions including cg04026937 and cg18052547 (located in HLA-DRB1 region), and cg13778567 (HLA-DQA1). We also identified 9 aberrant CpG sites in non-HLA gene regions including cg13979407, cg21075643, cg24290586, cg10135747 and cg22707857 (BTNL2), cg22155039 (NOTCH4), cg02605387 (TNXB), cg06255004 (AGPAT2) and cg18855195 (RIBC2). Increased mRNA levels of BTNL2, NOTCH4 and TNXB were identified in VKH patients when compared with healthy controls, consistent with the hypomethylated CpG status in these gene regions. Moreover, seven aberrantly methylated CpG sites may serve as a diagnostic marker for VKH disease (AUC = 84.95%, 95%CI: 79.49%-90.41%).

PATHWAYS ASSOCIATED WITH POSITIVE SEPSIS SURVIVAL OUTCOMES IN AFRICAN AMERICAN/BLACK AND NON-HISPANIC WHITE PATIENTS WITH URINARY TRACT INFECTION.

ABSTRACT: Urinary tract infections (UTIs) are a common cause of sepsis worldwide. Annually, more than 60,000 US deaths can be attributed to sepsis secondary to UTIs, and African American/Black adults have higher incidence and case-fatality rates than non-Hispanic White adults. Molecular-level factors that may help partially explain differences in sepsis survival outcomes between African American/Black and Non-Hispanic White adults are not clear. In this study, patient samples (N = 166) from the Protocolized Care for Early Septic Shock cohort were analyzed using discovery-based plasma proteomics. Patients had sepsis secondary to UTIs and were stratified according to self-identified racial background and sepsis survival outcomes. Proteomics results suggest patient heterogeneity across mechanisms driving survival from sepsis secondary to UTIs. Differentially expressed proteins (n = 122, false discovery rate-adjusted P < 0.05) in Non-Hispanic White sepsis survivors were primarily in immune system pathways, while differentially expressed proteins (n = 47, false discovery rate-adjusted P < 0.05) in African American/Black patients were mostly in metabolic pathways. However, in all patients, regardless of racial background, there were 16 differentially expressed proteins in sepsis survivors involved in translation initiation and shutdown pathways. These pathways are potential targets for prognostic intervention. Overall, this study provides information about molecular factors that may help explain disparities in sepsis survival outcomes among African American/Black and Non-Hispanic White patients with primary UTIs.

Global Epidemiology of Pediatric Traumatic Spine Injury: A Systematic Review and Meta-Analysis.

OBJECTIVE: Traumatic spine injury (TSI) leads to significant morbidity and mortality in children. However, the global epidemiology of pediatric TSI is currently unknown. We conducted a systematic review and meta-analysis to estimate the global incidence of pediatric TSI and the burden of cases. METHODS: PubMed, Embase, and Scopus were searched for reports in June 2021 and updated in March 2023 with no restrictions on language or year of publication. A meta-analysis was conducted to estimate the global incidence of pediatric TSI and, subsequently, the number of cases of pediatric TSI worldwide and the proportion requiring spine surgery. RESULTS: Of 6557 studies, 25 met the inclusion criteria. Road traffic accidents (64%) were responsible for most cases reported in the literature, followed by falls (18%). The global incidence of TSI in children aged ≤20 years was estimated to be 14.24 of 100,000 children, or 375,734 children, with an estimated 114,975 requiring spine surgery. Across the World Bank income classification groups, lower middle-income countries had the highest pediatric TSI case burden (186,886 cases, with 57,187 requiring spine surgery). Across the World Health Organization regions, countries in the Southeast Asia region had the largest number of projected cases at 88,566, with 27,101 requiring surgical management, followed closely by the African region, with 87,235 projected cases and 26,694 requiring surgical management. CONCLUSIONS: Pediatric TSI represents a large healthcare burden globally. Interventions targeting both injury prevention and strengthening of neurosurgical capacity, especially in low resource settings, are needed to address this global health challenge.

A Comparison of Surgery Wait Times and Postoperative Length of Hospital Stay Among Patients with Brain Tumors by Country-Level Income and Healthcare System: A Systematic Review and Meta-analysis.

OBJECTIVE: The current study highlights the differences in surgery wait times and postoperative length of hospital stay (LOS) for brain tumor patients between high income countries (HICs) and low- and middle-income countries (LMICs), and across countries with different payer health systems. METHODS: A systematic review and meta-analysis were performed in accordance with the Preferred Reporting Items of Systematic Reviews and Meta-analyses (PRISMA) guidelines. Outcomes of interest were surgery wait time and postoperative LOS. RESULTS: Fifty-three articles were included totaling 456,432 patients. Five studies discussed surgery wait times and 27 discussed LOS. Three HIC studies reported mean surgery wait time of 4 days (SD not reported), 33 ± 13 days, and 34 ± 39 days, and 2 LMIC studies reported median surgery wait time of 4.6 (1-15) and 50 (13-703) days. Mean LOS was 5.1 days (95% CI: 4.2-6.1 days) from 24 HIC studies and 10.0 days (95% CI: 4.6-15.6 days) from 8 LMIC studies respectively. Mean LOS was 5.0 days (95% CI: 3.9-6.0 days) from countries with mixed payer system, and 7.7 days (95% CI: 4.8-10.5 days) from countries with single payer systems. CONCLUSIONS: There are limited data on surgery wait-times yet slightly more data on postoperative LOS. Despite a wide range of wait times, mean LOS in brain tumor patients tended to be longer in LMICs than HICs and longer for countries with single payer health systems than mixed payer health systems. Further studies are needed to evaluate surgery wait times and LOS for brain tumor patients more accurately.

The characteristic of the key aroma-active components in white tea using GC-TOF-MS and GC-olfactometry combined with sensory-directed flavor analysis.

BACKGROUND: White tea has become more and more popular with consumers due to its health benefits and unique flavor. However, the key aroma-active compounds of white tea during the aging process are still unclear. Thus, the key aroma-active compounds of white tea during the aging process were investigated using gas chromatography-time-of-flight-mass spectrometry (GC-TOF-MS) and gas chromatography-olfactometry (GC-O) combined with sensory-directed flavor analysis. RESULTS: A total of 127 volatile compounds were identified from white tea samples with different aging years by GC-TOF-MS. Fifty-eight aroma-active compounds were then determined by GC-O, and 19 of them were further selected as the key aroma-active compounds based on modified frequency (MF) and odor activity value (OAV). CONCLUSION: Aroma recombination and omission testing confirmed that 1-octen-3-ol, linalool, phenethyl alcohol, geraniol, (E)-ß-ionone, α-ionone, hexanal, phenylacetaldehyde, nonanal, (E, Z)-(2,6)-nonadienal, safranal, γ-nonalactone and 2-amylfuran were the common key aroma-active compounds to all samples. Cedrol, linalool oxide II and methyl salicylate were confirmed peculiar in new white tea, while ß-damascenone and jasmone were peculiar in aged white tea. This work will offer support for further studies on the material basis of flavor formation of white tea. © 2023 Society of Chemical Industry.

Identification of the immune-related biomarkers in Behcet's disease by plasma proteomic analysis.

BACKGROUND: This study aimed to investigate the expression profile of immune response-related proteins of Behcet's disease (BD) patients and identify potential biomarkers for this disease. METHODS: Plasma was collected from BD patients and healthy controls (HC). Immune response-related proteins were measured using the Olink Immune Response Panel. Differentially expressed proteins (DEPs) were used to construct prediction models via five machine learning algorithms: naive Bayes, support vector machine, extreme gradient boosting, random forest, and neural network. The prediction performance of the five models was assessed using the area under the curve (AUC) value, recall (sensitivity), specificity, precision, accuracy, F1 score, and residual distribution. Subtype analysis of BD was performed using the consensus clustering method. RESULTS: Proteomics results showed 43 DEPs between BD patients and HC (P < 0.05). These DEPs were mainly involved in the Toll-like receptor 9 and NF-κB signaling pathways. Five models were constructed using DEPs [interleukin 10 (IL10), Fc receptor like 3 (FCRL3), Mannan-binding lectin serine peptidase 1 (MASP1), NF2, moesin-ezrin-radixin like (MERLIN) tumor suppressor (NF2), FAM3 metabolism regulating signaling molecule B (FAM3B), and O-6-methylguanine-DNA methyltransferase (MGMT)]. Among these models, the neural network model showed the best performance (AUC = 0.856, recall: 0.692, specificity: 0.857, precision: 0.900, accuracy: 0.750, F1 score: 0.783). BD patients were divided into two subtypes according to the consensus clustering method: one with high disease activity in association with higher expression of tripartite motif-containing 5 (TRIM5), SH2 domain-containing 1A (SH2D1A), phosphoinositide-3-kinase adaptor protein 1 (PIK3AP1), hematopoietic cell-specific Lyn substrate 1 (HCLS1), and DNA fragmentation factor subunit alpha (DFFA) and the other with low disease activity in association with higher expression of C-C motif chemokine ligand 11 (CCL11). CONCLUSIONS: Our study not only revealed a distinctive immune response-related protein profile for BD but also showed that IL10, FCRL3, MASP1, NF2, FAM3B, and MGMT could serve as potential immune biomarkers for this disease. Additionally, a novel molecular disease classification model was constructed to identify subsets of BD.

Evaluation of myopia-associated genes in a Han Chinese population with high myopia.

BACKGROUND: High myopia is a leading cause of blindness worldwide. However, the exact etiology and mechanism of high myopia remain unclear. Previous genome-wide association study has demonstrated that nine single nucleotide polymorphisms (SNPs) in East and Southeast Asian populations were associated with high myopia and proved that the nervous system was involved in the pathogenesis of high myopia. The present study was conducted to investigate whether these genetic variants retinal nervous system-related were associated with high myopia among Han Chinese. METHODS: Seven SNPs were genotyped by the MassARRAY iPLEX Gold method in a Han Chinese cohort with the majority from Henan region (central China), which included 361 patients with high myopia and 749 healthy controls. RESULTS: In terms of genotyped SNPs, the allele frequency of rs698047 locus of the HIVEP3 gene were statistically different between myopia and control groups initially, but the difference disappeared after Bonferroni method correction. When the genetic model analysis was performed, the rs698047 locus additive model 2 of the HIVEP3 gene was found to be different between the case and control groups in the Han Chinese population (Pc = 0. 049, OR = 1.64, 95% CI 1.14-2.36). CONCLUSIONS: There was no demonstrated association between the occurrence of high myopia in the Chinese Han population and polymorphisms in the following loci: HIVEP3 (rs698047), NFASC/CNTN2 (rs2246661), ZC3H11B (rs12032649), CNTN4/CNTN6 (rs17029206), FRMD4B (rs74633073), AKAP13 (rs72748160), and GJD2 (rs589135).

Association Between HLA Polymorphisms and Sympathetic Ophthalmia in Han Chinese.

PURPOSE: Sympathetic ophthalmia (SO) is considered as an autoimmune disease with unclear mechanisms. This study investigated the relationship between HLA polymorphisms and SO. METHODS: HLA typing was performed using the LABType reverse SSO DNA typing method. The allele and haplotype frequencies were assessed using the PyPop software. Statistical significance of genotype distributions between 116 patients and 84 healthy individuals (control) was determined using Fisher's exact test or Pearson's chi-squared test. RESULTS: The SO group had a higher frequency of HLA-DRB1 * 04:05, HLA-DQB1 * 04:01, DRB1 * 04:05-DQB1 * 04:01 haplotype as compared to the control group (Pc < 0.001 for all). CONCLUSION: This study revealed that DRB1 * 04:05 and DQB1 * 04:01 alleles, as well as DRB1 * 04:05-DQB1 * 04:01 haplotye could be potential risk factors for SO.

Identification of a highly promiscuous glucosyltransferase from Penstemon barbatus for natural product glycodiversification.

Glycosylation reactions mediated by UDP-glycosyltransferases (UGTs) are common post-modifications involved in plant secondary metabolism and significantly improve the solubility and bioactivity of aglycones. Penstemon barbatus is rich in phenylethanoid glycosides (PhGs), such as echinacoside and verbascoside. In this study, a promiscuous glycosyltransferase UGT84A95 was identified from P. barbatus. In vitro enzyme assays showed that UGT84A95 catalyzed the glucosylation of the phenol hydroxyl group of PhGs efficiently as well as other structurally diverse phenolic glycosides, including flavonoids, terpenoids, stilbene glycosides, coumarins, and simple polyphenols. By using UGT84A95, 12 glycosylated products were prepared and structurally identified by NMR spectroscopy, among which 7 are new compounds. These findings suggest that UGT84A95 could be a potential biocatalyst to synthesize multi-glycosylated glycosides.

Overall survival and toxicity of hepatocellular carcinoma Barcelona Clinic Liver Cancer B patients receiving Y90 radioembolization: analysis of the radiation-emitting SIR-spheres in non-resectable liver tumor (RESiN) registry.

Background: To evaluate overall survival (OS), progression-free survival (PFS) and toxicity after resin Yttrium-90 (Y-90) radioembolization in Barcelona Clinic Liver Cancer B (BCLC B) hepatocellular carcinoma (HCC) patients using the Bolondi subgroup classification. Methods: A total of 144 BCLC B patients were treated between 2015-2020. Patients were broken into 4 subgroups by tumor burden/liver function tests with 54, 59, 8 and 23 in subgroups 1, 2, 3 and 4. OS and PFS were calculated with Kaplan-Meier analysis with 95% confidence intervals. Toxicities were assessed using Common Terminology Criteria for Adverse Events (CTCAE) v5. Results: Prior resection and chemoembolization were performed in 19 (13%) and 34 (24%) of patients. There were no deaths within 30 days. Median OS and PFS for the cohort were 21.5 and 12.4 months. Median OS was not reached for subgroup 1 at a mean 28.8 months, and was 24.9, 11.0 and 14.6 months for subgroups 2-4 (χ2=19.8, P=0.0002). PFS by BCLC B subgroup was 13.8, 12.4, 4.5, and 6.6 months (χ2=16.8, P=0.0008). The most common Grade 3 or 4 toxicities were elevated bilirubin (n=16, 13.3%) and decreased albumin (n=15, 12.5%). Grade 3 or greater bilirubin (32% vs. 10%, P=0.03) and albumin (26% vs. 10%, P=0.03) toxicity were more common in the subgroup 4 patients. Conclusions: The Bolondi subgroup classification stratifies OS, PFS and development of toxicity in patients treated with resin Y-90 microspheres. OS in subgroup 1 approaches 2.5 years and Grade 3 or greater hepatic toxicity profile in subgroups 1-3 is low.