Hypogammaglobulinemia and Infection Events in Patients with Autoimmune Diseases Treated with Rituximab: 10 Years Real-Life Experience.

OBJECTIVES: To investigate predictors of hypogammaglobulinemia (HGG) and severe infection event (SIE) in patients with autoimmune disease (AID) receiving rituximab (RTX) therapy. METHODS: This was a retrospective study conducted in a tertiary medical center in China. Predictors of HGG or SIE were assessed using Cox analysis. Restricted cubic spline (RCS) analysis was applied to examine the correlation between glucocorticoid (GC) maintenance dose and SIE. RESULTS: A total of 219 patients were included in this study, with a cumulative follow-up time of 698.28 person-years. Within the study population, 117 patients were diagnosed with connective tissue disease, 75 patients presented with ANCA-associated vasculitis, and 27 patients exhibited IgG4-related disease. HGG was reported in 63.3% of the patients, where an obvious decline in IgG and IgM was shown three months after RTX initiation. The rate of SIE was 7.2 per 100 person-years. An increase in the GC maintenance dose was an independent risk factor for both hypo-IgG (HR 1.07, 95% CI 1.02-1.12, p = 0.003) and SIE (HR 1.06, 95% CI 1.02-1.1, p = 0.004). Further RCS analysis identified 7.48 mg/d prednisone as a safe threshold dose for patients who underwent RTX treatment to avoid a significantly increased risk for SIE. CONCLUSION: HGG was relatively common in RTX-treated AID patients. Patients with chronic lung disease or who were taking ≥ 7.5 mg/d prednisone during RTX treatment were at increased risk for SIE and warrant attention from physicians.

Expansion and surface makers of age-associated B cells in IgG4-related disease.

OBJECTIVES: To assess the expression of age-associated B cells (ABCs), and characterise the surface markers of ABCs in patients with IgG4-related disease (IgG4-RD). METHODS: Fifty-one newly diagnosed patients with IgG4-RD, 18 IgG4-RD patients with disease remission, 34 patients with other autoimmune diseases, and 61 age- and sex-matched healthy controls (HCs) were included. Circulating ABCs, as well as surface markers were detected by flow cytometry, and tissue infiltration of ABCs were assessed by immunofluorescence (IF). The expression of ABCs in the affected organs of LatY136F knock-in (LAT) mouse models (IgG4-RD mouse model) were explored by flow cytometry and IF. RESULTS: The percentages and absolute numbers of ABCs (gated as CD21-T-bet+CD11c+) in CD19+ B cells raised remarkably in untreated IgG4-RD patients than HC, and reduced significantly after treatment. The percentage of CD27+ABCs, DN2 B cells and activated naive B cells was higher in patients with IgG4-RD than in HCs and patients with multiple autoimmune diseases, whereas the percentage was comparable with that in patients with systemic lupus erythematosus. Phenotypical analysis revealed upregulated levels of CD86, TACI, CD38, and downregulated level of CXCR3 in peripheral CD19+CD21-CD11c+ B cells of IgG4-RD patients compared with that of HC. In IgG4-RD patients, CD19+CD21- CD11c+ cells expressed higher levels of CD80, CXCR3, TACI, CD95, and BAFF-R, while lower levels of CD86, CD27, CD38, and CXCR5 compared with CD19+ CD21- CD11c- B cells. ABCs (CD11c+T-bet+ gated in B220+ cells) were increased significantly in lungs of LAT mice than that of wild type (WT) mice. CONCLUSIONS: ABCs were expanded both in the peripheral blood and affected tissues of patients with IgG4-RD as well as in the lungs of LAT mice, indicating the potential roles of ABCs in IgG4-RD pathogenesis.

Development of a prediction nomogram for 1-month mortality in neonates with congenital diaphragmatic hernia.

OBJECTIVES: Although many prognostic factors in neonates with congenital diaphragmatic hernia (CDH) have been described, no consensus thus far has been reached on which and how many factors are involved. The aim of this study is to analyze the association of multiple prenatal and postnatal factors with 1-month mortality of neonates with CDH and to construct a nomogram prediction model based on significant factors. METHODS: A retrospective analysis of neonates with CDH at our center from 2013 to 2022 was conducted. The primary outcome was 1-month mortality. All study variables were obtained either prenatally or on the first day of life. Risk for 1-month mortality of CDH was quantified by odds ratio (OR) with 95% confidence interval (CI) in multivariable logistic regression models. RESULTS: After graded multivariable adjustment, six factors were found to be independently and consistently associated with the significant risk of 1-month mortality in neonates with CDH, including gestational age of prenatal diagnosis (OR, 95% CI, P value: 0.845, 0.772 to 0.925, < 0.001), observed-to-expected lung-to-head ratio (0.907, 0.873 to 0.943, < 0.001), liver herniation (3.226, 1.361 to 7.648, 0.008), severity of pulmonary hypertension (6.170, 2.678 to 14.217, < 0.001), diameter of defect (1.560, 1.084 to 2.245, 0.017), and oxygen index (6.298, 3.383 to 11.724, < 0.001). Based on six significant factors identified, a nomogram model was constructed to predict the risk for 1-month mortality in neonates with CDH, and this model had decent prediction accuracy as reflected by the C-index of 94.42%. CONCLUSIONS: Our findings provide evidence for the association of six preoperational and intraoperative factors with the risk of 1-month mortality in neonates with CDH, and this association was reinforced in a nomogram model.

Memory CD4+T cell profile is associated with unfavorable prognosis in IgG4-related disease: Risk stratification by machine-learning.

IgG4-related disease (IgG4-RD) is a chronic immune-mediated disease with heterogeneity. In this study, we used machine-learning approaches to characterize the immune cell profiles and to identify the heterogeneity of IgG4-RD. The XGBoost model discriminated IgG4-RD from HCs with an area under the receiver operating characteristic curve of 0.963 in the testing set. There were two clusters of IgG4-RD by k-means clustering of immunological profiles. Cluster 1 featured higher proportions of memory CD4+T cell and were at higher risk of unfavorable prognosis in the follow-up, while cluster 2 featured higher proportions of naïve CD4+T cell. In the multivariate logistic regression, cluster 2 was shown to be a protective factor (OR 0.30, 95% CI 0.10-0.91, P = 0.011). Therefore, peripheral immunophenotyping might potentially stratify patients with IgG4-RD and predict those patients with a higher risk of relapse at early time.

Preliminary study on the predictive value of the vasoactive-inotropic score for the prognosis of neonatal congenital diaphragmatic hernia.

BACKGROUND: No study has reported on the relationship between the vasoactive-inotropic score (VIS) and the prognosis of neonates with a severe congenital diaphragmatic hernia (CDH). This study aimed to identify potential risk factors for mortality in patients with CDH. We calculated the VIS based on the vasoactive drugs used during the perioperative period to investigate the relationship between VIS and infant prognosis. METHODS: We retrospectively analyzed the clinical data of 75 neonates with CDH who were treated at our center between January 2016 and October 2021. We calculated the maximum and mean VIS during the first 24 h of hospitalization (hosVIS [24max] and hosVIS [24mean], respectively) and after surgery (postVIS [24max] and postVIS [24mean], respectively). The relationship between the VIS and the prognosis of neonates with CDH was analyzed using a receiver operating characteristic (ROC) curve, t-test, chi-square test, rank-sum test, and logistic regression analysis. RESULTS: In total, 75 participants with CDH were included in the study. The chance of survival was 80%. Our results showed that hosVIS (24max) was an accurate predictor of prognosis (area under the ROC curve = 0.925, p = 0.007). The calculated optimal critical value of hosVIS (24max) for predicting a poor prognosis was 17 (J = 0.75). Multivariate analysis revealed that hosVIS (24max) was an independent risk factor for death in neonates with CDH. CONCLUSION: In neonates with CDH, a higher VIS, especially hosVIS (24max), suggests worsened cardiac function, a more severe condition, and a higher risk of death. The rising VIS score in infants prompts physicians to implement more aggressive treatment to improve cardiovascular function.

TSLP promoting B cell proliferation and polarizing follicular helper T cell as a therapeutic target in IgG4-related disease.

OBJECTIVE: To figure out the functions of thymic stromal lymphopoietin (TSLP) in IgG4-related disease (IgG4-RD). METHODS: Plasma TSLP levels were tested by Elisa, and its receptors were detected by flow cytometry. Expressions of TSLP and TSLPR in involved tissues were stained by immunohistochemistry and immunofluorescence. Proliferation, apoptosis, and B subsets of TSLP stimulated-B cells were analyzed by flow cytometry. TSLP-stimulated B cells were co-cultured with CD4+ Naïve T cells. Signaling pathway was identified by RNA-sequencing and western blot. Anti-TSLP therapy was adapted in LatY136F knock-in mice (Lat, IgG4-RD mouse model). RESULTS: Plasma TSLP level was increased in IgG4-RD patients and was positively correlated with serum IgG4 level and responder index (RI). TSLPR was co-localized with CD19+ B cells in the submandibular glands (SMGs) of IgG4-RD. TSLP promoted B cell proliferation, and TSLP-activated B cells polarized CD4+ naive T cells into follicular helper T (Tfh) cells through OX40L. RNA-sequencing identified JAK-STAT signaling pathway in TSLP-activated B cells and it was verified by western blot. Anti-TSLP therapy alleviated the inflammation of lung in Lat mice. CONCLUSION: Elevated TSLP in IgG4-RD promoted B cells proliferation and polarized Tfh cells and might be served as a potential therapeutic target.

Genome-wide identification, characterization, and expression analysis of the monovalent cation-proton antiporter superfamily in maize, and functional analysis of its role in salt tolerance.

Na+, K+ and pH homeostasis are important for plant life and they are controlled by the monovalent cation proton antiporter (CPA) superfamily. The roles of ZmCPAs in salt tolerance are not fully elucidated. In this study, we identified 35 ZmCPAs comprising 13 Na+/H+ exchangers (ZmNHXs), 16 cation/H+ exchanger (ZmCHXs), and 6 K+ efflux antiporters (ZmKEAs). All ZmCPAs have transmembrane domains and most of them were localized to plasma membrane or tonoplast. ZmCHXs were specifically highly expressed in anthers, while ZmNHXs and ZmKEAs showed high expression in various tissues. ZmNHX5 and ZmKEA2 were up-regulated in maize seedlings under both NaCl and KCl stresses. Yeast complementation experiments revealed the roles of ZmNHX5, ZmKEA2 in NaCl tolerance. Analysis of the maize mutants further validated the salt tolerance functions of ZmNHX5 and ZmKEA2. Our study highlights comprehensive information of ZmCPAs and provides new gene targets for salt tolerance maize breeding.

Impact of the COVID-19 pandemic on congenital diaphragmatic hernia patients: a single-center retrospective study.

PURPOSE: To investigate the impact of COVID-19 on the treatment of children with congenital diaphragmatic hernia (CDH). METHODS: We retrospectively collected and compared the data of patients with CDH admitted between January 1, 2020 and December 31, 2021(study group) with the CDH patients admitted before the pandemic between January 1, 2018 and December 31, 2019 (control group). RESULTS: During the pandemic, 41 patients with CDH diagnosed prenatally were transferred to our hospital, and 40 underwent surgical repair. The number of patients treated in our hospital increased by 24.2% compared with the 33 patients before the pandemic. During the pandemic, the overall survival rate, postoperative survival rate and recurrence rate were 85.4%, 87.5% and 7.3%, respectively, and there were no significant differences compared with the control group (75.8%, 83.3% and 9.1%, respectively). The average length of hospital stay in patients admitted during the pandemic was longer than that in the control group (31 days vs. 16 days, P < 0.001), and the incidence of nosocomial infection was higher than that in the control group (19.5% vs. 3%, P = 0.037). CONCLUSIONS: CDH patients confirmed to be SARS-CoV-2 infection-free can receive routine treatment. Our data indicate that the implementation of protective measures during the COVID-19 pandemic, along with appropriate screening and case evaluation, do not have a negative impact on the prognosis of children.

Molecular dissection of maize seedling salt tolerance using a genome-wide association analysis method.

Salt stress is a major devastating abiotic factor that affects the yield and quality of maize. However, knowledge of the molecular mechanisms of the responses to salt stress in maize is limited. To elucidate the genetic basis of salt tolerance traits, a genome-wide association study was performed on 348 maize inbred lines under normal and salt stress conditions using 557 894 single nucleotide polymorphisms (SNPs). The phenotypic data for 27 traits revealed coefficients of variation of >25%. In total, 149 significant SNPs explaining 6.6%-11.2% of the phenotypic variation for each SNP were identified. Of the 104 identified quantitative trait loci (QTLs), 83 were related to salt tolerance and 21 to normal traits. Additionally, 13 QTLs were associated with two to five traits. Eleven and six QTLs controlling salt tolerance traits and normal root growth, respectively, co-localized with QTL intervals reported previously. Based on functional annotations, 13 candidate genes were predicted. Expression levels analysis of 12 candidate genes revealed that they were all responsive to salt stress. The CRISPR/Cas9 technology targeting three sites was applied in maize, and its editing efficiency reached 70%. By comparing the biomass of three CRISPR/Cas9 mutants of ZmCLCg and one zmpmp3 EMS mutant with their wild-type plants under salt stress, the salt tolerance function of candidate genes ZmCLCg and ZmPMP3 were confirmed. Chloride content analysis revealed that ZmCLCg regulated chloride transport under sodium chloride stress. These results help to explain genetic variations in salt tolerance and provide novel loci for generating salt-tolerant maize lines.

Natural variations in the P-type ATPase heavy metal transporter gene ZmHMA3 control cadmium accumulation in maize grains.

Cadmium (Cd) accumulation in maize grains is detrimental to human health. Developing maize varieties with low Cd content is important for safe consumption of maize grains. However, the key genes controlling maize grain Cd accumulation have not been cloned. Here, we identified one major locus for maize grain Cd accumulation (qCd1) using a genome-wide association study (GWAS) and bulked segregant RNA-seq analysis with a biparental segregating population of Jing724 (low-Cd line) and Mo17 (high-Cd line). The candidate gene ZmHMA3 was identified by fine mapping and encodes a tonoplast-localized heavy metal P-type ATPase transporter. An ethyl methane sulfonate mutant analysis and an allelism test confirmed that ZmHMA3 influences maize grain Cd accumulation. A transposon in intron 1 of ZmHMA3 is responsible for the abnormal amino acid sequence in Mo17. Based on the natural sequence variations in the ZmHMA3 gene of diverse maize lines, four PCR-based molecular markers were developed, and these were successfully used to distinguish five haplotypes with different grain Cd contents in the GWAS panel and to predict grain Cd contents of widely used maize inbred lines and hybrids. These molecular markers can be used to breed elite maize varieties with low grain Cd contents.

Interaction between SNCA gene polymorphisms and T2DM with Parkinson's disease.

AIMS: To investigate the association of several single nucleotide polymorphisms (SNPs) within alpha-synuclein (SNCA) gene and additional gene-environment interaction with Parkinson's disease (PD) risk. METHODS: Hardy-Weinberg equilibrium (HWE) is tested for controls using SNPstats (http://bioinfo.iconcologia.net/SNPstats). Logistic regression is used to calculate the ORs (95% CI) for relations between the four SNPs and PD risk. The generalized multifactor dimensionality reduction (GMDR) model is used to evaluate the synergy between gene and environment. RESULTS: A total of 1161 people were included in this study, including 386 cases of PD and 775 normal controls. In this study, the genotype frequency of the control group was consistent with HWE distribution. Rs356219-G allele frequency was 30.0% in patients and 19.8% in control group. The rs356221-T allele frequency was 29.7% in the patients and 20.8% in the control group. Rs356219-G and rs356221-T alleles were associated with increased PD risk, with adjusted ORs (95% CI) of 1.92 (1.28-2.52) and 1.52 (1.05-2.02), respectively. We also found no significant correlation between rs2301134 and rs2301135 and susceptibility to PD. The best gene-environment interaction models were determined by GMDR analysis, which shown a significant gene-T2DM interaction combinations, but the gene-alcohol drinking interaction combinations were all not significant. We also conducted stratified analysis for interaction effect using logistic regression. We found that T2DM patients with rs356221-AT/ TT genotype have the highest PD risk, compared to subjects with rs356219-AA genotype, OR (95%CI) = 2.67 (1.83-3.46). CONCLUSIONS: The rs356219-G and rs356221-T, gene-environment interaction between rs356221 and T2DM were all associated with increased PD risk.

Mapping of a major QTL for salt tolerance of mature field-grown maize plants based on SNP markers.

BACKGROUND: Salt stress significantly restricts plant growth and production. Maize is an important food and economic crop but is also a salt sensitive crop. Identification of the genetic architecture controlling salt tolerance facilitates breeders to select salt tolerant lines. However, the critical quantitative trait loci (QTLs) responsible for the salt tolerance of field-grown maize plants are still unknown. RESULTS: To map the main genetic factors contributing to salt tolerance in mature maize, a double haploid population (240 individuals) and 1317 single nucleotide polymorphism (SNP) markers were employed to produce a genetic linkage map covering 1462.05 cM. Plant height of mature maize cultivated in the saline field (SPH) and plant height-based salt tolerance index (ratio of plant height between saline and control fields, PHI) were used to evaluate salt tolerance of mature maize plants. A major QTL for SPH was detected on Chromosome 1 with the LOD score of 22.4, which explained 31.2% of the phenotypic variation. In addition, the major QTL conditioning PHI was also mapped at the same position on Chromosome 1, and two candidate genes involving in ion homeostasis were identified within the confidence interval of this QTL. CONCLUSIONS: The detection of the major QTL in adult maize plant establishes the basis for the map-based cloning of genes associated with salt tolerance and provides a potential target for marker assisted selection in developing maize varieties with salt tolerance.

[Determination of indigo and brilliant blue in different types of food products by high performance liquid chromatography with solid phase extraction].

OBJECTIVE: To develop and validate a solid phase extraction-high performance liquid chromatographic( SPE-HPLC) method for the simultaneous determination of indigo and brilliant blue in different types of food products. METHODS: The artificial colors in food products were extracted by acetonitrile / water and purified by WAX SPE cartridges, The separation was achieved using a Waters Symmetry C_(18)( 5 µm, 4. 6 mm × 250 mm) column and a binary gradient mobile phase of methanol and 0. 02 mol/L ammonium acetate solution, detected by HPLC-PDA. RESULTS: The validated analytical method showed that there was a good linearity in the range of 0. 05- 20. 00 µg/mL for both indigo and brilliant blue( r > 0. 999). The lowest detection limits of indigo and brilliant blue were 0. 04 and 0. 02 mg/kg, respectively. The average recoveries were among 81. 8%- 101. 1%, with relative standard deviation( RSD) of 2. 1%- 4. 9%( n =6) for both artificial colors. CONCLUSION: The method has high selectivity, high sensitivity, good recovery and reproducibility. It is suitable to simultaneously monitor indigo and brilliant blue in several types of food products based on the food classification system of GB 2760-2014.

Association of Blood Manganese and Preeclampsia: A Systematic Review and Meta-analysis.

A systematic review and meta-analysis was performed to comprehensively evaluate the association between manganese (Mn) level and preeclampsia (PE) during pregnancy. Relevant observational studies were retrieved by searching Medline, Web of Science, Embase, and Cochrane Library from database inception to May 25, 2023. Pooling results was performed using a random-effects model incorporating heterogeneity. This meta-analysis incorporated 18 observational studies, which included 1113 women with PE and 5480 normotensive pregnant women. Pooled results showed that compared to normotensive control, women with PE had significantly lower blood Mn concentration (standardized mean difference: -0.36, 95% confidence interval: -0.50 to -0.22, p < 0.001; I2 = 67%). Subgroup analysis showed that the results were not significantly affected by study country (African, Asian, or Western), timing of blood sampling (before, at, or after the diagnosis of PE), mean blood Mn level of controls, or numbers of confounding factors adjusted (p for subgroup analysis all > 0.05), while methods for measuring blood Mn levels might affect the results (p for subgroup difference < 0.001). Finally, pooled results of three studies showed that a high level of blood Mn was related to a low risk of PE with blood Mn analyzed in continuous (risk ratio [RR]: 0.71, 95% CI: 0.59 to 0.85, p < 0.001; I2 = 0%) and categorized variables (RR: 0.50, 95% CI: 0.30 to 0.82, p = 0.006; I2 = 32%). In conclusion, a low blood level of Mn may be associated with PE in pregnant women.

Construction of MOFs@COFs composite material as stationary phase for efficient separation of diverse organic compounds.

BACKGROUND: The development of efficent chromatographic stationary phases (SP) with mixed-mode or multiple interactions in high-performance liquid chromatography (HPLC) for the separation of complex samples is a challenging task. Metal organic frameworks (MOFs)-based SP can provide desired multiple interactions and enable the separation of a diverse range of solutes, but have limitations of low column efficiency and poor stability. RESULTS: Herein, the hybrid MOFs@Covalent organic frameworks (COFs) materials were used as SP in HPLC due to their synergistic structural features. The SiO2@NH2-UiO-66@CTF SP was synthesized by integration of NH2-UiO-66 and covalent triazine framework (CTF) onto silica surface. Due to the unique structure of SiO2@NH2-UiO-66@CTF with hierarchical-pores, this column showed higher column efficiency (up to 49,369 plates m-1 for alkylbenzenes) than the reported columns packed with MOFs-based SP. Owing to the Zr4+-N coordination bonding between CTF and NH2-UiO-66, the structural stability of SiO2@NH2-UiO-66@CTF can be improved. Furthermore, this new column exhibited remarkable column stability with relative standard deviation of retention time of <0.40% after 400 injections. With the combined advantages of multifunctional properties, high column efficiency, and good stability, SiO2@NH2-UiO-66@CTF SP showed excellent selectivity for the separation of a variety of hydrophobic, aromatic, heteroatomic, and hydrophilic analytes. SIGNIFICANCE AND NOVELTY: This work not only offers a promising SP with multiple retention mechanisms for HPLC, but also provides an efficient strategy for development of high column efficiency MOFs-based SP with good stability. Moreover, the MOFs@COFs hybrid materials were expanded in application area through this study, and the research results can also afford the foundation for further explore its structural characteristics.

Ionic liquid-functionalized mesoporous multipod silica for simultaneously effective extraction of aflatoxin B1 and its two precursors from grain.

BACKGROUND: Aflatoxin B1 (AFB1) and its precursors contaminate food and agricultural products, posing a significant risk to food safety and human health, but simultaneous and effective extraction and determination of AFB1 and its precursors with varied structures is still a challenging task. RESULTS: In this study, a bisimidazolium-type ionic liquid functionalized mesoporous multipod silica (SiO2@mPMO-IL(im)2) was fabricated to extract AFB1 and its two precursors, i.e., averantin and sterigmatocystin. The SiO2@mPMO-IL(im)2 could simultaneously extract three targets with varied structures based on the multipods, mesopores, and multifunctional groups. The density functional theory calculations further verified the multiple interactions between SiO2@mPMO-IL(im)2 and targets. The fabricated SiO2@mPMO-IL(im)2 could effectively extract and determine three targets in grains by combing with dispersive solid-phase extraction and high-performance liquid chromatography. Good linearity (r2 > 0.9978), low LODs (0.9-1.5 µg kg-1) and LOQs (3.0-4.5 µg kg-1), satisfactory spiked recoveries (92.5%-106.8%) and high precisions (RSD<6.4%) were observed. SIGNIFICANCE AND NOVELTY: This work demonstrates the feasibility of SiO2@mPMO-IL(im)2 for simultaneous and effective extraction of toxins with varied structures and provides a promising sample preparation for the analysis of AFB1 and its precursors in grain samples.

A Novel and Highly Efficient Microextraction Method for the Determination of Aflatoxin Precursor Averantin in Fatty Grain Samples.

Averantin (AVN) is an important aflatoxin biosynthetic precursor and has been listed in the screening range of mycotoxins. Herein, a novel ionic liquid-based one-, two-, and three-phase transition microextraction (IL-OTTPTME) method was combined with high-performance liquid chromatography for the extraction and determination of AVN in fatty grain samples. The formation of a homogeneous solution and three-phase system during the IL-OTTPTME process allowed both efficient extraction and coextracted lipid cleanup. Density functional theory calculations and distribution coefficient determination results demonstrated that AVN extraction by IL mainly occurred through hydrogen-bond and π-π interactions. Under optimized conditions, the LOD and LOQ of the proposed method were 0.5 and 1.5 ng/g, respectively. Finally, the method was used to determine AVN in several grains with different fat contents, achieving satisfactory relative recoveries (86.0-107.8%) and RSDs (1.2-6.2%, n = 3).

The development and initial validation of IgG4-related disease damage index: a consensus report from Chinese IgG4-RD Consortium.

OBJECTIVE: To develop and conduct an initial validation of the Damage Index for IgG4-related disease (IgG4-RD DI). METHODS: A draft of index items for assessing organ damages in patients with IgG4-RD was generated by experts from the Chinese IgG4-RD Consortium (CIC). The preliminary DI was refined using the Delphi method, and a final version was generated by consensus. 40 IgG4-RD cases representing four types of clinical scenarios were then selected, each with two time points of assessment for at least 3 years of follow-up. 48 rheumatologists from 35 hospitals nationwide were invited to evaluate organ damage using the CIC IgG4-RD DI. The intraclass correlation coefficient (ICC) and the Kendall-W coefficient of concordance (KW) were used to assess the inter-rater reliability. The criterion validity of IgG4-RD DI was tested by calculating the sensitivity and specificity of raters. RESULTS: IgG4-RD DI is a cumulative index consisting of 14 domains of organ systems, including a total of 39 items. The IgG4-RD DI was capable of distinguishing stable and increased damage across the active disease subgroup and stable disease subgroup. In terms of scores at baseline and later observations by all raters, overall consistency in scores at baseline and later observations by all raters was satisfactory. ICC at the two time points was 0.69 and 0.70, and the KW was 0.74 and 0.73, respectively. In subgroup analysis, ICC and KW in all subgroups were over 0.55 and 0.61, respectively. The analysis of criterion validity showed a good performance with a sensitivity of 0.86 (95% CI 0.82 to 0.88), a specificity of 0.79 (95% CI 0.76 to 0.82) and an area under the curve of 0.88 (95% CI 0.85 to 0.91). CONCLUSION: The IgG4-RD DI is a useful approach to analyse disease outcomes, and it has good operability and credibility. It is anticipated that the DI will become a useful tool for therapeutic trials and studies of prognosis in patients with IgG4-RD.

Integrated analysis of transcriptome and metabolome revealed biological basis of sows from estrus to lactation.

Characterization of molecular mechanisms underlying pregnancy development of sows is important for the genetic improvement of pig breeding traits, and also provides resources for biomedical research on human pregnancy diseases. However, the transcriptome and metabolome across multiple developmental stages of sow pregnancy were still lacking. In this study, we obtained 84 distinct RNA sequencing and 42 metabolome datasets of pig blood across six development stages from estrus to lactation. We confirmed the initial sequence and exonic structural features, stage-specific molecules, expression or accumulation pattern of molecules, the regulatory mechanism of transcriptome and metabolome, and important pregnancy-related metabolites both in pigs and humans. In conclusion, we proposed the key differences among the stages of sows from estrus to lactation in RNAs and metabolites and put forward key markers. These data results were expected to provide essential resources for pig breeding and biomedical research on human pregnancy disease.

Fe3O4/ZIFs-based magnetic solid-phase extraction for the effective extraction of two precursors with diverse structures in aflatoxin B1 biosynthetic pathway.

The aflatoxin B1 (AFB1) early warning technique based on precursors is an effective strategy for the prevention of AFB1 contamination risk. The determination of precursors is imperative to ensure the efficiency of the early warning technique. Herein, a controllable magnetic adsorbent Fe3O4/ZIFs was first introduced for the effective extraction and determination of averantin (AVN) and sterigmatocystin (ST) precursors in cereal by combining magnetic solid-phase extraction (MSPE) and high-performance liquid chromatography (HPLC). Benefiting from the abundant adsorption sites and multifunctional groups matching the analytes, Fe3O4/ZIFs effectively and simultaneously extracted AVN and ST with great differences in polarity and structure via multiple interactions. AVN was extracted by Fe3O4/ZIFs mainly through π-π and hydrophobic interactions, while ST was extracted predominantly by electrostatic interactions and surface complexation. The limits of detection were 0.08 µg kg-1 (AVN) and 0.36 µg kg-1 (ST). The developed method exhibited satisfactory spiked recoveries (79.1%-105.4%) in the determination of AVN and ST in rice. This work provides a novel analytical strategy for further studying AFB1 early warning technique and the formation and transformation of aflatoxins.