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.

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.

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).

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.

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.

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.

B cell repopulation trajectory after rituximab treatment in autoimmune diseases: a longitudinal observational study.

To investigate B-cell repopulation trajectory and the associated factors in patients with autoimmune diseases (AIDs) who underwent rituximab (RTX) treatment. This is a retrospective study in a large tertiary medical center. Kaplan-Meier analysis and Cox regression were used to investigate factors associated with B-cell repopulation. Latent class trajectory modeling (LCTM) was employed to identify distinct B-cell repopulation trajectory longitudinally. A total of 224 patients were included, with a cumulative follow-up time of 193.6 person-years. Patients with antineutrophil cytoplasm antibody-associated vasculitis (AAV), connective tissue disease, and IgG4-related disease exhibited significant differences in B-cell repopulation time (p = 0.0055 by log-rank test). Multivariate Cox regression identified that higher levels of IgA (HR 1.21, 95%CI 1.01-1.45, p = 0.040) and concurrent glucocorticoid use (HR = 0.37,95%CI 0.20-0.67, p = 0.001) were associated with B-cell repopulation. The cluster showing prolonged B-cell depletion, identified by LCTM, had lower proportions of male (27% vs. 48.5%, p = 0.033), smoke history (17.6% vs. 38.7%, p = 0.025), higher proportions of AAV (44.3% vs. 15.2%, p = 0.004), RTX dose (p = 0.042), history of cyclophosphamide use (70.4% vs. 48.5%, p = 0.003), meanwhile glucocorticoid use (94.8% vs. 72.7%, p = 0.001). The trajectory of B-cell repopulation after RTX infusion in AIDs was heterogeneous. Certain factors were associated with B-cell repopulation, and a specific cluster of patients demonstrated prolonged B-cell depletion after RTX treatment.

Study on the mechanism of stir-fried Fructus Tribuli in enhancing the essential hypertension treatment by an integrated "spectrum-effect relationship-network pharmacology-metabolomics" strategy.

Essential hypertension (EH) is a leading cause of cardiovascular morbidity and mortality. Fructus Tribuli (FT), as a traditional medicine, has been frequently used for thousands of years. The crude Fructus Tribuli (CFT), decoction pieces being processed to remove impurities, have been listed as an important medicine for the treatment of hypertension in the elderly. According to the theory of traditional Chinese medicine, the CFT can enhance the EH treatment after being stir-fried into stir-fried Fructus Tribuli (SFT). At present, whether the SFT can enhance the EH treatment and its potential pharmacodynamic substances and mechanism are unknown. In this study, an integrated "spectrum-effect relationship-network pharmacology-metabolomics" strategy was used. Using male spontaneously hypertensive rats as an experimental model, we compared the therapeutic effects of CFT and SFT on EH. Subsequently, to define the pharmacodynamic material basis of SFT in enhancing the EH treatment, the steroidal saponins (main active components of FT) were selected for spectrum-effect relationship analysis. Furthermore, we applied the joint pathway analysis of network pharmacology and metabolomics to explore the underlying mechanism of SFT in enhancing the EH treatment. Results showed that SFT was better than CFT in the EH treatment. The steroidal saponins transformed by stir-frying were the potential pharmacodynamic substances that SFT could enhance the EH treatment. And the mechanism of action might be associated with regulating glycerophospholipid metabolism and arachidonic acid metabolism, especially arachidonic acid metabolism. This study provided a scientific basis for the clinical use of SFT as an important medicine for the EH treatment.

Network pharmacology-based approach uncovers the pharmacodynamic components and mechanism of Fructus Tribuli for improving endothelial dysfunction in hypertension.

ETHNOPHARMACOLOGICAL RELEVANCE: Fructus Tribuli (FT), a traditional Chinese medicinal herbal, has been used for the clinical treatment of cardiovascular diseases for many years and affects vascular endothelial dysfunction (ED) in patients with hypertension. AIM OF THE STUDY: This study aimed to demonstrate the pharmacodynamic basis and mechanisms of FT for the treatment of ED. MATERIALS AND METHODS: The present study used ultra-high-performance liquid chromatography coupled with quadruple-time-of-flight mass spectrometry (UHPLC-Q-TOF/MS) to analyze and identify the chemical components of FT. The active components in blood were determined after the oral administration of FT by comparative analysis to blank plasma. Then, based on the active components in vivo, network pharmacology was performed to predict the potential targets of FT in treating ED. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were also performed, and component-target-pathway networks were constructed. Interactions between the major active components and main targets were verified by molecular docking. Moreover, spontaneously hypertensive rats (SHRs) were divided into the normal, model, valsartan, low-dose FT, medium-dose FT, and high-dose FT experimental groups. In pharmacodynamic verification studies, treatment effects on blood pressure, serum markers (nitric oxide [NO], endothelin-1 [ET-1,], and angiotensin Ⅱ [Ang Ⅱ)]) of ED, and endothelial morphology of the thoracic aorta were evaluated and compared between groups. Finally, the PI3K/AKT/eNOS pathway was analyzed by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot of the thoracic aorta of rats in each group to detect the mRNA expression of PI3K, AKT, and eNOS and the protein expression of PI3K, AKT, p-AKT, eNOS, and p-eNOS. RESULTS: A total of 51 chemical components were identified in FT, and 49 active components were identified in rat plasma. Thirteen major active components, 22 main targets, and the PI3K/AKT signaling pathway were screened by network pharmacology. The animal experiment results showed that FT reduced systolic blood pressure and ET-1 and Ang Ⅱ levels and increased NO levels in SHRs to varying degrees. The therapeutic effects were positively correlated with the oral dose of FT. Hematoxylin-eosin (HE) staining confirmed that FT could alleviate the pathological damage of the vascular endothelium. qRT-PCR and Western blot analysis confirmed that up-regulated expression of the PI3K/AKT/eNOS signaling pathway could improve ED. CONCLUSIONS: In this study, the material basis of FT was comprehensively identified, and the protective effect on ED was confirmed. FT had a treatment effect on ED through multi-component, multi-target, and multi-pathways. It also played a role by up-regulating the PI3K/AKT/eNOS signaling pathway.

Pathological findings in congenital diaphragmatic hernia on necropsy studies: A single-center case series.

INTRODUCTION: Congenital diaphragmatic hernia (CDH) is associated with high mortality rates and significant pulmonary morbidities. The objective of this study was to delineate the histopathological features observed in necropsies of CDH patients and correlate these with their clinical manifestations. METHODS: We retrospectively reviewed the postmortem findings and corresponding clinical characteristics in eight CDH cases from 2017 to July 2022. RESULTS: The median survival time was 46 (8-624) hours. Autopsy reports showed that diffuse alveolar damage (congestion and hemorrhage) and hyaline membrane formation were the primary pathological lung changes observed. Notably, despite significant reduction in lung volume, the lung development appeared normal in 50% of the cases, while lobulated deformities were present in three (37.5%) cases. All patients displayed a large patent ductus arteriosus (PDA) and a patent foramen ovale, resulting in increased right ventricle (RV) volume, and myocardial fibers appeared slightly congested and swollen. The pulmonary vessels indicated thickening of the arterial media and adventitia. Lung hypoplasia and diffuse lung damage resulted in impaired gas exchange, while PDA and pulmonary hypertension led to RV failure, subsequent organ dysfunction and ultimately death. CONCLUSIONS: Patients with CDH typically succumb to cardiopulmonary failure, a condition driven by a complex interplay of pathophysiological factors. This complexity accounts for the unpredictable response to currently available vasodilators and ventilation therapies.

The external validation of the 2019 ACR/EULAR classification criteria for IgG4-related disease in a large cohort from China.

OBJECTIVE: To externally validate the performance of the 2019 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) classification criteria for IgG4-related disease (IgG4-RD) within a cohort from China and to compare the criteria with the 2020 revised comprehensive diagnostic (RCD) criteria for IgG4-RD. METHODS: This study included 875 IgG4-RD and 302 non-IgG4-RD cases (213 mimickers and 89 patients with other diseases). Using expert clinical judgment as the gold standard for diagnosis of IgG4-RD, the performance (sensitivity, specificity, area under the curve (AUC) of the 2019 ACR/EULAR criteria for IgG4-RD was evaluated. We also compared it with the 2020 RCD criteria. RESULTS: The 2019 ACR/EULAR classification criteria had a sensitivity of 76.6% (95% CI: 73.8% to 79.4%) and a specificity of 98.0% (96.0%-99.4%), an AUC of 0.873 (0.857-0.889) in the overall cohort. Those false negative cases under the 2019 ACR/EULAR classification criteria had significantly lower levels of serum IgG4, and fewer had pathological information, with a higher frequency in the involvement of those uncommon organs compared with the true positive cases. The cases judged as negative by the 2019 ACR/EULAR classification criteria yet judged as "definite" by the 2020 RCD criteria had more involvement of uncommon organs. CONCLUSIONS: The 2019 ACR/EULAR classification criteria for IgG4-RD show outstanding specificity and good sensitivity in real-world clinical practice. The 2020 RCD criteria are helpful for the diagnosis of IgG4-RD in clinical scenarios where IgG4-RD presents as involving an isolated organ, especially the unusual sites.

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.

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.

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.

Potential impact of autoimmune diseases family history in IgG4-related disease: a retrospective cohort study.

OBJECTIVE: Autoimmune comorbidities may be associated with IgG4-related disease (IgG4-RD), here we aimed to determine the correlation of autoimmune diseases (AID) family history and IgG4-RD in a Chinese cohort. METHODS: This retrospective cohort study identified 628 cases of IgG4-RD in Peking Union Medical College Hospital. Patients were classified into two groups, with AID family history group (AID-positive) and without AID family history group (AID-negative). We viewed the potential value of AID family history on IgG4-RD by comparing the differences between the two groups. In addition, Cox regression analysis estimated CIs and HR for IgG4-RD risk. RESULTS: 93 (14.8%) IgG4-RD patients had AID family history. Compared with AID-negative group, baseline data analysis revealed that AID-positive group patients had an earlier age of IgG4-RD onset (50.4±14.8 vs 54.2±12.6, p=0.014*), a higher percentage of antinuclear antibody (ANA) positivity (38.9% vs 22.7%, p=0.0277*) and Riedel thyroiditis (10.9% vs 2.4%, p=0.001*), were prone to comorbid with other AID (16.1% vs 6.2%, p=0.0238*). Cox analysis found that younger age (HR 0.97 (95% CI 0.94 to 0.99), p=0.0384*) and higher proportions of baseline peripheral eosinophils (HR 1.1 (95% CI 1.02 to 1.2), p=0.0199*) increased the risk of unfavourable prognosis for AID-positive IgG4-RD patients. CONCLUSIONS: 14.8% of IgG4-RD patients had AID family history, with younger age of disease onset age and higher frequency of ANA positivity in AID-positive group, indicating that IgG4-RD may share genetic background with other AID.

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.

Ex utero intrapartum therapy in infants with congenital diaphragmatic hernia: a propensity score matching analysis.

Objective: Previous studies have shown that ex utero intrapartum therapy (EXIT) is safe and feasible for newborns with congenital diaphragmatic hernia (CDH). This study reports our experience with EXIT in fetuses with CDH in an attempt to explore the efficacy of EXIT on the survival rate of this population. Methods: A retrospective analysis of the clinical data of 116 children with CDH was conducted. The children were assigned to EXIT and non-EXIT groups. Propensity score matching (PSM) toward clinical data was performed, and the clinical characteristics and outcomes were compared. Taking survival at discharge as the main outcome, logistic regression analysis was carried out to explore the efficacy of EXIT on survival. Results: During the study period, 30 of 116 children received EXIT. After PSM, the survival rates of the EXIT group and the non-EXIT group were 82.76% (24/29) and 48.28% (14/29), respectively (p=0.006). EXIT (OR=0.083, 95% CI=0.013to 0.525, p=0.008), liver herniation (OR=16.955, 95% CI=2.342 to 122.767, p=0.005), and gestational age at diagnosis (OR=0.662, 95% CI=0.497 to 0.881, p=0.005) were independent mortality-related risk factors of all children with CDH. Ninety-nine of 116 children underwent surgery. After PSM, the postoperative survival rates of the EXIT group and non-EXIT group were 84.6% (22/26) and 76.9% (20/26), respectively (p=0.754). Liver herniation (OR=10.451, 95% CI=1.641 to 66.544, p=0.013) and gestational age at diagnosis (OR=0.736, 95% CI=0.577 to 0.938, p=0.013) were independent mortality-related risk factors of children after surgery. Conclusion: EXIT can be performed safely for selected prenatally diagnosed CDH neonates with potentially better survival and does not cause more maternal complications compared with traditional cesarean section.

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.

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.

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.