Ethyl pyruvate alleviates pulmonary arterial hypertension via PI3K-Akt signaling.

Pulmonary arterial hypertension (PAH) is a pathophysiological syndrome that is extremely difficult to manage, and there is currently no effective treatment. We want to elucidate the therapeutic effect of ethyl pyruvate (EP) on PAH and its possible mechanism. Pulmonary artery endothelial cells (PAECs) were cultured in conventional low-oxygen environments, and cellular proliferation was monitored after treatment with EP. Expression of p-PI3K/Akt, LC3-II, and Beclin-1 was detected by Western blot. After hyperkinetic PAH rabbits' models were treated with EP, hemodynamic data were collected. Right ventricular hypertrophy and pulmonary vascular remodeling were evaluated. Expression of p-PI3K/Akt, LC3-II, and Beclin-1 protein was also detected after using autophagy inhibitor and agonists. We found that EP could inhibit PAECs proliferation. After EP treatment, expression of p-PI3K/Akt was upregulated in vitro and in vivo. LC3-II and Beclin-1 were inhibited and their expression was lower after autophagy inhibitor was given, while after administration of autophagy agonists, their expression was higher than that in the EP alone group. Besides, EP attenuated PAH, and right ventricular hypertrophy and pulmonary vascular remodeling were also reversed. EP can reduce PAH and reverse vascular remodeling which is associated with inhibition of autophagy in PAECs based on PI3K-Akt signaling pathway. The results of this study can provide surgical opportunities for patients with severe PAH caused by congenital heart disease in clinical cardiovascular surgery.

Ultrasound-mediated HGF Gene Microbubbles Mitigate Hyperkinetic Pulmonary Arterial Hypertension in Rabbits.

AIM: Hyperkinetic pulmonary arterial hypertension (PAH) is a complication of congenital heart disease. Gene therapy is a new experimental treatment for PAH, and ultrasound-mediated gene-carrying microbubble targeted delivery is a promising development for gene transfer. METHODS: This study successfully established a hyperkinetic PAH rabbit model by a common carotid artery and jugular vein shunt using the cuff style method. Liposome microbubbles carrying the hepatocyte growth factor (HGF) gene were successfully constructed. An in vitro experiment evaluated the appropriate intensity of ultrasonic radiation by Western blots and 3H-TdR incorporation assays. In an in vivo experiment, after transfection of ultrasound-mediated HGF gene microbubbles, catheterisation was applied to collect haemodynamic data. Hypertrophy of the right ventricle was evaluated by measuring the right ventricle hypertrophy index. Western blot and immunohistochemistry analyses were used to detect the expression of human (h)HGF and angiogenic effects, respectively. RESULTS: The most appropriate ultrasonic radiation intensity was 1.0 W/cm2 for 5 minutes. Two weeks after transfection, both systolic pulmonary arterial pressure and mean pulmonary arterial pressure were attenuated. Hypertrophy of the right ventricle was reversed. hHGF was transplanted into the rabbits, resulting in a high expression of hHGF protein and an increase in the number of small pulmonary arteries. Ultrasound-mediated HGF gene microbubble therapy was more effective at attenuating PAH and increasing the density of small pulmonary arteries than single HGF plasmid transfection. CONCLUSIONS: Ultrasound-mediated HGF gene microbubbles significantly improved the target of gene therapy in a rabbit PAH model and enhanced the tropism and transfection rates. Thus, the technique can effectively promote small pulmonary angiogenesis and play a role in the treatment of PAH without adverse reactions.

Serum levels of galactose-deficient IgA1 in Chinese children with IgA nephropathy, IgA vasculitis with nephritis, and IgA vasculitis.

OBJECTIVE: IgA nephropathy (IgAN) and IgA vasculitis with nephritis (IgAV-N) are related diseases. Galactose-deficient IgA1 (Gd-IgA1) plays an important role in the pathology of IgAV-N and IgAN, so we aim to compare the serum levels of Gd-IgA1 in Chinese pediatric patients with IgAN, IgAV-N, and IgAV. METHODS: We retrospectively enrolled 52 patients with IgAN, 57 patients with IgAV-N, 26 patients with IgAV, and 40 healthy children. The serum levels of Gd-IgA1 were measured at the time of biopsy using a lectin-based ELISA method. RESULTS: Gd-IgA1 levels in IgAV-N patients and IgAN patients were higher than in healthy controls (303.94 ± 39.37 U/ml, 314.91 ± 47.79 U/ml vs. 273.57 ± 48.29 U/ml, P < 0.001), and Gd-IgA1 levels in IgAV-N patients were higher than in IgAV patients (303.94 ± 39/ml vs. 286. 21 ± 38.81 U/ml, P = 0.059), but the latter result is not statistically significant. The Gd-IgA1 levels in IgAV patients were comparable with those in healthy controls (286.21 ± 38.81 U/ml vs. 273.57 ± 48.29 U/ml, P = 0.267). Among the four groups, we did not observe significant correlations of Gd-IgA1 levels with eGFR, proteinuria, or the MEST-C score. CONCLUSION: Serum Gd-IgA1 maybe involved in the pathogenesis of the IgAV-N and IgAN. However, we found no statistically significant correlation between Gd-IgA1 levels and clinical and pathological features.

Mesangial C3 deposition and serum C3 levels predict renal outcome in IgA nephropathy.

BACKGROUND: Complement activation plays an important role in the pathogenesis of IgA nephropathy (IgAN). We aimed to evaluate the relationship between mesangial C3 deposition and histologic lesions and to investigate the role of mesangial C3 deposition and serum C3 reduction in predicting renal outcome in IgAN children. METHODS: We performed a retrospective cohort study in children with biopsy-proven IgAN. Mesangial C3 deposition (< 2+ vs. ≥ 2+) was detected by the immunofluorescence. Histopathologic kidney grades were determined by the Oxford classification. A decreased serum C3 concentration (hypoC3) was defined when C3 < 90 mg/dl. The endpoint was composite kidney outcome with either a 30% decline in glomerular filtration rates from baseline or kidney failure during the follow-up period. RESULTS: A total of 98 children were analyzed. Mesangial hypercellularity (M) was an independent factor associated with mesangial C3 deposition (HR 3.267; 95% CI 1.028-10.389; P = 0.045). After a median follow-up period of 25 months (interquartile range 18-36 months), 6 (6.1%) children reached the endpoint. Compared with other children, a significantly higher proportion of children with composite kidney outcomes had mesangial C3 deposition ≥ 2+ and hypoC3 (3.4% versus 27.3%, P = 0.002). After adjustment for clinicopathologic risk factors, mesangial C3 deposition ≥ 2+ and hypoC3 were associated with renal outcome (HR 9.772; 95% CI 1.264-75.518; P = 0.029). CONCLUSION: Mesangial C3 deposition was associated with M in IgAN. Mesangial C3 deposition and hypoC3 were risk factors for renal outcome in children with IgAN.

Knockdown of miR-665 Protects Against Cardiomyocyte Ischemia/Reperfusion Injury-Induced ROS Accumulation and Apoptosis Through the Activation of Pak1/Akt Signaling in Myocardial Infarction.

Myocardial infarction (MI) is one of the major causes of death worldwide, and the therapeutic strategies of MI are still limited. In this study, we investigated the function of miR-665 in MI. In the present study, an ischemia/reperfusion (I/R) rat model and a hypoxia/reoxygenation (H/R)-induced H9c2 cell model were successfully established to mimic the MI for in vivo and in vitro studies. The concentrations of lactate dehydrogenase (LDH), creatine kinase-MB (CK-MB), tumor necrosis factor alpha (TNF-α), IL-6, and reactive oxygen species (ROS) were then measured. Moreover, cell viability and apoptosis were detected by MTT assay, TdT-mediated dUTP nick end labeling (TUNEL), and PI/FITC-annexin V assay. The binding of miR-665 and Pak1 was determined by luciferase assay. miR-665 was upregulated in I/R rats, and the overexpression of miR-665 significantly increased LDH, CK-MB, TNF-α, IL-6, and ROS concentrations and induced cell apoptosis, while knockdown of miR-665 had opposite results. Consistent with in vivo results, miR-665 induced cell apoptosis and ROS generation in H/R-treated H9c2 cells. More importantly, Pak1 was the target gene of miR-665, and knockdown of miR-665 depressed the accumulation of ROS and cell apoptosis by targeting Pak1 and promoting the phosphorylation of Akt, whereas knockdown of Pak1 could attenuate the protection of miR-665 inhibitor in H/R-treated H9c2 cells. Therefore, knockdown of miR-665 protects against cardiomyocyte ischemia/reperfusion injury-induced ROS accumulation and apoptosis through activating Pak1/Akt signaling in MI. In general, understanding the biology and modulation of miR-665 may have the potential to counteract the development of MI.

A clinicopathological comparison between IgA nephropathy and Henoch-Schönlein purpura nephritis in children: use of the Oxford classification.

BACKGROUND: There is controversy over whether IgA nephropathy (IgAN) and Henoch-Schönlein purpura nephritis (HSPN) are the same diseases. This study focuses on the clinicopathological comparison between HSPN and IgAN in children. METHODS: Children with IgAN and HSPN who had a diagnostic renal biopsy were enrolled. This study collected the clinical data of patients at biopsy, re-evaluated the pathological lesions of patients according to the Oxford Classification (MEST-C), and made a retrospective comparison between IgAN and HSPN on different stratifications of the course (Tc) and proteinuria. RESULTS: A total of 142 children with IgAN and 57 children with HSPN were enrolled. Various stratification showed the same result, which suggested that IgAN showed more mesangial proliferation (M). HSPN showed more segmental glomerulosclerosis in the Tc > 12 m group than IgAN (S 60.0% vs. 9.10%, P = 0.008). In the non-nephrotic-range and nephrotic-range proteinuria group, there were no significant differences in MEST-C scores between IgAN and HSPN. CONCLUSION: M is more common in IgAN. HSPN had more S than IgAN over the course of more than 12 months. These results indicate the differences in the pathogenesis in IgAN and HSPN. We propose early biopsy and active treatment of HSPN within 12 months to delay the development of chronic lesions.

Decoding the role of hypothetical protein All3255 of Anabaena PCC7120 in heavy metal stress management in Escherichia coli.

Cadmium is a non-essential toxic heavy metal for organisms, including plants and cyanobacteria. Cadmium resistance transporters involved in resistance of cells against various toxicants such as drugs and effluxes cytotoxic compounds from cells. However, cadmium resistance-associated protein (CadD) has never been reported from a diazotrophic cyanobacterium Anabaena sp. To test whether the hypothetical protein All3255 of Anabaena sp. PCC7120 a homolog of cadmium resistance-associated protein (CadD) involved in cadmium or heavy metal resistance or not, cloning and heterologous expression analysis of all3255 performed in Escherichia coli BL21 (DE3). Our results revealed that the strain transformed with pGEX-5X-2 + all3255 showed resistant towards not only to cadmium but also other heavy metals such as nickel, copper, zinc, lead and cobalt in addition to arsenic than those of transformed with empty vector (pGEX-5X-2). Furthermore, the results of metal accumulation analysis of these cells unveil a lower accumulation of tested heavy metals in all3255-overexpressing E. coli cells than those transformed with empty vector. This study strongly supports the role of All3255 of Anabaena sp. PCC7120 as a CadD efflux pump of heavy metals in E.coli.

Inhibitory Effect of 2R,3R-Dihydromyricetin on Biofilm Formation by Staphylococcus aureus.

The adherence and biofilm formation of Staphylococcus aureus on food contact surfaces are a major concern for the food industry. Development of antibiofilm agents from polyphenols has drawn much attention due to their potent activity. The present study explored the antibacterial and antibiofilm activities of 2R,3R-dihydromyricetin (DMY) against S. aureus ATCC 29213. It was found that DMY exerted excellent antibacterial and bactericidal properties against S. aureus with minimum inhibitory concentration and minimum bactericidal concentration values of 0.125 and 0.25 mg/mL, respectively. Crystal violet staining and 2,3-bis (2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide sodium salt reduction assay demonstrated that DMY significantly reduced the biofilm biomass of S. aureus and decreased the metabolic activity of biofilm cells. Micrographs of light microscope and scanning electron microscope confirmed that DMY inhibited the biofilm formation and caused a disintegration of the complex biofilm architecture. Moreover, DMY was highly efficient in reducing the number of sessile S. aureus cells adhered to stainless steel. These results suggested that DMY could have potential application to control S. aureus contamination in a food processing environment.

Effect of Dimethoate on the Activity of Hepatic CYP450 Based on Pharmacokinetics of Probe Drugs.

BACKGROUND: Dimethoate (DM), one of the most widely used systemic organophosphate insecticide, has been reported to exert toxic effects after long-time subchronic exposure. This study aims at investigating the toxic effect of DM on liver after repeated administration of low doses of DM in rats. METHODS: Twenty Sprague-Dawley rats were randomly divided into the control group (n = 10) and the DM group (n = 10). After 2 weeks' exposure to DM at low dosage (5 mg/kg), biochemical parameters of hepatic functions were measured, histology and CYP450 expressed in liver was detected. The activities of CYP1A2, CYP2C11, CYP2D1, and CYP3A2 were evaluated by the Cocktail method. RESULTS: The level of AChE (acetylcholinesterase) was significantly decreased, hepatic functions were damaged and the mRNA level of CYP2D1 was significantly increased in the DM group (p < 0.05). The pharmacokinetics of probe drug revealed AUC(0-t), AUC(0-∞), t1/2 and Cmax of metoprolol was shorten in the DM group (p < 0.05). However, there were no statistical differences in MRT, t1/2, CL and Tmax for phenacetin, tolbutamide and midazolam. CONCLUSIONS: A low dosage of DM could induce the activity of CYP2D1 in liver and increase the metabolism of metoprolol when exposed for 2 weeks.

How to achieve adequate quenching for DBP analysis in drinking water?

Quenching is an important step to terminate disinfection during preparation of disinfected water samples for the analysis of disinfection byproducts (DBPs). However, an incomplete quenching might result in continued reactions of residual chlorine, whereas an excessive quenching might decompose target DBPs. Therefore, an adequate quenching to achieve simultaneous disinfection termination and DBP preservation is of particular importance. In this study, the two-stage reaction kinetics of chlorine and three commonly used quenching agents (i.e., ascorbic acid, sodium thiosulfate, and sodium sulfite) were determined. Stopping quenching during the first stage prevented interactions of residual chlorine with natural organic matter. Complete quenching was achieved by minimizing the quenching time for ascorbic acid and sodium sulfite, while limiting the quenching time to less than 3 min for sodium thiosulfate. At the optimized quenching times, the molar ratios (MRs) of quenching agent to chlorine were 1.05, 1.10, and 0.75 for ascorbic acid, sodium sulfite, and sodium thiosulfate, respectively. The destructive effects of the three quenching agents on total organic halogen (TOX) followed the rank order of ascorbic acid (33.7-64.8 %) < sodium sulfite (41.6-72.8 %) < sodium thiosulfate (43.3-73.2 %), and the destructive effects on aliphatic DBPs also followed the rank order of ascorbic acid (29.5-44.5 %) < sodium sulfite (34.9-51.9 %) < sodium thiosulfate (46.9-53.2 %). For total organic chlorine (TOCl) and aliphatic DBPs, the quenching behavior itself had more significant destructive effect than the quenching agent type/dose and quenching time, but for total organic bromine (TOBr), the destructive effect caused by quenching agent type/dose and quenching time was more significant. High-dose, long-duration quenching enhanced the reduction of TOX, but had little effect on aliphatic DBPs. Additionally, the three quenching agents reduced the levels of halophenols (except for tribromophenol), while maintained or increased the levels of tribromophenol, halobenzoic/salicylic acids, and halobenzaldehydes/salicylaldehydes. To achieve adequate quenching for overall DBP analysis in chlorinated water samples, it is recommended to use ascorbic acid at a quenching agent-to-chlorine MR of 1.0 for a quenching time of < 0.5 h.

Maternal cerium nitrate exposure induces developmental immunotoxicity in BALB/c mouse offspring.

With the increasing application of cerium and rare-earth elements (REEs), cerium exposure is becoming more widespread. However, there remains a paucity of evidence on developmental immunotoxicity of cerium. This study was designed to examine the developmental immunotoxicity of gestational and postnatal exposure to cerium nitrate (CN) in BALB/C mouse offspring. Dams were given CN by oral gavage at 0, 0.002, 0.02 and 0.2 mg/kg from gestation day 5 (GD5) to postnatal day 21 (PND 21). On PND 21, the highest dose of CN significantly suppressed the NK cell cytotoxicity, and reduced the proportions of NK cells in peripheral blood and spleen of both female and male pups, however, the proportions of monocytes in peripheral blood and macrophages in spleen only increased in female pups. For adaptive immunity, on PND 21, the suppression of T/B lymphocyte proliferation, humoral and cellular immune responses (number of splenic plaque-forming cells, PFC, and delayed-type hypersensitivity, DTH) were observed in both female and male pup mice exposed to 0.2 mg/kg CN. However, the fall of proportions of T/B lymphocytes in peripheral blood (PB), spleen and mesenteric lymph node (MLN) only found in female pups at 0.2 mg/kg on PND 21. Most indications recovered to normal after 3-week cessation of CN exposure, except the reduction of DTH and PFC. From the findings in this study, the lowest-observed-adverse-effect level (LOAEL) of CN for developmental immunotoxicity was estimated to be 0.2 mg/kg bw per day.

Parallel evolution of two AIM24 protein subfamilies and their conserved functions in ER stress tolerance in land plants.

Despite decades of efforts in genome sequencing and functional characterization, some important protein families remain poorly understood. In this study, we report the classification, evolution, and functions of the largely uncharacterized AIM24 protein family in plants, including the identification of a novel subfamily. We show that two AIM24 subfamilies (AIM24-A and AIM24-B) are commonly distributed in major plant groups. These two subfamilies not only have modest sequence similarities and different gene structures but also are of independent bacterial ancestry. We performed comparative functional investigations on the two AIM24 subfamilies using three model plants: the moss Physcomitrium patens, the liverwort Marchantia polymorpha, and the flowering plant Arabidopsis thaliana. Intriguingly, despite their significant differences in sequence and gene structure, both AIM24 subfamilies are involved in ER stress tolerance and the unfolded protein response (UPR). In addition, transformation of the AIM24-A gene from P. patens into the AIM24-B null mutant of A. thaliana could at least partially rescue ER stress tolerance and the UPR. We also discuss the role of AIM24 genes in plant development and other cellular activities. This study provides a unique example of parallel evolution in molecular functions and can serve as a foundation for further investigation of the AIM24 family in plants.

Design and synthesis of novel pomegranate-like TiN@MXene microspheres as efficient sulfur hosts for advanced lithium sulfur batteries.

Lithium-sulfur (Li-S) batteries have the characteristics of low cost, environmental protection, and high theoretical energy density, and have broad application prospects in the new generation of electronic products. However, there are some problems that seriously hinder the Li-S batteries from going from the laboratory to the factory, such as poor stability caused by the large volume expansion of sulfur during charging and discharging, sluggish kinetics of the electrochemical reaction resulting from the low conductivity of the active materials, and loss of active materials arising from the dissolution and diffusion of the intermediate product lithium polysulfides (LiPSs). In this paper, the two-dimensional layered material MXene and TiN are firstly combined by spray drying method to prepare pomegranate-like TiN@MXene microspheres with both adsorption capacity and catalytic effect on LiPSs conversion. The interconnected skeleton composed of MXene not only solves the problem of easy stacking of MXene sheets but also ensures the uniform distribution of sulfur. Without affecting the excellent characteristics of MXene itself, the overall conductivity of the composite electrode material is improved. The TiN hollow nanospheres are coated with MXene layers to form a shell, catalyzing the adsorption of LiPSs and accelerating the transformation of high-order LiPSs to Li2S2/Li2S. As a result, the TiN@MXene cathode delivers a high initial discharge capacity of 1436 mA h g-1 at 0.1C, excellent rate performance of 636 mA h g-1 up to 3C, and an ultralong lifespan over 1000 cycles with a small capacity decay of 0.048% per cycle at the current density of 1.0C.

Liverwort bHLH transcription factors and the origin of stomata in plants.

Stomata are distributed in nearly all major groups of land plants, with the only exception being liverworts. Instead of having stomata on sporophytes, many complex thalloid liverworts possess air pores in their gametophytes. At present, whether stomata in land plants are derived from a common origin remains under debate.1,2,3 In Arabidopsis thaliana, a core regulatory module for stomatal development comprises members of the bHLH transcription factor (TF) family, including AtSPCH, AtMUTE, and AtFAMA of subfamily Ia and AtSCRM1/2 of subfamily IIIb. Specifically, AtSPCH, AtMUTE, and AtFAMA each successively form heterodimers with AtSCRM1/2, which in turn regulate the entry, division, and differentiation of stomatal lineages.4,5,6,7 In the moss Physcomitrium patens, two SMF (SPCH, MUTE and FAMA) orthologs have been characterized, one of which is functionally conserved in regulating stomatal development.8,9 We here provide experimental evidence that orthologous bHLH TFs in the liverwort Marchantia polymorpha affect air pore spacing as well as the development of the epidermis and gametangiophores. We found that the bHLH Ia and IIIb heterodimeric module is highly conserved in plants. Genetic complementation experiments showed that liverwort SCRM and SMF genes weakly restored a stomata phenotype in atscrm1, atmute, and atfama mutant backgrounds in A. thaliana. In addition, homologs of stomatal development regulators FLP and MYB88 also exist in liverworts and weakly rescued the stomatal phenotype of atflp/myb88 double mutant. These results provide evidence not only for a common origin of all stomata in extant plants but also for relatively simple stomata in the ancestral plant.

Genotype and phenotype analysis of epilepsy caused by ADGRV1 mutations in Chinese children.

OBJECTIVE: To investigate the genotype and phenotype of epilepsy caused by ADGRV1 variants in Chinese children. METHODS: A total of 625 patients with epilepsy who had undergone whole-exon gene sequencing or epilepsy and related paroxysmal disease gene panel sequencing were recruited. Variants were evaluated for susceptibility pathogenicity based on their frequency in the Genome Aggregation Database (≤ 0.001). We used six algorithms (sorting intolerant from tolerant (SIFT), PolyPhen-2, Mutation Taster, CADD, REVEL and Splice AI) that predicted that the ADGRV1 variant would have a harmful impact on the function of genes and gene products. We retrospectively reviewed the clinical information of patients with susceptible pathogenic ADGRV1 variants. The relationship between the genotype and phenotype was also analyzed. RESULTS: Eighteen patients with epilepsy were found to have likely pathogenic variants in ADGRV1. The rate of ADGRV1 variants in patients with epilepsy in this cohort was 2.88%. A total of 19 ADGRV1 variants were found, of which 13 were novel and 6 had been previously reported. Eleven out of the 18 children (61.1%) had febrile and afebrile seizures (FS and AS), two children had only FS, one child had infantile spasms, and the other four children had only AS that occurred during sleep (Rolandic epilepsy or atypical Rolandic epilepsy). SIGNIFICANCE: Our study showed a statistically significant association between ADGRV1 variants and FS and AS (p < 0.05), supporting the hypothesis that ADGRV1 is a susceptibility gene for Rolandic epilepsy and infantile spasms. Most epilepsy cases caused by ADGRV1 variants have a good prognosis.

Associations of maternal exposure to fine particulate matter with preterm and early-term birth in high-risk pregnant women.

BACKGROUND: Environmental pollution is a risk factor for adverse birth outcomes, especially preterm birth (PTB) and early-term birth (ETB). It has been revealed that exposure to fine particulate matter (PM2.5) during pregnancy increase the prevalence of PTB. However, the relationship between PM2.5 exposure and ETB has not been elucidated. In high-risk pregnancies, whether PM2.5 exposure will bring higher risk of PTB and ETB than in normal pregnancies is still unclear, and the susceptible exposure window is obscure. Therefore, it is worthy of assessing the risk on PTB and ETB and identifying the susceptible exposure windows of PM2.5 exposure in high-risk pregnant women. RESULTS: This paper collected the clinical data of 7974 singletons, high-risk pregnant women in Peking University First Hospital from 2014 to 2018, and analyzed them using logistic regression and stratified analysis. We observed that exposure to high-level (≥ 75 µg/m3) of PM2.5 during the third trimester of pregnancy increases the risk of PTB and ETB (PTB: odds ratio[OR] = 1.43, 95% confidence interval [CI]:1.05-1.93. ETB: OR = 1.29, 95%CI: 1.09-1.54). Furthermore, the effects of each 10ug/m3 increase in PM2.5 on PTB and ETB were significant during the third trimester (PTB: OR = 1.35, 95%CI:1.16-1.58. ETB: OR = 1.12, 95%CI:1.02-1.22) and the entire pregnancy (PTB: OR = 6.12, 95%CI:4.27-8.89. ETB: OR = 1.96, 95%CI:1.59-2.43) in the high-level exposure group. CONCLUSIONS: These results suggest that high-level PM2.5 exposure during pregnancy is associated with high risk of PTB and ETB in high-risk pregnancies. The third trimester of pregnancy is speculated to be the susceptible exposure window.

Corrigendum: Lymphatic reconstruction in kidney allograft aggravates chronic rejection by promoting alloantigen presentation.

[This corrects the article DOI: 10.3389/fimmu.2021.796260.].

Prognostic usefulness of clinical features and pretreatment 18F-FDG PET/CT metabolic parameters in patients with angiosarcoma.

Background: To investigate the prognostic value of clinical features and metabolic parameters in pretreatment 18F-2-fluoro-2-deoxy-D-glucose (18F-FDG) positron emission tomography/X-ray computed tomography (PET/CT) scans of patients with angiosarcoma, a rare neoplasm that has not been well characterized. Methods: In this retrospective study, 19 patients with a histopathologically confirmed diagnosis of angiosarcoma who had undergone pretreatment 18F-FDG PET/CT scans were enrolled. We recorded the age at presentation, sex, underlying diseases, sites of primary tumors, Karnofsky Performance Status (KPS) score, Eastern Cooperative Oncology Group (ECOG) score, time from onset to diagnosis, laboratory examinations, sites and sizes of primary tumors, treatment modalities, histologic features and American Joint Committee on Cancer (AJCC) stage, maximum standardized uptake value (SUVmax), average SUV (SUVavg), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) of primary tumors and the whole body. Univariate and multivariate survival analyses for overall survival were performed according to the metabolic parameters and other clinical variables. Results: Patients ranged in age from 27 to 79 years (median: 59 years) with different angiosarcoma types covering all tumor grades and subtypes. Seven (7/19) patients had anemia of varying degrees of severity. Lymph node metastases (n=10) and/or distant metastases (n=11) of angiosarcoma were common. Bone or bone marrow (10/19) and lung (8/19) were the most common distant metastatic organs. Patients with bone metastases, low hemoglobin levels and high ferritin levels had significantly poorer overall survival than those with non-bone metastases, normal hemoglobin levels and normal ferritin levels by the log-rank test, with P values of 0.027, 0.030 and 0.015, respectively. Patients with multiple organ metastases had significantly poorer overall survival than those with single organ metastasis (log-rank P=0.008). In multivariate survival analysis, only whole-body metabolic tumor volume using SUVmax cut-off value of 2.5 (wMTV2.5) was a significant independent prognostic factor. For wMTV2.5, 870.3 cm3 was the best cut-off point to discriminate between a good and poor prognosis (log-rank P=0.01). Conclusions: The systemic 18F-FDG PET/CT with high sensitivity and specificity has significant advantages in the evaluation of angiosarcoma, particularly in detecting occult metastases. Bone metastases on 18F-FDG PET/CT, low hemoglobin levels and high ferritin levels were all associated with a poorer prognosis. MTV2.5 of the whole body is a significant independent metabolic prognostic factor for overall survival in patients with angiosarcoma.

Effects of intrauterine and lactational exposure to lanthanum nitrate on BALB/c offspring mice: Developmental immunotoxicity and self-recovery.

Lanthanum, a major rare earth element, can exert detrimental effects on the adult immune system, but its developmental immunotoxicity (DIT) remains obscure. This study was designed to evaluate the DIT of lanthanum nitrate (LN) and the self-recovery of LN-induced DIT 21 days following cessation of exposure. BALB/c pregnant dams were exposed to 0, 0.1, 1, and 10 mg/kg body weight/day LN by gavage during gestation and lactation. Results showed that in male offspring, LN markedly inhibited the adaptive immunity at postanal day 21 (PND21) and the inhibitory effect on cellular immunity continued to PND42 (after three weeks of self-recovery). In female offspring, LN suppressed cellular immunity at both PND21 and PND42. Moreover, decreased relative organ weight of thymus, humoral immunity and proportion of double-positive T cells in thymus were also observed at PND42. Bcl-xl protein level decreased in thymus of female at PND42, while the level of ß-catenin increased. These changes might contribute to accelerating the degeneration and weight loss of thymus. Overall, in-utero and postanal exposure to LN could induce impairments of immunity in offspring, especially the female, and adaptive immunosuppression would persist throughout development into adulthood. The LOAEL of LN for DIT should be 1 mg/kg.

EEG theta responses induced by emoji semantic violations.

This study investigated emoji semantic processing by measuring changes in event-related electroencephalogram (EEG) power. The last segment of experimental sentences was designed as either words or emojis consistent or inconsistent with the sentential context. The results showed that incongruent emojis led to a conspicuous increase of theta power (4-7 Hz), while incongruent words induced a decrease. Furthermore, the theta power increase was observed at midfrontal, occipital and bilateral temporal lobes with emojis. This suggests a higher working memory load for monitoring errors, difficulty of form recognition and concept retrieval in emoji semantic processing. It implies different neuro-cognitive processes involved in the semantic processing of emojis and words.