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BACKGROUND: Toxoplasma gondii infection causes adverse pregnancy outcomes by affecting the expression of immunotolerant molecules in decidual immune cells. Galectin-9 (Gal-9) is widely expressed in decidual macrophages (dMφ) and is crucial for maintaining normal pregnancy by interacting with the immunomodulatory protein T-cell immunoglobulin and mucin domain-containing molecule 3 (Tim-3). However, the effects of T. gondii infection on Gal-9 expression in dMφ, and the impact of altered Gal-9 expression levels on the maternal-fetal tolerance function of decidual natural killer (dNK) cells, are still unknown. METHODS: Pregnancy outcomes of T. gondii-infected C57BL/6 and Lgals9-/- pregnant mice models were recorded. Expression of Gal-9, c-Jun N-terminal kinase (JNK), phosphorylated JNK (p-JNK), and Forkhead box protein O1 (FOXO1) was detected by western blotting, flow cytometry or immunofluorescence. The binding of FOXO1 to the promoter of Lgals9 was determined by chromatin immunoprecipitation-polymerase chain reaction (ChIP-PCR). The expression of extracellular signal-regulated kinase (ERK), phosphorylated ERK (p-ERK), cAMP-response element binding protein (CREB), phosphorylated CREB (p-CREB), T-box expressed in T cells (T-bet), interleukin 10 (IL-10), and interferon gamma (IFN-γ) in dNK cells was assayed by western blotting. RESULTS: Toxoplasma gondii infection increased the expression of p-JNK and FOXO1 in dMφ, resulting in a reduction in Gal-9 due to the elevated binding of FOXO1 with Lgals9 promoter. Downregulation of Gal-9 enhanced the phosphorylation of ERK, inhibited the expression of p-CREB and IL-10, and promoted the expression of T-bet and IFN-γ in dNK cells. In the mice model, knockout of Lgals9 aggravated adverse pregnancy outcomes caused by T. gondii infection during pregnancy. CONCLUSIONS: Toxoplasma gondii infection suppressed Gal-9 expression in dMφ by activating the JNK/FOXO1 signaling pathway, and reduction of Gal-9 contributed to dysfunction of dNK via Gal-9/Tim-3 interaction. This study provides new insights for the molecular mechanisms of the adverse pregnancy outcomes caused by T. gondii.

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NME1 is a metastatic suppressor inconsistently reported to have multiple roles as both a promoter and inhibitor of cancer metastasis. Nevertheless, the specific mechanism behind these results is still unclear. We observed that A549 cells with stable transfer of NME1 into the nucleus (A549-nNm23-H1) exhibited significantly increased migration and invasion activity compared to vector control cells, which was further enhanced by over-expressing CYP24A1 (p < 0.001). NME1 demonstrated the ability to safely attach to and amplify the transcription activation of JUN, consequently leading to the up-regulation of CYP24A1. Analysis of clinical data showed a positive relationship between nuclear NME1 levels and CYP24A1 expression. Furthermore, they were positively associated with postoperative distant metastasis and negatively correlated with prognosis in those with early stage lung adenocarcinoma. In conclusion, the data presented provides a new understanding of the probable pathways by which nuclear NME1 facilitates tumor metastasis, establishing the groundwork for future prediction and treatment of tumor metastasis.

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Myeloid-derived suppressor cells (MDSCs) play a crucial role in maintaining maternal-fetal tolerance by expressing some immune-suppressive molecules, such as indoleamine 2,3-dioxygenase (IDO). Toxoplasma gondii (T. gondii) infection can break the immune microenvironment of maternal-fetal interface, resulting in adverse pregnancy outcomes. However, whether T. gondii affects IDO expression in dMDSCs and the molecular mechanism of its effect are still unclear. Here we show, the mRNA level of IDO is increased but the protein level decreased in infected dMDSCs. Mechanistically, the upregulation of transcriptional levels of IDO in dMDSCs is regulated through STAT3/p52-RelB pathway and the decrease of IDO expression is due to its degradation caused by increased SOCS3 after T. gondii infection. In vivo, the adverse pregnancy outcomes of IDO-/- infected mice are more severe than those of wide-type infected mice and obviously improved after exogenous kynurenine treatment. Also, the reduction of IDO in dMDSCs induced by T. gondii infection results in the downregulation of TGF-ß and IL-10 expression in dNK cells regulated through Kyn/AhR/SP1 signal pathway, eventually leading to the dysfunction of dNK cells and contributing the occurrence of adverse pregnancy outcomes. This study reveals a novel molecular mechanism in adverse pregnancy outcome induced by T. gondii infection.

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BACKGROUND: Toxoplasma gondii is an obligate intracellular parasite that can lead to adverse pregnancy outcomes, particularly in early pregnancy. Previous studies have illustrated the landscape of decidual immune cells. However, the landscape of decidual immune cells in the maternal-fetal microenvironment during T. gondii infection remains unknown. METHODS: In this study, we employed single-cell RNA sequencing to analyze the changes in human decidual immune cells following T. gondii infection. The results of scRNA-seq were further validated with flow cytometry, reverse transcription-polymerase chain reaction, western blot, and immunofluorescence staining. RESULTS: Our results showed that the proportion of 17 decidual immune cell clusters and the expression levels of 21 genes were changed after T. gondii infection. Differential gene analysis demonstrated that T. gondii infection induced the differential expression of 279, 312, and 380 genes in decidual NK cells (dNK), decidual macrophages (dMφ), and decidual T cells (dT), respectively. Our results revealed for the first time that several previously unknown molecules in decidual immune cells changed following infection. This result revealed that the function of maternal-fetal immune tolerance declined, whereas the killing ability of decidual immune cells enhanced, eventually contributing to the occurrence of adverse pregnancy outcomes. CONCLUSIONS: This study provides valuable resource for uncovering several novel molecules that play an important role in the occurrence of abnormal pregnancy outcomes induced by T. gondii infection.

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BACKGROUND: Curcumin has been reported to have anti-hepatocellular carcinoma (HCC) effects, but the underlying mechanism is not well known. OBJECTIVES: To investigate whether membrane-associated RING-CH 1 (MARCH1) is involved in the curcumin-induced growth suppression in HCC and its underlying molecular mechanism. A few recent patents for curcumin for cancer are also reviewed in this article. METHODS: The effect of curcumin on growth inhibition of HCC cells was analyzed through in vitro and in vivo experiments, and the expression levels of MARCH1, Bcl-2, VEGF, cyclin B1, cyclin D1, and JAK2/STAT3 signaling molecules were measured in HCC cells and the xenograft tumors in nude mice. Cell transfection with MARCH1 siRNAs or expression plasmid was used to explore the role of MARCH1 in the curcumin-induced growth inhibition of HCC cells. RESULTS: Curcumin inhibited cell proliferation, promoted apoptosis, and arrested the cell cycle at the G2/M phase in HCC cells with the decrease of Bcl-2, VEGF, cyclin B1, and cyclin D1 expression as well as JAK2 and STAT3 phosphorylation, resulting in the growth suppression of HCC cells. MARCH1 is highly expressed in HCC cells, and its expression was downregulated after curcumin treatment in a dose-dependent manner. The knockdown of MARCH1 by siRNA decreased the phosphorylation levels of JAK2 and STAT3 and inhibited the growth of HCC cells. In contrast, opposite results were observed when HCC cells overexpressed MARCH1. A xenograft tumor model in nude mice also showed that curcumin downregulated MARCH1 expression and decelerated the growth of transplanted HCC with the downregulation of JAK2/STAT3 signaling and functional molecules. The ADC value of MRI analysis showed that curcumin slowed down the progression of HCC. CONCLUSION: Our results demonstrated that curcumin may inhibit the activation of JAK2/STAT3 signaling pathway by downregulating MARCH1 expression, resulting in the growth suppression of HCC. MARCH1 may be a novel target of curcumin in HCC treatment.

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Understanding and modeling perceived properties of sky-dome illumination is an important but challenging problem due to the interplay of several factors such as the materials and geometries of the objects present in the scene being observed. Existing models of sky-dome illumination focus on the physical properties of the sky. However, these parametric models often do not align well with the properties perceived by a human observer. In this work, drawing inspiration from the Hosek-Wilkie sky-dome model, we investigate the perceptual properties of outdoor illumination. For this purpose, we perform a large-scale user study via crowdsourcing to collect a dataset of perceived illumination properties (scattering, glare, and brightness) for different combinations of geometries and materials under a variety of outdoor illuminations, totaling 5,000 distinct images. We perform a thorough statistical analysis of the collected data which reveals several interesting effects. For instance, our analysis shows that when there are objects in the scene made of rough materials, the perceived scattering of the sky increases. Furthermore, we utilize our extensive collection of images and their corresponding perceptual attributes to train a predictor. This predictor, when provided with a single image as input, generates an estimation of perceived illumination properties that align with human perceptual judgments. Accurately estimating perceived illumination properties can greatly enhance the overall quality of integrating virtual objects into real scene photographs. Consequently, we showcase various applications of our predictor. For instance, we demonstrate its utility as a luminance editing tool for showcasing virtual objects in outdoor scenes.

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BACKGROUND: Toxoplasma gondii infection can cause adverse pregnancy outcomes, such as recurrent abortion, fetal growth restriction and infants with malformations, among others. Decidual myeloid-derived suppressor cells (dMDSCs) are a novel immunosuppressive cell type at the fetal-maternal interface which play an important role in sustaining normal pregnancy that is related to their high expression of the inhibitory molecule leukocyte immunoglobulin-like receptor B4 (LILRB4). It has been reported that the expression of LILRB4 is downregulated on decidual macrophages after T. gondii infection, but it remains unknown whether T. gondii infection can induce dMDSC dysfunction resulting from the change in LILRB4 expression. METHODS: LILRB4-deficient (LILRB4-/-) pregnant mice infected with T. gondii with associated adverse pregnancy outcomes, and anti-LILRB4 neutralized antibodies-treated infected human dMDSCs were used in vivo and in vitro experiments, respectively. The aim was to investigate the effect of LILRB4 expression on dMDSC dysfunction induced by T. gondii infection. RESULTS: Toxoplasma gondii infection was observed to reduce STAT3 phosphorylation, resulting in decreased LILRB4 expression on dMDSCs. The levels of the main functional molecules (arginase-1 [Arg-1], interleukin-10 [IL-10]) and main signaling molecules (phosphorylated Src-homology 2 domain-containing protein tyrosine phosphatase [p-SHP2], phosphorylated signal transducer and activator of transcription 6 [p-STAT6]) in dMDSCs were all significantly reduced in human and mouse dMDSCs due to the decrease of LILRB4 expression induced by T. gondii infection. SHP-2 was found to directly bind to STAT6 and STAT6 to bind to the promoter of the Arg-1 and IL-10 genes during T. gondii infection. CONCLUSIONS: The downregulation of LILRB4 expression on dMDSCs induced by T. gondii infection could regulate the expression of Arg-1 and IL-10 via the SHP-2/STAT6 pathway, resulting in the dysfunction of dMDSCs, which might contribute to adverse outcomes during pregnancy by T. gondii infection.

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Circulating tumor cells (CTCs) are cells shed from primary or metastatic tumors and spread into the peripheral bloodstream. Mutation detection in CTCs can reveal vital genetic information about the tumors and can be used for "liquid biopsy" to indicate cancer treatment and targeted medication. However, current methods to measure the mutations in CTCs are based on PCR or DNA sequencing which are cumbersome and time-consuming and require sophisticated equipment. These largely limited their applications especially in areas with poor healthcare infrastructure. Here we report a simple, convenient, and rapid method for mutation detection in CTCs, including an example of a deletion at exon 19 (Del19) of the epidermal growth factor receptor (EGFR). CTCs in the peripheral blood of NSCLC patients were first sorted by a double spiral microfluidic chip with high sorting efficiency and purity. The sorted cells were then lysed by proteinase K, and the E19del mutation was detected via real-time recombinase polymerase amplification (RPA). Combining the advantages of microfluidic sorting and real-time RPA, an accurate mutation determination was realized within 2 h without professional operation or complex data interpretation. The method detected as few as 3 cells and 1% target variants under a strongly interfering background, thus, indicating its great potential in the non-invasive diagnosis of E19del mutation for NSCLC patients. The method can be further extended by redesigning the primers and probes to detect other deletion mutations, insertion mutations, and fusion genes. It is expected to be a universal molecular diagnostic tool for real-time assessment of relevant mutations and precise adjustments in the care of oncology patients.

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Circular RNAs can regulate the development and progression of ischemic cerebral disease. However, it remains unclear whether they play a role in acute ischemic stroke. To investigate the role of the circular RNA Rap1b (circRap1b) in acute ischemic stroke, in this study we established an in vitro model of acute ischemia and hypoxia by subjecting HT22 cells to oxygen and glucose deprivation and a mouse model of acute ischemia and hypoxia by occluding the right carotid artery. We found that circRap1b expression was remarkably down-regulated in the hippocampal tissue of the mouse model and in the HT22 cell model. In addition, Hoxa5 expression was strongly up-regulated in response to circRap1b overexpression. Hoxa5 expression was low in the hippocampus of a mouse model of acute ischemia and in HT22-AIS cells, and inhibited HT22-AIS cell apoptosis. Importantly, we found that circRap1b promoted Hoxa5 transcription by recruiting the acetyltransferase Kat7 to induce H3K14ac modification in the Hoxa5 promoter region. Hoxa5 regulated neuronal apoptosis by activating transcription of Fam3a, a neuronal apoptosis-related protein. These results suggest that circRap1b regulates Hoxa5 transcription and expression, and subsequently Fam3a expression, ultimately inhibiting cell apoptosis. Lastly, we explored the potential clinical relevance of circRap1b and Hoxa5 in vivo. Taken together, these findings demonstrate the mechanism by which circRap1b inhibits neuronal apoptosis in acute ischemic stroke.

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Myeloid-derived suppressor cells (MDSCs) play a key role in maintaining maternal-fetal tolerance for a successful pregnancy, but the role of MDSCs in abnormal pregnancy caused by Toxoplasma gondii infection is unknown. Herein, we revealed a distinct mechanism by which T-cell immunoglobulin domain and mucin domain containing protein-3 (Tim-3), an immune checkpoint receptor that balances maternal-fetal tolerance during pregnancy, contributes to the immunosuppressive function of MDSCs during T. gondii infection. The expression of Tim-3 in decidual MDSCs was significantly downregulated following T. gondii infection. The proportion of monocytic MDSCs population, the inhibitory effect of MDSCs on T-cell proliferation, the levels of STAT3 phosphorylation, and the expression of functional molecules (Arg-1 and IL-10) in MDSCs were all decreased in T. gondii-infected pregnant Tim-3 gene knockout (Tim-3KO) mice compared with infected pregnant WT mice. After treatment with Tim-3-neutralizing Ab in vitro, the expression levels of Arg-1, IL-10, C/EBPß, and p-STAT3 were decreased, the interaction between Fyn and Tim-3 or between Fyn and STAT3 was weakened, and the binding ability of C/EBPß to the promoters of ARG1 and IL10 was decreased in human decidual MDSCs with T. gondii infection, while opposite results were observed following treatment with galectin-9 (a ligand for Tim-3). Inhibitors of Fyn and STAT3 also downregulated the expression of Arg-1 and IL-10 in decidual MDSCs and exacerbated adverse pregnancy outcomes caused by T. gondii infection in mice. Therefore, our studies discovered that the decrease of Tim-3 after T. gondii infection could downregulate the functional molecules of Arg-1 and IL-10 expression in decidual MDSCs through the Fyn-STAT3-C/EBPß signaling pathway and weaken their immunosuppressive function, which eventually contribute to the development of adverse pregnancy outcomes.

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Desmoplastic small round cell tumor (DSRCT) is a rare undifferentiated malignant soft tissue tumor with a poor prognosis and a lack of consensus on treatment. This study's objective was to build a nomogram based on clinicopathologic factors and an online survival risk calculator to predict patient prognosis and support therapeutic decision-making. A retrospective cohort analysis of the Surveillance, Epidemiology and End Results (SEER) database was performed for patients diagnosed with DSRCT between 2000 and 2019. The least absolute shrinkage and selection operator (LASSO) Cox regression analysis was applied to identify the individual variables related to overall survival (OS) and cancer-specific survival (CSS), as well as to construct online survival risk calculators and nomogram survival models. The nomogram was employed to categorize patients into different risk groups, and the Kaplan-Meier method was utilized to determine the survival rate of each risk category. Propensity score matching (PSM) was used to assess survival with different therapeutic approaches. A total of 374 patients were included, and the median OS and CSS were 25 (interquartile range 21.9-28.1) months and 27 (interquartile range 23.6-30.3) months, respectively. The nomogram models demonstrated high predictive accuracy. PSM found that patients with triple-therapy had better CSS and OS than those who received surgery plus chemotherapy (median survival times: 49 vs 34 months and 49 vs 35 months, respectively). The nomogram successfully predicted the DSRCT patients survival rate. This approach could assist doctors in evaluating prognoses, identifying high-risk populations, and implementing personalized therapy.

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BACKGROUND: Toxoplasma gondii infection during pregnancy can lead to fetal defect(s) or congenital complications. The inhibitory molecule B7-H4 expressed on decidual macrophages (dMφ) plays an important role in maternal-fetal tolerance. However, the effect of B7-H4 on the function of dMφ during T. gondii infection remains unclear. METHODS: Changes in B7-H4 expression on dMφ after T. gondii infection were explored both in vivo and in vitro. B7-H4-/- pregnant mice (pregnant mice with B7-H4 gene knockout) and purified primary human dMφ treated with B7-H4 neutralizing antibody were used to explore the role of B7-H4 signaling on regulating the membrane molecules, synthesis of arginine metabolic enzymes and cytokine production by dMφ with T. gondii infection. Also, adoptive transfer of dMφ from wild-type (WT) pregnant mice or B7-H4-/- pregnant mice to infected B7-H4-/- pregnant mice was used to examine the effect of B7-H4 on adverse pregnancy outcomes induced by T. gondii infection. RESULTS: The results illustrated that B7-H4-/- pregnant mice infected by T. gondii had poorer pregnancy outcomes than their wild-type counterparts. The expression of B7-H4 on dMφ significantly decreased after T. gondii infection, which resulted in the polarization of dMφ from the M2 toward the M1 phenotype by changing the expression of membrane molecules (CD80, CD86, CD163, CD206), synthesis of arginine metabolic enzymes (Arg-1, iNOS) and production of cytokines (IL-10, TNF-α) production. Also, we found that the B7-H4 downregulation after T. gondii infection increased iNOS and TNF-α expression mediated through the JAK2/STAT1 signaling pathway. In addition, adoptive transfer of dMφ from a WT pregnant mouse donor rather than from a B7-H4-/- pregnant mouse donor was able to improve adverse pregnancy outcomes induced by T. gondii infection. CONCLUSIONS: The results demonstrated that the downregulation of B7-H4 induced by T. gondii infection led to the dysfunction of decidual macrophages and contributed to abnormal pregnancy outcomes. Moreover, adoptive transfer of B7-H4+ dMφ could improve adverse pregnancy outcomes induced by T. gondii infection.

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BACKGROUND: Primary infection of Toxoplasma gondii can cause serious abnormal pregnancy outcomes such as miscarriage and stillbirth. Inhibitory molecule B7-H4 is abundantly expressed in dendritic cells (DCs) and plays an important role in maintaining immune tolerance. However, the role of B7-H4 in decidual DCs (dDCs) in T. gondii-induced abnormal pregnancy outcomes is not clear. METHODS: We established T. gondii-infected abnormal pregnancy model in wild-type (WT) and B7-H4 knockout (B7-H4-/-) pregnant mice in vivo and cultured primary human dDCs in vitro. The abnormal pregnancy outcomes were observed and the expression of B7-H4, functional molecules (CD80, CD86, and MHC-II or HLA-DR), indoleamine 2,3-dioxygenase (IDO), cytokines (IL-10 and IL-12), and signaling molecules JAK2/STAT3 in dDCs was detected by flow cytometry and Western blot. RESULTS: Our results showed that T. gondii infection significantly decreased B7-H4 expression in dDCs. In addition, B7-H4-/- infected pregnant mice showed much more severe abnormal pregnancy outcomes than their counterparts. Importantly, B7-H4-/- infection further regulated the expression of molecules (CD80, CD86, and MHC-II or HLA-DR), enzyme IDO, and cytokines (IL-10 and IL-12) in dDCs. We further discovered that B7-H4-/- infection impairs the JAK2/STAT3 pathway, contributing to dDC dysfunction. CONCLUSIONS: Taken together, the results show that reduction of B7-H4 by T. gondii infection significantly modulates the decrease in cytokine IL-10 and enzyme IDO and the increase in cytokine IL-12, contributing to dDC dysfunction. Moreover, the JAK2/STAT3 pathway is involved in the regulation of B7-H4 by T. gondii infection and in the subsequent IDO and cytokine production, which ultimately contributes to abnormal pregnancy outcomes.

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Vertical transmission of Toxoplasma gondii (T. gondii) infection during gestation can result in severe complications such as abortion, congenital malformation, fetal teratogenesis, etc. Immune inhibitory molecule Tim-3 was discovered to be expressed on some decidual immune cells and participates in the maintenance of maternal-fetal tolerance. Dysregulation of Tim-3 expression on decidual NK (dNK) cells was observed in several cases of pregnancy complications, whereas the role of Tim-3 on dNK cells during T. gondii infection remains unclear. In the present study, T. gondii infected Tim-3-/- pregnant mice, and anti-Tim-3 neutralizing antibody treated and infected human dNK cells were successfully established to explore the role of Tim-3 in dysfunction of dNK cells during abnormal pregnancy. Our results illustrated that Tim-3-/- pregnant mice displayed more worse pregnancy outcomes with T. gondii infection compared to infected WT pregnant mice. Also, it demonstrated that Tim-3 expression on dNK cells was significantly down-regulated following T. gondii infection. Data suggested a remarkable activation of dNK cells in Tim-3-/- mice and anti-Tim-3 neutralizing antibody treated and infected groups, with higher ratios of activating receptor NKG2D to inhibitory receptor NKG2A or KIR2DL4, IFN-γ/IL-10, and increased granule production compared with that of the infected group. Mechanism analysis proved that T. gondii-induced Tim-3 down-regulation significantly activated the phosphatidylinositol-3-kinase (PI3K)-AKT and JAK-STAT signaling pathway, by which the GranzymeB, Perforin, IFN-γ, and IL-10 production were further up-regulated. Our research demonstrated that the decrease of Tim-3 on dNK cells caused by T. gondii infection further led to dNK cells function disorder, which finally contributed to the development of abnormal pregnancy outcomes.

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At low temperature, collective excitations of one-dimensional (1D) interacting fermions exhibit spin-charge separation, a unique feature predicted by the Tomonaga-Luttinger liquid (TLL) theory, but a rigorous understanding remains challenging. Using the thermodynamic Bethe ansatz (TBA) formalism, we analytically derive universal properties of a 1D repulsive spin-1/2 Fermi gas with arbitrary interaction strength. We show how spin-charge separation emerges from the exact TBA formalism, and how it is disrupted by the interplay between the two degrees of freedom that brings us beyond the TLL paradigm. Based on the exact low-lying excitation spectra, we further evaluate the spin and charge dynamical structure factors (DSFs). The peaks of the DSFs exhibit distinguishable propagating velocities of spin and charge as functions of interaction strength, which can be observed by Bragg spectroscopy with ultracold atoms.

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INTRODUCTION: The evolution of computed tomography (CT) findings in patients with mild coronavirus disease 2019 (COVID-19) pneumonia has not been described in detail. A large-scale longitudinal study is urgently required. METHODS: We analyzed 606 CT scans of 182 patients. The dynamic evolution of CT scores was evaluated using two staging methods: one was divided into 10 periods based on decile intervals, and the other was one stage per week. Moreover, the latter was used to evaluate the dynamic evolution of imaging performance. A published severity scoring system was used to compare findings of the two methods. RESULTS: In the dynamic evolution of 10 stages, the total lesion CT score peaked during stage 3 (9-11 days) and stage 6 (17-18 days), with scores = 7.19 ± 3.66 and 8.00 ± 4.57, respectively. The consolidation score peaked during stage 6 (17-18 days; score = 2.72 ± 3.07). In contrast, when a 1-week interval was used and time was divided into five stages, the total lesion score peaked during week 3 (score = 7.3 ± 4.15). The consolidation score peaked during week 2 (score = 2.54 ± 3.25). The predominant CT patterns differed significantly during each stage (P < 0.01). Ground-glass opacities (GGO), with an increased trend during week 3 and beyond, was the most common pattern in each stage (33-46%). The second most common patterns during week 1 were GGO and consolidation (24%). The linear opacity pattern with an increased trend was the second most common pattern during week 2 and beyond (21-32%). CONCLUSIONS: The total lesion score of mild COVID-19 pneumonia peaked 17-18 days after disease onset. The consolidation scores objectively reflected the severity of the lung involvement compared with total lesion scores. Each temporal stage of mild COVID-19 pneumonia mainly manifested as GGO pattern. Moreover, good prognosis may be associated with increases in the proportions of the GGO and linear opacity patterns during the later stage of disease.

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The significant removal efficiency of microcystis aeruginosa was presented using Pt/Ti anode and activated carbon fiber/nickel foam (ACF/Ni) cathode by addition of Fe2+ slightly in a wide range of initial pH (3-9). Results showed that about 93% of the Microcystis aeruginosa cells were removed within 15 min for Pt/Ti-ACF/Ni-Fe2+ system. Dosage of Fe2+, current density, and initial pH had remarkable effects on the removal efficiency of microcystis aeruginosa. The mechanism of algae removal in the Pt/Ti-ACF/Ni-Fe2+ electrochemical system was revealed by the comparison between Pt/Ti-ACF/Ni-Fe2+ process and classical Fenton process, the analysis on Microcystis aeruginosa and ACF/Ni by SEM, the specific surface area and pore size analysis of ACF, and the determination of UV254, OD620 and microcystin-LR (MC-LR). Results showed that the main mechanism of this system was the electro-Fenton process, which was accompanied by electro-adsorption, electro-floatation, and electro-coagulation process. And the cooperation mechanism on the electrochemical removal system was further speculated. With the breakdown of algal cells during the electrolysis, the MC-LR and other substances released from the cells were effectively degraded. Besides, the new cathode exhibited favorable and stable reusability. This study built up a high-efficiency algae removal system, which broke through the limits of narrow working pH range and large consumption of exogenous chemicals in electro-Fenton process.

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Toxoplasma gondii infection during pregnancy can result in adverse pregnancy outcomes. Previously, we have reported that these outcomes are associated with the impaired function of decidual Treg cells; however, the detailed mechanisms involved were unclear. It has been reported that the suppressive capacity of Treg cells is dependent on PD-1 expression. The present study explored the role of decidual PD-1+ Treg cell function in adverse pregnancy outcomes due to T. gondii infection. Toxoplasma gondii-infected pregnant mice were sacrificed on gestational day 14 and their pregnancy outcomes were observed. The expression of PD-1 on decidual Treg cells and expressions of Foxp3, CTLA-4, TGF-ß, and IL-10 on decidual PD-1+ and PD-1- Treg cells were determined using flow cytometry. The results showed that the expression of PD-1 on decidual Treg cells was clearly higher in the T. gondii-infected mice than in the normal mice. Meanwhile, the expressions of Foxp3, CTLA-4, TGF-ß, and IL-10 on decidual PD-1+ Treg cells were higher in the infected mice than in the normal mice. The expressions were higher in decidual PD1+ Treg cells than in PD-1- Treg cells in the infected mice. However, these expressions on PD-1- Treg cells did not significantly differ between the infected and normal mice. Nonetheless, the absolute percentages of decidual PD-1+ Treg cells decreased significantly in the infected mice compared with those in the normal mice. These results suggest that T. gondii infection mainly influences the function of decidual PD-1+ Treg cells, which would result in an insufficiently immunotolerant microenvironment and consequently in adverse pregnancy outcomes.

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Vertical transmission of the intracellular parasite Toxoplasma gondii (T. gondii) can lead to devastating consequences during gestation. Tim-3, a negative immune regulator, is constitutively expressed on decidual macrophages, but its specific role during T. gondii infection has not yet been explored. In the present study, we discovered that Tim-3 plays an important role in the abnormal pregnancy due to T. gondii infection using Tim-3-/- pregnant mice and anti-Tim-3 neutralizing antibody treated human decidual macrophages. The results showed that abnormal pregnancy outcomes were more prevalent in Tim-3-/- infected pregnant mice than in wild-type infected pregnant mice. Tim-3 expression in decidual macrophages was significantly down-regulated after T. gondii infection both in vitro and in vivo. Tim-3 down-regulation by T.gondii infection could strengthen M1 activation and weaken M2 tolerance by changing the M1 and M2 membrane molecule expression, arginine metabolic enzymes synthesis, and cytokine secretion profiles of decidual macrophages. Moreover, Tim-3 down-regulation by T.gondii infection led to PI3K-AKT phosphorylation inhibition, downstream transcription factor C/EBPß expression, and SOCS1 activation, which resulted in enzymes synthesis regulation and cytokines secretion. Our study demonstrates that Tim-3 plays an indispensable role in the adverse pregnancy outcomes caused by T. gondii infection.

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PURPOSE: Papillary renal cell carcinoma (PRCC) gene, which located in 1q23.1, is recurrently amplified in non-small cell lung cancer (NSCLC). However, it is unknown whether PRCC is overexpressed in primary NSCLCs and whether PRCC overexpression contributes to lung tumorigenesis. In this study, we aimed to identify the profiles of PRCC expression in Korean NSCLC patients and to elucidate the role of PRCC overexpression on lung tumorigenesis. MATERIALS AND METHODS: We performed immunohistochemistry analysis with a tissue array containing 161 primary NSCLCs. Small interfering RNA targeting PRCC (siPRCC) was transfected into two lung cancer cell lines (NCI-H358 and A549), after which tumor growth, migration, and invasion were observed. Expressions of cell proliferation-, cell cycle-, and metastasis-related molecules were examined by Western blot analysis. We also explored the in vivo effect of PRCC silencing. RESULTS: PRCC overexpression was recurrently observed in NSCLCs (95/161, 59%). After siPRCC treatment, tumor cell proliferation, colony formation, and anchorage independent growth were significantly reduced (p<0.001 for all three effects). Migration and invasiveness were also significantly repressed (p<0.001 for both effects). Reflecting cell proliferation, cell cycle, and metastasis, the expressions of Ki67, cyclin D1, AKT-1, pAKT, NF-kB p65, vimentin and CXCL-12 were found to be downregulated. Through mouse xenograft analysis, we confirmed that PRCC silencing significantly repressed a xenograft tumor mass in vivo (p<0.001). CONCLUSION: The present data provide evidence that PRCC overexpression is involved in the tumorigenesis and progression of lung cancer.

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