KLF13 sustains thymic memory-like CD8+ T cells in BALB/c mice by regulating IL-4–generating invariant natural killer T cells

Transcription factor KLF13 regulates the elevated numbers of iNKT cells in the BALB/c versus C57BL/6 thymus that results in production of sufficient levels of IL-4 to generate memory-like CD8+ T cells

Implementation strategy and emission reduction effectiveness of carbon cap-and-trade in heterogeneous enterprises

In this research, a carbon emission reduction supply chain mechanism formed by government and enterprises is developed. Using a mixed game model, we study the impact of enterprise heterogeneity and social willingness-to-pay for environmental measures on the implementation strategy and effectiveness of cap-and-trade mechanism. The choice and effectiveness of the strategies are cross-influenced by the aforementioned two factors. The former has thresholds, which serve as a basic guarantee and adjustment; the latter is a key factor affecting government and enterprise decision-making and the fairness of the sharing of emission reduction responsibilities. The quotas allocation in compliance with the rule mainly affects the allocation of industry profits and consumers’ active payment among enterprises, and is an effective tool for achieving two-way incentives. The difference between quotas and the voluntary reduction of emissions is the main reason for the surplus or shortage of quotas. We propose an emission reduction integration mechanism, which is based on the social willingness-to-pay for environmental measures, the difference of carbon emissions per unit and the quota allocation schemes, can avoid negative incentives and lack of fairness. The emission reduction mechanism can only reduce the loss of social welfare, but the government can launch appropriate emission reduction practices based on the conception of carbon neutrality to improve social welfare

Subsidized gestational diabetes mellitus screening and management program in rural China: a pragmatic multicenter, randomized controlled trial

Background: The increasing prevalence of gestational diabetes mellitus (GDM) is a major challenge, particularly in rural areas of China where control rates are suboptimal. This study aimed to evaluate the effectiveness of a GDM subsidy program in promoting GDM screening and management in these underserved regions. Methods: This multicenter, randomized controlled trial (RCT) was conducted in obstetric clinics of six rural hospitals located in three provinces in China. Eligible participants were pregnant women in 24–28 weeks’ gestation, without overt diabetes, with a singleton pregnancy, access to a telephone, and provided informed consent. Participants were randomly assigned in a 1:1 ratio to either the intervention or control groups using an internet-based, computer-generated randomization system. The intervention group received subsidized care for GDM, which included screening, blood glucose retesting, and lifestyle management, with financial assistance provided to health care providers. In contrast, the control group received usual care. The primary outcomes of this study were the combined maternal and neonatal complications associated with GDM, as defined by the occurrence of at least one pre-defined complication in either the mother or newborn. The secondary outcomes included the GDM screening rate, rates of glucose retesting for pregnant women diagnosed with GDM, dietary patterns, physical activity levels, gestational weight gain, and antenatal visit frequency for exploratory purposes. Primary and secondary outcomes were obtained for all participants with and without GDM. Binary outcomes were analyzed by the generalized linear model with a link of logistic, and odds ratios (OR) with 95% confidence intervals (CIs) were reported. Count outcomes were analyzed by Poisson regression, and incidence rate ratios with 95% CIs were reported. Results: A total of 3294 pregnant women were randomly assigned to either the intervention group (n = 1649) or the control group (n = 1645) between 15 September 2018 and 30 September 2019. The proportion of pregnant women in the intervention group who suffered from combined maternal and/or neonatal complications was lower than in the control group with adjusted OR = 0.86 (0.80 to 0.94, P = 0.001), and a more significant difference was observed in the GDM subgroup (adjusted OR = 0.66, 95% CI 0.47 to 0.95, P = 0.025). No predefined safety or adverse events of ketosis or ketoacidosis associated with GDM management were detected in this study. Both the intervention and control groups had high GDM screening rates (intervention: 97.2% [1602/1649]; control: 94.5% [1555/1645], P < 0.001). Moreover, The intervention group showed a healthier lifestyle, with lower energy intake and more walking minutes (P values < 0.05), and more frequent blood glucose testing (1.5 vs. 0.4 visits; P = 0.001) compared to the control group. Conclusion: In rural China, a GDM care program that provided incentives for both pregnant women and healthcare providers resulted in improved maternal and neonatal health outcomes. Public health subsidy programs in China should consider incorporating GDM screening and management to further enhance reproductive health. Trial registration: China Clinical Trials Registry ChiCTR1800017488. https://www.chictr.org.cn/</p

Correction: Pandey et al. ROR1 Potentiates FGFR Signaling in Basal-Like Breast Cancer. <i>Cancers</i> 2019, <i>11</i>, 718

In the original publication [...

ROR1 Potentiates FGFR Signaling in Basal-Like Breast Cancer

Among all breast cancer types, basal-like breast cancer (BLBC) represents an aggressive subtype that lacks targeted therapy. We and others have found that receptor tyrosine kinase-like orphan receptor 1 (ROR1) is overexpressed in BLBC and other types of cancer and that ROR1 is significantly correlated with patient prognosis. In addition, using primary patient-derived xenografts (PDXs) and ROR1-knockout BLBC cells, we found that ROR1+ cells form tumors in immunodeficient mice. We developed an anti-ROR1 immunotoxin and found that targeting ROR1 significantly kills ROR1+ cancer cells and slows down tumor growth in ROR1+ xenografts. Our bioinformatics analysis revealed that ROR1 expression is commonly associated with the activation of FGFR-mediated signaling pathway. Further biochemical analysis confirmed that ROR1 stabilized FGFR expression at the posttranslational level by preventing its degradation. CRISPR/Cas9-mediated ROR1 knockout significantly reduced cancer cell invasion at cellular levels by lowering FGFR protein and consequent inactivation of AKT. Our results identified a novel signaling regulation from ROR1 to FGFR and further confirm that ROR1 is a potential therapeutic target for ROR1+ BLBC cells

Proteomic modification in gills and brains of medaka fish (Oryzias melastigma) after exposure to a sodium channel activator neurotoxin, brevetoxin-1

Although brevetoxins (PbTxs) produced by the marine dinoflagellate Karenia brevis are known to be absorbed across gill membranes and exert their acute toxic effects through an ion-channel mediated pathway in neural tissue, the exact biochemical mechanism concerning PbTxs neurotoxicity in neural tissue and gas-exchange organs has not been well elucidated. In this study, we calculated the LC 50 value of PbTx-1 using the medaka fish model, and presented the molecular responses of sub-acute exposure to PbTx-1 with proteomic method. By adopting two-dimensional electrophoresis, the abundances of 14 and 24 proteins were found to be remarkably altered in the gills and brains, respectively, in response to toxin exposure. Thirteen gill and twenty brain proteins were identified using matrix-assisted laser desorption/ionization tandem time-of-flight mass spectrometry analysis. These proteins could be categorized into diverse functional classes such as cell structure, macromolecule metabolism, signal transduction and neurotransmitter release. These findings can help to elucidate the possible pathways by which aquatic toxins affect marine organisms within target organs. © 2011 Elsevier B.V.link_to_subscribed_fulltex

Proteomic modification in gills and brains of medaka fish (Oryzias melastigma) after exposure to a sodium channel activator neurotoxin, brevetoxin-1

Research Grants Council of the Hong Kong Special Administrative Region, China [CityU3/CRF/08]; State Key Laboratory of Marine Environmental Science (Xiamen University) [MEL0607]Although brevetoxins (PbTxs) produced by the marine dinoflagellate Karenia brevis are known to be absorbed across gill membranes and exert their acute toxic effects through an ion-channel mediated pathway in neural tissue, the exact biochemical mechanism concerning PbTxs neurotoxicity in neural tissue and gas-exchange organs has not been well elucidated. In this study, we calculated the LC(50) value of PbTx-1 using the medaka fish model, and presented the molecular responses of sub-acute exposure to PbTx-1 with proteomic method. By adopting two-dimensional electrophoresis, the abundances of 14 and 24 proteins were found to be remarkably altered in the gills and brains, respectively, in response to toxin exposure. Thirteen gill and twenty brain proteins were identified using matrix-assisted laser desorption/ionization tandem time-of-flight mass spectrometry analysis. These proteins could be categorized into diverse functional classes such as cell structure, macromolecule metabolism, signal transduction and neurotransmitter release. These findings can help to elucidate the possible pathways by which aquatic toxins affect marine organisms within target organs. (C) 2011 Elsevier B.V. All rights reserved