Analytic and heuristic process for prudent antimicrobial use in animals: What are triggers and how do they work?

The over and misuse of antimicrobials in animal agriculture causes a prevailing crisis for humans, animals, and the environment. From the One Health approach perspective, the formation process of adopting prudent antimicrobial use (AMU), once established, can be used to mitigate this crisis. The study aimed to determine the analytic-based and heuristic-based process that evoked prudent AMU among animal farmers by synthesis of stimulus-organism-response framework and dual-system theory and to explore gender differences on risk-benefit trade-offs. A structural equation model was employed to test the proposed hypotheses with field survey data from 1100 small-scale farmers. The results reveal that for the analytic-based process, social influence, antimicrobial-related threats, and self-efficacy are all salient stimuli having indirect effects on intention via the two organisms of perceived risks and perceived benefits. For heuristic-based process, farmers' altruistic value orientations are positively associated with intention. An interesting fact is that threat awareness has two opposite effects on intention, namely, the suppression effect and the enhancement effect. Moreover, the negative effect of perceived risks on intention is greater among female farmers, compared to male counterparts. These findings provide valuable insights for the forming of theory-based intervention strategies to perfect China's national action plan.

The impact of river sand mining on remobilization of lead and cadmium in sediments - A case study of the Jialing River.

Due to the fast pace of urbanization worldwide, industrial sand mining activities have imposed great pressure on the environment, and consequently, these activities have led to serious environmental problems in aquatic ecosystems. However, the current understanding of the effect of sand mining on heavy metal remobilization in river sediments remains incomplete. The present study employed sediment quality guidelines (SQGs) and the sequential extraction (SE) and diffusive gradients in thin films (DGT) techniques to comprehensively investigate the effect of sand mining on the remobilization process of heavy metals in the aquatic system of the Jialing River. The SQGs results indicated that stations (S1 to S4) with sand mining disturbance exhibited Pb and Cd accumulation in surface sediments. Both Ctotal-Pb (61.78-122.04 mg·kg-1) and Ctotal-Cd (0.85-3.96 mg·kg-1) were higher than CSQGI (60 mg·kg-1 for Pb and 0.5 mg·kg-1 for Cd) and TEC (35.8 mg·kg-1 for Pb and 0.99 mg·kg-1 for Cd) limitation in most of sand mining stations. Pb and Cd were mainly bounded in the acid-soluble/exchangeable fraction (F1) and oxidizable fraction (F3) of the surface sediments. At the four stations with sand mining disturbance, about 5-10 folds of DGT-labile Pb and Cd were released in deep sediments (-9 to -12 cm), and Pb and Cd exhibited a transport trend from the sediments into the overlying water, while the above phenomenon was not observed at the two stations without sand mining activities. Correlation analysis revealed that DGT-labile Pb and Cd were suitably correlated with the F1 and F3 fractions, indicating that the acid-soluble/exchangeable and oxidizable fractions were the main sources leading to Pb and Cd remobilization in the sediments. A potential mechanism explanation may be that (1) intense sediment stirring could result in remobilization of the weakly bound fraction, which is related to the contribution of the F1 fraction, and (2) Cd/Pb experienced a corelease process with sulfur due to O2 introduction (elevation of the dissolved oxygen level) attributed to sediment evacuation, which is related to the contribution of the F3 fraction. The above results suggested that sand mining in the Jialing River should be paid high attention to prevent heavy metal pollution in aquatic ecosystem.

Assessing the environmental risk and mobility of cobalt in sediment near nonferrous metal mines with risk assessment indexes and the diffusive gradients in thin films (DGT) technique.

The Jialing River is the tributary of the Yangtze River with the largest drainage area. In recent years, the Jialing River has suffered a series of environmental problems, such as discharge of industrial effluent and sand mining activities, which have severely threatened the aquatic ecosystem of the river. In the present study, we employed risk assessment indexes, sequential extraction and the diffusive gradients in thin films (DGT) technique to assess environmental risks and study the remobilization of cobalt (Co) in sediments. The potential ecological risk index and risk assessment code results demonstrated that Co may pose a low environmental and ecological risk to the local aquatic environment. However, BCR sequential extraction showed that the sum of the F1, F2 and F3 fractions of Co still accounted for over 50% of the Co in the study areas, indicating that sediments may be a source of Co release. The DGT results showed an increasing trend for DGT-labile Co in deep sediments (-8 cm to -12 cm), and the calculated flux values ranged from 0.08 to 15.54 ng cm2·day-1, indicating that Co tends to transfer across the sediment-water interface at all sampling sites. Correlation analysis showed that F1-Co, F2-Co and F3-Co are the fractions readily captured by DGT and can be used for predicting Co remobilization in sediment. Sand mining activities contribute substantially to the release of Co from the F1 and F3 fractions as a result of strong stirring of sediments and introduction of oxygen into the sediments. The reductive dissolution of iron (Fe) and manganese (Mn) hydroxides or oxides causes the release of Co and Fe/Mn in the sediment, which leads to Co release from the reducible fraction. The above work suggests that sand mining in the Jialing River should be reasonably regulated to prohibit illegal sand mining activities.

IL20RA signaling enhances stemness and promotes the formation of an immunosuppressive microenvironment in breast cancer.

Rationale: Tumor microenvironment interacts with tumor cells to regulate their stemness properties through various cytokines and cytokine receptors. Previous studies revealed the possible role of interleukin 20 receptor subunit alpha (IL20RA) signaling in the progression of several types of tumors. However, its regulatory effects on the stemness and the microenvironment of breast cancer need to be studied. Methods: Immunohistochemical staining and western blot analysis were used to evaluate the association between IL20RA and SOX2 in breast tumors and noncancerous tissues. Enzyme-linked immunosorbent assay and TCGA dataset analysis were performed to determine the function of IL20RA signaling in breast cancer progression. Gain- and loss-of-function methods were performed to examine the effects of IL20RA on the stemness of breast cancer cells. The stemness features were analyzed by detecting the expression of core stemness genes, side population (SP), sphere formation ability, and aldehyde dehydrogenase (ALDH) activity. Flow cytometric analysis was applied to detect the changes of tumor-infiltration lymphocytes in tumor tissues in mice. Based on the relevant molecular mechanisms elucidated in this study, a novel IL20RA-targeted liposomal nanoparticle encapsulating the signal transducer and activator of transcription 3 (STAT3) inhibitor stattic (NP-Stattic-IL20RA) was synthesized. These NPs were combined with anti-programmed death ligand 1 (PD-L1) antibody and chemotherapy to inhibit the development of breast tumors in mice. Results: IL20RA is highly expressed in human breast cancers and is positively associated with the SOX2 expression. IL20RA increases the SP and ALDHbr proportions of breast cancer cells, enhances the sphere formation ability, and promotes the expression of core stemness genes, such as Sox2 and Oct4, as well as increases chemoresistance of breast cancer cells. IL20RA promotes the tumor-initiating ability and lung metastasis of breast cancer cells in vivo. In addition, IL20RA activates the Janus kinase 1 (JAK1)-STAT3-SOX2 signaling pathway, leading to increased expression of PD-L1 and reduced recruitment of anti-cancer lymphocytes, including CD8+ T cells and natural killer cells. Meanwhile, IL20RA signaling enhances the proportion of myeloid-derived suppressor cells. Combined with anti-PD-L1 antibody and NPs-Stattic-IL20RA, the chemotherapeutic efficacy was increased in breast cancer mouse models in vivo. Conclusion: Collectively, our results reveal that the IL20RA pathway is a novel signaling pathway involved in promoting the stemness features of breast cancer along with the formation of a tumor-favorable immune microenvironment. Targeting the IL20RAhi population with STAT3 signaling inhibition combined with anti-PD-L1 antibody can increase the therapeutic efficacy of chemotherapeutic agents for breast cancer. This study thus introduces a promising novel strategy for breast cancer therapy.

The differential magnetic relaxation behaviours of slightly distorted triangular dodecahedral dysprosium analogues in a type of cyano-bridged 3d-4f zig-zag chain compounds.

A class of cyano-bridged 3d-4f zig-zag chain compounds, {RE[TM(CN)6] (PNO)2(H2O)4}·(H2O) {RE = YIII, TM = [FeIII]LS (1); RE = DyIII, TM = [FeIII]LS (2), CoIII (3)}, have been synthesized and characterized by single-crystal X-ray diffraction. The rare earth ions in these compounds are situated in a slightly distorted triangular dodecahedral (D2d) coordination environment. The magnetic properties of compounds 1-3 have been comparatively studied in detail. Under a zero dc field, the temperature dependence of ac susceptibility measurements for YFe (1) indicates the absence of magnetic relaxation stemming from the single anisotropic [FeIII]LS ion. The dysprosium analogue DyFe (2) shows only magnetic relaxation behavior with a prominent QTM effect, while DyCo (3) exhibits SIM properties not completely covered by QTM, with an extracted energy barrier of 73 K under a zero dc field. The ab initio calculations indicate that both compounds 2 and 3 are SMMs with well-behaved magnetic relaxation properties primarily from the individual DyIII ion. Therefore, the different magnetic behaviors exhibited by compound 2 compared to 3 may be ascribed to the stronger QTM effect caused by the extra weak interaction of [FeIII]LS ions in 2 as a fluctuating transverse field around the DyIII ion. The QTM effect for both 2 and 3 is suppressed under an applied dc field with an effective energy barrier of 134 and 150 K, respectively. Compared with compound 2, the higher extracted Ueff/kB and χ''(T) peak temperature for 3 should be further attributed to its slightly higher single-ion axiality as calculated and the elimination of the transverse field from the [FeIII]LS ion.