Cortical GABAergic inhibitory interneurons have crucial roles in the development and function of the cerebral cortex. In rodents, nearly all neocortical interneurons are generated from the subcortical ganglionic eminences. In humans and nonhuman primates, however, the developmental origin of neocortical GABAergic interneurons remains unclear. Here we show that the expression patterns of several key transcription factors in the developing primate telencephalon are very similar to those in rodents, delineating the three main subcortical progenitor domains (the medial, lateral and caudal ganglionic eminences) and the interneurons tangentially migrating from them. On the basis of the continuity of Sox6, COUP-TFII and Sp8 transcription factor expression and evidence from cell migration and cell fate analyses, we propose that the majority of primate neocortical GABAergic interneurons originate from ganglionic eminences of the ventral telencephalon. Our findings reveal that the mammalian neocortex shares basic rules for interneuron development, substantially reshaping our understanding of the origin and classification of primate neocortical interneurons.
Astragalus polysaccharides (APS), which is widely used as a remedy to promote immunity of breast cancer patients, can enhance immune responses and exert anti-tumor effects. In this study, we investigated the effects and mechanisms of APS on macrophage RAW 264.7 and EAC tumor-bearing mice. Griess reaction and ELISA assays revealed that the concentrations of nitric oxide, TNF-α, IL-1β and IL-6 were increased by APS. However, this effect was diminished in the presence of TAK-242 (TLR4 inhibitor) or ST-2825(MyD88 inhibitor). In C57BL/10J (TLR4+/+wild-type) and C57BL/6J (MyD88+/+wild-type) tumor-bearing mice, the tumor apoptosis rate, immune organ indexes and the levels of TNF-α, IL-1β and IL-6 in blood increased and the tumor weight decreased by oral administration of APS for 25 days. APS had no obvious effects on IL-12p70. However, these effects were not significant in C57BL/10ScNJ (TLR4-deficient) and C57BL/B6.129P2(SJL)-Myd88m1.1Defr/J (MyD88-deficient) tumor-bearing mice. qRT-PCR and Western blot indicated that APS stimulated the key nodes in the TLR4-MyD88 dependent signaling pathway, including TLR4, MyD88, TRAF-6, NF-κB and AP-1, both in vitro and in vivo. However, TRAM was an exception. Moreover, TRAF-6 and NF-κB were not triggered by APS in gene-deficient tumor-bearing mice. Therefore, APS may modulate immunity of host organism through activation of TLR4-mediated MyD88-dependent signaling pathway.
A combination of conventional MR imaging, DWI, and DSC-PWI techniques produces a high sensitivity, specificity, positive predictive value, and negative predictive value for predicting mutations in grade II and III astrocytomas. The strategy of using advanced, semiquantitative MR imaging techniques may provide an important, noninvasive, surrogate marker that should be studied further in larger, prospective trials.
In this retrospective analysis, we evaluated associations between albumin to globulin ratio (AGR), clinicopathological characteristics, and survival in 592 patients with localized or locally advanced clear cell renal cell carcinoma (CCRCC) prior to nephrectomy. We found that low AGR was associated with more aggressive tumor behavior; patients with low AGR had poorer overall survival (OS) and cancer-specific survival (CSS) in Kaplan-Meier survival analyses both before and after propensity score matching, which was used to compensate for differences in baseline clinicopathological characteristics. AGR was an independent prognostic factor for both OS (HR: 6.799; 95% CI: 3.215−14.377; P < 0.001) and CSS (HR: 8.806; 95% CI: 3.891−19.928; P < 0.001), and its prognostic value was higher than that of other established inflammation-based prognostic scores. When AGR was incorporated into a prognostic model that included T stage, neutrophil to lymphocyte ratio (NLR), and monocyte to lymphocyte ratio (MLR), the resulting nomogram predicted 3- and 5-year OS in the patients more accurately than when AGR was not included. In conclusion, AGR may be particularly useful for improving clinical outcome predictions for patients with localized or locally advanced CCRCC.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.