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Systemic Lupus Erythematosus (SLE) is a complex autoimmune disease with limited therapeutic targets or clinical outcome predictors. This study aimed to gain more insights into the underlying immunological pathways and prognostic biomarkers of SLE. Integrated analyses of RNA-seq data from 64 SLE and 62 healthy controls, examining 27 immune cell types to explore the key pathways and driver genes in SLE pathogenesis. Single-cell RNA sequencing data from the skin and kidney were used to determine the association of COX5A expression with organ damage. The associations of COX5A with SLE phenotypes were further evaluated in two independent cohorts, and receiver operating characteristic (ROC) curves were constructed to assess the value of COX5A as a biomarker for disease activity and organ damage in SLE. We found that oxidative phosphorylation (OXPHOS) is the most significantly altered metabolic pathway in SLE, especially in effector T cells. Notably, we identified an OXPHOS-related enzyme, COX5A, whose expression was significantly higher in effector T cells than in naïve T cells and showed associations with disease activity, organ damage, and steroid treatment of SLE. Furthermore, ROC curves showed that COX5A is a robust biomarker for disease activity, kidney involvement, and new-onset skin lesions, with the area under the curve (AUC) values of 0.880, 0.801, and 0.805, respectively. Our results identified the OXPHOS signature as a prominent feature in SLE T cells, and COX5A as a potential candidate biomarker for disease activity and organ damage in SLE. [ABSTRACT FROM AUTHOR]

This study investigated the growth, physiological changes, and the transcript levels of NHX1 gene of Iris halophila in response to low NaCl concentration (50 mM) and high NaCl concentration (150 mM). Our results showed that both 50 and 150 mM NaCl had no obvious negative effects on plant growth; what is more, low NaCl concentration (50 mM) increased root length, root fresh weight, and the ratio of root length to leaf length compared with the control group. The malondialdehyde (MDA) contents in leaves and roots of I. halophila had no obvious difference as compared with control. Proline levels of I. halophila exhibited basically an enhancement under salt stress conditions. Particularly at 4 days, the proline contents in leaves reached 1.85 to 2.31-fold higher and the contents in roots reached 1.27 to 1.62-fold higher than that of control at 50 and 150 mM NaCl, respectively. The contents of the soluble sugar in leaves and roots of I. halophila under 150 mM NaCl at 7 days were 32.4 and 98.7% higher than that of control, respectively. The increase rate of K+ contents with the increasing concentration of salt was less than that of Na+ contents, but K+ contents in the seedlings under NaCl stress was still higher than Na+ contents and the ratio of K+ to Na+ was also greater than 1. The transcript levels of IhNHX1 in leaves of I. halophila at 4 and 7 days under 150 mM NaCl were higher than that of control; however, the transcript levels of IhNHX1 in roots had no significant difference compared with the control under low and high salt stress at 1, 4, and 7 days. Therefore, salt tolerance in I. halophila could be partially due to higher proline, soluble sugar, and K+ accumulation. [ABSTRACT FROM AUTHOR]

This study investigated the involvement of the klotho-associated signaling in the apoptosis of granulosa cells (GCs) from the ovaries of patients with polycystic ovary syndrome (PCOS) and PCOS animals. Primary GCs were obtained from 26 healthy women and 43 women with PCOS. The PCOS animal model was established by the injection of dehydroepiandrosterone (DHEA). Klotho protein and associated microRNA expression in human primary GCs and rats’ ovarian tissues were measured by Western blot and real-time polymerase chain reaction, respectively. Results showed that significantly lower miR-126-5p and miR-29a-5p microRNA expressions, higher klotho protein expression, lower insulin growth factor 1 (IGF-1R) and Wnt family member 1 (Wnt1) protein expressions, and lower Akt phosphorylation at Ser473 and Thr308 residues were observed in the GCs from patients with PCOS and the ovarian tissues of PCOS rats compared to that in GCs from healthy women and ovarian tissues of normal control rats, respectively. Knockdown of klotho gene expression normalized IGF-1R and Wnt1 protein expressions and Akt phosphorylation in GCs from patients with PCOS and the ovarian tissues from PCOS rats; it also blocked the effects of insulin on apoptosis and proliferation in GCs from patients with PCOS and inhibited caspase-3 activity in ovarian tissues of PCOS rats. Knockdown of klotho gene expression increased the pregnancy rate in DHEA-treated female rats and increased the body weight of their newborns through normalizing the ovarian function and decreasing the formation of cystic follicles. In conclusion, the miR-126-5p, miR-29a-5p/klotho/insulin-IGF-1, Wnt, and Akt signal pathway may be involved in the apoptosis of GCs and subsequent development of PCOS. [ABSTRACT FROM AUTHOR]

The vesicular glutamate transporters, VGLUT1 and VGLUT2, reportedly display complementary distribution in the rat brain. However, co-expression of them in single neurons has been reported in some brain areas. We previously found co-expression of VGLUT1 and VGLUT2 mRNAs in a number of single neurons in the principal sensory trigeminal nucleus (Vp) of the adult rat; the majority of these neurons sent their axons to the thalamic regions around the posteromedial ventral nucleus (VPM) and the posterior nuclei (Po). It is well known that trigeminothalamic (T-T) projection fibers arise not only from the Vp but also from the spinal trigeminal nucleus (Vsp), and that trigeminocerebellar (T-C) projection fibers take their origins from both of the Vp and Vsp. Thus, in the present study, we examined the expression of VGLUT1 and VGLUT2 in Vp and Vsp neurons that sent their axons to the VPM/Po regions or the cortical regions of the cerebellum. For this purpose, we combined fluorescence in situ hybridization (FISH) histochemistry with retrograde tract-tracing; immunofluorescence histochemistry was also combined with anterograde tract-tracing. The results indicate that glutamatergic Vsp neurons sending their axons to the cerebellar cortical regions mainly express VGLUT1, whereas glutamatergic Vsp neurons sending their axons to the thalamic regions express VGLUT2. The present data, in combination with those of our previous study, indicate that glutamatergic Vp neurons projecting to the cerebellar cortical regions express mainly VGLUT1, whereas the majority of glutamatergic Vp neurons projecting to the thalamus co-express VGLUT1 and VGLUT2. [ABSTRACT FROM AUTHOR]

Definitive hematopoiesis generates hematopoietic stem/progenitor cells (HSPCs) that give rise to all mature blood and immune cells, but remains poorly defined in human. Here, we resolve human hematopoietic populations at the earliest hematopoiesis stage by single-cell RNA-seq. We characterize the distinct molecular profiling between early primitive and definitive hematopoiesis in both human embryonic stem cell (hESC) differentiation and early embryonic development. We identify CD44 to specifically discriminate definitive hematopoiesis and generate definitive HSPCs from hESCs. The multipotency of hESCs-derived HSPCs for various blood and immune cells is validated by single-cell clonal assay. Strikingly, these hESCs-derived HSPCs give rise to blood and lymphoid lineages in vivo. Lastly, we characterize gene-expression dynamics in definitive and primitive hematopoiesis and reveal an unreported role of ROCK-inhibition in enhancing human definitive hematopoiesis. Our study provides a prospect for understanding human early hematopoiesis and a firm basis for generating blood and immune cells for clinical purposes. [ABSTRACT FROM AUTHOR]

The activities and gene expression of antioxidative enzymes and the ROS content were analyzed in two typical storage-tolerant cultivars (Xushu 32 and Shangshu 19) and another two storage-sensitive cultivars (Yanshu 25 and Sushu 16) to explore the association between the storage capacity of sweetpotato (Ipomoea batatas (L.) Lam) and ROS scavenging capability. The storage roots of the storage-tolerant cultivars maintained higher activities and expression levels of antioxidative enzymes, including ascorbate peroxidase (APX), peroxidase (POD), catalase (CAT), and superoxide dismutase (SOD); lower activity and expression of lipoxygenase (LOX); and lower accumulation of ROS metabolites compared with the storage-sensitive cultivars. The antioxidative capability and ROS parameters of leaves were positively correlated with those of storage roots. Our results provide valuable insight for evaluating the storability of sweetpotato cultivars by analyzing the capabilities of the antioxidative system and the contents of ROS metabolites. [ABSTRACT FROM AUTHOR]