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Several studies have investigated the multiple roles for DCs in kidney homeostasis and disease, but it has become clear that current tools and subset markers are not sufficient to accurately distinguish DCs from macrophages. Multidimensional transcriptomic analysis studies promise to improve mononuclear phagocyte classification and provide a clearer view of DC ontogeny and subsets.Temozolomide (TMZ) insensitivity and resistance are major causes of treatment failure and poor prognosis for GBM patients. Here, we identify LRRC4 as a novel autophagy inhibitor that restores the sensitivity of GBMs to TMZ. LRRC4 was associated with the DEPTOR/mTOR complex, and this interaction resulted in autophagy inhibition. Further investigation demonstrated that the PDZ binding domain of LRRC4 binds to the PDZ domain of DEPTOR. This binding decreases the half-life of DEPTOR via ubiquitination, thus inhibiting GBM cell autophagy and increasing the TMZ treatment response of GBM. Combined LRRC4 expression and TMZ treatment prolonged the survival of mice with tumour xenografts. Furthermore, the levels of LRRC4, DEPTOR and autophagy are clinically relevant for GBM, indicating that LRRC4 is likely to have significant potential as a therapeutic marker and target for TMZ treatment in glioma patients.Hepatocellular carcinoma (HCC) metastasis is largely responsible for HCC-associated recurrence and mortality. We aimed to identify metastasis-related long non-coding RNAs (lncRNAs) to understand the molecular mechanism of HCC metastasis. We first identified that miR-1258 was downregulated in HCC tissues both in The Cancer Genome Atlas (TCGA) and Sun Yat-sen University Cancer Center (SYSUCC) dataset. MiR-1258 expression negatively correlated with recurrence-free survival and overall survival of HCC patients. MiR-1258 overexpression inhibited migration and invasion of HCC cells both in vitro and in vivo, whereas miR-1258 downregulation promoted cell metastasis. Luciferase assays verified direct binding of miR-1258 to Smad2 and Smad3, thereby attenuating TGF-β/Smad signaling. We further established that lncRNA LINC01278 was a negative regulator of miR-1258. In vivo and in vitro assays demonstrated that LINC01278-mediated HCC metastasis was dependent on miR-1258 expression. Furthermore, miR-1258 downregulation in turn increased LINC01278 expression. We also observed that TCF-4 could bind to the LINC01278 promoter site. In addition, LINC01278 downregulation decreased migration and invasion of HCC cells induced by β-catenin and TGF-β1 both in vitro and in vivo. We uncovered a novel mechanism for β-catenin/TCF-4-LINC01278-miR-1258-Smad2/3 feedback loop activation in HCC metastasis, and the study indicated that LINC01278 could serve as a therapeutic target for HCC metastasis.Digital phenotyping has potential to quantify the lived experience of mental illness and generate real-time, actionable results related to recovery, such as the case of social rhythms in individuals with bipolar disorder. However, passive data features for social rhythm clinical targets in individuals with schizophrenia have yet to be studied. In this paper, we explore the relationship between active and passive data by focusing on temporal stability and variance at an individual level as well as large-scale associations on a population level to gain clinically actionable information regarding social rhythms. From individual data clustering, we found a 19% cluster overlap between specific active and passive data features for participants with schizophrenia. In the same clinical population, two passive data features in particular associated with social rhythms, "Circadian Routine" and "Weekend Day Routine," and were negatively associated with symptoms of anxiety, depression, psychosis, and poor sleep (Spearman ρ ranged from -0.23 to -0.30, p less then 0.001). Conversely, in healthy controls, more stable social rhythms were positively correlated with symptomatology (Spearman ρ ranged from 0.20 to 0.44, p less then 0.05). Our results suggest that digital phenotyping in schizophrenia may offer clinically relevant information for understanding how daily routines affect symptomatology. Specifically, negative correlations between smartphone reported anxiety, depression, psychosis, and poor sleep in individuals with schizophrenia, but not in healthy controls, offer an actionable clinical target and area for further investigation.Generation of bispecific antibodies (BsAbs) having two unique Fab domains requires heterodimerization of the two heavy chains and pairing of each heavy chain with its cognate light chain. An alternative bispecific scaffold (Bipod) comprising an scFv and a Fab on a heterodimeric Fc eliminates the possibility of light chain mispairing. However, unpredictable levels of chain expression and scFv-induced aggregation can complicate purification and reduce the yield of desired Bipod. AHPN agonist Here, we describe a high-throughput method for generation of Bipods based on protein A and CH1 domain affinity capture. This method exploits over-expression of the scFv chain to maximize heterodimer yield. Bipods purified by this method have purity suitable for cell-based functional assays and in vivo studies.Type C hepatic encephalopathy (type C HE) is increasingly suspected in children with chronic liver disease (CLD), and believed to underlie long-term neurocognitive difficulties. The molecular underpinnings of type C HE in both adults and children are incompletely understood. In the present study we combined the experimental advantages of in vivo high field 1H magnetic resonance spectroscopy with immunohistochemistry to follow longitudinally over 8 weeks the neurometabolic changes in the hippocampus of animals having undergone bile duct ligation as pups. Rats who develop CLD early in life displayed pronounced neurometabolic changes in the hippocampus characterized by a progressive increase in glutamine concentration which correlated with plasma ammonia levels and a rapid decrease in brain myo-inositol. Other neurometabolic findings included a decrease in other organic osmolytes (taurine, choline-containing compounds and creatine), ascorbate and glutamate. At the cellular level, we observed an increase in glial fibrillary acidic protein (GFAP) and aquaporin 4 (AQP4) expression in the hippocampus at 4 weeks post bile duct ligation (BDL), together with astrocytic morphological alterations.
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