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DietSee: An on-hand, portable, strip-type biosensor for lipolysis monitoring via real-time amperometric determination of glycerol in blood

Glycerol is a clinical biomarker of lipolysis that is mainly produced by adipose tissues. Blood glycerol content increases in pathological conditions such as metabolic and cardiovascular diseases or cancer cachexia, but also in response to energetic stress such as physical exercise. Accurate glycerol monitoring is therefore important in a range of healthcare contexts. However, current methods available for the quantification of glycerol are expensive, time-consuming, and require the extraction of plasma from blood, from which blood glycerol content is then extrapolated. Here, we report the development of a new point-of-care glycerometer device, DietSee, based on a strip-type biosensor that enables the quantification of glycerol directly from whole blood in 6 s...

Rituximab-resistant splenic memory B cells and newly engaged naive B cells fuel relapses in patients with immune thrombocytopenia

Rituximab (RTX), an antibody targeting CD20, is widely used as a first-line therapeutic strategy in B cell-mediated autoimmune diseases. However, a large proportion of patients either do not respond to the treatment or relapse during B cell reconstitution. Here, we characterize the cellular basis responsible for disease relapse in secondary lymphoid organs in humans, taking advantage of the opportunity offered by therapeutic splenectomy in patients with relapsing immune thrombocytopenia...

License to kill: microsatellite instability and immune contexture

Colorectal cancers (CRCs) with microsatellite instability (MSI) are due to a defect in the DNA mismatch repair (MMR) system resulting in an accumulation of frame-shift mutations. They are characterized by a tumor microenvironment richer in cytotoxic CD8 T-cells (CTLs) and a better prognosis compared to microsatellite stable (MSS) CRCs. The mechanisms by which defective MMR system may influence tumor-infiltrating immune cells and their impact on patient survival were still unclear. Thus, we performed a comprehensive analysis of MSI colorectal tumors.

Cholangiopathy aggravation is caused by VDR ablation and alleviated by VDR-independent vitamin D signaling in ABCB4 knockout mice

Cholangiopathies are chronic liver diseases in which damaged cholangiocytes trigger a proinflammatory and profibrotic reaction. The nuclear vitamin D receptor (VDR) is highly expressed in cholangiocytes and exerts immune-regulatory functions in these cells. In the present study, we examined the protective function of VDR and other vitamin D signaling pathways in chronic cholangiopathy and cholangiocytes. Vdr was invalidated in Abcb4 knockout mice, a widely used animal model of chronic cholangiopathy. The impact of vitamin D signaling on cholangiopathy features was examined in vivo and in cholangiocytes (primary and cell lines). Cholangiopathy features (i.e, cholestasis, ductular reaction and fibrosis) were aggravated in Vdr;Abcb4 double knockout mice compared to the Abcb4 simple knockout, and associated with an overexpression of proinflammatory factors...

Age and Sex-Related Changes in Human First-Trimester Placenta Transcriptome and Insights into Adaptative Responses to Increased Oxygen

Physiological oxygen tension rises dramatically in the placenta between 8 and 14 weeks of gestation. Abnormalities in this period can lead to gestational diseases, whose underlying mechanisms remain unclear. We explored the changes at mRNA level by comparing the transcriptomes of human placentas at 8-10 gestational weeks and 12-14 gestational weeks. A total of 20 samples were collected and divided equally into four groups based on sex and age. Cytotrophoblasts were isolated and sequenced using RNAseq. Key genes were identified using two different methods...

Maturation and persistence of the anti-SARS-CoV-2 memory B cell response

Memory B cells play a fundamental role in host defenses against viruses, but to date, their role has been relatively unsettled in the context of SARS-CoV-2. We report here a longitudinal single-cell and repertoire profiling of the B cell response up to 6 months in mild and severe COVID-19 patients. Distinct SARS-CoV-2 spike-specific activated B cell clones fueled an early antibody-secreting cell burst as well as a durable synchronous germinal center response. While highly mutated memory B cells, including pre-existing cross-reactive seasonal Betacoronavirus-specific clones, were recruited early in the response, neutralizing SARS-CoV-2 RBD-specific clones accumulated with time and largely contributed to the late, remarkably stable, memory B cell pool. Highlighting germinal center maturation, these cells displayed clear accumulation of somatic mutations in their variable region genes over time. Overall, these findings demonstrate that an antigen-driven activation persisted and matured up to 6 months after SARS-CoV-2 infection and may provide long-term protection.