Development and validation of diagnostic and activity-assessing models for relapsing polychondritis based on laboratory parameters

BackgroundRelapsing polychondritis (RP) as a rare autoimmune disease is characterized by recurrent inflammation of the organs containing cartilage. Currently, no biomarkers have been integrated into clinical practice. This study aimed to construct and evaluate models based on laboratory parameters to aid in RP diagnosis, assess activity assessment, and explore associations with the pathological process.MethodsRP patients and healthy controls (HCs) were recruited at the Peking Union Medical College Hospital from July 2017 to July 2023. Clinical data including Relapsing Polychondritis Disease Activity Index (RPDAI) score and laboratory tests were collected. Differences in laboratory data between RP patients and HCs and active and inactive patients were analyzed.ResultsThe discovery cohort (cohort 1) consisted of 78 RP patients and 94 HCs. A model based on monocyte counts and neutrophil to lymphocyte ratio (NLR) could effectively distinguish RP patients from HCs with an AUC of 0.845. Active RP patients exhibited increased erythrocyte sedimentation rate, complement 3, platelet to lymphocyte ratio (PLR), NLR, and C-reactive protein to albumin ratio (CAR) compared with stable patients, which were also positively correlated with RPDAI. Notably, CAR emerged as an independent risk factor of disease activity (OR = 4.422) and could identify active patients with an AUC of 0.758. To confirm the reliability and stability of the aforementioned models, a replication cohort (cohort 2) was enrolled, including 79 RP patients and 94 HCs. The monocyte-combined NLR and CAR showed a sensitivity of 0.886 and 0.577 and a specificity of 0.830 and 0.833 in RP diagnosis and activity prediction, respectively. Furthermore, lower natural killer cell levels in RP patients and higher B-cell levels in active patients may contribute to elucidating the pathological mechanisms of disease occurrence and exacerbation.ConclusionsThe utilization of laboratory parameters provides cost-effective and valuable markers that can assist in RP diagnosis, identify disease activity, and elucidate pathogenic mechanisms

Tunable hysteresis effect for perovskite solar cells

Perovskite solar cells (PSCs) usually suffer from a hysteresis effect in current–voltage measurements, which leads to an inaccurate estimation of the device e fficiency. Although ion migration, charge trapping/ detrapping, and accumulation have been proposed as a b asis for the hysteresis, the origin of the hysteresis has not been apparently unraveled. Herein we reporte d a tunable hysteresis effect based uniquely on open- circuit voltage variations in printable mesos copic PSCs with a simplified triple-layer TiO 2 /ZrO 2 /carbon architecture. The electrons are collected by the compact TiO 2 /mesoporous TiO 2 (c-TiO 2 /mp-TiO 2 )bilayer, and the holes are collected by the carbon layer. By adj usting the spray deposition cycles for the c-TiO 2 layer andUV-ozonetreatment,weachievedhysteresis-norm al, hysteresis-free, and hysteresis-inverted PSCs. Such unique trends of tunable hysteresis are anal yzed by considering the polarization of the TiO 2 /perovskite interface, which can accumulate positive charges reversibly. Successfully tuning of the hysteresis effect clarifies the critical importance of the c-TiO 2 /perovskite interface in controlling the hysteretic trends observed, providing important insights towards the understanding of this rapidly developing photovoltaic technology

RANKL/RANK promotes the migration of gastric cancer cells by interacting with EGFR

BACKGROUND: The incidence and mortality rates of gastric cancer (GC) rank in top five among all malignant tumors. Chemokines and their receptor-signaling pathways reportedly play key roles in the metastasis of malignant tumor cells. Receptor activator of nuclear factor κB ligand (RANKL) is a member of the tumor necrosis factor family, with strong chemokine-like effects. Some studies have pointed out that the RANKL/RANK pathway is vital for the metastasis of cancer cells, but the specific mechanisms in GC remain poorly understood. RESULTS: This study reports original findings in cell culture models and in patients with GC. Flow cytometry and western blotting analyses showed that RANK was expressed in BGC-823 and SGC-7901 cells in particular. Chemotaxis experiments and wound healing assay suggested that RANKL spurred the migration of GC cells. This effect was offset by osteoprotegerin (OPG), a decoy receptor for RANKL. RANKL contributed to the activation of human epidermal growth factor receptor (HER) family pathways. The lipid raft core protein, caveolin 1 (Cav-1), interacted with both RANK and human epidermal growth factor receptor-1(EGFR). Knockdown of Cav-1 blocked the activation of EGFR and cell migration induced by RANKL. Moreover, RANK-positive GC patients who displayed higher levels of EGFR expression had poor overall survival. CONCLUSIONS: In summary, we confirmed that with the promotion of RANKL, RANK and EGFR can form complexes with the lipid raft core protein Cav-1, which together promote GC cell migration. The formation of the RANK-Cav-1-EGFR complex provides a novel mechanism for the metastasis of GC. These observations warrant confirmation in independent studies, in vitro and in vivo. They also inform future drug target discovery research and innovation in the treatment of GC progression

Segmental Membranous Glomerulopathy in Adults

Introduction: The clinicopathological features of segmental membranous glomerulopathy (SMGN) have not been well characterized. The aim of this study was to investigate the prevalence and clinicopathological features of SMGN in adults. Methods: Adult patients with biopsy-confirmed SMGN in the native kidney at our center between January 2017 to September 2020 were identified. The clinicopathological features of SMGN were collected. The glomerular deposition of IgG subclasses, M-type phospholipase A2 receptor 1 (PLA2R), thrombospondin type 1 domain-containing 7A (THSD7A) and neural epidermal growth factor-like 1 protein (NELL1) were tested. Clinical and pathologic features were comparable between NELL1-positive and NELL1-negative SMGN. Results: A total of 167 patients with biopsy-proven SMGN were enrolled. During the same period, 32,640 (33.0%) out of 98,939 renal biopsies were diagnosed with membranous nephropathy (MN) in adults. SMGN accounted for 0.17% of total kidney biopsies and 0.51% of MN in adults. One hundred and fifty (89.8%) cases were isolated SMGN and 17 (10.2%) cases were complicated with other kidney disease. Clinically, the median age of isolated SMGN patients was 41.5 years, with female (74%) predominance, and 33.1% had full nephrotic syndrome. Pathologically, IgG1 was the dominant subclass (92.5%), followed by IgG4 (45.0%). PLA2R and THSD7A staining were done in 142 and 136 isolated SMGN cases, respectively. In which, all the cases showed negative. NELL1 staining was done in 135 isolated SMGN cases, 58 cases (43.0%) showed positive. Fifty-eight patients (41.1%) had diffuse (≥90%) foot process effacement, 119 patients (83.8%) had either stage I (38.0%) or stage II (45.8%) membranous alterations in patients with SMGN. Most patients with NELL1-positive SMGN were female. Patients with NELL1-positive SMGN were more likely with lower prevalence of full nephrotic syndrome than NELL1-negative SMGN. Conclusions: SMGN is a relatively rare pathological type. Majority of patients with isolated SMGN were female, with a median age of 41.5 years, 33.1% had full nephrotic syndrome, absence of PLA2R and THSD7A, 43.0% with NELL1-positive, and mainly stage I or II MN (83.8%). NELL1 is the major target antigen of SMGN in adults

A longitudinal resource for population neuroscience of school-age children and adolescents in China

During the past decade, cognitive neuroscience has been calling for population diversity to address the challenge of validity and generalizability, ushering in a new era of population neuroscience. The developing Chinese Color Nest Project (devCCNP, 2013–2022), the first ten-year stage of the lifespan CCNP (2013–2032), is a two-stages project focusing on brain-mind development. The project aims to create and share a large-scale, longitudinal and multimodal dataset of typically developing children and adolescents (ages 6.0–17.9 at enrolment) in the Chinese population. The devCCNP houses not only phenotypes measured by demographic, biophysical, psychological and behavioural, cognitive, affective, and ocular-tracking assessments but also neurotypes measured with magnetic resonance imaging (MRI) of brain morphometry, resting-state function, naturalistic viewing function and diffusion structure. This Data Descriptor introduces the first data release of devCCNP including a total of 864 visits from 479 participants. Herein, we provided details of the experimental design, sampling strategies, and technical validation of the devCCNP resource. We demonstrate and discuss the potential of a multicohort longitudinal design to depict normative brain growth curves from the perspective of developmental population neuroscience. The devCCNP resource is shared as part of the “Chinese Data-sharing Warehouse for In-vivo Imaging Brain” in the Chinese Color Nest Project (CCNP) – Lifespan Brain-Mind Development Data Community (https://ccnp.scidb.cn) at the Science Data Bank

A transcriptomic and epigenomic cell atlas of the mouse primary motor cortex.

Single-cell transcriptomics can provide quantitative molecular signatures for large, unbiased samples of the diverse cell types in the brain1-3. With the proliferation of multi-omics datasets, a major challenge is to validate and integrate results into a biological understanding of cell-type organization. Here we generated transcriptomes and epigenomes from more than 500,000 individual cells in the mouse primary motor cortex, a structure that has an evolutionarily conserved role in locomotion. We developed computational and statistical methods to integrate multimodal data and quantitatively validate cell-type reproducibility. The resulting reference atlas-containing over 56 neuronal cell types that are highly replicable across analysis methods, sequencing technologies and modalities-is a comprehensive molecular and genomic account of the diverse neuronal and non-neuronal cell types in the mouse primary motor cortex. The atlas includes a population of excitatory neurons that resemble pyramidal cells in layer 4 in other cortical regions4. We further discovered thousands of concordant marker genes and gene regulatory elements for these cell types. Our results highlight the complex molecular regulation of cell types in the brain and will directly enable the design of reagents to target specific cell types in the mouse primary motor cortex for functional analysis

Comparative cellular analysis of motor cortex in human, marmoset and mouse

The primary motor cortex (M1) is essential for voluntary fine-motor control and is functionally conserved across mammals1. Here, using high-throughput transcriptomic and epigenomic profiling of more than 450,000 single nuclei in humans, marmoset monkeys and mice, we demonstrate a broadly conserved cellular makeup of this region, with similarities that mirror evolutionary distance and are consistent between the transcriptome and epigenome. The core conserved molecular identities of neuronal and non-neuronal cell types allow us to generate a cross-species consensus classification of cell types, and to infer conserved properties of cell types across species. Despite the overall conservation, however, many species-dependent specializations are apparent, including differences in cell-type proportions, gene expression, DNA methylation and chromatin state. Few cell-type marker genes are conserved across species, revealing a short list of candidate genes and regulatory mechanisms that are responsible for conserved features of homologous cell types, such as the GABAergic chandelier cells. This consensus transcriptomic classification allows us to use patch-seq (a combination of whole-cell patch-clamp recordings, RNA sequencing and morphological characterization) to identify corticospinal Betz cells from layer 5 in non-human primates and humans, and to characterize their highly specialized physiology and anatomy. These findings highlight the robust molecular underpinnings of cell-type diversity in M1 across mammals, and point to the genes and regulatory pathways responsible for the functional identity of cell types and their species-specific adaptations