BACKGROUND: Existing models for predicting that biochemical recurrence (BCR) will occur in patients after radical prostatectomy (RP) vary in their predictive results from magnetic resonance imaging (MRI). This study aimed to assess the predictive value of preoperative prostate-specific antigen (PSA) levels combined with MRI features in determining BCR following radical prostatectomy.
METHODS: A retrospective analysis was conducted on a cohort comprising 102 patients who underwent radical prostatectomy at our hospital between January 2019 and December 2019. On the basis of the outcomes observed during a 4-year follow-up after surgery, the patients were categorised into BCR group (n = 52) and non-BCR group (n = 50). Differences in preoperative PSA levels and MRI characteristics between the two groups were compared, and factors influencing postoperative BCR were analysed. The receiver operating characteristic curve was drawn, and the sensitivity, specificity, area under the curve (AUC) and Youden index were calculated to observe the predictive value of the combination of preoperative PSA level and MRI features for BCR following radical prostatectomy.
RESULTS: Logistic regression analysis showed that preoperative PSA level, postoperative Gleason score, data system (Prostate Imaging-Reporting and Data System (PI-RADS)) score and clinical T stage were independent risk factors for BCR in patients following radical prostatectomy, with odds ratio (OR) greater than 1. The AUC value of preoperative PSA level combined with PI-RADS score was 0.921, surpassing the AUC values of 0.783, 0.822, 0.617 and 0.608 predicted by preoperative PSA level, postoperative Gleason score, PI-RADS score and clinical T stage alone, respectively.
CONCLUSIONS: Postoperative BCR in patients with prostate cancer undergoing radical prostatectomy is associated with preoperative PSA level, postoperative Gleason score, PI-RADS score and clinical T stage. The combination of preoperative PSA level and MRI features can improve the predictive efficiency for postoperative BCR.

Autoimmune diseases (AIDs) are immune system disorders where the body exhibits an immune response to its own antigens, causing damage to its own tissues and organs. The pathogenesis of AIDs is incompletely understood. However, recent advances in immune repertoire sequencing (IR-seq) technology have opened-up a new avenue to study the IR. These studies have revealed the prevalence in IR alterations, potentially inducing AIDs by disrupting immune tolerance and thereby contributing to our comprehension of AIDs. IR-seq harbors significant potential for the clinical diagnosis, personalized treatment, and prognosis of AIDs. This article reviews the application and progress of IR-seq in diseases, such as multiple sclerosis, systemic lupus erythematosus, rheumatoid arthritis, and type 1 diabetes, to enhance our understanding of the pathogenesis of AIDs and offer valuable references for the diagnosis and treatment of AIDs.

Contamination of soils by Molybdenum (Mo) has raised increasing concern worldwide. Both fulvic acid (FA) and humic acid (HA) possess numerous positive properties, such as large specific surface areas and microporous structure that facilitates the immobilization of the heavy metal in soils. Despite these characteristics, there have been few studies on the microbiology effects of FA and HA. Therefore, this study aimed to assess the Mo immobilization effects of FA and HA, as well as the associated changes in microbial community in Mo-contaminated soils (with application rates of 0%, 0.5% and 1.0%). The result of the incubation demonstrated a decrease in soil pH (from 8.23 ~ 8.94 to 8.05 ~ 8.77). Importantly, both FA and HA reduced the exchangeable fraction and reducible fraction of Mo in the soil, thereby transforming Mo into a more stable form. Furthermore, the application of FA and HA led to an increase in the relative abundance of Actinobacteriota and Firmicutes, resulting in alterations to the microbial community structure. However, it is worth noting that due to the differing structures and properties of FA and HA, these outcomes were not entirely consistent. In summary, the aging of FA and HA in soil enhanced their capacity to immobilization Mo as a soil amendment. This suggests that they have the potential to serve as effective amendments for the remediation of Mo-contaminated soils.

BACKGROUND: Primary Sjogren\'s syndrome (pSS) is a complex autoimmune disease featuring damage to salivary and lacrimal glands, with the possibility of manifestations across multiple organs. Antibody-producing B cells have long been appreciated to play a significant role in pSS pathogenesis, with a number of autoreactive antibody species having been identified to be elevated in pSS patients. While several studies have attempted to characterize the BCR repertoires of peripheral blood B cells in pSS patients, much remains unknown about the repertoire characteristics of gland-infiltrating B cells.
METHODS: Through paired scRNAseq and scBCRseq, we profiled the BCR repertoires of both infiltrating and circulating B cells in a small cohort of patients. We further utilize receptor reconstruction analyses to further investigate repertoire characteristics in a wider cohort of pSS patients previously profiled through RNAseq.
RESULTS: Via integrated BCR and transcriptome analysis of B cell clones, we generate a trajectory progression pattern for infiltrated memory B cells in pSS. We observe significant differences in BCR repertoires between the peripheral blood and labial gland B cells of pSS patients in terms of relative expansion, isotype usage, and BCR clustering. We further observe significant decreases in IgA2 isotype usage among pSS patient labial and parotid gland B cells these analyses relative to controls as well as a positive correlation between kappa/lambda light chain usage and clinical disease activity.
CONCLUSIONS: Through BCR repertoire analysis of pSS patient salivary glands, we identify a number of novel repertoire characteristics that may serve as useful indicators of clinical disease and disease activity. By collecting these BCR repertoires into an accessible database, we hope to also enable comparative analysis of patient repertoires in pSS and potentially other autoimmune disorders.

Myocarditis has emerged as a rare but lethal immune checkpoint inhibitor (ICI)-associated toxicity. However, the exact mechanism and the specific therapeutic targets remain underexplored. In this study, we aim to characterise the transcriptomic profiles based on single-cell RNA sequencing from ICI-related myocarditis. Peripheral blood mononuclear cell (PBMC) samples were collected from four groups for single-cell RNA sequencing: (1) patients with newly diagnosed lung squamous cell carcinoma before treatment (Control Group); (2) patients with lung squamous cell carcinoma with PD-1 inhibitor therapy who did not develop myocarditis (PD-1 Group); (3) patients during fulminant ICI-related myocarditis onset (Myocarditis Group); and (4) Patients with fulminant ICI-related myocarditis during disease remission (Recovery Group). Subcluster determination, functional analysis, single-cell trajectory and cell-cell interaction analysis were performed after scRNA-seq. Bulk-RNA sequencing was performed for further validation. Our results revealed the diversity of cellular populations in ICI-related myocarditis, marked by their distinct transcriptional profiles and biological functions. Monocytes, NKs as well as B cells contribute to the regulation of innate immunity and inflammation in ICI-related myocarditis. With integrated analysis of scRNA-seq and bulk sequencing, we identified S100A protein family as a potential serum marker for ICI-related myocarditis. Our study has created a cell atlas of PBMC during ICI-related myocarditis, which would shed light on the pathophysiological mechanism and potential therapeutic targets of ICI-related myocarditis in continuous exploration.

The development of vaccines, which induce effective immune responses while ensuring safety and affordability, remains a substantial challenge. In this study, we proposed a vaccine model of a restructured \"head-to-tail\" dimer to efficiently stimulate B cell response. We also demonstrate the feasibility of using this model to develop a paramyxovirus vaccine through a low-cost rice endosperm expression system. Crystal structure and small-angle X-ray scattering data showed that the restructured hemagglutinin-neuraminidase (HN) formed tetramers with fully exposed quadruple receptor binding domains and neutralizing epitopes. In comparison with the original HN antigen and three traditional commercial whole virus vaccines, the restructured HN facilitated critical epitope exposure and initiated a faster and more potent immune response. Two-dose immunization with 0.5 μg of the restructured antigen (equivalent to one-127th of a rice grain) and one-dose with 5 μg completely protected chickens against a lethal challenge of the virus. These results demonstrate that the restructured HN from transgenic rice seeds is safe, effective, low-dose useful, and inexpensive. We provide a plant platform and a simple restructured model for highly effective vaccine development.

Lead (Pb) is a highly toxic element and is not essential to the human body. Lead pollution caused by human activities and a high geological background is considered a global environmental issue. According to the China Geochemical Baseline (CGB) project, the Pearl River Basin had the highest Pb content in alluvial sediments of 30 first-level basins in China. For this reason, it is of great significance to determine the temporal and spatial variations in Pb and their influencing factors in the Pearl River Basin. In this study, 956 stream sediment samples collected in the 1980 s (early stage) and 129 river sediment samples collected from 2008 to 2010 (late stage) were used to study the background value and spatial-temporal variation characteristics of Pb in river sediments in the Pearl River Basin. The Pb source apportionment and an ecological risk assessment were also carried out. The background value of Pb (36.2 mg·kg-1) in the river sediments of the Pearl River Basin was significantly higher than that in China (22.1 mg·kg-1). The parent rocks determine the Pb background in sediments and the high Pb background areas mainly comprised carbonate rocks and acid volcanic rocks. Over 20 years of rapid industrialisation, the average Pb increased from 43.3 to 68.3 mg·kg-1 in the Pearl River Basin. The BCR analysis revealed that Pb mainly existed in the reducible phase (48 % on average) and residue phase (42 % on average). The enrichment factor and geo-accumulation index indicated that the late-stage sediments experienced more Pb pollution than the early-stage sediments. However, the risk assessment code (RAC) showed that there was a low ecological risk of Pb in the late-stage sediments. The factor analysis results for the two rounds of data were significantly different. The Pb content in early-stage sediments was closely related to Al2O3 and Zr, while Pb in the late-stage sediments was mainly related to Zn, As, Sb, Au and Hg, indicating that the increase in Pb in the later samples was mainly influenced by human activities. The Pb isotope composition of the late-stage sediments confirmed that low Pb content was mainly controlled by natural sources, while high Pb content was significantly affected by anthropogenic sources. Combining the results of spatial-temporal variation, chemical speciation and source apportionment indicated that the rapid rise of Pb in late-stage sediments in certain areas could be attributed to mining and smelting activities during the process of industrialisation over 20 years. The anthropogenic exogenous Pb could be immobilised by Fe-Mn (hydro)oxides when it entered the soil, so although there was a high background the ecological risk of Pb in river sediments was low. In the future, Pb pollution control and remediation needs to be strengthened in the Pearl River Basin to avoid the outbreak of potential ecological risks linked to Pb.

Advances in high-throughput sequencing technologies have facilitated the large-scale characterization of B cell receptor (BCR) repertoires. However, the vast amount and high diversity of the BCR sequences pose challenges for efficient and biologically meaningful analysis. Here, we introduce fastBCR, an efficient computational approach for inferring B cell clonal families from massive BCR heavy chain sequences. We demonstrate that fastBCR substantially reduces the running time while ensuring high accuracy on simulated datasets with diverse numbers of B cell lineages and varying mutation rates. We apply fastBCR to real BCR sequencing data from peripheral blood samples of COVID-19 patients, showing that the inferred clonal families display disease-associated features, as well as corresponding antigen-binding specificity and affinity. Overall, our results demonstrate the advantages of fastBCR for analyzing BCR repertoire data, which will facilitate the identification of disease-associated antibodies and improve our understanding of the B cell immune response.

Pulmonary arterial hypertension (PAH) is a rare complication of primary Sjögren\'s syndrome (pSS). Several genes have proven to be associated with pSS and PAH. However, there is no study specifically addressing the genetic susceptibility in pSS combined with PAH.
Thirty-four unrelated patients with pSS-PAH were recruited from April 2019 to July 2021 at Peking Union Medical College Hospital. Demographic and clinical data were recorded in detail, and peripheral blood samples were collected for whole-exome sequencing (WES). Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed to predict the functional effect of mutant genes. Genetic variants identified by WES were confirmed by polymerase chain reaction (PCR)-Sanger sequencing.
We totally identified 141 pathogenic variant loci of 129 genes in these 34 pSS-PAH patients, using WES analysis. Patients with a family history of rheumatic diseases are more likely to carry FLG mutations or carry gene variations related to the biosynthesis of the amino acids pathway (p < 0.05). According to Sanger sequencing confirmation and pathogenicity validation, we totally identified five candidate pathogenic variants including FLG c.12064A > T, BCR c.3275_3278dupCCGG, GIGYF2 c.3463C > A, ITK c.1741C > T, and SLC26A4 c.919-2A > G.
Our findings provide preliminary data of exome sequencing to identify susceptibility loci for pSS-PAH and enriched our understanding of the genetic etiology for pSS-PAH. The candidate pathogenic genes may be the potential genetic markers for early warning of this disease.

BACKGROUND: A predictive model for biochemical recurrence (BCR) of prostate cancer (PCa) after neoadjuvant androgen deprivation therapy (nADT) has not been established. This study was aimed at determining multiparameter variables that could be used to construct a nomogram to predict the post-nADT BCR of PCa.
METHODS: Overall, 43 radical prostatectomy specimens from PCa patients who had undergone nADT were collected. Multiparameter variables were analyzed by univariate and then multivariate logistic analyses to identify the independent prognostic factors for predicting BCR. The predictive model was established using Lasso regression analysis.
RESULTS: Univariate logistic analysis revealed six variables, pathology stage; margins; categorization as group A, B, or C; nucleolus grading; percentage of tumor involvement (PTI); and PTEN status were significantly associated with the BCR of PCa (all p < 0.05). Multivariate logistic regression analysis suggested that categorization as group C, severe nucleolus grading, PTI less than or equal to 5%, and PTEN loss were positively correlated with BCR (all p < 0.05). A nomogram comprising the four variables predicting BCR was constructed, and it exhibited good discrimination (AUC: 0.985; specificity: 86.2%; sensitivity: 100%). Calibration plots for the probability of freedom from BCR at 1 and 2 years showed a good match between the prediction by the nomogram.
CONCLUSIONS: We constructed and validated a nomogram to predict the risk of BCR in PCa patients after nADT. This nomogram is a complement to the existing risk stratification systems for PCa, which could have marked implications for clinical decision-making for PCa patients after nADT.