Integrated single-cell transcriptome and T cell receptor profiling reveals defects of T cell exhaustion in pulmonary tuberculosis.

Tuberculosis-affected lungs with chronic inflammation harbor abundant immunosuppressive immune cells but the nature of such inflammation is unclear. Dysfunction in T cell exhaustion, while implicated in chronic inflammatory diseases, remains unexplored in tuberculosis. Given that immunotherapy targeting exhaustion checkpoints exacerbates tuberculosis, we speculate that T cell exhaustion is dysfunctional in tuberculosis. Using integrated single-cell RNA sequencing and T cell receptor profiling we reported defects in exhaustion responses within inflamed tuberculosis-affected lungs. Tuberculosis lungs demonstrated significantly reduced levels of exhausted CD8+ T cells and exhibited diminished expression of exhaustion-related transcripts among clonally expanded CD4+ and CD8+ T cells. Additionally, clonal expansion of CD4+ and CD8+ T cells bearing T cell receptors specific for CMV was observed. Expanded CD8+ T cells expressed the cytolytic marker GZMK. Hence, inflamed tuberculosis-affected lungs displayed dysfunction in T cell exhaustion. Our findings likely hold implications for understanding the reactivation of tuberculosis observed in patients undergoing immunotherapy targeting the exhaustion checkpoint.

Microfluidic magnetic detection system combined with a DNA framework-mediated immune-sandwich assay for rapid and sensitive detection of tumor-derived exosomes.

Tumor-derived circulating exosomes (TDEs) are being pursued as informative and noninvasive biomarkers. However, quantitatively detecting TDEs is still challenging. Herein, we constructed a DNA tetrahedral-structured probe (TSP)-mediated microfluidic magnetic detection system (µFMS) to provide a rapid and sensitive platform for analyzing TDEs. CD63 aptamer-modified Fe3O4 magnetic nanoparticles (MNPs) were constructed to form magnetic nano-report probes (MNRs). The microfluidic chips were fabricated from glass functionalized with DNA TSP-modified aldehyde groups and a PDMS layer designed with serpentine microchannels. An induction coil-based magnetic detector was used to measure the magnetic signal. The linear dynamic range of the µFMS system for TDE assays was 1.98 × 103-1.98 × 107 particles/mL with a limit of detection of 1.98 × 103 particles/mL in PBS. There was no significant difference in TDE detection between the simulated serum and PBS, which indicated the feasibility of the constructed µFMS system for TDE analysis in complex biological systems. In terms of cost, reaction time and operation procedure, this µFMS has the potential to be developed as a clinical point-of-care testing tool for cancer diagnosis and therapeutics.

Plants acquired mitochondrial linear plasmids horizontally from fungi likely during the conquest of land.

Mitochondrial linear plasmids have been sporadically reported in fungi and plants. Yet, much remains obscure about the diversity, distribution, and evolution of mitochondrial linear plasmids. Here, through phylogenomic analyses across 7,163 cellular organisms (including 991 plants), we find that mitochondrial linear plasmids are widely present in land plants and fungi. Phylogenetic analyses indicate that plants are likely to have acquired mitochondrial linear plasmids horizontally from fungi before or during the conquest of terrestrial environments by plants. Gene content analyses show that mitochondrial linear plasmids harbor a highly dynamic and promiscuous repertoire of genes. Our study refines the understanding of the origin and evolution of mitochondrial linear plasmids.

Connection between health risk and heavy metals in agricultural soils of China: a study based on current field investigations.

Heavy metal pollution in agricultural soil is a threat to people's health and sustainable development. However, there is currently no nationwide health risk assessment in China. In this study, we performed a preliminary assessment of heavy metals in agricultural soils of the Chinese mainland, and found obvious carcinogenic risks (total lifetime carcinogenic risk (TLCR) > 1 × 10-5). A similar spatial distribution pattern was found in soil heavy metal and the mortality of esophagus and stomach cancers. Combining the potential carcinogenic risk assessed by LCR for individual heavy metal with Pearson correlation, Geographical Detector (q statistic > 0.75 for TLCR, p < 0.05), and redundancy analysis (RDA), it was found that long-term exposure and intake route of heavy metals exceeding the maximum safety threshold (Health Canada standard) may induce digestive system (esophagus, stomach, liver, and colorectum) cancers in rural populations. Through Partial Least Squares Path Model (PLS-PM), it was also revealed that the LCR of heavy metals was closely related to the soil environmental background (path coefficients = 0.82), which in turn was affected by factors such as economic development and pollution discharge. The current research results highlight the potential carcinogenic risk to the digestive system associated with low-dose and long-term exposure to heavy metals in agricultural soils, and policymakers should propose countermeasures and solutions according to the local conditions.

Development of a new cellular immunological detection method for tuberculosis based on HupB protein induced IL-6 release test.

Objective: As a virulence factor, HupB plays important roles in the survival of MTB after infection and modulates the host immune response. In the current study, we aim to explore a new cellular immunological detection method for tuberculosis infection detection based on HupB protein. Methods: HupB was used to stimulate PBMCs extracted from pulmonary tuberculosis (PTB) patients, and secreted cytokines was examined. Then, we constructed a single center and a multi-center clinical trials to collect PBMCs from PTB patients, nPTB patients, or healthy volunteers to verify our findings. Results: Cytokine's screening illustrated that IL-6 was the only cytokine released after HupB stimulation. Single-center and multi-center clinical trials showed that HupB stimulation significantly increased the level of IL-6 in the supernatant of PBMCs from PTB patients. Then we compared the specificity and sensitivity of HupB induced IL-6 release assay with ESAT-6 and CFP10 induced interferon γ release assay (IGRA), and found in smear positive PTB patients, the specificity and sensitivity of HupB induced IL-6 release assay was better than IGRA, and in smear negative PTB patients, the sensitivity was better. Combination of both assays provided an improved specificity and sensitivity for tuberculosis diagnosis. Conclusion: This study explored an immunological detection method for tuberculosis infection cells based on HupB protein-induced IL-6 release test, which can be used to enhance the diagnosis diagnostic accuracy of TB.

Cytokines and chemokines involved in HLA-B27-positive ankylosing spondylitis-associated acute anterior uveitis.

Purpose: Acute anterior uveitis (AAU) is the most common extra-articular symptom of ankylosing spondylitis (AS). This study aims to reveal the cytokines and chemokines involved in the immunopathogenesis of human leucocyte antigen (HLA)-B27+ AS-associated AAU. Methods: Twenty-one HLA-B27+ AS-associated AAU patients and 21 healthy controls (HCs) were recruited for this study. Serum cytokine concentrations in all 42 subjects were determined by the Meso Scale Discovery (MSD) electrochemiluminescence method. In each sample, 34 cytokines, 10 chemokines, eight angiogenesis mediators, and four vascular injury mediators were measured. The differences in cytokine and chemokine concentrations were compared between the two groups. Results: Concentrations of serum IL-3, TNF-α, IL-6, IL-17D, IL-22, IP10/CXCL10, MIP-3α/CCL20, sFlt-1/VEGFR-1, CRP, and MCP-4/CCL13 were significantly higher in patients with HL-B27+ AS-associated AAU than in HCs (p < 0.05). In contrast, concentrations of serum IL-4, IL-8, MIP-1α/CCL3, Eotaxin-3/CCL26, PlGF, VEGF-C, and VEGF-D were significantly lower in patients with HL-B27+ AS-associated AAU than in HCs (p < 0.05). Conclusions: Significant differences were detected in the levels of several cytokines and chemokines in the serum of HLA-B27+ AS-associated AAU compared with HCs. Some novel differential cytokines and chemokines that have not been reported in other kinds of uveitis were also identified. These results reveal the underlying pathogenesis of HLA-B27+ AS-associated AAU and could potentially aid in clinical diagnosis.

Spatial distribution of multi-elements in moss revealing heavy metal precipitation in London Island, Svalbard, Arctic.

The Arctic is a sink for major pollutants in the Northern Hemisphere, and is an ideal place to investigate the migration of concerned metals on the local environment. In this study, 13 elements including Li, Ti, V, Cr, Mn, Fe, Co, Cu, Zn, As, Cd, Hg, and Pb were determined in mosses (Dicranum angustum) from London Island in Ny-Ålesund. The results showed that the concentrations of different elements varied greatly at different altitudes, while their distributions in low (0-200 m) and high (200-300 m) altitudes based on cluster analysis were significantly different. Among them, Li, Ti, V, Cr, Mn, Fe, Co, Cu, and As showed significant positive correlations with elevation. This result may be due to the influence of key environmental factors such as elements transported by the airborne dust carried by winds, and surface runoff from snow meltwater. Multiple receptor models (PCA, PMF, and UNMIX) were employed to discuss the sources of metals in mosses from London Island. Elements that showed positive correlation with altitude were attributed to natural sources, and Zn, Cd, Hg, and Pb, which lacked apparent correlation with elevation, were interpreted as from anthropogenic sources by the models. Among them, Zn, Cd, and Hg were from long-range deposition, while Pb was from mixed industrial sources.

The diversity and evolution of retroviruses: Perspectives from viral "fossils".

Retroviruses exclusively infect vertebrates, causing a variety of diseases. The replication of retroviruses requires reverse transcription and integration into host genomes. When infecting germline cells, retroviruses become inherited vertically, forming endogenous retroviruses (ERVs). ERVs document past viral infections, providing molecular fossils for studying the evolutionary history of retroviruses. In this review, we summarize the recent advances in understanding the diversity and evolution of retroviruses from the perspectives of viral fossils, and discuss the effects of ERVs on the evolution of host biology.

Reciprocal relation between executive function and receptive vocabulary in Chinese preschoolers: Evidence from a two-year longitudinal study.

By using a three-time longitudinal design, the present study focuses on three components of executive function (EF), respectively, to examine whether the relation between EF and receptive vocabulary was reciprocal and whether the direction of the above relation would differ by EF components and child gender. A total of 320 Chinese preschool children were assessed when they enrolled in preschool the first year (T1), the second year (T2) and the third year (T3), respectively. Children's EF was assessed by six computerized tasks, and receptive vocabulary was assessed by the Peabody Picture Vocabulary test (PPVT-4). Data were analyzed in the random intercept cross-lagged panel model (RI-CLPM). Findings provided some support for within-person reciprocal relations between EF and receptive vocabulary, but the reciprocal patterns varied depending on EF components. In specific, inhibitory control/attention shift and receptive vocabulary were reciprocally predicted between T1 and T2, and inhibitory control/attention shift at T2 could significantly predict receptive vocabulary at T3, but not vice versa. In addition, working memory and receptive vocabulary were reciprocally predicted between T1 and T2 and between T2 and T3. Finally, no child gender differences were found in the above relations. Our findings suggest that the instructions and interventions integrating EF and language skills may be an important avenue for enhancing success across skills. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

lncSAMM50 Enhances Adipogenic Differentiation of Buffalo Adipocytes With No Effect on Its Host Gene.

Fat deposition is one of the most important traits that are mediated by a set of complex regulatory factors in meat animals. Several researches have revealed the significant role of long non-coding RNAs (lncRNAs) in fat deposition while the precise regulatory mechanism is still largely elusive. In this study, we investigated the lncRNA profiles of adipose and muscle tissues in buffalo by using the Illumina HiSeq 3000 platform. In total, 43,809 lncRNAs were finally identified based on the computer algorithm. A comparison analysis revealed 241 lncRNAs that are differentially expressed (DE) in adipose and muscle tissues. We focused on lncSAMM50, a DE lncRNA that has a high expression in adipose tissue. Sequence alignment showed that lncSAMM50 is transcribed from the antisense strand of the upstream region of sorting and assembly machinery component 50 homolog (SAMM50), a gene involved in the function of mitochondrion and is subsequently demonstrated to inhibit the adipogenic differentiation of 3T3-L1 adipocyte cells in this study. lncSAMM50 is highly expressed in adipose tissue and upregulated in the mature adipocytes and mainly exists in the nucleus. Gain-of-function experiments demonstrated that lncSAMM50 promotes the adipogenic differentiation by upregulating adipogenic markers but with no effect on its host gene SAMM50 in buffalo adipocytes. These results indicate that lncSAMM50 enhances fat deposition in buffalo and provide a new factor for the regulatory network of adipogenesis.

Parental Harsh Discipline and Preschooler's Inhibitory Control in China: Bidirectional Relations and Gender Differences.

The goals of this study were to examine the bidirectional associations between parental harsh discipline and Chinese preschool children's inhibitory control and to further explore the possible gender differences in these associations. Participants were Chinese preschool children and their parents. At Time 1 (T1) and Time 2 (T2), both fathers and mothers, respectively, reported their use of psychological aggression and corporal punishment, and children's inhibitory control was assessed by laboratory tasks and maternal rating. Structural equation modeling revealed that child inhibitory control significantly predicted both paternal and maternal psychological aggression and corporal punishment 1 year later, but the predictions from both types of parental harsh discipline to child inhibitory control were nonsignificant. Multiple-group analyses further suggested that boys' but not girls' inhibitory control could significantly predict paternal corporal punishment 1 year later, and no child gender differences existed for parental psychological aggression or for maternal corporal punishment. The findings suggest that the longitudinal associations between parental hash discipline and preschool children's inhibitory control in China may differ according to the types of harsh discipline and parental and children's gender.

Comparative transcriptome analysis reveals that PCK1 is a potential gene affecting IMF deposition in buffalo.

BACKGROUND: In China, although buffaloes are abundant, beef is mainly obtained from cattle, and this preference is mainly attributed to the low intramuscular fat (IMF) content of buffalo. Genetic factors are an important driver that affects IMF deposition. RESULTS: To reveal the intrinsic factors responsible for the low IMF content of buffalo, mRNA expression patterns in muscle and adipose tissue between buffalo and cattle were characterized by RNA sequencing analysis. The IMF content in Nanyang cattle was higher than that in Xinyang buffalo. A total of 1566 mRNAs expressed in adipose tissue showed differential expression between the longissimus dorsi muscles of buffalo and cattle. Functional annotation suggested a difference in the glycolysis/gluconeogenesis pathway between the two species. The results of RT-qPCR analysis and gain-of-function experiments confirmed the positive association between the IMF content and phosphoenolpyruvate carboxykinase 1 (PCK1) expression in buffalo. In both mouse C2C12 cells and cultured bovine myocytes, the activity of the PCK1 promoter in buffalo is lower than that in cattle. However, in mouse 3T3-L1 adipocytes and cultured bovine adipocytes, the activity of PCK1 in buffalo promoter is higher than that in cattle. CONCLUSIONS: These results indicate the important role of PCK1 in buffalo IMF deposition and illustrate the differences between buffalo and cattle promoter activity that drive PCK1 expression. This research helps to establish a foundation for further studies investigating IMF deposition in buffalo.

High throughput static channeled interference imaging spectropolarimeter based on a Savart polariscope.

A high throughput static channeled interference imaging spectropolarimeter (CIISP) over 480-960nm spectral range is presented. The CIISP system includes two birefringent retarders and a Savart interferometer employing tempo-spatially mixed modulated mode with no internal moving parts, and offers a robust system and a high optical throughput to resist the instrument noise. The optical layout and operation of the CIISP sensor are presented in addition to the radiometric, spectral and improved polarimetric calibration techniques used with the system. The performance of the system is verified through laboratory tests, and the outdoor measurement demonstrates the sensor's ability for target identification, color measurement, and agriculture monitoring applications.

Achromatic Savart polariscope: choice of materials.

This paper presents the achromatization of Savart Polariscope to decrease the lateral-shear dispersion in the lateral displacement. The achromatic Savart Polariscope can be made from two different birefringent crystal materials. The achromatic model for the choices of material is presented. The achievements and performances of different achromatic Savart Polariscopes are demonstrated with numerical simulations and ray tracing program. The chromatic variation in lateral displacement can be reduced by an order of magnitude across the spectral range 0.4µm to 0.9µm.