[Zuogui Pills improve testicular development of offspring rats exposed to prenatal stress via Cx43].

This study aims to reveal the mechanism of prenatal stress in affecting the testicular development of offspring rats and the intervention effects of Zuogui Pills via connexin 43(Cx43). Forty pregnant SD rats were randomized into a blank control group, a mo-del group, a high-dose(18.9 g·kg~(-1)) Zuogui Pills group, a low-dose(9.45 g·kg~(-1)) Zuogui Pills group, and a vitamin E(1.44 mg·kg~(-1)) group. The other groups except the blank control group was subjected to chronic unpredictable mild stress for the modeling of prenatal stress. The model was evaluated by sucrose preference test, open field test, and enzyme-linked immunosorbent assay(ELISA) of the glucocorticoid level. ELISA was employed to measure the thyroxine 4(T4), testosterone(T), and follicle-stimulating hormone(FSH) levels to assess kidney deficiency. Hematoxylin-eosin(HE) staining was employed to evaluate the status of testicular germ cells. An automatic sperm analyzer was used to measure the sperm quality. Immunofluorescence double staining was employed to detect the expression of Cx43 and follicle-stimulating hormone receptor(FSHR) in the testes of offspring rats. The mRNA and protein levels of Cx43, FSHR, phosphatidylinositol 3-kinase(PI3K), and protein kinase B(Akt) were determined by real-time fluorescence quantitative polymerase chain reaction and Western blot, respectively. Prenatal stress induced testicular development disorders in offspring rats. The HE staining results showed that on the day of birth, the model group had reduced seminiferous tubules in the testes, elevated FSH level in the serum, and lowered Cx43 level in the testicular tissue. Male offspring rats of 60 days old had reduced testicular spermatogenic function, decreased sperm quality, elevated FSH level and lowered T level in the serum, and down-regulated protein and mRNA levels of Cx43, FSHR, PI3K, and Akt in the testicular tissue. Zuogui Pills alleviated the abnormal development and dysfunction of testicles in the offspring rats caused by prenatal stress. In summary, Zuogui Pills may weaken the effects of prenatal stress on testicular development and spermatogenic function of offspring rats by activating the PI3K/Akt pathway to regulate Cx43 expression in the testicular tissue.

Targeting cytohesin-1 suppresses acute myeloid leukemia progression and overcomes resistance to ABT-199.

Adhesion molecules play essential roles in the homeostatic regulation and malignant transformation of hematopoietic cells. The dysregulated expression of adhesion molecules in leukemic cells accelerates disease progression and the development of drug resistance. Thus, targeting adhesion molecules represents an attractive anti-leukemic therapeutic strategy. In this study, we investigated the prognostic role and functional significance of cytohesin-1 (CYTH1) in acute myeloid leukemia (AML). Analysis of AML patient data from the GEPIA and BloodSpot databases revealed that CYTH1 was significantly overexpressed in AML and independently correlated with prognosis. Functional assays using AML cell lines and an AML xenograft mouse model confirmed that CYTH1 depletion significantly inhibited the adhesion, migration, homing, and engraftment of leukemic cells, delaying disease progression and prolonging animal survival. The CYTH1 inhibitor SecinH3 exerted in vitro and in vivo anti-leukemic effects by disrupting leukemic adhesion and survival programs. In line with the CYTH1 knockdown results, targeting CYTH1 by SecinH3 suppressed integrin-associated adhesion signaling by reducing ITGB2 expression. SecinH3 treatment efficiently induced the apoptosis and inhibited the growth of a panel of AML cell lines (MOLM-13, MV4-11 and THP-1) with mixed-lineage leukemia gene rearrangement, partly by reducing the expression of the anti-apoptotic protein MCL1. Moreover, we showed that SecinH3 synergized with the BCL2-selective inhibitor ABT-199 (venetoclax) to inhibit the proliferation and promote the apoptosis of ABT-199-resistant leukemic cells. Taken together, our results not only shed light on the role of CYTH1 in cell-adhesion-mediated leukemogenesis but also propose a novel combination treatment strategy for AML.

Traditional Chinese medicine for smoking cessation: An umbrella review of systematic reviews and meta-analysis of randomized controlled trials.

INTRODUCTION: Traditional Chinese medicine (TCM) may have special advantages in facilitating smoking cessation, but consensus on effectiveness is lacking. We aim to comprehensively review, update, and refine current evidence on TCM effectiveness and safety. METHODS: Nine databases were searched from their inception up to 28 February 2023. Systematic reviews (SRs) and meta-analysis of TCM for smoking cessation were identified and retrieved. Additional databases and hand searches of RCTs from included SRs were performed for data pooling. Cochrane ROB tools and AMSTAR-2 were used to evaluate the methodological quality of RCTs and SRs, respectively. RCT data are presented as relative risks (RR) or mean differences (MD) with 95% confidence intervals (CI) using RevMan 5.4. RESULTS: Thirteen SRs involving 265 studies with 33081 participants were included. Among these 265 studies, 157 were duplicates (58.36%) and 52 were non-RCTs (19.62%). Combined with the remaining 56 RCTs identified through hand searches, 88 RCTs involving 12434 participants were finally included for data synthesis. All the SRs focused on acupoint stimulation, and the majority were of low or very low quality. The methodological quality of RCTs was either unclear or high risk. For continuous abstinence rate, TCM external interventions were better than placebo in 6 months to 1 year (RR=1.60; 95% CI: 1.14-2.25; I2=27%; n=5533 participants). Compared with placebo, TCM external application was effective in reducing nicotine withdrawal symptoms, and the effect was gradually stable and obvious in the fourth week (MD= -4.46; 95% CI: -5.43 - -3.49; n=165 participants). Twelve RCTs reported adverse events as outcome indicators for safety evaluation, and no serious adverse events occurred. CONCLUSIONS: Despite the methodological limitations of the original studies, our review suggests that TCM intervention shows potential effectiveness on the continuous abstinence rate. Extending the intervention time can enhance the effect of TCM on nicotine withdrawal symptoms. Referred to adverse events, more data for safety evaluation are required.

Abbreviated Versus Full-Protocol MRI for Breast Cancer Neoadjuvant Chemotherapy Response Assessment: Diagnostic Performance by General and Breast Radiologists.

BACKGROUND. Abbreviated protocols could allow wider adoption of MRI in patients undergoing breast cancer neoadjuvant chemotherapy (NAC). However, abbreviated MRI has been explored primarily in screening settings. OBJECTIVE. The purpose of this article was to compare diagnostic performance of abbreviated MRI and full-protocol MRI for evaluation of breast cancer NAC response, stratifying by radiologists' breast imaging expertise. METHODS. This retrospective study included 203 patients with breast cancer (mean age, 52.1 ± 11.2 [SD] years) from two hospitals who underwent MRI before NAC initiation and after NAC completion before surgical resection from March 2017 to April 2021. Abbreviated MRI was extracted from full-protocol MRI and included the axial T2-weighted sequence and precontrast and single early postcontrast T1-weighted sequences. Three general radiologists and three breast radiologists independently interpreted abbreviated and full-protocol MRI in separate sessions, identifying enhancing lesions to indicate residual tumor and measuring lesion size. The reference standard was presence and size of residual tumor on pathologic assessment of post-NAC surgical specimens. RESULTS. A total of 50 of 203 patients had pathologic complete response (pCR). Intraobserver and interobserver agreement for abbreviated and full-protocol MRI for general and breast radiologists ranged from substantial to nearly perfect (κ = 0.70-0.81). Abbreviated MRI compared with full-protocol MRI showed no significant difference for general radiologists in sensitivity (54.7% vs 57.3%, p > .99), specificity (92.8% vs 95.6%, p = .29), or accuracy (83.4% vs 86.2%, p = .30), nor for breast radiologists in sensitivity (60.0% vs 61.3%, p > .99), specificity (94.6% vs 97.4%, p = .22), or accuracy (86.0% vs 88.5%, p = .30). Sensitivity, specificity, and accuracy were not significantly different between protocols for any reader individually (p > .05). Mean difference in residual tumor size on MRI relative to pathology for abbreviated protocol ranged for general radiologists from -0.19 to 0.03 mm and for breast radiologists from -0.15 to -0.05 mm, and for full protocol ranged for general radiologists from 0.57 to 0.65 mm and for breast radiologists from 0.66 to 0.79 mm. CONCLUSION. Abbreviated compared with full-protocol MRI showed similar intraobserver and interobserver agreement and no significant difference in diagnostic performance. Full-protocol MRI but not abbreviated MRI slightly overestimated pathologic tumor sizes. CLINICAL IMPACT. Abbreviated protocols may facilitate use of MRI for post-NAC response assessment by general and breast radiologists.

AnimalTFDB 4.0: a comprehensive animal transcription factor database updated with variation and expression annotations.

Transcription factors (TFs) are proteins that interact with specific DNA sequences to regulate gene expression and play crucial roles in all kinds of biological processes. To keep up with new data and provide a more comprehensive resource for TF research, we updated the Animal Transcription Factor Database (AnimalTFDB) to version 4.0 (http://bioinfo.life.hust.edu.cn/AnimalTFDB4/) with up-to-date data and functions. We refined the TF family rules and prediction pipeline to predict TFs in genome-wide protein sequences from Ensembl. As a result, we predicted 274 633 TF genes and 150 726 transcription cofactor genes in AnimalTFDB 4.0 in 183 animal genomes, which are 86 more species than AnimalTFDB 3.0. Besides double data volume, we also added the following new annotations and functions to the database: (i) variations (including mutations) on TF genes in various human cancers and other diseases; (ii) predicted post-translational modification sites (including phosphorylation, acetylation, methylation and ubiquitination sites) on TFs in 8 species; (iii) TF regulation in autophagy; (iv) comprehensive TF expression annotation for 38 species; (v) exact and batch search functions allow users to search AnimalTFDB flexibly. AnimalTFDB 4.0 is a useful resource for studying TF and transcription regulation, which contains comprehensive annotation and classification of TFs and transcription cofactors.

Nomogram for the prediction of triple-negative breast cancer histological heterogeneity based on multiparameter MRI features: A preliminary study including metaplastic carcinoma and non- metaplastic carcinoma.

Objectives: Triple-negative breast cancer (TNBC) is a heterogeneous disease, and different histological subtypes of TNBC have different clinicopathological features and prognoses. Therefore, this study aimed to establish a nomogram model to predict the histological heterogeneity of TNBC: including Metaplastic Carcinoma (MC) and Non-Metaplastic Carcinoma (NMC). Methods: We evaluated 117 patients who had pathologically confirmed TNBC between November 2016 and December 2020 and collected preoperative multiparameter MRI and clinicopathological data. The patients were randomly assigned to a training set and a validation set at a ratio of 3:1. Based on logistic regression analysis, we established a nomogram model to predict the histopathological subtype of TNBC. Nomogram performance was assessed with the area under the receiver operating characteristic curve (AUC), calibration curve and decision curve. According to the follow-up information, disease-free survival (DFS) survival curve was estimated using the Kaplan-Meier product-limit method. Results: Of the 117 TNBC patients, 29 patients had TNBC-MC (age range, 29-65 years; median age, 48.0 years), and 88 had TNBC-NMC (age range, 28-88 years; median age, 44.5 years). Multivariate logistic regression analysis demonstrated that lesion type (p = 0.001) and internal enhancement pattern (p = 0.001) were significantly predictive of TNBC subtypes in the training set. The nomogram incorporating these variables showed excellent discrimination power with an AUC of 0.849 (95% CI: 0.750-0.949) in the training set and 0.819 (95% CI: 0.693-0.946) in the validation set. Up to the cutoff date for this analysis, a total of 66 patients were enrolled in the prognostic analysis. Six of 14 TNBC-MC patients experienced recurrence, while 7 of 52 TNBC-NMC patients experienced recurrence. The DFS of the two subtypes was significantly different (p=0.035). Conclusions: In conclusion, we developed a nomogram consisting of lesion type and internal enhancement pattern, which showed good discrimination ability in predicting TNBC-MC and TNBC-NMC.

Recent advances in the intracellular delivery of macromolecule therapeutics.

Intracellular delivery of macromolecules is a critical procedure for biological research and drug discovery, including proteins, peptides, vaccines, antibodies and genes. The penetration of macromolecule therapeutics through the cell membrane to intracellular targets is a prerequisite for their biological activity, but most delivery systems rely on the endocytic pathway to enter the cell and confront an inability to escape from the lysosome. A profound understanding of the cellular internalization of transporting carriers can (i) optimize the design of drug delivery systems, (ii) maintain the biological activity of biomolecular drugs, (iii) improve the efficiency of intracellular macromolecule transport and release, (iv) bring new opportunities for the discovery of macromolecule therapeutics and treatment of refractory disease. This article summarizes the uptake pathway of intracellular delivery vehicles for macromolecule drugs, hoping to provide ideas and references for macromolecule therapeutics delivery systems.

Research progress on tumor hypoxia-associative nanomedicine.

Hypoxia at the solid tumor site is generally related to the unrestricted proliferation and metabolism of cancerous cells, which can cause tumor metastasis and aggravate tumor progression. Besides, hypoxia plays a substantial role in tumor treatment, and it is one of the main reasons that malignant tumors are difficult to cure and have a poor prognosis. On account of the tumor specific hypoxic environment, many hypoxia-associative nanomedicine have been proposed for tumor treatment. Considering the enhanced targeting effect, designing hypoxia-associative nanomedicine can not only minimize the adverse effects of drugs on normal tissues, but also achieve targeted therapy at the lesion site. Mostly, there can be three strategies for the treatment of hypoxic tumor, including improvement of hypoxic environment, hypoxia responsive drug release and hypoxia activated prodrug. The review describes the design principle and applications of tumor hypoxia-associative nanomedicine in recent years, and also explores its development trends in solid tumor treatment. Moreover, this review presents the current limitations of tumor hypoxia-associative nanomedicine in chemotherapy, radiotherapy, photodynamic therapy, sonodynamic therapy and immunotherapy, which may provide a reference for clinic translation of tumor hypoxia-associative nanomedicine.

Transcriptomic Features in a Single Extracellular Vesicle via Single-Cell RNA Sequencing.

Although many studies have investigated functional molecules in extracellular vesicles (EVs), the exact number of ribonucleic acid molecules in a single-EV is unknown. Therefore, it is critical to explore the transcriptomic features and heterogeneity at the level of a single-EV. Here, using the 10x Genomics platform, the RNA cargos are profiled in single EVs derived from human K562 and mesenchymal stem cells. The key steps are labeling intact EVs using calcein-AM, detecting the EV concentration via flow cytometry, and using the CB2 algorithm with adaptive thresholds to effectively distinguish real EVs from background. The gene number in a single-EV varied from 6 to 148, with a mean of 52. Ribosomal genes, mitochondrial genes, and eukaryotic translation elongation factor 1 alpha has a high EV percentage in all EV samples. Hemoglobin genes are uniquely highly expressed in K562-EVs, and cytoskeleton genes are enriched in MSC-EVs. Ten or more clusters with different marker genes in each single-EV dataset demonstrated EV heterogeneity. Moreover, integrating EVs and their parental cells reveal both EVs and cells in each cluster, indicating different cell origins of various EVs. To the best of the author's knowledge, this study provides the first high-throughput transcriptome at the single-EV level and improves the understanding of EVs.

Evaluation of the Effects of Anti-PD-1 Therapy on Triple-Negative Breast Cancer in Mice by Diffusion Kurtosis Imaging and Dynamic Contrast-Enhanced Imaging.

BACKGROUND: The monitoring of immunotherapies is still based on changes in the tumor size in imaging, with a long evaluation period and low sensitivity. PURPOSE: To investigate the effectiveness of diffusion kurtosis imaging (DKI) and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in assessing the therapeutic efficacy of anti-programmed death-1 (PD-1) therapy in a mouse triple negative breast cancer (TNBC) model. STUDY TYPE: Prospective. ANIMAL MODEL: A total of 54 BALB/c mouse subcutaneous 4 T1 transplantation models of TNBC. FIELD STRENGTH/SEQUENCE: A 3.0-T; turbo spin echo (TSE) T2-weighted imaging, DKI with seven b values (0, 500, 1000, 1500, 2000, 2500, and 3000 sec/mm2 ) and T1-twist DCE acquisition series. ASSESSMENT: DKI and DCE-MRI parameters were evaluated by two radiologists independently. Regions of interest (ROIs) were drawn manually on the maximum cross-sectional area of the lesion; care was taken to avoid necrotic areas. The tumor cell density, the CD45 and CD31 levels were analyzed by two pathologists. STATISTICAL TESTS: The two-tailed unpaired t-test, Mann-Whitney U test, Fisher's exact test and Pearson correlation coefficient were performed. A P < 0.05 was considered statistically significant. RESULTS: The apparent diffusion coefficient (ADC), mean diffusivity (MD), Ktrans and Kep values were significantly different between the two groups at each time point after treatment. There were significant differences in the mean kurtosis (MK) and Ve values between the two groups at 5 and 10 days after treatment but no significant differences at 15 days (P = 0.317 and 0.183, respectively). The ADC and MD values were significantly correlated with tumor cell density (ADC, r = -0.833; MD, r = 0.890) and the CD45 level (ADC, r = 0.720; MD, r = 0.718). The Ktrans and Kep values were significantly correlated with the CD31 level (Ktrans , r = 0.820; Kep , r = 0.683). DATA CONCLUSION: DKI and DCE-MRI could reflect the changes in tumor microstructure and tumor tissue vasculature after anti-PD-1 therapy, respectively. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY: Stage 4.

Intracellular Self-Immolative Polyprodrug with Near-Infrared Light Guided Accumulation and in Vivo Visualization of Drug Release.

The selective accumulation and real-time monitoring of drug release at tumor site are the key bottlenecks to the clinical translation of polyprodrug. Herein, an intracellular self-immolative polyprodrug (PMTO) is exploited, which not only shows the enhanced cellular internalization and selective accumulation in tumor site under the mild hyperthermia triggered by laser irradiation, but also possesses the self-monitoring drug release ability in vivo. The polyprodrug amphiphiles are synthesized by sequential esterification reaction, and hydrophilic poly(ethylene glycol) serves as blocking agent. On account of the mild hyperthermia produced by PMTO under the laser irradiation at tumor site, the cell membranous permeability increases, resulting in the enhanced cellular internalization and drug accumulation in tumor. After internalized by cells, the self-immolative PMTO nanoparticles can release free mitoxantrone (MTO) in intracellular reductive environment, and ratiometric photoacoustic imaging based on distinct signals between MTO and PMTO is presented to trace the drug release in vivo. Finally, this self-monitoring polyprodrug presents significant tumor suppression efficacy, which exhibits great potential for guiding the clinical medication in cancer treatment.

MicroRNA-Expression Profiling in Myopia: A Meta-Analysis and Systematic Review.

BACKGROUND: Myopia (nearsightedness) is currently the most common human eye disorder, worldwide. In the recent years, several studies have addressed the role of microRNAs (miRNAs) in the pathogenesis of myopia. OBJECTIVES: The aim of this study was to perform a meta-analysis on the miRNA-expression profiling studies in myopia to identify commonly dysregulated miRNAs in myopic tissues. METHOD: Seven independent studies were included in the meta-analysis. A vote-counting strategy was employed as the meta-analysis method. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis and Gene Ontology (GO) functional enrichment analysis were performed to identify the pathways most strongly affected by the dysregulated mouse miRNAs. RESULTS: According to the vote-counting method, eighteen miRNAs were reported in at least 2 studies with the consistent direction, of which 13 miRNAs were commonly upregulated in myopic samples compared with control samples, and five miRNAs were commonly downregulated. Subgroup analyses divided and compared the differentially expressed miRNAs according to species (human and animal) and ocular tissue types. The KEGG analysis showed that the dysregulated mouse miRNAs were most enriched in extracellular matrix-receptor interaction signal pathway. The most enriched GO process regulated by the dysregulated mouse miRNAs was cellular protein modification process. CONCLUSIONS: Our meta-analysis recommends several miRNAs may provide some clues of the potential biomarkers in myopia. Further mechanistic studies are warranted to elucidate the biological role of the dysregulated miRNAs in the development of myopia.

Resting-State Functional Magnetic Resonance Imaging and Functional Connectivity Density Mapping in Patients With Optic Neuritis.

Background: Using resting-state functional connectivity (rsFC), we investigated alternations in spontaneous brain activities reflected by functional connectivity density (FCD) in patients with optic neuritis (ON). Methods: We enrolled 28 patients with ON (18 males, 10 females) and 24 healthy controls (HCs; 16 males, 8 females). All subjects underwent functional magnetic resonance imaging (fMRI) in a quiet state to determine the values of rsFC, long-range FCD (longFCD), and short-range FCD (IFCD). Receiver operating characteristic (ROC) curves were generated to distinguish patients from HCs. Results: The ON group exhibited obviously lower longFCD values in the left inferior frontal gyrus triangle, the right precuneus and the right anterior cingulate, and paracingulate gyri/median cingulate and paracingulate gyri. The left median cingulate and paracingulate gyri and supplementary motor area (SMA) were also significantly lower. Obviously reduced IFCD values were observed in the left middle temporal gyrus/angular gyrus/SMA and right cuneus/SMA compared with HCs. Conclusion: Abnormal neural activities were found in specific brain regions in patients with ON. Specifically, they showed significant changes in rsFC, longFCD, and IFCD values. These may be useful to identify the specific mechanism of change in brain function in ON.

Regional brain changes in patients with diabetic optic neuropathy: a resting-state functional magnetic resonance imaging study.

BACKGROUND: To evaluate functional connection density (FCD) in patients with diabetic optic neuropathy (DON) using the resting functional connectivity (FC) method, and to determine the abnormal areas of brain activity. METHODS: Patients with DON (n=22; 10 male, 12 female) and healthy controls (HCs; n=22; 10 male, 12 female) were included in the study. The basic characteristics of the groups were matched. Functional magnetic resonance imaging (fMRI) was conducted with participants at rest, and long- and short-range FCD (long FCD and IFCD, respectively) were measured. Receiver operating characteristic (ROC) curve analysis was also conducted to determine whether DON and HC participants could be distinguished using fMRI indicators. RESULTS: Compared with HCs, the long FCD values of the left lingual gyrus, right lingual gyrus, right fusiform gyrus, and medial and lateral cingulate gyri were decreased in patients with DON. Further, the IFCD values of the left superior temporal gyrus, left inferior temporal gyrus, right inferior temporal gyrus, left cerebellar area 8, and right cerebellar Crus2 area were higher in patients with DON than in the HCs. CONCLUSIONS: DON is associated with abnormal spontaneous brain activity. Our findings contribute to elucidating the mechanisms underlying the neuropathology of DON, and provide direction for further clinical research.

Fractional amplitude of low-frequency fluctuation in patients with neovascular glaucoma: a resting-state functional magnetic resonance imaging study.

BACKGROUND: Neovascular glaucoma (NVG) is a secondary refractory disease with a poor prognosis, and there are few advanced studies on its pathogenesis and treatment. In this research, the fractional amplitude of low-frequency fluctuation (fALFF) technology was used in resting-state functional magnetic resonance imaging (rsfMRI) to investigate intrinsic neuron activity in the patient's brain with NVG. METHODS: Sixteen patients with NVG (eight males and eight females) and 16 healthy controls (HCs) of similar age and sex were included. All patients and controls received rsfMRI scans, and the differences between the two groups in fALFF values were compared by independent sample t-test. Receiver operating characteristic (ROC) curves were used to compare fALFF values in the brain regions of NVG patients and HCs and assess accuracy. Finally, Pearson linear correlation analysis assessed the correlation between fALFF signals in brain regions and the clinical evaluation indicators of patients with NVG. RESULTS: In patients with NVG, fALFF signal values in the right Rolandic operculum, left anterior cingulate and paracingulate gyri, and right caudate were significantly decreased. In contrast, fALFF signal values in the left precuneus were significantly higher than those recorded in the HCs. Analysis of the ROC curve for each brain region showed that the area under the ROC curve of NVG patients was large (close to 1), and the accuracy was good. In the NVG group, the hospital anxiety and depression scale (r=-0.952, P<0.001) and left best-corrected visual acuity (r=-0.802, P<0.001) had a negative linear correlation with the fALFF signal value of the right Rolandic operculum. The hospital anxiety and depression scale had a negative linear correlation with the fALFF signal value of the right caudate (r=-0.948, P<0.001). CONCLUSIONS: NVG patients showed dysfunction in several brain regions. These findings may assist in revealing the underlying neural mechanism of brain activity associated with NVG.

TCRdb: a comprehensive database for T-cell receptor sequences with powerful search function.

T cells and the T-cell receptor (TCR) repertoire play pivotal roles in immune response and immunotherapy. TCR sequencing (TCR-Seq) technology has enabled accurate profiling TCR repertoire and currently a large number of TCR-Seq data are available in public. Based on the urgent need to effectively re-use these data, we developed TCRdb, a comprehensive human TCR sequences database, by a uniform pipeline to characterize TCR sequences on TCR-Seq data. TCRdb contains more than 277 million highly reliable TCR sequences from over 8265 TCR-Seq samples across hundreds of tissues/clinical conditions/cell types. The unique features of TCRdb include: (i) comprehensive and reliable sequences for TCR repertoire in different samples generated by a strict and uniform pipeline of TCRdb; (ii) powerful search function, allowing users to identify their interested TCR sequences in different conditions; (iii) categorized sample metadata, enabling comparison of TCRs in different sample types; (iv) interactive data visualization charts, describing the TCR repertoire in TCR diversity, length distribution and V-J gene utilization. The TCRdb database is freely available at http://bioinfo.life.hust.edu.cn/TCRdb/ and will be a useful resource in the research and application community of T cell immunology.

CYFRA21-1/TG ratio as an accurate risk factor to predict eye metastasis in nasopharyngeal carcinoma: A STROBE-compliant article.

Nasopharyngeal carcinoma (NPC) has a distinctive geographical distribution in China, especially southern China. There are several risk factors for NPC, such as Epstein-Barr virus, genetics, and environmental exposures. Although the incidence of eye metastasis (EM) is lower than metastasis in other body parts, it often indicates poor prognosis.We assessed several serum biomarkers for their ability to predict EM in NPC. Patients with NPC were selected (n = 963), and were separated into two groups, EM and no eye metastasis. Ten factors were analyzed in both groups including triglyceride (TG), high-density lipoprotein, low-density lipoprotein, alkaline phosphatase, alpha fetoprotein, carbohydrate antigen-199, cancer antigen-153, apolipoproteins AI, apolipoprotein B, and cytokeratin fragment 19 (CYFRA21-1). Independent t tests, binary logistic regression, and receiver operating characteristic curves were used to assess the data.The EM group had significantly higher CYFRA21-1 and lower TG compared with the no eye metastasis group. Areas under the curve for CYFRA21-1, TG and CYFRA21-1/TG were 0.966, 0.771, and 0.976, respectively. The corresponding cut-off values were 12.12 ng/ml, 0.41 mmol/L, and 13.5. The sensitivity and specificity of CYFRA21-1/TG were 100% and 92.2%, respectively.The increased ratio of CYFRA21-1 to TG can be an accurate method to detect EM in patients with NPC.

Altered Brain Network Centrality in Patients with Adult Strabismus with Amblyopia: A Resting-State Functional Magnetic Resonance Imaging (fMRI) Study.

BACKGROUND The aim of this study was to explore potential changes in brain function network activity in patients with adult strabismus with amblyopia (SA) using the voxel-wise degree centrality (DC) method. MATERIAL AND METHODS We enrolled 15 patients with SA (6 males, 9 females) and 15 sex-matched healthy controls (HCs). All subjects completed resting functional magnetic resonance imaging scans. Independent-sample t tests and receiver operating characteristic (ROC) curves were used to assess DC value differences between groups, and Pearson correlation analysis was performed to evaluate correlations between DC-changed brain regions and clinical data of patients with SA. RESULTS Compared with the HC group, DC values that were lower in patients with SA included the left middle frontal gyrus and bilateral angular gyri. Increases were observed in the left fusiform gyrus, right lingual gyrus, right middle occipital gyrus, right postcentral gyrus, and left paracentral lobule. However, DC values were not correlated with clinical manifestations. ROC curve analysis showed high accuracy. CONCLUSIONS We found abnormal neural activity in specific brain regions in patients with SA. Specifically, we observed significant changes in DC values compared to HCs. These changes may be useful to identify the specific mechanisms involved in brain dysfunction in SA.

Abnormal Fractional Amplitude of Low-Frequency Fluctuation Changes in Patients with Monocular Blindness: A Functional Magnetic Resonance Imaging (MRI) Study.

BACKGROUND We used fractional amplitude of low-frequency fluctuation (fALFF) technology to investigate spontaneous cerebral activity in patients with monocular blindness (MB) and in healthy controls (HCs). MATERIAL AND METHODS Thirty MB patient and 15 HCs were included in this study. All subjects were scanned by resting-state functional magnetic resonance imaging (rs-fMRI). The independent sample t test and chi-squared test were applied to analyze demographics of MB patients and HCs. The 2-sample t test and receiver operating characteristic (ROC) curves were applied to identify the difference in average fALFF values between MB patients and HCs. Pearson's correlation analysis was applied to explore the relationship between the average fALFF values of brain areas and clinical behavior in the MB group. RESULTS MB patients had lower fALFF values in the left anterior cingulate and higher fALFF values in the left precuneus and right and left inferior parietal lobes than in HCs. Moreover, the mean fALFF values of MB patients in the left anterior cingulate had negative correlations with the anxiety scale score (r=-0.825, P<0.001) and the depression scale score (r=-0.871, P<0.001). CONCLUSIONS Our study found that MB patients had abnormal spontaneous activities in the visual and vision-related regions. The finding of abnormal neuronal activity helps to reveal the underlying neuropathologic mechanisms of vision loss.

An ultra-sensitive T-cell receptor detection method for TCR-Seq and RNA-Seq data.

MOTIVATION: T-cell receptors (TCRs) function to recognize antigens and play vital roles in T-cell immunology. Surveying TCR repertoires by characterizing complementarity-determining region 3 (CDR3) is a key issue. Due to the high diversity of CDR3 and technological limitation, accurate characterization of CDR3 repertoires remains a great challenge. RESULTS: We propose a computational method named CATT for ultra-sensitive and precise TCR CDR3 sequences detection. CATT can be applied on TCR sequencing, RNA-Seq and single-cell TCR(RNA)-Seq data to characterize CDR3 repertoires. CATT integrated de Bruijn graph-based micro-assembly algorithm, data-driven error correction model and Bayesian inference algorithm, to self-adaptively and ultra-sensitively characterize CDR3 repertoires with high performance. Benchmark results of datasets from in silico and experimental data demonstrated that CATT showed superior recall and precision compared with existing tools, especially for data with short read length and small size and single-cell sequencing data. Thus, CATT will be a useful tool for TCR analysis in researches of cancer and immunology. AVAILABILITY AND IMPLEMENTATION: http://bioinfo.life.hust.edu.cn/CATT or https://github.com/GuoBioinfoLab/CATT. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.