eccDNA-pipe: an integrated pipeline for identification, analysis and visualization of extrachromosomal circular DNA from high-throughput sequencing data.

Extrachromosomal circular DNA (eccDNA) is currently attracting considerable attention from researchers due to its significant impact on tumor biogenesis. High-throughput sequencing (HTS) methods for eccDNA identification are continually evolving. However, an efficient pipeline for the integrative and comprehensive analysis of eccDNA obtained from HTS data is still lacking. Here, we introduce eccDNA-pipe, an accessible software package that offers a user-friendly pipeline for conducting eccDNA analysis starting from raw sequencing data. This dataset includes data from various sequencing techniques such as whole-genome sequencing (WGS), Circle-seq and Circulome-seq, obtained through short-read sequencing or long-read sequencing. eccDNA-pipe presents a comprehensive solution for both upstream and downstream analysis, encompassing quality control and eccDNA identification in upstream analysis and downstream tasks such as eccDNA length distribution analysis, differential analysis of genes enriched with eccDNA and visualization of eccDNA structures. Notably, eccDNA-pipe automatically generates high-quality publication-ready plots. In summary, eccDNA-pipe provides a comprehensive and user-friendly pipeline for customized analysis of eccDNA research.

Mediating role of gestational weight gain in the relationship between socioeconomic status and preterm birth: a Chinese population-based study.

BACKGROUND: The modifiable mechanisms underlying the association between socioeconomic status (SES) and preterm birth remain unclear. This study aimed to investigate the relationship between preterm birth and maternal SES or gestational weight gain (GWG), as well as the role of GWG in mediating SES disparities in preterm birth. METHODS: Data was from a hospital-based sub-study of physical growth and development survey for Chinese newborns with various gestational ages. Singleton newborns aged from 24 to 42weeks' gestation and their mothers were included. Using information from maternal questionnaire, a composite SES was constructed with parental education and family annual income. GWG as mediator was calculated by deducting pre-pregnancy weight from maternal weight at delivery. Logistic regression model was adopted to investigate the association of preterm birth with SES or GWG. Causal mediation analysis was performed to measure mediating effect of GWG on the pathway from SES to preterm birth. RESULTS: After controlling for potential confounders, risk of preterm birth was reduced by 12.4% (OR = 0.876, 95%CI:0.855-0.879) for per one-kilogram increase of GWG, and risk of preterm birth was reduced by 24% (OR = 0.760, 95%CI: 0.717-0.806) for per one-unit increase of SES score. Mediation analysis supported a significant association between higher SES and decreased risk of preterm partly through higher GWG, in which estimated proportion mediated by GWG was 13.04% (95%CI: 11.89-16.25). GWG also played a significant role as a mediator when socioeconomic status was indicated by maternal education, paternal education or family income. GWG mediated approximately 11.03% (95% CI: 8.56-18.25) of the total effect of SES on very preterm birth, which was greater than that for moderate preterm birth (6.72%, 95%CI: 2.72-31.52) and late preterm birth (9.04%, 95%CI: 5.24-24.04). A series of sensitive analysis confirmed the robustness of association of interest. CONCLUSION: Increased GWG and higher socioeconomic status are strongly associated with a lower risk of preterm birth. GWG mediates socioeconomic disparities in preterm birth, most notably in very preterm birth. Understanding this mechanism will aid in the development of interventions and policy for maternal and child health care.

High-speed polarization tracking using thin film lithium niobate integrated dynamic polarization controller.

Dynamic polarization controllers (DPCs) are essential devices in various optical applications. We develop a thin film lithium niobate (TFLN) integrated DPC driven by the real-time implemented Jacobian control algorithm for fast polarization tracking. Experimental results demonstrate a high polarization tracking speed of 100 krad/s when targeting a specific linear state of polarization, with a low control loop delay of 420 ns, half-wave control voltages of 2.75 V, and a fast polarization restoring time of 1.6 us. Compared to previously reported integrated DPCs, the TFLN-based DPC achieves significantly higher tracking speed and lower loop delay. The results highlight the effectiveness of the Jacobian method and the outstanding performance of TFLN-based DPCs. The study opens up possibilities for further advancements in DPC solutions using TFLN technology.

Chemical Profiles and Simultaneous Quantification of Aurantii fructus by Use of HPLC-Q-TOF-MS Combined with GC-MS and HPLC Methods.

Aurantii fructus (AF) is a traditional Chinese medicine that has been used to improve gastrointestinal motility disorders for over a thousand years, but there is no exhaustive identification of the basic chemical components and comprehensive quality control of this herb. In this study, high-performance liquid chromatography coupled with quadrupole time of flight mass spectrometry (HPLC-Q-TOF-MS) and gas chromatography coupled mass spectrometry (GC-MS) were employed to identify the basic chemical compounds, and high-performance liquid chromatography (HPLC) was developed to determine the major biochemical markers from AF extract. There were 104 compounds belonging to eight structure types, including 13 amino acids or peptides, seven alkaloids, 18 flavanones, 14 flavones, 15 polymethoxyflavonoids, six triterpenoids, nine coumarins, and 18 volatile oils, as well as four other compounds that were systematically identified as the basic components from AF, and among them, 41 compounds were reported for the first time. Twelve bioactive ingredients were chosen as the benchmark markers to evaluate the quality of AF. The analysis was completed with a gradient elution at a flow rate of 0.7 mL/min within 55 min. This efficient method was validated showing good linearity, precision, stability, repeatability and recovery. Furthermore, the method was successfully applied to the simultaneous determination of 12 chemical markers in different samples of AF. This study could be applied to the identification of multiple bioactive substances and improve the quality control of AF.

Does Serum Uric Acid Mediate Relation between Healthy Lifestyle and Components of Metabolic Syndrome?

A healthy lifestyle is related to metabolic syndrome (MetS), but the mechanism is not fully understood. This study aimed to examine the association of components of MetS with lifestyle in a Chinese population and potential mediation role of serum uric acid (SUA) in the association between lifestyle behaviors and risk of components of MetS. Data were derived from a baseline survey of the Shaanxi urban cohort in the Regional Ethnic Cohort Study in northwest China. The relationship between components of MetS, healthy lifestyle score (HLS), and SUA was investigated by logistic or linear regression. A counterfactual-based mediation analysis was performed to ascertain whether and to what extent SUA mediated the total effect of HLS on components of MetS. Compared to those with 1 or less low-risk lifestyle factors, participants with 4-5 factors had 43.6% lower risk of impaired glucose tolerance (OR = 0.564; 95%CI: 0.408~0.778), 60.8% reduction in risk of high blood pressure (OR = 0.392; 95%CI: 0.321~0.478), 69.4% reduction in risk of hypertriglyceridemia (OR = 0.306; 95%CI: 0.252~0.372), and 47.3% lower risk of low levels of HDL cholesterol (OR = 0.527; 95%CI: 0.434~0.641). SUA mediated 2.95% (95%CI: 1.81~6.16%) of the total effect of HLS on impaired glucose tolerance, 14.68% (95%CI: 12.04~18.85%) on high blood pressure, 17.29% (95%CI: 15.01~20.5%) on hypertriglyceridemia, and 12.83% (95%CI: 10.22~17.48%) on low levels of HDL cholesterol. Increased HLS tends to reduce risk of components of MetS partly by decreasing the SUA level, which could be an important mechanism by which lifestyle influences MetS.

Alternative mRNA splicing events and regulators in epidermal differentiation.

Alternative splicing (AS) of messenger RNAs occurs in ∼95% of multi-exon human genes and generates diverse RNA and protein isoforms. We investigated AS events associated with human epidermal differentiation, a process crucial for skin function. We identified 6,413 AS events, primarily involving cassette exons. We also predicted 34 RNA-binding proteins (RBPs) regulating epidermal AS, including 19 previously undescribed candidate regulators. From these results, we identified FUS as an RBP that regulates the balance between keratinocyte proliferation and differentiation. Additionally, we characterized the function of a cassette exon AS event in MAP3K7, which encodes a kinase involved in cell signaling. We found that a switch from the short to long isoform of MAP3K7, triggered during differentiation, enforces the demarcation between proliferating basal progenitors and overlying differentiated strata. Our findings indicate that AS occurs extensively in the human epidermis and has critical roles in skin homeostasis.

Histone lysine methyltransferase SMYD3 promotes oral squamous cell carcinoma tumorigenesis via H3K4me3-mediated HMGA2 transcription.

BACKGROUND: Epigenetic dysregulation is essential to the tumorigenesis of oral squamous cell carcinoma (OSCC). SET and MYND domain-containing protein 3 (SMYD3), a histone lysine methyltransferase, is implicated in gene transcription regulation and tumor development. However, the roles of SMYD3 in OSCC initiation are not fully understood. The present study investigated the biological functions and mechanisms involved in the SMYD3-mediated tumorigenesis of OSCC utilizing bioinformatic approaches and validation assays with the aim of informing the development of targeted therapies for OSCC. RESULTS: 429 chromatin regulators were screened by a machine learning approach and aberrant expression of SMYD3 was found to be closely associated with OSCC formation and poor prognosis. Data profiling of single-cell and tissue demonstrated that upregulated SMYD3 significantly correlated with aggressive clinicopathological features of OSCC. Alterations in copy number and DNA methylation patterns may contribute to SMYD3 overexpression. Functional experimental results suggested that SMYD3 enhanced cancer cell stemness and proliferation in vitro and tumor growth in vivo. SMYD3 was observed to bind to the High Mobility Group AT-Hook 2 (HMGA2) promoter and elevated tri-methylation of histone H3 lysine 4 at the corresponding site was responsible for transactivating HMGA2. SMYD3 also was positively linked to HMGA2 expression in OSCC samples. Furthermore, treatment with the SMYD3 chemical inhibitor BCI-121 exerted anti-tumor effects. CONCLUSIONS: Histone methyltransferase activity and transcription-potentiating function of SMYD3 were found to be essential for tumorigenesis and the SMYD3-HMGA2 is a potential therapeutic target in OSCC.