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Biomedical subjects

Wenjuan Li

Publications and source records attributed to Wenjuan Li.

6 recordsLinked to original sources

Generation of eight-cell embryo-like cells from human pluripotent stem cells.

Mammalian embryonic development is a highly orchestrated process initiated by the fusion of the oocyte with sperm to generate the zygote. In humans, the zygote remains transcriptionally quiescent until the major wave of zygotic genome activation (ZGA) occurs around the eight-cell (8C) stage (day 3 after fertilization). These cells and the derived morula cells are totipotent: they have the capacity to form a whole individual. Our understanding of human totipotency is very limited because of ethical concerns using embryos and the scarcity of material available for research. Recently, we established a controllable transgene-free methodology to generate totipotent eight-cell embryo-like cells (8CLCs) from human pluripotent stem cells (PSCs) in vitro. These 8CLCs are produced using a novel medium, formulated by us, containing specific chemical compounds and cytokines. Here, we provide a detailed protocol for inducing, isolating and characterizing 8CLCs generated with this medium. The induction process can be done either in a stepwise manner (primed-naive-8CLC) that requires only 5 d starting from naive PSCs or directly from primed PSCs, which takes ~7 d. The resulting 8CLCs exhibit transcriptional and epigenetic features resembling those of human 8C embryo cells. On the basis of our experience, we expect that an individual with ~1 year of experience working with human PSC culture would be able to carry out this protocol. Our approach provides a valuable model for studying human early embryogenesis, particularly the molecular events surrounding ZGA.

Journal Article↗

Comparative evaluation of probe-capture and conventional metagenomic sequencing across multiple clinical sample types, with analysis of paired bronchoalveolar lavage fluid and blood samples.

Conventional metagenomic next-generation sequencing (mNGS) suffers from host nucleic acid interference and poor performance in low-biomass samples. Probe-capture metagenomic sequencing (PC-mNGS), which enriches microbial targets via hybridization probes, shows superior sensitivity but lacks systematic multi-sample evaluations. This study compared PC-mNGS and mNGS across diverse clinical specimens (bronchoalveolar lavage fluid [BALF], blood, cerebrospinal fluid [CSF]) and assessed the clinical utility of pathogen co-detection in paired BALF-blood samples from sepsis patients. A total of 282 samples (81 BALF, 141 blood, 25 CSF, 35 others) sequenced by both PC-mNGS and mNGS were analyzed. Additionally, 621 paired BALF-blood samples from sepsis patients with pulmonary infections were evaluated. PC-mNGS achieved higher pathogen detection rates (66.67% vs 57.10%, P = 0.000198) than mNGS, particularly in blood (66.67% vs 47.52%, P = 2.5 × 10⁻⁵). PC-mNGS detected more bacteria (19 species exclusive) and fungi (11 species exclusive) than mNGS. Viruses showed comparable detection. BALF and CSF exhibited high overall agreement (OPA: 96.30% and 88%, respectively), while blood had lower concordance (NPA: 54.05%, OPA: 70.92%). A total of 60.55% of BALF-positive samples (PC-mNGS) had co-detected pathogens in blood. Gram-negative bacteria (e.g., Klebsiella pneumoniae) and fungi (e.g., Candida albicans) showed higher blood co-detection rates than viruses. In this study, PC-mNGS detected more pathogens and showed a higher positivity rate than mNGS in blood samples. BALF sequencing data, particularly bacterial reads per million (RPM), may predict bloodstream co-detection, aiding in sepsis management. However, clinical validation and integration with traditional diagnostics are needed to confirm utility. This study highlights PC-mNGS as a promising tool for complex infections but underscores the need for rigorous multi-context validation.IMPORTANCEAccurate and rapid identification of pathogens is critical for effective treatment of severe infectious diseases, such as sepsis. This study demonstrates that probe-capture metagenomic sequencing (PC-mNGS) detected more pathogens in blood samples compared to conventional metagenomic sequencing, especially for bacterial and fungal infections. By analyzing paired lung and blood samples, we show that high pathogen levels in lung fluid may predict bloodstream infection, offering a potential early warning for clinicians. These findings support the use of PC-mNGS as a more sensitive diagnostic tool, which could lead to faster, more targeted therapies and better outcomes for patients with complex infections.

Humans↗

Decoding bipotency: a transient regulatory state bridging totipotency and lineage commitment.

Early mammalian embryogenesis entails a coordinated transition from totipotency to the first lineage bifurcation, giving rise to embryonic lineages and the extra-embryonic trophectoderm. The mechanisms by which totipotency is resolved into lineage-primed states remain incompletely understood. Emerging evidence supports a non-binary model in which cells traverse a continuum of potency states, passing through a transient bipotent intermediate that retains both embryonic and extra-embryonic potential while exiting totipotency. Here, we synthesize recent advances in the mechanisms that establish, maintain, and resolve bipotency. We emphasize the coordinated roles of transposable elements, transcription factors, and signaling pathways in regulating this transition. We also highlight newly developed bipotent stem cell models and their implications in generating advanced embryo models in vitro. Notably, current insights are largely derived from mouse systems; given key differences between mouse and human early embryogenesis, extending these findings to human models remains a critical next step.

Animals↗

Components of the metabolic syndrome as predictors of cardiovascular disease and type 2 diabetes in middle-aged Japanese men.

To determine whether the clustered features of the metabolic syndrome precede the 7 year incidence of cardiovascular disease (CVD) and type 2 diabetes, we examined 6182 Japanese male office workers aged 35-59 years without any history of CVD. The 5588 subjects without type 2 diabetes also constituted the nondiabetic cohort, and were re-examined over seven successive years. Components of the metabolic syndrome included glycemic disorder (type 2 diabetes for the risk of CVD and impaired fasting glucose for the risk of type 2 diabetes), systemic obesity, hypertension, dyslipidemia, proteinuria, and elevated white blood cell (WBC) count. After controlling for age, family history of diabetes, alcohol intake, and cigarette smoking, the multivariate-adjusted relative risk of incidence of CVD compared with absence of components was 3.18, 3.48, 12.55, and 14.15 (P for trend <0.001), for the presence of 1,2,3, and > or =4 components, respectively. The corresponding relative risks of incidence of type 2 diabetes were 1.92, 4.36, 6.44, and 15.08 (P for trend <0.001). In both non-smokers and current smokers, the multivariate-adjusted relative risks of incidence of CVD and type 2 diabetes increased as the number of components increased (P for trend <0.001 for all). Our findings indicate that clustered features of the metabolic syndrome are closely associated with development of CVD and type 2 diabetes in middle-aged Japanese.

Adult↗

Multiple risk factor clustering and risk of hypertension in Japanese male office workers.

Major risk factors associated with hypertension (a family history of hypertension, obesity, diabetes mellitus, hypercholesterolemia, hypertriglyceridemia, hyperuricemia, and increased white blood cell counts) were assessed in 5275 Japanese male office workers aged 23-59 years. After controlling for potential risk factors of hypertension, the odds ratio of hypertension compared with the absence of risk factors was 1.91, 2.65, 3.88, 6.54, and 8.18 for the presence of 1, 2, 3, 4, and > or = 5 risk factors, respectively (P for trend < 0.001). Systolic and diastolic blood pressure levels also increased in a dose-dependent manner as the number of risk factors increased. Among men not taking antihypertensive medication, the adjusted mean differences in systolic and diastolic blood pressures (mmHg) were 11.2 and 9.2 between men with the presence of > or = 5 risk factors and men without risk factors, respectively. These results indicate that the accumulation of risk factors is highly associated with the increased risk of hypertension in Japanese men.

Adult↗

Clinical analysis of 45 patients with severe acute respiratory syndrome.

OBJECTIVE: To explore the clinical and radiological features of severe acute respiratory syndrome (SARS). METHODS: Analysis of the clinical presentation, chest radiographs, course of disease and features of severe pneumonia in 45 SARS patients diagnosed at our hospital in Beijing between April 5 - 20, 2003. Also included is a summation of the clinical features of SARS. RESULTS: (1) SARS appears to have high infectivity; (2) the most common symptom is fever; (3) the count of leukocyte is normal or decreased; (4) most patients (35/45, 77.8%) had experienced a 24-hour fever prior to the abnormal chest X-ray changes which showed progression of pulmonary infiltrates within 48 hours in 71.1% (32/45) of the patients and, (5) the percentage of patients who developed severe pneumonia (24.4%) is higher than those who developed typical pneumonia. CONCLUSION: SARS is a disease with high infectivity and has its own clinical and radiological features. Early recognition, prompt isolation, and appropriate therapy are the key to combat this infection.

Adult↗