Heart failure (HF) is the end-stage of cardiovascular diseases, which is associated with a high mortality rate and high readmission rate. Household early diagnosis and real-time prognosis of HF at ...bedside are of significant importance. Here, we developed a highly sensitive and quantitative household prognosis platform (termed as UC-LFS platform), integrating a smartphone-based reader with multiplexed upconversion fluorescent lateral flow strip (LFS). Dual-color core–shell upconversion nanoparticles (UCNPs) were synthesized as probes for simultaneously quantifying two target antigens associated with HF, i.e., brain natriuretic peptide (BNP) and suppression of tumorigenicity 2 (ST2). With the fluorescent LFS, we achieved the specific detection of BNP and ST2 antigens in spiked samples with detection limits of 5 pg/mL and 1 ng/mL, respectively, both of which are of one order lower than their clinical cutoff. Subsequently, a smartphone-based portable reader and an analysis app were developed, which could rapidly quantify the result and share prognosis results with doctors. To confirm the usage of UC-LFS platform for clinical samples, we detected 38 clinical serum samples using the platform and successfully detected the minimal concentration of 29.92 ng/mL for ST2 and 17.46 pg/mL for BNP in these clinical samples. Comparing the detection results from FDA approved clinical methods, we obtained a good linear correlation, indicating the practical reliability and stability of our developed UC-LFS platform. Therefore, the developed UC-LFS platform is demonstrated to be highly sensitive and specific for sample-to-answer prognosis of HF, which holds great potential for risk assessment and health monitoring of post-treatment patients at home.
Spatially ordered embryo-like structures self-assembled from blastocyst-derived stem cells can be generated to mimic embryogenesis in vitro. However, the assembly system and developmental potential ...of such structures needs to be further studied. Here, we devise a nonadherent-suspension-shaking system to generate self-assembled embryo-like structures (ETX-embryoids) using mouse embryonic, trophoblast and extra-embryonic endoderm stem cells. When cultured together, the three cell types aggregate and sort into lineage-specific compartments. Signaling among these compartments results in molecular and morphogenic events that closely mimic those observed in wild-type embryos. These ETX-embryoids exhibit lumenogenesis, asymmetric patterns of gene expression for markers of mesoderm and primordial germ cell precursors, and formation of anterior visceral endoderm-like tissues. After transplantation into the pseudopregnant mouse uterus, ETX-embryoids efficiently initiate implantation and trigger the formation of decidual tissues. The ability of the three cell types to self-assemble into an embryo-like structure in vitro provides a powerful model system for studying embryogenesis.
The consumption of dairy products may influence the risk of type 2 diabetes mellitus (T2DM), but inconsistent findings have been reported. Moreover, large variation in the types of dairy intake has ...not yet been fully explored.
We conducted a systematic review and meta-analysis to clarify the dose-response association of dairy products intake and T2DM risk. We searched PubMed, EMBASE and Scopus for studies of dairy products intake and T2DM risk published up to the end of October 2012. Random-effects models were used to estimate summary relative risk (RR) statistics. Dose-response relations were evaluated using data from different dairy products in each study. We included 14 articles of cohort studies that reported RR estimates and 95% confidence intervals (95% CIs) of T2DM with dairy products intake. We found an inverse linear association of consumption of total dairy products (13 studies), low-fat dairy products (8 studies), cheese (7 studies) and yogurt (7 studies) and risk of T2DM. The pooled RRs were 0.94 (95% CI 0.91-0.97) and 0.88 (0.84-0.93) for 200 g/day total and low-fat dairy consumption, respectively. The pooled RRs were 0.80 (0.69-0.93) and 0.91 (0.82-1.00) for 30 g/d cheese and 50 g/d yogurt consumption, respectively. We also found a nonlinear association of total and low-fat dairy intake and T2DM risk, and the inverse association appeared to be strongest within 200 g/d intake.
A modest increase in daily intake of dairy products such as low fat dairy, cheese and yogurt may contribute to the prevention of T2DM, which needs confirmation in randomized controlled trials.
To determine the association between complement C1q and vulnerable plaque morphology among coronary artery disease (CAD) patients. We conducted a retrospective observational study of 221 CAD patients ...admitted to The Second Affiliated Hospital of Xi'an Jiaotong University. Intravascular optical coherence tomography was utilized to describe the culprit plaques' morphology. Using logistic regression analysis to explore the correlation between C1q and vulnerable plaques, and receiver operator characteristic (ROC) analysis assess the predictive accuracy. As reported, the complement C1q level was lower in ACS patients than CCS patients (18.25 ± 3.88 vs. 19.18 ± 4.25, P = 0.045). The low complement-C1q-level group was more prone to develop vulnerable plaques. In lipid-rich plaques, the complement C1q level was positively correlated with the thickness of fibrous cap (r = 0.480, P = 0.041). Univariate and multivariate logistic regression analyses suggested that complement C1q could be an independent contributor to plaques' vulnerability. For plaque rupture, erosion, thrombus, and cholesterol crystals, the areas under the ROC curve of complement C1q level were 0.873, 0.816, 0.785, and 0.837, respectively (P < 0.05 for all). In CAD patients, the complement C1q could be a valuable indicator of plaque vulnerability.
Diabetes is one of the typical chronic diseases, and its incidence is related to many environmental factors. At present, there is no radical cure for diabetes, so the prevention of diabetes is ...particularly important. In order to effectively prevent the occurrence of diabetes, it is necessary to understand the conditions leading to the occurrence of diabetes. Current studies have shown that long-term exposure to noise will increase the risk of diabetes. Literature was retrieved from Pubmed and Web of Science. The relationship between noise exposure and diabetes published in the past 10 years was retrieved from the literature. Two researchers screened the literatures and extracted the data according to the inclusion and exclusion criteria. Endnote software was used to manage the literature, and NOS (Newcastle-Ottawa Scale) scale was used to evaluate the quality of the included literatures. Random effects meta-analysis was used to comprehensively evaluate the noise exposure of diabetic patients, and stata13.1 was used for data analysis. After adherence to strict inclusion and exclusion criteria, eight studies on the association between noise and diabetes were selected, including five cohort studies and three cross-sectional studies, with a total of 514,570 participants and 23,708 diabetics. The results showed that exposure to noise increased the risk of developing diabetes (OR = 1.08; 95% CI = 1.03 ~ 1.12). From the analysis of these selected articles, it can be seen that there is a positive correlation between noise and the occurrence of diabetes. As a result, it is necessary to strengthen routine blood tests for people who have been exposed to noise for a long time, especially those who have to be exposed to noise due to their occupations.
Pig epiblast-derived pluripotent stem cells are considered to have great potential and broad prospects for human therapeutic model development and livestock breeding. Despite ongoing attempts since ...the 1990s, no stably defined pig epiblast-derived stem cell line has been established. Here, guided by insights from a large-scale single-cell transcriptome analysis of pig embryos from embryonic day (E) 0 to E14, specifically, the tracing of pluripotency changes during epiblast development, we developed an in vitro culture medium for establishing and maintaining stable pluripotent stem cell lines from pig E10 pregastrulation epiblasts (pgEpiSCs). Enabled by chemical inhibition of WNT-related signaling in combination with growth factors in the FGF/ERK, JAK/STAT3, and Activin/Nodal pathways, pgEpiSCs maintain their pluripotency transcriptome features, similar to those of E10 epiblast cells, and normal karyotypes after more than 240 passages and have the potential to differentiate into three germ layers. Strikingly, ultradeep in situ Hi-C analysis revealed functional impacts of chromatin 3D-spatial associations on the transcriptional regulation of pluripotency marker genes in pgEpiSCs. In practice, we confirmed that pgEpiSCs readily tolerate at least three rounds of successive gene editing and generated cloned gene-edited live piglets. Our findings deliver on the long-anticipated promise of pig pluripotent stem cells and open new avenues for biological research, animal husbandry, and regenerative biomedicine.
To explore whether trimetazidine could improve symptoms, cardiac functions and clinical outcomes in patients with heart failure (HF).
A systematic literature search was conducted to identify ...randomised controlled trials (RCT) of trimetazidine for HF between 1966 and May 2010 in Pubmed, the Cochrane Central Registry of Clinical Trials and EMBASE. Reports of trials were sought that compared trimetazidine with placebo control for chronic HF in adults, with outcomes including all-cause mortality, hospitalisation, cardiovascular events, changes in cardiac function parameters and exercise capacity.
17 trials with data for 955 patients were identified by the literature search. Trimetazidine therapy was associated with a significant improvement in left ventricular ejection fraction in patients with both ischaemic (weighted mean difference (WMD) with placebo 7.37%; 95% CI 6.05 to 8.70; p<0.01) and non-ischaemic HF (WMD 8.72%; 95% CI 5.51 to 11.92; p<0.01). With trimetazidine therapy, left ventricular end-systolic volume was significantly reduced (WMD 10.37 ml; 95% CI 15.46 to 5.29; p<0.01) and New York Heart Association classification was improved (WMD 0.41; 95% CI 0.51 to 0.31; p<0.01) as was exercise duration (WMD, 30.26 s; 95% CI 8.77 to 51.75; p<0.01). More importantly, trimetazidine had a significant protective effect for all-cause mortality (RR 0.29; 95% CI 0.17 to 0.49; p<0.00001) and cardiovascular events and hospitalisation (RR 0.42; 95% CI 0.30 to 0.58; p<0.00001).
Trimetazidine might be an effective strategy for treating HF. More studies, especially larger multicentre RCT, are warranted to clarify the effect of trimetazidine on HF.
Proper follicle development is very important for the production of mature oocytes, which is essential for the maintenance of female fertility. This complex biological process requires precise gene ...regulation. The most abundant modification of mRNA, N
-methyladenosine (m
A), is involved in many RNA metabolism processes, including RNA splicing, translation, stability, and degradation. Here, we report that m
A plays essential roles during oocyte and follicle development. Oocyte-specific inactivation of the key m
A methyltransferase Mettl3 with Gdf9-Cre caused DNA damage accumulation in oocytes, defective follicle development, and abnormal ovulation. Mechanistically, combined RNA-seq and m
A methylated RNA immunoprecipitation sequencing (MeRIP-seq) data from oocytes revealed, that we found METTL3 targets Itsn2 for m
A modification and then enhances its stability to influence the oocytes meiosis. Taken together, our findings highlight the crucial roles of mRNA m
A modification in follicle development and coordination of RNA stabilization during oocyte growth.
Cultured meat production has emerged as a breakthrough technology for the global food industry with the potential to reduce challenges associated with environmental sustainability, global public ...health, animal welfare, and competition for food between humans and animals. The muscle stem cell lines currently used for cultured meat cannot be passaged in vitro for extended periods of time. Here, we develop a directional differentiation system of porcine pre-gastrulation epiblast stem cells (pgEpiSCs) with stable cellular features and achieve serum-free myogenic differentiation of the pgEpiSCs. We show that the pgEpiSCs-derived skeletal muscle progenitor cells and skeletal muscle fibers have typical muscle cell characteristics and display skeletal muscle transcriptional features during myogenic differentiation. Importantly, we establish a three-dimensional differentiation system for shaping cultured tissue by screening plant-based edible scaffolds of non-animal origin, followed by the generation of pgEpiSCs-derived cultured meat. These advances provide a technical approach for the development of cultured meat.
Purpose
This study intended to explore the effect of C-Jun N-terminal kinases 1 (JNK1) polymorphisms on the sensitivity of individual hearing loss.
Methods
A total of 1333 subjects, including 683 ...NIHL workers and 650 normal-hearing workers from east China, were included in this cross-sectional study. Genotyping of three JNK1 single nucleotide polymorphisms (rs9284, rs8428, and rs11598320) was performed. The relationship between different genotypes and noise-induced hearing loss was analyzed.
Results
Results show that rs11598320 TT genotype was associated with a higher risk of NIHL (OR 1.57, 95% CI 0.91–2.70). Stratified analysis indicated that the rs11598320 AT + AA genotype was associated with a decreased risk of hearing loss in subjects exposed to noise ≤ 16 years or a noise level > 92 dB (OR 0.68, 95% CI 0.50–0.93 and OR 0.64, 95% CI 0.42–0.96, respectively). The rs8428 TT genotype was associated with an increased risk of noise-induced hearing loss when the noise level was > 92 dB (OR 1.73, 95% CI 1.11–2.70). Haplotype TCT (rs9284–rs8424–rs11598320) was associated with an increased risk of noise-induced hearing loss (OR 1.30, 95% CI 1.00–1.68).
Conclusion
Single nucleotide polymorphisms (rs11598320 and rs8424) in JNK1 can be used as new biomarkers of susceptibility for noise-induced hearing loss in Chinese workers.
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