Comprehensive maturity of nuclear pore complexes regulates zygotic genome activation.

Nuclear pore complexes (NPCs) are channels for nucleocytoplasmic transport of proteins and RNAs. However, it remains unclear whether composition, structure, and permeability of NPCs dynamically change during the cleavage period of vertebrate embryos and affect embryonic development. Here, we report that the comprehensive NPC maturity (CNM) controls the onset of zygotic genome activation (ZGA) during zebrafish early embryogenesis. We show that more nucleoporin proteins are recruited to and assembled into NPCs with development, resulting in progressive increase of NPCs in size and complexity. Maternal transcription factors (TFs) transport into nuclei more efficiently with increasing CNM. Deficiency or dysfunction of Nup133 or Ahctf1/Elys impairs NPC assembly, maternal TFs nuclear transport, and ZGA onset, while nup133 overexpression promotes these processes. Therefore, CNM may act as a molecular timer for ZGA by controlling nuclear transport of maternal TFs that reach nuclear concentration thresholds at a given time to initiate ZGA.

Endoplasmic reticulum-plasma membrane contact gradients direct cell migration.

Directed cell migration is driven by the front-back polarization of intracellular signalling1-3. Receptor tyrosine kinases and other inputs activate local signals that trigger membrane protrusions at the front2,4-6. Equally important is a long-range inhibitory mechanism that suppresses signalling at the back to prevent the formation of multiple fronts7-9. However, the identity of this mechanism is unknown. Here we report that endoplasmic reticulum-plasma membrane (ER-PM) contact sites are polarized in single and collectively migrating cells. The increased density of these ER-PM contacts at the back provides the ER-resident PTP1B phosphatase more access to PM substrates, which confines receptor signalling to the front and directs cell migration. Polarization of the ER-PM contacts is due to microtubule-regulated polarization of the ER, with more RTN4-rich curved ER at the front and more CLIMP63-rich flattened ER at the back. The resulting ER curvature gradient leads to small and unstable ER-PM contacts only at the front. These contacts flow backwards and grow to large and stable contacts at the back to form the front-back ER-PM contact gradient. Together, our study suggests that the structural polarity mediated by ER-PM contact gradients polarizes cell signalling, directs cell migration and prolongs cell migration.

Association Between Home Renovation and Sleeping Problems Among Children Aged 6-18 Years: A Nationwide Survey in China.

BACKGROUND: Although the indoor environment has been proposed to be associated with childhood sleep health, to our knowledge no study has investigated the association between home renovation and childhood sleep problems. METHODS: The study included 186,470 children aged 6-18 years from the National Chinese Children Health Study (2012-2018). We measured childhood sleeping problems via the Chinese version of the Sleep Disturbance Scale for Children (C-SDSC). Information on home renovation exposure within the recent 2 years was collected via parent report. We estimated associations between home renovation and various sleeping problems, defined using both continuous and categorized (binary) C-SDSC t-scores, using generalized mixed models. We fitted models with city as a random effect variable, and other covariates as fixed effects. RESULTS: Out of the overall participants, 89,732 (48%) were exposed to recent home renovations. Compared to the unexposed group, children exposed to home renovations had higher odds of total sleep disorder (odd ratios [OR] = 1.3; 95% confidence interval [CI] = 1.2, 1.4). Associations varied when we considered different types of home renovation materials. Children exposed to multiple types of home renovation had higher odds of sleeping problems. We observed similar findings when considering continuous C-SDSC t-scores. Additionally, sex and age of children modified the associations of home renovation exposure with some of the sleeping problem subtypes. CONCLUSIONS: We found that home renovation was associated with higher odds of having sleeping problems and that they varied when considering the type of renovation, cumulative exposure, sex, and age differences.

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.

Molecular basis for bipartite recognition of histone H3 by the PZP domain of PHF14.

Histone recognition constitutes a key epigenetic mechanism in gene regulation and cell fate decision. PHF14 is a conserved multi-PHD finger protein that has been implicated in organ development, tissue homeostasis, and tumorigenesis. Here we show that PHF14 reads unmodified histone H3(1-34) through an integrated PHD1-ZnK-PHD2 cassette (PHF14PZP). Our binding, structural and HDX-MS analyses revealed a feature of bipartite recognition, in which PHF14PZP utilizes two distinct surfaces for concurrent yet separable engagement of segments H3-Nter (e.g. 1-15) and H3-middle (e.g. 14-34) of H3(1-34). Structural studies revealed a novel histone H3 binding mode by PHD1 of PHF14PZP, in which a PHF14-unique insertion loop but not the core ß-strands of a PHD finger dominates H3K4 readout. Binding studies showed that H3-PHF14PZP engagement is sensitive to modifications occurring to H3 R2, T3, K4, R8 and K23 but not K9 and K27, suggesting multiple layers of modification switch. Collectively, our work calls attention to PHF14 as a 'ground' state (unmodified) H3(1-34) reader that can be negatively regulated by active marks, thus providing molecular insights into a repressive function of PHF14 and its derepression.

Exposure to ambient particulate matter and hyperuricemia: An eight-year prospective cohort study on male traffic officers in China.

BACKGROUND AND OBJECTIVES: Studies on the effects of airborne particulates of diameter ≤ 1 µm (PM1), airborne particulates of diameter ≤ 2.5 µm (PM2.5) and airborne particulates of diameter ranges from 1 to 2.5 µm (PM1-2.5) on incidence of hyperuricemia are limited. We aimed to investigate the associations between PM1, PM2.5, and PM1-2.5 and hyperuricemia among male traffic officers. METHODS: We conducted a prospective cohort study of 1460 traffic officers without hyperuricemia in Guangzhou, China from 2009 to 2016. Exposures of PM1 and PM2.5 were estimated with a spatiotemporal model. PM1-2.5 concentrations were calculated by subtracting PM1 from PM2.5 concentrations. Cox's proportional hazards regressions models were used to examine the association between PM1, PM2.5, and PM1-2.5 and hyperuricemia, adjusted for potential confounders. Associations between PM1, PM2.5, and PM1-2.5 and serum uric acid (SUA) levels were evaluated with multiple linear regression models. RESULTS: Hazard ratios (HRs) and 95% confidence intervals (CIs) of hyperuricemia associated with 10 µg/m3 increment in PM1, PM2.5, and PM1-2.5 were 1.67 (95% CI:1.30-2.36), 1.49 (95% CI: 1.27-1.75), and 2.18 (95% CI: 1.58-3.02), respectively. The SUA concentrations increased by 12.23 µmol/L (95% CI: 5.91-18.56), 6.93 µmol/L (95% CI: 3.02-10.84), and 8.72 µmol/L (95% CI: 0.76-16.68) per 10 µg/m3 increase in PM1, PM2.5, and PM1-2.5, respectively. Stratified analyses indicated the positive associations of PM2.5 and PM1-2.5 with SUA levels were stronger in non-smokers, and PM1, PM2.5, and PM1-2.5 with SUA levels were stronger in non-drinkers. CONCLUSION: Long-term PM1, PM2.5, and PM1-2.5 exposures may increase the risk of hyperuricemia and elevate SUA levels among male traffic officers, especially in non-smokers and non-drinkers.

Bazi Bushen maintains intestinal homeostasis through inhibiting TLR4/NFκB signaling pathway and regulating gut microbiota in SAMP6 mice.

BACKGROUND: Bazi Bushen is a Chinese patented medicine with multiple health benefits and geroprotective effects, yet, no research has explored its effects on intestinal homeostasis. In this study, we aimed to investigate the effect of Bazi Bushen on intestinal inflammation and the potential mechanism of gut microbiota dysbiosis and intestinal homeostasis in senescence-accelerated mouse prone 6 (SAMP6). The hematoxylin and eosin (H&E) staining and immunohistochemistry were performed to assess the function of the intestinal mucosal barrier. The enzyme-linked immunosorbent assay (ELISA) and Western blotting were used to determine the level of intestinal inflammation. The aging-related ß-galactosidase (SA-ß-gal) staining and Western blotting were used to measure the extent of intestinal aging. The 16S ribosomal RNA (16S rRNA) was performed to analyze the change in gut microbiota composition and distribution. RESULTS: Bazi Bushen exerted remarkable protective effects in SAMP6, showing a regulated mucosal barrier and increased barrier integrity. It also suppressed intestinal inflammation through down-regulating pro-inflammatory cytokines (IL-6, IL-1ß, and TNF-α) and inhibiting TLR4/NFκB signaling pathway (MYD88, p-p65, and TLR4). Bazi Bushen improved intestinal aging by reducing the area of SA-ß-gal-positive cells and the expression of senescence markers p16, p21, and p53. In addition, Bazi Bushen effectively rebuilt the gut microbiota ecosystem by decreasing the abundance of Bacteroides and Klebsiella, whiles increasing the ratio of Lactobacillus/Bacteroides and the abundance of Akkermansia. CONCLUSION: Our study shows that Bazi Bushen could serve as a potential therapy for maintaining intestinal homeostasis. © 2023 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Intra-Specialty Citation Pattern in Radiology and Gastroenterology/Hepatology Journals: A Cross-Specialty Comparison.

Objectives: To investigate intra-specialty citation patterns of radiology articles, compared with another medical specialty: gastroenterology/hepatology. Methods: Four radiology journals (Radiology, European Radiology, Diagnostic and Interventional Imaging, Canadian Association of Radiologists Journal) and four gastroenterology/hepatology journals (Journal of Hepatology, Journal of Gastroenterology, World Journal of Gastroenterology, Journal of Clinical Gastroenterology) with similar Web of Science in-category 2020 IF ranking were selected. The original research, review, letter, and editorial articles published in these journals in 2021 were identified. The average number of intra-specialty citations per article (intra-specialty citation count) and percentage of intra-specialty citations out of total citations per article (intra-specialty citation rate) were compared between radiology and gastroenterology/hepatology articles using Student's t-test. Results: The radiology articles demonstrated a lower total citation count per article (radiology: 29.7 ± .4 (mean ± SEM), n = 2063; gastroenterology/hepatology: 50.1 ± 1.4, n = 1335). The intra-specialty citation count was also lower in radiology articles than gastroenterology/hepatology articles (radiology: 12.9 ± .2, gastroenterology/hepatology: 19.6 ± .7; P < .001), both overall and in all article types. Additionally, the overall intra-specialty citation rate was not significantly different between the two specialties (radiology: 48.8% ± .5%; gastroenterology/hepatology: 47.1 ± .8%; P = .057), although the intra-specialty citation rates were higher in radiology original research and editorial article types. Conclusions: The significantly lower per-article intra-specialty citation counts in all radiology article types, a measurement that directly links to specialty IFs, may contribute to the lower impact factors of radiology journals compared with gastroenterology/hepatology ones.

Assessment of Radiology Artificial Intelligence Software: A Validation and Evaluation Framework.

Artificial intelligence (AI) software in radiology is becoming increasingly prevalent and performance is improving rapidly with new applications for given use cases being developed continuously, oftentimes with development and validation occurring in parallel. Several guidelines have provided reporting standards for publications of AI-based research in medicine and radiology. Yet, there is an unmet need for recommendations on the assessment of AI software before adoption and after commercialization. As the radiology AI ecosystem continues to grow and mature, a formalization of system assessment and evaluation is paramount to ensure patient safety, relevance and support to clinical workflows, and optimal allocation of limited AI development and validation resources before broader implementation into clinical practice. To fulfil these needs, we provide a glossary for AI software types, use cases and roles within the clinical workflow; list healthcare needs, key performance indicators and required information about software prior to assessment; and lay out examples of software performance metrics per software category. This conceptual framework is intended to streamline communication with the AI software industry and provide healthcare decision makers and radiologists with tools to assess the potential use of these software. The proposed software evaluation framework lays the foundation for a radiologist-led prospective validation network of radiology AI software. Learning Points: The rapid expansion of AI applications in radiology requires standardization of AI software specification, classification, and evaluation. The Canadian Association of Radiologists' AI Tech & Apps Working Group Proposes an AI Specification document format and supports the implementation of a clinical expert evaluation process for Radiology AI software.

Ultra-strong optical four-wave mixing signal induced by strong exciton-phonon and exciton-plasmon couplings.

We propose a scheme to generate ultra-strong four-wave mixing (FWM) signal based on a suspended monolayer graphene nanoribbon nanomechanical resonator (NR) coupled to an Au nanoparticle (NP). It is shown that, the FWM spectrum can switch among two-peaked, three-peaked, four-peaked or five-peaked via the modulation of exciton-phonon and exciton-plasmon couplings. This is mainly attributed to the vibrational properties of NR related to the exciton-phonon coupling, and the energy-level splitting of the localized exciton correlated to three classes of resonances consisting of three-photon resonance, Rayleigh Resonance, and AC-Stark atomic resonance. Especially, in a dual-strong coupling regime, the gains for these peaks can be as high as nine orders of magnitude (∼ 109) around the lower bistable threshold due to a combined effect of two couplings. Our findings not only offer an efficient way to measure the vibrational frequency of NR and the exciton-phonon coupling strength but also provide a possibility to fabricate high-performance optoelectronic nanodevices.

Genetic landscape of FOXC2 mutations in lymphedema-distichiasis syndrome: Different mechanism of pathogenicity for mutations in different domains.

Lymphedema-dissociated syndrome (LDS), of which the pathogenesis is not fully understood, afflicts many patients. In this study, we investigated the effect of FOXC2 gene loss-of-function on the development of LDS disease. Two Han Chinese families with LDS were recruited in this study, pathogenic mutations were identified by Sanger sequencing. Reverse-transcription PCR, subcellular localization, dual fluorescein enzymes, and other in vitro experiments were used to study the functional effects of eight FOXC2 mutations. Two pathogenic FOXC2 duplication mutations (c.930_936dup and c.931-937dup) were identified in the two families. Both mutations caused uneven distribution in the nucleus and a chromatin contraction phenotype, weakening the DNA binding activity and transcription activity. We then performed functional analysis on six additional mutations in different domains of FOXC2 that were reported to cause LDS. We found mutations located in the forkhead domain and central region dramatically reduced the transactivation ability, while mutations in activation domain-2 enhanced this ability. All 8 mutations down-regulated the transcription of ANGPT2 and affected the activity of the ERK-RAS pathway, which may cause abnormal formation of lymphatic vessels. Our findings also showed that all 8 mutations decreased the ability of interaction between FOXC2 and the Wnt4 promoter, suggesting mutations in FOXC2 may also affect the Wnt4-Frizzled-RYK signaling pathway, leading the abnormal differentiation of the meibomian glands into hair follicle cells during the embryonic period and causing distichiasis. This study expanded and revealed the potential pathogenesis mechanism.

[Association analysis of seven single nucleotide polymorphisms identified by genome-wide association study with age-related macular degeneration among ethnic Han Chinese population].

OBJECTIVE: To assess the association of 7 single nucleotide polymorphisms (SNPs) including rs13278062 (TNFRSF10A), rs3750846 (ARMS2-HTRA1), rs429358 (APOE), rs5817082 (CEPT), rs2043085 (LIPC), rs1626340 (TGFBR1), and rs8135665 (SLC16A8) identified through genome-wide association study (GWAS) with age-related macular degeneration (AMD) among ethnic Han Chinese from Sichuan, China. METHODS: A cohort of 576 AMD patients and 572 healthy controls were enrolled in a case-control study. The SNPs were genotyped by a Mass array MALDI-TOF System. On the premise that the genotype distribution of each SNP locus in both groups satisfied Hardy-Weinberg equilibrium, the genetic pattern was analyzed and the scores of allele and genotype frequencies ware compared. RESULTS: There was a significant association between TNFRSF10A rs13278062 and AMD under the heterozygous model (P = 0.000, OR = 1.529, 95%CI = 1.196-1.954) and the dominant model (P = 0.002, OR = 1.459, 95%CI = 1.154-1.865), suggesting that subjects carrying rs13278062GT and rs13278062TT + GT are more likely to develop the AMD, whereas no significant difference was observed for rs13278062 under other models. No association was detected with the other six SNPs and AMD under various genetic models. CONCLUSION: This case-control association study has indicated that TNFRSF10A rs13278062 is associated with AMD under the heterozygous and dominant models, suggesting that the TNFRSF10A variant may be involved in the development of AMD among ethnic Han Chinese population.

Evaluation of Caspase-3 and Ki-67 expression in squamous cell hyperplasia of the stomach induced by Platycodi radix water extract in Sprague-Dawley rats.

Platycodi radix is widely used in traditional herbal medicine for the treatment of bronchitis, asthma, pulmonary tuberculosis, hypertension, hyperlipidemia, and diabetes. This study aimed to investigate cell proliferation (Ki-67) and apoptosis (Caspase-3) potential in squamous cell hyperplasia of the stomach induced by a Platycodi radix water extract in a subchronic toxicity study. One hundred formalin-fixed, paraffin-embedded stomach tissues of rats treated with Platycodi radix at doses of 0, 500, 1,000, and 3,000 mg/kg body weight/day were used for the analysis. They were conventionally stained using hematoxylin and eosin (H&E) and immunohistochemically (IHC) stained using caspase-3 and Ki-67 antibodies. The incidence of squamous cell hyperplasia was significantly increased in the 3,000 mg/kg b.w./day treatment group in both sexes (p<0.01). However, the hyperplastic change was completely repaired after 4 weeks of recovery period. Ki-67 expression was similar in all groups, with no statistically significant differences among the groups. Caspase-3 expression was significantly increased in both sexes in the 3,000 mg/kg b.w./day treatment group (p<0.01), compared with the vehicle control groups, and then reduced to normal levels in the recovery groups in both sexes. In conclusion, this study showed that squamous cell hyperplasia induced by the Platycodi radix water extract in the limiting ridge of the stomach is not considered to be abnormal proliferative change; as a result, squamous cell hyperplasia is considered to be a non-adverse effect when induced by the oral administration of the Platycodi radix water extract once daily for 13 weeks in rats.

A Chimeric Conjugate of Antibody and Programmable DNA Nanoassembly Smartly Activates T Cells for Precise Cancer Cell Targeting.

Synthetically directing T-cells against tumors emerges as a promising strategy in immunotherapy, while it remains challenging to smartly engage T cells with tunable immune response. Herein, we report an intelligent molecular platform to engineer T-cell recognition for selective activation to potently kill cancer cells. To this end, we fabricated a hybrid conjugate that uses a click-type DNA-protein conjugation to equip the T cell-engaging antibody with two distinct programmable DNA nanoassemblies. By integrating multiple aptameric antigen-recognitions within a dynamic DNA circuit, we achieved combinatorial recognition of triple-antigens on cancer cells for selective T-cell activation after high-order logic operation. Moreover, by coupling a DNA nanostructure, we precisely defined the valence of the antigen-binding aptamers to tune avidity, realizing effective tumor elimination in vitro and in vivo. Together, we present a versatile and programmable strategy for synthetic immunotherapy.

Quantitative assessment of SARS-CoV-2 RNAemia and outcome in patients with coronavirus disease 2019.

The disease spectrum of coronavirus disease 2019 (COVID-19) varies from asymptomatic infection to critical illness and death. Identification of prognostic markers is vital for predicting progression and clinical practice. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA, known as RNAemia, has been detected in the blood. However, the potential clinical value of SARS-CoV-2 RNAemia remains unknown. We, therefore, conducted a meta-analysis using a random-effects model to estimate the pooled prevalence of SARS-CoV-2 RNAemia as well as summary strength of RNAemia in association with disease severity and unfavorable clinical outcomes. A total of 21 studies involving 2181 patients were included. SARS-CoV-2 RNAemia in COVID-19 patients varied from 9.4% to 74.1%, with a pooled estimate of 34% (95% confidene interval [CI]: 26%-43%). Overall, SARS-CoV-2 RNAemia was associated with COVID-19 severity with odds ratio (OR) of 5.43 (95% CI: 3.46-8.53). In addition, SARS-CoV-2 RNAemia was a significant risk factor for unfavorable clinical outcomes (OR = 6.54, 95% CI: 3.82-11.21). The summary OR was 4.28 (95% CI: 2.20-8.33) for intensive care unit (ICU) admission, 11.07 (95% CI: 5.60-21.88) for mortality. Furthermore, RNAemia was also a significant risk factor for invasive mechanical ventilation and multiple organ failure. SARS-CoV-2 RNAemia is associated with disease severity, ICU admission, death in COVID-19, and may serve as a clinical predictor. More prospective trials in evaluating the potential of SARS-CoV-2 RNAemia as a prognostic indicator are necessary.

Street view greenness is associated with lower risk of obesity in adults: Findings from the 33 Chinese community health study.

BACKGROUND: Urban greenness may protect against obesity, but very few studies have assessed 'street view' (SV) greenness metrics, which may better capture people's actual exposure to greenness compared to commonly-used satellite-derived metrics. We aimed to investigate these associations further in a Chinese adult study. METHODS: Our analysis included 24,845 adults in the 33 Chinese Community Health Study in 2009. SV images from Tencent Map, segmented by machine learning algorithms, were used to determine the average proportion of green vegetation in SV images at community level in 800m road network buffer. Sensitivity analyses were performed with an alternative buffer size. Overall greenness was assessed as normalized difference vegetation index (NDVI) in 800 m buffer. We used predicted PM2.5 and monitored NO2 as proxies of air pollution. Body mass index (BMI), waist circumference (WC) and hip circumference (HC) were regressed on SV greenness by generalized linear mixed models, with adjustment for covariates. Mediation analyses were performed to assess the mediation effects of air pollution. RESULTS: Each interquartile range (IQR = 3.6%) increase in street view greenness was associated with a 0.15 kg/m2 (95% CI: -0.22, -0.09) decrease in BMI and 0.23 cm (95% CI: -0.35, -0.11) reduction in HC, and was associated with 7% lower odds of overweight (OR = 0.93, 95% CI:0.90, 0.96) and 18% lower odds of obesity (OR = 0.82, 95% CI:0.76, 0.89). Similar effect estimation was observed compared with commonly-used NDVI measures. PM2.5 and NO2 mediated 15.5% and 6.1% of the effects of SV greenness with BMI, respectively. CONCLUSIONS: Our findings suggest beneficial associations between community-level SV greenness and lower body weight in Chinese adults. The effects were observed in women but not in men. Air pollution may partially mediate the association. These findings may have implications to support efforts to promote greening in urban areas.

A non-linear dose-response relation of female body mass index and in vitro fertilization outcomes.

PURPOSE: Obesity, measured by body mass index (BMI), is implicated in adverse pregnancy outcomes for women seeking in vitro fertilization (IVF) care. However, the shape of the dose-response relationship between BMI and IVF outcomes remains unclear. METHODS: We therefore conducted a dose-response meta-analysis using a random effects model to estimate summary relative risk (RR) for clinical pregnancy (CPR), live birth (LBR), and miscarriage risk (MR) after IVF. RESULTS: A total of 18 cohort-based studies involving 975,889 cycles were included. For each 5-unit increase in BMI, the summary RR was 0.95 (95% CI: 0.94-0.97) for CPR, 0.93 (95% CI: 0.92-0.95) for LBR, and 1.09 (95% CI: 1.05-1.12) for MR. There was evidence of a non-linear association between BMI and CPR (Pnon-linearity < 10-5) with CPR decreasing sharply among obese women (BMI > 30). Non-linear dose-response meta-analysis showed a relatively flat curve over a broad range of BMI from 16 to 30 for LBR (Pnon-linearity = 0.0009). In addition, we observed a J-shaped association between BMI and MR (Pnon-linearity = 0.006) with the lowest miscarriage risk observed with a BMI of 22-25. CONCLUSIONS: In conclusion, obesity contributed to increased risk of adverse IVF outcomes in a non-linear dose-response manner. More prospective trials in evaluating the effect of body weight control are necessary.

EpCAM inhibits differentiation of human liver progenitor cells into hepatocytes in vitro by activating Notch1 signaling.

In both normal turnover of the hepatic tissue and acute hepatic injury, the liver predominantly activates terminally differentiated hepatocytes to proliferate and repair. However, in chronic and severe chronic injury, this capacity fails, and liver progenitor cells (LPCs) can give rise to hepatocytes to restore both hepatic architecture and liver metabolic function. Although the promotion of LPC-to-hepatocyte differentiation to acquire a considerable number of functional hepatocytes could serve as a potentially new therapeutic option for patients with end-stage liver disease, its development first requires the identification of the molecular mechanisms driving this process. Here, we found that the epithelial cell adhesion molecule (EpCAM), a progenitor cell marker, regulates the differentiation of LPCs into hepatocytes through Notch1 signaling pathway. Western blotting (WB) revealed a consistent expression pattern of EpCAM and Notch1 during LPC-to-hepatocyte differentiation in vitro. Additionally, overexpression of EpCAM blocked LPC-to-hepatocyte differentiation, which was in consistent with the repressive role of Notch signaling during hepatic differentiation. WB and immunofluorescence data also showed that the upregulation of EpCAM expression increased the generation of Notch intracellular domain (N1ICD), indicating the promotion of Notch1 activity. Our results established the EpCAM-Notch1 signaling axis as an inhibitory mechanism preventing LPC-to-hepatocyte differentiation in vitro.

Determination of Saccharides in Environments Using a Sulfuric Acid-Fluorescence Approach.

Accurate, rapid, and reliable quantification of saccharides is essential for understanding their behaviors and roles in environmental processes. However, the conventional colorimetric method for saccharide quantification fails to discriminate between fructose and glucose, resulting in the misestimation of total saccharides. To solve this problem, a fluorescence approach, that is, parallel factor framework-linear regression analysis, was developed in this work to quantify the specific fluorescence signatures of the fluorescent products generated from the reaction between saccharides and sulfuric acid. The fluorescent derivatives of saccharides were recognized and the simultaneous quantification of glucose and fructose was achieved with a detection limit of 2.9 µg/mL and 1.3 µg/mL, respectively. Furthermore, 200 µg/mL of the treated sorbitol and gluconic acid only, respectively, equaled to 6 µg/mL and 3 µg/mL of the treated glucose, indicating their negligible interference for the saccharide quantification using this method. In addition, the feasibility and robustness of this method in environmental applications were validated with the recovery tests using spiked real water samples. This fluorescence-based approach offers a new tool to monitor saccharides in complex environments.

Exploring the value of the double source CT angiography in diagnosing in-stent restenosis in lower limb artery.

OBJECTIVES: This paper is aimed to explore the value of double source CT angiography (DS-CTA) for diagnosing in-stent restenosis in lower limb artery. METHODS: From January 2016 to October 2018, all patients with stent in lower limb artery in our hospital were investigated by both DS-CTA and digital subtraction angiography. We measured the minimum lumen diameter and the diameter of the proximal normal vessels under each stent placement. The in-stent restenosis is defined as restenosis when the lumen area decreased by more than 50%. Digital subtraction angiography was performed within 1 week after DS-CT scan. Relationship between DS-CTA and digital subtraction angiography for diagnosing in-stent restenosis in lower limb artery was analyzed. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of DS-CTA for diagnosis of in-stent restenosis were analyzed with digital subtraction angiography as the reference standard. A total of 68 stents were placed in 51 patients. Among these patients, 27 cases were diagnosed as in-stent restenosis, presenting as endovascular contrast agent bias or crescent filling defect with the lumen area reducing over 50%, 6 cases of which had no significant in-stent restenosis by digital subtraction angiography analysis. Furthermore, 12 cases were occlusion, in which there was no high density contrast agent in stents; the remaining 41 stents were unobstructed and the contrast agent was filled well, 8 cases of which had significant in-stent restenosis by digital subtraction angiography analysis. In addition, four stents were deformed or distorted. Statistical analysis demonstrated the concentrations of DS-CTA and digital subtraction angiography in diagnosing in-stent restenosis for lower limb artery were closely related, and the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of DS-CTA were 72.4%, 84.6%, 77.8%, 80.5%, and 79.4%, respectively. CONCLUSION: DS-CTA has a potential reliability for diagnosis of in-stent restenosis in lower limb artery, which may be further improved to be used for clinical interventional treatment of vascular diseases.