Janus plasmonic-aggregation induced emission nanobeads as high-performance colorimetric-fluorescent probe of immunochromatographic assay for the ultrasensitive detection of staphylococcal enterotoxin B in milk.

Herein, a colorimetric-fluorescent hybrid bifunctional nanobead with Janus structure (J-cf-HBN) was synthesized via one-pot microemulsification. Oleylamine-coated AuNPs and aggregation-induced emission luminogens (AIEgens) were suggested as building blocks to obtain high-performance colorimetric-fluorescent signals. The as-prepared J-cf-HBNs were used as a signal amplification probe to construct an immunochromatographic assay (J-cf-HBNs-ICA) platform for the ultrasensitive detection of staphylococcal enterotoxin B (SEB) in milk samples. Owing to the rational spatial distribution of AuNPs and AIEgens, the J-cf-HBNs present a highly retained photoluminescence and enhanced colorimetric signals. Combined with a pair of highly affinitive anti-SEB antibodies, the J-cf-HBN-ICA platform enabled the fast naked-eye visualization and fluorescent quantitative detection of SEB in various milk matrices. Given the advantages of the dual-mode high-performance J-cf-HBNs, the proposed strip achieved a high sensitivity for SEB qualitative determination with a visual limit of detection (LOD) of 1.56 ng mL-1 and exhibited ultrasensitivity for SEB quantitative detection with a LOD of 0.09 ng mL-1, which is 139-fold lower than that of ELISA using same antibodies. In conclusion, this work provides new insights into the construction of multimode immunochromatographic methods for food safety detection in the field.

Aggregation-induced emission nanoparticles facilitating multicolor lateral flow immunoassay for rapid and simultaneous detection of aflatoxin B1 and zearalenone.

Herein we developed a multicolor lateral flow immunoassay (LFIA) test strip for rapid and simultaneous quantitative detection of aflatoxin B1 (AFB1) and zearalenone (ZEN). Three differently colored aggregation-induced emission nanoparticles (AIENPs) were designed as LFIA signal tags, with red and green AIENPs for targeting AFB1 and ZEN at the test line, and yellow AIENPs for indicating the validity of the test strip at the control (C) line. After surface functionalization with antibodies, the developed AIENP-based multicolor LFIA allows simultaneous and accurate quantification of AFB1 and ZEN using an independent C-line assisted ratiometric signal output strategy. The detection limits of AFB1 and ZEN were 6.12 and 26 pg/mL, respectively. The potential of this method for real-world applications was well demonstrated in corn and wheat. Overall, this multicolor LFIA shows great potential for field screening of multiple mycotoxins and can be extended to rapid and simultaneous monitoring of other small molecule targets.

Comprehensive HRMS Screening and Risk Assessments of Aristolochic Acid Analogues in Asari Radix et Rhizoma and Related Commercial Health Products.

Aristolochic acid analogues (AAAs) are well-known toxins. We performed the first comprehensive screening on AAAs in Asari Radix et Rhizoma (underground part of Asarum heterotropoides Schmidt), the only Aristolochiaceae plant widely used in clinical practice. LC-HRMS revealed 70 trace AAAs using polygonal mass defect filtering and precursor ion list strategies, 38 of which were newly discovered in A. heterotropoides. UHPLC-QTrap-MS/MS was then utilized for quantitative/semiquantitative analysis of 26 abundant compounds. Seventeen AAAs were detected from 91 batches of A. heterotropoides and 20 AAAs from 166 consumable products. For 141 Asari-containing proprietary products, aristolactam I and aristolactam II-glucoside exhibited the widest distribution, present in 98% products. AA IVa was the most abundant, detected in 91%. Notably, 60% of the products contained AA I (0.03-0.79 ppm). The safety was assessed using linear extrapolation, permitted daily exposure, cumulative amount, and the margin of exposure. It is recommended that AA I content be limited to 3 ppm.

A positive association between RDW and coronary heart disease in the rheumatoid arthritis population: A cross-sectional study from NHANES.

Previous research has indicated that higher red blood cell distribution width (RDW) increases the risk of coronary heart disease. However, no studies have established a link between RDW and coronary heart disease in the rheumatoid arthritis population. This research aims to explore the association between RDW and coronary heart disease among individuals with rheumatoid arthritis. We selected demographic data, laboratory data, lifestyle, and medical history from the National Health and Nutrition Examination Survey (NHANES), specifically including age, gender, poverty, RDW, race, BMI, diabetes, education, coronary heart disease, hypertension, cholesterol, smoking, and drinking. RDW and coronary heart disease were found to have a positive association in the rheumatoid arthritis population (OR = 1.145, 95%CI: 1.036-1.266, P = .0098), even after adjusting for factors such as age, gender, race, education level, smoking, and drinking. Subgroup analysis showed a stronger positive association, particularly in individuals aged 55-66 years, males, and the Hispanic White population with diabetes or hypercholesterolemia. There is a significant correlation between RDW and coronary heart disease among individuals with rheumatoid arthritis.

Thymopentin plays a key role in restoring the function of macrophages to alleviate the sepsis process.

Immune dysfunction is one of the leading causes of death of sepsis. How to regulate host immune functions to improve prognoses of septic patients has always been a clinical focus. Here we elaborate on the efficacy and potential mechanism of a classical drug, thymopentin (TP5). TP5 could decrease peritoneal bacterial load, and reduce inflammatory cytokine levels both in the peritoneal lavage fluid (PLF) and serum, alleviate pathological injuries in tissue and organ, coaxed by cecal ligation and perforation (CLP) in mice, ultimately improve the prognosis of septic mice. Regarding the mechanism, using RNA-seq and flow cytometry, we found that TP5 induced peptidoglycan recognition protein 1 (PGLYRP1) expression, increased phagocytosis and restored TNF-α expression of small peritoneal macrophage (SPM) in the septic mice. This may be increased SPM's ability to clear peritoneal bacteria, thereby attenuates the inflammatory response both in the peritoneal cavity and the serum. It was shown that TP5 plays a key role in restoring the function of peritoneal macrophages to alleviate the sepsis process. We reckon that this is closely relevant to SPM phagocytosis, which might involve increased PGLYRP1 expression and restored TNF-α secretion.

MATLAB language assisted data acquisition and processing in liquid chromatography Orbitrap mass spectrometry: Application to the identification and differentiation of Radix Bupleuri from its adulterants.

Comprehensive and rapid analysis of secondary metabolites like saponins remains challenging. This study aimed to establish a semi-automated workflow for filtration, identification, and characterization of saikosaponins in six Bupleurum species. Radix Bupleuri, a high-sales herbal medicine, is often adulterated, restricting its quality control and applications. Two authentic Radix Bupleuri species and four major adulterants were analyzed through UHPLC-LTQ-Orbitrap-MS for targeted saikosaponin analysis. To reveal trace saikosaponins and obtain quality fragment data, a MATLAB-based process automatically enumerating "sugar chain + aglycone + side chain" combinations and deduplicating generated a predicted saikosaponin database covering all possible saikosaponins as a precursor ion list for comprehensive targeted acquisition. To focus on informative ions and reduce MS analysis workload, we utilized MATLAB to automatically filtrate the false positive ions by MS1 and MS2 spectrometry. The newly established MATLAB-assisted data acquisition approach exhibited 50 % improvement in characterization of targeted saikosaponins. Furthermore, positive and negative ionization workflows were designed for accurate saikosaponins characterization based on fragmentation rules. In total, 707 saikosaponins were characterized, including over 500 potential new compounds and previously unreported C29 aglycones. We identified 25 saikosaponins present in both authentic species but absent in adulterants as potential markers. This unprecedented comprehensive multi-origin species differentiation demonstrates the promise of MATLAB-assisted acquisition and processing to advance saponin identification and standardize the Radix Bupleuri market.

Association of autoimmune diseases with the occurrence and 28-day mortality of sepsis: an observational and Mendelian randomization study.

BACKGROUND: Observational studies have indicated a potential association between autoimmune diseases and the occurrence of sepsis, with an increased risk of mortality among affected patients. However, whether a causal relationship exists between the two remains unknown. METHODS: In the Mendelian randomization (MR) study, we accessed exposure Genome-wide association study (GWAS) data from both the MRC Integrative Epidemiology Unit (MRC-IEU) and the FinnGen consortium. GWAS data for sepsis and its 28-day mortality were obtained from MRC-IEU. We employed univariable, multivariable, and reverse MR analyses to explore potential associations between autoimmune disorders and sepsis and its 28-day mortality. Additionally, a two-step mediation MR analysis was performed to investigate indirect factors possibly influencing the relationship between autoimmune disorders and sepsis. Afterward, we conducted an observational analysis to further explore the relationship between autoimmune disease and occurrence as well as 28-day mortality of sepsis using a real-world database (the MIMIC-IV database). A cohort of 2537 patients diagnosed with autoimmune disease were extracted from the database for analysis. Multivariable logistic regression models were used to confirm the association between autoimmune diseases and the occurrence of sepsis, as well as the 28-day mortality associated with sepsis. RESULTS: In univariable MR analysis, there appeared to be causal relationships between genetically predicted type 1 diabetes (OR = 1.036, 95% CI = 1.023-1.048, p = 9.130E-09), rheumatoid arthritis (OR = 1.077, 95% CI = 1.058-1.097, p = 1.00E-15) and sepsis, while a potential causal link was observed between celiac disease and sepsis (OR = 1.013, 95% CI = 1.002-1.024, p = 0.026). In a subsequent multivariable MR analysis, only rheumatoid arthritis was found to be independently associated with the risk of sepsis (OR = 1.138, 95% CI = 1.044-1.240, p = 3.36E-03). Furthermore, there was no causal link between autoimmune disorders and 28-day mortality from sepsis. In reverse MR analysis, sepsis was suggested to potentially trigger the onset of psoriasis (OR = 1.084, 95% CI = 1.040-1.131, p = 1.488E-04). In the real-world observational study, adjusting for multiple confounders, rheumatoid arthritis (OR = 1.34, 95% CI = 1.11-1.64, p = 0.003) and multiple sclerosis (OR = 1.31, 95% CI = 1.03-1.68, p = 0.02) were associated with a higher risk of sepsis. In addition, we did not find that autoimmune diseases were associated with 28-day mortality from sepsis. CONCLUSION: Both in observational and MR analysis, only rheumatoid arthritis is highly correlated with occurrence of sepsis. However, autoimmune disease was not associated with an increased 28-day mortality in patient with sepsis. Sepsis may increase the risk of developing psoriasis.

Long noncoding RNA lnc_217 regulates hepatic lipid metabolism by modulating lipogenesis and fatty acid oxidation.

Nonalcoholic fatty liver disease (NAFLD) is considered a major health epidemic with an estimated 32.4% worldwide prevalence. No drugs have yet been approved and therapeutic nodes remain a major unmet need. Long noncoding RNAs are emerging as an important class of novel regulators influencing multiple biological processes and the pathogenesis of NAFLD. Herein, we described a novel long noncoding RNA, lnc_217, which was liver enriched and upregulated in high-fat diet-fed mice, and a genetic animal model of NAFLD. We found that liver specific knockdown of lnc_217 was resistant to high-fat diet-induced hepatic lipid accumulation and decreased serum lipid in mice. Mechanistically, we demonstrated that knockdown of lnc_217 not only decreased de novo lipogenesis by inhibiting sterol regulatory element binding protein-1c cleavage but also increased fatty acid ß-oxidation through activation of peroxisome proliferator-activated receptor α and carnitine palmitoyltransferase-1α. Taken together, we conclude that lnc_217 may be a novel regulator of hepatic lipid metabolism and a potential therapeutic target for the treatment of hepatic steatosis and NAFLD-related metabolic disorders.

Human blood metabolites and risk of severe COVID-19: A Mendelian randomization study.

BACKGROUND: Evidence supports the observational associations of human blood metabolites with the risk of severe COVID-19. However, little is known about the potential pathological mechanisms and the analysis of blood metabolites may offer a better understanding of the underlying biological processes. METHODS: We applied a two-sample Mendelian randomization (MR) analysis to evaluate relationships between 486 blood metabolites and the risk of severe COVID-19. The inverse-variance weighted (IVW) model was used as the primary two-sample MR analysis method to estimate the causal relationship of the exposure on the outcome. Sensitivity analyses were implemented with Cochran's Q test, MR-Egger intercept test, MR-PRESSO, leave-one-out analysis and the funnel plot. RESULTS: Four hunderd and eighty six metabolites were included for MR analysis following rigorous genetic variants selection. After MR analyses and sensitivity analysis filtration, we found weak evidence of an association between 3-hydroxybutyrate (odds ratio [OR] = 1.21, 95% CI, 1.07-1.38, p = .0036) and the risk of severe COVID-19. A series of sensitivity analyses have been carried out to confirm the rigidity of the above results. CONCLUSION: This study suggested a causal relationship between 3-hydroxybutyrate and the severity of COVID-19, thus providing novel insights into biomarkers and pathways for COVID-19 prevention and clinical interventions.

Unprecedented hetero-coordinated Ir(C

By using 2-(9-phenanthryl)pyridine (phpyr) and its derivatives as cyclometalated ligands, we synthesized a set of isomeric red-emitting complexes Ir(phpyr-R)2tmd (R = -H, -CF3, -F and -CH3, tmd = 2,2,6,6-tetramethylheptane-3,5-dione) with different coordinated modes, including bis-five-membered and five- + six-membered Ir-(C^N) ring chelating modes. The latter are the first examples of hetero-coordinated Ir(C^N)2(L^X)-type complexes containing both five- and six-membered Ir-(C^N) metallocycles. Their coordination geometries were distinctly determined using X-ray crystallographic analysis. Compared to typical bis-five-membered ring-chelated complexes, these novel hetero-coordinated isomers show bathochromic emission and lower quantum yields. On careful analysis of their electrochemical behavior and DFT calculations, it has been found that the regulatory effects of the solitary six-membered metallocycles in Ir(phpyr-R)2tmd could not only stabilize the LUMO but also destabilize the HOMO, leading to a narrower energy gap. More importantly, DFT calculations of the relative energies of these isomeric complexes demonstrated that bis-five-membered and five- + six-membered chelating modes are more stable compared to bis-six-membered rings, consistent with experiments. This work provides guidance for the structural design of Ir(C^N)2(L^X)-type complexes.

Highly Sensitive Immunochromatographic Detection of Zearalenone Based on Ultrabright Red-Emitted Aggregation-Induced Luminescence Nanoprobes.

Highly luminescent nanospheres have been demonstrated in enhancing the sensitivity of lateral flow immunoassay (LFIA) due to their loading numerous luminescent dyes. However, the photoluminescence intensities of existing luminescent nanospheres are limited due to the aggregation-caused quenching effect. Herein, highly luminescent aggregation-induced emission luminogens embedded nanospheres (AIENPs) with red emission were introduced as signal amplification probes of LFIA for quantitative detection of zearalenone (ZEN). Optical properties of red-emitted AIENPs were compared with time-resolved dye-embedded nanoparticles (TRNPs). Results showed that red-emitted AIENPs have stronger photoluminescence intensity on the nitrocellulose membrane and superior environmental tolerance. Additionally, we benchmarked the performance of AIENP-LFIA against TRNP-LFIA using the same set of antibodies, materials, and strip readers. Results showed that AIENP-LFIA exhibits good dynamic linearity with the ZEN concentration from 0.195 to 6.25 ng/mL, with half competitive inhibitory concentration (IC50) and detection of limit (LOD) at 0.78 and 0.11 ng/mL, respectively. The IC50 and LOD are 2.07- and 2.36-fold lower than those of TRNP-LFIA. Encouragingly, the precision, accuracy, specificity, practicality, and reliability of this AIENP-LFIA for ZEN quantitation were further characterized. The results verified that the AIENP-LFIA has good practicability for the rapid, sensitive, specific, and accurate quantitative detection of ZEN in corn samples.

Application of Neuromuscular Blockers in Patients with ARDS in ICU: A Retrospective Study Based on the MIMIC-III Database.

BACKGROUND: Although neuromuscular blocker agents (NMBAs) are recommended by guidelines as a treatment for ARDS patients, the efficacy of NMBAs is still controversial. Our study aimed to investigate the association between cisatracurium infusion and the medium- and long-term outcomes of critically ill patients with moderate and severe ARDS. METHODS: We performed a single-center, retrospective study of 485 critically ill adult patients with ARDS based on the Medical Information Mart for Intensive Care III (MIMIC-III) database. Propensity score matching (PSM) was used to match patients receiving NMBA administration with those not receiving NMBAs. The Cox proportional hazards model, Kaplan-Meier method, and subgroup analysis were used to evaluate the relationship between NMBA therapy and 28-day mortality. RESULTS: A total of 485 moderate and severe patients with ARDS were reviewed and 86 pairs of patients were matched after PSM. NMBAs were not associated with reduced 28-day mortality (hazard ratio (HR) 1.44; 95% CI: 0.85~2.46; p = 0.20), 90-day mortality (HR = 1.49; 95% CI: 0.92~2.41; p = 0.10), 1-year mortality (HR = 1.34; 95% CI: 0.86~2.09; p = 0.20), or hospital mortality (HR = 1.34; 95% CI: 0.81~2.24; p = 0.30). However, NMBAs were associated with a prolonged duration of ventilation and the length of ICU stay. CONCLUSIONS: NMBAs were not associated with improved medium- and long-term survival and may result in some adverse clinical outcomes.

Association between Mean Arterial Pressure during the First 24 Hours and Clinical Outcome in Critically Ill Stroke Patients: An Analysis of the MIMIC-III Database.

Abnormal blood pressure is common in critically ill stroke patients. However, the association between mean arterial pressure (MAP) and mortality of critically ill stroke patients remains unclear. We extracted eligible acute stroke patients from the MIMIC-III database. The patients were divided into three groups: a low MAP group (MAP ≤ 70 mmHg), a normal MAP group (70 mmHg < MAP ≤ 90 mmHg), and a high MAP group (MAP > 90 mmHg). The Cox proportional hazards model and restricted cubic splines were used to assess the association between MAP and mortality. Sensitivity analyses were conducted to investigate whether MAP had different effects on mortality in different subpopulations. A total of 2885 stroke patients were included in this study. The crude 7-day and 28-day mortality was significantly higher in the low MAP group than that in the normal MAP group. By contrast, patients in the high MAP group did not have higher crude 7-day and 28-day mortality than those in the normal MAP group. After multiple adjustments using the Cox regression model, patients with low MAP were consistently associated with higher 7-day and 28-day mortality than those with normal MAP in the following subgroups: age > 60 years, male, those with or without hypertension, those without diabetes, and those without CHD (p < 0.05), but patients with high MAP were not necessarily associated with higher 7-day and 28-day mortality after adjustments (most p > 0.05). Using the restricted cubic splines, an approximately L-shaped relationship was established between MAP and the 7-day and 28-day mortality in acute stroke patients. The findings were robust to multiple sensitivity analyses in stroke patients. In critically ill stroke patients, a low MAP significantly increased the 7-day and 28-day mortality, while a high MAP did not, suggesting that a low MAP is more harmful than a high MAP in critically ill stroke patients.

Chinese diabetes datasets for data-driven machine learning.

Data of the diabetes mellitus patients is essential in the study of diabetes management, especially when employing the data-driven machine learning methods into the management. To promote and facilitate the research in diabetes management, we have developed the ShanghaiT1DM and ShanghaiT2DM Datasets and made them publicly available for research purposes. This paper describes the datasets, which was acquired on Type 1 (n = 12) and Type 2 (n = 100) diabetic patients in Shanghai, China. The acquisition has been made in real-life conditions. The datasets contain the clinical characteristics, laboratory measurements and medications of the patients. Moreover, the continuous glucose monitoring readings with 3 to 14 days as a period together with the daily dietary information are also provided. The datasets can contribute to the development of data-driven algorithms/models and diabetes monitoring/managing technologies.

Establishment of models to predict factors influencing periodontitis in patients with type 2 diabetes mellitus.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is associated with periodontitis. Currently, there are few studies proposing predictive models for periodontitis in patients with T2DM. AIM: To determine the factors influencing periodontitis in patients with T2DM by constructing logistic regression and random forest models. METHODS: In this a retrospective study, 300 patients with T2DM who were hospitalized at the First People's Hospital of Wenling from January 2022 to June 2022 were selected for inclusion, and their data were collected from hospital records. We used logistic regression to analyze factors associated with periodontitis in patients with T2DM, and random forest and logistic regression prediction models were established. The prediction efficiency of the models was compared using the area under the receiver operating characteristic curve (AUC). RESULTS: Of 300 patients with T2DM, 224 had periodontitis, with an incidence of 74.67%. Logistic regression analysis showed that age [odds ratio (OR) = 1.047, 95% confidence interval (CI): 1.017-1.078], teeth brushing frequency (OR = 4.303, 95%CI: 2.154-8.599), education level (OR = 0.528, 95%CI: 0.348-0.800), glycosylated hemoglobin (HbA1c) (OR = 2.545, 95%CI: 1.770-3.661), total cholesterol (TC) (OR = 2.872, 95%CI: 1.725-4.781), and triglyceride (TG) (OR = 3.306, 95%CI: 1.019-10.723) influenced the occurrence of periodontitis (P < 0.05). The random forest model showed that the most influential variable was HbA1c followed by age, TC, TG, education level, brushing frequency, and sex. Comparison of the prediction effects of the two models showed that in the training dataset, the AUC of the random forest model was higher than that of the logistic regression model (AUC = 1.000 vs AUC = 0.851; P < 0.05). In the validation dataset, there was no significant difference in AUC between the random forest and logistic regression models (AUC = 0.946 vs AUC = 0.915; P > 0.05). CONCLUSION: Both random forest and logistic regression models have good predictive value and can accurately predict the risk of periodontitis in patients with T2DM.

The study of a novel high selectivity pyrenyl-based fluorescence probe with aggregation-induced emission characteristics for Fe3+ detection designed by a structure modulation strategy.

The past decades have witnessed the feat of fluorescent probes for Fe3+ detection, where eliminating the interference by other metal ions plays a pivotal role in its detection by probes in complex environments. Herein, by taking advantage of the substituent effects, the electron-withdrawing group (EWG) -CF3 and electron-donating group (EDG) -CH3 were introduced to 2-(1-pyrenyl)pyridine (pypyr) to prepare two turn-off fluorescence probes, 5-trifluoromethyl-2-(1-pyrenyl)pyridine (pypyr-CF3) and 5-methyl-2-(1-pyrenyl)pyridine (pypyr-CH3). Intriguingly, both probes displayed novel aggregation-induced emission (AIE) characteristics in MeCN/H2O mixtures and the size and morphology of the aggregated particles were studied via DLS and TEM. By the modulation strategy, pypyr-CF3 can detect Fe3+ in the presence of 29 different metal ions without interference. Comparatively, pypyr-CH3 experienced serious interference from other metal ions such as Hg2+ and Zr4+. Besides, pypyr-CF3 not only demonstrated a higher photoluminescence quantum yield (PLQY) of 65.25% and wider pH adaptability but is also capable of Fe3+ detection over a wide pH range of 2-11 with a short response time (5 seconds). A plausible quenching mechanism based on the inner filter effect has also been demonstrated. More importantly, the versatile applications of pypyr-CF3, such as the quantitative analysis of Fe3+ in actual water samples, anti-forgery ink, fingerprint identification, etc., further corroborate its superb capabilities. This study aims to lend concrete support to the design and selectivity modulation of probes.

Activating transcription factor 4 protects mice against sepsis-induced intestinal injury by regulating gut-resident macrophages differentiation.

BACKGROUND: Gut-resident macrophages (gMacs) supplemented by monocytes-to-gMacs differentiation play a critical role in maintaining intestinal homeostasis. Activating transcription factor 4 (ATF4) is involved in immune cell differentiation. We therefore set out to investigate the role of ATF4-regulated monocytes-to-gMacs differentiation in sepsis-induced intestinal injury. METHODS: Sepsis was induced in C57BL/6 wild type (WT) mice and Atf4- knockdown ( Atf4+/ - ) mice by cecal ligation and puncture or administration of lipopolysaccharide (LPS). Colon, peripheral blood mononuclear cells, sera, lung, liver, and mesenteric lymph nodes were collected for flow cytometry, hematoxylin and eosin staining, immunohistochemistry, quantitative reverse transcription polymerase chain reaction, and enzyme-linked immunosorbent assay, respectively. RESULTS: CD64, CD11b, Ly6C, major histocompatibility complex-II (MHC-II), CX3CR1, Ly6G, and SSC were identified as optimal primary markers for detecting the process of monocytes-to-gMacs differentiation in the colon of WT mice. Monocytes-to-gMacs differentiation was impaired in the colon during sepsis and was associated with decreased expression of ATF4 in P1 (Ly6C hi monocytes), the precursor cells of gMacs. Atf4 knockdown exacerbated the impairment of monocytes-to-gMacs differentiation in response to LPS, resulting in a significant reduction of gMacs in the colon. Furthermore, compared with WT mice, Atf4+/- mice exhibited higher pathology scores, increased expression of inflammatory factor genes ( TNF-α, IL-1ß ), suppressed expression of CD31 and vascular endothelial-cadherin in the colon, and increased translocation of intestinal bacteria to lymph nodes and lungs following exposure to LPS. However, the aggravation of sepsis-induced intestinal injury resulting from Atf4 knockdown was not caused by the enhanced inflammatory effect of Ly6C hi monocytes and gMacs. CONCLUSION: ATF4, as a novel regulator of monocytes-to-gMacs differentiation, plays a critical role in protecting mice against sepsis-induced intestinal injury, suggesting that ATF4 might be a potential therapeutic target for sepsis treatment.

[Clinical evaluation of true and false positive Z values among high-risk cases screened by non-invasive prenatal testing].

OBJECTIVE: To analyze the Z values of true and false positive cases by non-invasive prenatal testing (NIPT) in order to improve its accuracy in clinical practice. METHODS: Results of 24 384 NIPT tests were reviewed. For cases with high risks for trisomies 21, 18 and 13, the range of Z values in true and false positive cases was analyzed and discussed. RESULTS: A total of 335 high-risk cases were identified by NIPT, among which 256 had elected prenatal diagnosis, 153 (59.77%) were verified as true positives, and 103 (40.23%) were false positives, and the area under the curve (AUC) was 0.9994. For NIPT screening, the positive predictive value (PPV) for trisomy 21 was 100% when Z>13, regardless if the pregnant woman was over 35. When 335 and about 41.6% (5/12) for those<35. For trisomy 18, the PPV was 100% when Z>13, and only 14.3% (1/7) when 3