Circulating Lysophosphatidylcholines in Early Pregnancy and Risk of Gestational Diabetes in Chinese Women.

ObjectivesThis study aimed to explore associations of lysophosphatidylcholines (LPCs) in early pregnancy with gestational diabetes mellitus (GDM), and whether LPCs mediated the associations of bile acids with GDM risk or had interactive effects with bile acids on GDM risk.DesignWe conducted a 1:1 nested case-control study (n = 486) from a large prospective pregnant women cohort in urban Tianjin, China. Blood samples were collected at their first antenatal care visit (median at 10th gestational week). LPCs were measured by liquid chromatography-tandem mass spectrometry analysis. Conditional binary logistic regression and restricted cubic spline analysis were used to identify cutoff points of these metabolites for GDM risk.ResultsOf the 6 detectable LPCs, LPC14:0 less than 0.24 nmol/mL, LPC15:0 at 0.45 nmol/mL or greater, and LPC18:0 at 18.00 nmol/mL or greater were independently associated with GDM risk. Adjustment for LPC18:0 slightly attenuated odds ratios (ORs) of deoxycholic acid (DCA, ≤ 0.36 nmol/mL) and glycoursodeoxycholic acid (GUDCA, ≤ 0.07 nmol/mL) for GDM, and the correlations of DCA and GUDCA with LPC18:0 were weak. However, the presence of DCA at 0.36 nmol/mL or less greatly amplified the adjusted OR of LPC18:0 at 18.00 nmol/mL or greater alone for GDM from 8.18 (2.51-26.7) up to 17.7 (6.64-47.1), with significant additive interaction. Similarly, the presence of GUDCA at 0.07 nmol/mL or less also greatly amplified the adjusted OR of LPC18:0 at 18.00 nmol/mL or greater alone for GDM from 17.2 (1.77-168) up to 73.8 (12.7-429), with significant additive interaction.ConclusionsLPCs in early pregnancy were associated with GDM risk. Low DCA or GUDCA greatly amplified the effect of high LPC18:0 on GDM, and its molecular mechanism is worth further investigations

Effects of Normative Aging on Eye Movements during Reading

Substantial progress has been made in understanding the mostly detrimental effects of normative aging on eye movements during reading. This article provides a review of research on aging effects on eye movements during reading for different writing systems (i.e., alphabetic systems like English compared to non-alphabetic systems like Chinese), focused on appraising the importance of visual and cognitive factors, considering key methodological issues, and identifying vital questions that need to be addressed and topics for further investigation

Identification of an unfolded protein response-related signature for predicting the prognosis of pancreatic ductal adenocarcinoma

BackgroundPancreatic ductal adenocarcinoma (PDAC) is a highly aggressive lethal malignancy. An effective prognosis prediction model is urgently needed for treatment optimization.MethodsThe differentially expressed unfolded protein response (UPR)‒related genes between pancreatic tumor and normal tissue were analyzed using the TCGA-PDAC dataset, and these genes that overlapped with UPR‒related prognostic genes from the E-MTAB-6134 dataset were further analyzed. Univariate, LASSO and multivariate Cox regression analyses were applied to establish a prognostic gene signature, which was evaluated by Kaplan‒Meier curve and receiver operating characteristic (ROC) analyses. E‒MTAB‒6134 was set as the training dataset, while TCGA-PDAC, GSE21501 and ICGC-PACA-AU were used for external validation. Subsequently, a nomogram integrating risk scores and clinical parameters was established, and gene set enrichment analysis (GSEA), tumor immunity analysis and drug sensitivity analysis were conducted.ResultsA UPR-related signature comprising twelve genes was constructed and divided PDAC patients into high- and low-risk groups based on the median risk score. The UPR-related signature accurately predicted the prognosis and acted as an independent prognostic factor of PDAC patients, and the AUCs of the UPR-related signature in predicting PDAC prognosis at 1, 2 and 3 years were all more than 0.7 in the training and validation datasets. The UPR-related signature showed excellent performance in outcome prediction even in different clinicopathological subgroups, including the female (p<0.0001), male (p<0.0001), grade 1/2 (p<0.0001), grade 3 (p=0.028), N0 (p=0.043), N1 (p<0.001), and R0 (p<0.0001) groups. Furthermore, multiple immune-related pathways were enriched in the low-risk group, and risk scores in the low-risk group were also associated with significantly higher levels of tumor-infiltrating lymphocytes (TILs). In addition, DepMap drug sensitivity analysis and our validation experiment showed that PDAC cell lines with high UPR-related risk scores or UPR activation are more sensitive to floxuridine, which is used as an antineoplastic agent.ConclusionHerein, we identified a novel UPR-related prognostic signature that showed high value in predicting survival in patients with PDAC. Targeting these UPR-related genes might be an alternative for PDAC therapy. Further experimental studies are required to reveal how these genes mediate ER stress and PDAC progression

The etiology and differential diagnosis of “autoimmune hepatitis-like liver disease” in children: a single-center retrospective study

BackgroundChildren with autoimmune hepatitis (AIH) often present with symptoms similar to those of other liver diseases. This study consists of a comparison between the clinical and histological characteristics of AIH and those of other four AIH-like liver diseases [i.e., drug-induced liver injury (DILI), gene deficiency, infectious liver disease and other etiology of liver disease], as well as an evaluation of the AIH scoring system's diagnostic performance.MethodsAll children with AIH-like liver disease at our center from January 2013 to December 2022 were included. The clinical and histological characteristics of the AIH group were retrospectively analyzed and compared with those of the other four groups.ResultsA total of 208 children were included and divided into AIH group (18 patients), DILI group (38 patients), gene deficiency group (44 patients), infectious liver disease group (74 patients), and other etiology group (34 patients). The antinuclear antibodies (ANA) ≥ 1:320 rate was significantly higher in the AIH compared to the other four groups after multiple testing correction (p < 0.0125), while patients with positive antibodies to liver-kidney microsomal-1 (anti-LKM1, n = 3) and smooth muscle antibodies (SMA, n = 2) were only observed in the AIH group. The positive rates of antibodies to liver cytosol type1 (anti-LC1) and Ro52 were higher than those in the other four groups. The serum immunoglobulin G (IgG) and globulin levels, as well as the proportions of portal lymphoplasmacytic infiltration, lobular hepatitis with more than moderate interface hepatitis, and lobular hepatitis with lymphoplasmacytic infiltration, were significantly higher in the AIH group than in the other four groups after multiple testing correction (p < 0.0125). The cirrhosis rate in the AIH group was higher than that in the DILI and infectious liver disease groups (p < 0.0125). Both the simplified (AUC > 0.73) and the revised systems (AUC > 0.93) for AIH have good diagnostic performance, with the latter being superior (p < 0.05).ConclusionPositive autoantibodies (ANA ≥ 1:320 or anti-LKM1 positive, or accompanied by SMA, anti-LC1 or Ro-52 positive) and elevated serum IgG or globulin levels contribute to early recognition of AIH. The presence of lobular hepatitis with more than moderate interface hepatitis and lymphoplasmacytic infiltration contribute to the diagnosis of AIH

Variable density points pressure sensor with wide sensing range and spatial pressure mapping

Wearable flexible pressure sensors are a novel class of human activity detection device. However, the preparation of pressure sensors with high sensitivity and wide sensing range still faces great challenges. This study reveals an flexible heat-resistant variable density point pressure sensing array (PSA) with ultra-wide sensing range based on Ti3C2Tx-MXene. MXene containing polar oxygen-containing functional groups coated polyester fiber fabricated the pressure sensing layer while a stainless steel wire core is used as a flexible electrode for signal collection. The signal processing device rapidly converts the mechanical signal into electrical signal output to increase the transmission speed and range. Experimental results show that the PSA can effectively sense dynamic and static pressures with high sensitivity (0.14–0.87 kPa−1 over a pressure range of 7.2 Pa–2000 kPa), a wide sensing range (0–15000 kPa), fast response time (80 ms), 10,000 cycles (2000 kPa) stability and maintains a 81.25% current response. The noval fully woven structural flexible PSA exhibited larger area, of which the weave density is varied to control resolution and the pressure mapping is referenced to each pixel point to qualitatively and quantitatively analyze shape and pressure distribution. Variable density points pressure sensor with wide sensing range and spatial pressure mappinghas promising applications in healthcare

Comparison of drug safety data obtained from the monitoring system, literature, and social media : an empirical proof from a Chinese patent medicine

Objectives: To investigate the consistency of adverse events (AEs) and adverse drug reactions (ADRs) reported in the literature, monitoring and social media data. Methods: Using one Chinese patent medicine-Cordyceps sinensis extracts (CSE) as an example, we obtained safety data from the national monitoring system (July 2002 to February 2016), literature (up to November 2016) and social media (May 2019). For literature data, we searched the Chinese National Knowledge Infrastructure Database (CNKI), WanFang database, Chinese Science and Technology Periodical Database (VIP), Chinese Biomedical Literature Database (SinoMed), PubMed, Embase and the Cochrane Library. Social media data was from the Baidu post bar and Sina micro-blog. Two authors independently screened the literature and extracted data by PRISMA Harms checklist was followed. AEs and ADRs were coded using the World Health Organization Adverse Reaction Terminology (WHO-ART). AEs and ADRs were grouped into thirty-one organ-system classes for comparisons. Frequencies, relative frequencies and rank were used as metrics. Radar chart was used to manifest the features of the distributions and proportions. Results: 610 AEs reported in CFDA monitoring data were associated with CSE, of which 537 (88.03%) were suspected ADRs (10.49% certain). 5568 AEs were identified from 172 papers (63% RCTs, 37% other types of studies including case series, case reports, ADR monitoring reports and reviews), in which 86 (1.54%) were ADRs (1.54% certain). 15 AEs (0 certain ADR) were identified from social media. AEs, ADRs and their affected system-organ classes, looked largely similar, but different in every aspect when looking at details. Data from RCTs demonstrated the most disparity. Conclusions: In our study, the most prevalent AEs and ADRs, mainly gastro-intestinal system disorders including nausea, diarrhea and vomiting, in monitoring system were largely similar with those in literature and social media. But data from different sources varied if looked at details. Multiple data sources (the monitoring system, literature and social media) should be integrated to collect safety information of interventions. The distributions of AEs and ADRs from RCTs were least similar with the data from other sources. Our empirical proof is consistent with other similar studies

Microstructure and Properties of Nickel-Based Gradient Coatings Prepared Using Cold Spraying Combined with Laser Cladding Methods

A cold spray–laser cladding composite gradient coating (CLGC) was successfully formed on a Cu substrate. In comparison with traditional laser cladding gradient coatings (LGC), cold spraying the pre-set Ni-Cu alloy’s intermediate transition layer not only mitigates the negative impacts due to the high reflectivity of the copper substrate but also helps to minimize the difference in the coefficients of thermal expansion (CTE) between the substrate and coating. This reduces the overall crack sensitivity and improves the cladding quality of the coating. Besides this, the uniform distribution of hard phases in CLGC, such as Ni11Si12 and Mo5Si3, greatly increases its microhardness compared to the Cu substrate, thus resulting in the value of 478.8 HV0.5 being approximately 8 times that of the Cu substrate. The friction coefficient of CLGC is lowered compared to both the Cu substrate and LGC with respective values of 0.28, 0.54, and 0.43, and its wear rate is only one-third of the Cu substrate’s. These results suggest CLGC has excellent anti-wear properties. In addition, the wear mechanism was determined from the microscopic morphology and element distribution and was found to be oxidative and abrasive. This approach combines cold spraying and laser cladding to form a nickel-based gradient coating on a Cu substrate without cracks, holes, or other faults, thus improving the wear resistance of the Cu substrate and improving its usability

Microstructure and Wear Resistance of Laser-Clad Ni–Cu–Mo–W–Si Coatings on a Cu–Cr–Zr Alloy

To improve the wear resistance of high-strength and high-conductivity Cu–Cr–Zr alloys in high-speed and heavy load friction environments, coatings including Ni–Cu, Ni–Cu-10(W,Si), Ni–Cu–10(Mo,W,Si), and Ni–Cu–15(Mo,W,Si) (with an atomic ratio of Mo,W to Si of 1:2) were prepared using coaxial powder-feeding laser cladding technology. The microstructure and wear performance of coatings were chiefly investigated. The results revealed that (Mo,W)Si2 and MoNiSi phases are found in the Ni–Cu–10(Mo,W,Si) and Ni–Cu–15(Mo,W,Si) coating. WSi2 phases are found in the Ni–Cu–10(W,Si) coating. The degree of grain refinement in Ni–Cu–10(Mo,W,Si) was greater than that of the Ni–Cu–10(W,Si) coating after the effect of Mo. The excellent wear resistance and micro-hardness of the Ni–Cu–15(Mo,W,Si) coating were attributed to the increase in its dispersion phase, which were approximately 34.72 mg/km and 428 HV, 27.1% and 590% higher than the Cu–Cr–Zr substrate, respectively. The existence of silicide plays an important role in grain refinement due to the promotion of nucleation and the inhibition of grain growth. In addition, the wear mechanism transformed from adhesive wear in the Ni–Cu coating with no silicides to abrasive wear in the Ni–Cu–15(Mo,W,Si) coating with high levels of silicides