Tailoring the Holocellulose Fiber/Acrylic Resin Composite Interface with Hydrophobic Carboxymethyl Cellulose to Enhance Optical and Mechanical Properties.

Interface engineering is essential for cellulosic fiber-reinforced polymer composites to achieve high strength and toughness. In this study, carboxymethyl cellulose (CMC) functionalized with hydrophobic quaternary ammonium ions (QAs) were utilized to modify the interface between holocellulose fibers (HF) and acrylic resin. The wet HF/CMC papers were prepared by vacuum filtration, akin to papermaking, followed by cationic ion exchange with different hydrophobic QAs. Subsequently, the modified papers were dried, impregnated with an acrylic resin monomer, and cured to produce transparent composite films. The effect of the hydrophobic QA moieties on the structure and optical and mechanical properties of the HF/CMC/acrylic resin composites were investigated. The composite film with cetyltrimethylammonium (CTA)-functionalized CMC showed high optical transmittance (87%) with low haze (43%), while the composite film with phenyltrimethylammonium (PTMA)-functionalized CMC demonstrated high Young's modulus of 7.6 GPa and high tensile strength of 180 MPa. These properties are higher than those of the composites prepared through covalent interfacial modification strategies. The results highlighted the crucial role of hydrophobic functionalized CMCs in facilitating homogeneous resin impregnation in the HF fiber network, producing a composite with enhanced interfacial adhesion strength, increased optical transparency, and mechanical strength. This facile use of hydrophobic CMCs as interfacial compatibilizers provides an energy-efficient route for preparing transparent, thin, and flexible composite films favorable in optoelectronic applications.

Longitudinal impact of COVID-19 pandemic on the utilization of hemoglobin A1c testing in outpatients.

BACKGROUND: During the COVID-19 pandemic, concerns arose about disparate access to health care and laboratory testing. There is limited information about the pandemic's impact on the frequency of diabetic laboratory testing across demographic subgroups (e.g., sex, age over 65 y, and race). METHODS: This retrospective study examined outpatient hemoglobin A1c (HbA1c) testing in a large academic medical center in Upstate New York between March 2019 and March 2021. Multivariate Poisson regression models were used to evaluate the pandemic's effects on HbA1c utilization. RESULTS: Over 190,000 HbA1c results from predominately white (76.1 %) and older (mean age, 60.6 y) outpatients were analyzed. Compared to pre-pandemic time period, the average number of HbA1c tests per patient during COVID time period experienced a small, though significant, drop (1.3 to 1.2; p < 0.001) on aggregate and in outpatients, males, females, and seniors. The modest reduction was not significant by race except for the white seniors (p < 0.001). However, the testing frequency remained within recommendations from the American Diabetes Association for monitoring prediabetic patients and patients with stable glycemic control. CONCLUSION: Given the propensity for healthcare disruptions to widen disparities, it is reassuring that we did not observe a worsening of disparities in rates of HbA1c testing during the COVID-19 pandemic.

[Analysis on the Distribution Characteristics and Influence Mechanism of Migration and Transformation of Heavy Metals in Mining Wasteland].

In order to explore the distribution characteristics and the influence mechanism of migration and transformation of heavy metals in mining wasteland, soil and tailings samples were collected from the mining wasteland in the Dabaoshan Mining area, Guangdong Province, and the morphological characteristics of heavy metals were analyzed. At the same time, the pollution sources of the mining area were analyzed using Pb stable isotope analysis, and the characteristics and influencing factors of heavy metal migration and transformation in the mining area were expounded by combining X-ray diffraction analysis, transmission electron microscope-energy spectrum analysis (TEM-EDS), and Raman analysis of typical minerals in the mining area, as well as laboratory-simulated leaching experiments. Morphological analysis showed that the forms of Cd, Pb, and As in the soil and tailings samples in the mining area were mainly the residual phase, accounting for 85%-95% of the total, followed by the iron and manganese oxide-bound form (1%-15%). The main mineral types in the soil and tailings in the Dabaoshan Mining area were pyrite (FeS2), chalcopyrite (CuFeS2), and metal oxides, as well as a small amount of sphalerite (ZnS) and galena (PbS). Acidic conditions (pH=3.0) were beneficial to the release and migration of Cd and Pb from soil, tailings, and minerals (pyrite, chalcopyrite) and from the residual phase to the non-residual phase. Lead isotope analysis showed that the lead in the soil and tailings mainly came from the release of metal minerals in the mining area, and the contribution of diesel in the mining area was less than 30%. Multivariate statistical analysis showed that Pyrite, Chalcopyrite, Sphalerite, and Metal oxide were the main sources of heavy metals in the soil and tailings in the mining area, in which Cd, As, and Pb were mainly contributed by sphalerite and metal oxide. The form change in heavy metals in the mining wasteland was easily affected by environmental factors. The form characteristics and migration and transformation factors of heavy metals should be considered in the source control of heavy metal pollution in mining wasteland.

[Regulation of Mitochondria on Platelet Apoptosis and Activation].

OBJECTIVE: To explore the regulation of mitochondria on platelet apoptosis and activation, and the relationship between platelet apoptosis and activation. METHODS: Platelets were isolated from peripheral venous blood of healthy volunteers. Cyclosporin A (CsA), which has a protective effect on the function of platelet mitochondria, BAPTA, which can chelate calcium ions across membranes in platelets, and NAC, an antioxidant that reduces the level of intracellular reactive oxygen species, were selected for coincubation with washed platelets, respectively. By flow cytometry, platelet aggregator was used to detect the changes of platelet mitochondrial function and platelet activation indexes after different interventions. RESULTS: H89, staurosporine, and A23187 led to platelet mitochondrial abnormalities, while CsA could effectively reverse the decline of platelet mitochondrial membrane potential caused by them. Antioxidant NAC could reverse platelet mitochondrial damage correspondingly, and completely reverse platelet shrinkage and phosphatidylserine eversion induced by H89. BAPTA, prostaglandin E1, acetylsalicylic acid and other inhibitors could not reverse the decline of platelet mitochondrial membrane potential. CONCLUSION: Mitochondrial function plays an important role in platelet apoptosis and activation. Abnormal mitochondrial function causes the imbalance of reduction/oxidation state in platelets, which leads to platelet apoptosis. Platelet apoptosis and activation are independent signal processes.

Wood xerogel for fabrication of high-performance transparent wood.

Optically transparent wood has been fabricated by structure-retaining delignification of wood and subsequent infiltration of thermo- or photocurable polymer resins but still limited by the intrinsic low mesopore volume of the delignified wood. Here we report a facile approach to fabricate strong transparent wood composites using the wood xerogel which allows solvent-free infiltration of resin monomers into the wood cell wall under ambient conditions. The wood xerogel with high specific surface area (260 m2 g-1) and high mesopore volume (0.37 cm3 g-1) is prepared by evaporative drying of delignified wood comprising fibrillated cell walls at ambient pressure. The mesoporous wood xerogel is compressible in the transverse direction and provides precise control of the microstructure, wood volume fraction, and mechanical properties for the transparent wood composites without compromising the optical transmittance. Transparent wood composites of large size and high wood volume fraction (50%) are successfully prepared, demonstrating potential scalability of the method.

NADPH oxidase 4 regulate the glycolytic metabolic reprogramming of microglial cells to promote M1 polarization.

This work aimed to investigate the role and mechanism of NADPH oxidase 4 (NOX4) in the polarization of microglial cells. Microglial cells were transfected with the NOX4 overexpression plasmid (pGL3-NOX4), and later treated with lipopolysaccharide (LPS) and interferon-γ (IFN-γ) to induce its M1 polarization. Later, the F4/80 + CD86 + cell proportion was detected by flow cytometry (FCM), the inflammatory factor expression levels were analyzed through enzyme-linked immunosorbent assay (ELISA), while ionized calcium binding adapter molecule 1 (IBA-1) and PKM2 expression were measured by immunofluorescence (IF) staining. In addition, dichlorodihydrofluorescein diacetate probe was utilized to detect the reactive oxygen species (ROS) levels, glucose uptake, and glycolysis, as well as lactic acid level. The expression of glycolytic enzymes PKM2, HK2, and citrate (Si)-synthas (CS) was detected by Western-blot (WB) assay. Moreover, the polarization level of microglial cells was detected after ROS expression was suppressed by the ROS inhibitor N-acetylcysteine (NAC). In mouse experiments, LPS was applied in inducing central neuroinflammation in NOX4 knockdown mouse model (KO) and wild-type mice (WT). Thereafter, the inflammatory factor levels and lactic acid level in mouse tissues were detected; IBA-1 and CD86 expression in mice was measured by IF staining; and the expression of glycolytic enzymes PKM2, HK2, and CS in the central nervous system (CNS) was also detected. After NOX4 overexpression in microglial cells, the M1 polarization level was upregulated, the F4/80 + CD86 + cell proportion increased, and inflammatory factors were upregulated. At the same time, the expression of glycolytic enzymes PKM2, HK2, and CS was upregulated. NAC pretreatment suppressed the effects of NOX4, reduced the F4/80 + CD86 + cell proportion, and suppressed the expression of PKM2, HK2, and CS. In the mouse model, the expression levels of CD86 in KO group decreased, and the inflammatory factors were also downregulated. NOX4 promotes glycolysis of microglial cells via ROS, thus accelerating M1 polarization and inflammatory factor expression. In this regard, NOX4 is promising as a new target for the treatment of neuroinflammation.

Endocrine Tumor Classification via Machine-Learning-Based Elastography: A Systematic Scoping Review.

Elastography complements traditional medical imaging modalities by mapping tissue stiffness to identify tumors in the endocrine system, and machine learning models can further improve diagnostic accuracy and reliability. Our objective in this review was to summarize the applications and performance of machine-learning-based elastography on the classification of endocrine tumors. Two authors independently searched electronic databases, including PubMed, Scopus, Web of Science, IEEEXpress, CINAHL, and EMBASE. Eleven (n = 11) articles were eligible for the review, of which eight (n = 8) focused on thyroid tumors and three (n = 3) considered pancreatic tumors. In all thyroid studies, the researchers used shear-wave ultrasound elastography, whereas the pancreas researchers applied strain elastography with endoscopy. Traditional machine learning approaches or the deep feature extractors were used to extract the predetermined features, followed by classifiers. The applied deep learning approaches included the convolutional neural network (CNN) and multilayer perceptron (MLP). Some researchers considered the mixed or sequential training of B-mode and elastographic ultrasound data or fusing data from different image segmentation techniques in machine learning models. All reviewed methods achieved an accuracy of ≥80%, but only three were ≥90% accurate. The most accurate thyroid classification (94.70%) was achieved by applying sequential training CNN; the most accurate pancreas classification (98.26%) was achieved using a CNN-long short-term memory (LSTM) model integrating elastography with B-mode and Doppler images.

An Oxidative Enzyme Boosting Mechanical and Optical Performance of Densified Wood Films.

Nature has evolved elegant ways to alter the wood cell wall structure through carbohydrate-active enzymes, offering environmentally friendly solutions to tailor the microstructure of wood for high-performance materials. In this work, the cell wall structure of delignified wood is modified under mild reaction conditions using an oxidative enzyme, lytic polysaccharide monooxygenase (LPMO). LPMO oxidation results in nanofibrillation of cellulose microfibril bundles inside the wood cell wall, allowing densification of delignified wood under ambient conditions and low pressure into transparent anisotropic films. The enzymatic nanofibrillation facilitates microfibril fusion and enhances the adhesion between the adjacent wood fiber cells during densification process, thereby significantly improving the mechanical performance of the films in both longitudinal and transverse directions. These results improve the understanding of LPMO-induced microstructural changes in wood and offer an environmentally friendly alternative for harsh chemical treatments and energy-intensive densification processes thus representing a significant advance in sustainable production of high-performance wood-derived materials.

Mixed-linkage (1,3;1,4)-ß-d-glucans as rehydration media for improved redispersion of dried cellulose nanofibrils.

Improving the redispersion and recycling of dried cellulose nanofibrils (CNFs) without compromising their nanoscopic dimensions and inherent mechanical properties are essential for their large-scale applications. Herein, mixed-linkage (1,3;1,4)-ß-d-glucan (MLG) was studied as a rehydration medium for the redispersion and recycling of dried CNFs, benefiting from the intrinsic affinity of MLG to both cellulose and water molecules as inspired from plant cell wall. MLG from barley with a lower molar ratio of cellotriosyl to cellotetraosyl units was found homogeneously coated on CNFs, facilitating rehydration of the network of individualized CNFs. The addition of barley MLG did not impair the mechanical properties of the CNF/MLG composites as compared to neat CNFs nanopaper. With the addition of 10 wt% barley MLG, dry CNF/MLG composite film was successfully redispersed in water and recycled with well-maintained mechanical properties, while lichenan from Icelandic moss, cationic starch, and xyloglucan could not help the redispersion of dried CNFs.

Clinical significance of MMP-9 overexpression in endometrial cancer: A PRISMA-compliant meta-analysis.

Objective: Several studies have found that MMP-9, one of the extracellular matrix-degrading proteinases, was involved in EC's (endometrial cancer) clinical progression and prognosis. However, the results involving the associations of MMP-9 expression with risk, clinical features and prognosis of EC were conflicting. Therefore, we performed a systematic review and meta-analysis to clarify the correlation of MMP-9 expression with EC. Methods: Relative studies involving the associations between MMP-9 expression and EC were retrieved from PubMed, Embase, Web of Science and CNKI (China National Knowledge Infrastructure) electronic databases. OR (odds ratio) with 95% CI (confidence interval) was applied to evaluate the associations of MMP-9 expression with risk and clinical features of EC. Furthermore, we evaluated the role of MMP-9 expression in prognosis of EC using HR and 95% CI. The funnel plots and Begg test were used to assess the publication bias. Results: A total of 28 eligible studies were acquired from Pubmed, Embase, Web of science and CNKI databases. We found MMP-9 overexpression was significantly associated with the risk of EC (OR = 11.02, 95% CI = 7.51-16.16, P < 0.05). In the meantime, MMP-9 overexpression was significantly associated with the tumor grade, FIGO stage, lymph node metastasis and myometrial invasion (Tumor grade: OR = 1.68, 95% CI = 1.09-2.58, P < 0.05; FIGO stage: OR = 3.25, 95% CI = 1.73-6.08, P < 0.05; Lymph node metastasis: OR = 2.98, 95% CI = 1.27-7.03, P < 0.05; Myometrial invasion: OR = 2.42, 95% CI = 1.42-4.12, P < 0.05) in Asians. In addition, the overall results showed that MMP-9 overexpression predicted a worse prognosis of EC (OR = 1.82, 95% CI = 1.01-2.62, P < 0.05). Conclusions: MMP-9 overexpression might be a potential predictor of poor clinical progression and prognosis of EC.

The relationship between lipoprotein(a) and risk of cardiovascular disease: a Mendelian randomization analysis.

BACKGROUND: Lipoprotein(a) [Lp(a)] is one of the residual risk factors for cardiovascular disease (CVD) in the setting of optimal low-density lipoprotein cholesterol (LDL-C). The association between Lp(a) and CVD is still in the exploratory phase, with few studies indicating a causal connection between Lp(a) and various CVD. METHODS: Lp(a) (n = 377,590) was a genome-wide association study (GWAS) based on European populations from Neale Lab. Large GWAS datasets for CVD, including aortic aneurysm(AA) (n = 209,366), atrial fibrillation(AF) (n = 1,030,836), coronary heart disease(CHD) (n = 361,194), secondary hypertension(HBP) (n = 164,147), heart failure(HF) (n = 208,178), ischemic stroke (IS) (n = 218,792), large artery atherosclerosis stroke(ISL) (n = 150, 765), small vessel stroke(ISS) (n = 198,048), lacunar stroke(LIS) (n = 225,419), and pulmonary embolism(PE) (n = 218,413) were also based on European populations. We performed separate univariate two-sample Mendelian randomization (MR) analysis for Lp(a) and CVD as described above. We evaluated this connection mainly using the random-effects inverse variance weighted technique(IVW1) with a 95% confidence interval (CI) for the odds ratio (OR). This was supplemented by MR-Egger, weighted median, maximum likelihood, penalized weighted median, and fixed-effects inverse variance weighted methods. MR-PRESSO offers another means of statistical detection. RESULTS: Our two-sample MR, which was predominately based on IVW1, revealed a causal relationship between Lp(a) and AA (OR = 1.005, 95%CI: 1.001-1.010, P = 0.009), CHD (OR = 1.003, 95%CI 1.001-1.004, P = 0.010), and ISL (OR = 1.003, 9 5%CI 1.002-1.004, P = 9.50E-11), in addition, there is no causal association with AF, HBP, HF, IS, ISS, LIS, or PE. Similar conclusions were reached by the MR-PRESSO method. CONCLUSION: This MR study suggested a causal relationship between Lp(a) and CHD, AA, and ISL, but not associated with AF, HF, IS, LIS, ISS, HBP, or PE. Our work further verifies the association between Lp(a) and various CVD, resulting in improved Lp(a) management and a reduction in the prevalence of CVD.

Depth-Camera-Based Under-Blanket Sleep Posture Classification Using Anatomical Landmark-Guided Deep Learning Model.

Emerging sleep health technologies will have an impact on monitoring patients with sleep disorders. This study proposes a new deep learning model architecture that improves the under-blanket sleep posture classification accuracy by leveraging the anatomical landmark feature through an attention strategy. The system used an integrated visible light and depth camera. Deep learning models (ResNet-34, EfficientNet B4, and ECA-Net50) were trained using depth images. We compared the models with and without an anatomical landmark coordinate input generated with an open-source pose estimation model using visible image data. We recruited 120 participants to perform seven major sleep postures, namely, the supine posture, prone postures with the head turned left and right, left- and right-sided log postures, and left- and right-sided fetal postures under four blanket conditions, including no blanket, thin, medium, and thick. A data augmentation technique was applied to the blanket conditions. The data were sliced at an 8:2 training-to-testing ratio. The results showed that ECA-Net50 produced the best classification results. Incorporating the anatomical landmark features increased the F1 score of ECA-Net50 from 87.4% to 92.2%. Our findings also suggested that the classification performances of deep learning models guided with features of anatomical landmarks were less affected by the interference of blanket conditions.

Evaluation Value and Clinical Significance of Cardiac Troponin Level and Pediatric Sequential Organ Failure Score in the Definition of Sepsis 3.0 in Critically Ill Children.

Objective: A case-control study was conducted to explore the value and clinical significance of troponin level and pediatric sequential organ failure score in the evaluation of sepsis 3.0 definition in critically ill children. Methods: 180 children with sepsis who were admitted to the ICU from March 2019 to June 2021 were enrolled in our hospital as the research objects. In addition, 100 children with general infection did not meet the diagnostic criteria of systemic inflammatory response syndrome (SIRS) as controls. The creatine kinase MB (CK-MB) and cardiac troponin I (cTnI) data at the 1st and 24-72 h after admission to pediatric intensive care unit (PICU) were enrolled as the observation indexes of myocardial enzymology. In the meantime, the relevant literature was reviewed to obtain the indicators related to sepsis death. The data of the first examination in the medical history data were enrolled for analysis. According to the definition of sepsis 3.0 in critically ill children, they were assigned into sepsis and nonsepsis group. According to the survival outcome of discharge and 30 days after discharge, the patients were assigned into the death subgroup and survival subgroup and were assigned into the sequential organ failure assessment (SOFA) score ≥ 2 subgroup and< 2 subgroup according to SOFA score. COX proportional hazard regression was used to analyze the relationship between CK-MB, cTnI, and SOFA scores and prognosis. ROC curve was adopted to analyze the value of CK-MB, cTnI, and SOFA scores in the evaluation of critical sepsis in children. Results: Univariate analysis indicated that the prognosis of children with sepsis was correlated with abnormal levels of CK-MB and cTnI, SOFA score, oxygenation index < 200, mean arterial pressure, and Glasgow coma scale (GCS), and the difference was statistically significant (P < 0.05). The results of COX regression analysis indicated that the variables that were remarkably associated with death from sepsis in children were CK-MB, elevated cTnI levels, and SOFA score ≥ 2, and serum cTnI and/or CK-MB levels and SOFA score were remarkably higher correlation (r = 0.453, P < 0.05). In terms of the myocardial enzyme levels in the sepsis group and the nonsepsis group, the levels of CK-MB and (or) cTnI augmented in 121/180 cases (67.22%) in the sepsis group and in 19/100 cases (19.00%) in the nonsepsis group. The levels of CK-MB and (or) cTnI were augmented, and the difference was statistically significant (P < 0.05). The levels of CK-MB and cTnI in the sepsis group at admission to ICU and 24 to 72 hours after admission were remarkably higher compared to the nonsepsis group. The levels of CK-MB and cTnI at 24-72 h were higher compared to ICU. The myocardial enzyme levels of different SOFA scores and survival outcome subgroups in the sepsis group were compared. The subgroup with SFOA score ≥ 2 points had remarkably higher levels of CK-MB and (or) cTnI than the subgroup with <2 points. The survival subgroup of CK-MB and cTnI level was remarkably higher compared to the death subgroup, the CK-MB and cTnI levels in each subgroup at 224-72 hours were remarkably higher compared to the ICU, and the difference was statistically significant (P < 0.05). Kaplan-Meier method and log-rank test indicated that the survival rates of groups 1 to 4 at 30 days were 33.23%, 78.71%, 40.03%, and 100.00%, respectively. The average survival time and their 95% CI were 12.82 d (10.52~ 16.26 d), 22.34 d (18.76~ 25.81 d), 14.65 d (11.62~ 16.38 d), and 30 d (30.00~ 30.00 d), respectively. Pairwise comparison indicated that the survival time of children in group 1 was the shortest, and that in group 4 was the longest. The results of ROC curve research showed that the CK-MB, cTnI, and SOFA scores and AUC for the combination test were 0.778 (95% CI 0.642-0.914), 0.736 (95% CI 0.602-0.890), 0.848 (95% CI 0.733-0.963), and 0.934 (95% CI 0.854-0.999), respectively. The AUC of combined diagnosis was remarkably higher compared to single factor prediction, and the difference was statistically significant (P < 0.05). Predictive value showed the joint test > SOFA score > CK - MB > cTnI. Conclusion: Troponin level and pediatric SOFA score can be adopted as effective indicators to assess the severity and prognosis of patients with sepsis and can guide the formulation of a reasonable treatment plan.

Moronic acid improves intestinal inflammation in mice with chronic colitis by inhibiting intestinal macrophage polarization.

This study focuses on exploring the role and mechanism of moronic acid (MOA), a small triterpenoid molecule, against inflammatory bowel disease (IBD). Intestinal macrophages were cultured in vitro, and their M1 polarization was induced by lipopolysaccharide (LPS) and interferon gamma (IFN-γ). After intervention with MOA, the proportion of M1 macrophages was detected, and the levels of inflammatory cytokines (TNF-α, IL-6, and IL-1ß) were examined by ELISA. IFA staining was performed to determine the P50 and CD86 expressions, while DCFH-DA was used to determine the reactive oxygen species (ROS) level, as well as the p-P50 and NLRP3 protein levels. Additionally, we also used N-acetylcysteine, a ROS inhibitor, to further explore the association between MOA and ROS-NF-κB signaling. In murine experimentation, colitis was induced in mice with DSS. After MOA intervention, we assessed the mucosal barrier damage, tissue ROS, as well as protein and inflammatory cytokine levels. MOA could inhibit the M1 polarization of intestinal macrophages, suppress the expressions of inflammatory cytokines, and reduce the level of ROS-NF-κB-NLRP3 signaling. After inhibiting ROS through NAC treatment, the effect of MOA was evidently weakened. Clearly, MOA exerted its activity via ROS. In the murine model, MOA could lower the CD86 level in the intestinal tissues, inhibit the M1 polarization of macrophages, and reduce the tissue levels of inflammatory cytokines. This study finds that MOA can regulate ROS-NF-κB-NLRP3 signaling by inhibiting ROS, thereby suppressing the M1 polarization of intestinal macrophages, which plays a protective role in IBD.

Serum Fetuin-A and Risk of Gestational Diabetes Mellitus: An Observational Study and Mendelian Randomization Analysis.

CONTEXT: Fetuin-A was reported to be associated with risk of type 2 diabetes, but its association with incident gestational diabetes mellitus (GDM) was less studied. OBJECTIVE: We aimed to examine the association between fetuin-A levels in early pregnancy and risk of incident GDM and to evaluate whether this association was causal. METHODS: A total of 332 pregnant women with GDM and 664 matched controls were included in this nested case-control study. Multivariable conditional logistic regression was applied to investigate the prospective association between serum fetuin-A in early pregnancy and subsequent risk of GDM. Two-sample Mendelian randomization (MR) analysis was used to examine the causal association, using summary statistics from the CHARGE Consortium and the FinnGen consortium. RESULTS: The mean age of the participants was 28.0 years, and the mean gestational age was 11.0 weeks (range 6-15) at enrollment. In the final model, the odds ratio (OR) for GDM comparing the extreme quartiles of fetuin-A levels was 1.78 (95% CI 1.06, 2.98; P for trend = 0.009), and the restricted cubic spline analysis indicated a linear association (P for nonlinearity = 0.83). This positive association was found in women with waist circumference <80 cm but not in those with waist circumference ≥80 cm (P for interaction = 0.04). However, MR analyses showed no evidence of a causal association with an OR of 0.91 (95% CI 0.67, 1.23) per unit increment of fetuin-A. CONCLUSIONS: Serum fetuin-A levels in early pregnancy were positively associated with risk of GDM, particularly in those with normal waist circumference. However, we found no genetic evidence for a causal association.

Assembly of AIEgen-Based Fluorescent Metal-Organic Framework Nanosheets and Seaweed Cellulose Nanofibrils for Humidity Sensing and UV-Shielding.

Integrating synthetic low-dimensional nanomaterials such as metal-organic framework (MOF) nanosheets with a sustainable biopolymer is a promising strategy to endow composites with attractive structural and functional properties for expanded applications. Herein, aggregation-induced-emission luminogen (AIEgen)-based MOF bulk crystals are successfully exfoliated into ultrathin 2D nanosheets. Seaweed cellulose nanofibrils (CNFs) are assembled with low amounts (0.3 to 4.0 wt%) of the 2D nanosheets to generate luminescent composites. The 2D nanosheets are adsorbed onto the CNFs in dilute water suspensions owing to the flexibility of the MOF nanosheets and the high aspect ratio of the CNFs. Transparent films are prepared by solution casting from a water suspension of the CNF-MOF assembly. The fluorescence emission of the composite films is enhanced because of the favored affinity between MOF nanosheets and CNFs. Remarkably, these films demonstrate excellent UV-shielding capacity and high optical transmittance at the visible wavelength range. The composite films also show reversible changes in fluorescence emission intensity in response to ambient humidity. The tensile strength and modulus of the composite films are also enhanced owing to the increased adhesion between CNFs through the adsorbed MOF nanosheets. This work provides a novel pathway to fabricate luminescent CNFs-based composites with tunable optical properties for functional materials.

New Diagnostic Cutoffs for Adrenal Insufficiency After Cosyntropin Stimulation Using Abbott Architect Cortisol Immunoassay.

INTRODUCTION: The accurate interpretation of the cosyntropin (adrenocorticotropic hormone [ACTH]) stimulation test requires method- and assay-specific cutoffs of the level of cortisol. Compared with a historical cutoff (18 µg/dL) for polyclonal antibody-based immunoassays, lower thresholds were proposed for the Roche Elecsys II assay, which uses a monoclonal antibody. However, cutoffs for other commonly adopted, monoclonal antibody-based cortisol assays were not yet available. Here, we established the thresholds for the level of cortisol specific to the Abbott Architect immunoassay by comparing the measurements of the level of cortisol using 3 immunoassays. METHODS: The ACTH stimulation test was performed in patients with suspected adrenal insufficiency (n = 50). The serum cortisol level was measured using the Abbott Architect, Roche Elecsys II, and Siemens Centaur assays. The results of the Abbott assay were also compared with those of liquid chromatography-tandem mass spectrometry. The receiver operating characteristic analysis was performed to derive new diagnostic thresholds for the Abbott assay using the polyclonal antibody-based Siemens assay as the reference method. RESULTS: The concentrations of cortisol measured using the Abbott assay were similar to those measured using liquid chromatography-tandem mass spectrometry and the Roche Elecsys II assay but significantly lower than those measured using the Siemens assay. The optimized threshold for cortisol using the Abbott assay was 14.6 µg/dL at 60 minutes after stimulation (sensitivity, 92%; specificity, 96%) and 13.2 µg/dL at 30 minutes after stimulation (sensitivity, 100%; specificity, 89%). CONCLUSION: We recommend a threshold of 14.6 µg/dL for the level of cortisol at 60 minutes after ACTH stimulation for the Abbott assay. In comparison with the historical threshold of 18 µg/dL, the application of the new cutoff may significantly decrease false-positive results due to ACTH stimulation testing. The use of assay-specific cutoffs will be essential for reducing misclassification and overtreatment in patients with suspected adrenal insufficiency.

Ivabradine protects rats against myocardial infarction through reinforcing autophagy via inhibiting PI3K/AKT/mTOR/p70S6K pathway.

Ivabradine (Iva), a heart rate reducing agent that specifically inhibits the pacemaker I(f) ionic current, has been demonstrated to be cardioprotective in many cardiovascular diseases. Autophagy is an evolutionarily conserved metabolic process that regulates cardiac homeostasis. This study is aimed to explore whether autophagy is functionally involved in the cardioprotective effect of Iva in a rat model of myocardial infarction (MI). We observed that Iva treatment (po, 10 mg/kg/day) showed significant recovery on the hemodynamics parameters in MI rats, including left ventricular systolic pressure, left ventricular end diastolic pressure, and maximal ascending/descending rate of left ventricular pressure. Also, Iva treatment dramatically decreased infarct size, inhibited myocardial apoptosis, and reduced the levels of pro-inflammatory cytokines tumor necrosis factor (TNF)-α, interleukin (IL)-1ß and IL-6 in MI rats. Moreover, Iva treatment enhanced autophagy and inhibited PI3K/AKT/mTOR/p70S6K pathway in MI rats. Simultaneously, we observed that autophagy enhancer rapamycin (ip, 10 mg/kg/day) showed similar cardioprotective effects with Iva. Furthermore, we observed that addition of autophagy inhibitor 3-methyladenine (ip, 10 mg/kg/day) counteracted the therapeutic effect of Iva, addressing that Iva attenuated post-MI cardiac injury by enhancing autophagy. In summary, these findings demonstrated that Iva attenuated MI in rats by enhancing autophagy, and PI3K/AKT/mTOR/p70S6K pathway might be involved in the process. Autophagy activation by Iva may be a potential therapeutic strategy for the treatment of MI.

Association of Gut Microbiota during Early Pregnancy with Risk of Incident Gestational Diabetes Mellitus.

AIMS: We aimed to assess the association between gut bacterial biomarkers during early pregnancy and subsequent risk of gestational diabetes mellitus (GDM) in Chinese pregnant women. METHODS: Within the Tongji-Shuangliu Birth Cohort study, we conducted a nested case-control study among 201 incident GDM cases and 201 matched controls. Fecal samples were collected during early pregnancy (at 6-15 weeks), and GDM was diagnosed at 24 to 28 weeks of pregnancy. Community DNA isolated from fecal samples and V3-V4 region of 16S rRNA gene amplicon libraries were sequenced. RESULTS: In GDM cases versus controls, Rothia, Actinomyces, Bifidobacterium, Adlercreutzia, and Coriobacteriaceae and Lachnospiraceae spp. were significantly reduced, while Enterobacteriaceae, Ruminococcaceae spp., and Veillonellaceae were overrepresented. In addition, the abundance of Staphylococcus relative to Clostridium, Roseburia, and Coriobacteriaceae as reference microorganisms were positively correlated with fasting blood glucose, 1-hour and 2-hour postprandial glucose levels. Adding microbial taxa to the base GDM prediction model with conventional risk factors increased the C-statistic significantly (P < 0.001) from 0.69 to 0.75. CONCLUSIONS: Gut microbiota during early pregnancy was associated with subsequent risk of GDM. Several beneficial and commensal gut microorganisms showed inverse relations with incident GDM, while opportunistic pathogenic members were related to higher risk of incident GDM and positively correlated with glucose levels on OGTT.