Prevalence, Trends, and Subsequent Outcomes of Prediabetes in the United States, 1999-2018.

OBJECTIVE: To determine prevalence, trends, and subsequent outcomes of prediabetes defined by American Diabetes Association (ADA), World Health Organization (WHO), and International Expert Committee (IEC) criteria in the US between 1999 and 2018. METHODS: Ten cycles of cross-sectional National Health and Nutrition Examination Survey data were included. Prediabetes was defined by ADA, WHO, and IEC criteria. Unadjusted or covariate adjusted prevalence and trends of prediabetes were estimated. Cox proportional regression model was performed to evaluate the association between prediabetes and all-cause, cardiovascular, or diabetes-related mortality. RESULTS: Among the 59369 participants included (weighted mean age, 41.1 years; 48.7% male), the prevalence of prediabetes was 29.4% in ADA criteria, 16.3% in WHO criteria, and 5.0% in IEC criteria. The covariate adjusted prevalence of prediabetes defined by ADA criteria increased significantly in at least two folds from 15.6% in 1999-2002 to 37.3% in 2015-2018 (p < 0.001). Similar significant increased trends were observed in WHO and IEC criteria (p < 0.001). Compared with normal glycemia, prediabetes participants had higher adjusted risk of diabetes-related mortality irrespective of the criteria used (ADA: hazard ratio [HR] 9.11 [95% CI, 5.83-14.22]; WHO: HR 5.35 [95% CI, 3.01-9.51]; IEC: HR 9.64 [95% CI, 5.92-15.71]). No significant associations between prediabetes and all-cause or cardiovascular mortality were observed in the adjusted models. CONCLUSIONS: In the US, approximately 1 in 3 individuals have prediabetes according to ADA criteria. The prevalence of prediabetes has shown a significant and more than twofold increase over the past two decades, posing an elevated risk of diabetes-related mortality, regardless of the criteria applied.

A novel fluorescent probe for real-time imaging of thionitrous acid under inflammatory and oxidative conditions.

Thionitrous acid (HSNO), a crosstalk intermediate of two crucial gasotransmitters nitric oxide and hydrogen sulfide, plays a critical role in redox regulation of cellular signaling and functions. However, real-time and facile detection of HSNO with high selectivity and sensitivity remains highly challenging. Herein we report a novel fluorescent probe (SNP-1) for HSNO detection. SNP-1 has a simple molecular structure, but showing strong fluorescence, a low detection limit, a broad linear detection range (from nanomolar to micromolar concentrations), ultrasensitivity, and high selectivity for HSNO in both aqueous media and cells. Benefiting from these unique features, SNP-1 could effectively visualize changes of HSNO levels in mouse models of acute ulcerative colitis and renal ischemia/reperfusion injury. Moreover, the good correlation between colonic HSNO levels and disease activity index demonstrated that HSNO is a promising new diagnostic agent for acute ulcerative colitis. Therefore, SNP-1 can serve as a useful fluorescent probe for precision detection of HSNO in various biological systems, thereby facilitating mechanistic studies, therapeutic assessment, and high-content drug screening for corresponding diseases.

Identification of NFASC and CHL1 as Two Novel Hub Genes in Endometriosis Using Integrated Bioinformatic Analysis and Experimental Verification.

Background: Endometriosis (EMS) is a common and highly recurrent gynecological disease characterized by chronic pain and infertility. There are no definitive therapies for endometriosis since the pathogenesis remains undetermined. This study aimed to identify EMS-related functional modules and hub genes by integrated bioinformatics analysis. Methods: Three endometriosis expression profiling series (GSE25628, GSE23339, and GSE7305) were obtained from Gene Expression Omnibus (GEO). The EMS-related module was constructed by weighted gene co-expression network analysis (WGCNA), followed by Gene Ontology (GO) enrichment analyses. Cytohubba and the MCODE plug-ins of Cytoscape were used to screen out the hub genes, which were verified via receiver operating characteristic (ROC) curves. Immunohistochemistry was performed to verify the protein expression of the hub genes in ectopic endometrial tissues. Moreover, CIBERSORT was used to analyze the relationship between the abundance of immune cells infiltration and the expression of hub genes. Results: Among the 18 modules obtained, the darkmagenta module was identified as the EMS-related module, genes of which were significantly enriched to terms referring to cell migration and neurogenesis. NFASC and CHL1 were screened out and prioritized as hub genes through Cytoscape and confirmed to be differentially upregulated in ectopic endometrial samples. Finally, the expression of hub genes was related to the abundance of immune cells infiltration. The higher expression of NFASC or CHL1 correlated with increased M2 macrophages and decreased natural killer (NK) cells in ectopic lesions. Conclusion: This study provided new insights into the molecular factors underlying the pathogenesis of endometriosis and provided a theoretical basis for the potential that the two hub genes, NFASC and CHL1, might be novel biomarkers and therapeutic targets in the future.

Down-Regulating Scar Formation by Microneedles Directly via a Mechanical Communication Pathway.

Excessive extracellular matrix deposition drives fibroblasts into a state of high mechanical stress, exacerbating pathological fibrosis and hypertrophic scar formation, leading to tissue dysfunction. This study reports a minimally invasive and convenient approach to obtaining scarless tissue using a silk fibroin microneedle patch (SF MNs). We found that by tuning the MN size and density only, the biocompatible MNs significantly decreased the scar elevation index in the rabbit ear hypertrophic scar model and increased ultimate tensile strength close to regular skin. To advance our understanding of this recent approach, we built a fibroblast-populated collagen lattice system and finite element model to study MN-mediated cellular behavior of fibroblasts. We found that the MNs reduced the fibroblasts generated contraction and mechanical stress, as indicated by decreased expression of the mechanical sensitive gene ANKRD1. Specifically, SF MNs attenuated the integrin-FAK signaling and consequently down-regulated the expression of TGF-ß1, α-SMA, collagen I, and fibronectin. It resulted in a low-stress microenvironment that helps to reduce scar formation significantly. Microneedles' physical intervention via the mechanotherapeutic strategy is promising for scar-free wound healing.

A ROS-responsive, self-immolative and self-reporting hydrogen sulfide donor with multiple biological activities for the treatment of myocardial infarction.

Myocardial infarction (MI), as one of the leading causes of global death, urgently needs effective therapies. Recently, hydrogen sulfide (H2S) has been regarded as a promising therapeutic agent for MI, while its spatiotemporally controlled delivery remains a major issue limiting clinical translation. To address this limitation, we designed and synthesized a novel H2S donor (HSD-R) that can produce H2S and emit fluorescence in response to reactive oxygen species (ROS) highly expressed at diseased sites. HSD-R can specifically target mitochondria and provide red fluorescence to visualize and quantify H2S release in vitro and in vivo. Therapeutically, HSD-R significantly promoted the reconstruction of cardiac structure and function in a rat MI model. Mechanistically, myocardial protection is achieved by reducing cardiomyocyte apoptosis, attenuating local inflammation, and promoting angiogenesis. Furthermore, inhibition of typical pro-apoptotic genes (Bid, Apaf-1, and p53) played an important role in the anti-apoptotic effect of HSD-R to achieve cardioprotection, which were identified as new therapeutic targets of H2S against myocardial ischemia injury. This ROS-responsive, self-immolative, and fluorescent H2S donor can serve as a new theranostic agent for MI and other ischemic diseases.

Osteopontin Regulates Endometrial Stromal Cell Migration in Endometriosis through the PI3K Pathway : Osteopontin Regulates Endometrial Cell Migration in Endometriosis.

Endometriosis is generally characterized as a tumor-like disease because of its potential for distant metastasis and local tissue invasion, while whether osteopontin (OPN) plays a role in the pathogenesis of endometriosis has not been thoroughly investigated. We investigated the expression of OPN, urokinase plasminogen activator (uPA), phosphatidylinositol 3 kinase (PI3K), and phospho-PI3 kinase (p-PI3K) in endometrial stromal cells (ESCs). The serum concentration of OPN was determined by enzyme-linked immunosorbent assays (ELISA). OPN was downregulated to explore the corresponding change of uPA, p-PI3K, F-actin, and α-tubulin. The expression of OPN, uPA, PI3K, and p-PI3K was evaluated by western blot and quantitative real-time PCR (RT-qPCR) and the expression of F-actin and α-tubulin was confirmed by immunofluorescence assay. The proliferation and migration abilities of ESCs were investigated by CCK8, transwell, and wound scratch assays. Endometrial OPN, p-PI3K, and uPA expressions and serum OPN levels were increased in patients with endometriosis compared with the control. The expressions of p-PI3K, uPA, and α-tubulin were decreased by siRNA-OPN interference in ectopic ESCs. Activation and inhibition of the PI3K pathway apparently upregulate and downregulate uPA expression. Knockdown of OPN and inhibition of the PI3K pathway remarkably inhibited cell migration in ectopic ESCs. Meanwhile, activation of the PI3K pathway promoted the migration ability of ectopic ESCs. OPN may regulate the expression of uPA through the PI3K signal pathway to affect the migration ability of ESCs, indicating that OPN, uPA, and the PI3K pathway may be potential targets for interrupting development of endometriosis.

Violent video games exposure and aggression: The role of moral disengagement, anger, hostility, and disinhibition.

Based on the General Aggression Model (GAM), the current study investigated the interactive effect of personal factors (e.g., sensation-seeking) and situational factors (e.g., violent video games exposure [VVGE]) on the trait aggressive behavior, and the mediating role of individual difference trait (e.g., moral disengagement, anger, and hostility). We recruited 547 undergraduates (48.45% male) from five Chinese universities. The results showed that VVGE was positively associated with moral disengagement, disinhibition, and the four aggressive traits (physical aggression, verbal aggression, anger, and hostility), which were positively associated with each other. Moral disengagement was positively associated with both the disinhibition and the four aggressive traits. Disinhibition was positively associated with the four aggressive traits as well. When controlled for gender, moral disengagement, anger, and hostility wholly mediated the relationship between VVGE and aggression, but the moderation effect of disinhibition was not significant. These findings support the framework of GAM and indicate that moral disengagement, anger, and hostility may be the factors that increase the risk of a higher level of aggression following repeated exposure to violent video games.

Clinical and imaging features of pulmonary artery sling: The experience in one major medical center.

This case series describes echocardiographic and computed tomography angiographic (CTA) characteristics, clinical features, diagnosis, and treatment in 15 patients of Pulmonary artery sling (PAS). Echocardiography is effective in diagnosing PAS, when the main pulmonary artery extends to the right pulmonary artery directly with the left pulmonary artery arising from the right pulmonary artery. CTA, clearly demonstrating the position and extent of trachea compression, the anatomy of PAS and the spatial relationships among the PAS, trachea and the esophagus, is necessary for the final diagnosis. Clinical presentations are caused by the compression of the tracheobronchial tree rather than the PAS itself. Left pulmonary artery reimplantation is the treatment of choice.

Polychlorinated biphenyl 104 promotes migration of endometrial stromal cells in endometriosis.

Polychlorinated biphenyls (PCBs), as part of environmental contaminants, have been proved to be related to endometriosis. This study is to investigate the effect of PCB 104 on cell migration, invasion and resultant gene expression in endometrial stromal cells (ESCs). Fifty-three specimens of eutopic endometrial tissues were collected from twenty-four women with endometriosis (EU-EMS) and twenty-nine women without endometriosis (EU-NON). Both EU-EMS and EU-NON were divided into the PCB 104 exposure group and the control group according to whether they were exposed to PCB 104. Primary cultured ESCs were exposed to PCB 104 at the micro molar doses (2 × 10-3, 0.2 and 1 µmol/L) and concentrations of 2, 5 and 10 µmol/L in six-well plates. Cell mobility and proliferation assay were used to evaluate the effects of PCB 104 on the migration, invasion and proliferation of ESCs, and the effect of PCB 104 on actin cytoskeleton was also examined by immunofluorescence. Subsequently, the mRNA levels of related genes including matrix metalloproteinase (MMP) -2, -3, -9, -10, E-cadherin, Snail, Slug and tissue inhibitor of metalloproteinase (TIMP) -2 in ESCs were examined by using real-time PCR, as well as protein levels of MMP-3 and MMP-10 were detected by enzyme-linked immunosorbent assay (ELISA). We explored the role of epidermal growth factor receptor (EGFR) in the expression of MMP-3 and MMP-10 induced by PCB 104. Exposure to PCB 104 significantly increased the migration and invasion of ESCs. The mRNA and protein levels of MMP-3 and MMP-10 in ESCs treated with PCB 104 were higher than that in the control, with a dose- and time-dependent manner in mRNA level, while the expression of MMP-2, MMP-9, TIMP-2, E-cadherin, Snail and Slug did not change significantly. Taken together, PCB 104 promotes migration and invasion of ESCs by inducing the expression of MMP-3 and MMP-10, which may involved the EGFR signalling pathway.

Polychlorinated biphenyls and its potential role in endometriosis.

With the progress of global industrialization and environmental deterioration, the relationship between human health and the living environment has become an increasing focus of attention. Polychlorinated biphenyls (PCBs, including dioxin-like polychlorinated biphenyls and non-dioxin-like polychlorinated biphenyls), as part of the organic chlorine contaminants, have been suspected as playing a role in the etiopathogenesis of endometriosis. Several population-based studies have proposed that exposure to PCBs may increase the risk of developing endometriosis, while some epidemiological studies have failed to find any association between PCBs and endometriosis. The purpose of this review is to discuss the potential pathophysiological relationship between endometriosis and PCBs with a focus on both dioxin-like polychlorinated biphenyls and non-dioxin-like polychlorinated biphenyls.

Long-Time Exposure to Violent Video Games Does Not Show Desensitization on Empathy for Pain: An fMRI Study.

As a typical form of empathy, empathy for pain refers to the perception and appraisal of others' pain, as well as the corresponding affective responses. Numerous studies investigated the factors affecting the empathy for pain, in which the exposure to violent video games (VVGs) could change players' empathic responses to painful situations. However, it remains unclear whether exposure to VVG influences the empathy for pain. In the present study, in terms of the exposure experience to VVG, two groups of participants (18 in VVG group, VG; 17 in non-VVG group, NG) were screened from nearly 200 video game experience questionnaires. And then, the functional magnetic resonance imaging data were recorded when they were viewing painful and non-painful stimuli. The results showed that the perception of others' pain were not significantly different in brain regions between groups, from which we could infer that the desensitization effect of VVGs was overrated.

Cytotoxicity of gold nanoparticles with different structures and surface-anchored chiral polymers.

Nanoparticles (NPs) can have profound effects on cell biology. However, the potential adverse effects of gold nanoparticles (AuNPs) with different surface chirality and structures have not been elucidated. In this study, monolayers of poly(acryloyl-l(d)-valine (l(d)-PAV) chiral molecules were anchored on the surfaces of gold nanocubes (AuNCs) and nanooctahedras (AuNOs), respectively. The l-PAV-AuNCs and d-PAV-AuNCs, or the l-PAV-AuNOs and d-PAV-AuNOs, had identical physicochemical properties in terms of size, morphology and ligand density except of the reverse molecular chirality on the particle surfaces, respectively. The l-PAV capped AuNCs and AuNOs exhibited larger cytotoxicity to A549 cells than the D-PAV coated ones, and the PAV-AuNOs had larger cytotoxicity than PAV-AuNCs when being capped with the same type of enantiomers, respectively. The cytotoxicity was positively correlated with the cellular uptake amount, and thereby the production of intracellular reactive oxygen species (ROS). STATEMENT OF SIGNIFICANCE: • Gold nanoparticles with different structure and surface chirality are fabricated. • The structure and surface chirality at the nanoscale can influence cytotoxicity and genotoxicity. • A new perspective on designing nanoparticles for drug delivery, bioimaging and diagnosis.

Congenital renal arteriovenous fistula during the first trimester diagnosed with ultrasonography.

A case of congenital renal arteriovenous fistula (AVF) complicating pregnancy with gross hematuria was managed successfully by superselective embolization with metallic coils. The patient was in the first trimester of her pregnancy at 12 weeks of gestation. The AVF was detected by color Doppler sonography and confirmed by renal arteriography. Because of its easy accessibility and absence of irradiation, ultrasound is the first choice for pregnant patients. Color Doppler ultrasound is effective in diagnosing AVF, and it is also helpful in the long-term followup after treatment. The cirsoid-type renal congenital arteriovenous fistula has a characteristic sonographic appearance with a cluster of tubular anechoic structures in the kidney, which produce continuous turbulent high-velocity flow signals and a burr-like boundary flow spectrum. When the sonographic features are present, the diagnosis of renal AVF should be made, after which renal arteriography can be performed to confirm it. Selective embolization provided a safe and effective treatment with minimal damage to the parenchyma and without compromising renal function.

Surface-anchored poly(acryloyl-L(D)-valine) with enhanced chirality-selective effect on cellular uptake of gold nanoparticles.

Chirality is one of the ubiquitous phenomena in biological systems. The left handed (L-) amino acids and right handed (D-) sugars are normally found in proteins, and in RNAs and DNAs, respectively. The effect of chiral surfaces at the nanoscale on cellular uptake has, however, not been explored. This study reveals for the first time the molecular chirality on gold nanoparticles (AuNPs) functions as a direct regulator for cellular uptake. Monolayers of 2-mercaptoacetyl-L(D)-valine (L(D)-MAV) and poly(acryloyl-L(D)-valine (L(D)-PAV) chiral molecules were formed on AuNPs surface, respectively. The internalized amount of PAV-AuNPs was several times larger than that of MAV-AuNPs by A549 and HepG2 cells, regardless of the chirality difference. However, the D-PAV-AuNPs were internalized with significantly larger amount than the L-PAV-AuNPs. This chirality-dependent uptake effect is likely attributed to the preferable interaction between the L-phospholipid-based cell membrane and the D-enantiomers.

Influence of Albumin Configuration by the Chiral Polymer-Grafted Gold Nanoparticles.

The interaction between nanoparticles (NPs) and proteins is a topic of high relevance for the medical application of NPs. This study reveals the molecular chirality on NP surfaces as an indirect regulator of the interaction between proteins and NPs. Poly(N-acryloyl-valine) (PAV) polymers with d- and l-configurations were conjugated onto gold NPs with a size of 5 nm to obtain the l-PAV-AuNPs and d-PAV-AuNPs, respectively. They had same chemical composition and surface grafting density but different surface chirality. The isothermal titration calorimetry results showed that adsorption of bovine serum albumin onto the l-PAV-AuNPs and d-PAV-AuNPs was primarily driven by electrostatic interaction. Dynamic light scattering, circular dichroism spectroscopy, fluorescence quenching, and isothermal titration calorimetry characterizations revealed that bovine serum albumin molecules adopted both side-on and end-on configurations on the d-PAV-AuNPs, whereas only end-on configuration on the l-PAV-AuNPs.