Stretchable, Self-Healing, and Bioactive Hydrogel with High-Functionality N,N-bis(acryloyl)cystamine Dynamically Bonded Ag@polydopamine Crosslinkers for Wearable Sensors.

Hydrogels present attractive opportunities as flexible sensors due to their soft nature and tunable physicochemical properties. Despite significant advances, practical application of hydrogel-based sensor is limited by the lack of general routes to fabricate materials with combination of mechanical, conductive, and biological properties. Here, a multi-functional hydrogel sensor is reported by in situ polymerizing of acrylamide (AM) with N,N'-bis(acryloyl)cystamine (BA) dynamic crosslinked silver-modified polydopamine (PDA) nanoparticles, namely PAM/BA-Ag@PDA. Compared with traditional polyacrylamide (PAM) hydrogel, the BA-Ag@PDA nanoparticles provide both high-functionality crosslinks and multiple interactions within PAM networks, thereby endowing the optimized PAM/BA-Ag@PDA hydrogel with significantly enhanced tensile/compressive strength (349.80 kPa at 383.57% tensile strain, 263.08 kPa at 90% compressive strain), lower hysteresis (5.2%), improved conductivity (2.51 S m-1) and excellent near-infrared (NIR) light-triggered self-healing ability. As a strain sensor, the PAM/BA-Ag@PDA hydrogel shows a good sensitivity (gauge factor of 1.86), rapid response time (138 ms), and high stability. Owing to abundant reactive groups in PDA, the PAM/BA-Ag@PDA hydrogel exhibits inherent tissue adhesiveness and antioxidant, along with a synergistic antibacterial effect by PDA and Ag. Toward practical applications, the PAM/BA-Ag@PDA hydrogel can conformally adhere to skin and monitor subtle activities and large-scale movements with excellent reliability, demonstrating its promising applications as wearable sensors for healthcare.

Artificial sweeteners and risk of incident cardiovascular disease and mortality: evidence from UK Biobank.

BACKGROUND: Artificial sweeteners are widely popular worldwide as substitutes for sugar or caloric sweeteners, but there are still several important unknowns and controversies regarding their associations with cardiovascular disease (CVD). We aimed to extensively assess the association and subgroup variability between artificial sweeteners and CVD and CVD mortality in the UK Biobank cohort, and further investigate the modification effects of genetic susceptibility and the mediation role of type 2 diabetes mellitus (T2DM). METHODS: This study included 133,285 participants in the UK Biobank who were free of CVD and diabetes at recruitment. Artificial sweetener intake was obtained from repeated 24-hour diet recalls. Cox proportional hazard models were used to estimate HRs. Genetic predisposition was estimated using the polygenic risk score (PRS). Furthermore, time-dependent mediation was performed. RESULTS: In our study, artificial sweetener intake (each teaspoon increase) was significantly associated with an increased risk of incident overall CVD (HR1.012, 95%CI: 1.008,1.017), coronary artery disease (CAD) (HR: 1.018, 95%CI: 1.001,1.035), peripheral arterial disease (PAD) (HR: 1.035, 95%CI: 1.010,1.061), and marginally significantly associated with heart failure (HF) risk (HR: 1.018, 95%CI: 0.999,1.038). In stratified analyses, non-whites were at greater risk of incident overall CVD from artificial sweetener. People with no obesity (BMI < 30 kg/m2) also tended to be at greater risk of incident CVD from artificial sweetener, although the obesity interaction is not significant. Meanwhile, the CVD risk associated with artificial sweeteners is independent of genetic susceptibility, and no significant interaction exists between genetic susceptibility and artificial sweeteners in terms of either additive or multiplicative effects. Furthermore, our study revealed that the relationship between artificial sweetener intake and overall CVD is significantly mediated, in large part, by prior T2DM (proportion of indirect effect: 70.0%). In specific CVD subtypes (CAD, PAD, and HF), the proportion of indirect effects ranges from 68.2 to 79.9%. CONCLUSIONS: Our findings suggest significant or marginally significant associations between artificial sweeteners and CVD and its subtypes (CAD, PAD, and HF). The associations are independent of genetic predisposition and are mediated primarily by T2DM. Therefore, the large-scale application of artificial sweeteners should be prudent, and the responses of individuals with different characteristics to artificial sweeteners should be better characterized to guide consumers' artificial sweeteners consumption behavior.

Flexible Pressure Sensors in Human-Machine Interface Applications.

Flexible sensors are highly flexible, malleable, and capable of adapting todifferent shapes, surfaces, and environments, which opens a wide range ofpotential applications in the field of human-machine interface (HMI). Inparticular, flexible pressure sensors as a crucial member of the flexiblesensor family, are widely used in wearable devices, health monitoringinstruments, robots and other fields because they can achieve accuratemeasurement and convert the pressure into electrical signals. The mostintuitive feeling that flexible sensors bring to people is the change ofhuman-machine interface interaction, from the previous rigid interaction suchas keyboard and mouse to flexible interaction such as smart gloves, more inline with people's natural control habits. Many advanced flexible pressuresensors have emerged through extensive research and development, and to adaptto various fields of application. Researchers have been seeking to enhanceperformance of flexible pressure sensors through improving materials, sensingmechanisms, fabrication methods, and microstructures. This paper reviews the flexible pressure sensors in HMI in recent years, mainlyincluding the following aspects: current cutting-edge flexible pressuresensors; sensing mechanisms, substrate materials and active materials; sensorfabrication, performances, and their optimization methods; the flexiblepressure sensors for various HMI applications and their prospects.

The rising death burden of atrial fibrillation and flutter in low-income regions and younger populations.

Objective: The aim of the study was to depict the global death burden of atrial fibrillation and/or flutter (AFF) between 1990 and 2019 and predict this burden in the next decade. Methods: We retrieved annual death data on cases and rates of AFF between 1990 and 2019 from the Global Burden of Disease (GBD) Study 2019 and projected the trends for 2020-2029 by developing the Bayesian age-period-cohort model. Results: The global number of deaths from AFF increased from 117,038.00 in 1990 to 315,336.80 in 2019. This number is projected to reach 404,593.40 by 2029. The age-standardized mortality rates (ASMRs) of AFF have increased significantly in low- to middle-sociodemographic index (SDI) regions, which will surpass that in high SDI regions and reach above 4.60 per 100,000 by 2029. Globally, women have a higher ASMR than men, which is largely attributed to disproportionately higher mortality in women than men in lower SDI regions. Notably, AFF-related premature mortality continues to worsen worldwide. A pandemic of high systolic blood pressure and high body mass index (BMI) largely contributes to AFF-associated death. In particular, low- to middle-SDI regions and younger populations are increasingly affected by the rapidly growing current and future risk of high BMI. Conclusion: The global death burden of AFF in low-income countries and younger generations have not been sufficiently controlled in the past and will continue growing in the future, which is largely attributed to metabolic risks, particularly for high BMI. There is an urgent need to implement effective measures to control AFF-related mortality.

DEC1 represses cardiomyocyte hypertrophy by recruiting PRP19 as an E3 ligase to promote ubiquitination-proteasome-mediated degradation of GATA4.

Although the pro-hypertrophic role of GATA binding protein 4 (GATA4) during cardiac hypertrophy has been well established, the negative regulatory mechanism to counteract its hyperactivation remains elusive. We hypothesized that the hyperactivation of GATA4 could be a result of loss of interaction between GATA4 with specific suppressors. Using high throughput mass spectrometry technology, we carried out a proteomic screen for endogenous suppressor of GATA4, which disassociated with GATA4 during the hypertrophic response in a cultured cardiac myoblast cell line (H9C2 cells). We identified differentiated embryo chondrocyte 1 (DEC1) negatively regulated the function of GATA4 through physical interaction and negatively regulated cardiac hypertrophy both in vivo and in vitro. Particularly, DEC1 promoted the ubiquitination and proteasome-mediated degradation of GATA4, but did not function as an E3 ligase. Again, using mass spectrometry technology, we systematically identified pre-mRNA processing factor 19 (PRP19) as a newfound E3 ligase, which promoted the K6-linked ubiquitination of GATA4 at its lysine 256. Functional experiments performed in cultured neonatal rat ventricular myocytes and H9C2 cells demonstrated that both DEC1 and PRP19 negatively regulated agonist-induced cardiomyocyte hypertrophic responses. Furthermore, rescue experiments performed in these cells revealed that DEC1 and PRP19 suppressed cardiomyocyte hypertrophy by inhibiting the function of GATA4. Our study thus defined the novel DEC1-PRP19-GATA4 axis to be a previously unknown mechanism in regulating cardiomyocyte hypertrophy. Although GATA4 is indispensable for normal cardiac function, harnessing DEC1- or PRP19-mediated negative regulation to counteract the hyperactivation of GATA4 might serve as a novel therapeutic strategy for pathological cardiac hypertrophy.

High Remnant Cholesterol Level Potentiates the Development of Hypertension.

Background: Emerging evidence suggests an association between remnant cholesterol (RC) and vascular damage and hypertension. However, this association has not been explored in a large-scale population in China, and a temporal relationship between RC and hypertension also needs to be investigated. Methods: We conducted a retrospective cross-sectional study in 2,199,366 individuals and a longitudinal study in 24,252 individuals with repeated measurements of lipid profile and blood pressure in at least a 3-year follow-up. The logistic model was used to explore the association between lipid components and hypertension in the cross-sectional analysis. The Cox model was used to analyze the association between high RC (HRC) at baseline and the subsequent incidence of hypertension or the association between hypertension at baseline and incidence of HRC. The cross-lagged panel model was applied to analyze the temporal relationship between RC and hypertension. Results: RC level as a continuous variable had the highest correlation with hypertension among lipid profiles, including RC, low-density lipoprotein cholesterol, total cholesterol, non-high-density lipoprotein cholesterol, and triglycerides, with an odds ratio of 1.59 (95% confidence interval: 1.58-1.59). In the longitudinal cohort, HRC at baseline was associated with incident hypertension. We further explored the temporal relationship between RC and hypertension using the cross-lagged analysis, and the results showed that RC increase preceded the development of hypertension, rather than vice versa. Conclusions: RC had an unexpected high correlation with the prevalence and incidence of hypertension. Moreover, RC increase might precede the development of hypertension, suggesting the potential role of RC in the development of hypertension.

Safety and efficacy of angiotensin-converting enzyme inhibitors in aortic stenosis: A protocol for systematic review and meta-analysis.

BACKGROUND: Although there are many studies showing potential benefit in aortic stenosis (AS) patients taking angiotensin-converting enzyme inhibitors (ACEI), but these studies are subject to significant selection and other biases, making the results challenging to interpret. Furthermore, the evidence on the use of ACEI in AS patients has not been reviewed systematically; we thus conducted this protocol assess the clinical effectiveness and safety of ACEI for patients with AS. METHODS: The following search terms will be used in PUBMED, Scopus, EMBASE, and Cochrane Library databases on May, 2021, as the search algorithm: (angiotensin-converting enzyme inhibitors) OR (ACEI) AND (aortic stenosis) OR (AS). Two searchers will independently draft and carry out the search strategy, and the third member will further complete it. The studies on cohort study focusing on assessing the efficacy of ACEI on AS patients will be included in our meta-analysis. At least one of the following outcomes should have been measured: left ventricular mass, exercise tolerance, B-type natriuretic peptide, adverse event, functional outcomes, and aortic valve area. All outcomes are pooled on random-effect model. A P value of <.05 is considered to be statistically significant. RESULTS: The results of this research will be delivered in a peer-reviewed journal. CONCLUSION: Depending on the previous studies, we assumed that ACEI could possibly improve the clinical symptoms and outcomes of symptomatic AS. SYSTEMATIC REVIEW REGISTRATION NUMBER: 10.17605/OSF.IO/G9KPT.

[Influence of artificial insemination with donor sperm on the pregnancy outcomes and safety of the offspring].

OBJECTIVE: To investigate the factors influencing the pregnancy outcomes of artificial insemination with donor sperm (AID), improve the pregnancy rate, and evaluate the safety of the offspring. METHODS: We retrospectively analyzed 7,761 cycles of AID for 5,109 infertile couples performed between July 1, 2005 and June 30, 2013 in the Center of Reproductive Medicine of Shenyang No 204 Hospital, the outcomes of pregnancy, and the incidence of birth defects. RESULTS: Totally, 2 252 clinical pregnancies were achieved by AID, in which the pregnancy rate per cycle was 29. 02% and the cumulative pregnancy rate was 44. 08%. The clinical pregnancy rate was remarkably higher in the females of ≤ 35 years than in those of > 35 years old (30.31% vs 20.18%, P < 0.01), in the women with < 5-year infertility than in those with > 5-year infertility (30.83% vs 28.16%, P < 0.01), and in the patients of the ovarian stimulation group than in those of the natural cycle group (33.22% vs 28.68%, P < 0.01) The clinical pregnancy rate was the highest in the first treatment cycle (29.87%), with statistically significant difference from the fourth cycle (23.61%) (P < 0.05), but not between the other cycles (P > 0.05). There were 28 cases of birth defects in the offspring (1.40%), including 6 cases (21.43%) involving the cardiovascular system, 4 (14.29%) involving the musculoskeletal system, 3 (10.71%) involving the urogenital system, 3 (10.71%) involving the central nervous system, 2 cases (7.14%) of cleft lip and palate, 2 (7.14%) involving the respiratory system, 2 (7.14%) involving the gastrointestinal digestive system, and other anomalies. CONCLUSION: Female age, infertility duration, and ovarian stimulation treatment are important factors influencing the clinical pregnancy rate of AID. Artificial insemination with cryopreserved donor sperm does not increase the incidence of birth defects, which is considered as a relatively safe technique of assisted reproduction.

Comparison of the efficiency of Banna miniature inbred pig somatic cell nuclear transfer among different donor cells.

Somatic cell nuclear transfer (SCNT) is an important method of breeding quality varieties, expanding groups, and preserving endangered species. However, the viability of SCNT embryos is poor, and the cloned rate of animal production is low in pig. This study aims to investigate the gene function and establish a disease model of Banna miniature inbred pig. SCNT with donor cells derived from fetal, newborn, and adult fibroblasts was performed, and the cloning efficiencies among the donor cells were compared. The results showed that the cleavage and blastocyst formation rates did not significantly differ between the reconstructed embryos derived from the fetal (74.3% and 27.4%) and newborn (76.4% and 21.8%) fibroblasts of the Banna miniature inbred pig (P>0.05). However, both fetal and newborn fibroblast groups showed significantly higher rates than the adult fibroblast group (61.9% and 13.0%; P<0.05). The pregnancy rates of the recipients in the fetal and newborn fibroblast groups (60% and 80%, respectively) were higher than those in the adult fibroblast group. Eight, three, and one cloned piglet were obtained from reconstructed embryos of the fetal, newborn, and adult fibroblasts, respectively. Microsatellite analyses results indicated that the genotypes of all cloning piglets were identical to their donor cells and that the genetic homozygosity of the Banna miniature inbred pig was higher than those of the recipients. Therefore, the offspring was successfully cloned using the fetal, newborn, and adult fibroblasts of Banna miniature inbred pig as donor cells.