Enhanced quality of hESC-derived melanocytes through modified concentration of endothelin-1.

The study investigated the effectiveness of EDN1 and EDN3 cytokines in the differentiation of melanocytes from hESCs. The findings showed that 100 nM EDN1 was more effective in promoting hESC to CD117+/TYR+ melanoblasts compared to 100 nM EDN3. Additionally, maintaining melanoblasts is beneficial for preserving the ability to proliferate. The study found that 10 nM EDN1 helped maintain the proliferation of melanoblasts without over maturing them into melanocytes in the late stage of differentiation. Thus, using 100 nM EDN1 in the initial stage and 10 nM EDN1 in the late stage proved to be an efficient and cost-effective method for obtaining hESC-derived melanocytes. The preliminary results suggest that EDN1 promotes melanoblast formation during the initial differentiation stage through its binding to both the EDNRB receptor and EDNRA receptor. This study provides a valuable tool for studying the development of human melanocytes and modelling the biology of disease.

Longitudinal association of remnant cholesterol with joint arteriosclerosis and atherosclerosis progression beyond LDL cholesterol.

BACKGROUND: Arteriosclerosis and atherosclerosis are closely related with cardiovascular disease (CVD) risk. Remnant cholesterol (RC) could predict CVD. However, its effect on joint arteriosclerosis and atherosclerosis progression remains unclear. This study aims to evaluate the association of RC with joint arteriosclerosis and atherosclerosis progression trajectories in the general population. METHODS: This study collected data across five biennial surveys of the Beijing Health Management Cohort from 2010 to 2019. Multi-trajectory model was used to determine the joint arteriosclerosis and atherosclerosis progression patterns by brachial-ankle pulse wave velocity (baPWV) and ankle brachial index (ABI). We also performed discordance analyses for RC vs. low density lipoprotein cholesterol (LDL-C) using ordinal logistics model. RESULTS: A total of 3186 participants were included, with three clusters following distinct arteriosclerosis and atherosclerosis progression patterns identified using a multi-trajectory model. In the multivariable-adjusted ordinal logistics analyses, RC was significantly associated with baPWV and ABI progression (OR: 1.20; 95% CI: 1.13-1.28, per 10 mg/dL). For the discordance analyses, the discordant low RC group was associated with decreased risk compared to the concordant group (OR: 0.73; 95% CI: 0.60-0.89). People with a high RC level were at an increased risk of joint arteriosclerosis and atherosclerosis progression, even with optimal LDL-C. CONCLUSIONS: RC is independently associated with joint arteriosclerosis and atherosclerosis progression beyond LDL-C. RC could be an earlier risk factor than LDL-C of arteriosclerosis and atherosclerosis in the general population.

Divergent Reaction of Indoline-derived Azadienes with α-Bromohydroxamates: Synthesis of Spiro-indolinepyrrolidinones and Indoline-fused Diazepinones.

A divergent reaction of indoline-derived azadienes with α-bromohydroxamates for the selective synthesis of spiro-indolinepyrrolidinones and indoline-fused diazepinones was disclosed. This reaction sequence involved an initial formation of five-membered spirocyclic products followed by an intramolecular ring-opening and ring expansion to produce seven-membered diazepinones. We demonstrated that controlling the reaction time could modulate the reaction pathway for formation of different molecular frameworks for the same set of substrates. Based on the experimental results, the reaction mechanism was also discussed and proposed to explain the phenomena observed in the process.

Intraindividual difference in estimated GFR by creatinine and cystatin C, cognitive trajectories and motoric cognitive risk syndrome.

BACKGROUND: Intraindividual differences between estimated glomerular filtration rate (eGFR) based on cystatin C (eGFRcys) and creatinine (eGFRcr) can convey important clinical information regarding the health status. However, the clinical implications of these differences (eGFRdiff) for risk of cognitive decline and motoric cognitive risk syndrome (MCR) remains unclear. We aimed to investigate the longitudinal associations of eGFRdiff with cognitive trajectories and incident MCR. METHODS: Based on the China Health and Retirement Longitudinal Study, we identified two study sub-cohorts: one for cognitive trajectory follow-up (6423 participants; years:2011-2018) and another for incident MCR follow-up (2477 participants; years:2011-2015). The eGFRdiff was defined as eGFRcys minus eGFRcr. Adjusted ordinal and binary logistics regression models were separately used to assess the associations of eGFRdiff with cognitive trajectories and incident MCR. We also performed discordance analyses for eGFRdiff vs eGFRcys, eGFRcr or eGFR based on both creatinine and cystatin C (eGFRcys-cr). RESULTS: In the first sub-cohort, four distinct 7-year cognitive trajectories were identified. Each 1-SD higher eGFRdiff (value for eGFRcys minus eGFRcr) was associated with a lower risk of poorer cognitive trajectories (OR: 0.909, 95% CI: 0.877-0.942). In the second sub-cohort, 121 participants developed incident MCR after a 4-year follow-up. Each 1-SD higher eGFRdiff (value for eGFRcys minus eGFRcr) was linked with a 25.3% (95%CI: 16.6%-33.2%) decreased risk for MCR. The above associations persisted in individuals with normal kidney function. Additionally, the risk for cognitive decline and incident MCR was more strongly associated with eGFRcys than eGFRcr and eGFRcys-cr. For the discordance analyses, 'discordantly high eGFRdiff/low eGFR' group, but not 'discordantly low eGFRdiff/high eGFR', exhibited a significantly lower risk of poorer cognitive trajectories and MCR compared to the concordant group. CONCLUSIONS: A large negative difference between eGFRcys and eGFRcr (eGFRcys lower than eGFRcr) was associated with higher risk of cognitive decline and incident MCR. The eGFRdiff could capture additional valuable risk information beyond eGFRcys, eGFRcr, and eGFRcys-cr.

Associations of time-weighted individual exposure to ambient particulate matter with carotid atherosclerosis in Beijing, China.

BACKGROUND: Time-location information (time spent on commuting, indoors and outdoors around residential and work places and physical activity) and infiltrated outdoor pollution was less considered estimating individual exposure to ambient air pollution. Studies investigating the association between individual exposure to particulate matter (PM) with aerodynamic diameter < 10 µm (PM10) and < 2.5 µm (PM2.5) and carotid atherosclerosis presented inconsistent results. Moreover, combined effect of pollutants on carotid atherosclerosis was not fully explored. We aimed to investigate the association between long-term individual time-weighted average exposure to PM2.5 and PM10 and the risk of carotid atherosclerosis, and further explore the overall effect of co-exposure to pollutants on carotid atherosclerosis. METHODS: The study population included 3069 participants derived from the Beijing Health Management Cohort (BHMC) study. Daily concentration of ambient air pollutants was estimated by land-use regression model at both residential and work addresses, and one- and two-year time-weighted average individual exposure was calculated by further considering personal activity pattern and infiltration of ambient air pollution indoors. We explored the association of PM2.5 and PM10 with carotid atherosclerosis and pooled the overall effect of co-exposure to ambient air pollutants by quantile g-computation. RESULTS: A significant association between time-weighted average exposure to PM2.5 and PM10 and carotid atherosclerosis was observed. Per interquartile range increase in two-year exposure to PM2.5 (Hazard ratio (HR): 1.322, 95% confidence interval (CI): 1.219-1.434) and PM10 (HR:1.213, 95% CI: 1.116-1.319) showed the strongest association with carotid atherosclerosis, respectively. Individuals in higher quartiles of pollutants were at higher risk for carotid atherosclerosis compared with those in the lowest quartile group. Concentration response functions documented the nearly linear and nonlinear relationship and interpreted the upward trends of the risk for carotid atherosclerosis with increasing level of pollutant concentrations. Moreover, effect estimates for the mixture of pollutants and carotid atherosclerosis were larger than any of the individual pollutants (HR (95% CI) was 1.510 (1.338-1.704) and 1.613 (1.428-1.822) per quartile increase for one-year and two-year time-weighted average exposure, respectively). CONCLUSIONS: Individual time-weighted average exposure to PM2.5 and PM10 was associated with carotid atherosclerosis. Co-exposure to ambient air pollution was also positively associated with carotid atherosclerosis.

Association of visceral adiposity index with incident nephropathy and retinopathy: a cohort study in the diabetic population.

BACKGROUND: The association between visceral adiposity index (VAI) and diabetic complications has been reported in cross-sectional studies, while the effect of VAI on complication development remains unclear. This study aims to evaluate the longitudinal association of VAI and Chinese VAI (CVAI) with the incidence of diabetic nephropathy and retinopathy using a Chinese cohort. METHODS: A total of 8 948 participants with type 2 diabetes from Beijing Health Management Cohort were enrolled during 2013-2014, and followed until December 31, 2019. Nephropathy was confirmed by urine albumin/creatinine ratio and estimated glomerular filtration rate; retinopathy was diagnosed using fundus photograph. RESULTS: The mean (SD) age was 53.35 (14.66) years, and 6 154 (68.8%) were men. During a median follow-up of 4.82 years, 467 participants developed nephropathy and 90 participants developed retinopathy. One-SD increase in VAI and CVAI levels were significantly associated with an increased risk of nephropathy, and the adjusted hazard ratios (HR) were 1.127 (95% CI 1.050-1.210) and 1.165 (95% CI 1.003-1.353), respectively. On contrary, VAI and CVAI level were not associated with retinopathy after adjusting confounding factors. CONCLUSION: VAI and CVAI are independently associated with the development of nephropathy, but not retinopathy in Chinese adults with diabetes.

Human embryonic stem cell-derived melanocytes exhibit limited immunogenicity.

Although surgical interventions have become optional for refractory vitiligo, grafting related injuries is inevitable. Embryonic stem cell (ESC) derivatives can be used in transplantation to address this issue, but the immune rejection due to allogeneic transplantation is of great concern. To investigate the immunogenicity of ESC derived melanocytes (ES-MC), we established a co-culture system of ES-MC and allogeneic PBMC. The results showed that ES-MC were similar to human primary melanocytes, with low expression of immune related molecules, and limited capability of stimulating allogeneic lymphocytes in vitro. Taken together, our findings confirm that ES-MC are of limited immunogenicity, providing new insights into the application of ES-MC in the regenerative medicine such as treating vitiligo.

Association of TyG index and TG/HDL-C ratio with arterial stiffness progression in a non-normotensive population.

BACKGROUND: Cross-sectional studies have reported that insulin resistance (IR) is associated with arterial stiffness. However, the relationship between IR and arterial stiffness progression remains unclear. This study aims to evaluate the association of triglyceride glucose (TyG) index and triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio with arterial stiffness progression in a non-normotensive population. METHODS: A total of 1895 prehypertensive (systolic pressure 120-139 mmHg or diastolic pressure 80-90 mmHg) or hypertensive (systolic pressure ≥ 140 mmHg or diastolic pressure ≥ 90 mmHg or using antihypertensive medication) participants were enrolled in 2013 and 2014, and followed until December 31, 2019. Arterial stiffness progression was measured by brachial-ankle pulse wave velocity (baPWV) change (absolute difference between baseline and last follow-up), baPWV change rate (change divided by following years), and baPWV slope (regression slope between examination year and baPWV). RESULTS: During a median follow-up of 4.71 years, we observed an increasing trend of baPWV in the population. There were linear and positive associations of the TyG index and TG/HDL-C ratio with the three baPWV parameters. The difference (95% CI) in baPWV change (cm/s) comparing participants in the highest quartile versus the lowest of TyG index and TG/HDL-C ratio were 129.5 (58.7-200.0) and 133.4 (52.0-214.9), respectively. Similarly, the evaluated baPWV change rates (cm/s/year) were 37.6 (15.3-60.0) and 43.5 (17.8-69.2), while the slopes of baPWV were 30.6 (9.3-51.8) and 33.5 (9.0-58.0). The observed association was stronger in the hypertensive population. CONCLUSION: Our study indicates that the TyG index and TG/HDL-C ratio are significantly associated with arterial stiffness progression in hypertensive population, not in prehypertensive population.

Triglyceride glucose index and carotid atherosclerosis incidence in the Chinese population: A prospective cohort study.

BACKGROUND AND AIMS: The association of the triglyceride glucose (TyG) index with carotid atherosclerosis has not been reported in longitudinal studies. The present study aimed to investigate whether the TyG index increases the risk of carotid atherosclerosis incidence. METHODS AND RESULTS: This study included data from the Beijing Health Management Cohort (BHMC; n = 6955) and the Beijing Physical Examination Cohort (BPEC; n = 8473). Participants without a history of carotid atherosclerosis who underwent health examination in 2011 or 2012 were annually followed until 2019. The TyG index was denoted as ln [triglycerides (mmol/L)∗fasting glucose (mmol/L)/2]. During a median follow-up of 5.02 years and 5.36 years, 1441 individuals in the BHMC group and 2181 individuals in the BPEC group developed carotid plaque, respectively. The adjusted hazard ratios (HRs) of the continuous TyG index were 1.253 (95% CI, 1.044 to 1.505) and 1.252 (95% CI, 1.091 to 1.437) for the BHMC and BPEC groups, respectively. Individuals in the highest quartile of the TyG index were associated with an increased risk of carotid plaque compared with those in the lowest quartile (BHMC: HR, 1.366; 95% CI, 1.101 to 1.695, P for trend = 0.010; BPEC: HR, 1.379; 95% CI, 1.196 to 1.591, P for trend = 0.013). CONCLUSION: These findings suggested that a higher TyG index increases the risk of carotid atherosclerosis incidence in the general population.

A constructed wetland system with aquatic macrophytes for cleaning contaminated runoff/storm water from urban area in Florida.

A community of aquatic macrophytes has an important role in reducing nutrient load and organic and inorganic contaminants in storm/runoff water. However, minimal information is available regarding the efficiency of constructed wetlands for cleaning runoff water from urban areas, especially in the tropical and subtropical regions. This study investigated the effectiveness of constructed wetland integrated with aquatic macrophytes for removal of chemical and microbial contaminants in the storm/runoff water from the urban areas. Water samples were monthly collected in the constructed wetland from the inlet of storm/runoff water, middle and outlet of discharge, and analyzed for physical and chemical properties, concentrations of nutrients, metals, and fecal coliform (FC) during the period of November, 2016 to April, 2018 in St. Lucie county, Florida, USA. The dominant plant species in the constructed wetland included cattail (Typha latifolia), waterthyme (Hydrilla verticillata) and water hyacinth (Eichhornia crassipes), and periphyton filamentous algae (Spirogyra). The improvement of pH and electrical conductivity (EC) was not obvious, but the concentration of total suspended solids was significantly reduced. This system was effective in the removal of fecal coliform (by 68%) and particulate phosphorus (P, 72%), followed by total P (42%) and N (35%). Concentrations of metallic pollutants including cadmium (Cd), lead (Pb), chromium (Cr), and copper (Cu) were mostly below the detection limit (<1 ppb) except for zinc (Zn), of which concentration was reduced by 23%. The removal of FC was consistently effective all the year round, whereas the removal of total N, P and particulate-P was effective in spring and summer, and less in autumn and winter. These results indicate that constructed wetland with a natural aquatic plant community can effectively reduce the loads of nutrients, metals, and fecal coliforms in water column. Regular harvest of aquatic macrophytes communities and collecting litters may further improve the system efficiency for cleaning storm water from urban areas.

Biomass decay rate and influencing factors of four submerged aquatic vegetation in Everglades wetland.

Submerged aquatic vegetation (SAV) enhances assimilation efficiency of nutrients in wetlands, and improves the water quality, but may serve as secondary sources when their litter residues are decomposed. A laboratory incubation was conducted to investigate the biomass decay rate of four common SAV species: Hydrilla (Hydrilla verticillata), Naiad (Najas guadalupensis), Potamogeton (P. illinoensis), and Chara (Chara spp). Plant biomass samples were collected from the stormwater treatment areas in south Florida, USA and incubated in water at 40 °C for 126 days. At the end of incubation, the mixtures were passed through a 1 m sieve, and the plant debris above the screen were rinsed, oven-dried, and weighed. Biomass (dry matter) was measured and the decay rate was calculated, and total concentration of carbon (C), nitrogen (N), phosphorus (P) and other elements (K, Na, Ca, Mg, Al, Fe, and Mn) in the SAV plants were determined. Subsamples (5 mL) of the suspension (representing floc solution) were used for bacteria and fungi colony counting. The relationships between the decay rate and nutrient features or chemical components were analyzed. The results showed that Hydrilla had the highest decay rate (0.007930 d-1), and Chara had the lowest (0.002798 d-1). Concentrations of N, P, C and cations (K, Na, and Mn), and the ratio (K + Na)/(Ca + Al) in the SAVs had positive correlations with the biomass decay rate, whereas concentrations of Ca and Al, and the ratios of C/N and C/P in the plants were negatively correlated with the decay rate. However, the effect of microorganisms in the biomass decay rate of SAVs was not significant. These results suggest that high C concentration and more Ca and Al in the plant tissues can retard SAV biomass decomposition.

A Plastic Optical Fiber Sensing System for Bridge Deflection Measurement.

Deflection is one of the key parameters that reflects the state of a bridge. However, deflection measurement is difficult for a bridge that is under operation. Most existing sensors and measuring techniques often do not meet the requirements for health monitoring for various types of bridges. Therefore, based on changes of optical fiber intensity, a novel sensing system using connected pipes to measure bridge deflection in different positions is proposed in this paper. As an absolute reference, the liquid level position along the structure is adopted for the deflection measurement, and an additional external reference to the ground is not needed in this system. The proposed system consists of three parts: connected pipes to connect the measurement points along the structure, liquid to fill in the connected pipes, and the sensing element to detect the change of level. A plastic optical fiber sensor based on the intensity change is used as the sensing element of the developed system. Then, a set of experimental tests are conducted for performance evaluation purposes. Results show that this system has an accurate linear response and high reliability under various environmental conditions. The deflection of the test beam measured by the sensor agrees with linear variable differential transformer (LVDT) within an error margin of 2.1%. The proposed system shows great potential applicability for future health monitoring of long-span bridges.

A Flexible Temperature Sensor Based on Reduced Graphene Oxide for Robot Skin Used in Internet of Things.

Flexible electronics, which can be distributed on any surface we need, are highly demanded in the development of Internet of Things (IoT), robot technology and electronic skins. Temperature is a fundamental physical parameter, and it is an important indicator in many applications. Therefore, a flexible temperature sensor is required. Here, we report a simple method to fabricate three lightweight, low-cost and flexible temperature sensors, whose sensitive materials are reduced graphene oxide (r-GO), single-walled carbon nanotubes (SWCNTs) and multi-wall carbon nanotubes (MWCNTs). By comparing linearity, sensitive and repeatability, we found that the r-GO temperature sensor had the most balanced performance. Furthermore, the r-GO temperature sensor showed good mechanical properties and it could be bent in different angles with negligible resistance change. In addition, the performance of the r-GO temperature sensor remained stable under different kinds of pressure and was unaffected by surrounding environments, like humidity or other gases, because of the insulating layer on its sensitive layer. The easy-fabricated process and economy, together with the remarkable performance of the r-GO temperature sensor, suggest that it is suitable for use as a robot skin or used in the environment of IoT.

Reconfigurable terahertz metamaterial device with pressure memory.

We demonstrate a liquid metal-based reconfigurable terahertz (THz) metamaterial device that is not only pressure driven, but also exhibits pressure memory. The discrete THz response is obtained by injecting eutectic gallium indium (EGaIn) into a microfluidic structure that is fabricated in polydimethylsiloxane (PDMS) using conventional soft lithography techniques. The shape of the injected EGaIn is mechanically stabilized by the formation of a thin oxide surface layer that allows the fluid to maintain its configuration within the microchannels despite its high intrinsic surface energy. Although the viscosity of EGaIn is twice that of water, the formation of the surface oxide layer prevents flow into a microchannel unless a critical pressure is exceeded. Using a structure in which the lateral channel dimensions vary, we progressively increase the applied pressure beyond the relevant critical pressure for each section of the device, enabling switching from one geometry to another (split ring resonator to closed ring resonator to an irregular closed ring resonator). As the geometry changes, the transmission spectrum of the device changes dramatically. When the external applied pressure is removed between device geometry changes, the liquid metal morphology remains unchanged, which can be regarded as a form of pressure memory. Once the device is fully filled with liquid metal, it can be erased through the use of mechanical pressure and exposure to acid vapors.

Rapid determination of the chemical oxygen demand of water using a thermal biosensor.

In this paper we describe a thermal biosensor with a flow injection analysis system for the determination of the chemical oxygen demand (COD) of water samples. Glucose solutions of different concentrations and actual water samples were tested, and their COD values were determined by measuring the heat generated when the samples passed through a column containing periodic acid. The biosensor exhibited a large linear range (5 to 3000 mg/L) and a low detection limit (1.84 mg/L). It could tolerate the presence of chloride ions in concentrations of 0.015 M without requiring a masking agent. The sensor was successfully used for detecting the COD values of actual samples. The COD values of water samples from various sources were correlated with those obtained by the standard dichromate method; the linear regression coefficient was found to be 0.996. The sensor is environmentally friendly, economical, and highly stable, and exhibits good reproducibility and accuracy. In addition, its response time is short, and there is no danger of hazardous emissions or external contamination. Finally, the samples to be tested do not have to be pretreated. These results suggest that the biosensor is suitable for the continuous monitoring of the COD values of actual wastewater samples.

The Treatment of Refractory Vitiligo With Autologous Cultured Epithelium Grafting: A Real-World Retrospective Cohort Study.

BACKGROUND: Surgical intervention is the main therapy for refractory vitiligo. We developed a modified autologous cultured epithelial grafting (ACEG) technique for vitiligo treatment. Between January 2015 and June 2019, a total of 726 patients with vitiligo underwent ACEG in China, with patient characteristics and clinical factors being meticulously documented. Using a generalized linear mixed model, we were able to assess the association between these characteristics and the repigmentation rate. RESULTS: ACEG demonstrated a total efficacy rate of 82.81% (1754/2118) in treating 726 patients, with a higher repigmentation rate of 64.87% compared to conventional surgery at 52.69%. Notably, ACEG showed a better response in treating segmental vitiligo, lesions on lower limbs, age ≤ 18, and stable period > 3 years. A keratinocyte:melanocyte ratio below 25 was found to be advantageous too. Single-cell RNA sequencing analysis revealed an increase in melanocyte count and 2 subclusters of keratinocytes after ACEG, which remained higher in repigmented sites even after 1 year. CONCLUSIONS: ACEG is a promising therapy for refractory vitiligo. Patient age, clinical type, lesion site, and stability before surgery influence repigmentation in ACEG. The mechanism of repigmentation after ACEG treatment is likely not confined to the restoration of melanocyte populations. It may also involve an increase in the number of keratinocytes that support melanocyte function within the affected area. These keratinocytes may aid the post-transplant survival and function of melanocytes by secreting cytokines and extracellular matrix components. TRIAL REGISTRATION: registered with Chictr.org.cn (ChiCTR2100051405).

Association Between Long-Term Exposure to Fine Particulate Matter Constituents and Progression of Cerebral Blood Flow Velocity in Beijing: Modifying Effect of Greenness.

Few studies have explored the effects of fine particulate matter (PM2.5) and its constituents on the progression of cerebral blood flow velocity (BFV) and the potential modifying role of greenness. In this study, we investigated the association of PM2.5 and its constituents, including sulfate (SO4 2-), nitrate (NO3 -), ammonium (NH4 +), organic matter (OM), and black carbon (BC), with the progression of BFV in the middle cerebral artery. Participants from the Beijing Health Management Cohort who underwent at least two transcranial Doppler sonography examinations during 2015-2020 were recruited. BFV change and BFV change rate were used to define the progression of cerebral BFV. Linear mixed effects models were employed to analyze the data, and the weighted quantile sum regression assessed the contribution of PM2.5 constituents. Additionally, greenness was examined as a modifier. Among the examined constituents, OM exhibited the strongest association with BFV progression. An interquartile range increase in PM2.5 and OM exposure concentrations was associated with a decrease of -16.519 cm/s (95% CI: -17.837, -15.201) and -15.403 cm/s (95% CI: -16.681, -14.126) in BFV change, and -10.369 cm/s/year (95% CI: -11.387, -9.352) and -9.615 cm/s/year (95% CI: -10.599, -8.632) in BFV change rate, respectively. Furthermore, stronger associations between PM2.5 and BFV progression were observed in individuals working in areas with lower greenness, those aged under 45 years, and females. In conclusion, reducing PM2.5 levels in the air, particularly the OM constituent, and enhancing greenness could potentially contribute to the protection of cerebrovascular health.

Separate and Joint Associations of Remnant Cholesterol Accumulation and Variability With Carotid Atherosclerosis: A Prospective Cohort Study.

Background We aimed to examine separate and joint associations of remnant cholesterol (RC) accumulation and variability with the risk of carotid atherosclerosis (CAS) in the general population. Methods and Results A total of 6213 participants who underwent 3 sequential health examinations during 2010 to 2015 were enrolled and were followed up until December 31, 2021. Cumulative RC (cumRC) and RC variability among the 3 visits were the exposure of interest in our study. Adjusted Cox models were performed to calculate the hazard ratio (HR) and 95% CI. C-statistics, integrated discrimination improvement, and the net reclassification index were used to estimate the incremental predictive ability. During a median follow-up of 4.00 years, 2613 participants developed CAS. Higher cumRC (HR, 1.33 [95% CI, 1.17-1.52]) and greater RC variability (HR, 1.22 [95% CI, 1.08-1.39]) were significantly associated with elevated risk of CAS, independent of traditional cardiovascular risk factors and low-density lipoprotein cholesterol. Participants were divided into 4 groups according to the median of cumRC and RC variability to assess their joint associations. Compared with "low cumRC and low variability," "high cumRC and high variability" had the highest risk of CAS, followed by "high cumRC and low variability" and "low cumRC and high variability." Finally, joint assessment of RC accumulation and variability had the significantly highest incremental effect on the predictive value of CAS versus single-time-point measures of RC. Conclusions Excessive cumRC levels and greater RC variability were each independently associated with higher incidence of CAS, and their coexistence could further yield significantly higher risks.

Combined Evaluation of Arterial Stiffness and Blood Pressure Promotes Risk Stratification of Peripheral Arterial Disease.

Background: Previous studies have reported the separate association of arterial stiffness (AS) and blood pressure with peripheral arterial disease (PAD). Objectives: The aim of this study was to investigate the risk stratification capacity of AS on incident PAD beyond blood pressure status. Methods: A total of 8,960 participants from Beijing Health Management Cohort were enrolled at the first health visit between 2008 and 2018 and then followed until the incidence of PAD or 2019. Elevated AS was defined as brachial-ankle pulse-wave velocity (baPWV) >1,400 cm/s, including moderate stiffness (1,400 ≤ baPWV <1,800 cm/s) and severe stiffness (baPWV ≥1,800 cm/s). PAD was defined as ankle-brachial index <0.9. A frailty Cox model was used to calculate the HR, integrated discrimination improvement, and net reclassification improvement. Results: During follow-up, 225 participants (2.5%) developed PAD. After adjusting for confounding factors, the highest risk for PAD was observed in the group with elevated AS and blood pressure (HR: 2.253; 95% CI: 1.472-3.448). Among participants with ideal blood pressure and those with well-controlled hypertension, PAD risk was still significant for severe AS. The results remained consistent in multiple sensitivity analyses. In addition, baPWV significantly improved the predictive capacity for PAD risk beyond systolic and diastolic blood pressures (integrated discrimination improvement 0.020 and 0.190, net reclassification improvement 0.037 and 0.303). Conclusions: This study suggests the clinical importance of combined evaluation and control of AS and blood pressure for the risk stratification and prevention of PAD.

Reconfigurable plasmonic devices using liquid metals.

We experimentally demonstrate an approach to create reconfigurable plasmonic devices in which the geometry of the device can be changed dramatically. The specific embodiment we present utilizes eutectic gallium indium (EGaIn), a metal that is liquid at room temperature, which is injected into or withdrawn from channels encapsulated by a polydimethylsiloxane (PDMS) bullseye mold fabricated on a gold coated substrate. Using terahertz (THz) time-domain spectroscopy, we measure the enhanced transmission properties of a single subwavelength aperture surrounded by differing numbers of concentric annular EGaIn rings. The results obtained from different device geometries, with either a single or multiple rings, are performed using a single device, demonstrating true reconfigurability. We explain the properties of the observed temporal waveforms using a simple time-domain model. This represents, we believe, a first step in developing more complex reconfigurable plasmonic devices.