Clinical demographics of study population.

<p>^a<i>P</i> value < 0.05 compared with non-MetS control subject in multiple comparison using Dunnett’s test.</p><p>^b<i>P</i> value < 0.05 compared with non-MetS T2D patients in multiple comparison using Dunnett’s test.</p><p>Abbreviations: BMI, body mass index; HDL-C, high density lipoprotein-cholesterol; HOMA-B, the homeostasis model assessment for β-cell function; HOMA-IR, the homeostasis model assessment for insulin resistance; ISIm, Matsuda index; MetS, metabolic syndrome; OGTT, oral glucose tolerance test; T2D, type 2 diabetes. Data are shown as median (interquartile range) or %. All non-Gaussian distributed quantitative traits were natural logarithmically transformed to normalize distributions. <i>P</i> values were calculated to assess the intergroup differences using χ² test or one-way ANOVA.</p

Bound state in the continuum and polarization-insensitive electric mirror in low-contrast metasurface

High-contrast refractive indexes are pivotal in dielectric metasurfaces for inducing various exotic phenomena, such as the bound state in the continuum (BIC) and electric mirror (EM). However, the limitations of high-index materials are adverse to the practical applications, thus low-contrast metasurfaces with comparable performance are highly desired. Here we present a low-contrast dielectric metasurface comprising radially anisotropic cylinders, which are SiO2 cylinders doped with a small amount of WS2. The cylinder exhibits unidirectional forward superscattering originating from the overlapping of the electric and magnetic dipole resonances. When normal illumination by a near-infrared plane wave, the metasurface consisting of the superscattering constituents manifests a polarization-insensitive EM. Conversely, when subjected to an in-plane incoming wave, the metasurface generates a symmetry-protected BIC characterized by an ultrahigh Q factor and nearly negligible out-of-plane energy radiation. Our work highlights the doping approach as an efficient strategy for designing low-contrast functional metasurfaces and sheds new light on the potential applications in photonic integrated circuits and on-chip optical communication

The Association of Type 2 Diabetes Loci Identified in Genome-Wide Association Studies with Metabolic Syndrome and Its Components in a Chinese Population with Type 2 Diabetes

<div><p>Metabolic syndrome (MetS) is prevalent in type 2 diabetes (T2D) patients. The comorbidity of MetS and T2D increases the risk of cardiovascular complications. The aim of the present study was to determine the T2D-related genetic variants that contribute to MetS-related components in T2D patients of Chinese ancestry. We successfully genotyped 25 genome wide association study validated T2D-related single nucleotide polymorphisms (SNPs) among 5,169 T2D individuals and 4,560 normal glycemic controls recruited from the Chinese National Diabetes and Metabolic Disorders Study (DMS). We defined MetS in this population using the harmonized criteria (2009) combined with the Chinese criteria for abdominal obesity. The associations between SNPs and MetS-related components, as well as the associations between SNPs and risk for T2D with or without MetS, were subjected to logistic regression analysis adjusted for age and sex. Results showed that the T2D risk alleles of rs243021 located near <i>BCL11A</i>, rs10830963 in <i>MTNR1B</i>, and rs2237895 in <i>KCNQ1</i> were related to a lower risk for abdominal obesity in T2D patients (rs243021: 0.92 (0.84, 1.00), <i>P</i> = 4.42 × 10⁻²; rs10830963: 0.92 (0.85, 1.00), <i>P</i> = 4.07 × 10⁻²; rs2237895: 0.89 (0.82, 0.98), <i>P</i> = 1.29 × 10⁻²). The T2D risk alleles of rs972283 near <i>KLF14</i> contributed to a higher risk of elevated blood pressure (1.10 (1.00, 1.22), <i>P</i> = 4.48 × 10⁻²), while the T2D risk allele of rs7903146 in <i>TCF7L2</i> was related to a lower risk for elevated blood pressure (0.74 (0.61, 0.90), <i>P</i> = 2.56 × 10⁻³). The T2D risk alleles of rs972283 near <i>KLF14</i> and rs11634397 near <i>ZFAND6</i> were associated with a higher risk for elevated triglycerides (rs972283: 1.11 (1.02, 1.24), <i>P</i> = 1.46 × 10⁻²; rs11634397: 1.14 (1.00, 1.29), <i>P</i> = 4.66 × 10⁻²), while the T2D risk alleles of rs780094 in <i>GCKR</i> and rs7903146 in <i>TCF7L2</i> were related to a lower risk of elevated triglycerides (rs780094: 0.86 (0.80, 0.93), <i>P</i> = 1.35 × 10⁻⁴; rs7903146: 0.82 (0.69, 0.98), <i>P</i> = 3.18 × 10⁻²). The genotype risk score of the 25 T2D-related SNPs was related to a lower risk for abdominal obesity (<i>P</i>_trend = 1.29 × 10⁻²) and lower waist circumference (<i>P</i> = 2.20 × 10⁻³). Genetic variants of <i>WFS1</i>, <i>CDKAL1</i>, <i>CDKN2BAS</i>, <i>TCF7L2</i>, <i>HHEX</i>, <i>KCNQ1</i>, <i>TSPAN8/LGR5</i>, <i>FTO</i>, and <i>TCF2</i> were associated with the risk for T2D with MetS, as well as the risk for development of T2D with at least one of the MetS components (<i>P</i> < 0.05). In addition, genetic variants of <i>BCL11A</i>, <i>GCKR</i>, <i>ADAMTS9</i>, <i>CDKAL1</i>, <i>KLF14</i>, <i>CDKN2BAS</i>, <i>TCF7L2</i>, <i>CDC123/CAMK1D</i>, <i>HHEX</i>, <i>MTNR1B</i>, and <i>KCNQ1</i> contributed to the risk for T2D without MetS (<i>P</i> < 0.05). In conclusion, these findings highlight the contribution of T2D-related genetic loci to MetS in a Chinese Han population. The study also provides insight into the pleotropic effects of genome-wide association loci of diabetes on metabolic regulation.</p></div

Presentation_1_Notoginsenoside R1 Protects Against Diabetic Cardiomyopathy Through Activating Estrogen Receptor α and Its Downstream Signaling.pdf

Diabetic cardiomyopathy (DCM) leads to heart failure and death in diabetic patients, no effective treatment is available. Notoginsenoside R1 (NGR1) is a novel saponin that is derived from Panax notoginseng and our previous studies have showed cardioprotective and neuroprotective effects of NGR1. However, its role in protecting against DCM remains unexplored. Herein, we examine potential effects of NGR1 on cardiac function of diabetic db/db mice and H9c2 cardiomyocytes treated by advanced glycation end products (AGEs). In vitro experiments revealed that pretreatment with NGR1 significantly decreased AGEs-induced mitochondria injury, limited an increase in ROS, and reduced apoptosis in H9c2 cells. NGR1 eliminated ROS by promoting estrogen receptor α expression, which subsequently activated Akt and Nrf2-mediated anti-oxidant enzymes. In vivo investigation demonstrated that NGR1 significantly reduced serum lipid levels, insulin resistance, the expression of enzymes related to cardiomyopathy, and the expression of apoptotic proteins. Finally, NGR1 improved cardiac dysfunction and attenuated histological abnormalities, as evidenced by elevating ejection fraction and fractional shortening, and reducing cardiac fibrosis. Mechanistically, NGR1 promoted ERα expression, which led to the activation of Akt-Nrf2 signaling and the inhibition of the TGFβ pathway. Collectively, these results strongly indicate that NGR1 exerts cardioprotective effects against DCM through its inhibition of oxidative stress and apoptosis, and eventually suppresses cardiac fibrosis and hypertrophy, which suggests that NGR1 is a potential therapeutic medicine for the treatment of DCM.</p

Tunable Resistive Switching in 2D MXene Ti₃C₂ Nanosheets for Non-Volatile Memory and Neuromorphic Computing

An artificial synapse is essential for neuromorphic computing which has been expected to overcome the bottleneck of the traditional von-Neumann system. Memristors can work as an artificial synapse owing to their tunable non-volatile resistance states which offer the capabilities of information storage, processing, and computing. In this work, memristors based on two-dimensional (2D) MXene Ti3C2 nanosheets sandwiched by Pt electrodes are investigated in terms of resistive switching (RS) characteristics, synaptic functions, and neuromorphic computing. Digital and analog RS behaviors are found to coexist depending on the magnitude of operation voltage. Digital RS behaviors with two resistance states possessing a large switching ratio exceeding 103 can be achieved under a high operation voltage. Analog RS behaviors with a series of resistance states exhibiting a gradual change can be observed at a relatively low operation voltage. Furthermore, artificial synapses can be implemented based on the memristors with the basic synaptic functions, such as long-term plasticity of long-term potentiation and depression and short-term plasticity of the paired-pulse facilitation and depression. Moreover, the “learning–forgetting” experience is successfully emulated based on the artificial synapses. Also, more importantly, the artificial synapses can construct an artificial neural network to implement image recognition. The coexistence of digital and analog RS behaviors in the 2D Ti3C2 nanosheets suggests the potential applications in non-volatile memory and neuromorphic computing, which is expected to facilitate simplifying the manufacturing complexity for complex neutral systems where analog and digital switching is essential for information storage and processing

Image_2_Notoginsenoside R1 Protects Against Diabetic Cardiomyopathy Through Activating Estrogen Receptor α and Its Downstream Signaling.JPEG

Diabetic cardiomyopathy (DCM) leads to heart failure and death in diabetic patients, no effective treatment is available. Notoginsenoside R1 (NGR1) is a novel saponin that is derived from Panax notoginseng and our previous studies have showed cardioprotective and neuroprotective effects of NGR1. However, its role in protecting against DCM remains unexplored. Herein, we examine potential effects of NGR1 on cardiac function of diabetic db/db mice and H9c2 cardiomyocytes treated by advanced glycation end products (AGEs). In vitro experiments revealed that pretreatment with NGR1 significantly decreased AGEs-induced mitochondria injury, limited an increase in ROS, and reduced apoptosis in H9c2 cells. NGR1 eliminated ROS by promoting estrogen receptor α expression, which subsequently activated Akt and Nrf2-mediated anti-oxidant enzymes. In vivo investigation demonstrated that NGR1 significantly reduced serum lipid levels, insulin resistance, the expression of enzymes related to cardiomyopathy, and the expression of apoptotic proteins. Finally, NGR1 improved cardiac dysfunction and attenuated histological abnormalities, as evidenced by elevating ejection fraction and fractional shortening, and reducing cardiac fibrosis. Mechanistically, NGR1 promoted ERα expression, which led to the activation of Akt-Nrf2 signaling and the inhibition of the TGFβ pathway. Collectively, these results strongly indicate that NGR1 exerts cardioprotective effects against DCM through its inhibition of oxidative stress and apoptosis, and eventually suppresses cardiac fibrosis and hypertrophy, which suggests that NGR1 is a potential therapeutic medicine for the treatment of DCM.</p

Genetic Variants Associated with Lipid Profiles in Chinese Patients with Type 2 Diabetes

<div><p>Dyslipidemia is a strong risk factor for cardiovascular disease among patients with type 2 diabetes (T2D). The aim of this study was to identify lipid-related genetic variants in T2D patients of Han Chinese ancestry. Among 4,908 Chinese T2D patients who were not taking lipid-lowering medications, single nucleotide polymorphisms (SNPs) in seven genes previously found to be associated with lipid traits in genome-wide association studies conducted in populations of European ancestry (<i>ABCA1</i>, <i>GCKR</i>, <i>BAZ1B</i>, <i>TOMM40</i>, <i>DOCK7</i>, <i>HNF1A</i>, and <i>HNF4A</i>) were genotyped. After adjusting for multiple covariates, SNPs in <i>ABCA1</i>, <i>GCKR</i>, <i>BAZ1B</i>, <i>TOMM40</i>, and <i>HNF1A</i> were identified as significantly associated with triglyceride levels in T2D patients (<i>P</i> < 0.05). The associations between the SNPs in <i>ABCA1</i> (rs3890182), <i>GCKR</i> (rs780094), and <i>BAZ1B</i> (rs2240466) remained significant even after correction for multiple testing (<i>P</i> = 8.85×10⁻³, 7.88×10⁻⁷, and 2.03×10⁻⁶, respectively). <i>BAZ1B</i> (rs2240466) also was associated with the total cholesterol level (<i>P</i> = 4.75×10⁻²). In addition, SNP rs157580 in <i>TOMM40</i> was associated with the low-density lipoprotein cholesterol level (<i>P</i> = 6.94×10⁻³). Our findings confirm that lipid-related genetic loci are associated with lipid profiles in Chinese patients with type 2 diabetes.</p></div

Clinical characteristics of the study population.

<p>Abbreviations: BMI, body mass index; HDL-C, high-density lipoprotein cholesterol; HOMA-B, the homeostasis model assessment for β-cell function; HOMA-IR, the homeostasis model assessment for insulin resistance; LDL-C, low-density lipoprotein cholesterol; OGTT, oral glucose tolerance test; ISIm, Matsuda index; WC, waist circumference. Data are shown as median (interquartile range) or %.</p><p>Clinical characteristics of the study population.</p

Table_1_Notoginsenoside R1 Protects Against Diabetic Cardiomyopathy Through Activating Estrogen Receptor α and Its Downstream Signaling.XLSX

Diabetic cardiomyopathy (DCM) leads to heart failure and death in diabetic patients, no effective treatment is available. Notoginsenoside R1 (NGR1) is a novel saponin that is derived from Panax notoginseng and our previous studies have showed cardioprotective and neuroprotective effects of NGR1. However, its role in protecting against DCM remains unexplored. Herein, we examine potential effects of NGR1 on cardiac function of diabetic db/db mice and H9c2 cardiomyocytes treated by advanced glycation end products (AGEs). In vitro experiments revealed that pretreatment with NGR1 significantly decreased AGEs-induced mitochondria injury, limited an increase in ROS, and reduced apoptosis in H9c2 cells. NGR1 eliminated ROS by promoting estrogen receptor α expression, which subsequently activated Akt and Nrf2-mediated anti-oxidant enzymes. In vivo investigation demonstrated that NGR1 significantly reduced serum lipid levels, insulin resistance, the expression of enzymes related to cardiomyopathy, and the expression of apoptotic proteins. Finally, NGR1 improved cardiac dysfunction and attenuated histological abnormalities, as evidenced by elevating ejection fraction and fractional shortening, and reducing cardiac fibrosis. Mechanistically, NGR1 promoted ERα expression, which led to the activation of Akt-Nrf2 signaling and the inhibition of the TGFβ pathway. Collectively, these results strongly indicate that NGR1 exerts cardioprotective effects against DCM through its inhibition of oxidative stress and apoptosis, and eventually suppresses cardiac fibrosis and hypertrophy, which suggests that NGR1 is a potential therapeutic medicine for the treatment of DCM.</p