The HACE1 E3 ligase mediates RAC1-dependent control of mTOR signaling complexes.

HACE1 is a HECT family E3 ubiquitin-protein ligase with broad but incompletely understood tumor suppressor activity. Here, we report a previously unrecognized link between HACE1 and signaling complexes containing mammalian target of rapamycin (mTOR). HACE1 blocks mTORC1 and mTORC2 activities by reducing mTOR stability in an E3 ligase-dependent manner. Mechanistically, HACE1 binds to and ubiquitylates Ras-related C3 botulinum toxin substrate 1 (RAC1) when RAC1 is associated with mTOR complexes, including at focal adhesions, leading to proteasomal degradation of RAC1. This in turn decreases the stability of mTOR to reduce mTORC1 and mTORC2 activity. HACE1 deficient cells show enhanced mTORC1/2 activity, which is reversed by chemical or genetic RAC1 inactivation but not in cells expressing the HACE1-insensitive mutant, RAC1K147R . In vivo, Rac1 deletion reverses enhanced mTOR expression in KRasG12D -driven lung tumors of Hace1-/- mice. HACE1 co-localizes with mTOR and RAC1, resulting in RAC1-dependent loss of mTOR protein stability. Together, our data demonstrate that HACE1 destabilizes mTOR by targeting RAC1 within mTOR-associated complexes, revealing a unique ubiquitin-dependent process to control the activity of mTOR signaling complexes.

Tunable origami metastructure based on liquid crystal for curvature sensing.

In this paper, a liquid crystal (LC) tunable origami metastructure (OMS) designed for curvature sensing on cylindrical surfaces to measure their curvature is introduced. The LC employed is K15 (5CB) and the applicable band is 0.36∼23 GHz. When excited by electromagnetic waves (EMWs) within the 4∼16 GHz, the resonance frequency of the OMS shifts from 10.24 GHz to 10.144 GHz, corresponding to a change in absorption amplitude ranging from 0.773 to 0.920. In terms of curvature sensing, the detectable range of curvature spans from 0 to 0.327 mm-1. The maximum sensitivity (S) achieved for curvature measurement reaches 0.918/mm-1, accompanied by a quality factor (Q-factor) of 25.88. The proposed OMS embodies numerous excellent traits, including wide-range sensing capabilities and heightened S, promising for applications in bionic skin, smart robotics, and related fields.

Arithmetic logic unit based on the metastructure with coherent absorption: erratum.

We present a corrigendum to our Letter [Opt. Lett.48, 5699 (2023)10.1364/OL.505761]. In section 3 of the original supplementary material, the absolute value is incorrectly taken in resolving the Kubo formula for describing the conductivity of graphene. Because this is a mistake with the conductivity of graphene, the coupling of the original structure is broken when the correct result is inserted into the code of the transfer matrix. So, the structure of the arithmetic logic unit (ALU), characteristic frequency point, and phase control have been modified accordingly. However, the ultimate function and the conclusion of this work remain unchanged.

Cardiovascular health metrics defined by Life's Essential 8 scores and subsequent macrovascular and microvascular complications in individuals with type 2 diabetes: A prospective cohort study.

AIM: To investigate the association between cardiovascular health metrics defined by Life's Essential 8 (LE8) scores and vascular complications among individuals with type 2 diabetes (T2D). MATERIALS AND METHODS: This prospective study included 11 033 participants with T2D, all devoid of macrovascular diseases (including cardiovascular and peripheral artery disease) and microvascular complications (e.g. diabetic retinopathy, neuropathy and nephropathy) at baseline from the UK Biobank. The LE8 score comprised eight metrics: smoking, body mass index, physical activity, non-high-density lipoprotein cholesterol, blood pressure, glycated haemoglobin, diet and sleep duration. Cox proportional hazards models were established to assess the associations of LE8 scores with incident macrovascular and microvascular complications. RESULTS: During a median follow-up of 12.1 years, we identified 1975 cases of incident macrovascular diseases and 1797 cases of incident microvascular complications. After adjusting for potential confounders, each 10-point increase in the LE8 score was associated with an 18% lower risk of macrovascular diseases and a 15% lower risk of microvascular complications. Comparing individuals in the highest and lowest quartiles of LE8 scores revealed hazard ratios of 0.55 (95% confidence interval 0.47-0.62) for incident macrovascular diseases, and 0.61 (95% confidence interval 0.53-0.70) for incident microvascular complications. This association remained robust across a series of sensitivity analyses and nearly all subgroups. CONCLUSION: Higher LE8 scores were associated with a lower risk of incident macrovascular and microvascular complications among individuals with T2D. These findings underscore the significance of adopting fundamental strategies to maintain optimal cardiovascular health and curtail the risk of developing diabetic vascular complications.

Upregulated LncRNA H19 Sponges MiR-106a-5p and Contributes to Aldosterone-Induced Vascular Calcification via Activating the Runx2-Dependent Pathway.

BACKGROUND: Excess aldosterone is implicated in vascular calcification (VC), but the mechanism by which aldosterone-MR (mineralocorticoid receptor) complex promotes VC is unclear. Emerging evidence indicates that long-noncoding RNA H19 (H19) plays a critical role in VC. We examined whether aldosterone-induced osteogenic differentiation of vascular smooth muscle cells (VSMCs) through H19 epigenetic modification of Runx2 (runt-related transcription factor-2) in a MR-dependent manner. METHODS: We induced in vivo rat model of chronic kidney disease using a high adenine and phosphate diet to explore the relationship among aldosterone, MR, H19, and VC. We also cultured human aortic VSMCs to explore the roles of H19 in aldosterone-MR complex-induced osteogenic differentiation and calcification of VSMCs. RESULTS: H19 and Runx2 were significantly increased in aldosterone-induced VSMC osteogenic differentiation and VC, both in vitro and in vivo, which were significantly blocked by the MR antagonist spironolactone. Mechanistically, our findings reveal that the aldosterone-activated MR bound to H19 promoter and increased its transcriptional activity, as determined by chromatin immunoprecipitation, electrophoretic mobility shift assay, and luciferase reporter assay. Silencing H19 increased microRNA-106a-5p (miR-106a-5p) expression, which subsequently inhibited aldosterone-induced Runx2 expression at the posttranscriptional level. Importantly, we observed a direct interaction between H19 and miR-106a-5p, and downregulation of miR-106a-5p efficiently reversed the suppression of Runx2 induced by H19 silencing. CONCLUSIONS: Our study clarifies a novel mechanism by which upregulation of H19 contributes to aldosterone-MR complex-promoted Runx2-dependent VSMC osteogenic differentiation and VC through sponging miR-106a-5p. These findings highlight a potential therapeutic target for aldosterone-induced VC.

A multiple cancer cell optical biosensing metastructure realized by CPA.

A one-dimensional optical biosensing metastructure (OBM) with graphene layers is presented in this paper. It is realized by coherent perfect absorption (CPA) and operates in the transverse electric mode. It shows a strong linear fitting relationship between the refractive index (RI) of the analysis layer and the frequency corresponding to the absorption peak, and the R-square is up to 1. Additionally, based on the principle of CPA, the OBM can realize the function of multiple cancer cell detection by adjusting the detection range by controlling the phase difference of coherent electromagnetic waves. Its detection ranges are 1.34-1.355 and 1.658-1.662. Thanks to its high-quality factor, great figure of merit, and low detection limit, whose best values are, respectively, 6.9 × 104, 1.2 × 104 RIU-1, and 3.6 × 10-6 RIU, the detection of weak changes in the RI of a cancer cell is possible. Additionally, its sensitivity can reach 26.57 THz RIU-1. This OBM based on CPA has major implications for advancing the study and investigation into the application of CPA. It also provides a simple and efficient approach to distinguish cancer cells and may be widely used in the biomedical field.

Dietary vitamin C and vitamin E with the risk of aortic aneurysm and dissection: A prospective population-based cohort study.

BACKGROUND AND AIMS: The associations between dietary vitamin C (VC), vitamin E (VE) intake and aortic aneurysm and dissection (AAD) remain unclear. This study aimed to prospectively investigate the associations between dietary VC and VE with the incident risk of AAD. METHODS AND RESULTS: A total of 139 477 participants of UK Biobank cohort were included in the analysis. Dietary VC and VE consumptions were acquired through a 24-h recall questionnaire. Cox proportional regression models were used to examine the associations between VC, VE intake and the risk of AAD. Incident AAD was ascertained through hospital inpatient records and death registers. During a median follow-up of 12.5 years, 962 incident AAD events were documented. Both dietary VC [adjusted hazard ratio (HR), 0.77; 95 % confidence intervals (CI), 0.63-0.93; P-trend = 0.008] and VE (adjusted HR, 0.70; 95 % CI, 0.57-0.87; P-trend = 0.002) were inversely associated with incident AAD when comparing the participants in the highest quartile with those in the lowest. In subgroup analyses, the associations were more pronounced in participants who were over 60 years old, participants with smoking history, hypertension or hyperlipidemia, who were under the high risk of AAD. CONCLUSION: Higher dietary VC and VE intakes are associated with reduced risk of AAD. Our study emphasizes the importance of diet adjustment strategies targeted on VC and VE to lower the incidence rate of AAD especially in the high-risk population.

AHA Life's Essential 8 and new-onset CKD: a prospective cohort study from the UK Biobank.

BACKGROUND: The AHA has recently introduced a novel metric, Life's Essential 8, to assess cardiovascular health (CVH). Nevertheless, the association between varying levels of LE8 and the propensity for CKD is still unclear from a large prospective cohort. Our objective is to meticulously examine the relationship between LE8 and its associated susceptibilities to CKD. METHODS: A total of 251,825 participants free of CKD from the UK Biobank were included. Cardiovascular health was scored using LE8 and categorized as low, moderate, and high. Cox proportional hazard models were employed to evaluate the associations of LE8 scores with new-onset CKD. The genetic risk score for CKD was calculated by a weighted method. RESULTS: Over a median follow-up of 12.8 years, we meticulously documented 10,124 incident cases of CKD. Remarkably, an increased LE8 score correlated with a significant reduction of risk in new-onset CKD (high LE8 score vs. low LE8 score: HR = 0.300, 95% CI 0.270-0.330, p < 0.001; median LE8 score vs. low LE8 score: HR = 0.531, 95% CI 0.487-0.580, p < 0.001). This strong LE8-CKD association remained robust in extensive subgroup assessments and sensitivity analysis. Additionally, these noteworthy associations between LE8 scores and CKD remained unaffected by genetic predispositions to CKD. CONCLUSIONS: An elevated degree of CVH, as delineated by the discerning metric LE8, exhibited a pronounced and statistically significant correlation with a marked reduction in the likelihood of CKD occurrence.

Deep-learning reconstruction of complex dynamical networks from incomplete data.

Reconstructing complex networks and predicting the dynamics are particularly challenging in real-world applications because the available information and data are incomplete. We develop a unified collaborative deep-learning framework consisting of three modules: network inference, state estimation, and dynamical learning. The complete network structure is first inferred and the states of the unobserved nodes are estimated, based on which the dynamical learning module is activated to determine the dynamical evolution rules. An alternating parameter updating strategy is deployed to improve the inference and prediction accuracy. Our framework outperforms baseline methods for synthetic and empirical networks hosting a variety of dynamical processes. A reciprocity emerges between network inference and dynamical prediction: better inference of network structure improves the accuracy of dynamical prediction, and vice versa. We demonstrate the superior performance of our framework on an influenza dataset consisting of 37 US States and a PM2.5 dataset covering 184 cities in China.

Lymphangiogenesis, a potential treatment target for myocardial injury.

The lymphatic vascular system is crucial for the regulation of tissue fluid homeostasis, lipid metabolism, and immune function. Cardiac injury quickly leads to myocardial edema, cardiac lymphatic dysfunction, which ultimately results in myocardial fluid imbalance and cardiac dysfunction. Therefore, lymphangiogenesis-targeted therapy may improve the recovery of myocardial function post cardiac ischemia as observed in myocardial infarction (MI). Indeed, a promising strategy for the clinical treatment of MI relies on vascular endothelial growth factor-C (VEGF-C)-targeted therapy, which promotes lymphangiogenesis. However, much effort is needed to identify the mechanisms of lymphatic transport in response to heart disease. This article reviews regulatory factors of lymphangiogenesis, and discusses the effects of lymphangiogenesis on cardiac function after cardiac injury and its regulatory mechanisms. The involvement of stem cells on lymphangiogenesis was also discussed as stem cells could differentiate into lymphatic endothelial cells (LECs) and stimulate phenotype of LECs.

Tunable Janus absorptive frequency-selective reflector with octave frequency absorption.

A tunable Janus absorptive frequency-selective reflector (AFSR) utilizing a graphene-based hyperbolic that showcases exceptional doubling octave frequency absorption (DOFA) or tripling octave frequency absorption (TOFA) is proposed. The multi-objective gray wolf optimization algorithm is employed to drive the transfer matrix method, optimizing parameters such as the dielectric permittivity, thickness, and the Fermi level (Ef) to achieve harmonic absorption. By manipulating the Ef of graphene, the dimensions of the absorption band and reflection window can be finely adjusted. Additionally, a frequency-selective reflector is introduced, enabling a seamless transition between selective absorption and transmission by adjusting the Ef. This AFSR represents a groundbreaking approach to achieving DOFA or TOFA while simultaneously offering valuable insights into the design of intelligent AFSRs.

Tunable and controllable multi-channel time-comb absorber based on continuous photonic time crystals.

To date there have been many studies on multi-channel absorbers for conventional photonic crystals (PCs). However, the number of absorption channels is small and uncontrollable, which cannot satisfy applications such as multispectral or quantitative narrowband selective filters. To address these issues, a tunable and controllable multi-channel time-comb absorber (TCA) based on continuous photonic time crystals (PTCs), is theoretically proposed. Compared with conventional PCs with fixed refractive index (RI), this system forms a stronger local electric field enhancement in the TCA by absorbing externally modulated energy, resulting in sharp multi-channel absorption peaks (APs). Tunability can be achieved by adjusting the RI, angle, and time period unit (T) of the PTCs. Diversified tunable methods allow the TCA to have more potential applications. In addition, changing T can adjust the number of multi-channels. More importantly, changing the primary term coefficient of n1(t) of PTC1 can control the number of time-comb absorption peaks (TCAPs) in multi-channels within a certain range, and the mathematical relationship between the coefficients and the number of multiple channels is summarized. This will have potential applications in the design of quantitative narrowband selective filters, thermal radiation detectors, optical detection instruments, etc.

Arithmetic logic unit based on the metastructure with coherent absorption.

An arithmetic logic unit (ALU) based on the metastructure (MS) with coherent absorption (CA) is proposed in this Letter. The ALU can perform AND and exclusive OR logical operations at the same frequency point. So it can be regarded as an optical half-adder. By controlling the chemical potential of graphene and the phase difference of coherent electromagnetic waves (EWs), two different binary numbers are input into the ALU. The dynamic absorption peaks, which are generated based on the CA, output the outcomes of the carry-digit bit and non-carry sum bit. This ALU can be used in the field of optical processing and encryption, such as processing hamming code. This given ALU based on the MS with CA has major implications for advancing the study and investigation into the application of CA. Furthermore, it also provides a new, to the best of our knowledge, idea for the study of MS with logical operation.

Anapole-excited terahertz multifunctional spoof surface plasmon polariton directional Janus metastructures.

The anapole mode, in which a distinct radiationless electromagnetic (EM) response in artificial media can be achieved, has attracted significant attention and been regarded as a promising candidate to initiate novel avenues to control the intrinsic radiative losses in nanophotonics and plasmonics, whose current research studies mainly focus on the manipulation of the one-directional incident wave. To exploit the propagation characteristic of incident waves in anapole-excited (AE) media, a set of terahertz (THz) multifunctional Janus metastructures (JMSs) for the opposite linear-polarized (LP) light excitation is presented in this paper. By introducing the directional-selective spoof surface plasmon polariton (SSPP) excited by anapole mode, a metastructure rasorber (MSR) possessing an absorption band of 2-3.08 THz (42.5%) and a co-polarized transmission window of 3.77-5.55 THz (38.2%) for the forward normal-incident LP wave is attained. Furthermore, the integration of the MSR and a polarization-conversation structure (PCS) can be used to fabricate a multifunctional Janus metadevice thus achieving the integration of EM energy harvesting, the co-polarized transmission, and cross-polarized reflection of light with opposite propagation directions, i.e., an absorption band of 2.14-3.09 THz (36.3%) for the forward normal-incident LP wave, and a cross-polarized reflection band of 2.08-3.03 THz (37.2%) for the backward vertical-incident LP wave, while attaining an identical co-polarized transmission window of 3.95-5.2 THz (27.3%). Moreover, by utilizing the substantial field-localization properties of anapole modes supported by the nested opposite-directional SSPP with different sizes, the Janus metastructure absorber (JMA) can achieve non-overlapped absorption bands of 2.02-2.84 THz (33.7%) and 2.88-4.58 THz (45.6%) for the bidirectional normal-incident LP waves, respectively. A series of passive JMSs based on the anapole modes excited by the opposite-directional incident waves significantly extend the theoretical framework and application field of multipole electrodynamics, especially aimed at directional-selective management.

The multiple physical quantity sensor based on cylindrical photonic crystals with XOR logic gates.

Based on cylindrical photonic crystals in one dimension, a multi-scale sensor device with a logic operation is being proposed. At the same time, it can satisfy the functions of refractive index (RI) and magnetic field detection. Under the modulation of an external magnetic field, sharp absorption peaks (APs) are obtained in the terahertz (THz) range. In a certain frequency range (AP value above 0.9), as the particular InSb layers are applied to two different magnetic fields, APs of the same frequency can be implemented to operate as XOR logic gates. The results show that with a change in the detected physical quantity, the frequency point of the corresponding AP also moves. Therefore, by adjusting the position of the AP, the magnetic field and RI can be sensed, and the device shows relatively excellent performance of 6879.88 and 6943.65 in terms of quality factor. In addition, the optimal performance of sensitivity, detection limit, and corresponding figure of merit is 0.01264(2πc/d0) T-1, 2.25 × 10-4 T, 227.23 T-1, and -0.003779(2πc/d0) RIU-1, 7.69 × 10-3 RIU, 67.74 RIU-1. In terms of overall sensors, the proposed device is highly innovative in structure and meets the requirements of multi-scale measurements.

Broadband plasmon-induced transparency to an anapole mode induced absorption conversion Janus metastructure by a waveguide structure in the terahertz region.

A Janus metastructure (MS) assisted by a waveguide structure (WGS) resting on anapole modes and exhibiting direction-dependent behavior has been developed in the terahertz (THz) region. Ultra-broadband absorption is formed by the destructive interference through the anapole as well as Janus trait and is shaped by nested WGS. In this design, vanadium dioxide (VO2) is expected to attain functional transformation from plasmon-induced transparency (PIT) to absorption. The insulating nature of the VO2 results in the creation of the PIT, which is characterized by a wide and high transmission window ranging from 1.944 THz to 2.284 THz, corresponding to the relative bandwidth of 7.4% above 0.9. However, when the VO2 reaches the metallic state, a high absorptivity of 0.921 at 2.154 THz can be implemented in the -z-direction owing to the excitement of the toroidal dipole and electric dipole moments in the near-infrared region. And in the +z-direction, the broadband absorption above 0.9 in the 1.448-2.497 THz range takes shape in virtue of surface plasmon polariton modes, in which intensely localized oscillation of free electrons is confined to the metal-dielectric interface supported by the WGS. Noting that the MS is equipped with a favorable sensitivity to the incidence angle, we develop an ultra-broadband backward absorption in the TM mode from 0.7-10 THz nearly all above 0.9 when the incidence angle changes from 30°-70°. Moreover, owing to the highly symmetrical structure, the MS exhibits exotic polarization angular stability. All the awesome properties make this MS a good candidate for various applications such as in electromagnetic wave steering, spectral analysis, and sensors.

Advanced optical terahertz fingerprint sensor based on coherent perfect absorption.

An advanced optical terahertz (THz) fingerprint sensor based on coherent perfect absorption (CPA) is proposed. Based on a one-dimensional layered photonic structure, the sensor contains a cavity that is developed for THz fingerprint measurement. Utilizing the magneto-optical effect of magnetized InSb, CPA is excited in the structure of the sensor. Taking α-lactose as exemplar material, this numerical simulation is integrated with a Drude-Lorentz model. The transfer matrix method (TMM) is used to calculate the sensitivity (S), linear range (LR), quality (Q), the figure of merit (FOM*), and detection limit (DL) theoretically. Employing the amplitude modulation detection method, the qualitative and quantitative analysis of the α-lactose thickness of 0-0.5 µm could be realized. Because of the fragility of CPA, the S is 0.78255 µm-1, the value of average Q is up to 8019.2, the value of average FOM* is 13 234.4 (THz µm)-1, and the lower DL is 4.21 × 10-6. Moreover, the evolutions of ensemble-averaged absorption in the vicinity of the absorption peaks for different types of disorder effects are considered, which will be considered in the fabrication of sensors.

A theoretical study based on coherent perfect absorption and polarization separation in one-dimensional magnetized plasma photonic crystals.

This article presents a study on tunable narrowband coherent perfect absorption (CPA), which can be altered by adjusting the initial phase to the ranges of 1.03α-1.13α (with α = 2πc/d) and 1.29α-1.43α. The relative bandwidths of these ranges are determined to be 8.5% and 7.4%, respectively. The study utilizes the transfer matrix method for calculations of the largest CPA amplitudes within one-dimensional (1D) magnetized plasma photonic crystals (MPPCs) across two absorption bands, achieving a maximum of 0.99 and 0.98, respectively. In addition, the phase modulation and amplitude modulation characteristics of the CPA are also discussed, and the results show that its absorption amplitude can be gradually modulated from 0.08 to 0.99 by the former and from 0.60 to 0.98 by the latter. The external magnetic fields have also been shown to limit the CPA amplitude between 0.41 and 0.99 within one band and between 0.52 and 0.99 within another band. The study further highlights the effect of plasma frequency and dielectric layer thickness on coherent band shifts towards high or low frequencies. Notably, the article presents the multiband polarization separation properties of 1D MPPCs, with calculated transmittance differences between the TM and TE waves of up to 0.70 and 0.74 at 1.13α and 1.37α, respectively.

A multi-physical quantity sensor based on a layered photonic structure containing layered graphene hyperbolic metamaterials.

The layered photonic structure (LPS) sensor presented in this paper utilizes the intrinsic absorption principle of graphene which can improve the absorption rate by stacking layers to generate an absorption peak within the terahertz (THz) frequency range. The absorption peak can be used for multi-dimensional detection of glucose solution, alcohol solution, the applied voltage of graphene, the thickness of hyperbolic metamaterials (HMs), and room temperature. LPS is endowed with characteristics of a Janus metastructure through the non-stacked arrangement of different media and can have different sensing properties when the electromagnetic waves (EWs) are incident forward and backward. The Janus metastructure features in the forward and backward direction make it have different physical characteristics, forming sensors with different resolutions and qualities, so as to realize the detection of multiple physical quantities. One device has the detection performance of multiple substances, which greatly improves the utilization rate of the design structure. Furthermore, the addition of HM to the sensor structure enables it to exhibit angle-insensitive characteristics in both forward and backward directions. To further enhance the sensor's performance, the particle swarm optimization (PSO) algorithm is used to optimize structural parameters. The resulting sensor exhibits excellent sensing performance, with a high sensitivity (S) of 940.34 THz per RIU and quality factor (Q) and figure of merit (FOM) values of 37 4700 RIU-1, respectively, when measuring voltage. For glucose and alcohol solutions, the sensor demonstrates S values of 5.52 THz per RIU and 4.44 THz per RIU, Q values of 8.3 and 37.2, and FOM values of 6.2 RIU-1 and 20.2 RIU-1, respectively in different directions.

Design, Synthesis, Antifungal Activity, and Molecular Docking of Streptochlorin Derivatives Containing the Nitrile Group.

Based on the structures of natural products streptochlorin and pimprinine derived from marine or soil microorganisms, a series of streptochlorin derivatives containing the nitrile group were designed and synthesized through acylation and oxidative annulation. Evaluation for antifungal activity showed that compound 3a could be regarded as the most promising candidate-it demonstrated over 85% growth inhibition against Botrytis cinerea, Gibberella zeae, and Colletotrichum lagenarium, as well as a broad antifungal spectrum in primary screening at the concentration of 50 µg/mL. The SAR study revealed that non-substituent or alkyl substituent at the 2-position of oxazole ring were favorable for antifungal activity, while aryl and monosubstituted aryl were detrimental to activity. Molecular docking models indicated that 3a formed hydrogen bonds and hydrophobic interactions with Leucyl-tRNA Synthetase, offering a perspective for the possible mechanism of action for antifungal activity of the target compounds.