Observational studies have suggested an association between metabolic syndrome (MetS) and hidradenitis suppurativa (HS), but whether this relationship is causal remains unclear. Elucidating the causal direction could provide insights into disease mechanisms and potential interventions. We performed bidirectional two-sample Mendelian randomization (MR) using summary statistics from genome-wide association studies (GWAS) of MetS and HS. For validation, we replicated the MetS analysis using data from an independent GWAS. We applied multiple MR methods, primarily inverse variance-weighted (IVW) regression, and conducted sensitivity analyses to assess heterogeneity and pleiotropy. The MR analysis demonstrated MetS causally increased HS risk (IVW odds ratio [OR], 1.428 [95% CI, 1.193-1.710]; p < 0.001), with consistent evidence from sensitivity analyses. However, HS did not appear to causally influence MetS risk (IVW OR, 1.008 [95% CI, 0.988-1.028]; p = 0.438). This study provides evidence that MetS causally increases the risk of developing HS. However, we found no evidence for a causal relationship in the reverse direction from HS to MetS. Further research is warranted to elucidate the mechanisms underlying the identified causal association between MetS and subsequent HS development.
Background: Diabetic kidney disease (DKD) is one of diabetic complications, which has become the leading cause of end-stage kidney disease. In addition to angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker(ACEI/ARB) and sodium-glucose cotransporter-2 inhibitor (SGLT2i), traditional Chinese medicine (TCM) is an effective alternative treatment for DKD. In this study, the effect of Qufeng Tongluo (QFTL) decoction in decreasing proteinuria has been observed and its mechanism has been explored based on autophagy regulation in podocyte. Methods: In vivo study, db/db mice were used as diabetes model and db/m mice as blank control. Db/db mice were treated with QFTL decoction, rapamycin, QFTL + 3-Methyladenine (3-MA), trehalose, chloroquine (CQ) and QFTL + CQ. Mice urinary albumin/creatinine (UACR), nephrin and autophagy related proteins (LC3 and p62) in kidney tissue were detected after intervention of 9 weeks. Transcriptomics was operated with the kidney tissue from model group and QFTL group. In vitro study, mouse podocyte clone-5 (MPC-5) cells were stimulated with hyperglycemic media (30 mmol/L glucose) or cultured with normal media. High-glucose-stimulated MPC-5 cells were treated with QFTL freeze-drying powder, rapamycin, CQ, trehalose, QFTL+3-MA and QFTL + CQ. Cytoskeletal actin, nephrin, ATG-5, ATG-7, Beclin-1, cathepsin L and cathepsin B were assessed. mRFP-GFP-LC3 was established by stubRFP-sensGFP-LC3 lentivirus transfection. Results: QFTL decoction decreased the UACR and increased the nephrin level in kidney tissue and high-glucose-stimulated podocytes. Autophagy inhibitors, including 3-MA and chloroquine blocked the effects of QFTL decoction. Further study showed that QFTL decoction increased the LC3 expression and relieved p62 accumulation in podocytes of db/db mice. In high-glucose-stimulated MPC-5 cells, QFTL decoction rescued the inhibited LC3 and promoted the expression of ATG-5, ATG-7, and Beclin-1, while had no effect on the activity of cathepsin L and cathepsin B. Results of transcriptomics also showed that 51 autophagy related genes were regulated by QFTL decoction, including the genes of ATG10, SCOC, ATG4C, AMPK catalytic subunit, PI3K catalytic subunit, ATG3 and DRAM2. Conclusion: QFTL decoction decreased proteinuria and protected podocytes in db/db mice by regulating autophagy.
PURPOSE: This study employs a two-sample Mendelian randomization (MR) approach to investigate the variation in ischemic stroke risk across novel subtypes of adult-onset type 2 diabetes. METHODS: Leveraging pooled genome-wide association study (GWAS) data from the Swedish ANDIS cohort, we explored the association of four newly identified type 2 diabetes subtypes-severe insulin-deficient diabetes (SIDD), severe insulin-resistant diabetes (SIRD), mild obesity-related diabetes (MOD), and mild age-related diabetes (MARD)-with ischemic stroke risk. The outcome data for ischemic stroke and its three subtypes (large artery, cardioembolic, and small vessel stroke) were sourced from the MEGASTROKE Consortium. Our analysis applied multiple MR methods, focusing on the inverse-variance weighted (IVW) technique, complemented by thorough sensitivity analyses to examine heterogeneity and potential horizontal pleiotropy. RESULTS: Our findings reveal a significant causal relationship between the SIDD subtype and small vessel stroke (OR = 1.06, 95% CI: 1.01-1.11, p = 0.025), while no causal associations were observed for SIRD with any stroke subtype. MOD was causally linked to small vessel stroke (OR = 1.07, 95% CI: 1.02-1.12, p = 0.004) and large artery stroke (OR = 1.07, 95% CI: 1.01-1.13, p = 0.015). Similarly, MARD showed a causal relationship with small vessel stroke (OR = 1.09, 95% CI: 1.03-1.16, p = 0.006) and overall ischemic stroke risk (OR = 1.04, 95% CI: 1.01-1.08, p = 0.010). CONCLUSIONS: Our study highlights distinct causal links between specific type 2 diabetes subtypes and ischemic stroke risks, emphasizing the importance of subtype-specific prevention and treatment strategies.
Signal processing is of critical importance for various science and technology fields. Analog optical processing can provide an effective solution to perform large-scale and real-time data processing, superior to its digital counterparts, which have the disadvantages of low operation speed and large energy consumption. As an important branch of modern optics, Fourier optics exhibits great potential for analog optical image processing, for instance for edge detection. While these operations have been commonly explored to manipulate the spatial content of an image, mathematical operations that act directly over the angular spectrum of an image have not been pursued. Here, we demonstrate manipulation of the angular spectrum of an image, and in particular its differentiation, using dielectric metasurfaces operating across the whole visible spectrum. We experimentally show that this technique can be used to enhance desired portions of the angular spectrum of an image. Our approach can be extended to develop more general angular spectrum analog meta-processors, and may open opportunities for optical analog data processing and biological imaging.
Non-Hermitian skin effect and photonic topological edge states are of great interest in non-Hermitian physics and optics. However, the interplay between them is largely unexplored. Here, we propose and demonstrate experimentally the non-Hermitian skin effect constructed from the nonreciprocal flow of Floquet topological edge states, which can be dubbed "Floquet skin-topological effect." We first show the non-Hermitian skin effect can be induced by structured loss when the one-dimensional (1D) system is periodically driven. Next, based on a two-dimensional (2D) Floquet topological photonic lattice with structured loss, we investigate the interaction between the non-Hermiticity and the topological edge states. We observe that all the one-way edge states are imposed onto specific corners, featuring both the non-Hermitian skin effect and topological edge states. Furthermore, a topological switch for the skin-topological effect is presented by utilizing the phase-transition mechanism. Our experiment paves the way for realizing non-Hermitian topological effects in nonlinear and quantum regimes.
Recently various physical systems have been proposed for modeling Ising spin Hamiltonians appealing to solve combinatorial optimization problems with remarkable performance. However, how to implement arbitrary spin-spin interactions is a critical and challenging problem in unconventional Ising machines. Here, we propose a general gauge transformation scheme to enable arbitrary spin-spin interactions and external magnetic fields as well, by decomposing an Ising Hamiltonian into multiple Mattis-type interactions. With this scheme, a wavelength-division multiplexing spatial photonic Ising machine (SPIM) is developed to show the programmable capability of general spin coupling interactions. We exploit the wavelength-division multiplexing SPIM to simulate three spin systems: ±J models, Sherrington-Kirkpatrick models, and only locally connected J1-J2 models and observe the phase transitions. We also demonstrate the ground-state search for solving Max-Cut problem with the wavelength-division multiplexing SPIM. These results promise the realization of ultrafast-speed and high-power efficiency Boltzmann sampling to a generalized large-scale Ising model.
BACKGROUND: The causal relationship and the direction of the effect between depression and aging remain controversial. METHODS: We used a bidirectional two-sample Mendelian randomization analysis to examine the relationship between depression and age proxy indicators. We obtained pooled statistics from genome-wide association studies (GWAS) on depression and the age proxy indicators. We employed five MR analysis methods to address potential biases and ensure robustness of our results, with the inverse variance weighted (IVW) method being the primary outcome. We also conducted outlier exclusion using Radial MR, MRPRESSO, and MR Steiger filters. Additionally, sensitivity analyses were performed to assess heterogeneity and pleiotropy. RESULTS: Our MR analysis revealed that depression causally leads to shortened telomere length (ß = - 0.014; P = 0.038), increased frailty index (ß = 0.076; P = 0.000), and accelerated GrimAge (ß = 0.249; P = 0.024). Furthermore, our findings showed that the frailty index (OR = 1.679; P = 0.001) was causally associated with an increased risk of depression. Additionally, we found that appendicular lean mass (OR = 0.929; P = 0.000) and left-hand grip strength (OR = 0.836; P = 0.014) were causally associated with a reduced risk of depression. Sensitivity analyses demonstrated the robustness of our findings. CONCLUSIONS: Our study provides evidence that depression contributes to the accelerated aging process, resulting in decreased telomere length, increased frailty index, and accelerated GrimAge. Additionally, we found that the frailty index increases the risk of depression, while appendicular lean mass and left-handed grip strength reduce the risk of depression.
Depression , Frailty , Humans , Depression/genetics , Genome-Wide Association Study , Hand Strength , Mendelian Randomization Analysis , Telomere , Telomere Shortening , Aging/genetics
Vortices in fluids and gases have piqued the human interest for centuries. Development of classical-wave physics and quantum mechanics highlighted wave vortices characterized by phase singularities and topological charges. In particular, vortex beams have found numerous applications in modern optics and other areas. Recently, optical spatiotemporal vortex states exhibiting the phase singularity both in space and time have been described. Here, we report the topologically robust generation of acoustic spatiotemporal vortex pulses. We utilize an acoustic meta-grating with broken mirror symmetry which exhibits a topological phase transition with a pair of phase singularities with opposite topological charges emerging in the momentum-frequency domain. We show that these vortices are topologically robust against structural perturbations of the meta-grating and can be employed for the generation of spatiotemporal vortex pulses. Our work paves the way for studies and applications of spatiotemporal structured waves in acoustics and other wave systems.
OBJECTIVE: Observational studies have suggested a link between telomere length (TL) and epilepsy, but the direction of the effect and whether it is causal or not is still being debated. The objective of this study was to investigate the causal relationship between TL and epilepsy using Mendelian randomization (MR) analysis. METHODS: We performed a bidirectional two-sample MR analysis using pooled statistics from genome-wide association studies (GWAS) of TL and epilepsy. Additionally, we conducted a replication analysis using data from another GWAS study on epilepsy to validate our findings. The final results were analyzed using five MR methods, with the inverse-variance weighted (IVW) method as the primary outcome. We applied methods such as radial MR, MR pleiotropy residual and outlier test and MR Steiger filters to exclude outliers. Sensitivity analyses were also conducted to assess heterogeneity and pleiotropy. RESULTS: Our analysis found no evidence of a causal relationship between epilepsy and TL (all p-values >0.05). The sensitivity analysis confirms the robustness of these results. SIGNIFICANCE: In summary, our study contradicts existing observational reports by not finding any evidence to support a causal relationship between epilepsy and TL. Further research is necessary to determine the underlying mechanism behind the association observed in observational studies.
Epilepsy , Genome-Wide Association Study , Humans , Mendelian Randomization Analysis , Epilepsy/genetics , Causality , Telomere/genetics
OBJECTIVE: Observational studies have shown an association between 25-hydroxyvitamin D (25 (OH) D) and epilepsy, but it is unclear whether the association is causal. Therefore, we applied Mendelian randomization (MR) analysis to determine the causal relationship between serum 25 (OH) D levels and epilepsy. METHODS: We conducted a two-sample Mendelian randomization (TSMR) study to investigate the association between serum 25 (OH) D levels and epilepsy using pooled statistics from genome-wide association studies (GWAS). Data for 25 (OH) D came from a GWAS comprising 417,580 participants, and data for epilepsy were obtained from the International League Against Epilepsy (ILAE) consortium. Five methods were used to analyze TSMR, including the inverse variance weighting method, MR Egger method, weighted median method, simple model, and weighted model. In the sensitivity analysis, MR Egger and MR PRESSO methods were used to test for pleiotropy, inverse variance weighting and MR Egger in Cochran's Q statistics were used to test for heterogeneity. RESULTS: MR analyzed the relationship between 25 (OH) D and different types of epilepsy, and the results showed that a 1 standard deviation increase in natural log-transformed serum 25 (OH) D levels was associated with reduced risk for juvenile absence epilepsy (IVW OR = 0.985; 95% confidence interval [CI]: 0.971-0.999; P-value = 0.038). There was no apparent heterogeneity and horizontal gene pleiotropy. SIGNIFICANCE: Higher serum levels of 25 (OH) D were a protective factor for adolescent absence epilepsy, but had no effect on other types of epilepsy.
Epilepsy, Absence , Genome-Wide Association Study , Adolescent , Humans , Mendelian Randomization Analysis , Vitamin D , Calcifediol
Matrix computation, as a fundamental building block of information processing in science and technology, contributes most of the computational overheads in modern signal processing and artificial intelligence algorithms. Photonic accelerators are designed to accelerate specific categories of computing in the optical domain, especially matrix multiplication, to address the growing demand for computing resources and capacity. Photonic matrix multiplication has much potential to expand the domain of telecommunication, and artificial intelligence benefiting from its superior performance. Recent research in photonic matrix multiplication has flourished and may provide opportunities to develop applications that are unachievable at present by conventional electronic processors. In this review, we first introduce the methods of photonic matrix multiplication, mainly including the plane light conversion method, Mach-Zehnder interferometer method and wavelength division multiplexing method. We also summarize the developmental milestones of photonic matrix multiplication and the related applications. Then, we review their detailed advances in applications to optical signal processing and artificial neural networks in recent years. Finally, we comment on the challenges and perspectives of photonic matrix multiplication and photonic acceleration.
Statistical spin dynamics plays a key role in understanding the working principle for novel optical Ising machines. Here, we propose the gauge transformation for a spatial photonic Ising machine, where a single spatial phase modulator simultaneously encodes spin configurations and programs interaction strengths. Using gauge transformation, we experimentally evaluate the phase diagram of a high-dimensional spin-glass equilibrium system with 100 fully connected spins. We observe the presence of paramagnetic, ferromagnetic, and spin-glass phases and determine the critical temperature T_{c} and the critical probability p_{c} of the phase transitions, which agree well with the mean-field theory predictions. Thus, the approximation of the mean-field model is experimentally verified in the spatial photonic Ising machine. Furthermore, we discuss the phase transition in parallel with solving combinatorial optimization problems during the cooling process and identify that the spatial photonic Ising machine is robust with sufficient many-spin interactions even when the system is associated with optical aberrations and measurement uncertainty.
In order to stabilize the extinction cross section measurement of a single nanoparticle, we propose to analyze the blurriness parameter of aperture edge images in real time, which provides a feedback to lock the sample position. Unlike the conventional spatial modulation spectroscopy (SMS) technique, a probe beam experiences both the spatial modulation by a piezo stage and the temporal modulation by a chopper. We experimentally demonstrate that the measurement uncertainty is one order magnitude less than that in the previous report. The proposed method can be readily implemented in conventional SMS systems and can help to achieve high stability for sensing based on light extinction by a single nanoparticle, which alleviate the impact from laboratory environment and increase the experimental sensitivity.
Optical computing holds significant promise of information processing with ultrahigh speed and low power consumption. Recent developments in nanophotonic structures have generated renewed interests due to the prospects of performing analog optical computing with compact devices. As one prominent example, spatial differentiation has been demonstrated with nanophotonic structures and directly applied for edge detection in image processing. However, broadband isotropic two-dimensional differentiation, which is required in most imaging processing applications, has not been experimentally demonstrated yet. Here, we establish a connection between two-dimensional optical spatial differentiation and a nontrivial topological charge in the optical transfer function. Based on this connection, we experimentally demonstrate an isotropic two-dimensional differentiation with a broad spectral bandwidth, by using the simplest photonic device, i.e. a single unpatterned interface. Our work indicates that exploiting concepts from topological photonics can lead to new opportunities in optical computing.
We investigate the time response of plasmonic spatial differentiators based on prism coupling configurations. We show that when the incident light is time-modulated, in addition to the spatial differentiation, the output field is also contributed by the signal derivative with respect to time. To reduce this impact, the incident pulse needs a steady time span, and the shortest steady time span is about 100 fs. We further show that the time modulation does not degrade the resolution of the spatial differentiation. Also, we numerically demonstrate the image processing of edge detection by the plasmonic spatial differentiator, with the time-modulated signal.
We propose a grating-based spatial differentiator to process a synthetic three-dimensional optical field, where several conventional two-dimensional optical images are stacked at multiple wavelengths. The device simultaneously enables both spatial differentiation and demultiplexing during light diffraction. We show the spatial differentiation resulting from coupling and interference of spatial modes and derive the theoretical condition for spatial differentiation based on spatial coupled-mode theory. We numerically investigate field transformation during diffraction and demonstrate spatial differentiation with image processing of edge detection for a synthetic three-dimensional optical field, where four images are stored at different wavelengths.
We propose a graphene-on-grating nanostructure to enable second-order spatial differentiation computation in the terahertz (THz) region. The differentiation operation is based on the interference between the direct reflected field and the leakage of two excited surface plasmon polaritons counter-propagating along the graphene sheet. With the spatial coupled-mode theory, we derive that the requirement for the second-order spatial differentiation is the critical coupling condition. We numerically demonstrate such an analog computation with Gaussian beams. It shows that the spatial bandwidth of the proposed differentiator is large enough such that even when the waist radius of the Gaussian beam is as narrow as w0=0.68λ (λ is the free-space wavelength), the accuracy of the differentiator is higher than 95%. The proposed differentiator is ultra-compact, with a thickness less than 0.1λ, and useful for real-time imaging applications in THz security detections.
Optical analog computing offers high-throughput low-power-consumption operation for specialized computational tasks. Traditionally, optical analog computing in the spatial domain uses a bulky system of lenses and filters. Recent developments in metamaterials enable the miniaturization of such computing elements down to a subwavelength scale. However, the required metamaterial consists of a complex array of meta-atoms, and direct demonstration of image processing is challenging. Here, we show that the interference effects associated with surface plasmon excitations at a single metal-dielectric interface can perform spatial differentiation. And we experimentally demonstrate edge detection of an image without any Fourier lens. This work points to a simple yet powerful mechanism for optical analog computing at the nanoscale.
Semiconductor nanowires supporting leaky mode resonances have been used to increase light absorption in optoelectronic applications from solar cell to photodetector and sensor. The light conventionally illuminates these devices with a wide range of different incident angles from half space. Currently, most of the investigated nanowires have centrosymmetric geometry cross section, such as circle, hexagon, and rectangle. Here we show that the absorption capability of these symmetrical nanowires has an upper limit under the half-space illumination. Based on the temporal coupled-mode equation, we develop a reciprocity theory for leaky mode resonances in order to connect the angle-dependent absorption cross section and the radiation pattern. We show that in order to exceed such a half-space limit the radiation pattern should be noncentrosymmetric and dominate in the direction reciprocal to the illumination. As an example, we design a metal trough structure to achieve the desired radiation pattern for an embedded nanowire. In comparison to a single nanowire case the trough structure indeed overcomes the half-space limit and leads to 39% and 64% absorption enhancement in TM and TE polarizations, respectively. Also the trough structure enables the enhancement over a broad wavelength range.
