11 TOPS photonic convolutional accelerator for optical neural networks.

Convolutional neural networks, inspired by biological visual cortex systems, are a powerful category of artificial neural networks that can extract the hierarchical features of raw data to provide greatly reduced parametric complexity and to enhance the accuracy of prediction. They are of great interest for machine learning tasks such as computer vision, speech recognition, playing board games and medical diagnosis1-7. Optical neural networks offer the promise of dramatically accelerating computing speed using the broad optical bandwidths available. Here we demonstrate a universal optical vector convolutional accelerator operating at more than ten TOPS (trillions (1012) of operations per second, or tera-ops per second), generating convolutions of images with 250,000 pixels-sufficiently large for facial image recognition. We use the same hardware to sequentially form an optical convolutional neural network with ten output neurons, achieving successful recognition of handwritten digit images at 88 per cent accuracy. Our results are based on simultaneously interleaving temporal, wavelength and spatial dimensions enabled by an integrated microcomb source. This approach is scalable and trainable to much more complex networks for demanding applications such as autonomous vehicles and real-time video recognition.

Calcium-induced upregulation of energy metabolism heats neurons during neural activity.

Cellular temperature affects every biochemical reaction, underscoring its critical role in cellular functions. In neurons, temperature not only modulates neurotransmission but is also a key determinant of neurodegenerative diseases. Considering that the brain consumes a disproportionately high amount of energy relative to its weight, neural circuits likely generate a lot of heat, which can increase cytosolic temperature. However, the changes in temperature within neurons and the mechanisms of heat generation during neural excitation remain unclear. In this study, we achieved simultaneous imaging of Ca2+ and temperature using the genetically encoded indicators, B-GECO and B-gTEMP. We then compared the spatiotemporal distributions of Ca2+ responses and temperature. Following neural excitation induced by veratridine, an activator of the voltage-gated Na+ channel, we observed an approximately 2 °C increase in cytosolic temperature occurring 30 s after the Ca2+ response. The temperature elevation was observed in the non-nuclear region, while Ca2+ increased throughout the cell body. Moreover, this temperature increase was suppressed under Ca2+-free conditions and by inhibitors of ATP synthesis. These results indicate that Ca2+-induced upregulation of energy metabolism serves as the heat source during neural excitation.

Magnetic resonance imaging-based approaches for detecting the efficacy of combining therapy following VEGFR-2 and PD-1 blockade in a colon cancer model.

BACKGROUND: Angiogenesis inhibitors have been identified to improve the efficacy of immunotherapy in recent studies. However, the delayed therapeutic effect of immunotherapy poses challenges in treatment planning. Therefore, this study aims to explore the potential of non-invasive imaging techniques, specifically intravoxel-incoherent-motion diffusion-weighted imaging (IVIM-DWI) and blood oxygenation level-dependent magnetic resonance imaging (BOLD-MRI), in detecting the anti-tumor response to the combination therapy involving immune checkpoint blockade therapy and anti-angiogenesis therapy in a tumor-bearing animal model. METHODS: The C57BL/6 mice were implanted with murine MC-38 cells to establish colon cancer xenograft model, and randomly divided into the control group, anti-PD-1 therapy group, and combination therapy group (VEGFR-2 inhibitor combined with anti-PD-1 antibody treatment). All mice were imaged before and, on the 3rd, 6th, 9th, and 12th day after administration, and pathological examinations were conducted at the same time points. RESULTS: The combination therapy group effectively suppressed tumor growth, exhibiting a significantly higher tumor inhibition rate of 69.96% compared to the anti-PD-1 group (56.71%). The f value and D* value of IVIM-DWI exhibit advantages in reflecting tumor angiogenesis. The D* value showed the highest correlation with CD31 (r = 0.702, P = 0.001), and the f value demonstrated the closest correlation with vessel maturity (r = 0.693, P = 0.001). While the BOLD-MRI parameter, R2* value, shows the highest correlation with Hif-1α(r = 0.778, P < 0.001), indicating the capability of BOLD-MRI to evaluate tumor hypoxia. In addition, the D value of IVIM-DWI is closely related to tumor cell proliferation, apoptosis, and infiltration of lymphocytes. The D value was highly correlated with Ki-67 (r = - 0.792, P < 0.001), TUNEL (r = 0.910, P < 0.001) and CD8a (r = 0.918, P < 0.001). CONCLUSIONS: The combination of VEGFR-2 inhibitors with PD-1 immunotherapy shows a synergistic anti-tumor effect on the mouse colon cancer model. IVIM-DWI and BOLD-MRI are expected to be used as non-invasive approaches to provide imaging-based evidence for tumor response detection and efficacy evaluation.

Investigating causal associations between pneumonia and lung cancer using a bidirectional mendelian randomization framework.

BACKGROUND: Pneumonia and lung cancer are both major respiratory diseases, and observational studies have explored the association between their susceptibility. However, due to the presence of potential confounders and reverse causality, the comprehensive causal relationships between pneumonia and lung cancer require further exploration. METHODS: Genome-wide association study (GWAS) summary-level data were obtained from the hitherto latest FinnGen database, COVID-19 Host Genetics Initiative resource, and International Lung Cancer Consortium. We implemented a bidirectional Mendelian randomization (MR) framework to evaluate the causal relationships between several specific types of pneumonia and lung cancer. The causal estimates were mainly calculated by inverse-variance weighted (IVW) approach. Additionally, sensitivity analyses were also conducted to validate the robustness of the causalty. RESULTS: In the MR analyses, overall pneumonia demonstrated a suggestive but modest association with overall lung cancer risk (Odds ratio [OR]: 1.21, 95% confidence interval [CI]: 1.01 - 1.44, P = 0.037). The correlations between specific pneumonia types and overall lung cancer were not as significant, including bacterial pneumonia (OR: 1.07, 95% CI: 0.91 - 1.26, P = 0.386), viral pneumonia (OR: 1.00, 95% CI: 0.95 - 1.06, P = 0.891), asthma-related pneumonia (OR: 1.18, 95% CI: 0.92 - 1.52, P = 0.181), and COVID-19 (OR: 1.01, 95% CI: 0.78 - 1.30, P = 0.952). Reversely, with lung cancer as the exposure, we observed that overall lung cancer had statistically crucial associations with bacterial pneumonia (OR: 1.08, 95% CI: 1.03 - 1.13, P = 0.001) and viral pneumonia (OR: 1.09, 95% CI: 1.01 - 1.19, P = 0.037). Sensitivity analysis also confirmed the robustness of these findings. CONCLUSION: This study has presented a systematic investigation into the causal relationships between pneumonia and lung cancer subtypes. Further prospective study is warranted to verify these findings.

Influence of diffraction distance on image restoration in deep learning networks.

In recent years, significant advancements have been made in the field of computational imaging, particularly due to the application of deep learning methods to imaging problems. However, only a few studies related to deep learning have examined the impact of diffraction distance on image restoration. In this paper, the effect of diffraction distance on image restoration is investigated based on the PhysenNet neural network. A theoretical framework for diffraction images at various diffraction distances is provided along with the applicable propagators. In the experiment, the PhysenNet network is selected to train on diffraction images with different distances and the impact of using different propagators on network performance is studied. Optimal propagators required to recover images at different diffraction distances are determined. Insights obtained through these experiments can expand the scope of neural networks in computational imaging.

Effect of the optical power factors on the laser-linewidth measurements.

In this paper, the effects of optical power factors like laser power, the powers of the laser beams in the two arms of the optical system, and the power of the photodetector on laser-linewidth measurements are studied. From the experiments, it can be found that when the average optical input power for the photodetector is about 50% of its linear saturation power, the measured laser line width is a minimum. When the optical powers of the laser beams in the two arms are equal in short-delay self-homodyne system, the measured laser line width is narrowest. In the low output power range of the laser, its line width decreases with the increase in optical power. By comparing experiments, it can also be clear that the conventional measurement method is seriously affected by different noise types, which causes the measured line width to become wider and not change even if the laser linewidth changes. However, based on the short-delay coherent envelope method, the measured coherent envelope changes significantly when the laser line width changes slightly, and its corresponding laser-linewidth values are also clearly visible. It confirms the low noise and high resolution of the short-delay self-homodyne coherent-envelope laser-measurement method. The outcomes of this study can provide helpful information for precision ultra-narrow laser-linewidth measurements.

Thermo-Optic Response and Optical Bistablility of Integrated High-Index Doped Silica Ring Resonators.

The engineering of thermo-optic effects has found broad applications in integrated photonic devices, facilitating efficient light manipulation to achieve various functionalities. Here, we perform both an experimental characterization and a theoretical analysis of these effects in integrated microring resonators made from high-index doped silica, which have had many applications in integrated photonics and nonlinear optics. By fitting the experimental results with theory, we obtain fundamental parameters that characterize their thermo-optic performance, including the thermo-optic coefficient, the efficiency of the optically induced thermo-optic process, and the thermal conductivity. The characteristics of these parameters are compared to those of other materials commonly used for integrated photonic platforms, such as silicon, silicon nitride, and silica. These results offer a comprehensive insight into the thermo-optic properties of doped silica-based devices. Understanding these properties is essential for efficiently controlling and engineering them in many practical applications.

Altered lncRNAs Transcriptomic Profiles in Atherosclerosis-Induced Ischemic Stroke.

Long non-coding RNAs (lncRNAs) can not only regulate gene transcription and translation, but also participate in the development of central nervous system diseases as epigenetic modification factors. However, their functional significance in atherosclerosis-induced ischemic stroke (AIIS) is unclear. The study aimed to screen out differentially expressed lncRNAs (delncRNAs), and to elucidate their potential regulatory mechanisms in the pathophysiology of AIIS. Based on the clinicopathological features and clinical images, we screened out 10 patients with AIIS and recruited 10 healthy volunteers. Then we used microarray to detect the whole blood RNA of subjects, and explored the biological functions of delncRNAs by GO and KEGG analysis. After further analyzing the delncRNAs of THP-1 stimulated with ox-LDL, selective lncRNAs were screened and a corresponding lncRNA-mRNA interaction network was constructed through co-expression analysis. We yielded 180 delncRNAs (44 up-regulated and 136 down-regulated) and 218 demRNAs (45 up-regulated and 173 down-regulated). Lnc-SCARNA8 and lnc-SNRPN-2 are the most significant elevated and decreased lncRNA in AIIS, respectively. The delncRNAs may play a significant role in ubiquitination-mediated protein degradation signaling pathways. According to lncRNA-mRNA network, the expression of vacuolar protein sorting 13 homolog B (VPS13B) and biliverdin reductase B (BLVRB) were significantly regulated. Our findings suggest that the ubiquitinated proteasome pathway, VPS13B and BLVRB may play a fundamental role in the pathological process of AIIS.

Precise laser linewidth measurement by feature extraction with short-delay self-homodyne.

We propose a precision measurement method of laser linewidth based on short-delay self-homodyne, using the second peak-valley difference (SPVD) feature of the coherent power spectrum to fit laser linewidth. The SPVD model of the self-homodyne coherent envelope spectrum was established. One-to-one correspondence among the values of SPVD, the delay length, and the laser linewidth was determined theoretically and through simulations, while the reliability and stability of the method was verified experimentally. By comparing the detected results, it is found that the fitted laser linewidth obtained by the self-homodyne system is closer to its true value than that obtained by the self-heterodyne system. Hence, the simpler structure of the short-delay self-homodyne coherent envelope laser linewidth measurement method proposed is expected to substitute the previous laser linewidth measurement method, including complex short-delay self-heterodyne coherent envelope laser linewidth measurement method and traditional self-homodyne/heterodyne laser linewidth measurement method, to achieve more precise laser linewidth value.

Full-Stokes Polarization Perfect Absorption with Diatomic Metasurfaces.

Metamaterial-based perfect absorbers provide efficient ways for selective absorption of light with both linear or circular polarizations. Perfect absorption for an arbitrary polarization requires the development of subwavelength structures absorbing efficiently elliptically polarized light, but they remain largely unexplored. Here, we design and realize experimentally novel plasmonic metasurfaces for full-Stokes polarization perfect absorption in the mid-infrared. The metasurface unit cell consists of coupled anisotropic meta-atoms forming a diatomic metamolecule. The designed plasmonic metastructures provide a strong field enhancement by at least 1 order of magnitude higher than conventional perfect absorbers. In experiment, our plasmonic metasurfaces demonstrate sharp differentiation of spectral responses for an arbitrary pair of orthogonal polarization states (linear, circular, or elliptical) providing perfect absorption for one polarization with strong reflection for its counterpart. Our results suggest a novel route for efficient control of light polarization in metasurfaces offering numerous potential applications ranging from thermal imaging to chiral molecule detection.

Hybrid anisotropic plasmonic metasurfaces with multiple resonances of focused light beams.

Plasmonic metasurfaces supporting collective lattice resonances have attracted increasing interest due to their exciting properties of strong spatial coherence and enhanced light-matter interaction. Although the focusing of light by high-numerical-aperture (NA) objectives provides an essential way to boost the field intensities, it remains challenging to excite high-quality resonances by using high-NA objectives due to strong angular dispersion. Here, we address this challenge by employing the physics of bound states in the continuum (BICs). We design a novel anisotropic plasmonic metasurface combining a two-dimensional lattice of high-aspect-ratio pillars with a one-dimensional plasmonic grating, fabricated by a two-photon polymerization technique and gold sputtering. We demonstrate experimentally multiple resonances with absorption amplitudes exceeding 80% at mid-IR using an NA = 0.4 reflective objective. This is enabled by the weak angular dispersion of quasi-BIC resonances in such hybrid plasmonic metasurfaces. Our results suggest novel strategies for designing photonic devices that manipulate focused light with a strong field concentration.

The landscape of immune checkpoint inhibitor therapy in advanced lung cancer.

BACKGROUND: The advent of immune checkpoint inhibitors (ICIs) therapy has resulted in significant survival benefits in patients with non-small-cell lung cancer (NSCLC) without increasing toxicity. However, the utilisation of immunotherapy for small-cell lung cancer (SCLC) remains unclear, with a scarcity of systematic comparisons of therapeutic effects and safety of immunotherapy in these two major lung cancer subtypes. Herein, we aimed to provide a comprehensive landscape of immunotherapy and systematically review its specific efficacy and safety in advanced lung cancer, accounting for histological types. METHODS: We identified studies assessing immunotherapy for lung cancer with predefined endpoints, including overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and treatment-related adverse events (TRAE), from PubMed, Embase, Medline, and Cochrane library. A random-effects or fixed-effect model was adopted according to different settings. RESULTS: Overall, 38 trials with 20,173 patients with lung cancer were included in this study. ICI therapy resulted in a significantly prolonged survival in both patients with NSCLC and SCLC when compared with chemotherapy (hazard ratio [HR] = 0.74; 95% confidence interval [CI], 0.70-0.79] and [HR = 0.82; 95% CI, 0.75-0.90], respectively). The magnitude of disease control and survival benefits appeared superior with ICI plus standard of care (SOC) when compared with SOC alone. OS and PFS advantages were observed only when immunotherapy was employed as the first-line treatment in patients with SCLC. CONCLUSION: ICI therapy is a promising therapeutic option in patients with NSCLC and SCLC. ICI plus SOC can be recommended as the optimal first-line treatment for patients with SCLC, and double-target ICIs combined with SOC are recommended in patients with NSCLC as both the first and subsequent lines of treatment. Additionally, non-first-line immunotherapy is not recommended in patients with SCLC.

Bound States in the Continuum in Anisotropic Plasmonic Metasurfaces.

The concept of optical bound states in the continuum (BICs) currently drives the field of dielectric resonant nanophotonics, providing an important physical mechanism for engineering high-quality (high-Q) optical resonances in high-index dielectric nanoparticles and structured dielectric metasurfaces. For structured metallic metasurfaces, realization of BICs remains a challenge associated with strong dissipative losses of plasmonic materials. Here, we suggest and realize experimentally anisotropic plasmonic metasurfaces supporting high-Q resonances governed by quasi-BIC collective resonant modes. Our metasurfaces are composed of arrays of vertically oriented double-pillar meta-molecules covered by a thin layer of gold. We engineer quasi-BIC modes and observe experimentally sharp resonances in mid-IR reflectance spectra. Our work suggests a direct route to boost the resonant field enhancement in plasmonic metasurfaces via combining a small effective mode volume of plasmonic systems with engineered high-Q resonances provided by the BIC physics, with multiple applications to enhance light-matter interaction for nano-optics and quantum photonics.

2D Layered Graphene Oxide Films Integrated with Micro-Ring Resonators for Enhanced Nonlinear Optics.

Layered 2D graphene oxide (GO) films are integrated with micro-ring resonators (MRRs) to experimentally demonstrate enhanced nonlinear optics. Both uniformly coated (1-5 layers) and patterned (10-50 layers) GO films are integrated on complementary-metal-oxide-semiconductor (CMOS)-compatible doped silica MRRs using a large-area, transfer-free, layer-by-layer GO coating method with precise control of the film thickness. The patterned devices further employ photolithography and lift-off processes to enable precise control of the film placement and coating length. Four-wave-mixing (FWM) measurements for different pump powers and resonant wavelengths show a significant improvement in efficiency of ≈7.6 dB for a uniformly coated device with 1 GO layer and ≈10.3 dB for a patterned device with 50 GO layers. The measurements agree well with theory, with the enhancement in FWM efficiency resulting from the high Kerr nonlinearity and low loss of the GO films combined with the strong light-matter interaction within the MRRs. The dependence of GO's third-order nonlinearity on layer number and pump power is also extracted from the FWM measurements, revealing interesting physical insights about the evolution of the GO films from 2D monolayers to quasi bulk-like behavior. These results confirm the high nonlinear optical performance of integrated photonic resonators incorporated with 2D layered GO films.

Advanced RF and microwave functions based on an integrated optical frequency comb source.

We demonstrate advanced transversal radio frequency (RF) and microwave functions based on a Kerr optical comb source generated by an integrated micro-ring resonator. We achieve extremely high performance for an optical true time delay aimed at tunable phased array antenna applications, as well as reconfigurable microwave photonic filters. Our results agree well with theory. We show that our true time delay would yield a phased array antenna with features that include high angular resolution and a wide range of beam steering angles, while the microwave photonic filters feature high Q factors, wideband tunability, and highly reconfigurable filtering shapes. These results show that our approach is a competitive solution to implementing reconfigurable, high performance and potentially low cost RF and microwave signal processing functions for applications including radar and communication systems.

On chip chirality-distinguishing beamsplitter.

The chirality of photons plays a fundamental role in light-matter interactions. However, a limiting factor in photonic integrated circuits is the lack of a miniaturized component, which can distinguish the chirality in a low cost and integrated manner. Herein we numerically demonstrate a chirality-distinguishing beamsplitter that can address this challenge. It consists of an integrated polarization rotator and a linear polarization beamsplitter, which together can fulfill the task of distinguishing and splitting left- and right-handed quasi-circularly polarized modes on a chip with an ultra-broadband operation range from 1.45 µm to 1.65 µm. Owning to the reciprocity, the device can emit photons with selectable spin angular momentum depending on the chosen feeding waveguide. The device is compatible with complementary metal-oxide semiconductor technology and it may open up new avenues in the fields of on-chip nano-photonics, bio-photonics and quantum information science.

Wavelength and bandwidth-tunable silicon comb filter based on Sagnac loop mirrors with Mach-Zehnder interferometer couplers.

We propose and experimentally demonstrate a wavelength and bandwidth-tunable comb filter based on silicon Sagnac loop mirrors (SLMs) with Mach-Zehnder interferometer (MZI) couplers. By thermally tuning the MZI couplers in common and differential modes, the phase shift and reflectivity of the SLMs can be changed, respectively, leading to tunable wavelength and bandwidth of the comb filter. The fabricated comb filter has 93 comb lines in the wavelength range from 1535 nm to 1565 nm spaced by ~0.322 nm. The central wavelength can be red-shifted by ~0.462 nm with a tuning efficiency of ~0.019 nm/mW. A continuously tunable bandwidth from 5.88 GHz to 24.89 GHz is also achieved with a differential heating power ranging from 0.00 mW to 0.53 mW.

High-extinction-ratio silicon polarization beam splitter with tolerance to waveguide width and coupling length variations.

We demonstrate a compact silicon polarization beam splitter (PBS) based on grating-assisted contradirectional couplers (GACCs). Over 30-dB extinction ratios and less than 1-dB insertion losses are achieved for both polarizations. The proposed PBS exhibits tolerance in width variation, and the polarization extinction ratios remain higher than 20 dB for both polarizations when the width variation is adjusted from + 10 to -10 nm. Benefiting from the enhanced coupling by the GACCs, the polarization extinction ratio can be kept higher than 15 dB and the insertion loss is lower than 2 dB for both polarizations when the coupling length varies from 30.96 to 13.76 µm.

Compact silicon photonic interleaver based on a self-coupled optical waveguide.

We propose and experimentally demonstrate a new scheme to realize an on-chip silicon photonic interleaver by using a self-coupled optical waveguide (SCOW). Benefiting from the high-order filtering property of a multistage SCOW resonator, the device has a smaller footprint and higher extinction ratio compared to conventional ring-assisted Mach-Zehnder interferometer interleavers. Its high fabrication tolerance is also demonstrated in this paper. The operation principle of the proposed interleaver is theoretically analyzed. The designed device is fabricated on a silicon-on-insulator wafer under standard complementary metal oxide semiconductor compatible fabrication processes. Experimental results show that 20 dB extinction ratio and about 8 dB insertion loss can be achieved in the entire C-band without any thermo-optic tuning, verifying the effectiveness of the proposed device as an on-chip interleaver with a compact footprint and high extinction ratio.

Analysis of an electro-optic modulator based on a graphene-silicon hybrid 1D photonic crystal nanobeam cavity.

We propose and numerically study an on-chip graphene-silicon hybrid electro-optic (EO) modulator operating at the telecommunication band, which is implemented by a compact 1D photonic crystal nanobeam (PCN) cavity coupled to a bus waveguide with a graphene sheet on top. Through electrically tuning the Fermi level of the graphene, both the quality factor and the resonance wavelength can be significantly changed, thus the in-plane lightwave can be efficiently modulated. Based on finite-difference time-domain (FDTD) simulation results, the proposed modulator can provide a large free spectral range (FSR) of 125.6 nm, a high modulation speed of 133 GHz, and a large modulation depth of ~12.5 dB in a small modal volume, promising a high performance EO modulator for wavelength-division multiplexed (WDM) optical communication systems.