2D Graphene Oxide Films Expand Functionality of Photonic Chips.

On-chip integration of 2D materials with unique structures and properties endow integrated devices with new functionalities and improved performance. With high flexibility in ways to modify its properties and compatibility with integrated platforms, graphene oxide (GO) is an exceptionally attractive 2D material for hybrid integrated photonic chips. Here, by harnessing unique property changes induced by photothermal effects in 2D GO films, novel functionalities beyond the capability of photonic integrated circuits are demonstrated. These include all-optical control and tuning, optical power limiting, and nonreciprocal light transmission. The 2D layered GO films are integrated onto photonic chips with precise control of their thickness and size. Benefitting from the broadband optical response of 2D GO films, all three functionalities feature a very wide operational optical bandwidth. By fitting the experimental results with theory, the changes in GO film properties induced by the photothermal effects are analyzed, revealing interesting insights about the physics of 2D GO films. These results highlight the versatility of 2D GO films in implementing new functions for integrated photonic devices for a wide range of applications.

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.

The real-world treatment characteristic and efficacy of immune checkpoint inhibitors in non-small cell lung cancer: Data from a retrospective cohort study.

BACKGROUND: The efficacy and prognosis of immune checkpoint inhibitors (ICIs) remain unresolved issues. Here, we assessed the treatment characteristics and efficacy of ICIs in non-small cell lung cancer (NSCLC) using real-world data and evaluated the predictive value of factors, including programmed death-ligand 1 (PD-L1) expression, for the clinical outcome of ICIs in NSCLC. METHODS: Analyzed data was collected from hospitalized patients in the West China Hospital of Sichuan University between January 2017 and March 2023. The Kaplan-Meier method was utilized for analyzing real-world progression-free survival (rwPFS), while Cox regression models was employed to access the correlation between the efficacy of immunotherapy and sociodemographic characteristics, disease information, and characteristics of ICI treatment. RESULTS: A total of 545 patients were included in the retrospective study and characteristics of immunotherapy varied significantly among PD-L1 expression groups. The median rwPFS for the entire population was 9.76 months. Subgroup analyses revealed that patients with high PD-L1 expression, early TNM stage, first-line immunotherapy, EGFR wild-type and those who have not received radiotherapy and targeted therapy previously were more likely to have better rwPFS. Furthermore, multivariate Cox regression analyses identified PD-L1 expression, EGFR mutation status and previous radiotherapy as the most influential predictors of the response to ICI treatment. CONCLUSIONS: This study presents the real-world experience of Chinese NSCLC patients undergoing ICI treatment, offering guidance for clinical decision-making based on various patient conditions, preferences, and indications for ICIs, through the evaluation of immunotherapy efficacy and predictors in NSCLC patients.

The rupture risk of intracranial saccular aneurysm: a case-control study based on a three-dimensional computed tomography angiography model.

Background: Assessing the risk of rupture in intracranial aneurysms is crucial. Advancements in medical imaging now allow for three-dimensional (3D) assessments of aneurysms, providing a more detailed understanding of their morphology and associated risks. This study aimed to compare the 3D morphological parameters of ruptured and unruptured intracranial saccular aneurysms (ISAs) using computed tomography angiography (CTA) and to analyze risk factors linked to ISA rupture. Methods: This retrospective case-control study included patients diagnosed with ISAs via CTA, for which data were sourced from both the Emergency Department and Inpatient Unit in The First Affiliated Hospital of Jinan University. The patients were categorized into rupture and unrupture groups. We used 3D-Slicer (version 5.2.2, Slicer Community) to construct morphological models of the ISAs and their parent arteries. These models facilitated assessments of intracranial aneurysmal volume (IAV), aneurysmal surface area (ASA), and maximum sectional area (MSA). Differences in 3D morphological parameters between ruptured and unruptured ISAs were then analyzed. For statistical analysis, we first performed single factor analysis on the data, constructed a receiver operating characteristic (ROC) curve one by one with statistically significant parameters, and screened out ROC curves that met the sample requirements. Second, we performed multiparameter logistic regression analysis to construct a ROC curve model and analyzed its predictive performance. Results: The analysis encompassed 97 patients comprising 97 ISAs diagnosed from March 2016 to March 2022. Significant differences in morphological parameters were observed between the rupture and unrupture groups (P<0.05), including IAV, ASA, MSA, IAV/diameter (IAV/D), IAV/neck width (IAV/N), MSA/diameter (MSA/D), MSA/neck width (MSA/N), ASA/neck width (ASA/N), and ASA/MSA. It was found that the IAV, ASA, and MSA values of the rupture group were larger than those of the unrupture group. Meanwhile, the IAV/D, IAV/N, MSA/D, MSA/N, and ASA/N values were larger in the rupture group, while ASA/MSA and ASA/IAV were smaller. Conclusions: This study underscores the significance of specific morphological indicators, such as ASA/N and ASA/MSA, in predicting the rupture risk of ISAs. The IAV, MSA, and ASA parameters, especially in relation to diameter and neck width, provide crucial insights into the rupture potential of ISAs.

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.

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.

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.

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.

Comparison of Microcomb-Based Radio-Frequency Photonic Transversal Signal Processors Implemented with Discrete Components Versus Integrated Chips.

RF photonic transversal signal processors, which combine reconfigurable electrical digital signal processing and high-bandwidth photonic processing, provide a powerful solution for achieving adaptive high-speed information processing. Recent progress in optical microcomb technology provides compelling multi-wavelength sources with a compact footprint, yielding a variety of microcomb-based RF photonic transversal signal processors with either discrete or integrated components. Although they operate based on the same principle, the processors in these two forms exhibit distinct performances. This paper presents a comparative investigation of their performances. First, we compare the performances of state-of-the-art processors, focusing on the processing accuracy. Next, we analyze various factors that contribute to the performance differences, including the tap number and imperfect response of experimental components. Finally, we discuss the potential for future improvement. These results provide a comprehensive comparison of microcomb-based RF photonic transversal signal processors implemented using discrete and integrated components and provide insights for their future development.

Hydroformylation of pyrolysis oils to aldehydes and alcohols from polyolefin waste.

Waste plastics are an abundant feedstock for the production of renewable chemicals. Pyrolysis of waste plastics produces pyrolysis oils with high concentrations of olefins (>50 weight %). The traditional petrochemical industry uses several energy-intensive steps to produce olefins from fossil feedstocks such as naphtha, natural gas, and crude oil. In this work, we demonstrate that pyrolysis oil can be used to produce aldehydes through hydroformylation, taking advantage of the olefin functionality. These aldehydes can then be reduced to mono- and dialcohols, oxidized to mono- and dicarboxylic acids, or aminated to mono- and diamines by using homogeneous and heterogeneous catalysis. This route produces high-value oxygenated chemicals from low-value postconsumer recycled polyethylene. We project that the chemicals produced by this route could lower greenhouse gas emissions ~60% compared with their production through petroleum feedstocks.

Epigenetic regulation of stem cells in lung cancer oncogenesis and therapy resistance.

Epigenetics plays an important role in regulating stem cell signaling, as well as in the oncogenesis of lung cancer and therapeutic resistance. Determining how to employ these regulatory mechanisms to treat cancer is an intriguing medical challenge. Lung cancer is caused by signals that cause aberrant differentiation of stem cells or progenitor cells. The different pathological subtypes of lung cancer are determined by the cells of origin. Additionally, emerging studies have demonstrated that the occurrence of cancer treatment resistance is connected to the hijacking of normal stem cell capability by lung cancer stem cells, especially in the processes of drug transport, DNA damage repair, and niche protection. In this review, we summarize the principles of the epigenetic regulation of stem cell signaling in relation to the emergence of lung cancer and resistance to therapy. Furthermore, several investigations have shown that the tumor immune microenvironment in lung cancer affects these regulatory pathways. And ongoing experiments on epigenetics-related therapeutic strategies provide new insight for the treatment of lung cancer in the future.

Graphene oxide for photonics, electronics and optoelectronics.

Graphene oxide (GO) was initially developed to emulate graphene, but it was soon recognized as a functional material in its own right, addressing an application space that is not accessible to graphene and other carbon materials. Over the past decade, research on GO has made tremendous advances in material synthesis and property tailoring. These, in turn, have led to rapid progress in GO-based photonics, electronics and optoelectronics, paving the way for technological breakthroughs with exceptional performance. In this Review, we provide an overview of the optical, electrical and optoelectronic properties of GO and reduced GO on the basis of their chemical structures and fabrication approaches, together with their applications in key technologies such as solar energy harvesting, energy storage, medical diagnosis, image display and optical communications. We also discuss the challenges of this field, together with exciting opportunities for future technological advances.

Neutralizing IL-8 potentiates immune checkpoint blockade efficacy for glioma.

Malignant gliomas are largely refractory to immune checkpoint blockade (ICB) therapy. To explore the underlying immune regulators, we examine the microenvironment in glioma and find that tumor-infiltrating T cells are mainly confined to the perivascular cuffs and express high levels of CCR5, CXCR3, and programmed cell death protein 1 (PD-1). Combined analysis of T cell clustering with T cell receptor (TCR) clone expansion shows that potential tumor-killing T cells are mainly categorized into pre-exhausted/exhausted and effector CD8+ T subsets, as well as cytotoxic CD4+ T subsets. Notably, a distinct subpopulation of CD4+ T cells exhibits innate-like features with preferential interleukin-8 (IL-8) expression. With IL-8-humanized mouse strain, we demonstrate that IL-8-producing CD4+ T, myeloid, and tumor cells orchestrate myeloid-derived suppressor cell infiltration and angiogenesis, which results in enhanced tumor growth but reduced ICB efficacy. Antibody-mediated IL-8 blockade or the inhibition of its receptor, CXCR1/2, unleashes anti-PD-1-mediated antitumor immunity. Our findings thus highlight IL-8 as a combinational immunotherapy target for glioma.

Third-Order Optical Nonlinearities of 2D Materials at Telecommunications Wavelengths.

All-optical signal processing based on nonlinear optical devices is promising for ultrafast information processing in optical communication systems. Recent advances in two-dimensional (2D) layered materials with unique structures and distinctive properties have opened up new avenues for nonlinear optics and the fabrication of related devices with high performance. This paper reviews the recent advances in research on third-order optical nonlinearities of 2D materials, focusing on all-optical processing applications in the optical telecommunications band near 1550 nm. First, we provide an overview of the material properties of different 2D materials. Next, we review different methods for characterizing the third-order optical nonlinearities of 2D materials, including the Z-scan technique, third-harmonic generation (THG) measurement, and hybrid device characterization, together with a summary of the measured n2 values in the telecommunications band. Finally, the current challenges and future perspectives are discussed.

Prediction of Changes in Tumor Regression during Radiotherapy for Nasopharyngeal Carcinoma by Using the Computed Tomography-Based Radiomics.

This work aimed to explore the application value of computed tomography (CT)-based radiomics in predicting changes in tumor regression during radiotherapy for nasopharyngeal carcinoma. In this work, 144 patients with nasopharyngeal carcinoma who underwent concurrent chemoradiotherapy (CCRT) in our hospital from January 2015 to December 2021 were selected. The patients were divided into a radiosensitive group (79 cases) and an insensitive group (65 cases) according to the tumor volume shrinkage during radiotherapy. The 3D Slicer 4.10.2 software was used to delineate the tumor region of interest (ROI), and a total of 1223 radiomics features were extracted using the radiomics module under the software. After between-group and within-group consistency tests, one-way ANOVA, and LASSO dimensionality reduction, three omics features were finally selected for the establishment of predictive models. At the same time, the age, gender, tumor T stage and N stage, hemoglobin, and albumin of the patients were collected to establish a clinical prediction model. The results showed that compared with logistic regression, decision tree, random forest, and AdaBoost models, the SVM model based on CT radiomics features had the best performance in predicting tumor regression changes during tumor radiotherapy (training group area under the receiver operating characteristic curve (AUC): 0.840 (95% confidence interval (CI): 0.764-0.916); validation group: AUC: 0.810 (95% CI: 0.676-0.944)). Compared with the supported vector machine (SVM) prediction model based on clinical features, the SVM model based on radiomics features had better performance in predicting the change of retraction during tumor radiotherapy (training group: omics feature SVM model AUC: 0.84, clinical feature SVM model: 0.78; validation group: omics feature SVM model AUC: 0.8, clinical feature SVM model: 0.58, P = 0.044). Based on the radiomics characteristics and clinical characteristics of patients, a nomo prediction map was established, and the calibration curve shows good consistency, which can be visualized to assist clinical judgment. In this work, the prediction model composed of CT-based radiomic features combined with clinical features can accurately predict withdrawal changes during tumor radiotherapy, ensuring the accuracy of treatment planning, and minimizing the number of CT scans during radiotherapy.

Photo-Thermal Tuning of Graphene Oxide Coated Integrated Optical Waveguides.

We experimentally investigate power-sensitive photo-thermal tuning (PTT) of two-dimensional (2D) graphene oxide (GO) films coated on integrated optical waveguides. We measure the light power thresholds for reversible and permanent GO reduction in silicon nitride (SiN) waveguides integrated with one and two layers of GO. For the device with one layer of GO, the power threshold for reversible and permanent GO reduction are ~20 and ~22 dBm, respectively. For the device with two layers of GO, the corresponding results are ~13 and ~18 dBm, respectively. Raman spectra at different positions of a hybrid waveguide with permanently reduced GO are characterized, verifying the inhomogeneous GO reduction along the direction of light propagation through the waveguide. The differences between the PTT induced by a continuous-wave laser and a pulsed laser are also compared, confirming that the PTT mainly depend on the average input power. These results reveal interesting features for 2D GO films coated on integrated optical waveguides, which are of fundamental importance for the control and engineering of GO's properties in hybrid integrated photonic devices.

Enhanced Spectral Broadening of Femtosecond Optical Pulses in Silicon Nanowires Integrated with 2D Graphene Oxide Films.

We experimentally demonstrate enhanced spectral broadening of femtosecond optical pulses after propagation through silicon-on-insulator (SOI) nanowire waveguides integrated with two-dimensional (2D) graphene oxide (GO) films. Owing to the strong mode overlap between the SOI nanowires and the GO films with a high Kerr nonlinearity, the self-phase modulation (SPM) process in the hybrid waveguides is significantly enhanced, resulting in greatly improved spectral broadening of the femtosecond optical pulses. A solution-based, transfer-free coating method is used to integrate GO films onto the SOI nanowires with precise control of the film thickness. Detailed SPM measurements using femtosecond optical pulses are carried out, achieving a broadening factor of up to ~4.3 for a device with 0.4-mm-long, 2 layers of GO. By fitting the experimental results with the theory, we obtain an improvement in the waveguide nonlinear parameter by a factor of ~3.5 and in the effective nonlinear figure of merit (FOM) by a factor of ~3.8, relative to the uncoated waveguide. Finally, we discuss the influence of GO film length on the spectral broadening and compare the nonlinear optical performance of different integrated waveguides coated with GO films. These results confirm the improved nonlinear optical performance of silicon devices integrated with 2D GO films.

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.

Fabrication Technologies for the On-Chip Integration of 2D Materials.

With compact footprint, low energy consumption, high scalability, and mass producibility, chip-scale integrated devices are an indispensable part of modern technological change and development. Recent advances in 2D layered materials with their unique structures and distinctive properties have motivated their on-chip integration, yielding a variety of functional devices with superior performance and new features. To realize integrated devices incorporating 2D materials, it requires a diverse range of device fabrication techniques, which are of fundamental importance to achieve good performance and high reproducibility. This paper reviews the state-of-art fabrication techniques for the on-chip integration of 2D materials. First, an overview of the material properties and on-chip applications of 2D materials is provided. Second, different approaches used for integrating 2D materials on chips are comprehensively reviewed, which are categorized into material synthesis, on-chip transfer, film patterning, and property tuning/modification. Third, the methods for integrating 2D van der Waals heterostructures are also discussed and summarized. Finally, the current challenges and future perspectives are highlighted.