Cancer-derived exosomes as novel biomarkers in metastatic gastrointestinal cancer.

Gastrointestinal cancer (GIC) is the most prevalent and highly metastatic malignant tumor and has a significant impact on mortality rates. Nevertheless, the swift advancement of contemporary technology has not seamlessly aligned with the evolution of detection methodologies, resulting in a deficit of innovative and efficient clinical assays for GIC. Given that exosomes are preferentially released by a myriad of cellular entities, predominantly originating from neoplastic cells, this confers exosomes with a composition enriched in cancer-specific constituents. Furthermore, exosomes exhibit ubiquitous presence across diverse biological fluids, endowing them with the inherent advantages of non-invasiveness, real-time monitoring, and tumor specificity. The unparalleled advantages inherent in exosomes render them as an ideal liquid biopsy biomarker for early diagnosis, prognosticating the potential development of GIC metastasis.In this review, we summarized the latest research progress and possible potential targets on cancer-derived exosomes (CDEs) in GIC with an emphasis on the mechanisms of exosome promoting cancer metastasis, highlighting the potential roles of CDEs as the biomarker and treatment in metastatic GIC.

A wideband, high-resolution vector spectrum analyzer for integrated photonics.

The analysis of optical spectra-emission or absorption-has been arguably the most powerful approach for discovering and understanding matter. The invention and development of many kinds of spectrometers have equipped us with versatile yet ultra-sensitive diagnostic tools for trace gas detection, isotope analysis, and resolving hyperfine structures of atoms and molecules. With proliferating data and information, urgent and demanding requirements have been placed today on spectrum analysis with ever-increasing spectral bandwidth and frequency resolution. These requirements are especially stringent for broadband laser sources that carry massive information and for dispersive devices used in information processing systems. In addition, spectrum analyzers are expected to probe the device's phase response where extra information is encoded. Here we demonstrate a novel vector spectrum analyzer (VSA) that is capable of characterizing passive devices and active laser sources in one setup. Such a dual-mode VSA can measure loss, phase response, and dispersion properties of passive devices. It also can coherently map a broadband laser spectrum into the RF domain. The VSA features a bandwidth of 55.1 THz (1260-1640 nm), a frequency resolution of 471 kHz, and a dynamic range of 56 dB. Meanwhile, our fiber-based VSA is compact and robust. It requires neither high-speed modulators and photodetectors nor any active feedback control. Finally, we employ our VSA for applications including characterization of integrated dispersive waveguides, mapping frequency comb spectra, and coherent light detection and ranging (LiDAR). Our VSA presents an innovative approach for device analysis and laser spectroscopy, and can play a critical role in future photonic systems and applications for sensing, communication, imaging, and quantum information processing.

Identification of Single Nucleotide Polymorphic Loci and Candidate Genes for Seed Germination Percentage in Okra under Salt and No-Salt Stresses by Genome-Wide Association Study.

Excessive soil salinity is a major stressor inhibiting crops' growth, development, and yield. Seed germination is a critical stage of crop growth and development, as well as one of the most salt-sensitive stages. Salt stress has a significant inhibitory effect on seed germination. Okra is a nutritious vegetable, but its seed germination percentage (GP) is low, whether under salt stress conditions or suitable conditions. In this study, we used 180 okra accessions and conducted a genome-wide association study (GWAS) on the germination percentage using 20,133,859 single nucleotide polymorphic (SNP) markers under 0 (CK, diluted water), 70 (treatment 1, T1), and 140 mmol/L (treatment 2, T2) NaCl conditions. Using the mixed linear model (MLM) in Efficient Mixed-model Association eXpedated (EMMAX) and Genome-wide Efficient Mixed Model Association (GEMMA) software, 511 SNP loci were significantly associated during germination, of which 167 SNP loci were detected simultaneously by both programs. Among the 167 SNPs, SNP2619493 on chromosome 59 and SNP2692266 on chromosome 44 were detected simultaneously under the CK, T1, and T2 conditions, and were key SNP loci regulating the GP of okra seeds. Linkage disequilibrium block analysis revealed that nsSNP2626294 (C/T) in Ae59G004900 was near SNP2619493, and the amino acid changes caused by nsSNP2626294 led to an increase in the phenotypic values in some okra accessions. There was an nsSNP2688406 (A/G) in Ae44G005470 near SNP2692266, and the amino acid change caused by nsSNP2688406 led to a decrease in phenotypic values in some okra accessions. These results indicate that Ae59G004900 and Ae44G005470 regulate the GP of okra seeds under salt and no-salt stresses. The gene expression analysis further demonstrated these results. The SNP markers and genes that were identified in this study will provide reference for further research on the GP of okra, as well as new genetic markers and candidate genes for cultivating new okra varieties with high GPs under salt and no-salt stress conditions.

TransVFS: A spatio-temporal local-global transformer for vision-based force sensing during ultrasound-guided prostate biopsy.

Robot-assisted prostate biopsy is a new technology to diagnose prostate cancer, but its safety is influenced by the inability of robots to sense the tool-tissue interaction force accurately during biopsy. Recently, vision based force sensing (VFS) provides a potential solution to this issue by utilizing image sequences to infer the interaction force. However, the existing mainstream VFS methods cannot realize the accurate force sensing due to the adoption of convolutional or recurrent neural network to learn deformation from the optical images and some of these methods are not efficient especially when the recurrent convolutional operations are involved. This paper has presented a Transformer based VFS (TransVFS) method by leveraging ultrasound volume sequences acquired during prostate biopsy. The TransVFS method uses a spatio-temporal local-global Transformer to capture the local image details and the global dependency simultaneously to learn prostate deformations for force estimation. Distinctively, our method explores both the spatial and temporal attention mechanisms for image feature learning, thereby addressing the influence of the low ultrasound image resolution and the unclear prostate boundary on the accurate force estimation. Meanwhile, the two efficient local-global attention modules are introduced to reduce 4D spatio-temporal computation burden by utilizing the factorized spatio-temporal processing strategy, thereby facilitating the fast force estimation. Experiments on prostate phantom and beagle dogs show that our method significantly outperforms existing VFS methods and other spatio-temporal Transformer models. The TransVFS method surpasses the most competitive compared method ResNet3dGRU by providing the mean absolute errors of force estimation, i.e., 70.4 ± 60.0 millinewton (mN) vs 123.7 ± 95.6 mN, on the transabdominal ultrasound dataset of dogs.

Chidamide improves gefitinib treatment outcomes in NSCLC by attenuating recruitment and immunosuppressive function of myeloid-derived suppressor cells.

Clinical resistance to EGFR tyrosine kinase inhibitors in non-small-cell lung cancer (NSCLC) remains a significant challenge. Recent studies have indicated that the number of myeloid-derived suppressor cells (MDSCs) increases following gefitinib treatment, correlating with a poor patient response in NSCLC. Our study revealed that gefitinib treatment stimulates the production of CCL2, which subsequently enhances monocyte (M)-MDSC migration to tumor sites. Chidamide, a selective inhibitor of the histone deacetylase subtype, counteracted the gefitinib-induced increase in CCL2 levels in tumor cells. Additionally, chidamide down-regulated the expression of CCR2 in M-MDSCs, inhibiting their migration. Furthermore, chidamide attenuated the immunosuppressive function of M-MDSCs both alone and in combination with gefitinib. Chidamide also alleviated tumor immunosuppression by reducing the number of M-MDSCs in LLC-bearing mice, thereby enhancing the antitumor efficacy of gefitinib. In conclusion, our findings suggest that chidamide can improve gefitinib treatment outcomes, indicating that MDSCs are promising targets in NSCLC.

Design of an optimized Alvarez lens based on the fifth-order polynomial combination.

This paper proposes an optimized design of the Alvarez lens by utilizing a combination of three fifth-order X-Y polynomials. It can effectively minimize the curvature of the lens surface to meet the manufacturing requirements. The phase modulation function and aberration of the proposed lens are evaluated by using first-order optical analysis. Simulations compare the proposed lens with the traditional Alvarez lens in terms of surface curvature, zoom capability, and imaging quality. The results demonstrate the exceptional performance of the proposed lens, achieving a remarkable 26.36% reduction in the maximum curvature of the Alvarez lens (with a coefficient A value of 4×10-4 and a diameter of 26 mm) while preserving its original zoom capability and imaging quality.

Preliminary evaluation for ultrasound-guided targeted prostate biopsy using a portable surgical robot: Ex vivo results.

BACKGROUND: Robotic systems are increasingly used to enhance clinical outcomes in prostate intervention. To evaluate the clinical value of the proposed portable robot, the robot-assisted and robot-targeted punctures were validated experimentally. METHOD: The robot registration utilising the electromagnetic tracker achieves coordinate transformation from the ultrasound (US) image to the robot. Subsequently, Transrectal ultrasound (TRUS)-guided phantom trials were conducted for robot-assisted, free-hand, and robot-targeted punctures. RESULTS: The accuracy of robot registration was 0.95 mm, and the accuracy of robot-assisted, free-hand, and robot-targeted punctures was 2.38 ± 0.64 mm, 3.11 ± 0.72 mm, and 3.29 ± 0.83 mm sequentially. CONCLUSION: The registration method has been successfully applied to robot-targeted puncture. Current results indicate that the accuracy of robot-targeted puncture is slightly inferior to that of manual operations. Moreover, in manual operation, robot-assisted puncture improves the accuracy of free-hand puncture. Accuracy superior to 3.5 mm demonstrates the clinical applicability of both robot-assisted and robot-targeted punctures.

Image restoration for optical zooming system based on Alvarez lenses.

Alvarez lenses are known for their ability to achieve a broad range of optical power adjustment by utilizing complementary freeform surfaces. However, these lenses suffer from optical aberrations, which restrict their potential applications. To address this issue, we propose a field of view (FOV) attention image restoration model for continuous zooming. In order to simulate the degradation of optical zooming systems based on Alvarez lenses (OZA), a baseline OZA is designed where the polynomial for the Alvarez lenses consists of only three coefficients. By computing spatially varying point spread functions (PSFs), we simulate the degraded images of multiple zoom configurations and conduct restoration experiments. The results demonstrate that our approach surpasses the compared methods in the restoration of degraded images across various zoom configurations while also exhibiting strong generalization capabilities under untrained configurations.

Surpassing the nonlinear conversion efficiency of soliton microcombs.

Laser frequency combs are enabling some of the most exciting scientific endeavours in the twenty-first century, ranging from the development of optical clocks to the calibration of the astronomical spectrographs used for discovering Earth-like exoplanets. Dissipative Kerr solitons generated in microresonators currently offer the prospect of attaining frequency combs in miniaturized systems by capitalizing on advances in photonic integration. Most of the applications based on soliton microcombs rely on tuning a continuous-wave laser into a longitudinal mode of a microresonator engineered to display anomalous dispersion. In this configuration, however, nonlinear physics precludes one from attaining dissipative Kerr solitons with high power conversion efficiency, with typical comb powers amounting to ~1% of the available laser power. Here we demonstrate that this fundamental limitation can be overcome by inducing a controllable frequency shift to a selected cavity resonance. Experimentally, we realize this shift using two linearly coupled anomalous-dispersion microresonators, resulting in a coherent dissipative Kerr soliton with a conversion efficiency exceeding 50% and excellent line spacing stability. We describe the soliton dynamics in this configuration and find vastly modified characteristics. By optimizing the microcomb power available on-chip, these results facilitate the practical implementation of a scalable integrated photonic architecture for energy-efficient applications.

A repeat-dose toxicity study of human umbilical cord mesenchymal stem cells in NOG mice by intravenous injection.

BACKGROUND: Stem cell-based therapies have demonstrated great potential in several clinical trials. However, safety data on stem cell application remain inadequate. This study evaluated the toxicity of human umbilical cord mesenchymal stem cells (hUC-MSCs) in NOD/Shi-scid/IL-2 Rγnull (NOG) mice. RESEARCH DESIGN AND METHODS: Mice were administered hUC-MSCs intravenously at doses of 3.5 × 106 cells/kg and 3.5 × 107 cells/kg. Toxicity was assessed by clinical observation, behavioral evaluation, pathology, organ weight, and histopathology. We determined the distribution of hUC-MSCs using a validated qPCR method and colonization using immunohistochemistry. RESULTS: No significant abnormal effects on clinical responses, body weight, or food intake were observed in the mice, except for two in the high-dose group that died during the last administration. Mouse activity in the high-dose group decreased 6 h after the first administration. Terminal examination revealed dose-dependent changes in hematology. The mice in the high-dose group displayed pulmonary artery wall plaques and mild alveolar wall microthrombi. hUC-MSCs colonized primarily the lung tissues and were largely distributed there 24 h after the final administration. CONCLUSIONS: The no observed adverse effect level for intravenous administration of hUC-MSCs in NOG mice over a period of 3 w was 3.5 × 106 cells/kg.

Elevating Second Near-Infrared Photothermal Conversion Efficiency of Hollow Gold Nanorod for a Precise Theranostic of Orthotopic Bladder Cancer.

The second near-infrared (NIR-II) window laser-activated agents have attracted broad interest in an orthotopic cancer theranostic. However, developing NIR-II photothermal agents (PTAs) with advanced photothermal conversion efficiency (PTCE) and tumor-specific response elevation remains a crucial challenge. Herein, a hollow gold nanorod (AuHNR) with a strong localized surface plasmon resonance (LSPR) peak in the NIR-II window was coated with MnO2 and chitosan to obtain AuHNR@MnO2@CS (termed AuMC) by a one-step method. Upon exposure to the tumor microenvironment (TME), the overexpressed GSH triggered degradation of the MnO2 layer to release Mn2+ and resulted in the PTCE elevation owing to exposure of the AuHNR. Consequently, photoacoustic and magnetic resonance imaging for accurate diagnosis, Mn2+-mediated chemodynamic therapy, and AuHNR elevating PT therapy for precise treatment could be achieved. Both in vitro and in vivo experiments confirmed the good performance of the AuMC on an orthotopic bladder cancer precise theranostic. This study provided NIR-II activated, TME-response PT conversion efficiency enhanced PTAs and offered a tumor-selective theranostic agent for orthotopic bladder cancer in clinical application.

Compact lithium niobate microring resonators in the ultrahigh Q/V regime.

Lithium niobate (LN) is a promising material for future complex photonic-electronic circuits, with wide applications in such fields as communications, sensing, quantum optics, and computation. LN took a great stride toward compact photonic integrated circuits (PICs) with the development of partially etched LN on insulator (LNOI) waveguides. However, integration density is still limited for future highly compact PICs, owing to the partial etching nature of their waveguides. Here, we demonstrate a fully etched LN PIC platform, which, for the first time to our knowledge, simultaneously achieves ultralow propagation loss and compact circuit size. The tightly confined fully etched LN waveguides with smooth sidewalls allow us to bring the bending radius down to 20 µm (corresponding to 1 THz free spectral range). We have achieved compact high Q microring resonators with Q/V of 8.7 × 104 µm-3, almost one order of magnitude larger than previous demonstrations. The statistical mean propagation losses of our LN waveguides is 8.5 dB/m (corresponding to a mean Q factor of 4.9 × 106), even with a small bending radius of 40 µm. Our compact and ultralow-loss LN platform shows great potential in future miniaturized multifunctional integration systems. As complementary evidence to show the utility of our platform, we demonstrate soliton microcombs with an ultrahigh repetition rate of 500 GHz in LN.

Hyperparametric Oscillation via Bound States in the Continuum.

Optical hyperparametric oscillation based on the third-order nonlinearity is one of the most significant mechanisms to generate coherent electromagnetic radiation and produce quantum states of light. Advances in dispersion-engineered high-Q microresonators allow for generating signal waves far from the pump and decrease the oscillation power threshold to submilliwatt levels. However, the pump-to-signal conversion efficiency and absolute signal power are low, fundamentally limited by parasitic mode competition and attainable cavity intrinsic Q to coupling Q ratio, i.e., Q_{i}/Q_{c}. Here, we use Friedrich-Wintgen bound states in the continuum (BICs) to overcome the physical challenges in an integrated microresonator-waveguide system. As a result, on-chip coherent hyperparametric oscillation is generated in BICs with unprecedented conversion efficiency and absolute signal power. This work not only opens a path to generate high-power and efficient continuous-wave electromagnetic radiation in Kerr nonlinear media but also enhances the understanding of a microresonator-waveguide system-an elementary unit of modern photonics.

Paper-based microfluidics in sweat detection: from design to application.

Sweat, as a sample that includes a lot of biochemical information, is good for non-invasive monitoring. In recent years, there have been an increasing number of studies on in situ monitoring of sweat. However, there are still some challenges for the continuous analysis of samples. As a hydrophilic, easy-to-process, environmentally friendly, inexpensive and easily accessible material, paper is an ideal substrate material for making in situ sweat analysis microfluidics. This review introduces the development of paper as a sweat analysis microfluidic substrate material, focusing on the advantages of the structural characteristics of paper, trench design and equipment integration applications to expand the design and research ideas for the development of in situ sweat detection technology.

NIR-II-triggered doxorubicin release for orthotopic bladder cancer chemo-photothermal therapy.

Intravesical instillation has been widely utilized for bladder cancer treatment in clinic. However, due to the bladder mucosal barrier, its poor penetration efficiency and drug utilization limit the clinical therapeutic effectiveness and result in a high recurrence rate. Therefore, designing an efficient and controllable drug delivery nanoplatform is of great significance for bladder cancer treatment. Non-invasive therapy based on near-infrared-II (NIR-II) photothermal therapy (PTT) conduces to overcome bladder mucosal barrier and enhance drug delivery. Also, the photothermal nanomaterials, Au Hollow Nanorods (AuHNRs), demonstrate strong photothermal properties and drug loading capacity. Herein, a quaternized chitosan N-(2-hydroxyl)propyl-3-trimethyl ammonium chitosan chloride (HTCC)-modified nanocarrier Dox/NH4HCO3@AuHNRs-HTCC (DNAH) was designed for controlled drug release and enhanced penetration. The drug loading capacity of DNAH reached 117.20%. Also, the thermal decomposition of NH4HCO3 realized NIR-II-triggered gas-driven drug burst release, and the doxorubicin release was 2.79 times higher within 1 h after NIR-II irradiation. Also, the HTCC-modified nanocarriers significantly enhanced the bladder mucosal permeability as well as long-term drug retention, and the penetration efficiency of DNAH increased by 144%. In the orthotopic bladder cancer model, the tumor suppression rate and mouse survival time were significantly improved. DNAH showed potent inhibition of the orthotopic bladder tumor growth owing to the enhanced penetration and drug delivery. This work presents a potential drug delivery nanocarrier, which is promising for optimized bladder mucosal permeability and controlled drug burst release.

CoLi-BA: Compact Linearization based Solver for Bundle Adjustment.

Bundle adjustment (BA) is widely used in SLAM and SfM, which are key technologies in Augmented Reality. For real-time SLAM and large-scale SfM, the efficiency of BA is of great importance. This paper proposes CoLi-BA, a novel and efficient BA solver that significantly improves the optimization speed by compact linearization and reordering. Specifically, for each reprojection function, the redundant matrix representation of Jacobian is replaced with a tiny 3D vector, by which the computational complexity, memory storage, and cache missing for Hessian matrix construction and Schur complement are significantly reduced. Besides, we also propose a novel reordering strategy to improve the cache efficiency for Schur complement. Experiments on diverse datasets show that the speed of the proposed CoLi-BA is five times that of Ceres and two times that of g2o without sacrificing accuracy. We further verify the effectiveness by porting CoLi-BA to the open-source SLAM and SfM systems. Even when running the proposed solver in a single thread, the local BA of SLAM only takes about 20ms on a desktop PC, and the reconstruction of SfM with seven thousand photos only takes half an hour. The source code is available on the webpage: https://github.com/zju3dv/CoLi-BA.

Differential phase reconstruction of microcombs.

Measuring microcombs in amplitude and phase provides unique insight into the nonlinear cavity dynamics, but spectral phase measurements are experimentally challenging. Here, we report a linear heterodyne technique assisted by electro-optic downconversion that enables differential phase measurement of such spectra with unprecedented sensitivity (-50 dBm) and bandwidth coverage (>110 nm in the telecommunications range). We validate the technique with a series of measurements, including single-cavity and photonic molecule microcombs.

Optical linewidth of soliton microcombs.

Soliton microcombs provide a versatile platform for realizing fundamental studies and technological applications. To be utilized as frequency rulers for precision metrology, soliton microcombs must display broadband phase coherence, a parameter characterized by the optical phase or frequency noise of the comb lines and their corresponding optical linewidths. Here, we analyse the optical phase-noise dynamics in soliton microcombs generated in silicon nitride high-Q microresonators and show that, because of the Raman self-frequency shift or dispersive-wave recoil, the Lorentzian linewidth of some of the comb lines can, surprisingly, be narrower than that of the pump laser. This work elucidates information about the physical limits in phase coherence of soliton microcombs and illustrates a new strategy for the generation of spectrally coherent light on chip.

Coherent supercontinuum generation in all-normal dispersion Si3N4 waveguides.

Spectral broadening of optical frequency combs with high repetition rate is of significant interest in optical communications, radio-frequency photonics and spectroscopy. Silicon nitride waveguides (Si3N4) in the anomalous dispersion region have shown efficient supercontinuum generation spanning an octave-bandwidth. However, the broadening mechanism in this regime is usually attained with femtosecond pulses in order to maintain the coherence. Supercontinuum generation in the normal dispersion regime is more prone to longer (ps) pulses, but the implementation in normal dispersion silicon nitride waveguides is challenging as it possesses strong requirements in propagation length and losses. Here, we experimentally demonstrate the use of a Si3N4 waveguide to perform coherent spectral broadening using pulses in the picosecond regime with high repetition rate. Moreover, our work explores the formation of optical wave breaking using a higher energy pulse which enables the generation of a coherent octave spanning spectrum. These results offer a new prospect for coherent broadening using long duration pulses and replacing bulky optical components.

A One-Step Electropolymerized Biomimetic Polypyrrole Membrane-Based Electrochemical Sensor for Selective Detection of Valproate.

Bipolar disorder is a chronic mental disease with a heavy social and economic burden that causes extreme mood swings in patients. Valproate is a first-line drug for bipolar disorder patients to stabilize their daily mood. However, an excessive amount of valproate in the blood could induce severe adverse effects, which necessitates the monitoring of blood valproate levels for patients. Here, we developed an innovative electrochemical sensor for selective and simple detection of valproate based on a molecularly imprinted polymer membrane via one-step electropolymerization. Gold nanoparticles were electrochemically modified to the screen-printed electrode under the selective membrane to enhance its conductivity and stability. The successfully fabricated biosensor was characterized by scanning electron microscopy, cyclic voltammetry, and differential pulse voltammetry methods. The binding of the target molecules to the valproate-customized biomimetic polypyrrole membrane blocks cavities in the membrane and alters its electric properties, which can be detected as a decrease in the peak current by differential pulse voltammetry method. The peak current change presents a great log-linear response to the valproate concentration around the therapeutic window. The limit of detection of this method was 17.48 µM (LOD, S/N = 3) and the sensitivity was 31.86 µM µA-1. Furthermore, the biosensors exhibited both satisfying specificity with the interference of other psychological pharmaceutical drugs and uniformity among sensors, indicating their potential and reliability in translational application. This simple and reliable method of sensing valproate molecules primarily provides an exceptional solution to valproate point-of-care testing in clinical practice.