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.

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.

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.

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.

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.

Thermal noise reduction in soliton microcombs via laser self-cooling.

Thermal noise usually dominates the low-frequency region of the optical phase noise of soliton microcombs, which leads to decoherence that limits many aspects of applications. In this work, we demonstrate a simple and reliable way to mitigate this noise by laser cooling with a pump laser. The key is rendering the pump laser to simultaneously excite two neighboring cavity modes from different families that are respectively red and blue detuned, one for soliton generation and the other for laser cooling.

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.

Frequency-comb-calibrated swept-wavelength interferometry.

Lasers are often used to characterize samples in a non-destructive manner and retrieve sensing information transduced in changes in amplitude and phase. In swept wavelength interferometry, a wavelength-tunable laser is used to measure the complex response (i.e. in amplitude and phase) of an optical sample. This technique leverages continuous advances in rapidly tunable lasers and is widely used for sensing, bioimaging and testing of photonic integrated components. However, the tunable laser requires an additional calibration step because, in practice, it does not tune at a constant rate. In this work, we use a self-referenced frequency comb as an optical ruler to calibrate the laser used in swept-wavelength interferometry and optical frequency domain reflectometry. This allows for realizing high-resolution complex spectroscopy over a bandwidth exceeding 10 THz. We apply the technique to the characterization of low-loss integrated photonic devices and demonstrate that the phase information can disentangle intrinsic from coupling losses in the characterization of high-Q microresonators. We also demonstrate the technique in reflection mode, where it can resolve attenuation and dispersion characteristics in integrated long spiral waveguides.

Effects of reductive inorganics and NOM on the formation of chlorite in the chlorine dioxide disinfection of drinking water.

Chlorine dioxide (ClO2) disinfection usually does not produce halogenated disinfection by-products, but the formation of the inorganic by-product chlorite (ClO2-) is a serious consideration. In this study, the ClO2- formation rule in the ClO2 disinfection of drinking water was investigated in the presence of three representative reductive inorganics and four natural organic matters (NOMs), respectively. Fe2+ and S2- mainly reduced ClO2 to ClO2- at low concentrations. When ClO2 was consumed, the ClO2- would be further reduced by Fe2+ and S2-, leading to the decrease of ClO2-. The reaction efficiency of Mn2+ with ClO2 was lower than that of Fe2+ and S2-. It might be the case that MnO2 generated by the reaction between Mn2+ and ClO2 had adsorption and catalytic oxidation on Mn2+. However, Mn2+ would not reduce ClO2-. Among the four NOMs, humic acid and fulvic acid reacted with ClO2 actively, followed by bovine serum albumin, while sodium alginate had almost no reaction with ClO2. The maximum ClO2- yields of reductive inorganics (70%) was higher than that of NOM (around 60%). The lower the concentration of reductive substances, the more ClO2- could be produced by per unit concentration of reductive substances. The results of the actual water samples showed that both reductive inorganics and NOM played an important role in the formation of ClO2- in disinfection.

Waveguide tapering for improved parametric amplification in integrated nonlinear Si3N4 waveguides.

In this paper, we propose and numerically investigate waveguide tapering to improve optical parametric amplification in integrated nonlinear Si3N4 circuits. The phase matching condition of parametric amplification changes along the length of uniform Si3N4 waveguides, due to the non-negligible propagation loss, potentially causing peak-gain wavelength shifts of more than 20 nm. By tapering the waveguide width along propagation, we can achieve a 2.5 dB higher maximum parametric gain thanks to the improved phase matching, which can also broaden the amplification bandwidth. Therefore, the length of an optimally tapered Si3N4 waveguide can be 23% shorter than a uniform one in the case of a 3.0 dB/m propagation loss and a single continuous-wavelength pump. Quasi-continuous tapers are efficient to approximate continuous ones and might simplify the fabrication of long tapered nonlinear Si3N4 waveguides, which are promising for optical signal processing and optical communications.

Si3N4 photonic integration platform at 1 µm for optical interconnects.

Vertical-cavity surface-emitting lasers (VCSELs) are the predominant technology for high-speed short-range interconnects in data centers. Most short-range interconnects rely on GaAs-based multi-mode VCSELs and multi-mode fiber links operating at 850 nm. Recently, GaAs-based high-speed single-mode VCSELs at wavelengths > 1 µm have been demonstrated, which increases the interconnect reach using a single-mode fiber while maintaining low energy dissipation. If a suitable platform for passive wavelength- and space-multiplexing were developed in this wavelength range, this single-mode technology could deliver the multi-Tb/s interconnect capacity that will be required in future data centers. In this work, we show the first passive Si3N4 platform in the 1-µm band (1030-1075 nm) with an equivalent loss < 0.3 dB/cm, which is compatible with the system requirements of high-capacity interconnects. The waveguide structure is optimized to achieve simultaneously single-mode operation and low bending radius, and we demonstrate a wide range of high-performance building blocks, including arrayed waveguide gratings, Mach-Zehnder interferometers, splitters and low-loss fiber interfaces. This technology could be instrumental in scaling up the capacity and reducing the footprint of VCSEL-based optical interconnects and, thanks to the broad transparency in the near-infrared and compatibility with the Yb fiber amplifier window, enabling new applications in other domains as optical microscopy and nonlinear optics.

High-Q Si3N4 microresonators based on a subtractive processing for Kerr nonlinear optics.

Microresonator frequency combs (microcombs) are enabling new applications in frequency synthesis and metrology - from high-speed laser ranging to coherent optical communications. One critical parameter that dictates the performance of the microcomb is the optical quality factor (Q) of the microresonator. Microresonators fabricated in planar structures such as silicon nitride (Si3N4) allow for dispersion engineering and the possibility to monolithically integrate the microcomb with other photonic devices. However, the relatively large refractive index contrast and the tight optical confinement required for dispersion engineering make it challenging to attain Si3N4 microresonators with Qs > 107 using standard subtractive processing methods - i.e. photonic devices are patterned directly on the as-deposited Si3N4 film. In this work, we achieve ultra-smooth Si3N4 microresonators featuring mean intrinsic Qs around 11 million. The cross-section geometry can be precisely engineered in the telecommunications band to achieve either normal or anomalous dispersion, and we demonstrate the generation of mode-locked dark-pulse Kerr combs as well as soliton microcombs. Such high-Qs allow us to generate 100 GHz soliton microcombs, demonstrated here for the first time in Si3N4 microresonators fabricated using a subtractive processing method. These results enhance the possibilities for co-integration of microcombs with high-performance photonic devices, such as narrow-linewidth external-cavity diode lasers, ultra-narrow filters and demultiplexers.

Low-loss high-Q silicon-rich silicon nitride microresonators for Kerr nonlinear optics.

Silicon nitride is a dielectric material widely used for applications in linear and nonlinear optics. It has an ultra-broad transparency window, low intrinsic loss, and a refractive index that allows for moderate optical field confinement in waveguides. The chemical composition of this material can be precisely set during the fabrication process, leading to an extra degree of freedom for tailoring the optical and mechanical properties of photonic chips. Silicon-rich silicon nitride waveguides are appealing for nonlinear optics, because they have a higher nonlinear Kerr coefficient and refractive index than what is possible with stoichiometric silicon nitride. This is a direct consequence of the increased silicon content. However, silicon-rich silicon nitride waveguides typically display higher absorption losses. In this Letter, we report low-loss (∼0.4 dB/cm) silicon-rich silicon nitride waveguides. The structures feature high optical confinement and can be engineered with low anomalous dispersion. We find an optimum silicon composition that, through an annealing process, overcomes optical losses associated to N-H bonds in the telecom band. Based on this technology, we successfully fabricate microresonators with mean quality factors (Q) ∼0.8×106 in the C and L bands. Broadband coherent microresonator frequency combs are generated in this platform, indicating its potential for efficient Kerr nonlinear optics.

Novel solute carrier family 26, member 3 mutation in a prenatal recurrent case with congenital chloride diarrhea.

Congenital chloride diarrhea (CCD) is an autosomal recessive hereditary disease manifested by persistent, watery, profuse diarrhea with high chloride concentration (>90 mmol/L). Postnatally, neonates suffer from hypochloremia, hyponatremia, hypokalemia, metabolic alkalosis, dehydration, developmental retardation, or even death. Prenatal diagnosis is of great importance for the prognosis of CCD. We report a prenatal recurrent case of CCD. Prenatal ultrasound revealed fetal diffuse intestinal dilation with the typical honeycomb sign and polyhydramnios with high amniotic fluid index. The whole exome capture and massively-parallel DNA sequencing showed an abnormal mutation of Solute Carrier Family 26, Member 3 (SLC26A3), c.1039G>A (p.Ala347Thr), and the mutation sites were verified by sanger sequencing. When prenatal ultrasound shows polyhydramnios and diffuse intestinal dilation, CCD should be suspected. Molecular genetic testing can be helpful for the diagnosis.

Optical bandgap engineering in nonlinear silicon nitride waveguides.

Silicon nitride is a well-established material for photonic devices and integrated circuits. It displays a broad transparency window spanning from the visible to the mid-IR and waveguides can be manufactured with low losses. An absence of nonlinear multi-photon absorption in the erbium lightwave communications band has enabled various nonlinear optic applications in the past decade. Silicon nitride is a dielectric material whose optical and mechanical properties strongly depend on the deposition conditions. In particular, the optical bandgap can be modified with the gas flow ratio during low-pressure chemical vapor deposition (LPCVD). Here we show that this parameter can be controlled in a highly reproducible manner, providing an approach to synthesize the nonlinear Kerr coefficient of the material. This holistic empirical study provides relevant guidelines to optimize the properties of LPCVD silicon nitride waveguides for nonlinear optics applications that rely on the Kerr effect.

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.

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.