Numerical optimization of auxiliary biaxial receiver to detect blind zone of pulsed coherent wind lidar.

The conventional pulsed monostatic coaxial coherent Doppler wind lidar (CDWL) has a blind detection zone of tens of meters, causing the loss of near-field wind field data. While maintaining the long-range detection capabilities of pulsed lidar, we introduce a novel auxiliary biaxial receiver (ABR) aimed at acquiring dependable coherent signals within blind zones. This is achieved by incorporating a receiver in close proximity to the monostatic coaxial transceiver (MCT), thereby mitigating end-face reflections and laser pulse tailing effects. A specific model of multiple aperture coherent wind detection is established for the ABR system without blind zone problem (BZP). The numerical simulations demonstrate that the biaxial receiver with reasonable design can meet the detection needs of the entire range of the blind zone. By using an ABR with a smaller focal length under appropriate transceiver pointing and general pointing accuracy, the BZP can be solved. The study also exhaustively obtained all parameter combinations that can solve the near-field BZP for a specific system. The results provide a new idea and engineering design guidance for the optical system design of pulsed CDWL without BZP.

Prevention and treatment of HPV-related cancer through a mRNA vaccine expressing APC-targeting antigen.

Persistent human papillomavirus (HPV) infection is associated with multiple malignancies. Developing therapeutic vaccines to eliminate HPV-infected and malignant cells holds significant value. In this study, we introduced a lipid nanoparticle encapsulated mRNA vaccine expressing tHA-mE7-mE6. Mutations were introduced into E6 and E7 of HPV to eliminate their tumourigenicity. A truncated influenza haemagglutinin protein (tHA), which binds to the CD209 receptor on the surface of dendritic cells (DCs), was fused with mE7-mE6 in order to allow efficient uptake of antigen by antigen presenting cells. The tHA-mE7-mE6 (mRNA) showed higher therapeutic efficacy than mE7-mE6 (mRNA) in an E6 and E7+ tumour model. The treatment resulted in complete tumour regression and prevented tumour formation. Strong CD8+ T-cell immune response was induced, contributing to preventing and curing of E6 and E7+ tumour. Antigen-specific CD8+ T were found in spleens, peripheral blood and in tumours. In addition, the tumour infiltration of DC and NK cells were increased post therapy. In conclusion, this study described a therapeutic mRNA vaccine inducing strong anti-tumour immunity in peripheral and in tumour microenvironment, holding promising potential to treat HPV-induced cancer and to prevent cancer recurrence.

Improving Vehicle Heading Angle Accuracy Based on Dual-Antenna GNSS/INS/Barometer Integration Using Adaptive Kalman Filter.

High-accuracy heading angle is significant for estimating autonomous vehicle attitude. By integrating GNSS (Global Navigation Satellite System) dual antennas, INS (Inertial Navigation System), and a barometer, a GNSS/INS/Barometer fusion method is proposed to improve vehicle heading angle accuracy. An adaptive Kalman filter (AKF) is designed to fuse the INS error and the GNSS measurement. A random sample consensus (RANSAC) method is proposed to improve the initial heading angle accuracy applied to the INS update. The GNSS heading angle obtained by a dual-antenna orientation algorithm is additionally augmented to the measurement variable. Furthermore, the kinematic constraint of zero velocity in the lateral and vertical directions of vehicle movement is used to enhance the accuracy of the measurement model. The heading errors in the open and occluded environment are 0.5418° (RMS) and 0.636° (RMS), which represent reductions of 37.62% and 47.37% compared to the extended Kalman filter (EKF) method, respectively. The experimental results demonstrate that the proposed method effectively improves the vehicle heading angle accuracy.

Digital Twin Modeling of Flexible Perovskite Nano-Films with In-Situ Mechanical Microscopy Validation.

Flexible perovskite solar cells introduce opportunities for high throughput, high specific weight, and short energy payback time photovoltaics. However, they require additional investigation into their mechanical resiliency. This work investigates the mechanical properties and behaviors of perovskite thin films and builds a robust model for future research. A two-pronged approach was utilized. Perovskite thin films were flexed in a three-point bend mode with in-situ SEM. Novel insights into the perovskite mechanical behaviors with varying substrate layers were gained. Modeling and validation, the second prong, was completed with finite element analysis. Model coupons of the imaged perovskite architectures were built, with sensitivity analysis completed to provide mechanical property estimates. The results demonstrate that mechanical degradation of perovskite thin films on polyethylene terephthalate (PET) primarily presents as a crack in the grain boundaries between crystals. Perovskite thin films on Indium Tin Oxide (ITO) and PET primarily crack in a periodic pattern regardless of the placement of perovskite crystals.

mRNA vaccines encoding fusion proteins of monkeypox virus antigens protect mice from vaccinia virus challenge.

The recent outbreaks of mpox have raised concerns over the need for effective vaccines. However, the current approved vaccines have either been associated with safety concerns or are in limited supply. mRNA vaccines, which have shown high efficacy and safety against SARS-CoV-2 infection, are a promising alternative. In this study, three mRNA vaccines are developed that encode monkeypox virus (MPXV) proteins A35R and M1R, including A35R extracellular domain -M1R fusions (VGPox 1 and VGPox 2) and a mixture of encapsulated full-length mRNAs for A35R and M1R (VGPox 3). All three vaccines induce early anti-A35R antibodies in female Balb/c mice, but only VGPox 1 and 2 generate detectable levels of anti-M1R antibodies at day 7 after vaccination. However, all three mRNA vaccine groups completely protect mice from a lethal dose of vaccinia virus (VACV) challenge. A single dose of VGPox 1, 2, and 3 provide protection against the lethal viral challenge within 7 days post-vaccination. Long-term immunity and protection were also observed in all three candidates. Additionally, VGPox 2 provided better passive protection. These results suggest that the VGPox series vaccines enhance immunogenicity and can be a viable alternative to current whole-virus vaccines to defend against mpox.

Stretchable Photodiodes with Polymer-Engineered Semiconductor Nanowires for Wearable Photoplethysmography.

Healthcare systems worldwide have been stressed to provide sufficient resources to serve the increasing and aging population in our society. The situation became more challenging at the time of pandemic. Technology advancement, especially the adoption of wearable health monitoring devices, has provided an important supplement to current clinical equipment. Most health monitoring devices are rigid, however, human tissues are soft. Such a difference has prohibited intimate contact between the two and jeopardized wearing comfortableness, which hurdles measurement accuracy especially during longtime usage. Here, we report a soft and stretchable photodiode that can conformally adhere onto the human body without any pressure and measure cardiovascular variables for an extended period with higher reliability than commercial devices. The photodiode used a composite light absorber consisting of an organic bulk heterojunction embedded into an elastic polymer matrix. It is discovered that the elastic polymer matrix not only improves the morphology of the bulk heterojunction for obtaining the desired mechanical properties but also alters its electronic band structure and improves the electrical properties that lead to a reduced dark current and enhanced photovoltage in the stretchable photodiode. The work has demonstrated high fidelity measurements and longtime monitoring of heat rate variability and oxygen saturation, potentially enabling next-generation wearable photoplethysmography devices for point-of-care diagnosis of cardiovascular diseases in a more accessible and affordable way.

A Treg-specific long noncoding RNA maintains immune-metabolic homeostasis in aging liver.

Regulatory T (Treg) cells modulate several aging-related liver diseases. However, the molecular mechanisms regulating Treg function in this context are unknown. Here we identified a long noncoding RNA, Altre (aging liver Treg-expressed non-protein-coding RNA), which was specifically expressed in the nucleus of Treg cells and increased with aging. Treg-specific deletion of Altre did not affect Treg homeostasis and function in young mice but caused Treg metabolic dysfunction, inflammatory liver microenvironment, liver fibrosis and liver cancer in aged mice. Depletion of Altre reduced Treg mitochondrial integrity and respiratory capacity, and induced reactive oxygen species accumulation, thus increasing intrahepatic Treg apoptosis in aged mice. Moreover, lipidomic analysis identified a specific lipid species driving Treg aging and apoptosis in the aging liver microenvironment. Mechanistically, Altre interacts with Yin Yang 1 to orchestrate its occupation on chromatin, thereby regulating the expression of a group of mitochondrial genes, and maintaining optimal mitochondrial function and Treg fitness in the liver of aged mice. In conclusion, the Treg-specific nuclear long noncoding RNA Altre maintains the immune-metabolic homeostasis of the aged liver through Yin Yang 1-regulated optimal mitochondrial function and the Treg-sustained liver immune microenvironment. Thus, Altre is a potential therapeutic target for the treatment of liver diseases affecting older adults.

Observation of Long-Lived Charge-Separated States in Anthraquinone-Phenothiazine Electron Donor-Acceptor Dyads: Transient Optical and Electron Paramagnetic Resonance Spectroscopic Studies.

We prepared a series of phenothiazine (PTZ)-anthraquinone (AQ) electron donor-acceptor dyads to study the relationship between molecular structures and the possibility of charge transfer (CT) and intersystem crossing (ISC). As compared to the previously reported PTZ-AQ dyad with a direct connection of two units via a C-N single bond, the PTZ and AQ units are connected via a p-phenylene or p-biphenylene linker. Conformation restriction is imposed by attaching ortho-methyl groups on the phenylene linker. UV-vis absorption spectra indicate electronic coupling between the PTZ and AQ units in the dyads without conformation restriction. Different from the previously reported PTZ-AQ, thermally activated delayed fluorescence (TADF) is observed for the dyads containing one phenylene linker (PTZ-Ph-AQ and PTZ-PhMe-AQ). The prompt fluorescence lifetime in cyclohexane is exceptionally long (τPF = 62.0 ns, population ratio: 99.2%) and 245.0 ns (93.5%) for PTZ-Ph-AQ and PTZ-PhMe-AQ, respectively (normally τPF <20 ns); the delayed fluorescence lifetimes for these two dyads were determined as τDF = 2.4 µs (6.5%) and 7.6 µs (0.8%), respectively. For the dyad containing a biphenylene linker (PTZ-Ph2Me-AQ), no TADF was observed. Charge-separated (CS) states were observed for PTZ-Ph-AQ and PTZ-PhMe-AQ, and the lifetimes were determined as 7.0 and 1.3 µs, respectively, indicating the triplet spin multiplicity of the CS state. The 3CS state lifetimes are shortened to 100 ns and 440 ns for the two dyads, respectively, in the polar solvent acetonitrile. For dyads with a longer linker, i.e., PTZ-Ph2Me-AQ, the CS state lifetime is not sensitive to solvent polarity (τCS = 1.8 and 1.3 µs in cyclohexane and acetonitrile, respectively). In reference dyads, where the PTZ unit is oxidized to sulfoxide, no CT absorption band and TADF were observed, which is attributed to the increased CS state energy (>3 eV) becoming higher than that of the AQ triplet (3AQ*) state (ca. 2.7 eV). These experimental evidence show that the presence of 1CS, 3CS, and 3LE (LE: locally excited) states sharing similar energy is essential for the occurrence of TADF. Population of the long-lived 3CS state (with a lifetime of a few µs) does not produce by itself TADF, because the ISC process of 1CS→3CS is nonsufficient. Femtosecond transient absorption spectra show that charge separation (CS) occurs readily (<5 ps) for most dyads, even in nonpolar solvents. Nanosecond pulsed laser-excited time-resolved electron paramagnetic resonance (TREPR) spectra show that either a spin correlated radical pair (SCRP) is formed, with the electron exchange energy 2J = +2.14 mT, or radical pairs with stronger interaction, |2J| > 6.57 mT. These studies are useful for in-depth understanding of the CS and ISC in compact electron donor-acceptor dyads and for design of efficient TADF emitters.

Metabolites and gene expression in the myocardium of fasting rats in an acute hypoxic environment.

With the rising demand for entry to extremely high altitudes (HAs), rapid adaptability to extremely hypoxic environments is a challenge that we need to explore. Fasting was used to evaluate acute hypoxia tolerance at HA and was proven to be an effective method for improving the survival rate at extreme HA. Our experiments also showed that fasting pretreatment for 72 h significantly increased the 24 h survival rate of rats at 7620 m from 10 to 85% and protected the myocardium cells of rats. Here, we compared the metabolites and gene expression in the myocardium of SD rats pretreated with fasting and nonfasting at normal altitude and extreme HA. Our findings demonstrated that the dynamic contents of detected differential metabolites (DMs) between different rat groups were consistent with the expression of differentially expressed genes (DEGs), and DM clusters also showed strong correlations with DEG clusters. DM clusters related to amino acids and lipids were significantly lower in the fasting groups, and the correlated DEG clusters were enriched in mitotic pathways, including CDK1, CDC7, NUF2, and MCM6, suggesting that fasting can attenuate mitotic processes in cardiac tissues and reduce the synthesis of amino acids and lipids. L-Glutamine-related metabolites were particularly low at extreme HA without pretreatment but were normal in the fasting groups. The DEGs in the cluster related to L-glutamine-related metabolites were enriched for T-cell receptor V(D)J recombination, the Hippo signaling pathway, the Wnt signaling pathway, the cGMP-PKG signaling pathway, and the mTOR signaling pathway and were significantly downregulated, indicating that the content of L-glutamine decreased at extreme HA, while fasting increased it to adapt to the environment. Moreover, abundant fatty acids were detected when rats were exposed to extreme HA without pretreatment. Our study revealed the fasting and hypoxic environment-related factors in SD rats and provided new insights into the genetic and molecular characteristics in the myocardium, which is critical to developing more potential rapid adaptation methods to extreme HA.

Engineering Extracellular Matrix-Bound Nanovesicles Secreted by Three-Dimensional Human Mesenchymal Stem Cells.

Extracellular matrix (ECM) in the human tissue contains vesicles, which are defined as matrix-bound nanovesicles (MBVs). MBVs serve as one of the functional components in ECM, recapitulating part of the regulatory roles and in vivo microenvironment. In this study, extracellular vesicles from culture supernatants (SuEVs) and MBVs are isolated from the conditioned medium or ECM, respectively, of 3D human mesenchymal stem cells. Nanoparticle tracking analysis shows that MBVs are smaller than SuEVs (100-150 nm). Transmission electron microscopy captures the typical cup shape morphology for both SuEVs and MBVs. Western blot reveals that MBVs have low detection of some SuEV markers such as syntenin-1. miRNA analysis of MBVs shows that 3D microenvironment enhances the expression of miRNAs such as miR-19a and miR-21. In vitro functional analysis shows that MBVs can facilitate human pluripotent stem cell-derived forebrain organoid recovery after starvation and promote high passage fibroblast proliferation. In macrophage polarization, 2D MBVs tend to suppress the pro-inflammatory cytokine IL-12ß, while 3D MBVs tend to enhance the anti-inflammatory cytokine IL-10. This study has the significance in advancing the understanding of the bio-interface of nanovesicles with human tissue and the design of cell-free therapy for treating neurological disorders such as ischemic stroke.

A Review of Skin-Wearable Sensors for Non-Invasive Health Monitoring Applications.

The early detection of fatal diseases is crucial for medical diagnostics and treatment, both of which benefit the individual and society. Portable devices, such as thermometers and blood pressure monitors, and large instruments, such as computed tomography (CT) and X-ray scanners, have already been implemented to collect health-related information. However, collecting health information using conventional medical equipment at home or in a hospital can be inefficient and can potentially affect the timeliness of treatment. Therefore, on-time vital signal collection via healthcare monitoring has received increasing attention. As the largest organ of the human body, skin delivers significant signals reflecting our health condition; thus, receiving vital signals directly from the skin offers the opportunity for accessible and versatile non-invasive monitoring. In particular, emerging flexible and stretchable electronics demonstrate the capability of skin-like devices for on-time and continuous long-term health monitoring. Compared to traditional electronic devices, this type of device has better mechanical properties, such as skin conformal attachment, and maintains compatible detectability. This review divides the health information that can be obtained from skin using the sensor aspect's input energy forms into five categories: thermoelectrical signals, neural electrical signals, photoelectrical signals, electrochemical signals, and mechanical pressure signals. We then summarize current skin-wearable health monitoring devices and provide outlooks on future development.

Heterologous boost with mRNA vaccines against SARS-CoV-2 Delta/Omicron variants following an inactivated whole-virus vaccine.

The coronavirus SARS-CoV-2 has mutated quickly and caused significant global damage. This study characterizes two mRNA vaccines ZSVG-02 (Delta) and ZSVG-02-O (Omicron BA.1), and associating heterologous prime-boost strategy following the prime of a most widely administrated inactivated whole-virus vaccine (BBIBP-CorV). The ZSVG-02-O induces neutralizing antibodies that effectively cross-react with Omicron subvariants. In naïve animals, ZSVG-02 or ZSVG-02-O induce humoral responses skewed to the vaccine's targeting strains, but cellular immune responses cross-react to all variants of concern (VOCs) tested. Following heterologous prime-boost regimes, animals present comparable neutralizing antibody levels and superior protection against Delta and Omicron BA.1variants. Single-boost only generated ancestral and omicron dual-responsive antibodies, probably by "recall" and "reshape" the prime immunity. New Omicron-specific antibody populations, however, appeared only following the second boost with ZSVG-02-O. Overall, our results support a heterologous boost with ZSVG-02-O, providing the best protection against current VOCs in inactivated virus vaccine-primed populations.

Integration of anaerobic digestion with heat Pump: Machine learning-based technical and environmental assessment.

Anaerobic digestion (AD)-based biogas production mitigates the environmental footprint of organic wastes (e.g., food waste and sewage sludge) and facilitates a circular economy. The work proposed an integrated system where the thermal energy demand of an AD is supplied using an air source heat pump (ASHP). The proposed system is compared to a baseline system, where the thermal energy is supplied by a natural gas-based heating system. Several machine learning models are developed for predicting biogas production, among which the Gaussian Process Regression (GPR) showed a superior performance (R2 = 0.84 and RMSE = 0.0755 L gVS-1 day-1). The GPR model further informed a thermodynamic model of the ASHP, which revealed the maximum biogas yield to be approximately 0.585 L.gVS-1.day-1 at an optimal temperature of 55 °C (thermophilic). Subsequently, life cycle assessment showed that ASHP-based AD heating systems achieved 28.1 % (thermophilic) and 36.8 % (mesophilic) carbon abatement than the baseline system.

Atomic-level flatness on oxygen-free copper surface in lapping and chemical mechanical polishing.

Oxygen-free copper (OFC) serves as a core component of high-end manufacturing, and requires high surface quality. It is always a significant challenge to manufacture high-quality atomic-level surfaces. In this study, SiO2 nanospheres with good dispersibility were prepared and a late-model environmentally friendly chemical mechanical polishing (CMP) slurry was developed. The CMP slurry consists of SiO2 nanospheres, CeO2 nanospheres, H2O2, NaHCO3, polyaspartic acid and deionized water. After CMP, the average roughness (Sa) of the OFC wafer reached 0.092 nm with an area of 50 × 50 µm2. Atomic-level flatness on the oxygen-free copper surface was acquired, which has never been reported before. Moreover, the mechanical removal mechanism of abrasive particles and the chemical reactions during lapping and CMP are proposed in detail. The thickness and composition of the damaged layer after lapping and polishing were analyzed. The lapping-damaged layer consists of a lattice distortion region, moiré fringes, grain boundary, superlattice and edge dislocations, and the polishing-damaged layer contains a handful of stacking faults with single-layer or multi-layer atoms. The chemical action involves three reactions: oxidation, corrosion and chelation. The processing method and its mechanistic explanation pave the way for the fabrication of high-performance OFC surfaces for use in vacuum, aerospace, military and electronic industries.

Cardiac-specific overexpression of Claudin-5 exerts protection against myocardial ischemia and reperfusion injury.

Claudin-5 has recently attracted increasing attention by its potential as a novel treatment target in the early stage of heart failure. However, whether Claudin-5 produces beneficial effects on myocardial ischemia and reperfusion (IR) injury has not been elucidated yet. In this study, we identified reduced levels of Claudin-5 in the hearts of mice subjected to acute myocardial IR injury and murine HL-1 cardiomyocytes subjected to hypoxia and reoxygenation (HR). We then constructed cardiac-specific Cldn5-overexpressing mice using an adeno-associated virus (AAV9) vector and demonstrated that Cldn5 overexpression ameliorated cardiac dysfunction and myocardial damage in mice subjected to myocardial IR injury. Moreover, Cldn5 overexpression attenuated myocardial oxidative stress (DHE and protein levels of Nrf2, HO-1, and NQO1), inflammatory response (levels of MPO, F4/80, Ly6C, and circulating inflammatory cells), mitochondrial dysfunction (protein levels of PGC-1α, NRF1, and TFAM), endoplasmic reticulum stress (protein levels of GRP78, ATF6, and CHOP and p-PERK), energy metabolism disorder (p-AMPK and ACC), and apoptosis (TUNEL assay and protein levels of Bax and Bcl2) in mice subjected to myocardial IR. Next, we generated Cldn5 knockdown cells by lentiviral shRNA and observed that Cldn5 knockdown inhibited cell viability and affected the expression or activation of these IR-related signalings in HL-1 cardiomyocytes subjected to HR. Mechanistically, SIRT1 was proved to be involved in regulating the expression of Claudin-5 by co-immunoprecipitation analysis and Sirt1 knockdown experiments. Our data demonstrated that targeting Claudin-5 may represent a promising approach for preventing and treating acute myocardial IR injury.

RNA m6A demethylase ALKBH5 regulates the development of γδ T cells.

γδ T cells are an abundant T cell population at the mucosa and are important in providing immune surveillance as well as maintaining tissue homeostasis. However, despite γδ T cells' origin in the thymus, detailed mechanisms regulating γδ T cell development remain poorly understood. N6-methyladenosine (m6A) represents one of the most common posttranscriptional modifications of messenger RNA (mRNA) in mammalian cells, but whether it plays a role in γδ T cell biology is still unclear. Here, we show that depletion of the m6A demethylase ALKBH5 in lymphocytes specifically induces an expansion of γδ T cells, which confers enhanced protection against gastrointestinal Salmonella typhimurium infection. Mechanistically, loss of ALKBH5 favors the development of γδ T cell precursors by increasing the abundance of m6A RNA modification in thymocytes, which further reduces the expression of several target genes including Notch signaling components Jagged1 and Notch2. As a result, impairment of Jagged1/Notch2 signaling contributes to enhanced proliferation and differentiation of γδ T cell precursors, leading to an expanded mature γδ T cell repertoire. Taken together, our results indicate a checkpoint role of ALKBH5 and m6A modification in the regulation of γδ T cell early development.

Analysis of international competitiveness of the China's licorice industry from the perspective of global trade.

ETHNOPHARMACOLOGICAL RELEVANCE: Licorice is a multi-purpose plant raw material, which is widely used in the pharmaceutical industry and food industry, cosmetic industry, etc. It has a wide application in various countries and regions around the world. AIM OF STUDY: This paper studied the trade situation of licorice-related products among major countries and regions in the world, providing a practical reference for the sustainable development of the global licorice industry. MATERIALS AND METHODS: The licorice trade data of licorice-related products came from the United Nations Commodity Trade Database and China Customs data. We analyzed the world's major trading countries by using international market share (IMS), trade competitiveness index (TC), average export price (AEP) and average import price (AIP), and analyzed global trade flows with chord diameter. RESULTS: Uzbekistan, Kazakhstan and Iran mainly export licorice raw materials and low value-added products. China is both a producer and a consumer of licorice raw materials and licorice products. The processing trade of the licorice industry in China has advantages, and the structure of import and export trade has been continuously improved. The United States, France, Germany and other developed countries are still important consumers who rely on the intellectual property rights and brand advantages of licorice products, which have stronger global trade radiation capacity. CONCLUSIONS: China's trade structure has been optimized and its industrial competitiveness has been enhanced. China's experience can be used for reference by other countries, especially those with rich licorice resources among the SCO members.

Life cycle assessment of biodiesel production from rapeseed oil: Influence of process parameters and scale.

Biodiesel has the potential to mitigate the fossil fuel-related carbon emission and energy insecurity challenges. There are limited studies examining the impacts of biodiesel production scales on the environmental impacts, while such information will be valuable for guiding practical system design. This work applied the approach of life cycle assessment to evaluate the environmental impacts of biodiesel production from rapeseed oil which accounts for 80% of the European biofuel market. It was shown that the centralized large-scale and localized small-scale biodiesel production schemes have annual global warming potential (GWP) of 2.63 and 2.88 tCO2-eq/t biodiesel, where the rapeseed agriculture stage caused more than 65% carbon emissions. Sensitivity analysis revealed a high dependence of GWP on rapeseed yields, glycerol re-utilization strategy, and nitrogen nutrient in fertilizer. An alternative scenario was proposed for the large- and small-scale systems that could reduce carbon emissions by 14.1% and 33.6%.

The Discovery of Novel Circulating Cancer-Related Cells in Circulation Poses New Challenges to Microfluidic Devices for Enrichment and Detection.

Circulating tumor cells (CTCs) enumeration has been widely used as a surrogate predictive marker for early diagnoses, the evaluation of chemotherapy efficacy, and cancer prognosis. Microfluidic technologies for CTCs enrichment and detection have been developed and commercialized as automation platforms. Currently, in addition to CTCs, some new types of circulating cancer-related cells (e.g., CCSCs, CTECs, CAMLs, and heterotypic CTC clusters) in circulation are also reported to be correlated to cancer diagnosis, metastasis, or prognosis. And they widely differ from the conventional CTCs in positive markers, cellular morphology, or size, which presents a new technological challenge to microfluidic devices that use affinity-based capture methods or size-based filtration methods for CTCs detection. This review focuses on the biological and physical properties as well as clinical significance of the novel circulating cancer-related cells, and discusses the challenges of their discovery to microfluidic chip for enrichment. Finally, the current challenges of CTCs detection in clinical application and future opportunities are also discussed.

Not every sample is efficient: Analogical generative adversarial network for unpaired image-to-image translation.

Image translation is to learn an effective mapping function that aims to convert an image from a source domain to another target domain. With the proposal and further developments of generative adversarial networks (GANs), the generative models have achieved great breakthroughs. The image-to-image (I2I) translation methods can mainly fall into two categories: Paired and Unpaired. The former paired methods usually require a large amount of input-output sample pairs to perform one-side image translation, which heavily limits its practicability. To address the lack of the paired samples, CycleGAN and its extensions utilize the cycle-consistency loss to provide an elegant and generic solution to perform the unpaired I2I translation between two domains based on unpaired data. This thread of dual learning-based methods usually adopts the random sampling strategy for optimizing and does not consider the content similarity between samples. However, not every sample is efficient and effective for the desired optimization and leads to optimal convergence. Inspired by analogical learning, which is to utilize the relationships and similarities between sample observations, we propose a novel generic metric-based sampling strategy to effectively select samples from different domains for training. Besides, we introduce a novel analogical adversarial loss to force the model to learn from the effective samples and alleviate the influence of the negative samples. Experimental results on various vision tasks have demonstrated the superior performance of the proposed method. The proposed method is also a generic framework that can be easily extended to other I2I translation methods and result in a performance gain.