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Abstract Background Uveal melanoma (UM) is the most common primary intraocular tumor in adults, and early detection is critical to improve the clinical outcome of this disease. In this study, the diagnostic effectiveness of [18F]AlF-NOTA-PRGD2 (an investigational medicinal product) positron emission tomography (PET) imaging in UM xenografts and UM patients were evaluated. The cell uptake, cell binding ability and in vitro stability of [18F]AlF-NOTA-PRGD2 were evaluated in 92-1 UM cell line. MicroPET imaging and biodistribution study of [18F]AlF-NOTA-PRGD2 were conducted in 92-1 UM xenografts. Then, UM patients were further recruited for evaluating the diagnostic effectiveness of [18F]AlF-NOTA-PRGD2 PET imaging (approval no. NCT02441972 in clinicaltrials.gov). In addition, comparison of [18F]AlF-NOTA-PRGD2 and 18F-labelled fluorodeoxyglucose ([18F]FDG) PET imaging in UM xenografts and UM patients were conducted. Results The in vitro data showed that [18F]AlF-NOTA-PRGD2 had a high cell uptake, cell binding ability and in vitro stability in 92-1 UM cell line. The in vivo data indicated that 92-1 UM tumors were clearly visualized with the [18F]AlF-NOTA-PRGD2 tracer in the subcutaneous and ocular primary UM xenografts model at 60 min post-injection. And the tumor uptake of the tracer was 2.55 ± 0.44%ID/g and 1.73 ± 0.15%ID/g at these two tissue locations respectively, at 7 days after animal model construction. The clinical data showed that tumors in UM patients were clearly visualized with the [18F]AlF-NOTA-PRGD2 tracer at 60 min post-injection. In addition, [18F]AlF-NOTA-PRGD2 tracer showed higher sensitivity and specificity for PET imaging in UM xenografts and UM patients compared to [18F]FDG tracer. Conclusion [18F]AlF-NOTA-PRGD2 PET imaging may be a more preferred approach in the diagnosis of primary UM compared to [18F]FDG PET imaging. Additionally, due to the high tumor-to-background ratio, [18F]AlF-NOTA-PRGD2 PET imaging seems also to be applicable for the diagnosis of UM patients with liver metastasis. Trial registration: ClinicalTrials.gov: NCT02441972, Registered 1 January 2012, https://clinicaltrials.gov/study/NCT02441972 .

IntroductionAcne vulgaris, one of the most common skin conditions, affects up to 85% of late adolescents, currently no universally accepted assessment system. The biomechanical properties of skin provide valuable information for the assessment and management of skin conditions. Wave-based optical coherence elastography (OCE) quantitatively assesses these properties of tissues by analyzing induced elastic wave velocities. However, velocity estimation methods require significant expertise and lengthy image processing times, limiting the clinical translation of OCE technology. Recent advances in machine learning offer promising solutions to simplify velocity estimation process.MethodsIn this study, we proposed a novel end-to-end deep-learning model, named velocity prediction network (VP-Net), aiming to accurately predict elastic wave velocity from raw OCE data of in vivo healthy and abnormal human skin. A total of 16,424 raw phase slices from 1% to 5% agar-based tissue-mimicking phantoms, 28,270 slices from in vivo human skin sites including the palm, forearm, back of the hand from 16 participants, and 580 slices of facial closed comedones were acquired to train, validate, and test VP-Net.ResultsVP-Net demonstrated highly accurate velocity prediction performance compared to other deep-learning-based methods, as evidenced by small evaluation metrics. Furthermore, VP-Net exhibited low model complexity and parameter requirements, enabling end-to-end velocity prediction from a single raw phase slice in 1.32 ms, enhancing processing speed by a factor of ∼100 compared to a conventional wave velocity estimation method. Additionally, we employed gradient-weighted class activation maps to showcase VP-Net’s proficiency in discerning wave propagation patterns from raw phase slices. VP-Net predicted wave velocities that were consistent with the ground truth velocities in agar phantom, two age groups (20s and 30s) of multiple human skin sites and closed comedones datasets.DiscussionThis study indicates that VP-Net could rapidly and accurately predict elastic wave velocities related to biomechanical properties of in vivo healthy and abnormal skin, offering potential clinical applications in characterizing skin aging, as well as assessing and managing the treatment of acne vulgaris.

IntroductionEarly diagnosis of oral squamous cell carcinoma can greatly improve treatment success rate and patient survival. Although Optical Coherence Tomography (OCT) based Angiography (OCTA) is a promising in vivo technique in oral imaging, there is a need for objective assessment of oral microvasculature.MethodsThis study aimed to demonstrate a comprehensive methodology of quantitative assessing OCTA intraoral scanning results to provide measurable, reproducible data and to avoid subjective visual interpretations. Data were collected from 37 healthy subjects in total across four intraoral sites—buccal mucosa (n = 32), labial mucosa (n = 24), floor of the mouth (n = 13), and hard palate (n = 8)—using a non-invasive swept-source OCT system. Four quantitative metrics—vessel area density, vessel skeleton density, vessel diameter index, and a newly proposed weighted Tortuosity Index—were used to assess OCTA images in oral applications.ResultsThe quadruple quantitative assessment’s repeatability was evaluated to be reliable. Analysis of a benign ulcer case revealed differences in these metrics compared to healthy cases.Discussion/ConclusionIn conclusion, we demonstrated a comprehensive method to quantify microvasculature in the oral cavity, showing considerable promise for early diagnosis and clinical management of oral diseases.

Vibrio rotiferianus is a pathogenic bacterium that is widely distributed in the ocean and can cause diseases in a variety of marine animals, including fish, shrimp and shellfish. In this study, we isolated and identified V. rotiferianus strain TO-01 from diseased Trachinotus ovatus. Infected fish exhibited a range of pathological symptoms, including lethargy in swimming, blackened body coloration, skin ulceration and erratic side swimming. Tissue section examination revealed pronounced damage to the liver, spleen and gills of the infected fish. An analysis of immune factor expression revealed a significant increase in the expression of inflammatory factors, including interleukin (IL)-1, IL-2, IL-6 receptor and IL-21, in the spleen and kidney of fish infected with TO-01 at 6 h post-infection. To gain a more in-depth comprehension of the pathogenicity and drug resistance of V. rotiferianus, we conducted whole genome sequencing. The total genome length of V. rotiferianus was 4734,075 bp, and 74 virulence factors were predicted within the genome. Most of these virulence genes were associated with bacterial adhesion and flagellar motility. A gene associated with group sensing, cqsA, and a gene associated with hemolysin, tlh, were also identified. The prediction of drug resistance genes was in agreement with the results of drug sensitivity assays, both of which indicated that TO-01 has significant resistance to β-lactams. The findings of this study significantly enhance our understanding of the pathogenic mechanism of V. rotiferianus and give crucial insights into disease prevention and control in the management of T. ovatus.

Benzophenone (BP)-type UV filters are commonly added to sunscreens and cosmetics to protect against UV radiation for human skin and hair. As a result, BPs are ubiquitous in the environment and human body, and their endocrine-disrupting characteristics have been a hot topic of discussion. However, our knowledge regarding the detrimental effects of prenatal exposure to BPs on pregnant women and their offspring remains limited. To fill this gap, we determined five BP derivatives in 600 serum samples obtained from pregnant women. All the target analytes, except 2,4-dihydroxybenzophenone (BP-1), have achieved a 100 % detection rate. The most prevalent compound was 2-hydroxy-4-methoxybenzophenone (BP-3), with a median concentration of 0.545 ng/mL. Significant and positive correlations were observed among BP derivatives, indicating both endogenous metabolism and common external sources. Utilizing Bayesian kernel machine regression (BKMR) and quantile-based g-computation (QGC) models, we found relationships between BP exposure and reduced neonatal birth weight (BW) and birth chest circumference (BC) during the third trimester. Notably, the adverse effect of BPs on birth size was sex-specific. Moreover, triglyceride (TG) was identified as a potential mediator of the effect of BPs on blood pressure, and co-exposure to BPs was linked to disruptions in thyroid hormone levels and glucose regulation. Further research is warranted to unravel the toxicity of BPs and their detrimental effects on pregnant women and fetuses.

This paper presents a broadband optical receiver that employs multiple bandwidth extension techniques in analog front-end (AFE) and has efficient digital clock and data recovery (CDR). The AFE is implemented exclusively with inverter-based stages. It consists of a shunt feedback transimpedance amplifier followed by a continuous time linear equalizer (CTLE) and variable gain amplifier (VGA). High RF value, $400\Omega $ , was employed to have better sensitivity at the cost of narrow bandwidth. Total AFE bandwidth is extended by 5.5X with CTLE peaking, series inductances between each AFE stage, and active inductor loads in the CTLE output and VGA stages. Quarter-rate, phase-locked loop (PLL) based digital CDR is implemented for clocking. The resolution of a digitally controlled oscillator (DCO) is optimized at 9-bit to balance jitter and hardware cost from the CDR. Multi-phase clock generation is accomplished by a delay locked loop (DLL). Fabricated in 28nm CMOS, the 42.7Gb/s optical receiver achieves an optical modulation amplitude (OMA) sensitivity of −3.6dBm at a bit error rate (BER) $\lt 10{^{\text {-12}}}$ , 10MHz CDR bandwidth, and 3.4pJ/bit energy efficiency.

Abstract Optical interconnects have been recognized as the most promising solution to accelerate data transmission in the artificial intelligence era. Benefiting from their cost-effectiveness, compact dimensions, and wavelength multiplexing capability, silicon microring resonator modulators emerge as a compelling and scalable means for optical modulation. However, the inherent trade-off between bandwidth and modulation efficiency hinders the device performance. Here we demonstrate a dense wavelength division multiplexing microring modulator array on a silicon chip with a full data rate of 1 Tb/s. By harnessing the two individual p-n junctions with an optimized Z-shape doping profile, the inherent trade-off of silicon depletion-mode modulators is greatly mitigated, allowing for higher-speed modulation with energy consumption of sub-ten fJ/bit. This state-of-the-art demonstration shows that all-silicon modulators can practically enable future 200 Gb/s/lane optical interconnects.

Abstract Sonodynamic therapy (SDT) is currently on critical path for glioblastoma therapeutics. SDT is a non-invasive approach utilising focused ultrasound to activate photosensitisers like 5-ALA to impede tumour growth. Unfortunately, the molecular mechanisms underlying the therapeutic functions of SDT remain enigmatic. This is primarily due to the lack of intricately optimised instrumentation capable of modulating SDT delivery to glioma cells in vitro. Consequently, very little information is available on the effects of SDT on glioma stem cells which are key drivers of gliomagenesis and recurrence. To address this, the current study has developed and validated an automated in vitro SDT system to allow the application and mapping of focused ultrasound fields under varied exposure conditions and setup configurations. The study optimizes ultrasound frequency, intensity, plate base material, thermal effect, and the integration of live cells. Indeed, in the presence of 5-ALA, focused ultrasound induces apoptotic cell death in primary patient-derived glioma cells with concurrent upregulation of intracellular reactive oxygen species. Intriguingly, primary glioma stem neurospheres also exhibit remarkably reduced 3D growth upon SDT exposure. Taken together, the study reports an in vitro system for SDT applications on tissue culture-based disease models to potentially benchmark the novel approach to the current standard-of-care.

Optical Coherence Tomography (OCT)-based angiography (OCTA) is a high-resolution, high-speed, and non-invasive imaging method that can provide vascular mapping of subcutaneous tissue up to approximately 2 mm. In dermatology applications of OCTA, handheld probes are always designed with a piece of transparent but solid contact window placed at the end of the probe to directly contact the skin for achieving better focusing between the light source and the tissue, reducing noise caused by minor movements. The pressure between the contact window and the skin is usually uncontrollable, and high external pressure affects the quality of microvascular imaging by compressing the vessels and obstructing the underlying blood flow. Therefore, it is necessary to determine a pressure range to ensure that the vessels can be fully imaged in high-quality images. In this paper, two pressure sensors were added to the existing handheld OCT probe, and the imaging probe was fixed to a metal stand and adjusted vertically to change the pressure between the probe and the tested skin site, a gradient of roughly 4 kPa (with 1–2 kPa error) increase was applied in each experiment, and the impact of pressure to the vessel was calculated. The experiment involved a total of five subjects, three areas of which were scanned (palm, back of the hand, and forearm). The vessel density was calculated to evaluate the impact of external pressure on angiography. In addition, PSNR was calculated to ensure that the quality of different tests was at a similar level. The angiography showed the highest density (about 10%) when the pressure between the contact window on the probe and the test area was between 3 and 5 kPa. As the pressure increased, the vascular density decreased, and the rate of decrease varied in different test areas. After fitting all the data points according to the different sites, the slope of the fitted line, i.e., the rate of decrease in density per unit value of pressure, was found to be 4.05% at the palm site, 6.93% at the back of the hand, and 4.55% at the forearm site. This experiment demonstrates that the pressure between the skin and contact window is a significant parameter that cannot be ignored. It is recommended that in future OCTA data collection processes and probe designs, the impact of pressure on the experiment be considered.

In the context of distribution networks, constructing 3D point cloud maps is crucial, particularly for UAV navigation and path planning tasks. Methods that utilize reflections from surfaces, such as laser and structured light, to obtain depth point clouds for surface modeling and environmental depth estimation are already quite mature in some professional scenarios. However, acquiring dense and accurate depth information typically requires very high costs. In contrast, monocular image-based depth estimation methods do not require relatively expensive equipment and specialized personnel, making them available for a wider range of applications. To achieve high precision and efficiency in UAV distribution networks, inspired by knowledge distillation, we employ a teacher–student architecture to enable efficient inference. This approach maintains high-quality depth estimation while optimizing the point cloud to obtain more precise results. In this paper, we propose KD-MonoRec, which integrates knowledge distillation into the semi-supervised MonoRec framework for UAV distribution networks. Our method demonstrates excellent performance on the KITTI dataset and performs well in collected distribution network environments.

The current methods to generate projections for structural and angiography imaging of Fourier-Domain optical coherence tomography (FD-OCT) are significantly slow for prediagnosis improvement, prognosis, real-time surgery guidance, treatments, and lesion boundary definition. This study introduced a robust ultrafast projection pipeline (RUPP) and aimed to develop and evaluate the efficacy of RUPP. RUPP processes raw interference signals to generate structural projections without the need for Fourier Transform. Various angiography reconstruction algorithms were utilized for efficient projections. Traditional methods were compared to RUPP using PSNR, SSIM, and processing time as evaluation metrics. The study used 22 datasets (hand skin: 9; labial mucosa: 13) from 8 volunteers, acquired with a swept-source optical coherence tomography system. RUPP significantly outperformed traditional methods in processing time, requiring only 0.040 s for structural projections, which is 27 times faster than traditional summation projections. For angiography projections, the best RUPP variation took 0.15 s, making it 7518 times faster than the windowed eigen decomposition method. However, PSNR decreased by 41–45% and SSIM saw reductions of 25–74%. RUPP demonstrated remarkable speed improvements over traditional methods, indicating its potential for real-time structural and angiography projections in FD-OCT, thereby enhancing clinical prediagnosis, prognosis, surgery guidance, and treatment efficacy.

Medical imaging has allowed for significant advancements in the field of ultrasound procedures over the years. However, each imaging modality exhibits distinct limitations that differently affect their accuracy. It is imperative to ensure the quality of each modality to identify and eliminate these limitations. To achieve this, a tissue-mimicking material (TMM) phantom is utilised for validation. This study aims to perform a systematic analysis of tissue-mimicking materials used for creating ultrasound phantoms. We reviewed 234 studies on the use of TMM phantoms in ultrasound that were published from 2013 to 2023 from two research databases. Our focus was on studies that discussed TMMs’ properties and fabrication for ultrasound, elastography, and flow phantoms. The screening process led to the selection of 16 out of 234 studies to include in the analysis. The TMM ultrasound phantoms were categorised into three groups based on the solvent used; each group offers a broad range of physical properties. The water-based material most closely aligns with the properties of ultrasound. This study provides important information about the materials used for ultrasound phantoms. We also compared these materials to real human tissues and found that PVA matches most of the human tissues the best.

Abstract Background A large proportion of the patients with cancer do not respond to immunotherapies. Recent studies suggested an important role for tumor-infiltrating cytotoxic T lymphocytes (CTL) in enhancing response to immunotherapy. Here, we aim to identify gene that induce proliferative and cytotoxic states of CD8+ T cells, and to investigate its effect on CAR-T cells against colorectal cancer. Methods Correlation between the expression of IFI35 with the activation and cytotoxicity of CD8+ T cells was assessed with TCGA and proteomic databases. Then we constructed murine colon cancer cells over-expressing IFI35 and tested their effect on anti-tumor immunity in both immunodeficient and immunocompetent mouse models. Flow cytometry and immunohistochemistry were performed to assess the immune microenvironment. Western blot analysis was used to identify the potential down-stream signaling pathway regulated by IFI35. We further investigated the efficacy of the rhIFI35 protein in combination with immunotherapeutic treatment. Results The transcriptional and proteomic analysis of the activation and cytotoxicity of CD8+ T cells in human cancer samples demonstrated that IFI35 expression is correlated with increased CD8+ T cell infiltration and predicted a better outcome in colorectal cancer. The number and cytotoxicity of CD8+ T cells were significantly increased in IFI35-overexpressing tumors. Mechanistically, we identified that the IFNγ-STAT1-IRF7 axis stimulated IFI35 expression, and that IFI35-mediated regulation of CD8+ T cell proliferation and cytotoxicity was dependent on PI3K/AKT/mTOR signaling pathway in vitro. Furthermore, IFI35 protein enhanced the efficacy of CAR-T cells against colorectal cancer cells. Conclusion Our findings identify IFI35 as a new biomarker that can enhance the proliferation and function of CD8+ T cells, as well as increase the efficacy of CAR-T cells against colorectal cancer cells. Graphical Abstract

Abstract Two novel compounds including a cyclohelminthol type polyketide (namely oxaleimide K, 1) and a maleimide derivative (namely peniroquefortine A, 2), and a new natural product (namely 2-(acetylamino)-N-[(1E)-2-phenylethenyl]-acetamide, 3), together with four known compounds (4–7), were isolated and identified from fungus Penicillium roqueforti, which was separated from the root soil of Hypericum beanii N. Robson collected from the Shennongjia Forestry District, Hubei Province. Their structures including absolute configurations were mainly established by the NMR spectroscopy analyses and single-crystal X-ray diffraction experiment. Compound 1 represents the second example of a cyclohelminthol type polyketide, which features a rare 6/6/5/5 tetracyclic system and a branched aliphatic chain containing a terminal olefin (oct-1-en-3-yl) moiety, and compound 2 possesses an unprecedented carbon skeleton that is uniquely defined by a maleimide moiety linked to the respective 4-methylene-2-(3-methylbut-2-en-1-yl)-phenol and para-substituted aromatic moieties via the carbon-carbon bonds. Remarkably, the absolute configuration of a cyclohelminthol type polyketide as exemplified by compound 1 is determined by the single-crystal diffraction analysis for the first time, highlighting an E-configuration for the linkage of a succinimide moiety and a tetrahydrofuran moiety for 1 rather than a Z-configuration as previously reported in the biosynthesis study, which gives a new insight into the structural elucidation of this category of polyketides. Additionally, compound 1 exhibited significant cytotoxic activity against multiple tumor cells, especially against the Farage and SU-DHL-2 cells (IC50

Abstract Background Yinzhihuang granules (YZHG) is a commonly used Chinese patent medicine for the treatment of liver disease. However, the mechanism of YZHG in alcoholic liver disease (ALD) is still unclear. Methods This study combined liquid chromatography-mass spectrometry technology, pharmacodynamics, network pharmacology and molecular docking methods to evaluate the potential mechanism of YZHG in the treatment of ALD. Results A total of 25 compounds including 4-hydroxyacetophenone, scoparone, geniposide, quercetin, baicalin, baicalein, chlorogenic acid and caffeic acid in YZHG were identified by ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS). The pharmacodynamic investigations indicated that YZHG could improve liver function and the degree of liver tissue lesions, and reduce liver inflammation and oxidative stress in ALD mice. Network pharmacology analysis showed that YZHG treated ALD mainly by regulating inflammation-related signaling pathways such as the PI3K-Akt signaling pathway. The results of the PPI network and molecular docking showed that the targets of SRC, HSP90AA1, STAT3, EGFR and AKT1 could be the key targets of YZHG in the treatment of ALD. Conclusion This study explored the potential compounds, potential targets and signaling pathways of YZHG in the treatment of ALD, which is helpful to clarify the efficacy and mechanism of YZHG and provide new insights for the clinical application of YZHG.

Targeting the problem of traditional sparrow search algorithms being prone to falling into local optima, a new algorithm called the Chaotic Sparrow Search Algorithm with Manta Ray Spiral Foraging (abbreviated as MSSA) is proposed. The Logistic-Sine-Cosine chaotic map and elite Reverse learning strategy are fused to initialize the population. It is experimentally demonstrated that this hybrid strategy outperforms the population after random initialization in reducing ineffective sparrow individuals. In the vigilante update stage, the spiral foraging behaviour of the manta ray population in the integrated manta ray optimization algorithm, the sparrows search around the best food source, which enhances the sparrow search algorithm's ability to explore the optimal solution. To enhance the stability of the algorithm to search for the optimum, a mixed Gaussian variational and logistic perturbation strategy is proposed to further improve the performance of the algorithm. Finally, using 12 commonly used benchmark test functions and the Wilcoxon rank sum test, MSSA was compared with other original algorithms and advanced improved algorithms, it is demonstrated that MSSA has higher accuracy and convergence performance, and the improved MSSA algorithm is applied to three types of engineering optimization problems with constraints, demonstrating its feasibility and effectiveness.

Based on the hourly surface ozone (O3) observations and meteorological data from Zhuzhou in 2021, the pollution characteristics and influencing factors of O3 in Zhuzhou were investigated in the study. In addition, the Potential Source Contribution Function (PSCF) and Concentration Weighted Trajectory (CWT) analysis methods were employed to analyze the transmission paths and potential pollution sources of O3 pollution in Zhuzhou. The results showed that the total number of days with O3 exceeding the standard at all monitoring stations in Zhuzhou was 142 days in 2021. The overall air quality was less affected by SO2, NO2, and CO, and the trend of O3 pollution was still increasing. The concentrations of O3, CO, and NO2 varied significantly in different months, and the variation of O3 exhibited a “double-peak” pattern, with the peak value occurring in September. The O3 concentration in urban areas was significantly higher than that in suburban areas. Meteorological conditions had a significant impact on the degree of O3 pollution in Zhuzhou. The average wind speed in Zhuzhou throughout the year was 1.7 m/s, and the prevailing wind direction in summer was southeast, with a frequency of 16%. O3 pollution was mainly transported by short-distance airflow during the over-standard periods in 2021, accounting for 37.64%. The main source of O3 pollutant was from Jiangxi Province in the east, with the shortest distance of regional transport and the highest O3 concentration. In addition, transportation from central Guangdong Province, western Jiangxi Province, and central Hubei Province also had a significant impact.

This study was performed to investigate the effects of structural nonlinearity and large deformations on the aeroelastic loads of flexible wind turbine blades. First, a blade structural analysis model was established using the geometrically exact beam (GEB) theory. Subsequently, the blade element momentum (BEM) theory was corrected using the geometrically exact method leading to the development of a geometrically exact blade element momentum (GE-BEM) model. The results from the GE-BEM model indicated that flapwise deformations always reduce blade fatigue loads, while torsional deformations decrease fatigue loads under low wind speeds but increase them under high wind speeds. Finally, the linear Euler–Bernoulli beam and the GEB were compared to explore the influence of geometric nonlinearity on the blade aeroelastic loads, which revealed that the Euler beam model underestimates the blade loads. The simulations that used the GEB model produced torsional root twist fatigue loads that were 57.49% greater than those generated when the Euler beam model was used. Furthermore, the flapwise bending moment fatigue loads at the root were 8.24% greater than those obtained by the Euler beam model. The smallest discrepancy between the results of the two models was 7.26%, and it corresponded to the edgewise fatigue load.

Ultrasound-guided regional anaesthesia with real-time visualization of anatomical structures and needle trajectory has become the standard method for accurately achieving nerve block procedures. Nevertheless, ultrasound is particularly limited in accurately detecting the needle tip in tissues with complex echogenicity. Fat-filled circumneural fascial tissue provides a barrier to local anaesthetic diffusion. Injection during gentle needle nerve contact is more likely to spread under the circumneurium (halo sign). On the other hand, excessive force may cause hematoma or activate the piezo ion channels and intraneural calcium release. Therefore, it is vital to understand the mechanics of needle–tissue interaction for optimizing the procedural outcomes and patients’ safety. We hypothesised that continuous fluid infusion would reduce the needle force applied on the nerve compared to that of bolus injection. Thus, the primary objective of this study was to compare the forces associated with the bolus injection and continuous infusion techniques on the sciatic nerves of fresh lamb legs ex vivo. A needle combining pressure and force was inserted into six legs of lambs ex vivo using a motor stage at a constant velocity and imaged with a linear transducer. Saline injections were block randomised to bolus injection or infusion in the muscle upon gently touching and indenting of the epineurium at nine sites on six sciatic nerves at three angles (30°, 45° and 60°) in each location. The bolus was delivered over 6 s and infused for over 60 s. The result showed less force was generated during the infusion technique when gently touching the epineurium than that of the bolus technique, with p = 0.004, with significant differences observed at a 60° angle (0.49 N, p = 0.001). The injection pressure was also lower when light epineurium touches were applied (9.6 kPa, p = 0.02) and at 60° (8.9 kPa). The time to peak pressure varied across the insertion angles (p < 0.001), with the shortest time at 60° (6.53 s). This study explores future applications by emphasizing the significance of understanding needle–tissue interaction mechanics. This understanding is crucial for optimizing the procedural outcomes and enhancing patients’ safety in ultrasound-guided regional anaesthesia administration. Specifically, continuous infusion demonstrated a notable reduction in needle force compared to that of the bolus injection, especially during gentle epineurium contact.

Increased stiffness of tissues has been recognised as a diagnostic feature of pathologies. Tissue stiffness characterisation usually involves the detection of tissue response from mechanical stimulation. Air-puff optical coherence elastography (OCE) can generate impulse surface acoustic waves (SAWs) on tissue surface without contact and evaluate the mechanical properties of tissue. This study endeavours to explore the optimal excitation angle for air-puff OCE, a parameter that lacks standardisation at present, by investigating the relationship between the frequency bandwidth and peak-to-peak signal-to-noise ratio (SNR) of SAWs for different excitation angles (relative to the normal surface) of air-puff on the sample, from 5° to 85°, with an interval of 5° applied on the phantom. Due to the unevenness of human hands, 20°, 45° and 70° angles were employed for human skin (10 healthy adults). The results show that a smaller excitation angle could produce higher wave frequency bandwidth; a 5° angle generated an SAW with 1747 Hz frequency bandwidth, while an 85° angle produced an SAW with 1205 Hz. Significant differences were not shown in peak-to-peak SNR comparison between 5° and 65° on the phantom, but between 65° and 85° at the excitation position, a reduction of 48.6% was observed. Furthermore, the group velocity of the SAWs was used to evaluate the bulk Young’s modulus of the human tissue. The outcomes could provide essential guidance for air-puff-based elastography studies in clinical applications and future tissue research.

Drought (D) and heat (H) are the two major abiotic stresses hindering cereal crop growth and productivity, either singly or in combination (D/+H), by imposing various negative impacts on plant physiological and biochemical processes. Consequently, this decreases overall cereal crop production and impacts global food availability and human nutrition. To achieve global food and nutrition security vis-a-vis global climate change, deployment of new strategies for enhancing crop D/+H stress tolerance and higher nutritive value in cereals is imperative. This depends on first gaining a mechanistic understanding of the mechanisms underlying D/+H stress response. Meanwhile, functional genomics has revealed several stress-related genes that have been successfully used in target-gene approach to generate stress-tolerant cultivars and sustain crop productivity over the past decades. However, the fast-changing climate, coupled with the complexity and multigenic nature of D/+H tolerance suggest that single-gene/trait targeting may not suffice in improving such traits. Hence, in this review-cum-perspective, we advance that targeted multiple-gene or metabolic pathway manipulation could represent the most effective approach for improving D/+H stress tolerance. First, we highlight the impact of D/+H stress on cereal crops, and the elaborate plant physiological and molecular responses. We then discuss how key primary metabolism- and secondary metabolism-related metabolic pathways, including carbon metabolism, starch metabolism, phenylpropanoid biosynthesis, γ-aminobutyric acid (GABA) biosynthesis, and phytohormone biosynthesis and signaling can be modified using modern molecular biotechnology approaches such as CRISPR-Cas9 system and synthetic biology (Synbio) to enhance D/+H tolerance in cereal crops. Understandably, several bottlenecks hinder metabolic pathway modification, including those related to feedback regulation, gene functional annotation, complex crosstalk between pathways, and metabolomics data and spatiotemporal gene expressions analyses. Nonetheless, recent advances in molecular biotechnology, genome-editing, single-cell metabolomics, and data annotation and analysis approaches, when integrated, offer unprecedented opportunities for pathway engineering for enhancing crop D/+H stress tolerance and improved yield. Especially, Synbio-based strategies will accelerate the development of climate resilient and nutrient-dense cereals, critical for achieving global food security and combating malnutrition.

Abstract Stomach adenocarcinoma (STAD) is a type of cancer which often at itsadvanced stage apon diagnosis and mortality in clinical practice. Several factors influencethe prognosis of STAD, including the expression and regulation of immune cells in the tumor microenvironment. We here investigated the biomarkers related to the diagnosis and prognosis of gastric cancer, hoping to provide insights for the diagnosis and treatment of gastric cancer in the future. STAD and normal patient RNA sequencing data sets were accessed from the cancer genome atlas (TCGA database). Differential genes were determined and obtained by using the R package DESeq2. The stromal, immune, and ESTIMATE scores are calculated by the ESTIMATE algorithm, followed by the modular genes screening using the R package WGCNA. Subsequently, the intersection between the modular gene and the differential gene was taken and the STRING database was used for PPI network module analysis. The R packages clusterProfiler, enrichplot, and ggplot2 were used for GO and KEGG enrichment analysis. Cox regression analysis was used to screen survival-related genes, and finally, the R package Venn Diagram was used to take the intersection and obtain 7 hub genes. The time-dependent ROC curve and Kaplan–Meier survival curve were used to find the SERPINE1 gene, which plays a critical role in prognosis. Finally, the expression pattern, clinical characteristics, and regulatory mechanism of SERPINE1 were analyzed in STAD. We revealed that the expression of SERPINE1 was significantly increased in the samples from STAD compared with normal samples. Cox regression, time-dependent ROC, and Kaplan–Meier survival analyses demonstrated that SERPINE1 was significantly related to the adverse prognosis of STAD patients. The expression of SERPINE1 increased with the progression of T, N, and M classification of the tumor. In addition, the results of immune infiltration analysis indicated that the immune cells’ expression were higher in high SERPINE1 expression group than that in low SERPINE1 expression group, including CD4+ T cells, B cells, CD8+ T cells, macrophages, neutrophils and other immune cells. SERPINE1 was closely related to immune cells in the STAD immune microenvironment and had a synergistic effect with the immune checkpoints PD1 and PD-L1. In conclusion, we proved that SERPINE1 is a promising prognostic and diagnostic biomarker for STAD and a potential target for immunotherapy.

Graphical Abstract

In order to study the dynamic characteristics of the undisturbed lateritic soil subgrade under cyclic loading, the dynamic triaxial tests of undisturbed laterite are carried out with the SDT-20 dynamic triaxial apparatus. The effects of confining pressure, frequency and dynamic stress amplitude on dynamic stress, elastic modulus-strain（Ed-εd ） and shear modulus-shear strain（Gd-γd） on dynamic behavior are studied. The results show that the development law of the dynamic stress-strain curve of the undisturbed laterite can be described by the Kondner model. The dynamic stress increases rapidly with the dynamic strain and then tends to be stable, and the range of the dynamic strain value is given, that is, 0～0.05%. The elastic modulus-strain and shear modulus-shear strain on dynamic behavior of laterite under different confining pressure and vibration frequency are analyzed. When the dynamic strain is less than the critical value, the dynamic elastic modulus of laterite increases with the increase of dynamic strain. When the dynamic strain is greater than the critical value, the dynamic elastic modulus of laterite decreases with the increase of dynamic strain, and the dynamic shear modulus has the same change rule. Combined with the dynamic characteristics of the laterite material, the dynamic elastic modulus is reduced by the confining pressure, which is established on the basis of the Darendeli model. The segmented prediction model of the dynamic elastic modulus and dynamic shear modulus of laterite subgrade material is proposed in the paper. The applicability of the segmented model is verified by the fitting method, which can predict the development trend of Ed-εd and Gd-γd curves of laterite under the graded cyclic loading.

IntroductionEpstein-Barr virus (EBV) is a widely spread pathogen associated with lymphoproliferative diseases, B/ T/ NK cell lymphomas, nasopharyngeal carcinoma (NPC) and gastric carcinoma (GC). EBV lytic reactivations contribute to the genomic instability, inflammation and tumorigenesis of NPC, promoting cancer progression. Patients with NPC refractory to standard therapies show dismal survival. EBV gp350 is an envelope protein detectable in NPC specimens intracellularly and on the cell membrane of malignant cells, and is a potential viral antigen for T cell-directed immunotherapies. The potency of T cells engineered with a chimeric antigen receptor (CAR) targeting gp350 against EBV+ lymphoproliferative disease was previously shown.MethodsHere, we advanced towards preclinical and non-clinical developments of this virus-specific CAR-T cell immunotherapy against NPC. Different gp350CAR designs were inserted into a lentiviral vector (LV) backbone.ResultsA construct expressing the scFv 7A1-anti−gp350 incorporating the CD8 transmembrane and CD28.CD3ζ signaling domain (ZT002) was selected. High titer ZT002 (~1x108 TU/ml) was manufactured in HEK 293T/17 suspension cells in serum free media as large-scale production under good manufacturing practices (GMP). A LV multiplicity of infection (MOI) of 1 resulted in high frequencies of functional gp350CAR+ T cells (>70%) at a low (80% CD3+ gp350CAR-T cells bound to purified gp350 protein. In vitro cytotoxicity and cytokine secretion assays (IFN-γ and TNF-α) confirmed the specificity of gp350CAR-T cells against gp350+ NPC, GC and lymphoma cell targets. Immunocompromised B-NDG mice (NOD.CB17-PrkdcscidIl2rgtm1/Bcgen) were challenged s.c. with a EBV+ NPC C666.1 cell line expressing gp350 and then treated with escalating doses of gp350CAR-T cells or with non-transduced T cells. gp350CAR-T cells promoted antitumor responses, bio-distributed in several tissues, infiltrated in tumors and rejected gp350+ tumor cells.DiscussionThese results support the use of gp350CAR-T cells generated with ZT002 as an Innovative New Drug to treat patients with solid and liquid EBV-associated malignancies.

Abstract Background Compound Kushen Injection (CKI) is a Chinese patent drug that exerts curative effects in the clinical treatment of hepatocellular carcinoma (HCC). This study aimed to explore the targets and potential pharmacological mechanisms of CKI in the treatment of HCC. Methods In this study, network pharmacology was used in combination with molecular biology experiments to predict and verify the molecular mechanism of CKI in the treatment of HCC. The constituents of CKI were identified by UHPLC-MS/MS and literature search. The targets corresponding to these compounds and the targets related to HCC were collected based on public databases. To screen out the potential hub targets of CKI in the treatment of HCC, a compound-HCC target network was constructed. The underlying pharmacological mechanism was explored through the subsequent enrichment analysis. Interactive Gene Expression Profiling Analysis and Kaplan-Meier plotter were used to examine the expression and prognostic value of hub genes. Furthermore, the effects of CKI on HCC were verified through molecular docking simulations and cell experiments in vitro. Results Network analysis revealed that BCHE, SRD5A2, EPHX2, ADH1C, ADH1A and CDK1 were the key targets of CKI in the treatment of HCC. Among them, only CDK1 was highly expressed in HCC tissues, while the other 5 targets were lowly expressed. Furthermore, the six hub genes were all closely related to the prognosis of HCC patients in survival analysis. Molecular docking revealed that there was an efficient binding potential between the constituents of CKI and BCHE. Experiments in vitro proved that CKI inhibited the proliferation of HepG2 cells and up-regulated SRD5A2 and ADH1A, while down-regulated CDK1 and EPHX2. Conclusions This study revealed and verified the targets of CKI on HCC based on network pharmacology and experiments and provided a scientific reference for further mechanism research.

Abstract Preterm prelabour rupture of membranes is the leading cause of preterm birth and its associated infant mortality and morbidity. However, its underlying mechanism remains unknown. We utilized two novel biomechanical assessment techniques, ball indentation and Optical Coherence Elastography (OCE), to compare the mechanical properties and behaviours of term (≥ 37 weeks) and preterm (33–36 weeks) human fetal membranes from ruptured and non-ruptured regions. We defined the expression levels of collagen, sulfated glycosaminoglycans (sGAG), matrix metalloproteinase (MMP-9, MMP-13), fibronectin, and interleukin-1β (IL-1β) within membranes by biochemical analysis, immunohistochemical staining and Western blotting, both with and without simulated fetal movement forces on membrane rupture with a new loading system. Preterm membranes showed greater heterogeneity in mechanical properties/behaviours between ruptured and non-ruptured regions compared with their term counterparts (displacement rate: 36% vs. 15%; modulus: 125% vs. 34%; thickness: 93% vs. 30%; collagen content: 98% vs. 29%; sGAG: 85% vs 25%). Furthermore, simulated fetal movement forces triggered higher MMP-9, MMP-13 and IL-1β expression in preterm than term membranes, while nifedipine attenuated the observed increases in expression. In conclusion, the distinct biomechanical profiles of term and preterm membranes and the abnormal biochemical expression and activation by external forces in preterm membranes may provide insights into mechanisms of preterm rupture of membranes.

Partial discharge is a common fault type in the operation of power equipment. Recently, deep learning methods have shown great potential in partial discharge (PD) diagnosis. These methods construct a fitting relationship between input and output with mass training samples. Due to the scarcity of PD samples, it is hard to train a classification model. Thus, it is challenging to apply traditional deep learning methods for diagnosing PD. To overcome this issue, this paper introduces a siamese fusion network to diagnose PD. This method comprises three main steps. First, an ultra-high-frequency (UHF) sensor generates two spectrums from power equipment, including phase resolved partial discharge (PRPD) and phase resolved pulse sequence (PRPS). Based on a few-shot learning strategy, a support set is constructed. There are four different types of PD samples and a normal sample. Then, two siamese networks are employed to estimate similarity scores between a test sample and support set samples. One network measures similarity scores in PRPS, and the other measures similarity scores in PRPD. Based on similarity scores, initial diagnosis results are generated. Last, a simple and effective decision fusion technique fuses initial diagnosis results. The final diagnosis result can be generated by jointly exploiting complementary information in two spectrums. With limited training samples, experimental results show that the proposed SFN method can achieve an outstanding diagnosis performance, compared with several classical classification methods.

Abstract Background Cervical cancer is the most fatal gynecological carcinoma in the world. It is urgent to explore novel prognostic biomarkers and intervention targets for cervical cancer. Methods Through integrated quantitative proteomic strategy, we investigated the protein expression profiles of cervical cancer; 28 fresh frozen tissue samples (11 adenocarcinoma (AC), 12 squamous cell carcinoma (SCC) and 5 normal cervixes (HC)) were included in discover cohort; 45 fresh frozen tissue samples (19 AC, 18 SCC and 8 HC) were included in verification cohort; 140 paraffin-embedded tissues samples of cervical cancer (85 AC and 55 SCC) were used for immunohistochemical evaluation (IHC) of coatomer protein subunit alpha (COPA) as a prognostic biomarker for cervical cancer; how deficiency of COPA affects cell viability and tumorigenic ability of cervical cancer cells (SiHa cells and HeLa cells) were evaluated by cell counting kit-8 and clone formation in vitro. Results We identified COPA is a potential prognostic biomarker for cervical cancer in quantitative proteomics analysis. By retrospective IHC analysis, we additionally verified the proteomics results and demonstrated moderate or strong IHC staining for COPA is an unfavourable independent prognostic factor for cervical cancer. We also identified COPA is a potential pharmacological intervention target of cervical cancer by a series of in vitro experiments. Conclusion This study is the first to demonstrate that COPA may contribute to progression of cervical cancer. It can serve as a potential prognostic biomarker and promising intervention target for cervical cancer.

Abstract Background Cancer is one of the devastating diseases in the world. The development of nanocarrier provides a promising perspective for improving cancer therapeutic efficacy. However, the issues with potential toxicity, quantity production, and excessive costs limit their further applications in clinical practice. Results Herein, we proposed a nanocarrier obtained from aloe with stability and leak-proofness. We isolated nanovesicles from the gel and rind of aloe (gADNVs and rADNVs) with higher quality and yield by controlling the final centrifugation time within 20 min, and modulating the viscosity at 2.98 mPa S and 1.57 mPa S respectively. The gADNVs showed great structure and storage stability, antioxidant and antidetergent capacity. They could be efficiently taken up by melanoma cells, and with no toxicity in vitro or in vivo. Indocyanine green (ICG) loaded in gADNVs (ICG/gADNVs) showed great stability in both heating system and in serum, and its retention rate exceeded 90% after 30 days stored in gADNVs. ICG/gADNVs stored 30 days could still effectively damage melanoma cells and inhibit melanoma growth, outperforming free ICG and ICG liposomes. Interestingly, gADNVs showed prominent penetrability to mice skin which might be beneficial to noninvasive transdermal administration. Conclusions Our research was designed to simplify the preparation of drug carrier, and reduce production cost, which provided an alternative for the development of economic and safe drug delivery system. Graphical Abstract

Abstract Objective d-Serine is a crucial endogenous co-agonist of N-methyl-d-aspartate receptors (NMDARs) in the central nervous system and can affect the function of the brain derived neurotrophic factor (BDNF) system, which plays an essential role in modulating synaptic plasticity. The current study aimed to systematically evaluate the role and mechanisms of d-serine in depressive behavior in nucleus accumbens (NAc). Methods d-Serine concentration in the chronic social defeat stress (CSDS) model in NAc was measured using high-performance liquid chromatography (HPLC). The antidepressant-like effects of d-serine were identified using forced swim test (FST) and tail suspension test (TST) in control mice and then assessed in CSDS model. We applied social interaction and sucrose preference tests to identify the susceptibility of CSDS model. Western blotting was further performed to assess the changes of BDNF signaling cascade in NAc after CSDS and d-serine treatment. The BDNF signaling inhibitor (K252a) was also used to clarify the antidepressant-like mechanism of d-serine. Moreover, d-serine effects on synaptic plasticity in NAc were investigated using electrophysiological methods. Results d-Serine concentration was decreased in depression susceptible mice in NAc. d-Serine injections into NAc exhibited antidepressant-like effects in FST and TST without affecting the locomotor activity of mice. d-Serine was also effective in CSDS model of depression. Moreover, d-serine down-regulated the BDNF signaling pathway in NAc during CSDS procedure. Furthermore, BDNF signaling inhibitor (K252a) enhanced the antidepressant effects of d-serine. We also found that d-serine was essential for NMDARs-dependent long-term depression (LTD). Conclusion d-Serine exerts antidepressant-like effects in mice mediated through restraining the BDNF signaling pathway and regulating synaptic plasticity in NAc.

BackgroundDue to lack of enough specific targets and the immunosuppressive tumor microenvironment (TME) of triple-negative breast cancer (TNBC), TNBC patients often cannot benefit from a single treatment option. This study aims to explore the regulatory effects of Compound kushen injection (CKI) plus chemotherapy on the TME of TNBC from a single cell level.MethodsA mouse TNBC model in BALB/c mice was established to evaluate the antitumor efficacy and toxicity of CKI combined with chemotherapy. Flow cytometry was used to observe the influence of CKI on the lymphocyte populations in the tumor bearing mice. Both bulk RNA sequencing (RNA-seq) and single-cell RNA-seq (scRNA-seq) were applied to portray the modulation of CKI combined with chemotherapy on the TME of TNBC mice.ResultsCKI significantly enhanced the anticancer activity of chemotherapy in vivo with no obvious side effects. Flow cytometry results revealed a significantly higher activation of CD8+ T lymphocytes in the spleens and tumors of the mice with combination therapy. Bulk RNA-seq indicated that CKI could promote the cytotoxic immune cell infiltrating into tumor tissues. Meanwhile, scRNA-seq further revealed that CKI combined with chemotherapy could enhance the percentage of tumor-infiltrating CD8+ T cells, inhibit tumor-promoting signaling pathways, and promote T cell activation and positive regulation of immune response. In addition, CKI showed obvious anticancer activity against MDA-MB-231 breast tumor cells in vitro.ConclusionsThe combination of CKI and chemotherapy might provide a higher efficiency and lower toxicity strategy than a single chemotherapy drug for TNBC. CKI potentiates the anti-TNBC effects of chemotherapy by activating anti-tumor immune response in mice.

Stalk lodging, or breakage of the stalk at or below the ear, is one of the vital factors causing substantial yield losses in maize (Zea mays. L). Lodging affects maize plants’ physiological and molecular processes, eventually impacting plant growth and productivity. Despite this known fact, few researchers have investigated the genetic architecture underlying lodging in maize. Herein, through integrated transcriptome, metabolome, and phenotypic analyses of stalks of three diverse hybrid cultivars (highly resistant JNK738, mildly resistant JNK728, and lowly resistant XY335) at the tasseling (10 days to silking, 10 DTS) stage, we identified key genes and metabolic pathways modulating lodging resistance in maize. Based on the RNA-Seq analysis, a total of 10093 differentially expressed genes (DEGs) were identified from the comparison of the three varieties in pairs. Additionally, key lodging resistance–related metabolic pathways were obtained by KEGG enrichment analysis, and the DEGs were found predominantly enriched in phenylpropanoid and secondary metabolites biosynthesis pathways in the L_vs._H and M_vs._H comparison groups. Moreover, K-means analysis clustered the DEGs into clear and distinct expression profiles for each cultivar, with several functional and regulatory genes involved in the cell wall assembly, lignin biosynthetic process and hormone metabolic process being identified in the special clusters related to lodging resistance. Subsequently, integrating metabolome and transcriptome analyses revealed nine key lignin-associated metabolites that showed different expression trends in the three hybrid cultivars, among which L-phenylalanine and p-coumaric acid were regarded as differentially changed metabolites (DCMs). These two DCMs belonged to phenylalanine metabolism and biosynthesis pathways and were also supported by the RNA-Seq data. Furthermore, plant hormone signal transduction pathway–related genes encoding auxin, abscisic acid, jasmonates, and salicylic acid were differentially expressed in the three comparisons of lodging resistance, indicating these DEGs were valuable potential targets for improving maize lodging resistance. Finally, comparative physiological and qRT-PCR analyses results supported our transcriptome-based findings. Our research not only provides a preliminary theoretical basis and experimental ideas for an in-depth study of the regulatory networks involved in maize lodging resistance regulation but also opens up new avenues for molecular maize stalk lodging resistance breeding.

Muscle stiffness provides a key insight toward clinical assessment for rehabilitation. Regarding the high-cost and technical skill requirement of ultrasound shear wave elastography (SWE) restricting extensive clinical use, MyotonPRO has been proposed as a complementary tool for muscle stiffness measurement. There is a deficiency of studies revealing the use of this tool for measuring muscle stiffness contributing to hand control. The purpose of this study was to assess the capability and effectiveness of MyotonPRO and SWE for hand muscle stiffness characterization. The stiffness of the dominant flexor digitorum superficialis (FDS) muscle of 25 healthy participants (12 males and 13 females) aged 29.60 ± 9.81 years was evaluated while they performed grip tasks. The muscle stiffness of males and females was compared. The correlation between dynamic muscle stiffness given by MyotonPRO and Young’s modulus obtained from SWE was investigated. Statistical analysis indicated a significant difference in the dynamic muscle stiffness between genders in all conditions (p < 0.05), whereas a significant difference in Young’s modulus was found only at the resting state. A moderate correlation was found between dynamic muscle stiffness and Young’s modulus (r ranged from 0.243 to 0.489). Therefore, MyotonPRO can be used to assess the muscle stiffness of the FDS muscle at rest and during muscle contraction.

Mineral precipitation or scale formation in oil and gas wellbore is recognized as an obstacle to hydrocarbon recovery. A method using computational fluid dynamics for structure optimization of downhole descaling tools is presented in this paper. The effects of key parameters, such as the nozzle structure style, cone angle, and incidence angle on the descaling performance, are systemically investigated. Numerical results indicate that the cone nozzle has higher jet efficiency because of its smoother velocity and pressure changes, as well as less energy loss. Under the conditions considered, key parameters of the downhole descaling tool are optimized as an incidence angle of 10° and a cone angle of 14°. Furthermore, the numerical results are validated with experimental results, in which the average error between the experimental and numerical results is ∼7.1%. The proposed numerical approaches can accurately predict the jetting status, which consequently has technical guiding significance for the design of downhole descaling tools.

Optical coherence tomography (OCT) has attracted attention in dermatology applications for skin disease characterization and diagnosis because it provides high-resolution (

The mechanical properties and structure alteration (e.g., layer morphology and thickness) of the oesophagus wall can reflect its pathological conditions. Hence, quantitative measurement of the above-mentioned properties can play a significant role in aiding the disease diagnosis in clinical application. As a fast and non-invasive imaging modality, Optical coherence tomography (OCT) and vibrational elastography can provide high resolution (

This work proposes a new morphological random walker (MRW) method for hyperspectral anomaly detection. The proposed method introduces a morphology-based objective function into a random walker (RW) algorithm, sufficiently exploiting spatial morphological property and spatial similarity of HSIs for detection. The MRW method comprises two major stages. Firstly, we employ the extended morphological profiles (EMPs) and different operations to extract the spatial morphological property of HSIs. Second, according to the morphological property, we construct a morphology-based objective function. This function is incorporated into the RW-based optimization model, encoding the spatial similarity of HSIs in a weighted graph. Two factors determine the class of test pixels, including the spatial morphological information learned by EMPs, and the spatial correlation among adjoining pixels modeled by the weighted graph. Since the two factors are well considered in the MRW method, the proposed method illustrates outstanding detection performances for several widely used real HSIs.

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Introduction: Danhong injection (DHI) is a traditional Chinese medicine preparation commonly used in the clinical treatment of acute myocardial infarction (AMI). In this study, the active components of DHI and its mechanism in the treatment of AMI were investigated.Methods: The chemical components of DHI were detected by the ultra-high-performance liquid chromatography-linear trap quadrupole-orbitrap-tandem mass spectrometry (UHPLC-LTQ-Orbitrap-MS/MS), and the targets and pathways of DHI in the treatment of AMI were analyzed by systems pharmacology, which was verified by molecular docking and animal experiments.Results: A total of 12 active components of DHI were obtained, and 158 common targets of component and disease were identified by systems pharmacology. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis results showed that DHI is closely related to the calcium signaling pathway in the treatment of AMI. Molecular docking showed that the key target protein has good binding affinity to related compounds. The experimental results showed that compared with the model group, LVAWs, EF, and FS significantly (p < 0.05) increased in the DHI group. The percentage of myocardial infarction significantly (p < 0.01) decreased, both in the ventricular and total cardiac regions, and the pathological damage of myocardial tissue also decreased. In addition, the expression of the protein CaMK II decreased (p < 0.01) and the expression of SERCA significantly increased (p < 0.01).Conclusion: This study revealed that ferulic acid, caffeic acid and rosmarinic acid could inhibit AMI by regulating PLB, CaMK II, SERCA, etc. And mechanistically, calcium signaling pathway was critically involved. Combination of systems pharmacology prediction with experimental validation may provide a scientific basis for in-depth clinical investigation of the material basis of DHI.

Stomach adenocarcinoma (STAD) is one of the most malignant cancers that endanger human health. There is growing evidence that competitive endogenous RNA (ceRNA) regulatory networks play an important role in various human tumors. However, the complexity and behavioral characteristics of the ceRNA network in STAD are still unclear. In this study, we constructed a ceRNA regulatory network to identify the potential prognostic biomarkers associated with STAD. The expression profile of lncRNA, miRNA, and mRNA was downloaded from The Cancer Genome Atlas (TCGA). After performing bioinformatics analysis, the CCDC144NL-AS1/hsa-miR-145-5p/SERPINE1 ceRNA network associated to STAD prognosis of STAD was obtained. The CCDC144NL-AS1/SERPINE1 axis in the ceRNA network was identified by correlation analysis and considered as a clinical prognosis model by Cox regression analysis. In addition, methylation analysis indicated that the abnormal upregulation of CCDC144NL-AS1/SERPINE1 axis might be related to the aberrant methylation of some sites, and immune infiltration analysis suggested that CCDC144NL-AS1/SERPINE1 axis probably influences the alteration of tumor immune microenvironment and the occurrence and development of STAD. In particular, the CCDC144NL-AS1/SERPINE1 axis based on the ceRNA network constructed in the present study might be an important novel factor correlating with the diagnosis and prognosis of STAD.

Wall shear stress (WSS) plays an important role in the formation, growth, and rupture of atherosclerotic plaques in arteries. This study measured WSS in diseased carotid artery phantoms with degrees of stenosis varying from 0 to 60% with both steady and pulsatile flow. Experiments were performed using in silico and real flow phantoms. Blood velocities were estimated using plane wave (PW) vector Doppler. Wall shear stress was then estimated from the velocity gradient near the wall multiplied by the viscosity of a blood-mimicking fluid. The estimated WSS using the in silico phantom agreed within 10% of the ground-truth values (root-mean-square error). The phantom experiment showed that the mean WSS and maximum WSS increased with the increasing degree of stenosis. The simulation and experiment results provide the necessary validation data to give confidence in WSS measurements in patients using the PW vector Doppler technique.

Mergers and acquisitions (M&As) are among the most important investment activities for companies, but they contain great risks. We investigate the role of accounting conservatism in M&A target selection and risk. We find that for risk-averse reasons, firms with high accounting conservatism are likely to acquire profitable targets and avoid loss-making targets. When such firms acquire loss-making targets, the conservatism’s risk-control role reduces M&A risk and increases M&A performance, but only when control of the target is transferred and the acquirer has high long-term debt and low management power. Furthermore, accounting conservatism reduces risk by increasing the maturity match between cash flow and debt. Our results suggest that accounting conservatism plays not only a risk-averse role but also a risk-control role, providing new evidence for the usefulness of accounting conservatism in M&A decisions.

Optical coherence tomography-based angiography (OCTA) has attracted attention in clinical applications as a non-invasive and high-resolution imaging modality. Motion artifacts are the most seen artifact in OCTA. Eigen-decomposition (ED) algorithms are popular choices for OCTA reconstruction, but have limitations in the reduction of motion artifacts. The OCTA data do not meet one of the requirements of ED, which is that the data should be normally distributed. To overcome this drawback, we propose an easy-to-deploy development of ED, windowed-ED (wED). wED applies a moving window to the input data, which can contrast the blood-flow signals with significantly reduced motion artifacts. To evaluate our wED algorithm, pre-acquired dorsal wound healing data in a murine model were used. The ideal window size was optimized by fitting the data distribution with the normal distribution. Lastly, the cross-sectional and en face results were compared among several OCTA reconstruction algorithms, Speckle Variance, A-scan ED (aED), B-scan ED, and wED. wED could reduce the background noise intensity by 18% and improve PSNR by 4.6%, compared to the second best-performed algorithm, aED. This study can serve as a guide for utilizing wED to reconstruct OCTA images with an optimized window size.

Over the last few years, a number of studies have quantified the role of radiomics, dynamic contrast enhancement and standard MRI (T2WI + DWI) in detecting prostate cancer; however, the aim of this paper was to assess the advantage of combining radiomics with other multiparametric magnetic resonance imaging (mpMRI) (T2-DWI-DCE) in improving the detection of prostate cancer. This study used 10 prostate-cancer-tissue-mimicking phantoms to obtain preclinical data. We then focused on 46 patients who underwent mpMRI and Transrectal Ultrasound (TRUS) guided biopsy between September 2016 and December 2017. The texture analysis parameters combined with the mpMRI and compared with the histopathology of TRUS biopsy have been assessed statistically by principal component analysis (PCA) and discriminant component analysis (DCA). The prediction model and goodness-of-fit were examined with the Akaike information criterion (AIC) and McFadden pseudo-R-squared. In the PCA, there was a higher separation between cancerous and noncancerous tissue in the preclinical compared with the clinical data. Both AIC and R2 showed an improvement in the model in cancer prediction by adding the radiomics to mpMRI. The discriminant analysis showed an accuracy of cancer prediction of 81% compared with 100% in the pre-clinical phantom data. Combining radiomics with mpMRI showed an improvement in prostate cancer prediction. The ex vivo experiments validated the findings of this study.

As the most important intestinal mucosal barrier of the main body, the innate immune barrier in intestinal tract plays especially pivotal roles in the overall health conditions of infants and young children; therefore, how to strengthen the innate immune barrier is pivotal. A variety of bioactivities of lactoferrin (LF) has been widely proved, including alleviating enteritis and inhibiting colon cancer; however, the effects of LF on intestinal immune barrier in infants and young children are still unclear, and the specific mechanism on how LF inhibits infantile enteritis by regulating immune signaling pathways is unrevealed. In the present study, we firstly performed pharmacokinetic analyses of LF in mice intestinal tissues, stomach tissues and blood, through different administration methods, to confirm the metabolic method of LF in mammals. Then we constructed in Vitro and in Vivo infantile intestinal immune barrier damage models utilizing lipopolysaccharide (LPS), and evaluated the effects of LF in alleviating LPS-induced intestinal immune barrier damage. Next, the related immune molecular mechanism on how LF exerted protective effects was investigated, through RNA-seq analyses of the mouse primary intestinal epithelial cells, and the specific genes were analyzed and screened out. Finally, the genes and their related immune pathway were validated in mRNA and protein levels; the portions of special immune cells (CD4+ T cells and CD8+ T cells) were also detected to further support our experimental results. Pharmacokinetic analyses demonstrated that the integrity of LF could reach mice stomach and intestine after oral gavage within 12 h, and the proper administration of LF should be the oral route. LF was proven to down–regulate the expression levels of inflammatory cytokines in both the primary intestinal epithelial cells and mice blood, especially LF without iron (Apo-LF), indicating LF alleviated infantile intestinal immune barrier damage induced by LPS. And through RNA-seq analyses of the mouse primary intestinal epithelial cells treated with LPS and LF, embryonic lethal abnormal vision Drosophila 1 (ELAVL1) was selected as one of the key genes, then the ELAVL1/PI3K/NF-κB pathway regulated by LF was verified to participate in the protection of infantile intestinal immune barrier damage in our study. Additionally, the ratio of blood CD4+/CD8+ T cells was significantly higher in the LF-treated mice than in the control mice, indicating that LF distinctly reinforced the overall immunity of infantile mice, further validating the strengthening bioactivity of LF on infantile intestinal immune barrier. In summary, LF was proven to alleviate LPS-induced intestinal immune barrier damage in young mice through regulating ELAVL1-related immune signaling pathways, which would expand current knowledge of the functions of bioactive proteins in foods within different research layers, as well as benefit preclinical and clinical researches in a long run.

Long noncoding RNAs (lncRNAs) constitute an emerging group of ncRNAs that modulate gene expression at the transcriptional or translational level. Koi herpesvirus (KHV), also known as Cyprinus herpesvirus type 3 (CyHV-3) and characterized by high pathogenicity and high mortality, has caused substantial economic losses in the common carp and koi carp fisheries industry. In this work, we sequenced the lncRNA and mRNA of host koi carp infected with KHV. A total of 20,178 DEmRNAs were obtained, of which 5021 mRNAs were upregulated and 15,157 mRNAs were downregulated. Both KEGG pathways and GO terms were enriched in many important immune pathways. The KEGG analysis showed that DEGs were significantly enriched in many important immune pathways, such as apoptosis, NOD-like receptor signaling pathway, Jak-STAT signaling pathway, TNF signaling pathway, IL-17 signaling pathway, NF-kappa B signaling pathway, and so on. Furthermore, a total of 32,697 novel lncRNA transcripts were obtained from koi carp immune tissues; 9459 of these genes were differentially expressed. Through antisense, cis-acting, and trans-acting analyses, the target genes of differentially expressed lncRNAs (DElncRNAs) were predicted. Gene ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses showed that the DElncRNA expression pattern was consistent with the differential mRNA expression pattern. The lncRNA–mRNA network analysis, which included many immune pathways, showed that after KHV infection, the expression of most lncRNAs and their target mRNAs were downregulated, suggesting that these lncRNAs engage in a positive regulatory relationship with their target mRNAs. Considering that many studies have shown that herpesviruses can escape the immune system by negatively regulating these immune pathways, we speculated that these lncRNAs play a significant role in KHV’s escape from host immunity. Furthermore, 10 immune-related genes and 20 lncRNAs were subsequently verified through RT–qPCR, to confirm the accuracy of the high-throughput sequencing results. In this study, we aimed to explore lncRNA functions in the immune response of lower vertebrates and provide a theoretical basis for the study of noncoding RNAs in teleosts. Therefore, exploring lncRNA expression in KHV-infected koi carp helped us better understand the biological role played by lncRNA-dependent pathways in aquaculture animal viral infection.

Introduction: As non-small cell lung cancer (NSCLC) seriously threatens human health, several clinical studies have reported that Chinese herbal injections (CHIs) in combination with and gemcitabine plus cisplatin (GP) are beneficial. This multidimensional network meta-analysis aimed to compare the clinical efficacy and safety of different CHIs in combination with GP against NSCLC.Methods: Randomized controlled trials (RCTs) for the treatment of NSCLC were retrieved from seven electronic databases from inception to April 30, 2020. Study selection and data extraction were based on a priori criteria. Data analysis was performed using Stata 13.0, WinBUGS 14.0 software. Multidimensional cluster analysis was performed using the “scatterplot3d” package in R 3.6.1 software.Results: This network meta-analysis included 71 eligible RCTs and 10 Chinese herbal injections. Delisheng injection and Kangai injection had the highest probability in terms of clinical effectiveness rate (94.60%) and gastrointestinal reactions (82.62%) when combined with GP compared with the other interventions. Compound Kushen injection combined with GP ranked ahead of the other interventions in terms of performance status (73.36%) and abnormal liver function (87.17%). Shenmai injection combined with GP had the highest probability in terms of leukopenia (94.59%) and thrombocytopenia (99.18%).Conclusion: The current evidence revealed that CHIs combined with GP have a better impact on patients with NSCLC than GP alone. Aidi injection, Compound kushen injection, and Kanglaite injection deserve more attention of clinicians when combined with GP in patients with NSCLC. Additionally, due to the limitations of this network meta-analysis, further well-designed, large-sample, multicenter RCTs are required to support our findings adequately.