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Abstract Objective In observational studies, testosterone has been reported to be associated with some types of cancers. However, the direction and magnitude of the causal association between testosterone and different types of cancer remain unclear. This Mendelian randomization study assessed the causal associations of total testosterone (TT) and bioavailable testosterone (BT) with cancer risk in men. Methods We performed two-sample Mendelian randomization using publicly available GWAS summary statistics to investigate the genetically causal association between testosterone and the risk of 22 kinds of cancers in men. Causal estimates were calculated by the inverse variance weighted method. We also performed additional sensitivity tests to evaluate the validity of the casualty. Results Genetically predicted BT level were significantly associated with an increased risk of prostate cancer [odds ratio (OR) = 1.17 95% confidence interval (CI): 1.09–1.26, P = 2.51E−05] in the MR analysis with the IVW method. TT was found to be the suggestive protective factor against stomach cancer (OR = 0.66, 95% CI: 0.48–0.93, P = 0.0116) as well as pancreatic cancer (OR = 0.59, 95% CI: 0.36–0.96, P = 0.0346). A suggestive association was found between TT and the occurrence of small intestine cancer (OR = 1.0004, 95% CI: 1.0001–1.0007, P = 0.0116). However, testosterone had no significant association with other cancers. Conclusion This study investigated the role of testosterone in the development of prostate cancer, stomach cancer, pancreatic cancer, and small intestine cancer but found no strong association with the other cancers in men.

The unbalance of neutral-point potential (NPP) is an important problem in three-level converter. This paper proposes a neutral-point potential balancing control method with the third harmonic injected pulse width modulation (PWM) for three-level converters, which can a) realize better steady and dynamic performance of restraining the NPP unbalance; b) realize the similar performance with the space vector pulse width modulation (SVPWM) but with less amount of calculation; c) be applied in multiple operating modes such as grid-tied/off-grid mode, voltage-source/current-source mode. Finally, simulation results are presented, which validate the performance of the proposed method.

Cavitation is a challenging flow phenomenon that can adversely affect the hydraulic performance of centrifugal pumps. In this study, numerical investigations were carried out incorporating the Zwart cavitation model derived from Rayleigh–Plesset equation with the Navier–Stokes equations to study a damaged turbofan pump. Pressure fluctuation was analyzed with fast Fourier transform (FFT) in both non-cavitation and cavitation flow fields. The entropy production theory was used to further analyze the positions of vortex cores and energy-loss behaviors inside the pump. The results demonstrate that the numerically predicted positions of vortex cores in high-pressure regions agree well with the erosion positions determined under real working conditions. Herein, through combined analysis of the pressure contours and the vortex-core locations, we demonstrate that the erosion failure of the surface is caused by fatigue failure due to the collapse of cavities at vortex cores. The percentages of different kinds of entropy production rates under different mass flow rates in the whole calculation domain were calculated, and it was found that the impeller suffered the most energy loss. The results of the entropy production analysis can provide guidance for subsequent optimization of turbofan pumps.

Context Qiangli Wuhu (QLWH) mixture is a concoction approved and registered by Ningxia Medical Products Administration. It has therapeutic effects on various types of pneumonia.Objective To clarify the mechanisms of QLWH in treating pneumonia.Materials and methods The potential targets of QLWH in the treatment of pneumonia were predicted by network pharmacology. Male, Institute of Cancer Research (ICR) mice were randomly divided into five groups of 12 mice, control, vehicle, QLWH (10 and 20 mg/kg) and dexamethasone (DXM), and orally treated twice daily with normal saline, QLWH or DXM. The pneumonia model was established by tracheal instillation of lipopolysaccharide (LPS). After treatment five days, ELISA, H&E staining and Western blot were used to investigate protective effects of QLWH.Results Nine hundred and ninety-four active ingredients were found through network pharmacology, corresponding to 135 targets for the treatment of pneumonia; compared to the vehicle group, QLWH (10 and 20 mg/kg) significantly decreased the levels of TNF-α (14.3% and 28.8%), IL-1β (23.9% and 42.8%) and IL-6 (13.2% and 16.1%), increased the levels of IL-10 (134.3% and 172.9%); in terms of mechanism, QLWH down-regulated TLR4/NF-κB/NLRP3 axis related proteins in lung tissue of pneumonia model mice (p

Introduction: Predicting pathological complete response (pCR) for patients receiving neoadjuvant chemotherapy (NAC) is crucial in establishing individualized treatment. Whole-slide images (WSIs) of tumor tissues reflect the histopathologic information of the tumor, which is important for therapeutic response effectiveness. In this study, we aimed to investigate whether predictive information for pCR could be detected from WSIs. Materials and methods: We retrospectively collected data from four cohorts of 874 patients diagnosed with biopsy-proven breast cancer. A deep learning pathological model (DLPM) was constructed to predict pCR using biopsy WSIs in the primary cohort, and it was then validated in three external cohorts. The DLPM could generate a deep learning pathological score (DLPs) for each patient; stromal tumor-infiltrating lymphocytes (TILs) were selected for comparison with DLPs. Results: The WSI feature-based DLPM showed good predictive performance with the highest area under the curve (AUC) of 0.72 among the cohorts. Alternatively, the combination of the DLPM and clinical characteristics offered a better prediction performance (AUC >0.70) in all cohorts. We also evaluated the performance of DLPM in three different breast subtypes with the best prediction for the triple-negative breast cancer (TNBC) subtype (AUC: 0.73). Moreover, DLPM combined with clinical characteristics and stromal TILs achieved the highest AUC in the primary cohort (AUC: 0.82) and validation cohort 1 (AUC: 0.80). Conclusion: Our study suggested that WSIs integrated with deep learning could potentially predict pCR to NAC in breast cancer. The predictive performance will be improved by combining clinical characteristics. DLPs from DLPM can provide more information compared to stromal TILs for pCR prediction.

Abstract Many industrial applications require time-consuming and resource-intensive evaluations of suitable solutions within very limited time frames. Therefore, many surrogate-assisted evaluation algorithms (SAEAs) have been widely used to optimize expensive problems. However, due to the curse of dimensionality and its implications, scaling SAEAs to high-dimensional expensive problems is still challenging. This paper proposes a variable surrogate model-based particle swarm optimization (called VSMPSO) to meet this challenge and extends it to solve 200-dimensional problems. Specifically, a single surrogate model constructed by simple random sampling is taken to explore different promising areas in different iterations. Moreover, a variable model management strategy is used to better utilize the current global model and accelerate the convergence rate of the optimizer. In addition, the strategy can be applied to any SAEA irrespective of the surrogate model used. To control the trade-off between optimization results and optimization time consumption of SAEAs, we consider fitness value and running time as a bi-objective problem. Applying the proposed approach to a benchmark test suite of dimensions ranging from 30 to 200 and comparisons with four state-of-the-art algorithms show that the proposed VSMPSO achieves high-quality solutions and computational efficiency for high-dimensional problems.

Abstract Background Although immune checkpoint inhibitors (ICIs) have influenced the treatment paradigm for multiple solid tumors, increasing evidence suggests that primary and adaptive resistance may limit the long-term efficacy of ICIs. New therapeutic strategies with other drug combinations are hence warranted to enhance the antitumor efficacy of ICIs. As a novel tumor suppressor, histone deacetylase (HDAC) inhibitor tucidinostat has been successfully confirmed to act against hematological malignancies. However, the underlying mechanisms of action for tucidinostat and whether it can manipulate the tumor microenvironment (TME) in solid tumors remain unclear. Methods Three murine tumor models (4T1, LLC, and CT26) were developed to define the significant role of different doses of tucidinostat in TME. The immunotherapeutic effect of tucidinostat combined with anti-programmed cell death ligand 1 antibody (aPD-L1) was demonstrated. Furthermore, the effect of tucidinostat on phenotypic characteristics of peripheral blood mononuclear cells (PBMCs) from lung cancer patients was investigated. Results With an optimized dose, tucidinostat could alter TME and promote the migration and infiltration of CD8+ T cells into tumors, partially by increasing the activity of C-C motif chemokine ligand 5 (CCL5) via NF-κB signaling. Moreover, tucidinostat significantly promoted M1 polarization of macrophages and increased the in vivo antitumor efficacy of aPD-L1. Tucidinostat also enhanced the expression of the costimulatory molecules on human monocytes, suggesting a novel and improved antigen-presenting function. Conclusions A combination regimen of tucidinostat and aPD-L1 may work synergistically to reduce tumor burden in patients with cancer by enhancing the immune function and provided a promising treatment strategy to overcome ICI treatment resistance.

In the past studies, it is shown that cardiac troponin I (cTnI, encoded by TNNI3), as a cytoplasmic protein, is an inhibitory subunit in troponin complex, and involves in cardiomyocyte diastolic regulation. Here, we assessed a novel role of cTnI as a nucleoprotein. Firstly, the nuclear translocation of cTnI was found in mouse, human fetuses and rat heart tissues. In addition, there were differences in percentage of intranuclear cTnI in different conditions. Based on weighted gene co-expression network analyses (WGCNA) and verification in cell experiments, a strong expression correlation was found between TNNI3 and Atp2a2, which encodes sarco-endoplasmic reticulum Ca2+ ATPase isoform 2a (SERCA2a), and involves in ATP hydrolysis and Ca2+ transient. TNNI3 gain and loss caused Atpa2a2 increase/decrease in a dose-dependent manner both in mRNA and protein levels, in vivo and in vitro. By using ChIP-sequence we demonstrated specific binding DNA sequences of cTnI were enriched in ATP2a2 promoter −239∼–889 region and the specific binding sequence motif of cTnI was analyzed by software as ''CCAT'', which has been reported to be required for YY1 binding to the promoter region of YY1-related genes. Moreover, it was further verified that pcDNA3.1 (−)-TNNI3 could express cTnI proteins and increase the promoter activity of Atp2a2 through luciferase report assay. In the end, we evaluated beat frequencies, total ATP contents, Ca2+ transients in TNNI3-siRNA myocardial cells. These findings indicated, for the first time, cTnI may regulate Atp2a2 in cardiomyocytes as a co-regulatory factor and participate in the regulation of intracellular Ca ions.

Device-to-Device (D2D) communication-enabled Heterogeneous Cellular Networks (HCNs) have been a promising technology for satisfying the growing demands of smart mobile devices in fifth-generation mobile networks. The introduction of Millimeter Wave (mm-wave) communications into D2D-enabled HCNs allows higher system capacity and user data rates to be achieved. However, interference among cellular and D2D links remains severe due to spectrum sharing. In this paper, to guarantee user Quality of Service (QoS) requirements and effectively manage the interference among users, we focus on investigating the joint optimization problem of mode selection and channel allocation in D2D-enabled HCNs with mm-wave and cellular bands. The optimization problem is formulated as the maximization of the system sum-rate under QoS constraints of both cellular and D2D users in HCNs. To solve it, a distributed multiagent deep Q-network algorithm is proposed, where the reward function is redefined according to the optimization objective. In addition, to reduce signaling overhead, a partial information sharing strategy that does not observe global information is proposed for D2D agents to select the optimal mode and channel through learning. Simulation results illustrate that the proposed joint optimization algorithm possesses good convergence and achieves better system performance compared with other existing schemes.

Abstract Magnetic particle imaging (MPI) is an emerging molecular imaging technique with high sensitivity and temporal-spatial resolution. Image reconstruction is an important research topic in MPI, which converts an induced voltage signal into the image of superparamagnetic iron oxide particles concentration distribution. MPI reconstruction primarily involves system matrix- and x-space-based methods. In this review, we provide a detailed overview of the research status and future research trends of these two methods. In addition, we review the application of deep learning methods in MPI reconstruction and the current open sources of MPI. Finally, research opinions on MPI reconstruction are presented. We hope this review promotes the use of MPI in clinical applications.

Abstract Background Accurate diagnosis of unexplained cervical lymphadenopathy (CLA) using medical images heavily relies on the experience of radiologists, which is even worse for CLA patients in underdeveloped countries and regions, because of lack of expertise and reliable medical history. This study aimed to develop a deep learning (DL) radiomics model based on B-mode and color Doppler ultrasound images for assisting radiologists to improve their diagnoses of the etiology of unexplained CLA. Methods Patients with unexplained CLA who received ultrasound examinations from three hospitals located in underdeveloped areas of China were retrospectively enrolled. They were all pathologically confirmed with reactive hyperplasia, tuberculous lymphadenitis, lymphoma, or metastatic carcinoma. By mimicking the diagnosis logic of radiologists, three DL sub-models were developed to achieve the primary diagnosis of benign and malignant, the secondary diagnosis of reactive hyperplasia and tuberculous lymphadenitis in benign candidates, and of lymphoma and metastatic carcinoma in malignant candidates, respectively. Then, a CLA hierarchical diagnostic model (CLA-HDM) integrating all sub-models was proposed to classify the specific etiology of each unexplained CLA. The assistant effectiveness of CLA-HDM was assessed by comparing six radiologists between without and with using the DL-based classification and heatmap guidance. Results A total of 763 patients with unexplained CLA were enrolled and were split into the training cohort (n=395), internal testing cohort (n=171), and external testing cohorts 1 (n=105) and 2 (n=92). The CLA-HDM for diagnosing four common etiologies of unexplained CLA achieved AUCs of 0.873 (95% CI: 0.838–0.908), 0.837 (95% CI: 0.789–0.889), and 0.840 (95% CI: 0.789–0.898) in the three testing cohorts, respectively, which was systematically more accurate than all the participating radiologists. With its assistance, the accuracy, sensitivity, and specificity of six radiologists with different levels of experience were generally improved, reducing the false-negative rate of 2.2–10% and the false-positive rate of 0.7–3.1%. Conclusions Multi-cohort testing demonstrated our DL model integrating dual-modality ultrasound images achieved accurate diagnosis of unexplained CLA. With its assistance, the gap between radiologists with different levels of experience was narrowed, which is potentially of great significance for benefiting CLA patients in underdeveloped countries and regions worldwide.

Modern power systems contain different types of cables and that makes it important to diagnose defects before they result in faults. Existing cable inspection methods, such as dielectric loss measurement and partial discharge, still fail to detect and locate weak cable defects. This paper presents a novel non-destructive method for detecting wear and aging defects based on broadband impedance spectroscopy (BIS) is proposed. A digital model of the cable distribution parameters is developed in this paper. The effects of different angular wear defects on the impedance spectroscopy were compared, and the degree of defects was successfully distinguished by discrete Fourier transform (DFT). The severity of the defect can be determined from the difference in peak height at the defect location after normalization. By using DFT and the Chebyshev Window it was also possible to identify two defects in the cable within 0.47% deviation of the defect position.

Abstract Carbonaceous aerosol plays an important role in climate, but its sources and atmospheric processes are least understood in the Tibetan Plateau (TP), a remote yet climatically sensitive region. This study presents the first seasonal cycle of radiocarbon and stable isotope 13C of organic and elemental carbon (OC and EC) in the atmosphere of the northeastern TP. Large seasonal variations of EC and OC concentrations were explained by non‐fossil sources. Regardless of the season, fossil contribution to OC was strongly correlated with inverse OC concentrations. This allowed the separating a constant background source and a source responsible for OC variability that was mostly of non‐fossil origin. The 13C signature of OC shows that OC was highly atmospherically processed and thus less volatile than OC found near sources or in urban areas. The 13C‐depleted secondary sources contributed strongly to more volatile OC, whereas the 13C‐enriched less volatile OC suggests the influence of atmospheric aging.

Abstract We aimed to develop a new biocompatible gastrin‐releasing peptide receptor (GRPR) targeted optical probe, IRDye800‐RM26, for fluorescence image‐guided surgery (FGS) of brain malignancies in near‐infrared window II (NIR‐II) imaging. We developed a novel GRPR targeting probe using a nine‐amino‐acid bombesin antagonist analog RM26 combined with IRDye800CW, and explored the fluorescent probe according to optical properties. Fluorescence imaging characterization in NIR‐I/II region was performed in vitro and in vivo. Following simulated NIR‐II image‐guided surgery, we obtained time‐fluorescent intensity curves and time‐signal and background ratio curves. Further, we used histological sections of brain from tumor‐beating mice model to compare imaging specificity between 5‐aminolevulinic acid (5‐ALA) and IRDye800‐RM26, and evaluated biodistribution and biocompatibility. IRDye800‐RM26 had broad emission ranging from 800 to 1200 nm, showing considerable fluorescent intensity in NIR‐II region. High‐resolution NIR‐II imaging of IRDye800‐RM26 can enhance the advantages of NIR‐I imaging. Dynamic and real time fluorescence imaging in NIR‐II region showed that the probe can be used to treat brain malignancies in mice between 12 and 24 h post injection. Its specificity in targeting glioblastoma was superior to 5‐ALA. Biodistribution analysis indicated IRDye800‐RM26 excretion in the kidney and liver. Histological and blood test analyses did not reveal acute severe toxicities in mice treated with effective dose (40 μg) of the probe for NIR‐II imaging. Because of the considerable fluorescent intensity in NIR‐II region and high spatial resolution, biocompatible and excretable IRDye800‐RM26 holds great potentials for FGS, and is essential for translation into human use.

Abstract Early diagnosis can effectively improve the survival of glioblastoma multiforme (GBM). A specific imaging technique that is simultaneously deep penetrating and sensitive to small tissue changes is desired to identify GBM. Due to its excellent features in signal contrast, detection sensitivity, and none or little attenuation in tissue, magnetic particle imaging (MPI) possesses great potential in cancer diagnosis, especially when the imaging modality is equipped with specifically targeted nanoprobes. However, when gliomas are small, the blood–brain barrier (BBB) is complete and prevents nanoprobes from entering the brain, which negates the theranostic effect. This study proposes a biomimetic nanoplatform that assist the MPI tracers in breaking through the BBB and then demonstrate a targeted and sensitive diagnosis of GBM. Afterward, the photothermal therapy and immune regulation show an excellent therapeutic effect on the GBM. It is experimentally confirmed that the MPI signal does not decay with tissue depth and shows excellent sensitivity for thousands‐cells. Only small animals are conducted in this study due to the limitations of the current commercial MPI scanner, however, this research theoretically enables large animal and human studies, which encourages a promising pathway toward the noninvasive diagnosis of early‐stage GBM in clinics.

Abstract Cardiomyopathies comprise a group of disorders wherein the primary defect is in cardiac myocytes. The common forms of pediatric cardiomyopathies, classified according to their morphological and functional manifestations, include dilated cardiomyopathy (DCM), restrictive cardiomyopathy (RCM), hypertrophic cardiomyopathy (HCM), and others. Cardiac gene mutations caused abnormal myofibril Ca2+ sensitivity may be involved in the underlying molecular mechanisms of cardiomyopathies. Thus far, no effective treatment for cardiomyopathies has been developed, especially for HCM and RCM in which diastolic dysfunction occurs early and followed by diastolic heart failure. Our laboratory is among the first in the field to investigate the mechanisms underlying various cardiomyopathies and search for the treatment for these disorders. In the past, we and other researchers have found that (−)‐epigallocatechin‐3‐gallate (EGCg), the major biomedical polyphenol extracted from green tea, possess multiple therapeutic effects on protecting cardiac function and correcting impaired relaxation. Given its therapeutic effects, EGCg might be a potential drug candidate for administration to patients with cardiomyopathy and heart failure. In this review, we will discuss the molecular mechanisms associated with the pathogenesis of diastolic dysfunction and summarize the pharmacological effects of EGCg on experimental animals and pediatric patients with cardiomyopathies and diastolic dysfunction.

Atherosclerosis preferentially develops at bifurcations exposed to disturbed flow. Plexin D1 (PLXND1) responds to mechanical forces and drives macrophage accumulation in atherosclerosis. Here, multiple strategies were used to identify the role of PLXND1 in site-specific atherosclerosis. Using computational fluid dynamics and three-dimensional light-sheet fluorescence-microscopy, the elevated PLXND1 in M1 macrophages was mainly distributed in disturbed flow area of ApoE−/− carotid bifurcation lesions, and visualization of atherosclerosis in vivo was achieved by targeting PLXND1. Subsequently, to simulate the microenvironment of bifurcation lesions in vitro, we co-cultured oxidized low-density lipoprotein (oxLDL)-treated THP-1-derived macrophages with shear-treated human umbilical vein endothelial cells (HUVECs). We found that oscillatory shear induced the increase of PLXND1 in M1 macrophages, and knocking down PLXND1 inhibited M1 polarization. Semaphorin 3E, the ligand of PLXND1 which was highly expressed in plaques, strongly enhanced M1 macrophage polarization via PLXND1 in vitro. Our findings provide insights into pathogenesis in site-specific atherosclerosis that PLXND1 mediates disturbed flow-induced M1 macrophage polarization.

BackgroundCoarctation of the aorta (CoA), is a congenital malformation, often combined with several cardiac abnormalities. At present, the operation effect is satisfactory, but postoperative restenosis is still a matter. Identification of risk factors for restenosis and prompt therapy adjustments may improve patient outcomes.Materials and methodsA retrospective clinical study of patients under 12 who had CoA repair in 2012–2021, with a randomized cohort population of 475 patients.ResultsA total of 51 patients (M/F: 30/21) with a mean age of 5.33 (2.00–15.00) months and a median weight of 5.60 (4.20–10.00) kg. The mean follow-up was 8.93 (3.77–19.37) months. Patients were divided into 2 groups: no-restenosis (n-reCoA) (G1, 38 patients) and restenosis (reCoA) (G2, 13 patients). ReCoA was defined as a restenosis requiring interventional or surgery or a pressure gradient >20 mmHg at the repair site as reported by B-ultrasound with the presence of an upper and lower limb blood pressure gradient or growing dysplasia. The overall reCoA incidence was 25% (13/51). In multivariate COX regression, smaller preoperative z-score of the ascending aorta (P = 0.009, HR = 0.68) and transverse aortic arch (P = 0.015, HR = 0.66), arm-leg systolic pressure gradient ≥12.5 mmHg at discharge (P = 0.003, HR = 1.09) were independent risk factors for reCoA.ConclusionThe overall outcome of CoA surgery is successful. Smaller preoperative z-score of the ascending aorta and transverse aortic arch, and an arm-leg systolic pressure gradient ≥12.5 mmHg at discharge increase reCoA risk, and closer follow-up for such patients are required especially within 1 postoperative year.

IntroductionBlood–brain barrier (BBB) breakdown is closely associated with cognitive dysfunction. This study aimed to categorize and summarize research topics on the correlation between BBB breakdown and its effects on cognitive function.MethodsBibliometric analysis methods were used to quantitatively and qualitatively assess research progress and predict future research hotspots. Relevant publications from the Web of the Science Core Collection were extracted on November 5, 2022 and analyzed to predict trends and hotspots in the field.ResultsWe identified 5518 articles published from 2000 to 2021 about the BBB and cognition. The number of manuscripts on this topic increased steadily during this time period, especially after 2013. We found that the number of articles published in China increased gradually and is in second place behind the United States of America (USA). In the research field of BBB breakdown and cognitive function, the USA is still far ahead. Keyword burst detection suggested that cognitive impairment, neurodegeneration disease and neuroinflammation are emerging research hotspots.DiscussionThe mechanisms of BBB integrity breakdown and its effects on the deterioration of cognitive function are complex, and clinical treatment of the affected diseases has been a hot topic in the field over the past 22 years. Looking forward, this body of research is aimed at improving or maintaining patients’ cognitive abilities, by finding preventive measures and to provide a basis for finding new treatments of cognitive disorders.

Careful scrutiny of the single pulse emissions from PSR B2110+27 has been conducted through highly sensitive observations using the Five-hundred-meter Aperture Spherical radio Telescope (FAST) at a central frequency of 1250 MHz. Our investigation revealed significant subpulse drift behavior and nulling in this pulsar. Moreover, we observed that the nulling events tend to be of short duration, with an estimated overall nulling fraction of approximately 27% ± 3%. It is noteworthy that the drift direction of the subpulses exhibits abrupt changes, occasionally transitioning into a steady state or displaying a low drift rate. Analysis using longitude resolved fluctuation spectra indicates the presence of two distinct repetition periods for the pulsar: P _3 = (10.8 ± 2.5)P and P _3 = (31.6 ± 4.2)P, where P denotes the pulsar period. Our investigation revealed that the subpulse separation remains consistent across different drift patterns, with P _2 = 2.°3 ± 0.°2. A more comprehensive analysis indicates that the unique drift behavior observed can be explained by a carousel model of the dipole field. Minor changes in P _2 and drift rate caused significant variations in the apparent P _3 and abrupt shifts in the drift direction, while the true repetition period (assuming first-order aliasing) changed by only ∼10%. We observe a drift band memory and apparent phase memory across the null state in this pulsar, as well as variations in the drift rate and drift direction across the null state, though we have not detected significant periodicity of the nulling itself. This suggests that these phenomena may arise from random null pulses intersecting with the frequently aliased drift bands.

In this study, electrically insulating polyolefin elastomer (POE)-based phase change materials (PCMs) comprising alumina (Al2O3) and graphene nanoplatelets (GNPs) are prepared using a conventional injection moulding technique, which exhibits promising applications for solar energy storage due to the reduced interfacial thermal resistance, excellent stability, and proficient photo-thermal conversion efficiency. A synergistic interplay between Al2O3 and GNPs is observed, which facilitates the establishment of thermally conductive pathways within the POE/paraffin wax (POE/PW) matrix. The in-plane thermal conductivity of POE/PW/GNPs 5 wt%/Al2O3 40 wt% composite reaches as high as 1.82 W m−1K−1, marking a remarkable increase of ≈269.5% when compared with that of its unfilled POE/PW counterpart. The composite exhibits exceptional heat dissipation capabilities, which is critical for thermal management applications in electronics. Moreover, POE/PW/GNPs/Al2O3 composites demonstrate outstanding electrical insulation, enhanced mechanical performance, and efficient solar energy conversion and transportation. Under 80 mW cm−2 NIR light irradiation, the temperature of the POE/PW/GNPs 5 wt%/Al2O3 40 wt% composite reaches approximately 65 °C, a notable 20 °C improvement when compared with the POE/PW blend. The pragmatic and uncomplicated preparation method, coupled with the stellar performance of the composites, opens a promising avenue and broader possibility for developing flexible PCMs for solar conversion and thermal storage applications.

The DS-1 satellite was launched successfully on 3 June 2021 from the Taiyuan Satellite Launch Center. The satellite is equipped with a 1 m panchromatic and a 4 m multispectral sensor, providing high-resolution and wide-field optical remote sensing imaging capabilities. For satellites equipped with panchromatic and multispectral sensors, conventional geometric processing methods in the past involved separate calibration for the panchromatic sensor and the multispectral sensor. This method produced distinct internal and external calibration parameters in the respective bands, and also resulted in nonlinear geometric misalignments between the panchromatic and multispectral images due to satellite chattering and other factors. To better capitalize on the high spatial resolution of panchromatic imagery and the superior spectral resolution of multispectral imagery, it is necessary to perform registration on the calibrated panchromatic and multispectral images. When registering separately calibrated panchromatic and multispectral images, poor consistency between panchromatic and multispectral images leads to a small number of corresponding points, resulting in poor accuracy and registration effects. To address this issue, we propose a joint panchromatic and multispectral calibration method to register the panchromatic and multispectral images. Before geometric calibration, it is necessary to perform corresponding points matching. When matching, the small interval between the panchromatic and multispectral Charge-Coupled Devices (CCDs) results in a small intersection angle of the corresponding points between the panchromatic and multispectral images. As a result of this, the consistency between the spectral bands significantly improves, and the corresponding points match to have a more uniform distribution and a wider coverage. The technique enhances the consistent registration accuracy of both the panchromatic and multispectral bands. Experiments demonstrate that the joint calibration method yields a registration accuracy of panchromatic and multispectral bands exceeding 0.3 pixels.

Time-hopping pulse position modulation (TH-PPM) stands out as a secure communication due to the pseudo-random characteristics of its time-hopping sequence. However, the conventional TH-PPM transceiver encounters challenges in implementation, particularly in achieving the requisite high precision for synchronization. This paper introduces a novel non-coherent Q-ary TH-PPM transceiver, designed to surpass the Bit error rate (BER) performance of conventional TH-PPM transceivers in scenarios under non-ideal synchronization conditions, which also being straightforward to implement. Firstly, we provide an overview of the conventional TH-PPM transceiver. Secondly, the novel TH-PPM transceiver is introduced. In this context, a novel method for generating the TH-PPM signal is proposed for the transmitter, and a parallel matched-filter algorithm, adapted to the new TH-PPM signal, is presented for the receiver. Subsequently, the investigation delves into an in-depth analysis of BER performance, considering both ideal synchronization conditions and non-ideal synchronization conditions, for both the conventional and the new TH-PPM transceiver. Furthermore, the paper proposes a numerical simulation to validate the theoretical findings. The results demonstrate that the new TH-PPM transceiver outperforms the conventional counterpart by showing better BER performance in scenarios with non-ideal synchronization conditions.

The potato green tea sugar-free chiffon cake was made by using potato flour and green tea flour instead of some low gluten flour, and using xylitol instead of sugar in traditional chiffon cake. With texture characteristics, specific volumes and sensory evaluation as evaluation indexes, the optimal formula was determined by single factors and orthogonal tests: 20% potato powder, 6% green tea powder, 230% egg white and 70% xylitol. The potato green tea sugar-free chiffon cake was light green color, sweet and not greasy, rich in flavor. Compared with traditional chiffon cakes, the total sugar content was low (6.03%) and the content of crude fiber was high (7.89%). It also had some oxidation resistance (antioxidant capacity 0.0560 mmol/g).

Abstract Background Bone marrow mesenchymal stem cell (BMSCs) therapy is an important cell transplantation strategy in the regenerative medicine field. However, a severely ischemic microenvironment, such as nutrient depletion and hypoxia, causes a lower survival rate of transplanted BMSCs, limiting the application of BMSCs. Therefore, improving BMSCs viability in adverse microenvironments is an important means to improve the effectiveness of BMSCs therapy. Objective To illustrate the protective effect of andrographolide (AG) against glucose and serum deprivation under hypoxia (1% O2) (GSDH)-induced cell injury in BMSCs and investigate the possible underlying mechanisms. Methods An in vitro primary rat BMSCs cell injury model was established by GSDH, and cellular viability, proliferation and apoptosis were observed after AG treatment under GSDH. Reactive oxygen species levels and oxidative stress-related genes and proteins were measured by flow cytometry, RT-qPCR and Western blotting. Mitochondrial morphology, function and number were further assessed by laser confocal microscopy and flow cytometry. Results AG protected BMSCs against GSDH-induced cell injury, as indicated by increases in cell viability and proliferation and mitochondrial number and decreases in apoptosis and oxidative stress. The metabolic status of BMSCs was changed from glycolysis to oxidative phosphorylation to increase the ATP supply. We further observed that the NRF2 pathway was activated by AG, and treatment of BMSCs with a specific NRF2 inhibitor (ML385) blocked the protective effect of AG. Conclusion Our results suggest that AG is a promising agent to improve the therapeutic effect of BMSCs.

Abstract A hybrid redundancy (HR) scheme is proposed for the medium‐voltage three‐phase cascaded H‐bridge electronic power transformer (CHB‐EPT) based on the combination of the global redundant power modules and local redundant power modules. A “HOT‐FIRST‐LOCAL‐FIRST” transition strategy is designed to achieve a short transition time. Furthermore, to reduce the power loss of the redundant power modules, an intermittent charging (IC) strategy is proposed for the hot‐reserved redundant power modules. The detailed analysis of the topology shows that the proposed scheme can achieve low cost, high reliability, low power loss, and good transition performance. The performances are verified by simulations and experimental results.

Expanding the responsive dyes repertoire is currently a developing field in biorthogonal chemistry. In this article, the authors develop fluorophores that turn on their near-infrared fluorescence upon biorthogonal reaction based on a “torsion-induced disaggregation” approach, allowing for sensitive in vivo imaging of tumors.

Abstract Background Breast cancer and lung cancer are the top two malignancies in the female population and the number of patients with breast cancer and subsequent primary lung cancer has increased significantly in recent years. However, the unique molecular characteristics of this group of patients remains unclear. Purpose To identify the genomic and transcriptome characteristics of primary lung adenocarcinoma patients with previous breast cancer by comparison with single primary lung adenocarcinoma (SPLA) patients. Methods The tumor and normal pulmonary tissue specimens of ten primary pulmonary adenocarcinoma patients with previous breast cancer (multiple primary cancer, MPC) and ten SPLA patients were prospectively collected. The whole exome sequencing (WES) and RNA sequencing (RNA-seq) were performed to analyze the gene mutation and expression differences between MPC and SPC patients. Results The results of WES indicated that the mutations of TRIM73, DLX6 and CNGB1 only existed in MPC patients. The results of RNA-seq manifested the occurrence of second primary lung adenocarcinoma in breast cancer patients was closely associated with cytokine-cytokine receptor action, autophagy, PI3L-Akt, cAMP and calcium ion signaling pathways. Besides, the expression levels of FGF10 and VEGFA genes were significantly increased in MPC patients. Conclusion The occurrence of second primary lung adenocarcinoma may be related to the cytokine-cytokine receptor action, autophagy, PI3L-Akt, cAMP and calcium ion signaling pathways. Furthermore, the mutations of TRIM73, DLX6 and CNGB1 and high expression of FGF10 and VEGFA might play an important role in the development of lung adenocarcinoma in breast cancer patients. However, more in-depth investigations are needed to verify above findings.

Abstract Background Applying traditional fluorescence navigation technologies in hepatocellular carcinoma is severely restricted by high false-positive rates, variable tumor differentiation, and unstable fluorescence performance. Results In this study, a green, economical and safe nanomedicine formulation technology was developed to construct carrier-free indocyanine green nanoparticles (nanoICG) with a small uniform size and better fluorescent properties without any molecular structure changes compared to the ICG molecule. Subsequently, nanoICG dispersed into lipiodol via a super-stable homogeneous intermixed formulation technology (SHIFT&nanoICG) for transhepatic arterial embolization combined with fluorescent laparoscopic hepatectomy to eliminate the existing shortcomings. A 52-year-old liver cancer patient was recruited for the clinical trial of SHIFT&nanoICG. We demonstrate that SHIFT&nanoICG could accurately identify and mark the lesion with excellent stability, embolism, optical imaging performance, and higher tumor-to-normal tissue ratio, especially in the detection of the microsatellite lesions (0.4 × 0.3 cm), which could not be detected by preoperative imaging, to realize a complete resection of hepatocellular carcinoma under fluorescence laparoscopy in a shorter period (within 2 h) and with less intraoperative blood loss (50 mL). Conclusions This simple and effective strategy integrates the diagnosis and treatment of hepatocellular carcinoma, and thus, it has great potential in various clinical applications.

Abstract Background This study aimed to investigate the association between dietary fiber intake and long-term cardiovascular disease (CVD) risk based on the National Health and Nutrition Examination Survey (NHANES) database. Methods A total of 14,947 participants aged 20–79 from the NHANES database were included in this study between 2009 and 2018. The atherosclerotic cardiovascular disease (ASCVD) score was utilized to predict the 10-year risk of CVD in individuals (low, borderline, intermediate, and high risk). Weighted univariate and multinomial multivariate logistic regression analyses were used to analyze the association between dietary fiber intake and long-term CVD risk. Results Higher dietary fiber density may be associated with a reduced ASCVD risk in participants with intermediate risk [odds ratio (OR) = 0.76; 95% confidence interval (CI), 0.61–0.94] and high risk (OR = 0.60; 95%CI, 0.45–0.81) compared with those in the group with low risk. Higher total dietary fiber intake may also reduce ASCVD risk in participants with high risk (OR = 0.84; 95%CI, 0.75–0.95). Subgroup analyses showed that higher dietary fiber density may be related to reduced ASCVD risk in intermediate-risk participants aged 20–39 (OR = 0.62; 95%CI, 0.43–0.89) and 40–59 (OR = 0.67; 95%CI, 0.49–0.94). In high-risk participants, higher dietary fiber density may reduce ASCVD risk in 20–39-year-old (OR = 0.38; 95%CI, 0.19–0.77), 40–59-year-old (OR = 0.37; 95%CI, 0.20–0.70), male (OR = 0.47; 95%CI, 0.23–0.97) and female (OR = 0.57; 95%CI, 0.38–0.86) participants. Conclusion Higher dietary fiber density and total dietary fiber intake were associated with a lower long-term CVD risk, especially in the 20–39 and 40–59 age groups, where the reduction was most significant.

Abstract Fire safety issues hinder the large‐scale application of lithium‐ion batteries (LiBs). Here, a new type of fire‐response separators is prepared by loading the microcapsule fire extinguishing agent on the surface of the separator. The shell of the microcapsule will break automatically at a certain temperature and release the fire extinguishing agent when thermal runaway of LiBs occurs, which can quickly absorb heat through endothermic reaction and ensure LiBs will not burn or explode. The porosity of fire‐response separator is 53.6%, the electrolyte uptake is 132% and the ionic conductivity is 1.00 mS cm‐1. The initial specific capacity is 2643 mAh g‐1 at 4°C and the capacity retention rate is 93% after 200 cycles for NCM523 battery based fire‐response separator. The temperature of LiBs based on the fire‐response separator can automatically drop to room temperature in 20 seconds, which ensures the safety of other adjacent LiBs. This work proposes a new active protection concept to solve the safety problem of LiBs.

Summary: Background: Intraplaque haemorrhage (IPH) drives atherosclerosis progression and is a key imaging biomarker of unstable plaques. Non-invasive and sensitive monitoring of IPH is challenging due to the compositional complexity and dynamic nature of atherosclerotic plaques. Magnetic particle imaging (MPI) is a highly sensitive, radiation-free, and no-tissue-background tomographic technique that detects superparamagnetic nanoparticles. Thus, we aimed to investigate whether MPI can in vivo detect and monitor IPH. Methods: Thirty human carotid endarterectomy samples were collected and scanned with MPI. The tandem stenosis (TS) model was employed to establish unstable plaques with IPH in ApoE−/− mice. MPI and 7 T T1-weighted magnetic resonance imaging (MRI) were performed on TS ApoE−/− mice. Plaque specimens were analyzed histologically. Findings: Human carotid endarterectomy samples exhibited endogenous MPI signals, which histologically colocalized with IPH. In vitro experiments identified haemosiderin, a haemoglobin degradation product, as a potential source of MPI signals. Longitudinal MPI of TS ApoE−/− mice detected IPH at unstable plaques, of which MPI signal-to-noise ratio values increased from 6.43 ± 1.74 (four weeks) to 10.55 ± 2.30 (seven weeks) and reduced to 7.23 ± 1.44 (eleven weeks). In contrast, 7 T T1-weighted MRI did not detect the small-size IPH (329.91 ± 226.82 μm2) at four weeks post-TS. The time-course changes in IPH were shown to correlate with neovessel permeability providing a possible mechanism for signal changes over time. Interpretation: MPI is a highly sensitive imaging technology that allows the identification of atherosclerotic plaques with IPH and may help detect and monitor unstable plaques in patients. Funding: This work was supported in part by the Beijing Natural Science Foundation under Grant JQ22023; the National Key Research and Development Program of China under Grant 2017YFA0700401; the National Natural Science Foundation of China under Grant 62027901, 81827808, 81730050, 81870178, 81800221, 81527805, and 81671851; the CAS Youth Innovation Promotion Association under Grant Y2022055 and CAS Key Technology Talent Program; and the Project of High-Level Talents Team Introduction in Zhuhai City (Zhuhai HLHPTP201703).

Frequency Domain Spectroscopy (FDS) is widely used to estimate oil–paper insulation. The high moisture and long aging change the FDS characteristics of the insulating oil–paper, so normalization processing is required. Still, the choice of single activation energy needs further research. This paper studies the FDS characteristic of oil–paper insulation samples with different moisture and aging degrees and improves the traditional temperature correction method. The enhanced Arrhenius model uses the segmented activation energy to make the normalized FDS curve coincide better with the target curve, and the error is reduced. In addition, to verify the method’s effectiveness, this paper proposes an iterative correction process. It corrects the tan δ-f curve of the bushing with an aging time of 800 h based on segmented activation energy, and the overall normalization effect is improved.

BackgroundHepatocellular carcinoma (HCC), one of the most common cancers worldwide, exhibits high immune heterogeneity and mortality. Emerging studies suggest that copper (Cu) plays a key role in cell survival. However, the relationship between Cu and tumor development remains unclear.MethodsWe investigated the effects of Cu and cuproptosis-related genes (CRGs) in patients with HCC in the TCGA-LIHC (The Cancer Genome Atlas-Liver cancer, n = 347) and ICGC-LIRI-JP (International Cancer Genome Consortium-Liver Cancer-Riken-Japan, n = 203) datasets. Prognostic genes were identified by survival analysis, and a least absolute shrinkage and selection operator (Lasso) regression model was constructed using the prognostic genes in the two datasets. Additionally, we analyzed differentially expressed genes and signal pathway enrichment. We also evaluated the effects of CRGs on tumor immune cell infiltration and their co-expression with immune checkpoint genes (ICGs) and performed validation in different tumor immune microenvironments (TIMs). Finally, we performed validation using clinical samples and predicted the prognosis of patients with HCC using a nomogram.ResultsA total of 59 CRGs were included for analysis, and 15 genes that significantly influenced the survival of patients in the two datasets were identified. Patients were grouped by risk scores, and pathway enrichment analysis suggested that immune-related pathways were substantially enriched in both datasets. Tumor immune cell infiltration analysis and clinical validation revealed that PRNP (Prion protein), SNCA (Synuclein alpha), and COX17 (Cytochrome c oxidase copper chaperone COX17) may be closely correlated with immune cell infiltration and ICG expression. A nomogram was constructed to predict the prognosis of patients with HCC using patients’ characteristics and risk scores.ConclusionCRGs may regulate the development of HCC by targeting the TIM and ICGs. CRGs such as PRNP, SNCA, and COX17 could be promising targets for HCC immune therapy in the future.

BackgroundAlthough dexmedetomidine (DEX) is widely used during the perioperative period in patients with hepatocellular carcinoma (HCC), its clinical effects on liver function and postoperative inflammation are unclear. This study aimed to explore effects of DEX on postoperative liver function and inflammation in patients with HCC after hepatectomy.MethodsA retrospective cohort study with propensity score matching was performed. A total of 494 patients who underwent hepatectomy from June 2019 to July 2020 and fulfilled the eligibility criteria were included in this study. Baseline data, liver function indexes and inflammation-related biomarkers were collected and compared between the two groups. Survival analysis was conducted to investigate the effects of DEX on the overall survival (OS) of patients. Propensity score matching (PSM) was used to minimize bias between the two groups.ResultsThe study cohort comprised 189 patients in the DEX-free group and 305 patients in the DEX group. Patients in the DEX group had lower levels of alanine transaminase (ALT, P = 0.018) and lactate dehydrogenase (LDH, P = 0.046) and higher level of serum albumin (ALB, P < 0.001) than patients in the DEX-free group before discharge. A total of 107 pairs of patients were successfully matched by PSM. Results consistently suggested that ALT and LDH levels were significantly lower (P = 0.044 and P = 0.046, respectively) and ALB levels were significantly higher (P = 0.002) in the DEX group than in the DEX-free group in the early postoperative period. No significant differences of inflammation-related biomarkers were observed between two groups after PSM. Neither the Kaplan–Meier survival analysis nor the multiple Cox regression survival analysis identified DEX as a contributing factor that would affect the OS of patients after PSM.ConclusionDEX exerts protective effects on liver function while has little effects on inflammation-related biomarkers in the early postoperative period in patients undergoing hepatectomy due to HCC.

Summary: Chemerin, an adipocyte-secreted protein, has been recently suggested to be linked to metabolic syndrome and cardiac function in obese and diabetes mellitus. This study aimed to investigate the potential roles of adipokine chemerin on high fat-induced cardiac dysfunction. Chemerin (Rarres2) knockout mice, which were fed with either a normal diet or a high-fat diet for 20 weeks, were employed to observe whether adipokine chemerin affected lipid metabolism, inflammation, and cardiac function. Firstly, we found normal metabolic substrate inflexibility and cardiac function in Rarres2−/− mice with a normal diet. Notably, in a high-fat diet, Rarres2−/− mice showed lipotoxicity, insulin resistance, and inflammation, thus causing metabolic substrate inflexibility and cardiac dysfunction. Furthermore, by using in vitro model of lipid-overload cardiomyocytes, we found chemerin supplementation reversed the lipid-induced abnormalities above. Herein, in the presence of obesity, adipocyte-derived chemerin might function as an endogenous cardioprotective factor against obese-related cardiomyopathy.

The vegetation carbon uptake plays an important role in the terrestrial carbon cycle on the Qinghai–Tibet Plateau (QTP), while it is extremely sensitive to the impact of natural external forcings. Until now, there is limited knowledge on the spatial-temporal patterns of vegetation net carbon uptake (VNCU) after the force that caused by tropical volcanic eruptions. Here, we conducted an exhaustive reconstruction of VNCU on the QTP over the last millennium, and used a superposed epoch analysis to characterize the VNCU response of the QTP after the tropical volcanic eruptions. We then further investigated the divergent changes of VNCU response across different elevation gradients and vegetation types, and the impact of teleconnection forcing on VNCU after volcanic eruptions. Within a climatic background, we found that VNCU of the QTP tends to decrease after large volcanic eruptions, lasting until about 3 years, with a maximum decrease value occurring in the following 1 year. The spatial and temporal patterns of the VNCU were mainly driven by the post-eruption climate and moderated by the negative phase trends of El Niño-Southern Oscillation and the Atlantic multidecadal oscillation. In addition, elevation and vegetation types were undeniable driving forces associated with VNCU on QTP. Different water-heat conditions and vegetation types contributed to significant differences in the response and recovery processes of VNCU. Our results emphasized the response and recovery processes of VNCU to volcanic eruptions without the strong anthropogenic forcings, while the influence mechanisms of natural forcing on VNCU should receive more attention.

Abstract The clinical applications of transcatheter arterial embolization (TAE) conversion therapy combined with hepatectomy have been severely restricted by ill‐defined tumoral boundaries and miniscule hidden lesions. Fluorescent surgical navigation is a promising method for overcoming these barriers. However, sufficient delivery of the fluorescent probe into the tumor region after long‐term TAE is challenging due to blockade of the tumor‐supplying artery. Here, a super‐stable homogeneous intermix formulating technology (SHIFT) to physically mix lipiodol and indocyanine green (ICG) formulation (SHIFT and ICG) for fluorescent surgical navigation after long‐term TAE conversion therapy is provided. Through the retrospective study of 45 clinical liver cancer patients, it is found that SHIFT and ICG formulation have excellent tumor deposition effect and safety. During surgical resection after long‐term TAE conversion therapy, SHIFT and ICG could clearly identify in real time the full tumor regions and boundaries and had a high signal‐to‐normal tissues ratio—even the indistinguishable satellite lesions could be identified with a strong fluorescence intensity. Meanwhile, SHIFT and ICG could improve operative, anesthetic, and postoperative variables associated with postoperative complications. This simple and effective SHIFT could provide precise fluorescent navigation for surgical resection following long‐term embolization therapy in clinical practice and has great potential for a translational pipeline.

Background: This study aimed to develop an artificial intelligence-based computer-aided diagnosis system (AI-CAD) emulating the diagnostic logic of radiologists for lymph node metastasis (LNM) in esophageal squamous cell carcinoma (ESCC) patients, which contributed to clinical treatment decision-making. Methods: A total of 689 ESCC patients with PET/CT images were enrolled from three hospitals and divided into a training cohort and two external validation cohorts. 452 CT images from three publicly available datasets were also included for pretraining the model. Anatomic information from CT images was first obtained automatically using a U-Net-based multi-organ segmentation model, and metabolic information from PET images was subsequently extracted using a gradient-based approach. AI-CAD was developed in the training cohort and externally validated in two validation cohorts. Results: The AI-CAD achieved an accuracy of 0.744 for predicting pathological LNM in the external cohort and a good agreement with a human expert in two external validation cohorts (kappa = 0.674 and 0.587, p

Herein, we report two cases of successful application of indocyanine green (ICG) fluorescence imaging for detecting intraoperative bile leakage during laparoscopic cholecystectomy (LC). Bile leakage was detected rapidly and accurately using fluorescence guidance. Based on our findings, we recommend using ICG fluorescence imaging during LC because it is effective and feasible for detecting intraoperative bile leakage.

Summary: Background: Surgery is the cornerstone of colorectal cancer (CRC) treatment, yet complete removal of the tumour remains a challenge. The second near-infrared window (NIR-II, 1000–1700 nm) fluorescent molecular imaging is a novel technique, which has broad application prospects in tumour surgical navigation. We aimed to evaluate the ability of CEACAM5-targeted probe for CRC recognition and the value of NIR-II imaging-guided CRC resection. Methods: We constructed the probe 2D5-IRDye800CW by conjugated anti-CEACAM5 nanobody (2D5) with near-infrared fluorescent dye IRDye800CW. The performance and benefits of 2D5-IRDye800CW at NIR-II were confirmed by imaging experiments in mouse vascular and capillary phantom. Then mouse colorectal cancer subcutaneous tumour model (n = 15), orthotopic model (n = 15), and peritoneal metastasis model (n = 10) were constructed to investigate biodistribution of probe and imaging differences between NIR-I and NIR-II in vivo, and then tumour resection was guided by NIR-II fluorescence. Fresh human colorectal cancer specimens were incubated with 2D5-IRDye800CW to verify its specific targeting ability. Findings: 2D5-IRDye800CW had an NIR-II fluorescence signal extending to 1600 nm and bound specifically to CEACAM5 with an affinity of 2.29 nM. In vivo imaging, 2D5-IRDye800CW accumulated rapidly in tumour (15 min) and could specifically identify orthotopic colorectal cancer and peritoneal metastases. All tumours were resected under NIR-II fluorescence guidance, even smaller than 2 mm tumours were detected, and NIR-II had a higher tumour-to-background ratio than NIR-I (2.55 ± 0.38, 1.94 ± 0.20, respectively). 2D5-IRDye800CW could precisely identify CEACAM5-positive human colorectal cancer tissue. Interpretation: 2D5-IRDye800CW combined with NIR-II fluorescence has translational potential as an aid to improve R0 surgery of colorectal cancer. Fundings: This study was supported by Beijing Natural Science Foundation (JQ19027), the National Key Research and Development Program of China (2017YFA0205200), National Natural Science Foundation of China (NSFC) (61971442, 62027901, 81930053, 92059207, 81227901, 82102236), Beijing Natural Science Foundation (L222054), CAS Youth Interdisciplinary Team (JCTD-2021-08), the Strategic Priority Research Program of the Chinese Academy of Sciences (XDA16021200), the Zhuhai High-level Health Personnel Team Project (Zhuhai HLHPTP201703), the Fundamental Research Funds for the Central Universities (JKF-YG-22-B005) and Capital Clinical Characteristic Application Research (Z181100001718178). The authors would like to acknowledge the instrumental and technical support of the multi-modal biomedical imaging experimental platform, Institute of Automation, Chinese Academy of Sciences.

Abstract Objectives This study aims to further investigate the association of COVID-19 disease severity with numerous patient characteristics, and to develop a convenient severity prediction scale for use in self-assessment at home or in preliminary screening in community healthcare settings. Setting and participants Data from 45,450 patients infected with COVID-19 from January 1 to February 27, 2020 were extracted from the municipal Notifiable Disease Report System in Wuhan, China. Primary and secondary outcome measures We categorized COVID-19 disease severity, based on The Chinese Diagnosis and Treatment Protocol for COVID-19, as “nonsevere” (which grouped asymptomatic, mild, and ordinary disease) versus “severe” (grouping severe and critical illness). Results Twelve scale items—age, gender, illness duration, dyspnea, shortness of breath (clinical evidence of altered breathing), hypertension, pulmonary disease, diabetes, cardio/cerebrovascular disease, number of comorbidities, neutrophil percentage, and lymphocyte percentage—were identified and showed good predictive ability (area under the curve = 0·72). After excluding the community healthcare laboratory parameters, the remaining model (the final self-assessment scale) showed similar area under the curve (= 0·71). Conclusions Our COVID-19 severity self-assessment scale can be used by patients in the community to predict their risk of developing severe illness and the need for further medical assistance. The tool is also practical for use in preliminary screening in community healthcare settings. Summary Our study constructed a COVID-19 severity self-assessment scale that can be used by patients in the community to predict their risk of developing severe illness and the need for further medical assistance.

Abstract Background Accurate and non-invasive diagnosis of pancreatic ductal adenocarcinoma (PDAC) and chronic pancreatitis (CP) can avoid unnecessary puncture and surgery. This study aimed to develop a deep learning radiomics (DLR) model based on contrast-enhanced ultrasound (CEUS) images to assist radiologists in identifying PDAC and CP. Methods Patients with PDAC or CP were retrospectively enrolled from three hospitals. Detailed clinicopathological data were collected for each patient. Diagnoses were confirmed pathologically using biopsy or surgery in all patients. We developed an end-to-end DLR model for diagnosing PDAC and CP using CEUS images. To verify the clinical application value of the DLR model, two rounds of reader studies were performed. Results A total of 558 patients with pancreatic lesions were enrolled and were split into the training cohort (n=351), internal validation cohort (n=109), and external validation cohorts 1 (n=50) and 2 (n=48). The DLR model achieved an area under curve (AUC) of 0.986 (95% CI 0.975–0.994), 0.978 (95% CI 0.950–0.996), 0.967 (95% CI 0.917–1.000), and 0.953 (95% CI 0.877–1.000) in the training, internal validation, and external validation cohorts 1 and 2, respectively. The sensitivity and specificity of the DLR model were higher than or comparable to the diagnoses of the five radiologists in the three validation cohorts. With the aid of the DLR model, the diagnostic sensitivity of all radiologists was further improved at the expense of a small or no decrease in specificity in the three validation cohorts. Conclusions The findings of this study suggest that our DLR model can be used as an effective tool to assist radiologists in the diagnosis of PDAC and CP.

Abstract Background While a COVID-19 vaccine protects people from serious illness and death, it remains a concern when and how to lift the high-cost and strict non-pharmaceutical interventions (NPIs). This study examined the joint effect of vaccine coverage and NPIs on the control of local and sporadic resurgence of COVID-19 cases. Methods Between July 2021 and January 2022, we collected the large-scale testing information and case number of imported COVID-19 patients from the website of the National Health Commission of China. A compartment model was developed to identify the level of vaccine coverage that would allow safe relaxation of NPIs, and vaccination strategies that can best achieve this level of coverage. We applied Monte Carlo simulation 50 000 times to remove random fluctuation effects and obtain fitted/predicted epidemic curve based on various parameters with 95% confidence interval at each time point. Results We found that a vaccination coverage of 50.4% was needed for the safe relaxation of NPIs, if the vaccine effectiveness was 79.3%. The total number of incidence cases under the key groups firstly strategy was 103 times higher than that of accelerated vaccination strategy. It needed 35 months to fully relax NPIs if the key groups firstly strategy was implemented, and 27 months were needed with the accelerated vaccination strategy. If combined the two strategies, only 8 months are needed to achieve the vaccine coverage threshold for the fully relaxation of NPIs. Sensitivity analyses results shown that the higher the transmission rate of the virus and the lower annual vaccine supply, the more difficult the epidemic could be under control. When the transmission rate increased 25% or the vaccination effectiveness rate decreased 20%, 33 months were needed to reduce the number of total incidence cases below 1000. Conclusions As vaccine coverage improves, the NPIs can be gradually relaxed. Until that threshold is reached, however, strict NPIs are still needed to control the epidemic. The more transmissible SARS-CoV-2 variant led to higher resurgence probability, which indicates the importance of accelerated vaccination and achieving the vaccine coverage earlier. Graphical Abstract