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Abstract Background Dietary rationality and health concept have certain influence on individual health level. This study aims to explore the characteristics and existing problems of Chinese residents’ health behaviors from both macro and micro perspectives, and explore the feasibility and realization path of Healthy China strategy. Methods We utilized regression models to evaluate the correlation between diet and the risk of disease causes of death. By use of the linear regression analysis model, we distinguished the impact of each dimension on health literacy index at the individual level. Then, we explored the influential factors of the diet health index using the binary logit regression model. Results Increased consumption of animal-derived foods in China has contributed to the burden of non-communicable diseases. The individuals’ health awareness is still weak, and the health literacy index is greatly affected by the diet, while the individual gender and age are positively correlated with the diet health index, and the individual body mass index (BMI) level is negatively correlated with the diet health index. Conclusions This study provided a comprehensive understanding of existing problems of Chinese residents’ health behaviors. We have proposed a path model for the implementation of the Healthy China strategy from the perspectives of “diet health, physical health, conceptual health and environmental health,” which is also a great contribution to the world.

Abstract Background The clinical application of immune checkpoint inhibitors (ICIs) is limited by their drug resistance, necessitating the development of ICI sensitizers to improve cancer immunotherapy outcomes. Huang Lian Jie Du Decoction (HLJD, Oren-gedoku-to in Japanese, Hwangryunhaedok-tang in Korean), a famous traditional Chinese medicinal prescription, has exhibited potential in the field of cancer treatment. This study aims to investigate the impact of HLJD on the efficacy of ICIs in melanoma and elucidate the underlying mechanisms. Methods The potential synergistic effects of HLJD and ICIs were investigated on the tumor-bearing mice model of B16F10 melanoma, and the tumor infiltration of immune cells was tested by flow cytometry. The differential gene expression in tumors between HLJD and ICIs group and ICIs alone group were analyzed by RNA-seq. The effects of HLJD on oxidative stress, TLR7/8, and type I interferons (IFN-Is) signaling were further validated by immunofluorescence, PCR array, and immunochemistry in tumor tissue. Results HLJD enhanced the anti-tumor effect of ICIs, significantly inhibited tumor growth, and prolonged the survival duration in melanoma. HLJD increased the tumor infiltration of anti-tumor immune cells, especially DCs, CD4+ T cells and CD8+T cells. Mechanically, HLJD activated the oxidative stress and TLR7/8 signaling pathway and IFN-Is-related genes in tumors. Conclusions HLJD enhanced the therapeutic benefits of ICIs in melanoma, through increasing reactive oxygen species (ROS), promoting the TLR7/8 pathway, and activating IFN-Is signaling, which in turn activated DCs and T cells.

Background: Gastric cancer (GC) is one of the most common malignant tumors in the world. It has become increasingly difficult to meet the needs of precision therapy using the existing molecular typing system. Therefore, developing a more effective molecular typing system for GC is urgent. Methods: In this study, 100 Chinese GC patients were included. Whole-exome sequencing (WES) and metabolomics analysis were performed to reveal the characteristics of genomic and metabolic changes. Results: In WES, nonsynonymous mutations accounted for the majority. Based on metabolomics, GC has been divided into three subtypes with distinct metabolic features. Importantly, we ultimately divided GC into four subtypes with different metabolic characteristics, genomic alterations, and clinical prognoses by incorporating biomics analysis. Conclusions: Integrating biological features, we constructed a novel molecular system for GC that was closely related to genetics and metabolism, providing new insights for further understanding the heterogeneity and formulating precise treatment strategies.

Abstract Background Gastric cancer (GC) is associated with high mortality and heterogeneity and poses a great threat to humans. Gene therapies for the receptor tyrosine kinase RON and its spliceosomes are attracting increasing amounts of attention due to their unique characteristics. However, little is known about the mechanism involved in the formation of the RON mRNA alternative spliceosome RONΔ160. Methods Fourteen human GC tissue samples and six normal gastric tissue samples were subjected to label-free relative quantitative proteomics analysis, and MAGOH was identified as a candidate protein for subsequent studies. The expression of MAGOH in clinical specimens was verified by quantitative real-time PCR and western blotting. We then determined the biological function of MAGOH in GC through in vitro and in vivo experiments. RNA pulldown, RNA sequencing and RNA immunoprecipitation (RIP) were subsequently conducted to uncover the underlying mechanism by which MAGOH regulated the formation of RONΔ160. Results Proteomic analysis revealed that MAGOH, which is located at key nodes and participates in RNA processing and mRNA splicing, was upregulated in GC tissue and GC cell lines and was associated with poor prognosis. Functional analysis showed that MAGOH promoted the proliferation, migration and invasion of GC cells in vitro and in vivo. Mechanistically, MAGOH inhibited the expression of hnRNPA1 and reduced the binding of hnRNPA1 to RON mRNA, thereby promoting the formation of RONΔ160 to activate the PI3K/AKT signaling pathway and consequently facilitating GC progression. Conclusions Our study revealed that MAGOH could promote the formation of RONΔ160 and activate the PI3K/AKT signaling pathway through the inhibition of hnRNPA1 expression. We elucidate a novel mechanism and potential therapeutic targets for the growth and metastasis of GC based on the MAGOH-RONΔ160 axis, and these findings have important guiding significance and clinical value for the future development of effective therapeutic strategies for GC.

Hydraulic-electric rock fragmentation (HERF) plays a significant role in improving the efficiency of high voltage pulse rock breaking. However, the underlying mechanism of HERF remains unclear. In this study, considering the heterogeneity of the rock, microscopic thermodynamic properties, and shockwave time domain waveforms, based on the shockwave model, digital imaging technology and the discrete element method, the cyclic loading numerical simulations of HERF is achieved by coupling electrical, thermal, and solid mechanics under different formation temperatures, confining pressure, initial peak voltage, electrode bit diameter, and loading times. Meanwhile, the HERF discharge system is conducive to the laboratory experiments with various electrical parameters and the resulting broken pits are numerically reconstructed to obtain the geometric parameters. The results show that, the completely broken area consists of powdery rock debris. In the pre-broken zone, the mineral cementation of the rock determines the transition of type CⅠ cracks to type CⅡ and type CⅢ cracks. Furthermore, the peak pressure of the shockwave increased with initial peak voltage but decreased with electrode bit diameter, while the wave front time reduced. Moreover, increasing well depth, formation temperature and confining pressure augment and inhibit HERF, but once confining pressure surpassed the threshold of 60 MPa for 152.40, 215.90, and 228.60 mm electrode bits, and 40 MPa for 309.88 mm electrode bits, HERF is promoted. Additionally, for the same kind of rock, the volume and width of the broken pit increase with higher initial peak voltage and rock fissures will promote HERF. Eventually, the electrode drill bit with a 215.90 mm diameter is more suitable for drilling pink granite. This research contributes to a better microscopic understanding of HERF and provides valuable insights for electrode bit selection, as well as the optimization of circuit parameters for HERF technology.

Abstract Background The low absorption of x-rays in lung tissue and the poor resolution of conventional computed tomography (CT) limits its use to detect lung disease. However, x-ray dark-field imaging can sense the scattered x-rays deflected by the structures being imaged. This technique can facilitate the detection of small alveolar lesions that would be difficult to detect with conventional CT. Therefore, it may provide an alternative imaging modality to diagnose lung disease at an early stage. Methods Eight mice were inoculated with lung cancers simultaneously. Each time two mice were scanned using a grating-based dark-field CT on days 4, 8, 12, and 16 after the introduction of the cancer cells. The detectability index was calculated between nodules and healthy parenchyma for both attenuation and dark-field modalities. High-resolution micro-CT and pathological examinations were used to crosscheck and validate our results. Paired t-test was used for comparing the ability of dark-field and attenuation modalities in pulmonary nodule detection. Results The nodules were shown as a signal decrease in the dark-field modality and a signal increase in the attenuation modality. The number of nodules increased from day 8 to day 16, indicating disease progression. The detectability indices of dark-field modality were higher than those of attenuation modality (p = 0.025). Conclusions Compared with the standard attenuation CT, the dark-field CT improved the detection of lung nodules. Relevance statement Dark-field CT has a higher detectability index than conventional attenuation CT in lung nodule detection. This technique could improve the early diagnosis of lung cancer. Key points • Lung cancer progression was observed using x-ray dark-field CT. • Dark-field modality complements with attenuation modality in lung nodule detection. • Dark-field modality showed a detectability index higher than that attenuation in nodule detection. Graphical Abstract

Background: Acute myeloid leukemia (AML) with t(8;21) manifests as a diverse hematological malignancy. Although it was categorized into a favorable subtype, 30–40% of patients experience relapse. The objective of this research was to devise a nomogram for the accurate anticipation of both overall survival (OS) and cancer-specific survival (CSS) in t(8;21) AML.Methods: From the Surveillance, Epidemiology, and End Results (SEER) database, individuals diagnosed with t(8;21) AML from 2000 to 2018 were selected. Prognostic factors for t(8;21) AML were identified using Cox regression analysis and Akaike Information Criterion (AIC), forming the basis for constructing prognostic nomograms.Results: Key variables, including first primary tumor, age group, race, and chemotherapy, were identified and integrated into the nomogram. The C-index values for the nomograms predicting OS and CSS were 0.753 (validation: 0.765) and 0.764 (validation: 0.757), respectively. Ultimately, based on nomogram scores, patients were stratified into high-risk and low-risk groups, revealing significant disparities in both OS and CSS between these groups (P

Abstract Background Owing to the advances in diagnosis and therapy, survival or remission rates for lymphoma have improved prominently. Apart from the lymphoma- and chemotherapy-related somatic symptom burden, increasing attention has been drawn to the health-related quality of life. The application of 18F-fluorodeoxyglucose positron emission tomography-computed tomography (18F-FDG PET/CT) has been routinely recommended for the staging and response assessment of FDG-avid lymphoma. However, up till now, only a few researches have investigated the brain metabolic impairments in patients with pre-treatment lymphoma. The determination of the lymphoma-related metabolic brain pattern would facilitate exploring the tailored therapeutic regimen to alleviate not only the physiological, but also the psychological symptoms. In this retrospective study, we aimed to establish the diffuse large B-cell lymphoma-related pattern (DLBCLRP) of metabolic brain network and investigate the correlations between DLBCLRP and several indexes of the staging and response assessment. Results The established DLBCLRP was characterized by the increased metabolic activity in bilateral cerebellum, brainstem, thalamus, striatum, hippocampus, amygdala, parahippocampal gyrus and right middle temporal gyrus and by the decreased metabolic activity in bilateral occipital lobe, parietal lobe, anterior cingulate gyrus, midcingulate cortex and medial frontal gyrus. Significant difference in the baseline expression of DLBCLRP was found among complete metabolic response (CMR), partial metabolic response (PMR) and progressive metabolic disease (PMD) groups (P 0.05), the post-treatment declines of DLBCLRP expression were significantly positively correlated with Ann Arbor staging (r s = 0.284, P

Avian primordial germ cells (PGCs) are essential in avian transgenic research, germplasm conservation, and disease resistance breeding. However, cultured PGCs are prone to fragmentation and apoptosis, regulated at transcriptional and translational levels, with N6-methyladenosine (m6A) being the most common mRNA modification. Resveratrol (RSV) is known for its antioxidant and anti-apoptotic properties, but its effects on PGCs and the underlying mechanisms are not well understood. This study shows that RSV supplementation in cultured PGCs improves cell morphology, significantly enhances total antioxidant capacity (p < 0.01), reduces malondialdehyde levels (p < 0.05), increases anti-apoptotic BCL2 expression, and decreases Caspase-9 expression (p < 0.05). Additionally, RSV upregulates the expression of m6A reader proteins YTHDF1 and YTHDF3 (p < 0.05). m6A methylation sequencing revealed changes in mRNA m6A levels after RSV treatment, identifying 6245 methylation sites, with 1223 unique to the control group and 798 unique to the RSV group. Combined analysis of m6A peaks and mRNA expression identified 65 mRNAs with significantly altered methylation and expression levels. Sixteen candidate genes were selected, and four were randomly chosen for RT-qPCR validation, showing results consistent with the transcriptome data. Notably, FAM129A and SFRP1 are closely related to apoptosis, indicating potential research value. Overall, our study reveals the protective effects and potential mechanisms of RSV on chicken PGCs, providing new insight into its use as a supplement in reproductive stem cell culture.

In recent years, the high-frequency hybrid sky-surface wave radar (HSSWR) has been increasingly used for target detection applications. Nevertheless, the specific bistatic system layout and the phase path disturbances induced by the ionospheric propagation channel may severely spread the sea clutter spectrum, thereby deteriorating the detection ability of the HSSWR for slow-moving targets. In this work, a novel subspace method based on the hybrid use of the amplitude and phase estimator (APES) and the orthogonal projection (OP) in the spatial–temporal domain, denoted as the APES-OP method, is proposed to suppress the spreading first-order sea clutter of the HSSWR. The distribution characteristics of targets and first-order sea clutter in the spatial–temporal domain were investigated, and a time-domain subspace signal model was adopted to describe targets perturbed by ionospheric phase path modulation. An APES filter was adopted to filter out the potential targets with a traversal approach to avoid attenuating desired signals while suppressing sea clutter. After that, sampling data from multi-channels and slow-time domains at the cell under test were employed to construct a spatial–temporal matrix, which was then utilized to obtain the sea clutter subspace by singular value decomposition. Simulation results indicate that the proposed algorithm can suppress sea clutter while retaining the target, even if the target is buried by sea clutter. The processing results of measured data further demonstrate the efficiency of the proposed algorithm. After sea clutter suppression, the target obscured by clutter can be revealed, and the signal-to-clutter ratio of the target is greatly improved.

Abstract Immunosuppressive cells are pivotal players in tumor progression by affecting the efficacy of conventional therapies and the prognosis of cancer patients. Visualization and real‐time evaluation of these cells are very important to achieve patient‐oriented precision oncological medicine. Noninvasive imaging techniques are excellent tools for this purpose, and various molecular imaging probes have been developed to monitor these protumoral immunosuppressive cells in the tumor microenvironment. In this review, we provide a brief update on the biology of immunosuppressive cells and outline recent progress in their visualization.

Abstract Millimetre‐wave radar offers high ranging accuracy and can capture subtle vibration information of the human heart. This study proposes a heartbeat prediction method based on the transformer model using millimetre‐wave radar. Firstly, the millimetre‐wave radar was used to collect the heartbeat data and conduct normalisation processing. Secondly, a position coding was introduced to assign sine or cosine variables to input data and extract their relative position relationship. Subsequently, the transformer encoder was adopted to allocate attention to input data through the multi‐head attention mechanism, using a mask layer before the decoding layer to prevent the leakage of future information. Finally, we employ the fully connected layer was employed in the linear decoder for regression and output the predicted results. Our experimental results demonstrate that the proposed transformer model achieves nearly 30% higher prediction accuracy than traditional long short‐term memory models while improving both the prediction accuracy and convergence rate. The proposed method has great potential in predicting the heartbeat state of elderly and sick patients.

This retrospective study aimed to analyze the treatment effect and prognostic factors of pediatric acute myeloid leukemia (AML) patients with t(8;21). A total of 268 newly diagnosed pediatric AML (pAML) enrolled from 1 January 2005 to 31 December 2022 were retrospectively reviewed, and 50 (18.7%) patients harbored t(8;21) translocation. CR rate, OS, EFS, and RFS were assessed by multivariate Logistic and Cox regression models in these patients. Of the 50 patients, 2 patients abandoned treatment during the first induction course. Of the remaining 48 patients who received double-induction therapy and were included in the final analyses, CR1 and CR2 were 75.0% (36/48) and 95.8% (46/48), respectively. The overall three-year OS, EFS, and RFS were 68.4% (95% CI, 55.0–85.1), 64.2% (95% CI, 50.7–81.4), and 65.5% (95% CI, 51.9–82.8), respectively. The presence of loss of sex chromosome (LOS) at diagnosis (n = 21) was associated with a better 3-year OS [87.5% (95% CI, 72.7–100) vs. 52.7% (95% CI, 35.1–79.3), p = 0.0089], 3-year EFS [81.6% (95% CI, 64.7–100) vs. 49.7% (95% CI, 32.4–76.4), p = 0.023], and 3-year RFS [81.6% (95% CI, 64.7–100) vs. 51.7% (95% CI, 33.9–78.9), p = 0.036] than those without LOS (n = 27), and it was also an independent good prognostic factor of OS (HR, 0.08 [95% CI, 0.01–0.48], p = 0.005), EFS (HR, 0.22 [95% CI, 0.05–0.85], p = 0.029), and RFS (HR, 0.21 [95% CI, 0.05–0.90], p = 0.035). However, extramedullary leukemia (EML) featured the independent risk factors of inferior OS (HR, 10.99 [95% CI, 2.08–58.12], p = 0.005), EFS (HR, 4.75 [95% CI, 1.10–20.61], p = 0.037), and RFS (HR, 6.55 [95% CI, 1.40–30.63], p = 0.017) in pediatric individuals with t(8;21) AML. Further analysis of combining LOS with EML indicated that the EML+LOS− subgroup had significantly inferior OS (92.9%, [95% CI, 80.3–100]), EFS (86.2%, [95% CI, 70.0–100]), and RFS (86.2%, [95% CI, 80.3–100]) compared to the other three subgroups (all p < 0.001). LOS and EML are independent prognostic factors of OS, EFS, and RFS with t(8;21) pAML patients. LOS combined with EML may help improve risk stratification.

In this paper, we prove an existence result for Kähler-Einstein metrics on $ \mathbb Q $-Fano compactifications of Lie groups by the variational method, provided their moment polytopes satisfy a fine condition. As an application, we prove that there is no $ \mathbb Q $-Fano $ {\rm SO}_4(\mathbb C) $-compactification which admits a Kähler-Einstein metric with the same volume as that of a smooth K-unstable Fano $ {\rm SO}_4(\mathbb C) $-compactification.

Objective: A liquid chromatography-tandem mass spectrometry coupled with immunoaffinity column clean-up method was established for the determination of 8 mycotoxins in aquatic products. Methods: The samples were extracted with acetonitrile water (84:16, V:V), and purified by multifunctional immunoaffinity columns. The chromatographic column was Agilent Proshell 120 SB·C18 column (2.1 mm×100 mm, 2.7 μm). Mobile phase was methanol and 5 mmol/L ammonium acetate (containing 0.1% formic acid), gradient elution. The flow rate was 0.4 mL/min, and the column temperature was 40 ℃. The electrospray was operated in both positive and negative mode at the same time, and the samples were detected by multiple reaction monitoring mode (MRM). Results: The linear relations of the eight mycotoxins were good within the concentration range of 1.0~50.0 ng/mL (R2>0.992). The limits of detection were between 0.05~0.50 μg/kg, and the limits of quantification were between 0.17~1.65 μg/kg. The average recoveries were 75.6%~106.3%, and the relative standard deviations (RSDs) were 3.5%~9.3%. Conclusion: The method is simple, sensitive and accurate for the rapid analysis of mycotoxin residues in aquatic products.

This study demonstrates a novel colorimetric method for clenbuterol (CLB) detection based on the peroxidase-like activity of SiO2-coated Fe3O4 nanoparticles (Fe3O4@mSiO2) modified with montmorillonite (MMT) and sodium dodecyl sulfate (SDS), namely, Fe3O4@mSiO2@MMT-SDS. Fe3O4@mSiO2@MMT-SDS nanoparticles were prepared by modifying Fe3O4@mSiO2 with MMT and SDS to impart negative charges to the particle surfaces. The structural properties, steady-state kinetics, catalytic performance, and reaction conditions of the as-prepared nanoparticles were analyzed. Fe3O4@mSiO2@MMT-SDS nanoparticles exhibited excellent dispersion and enzyme-like activity, which improved the affinity with substrate (TMB and H2O2) for the catalytic oxidation of CLB by H2O2, turning the solution blue in the presence of the 3,3ʹ, 5,5ʹ-tetramethylbenzidine chromogen. Under optimal reaction conditions, a strong linear correlation between the absorbance of solution and CLB concentration (R2 = 0.9983) was observed. Here, the limit of detection, spike recovery, and relative standard deviation were 9.6 × 10-9 mol·L-1, 94.2 %–102.2 %, and 2.2 %–4.4 %, respectively. The proposed method is a simple, fast, cost-efficient, and sensitive assay, which can be used to rapidly and accurately screen CLB in pork and animal feeds.

PIWI-interacting RNAs (piRNAs), an emergent type of non-coding RNAs during oncogenesis, play critical roles in regulating tumor microenvironment. Systematic analysis of piRNAs’ roles in modulating immune pathways is important for tumor immunotherapy. In this study, in-depth analysis of piRNAs was performed to develop an integrated computational algorithm, the immunology piRNA (ImmPI) pipeline, for uncovering the global expression landscape of piRNAs and identifying their regulatory roles in immune pathways. The immunology piRNAs show a tendency towards overexpression patterns in immune cells, causing perturbations in tumors, being significantly associated with infiltration of immune cells, and having prognostic value. The ImmPI score can contribute to prioritizing tumor-related piRNAs and distinguish two subtypes of SKCM (immune-cold and hot phenotypes), as characterized by different prognoses, immunogenicity and antitumor immunity. Finally, we developed an interactive web resource (ImmPI portal: http://www.hbpding.com/ImmPi) for the biomedical research community, with several useful modules to browse, visualize, and download the results of immunology piRNAs analysis. Overall, our work provides a comprehensive landscape of piRNAs across multiple cancer types and sheds light on their regulatory and functional roles in tumor immunity. These findings pave the way for future research and development of piRNA-based immunotherapies for cancer treatment.

Acute kidney injury (AKI) leads to unacceptably high mortality due to difficulties in timely intervention and less efficient renal delivery of therapeutic drugs. Here, a series of polyvinylpyrrolidone (PVP)-curcumin nanoparticles (PCurNP) are designed to meet the renal excretion threshold (∼45 kDa), presenting a controllable delivery nanosystem for kidney targeting. Renal accumulation of the relatively small nanoparticles, 89Zr-PCurNP M10 with the diameter between 5 and 8 nm, is found to be 1.7 times and 1.8 times higher than the accumulation of 89Zr-PCurNP M29 (20–50 nm) and M40 (20–50 nm) as revealed by PET imaging. Furthermore, serum creatinine analysis, kidney tissues histology, and tubular injury scores revealed that PCurNP M10 efficiently treated cisplatin-induced AKI. Herein, PCurNP offers a novel and simple strategy for precise PET image-guided drug delivery of renal protective materials.

Aboveground biomass (AGB) is an important indicator of the grassland ecosystem. It can be used to evaluate the grassland productivity and carbon stock. Satellite remote sensing technology is useful for monitoring the dynamic changes in AGB across a wide range of grasslands. However, due to the scale mismatch between satellite observations and ground surveys, significant uncertainties and biases exist in mapping grassland AGB from satellite data. This is also a common problem in low- and medium-resolution satellite remote sensing modeling that has not been effectively solved. The rapid development of uncrewed aerial vehicle (UAV) technology offers a way to solve this problem. In this study, we developed a method with UAV and satellite synergies for estimating grassland AGB that filled the gap between satellite observation and ground surveys and successfully mapped the grassland AGB in the Hulunbuir meadow steppe in the northeast of Inner Mongolia, China. First, based on the UAV hyperspectral data and ground survey data, the UAV-based AGB was estimated using a combination of typical vegetation indices (VIs) and the leaf area index (LAI), a structural parameter. Then, the UAV-based AGB was aggregated as a satellite-scale sample set and used to model satellite-based AGB estimation. At the same time, spatial information was incorporated into the LAI inversion process to minimize the scale bias between UAV and satellite data. Finally, the grassland AGB of the entire experimental area was mapped and analyzed. The results show the following: (1) random forest (RF) had the best performance compared with simple regression (SR), partial least squares regression (PLSR) and back-propagation neural network (BPNN) for UAV-based AGB estimation, with an R2 of 0.80 and an RMSE of 76.03 g/m2. (2) Grassland AGB estimation through introducing LAI achieved higher accuracy. For UAV-based AGB estimation, the R2 was improved by an average of 10% and the RMSE was reduced by an average of 9%. For satellite-based AGB estimation, the R2 was increased from 0.70 to 0.75 and the RMSE was decreased from 78.24 g/m2 to 72.36 g/m2. (3) Based on sample aggregated UAV-based AGB and an LAI map, the accuracy of satellite-based AGB estimation was significantly improved. The R2 was increased from 0.57 to 0.75, and the RMSE was decreased from 99.38 g/m2 to 72.36 g/m2. This suggests that UAVs can bridge the gap between satellite observations and field measurements by providing a sufficient training dataset for model development and AGB estimation from satellite data.

Bifunctional chelators (BFCs), which link metallic radionuclide and a targeting vector, are some of the most crucial components of metallic radionuclide-based radiopharmaceuticals for positron-emission computed tomography (PET) imaging. In this study, we designed and synthesized two versatile BFCs, p-NCS-Ph-DE4TA and p-NCS-Ph-AAZ4TA, and we conjugated them with a prostate-specific membrane antigen (PSMA) inhibitor. These two chelators showed high affinity for Ga (III) according to a study of the thermodynamics and kinetics and DFT calculations. The labeled PSMA targeted probes, [68Ga]Ga-p-NCS-Ph-DE4TA-PSMA and [68Ga]Ga-p-NCS-Ph-AAZ4TA-PSMA, maintained excellent stability in vitro, and they exhibited high specific activity when binding to PSMA. A PET/CT imaging study in mice bearing SMMC-7721 hepatocellular carcinoma xenografts demonstrated clear visualization of tumors with a high tumor uptake and low background level, indicating the excellent performance in vivo and specific activity when targeting hepatocellular carcinomas. In summary, p-NCS-Ph-DE4TA and p-NCS-Ph-AAZ4TA are leading developmental candidates for PET imaging for tumor diagnosis.

The Oenothein B (OEB) rich in eucalyptus is a kind of extremely development of prospects of antioxidant activity, but low oral bioavailability limits its application. The novel polyelectrolyte nanoparticle was designed for OEB delivery through the self-assembly of casein phosphopeptides (CPP) and natural active polysaccharides-chitosan (CS). The OEB nanoparticle with small particle size and high embedding rate were constructed to solve the problem of low oral bioavailability of OEB, and its stability as well as in vivo absorption were investigated. The storage stability analysis, digital inverted fluorescence microscopy and emission field scanning electron microscopy showed that the particle size and total amount of OEB nanoparticles did not vary significantly after 96 h of continuous storage at room temperature, and the particle size distribution was uniform, and the particles kept their integrity pH 1.2. The maximum release rate of OEB nanoparticles was only 0.72% in artificial gastric fluid and 21.77% in artificial intestinal fluid. It greatly reduces the risk of its decomposition and plays a better protective role. The results of in vivo absorption showed that OEB nanoparticle gavage mice did not detect OEB in blood and its metabolites except for OEB in gastric juice, indicating that OEB changes in vivo after release. Therefore, although OEB nanoparticles can effectively protect their decomposition in gastrointestinal fluid, it is best to achieve sustained release at the target location in order to improve the absorption and utilization effect.

Stick-slip vibration is a common phenomenon met in oil gas drilling, especially in the complex trajectory wells such as highly-deviated wells, it will cause the earlier failure of BHA (bottom hole assembly) and lower drilling efficiency. In this present paper, a finite element model of highly-deviated well, which consists of a drill string system, a borehole, a PDC bit (Polycrystalline Diamond Compact bit) and a rock model, is carried out to investigate the stick–slip vibration behaviors of drill bit and BHA. Besides, the torsional impact drilling method is proposed in the context to control the stick–slip vibration of BHA. The research results show that, the phenomenon of stick–slip vibration of BHA gradually weaken and disappear with the distance from the drill bit increases, and the stick–slip vibration mainly occurs at the BHA which near drill bit. The high frequency torsional impact drilling method can reduce the resistance torque of the bit by 34.71%, and increase the drilling depth by about 58.28%. It can effectively improve the drilling efficiency of the bit, making the rotation of drill bit becomes relatively more stable, and reducing or even eliminating the stick–slip vibration. These results lead to an enhanced understanding of stick–slip vibration behaviors of drill bit and BHA in highly-deviated wells, and provide the basis for improving the drilling efficiency.

Shale gas production has become the main driver of global gas production growth. Deep shale gas is difficult to extract, which puts forward higher requirements for drilling speed increase. The downhole power drilling tools are mainly screw drilling tools. Conventional screw drill tool stator bushing has poor heat dissipation, which is prone to thermal hysteresis failure, shortening drilling tool life, and is not suitable for high temperature and high pressure environment of deep shale gas wells. Equal wall thickness screw drilling tools and hydrogenated nitrile rubber have better high temperature resistance. Therefore, based on the thermal aging experiment and constitutive model of the rubber changes the displacement of the inner cavity of the stator bushing and the difference between the front and the back is up to 21.6%. The increase of the interference and eccentricity between rotor and motor leads to the increase of the maximum von Mises stress of the stator bushing and the thermal hysteresis temperature. The influence of the interference is greater than the influence of the eccentricity so that the interference should be given priority in the design. This paper provides a theoretical reference for the design and optimization of equal wall thickness bushing of positive displacement motor.

The nano-scale pore systems in shale reservoirs control shale gas transportation and aggregation, which is of great significance for the resource evaluation of shale oil and gas and the selection of a “sweet spot”. Taking twelve marine shale samples from the Wufeng–Longmaxi Formation in the Zigong area, southwest Sichuan Basin, as the research target, we carried out a series of experiments, including total organic carbon (TOC) analysis, X-ray diffraction (XRD), gas adsorption (CO2 + N2), and mercury intrusion porosimetry (MIP), to study the full-scale pore structure characterization and controlling factors of pore volume and specific surface area. The results presented the following findings. (1) Marine shale samples from the target area are rich in organic matter, with an average TOC value of 3.86%; additionally, the mineral composition was dominated by quartz and clay minerals, with average contents of 44.1% and 31.4%, respectively. (2) The full-scale pore size distribution curves of pore volume developed multimodally, with the main peaks at 0.5 nm–2 nm, 3 nm–6 nm, and 700 nm–2.2 um; moreover, the full-scale pore size distribution curves of a specific surface area developed unimodally, with the main peak ranging from 0.5 nm to 1.2 nm. (3) Pore volume was mainly contributed by mesopores and macropores, with an average contribution of 46.66% and 42.42%, respectively, while the contribution of micropores was only 10.91%. The specific surface area was mainly contributed by micropores and mesopores, with an average contribution of 64.63% and 29.22%, respectively, whereas the contribution of micropores was only 6.15%. (4) The TOC content mainly controlled the pore volume and specific surface area of micropores and mesopores, while the clay and feldspar content generally controlled the pore volume and specific surface area of macropores. Additionally, the quartz content had an inhibitory effect on the development of all pore types. These results will help researchers understand the laws of gas accumulation and migration.

Abstract Background Adnectin is a protein family derived from the 10th type III domain of human fibronectin (10Fn3) with high-affinity targeting capabilities. Positron emission tomography (PET) probes derived from anti-programmed death ligand-1 (PD-L1) Adnectins, including 18F- and 68Ga-labeled BMS-986192, are recently developed for the prediction of patient response to immune checkpoint blockade. The 68Ga-labeled BMS-986192, in particular, is an attractive probe for under-developed regions due to the broader availability of 68Ga. However, the pharmacokinetics and biocompatibility of 68Ga-labeled BMS-986192 are still unknown, especially in non-human primates, impeding its further clinical translation. Methods We developed a variant of 68Ga-labeled BMS-986192 using 1,4,7-triazacyclononane,1-glutaric acid-4,7-acetic acid (NODAGA) as the radionuclide–chelator. The resultant probe, 68Ga-NODAGA-BMS986192, was evaluated in terms of targeting specificity using a bilateral mouse tumor model inoculated with wild-type B16F10 and B16F10 transduced with human PD-L1 (hPD-L1-B16F10). The dynamic biodistribution and radiation dosimetry of this probe were also investigated in non-human primate cynomolgus. Results 68Ga-NODAGA-BMS986192 was prepared with a radiochemical purity above 99%. PET imaging with 68Ga-NODAGA-BMS986192 efficiently delineated the hPD-L1-B16F10 tumor at 1 h post-injection. The PD-L1-targeting capability of this probe was further confirmed using in vivo blocking assay and ex vivo biodistribution studies. PET dynamic imaging in both mouse and cynomolgus models revealed a rapid clearance of the probe via the renal route, which corresponded to the low background signals of the PET images. The probe also exhibited a favorable radiation dosimetry profile with a total-body effective dose of 6.34E-03 mSv/MBq in male cynomolgus. Conclusions 68Ga-NODAGA-BMS986192 was a feasible and safe tool for the visualization of human PD-L1. Our study also provided valuable information on the potential of targeted PET imaging using Adnectin-based probes.

Abstract Diamond exhibits large application potential in the field of power electronics, owing to its excellent and desirable electronic properties. However, the main obstacles to its development originate from the small‐sized single‐crystal wafers and the instability of the electrical conductivity. This work presents a metal‐oxide‐semiconductor field‐effect transistor (MOSFET) on a diamond substrate derived from a five‐inch (110) highly preferred polycrystalline diamond film. The MOSFETs with excellent performance are fabricated by combining an H‐terminated channel and an epitaxially grown boron‐doped layer as the source/drain contacts of the diamond devices. According to the electrical statistical results of ≈110 devices on the polycrystalline diamond substrate, 44% of devices show normally‐off operation with a maximum current density of 400 mA mm−1, while 56% of devices demonstrate normally‐on operation with a maximum current density of 525 mA mm−1. The normally‐off characteristics are more related to the higher amounts of nitrogen concentration than the grain boundaries. The stable boron‐doped source and drain provide a high concentration of holes, which facilitate transport in the surface p‐type channel induced by the H‐termination. The characteristics of the MOSFETs are inspiring for the fabrication of complementary inverter circuits on large diamond wafers.

Aflatoxin B1 (AFB1), with the strong toxicity and carcinogenicity, has been reported to great toxicity to the liver and other organs of animals. It cause huge economic losses to breeding industry, including the aquaculture industry. Chinese mitten crabs (Eriocheir sinensis), as one of important species of freshwater aquaculture in China, are deeply disturbed by it. However, the molecular and metabolic mechanisms of hepatopancreas and ovary in crabs underlying coping ability are still unclear. Hence, we conducted targeted injection experiment with or without AFB1, and comprehensively analyzed transcriptome and metabolomics of hepatopancreas and ovary. As a result, 210 and 250 DEGs were identified in the L-C vs. L-30 m and L-C vs. L-60 m comparison, among which 14 common DEGs were related to six major functional categories, including antibacterial and detoxification, ATP energy reaction, redox reaction, nerve reaction, liver injury repair and immune reaction. A total of 228 and 401 DAMs in the ML-C vs. ML-30 m and ML-C vs. ML-60 m comparison both enriched 12 pathways, with clear functions of cutin, suberine and wax biosynthesis, tyrosine metabolism, purine metabolism, nucleotide metabolism, glycine, serine and threonine metabolism, ABC transporters and tryptophan metabolism. Integrated analysis of metabolomics and transcriptome in hepatopancreas discovered three Co-enriched pathways, including steroid biosynthesis, glycine, serine and threonine metabolism, and sphingolipid metabolism. In summary, the expression levels and functions of related genes and metabolites reveal the regulatory mechanism of Chinese mitten crab (Eriocheir sinensis) adaptability to the Aflatoxin B1, and the findings contribute to a new perspective for understanding Aflatoxin B1 and provide some ideas for dealing with it.

Abstract Background Nucleosome assembly protein 1-like 1 (NAP1L1) is highly expressed in various types of cancer and plays an important role in carcinogenesis, but its specific role in tumor development and progression remains largely unknown. In this study, we suggest the potential of NAP1L1 as a prognostic biomarker and therapeutic target for the treatment of ovarian cancer (OC). Methods In our study, a tissue microarray (TMA) slide containing specimens from 149 patients with OC and 11 normal ovarian tissues underwent immunohistochemistry (IHC) to analyze the correlation between NAP1L1 expression and clinicopathological features. Loss-of- function experiments were performed by transfecting siRNA and following lentiviral gene transduction into SKOV3 and OVCAR3 cells. Cell proliferation and the cell cycle were assessed by the Cell Counting Kit-8, EDU assay, flow cytometry, colony formation assay, and Western blot analysis. In addition, co-immunoprecipitation (Co-IP) and immunofluorescence assays were performed to confirm the relationship between NAP1L1 and its potential targets in SKOV3/OVCAR3 cells. Results High expression of NAP1L1 was closely related to poor clinical outcomes in OC patients. After knocking down NAP1L1 by siRNA or shRNA, both SKOV3 and OVCAR3 cells showed inhibition of cell proliferation, blocking of the G1/S phase, and increased apoptosis in vitro. Mechanism analysis indicated that NAP1L1 interacted with hepatoma-derived growth factor (HDGF) and they were co-localized in the cytoplasm. Furthermore, HDGF can interact with jun proto-oncogene (C-JUN), an oncogenic transformation factor that induces the expression of cyclin D1 (CCND1). Overexpressed HDGF in NAP1L1 knockdown OC cells not only increased the expression of C-JUN and CCND1, but it also reversed the suppressive effects of si-NAP1L1 on cell proliferation. Conclusions Our data demonstrated that NAP1L1 could act as a prognostic biomarker in OC and can interact with HDGF to mediate the proliferation of OC, and this process of triggered proliferation may contribute to the activation of HDGF/C-JUN signaling in OC cells.

Chromophoric dissolved organic matter (CDOM) in aquatic ecosystems can reflect the impacts of human activities on the carbon-cycling process. However, direct evidence of the combined effect of land use and anthropogenic nutrients on CDOM characteristics in river ecosystems is limited. Herein, we collected water samples from 18 sites in the Nanchong section of Jialing River in December 2019 to elucidate how the land use and nutrients affect the source and composition of CDOM through parallel factor (PARAFAC) analysis of excitation–emission matrices (EEMs). First, the absorption coefficient a254 (r2=0.29, p

Carbon dioxide (CO2) dissolution is the secondary trapping mechanism enhancing the long-term security of CO2 in confined geological formations. CO2 injected into a randomly multilayered formation will preferentially migrate along high permeability layers, increasing CO2 dissolution efficiency. In this study, sequential Gaussian simulation is adopted to construct the stratified saline formations, and two-phase flow based on MRST is established to illustrate the spatial mobility and distribution of CO2 migration. The results show that gravity index G and permeability heterogeneity σY2 are the two predominant factors controlling the spatial mobility and distribution of CO2 transports. The CO2 migration shows a totally different spatial mobility under different gravity index and heterogeneity. When the permeability discrepancy is relatively larger, CO2 preferentially migrates along the horizontal layer without accompanying the vertical migration. For the formation controlled by gravity index, CO2 migration is governed by supercritical gaseous characteristics. For the medium gravity index, the upward and lateral flow characteristics of the CO2 plume is determined by gravity index and heterogeneity. When the gravity index is smaller, permeability heterogeneity is the key factor influencing CO2 plume characteristics. Permeability heterogeneity is the decisive factor in determining final CO2 dissolution efficiency. This investigation of CO2 mobility in randomly multilayered reservoirs provides an effective reference for CO2 storage.

Abstract Frequency agile radar (FAR) systems have been demonstrated to have outstanding performance in electronic counter‐countermeasures (ECCM). With increased bandwidth in which FAR can switch carrier frequency, the phase errorswill appear at the corresponding frequency point, resulting in the decrease of coherence of the system. To accomplish phase error correction and range and velocity information extraction of the target simultaneously, a joint phase error estimation and sparse scene restoration algorithm based on sparse recovery (JPSA‐SR) is proposed here. To further reduce the computational complexity of the algorithm, a joint phase error estimation and sparse scene restoration algorithm based on alternating direction method of multipliers (JPSA‐ADMM) is also proposed. Numerical examples show the effectiveness of the proposed algorithms.

This study aimed to explore the glucose metabolic profile of extrapyramidal system in patients with crossed cerebellar diaschisis (CCD). Furthermore, the metabolic connectivities in cortico-ponto-cerebellar and cortico-rubral pathways associated with CCD were also investigated. A total of 130 CCD positive (CCD+) and 424 CCD negative (CCD-) patients with unilateral cerebral hemisphere hypometabolism on 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) were enrolled. Besides, the control group consisted of 56 subjects without any brain structural and metabolic abnormalities. Apart from the “autocorrelation”, metabolic connectivity pattern of right or left affected cerebellar hemisphere involved unilateral (left or right, respectively) caudate, pallidum, putamen, thalamus and red nucleus, in CCD+ patients with left or right supratentorial lesions, respectively (Puncorrected < 0.001, cluster size > 200). CCD+ group had significantly lower asymmetry index (AI) in cortico-ponto-cerebellar pathway (including ipsilateral cerebral white matter, ipsilateral pons, contralateral cerebellum white matter and contralateral cerebellum exterior cortex) and cortico-rubral pathway (including ipsilateral caudate, thalamus proper, pallidum, putamen, ventral diencephalon and red nucleus) than those of both CCD- and control groups (all P

In this paper, computational fluid dynamics is used to study how wavelike bumps influence the suppression of drilling-riser vortex-induced vibration (VIV). The numerical model involves two-dimensional unsteady incompressible turbulent flow around a cylinder, with the flow characteristics regarded as being constant. The results show that wavelike bumps are effective in mitigating the VIV, but the degree of mitigation does not increase indefinitely with the number of bumps. The mitigation is greatest with either 5 or 7 wavelike bumps, reducing the vibration amplitudes of the cylinder in the in-line and cross-flow directions to negligible levels. To know how equipping a circular cylinder with wavelike bumps affected its VIV response, cases with wavelike bumps of 1, 3, 5, 7, 9, and 11 are studied.

Pediatric acute megakaryoblastic leukemia (AMKL) is a subtype of acute myeloid leukemia (AML) characterized by abnormal megakaryoblasts, and it is divided into the AMKL patients with Down syndrome (DS-AMKL) and AMKL patients without DS (non-DS-AMKL). Pediatric non-DS-AMKL is a heterogeneous disease with extremely poor outcome. We performed single-cell RNA sequencing (scRNA-seq) of the bone marrow from two CBFA2T3-GLIS2 fusion-positive and one RBM15-MKL1 fusion-positive non-DS-AMKL children. Meanwhile, we downloaded the scRNA-seq data of normal megakaryocyte (MK) cells of the fetal liver and bone marrow from healthy donors as normal controls. We conducted cell clustering, cell-type identification, inferCNV analysis, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment, and Monocle2 analysis to investigate the intratumoral heterogeneity of AMKL. Using canonical markers, we identified and characterized the abnormal blasts and other normal immune cells from three AMKL samples. We found intratumoral heterogeneity of AMKL in various cell-type proportions, malignant cells’ diverse copy number variations (CNVs), maturities, significant genes expressions, and enriched pathways. We also identified potential markers for pediatric AMKL, namely, RACK1, ELOB, TRIR, NOP53, SELENOH, and CD81. Our work offered insight into the heterogeneity of pediatric acute megakaryoblastic leukemia and established the single-cell transcriptomic landscape of AMKL for the first time.

BackgroundMyeloid sarcoma (MS) is a rare hematological tumor that presents with extramedullary tumor masses comprising myeloid blasts. A controversial issue is whether MS involving normal hematopoietic sites (liver, spleen, and lymph nodes) should be excluded in future studies. We aimed to compare MS characteristics and outcomes involving hematopoietic and non-hematopoietic sites and construct a prognostic nomogram exclusively for the latter.MethodsData from patients diagnosed with MS between 2000 and 2018 were collected from the Surveillance, Epidemiology, and End Results (SEER) database. According to the primary site, patients were classified as having MS involving hematopoietic sites (hMS) or non-hematopoietic sites (eMS). Clinical characteristics and survival outcomes were compared between the two groups using Wilcoxon, chi-square, and log-rank tests. Cox regression analysis was used to identify eMS prognostic factors to establish prognostic nomograms. The models’ efficiency and value were assessed using receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA).ResultsIn total, 694 patients were enrolled, including 86 with hMS and 608 with eMS. There were no sex, race or marital status distribution differences between the two groups. Patients with eMS had better overall and cancer-specific survival rates than those with hMS. Additionally, prognostic factor effects differed between the two groups. Patients with eMS were randomly divided into the training (number of patiens, n=425) and validation cohorts (n=183). Age, first primary tumor, primary site, and chemotherapy were used to establish nomograms. The C-index values of overall survival (OS) and cancer-specific survival (CSS) nomograms were 0.733 (validation: 0.728) and 0.722 (validation: 0.717), respectively. Moreover, ROC, calibration curves, and DCA confirmed our models’ good discrimination and calibration ability and potential clinical utility value.ConclusionOur study described the differences between patients with eMS and those with hMS. Moreover, we developed novel nomograms based on clinical and therapeutic factors to predict patients with eMS’ 1-, 3- and 5-year survival rates.

Leaf area index (LAI) and leaf chlorophyll content (Cab) are two important indicators of vegetation growth. Due to the high-coupling of spectral signals of leaf area and chlorophyll content, simultaneous retrieval of LAI and Cab from remotely sensed date is always challenging. In this paper, an approach for joint estimation of grassland LAI and Cab from unmanned aerial vehicle (UAV) hyperspectral data was proposed. Firstly, based on a PROSAIL model, 15 typical hyperspectral vegetation indices (VIs) were calculated and analyzed to identify optimal VIs for LAI and Cab estimation. Secondly, four pairs of VIs were established and their discreteness was also calculated for building a two-dimension matrix. Thirdly, a two-layer VI matrix was generated to determine the relationship of VIs with LAI values and Cab values. Finally, LAI and Cab were jointly retrieved according to the cells of the two-layer matrix. The retrieval reduced the cross-influence between LAI and Cab. Compared with the VI empirical model and the single-layer VI matrix, the accuracy of LAI and Cab retrieved from UAV hyperspectral data based on the two-layer VI matrix was significantly improved (for LAI: R2 = 0.73, RMSE = 0.91 m2/m2 and u(SD) = 0.82 m2/m2; for Cab: R2 = 0.79, RMSE = 11.7 μg/cm2 and u(SD) = 10.84 μg/cm2). The proposed method has the potential for rapid retrieval of LAI and Cab from hyperspectral data. As a method similar to look-up table, the two-layer matrix can be used directly for LAI and Cab estimation without the need for prior measurements for training.

Background Cardiomyocytes apoptosis is the basic pathological process of myocardial ischaemia/reperfusion (MI/R) injury, so inhibiting apoptosis of cardiomyocytes can effectively improve MI/R injury. Long non-coding RNA colorectal neoplasia differentially expressed (lncRNA CRNDE) can inhibit cell apoptosis, but its specific role in MI/R injury has not been studied. The aim of this study is to explore the specific effect of lncRNA CRNDE on cardiomyocytes apoptosis. Methods MI/R model in vivo and hypoxia/re-oxygenation (H/R) model in vitro were constructed. Apoptotic levels were assessed by TUNEL staining assay. QRT-PCR was used to validate lncRNA CRNDE level in myocardial tissues and HL-1 cells. The protein expressions of YAP1, Bcl-2 and cleaved caspase-3 were detected by western blot analysis. Flow cytometry was used to determine the apoptosis rate of cardiomyocytes. RIP assay was used to detect the interaction between lncRNA CRNDE and YAP1. Results The extent of cardiomyocytes apoptosis was significantly increased, and the levels of lncRNA CRNDE, YAP1 and Bcl-2 were down-regulated, while cleaved caspase-3 expression was up-regulated in MI/R mice and H/R-treated HL-1 cells. The expressions of YAP1 and Bcl-2 were decreased, while the expression of cleaved caspase-3 was increased after the knockdown of lncRNA CRNDE. Furthermore, lncRNA CRNDE could bind to YAP1 and regulated the protein level of YAP1 by ubiquitination and proteasomal degradation pathway. After transfection of Si-YAP1 in the H/R-treated HL-1 cells transfected with pc-DNA CRNDE, the protein level of Bcl-2 was decreased, while cleaved caspase-3 expression and the apoptosis rate were increased. Conclusion Our study suggested that lncRNA CRNDE could regulate YAP1 level by ubiquitination and proteasomal degradation pathway, thus inhibiting cardiomyocytes apoptosis in MI/R injury.

Background Psoriasis is a chronic, inflammatory skin disease. It was reported that lncRNA Non-coding RNA-activated by DNA damage (NORAD) has potential regulatory effects on skin diseases. Our previous studies found that lncRNA NORAD was highly expressed and its potential target miR-26a was down-regulated in psoriasis model mice. Here, we aimed to investigate the role of NORAD in the development of psoriasis. Methods IL-22/LPS (interleukin-22/lipopolysaccharide)-stimulated HaCaT (human immortalized keratinocytes) cell model and imiquimod-induced mouse model were established. Keratin 6 (K6), Keratin 16 (K16), Keratin 17 (K17), and Cell division cycle 6 (CDC6) levels were detected by western blot. Cell activity was detected by CCK-8, MTT, and EdU assays. Quantitative real-time PCR was performed to examine the levels of NORAD, miR-26a, CDC6, K6, K16, and K17. Haematoxylin-eosin staining was applied to observe the degree of skin thickening and hyperplasia. Fluorescence in situ hybridization detects the location of NORAD. RNA immunoprecipitation, RNA pull-down, and Luciferase test were performed to detect the interaction between NORAD and miR-26a. Results In IL-22/LPS-stimulated HaCaT cells, NORAD, CDC6, and keratinocyte proliferation-related proteins (K6, K16, and K17) were up-regulated and miR-26a was down-regulated. Cell survival and proliferation were also increased. However, the results were reversed after interference with NORAD. Also, in vitro experiments revealed that NORAD negatively regulated miR-26a. In IL-22/LPS-stimulated HaCaT cells and skin of imiquimod-induced mice, we found that lower NORAD resulted in an increase of miR-26a and a decrease of CDC6, further decreased levels of keratinocyte proliferation-related proteins (K6, K16, and K17).

Spatiotemporal changes in the water quality index are important measures with which to analyze water quality. Fifteen water quality indices at the Longdong, Luoguo, and Jinjiang stations in the Panzhihua Section of the Jinsha River Basin from 2016 to 2018 were analyzed using cluster analysis (CA), discriminant analysis (DA), independent sample t-test and correlation analysis. The results of CA showed that the months can be divided into the following groups based on the similarities in the water quality characteristics: group 1 (dry season), January-April and December; group 2 (flood season), August-September; and group 3 (flat season), May-July and October-November. In group 1 the river is remarkably polluted. The main parameters that distinguish the spatial differences are pH level, chemical oxygen demand, chlorophyll a, fecal coliforms, and electrical conductivity. All sections of the river meet the National Level III standard, and the water quality of the Jinsha River is generally good. Spatial results show that the Luoguo station is seriously polluted compared with the other two stations. Significant negative correlation is found between forest land and COD (P < 0.05). Therefore, the management of land use and pollutant discharge should still be strengthened in the Luoguo section to improve the overall water quality of the Jinsha River.

Abstract Nanobodies are the recombinant variable domains of heavy-chain-only antibodies, with many unique properties such as small size, excellent solubility, superior stability, quick clearance from blood, and deep tissue penetration. As a result, nanobodies have become a promising tool for the diagnosis and therapy of diseases. As imaging tracers, nanobodies allow an early acquisition of high-quality images, provide a comprehensive evaluation of the disease, and subsequently enable a personalized precision therapy. As therapeutic agents, nanobodies enable a targeted therapy by lesion-specific delivery of drugs and effector domains, thereby improving the specificity and efficacy of the therapy. Up to date, a wide variety of nanobodies have been developed for a broad range of molecular targets and have played a significant role in patients with a broad spectrum of diseases. In this review, we aim to outline the current state-of-the-art research on the nanobodies for medical applications and then discuss the challenges and strategies for their further clinical translation.

(1) Purpose: The glycoprotein non-metastatic melanoma B (gpNMB) is a type 1 transmembrane protein that is overexpressed in numerous cancers, including triple-negative breast cancer (TNBC). Its overexpression is associated with lower overall survival of patients with TNBC. Tyrosine kinase inhibitors such as dasatinib can upregulate gpNMB expression, which has the potential to enhance therapeutic targeting with anti-gpNMB antibody drug conjugates such as glembatumumab vedotin (CDX-011). Our primary aim is to quantify the degree and identify the timeframe of gpNMB upregulation in xenograft models of TNBC after treatment with the Src tyrosine kinase inhibitor, dasatinib, by longitudinal positron emission tomography (PET) imaging with the 89Zr-labeled anti-gpNMB antibody ([89Zr]Zr-DFO-CR011). The goal is to identify the timepoint at which to administer CDX-011 after treatment with dasatinib to enhance therapeutic efficacy using noninvasive imaging. (2) Methods: First, TNBC cell lines that either express gpNMB (MDA-MB-468) or do not express gpNMB (MDA-MB-231) were treated with 2 μM of dasatinib in vitro for 48 h, followed by Western blot analysis of cell lysates to determine differences in gpNMB expression. MDA-MB-468 xenografted mice were also treated with 10 mg/kg of dasatinib every other day for 21 days. Subgroups of mice were euthanized at 0-, 7-, 14-, and 21-days post treatment, and tumors were harvested for Western blot analysis of tumor cell lysates for gpNMB expression. In a different cohort of MDA-MB-468 xenograft models, longitudinal PET imaging with [89Zr]Zr-DFO-CR011 was performed before treatment at 0 (baseline) and at 14 and 28 days after treatment with (1) dasatinib alone (2) CDX-011 (10 mg/kg) alone, or (3) sequential treatment of dasatinib for 14 days then CDX-011 to determine changes in gpNMB expression in vivo relative to baseline. As a gpNMB-negative control, MDA-MB-231 xenograft models were imaged 21 days after treatment with dasatinib, combination of CDX-011 and dasatinib, and vehicle control. (3) Results: Western blot analysis of MDA-MB-468 cell and tumor lysates showed that dasatinib increased expression of gpNMB in vitro and in vivo at 14 days post treatment initiation. In PET imaging studies of different cohorts of MDA-MB-468 xenografted mice, [89Zr]Zr-DFO-CR011 uptake in tumors (SUVmean = 3.2 ± 0.3) was greatest at 14 days after treatment initiation with dasatinib (SUVmean = 4.9 ± 0.6) or combination of dasatinib and CDX-011 (SUVmean= 4.6 ± 0.2) compared with that at baseline (SUVmean = 3.2 ± 0.3). The highest tumor regression after treatment was observed in the combination-treated group with a percent change in tumor volume relative to baseline (%CTV) of −54 ± 13 compared with the vehicle control-treated group (%CTV = +102 ± 27), CDX-011 group (%CTV = −25 ± 9.8), and dasatinib group (%CTV = −23 ± 11). In contrast, the PET imaging of MDA-MB-231 xenografted mice indicated no significant difference in the tumor uptake of [89Zr]Zr-DFO-CR011 between treated (dasatinib alone or in combination with CDX-011) and vehicle-control groups. (4) Conclusions: Dasatinib upregulated gpNMB expression in gpNMB-positive MDA-MB-468 xenografted tumors at 14 days post treatment initiation, which can be quantified by PET imaging with [89Zr]Zr-DFO-CR011. Furthermore, combination therapy with dasatinib and CDX-011 appears to be a promising therapeutic strategy for TNBC and warrants further investigation.

Extracellular Vesicles (EVs) are small vesicles that can be actively secreted by most cell types into the extracellular environment. Evidence indicates that EVs can carry microRNAs (miRNAs), long non-coding RNAs (lncRNAs), tRNA-derived small RNAs (tsRNAs), proteins, and lipids to target cells or tissue organizations. Latest studies show that EVs play a vital role in the immune modulation and may contribute to the pathogenesis of autoimmune diseases. Systemic lupus erythematosus (SLE) is a common autoimmune disease characterized by abnormal T cell activation and sustained production of autoantibodies against self-antigens, resulting in inflammation and damage to multiple systems. Pathogenic mechanisms of SLE, however, are still not well understood. In this review, we summarize the latest research advances on the functions and mechanisms of EVs, and its role in the pathogenesis, diagnosis, and treatment of SLE.

Crossed cerebellar diaschisis (CCD) has been widely investigated in patients with supratentorial hypometabolism, however, the available evidence about the metabolic feature of CCD in patients with contralateral supratentorial hypermetabolism is lacking. This study aimed to assess the metabolic asymmetrical profile, network pattern and predisposing factors for the hypermetabolism-associated CCD, by using voxel-based asymmetry index (AI) and brain network analyses. Seventy CCD positive (CCD+) and 99 CCD negative (CCD-) patients with unilateral supratentorial hypermetabolism were introduced. Among different brain regions with AImax or AImin, striatum & thalamus was accompanied by the highest positive rate of CCD (85.7% or 70.1%, respectively). CCD+ group had significantly greater AImax (median [IQR], 0.62 [0.44–0.84] vs. 0.47 [0.35–0.61]), supratentorial hypermetabolic volume (1183.5 [399.3–3026.8] vs. 386.0 [152.0–1193.0]) and hypometabolic volume (37796.5 [24741.8–53278.0] vs. 3337.0 [1020.0–17193.0]), and lower AImin (−0.85 [-1.05–−0.73] vs. −0.49 [−0.68–−0.35]) compared with CCD- group (all P

The sealing performance of end fittings is very important for offshore oil and gas pipelines. To investigate the sealing behavior of a ring-shaped wedge seal, global and local numerical models of the ring–pipe interaction have been developed based on the finite-element method. First, the sealing process of the ring under pressure is simulated. Second, a criterion for the penetration of fluid pressure is applied in these models to assess how the sealing capacity changes along the contact surface. Finally, the contact magnitude of interference and the shape of the sawtooth heaves on the sealing ring are predicted and compared. The results show an interesting concentration of von Mises stress in the sealing ring and also that the peak contact pressure appears in the sealing zone. However, the penetration of fluid pressure has obvious effects on the distributions of von Mises stress and contact pressure. The best sealing performance is when the axial displacement of the sealing ring is 1.4 mm and the contact magnitude of interference is 0.3 mm. Given the sawtooth heave of sealing ring, semicircular heave gives the better sealing capacity compared with trapezoidal heave.

Remote techniques for measuring human vital signs have attracted great interests due to the benefits shown in medical monitoring and military applications. Compared with continuous-wave Doppler radar, frequency-modulated continuous-wave (FMCW) radar which can discriminate vital signs from different distances, shows potential for reducing the interferences from other targets and the environment. However, in the state-of-the-art algorithms, only one chirp per frame is utilized for FMCW-based vital sign monitoring. Moreover, the vital signal is extracted from only one range bin of the fast Fourier transform. Which does not make full utilization of the long system idle time, and loses the power distributed on other range bins. By exploiting the relationship between respiration and heartbeat vibrations, an adaptive identification embedded ensemble empirical mode decomposition (EEMD) method for joint-range spectral estimation is proposed to measure the heart rate. First, A multi-chirp processing is presented for a 2-dimensional phase accumulation. Then the phase signals from a sequence of range bins are decomposed with a fast adaptive identification process. Finally, with the identified heartbeat components, we solve a multiple measurement vectors problem to estimate the heart rate. Experimental results showed that, at the detection range from 1 m~ 2.5 m, the proposed method can robustly distinguish the heartbeat from respiration and its harmonics and accurately estimate the heart rate with a root mean square error less than 6 bpm.

Frequency diverse array (FDA) radar have attracted great interests due to the range-angle-dependent transmit beampattern which is different from phased array radar providing only angle-dependent transmit beampattern. In this paper, we firstly proposed a receiver processing strategy based on signal separation method which eliminates the need for employing a bank of bandpass filters at the receiver of FDA radar. In the proposed separation scheme, the received signal at each receiving element was separated into M channels, where M represents the transmitting element number. After time-invariant processing of the separated signal, the angle and range were estimated by two-stage multiple signal classification (MUSIC) algorithm. For velocity estimation, we proposed a novel unambiguous velocity estimation algorithm. This novel algorithm was implemented to calculate the phase of each element and then the differential phase within the adjacent elements is calculated. The velocity of the target was estimated by the differential phase. This mechanism for extending the Nyquist velocity range is that the differential phase of the two adjacent channels has a much smaller variance than the individual channel phase estimated. All estimated parameter performance is verified by analyzing the Cramér-Rao lower bound (CRLB) and the root mean square errors (RMSE).

Penetrating through hot dry rocks for geothermal resources with high geothermal gradients, high degrees of hardness and abrasivity will be extremely difficult, and a reasonable tooth distribution is a key factor to improve its rock-breaking efficiency. In order to explore an available cutter arrangement design of PDC cutters in hot dry rock drilling, we based on elastic–plastic mechanics and rock mechanics, established a dynamic 3D numerical simulation model of rock breaking with PDC cutters by using the Drucker–Prager yield criterion as the rock strength judgment principle. On the basis of this, we studied, under the confining pressure of 60 MPa, the effects of cutting depth, temperature, back rake angle and cutting speed on the mechanical specific energy of PDC cutters. The following results were achieved. (1) When a PDC cutter cuts a rock with the speed of 0.5 m/s and the back rake angle of 5–25°, the rock destruction specific energy of the cutter decreases significantly with the rise of cutting depth, while increases first and then decreases with the increasing temperature. And the critical temperature is 200 °C. (2) When a PDC cutter cuts a rock with the speed of 0.5 m/s and the cutting depth of 1–3 mm, the rock destruction specific energy of the cutter decreases first and then increases with the increase of back rack angle. And the optimal rack angle is 20°. (3) Within the temperature range of 20–300 °C, a PDC cutter cuts a rock with the back rake angle of 5°, the rock destruction specific energy of the cutter increases with the cutting speed but decreases with the increase of cutting depth. Keywords: Hot dry rock, Geothermal exploitation, PDC cutter, Mechanical specific energy, Rock-breaking efficiency, Numerical simulation, Drucker–Prager yield criteria, Rack angle

Objective: To observe the efficacy and safety of Lishi Oral Liquid (LOL), a Chinese herbs formula, combined with levocetirizine, an antihistamine drug, in patients with damp-heat atopic dermatitis (AD). Methods: A randomized double-blind placebo-controlled clinical trial was conducted. Ninety patients diagnosed with damp-heat atopic dermatitis were randomly assigned to Lishi Oral Liquid group and control group at the ratio of 1:1. Patients were given one Lishi Oral Liquid or placebo three times per day. Both groups were treated with allantoin and vitamin E cream by topical use and levocetirizine by oral administration. Patients were followed up at the second and fourth week. The primary outcome was the scoring of atopic dermatitis (SCORAD). The secondary outcomes were visual analogue scale (VAS) and dermatology life quality index (DLQI). Results: After two weeks of treatment, there were statistical differences in SCORAD between these two groups (P

PurposeTumor microenvironment immune types (TMITs) are closely related to the efficacy of immunotherapy. We aimed to assess the predictive ability of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT)-based radiomics of TMITs in treatment-naive patients with non-small cell lung cancer (NSCLC).MethodsA retrospective analysis was performed in 103 patients with NSCLC who underwent 18F-FDG PET/CT scans. The patients were randomly assigned into a training set (n = 71) and a validation set (n = 32). Tumor specimens were analyzed by immunohistochemistry for the expression of programmed death-ligand 1 (PD-L1), programmed death-1 (PD-1), and CD8+ tumor-infiltrating lymphocytes (TILs) and categorized into four TMITs according to their expression of PD-L1 and CD8+ TILs. LIFEx package was used to extract radiomic features. The optimal features were selected using the least absolute shrinkage and selection operator (LASSO) algorithm, and a radiomics signature score (rad-score) was developed. We constructed a combined model based on the clinical variables and radiomics signature and compared the predictive performance of models using receiver operating characteristic (ROC) curves.ResultsFour radiomic features (GLRLM_LRHGE, GLZLM_SZE, SUVmax, NGLDM_Contrast) were selected to build the rad-score. The rad-score showed a significant ability to discriminate between TMITs in both sets (p < 0.001, p < 0.019), with an area under the ROC curve (AUC) of 0.800 [95% CI (0.688–0.885)] in the training set and that of 0.794 [95% CI (0.615–0.916)] in the validation set, while the AUC values of clinical variables were 0.738 and 0.699, respectively. When clinical variables and radiomics signature were combined, the complex model showed better performance in predicting TMIT-I tumors, with the AUC values increased to 0.838 [95% CI (0.731–0.914)] in the training set and 0.811 [95% CI (0.634–0.927)] in the validation set.ConclusionThe FDG-PET/CT-based radiomic features showed good performance in predicting TMIT-I tumors in NSCLC, providing a promising approach for the choice of immunotherapy in a clinical setting.