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In various engineering fields, the fusion of infrared and visible images has important applications. However, in the current process of fusing infrared and visible images, there are problems with unclear texture details in the fused images and unbalanced displays of infrared targets and texture details, resulting in information loss. In this article, we propose an improved generative adversarial network (GAN) fusion model for fusing infrared and visible images. In the generator and discriminator network structure, we introduce densely connected blocks to connect the features between layers, improve network efficiency, enhance the network’s ability to extract source image information, and construct a content loss function using four losses, including an infrared gradient, visible intensity, infrared intensity, and a visible gradient, to maintain a balance between infrared radiation information and visible texture details, enabling the fused image to achieve ideal results. The effectiveness of the fusion method is demonstrated through ablation experiments on the TNO dataset, and compared with four traditional fusion methods and three deep learning fusion methods. The experimental results show that our method achieves five out of ten optimal evaluation indicators, with a significant improvement compared to other methods.

Mulberry (Morus, Moraceae) is an important economic plant that is considered zinc-rich. Zinc (Zn) is a micronutrient that plays vital roles in various bio-processes in plants and animals. In the present study, a comparative transcriptome analysis associated with physiological indicators was performed to reveal the potential mechanism in different organs in response to zinc toxicity in mulberry. Physiological indicators in mulberry plants treated with increasing concentrations of zinc were monitored to reveal the tolerance limits to zinc concentration. Transcriptome analysis of different organs in mulberry under excess zinc stress was performed to reveal the spatial response to zinc stress. The results show that the hormone signaling pathway and secondary metabolism including lignin biosynthesis, flavonoid biosynthesis and sugar metabolism are important for excess zinc treatment responses. In addition, the organ-based spatial response of these pathways is indicated. Lignin biosynthesis mainly responds to zinc stress in lignified tissues or organs such as stems, flavonoid biosynthesis is the main response to zinc stress in leaves, and sugar metabolism is predominant in roots. Further co-expression network analysis indicated candidate genes involved in the organ-based spatial response. Several transcription factors and genes involved in phenylpropanoid biosynthesis, cell wall biogenesis and sugar metabolism were further validated and designed as organ-based response genes for zinc stress.

In recent years, high-quality surfaces with large areas and curvatures have been increasingly used in engineering, but the precision machining and inspection of such surfaces is a particular challenge. Surface machining equipment needs to have a large working space, high flexibility, and motion accuracy to meet the demands of micron-scale precision machining. However, meeting these requirements may result in extremely large equipment sizes. To solve this problem, an eight-degree-of-freedom redundant manipulator with one linear and seven rotational joints is designed to assist in the machining described in this paper. The configuration parameters of the manipulator are optimized by an improved multi-objective particle swarm optimization algorithm to ensure that the working space of the manipulator completely covers the working surface and that the size of the manipulator is small. In order to improve the smoothness and accuracy of manipulator motion on large surface areas, an improved trajectory planning strategy for a redundant manipulator is proposed. The idea of the improved strategy is to pre-process the motion path first and then use a combination of the clamping weighted least-norm method and the gradient projection method to plan the trajectory, while adding a reverse planning step to solve the singularity problem. The resulting trajectories are smoother than those planned by the general method. The feasibility and practicality of the trajectory planning strategy are verified through simulation.

To alleviate the fire hazard of epoxy resin (EP), layered ammonium vanadium oxalate-phosphate (AVOPh) with the structural formula of (NH4)2[VO(HPO4)]2(C2O4)·5H2O is synthesized using the hydrothermal method and mixed into an EP matrix to prepare EP/AVOPh composites. The thermogravimetric analysis (TGA) results show that AVOPh exhibits a similar thermal decomposition temperature to EP, which is suitable for flame retardancy for EP. The incorporation of AVOPh nanosheets greatly improves the thermal stability and residual yield of EP/AVOPh composites at high temperatures. The residue of pure EP is 15.3% at 700 °C. In comparison, the residue of EP/AVOPh composites is increased to 23.0% with 8 wt% AVOPh loading. Simultaneously, EP/6 wt% AVOPh composites reach UL-94 V1 rating (t1 + t2 =16 s) and LOI value of 32.8%. The improved flame retardancy of EP/ AVOPh composites is also proven by the cone calorimeter test (CCT). The results of CCT of EP/8 wt% AVOPh composites show that the peak heat release rate (PHHR), total smoke production (TSP), peak of CO production (PCOP), and peak of CO2 production (PCO2P) decrease by 32.7%, 20.4%, 37.1%, and 33.3% compared with those of EP, respectively. This can be attributed to the lamellar barrier, gas phase quenching effect of phosphorus-containing volatiles, the catalytic charring effect of transition metal vanadium, and the synergistic decomposition of oxalic acid structure and charring effect of phosphorus phase, which can insulate heat and inhibit smoke release. Based on the experimental data, AVOPh is expected to serve as a new high-efficiency flame retardant for EP.

Automatic road extraction from remote sensing images has an important impact on road maintenance and land management. While significant deep-learning-based approaches have been developed in recent years, achieving a suitable trade-off between extraction accuracy, inference speed and model size remains a fundamental and challenging issue for real-time road extraction applications, especially for rural roads. For this purpose, we developed a lightweight dynamic addition network (LDANet) to exploit rural road extraction. Specifically, considering the narrow, complex and diverse nature of rural roads, we introduce an improved Asymmetric Convolution Block (ACB)-based Inception structure to extend the low-level features in the feature extraction layer. In the deep feature association module, the depth-wise separable convolution (DSC) is introduced to reduce the computational complexity of the model, and an adaptation-weighted overlay is designed to capture the salient features. Moreover, we utilize a dynamic weighted combined loss, which can better solve the sample imbalance and boosts segmentation accuracy. In addition, we constructed a typical remote sensing dataset of rural roads based on the Deep Globe Land Cover Classification Challenge dataset. Our experiments demonstrate that LDANet performs well in road extraction with fewer model parameters (

Remotely sensed spectral diversity is a promising method for investigating biodiversity. However, studies designed to assess the effectiveness of tracking changes in diversity using historical satellite imagery are lacking. This study employs open-access multispectral Landsat imagery and the BiodivMapR package to estimate the multi-temporal alpha diversity in drylands affected by mining. Multi-temporal parameters of alpha diversity were identified, such as vegetation indices, buffer zone size, and the number of clusters. Variations in alpha diversity were compared for various plant communities over time. The results showed that this method could effectively assess the alpha diversity of vegetation (R2, 0.68). The optimal parameters used to maximize the accuracy of alpha diversity were NDVI threshold, 0.01; size of buffer zones, 120 m × 120 m; number of clusters, 100. The root mean square error of the alpha diversity of herbs was lowest (0.26), while those of shrub and tree communities were higher (0.34–0.41). During the period 1990–2020, the study area showed an overall trend of increasing diversity, with surface mining causing a significant decrease in diversity when compared with underground mining. This illustrates that the quick development of remote sensing and image processing techniques offers new opportunities for monitoring diversity in both single and multiple time phases. Researchers should consider the plant community types involved and select locally suitable parameters. In the future, the generation of long-time series and finer resolution maps of diversity should be studied further in the aspects of spatial, functional, taxonomic, and phylogenetic diversity.

A transformer’s acoustic signal contains rich information. The acoustic signal can be divided into a transient acoustic signal and a steady-state acoustic signal under different operating conditions. In this paper, the vibration mechanism is analyzed, and the acoustic feature is mined based on the transformer end pad falling defect to realize defect identification. Firstly, a quality–spring–damping model is established to analyze the vibration modes and development patterns of the defect. Secondly, short-time Fourier transform is applied to the voiceprint signals, and the time–frequency spectrum is compressed and perceived using Mel filter banks. Thirdly, the time-series spectrum entropy feature extraction algorithm is introduced into the stability calculation, and the algorithm is verified by comparing it with simulated experimental samples. Finally, stability calculations are performed on the voiceprint signal data collected from 162 transformers operating in the field, and the stability distribution is statistically analyzed. The time-series spectrum entropy stability warning threshold is given, and the application value of the threshold is demonstrated by comparing it with actual fault cases.

This retrospective study aimed to derive the clinical phenotypes of ventilated ICU patients to predict the outcomes on the first day of ventilation. Clinical phenotypes were derived from the eICU Collaborative Research Database (eICU) cohort via cluster analysis and were validated in the Medical Information Mart for Intensive Care (MIMIC-IV) cohort. Four clinical phenotypes were identified and compared in the eICU cohort (n = 15,256). Phenotype A (n = 3112) was associated with respiratory disease, had the lowest 28-day mortality (16%), and had a high extubation success rate (~80%). Phenotype B (n = 3335) was correlated with cardiovascular disease, had the second-highest 28-day mortality (28%), and had the lowest extubation success rate (69%). Phenotype C (n = 3868) was correlated with renal dysfunction, had the highest 28-day mortality (28%), and had the second-lowest extubation success rate (74%). Phenotype D (n = 4941) was associated with neurological and traumatic diseases, had the second-lowest 28-day mortality (22%), and had the highest extubation success rate (>80%). These findings were validated in the validation cohort (n = 10,813). Additionally, these phenotypes responded differently to ventilation strategies in terms of duration of treatment, but had no difference in mortality. The four clinical phenotypes unveiled the heterogeneity of ICU patients and helped to predict the 28-day mortality and the extubation success rate.

The limb-driving force mutation of the modular combination parallel manipulator (MCPM) affects the alignment process of optical axis. In this paper, a novel optimization method based on the force mutation penalty term is proposed to solve the problem of driving force mutation. The kinematics and dynamics models of the manipulator are established using a modularization idea, reducing the complexity of the modeling process, and verified using co-simulation. Moreover, particle swarm optimization (PSO) is applied as an optimization tool. The effectiveness of the proposed method is confirmed by comparing it with the minimize-the-maximum and Moore–Penrose (M–P) methods, which are widely used to solve parallel manipulators with redundant drives.

Oil recovery is an essential parameter for reservoir development performance evaluation, but there is no specific research on the theoretical oil recovery prediction model of polymer microspheres (PMs)’ conformance control. This research aims to establish an oil recovery prediction model that depends on the definition of oil recovery based on stream tube theory. PMs’ enhanced oil recovery mechanism is to plug the pore throat to expand the swept area. The assumption that the stream tube between injection and production wells is trapezoidal is proposed. Based on this premise, the area sweep efficiency equation suitable for the rhombus inverse nine-spot well pattern is established based on the stream tube theory. The vertical sweep efficiency equation is optimized by introducing the equivalent mobility ratio. Additionally, the model’s adaptability and validity are studied. The analysis results show that oil recovery decreases with increasing injection rate, injection concentration, and PMs size but increases with the increasing injection period. The theoretical oil recovery is 1.37%, and the actual oil recovery of the field application is 1.22%, with an error of 0.15%. This model has good consistency with the actual physical process of the field application. The oil recovery prediction model can provide oil recovery and optimize PMs’ conformance control injection scheme. This study fills the gap in the mathematical model for oil recovery prediction of PMs’ conformance control.

Due to the mechanistic coupling between solar-induced chlorophyll fluorescence (SIF) and photosynthesis, SIF has an advantage over greenness-based vegetation indices in detecting drought. Since photosystem I (PSI) contributes very little to red SIF, red SIF is assumed to be more responsive to environmental stress than far-red SIF. However, in addition to affecting photosynthesis, drought also has an impact on vegetation chlorophyll concentration and thus affects the reabsorption process of red SIF. When these responses are entangled, the sensitivity of SIF in the red and far-red regions in response to drought is not yet clear. In this study, we conducted a water stress experiment on maize in the field and measured the upward and downward leaf SIF spectra by a spectrometer assembled with a leaf clip. Simultaneously, leaf-level active fluorescence was measured with a pulse-amplified modulation (PAM) fluorometer. We found that SIF, after normalization by photosynthetically active radiation (PAR) and dark-adapted minimal fluorescence (Fo), is a better estimation of SIF yield. By comparing the wavelength-dependent link between SIF yield and nonphotochemical quenching (NPQ) across the range of 660 to 800 nm, the results show that red SIF and far-red SIF have different sensitivities in response to drought. SIF yield in the far-red region has a strong and stable correlation with NPQ. Drought not only reduces red SIF due to photosynthetic regulation, but it also increases red SIF by reducing chlorophyll content (weakening the reabsorption effect). The co-existence of these two contradictory effects makes the red SIF of leaf level unable to reliably indicate NPQ. In addition, the red:far-red ratio of downward SIF and the ratio between the downward SIF and upward SIF at the red peak can be good indicators of chlorophyll content. These findings can help to interpret SIF variations in remote sensing techniques and fully exploit SIF information in red and far-red regions when monitoring plant water stress.

The application of wearable devices for fall detection has been the focus of much research over the past few years. One of the most common problems in established fall detection systems is the large number of false positives in the recognition schemes. In this paper, to make full use of the dependence between human joints and improve the accuracy and reliability of fall detection, a fall-recognition method based on the skeleton and spatial-temporal graph convolutional networks (ST-GCN) was proposed, using the human motion data of body joints acquired by inertial measurement units (IMUs). Firstly, the motion data of five inertial sensors were extracted from the UP-Fall dataset and a human skeleton model for fall detection was established through the natural connection relationship of body joints; after that, the ST-GCN-based fall-detection model was established to extract the motion features of human falls and the activities of daily living (ADLs) at the spatial and temporal scales for fall detection; then, the influence of two hyperparameters and window size on the algorithm performance was discussed; finally, the recognition results of ST-GCN were also compared with those of MLP, CNN, RNN, LSTM, TCN, TST, and MiniRocket. The experimental results showed that the ST-GCN fall-detection model outperformed the other seven algorithms in terms of accuracy, precision, recall, and F1-score. This study provides a new method for IMU-based fall detection, which has the reference significance for improving the accuracy and robustness of fall detection.

Abstract Inflammation plays a crucial role in the occurrence and development of renal fibrosis, which ultimately results in end-stage renal disease (ESRD). There is new focus on lymphangiogenesis in the field of inflammation. Recent studies have revealed the association between lymphangiogenesis and renal fibrosis, but the source of lymphatic endothelial cells (LECs) is not clear. It has also been reported that macrophages are involved in lymphangiogenesis through direct and indirect mechanisms in other tissues. We hypothesized that there was a close relationship between macrophages and lymphatic endothelial progenitor cells in renal fibrosis. In this study, we demonstrated that lymphangiogenesis occurred in a renal fibrosis model and was positively correlated with the degree of fibrosis and macrophage infiltration. Compared to resting (M0) macrophages and alternatively activated (M2) macrophages, classically activated (M1) macrophages predominantly transdifferentiated into LECs in vivo and in vitro. VEGF-C further increased M1 macrophage polarization and transdifferentiation into LECs by activating VEGFR3. It was suggested that VEGF-C/VEGFR3 pathway activation downregulated macrophage autophagy and subsequently regulated macrophage phenotype. The induction of autophagy in macrophages by rapamycin decreased M1 macrophage polarization and differentiation into LECs. These results suggested that M1 macrophages promoted lymphangiogenesis and contributed to newly formed lymphatic vessels in the renal fibrosis microenvironment, and VEGF-C/VEGFR3 signaling promoted macrophage M1 polarization by suppressing macrophage autophagy and then increased the transdifferentiation of M1 macrophages into LECs.

Abstract. Background. Previous studies have demonstrated that various circular RNAs are involved in the malignant proliferation of cancers, such as liver cancer, lung cancer, breast cancer, and others. The potential role of circular RNAs in glioblastoma, however, is still uncertain. In this study, we aimed to study the potential role of hsa_circ_01844 in glioblastoma. Methods. Using reverse transcription-polymerase chain reaction (RT-PCR) method, hsa_circ_01844 expression was measured in five glioblastoma samples and five normal brain samples. To evaluate the potential function of hsa_circ_01844 in glioblastoma, hsa_circ_01844 was overexpressed in glioblastoma cell lines (U251 and U87 cells). Using these two cell lines, in vitro experiments including the flow cytometry assay, 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide assay, Transwell assay, and cell apoptosis assay were performed to investigate the role of hsa_circ_01844 in glioblastoma. Student t test and one-way analysis of variance were used for statistical analysis. Results. The expression of circular RNA hsa_circ_01844 was lower in glioblastoma tissues when compared with the normal brain tissues by RT-PCR method (0.034 ± 0.036 vs. 1.630 ± 0.891, P

To overcome the problems of wind power forecast for the current deterministic wind power turbine output model cannot accurately describe the statistical characterization of wind turbine output, this article proposes a novel wind power stochastic cloud model. There are three steps to build this model. Firstly, it is necessary to analyze the power data and to filter out the disturbed data by utilizing the improved Bin method and data fitting. Secondly, it is available to obtain respectively two groups of the expectation, entropy and hyper entropy of the waist and upper data of stochastic cloud model by the known and unknown membership of backward cloud generators. Finally, the wind-speed data can be transformed into a stochastic cloud model, which is composed of X condition cloud generator and the positive cloud generator component. In short, the comparative data of the wind power cloud droplets and the measured data of wind power show that the line correlation coefficient of the wind power frequency of the proposed model reaches to 0.8868, which could simulate the statistical characterization of wind turbine output effectively.

In air cushion furnace, the floating height is a key process parameter which greatly affects the quality and production efficiency of high quality metal strips. However, the floating height is hard to be collected in the complex and abominable industry environment. Furthermore, due to the flow field characteristics, some important process variables are difficult to accurately calculate by traditional mechanism modeling methods. In order to accurately predict the floating height, firstly, a low discrepancy heuristic evolution ELM and ground effect theory based serial hybrid soft sensor model is proposed, which constituted by a mechanism model and two data driven models. Secondly, based on the force equilibrium equation and ground effect theory, the mechanism model is constructed, which describes the relationship between the floating height and the process variables including the jet impact angle. Thirdly, a low discrepancy heuristic evolution ELM is proposed as the data driven model to predict the jet impinging angle. In the data driven model, the novel dual mutation strategies collaboration differential evolution is proposed to guarantee the low discrepancy and physical applicability of data driven model. The effectiveness of the proposed method was validated on the self-developed air cushion experiment platform and got desirable experimental results. The research lays an important foundation for the successful implementation of monitoring and control of the strip floating process.

An improved fuzzy method is proposed to derive a fuzzy number for characterizing uncertain wind power. The input measurement data are firstly converted into nested sets, and the fuzzy number is further obtained based on nested set transformation method. Numerical studies have demonstrated the effectiveness and advantages of the improved fuzzy method.

Abstract A new type of orange emission carbon dots (OCDs) was prepared by hydrothermal method using 1,2,4‐triaminobenzene and p‐aminobenzenesulphonic acid as precursors. TEM characterization showed that the new OCDs were uniform in size with an average particle size of 4–7 nm. Infrared spectroscopy and XPS analysis showed that the surface of the OCDs were rich in hydrophilic functional groups. Fluorescence spectroscopy results showed that the obtained OCDs exhibited excellent fluorescence with an absolute quantum yield as high as 14.9%. The OCDs were further applied to the detection of metal ions. It was found that the fluorescence of OCDs could be effectively quenched by Cr(Ш) with a detection limit of 0.38 μm. Notably, the obtained OCDs have been successfully used for fluorescence detection of Cr3+ ions in cell level.

Functionally graded materials (FGMs) used in electrical insulation have spatially inhomogeneous dielectric properties (i.e., permittivity or conductivity), which can be applied to relieve localized electric field (E-field) intensification and improve insulation performance. However, previous research shows some limitations in inadequate considerations on the material feasibility, and insufficient universality on material grading type and voltage form. In this study, a material study of silicone rubber (SiR) nanocomposites containing carbon nanotubes (CNTs) is conducted to determine the practical variation range of dielectric properties (both permittivity and conductivity) in joint insulation materials. Then, the optimal design of both multilayer and pointwise FGM joint insulation is investigated under both AC and DC voltage, in which the lower and upper limits of permittivity and conductivity were derived from the experimental results. Experimental results on SiR/CNT nanocomposites indicate that low-amount doping of the CNTs (0-0.5% wt%) can effectively increase the permittivity and conductivity of joint insulation materials. The successive simulation study indicates that compared to uniform joints, cable joints employing optimally designed FGM insulation show a considerable increase in the E-field utilization factor (from 0.08-0.17 to 0.23-0.56), indicating elevated E-field uniformity. Finally, the optimal range of CNT doping ratios is determined to be 0-0.3 wt% from both experimental and simulation results. This study systematically verifies the applicability of FGMs in enhancing the performance of power cable accessories, which can show some guidance to the design and fabrication of advanced power cable systems.

To address the problems of edge blur and weak detail resolution when fusing infrared and visible images with traditional methods, a novel image fusion approach based on fast super-resolution convolutional neural network and anisotropic diffusion is proposed. The proposed method first employs super-resolution reconstruction based on fast convolutional neural networks to get high-resolution infrared images. Second, the visible and high-resolution infrared images are anisotropically diffused to obtain the corresponding base layers and detail layers. Next, the fusion of the detail layer is performed through Karhunen-Loeve transform, and an adaptive saliency module is constructed to fuse the base layer. Finally, the fusion result is obtained by applying linear reconstruction on the fused detail layer and base layer. Compared with other algorithms, the experimental results show that the proposed algorithm not only has better objective evaluation indexes but also can better retain the details of the original image.

Hyperspectral images with high spatial resolution play an important role in material classification, change detection, and others. However, owing to the limitation of imaging sensors, it is difficult to directly acquire images with both high spatial resolution and high spectral resolution. Therefore, the fusion of remotely sensed images is an effective way to obtain high-resolution desired data, which is usually an ill-posed inverse problem and susceptible to noise corruption. To address these issues, a low-rank model based on tensor decomposition is proposed to fuse hyperspectral and multispectral images by incorporating graph regularization, in which the logarithmic low-rank function is utilized to suppress the small components for denoising. Furthermore, this article takes advantage of the local spatial similarity of remotely sensed images to enhance the reconstruction performance by constructing spatial graphs, and also promotes signature smoothing between adjacent endmember spectra using the neighborhood-based spectral graph regularization. Finally, a set of efficient solvers is carefully designed via alternating optimization for closed-from solutions and computational reduction, in which vector-matrix operators are adapted to solve the 3-D core tensor. Experimental tests on several real datasets illustrate that the proposed fusion method yields better reconstruction performance than the current state-of-the-art methods, and can significantly suppress noise at the same time.

Identification of exact causative genes is important for in silico drug repositioning based on drug-gene-disease relationships. However, the complex polygenic etiology of the autism spectrum disorder (ASD) is a challenge in the identification of etiological genes. The network-based core gene identification method can effectively use the interactions between genes and accurately identify the pathogenic genes of ASD. We developed a novel network-based drug repositioning framework that contains three steps: network-specific core gene (NCG) identification, potential therapeutic drug repositioning, and candidate drug validation. First, through the analysis of transcriptome data for 178 brain tissues, gene network analysis identified 365 NCGs in 18 coexpression modules that were significantly correlated with ASD. Second, we evaluated two proposed drug repositioning methods. In one novel approach (dtGSEA), we used the NCGs to probe drug-gene interaction data and identified 35 candidate drugs. In another approach, we compared NCG expression patterns with drug-induced transcriptome data from the Connectivity Map database and found 46 candidate drugs. Third, we validated the candidate drugs using an in-house mental diseases and compounds knowledge graph (MCKG) that contained 7509 compounds, 505 mental diseases, and 123,890 edges. We found a total of 42 candidate drugs that were associated with mental illness, among which 10 drugs (baclofen, sulpiride, estradiol, entinostat, everolimus, fluvoxamine, curcumin, calcitriol, metronidazole, and zinc) were postulated to be associated with ASD. This study proposes a powerful network-based drug repositioning framework and also provides candidate drugs as well as potential drug targets for the subsequent development of ASD therapeutic drugs.

To investigate the seismic performance of a wind turbine that is influenced by both the ice load and the seismic load, the research proposes a numerical approach for simulating the seismic behavior of a wind turbine on a monopile foundation. First, the fluid–solid coupled equation for the water–ice–wind turbine is simplified by assigning reasonable boundary conditions and solving the motion equation, and the seismic motion equation of the wind turbine is developed. Then, on this basis, we propose a simplified 3D numerical model that can simulate the interactions among the wind turbine, water and sea ice. By conducting shaking table tests, the results demonstrate that the established numerical model is effective. Finally, we investigate the effect of the boundary range and ice thickness on the seismic performance of a turbine under near-field and far-field seismic actions. Research results illustrate that ice changes the distribution form of the hydrodynamic pressure. Moreover, the thickness of the ice greatly influences the seismic behavior, while the influence of the ice boundary range is only within a certain range. Additionally, the ice load decreases the energy-dissipating capacity of the wind turbine, so the earthquake resilience of the wind turbine is significantly decreased.

The vascular endothelial growth factor receptor 2 (VEGFR2) is considered to be a pivotal target for anti-tumor therapy against angiogenesis of non-small cell lung cancer (NSCLC). However, effective and low-toxicity targeted therapies to inhibit VEGFR2 are still lacking. Here, biRGD–siVEGFR2 conjugate comprising murine VEGFR2 siRNA and [cyclo(Arg-Gly-Asp-D-Phe-Lys)-Ahx]2-Glu-PEG-MAL (biRGD) peptide which selectively binds to integrin αvβ3 receptors expressing on neovascularization endothelial cell was synthesized. The anti-tumor activity and renal toxicity of biRGD–siVEGFR2 or its combination therapy with low-dose apatinib were investigated on NSCLC xenografts. The immunogenicity of biRGD–siVEGFR2 was also evaluated in C57BL/6J mice. In vivo, intravenously injected biRGD–siVEGFR2 substantially inhibited NSCLC growth with a marked reduction of vessels and a down-regulation of VEGFR2 in tumor tissue. Furthermore, biRGD–siVEGFR2 in combination with low-dose apatinib achieved powerful anti-tumor effect with less nephrotoxicity compared with the regular dose of apatinib. Besides, no obvious immunogenicity of biRGD–siVEGFR2 was found. These findings demonstrate that biRGD–siVEGFR2 conjugate can be used as a new candidate for the treatment of NSCLC and its combination therapy with apatinib may also provide a novel strategy for cancer treatment in clinic.

Abstract Background As core units of organ tissues, cells of various types play their harmonious rhythms to maintain the homeostasis of the human body. It is essential to identify the characteristics of cells in human organs and their regulatory networks for understanding the biological mechanisms related to health and disease. However, a systematic and comprehensive single-cell transcriptional profile across multiple organs of a normal human adult is missing. Results We perform single-cell transcriptomes of 84,363 cells derived from 15 tissue organs of one adult donor and generate an adult human cell atlas. The adult human cell atlas depicts 252 subtypes of cells, including major cell types such as T, B, myeloid, epithelial, and stromal cells, as well as novel COCH + fibroblasts and FibSmo cells, each of which is distinguished by multiple marker genes and transcriptional profiles. These collectively contribute to the heterogeneity of major human organs. Moreover, T cell and B cell receptor repertoire comparisons and trajectory analyses reveal direct clonal sharing of T and B cells with various developmental states among different tissues. Furthermore, novel cell markers, transcription factors, and ligand-receptor pairs are identified with potential functional regulations in maintaining the homeostasis of human cells among tissues. Conclusions The adult human cell atlas reveals the inter- and intra-organ heterogeneity of cell characteristics and provides a useful resource in uncovering key events during the development of human diseases in the context of the heterogeneity of cells and organs.

Abstract Background Gliomas are one of the most common primary tumors of the central nervous system, and have an unfavorable prognosis. SLC39A1 is a zinc ion transport protein which inhibits the progression of prostate cancer. By studying the role and mechanism of SLC39A1 in the progression of gliomas, perhaps a new therapeutic target can be provided for their treatment. Method The TCGA, CCGA, GSE16011, GSE44971 and GSE11260 data sets were employed to evaluate the expression level of SLC39A1 in paracancerous and glioma tissues. In addition, Kaplan–Meier analysis, Cox analysis, and the ESTIMATE and CIBERSORT algorithms were used to analyze its prognostic value and immune infiltration correlation. A CCK-8 and flow cytometer were used to measure the effects of SLC39A1 on U87 cell proliferation or apoptosis; RT-qPCR and western blot were used to detect its effects on the expression of MMP2\MMP9. Results SLC39A1 has up-regulated expression in glioma tissues. High SLC39A1 expression predicted significantly worse survival. Univariate and multivariate analysis show that SLC39A1 independently indicated poor prognosis in patients with gliomas. The expression of SLC39A1 is significantly correlated with clinical pathological parameters such as Grade, IDH mutation status, and 1p19q codeletion status. In vitro experimental results show that SLC39A1 promotes proliferation of glioma cells, inhibits their apoptosis, and promotes expression of MMP2\MMP9. In addition, it may affect infiltration of immune cells into the glioma microenvironment. Conclusion SLC39A1 may serve as a new prognostic biomarker and potential target for treatment of gliomas.

ObjectiveTo evaluate alterations in the fetal Doppler parameters of pump fetuses before and 24 h after radiofrequency ablation surgery for twin reversed arterial perfusion sequence (TRAPs).MethodsThis is a retrospective study of 28 pump fetuses in TRAPs and 28 normal control twins between 2016 and 2021. The fetal Doppler parameters, including the umbilical artery pulsatility index (UA-PI), middle cerebral artery peak systolic velocity (MCA-PSV), middle cerebral artery pulsatility index (MCA-PI), and cerebroplacental ratio (CPR), of the controls, and pump fetuses before and 24 h after surgery were compared.ResultsAn increasing trend and a further increase in the MCA-PSV, MCA-PI, MCA-PSV Z score, and MCA-PI Z score after surgery were observed in pump fetuses with gestational age (GA) ≥20 weeks; however, such changes were not observed in those with a GA of

BackgroundAntibody–drug conjugates (ADC), such as enfortumab vedotin (EV), sacituzumab govitecan (SG), and RC-48, have shown outstanding response rates to local advanced or metastatic urothelial carcinoma (UC). However, their corresponding target expression characteristics in UC and its histologic variants were unknown.MethodsWe detected the expression of NECTIN-4, TROP-2, and HER2, which are the corresponding targets of ADCs EV, SG, and RC-48 in muscle-invasive UC through immunohistochemistry.Results161 consecutive samples from 2017 to 2021 of muscle-invasive UC and its histologic variants were obtained in Peking University First Hospital. Variant histology types included 72UC, 10 squamous carcinomas, 23 glandular carcinomas, 19 small cell carcinomas, 19 micropapillary variants, and 18 nested variants. NECTIN-4 expression was found to be 57/72 (79.2%), 10/10 (100%), 15/23 (65.2%), 4/19 (21.1%), 15/19 (78.9%), and 16/18 (88.9%) in conventional UC, squamous carcinoma, glandular carcinoma, small cell carcinoma, micropapillary, and nested variant, respectively, compared with 65/72 (90.3%), 8/10 (80.0%), 13/23 (56.5%), 3/19 (15.8%), 16/19 (84.2%), and 15/18 (83.3%) of TROP-2, and 26/72 (36.1%), 0, 5/23 (21.7%), 6/19 (31.6%), 5/19 (26.3%), and 7/18 (38.9%) of HER2.

The production efficiency of dairy cows is affected by altitude, with lower efficiency reported at higher altitudes. However, only a few studies have investigated the digestion performance, serum antioxidative characteristics, rumen fermentation performance, and rumen bacteria of Sanhe heifers at different altitudes. Therefore, in this study, we explored the effects of altitude on these aspects of Sanhe heifers. We evaluated the effects of altitude on the apparent digestibility of nutrients, serum antioxidative characteristics, rumen fermentation parameters, and rumen bacteria in Sanhe heifers. Twenty Sanhe heifers from the same herd and managed with the same practice were used. However, the heifers were from two regions in China: 10 were fed in Hulunbuir City, Inner Mongolia Autonomous Region (119°57′E, 47°17′N; approximately 700 m altitude, named LA) and 10 were fed in Lhasa City, Tibet Autonomous Region (91°06′E, 29°36′N; approximately 3,750 m altitude, named HA). The dry matter intake (DMI), average daily gain (ADG), and DMI/ADG ratio were higher (p

As a type of functional food additives, phycocyanin is well-known for its extraordinary antineoplastic activity in non-small cell lung cancer (NSCLC). Previously, a high-throughput miRNA sequencing was employed to excavate miRNAs altered by phycocyanin in A549 cells, while the in-depth regulatory mechanism was inadequate. In this work, three significant up-regulated miRNAs in phycocyanin-treated cells are identified for the first time, including miR-3150a-3p, miR-6883-3p and miR-627-5p. Overexpression of miRNAs obviously diminished the cell growth and colony formation capacity, respectively. Dual-luciferase reporter assay verified that toll/interleukin 1 receptor domain-containing adaptor protein (TIRAP) was a direct shared target of three miRNAs. Knockdown the expression of TIRAP resulted in similar cell growth inhibition phenotype as miRNAs overexpression. Strikingly, overexpression of TIRAP could significantly restore the diminished cell viability caused by miRNAs up-regulation, as well as phycocyanin treatment. Consequently, this study proposes that phycocyanin plays an inhibitory effect of NSCLC cells via a miR-3150a-3p/miR-6883-3p/miR-627-5p-TIRAP axis.

Objectives: To investigate metabolomic perturbations caused by twin-twin transfusion syndrome, metabolic changes associated with fetoscopic laser coagulation in both placental tissue and cord plasma, and to investigate differential metabolites pertinent to varying fetal outcomes, including hemodynamic status, birth weight, and cardiac function, of live-born babies.Methods: Placental tissue and cord plasma samples from normal term or uncomplicated preterm-born monochorionic twins and those complicated by twin-twin transfusion syndrome treated with or without fetoscopic laser coagulation were analyzed by high-performance liquid chromatography metabolomic profiling. Sixteen comparisons of different co-twin groups were performed. Partial least squares–discriminant analysis, metabolic pathway analysis, biomarker analysis, and Spearman’s correlation analysis were conducted based on differential metabolites used to determine potential biomarkers in different comparisons and metabolites that are pertinent to neonatal birth weight and left ventricular ejection fraction.Results: These metabolomic investigations showed that the cord plasma metabolome has a better performance in discriminating fetuses among different hemodynamic groups than placental tissue. The metabolic alteration of twin-twin transfusion syndrome in these two types of samples centers on fatty acid and lipid metabolism. The fetoscopic laser coagulation procedure improves the metabolomic change brought by this syndrome, making the metabolomes of the treated group less distinguishable from those of the control and preterm birth groups. Certain compounds, especially lipids and lipid-like molecules, are noted to be potential biomarkers of this morbid disease and pertinent to neonatal birth weight and ejection fraction.Conclusions: Fetoscopic laser coagulation can ameliorate the metabolomic alteration caused by twin-twin transfusion syndrome in placental tissue and cord plasma, which are involved mainly in fatty acid and lipid-like molecule metabolism. Certain lipids and lipid-like molecules are helpful in differentiating co-twins of different hemodynamic statuses and are significantly correlated with neonatal birth weight or ejection fraction.

The strong invasive and metastatic abilities of oral squamous cell carcinoma (OSCC) cells in the early stage are the main reason for its poor prognosis. The early diagnosis and treatment of OSCC may reduce the metastasis rate and improve the survival rate. The aim of this study was to explore candidate biomarkers related to the prognosis and progression of OSCC. We performed weighted gene coexpression network analysis to identify key modules and genes associated with OSCC and intersected the differentially expressed genes (DEGs) in The Cancer Genome Atlas (TCGA)-OSCC and GSE30784 datasets. Next, we performed survival analysis and immunohistochemistry to screen and validate the hub gene insulin-like growth factor 2 (IGF2) mRNA binding protein 2 IGF2BP2. We also used TCGA pan-cancer data to verify that IGF2BP2 was expressed at high levels in a variety of cancers and was related to a poor prognosis in patients. Furthermore, we divided patients with OSCC into high and low expression groups based on the median expression level of IGF2BP2. Gene set enrichment analysis (GSEA) showed that IGF2BP2 led to a poor prognosis in OSCC by affecting cancer-related (epithelial-mesenchymal transition, glycolysis, cell cycle, etc.) and immune-related biological functions and pathways. Single-sample GSEA (ssGSEA), CIBERSORT, and xCell algorithms helped reveal that high IGF2BP2 expression was accompanied by a significant reduction in the immune score, stromal score, and microenvironment score and a decrease in the number of infiltrating CD8+ T cells in OSCC. In addition, silencing IGF2BP2 suppressed the proliferation, migration, and invasion of OSCC cells. In general, IGF2BP2 is a potential biomarker for the progression, immunotherapy response, and prognosis of OSCC.

Abstract Smad4, a key mediator of the transforming growth factor‐β signaling, is mutated or deleted in 20% of pancreatic ductal adenocarcinoma (PDAC) cancers and significantly affects cancer development. However, the effect of Smad4 loss on the immunogenicity and tumor immune microenvironment of PDAC is still unclear. Here, a surprising function of Smad4 in suppressing mouse PDAC tumor immunogenicity is identified. Although Smad4 deletion in tumor cells enhances proliferation in vitro, the in vivo growth of Smad4‐deficient PDAC tumor is significantly inhibited on immunocompetent C57BL/6 (B6) mice, but not on immunodeficient mice or CD8+ cell‐depleted B6 mice. Mechanistically, Smad4 deficiency significantly increases tumor cell immunogenicity by promoting spontaneous DNA damage and stimulating STING‐mediated type I interferon signaling,which contributes to the activation of type 1 conventional dendritic cells (cDC1) and subsequent CD8+ T cells for tumor control. Furthermore, retarded tumor growth of Smad4‐deficient PDAC cells on B6 mice is largely reversed when Sting is codeleted, or when the cells are implanted into interferon‐alpha receptor‐deficientmice or cDC1‐deficientmice. Accordingly, Smad4 deficiency promotes PDAC immunogenicity by inducing tumor‐intrinsic DNA damage‐elicited type I interferon signaling.

Glioma is the most common malignant tumor of the central nervous system (CNS), with high degree of malignancy and poor prognosis. The gut microbiome (GM) is composed of microorganisms with different properties and functions, which play an important role in human physiology and biological activities. It has been proved that GM can affect the development of glioma through natural immunity, but whether GM can affect glioma through adaptive immunity and whether there are some microorganisms in the GM that may affect glioma growth still remain unclear. In our study, we evaluated the relationship between GM and glioma. We proved that (I) glioma growth can induce structural changes of mouse GM, including the decreased abundance of Bacteroidia and increased abundance of Firmicutes. (II) GM dysbiosis can downregulate Foxp3 expression in the brain and promote glioma growth. A balanced environment of GM can upregulate the expression of Foxp3 in the brain and delay the development of glioma. (III) The increased abundance of Bacteroidia is associated with accelerated glioma progression, while its decreased abundance is associated with delayed glioma progression, which may be one of the key microorganisms affecting glioma growth. This study is helpful to reveal the relationship between GM and glioma development and provide new ideas for adjuvant therapy of glioma.

Under a persistent warming climate and increasing human activities, permafrost in the Source Area of the Yellow River (SAYR) has been degrading regionally, resulting in many eco-environmental problems. This paper reviews the changes in air temperature and precipitation over the past 60 years and presents the distribution and degradation of alpine permafrost in the SAYR. The review is focused on the permafrost degradation–induced changes in hydrology, wetlands, thermokarst lakes, ponds, and vegetation. Mean annual air temperatures have been rising at an average rate of 0.4°C/10a over the past 60 years, while precipitation has increased only slightly (16 mm/10a). Borehole temperature monitoring at the depth of 15 m shows the permafrost warming rates of 0.01–0.21°C/10a in the Headwater Aera of the Yellow River. As a result of permafrost thaw, the amount of surface waters has declined while groundwater storage has increased. Due to permafrost degradation, the supra-permafrost water table lowers gradually, resulting in a reduction in areal extents of wetlands and lakes in the SAYR. We further renamed the concept of the burial depth of the ecologically-safe supra-permafrost water table, the minimum depth of the groundwater table for sustaining the normal growth of alpine grassland vegetation, for the SAYR to describe the relationship between the lowering permafrost table and succeeding alpine vegetation. Furthermore, we recommended more studies focusing on snow cover and carbon stock and emissions related to permafrost degradation under a warming climate. We also advised to timely establish the long-term monitoring networks for the rapidly changing mountain cryosphere, alpine ecology, alpine hydrology, eco-hydrology, cryo-hydrogeology, and carbon fluxes. Moreover, process-based models should be developed and improved to better simulate and predict the responses of alpine ecosystem changes to the interacting cryospheric and other environmental variables and their ecological and ecohydrological impacts in the SAYR and downstream Yellow River basins. This study can help better manage the ecological and hydrological environments in the Upper Yellow River that are sensitive to changes in the alpine climate and cryosphere.

Background: Breast cancer (BRCA) is the most common cancer worldwide and a serious threat to human health. MDN1 mutations have been observed in several cancers. However, the associations of MDN1 mutation with tumor mutation burden (TMB) and prognosis of BRCA have not been investigated.Methods: Genomic, transcriptomic, and clinical data of 973 patients with BRCA from The Cancer Genome Atlas (TCGA) database were analyzed. The clinical attributes of BRCA based on the MDN1 mutation status were assessed by comparing TMB and tumor infiltrating immune cells. Gene ontology analysis and gene set enrichment analysis (GSEA) were conducted to identify the key signaling pathways associated with MDN1 mutation. Moreover, univariate and multivariate Cox regression analyses were performed to assess the association between prognostic factors and survival outcomes. Finally, nomograms were used to determine the predictive value of MDN1 mutation on clinical outcomes in patients with BRCA.Results: MDN1 was found to have a relatively high mutation rate (2.77%). Compared to the MDN1 wild-type patients, the TMB value was significantly higher in MDN1 mutant patients (p < 0.001). Prognostic analysis revealed that MDN1 mutant patients had a worse survival probability than MDN1 wild-type patients (hazard ratio = 2.91; 95% CI:1.07–7.92; p = 0.036). GSEA revealed samples with MDN1 mutation enriched in retinol metabolism, drug metabolism cytochrome P450, glucuronidation, miscellaneous transport, and binding event pathways.Conclusion: MDN1 mutation was found to be associated with high TMB and inferior prognosis, suggesting that MDN1 mutation may play a potential role in prognosis prediction and immunotherapy guidance in BRCA.

PurposeThe purpose of this study was to develop and validate a preoperative nomogram of differentiating benign and malignant gallbladder polypoid lesions (GPs) combining clinical and radiomics features.MethodsThe clinical and imaging data of 195 GPs patients which were confirmed by pathology from April 2014 to May 2021 were reviewed. All patients were randomly divided into the training and testing cohorts. Radiomics features based on 3 sequences of contrast-enhanced computed tomography were extracted by the Pyradiomics package in python, and the nomogram further combined with clinical parameters was established by multiple logistic regression. The performance of the nomogram was evaluated by discrimination and calibration.ResultsAmong 195 GPs patients, 132 patients were pathologically benign, and 63 patients were malignant. To differentiate benign and malignant GPs, the combined model achieved an area under the curve (AUC) of 0.950 as compared to the radiomics model and clinical model with AUC of 0.929 and 0.925 in the training cohort, respectively. Further validation showed that the combined model contributes to better sensitivity and specificity in the training and testing cohorts by the same cutoff value, although the clinical model had an AUC of 0.943, which was higher than 0.942 of the combined model in the testing cohort.ConclusionThis study develops a nomogram based on the clinical and radiomics features for the highly effective differentiation and prediction of benign and malignant GPs before surgery.

AIM:To observe the clinical effect of retrograde lacrimal duct drainage tube(RS-1 type)in the treatment of lacrimal canaliculus rupture in children.METHODS: The clinical data of 37 cases(37 eyes)with lacrimal canaliculus rupture admitted to Handan Eye Hospital and Handan Central Hospital from March 2016 to November 2019 were retrospectively analyzed. New silicone tubes were retrograde implanted in all patients during the operation. 8-0 absorbable sutures were used to anastomose the broken end of the lacrimal canaliculus, 6-0 absorbable sutures were used to anastomose the “medial canthus ligament-orbicularis” complex intermittently, and muscle, subcutaneous tissue, skin wounds and conjunctival wounds were sutured intermittently. The catheter was extubated 2-3mo after operation, and the lacrimal passage patency and lacrimal ectorrhea were observed for 6-12mo. RESULTS: Totally 31 eyes(84%)were cured, 5 eyes(14%)were improved, and 1 eyes(3%)was ineffective. The total effective rate reached 97%. None of the patients had lacrimal dot tearing, abnormal location of lacrimal dot, angulation deformity and other related complications, and 1 invalid eyes(3%)was combined with bone lacrimal tubule fracture, without obvious lacrimal ectorsion symptoms.CONCLUSION: The new type of silicone tube combined with retrograde catheterization has the characteristics of simple operation, light postoperative stimulation, safe catheterization state and significant anastomosis effect. The retrograde catheterization can better protect the small lacrimal spots.

Abstract Background Glioblastoma is a common disease of the central nervous system (CNS), with high morbidity and mortality. In the infiltrate in the tumor microenvironment, tumor-associated macrophages (TAMs) are abundant, which are important factors in glioblastoma progression. However, the exact details of TAMs in glioblastoma progression have yet to be determined. Methods The clinical relevance of SET domain bifurcated 1 (SETDB1) was analyzed by immunohistochemistry, real-time PCR and Western blotting of glioblastoma tissues. SETDB1-induced cell proliferation, migration and invasion were investigated by CCK-8 assay, colony formation assay, wound healing and Transwell assay. The relationship between SETDB1 and colony stimulating factor 1 (CSF-1), as well as TAMs recruitment was examined by Western blotting, real-time PCR and syngeneic mouse model. Results Our findings showed that SETDB1 upregulated in glioblastoma and relative to poor progression. Gain and loss of function approaches showed the SETDB1 overexpression promotes cell proliferation, migration and invasion in glioblastoma cells. However, knockdown SETDB1 exerted opposite effects in vitro. Moreover, SETDB1 promotes AKT/mTOR-dependent CSF-1 induction and secretion, which leads to macrophage recruitment in the tumor, resulted in tumor growth. Conclusion Our research clarified that SETDB1 regulates of tumor microenvironment and hence presents a potential therapeutic target for treating glioblastoma.

Abstract Background A national control program for echinococcosis has been in effect since 2005 in China. This program has applied a comprehensive strategy, and good control results have been achieved. Human echinococcosis prevalence rate decrease from 1.08% in 2004 to 0.24% in 2012. The objective of this study is focusing on assessment of the programme with two indices, including patient treatment and registered dogs deworming, in endemic areas of echincoccosis control over the period of 10 years (2004–2014) in China. Methods We established the database including demography at county and township levels with coverage for ten provinces and autonomous regions of China in this study. We using methods of epidemiological descriptive, instead the expectation-maximization for missing value filling for grouping available patients into those subjected to surgery and those receiving drug treatment after population screening and the dogs population after registered by deworming. We performed Microsoft Excel software and SPSS software on the results as percentages with the corresponding 95% confidence intervals (95% CIs). We also statistically analyzed the economics data on patient treatment and dogs deworming after the corresponding discount with annual bank interest rates (USD 1 = CNY 6.5, bank discount average changes of 2.3–3.3%). Results During 2004–2014, the grant total average rate of surgical patient (after surgical operation) treatment had increased with 32.4% and with 81.3% for medical treatment with albendazole. Meanwhile, it increased by 58.6% for the deworming of registered dog since 2007. The accumulated costs amounted to USD 27.03 million after discount for patients and registered dog treatment, which is 1/4 of the total accumulated financial inputs (USD 110.67 million from the Chinese Government). Since the implementation of the national program, it has increased 57 times with respect to the annual financial inputs (costs) and 368 times with respect to all accumulated financial inputs (costs). Conclusions This study showed that in endemic areas, patient diagnosis and management, dog management and treatment over this period helped reduce the parasite load to control the disease. More attention should be paid to controlling wild canines during the ongoing program period and sustainable follow-up evaluations are crucial for success and continued implementation of the national program.

Gefitinib is a first-line treatment for patients with non-small-cell lung cancer (NSCLC), but acquired resistance is a major obstacle to its therapeutic efficacy, and the underlying mechanisms are not fully elucidated. Recent studies have indicated that circular RNAs play a crucial role in chemoresistance, but their expression and function in NSCLC cells with acquired resistance to gefitinib are largely unknown. In this study, we determined that circSETD3 was significantly upregulated in gefitinib-resistant NSCLC cell lines and the plasma of gefitinib-resistant NSCLC patients. circSETD3 markedly decreased the gefitinib sensitivity of NSCLC cells both in vitro and in nude mice xenografts. It could directly bind to miR-520h and lead to the upregulation of ATP-binding cassette subfamily G member 2 (ABCG2), an efflux transporter of gefitinib, resulting in a reduced intracellular gefitinib concentration. Moreover, we reported that the downregulation of serine/arginine splicing factor 1 (SRSF1) contributed to, at least in part, the increased expression of circSETD3 in NSCLC cells with acquired resistance to gefitinib. Taken together, our findings indicated that circSETD3 may serve as a prognostic biomarker and a potential therapeutic target for acquired resistance to gefitinib in NSCLC.

Abstract The dynamics of the community structure and composition of the dairy cow fecal bacterial communities during early lactation is unclear, therefore this study was conducted to characterize the fecal bacterial communities in dairy cows during early lactation using 16S rRNA gene sequencing. Feces were sampled from 20 healthy fresh Holstein dairy cows on day 1 (Fresh1d group) and day 14 (Fresh14d group) after calving. After calving, cows were fed the same fresh diet. The dominant phyla Firmicutes and Proteobacteria were decreased (P ≤ 0.01) with lactating progress and phyla Bacteroidetes were increased (P = 0.008) with lactating progress and dietary transition. At family level, the predominant families were Ruminococcaceae (35.23%), Lachnospiraceae (11.46%), Rikenellaceae (10.44%) and Prevotellaceae (6.89%). A total of 14 genera were different between fecal samples from Fresh1d and Fresh14d, included the predominant genera, such as Ruminococcaceae_UCG-005 (P = 0.008), Rikenellaceae_RC9_gut_group (P = 0.043) and Christensenellaceae_R-7_group (P = 0.008). All fecal bacterial communities shared members of the genera Ruminococcaceae_UCG-005, Bacteroides and Rikenellaceae_RC9_gut_group. These findings help to improve our understanding of the composition and structure of the fecal microbial community in fresh cows and may provide insight into bacterial adaptation time and dietary in lactating cows.

Egg-laying behavior in Caenorhabditis elegans is a well-known model for investigating fundamental cellular processes. In egg-laying, muscle contraction is the relaxation of the vulval muscle to extrude eggs from the vulva. Unlike skeletal muscle, vulval muscle lacks visible striations of the sarcomere. Therefore, vulval muscle must counteract the mechanical stress, caused by egg extrusion and body movement, from inducing cell-shape distortion by maintaining its cytoskeletal integrity. However, the underlying mechanisms that regulate the cellular integrity in vulval muscles remain unclear. Here, we demonstrate that C. elegans egg-laying requires proper vulval muscle 1 (vm1), in which the actin bundle organization of vm1 muscles is regulated by Ras suppressor protein 1 (RSU-1). In the loss of RSU-1, as well as RasLET-60 overactivation, blister-like membrane protrusions and disorganized actin bundles were observed in the vm1 muscles. Moreover, RasLET-60 depletion diminished the defected actin-bundles in rsu-1 mutant. These results reveal the genetic interaction of RSU-1 and RasLET-60 in vivo. In addition, our results further demonstrated that the fifth to seventh leucine-rich region of RSU-1 is required to promote actin-bundling protein, α-actinin, for actin bundle stabilization in the vm1 muscles. This expands our understanding of the molecular mechanisms of actin bundle organization in a specialized smooth muscle.

Background: Radix et Rhizoma Ginseng (thereafter called ginseng) has been used as a medicinal herb for thousands of years to maintain people's physical vitality and is also a non–organ-specific cancer preventive and therapeutic traditional medicine in several epidemiologic and preclinical studies. Owing to few toxic side effects and strong enhancement on body immunity, ginseng has admirable application potential and value in cancer chemoprevention. The study aims at investigating the chemopreventive effects of ginseng on cutaneous carcinoma and the underlying mechanisms. Methods: The mouse skin cancer model was induced by 7,12-dimethylbenz[a]anthracene/12-O-tetradecanoylphorbol-13-acetate. Ultraperformance liquid chromatography/mass spectrometry was used for identifying various ginsenosides, the main active ingredients of ginseng. Comprehensive approaches (including network pharmacology, bioinformatics, and experimental verification) were used to explore the potential targets of ginseng. Results: Ginseng treatment inhibited cutaneous carcinoma in terms of initiation and promotion. The content of Rb1, Rb2, Rc, and Rd ginsenosides was the highest in both mouse blood and skin tissues. Ginseng and its active components well maintained the redox homeostasis and modulated the immune response in the model. Specifically, ginseng treatment inhibited the initiation of skin cancer by enhancing T-cell–mediated immune response through upregulating HSP27 expression and inhibited the promotion of skin cancer by maintaining cellular redox homeostasis through promoting nuclear translocation of Nrf2. Conclusion: According to the study results, ginseng can be potentially used for cutaneous carcinoma as a chemopreventive agent by enhancing cell-mediated immunity and maintaining redox homeostasis with multiple components, targets, and links.

Osimertinib, a third‐generation irreversible epidermal growth factor receptor tyrosine kinase inhibitor (EGFR‐TKI), provides marked clinical benefit for patients with EGFR‐activating mutations. Unfortunately, limited treatments exist for patients who acquire osimertinib resistance. We observed two ‘special’ patients who regained an antitumor response with osimertinib plus aspirin treatment. As previous data indicate that aspirin induces antiproliferative effects in tumor cells, we designed a preclinical study to explore whether aspirin combined with osimertinib could synergistically sensitize osimertinib‐resistant non‐small‐cell lung cancer (NSCLC) cells. The effects of combined treatment with osimertinib and aspirin on osimertinib‐resistant NSCLC cell lines were examined in vitro and in vivo. The combination of osimertinib and aspirin induced strong antiproliferative and proapoptotic effects in osimertinib‐resistant NSCLC cells through inhibition of Akt/FoxO3a signaling component phosphorylation and increased Bim expression. Furthermore, Bim knockdown by siRNA significantly attenuated osimertinib resensitization by aspirin. In vivo, combination of aspirin and osimertinib significantly decreased tumor growth of PC‐9GROR cell xenografts. Data of patients with NSCLC who received osimertinib treatment at Daping Hospital between January 2015 and January 2019 were reviewed retrospectively. According to clinical data for 45 patients with NSCLC, retrospective analysis showed that the median progression‐free survival was significantly longer in the osimertinib plus aspirin group than in the osimertinib group. In summary, aspirin synergistically enhances the antitumor activity of osimertinib in osimertinib‐resistant lung cancer cells through promoting Bim‐dependent apoptosis. This combination therapy may be effective in overcoming acquired resistance to osimertinib and prolonging survival in patients with NSCLC.

miR-532-3p is a widely documented microRNA (miRNA) involved in multifaceted processes of cancer tumorigenesis and metastasis. However, the clinical significance and biological functions of miR-532-3p in bone metastasis of prostate cancer (PCa) remain largely unknown. Herein, we report that miR-532-3p was downregulated in PCa tissues with bone metastasis, and downexpression of miR-532-3p was significantly associated with Gleason grade and serum prostate-specific antigen (PSA) levels and predicted poor bone metastasis-free survival in PCa patients. Upregulating miR-532-3p inhibited invasion and migration abilities of PCa cells in vitro, while silencing miR-532-3p yielded an opposite effect on invasion and migration abilities of PCa cells. Importantly, upregulating miR-532-3p repressed bone metastasis of PCa cells in vivo. Our results further demonstrated that overexpression of miR-532-3p inhibited activation of nuclear facto κB (NF-κB) signaling via simultaneously targeting tumor necrosis factor receptor-associated factor 1 (TRAF1), TRAF2, and TRAF4, which further promoted invasion, migration, and bone metastasis of PCa cells. Therefore, our findings reveal a novel mechanism contributing to the sustained activity of NF-κB signaling underlying the bone metastasis of PCa.