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Abstract Pyroptosis may play an important role in the resistance of ovarian cancer (OC) to chemotherapy. However, the mechanism by which pyroptosis modulation can attenuate chemotherapy resistance has not been comprehensively studied in OC. Here, we demonstrated that RAS‐associated C3 botulinum toxin substrate 1 (RAC1) is highly expressed in OC and is negatively correlated with patient outcomes. Through cell function tests and in vivo tumor formation tests, we found that RAC1 can promote tumor growth by mediating paclitaxel (PTX) resistance. RAC1 can mediate OC progression by inhibiting pyroptosis, as evidenced by high‐throughput automated confocal imaging, the release of lactate dehydrogenase (LDH), the expression of the inflammatory cytokines IL‐1β/IL‐18 and the nucleotide oligomerization domain‐like receptor family pyrin domain‐containing 3 (NLRP3) inflammasome. Mechanically, RNA‐seq, gene set enrichment analysis (GSEA), coimmunoprecipitation (Co‐IP), mass spectrometry (MS), and ubiquitination tests further confirmed that RAC1 inhibits caspase‐1/gasdermin D (GSDMD)‐mediated canonical pyroptosis through the P21‐activated kinase 4 (PAK4)/mitogen‐activated protein kinase (MAPK) pathway, thereby promoting PTX resistance in OC cells. Finally, the whole molecular pathway was verified by the results of in vivo drug combination tests, clinical specimen detection and the prognosis. In summary, our results suggest that the combination of RAC1 inhibitors with PTX can reverse PTX resistance by inducing pyroptosis through the PAK4/MAPK pathway.

Abstract Background Research has suggested significant correlations among ageing, immune microenvironment, inflammation and tumours. However, the relationships among ageing, immune microenvironment, cystitis and bladder urothelial carcinoma (BLCA) in the bladder have rarely been reported. Methods Bladder single-cell and transcriptomic data from young and old mice were used for immune landscape analysis. Transcriptome, single-cell and The Cancer Genome Atlas Program datasets of BLCA and interstitial cystitis/bladder pain syndrome (IC/BPS) were used to analyse immune cell infiltration and molecular expression. Bladder tissues from mice, IC/BPS and BLCA were collected to validate the results. Results Eight types of immune cells (macrophages, B-cells, dendritic cells, T-cells, monocytes, natural killer cells, γδ T-cells and ILC2) were identified in the bladder of mice. Aged mice bladder tissues had a significantly higher number of T-cells, γδ T-cells, ILC2 and B-cells than those in the young group (P

Summary: Isolation of antigen-specific plasma B cells had been challenging until the recent arrival of the Beacon platform. Leveraging light-sorting technology, Beacon can perform high-throughput screening of plasma B cells on a chip to sort single cells with the desired antigen specificity. Here, we present a protocol for isolating antigen-specific plasma B cells from immunized mice using Beacon, sequencing the encoded B cell receptors (BCRs), and cloning and expressing the resulting antibodies. This protocol can easily be extended to human samples. : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.

The black soil region experiences complex erosion due to natural processes and intense human activities, leading to soil degradation and adverse ecological and agricultural impacts. However, the complexities involved in quantifying regional erosion poses remarkable challenges in accurately assessing the current status of regional soil erosion for effective soil conservation. To solve this issue, we proposed a new method for monitoring soil erosion using Interferometric synthetic aperture radar (InSAR) technology and machine learning algorithms within the Google Earth Engine platform. The new method not only enables regional-scale monitoring, but also ensures high accuracy in measurement (millimeter-level). The erosion susceptibility of the study area (Yanshou County, Heilongjiang Province, Northeastern China) was also classified using random forest algorithms to refine the monitored and predicted soil erosion. The results indicate that the five-year (2016–2021) deformation in Yanshou County was −11.08 mm, with a significant mean cumulative deformation of −8.08 mm yr−1 occurring in 2017. The driving factor analysis shows that the region was subject to the compound effect of water and freeze–thaw erosion, closely related to crop phenological stages. The susceptibility analysis indicates that 73.3% of the region was susceptible to erosion, with a higher probability in river areas, at high altitudes, and on steep slopes. However, good vegetation cover can reduce the risk of soil erosion to some extent. This study offers a new perspective on monitoring regional soil erosion in the black soil region of China. The proposed method holds potential for future expansion to monitor soil erosion in a larger areas, thereby guiding the strategies development for protection of the agriculturally important black soil.

IntroductionAlternol is a natural compound isolated from the fermentation of a mutated fungus. We have demonstrated its potent anti-cancer effect via the accumulation of radical oxygen species (ROS) in prostate cancer cells in vitro and in vivo. In this study, we tested its anti-cancer spectrum in multiple platforms.MethodsWe first tested its anti-cancer spectrum using the National Cancer Institute-60 (NCI-60) screening, a protein quantitation-based assay. CellTiter-Glo screening was utilized for ovarian cancer cell lines. Cell cycle distribution was analyzed using flow cytometry. Xenograft models in nude mice were used to assess anti-cancer effect. Healthy mice were tested for the acuate systemic toxicity.ResultsOur results showed that Alternol exerted a potent anti-cancer effect on 50 (83%) cancer cell lines with a GI50 less than 5 µM and induced a lethal response in 12 (24%) of those 50 responding cell lines at 10 µM concentration. Consistently, Alternol displayed a similar anti-cancer effect on 14 ovarian cancer cell lines in an ATP quantitation-based assay. Most interestingly, Alternol showed an excellent safety profile with a maximum tolerance dose (MTD) at 665 mg/kg bodyweight in mice. Its therapeutic index was calculated as 13.3 based on the effective tumor-suppressing doses from HeLa and PC-3 cell-derived xenograft models.ConclusionTaken together, Alternol has a broad anti-cancer spectrum with a safe therapeutic index in vivo.

Background: Alternol is a small molecular compound isolated from the fermentation of a mutant fungus obtained from Taxus brevifolia bark. Our previous studies showed that Alternol treatment induced reactive oxygen species (ROS)-dependent immunogenic cell death. This study conducted a comprehensive investigation to explore the mechanisms involved in Alternol-induced immunogenic cell death.Methods: Prostate cancer PC-3, C4-2, and 22RV1 were used in this study. Alternol interaction with heat shock proteins (HSP) was determined using CETSA assay. Alternol-regulated ER stress proteins were assessed with Western blot assay. Extracellular adenosine triphosphate (ATP) was measured using ATPlite Luminescence Assay System.Results: Our results showed that Alternol interacted with multiple cellular chaperone proteins and increased their expression levels, including endoplasmic reticulum (ER) chaperone hypoxia up-regulated 1 (HYOU1) and heat shock protein 90 alpha family class B member 1 (HSP90AB1), as well as cytosolic chaperone heat shock protein family A member 8 (HSPA8). These data represented a potential cause of unfolded protein response (UPR) after Alternol treatment. Further investigation revealed that Alternol treatment triggered ROS-dependent (ER) stress responses via R-like ER kinase (PERK), inositol-requiring enzyme 1α (IRE1α). The double-stranded RNA-dependent protein kinase (PKR) but not activating transcription factor 6 (ATF6) cascades, leading to ATF-3/ATF-4 activation, C/EBP-homologous protein (CHOP) overexpression, and X-box binding protein XBP1 splicing induction. In addition, inhibition of these ER stress responses cascades blunted Alternol-induced extracellular adenosine triphosphate (ATP) release, one of the classical hallmarks of immunogenic cell death.Conclusion: Taken together, our data demonstrate that Alternol treatment triggered multiple ER stress cascades, leading to immunogenic cell death.

Abstract Background Peste des petits ruminants virus (PPRV) is a highly contagious pathogen that strongly influences the productivity of small ruminants worldwide. Acetylation is an important post-translational modification involved in regulation of multiple biological functions. However, the extent and function of acetylation in host cells during PPRV infection remains unknown. Methods Dimethylation-labeling-based quantitative proteomic analysis of the acetylome of PPRV-infected Vero cells was performed. Results In total, 1068 proteins with 2641 modification sites were detected in response to PPRV infection, of which 304 differentially acetylated proteins (DAcPs) with 410 acetylated sites were identified (fold change 1.2 and P

Abstract Purpose Flap endonuclease 1 (FEN1) is highly upregulated in prostate cancer and promotes the growth of prostate cancer cells. Androgen receptor (AR) is the most critical determinant of the occurrence, progression, metastasis, and treatment of prostate cancer. However, the effect of FEN1 on docetaxel (DTX) sensitivity and the regulatory mechanisms of AR on FEN1 expression in prostate cancer need to be further studied. Methods Bioinformatics analyses were performed using data from the Cancer Genome Atlas and the Gene Expression Omnibus. Prostate cancer cell lines 22Rv1 and LNCaP were used. FEN1 siRNA, FEN1 overexpression plasmid, and AR siRNA were transfected into cells. Biomarker expression was evaluated by immunohistochemistry and Western blotting. Apoptosis and the cell cycle were explored using flow cytometry analysis. Luciferase reporter assay was performed to verify the target relationship. Xenograft assays were conducted using 22Rv1 cells to evaluate the in vivo conclusions. Results Overexpression of FEN1 inhibited cell apoptosis and cell cycle arrest in the S phase induced by DTX. AR knockdown enhanced DTX‐induced cell apoptosis and cell cycle arrest at the S phase in prostate cancer cells, which was attenuated by FEN1 overexpression. In vivo experiments showed that overexpression of FEN1 significantly increased tumour growth and weakened the inhibitory effect of DTX on prostate tumour growth, while AR knockdown enhance the sensitivity of DTX to prostate tumour. AR knockdown resulted in FEN1, pho‐ERK1/2, and pho‐ELK1 downregulation, and the luciferase reporter assay confirmed that ELK1 can regulate the transcription of FEN1. Conclusion Collectively, our studies demonstrate that AR knockdown improves the DTX sensitivity of prostate cancer cells by downregulating FEN1 through the ERK/ELK1 signalling pathway.

TMP269, a small molecular inhibitor of IIa histone deacetylase, plays a vital role in cancer therapeutic. However, the effect of TMP269 on the regulation of viral replication has not been studied. In the present study, we found that TMP269 treatment significantly inhibited RABV replication at concentrations without significant cytotoxicity in a dose-dependent manner. In addition, TMP269 can reduce the viral titers and protein levels of RABV at an early stage in the viral life cycle. RNA sequencing data revealed that immune-related pathways and autophagy-related genes were significantly downregulated after RABV infection treated with TMP269. Further exploration shows that autophagy enhances RABV replication in HEK-293T cells, while TMP269 can inhibit autophagy to decrease RABV replication. Together, these results provide a novel treatment strategy for rabies.

Machine learning can handle an ever-increasing amount of data with the ability to learn models from the data. It has been widely used in a variety of disciplines and is gaining increasingly more attention nowadays. As it is challenging to map soil and hydrological information that are characterised with high spatial and temporal variability, applications of machine learning in soil science and hydrology (AMLSH) have become popularised. To better understand the current state of AMLSH research, a scientific and quantitative approach was performed to statistically analyse publication information from 1973 to 2021 archived in the Scopus database using scientometric analysis tools, including VOSviewer, CiteSpace, and the open-source R package "bibliometrix". The results show a significant increase in the number of publications on AMLSH since 2006. The major contributions were identified based on country origins (China, the USA, and India), institutions (Hohai University, Islamic Azad University, and Wuhan University), and journals (Journal of Hydrology, Remote Sensing, and Geoderma). The keywords analysis of the AMLSH research demonstrates four research hotspots: neural network, artificial intelligence, machine learning, and soil. The most frequently utilised machine learning (ML) methods are neural networks, decision trees, random forests and other methods for image processing and predictive analysis. McBratney et al. 2003 is the most highly cited article. Our research sheds light on the research process on AMLSH and concludes with future research perspectives.

With the widespread adoption of flexible stealth materials (FSMs) in radar stealth application, understanding their electromagnetic scattering information has become increasingly crucial. However, acquiring the electromagnetic scattering properties of FSMs solely through measurement can be challenging. Hence, this study proposes an electromagnetic scattering model for FSMs based on random undulating units formed by sweeping two parabola functions. Specifically, the multi-layer fast multipole method (MLFMM) is applied to calculate the model’s monostatic RCS within 8–12 GHz, enabling a comprehensive analysis of FSM’s electromagnetic scattering characteristics (ESCs). We fabricate an FSM sample for experimental validation and conduct meticulous measurements alongside theoretical calculations. Impressively, the calculated results exhibit relatively good agreement with the measured data, signifying our model’s reliability. Furthermore, by leveraging the proposed model and the MLFMM, we delve into the influence of various electromagnetic parameters, the undulating angle, and the size of undulation units on the ESCs of FSM. Our numerical results demonstrate that the ESCs of FSM exhibit regular variations in response to the changes in these parameters. In addition, we meticulously examine the interaction between electromagnetic waves and the material, further enriching our understanding of the observed results. This research provides valuable references for ESC investigation of flexible stealth material and radar stealth experimental design.

In the family of histone-deacetylases, histone deacetylase 6 (HDAC6) stands out. The cytoplasmic class IIb histone deacetylase (HDAC) family is essential for many cellular functions. It plays a crucial and debatable regulatory role in innate antiviral immunity. This review summarises the current state of our understanding of HDAC6’s structure and function in light of the three mechanisms by which it controls DNA and RNA virus infection: cytoskeleton regulation, host innate immune response, and autophagy degradation of host or viral proteins. In addition, we summed up how HDAC6 inhibitors are used to treat a wide range of diseases, and how its upstream signaling plays a role in the antiviral mechanism. Together, the findings of this review highlight HDAC6’s importance as a new therapeutic target in antiviral immunity, innate immune response, and some diseases, all of which offer promising new avenues for the development of drugs targeting the immune response.

Abstract Background The number of patients with diabetes is increasing worldwide. Diabetic testicular damage can cause spermiogenesis disorders and sexual dysfunction. We thus explored the role of miRNAs in diabetic testicular damage, and revealed that they could serve as effective prevention and treatment therapeutic targets. Methods Streptozotocin (STZ) was used to generate a rat model of type 2 diabetes. Rat testicular tissues were used for miRNA and mRNA sequencing. Through bioinformatics analysis, we constructed an miRNA–mRNA diabetic testicular damage regulatory network and screened for key miRNAs. We also used Leydig cells to generate a diabetic cell model and detected the downstream target genes of miRNAs, secretion of testosterone, and proliferation and apoptotic levels to elucidate the role and mechanism of the selected miRNAs in diabetic testicular damage. Results Using second-generation sequencing, we identified 19 differentially expressed miRNAs and 555 mRNAs in the testes of diabetic rats. Based on computational prediction of targets and negative regulation relationships, we constructed a miRNA–mRNA regulatory network, including 12 miRNAs and 215 mRNAs. KEGG enrichment analysis revealed that genes were more concentrated on the survival signalling pathway. Based on this, we screened 2 key miRNAs, miR-504 and miR-935. In vitro, glucose could induce an increase in miR-504 and miR-935, whereas a decrease in MEK5 and MEF2C in a dose-dependent manner. Overexpression of miR-504 and miR-935 led to the decreased expression of MEK5 and MEF2C, decreased proliferation rate of Leydig cells, increased apoptotic rate, and decreased secretion of testosterone. Whereas, knockdown of miR-504 and miR-935 displayed opposite tendencies. Conclusions miRNAs play important roles in diabetic testicular damage. miR-504 and miR-935 might regulate testicular damage through the classic survival pathway of MEK5-ERK5-MEF2C. Targeted inhibition of miR-504 and miR-935 could reverse the high-glucose-induced testicular complications, thus posing as a potential therapeutic approach in diabetic testicular injury.

Lumpy skin disease is caused by lumpy skin disease virus (LSDV), which can induce cattle with high fever and extensive nodules on the mucosa or the scarfskin, seriously influencing the cattle industry development and international import and export trade. Since 2013, the disease has spread rapidly and widely throughout the Russia and Asia. In the past few decades, progress has been made in the study of LSDV. It is mainly transmitted by blood-sucking insects, and various modes of transmission with distinct seasonality. Figuring out how the virus spreads will help eradicate LSDV at its source. In the event of an outbreak, selecting the most effective vaccine to block and eliminate the threat posed by LSDV in a timely manner is the main choice for farmers and authorities. At present, a variety of vaccines for LSDV have been developed. The available vaccine products vary in quality, protection rate, safety and side effects. Early detection of LSDV can help reduce the cost of disease. In addition, because LSDV has a huge genome, it is currently also used as a vaccine carrier, forming a new complex with other viral genes through homologous recombination. The vaccine prepared based on this can have a certain preventive effect on many kinds of diseases. Clinical detection of disease including nucleic acid and antigen level. Each method varies in convenience, accuracy, cost, time and complexity of equipment. This article reviews our current understanding of the mode of transmission of LSDV and advances in vaccine types and detection methods, providing a background for further research into various aspects of LSDV in the future.

To model the atmospheric dispersion of radionuclides released from nuclear accident is very important for nuclear emergency. But the uncertainty of model parameters, such as source term and meteorological data, may significantly affect the prediction accuracy. Data assimilation (DA) is usually used to improve the model prediction with the measurements. The paper proposed a parameter bias transformation method combined with Lagrangian puff model to perform DA. The method uses the transformation of coordinates to approximate the effect of parameters bias. The uncertainty of four model parameters is considered in the paper: release rate, wind speed, wind direction and plume height. And particle swarm optimization is used for searching the optimal parameters. Twin experiment and Kincaid experiment are used to evaluate the performance of the proposed method. The results show that the proposed method can effectively increase the reliability of model prediction and estimate the parameters. It has the advantage of clear concept and simple calculation. It will be useful for improving the result of atmospheric dispersion model at the early stage of nuclear emergency.

Change detection (CD) is a technique widely used in remote sensing for identifying the differences between data acquired at different times. Most existing 3D CD approaches voxelize point clouds into 3D grids, project them into 2D images, or rasterize them into digital surface models due to the irregular format of point clouds and the variety of changes in three-dimensional (3D) objects. However, the details of the geometric structure and spatiotemporal sequence information may not be fully utilized. In this article, we propose PBFormer, a transformer network with Siamese architecture, for directly inferring pointwise changes in bi-temporal 3D point clouds. First, we extract point sequences from irregular 3D point clouds using the k-nearest neighbor method. Second, we uniquely use a point transformer network as an encoder to extract point feature information from bitemporal 3D point clouds. Then, we design a module for fusing the spatiotemporal features of bi-temporal point clouds to effectively detect change features. Finally, multilayer perceptrons are used to obtain the CD results. Extensive experiments conducted on the Urb3DCD benchmark show that PBFormer outperforms other excellent approaches for 3D point cloud CD tasks.

Humidity is a key factor affecting proton exchange membrane fuel cell (PEMFC) efficiency and output performance. Different working conditions have different requirements for humidity. Improper humidity may cause too high or too low water content inside the PEMFC, which will damage the output performance and even shorten the remaining useful life of PEMFC. Therefore, how to control humidity appropriately is a crucial subject. This paper establishes a PEMFC internal water management and inlet humidity model, and the influence of the change of anode inlet humidity on the performance of the PEMFC and the water content of the membrane is analyzed through computational fluid dynamics (CFD) simulation. And the direct control of the inlet humidity, which is difficult to be accurately measured, is converted to the temperature control of the bubble humidifier according to the proposed model, and a back propagation neural network proportion integration differentiation (BPPID) controller is proposed, which combines artificial neural network and digital PID control to adjust PID parameters in real time. The controller is applied to the temperature control of the bubble humidifier and compared with the traditional PID controller and the fuzzy PID controller. It is found that the performance of the BPPID controller is better through the comparison with the experimental results and the stabilization time it takes is only about 50% of that of other controllers.

To curb the pandemic of coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), multiple platforms have been employed toward a safe and highly effective vaccine. Here, we develop a novel cell-based vaccine candidate, namely K562-S, by utilizing human cell K562 as a cellular carrier to display Spike (S) protein of SARS-CoV-2 on the membrane. Analogous to the traditional inactivated vaccine, K562-S cells can be propagated to a large scale by culturing and completely lose their viability after exposure to X-ray irradiation or formalin. We in turn demonstrated high immunogenicity of formalin-inactivated K562-S vaccine in both mouse and non-human primates and its protective efficacy in mice. In mice, immunization with inactivated K562-S vaccines can elicit potent neutralizing antibody (nAb) responses persisting longer than 5 months. We consequently showed in a hACE2 mouse model of SARS-CoV-2 infection that a two-shot vaccination with adjuvanted K562-S rendered greater than 3 log reduction in viral lung load and concomitant ameliorated lung pathology. Of importance, the administration of the same regimen in non-human primates was able to induce a neutralizing antibody titer averaging three-fold higher relative to human convalescent serum. These results together support the promise of K562-based, S-protein-expressing vaccines as a novel vaccination approach against SARS-CoV-2. Importantly, with a powerful capacity to carry external genes for cell-based vectors, this platform could rapidly generate two- and multiple-valent vaccines by incorporating SARS-CoV-2 mutants, SARS-CoV, or MERS-CoV.

Monocular visual odometry, with the ability to help robots to locate themselves in unexplored environments, has been a crucial research problem in robotics. Though the existed learning-based end-to-end methods can reduce engineering efforts such as accurate camera calibration and tedious case-by-case parameter tuning, the accuracy is still limited. One of the main reasons is that previous works aim to learn six-degrees-of-freedom motions despite the constrained motion of a ground vehicle by its mechanical structure and dynamics. To push the limit, we analyze the motion pattern of a ground vehicle and focus on learning two-degrees-of-freedom motions by proposed motion focusing and decoupling. The experiments on KITTI dataset show that the proposed motion focusing and decoupling approach can improve the visual odometry performance by reducing the relative pose error. Moreover, with the dimension reduction of the learning objective, our network is much lighter with only four convolution layers, which can quickly converge during the training stage and run in real-time at over 200 frames per second during the testing stage.

Foot-and-mouth disease virus (FMDV) is a highly contagious viral disease that mainly infects cloven-hoofed animals. Propagation of FMDV by cell culture is an important method to preserve viral biological and antigenic characteristics, which is crucial in FMD monitoring and vaccine production. However, only a few cell lines are sensitive to FMDV, and there is still a lot of room for improvement. Acetylation is an important post-translational modification, which is dynamically regulated by histone acetyltransferases (HATs) and histone deacetylases (HDACs). However, the study of the relationship between FMDV and HDACs is still unclear. HDAC9 belongs to the class II of HDACs family; in this study, HDAC9 knockout (KO) BHK-21 cells were successfully established using CRISPR/cas9 technology. The results of karyotype analysis, growth curve analysis, and morphological observation showed that the HDAC9 knockout cell line was stable in growth and morphological characteristics. After infection with FMDV, the expression of viral RNA and protein, viral titers, and the copies of viral RNA in HDAC9-KO cells were significantly higher than those in NC cells. Meanwhile, RNA-seq technology was used to sequence HDAC9-KO cells and NC cells infected and uninfected with FMDV. It was found that the differentially expressed innate immune factors containing NFKBIA, SOD2, IL2RG, BCL2L1, CXCL1/2/3, and IL1RAP have significantly enriched in the Jak-STAT, NOD-like receptor, Toll-like receptor, NF-κB, and MAPK signaling pathway. RT-qPCR was performed to detect the expression level of differentially expressed genes and showed consistency with the RNA-seq data. These results preliminarily reveal the role of HDAC9 in host antiviral innate immune response, and the HDAC9-KO cell line could also serve as a useful tool for FMDV research.

For efficient replication, viruses have developed multiple strategies to evade host antiviral innate immunity. Paramyxoviruses are a large family of enveloped RNA viruses that comprises diverse human and animal pathogens which jeopardize global public health and the economy. The accessory proteins expressed from the P gene by RNA editing or overlapping open reading frames (ORFs) are major viral immune evasion factors antagonizing type I interferon (IFN-I) production and other antiviral innate immune responses. However, the antagonistic mechanisms against antiviral innate immunity by accessory proteins differ among viruses. Here, we summarize the current understandings of immune evasion mechanisms by paramyxovirus accessory proteins, specifically how accessory proteins directly or indirectly target the adaptors in the antiviral innate immune signaling pathway to facilitate virus replication. Additionally, some cellular responses, which are also involved in viral replication, will be briefly summarized.

To effectively address the challenges posed by intricate and dynamic electromagnetic environments, we propose a wideband and tunable radar absorber in this paper. The proposed absorber, composed of graphene capacitor, plasma enclosed within a sealed glass cavity, radar absorbing material (RAM), FR-4 and copper plate, allows for tunable radar absorbing performance through the manipulation of the electromagnetic properties of the graphene capacitor and plasma. Based on the equivalent circuit model, the reflectivity of the radar absorber is analyzed using transmission line theory (TLT). Good agreement is observed between the full-wave simulations and the TLT. The study thoroughly investigates the influence of graphene, plasma, and RAM components, as well as their sequential arrangement within the radar absorber, on its reflectivity, expounding the fundamental mechanism of these materials’ synergistic integration. Additionally, the effects of key factors, including the surface resistance R _g of graphene, plasma frequency ${w}_{p},$ collision frequency ${v}_{p}\,$ and plasma thickness ${t}_{{plasma}},$ on the radar absorbing performance are examined. Our findings reveal that adjusting surface resistance R _g controls the absorbing amplitude, and manipulation of the plasma frequency and collision frequency tunes the absorbing frequency and effective absorbing band. By appropriately adjusting the surface resistance R _g of graphene, plasma frequency ${w}_{p}\,$ and collision frequency ${v}_{p},$ the proposed radar absorber exhibits superior performance in the frequency range of 1 GHz to 10 GHz. The radar absorber we propose serves as a significant reference for the application of tunable radar absorbers and adaptive radar stealth techniques.

Boosting and prolonging SARS-CoV-2 vaccine-elicited immunity is paramount for containing the COVID-19 pandemic, which wanes substantially within months after vaccination. Here we demonstrate that the unique strain of probiotic Lactobacillus plantarum GUANKE (LPG) could promote SARS-CoV-2-specific immune responses in both effective and memory phases through enhancing interferon signaling and suppressing apoptotic and inflammatory pathways. Interestingly, oral LPG administration promoted SARS-CoV-2 neutralization antibodies even 6 months after immunization. Furthermore, when LPG was given immediately after SARS-CoV-2 vaccine inoculation, specific neutralization antibodies could be boosted >8-fold in bronchoalveolar lavage (BAL) and >2-fold in sera, T-cell responses were persistent and stable for a prolonged period both in BAL and the spleen. Transcriptional analyses showed that oral application of LPG mobilized immune responses in the mucosal and systemic compartments; in particular, gut-spleen and gut-lung immune axes were observed. These results suggest that LPG could be applied in combination with SARS-CoV-2 vaccines to boost and prolong both the effective and memory immune responses in mucosal and systemic compartments, thereby improving the efficacy of SARS-CoV-2 vaccination.

Abstract Background ER-α36, a novel ER-α66 variant, has been demonstrated to promote tamoxifen resistance in breast cancer cells. However, the role and mechanisms of ER-α36 in cisplatin resistance of breast cancer cells remain unclear. This study investigates the expression and role of ER-α36 in cisplatin resistance of breast cancer cells and elucidates its underlying mechanisms. Methods The expression of ER-α36 and the proteins involved in nongenomic estrogen signaling was evaluated by western blot analysis. Cisplatin sensitivity was explored by CCK-8 assay, monolayer colony formation assay and apoptosis assays, respectively. ER-α36 siRNAs/shRNAs and overexpression vector were transfected into cells to down-regulate or up-regulate ER-α36 expression. Loss-and gain-of function assays were performed to investigate the role of ER-α36 in cisplatin sensitivity. The interaction between ER-α36 and EGFR/HER-2 were detected using CoIP. A mouse xenograft model of breast cancer was established to verify the role of ER-α36 in vivo. Results ER-α36 is expressed at higher levels in cisplatin-resistant breast cancer cells compared to cisplatin sensitive cells. Cisplatin induced up-regulation of ER-α36 in a dose-dependent manner in breast cancer cells. Overexpression of ER-α36 leaded to cell resistant to cisplatin and knockdown of ER-α36 in cisplatin-resistant breast cancer cells restored cisplatin sensitivity. The up-regulation of ER-α36 resulted in increased activation of nongenomic estrogen signaling, which was responsible for cisplatin resistance. Disruption of ER-α36-mediated nongenomic estrogen signaling with kinase inhibitors significantly inhibited cisplatin-induced expression of ER-α36 and increased cisplatin sensitivity. The in vivo experiment also confirmed that up-regulation of ER-α36 attenuated cisplatin sensitivity in a mouse xenograft model of breast cancer. Conclusions The results for the first time demonstrated that ER-α36 mediates cisplatin resistance in breast cancer cells through nongenomic estrogen signaling, suggesting that ER-α36 may serve as a novel target for cisplatin resistance and a potential indicator of cisplatin sensitivity in breast cancer treatment.

Newcastle disease virus (NDV) is one of the highly contagious pathogens causing devastating economic effects on the global poultry industry. In the present study, three 1-formyl-β-carboline derivatives (compounds 6, 7, and 9) were found to be potent inhibitors of different genotypes of NDV with IC50 values within 10 μM, which are similar to ribavirin. The virus titers were decreased by the presence of 1-formyl-β-carboline derivatives in a dose-dependent manner, and the inhibition rate was found to exceed 90% at the concentration of 20 μM. These compounds mainly suppressed the adsorption and entry processes of NDV lifecycle. Through DARTS, CETSA, and RBC binding assay, these compounds were identified as novel HN inhibitors, which could directly interact with the NDV HN protein to affect the adsorption of NDV. Furthermore, they could inhibit the entry of NDV through suppressing the PI3K/Akt pathway rather than the ERK pathway. The PI3K/Akt pathway was proved to be involved in NDV entry. Our findings reveal a unique mechanism through which 1-formyl-β-carboline derivatives restrain NDV infection. Moreover, these compounds represent suitable scaffolds for designing novel HN inhibitors.

Rabies is a lethal zoonotic disease caused by lyssaviruses, such as rabies virus (RABV), that results in nearly 100% mortality once clinical symptoms appear. There are no curable drugs available yet. RABV contains five structural proteins that play an important role in viral replication, transcription, infection, and immune escape mechanisms. In the past decade, progress has been made in research on the pathogenicity of RABV, which plays an important role in the creation of new recombinant RABV vaccines by reverse genetic manipulation. Here, we review the latest advances on the interaction between RABV proteins in the infected host and the applied development of rabies vaccines by using a fully operational RABV reverse genetics system. This article provides a background for more in-depth research on the pathogenic mechanism of RABV and the development of therapeutic drugs and new biologics.

Prostate carcinoma may develop into metastatic castration-resistant prostate carcinoma (mCRPC) after endocrine therapy. Exosomal microRNAs play an important role in the regulation of tumor microenvironment. Our study aimed to investigate the effect of exosomal miR-26a on tumor phenotype of prostate carcinoma. Low-grade prostate carcinoma cell line (LNCAP) and mCRPC cell line (PC-3) were treated as experimental subjects according to their miR-26a expressions. Wound healing, transwell and colony-forming unit assays were performed after miR-26a mimic/inhibitor transfection. Then, exosomes were isolated from LNCAP and PC-3 cells, and the levels of exosomal miR-26a were determined. After co-culture of LNCAP (PC-3) cells with PC-3 (LNCAP) exosomes, changes in malignant behaviors were measured. Moreover, LNCAP/PC-3 exosomes were injected into xenograft tumor mice to determine effects of the exosomes on tumorigenicity of LNCAP and PC-3 cells. MiR-26a showed a potently inhibitory effect on cell proliferation, migration and invasion of LNCAP and PC-3 cells. LNCAP exosomes had a higher miR-26a level, compared with PC-3 exosomes. Overexpression of miR-26a attenuated the enhanced malignant behavior of LNCAP cells induced by PC-3 exosomes, and miR-26a inhibition could reverse the inhibitory effects of LNCAP exosomes on PC-3 cells. Exosomal miR-26a could significantly alter the expressions of epithelial-mesenchymal transition (EMT)-related factors. Moreover, LNCAP exosomes suppressed the tumorigenicity of PC-3 cells, while PC-3 exosomes could promote the tumorigenicity of LNCAP cells. Our data suggest that exosomal miR-26a derived from prostate carcinoma cells had a suppressive effect on the metastasis and tumor growth of prostate carcinoma.

Newcastle disease virus (NDV) causes serious economic losses to the poultry industry. In our previous study, we found that NDV induced a strong innate immune response in the chicken embryo and bursa of Fabricius (BF). However, the underlying mechanisms by which NDV escapes the host innate immunity are not well-understood. The suppressor of cytokine signaling 3 (SOCS3) inhibits the type I interferon-dependent antiviral signaling pathway by utilizing a feedback loop. In this study, we analyzed the transcriptome data of the chicken embryo and BF infected with NDV and found significant upregulation of SOCS3. Next, we demonstrated that NDV infection and nonstructural V protein induced the up-regulation of SOCS3. Furthermore, we showed that overexpression of SOCS3 facilitated viral replication and reduced the expression of phosphorylation STAT1, MX1, and OASL, while inhibition of SOCS3 with siRNAs reduced virus replication and promoted the expression of phosphorylation STAT1, MX1, and OASL. Finally, we demonstrated that the MEK/ERK signaling pathway was involved in the expression of SOCS3 mediated by NDV infection and V protein transfection, and using specific inhibitor U0126 to block this signaling pathway attenuated SOCS3 expression and inhibited NDV replication through promoting the expression of type I interferon, OASL and MX1. Taken together, these data demonstrate that NDV infection and NDV nonstructural V protein activates the expression of SOCS3 at the mRNA and protein level through a mechanism dependent on the MEK/ERK signaling pathway, which benefits virus replication.

In recent years, the number of College Students' emergencies in China is gradually increasing, which is bound to affect the stability and development of colleges and society. This paper takes the college students' emergency in Liaoning Province as an example, analyzes the current situation of College Students' emergency and emergency management mechanism in China, and puts forward countermeasures and suggestions for college students' emergency management mechanism in China. The countermeasures include: to cultivate the crisis awareness of students and university staff; to establish and improve the prevention and early warning mechanism of College Students' emergencies; to strengthen the legal construction of colleges and universities, and to promote the legalization of emergency management in Colleges and universities.

This study devised an effective method for the direct production of hydroxyfatty acids (HFAs) from free fatty acids (FFAs) using Escherichia coli. By employing fatty acid hydroxylase P450BM3 and glucose dehydrogenase (GDH) to convert FFAs to HFAs, high-specificity production of C12 HFAs was achieved. By further knocking out the endogenous fadD gene of E. coli, an engineered strain capable of producing 702.3 mg/L C12 HFA was finally obtained, accounting for 92.9% of the total HFAs production, representing a higher titre reported in shake flask so far. This study provides an attractive strategy for increasing HFAs production in E. coli by increasing NADPH accumulation.

Colchicine (Col) is considered a kind of highly effective alkaloid for preventing and treating acute gout attacks (flares). However, little is known about the underlying mechanism of Col in pain treatment. We have previously developed a customized virtual target identification method, termed IFPTarget, for small-molecule target identification. In this study, by using IFPTarget and ligand similarity ensemble approach (SEA), we show that the glycine receptor alpha 3 (GlyRα3), which play a key role in the processing of inflammatory pain, is a potential target of Col. Moreover, Col binds directly to the GlyRα3 as determined by the immunoprecipitation and bio-layer interferometry assays using the synthesized Col-biotin conjugate (linked Col and biotin with polyethylene glycol). These results suggest that GlyRα3 may mediate Col-induced suppression of inflammatory pain. However, whether GlyRα3 is the functional target of Col and serves as potential therapeutic target in gouty arthritis requires further investigations.

Newcastle disease virus (NDV) has been classified by the World Organization for Animal Health (OIE) as a notable disease-causing virus, and this virus has the ability to infect a wide range of birds. V protein is a non-structural protein of NDV. V protein has been reported to inhibit cell apoptosis (Park et al., 2003a) and promote viral replication (Huang et al., 2003), however, the mechanisms of action of V protein have not been elucidated. In the present study, a yeast two-hybrid screen was performed, and V protein was found to interact with the CacyBP/SIP protein. The results of co-immunoprecipitation and immuno-colocalization assays confirmed the interaction between V protein and CacyBP/SIP. The results of quantitative-PCR and viral plaque assays showed that overexpression of CacyBP/SIP inhibited viral replication in DF-1 cells. Overexpression of CacyBP/SIP in DF-1 cells induced caspase3-dependent apoptosis. The effect of knocking down CacyBP/SIP by siRNA was the opposite of that observed upon overexpression. Moreover, it is known that NDV induces cell apoptosis via multiple caspase-dependent pathways. Furthermore, V protein inhibited cell apoptosis and downregulated CacyBP/SIP expression in DF-1 cells. Taken together, the findings of the current study indicate that V protein interacts with CacyBP/SIP, thereby regulating cell apoptosis and viral replication.

Induction of differentiation is a therapeutic strategy in neuroblastoma, a common pediatric cancer of the sympathetic nervous system. The homeobox protein HOXC9 is a key regulator of neuroblastoma differentiation. To gain a molecular understanding of the function of HOXC9 in promoting differentiation of neuroblastoma cells, we conducted a genome-wide analysis of the HOXC9-induced differentiation program by microarray gene expression profiling and chromatin immunoprecipitation in combination with massively parallel sequencing (ChIP-seq). Here we describe in detail the experimental system, methods, and quality control for the generation of the microarray and ChIP-seq data associated with our recent publication [1].

The varied NER genes and smoking are two important risk factors of bladder cancer, but the mechanism of the NER protein and smoking in cancer progression, however, remains unclear. In this report, we compared the expressions of NER genes in 79 bladder cancer tissues with or without any recurrence by real-time PCR and then analyzed the varied NER genes by immunochemistry in 219 bladder cancer tissue samples. Based on the clinical data, we analyzed the clinical value of varied NER genes and smoking in 219 bladder cancers by the Kaplan-Meier method and Cox proportional hazards regression. We found the expressions of the NER gene XPF and XPC were significantly lower in bladder cancer tissues with a recurrence compared with those without a recurrence at mRNA level. Also, the patients with the XPF and XPC defect had a statistically significant lower median recurrence-free survival time than those without the XPF and XPC defect, and smoking can make this difference more remarkable. Our results suggest that XPF and XPC expression may be a potential predictive factor for bladder cancer, and smoking can not only influence the recurrence of bladder cancer as a single factor but also aggravate the results of the XPF defect and XPC defect.

BACKGROUND: A lot of studies have investigated the correlation between x-ray cross complementing group 1 (XRCC1) polymorphisms and bladder cancer risk, but the results in Asian population were still inconclusive. We conducted a meta-analysis to ascertain the association of XRCC1 Arg194Trp, Arg280His and Arg399Gln polymorphisms with bladder cancer risk in Asian population. METHODOLOGY/PRINCIPAL FINDINGS: The association strength was measured with odds ratios (ORs) and 95% confidence intervals (95% CIs). A total of 9 eligible studies, conducted in China, India and Japan, were identified. We observed a significant increased risk of bladder cancer in dominant model (OR = 1.199, 95% CI: 1.021,1.408, Pheterogeneity = 0.372), allele comparison (OR = 1.200, 95% CI: 1.057,1.362, Pheterogeneity = 0.107) of Arg194Trp, heterozygote comparison (OR = 1.869, 95% CI: 1.205,2.898, Pheterogeneity = 0.011) and dominant model (OR = 1.748, 95% CI: 1.054,2.900, Pheterogeneity = 0.01) of Arg280His. Pooled results estimated from adjusted ORs further validated these findings. No publication bias was detected. Subgroup analyses found that significant increased risk was only found among community-based studies not hospital-based studies. There was no evidence of publication bias. CONCLUSION: This is the first meta-analysis conducted in Asian investigating the correlation between XRCC1 polymorphisms and susceptibility to bladder cancer. Our meta-analysis shows that XRCC1 Arg194Trp and Arg280His polymorphisms are associated with a significantly increased risk of bladder cancer in Asian population.

Retinoic acid (RA) can induce growth arrest and neuronal differentiation of neuroblastoma cells and has been used in clinic for treatment of neuroblastoma. It has been reported that RA induces the expression of several HOXD genes in human neuroblastoma cell lines, but their roles in RA action are largely unknown. The HOXD cluster contains nine genes (HOXD1, HOXD3, HOXD4, and HOXD8-13) that are positioned sequentially from 3' to 5', with HOXD1 at the 3' end and HOXD13 the 5' end. Here we show that all HOXD genes are induced by RA in the human neuroblastoma BE(2)-C cells, with the genes located at the 3' end being activated generally earlier than those positioned more 5' within the cluster. Individual induction of HOXD8, HOXD9, HOXD10 or HOXD12 is sufficient to induce both growth arrest and neuronal differentiation, which is associated with downregulation of cell cycle-promoting genes and upregulation of neuronal differentiation genes. However, induction of other HOXD genes either has no effect (HOXD1) or has partial effects (HOXD3, HOXD4, HOXD11 and HOXD13) on BE(2)-C cell proliferation or differentiation. We further show that knockdown of HOXD8 expression, but not that of HOXD9 expression, significantly inhibits the differentiation-inducing activity of RA. HOXD8 directly activates the transcription of HOXC9, a key effector of RA action in neuroblastoma cells. These findings highlight the distinct functions of HOXD genes in RA induction of neuroblastoma cell differentiation.

To address the challenge of high switching voltages in polymer dispersed liquid crystal (PDLC) films, BaTiO3 nanoparticles of various dimensions were incorporated into a PDLC matrix. This study utilized a polymerisation-induced phase separation (PIPS) method, employing a UV curable photopolymer (NOA65), nematic liquid crystals (E7), and BaTiO3 (BTO) nanoparticles in zero-dimensional (0-BTO), onedimensional (1-BTO), and two-dimensional (2-BTO) forms. The integration of different dimensional BTO nanoparticles significantly influenced the dielectric properties of the PDLC films, as demonstrated by the micro-morphology and electro-optical performance analysis. Notably, the incorporation of 1-BTO nanoparticles resulted in the lowest saturation voltage of 17 V, a 58% reduction, attributed to the increased dipole moment. Additionally, the introduction of 1-BTO nanoparticles did not compromise the transmittance and long-term cycling stability of the PDLC films. [ABSTRACT FROM AUTHOR]