Identification of QTLs and candidate genes for water-soluble protein content in soybean seeds.

Soybean represents a vital source of premium plant-based proteins for human nutrition. Importantly, the level of water-soluble protein (WSP) is crucial for determining the overall quality and nutritional value of such crops. Enhancing WSP levels in soybean plants is a high-priority goal in crop improvement. This study aimed to elucidate the genetic basis of WSP content in soybean seeds by identifying quantitative trait loci (QTLs) and set the foundation for subsequent gene cloning and functional analysis. Using 180 F10 recombinant inbred lines generated by crossing the high-protein soybean cultivar JiDou 12 with the wild variety Ye 9, our researcher team mapped the QTLs influencing protein levels, integrating Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis and gene expression profiling to identify candidate genes. During the 2020 and 2022 growing seasons, a standard bell-shaped distribution of protein content trait data was observed in these soybean lines. Eight QTLs affecting protein content were found across eight chromosomes, with LOD scores ranging from 2.59 to 7.30, explaining 4.15-11.74% of the phenotypic variance. Notably, two QTLs were newly discovered, one with a elite allele at qWSPC-15 from Ye 9. The major QTL, qWSPC-19, on chromosome 19 was stable across conditions and contained genes involved in nitrogen metabolism, amino acid biosynthesis, and signaling. Two genes from this QTL, Glyma.19G185700 and Glyma.19G186000, exhibited distinct expression patterns at maturity, highlighting the influence of these genes on protein content. This research revealed eight QTLs for WSP content in soybean seeds and proposed a gene for the key QTL qWSPC-19, laying groundwork for gene isolation and enhanced soybean breeding through the use of molecular markers. These insights are instrumental for developing protein-rich soybean cultivars.

Development of a prognostic model to predict BLCA based on anoikis-related gene signature: preliminary findings.

BACKGROUND: The prevalence of bladder urothelial carcinoma (BLCA) is significant on a global scale. Anoikis is a type of procedural cell death that has an important role in tumor invasion and metastasis. The advent of single-cell RNA sequencing (scRNA-seq) approaches has revolutionized the genomics field by providing unprecedented opportunities for elucidating cellular heterogeneity. Understanding the mechanisms associated with anoikis in BLCA is essential to improve its survival rate. METHODS: Data on BLCA and clinical information were acquired from the databases of The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). ARGs were obtained from Genecards and Harmonizome databases. According to univariate Cox regression analysis, the least absolute shrinkage and selection operator (LASSO) algorithm was utilized to select the ARGs associated with the overall rate (OS). A multivariate Cox regression analysis was carried out to identify eight prognostic ARGs, leading to the establishment of a risk model. The OS rate of BLCA patients was evaluated using Kaplan-Meier survival analysis. To explore the molecular mechanism in low- and high-risk groups, we employed Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSVA). Immune infiltration landscape estimation was performed using ESTIMATE, CIBERSOT, and single sample gene set enrichment analysis (ssGSEA) algorithms. Patients were categorized into different subgroups through consensus clustering analysis. We employed biological functional enrichment analysis and conducted immune infiltration analysis to examine the disparities in potential biological functions, infiltration of immune cells, immune activities, and responses to immunotherapy. RESULTS: We identified 647 ARGs and 37 survival-related genes. We further developed a risk scoring model to quantitatively assess the predictive capacity of ARGs. The high-risk score group exhibited an unfavorable prognosis, whereas the low-risk score group demonstrated a converse effect. We also found that the two groups of patients might respond differently to immune targets and anti-tumor drugs. CONCLUSION: The nomogram with 8 ARGs may help guide treatment of BLCA. The systematic assessment of risk scores can help to design more individualized and precise treatment strategies for BLCA patients.

The aging of polyethylene mulch films in the presence of cadmium.

To determine the fates of the persistent pollutants cadmium (Cd) and micro-plastics in agricultural soils, an in-depth understanding of the interactions between Cd and mulching film is required. In the present work, pot experiments are conducted under natural conditions to study the influence of various Cd concentrations on the aging process of polyethylene mulching film in soil collected from Changzhi, Shanxi Province. The results indicate that during 150 days, the aging degree of the mulch film increases gradually as the increased Cd concentration in the soil. Further, the results of attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectrometry and X-ray photoelectron spectroscopy (XPS) demonstrate that the average vinyl index (VI) of the aging mulch film increases from 1.29 to 1.82, while the oxygen-to-carbon (O/C) ratio of the mulch film decreases significantly from 0.344 to 0.045, as the Cd concentration is increased from 0 to 10 mg kg-1. When the aging time exceeds 90 days, the oxygen-containing functional groups (C-O and CO) generated consumed by the adsorbed Cd. In addition, electron paramagnetic resonance (EPR) measurements indicate that Cd both enhances the formation of hydroxyl radical (·OH) on the surface of the mulch film and prevents the combination of ·OH and electrons, thereby accelerating the aging of the mulch. Hence, the present study indicates that the presence of Cd will hasten the decomposition of mulch, which will inevitably result in the faster release of micro-plastics from the mulch into the soil environment.

On the Acquisition of High-Quality Digital Images and Extraction of Effective Color Information for Soil Water Content Testing.

Soil water content (SWC) is a critical indicator for engineering construction, crop production, and the hydrologic cycle. The rapid and accurate assessment of SWC is of great importance. At present, digital images are becoming increasingly popular in environmental monitoring and soil property analysis owing to the advantages of non-destructiveness, cheapness, and high-efficiency. However, the capture of high-quality digital image and effective color information acquisition is challenging. For this reason, a photographic platform with an integrated experimental structure configuration was designed to yield high-quality soil images. The detrimental parameters of the platform including type and intensity of the light source and the camera shooting angle were determined after systematic exploration. A new method based on Gaussian fitting gray histogram for extracting RGB image feature parameters was proposed and validated. The correlation between 21 characteristic parameters of five color spaces (RGB, HLS, CIEXYZ, CIELAB, and CIELUV) and SWC was investigated. The model for the relationship between characteristic parameters and SWC was constructed by using least squares regression (LSR), stepwise regression (STR), and partial least squares regression (PLSR). Findings showed that the camera platform equipped with 45° illumination D65 light source, 90° shooting angle, 1900~2500 lx surface illumination, and operating at ambient temperature difference of 5 °C could produce highly reproducible and stable soil color information. The effects of image scale had a great influence on color feature extraction. The entire area of soil image, i.e., 3,000,000 pixels, was chosen in conjunction with a new method for obtaining color features, which is beneficial to eliminate the interference of uneven lightness and micro-topography of soil samples. For the five color spaces and related 21 characteristic parameters, RGB and CIEXYZ spaces and characteristic parameter of lightness both exhibited the strongest correlation with SWC. The PLSR model based on soil specimen images ID had an excellent predictive accuracy and the best stability (R2 = 0.999, RMSE = 0.236). This study showed the potential of the application of color information of digital images to predict SWC in agriculture and geotechnical engineering.

NC-OFDM Satellite Communication Based on Compressed Spectrum Sensing.

With the fast development of giant LEO constellations, the effective spectrum utilization has been regarded as one of the key orientations for satellite communications. This paper focuses on improving the spectrum utilization efficiency of satellite communications by proposing a non-continuous orthogonal frequency division multiplexing (NC-OFDM) method. Based on the models of NC-OFDM system, we first propose a sub-carrier allocation method by using spectrum sensing to efficiently perceive and utilize the spectrum holes in the satellite communication system. Then, a hybrid genetic particle swarm optimization method is adopted to allocate the channel resources effectively. Finally, simulation results verify that the proposed algorithm can significantly improve the spectrum efficiency of satellite communications.

Security Performance Analysis of LEO Satellite Constellation Networks under DDoS Attack.

Low Earth orbit satellite constellation networks (LSCNs) have attracted significant attention around the world due to their great advantages of low latency and wide coverage, but they also bring new challenges to network security. Distributed denial of service (DDoS) attacks are considered one of the most threatening attack methods in the field of Internet security. In this paper, a space-time graph model is built to identify the key nodes in LSCNs, and a DDoS attack is adopted as the main means to attack the key nodes. The scenarios of two-satellite-key-node and multi-satellite-key-node attacks are considered, and their security performance against DDoS attacks is also analyzed. The simulation results show that the transmission path of key satellite nodes will change rapidly after being attacked, and the average end-to-end delay and packet loss are linearly related to the number of key-node attacks. This work provides a comprehensive analysis of the security performance of LSCNs under a DDoS attack and theoretical support for future research on anti-DDoS attack strategies for LSCNs.

Overexpression of GmPHR1 Promotes Soybean Yield through Global Regulation of Nutrient Acquisition and Root Development.

MYB-CC transcription factors (TFs) are essential for plant growth and development. Members of the MYB-CC subfamily with long N terminal domains, such as phosphate starvation response 1 (PHR1) or PHR1-like TFs, have well documented functions, while those with short N terminal domains remain less understood. In this study, we identified a nodule specific MYB-CC transcription factor 1 (GmPHR1) in soybean that is different from other canonical PHR family genes in that GmPHR1 harbors a short N terminal ahead of its MYB-CC domain and was highly induced by rhizobium infection. The overexpression of GmPHR1 dramatically increased the ratio of deformed root hairs, enhanced subsequent soybean nodulation, and promoted soybean growth in pot experiments. The growth promotion effects of GmPHR1 overexpression were further demonstrated in field trails in which two GmPHR1-OE lines yielded 10.78% and 8.19% more than the wild type line. Transcriptome analysis suggested that GmPHR1 overexpression led to global reprogramming, with 749 genes upregulated and 279 genes downregulated, especially for genes involved in MYB transcription factor activities, root growth, and nutrient acquisition. Taken together, we conclude that GmPHR1 is a key gene involved in the global regulation of nodulation, root growth, and nutrient acquisition in soybeans, and is thus a promising candidate gene to target for soybean yield enhancement.

Outbreak of vibriosis associated with Vibrio parahaemolyticus in the mud crab Scylla paramamosain cultured in China.

In this study, a Gram-negative bacterium was isolated from diseased Scylla paramamosain and tentatively named strain QX17. The bacterial isolate was identified as Vibrio parahaemolyticus based on morphological and biochemical characteristics and molecular identification with the 16S rRNA and HSP60 genes. In the challenge experiment, S. paramamosain injected intramuscularly with the V. parahaemolyticus isolate developed pathological signs similar to the naturally diseased mud crabs. The infection experiment also showed that the median lethal dosage (LD50) for QX17 was 4.79 × 102 CFU g-1 (crab weight). Histopathological analysis of the diseased mud crabs infected with V. parahaemolyticus showed deformation and basement membrane rupture of hepatopancreatic tubules in the hepatopancreas, and disordered and broken muscle fiber in the muscle. Antimicrobial susceptibility tests revealed that QX17 was highly sensitive to most of the tested aminoglycosides, tetracyclines, and quinolones. To the best of our knowledge, this is the first study reporting isolation and antibiotic sensitivities of V. parahaemolyticus from cultured mud crabs. The discovery of V. parahaemolyticus in cultured mud crabs not only adds to the growing list of emerging pathogens in crab aquaculture in China, but also highlights the necessity of developing early detection strategies and appropriate interventions to reduce the damage caused by V. parahaemolyticus in mud crab aquaculture.

Diversity patterns of soil microbial communities in the Sophora flavescens rhizosphere in response to continuous monocropping.

BACKGROUND: Continuous monocropping can affect the physicochemical and biological characteristics of cultivated soil. Sophora flavescens is a valuable herbal medicine and sensitive to continuous monocropping. Currently, diversity patterns of soil microbial communities in soil continuous monocropping with S. flavescens have not been extensively elucidated. RESULTS: In this study, comparative 16S rDNA and internal transcribed spacer (ITS) MiSeq sequencing analyses were used to examine the taxonomic community structure and microbial diversity in nonrhizosphere soil (CK) and rhizosphere soils (SCC, TCC, and FCC) sampled from fields that had undergone two, three, and five years of continuous monocropping, respectively. Among the microbial communities, a decreased abundance of Acidobacteria and increased abundances of Proteobacteria and Bacteroidetes were found with the increase in monocropping years of S. flavescens. As the continuous monocropping time increased, the diversity of the bacterial community decreased, but that of fungi increased. Redundancy analysis also showed that among the properties of the rhizosphere soil, the available phosphorus, organic matter, total nitrogen, and sucrase had the greatest impacts on the diversity of the rhizosphere microbial community. Moreover, a biomarker for S. flavescens soil was also identified using the most differentially abundant bacteria and fungi in soil samples. CONCLUSIONS: Our study indicates that long-term monocropping exerted great impacts on microbial community distributions and soil physicochemical properties. The relationship between microbial community and physicochemical properties of rhizosphere soil would help clarify the side effects of continuous S. flavescens monocropping. Our study may aid in uncovering the theoretical basis underlying obstacles to continuous monocropping and provide better guidance for crop production.

Soybean AP1 homologs control flowering time and plant height.

Flowering time and plant height are key agronomic traits that directly affect soybean (Glycine max) yield. APETALA1 (AP1) functions as a class A gene in the ABCE model for floral organ development, helping to specify carpel, stamen, petal, and sepal identities. There are four AP1 homologs in soybean, all of which are mainly expressed in the shoot apex. Here, we used clustered regularly interspaced short palindromic repeats (CRISPR) - CRISPR-associated protein 9 technology to generate a homozygous quadruple mutant, gmap1, with loss-of-function mutations in all four GmAP1 genes. Under short-day (SD) conditions, the gmap1 quadruple mutant exhibited delayed flowering, changes in flower morphology, and increased node number and internode length, resulting in plants that were taller than the wild type. Conversely, overexpression of GmAP1a resulted in early flowering and reduced plant height compared to the wild type under SD conditions. The gmap1 mutant and the overexpression lines also exhibited altered expression of several genes related to flowering and gibberellic acid metabolism, thereby providing insight into the role of GmAP1 in the regulatory networks controlling flowering time and plant height in soybean. Increased node number is the trait with the most promise for enhancing soybean pod number and grain yield. Therefore, the mutant alleles of the four AP1 homologs described here will be invaluable for molecular breeding of improved soybean yield.

Bimatoprost Imprinted Silicone Contact Lens to Treat Glaucoma.

Bimatoprost is widely used for the management of glaucoma. Currently, it is delivered via eye drop solution, which is highly inefficient due to low bioavailability. To control the release of ocular drugs, contact lenses are used by scientists. However, the conventional soaking method showed high burst release due to absence of any efficient controlling membrane. The objective of the paper was to apply molecular imprinting technology to improve the loading of bimatoprost from the soaking solution and to sustain the release of drug from the contact lens. The bimatoprost was loaded by conventional soaking method (BT-SM) and compared with the molecular imprinted contact lenses (BT-MP). The loading of bimatoprost by molecular imprinting technology affect the swelling of the contact lens; however, the batch BT-MP-10 did not showed significant alterations. The uptake study showed improvement in the bimatoprost loading by molecular imprinting technology in comparison to the conventional soaking technology. The in vitro bimatoprost release data showed improvement in the bimatoprost release rate profiles with BT-MP contact lenses (up to 36-60 h) lenses in comparison to BT-SM contact lenses (up to 24-36 h). The in vivo rabbit tear fluid data with BT-MP batch showed improvement in the bimatoprost retention time in comparison to BT-SM contact lens and eye drop solution. The rabbit model failed to respond bimatoprost; thus, the efficacy studies need to be conducted on canines or human primates. The paper revealed the potential of using molecular imprinting technology to improve the uptake of bimatoprost and to achieve sustain release kinetics without altering the swelling, transmittance and folding endurance properties of the contact lens.

Genetic improvement of the shoot architecture and yield in soya bean plants via the manipulation of GmmiR156b.

The optimization of plant architecture in order to breed high-yielding soya bean cultivars is a goal of researchers. Tall plants bearing many long branches are desired, but only modest success in reaching these goals has been achieved. MicroRNA156 (miR156)-SQUAMOSA PROMOTER BINDING PROTEIN-LIKE (SPL) gene modules play pivotal roles in controlling shoot architecture and other traits in crops like rice and wheat. However, the effects of miR156-SPL modules on soya bean architecture and yield, and the molecular mechanisms underlying these effects, remain largely unknown. In this study, we achieved substantial improvements in soya bean architecture and yield by overexpressing GmmiR156b. Transgenic plants produced significantly increased numbers of long branches, nodes and pods, and they exhibited an increased 100-seed weight, resulting in a 46%-63% increase in yield per plant. Intriguingly, GmmiR156b overexpression had no significant impact on plant height in a growth room or under field conditions; however, it increased stem thickness significantly. Our data indicate that GmmiR156b modulates these traits mainly via the direct cleavage of SPL transcripts. Moreover, we found that GmSPL9d is expressed in the shoot apical meristem and axillary meristems (AMs) of soya bean, and that GmSPL9d may regulate axillary bud formation and branching by physically interacting with the homeobox gene WUSCHEL (WUS), a central regulator of AM formation. Together, our results identify GmmiR156b as a promising target for the improvement of soya bean plant architecture and yields, and they reveal a new and conserved regulatory cascade involving miR156-SPL-WUS that will help researchers decipher the genetic basis of plant architecture.

Mode detection of misaligned orbital angular momentum beams based on convolutional neural network.

The utilization of beam-carrying orbital angular momentum (OAM) for free-space optical (FSO) communication can increase channel capacity. However, the misalignment of the beam is an effect that must be mitigated in FSO communication systems. Due to the robustness of deep learning technology in pattern recognition, a neural network structure is proposed and improved to mitigate the effect of misalignment error. First, compared with the simple convolutional neural network proposed, data augmentation is adopted in the training. Then, a view-pooling layer is added after the convolutional layer. This layer can longitudinally compress feature maps from multiple receiving angles. In order to verify the performance of the proposed method, related experiments are reported in this paper. It can be seen from the results that when the tilt angle is less than 35°, the accuracy of OAM mode detection is above 99%, 93%, and 88%, respectively, corresponding to the condition of weak (Cn2=1×10-15 m-2/3), medium (Cn2=1×10-14 m-2/3) and strong (Cn2=1×10-13 m-2/3) turbulence.

Improvement of soybean transformation via Agrobacterium tumefaciens methods involving α-aminooxyacetic acid and sonication treatments enlightened by gene expression profile analysis.

KEY MESSAGE: Antagonists and sonication treatment relieved the structural barriers of Agrobacterium entering into cells; hindered signal perception and transmission; alleviated defense responses and increased cell susceptibility to Agrobacterium infection. Soybean gene expression analysis was performed to elucidate the general response of soybean plant to Agrobacterium at an early stage of infection. Agrobacterium infection stimulated the PAMPs-triggered immunity (BRI1, BAK1, BZR1, FLS2 and EFR) and effector-triggered immunity (RPM1, RPS2, RPS5, RIN4, and PBS1); up-regulated the transcript factors (WRKY25, WRKY29, MEKK1P, MKK4/5P and MYC2) in MAPK pathway; strengthened the biosynthesis of flavonoid and isoflavonoid in the second metabolism; finally led to a fierce defense response of soybean to Agrobacterium infection and thereby lower transformation efficiency. To overcome it, antagonist α-aminooxyacetic acid (AOA) and sonication treatment along with Agrobacterium infection were applied. This novel method dramatically decreased the expression of genes coding for F3'H, HCT, ß-glucosidase and IF7GT, etc., which are important for isoflavone biosynthesis or the interconversion of aglycones and glycon; genes coding for peroxidase, FLS2, PBS1 and transcription factor MYC2, etc., which are important components in plant-pathogen interaction; and genes coding for GPAT and α-L-fucosidase, which are important in polyesters formation in cell membrane and the degradation of fucose-containing glycoproteins and glycolipids on the external surface of cell membrane, respectively. This analysis implied that AOA and sonication treatment not only relieved the structural membrane barriers of Agrobacterium entering into cells, but also hindered the perception of 'invasion' signal on cell membrane and intercellular signal transmission, thus effectively alleviated the defense responses and increased the cell susceptibility to Agrobacterium infection. All these factors benefit the transformation process; other measures should also be further explored to improve soybean transformation.

Deciphering Immune-Related Gene Signatures in Diabetic Retinopathy: Insights from In Silico Analysis and In vitro Experiment.

BACKGROUND: Diabetes retinopathy (DR) is one of the most common microvascular consequences of diabetes, and the economic burden is increasing. Our aim is to decipher the relevant mechanisms of immune-related gene features in DR and explore biomarkers targeting DR. Provide a basis for the treatment and prevention of DR. METHOD: The immune infiltration enrichment score of DR patients was evaluated from the single- cell RNA sequencing dataset, and the samples were divided into low immune subgroups and high immune subgroups based on this result. Through weighted gene correlation network analysis, differentially expressed genes (DEGs) between two subgroups were identified and crossed with genes with the strongest immune association, resulting in significant key genes. Then divide the DR individuals into two immune related differentially expressed gene (IDEG) clusters, A and B. Submit cross DEGs between two clusters through Gene Set Enrichment Analysis (GSEA) to further explore their functions. A protein-protein interaction (PPI) network of IDEG was established to further identify central genes associated with DR. Use the discovered central genes to predict the regulatory network involved in the pathogenesis of DR. Then, the role of the identified hub gene in the pathogenesis of DR was further studied through in vitro experiments. RESULT: We found that the immune scores of DR and control groups were different, and 27 IDEGs were found in the DR subgroup. Compared with cluster A, the proportion of cytotoxic lymphocytes, B lineage, monocyte lineage, and fibroblasts in DR patients in cluster B is significantly enriched. GSEA indicates that these genes are associated with T cell activation, regulation of immune response processes, lymphocyte-mediated immunity, TNF signaling pathway, and other signaling pathways. The PPI network subsequently identified 10 hub genes in DR, including SIGLEC10, RGS10, PENK, FGD2, LILRA6, CIITA, EGR2, SIGLEC7, LILRB1, and CD300LB. The upstream regulatory network and lncRNA miRNA mRNA ceRNA network of these hub genes were ultimately constructed. The discovery and identification of these genes will provide biomarkers for targeted prediction and treatment of DR. CONCLUSION: By integrating bioinformatics analysis and in vitro experiments, we have identified a set of central genes, indicating that these genes can serve as potential biomarkers for DR, which may be promising targets for future DR immunotherapy interventions.

Study on Stamping-Bulging Process of Thin-Walled Superalloy Diaphragm for S-Shaped Bellows.

A combined stamping-bulging forming process was proposed to achieve high-precision forming of large-diameter, ultra-thin-walled, superalloy welded S-type corrugated diaphragms. The underlying principle is to enhance the diaphragm's forming accuracy by increasing the plastic deformation region and reducing springback. Using the ABAQUS version 6.14 finite element analysis software, finite element models were constructed for the stamping, hydraulic bulging, and combined stamping-bulging forming processes of the welded S-type metal corrugated diaphragms. A comparative analysis was conducted on the forming processes of the welded S-type metal corrugated diaphragms under the three forming methods, focusing on equivalent stress, distribution of wall thickness, and forming accuracy. This analysis determined the optimal forming process and the corresponding process parameters for superalloy welded S-type metal corrugated diaphragms. The results show that under a constant drawing force, as the bulging pressure increases, the plastic deformation of the straight sections of the diaphragm becomes more pronounced, resulting in improved shape accuracy. The combined stamping-bulging forming process guarantees the highest degree of shape accuracy for the diaphragm. The optimal process parameters were identified as a 30 t force and a 5 MPa pressure, with a maximum shape error of 0.02 mm. Concerning a plate thickness of 0.3 mm, the maximum deviation rate was found to be 6.7%, which represents a 30% improvement over traditional stamping processes. The maximum wall thinning rate was found to be 3.3%, a 1% reduction compared to traditional stamping processes, confirming the process's feasibility.

Magnetic propelled hydrogel microrobots for actively enhancing the efficiency of lycorine hydrochloride to suppress colorectal cancer.

Research and development in the field of micro/nano-robots have made significant progress in the past, especially in the field of clinical medicine, where further research may lead to many revolutionary achievements. Through the research and experiment of microrobots, a controllable drug delivery system will be realized, which will solve many problems in drug treatment. In this work, we design and study the ability of magnetic-driven hydrogel microrobots to carry Lycorine hydrochloride (LH) to inhibit colorectal cancer (CRC) cells. We have successfully designed a magnetic field driven, biocompatible drug carrying hydrogel microsphere robot with Fe3O4 particles inside, which can achieve magnetic field response, and confirmed that it can transport drug through fluorescence microscope. We have successfully demonstrated the motion mode of hydrogel microrobots driven by a rotating external magnetic field. This driving method allows the microrobots to move in a precise and controllable manner, providing tremendous potential for their use in various applications. Finally, we selected drug LH and loaded it into the hydrogel microrobot for a series of experiments. LH significantly inhibited CRC cells proliferation in a dose- and time-dependent manner. LH inhibited the proliferation, mobility of CRC cells and induced apoptosis. This delivery system can significantly improve the therapeutic effect of drugs on tumors.

Targeting high circDNA2v levels in colorectal cancer induces cellular senescence and elicits an anti-tumor secretome.

The efficacy of immunotherapy against colorectal cancer (CRC) is impaired by insufficient immune cell recruitment into the tumor microenvironment. Our study shows that targeting circDNA2v, a circular RNA commonly overexpressed in CRC, can be exploited to elicit cytotoxic T cell recruitment. circDNA2v functions through binding to IGF2BP3, preventing its ubiquitination, and prolonging the IGF2BP3 half-life, which in turn sustains mRNA levels of the protooncogene c-Myc. Targeting circDNA2v by gene silencing downregulates c-Myc to concordantly induce tumor cell senescence and the release of proinflammatory mediators. Production of CXCL10 and interleukin-9 by CRC cells is elicited through JAK-STAT1 signaling, in turn promoting the chemotactic and cytolytic activities of CD8+ T cells. Clinical evidence associates increased circDNA2v expression in CRC tissues with reductions in CD8+ T cell infiltration and worse outcomes. The regulatory relationship between circDNA2v, cellular senescence, and tumor-infiltrating lymphocytes thus provides a rational approach for improving immunotherapy in CRC.

IL­37 suppresses macrophage ferroptosis to attenuate diabetic atherosclerosis via the NRF2 pathway.

IL-37 is a newly discovered inflammatory factor. However, the protective effect and underlying mechanisms of IL-37 on atherosclerosis remain unclear. In the present study, IL-37 was used for intraperitoneal injection in diabetic ApoE-/- mice caused by streptozotocin. High glucose (HG)/ox-LDL was used to stimulate THP-1 original macrophage followed by IL-37 pretreatment in vitro. The atheromatous plaque area, oxidative stress and inflammation levels in ApoE-/- mice were evaluated, and the level of macrophage ferroptosis was detected in vivo and in vitro. It was identified that IL-37 treatment significantly decreased plaque area in diabetic ApoE-/- mice. IL-37 not only improved blood lipid levels in mice, but also reduced serum levels of inflammatory factors including IL-1ß and IL-18. Furthermore, IL-37 increased GPX4 and nuclear factor erythroid 2-related factor 2 (NRF2) in the aorta of diabetic mice. In vitro experiment revealed that IL-37 inhibited HG/ox-LDL-induced ferroptosis in macrophages, as evidenced by improved cell membrane oxidation, reduced malondialdehyde production and increased GPX4 expression. Moreover, it was also found that IL-37 enhanced the nuclear translocation of NRF2 in macrophages, while ML385, a specific NRF2 inhibitor, significantly attenuated the protective effect of IL-37 on macrophage ferroptosis caused by HG/ox-LDL. In conclusion, IL-37 suppressed macrophage ferroptosis to attenuate atherosclerosis progression via activating the NRF2 pathway.