The adaptor proteins Crk (CT10 (chicken tumor virus number 10) regulator of kinase), including CrkI, CrkII and Crk-like, are important signal molecules that regulate a variety of cellular processes. ...Considerable progress has been made in understanding the roles of the Crk family proteins in signal transduction, with a focus on cellular transformation and differentiation. However, since Crk was identified in 1988, very few studies have addressed how Crk regulates the immune response. Recent work demonstrates that Crk proteins function as critical signal molecules in regulating immune cell functions. Emerging data on the roles of Crk in activation and inhibitory immunoreceptor signaling suggest that Crk proteins are potential immunotherapeutic targets in cancer and infectious diseases. The aim of this review is to summarize recent key findings regarding the role of Crk in immune responses mediated by T, B and natural killer (NK) cells. In particular, the roles of Crk in NK cell functions are discussed.
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•Green algal-bacterial granules were obtained with illuminance ≥135 µmol m−2 s−1.•≥90 µmol m−2 s−1 illumination created an aerobic/anoxic zone in the core of granule.•High light ...intensity enhanced lipid content and affected FAMEs (C15–18) composition.•Nitratation was remarkably inhibited when exposed to illuminance ≥180 µmol m−2 s−1.•Enriched AOB and algae were the major contributors to the enhanced N and P removals.
The effects of light intensity (0–225 µmol m−2 s−1) on oxygen distribution, lipid production and biological community structure of algal-bacterial granules were investigated in six identical photo-sequencing batch reactors (with a dark/light cycle of 12 h/12 h). Typically green algal-bacterial granules could be developed at a light intensity of ≥135 µmol m−2 s−1. The lipid content was significantly increased under higher light intensity, while the percentage of saturated fatty acid methyl esters was remarkably decreased. Results showed that light intensity ≥90 µmol m−2 s−1 yielded enough O2 production from algae, creating aerobic/anoxic zone (0.3–0.6 mg-O2/L) in the core of granules and thus efficient algal-bacterial symbiosis system. Enhanced nitrogen and phosphorus removals were achieved in the reactors with stronger light illumination, probably attributable to the enrichment of ammonia oxidizing bacteria (Comamonadaceae and Nitrosomonadaceae) and algae (Navicula and Stigeoclonium). Illuminance ≥180 µmol m−2 s−1 was found to be unfavorable for Nitrospiraceae.
Video instance segmentation (VIS) is a new and critical task in computer vision. To date, top-performing VIS methods extend the two-stage Mask R-CNN by adding a tracking branch, leaving plenty of ...room for improvement. In contrast, we approach the VIS task from a new perspective and propose a one-stage spatial granularity network (SG-Net). Compared to the conventional two-stage methods, SG-Net demonstrates four advantages: 1) Our method has a one-stage compact architecture and each task head (detection, segmentation, and tracking) is crafted interdependently so they can effectively share features and enjoy the joint optimization; 2) Our mask prediction is dynamically performed on the sub-regions of each detected instance, leading to high-quality masks of fine granularity; 3) Each of our task predictions avoids using expensive proposal-based RoI features, resulting in much reduced runtime complexity per instance; 4) Our tracking head models objects' centerness movements for tracking, which effectively enhances the tracking robustness to different object appearances. In evaluation, we present state-of-the-art comparisons on the YouTube-VIS dataset. Extensive experiments demonstrate that our compact one-stage method can achieve improved performance in both accuracy and inference speed. We hope our SG-Net could serve as a strong and flexible base-line for the VIS task. Our code will be available here 1 .
•Aerobic granule-continuous flow reactor was applied for saline wastewater treatment.•Algal-bacterial granule exhibited better overall performance and stability than AGS.•High salinity improved the ...symbiotic relationship between bacteria and algae.•Algae grew rapidly with 2 times lipid yield achieved at 4% salinity.•Salt tolerant Halomonas and Nitzschia significantly were enriched in granules.
In this study a continuous flow reactor (CFR) was employed to compare the feasibility of bacterial aerobic granular sludge (AGS-CFR) and algal-bacterial granular sludge (ABGS-CFR) for treating 1–4% saline wastewater. High salinity was found to enhance algae growth in ABGS-CFR, which exhibited slightly higher total nitrogen and phosphorus removal efficiencies at 1–3% salinity. ABGS-CFR maintained good granular stability at 1–4% salinity, while AGS-CFR gradually disintegrated at 4% salinity with 39.3% less accumulation of alginate-like exopolysaccharides in the extracellular polymeric substances. Indole-3-acetic acid (IAA) and superoxide dismutase (SOD) analysis suggested that bacteria and algae (Nitzschia) in ABGS-CFR formed a good symbiotic relationship under high salinity conditions, achieving rapid algae growth and 2 times lipid production. High salinity was conducive to enriching Halomonas and Nitzschia but unfavorable for Nitrosomonas and Flavobacterium. Results from this study could provide useful information on interactions between bacteria and algae in ABGS-CFR for its future practical application.
Understanding how signals are integrated to control natural killer (NK) cell responsiveness in the absence of antigen-specific receptors has been a challenge, but recent work has revealed some ...underlying principles that govern NK cell responses. NK cells use an array of innate receptors to sense their environment and respond to alterations caused by infections, cellular stress, and transformation. No single activation receptor dominates; instead, synergistic signals from combinations of receptors are integrated to activate natural cytotoxicity and cytokine production. Inhibitory receptors for major histocompatibility complex class I (MHC-I) have a critical role in controlling NK cell responses and, paradoxically, in maintaining NK cells in a state of responsiveness to subsequent activation events, a process referred to as licensing. MHC-I-specific inhibitory receptors both block activation signals and trigger signals to phosphorylate and inactivate the small adaptor Crk. These different facets of inhibitory signaling are incorporated into a revocable license model for the reversible tuning of NK cell responsiveness.
Abstract
Chimeric antigen receptor (CAR) therapy is a promising immunotherapeutic strategy for treating multiple refractory blood cancers, but further advances are required for solid tumor CAR ...therapy. One challenge is identifying a safe and effective tumor antigen. Here, we devise a strategy for targeting hepatocellular carcinoma (HCC, one of the deadliest malignancies). We report that T and NK cells transduced with a CAR that recognizes the surface marker, CD147, also known as Basigin, can effectively kill various malignant HCC cell lines in vitro, and HCC tumors in xenograft and patient-derived xenograft mouse models. To minimize any on-target/off-tumor toxicity, we use logic-gated (log) GPC3–synNotch-inducible CD147-CAR to target HCC. LogCD147-CAR selectively kills dual antigen (GPC3
+
CD147
+
), but not single antigen (GPC3
-
CD147
+
) positive HCC cells and does not cause severe on-target/off-tumor toxicity in a human CD147 transgenic mouse model. In conclusion, these findings support the therapeutic potential of CD147-CAR-modified immune cells for HCC patients.
Partial nitrification-Anammox process is an efficient and energy-saving method for nitrogen removal from low C/N wastewaters. In this study, partial nitrification was achieved in an algal-bacterial ...granular sludge system when treating low COD/NH4–N (309.4 mg L−1/213.6 mg L−1) wastewater under sunlight irradiation (RS). Sunlight irradiation, algae growth and free nitrous acid (FNA) decreased the activity of ammonia oxidizing bacteria (AOB) by 25.7% and completely inhibited the activity of nitrite oxidizing bacteria (NOB), resulting in a NH4–N removal efficiency of ≥99% and a nitrite accumulation efficiency of 96.5% in Rs. Compared with the control without sunlight irradiation (RC), the algal-bacterial granules in RS produced 34.7% and 13.1% more proteins and polysaccharides, respectively, and exhibited a higher structure stability. The lipid content in the algal-bacterial granules was 68.7 mg g-SS−1, which was about 2.1 times higher than that in the granules from RC, making the algal-bacterial granule a value-added biomass. Meanwhile, the content of unsaturated fatty acid methyl esters increased remarkably due to the growth of algae (Stigeoclonium, Scenedesmus and Navicula). The combined stress of sunlight irradiation, algae growth and high FNA in RS only slightly lowered the relative abundance of Nitrosomonadaceae (AOB family) from 7.5% to 5.8%, while Nitrospiraceae (NOB family) was severely inhibited and became undetectable.
•Partial nitrification was achieved in an algal-bacterial granular sludge system.•Algal-bacterial granules exhibited greater stability and higher lipid productivity.•Nitratation process was significantly inhibited by sunlight, algae and FNA.•NOB was more sensitive and unfavorable than AOB in the new system.•Stigeoclonium, Scenedesmus, Navicula were dominant algae in algal-bacterial granule.
Particleboard surface defect detection technology is of great significance to the automation of particleboard detection, but the current detection technology has disadvantages such as low accuracy ...and poor real-time performance. Therefore, this paper proposes an improved lightweight detection method of You Only Live Once v5 (YOLOv5), namely PB-YOLOv5 (Particle Board-YOLOv5). Firstly, the gamma-ray transform method and the image difference method are combined to deal with the uneven illumination of the acquired images, so that the uneven illumination is well corrected. Secondly, Ghost Bottleneck lightweight deep convolution module is added to Backbone module and Neck module of YOLOv5 detection algorithm to reduce model volume. Thirdly, the SELayer module of attention mechanism is added into Backbone module. Finally, replace Conv in Neck module with depthwise convolution (DWConv) to compress network parameters. The experimental results show that the PB-YOLOv5 model proposed in this paper can accurately identify five types of defects on the particleboard surface: Bigshavings, SandLeakage, GlueSpot, Soft and OliPollution, and meet the real-time requirements. Specifically, recall, F1 score, mAP@.5, mAP@.5:.95 values of pB-Yolov5s model were 91.22%, 94.5%, 92.1%, 92.8% and 67.8%, respectively. The results of Soft defects were 92.8%, 97.9%, 95.3%, 99.0% and 81.7%, respectively. The detection of single image time of the model is only 0.031 s, and the weight size of the model is only 5.4 MB. Compared with the original YOLOv5s, YOLOv4, YOLOv3 and Faster RCNN, the PB-Yolov5s model has the fastest Detection of single image time. The Detection of single image time was accelerated by 34.0%, 55.1%, 64.4% and 87.9%, and the weight size of the model is compressed by 62.5%, 97.7%, 97.8% and 98.9%, respectively. The mAP value increased by 2.3%, 4.69%, 7.98% and 13.05%, respectively. The results show that the PB-YOLOV5 model proposed in this paper can realize the rapid and accurate detection of particleboard surface defects, and fully meet the requirements of lightweight embedded model.
When analyzing data from in situ RNA detection technologies, cell segmentation is an essential step in identifying cell boundaries, assigning RNA reads to cells, and studying the gene expression and ...morphological features of cells. We developed a deep-learning-based method, GeneSegNet, that integrates both gene expression and imaging information to perform cell segmentation. GeneSegNet also employs a recursive training strategy to deal with noisy training labels. We show that GeneSegNet significantly improves cell segmentation performances over existing methods that either ignore gene expression information or underutilize imaging information.
Background/Aims: Mounting evidence suggests that epitranscriptional modifications regulate multiple cellular processes. N6-Methyladenosine (m6A), the most abundant reversible methylation of mRNA, has ...critical roles in cancer pathogenesis. However, the mechanisms and functions of long non-coding RNA (lncRNA) methylation remain unclear. Pancreatic cancer resulted in 411,600 deaths globally in 2015. By the time of pancreatic cancer diagnosis, metastasis has often occurred in other parts of the body. The present study sought to investigate lncRNA m6A modification and its roles in pancreatic cancer. Methods: Differential expression between cancer cells and matched normal cells was evaluated to identify candidate lncRNAs. The lncRNA KCNK15-AS1 was detected in cancer tissues and various pancreatic cells using RT-qPCR. KCNK15-AS1 was transfected into cells to explore its role in migration and invasion. Then, m6A RNA immunoprecipitation was performed to detect methylated KCNK15-AS1 in tissues and cells. Epithelial–mesenchymal transition (EMT) markers were used to evaluate KCNK15-AS1-mediated EMT processes. Results: KCNK15-AS1 was downregulated in pancreatic cancer tissues compared with paired adjacent normal tissues. KCNK15-AS1 inhibited migration and invasion in MIA PaCa-2 and BxPC-3 cells. Furthermore, total RNA methylation in cancer cells was significantly enriched relative to that in immortalized human pancreatic duct epithelial (HPDE6-C7) cells. In addition, the m6A eraser ALKBH5 was downregulated in cancer cells, which can demethylate KCNK15-AS1 and regulate KCNK15-AS1-mediated cell motility. Conclusion: Our results have revealed a novel mechanism by which ALKBH5 inhibits pancreatic cancer motility by demethylating lncRNA KCNK15-AS1, identifying a potential therapeutic target for pancreatic cancer.
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