KRAS-mediated upregulation of CIP2A promotes suppression of PP2A-B56α to initiate pancreatic cancer development.

Oncogenic mutations in KRAS are present in approximately 95% of patients diagnosed with pancreatic ductal adenocarcinoma (PDAC) and are considered the initiating event of pancreatic intraepithelial neoplasia (PanIN) precursor lesions. While it is well established that KRAS mutations drive the activation of oncogenic kinase cascades during pancreatic oncogenesis, the effects of oncogenic KRAS signaling on regulation of phosphatases during this process is not fully appreciated. Protein Phosphatase 2A (PP2A) has been implicated in suppressing KRAS-driven cellular transformation. However, low PP2A activity is observed in PDAC cells compared to non-transformed cells, suggesting that suppression of PP2A activity is an important step in the overall development of PDAC. In the current study, we demonstrate that KRASG12D induces the expression of both an endogenous inhibitor of PP2A activity, Cancerous Inhibitor of PP2A (CIP2A), and the PP2A substrate, c-MYC. Consistent with these findings, KRASG12D sequestered the specific PP2A subunit responsible for c-MYC degradation, B56α, away from the active PP2A holoenzyme in a CIP2A-dependent manner. During PDAC initiation in vivo, knockout of B56α promoted KRASG12D tumorigenesis by accelerating acinar-to-ductal metaplasia (ADM) and the formation of PanIN lesions. The process of ADM was attenuated ex vivo in response to pharmacological re-activation of PP2A utilizing direct small molecule activators of PP2A (SMAPs). Together, our results suggest that suppression of PP2A-B56α through KRAS signaling can promote the MYC-driven initiation of pancreatic tumorigenesis.

The PP2A Inhibitor LB-100 Mitigates Lupus Nephritis by Suppressing Tertiary Lymphoid Structure Formation.

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by multi-organ involvement and autoantibody production. Patients with SLE face a substantial risk of developing lupus nephritis (LN), which imposes a substantial burden on both patients and their families. Protein phosphatase 2A (PP2A) is a widely distributed serine/threonine phosphatase participated in regulating multiple signaling pathways and immune responses. Inhibition of PP2A is implicated in the treatment of diseases. LB-100, a small molecule inhibitor of PP2A, is currently undergoing preclinical trials for its therapeutic potential against tumors. However, the role of PP2A and its inhibitor has been insufficiently studied in LN. In this study, we assessed the potential effects of LB-100 in both MRL/lpr mice and R848-induced BALB/c mice. Our findings indicated that LB-100 administration led to reduced spleen enlargement, decreased deposition of immune complexes, ameliorated renal damage, and improved kidney function in two distinct lupus mouse models. Importantly, we observed the formation of tertiary lymphoid structures (TLS) in the kidneys of both spontaneous and induced lupus mouse models. The levels of chemokines inducing T cell infiltration were elevated in the kidneys of lupus mice, whereas LB-100 mitigated chemokines production and inhibited TLS formation. In summary, our study identified the role of PP2A in LN and highlighted the renal protective potential of the PP2A inhibitor LB-100 in two distinct lupus mouse models, suggesting its potential as a novel strategy for LN and other autoimmune diseases.

Phosphorylated transcription factor PuHB40 mediates ROS-dependent anthocyanin biosynthesis in pear exposed to high light.

Plants are increasingly vulnerable to environmental stresses because of global warming and climate change. Stress-induced reactive oxygen species (ROS) accumulation results in plant cell damage and even cell death. Anthocyanins are important antioxidants that scavenge ROS to maintain ROS homeostasis. However, the mechanism underlying ROS-induced anthocyanin accumulation is unclear. In this study, we determined that the HD-Zip I family member transcription factor PuHB40 mediates ROS-dependent anthocyanin biosynthesis under high-light stress in pear (Pyrus ussuriensis). Specifically, PuHB40 induces the PuMYB123-like-PubHLH3 transcription factor complex for anthocyanin biosynthesis. PuHB40-mediated transcriptional activation depends on its phosphorylation level, which is regulated by protein phosphatase PP2A. Elevated ROS content maintains high PuHB40 phosphorylation levels, while also enhancing PuHB40-induced PuMYB123-like transcription by decreasing PuPP2AA2 expression, ultimately leading to increased anthocyanin biosynthesis. Our study reveals a pathway regulating ROS-induced anthocyanin biosynthesis in pear, further clarifying the mechanism underlying abiotic stress-induced anthocyanin biosynthesis, which may have implications for improving plant stress tolerance.

Halloysite nanotubes enhanced polyimide/oxidized-lignin nanofiber separators for long-cycling lithium metal batteries.

The high energy density and robust cycle properties of lithium-ion batteries contribute to their extensive range of applications. Polyolefin separators are often used for the purpose of storing electrolytes, hence ensuring the efficient internal ion transport. Nevertheless, the electrochemical performance of lithium-ion batteries is constrained by its limited interaction with electrolytes and poor capacity for cation transport. This work presents the preparation of a new bio-based nanofiber separator by combining oxidized lignin (OL) and halloysite nanotubes (HNTs) with polyimide (PI) using an electrospinning technique. Analysis was conducted to examine and compare the structure, morphology, thermal characteristics, and EIS of the separator with those of commercially available polypropylene separator (PP). The results indicate that the PI@OL and PI-OL@ 10 % HNTs separators exhibit higher lithium ion transference number and ionic conductivity. Moreover, the use of HNTs successfully impeded the proliferation of lithium dendrites, hence exerting a beneficial impact on both the cycle performance and multiplier performance of the battery. Consequently, after undergoing 300 iterations, the battery capacity of LiFePO4|PI-OL@ 10 % HNTs|Li stays at 92.1 %, surpassing that of PP (86.8 %) and PI@OL (89.6 %). These findings indicate that this new bio-based battery separator (PI-OL@HNTs) has the great potential to serve as a substitute for the commonly used PP separator in lithium metal batteries.

Promoting Li2S Nucleation/Dissolution Kinetics via Multiple Active Sites over TiVCrMoC3Tx Interface.

Lithium-sulfur batteries (LSBs) are still limited by some issues such as polysulfides shuttle and lithium dendrites. Recently, the concept "high-entropy" has been considered as the research hotspot and international frontier. Herein, a high entropy MXene (TiVCrMoC3Tx, HE-MXene) doped graphene is designed as the modified coating on commercial separators for LSBs. The HE-MXene affords multiple metal active sites, fast Li+ diffusion rate, and efficient adsorption toward polysulfide intermediates. Furthermore, strong lithophilic property is favorable for uniform Li+ deposition. The combination of in situ characterizations confirms TiVCrMoC3Tx effectively promotes the Li2S nucleation/dissolution kinetics, reduces the Li+ diffusion barrier, and exhibits favorable lithium uniform deposition behavior. This TiVCrMoC3Tx/G@PP provides a high-capacity retention rate after 1000 cycles at 1 C and 2 C, with a capacity decay rate of merely 0.021% and 0.022% per cycle. Surprisingly, the cell operates at a low potential of 48 mV while maintaining at 5 mA cm-2/5 mAh cm-2 for 4000 h. Furthermore, it still maintains a high-capacity retention rate under a high sulfur loading of 4.8/6.4 mg cm-2 and a low E/S ratio of 8.6/7.5 µg mL-1. This work reveals a technical roadmap for simultaneously addressing the cathode and anode challenge, thus achieving potential commercially viable LSBs.

Alternations (at) that time: NP versus PP time adjuncts in the history of English.

The present paper investigates variation between nominal and prepositional adjuncts of time as in, for example, [on] that day, they left. The main goals are (i) to assess potential changes in the distribution of these variants in the history of English, specifically from Middle English to Late Modern English (1150-1914), and (ii) to test which factors most strongly impact the choice between the two variants, with a focus on the impact of different complexity measures. To address these questions, the paper makes use of data from the Penn-Helsinki Parsed Corpora of Historical English (PPCME2; PPCEME; PPCMBE), explored by means of logistic regression modelling. The results suggest that there is no dramatic, sweeping change in this abstract alternation over time, but that this variation may mainly plays out on lower, noun-specific levels.

Mitochondria-targeted Catalase induced cell malignant transformation by the downregulation of p53 protein stability via USP28/miR-200b/PP2A-Cα axis.

Antioxidants exert a paradoxical influence on cancer prevention. The latest explanation for this paradox is the different target sites of antioxidants. However, it remains unclear how mitochondria-targeted antioxidants trigger specific p53-dependent pathways in malignant transformation models. Our study revealed that overexpression of mitochondria-targeted catalase (mCAT) instigated such malignant transformation via mouse double minute 2 homolog (MDM2) -mediated p53 degradation. In mouse epithelial JB6 Cl41 cells, the stable expression of mCAT resulted in MDM2-mediated p53 degradation, unlike in catalase-overexpressed Cl41 cells. Further, we demonstrated that mCAT overexpression unregulated ubiquitin-specific protease 28 (USP28) expression, which in turn stabilized c-Jun protein levels. This alteration initiated the activation of the miR-200b promoter transcription activity and a subsequent increase in miR-200b expression. Furthermore, elevated miR-200b levels then promoted its binding to the 3'-untranslated region of protein phosphatase 2A catalytic subunit (PP2A-C) α-isoform mRNA, consequently resulting in PP2A-C protein downregulation. This cascade of events ultimately contributed to increased MDM2 phosphorylation and p53 protein degradation. Thus, the mCAT overexpression triggers MDM2/p53-dependent malignant transformation through USP28/miR-200b/PP2A-Cα pathway, which may provide a new information of understanding mitochondria-targeted antioxidant facilitates the progression to the tumorigenic state.

Mechanism insights into the histopathological changes of polypropylene microplastics induced gut and liver in zebrafish.

Microplastics (MPs), emerging as significant pollutants, have been consistently detected in aquatic environments, with the Yangtze River experiencing a particularly severe level of microplastic pollution, exceeding all other watersheds in China. Polypropylene (PP), the plastic most abundantly found in the middle and lower reaches of the Yangtze River Basin, has less comprehensive research results into its toxic effects. Consequently, the present investigation employed zebrafish as a model organism to delve into the toxicological impacts of polypropylene microplastics (PP-MPs) with a diameter of 5 µm across varying concentrations (300 mg/L and 600 mg/L). Using histopathological, microbiota profiling, and transcriptomic approaches, we systematically evaluated the impact of PP-MPs exposure on the intestine and liver of zebrafish. Histopathological analysis revealed that exposure to PP-MPs resulted in thinner intestinal walls, damaged intestinal mucosa, and hepatic cellular damage. Intestinal microbiota profiling demonstrated that, the richness, uniformity, diversity, and homogeneity of gut microbes significantly increased after the PP-MPs exposure at high concentration. These alterations were accompanied by shifts in the relative abundance of microbiota associated with intestinal pathologies, suggesting a profound impact on the intestinal microbial community structure. Concurrently, hepatic transcriptome analysis and RT-qPCR indicated that the downregulation of pathways and genes associated with cell proliferation regulation and DNA damage repair mechanisms contributed to hepatic cellular damage, ultimately exerting adverse effects on the liver. Correlation analysis between the intestinal microbiota and liver transcriptome profiles further highlighted significant associations between intestinal microbiota and the downregulated hepatic pathways. Collectively, these results provide novel insights into the subacute toxicological mechanisms of PP-MPs in aquatic organisms and highlight the need for further research on the ecological and health risks associated with PP-MPs pollution.

Identification of PP2Cs in six rosaceae species highlights RcPP2C24 as a negative regulator in rose drought tolerance.

Drought is a major environmental stress that limits plant growth, so it's important to identify drought-responsive genes to understand the mechanism of drought response and breed drought-tolerant roses. Protein phosphatase 2C (PP2C) plays a crucial role in plant abiotic stress response. In this study, we identified 412 putative PP2Cs from six Rosaceae species. These genes were divided into twelve clades, with clade A containing the largest number of PP2Cs (14.1%). Clade A PP2Cs are known for their important role in ABA-mediated drought stress response; therefore, the analysis focused on these specific genes. Conserved motif analysis revealed that clade A PP2Cs in these six Rosaceae species shared conserved C-terminal catalytic domains. Collinearity analysis indicated that segmental duplication events played a significant role in the evolution of clade A PP2Cs in Rosaceae. Analysis of the expression of 11 clade A RcPP2Cs showed that approximately 60% of these genes responded to drought, high temperature, and salt stress. Among them, RcPP2C24 exhibited the highest responsiveness to both drought and ABA. Furthermore, overexpression of RcPP2C24 significantly reduced drought tolerance in transgenic tobacco by increasing stomatal aperture after exposure to drought stress. The transient overexpression of RcPP2C24 weakened the dehydration tolerance of rose petal discs, while its silencing increased their dehydration tolerance. In summary, our study identified PP2Cs in six Rosaceae species and highlighted the negative role of RcPP2C24 on rose's drought tolerance by inhibiting stomatal closure. Our findings provide valuable insights into understanding the mechanism behind rose's response to drought.

NPYR modulation: Potential for the next major advance in obesity and type 2 diabetes management?

The approval of the glucagon-like peptide 1 (GLP-1) mimetics semaglutide and liraglutide for management of obesity, independent of type 2 diabetes (T2DM), has initiated a resurgence of interest in gut-hormone derived peptide therapies for the management of metabolic diseases, but side-effect profile is a concern for these medicines. However, the recent approval of tirzepatide for obesity and T2DM, a glucose-dependent insulinotropic polypeptide (GIP), GLP-1 receptor co-agonist peptide therapy, may provide a somewhat more tolerable option. Despite this, an increasing number of non-incretin alternative peptides are in development for obesity, and it stands to reason that other hormones will take to the limelight in the coming years, such as peptides from the neuropeptide Y family. This narrative review outlines the therapeutic promise of the neuropeptide Y family of peptides, comprising of the 36 amino acid polypeptides neuropeptide Y (NPY), peptide tyrosine-tyrosine (PYY) and pancreatic polypeptide (PP), as well as their derivatives. This family of peptides exerts a number of metabolically relevant effects such as appetite regulation and can influence pancreatic beta-cell survival. Although some of these actions still require full translation to the human setting, potential therapeutic application in obesity and type 2 diabetes is conceivable. However, like GLP-1 and GIP, the endogenous NPY, PYY and PP peptide forms are subject to rapid in vivo degradation and inactivation by the serine peptidase, dipeptidyl-peptidase 4 (DPP-4), and hence require structural modification to prolong circulating half-life. Numerous protective modification strategies are discussed in this regard herein, alongside related impact on biological activity profile and therapeutic promise.

Penile prosthesis in priapism: a systematic review of outcomes and complications.

Background: Priapism is a rare condition characterized by persistent erection of the penis that lasts more than 4 hours in the absence of sexual stimulation and is associated with significant morbidity and complications, including erectile dysfunction and penile fibrosis. Surgical management of priapism can be extremely challenging. We herein provide a comprehensive review that aims to evaluate the role of penile prosthesis (PP) implantation in the management of priapism. Methods: A systematic literature search was performed using the following databases: PubMed, Embase, and Scopus to identify studies that evaluated the effectiveness of PP implantation in treating priapism and the long-term complications, outcomes, and patients' satisfaction rate. Results: Out of 717 English-language studies published between 2002 and 2022, 17 were chosen for this review. Majority of patients had a malleable PP (MPP) implant, either early or delayed after the priapism episode. Early placement (EP) of PP is widely defined between studies ranging from less than 72 hours, within 1 week, and within 3 weeks. Most common causes of priapism were sickle cell anemia (SCA), medication-induced, and idiopathic. Studies show a higher satisfaction rate ranging between 80% and 100%, with sexual intercourse achievement ranging between 64.2% and 100%. Based on the GRADE system, included studies rated as very low quality of evidence. Commonly reported complications that arise after PP procedures, include device infection, erosion, curvature, and mechanical malfunction, such as auto-inflation. Conclusions: PP can be an effective treatment option for priapism, particularly in cases of ischemic priapism lasting more than 36 hours or recurrent priapism that is medically refractory. However, due to the very low quality of evidence, larger, well-designed studies are warranted where long-term outcomes, patients' satisfaction, and complications following priapism-related PP implantation are measured as endpoints.

Overcoming barriers to immediate penile implant salvage surgery: a narrative review.

Background and Objective: Since immediate salvage (IS) surgery for infected penile prosthesis (PP) was introduced nearly 30 years ago, an abundance of evidence has emerged in support of its use. IS remains underutilized by the modern urologist despite its distinct advantages. While some medical literature proposes reasons for the underuse of IS, no comprehensive review attempts to address the numerous factors limiting its implementation. Our objective is to analyze the barriers to IS surgery for infected PP with the goal of expanding utilization of this technique through a practical and standardized approach for treating urologists. Methods: A narrative review of available English, peer-reviewed, medical literature relevant to the barriers to IS was completed. Searches were expanded to include literature from surgical specialties in general if hypothesized barriers were incompletely described in available PP publications. Key Content and Findings: The major barriers that are likely contributing to the low rates of IS for PP surgery can be broadly classified into three major categories: institutional/systemic, medical/surgical, and patient preference. Institutional/systemically driven barriers include surgeon comfort with PP surgery, low national availability of urologists, inaccessibility of prosthetics or critical ancillary staff at the time of patient presentation and limited operating room (OR) access. Medical/surgical barriers primarily relate to reinfection fears, perceived contraindications to IS, and overall patient stability at the time of presentation. Patient preference factors inhibiting IS involve loss of trust in the medical team, psychosocial distress, dissatisfaction with the initial device prior to infection and anxiety regarding postoperative recovery. Many of the identified barriers can be overcome with increased surgical training, improved patient and surgeon understanding of PP infection, or precautionary planning. Conclusions: Of the factors that contribute to low utilization of IS, many are misunderstood or unknown. Recognition of these barriers may equip urologists to provide better care to patients with prosthesis infection.

A contemporary systematic review of penile lengthening procedures with penile prosthesis.

Background: Penile prosthetic devices are the standard treatment for erectile dysfunction (ED) after failure of maximum medical therapy and conservative options. Several penile lengthening procedures (PLPs) can be performed concurrently with penile prosthesis (PP) insertion in patients with severe ED, penile shortening, and/or Peyronie's disease to help combat negative emotional and psychological concerns from penile length loss with penile prosthetic device placement. Methods: An extensive, systematic literature review of the various pre-, intra-, and post-operative techniques that can be applied to preserve, restore or enhance penile length at the time of penile prosthetic implantation. Results: Numerous pre-operative and post-operative inflation protocols exists with vacuum erection devices and penile traction therapy. Intraoperative surgical techniques include cavernosal sparing and channeling without dilatation, subcoronal incision with circumferential penile degloving and grafting, the sliding technique, the modified sliding technique, the multiple-slit technique, the tunical expansion procedure (TEP), modified TEP, and the auxetic expansion procedure. These approaches can be meaningful to restore and/or preserve length for patients undergoing PP insertion. Conclusions: PLPs can be performed by surgeons who have extensive penile reconstruction experience and have been trained to do these procedures, as there is significant risk to the patient and limitations to what can be expected. Each patient must be counseled in detail about the risks and benefits of these procedures and have their expectations managed as the average postoperative penile length recovery is around 3 cm and can range from 0-4.0 cm. Future research is needed to identify the appropriate candidate for each approach, and how much length gain the patient can expect.

PIM1 inhibitor SMI-4a attenuated concanavalin A-induced acute hepatitis through suppressing inflammatory responses.

Background: Serine/threonine kinase 1 (PIM1) plays a crucial role in cell growth, differentiation, and apoptosis. However, its role in the pathogenesis of concanavalin A (ConA)-induced acute hepatitis is not well understood. PIM1 kinase inhibitor can reduce the expression of PIM1. This study aims to investigate the effects of PIM1 kinase inhibitor and its protective mechanism in ConA-induced acute hepatitis. Methods: C57/BL six mice were injected with ConA (20, 15, and 12 mg/kg) to induce acute hepatitis, and PIM1 kinase inhibitor SMI-4a (60 mg/kg) was administered orally 24 h before ConA injection. The survival rate of the mice was observed after ConA injection. The levels of serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were measured. Serum inflammatory factors were detected by enzyme-linked immunosorbent assay (ELISA). Hematoxylin-eosin (HE) staining was performed on liver tissue collected at different time points. The major cytokines expression in liver tissue was detected by quantitative real-time polymerase chain reaction (qRT-PCR). The number of macrophages, T-cell and neutrophils in liver tissue were detected by flow cytometry (FCM). PIM1 in liver tissue was detected by western blot (WB) and qRT-PCR. SMI-4a (80 µM) was pretreated for 24 h and ConA (400 µg/mL) was stimulated for 12 h in RAW264.7 cell model. Phosphorylated p65 (p-p65) and cleaved caspase-3 (c-caspase-3) in liver tissue and macrophages were detected by WB. Results: Different concentrations of ConA caused different acute hepatitis mortality, 12 mg/kg concentration within 24 h of the mortality showed a gradient increase. The levels of AST and ALT increased significantly at 12 h after ConA injection. PIM1 expression was upregulated at 12 h. SMI-4a can suppress the PIM1 expression. SMI-4a suppressed cytokines production, AST, and ALT in ConA-treated serum. SMI-4a suppressed the major cytokines in liver tissue. Tests in liver tissue showed that SMI-4a reduced the number of T cells, neutrophils, and macrophages. SMI-4a inhibited the inflammatory response by downregulating the expression of p-p65. Meanwhile, apoptosis was decreased by decreasing the expression of c-caspase-3. Conclusions: In conclusion, the protective effect of SMI-4a against acute hepatitis is by reducing the inflammatory response and apoptosis. These findings suggest that SMI-4a may have therapeutic potential in the treatment of autoimmune hepatitis.

Successful management of maternal anti-PP1Pk alloimmunization in pregnancy with therapeutic plasma exchange and intravenous immunoglobulin.

Anti-PP1PK alloimmunization is rare given ubiquitous P1PK expression. Prevention of recurrent miscarriages and hemolytic disease of the fetus and newborn (HDFN) in pregnant individuals with anti-PP1PK antibodies has relied upon individual reports. Here, we demonstrate the successful management of maternal anti-PP1PK alloimmunization in a 23-year-old, G2P0010, with therapeutic plasma exchange (TPE), intravenous immunoglobulin (IVIG), and monitoring of anti-PP1Pk titers. Twice-weekly TPE (1.5 plasma volume [PV], 5% albumin replacement) with weekly titers and IVIG (1 g/kg) was initiated at 9 weeks of gestation (WG). The threshold titer was ≥16. Weekly middle cerebral artery-peak systolic velocities (MCA-PSV) for fetal anemia monitoring was initiated at 16 WG. PVs were adjusted throughout pregnancy based on treatment schedule, titers, and available albumin. Antigen-negative, ABO-compatible RBCs were obtained through the rare donor program and directed donation. An autologous blood autotransfusion system was reserved for delivery. Titers decreased from 128 to 8 by 10 WG. MCA-PSV remained stable. At 24 WG, TPE decreased to once weekly. After titers increased to 32, twice-weekly TPE resumed at 27 WG. Induction of labor was scheduled at 38 WG. Vaginal delivery of a 2950 g neonate (APGAR score: 9, 9) occurred without complication (Cord blood: 1+ IgG DAT; Anti-PP1Pk eluted). Newborn hemoglobin and bilirubin were unremarkable. Discharge occurred postpartum day 2. Anti-PP1Pk alloimmunization is rare but associated with recurrent miscarriages and HDFN. With multidisciplinary care, a successful pregnancy is possible with IVIG and TPE adjusted to PV and titers. We also propose a patient registry and comprehensive management plan.

Sch9S6K controls DNA repair and DNA damage response efficiency in aging cells.

Survival from UV-induced DNA lesions relies on nucleotide excision repair (NER) and the Mec1ATR DNA damage response (DDR). We study DDR and NER in aging cells and find that old cells struggle to repair DNA and activate Mec1ATR. We employ pharmacological and genetic approaches to rescue DDR and NER during aging. Conditions activating Snf1AMPK rescue DDR functionality, but not NER, while inhibition of the TORC1-Sch9S6K axis restores NER and enhances DDR by tuning PP2A activity, specifically in aging cells. Age-related repair deficiency depends on Snf1AMPK-mediated phosphorylation of Sch9S6K on Ser160 and Ser163. PP2A activity in old cells is detrimental for DDR and influences NER by modulating Snf1AMPK and Sch9S6K. Hence, the DDR and repair pathways in aging cells are influenced by the metabolic tuning of opposing AMPK and TORC1 networks and by PP2A activity. Specific Sch9S6K phospho-isoforms control DDR and NER efficiency, specifically during aging.

Optimized Design of EdgeBoard Intelligent Vehicle Based on PP-YOLOE.

Advances in deep learning and computer vision have overcome many challenges inherent in the field of autonomous intelligent vehicles. To improve the detection accuracy and efficiency of EdgeBoard intelligent vehicles, we proposed an optimized design of EdgeBoard based on our PP-YOLOE+ model. This model innovatively introduces a composite backbone network, incorporating deep residual networks, feature pyramid networks, and RepResBlock structures to enrich environmental perception capabilities through the advanced analysis of sensor data. The incorporation of an efficient task-aligned head (ET-head) in the PP-YOLOE+ framework marks a pivotal innovation for precise interpretation of sensor information, addressing the interplay between classification and localization tasks with high effectiveness. Subsequent refinement of target regions by detection head units significantly sharpens the system's ability to navigate and adapt to diverse driving scenarios. Our innovative hardware design, featuring a custom-designed mainboard and drive board, is specifically tailored to enhance the computational speed and data processing capabilities of intelligent vehicles. Furthermore, the optimization of our Pos-PID control algorithm allows the system to dynamically adjust to complex driving scenarios, significantly enhancing vehicle safety and reliability. Besides, our methodology leverages the latest technologies in edge computing and dynamic label assignment, enhancing intelligent vehicles' operations through seamless sensor integration. Our custom dataset, specifically designed for this study, includes 4777 images captured by intelligent vehicles under a variety of environmental and lighting conditions. The dataset features diverse scenarios and objects pertinent to autonomous driving, such as pedestrian crossings and traffic signs, ensuring a comprehensive evaluation of the model's performance. We conducted extensive testing of our model on this dataset to thoroughly assess sensor performance. Evaluated against metrics including accuracy, error rate, precision, recall, mean average precision (mAP), and F1-score, our findings reveal that the model achieves a remarkable accuracy rate of 99.113%, an mAP of 54.9%, and a real-time detection frame rate of 192 FPS, all within a compact parameter footprint of just 81 MB. These results demonstrate the superior capability of our PP-YOLOE+ model to integrate sensor data, achieving an optimal balance between detection accuracy and computational speed compared with existing algorithms.

Mechanical, Flame-Retardant and Dielectric Properties of Intumescent Flame Retardant/Glass Fiber-Reinforced Polypropylene through a Novel Dispersed Distribution Mode.

The application of continuous glass fiber-reinforced polypropylene thermoplastic composites (GF/PP) is limited due to the inadequate flame retardancy of the polypropylene (PP) matrix. Apart from altering the composition of the flame retardants, the distribution modes of flame retardants also impact material performance. In this study, an alternative approach involving non-uniform distribution is proposed, namely, dispersed distribution, in which non-flame-retardant-content layers (NFRLs) and/or low-flame-retardant-content layers (LFRLs) are dispersed among high-flame-retardant-content layers (HFRLs). The mechanical, flame retardant and dielectric properties of GF/PP with intumescent flame retardant (IFR/GF/PP) are investigated comparatively under uniform, gradient, and dispersed distributions of the flame retardants. The results demonstrate that non-uniform distribution exhibits superior flame retardant performance compared to uniform distribution. Dispersed distribution enables IFR/GF/PP to attain enhanced mechanical properties and reduced dielectric constants while maintaining excellent flame-retardant properties.

Biochemical characterization of the Eya and PP2A-B55α interaction.

The Eyes Absent (Eya) proteins were first identified as co-activators of the Six homeobox family of transcription factors and are critical in embryonic development. These proteins are also re-expressed in cancers after development is complete, where they drive tumor progression. We have previously shown that the Eya3 N-terminal domain (NTD) contains Ser/Thr phosphatase activity through an interaction with the protein phosphatase 2A (PP2A)-B55α holoenzyme, and that this interaction increases the half-life of Myc through pT58 dephosphorylation. Here we showed that Eya3 directly interacted with the NTD of Myc, recruiting PP2A-B55α to Myc. We also showed that Eya3 increased the Ser/Thr phosphatase activity of PP2A-B55α but not PP2A-B56α. Furthermore, we demonstrated that the NTD (∼250 amino acids) of Eya3 was completely disordered, and it used a 38-residue segment to interact with B55α. In addition, knockdown and phosphoproteomic analyses demonstrated that Eya3 and B55α affected highly similar phosphosite motifs with a preference for Ser/Thr followed by Pro, consistent with Eya3's apparent Ser/Thr phosphatase activity being mediated through its interaction with PP2A-B55α. Intriguingly, mutating this Pro to other amino acids in a Myc peptide dramatically increased dephosphorylation by PP2A. Not surprisingly, MycP59A, a naturally occurring mutation hotspot in several cancers, enhanced Eya3-PP2A-B55α mediated dephosphorylation of pT58 on Myc, leading to increased Myc stability and cell proliferation, underscoring the critical role of this phosphosite in regulating Myc stability.

The protein phosphatase PP6 promotes RIPK1-dependent PANoptosis.

BACKGROUND: The innate immune system serves as the first line of host defense. Transforming growth factor-ß-activated kinase 1 (TAK1) is a key regulator of innate immunity, cell survival, and cellular homeostasis. Because of its importance in immunity, several pathogens have evolved to carry TAK1 inhibitors. In response, hosts have evolved to sense TAK1 inhibition and induce robust lytic cell death, PANoptosis, mediated by the RIPK1-PANoptosome. PANoptosis is a unique innate immune inflammatory lytic cell death pathway initiated by an innate immune sensor and driven by caspases and RIPKs. While PANoptosis can be beneficial to clear pathogens, excess activation is linked to pathology. Therefore, understanding the molecular mechanisms regulating TAK1 inhibitor (TAK1i)-induced PANoptosis is central to our understanding of RIPK1 in health and disease. RESULTS: In this study, by analyzing results from a cell death-based CRISPR screen, we identified protein phosphatase 6 (PP6) holoenzyme components as regulators of TAK1i-induced PANoptosis. Loss of the PP6 enzymatic component, PPP6C, significantly reduced TAK1i-induced PANoptosis. Additionally, the PP6 regulatory subunits PPP6R1, PPP6R2, and PPP6R3 had redundant roles in regulating TAK1i-induced PANoptosis, and their combined depletion was required to block TAK1i-induced cell death. Mechanistically, PPP6C and its regulatory subunits promoted the pro-death S166 auto-phosphorylation of RIPK1 and led to a reduction in the pro-survival S321 phosphorylation. CONCLUSIONS: Overall, our findings demonstrate a key requirement for the phosphatase PP6 complex in the activation of TAK1i-induced, RIPK1-dependent PANoptosis, suggesting this complex could be therapeutically targeted in inflammatory conditions.