Multiple input multiple output (MIMO) technology necessitates detection methods with high performance and low complexity; however, the detection problem becomes severe when high-order constellations ...are employed. Variational approximation-based algorithms prove to deal with this problem efficiently, especially for high-order MIMO systems. Two typical algorithms named Gaussian tree approximation (GTA) and expectation consistency (EC) attempt to approximate the true likelihood function under discrete finite-set constraints with a new distribution by minimizing the Kullback-Leibler (KL) divergence. As the KL divergence is not a true distance measure, 'exclusive' and 'inclusive' KL divergences are utilized by GTA and EC, respctively, demonstrating different performances. In this paper, we further combine the two asymmetric KL divergences in a nested way by proposing a generic algorithm framework named nested variational chain. Acting as an initial application, a MIMO detection algorithm named Gaussian tree approximation expectation consistency (GTA-EC) can thus be presented along with its alternative version for better understanding. With less computational burden compared to its counterparts, GTA-EC is able to provide better detection performance and diversity gain, especially for large-scale high-order MIMO systems.
Microscopic examination of peripheral blood plays an important role in the field of diagnosis and control of major diseases. Peripheral leukocyte recognition by manual requires medical technicians to ...observe blood smears through light microscopy, using their experience and expertise to discriminate and analyze different cells, which is time-consuming, labor-intensive and subjective. The traditional systems based on feature engineering often need to ensure successful segmentation and then manually extract certain quantitative and qualitative features for recognition but still remaining a limitation of poor robustness. The classification pipeline based on convolutional neural network is of automatic feature extraction and free of segmentation but hard to deal with multiple object recognition. In this paper, we take leukocyte recognition as object detection task and apply two remarkable object detection approaches, Single Shot Multibox Detector and An Incremental Improvement Version of You Only Look Once. To improve recognition performance, some key factors involving these object detection approaches are explored and the detection models are generated using the train set of 14,700 annotated images. Finally, we evaluate these detection models on test sets consisting of 1,120 annotated images and 7,868 labeled single object images corresponding to 11 categories of peripheral leukocytes, respectively. A best mean average precision of 93.10% and mean accuracy of 90.09% are achieved while the inference time is 53 ms per image on a NVIDIA GTX1080Ti GPU.
The molecular categorization of colon cancer patients remains elusive. Gene set enrichment analysis (GSEA), which investigates the dysregulated genes among tumor and normal samples, has revealed the ...pivotal role of epithelial-to-mesenchymal transition (EMT) in colon cancer pathogenesis. In this study, we employed multi-clustering method for grouping data, resulting in the identification of two clusters characterized by varying prognostic outcomes. These two subgroups not only displayed disparities in overall survival (OS) but also manifested variations in clinical variables, genetic mutation, and gene expression profiles. Using the nearest template prediction (NTP) method, we were able to replicate the molecular classification effectively within the original dataset and validated it across multiple independent datasets, underscoring its robust repeatability. Furthermore, we constructed two prognostic signatures tailored to each of these subgroups. Our molecular classification, centered on EMT, hold promise in offering fresh insights into the therapy strategies and prognosis assessment for colon cancer.
EZH2 mediates both PRC2-dependent gene silencing via catalyzing H3K27me3 and PRC2-independent transcriptional activation in various cancers. Given its oncogenic role in cancers, EZH2 has constituted ...a compelling target for anticancer therapy. However, current EZH2 inhibitors only target its methyltransferase activity to downregulate H3K27me3 levels and show limited efficacy because of inadequate suppression of the EZH2 oncogenic activity. Therefore, therapeutic strategies to completely block the oncogenic activity of EZH2 are urgently needed. Herein, we report a series of EZH2-targeted proteolysis targeting chimeras (PROTACs) that induce proteasomal degradation of PRC2 components, including EZH2, EED, SUZ12, and RbAp48. Preliminary assessment identified E7 as the most active PROTAC molecule, which decreased PRC2 subunits and H3K27me2/3 levels in various cancer cells. Furthermore, E7 strongly inhibited transcriptional silencing mediated by EZH2 dependent on PRC2 and transcriptional activation mediated by EZH2 independent of PRC2, showing significant antiproliferative activities against cancer cell lines dependent on the enzymatic and nonenzymatic activities of EZH2.
Ischemic stroke (IS) and malignant tumor (MT) have high morbidity and mortality rates worldwide, and several associations exist between them. This study aimed to determine the effect of MT on ...hospital mortality in patients with IS.
Based on their MT status, participants with IS in the Medical Information Mart for Intensive Care IV (MIMIC-IV) were divided into two groups. The primary outcome was in-hospital all causes mortality. Kaplan-Meier survival analysis was performed to evaluate the intergroup in-hospital mortality, and three Cox regression models were used to determine the association between MT and in-hospital mortality.
A total of 1605 participants (749 males and 856 females) were included in the study. The mean age was 72.030 ± 15.463 years. Of these, 257 (16%) patients died in the hospital. Kaplan-Meier analysis showed that the MT group had a significantly lower possibility of in-hospital survival than the non-MT group. In the unadjusted model, in-hospital mortality among MT patients had a higher odds ratio (OR) of 1.905 (95% CI, 1.320-2.748; P < 0.001) than the non-MT group. After adjusting for basic information, vital signs, and laboratory data, MT was also associated with increased in-hospital mortality (OR = 1.844, 95% CI: 1.255-2.708; P = 0.002).
Among the patients with IS, the risk of all causes in-hospital mortality was higher for MT than for patients non-MT. This finding can assist clinicians in more accurately assessing prognosis and making informed treatment decisions.
Cardiovascular disease is the leading cause of mortality worldwide. Atherosclerosis, one of the most common forms of the disease, is characterized by a gradual formation of atherosclerotic plaque, ...hardening, and narrowing of the arteries. Nanomaterials can serve as powerful delivery platforms for atherosclerosis treatment. However, their therapeutic efficacy is substantially limited in vivo due to nonspecific clearance by the mononuclear phagocytic system. In order to address this limitation, rapamycin (RAP)‐loaded poly(lactic‐co‐glycolic acid) (PLGA) nanoparticles are cloaked with the cell membrane of red blood cells (RBCs), creating superior nanocomplexes with a highly complex functionalized bio‐interface. The resulting biomimetic nanocomplexes exhibit a well‐defined “core–shell” structure with favorable hydrodynamic size and negative surface charge. More importantly, the biomimetic nature of the RBC interface results in less macrophage‐mediated phagocytosis in the blood and enhanced accumulation of nanoparticles in the established atherosclerotic plaques, thereby achieving targeted drug release. The biomimetic nanocomplexes significantly attenuate the progression of atherosclerosis. Additionally, the biomimetic nanotherapy approach also displays favorable safety properties. Overall, this study demonstrates the therapeutic advantages of biomimetic nanotherapy for atherosclerosis treatment, which holds considerable promise as a new generation of drug delivery system for safe and efficient management of atherosclerosis.
Biomimetic nanocomplexes with typical “core–shell” structure consisting of a RAP‐loaded PLGA nanoparticle “core” and a RBC membrane “shell” (RBC/RAP@PLGA), exhibit the biomimetic nature of the RBC interface to enhance targeted drug delivery to atherosclerotic plaques. RBC/RAP@PLGA not only significantly attenuates the progression of atherosclerosis, but also shows a desirable safety profile without any significant long‐term side effects.
The classification of coal bursting liability (CBL) is essential for the mitigation and management of coal bursts in mining operations. This study establishes an index system for CBL classification, ...incorporating dynamic fracture duration (DT), elastic strain energy index (WET), bursting energy index (KE), and uniaxial compressive strength (RC). Utilizing a dataset comprising 127 CBL measurement groups, the impacts of various optimization algorithms were assessed, and two prominent machine learning techniques, namely the back propagation neural network (BPNN) and the support vector machine (SVM), were employed to develop twelve distinct models. The models’ efficacy was evaluated based on accuracy, F1-score, Kappa coefficient, and sensitivity analysis. Among these, the Levenberg–Marquardt back propagation neural network (LM-BPNN) model was identified as superior, achieving an accuracy of 96.85%, F1-score of 0.9113, and Kappa coefficient of 0.9417. Further validation in Wudong Coal Mine and Yvwu Coal Industry confirmed the model, achieving 100% accuracy. These findings underscore the LM-BPNN model’s potential as a viable tool for enhancing coal burst prevention strategies in coal mining sectors.
Under the background of green and low‐carbon transformation of industrial high‐energy‐consuming parks, in order to realize the coordinated development planning of energy and transportation under ...different peaking capacity requirements, this paper proposes a collaborative optimization model of industrial high‐energy‐consuming parks under green and low‐carbon. Firstly, by studying the energy balance mechanism between industrial load and new energy, an energy topology prior model of energy interaction in the next generation of industrial new energy power grid is constructed. Then, based on the probability characteristics of the equilibrium state of different regions in the high‐energy‐consuming industrial zone, combined with the prior knowledge of industrial load and low‐carbon power system, a collaborative development planning model of high‐energy‐consuming industrial parks is constructed. Finally, the proposed model is simulated. From the simulation results the authors can see the dynamic division model and solution algorithm of energy balance region established in this paper can effectively improve the energy balance ability of power grid, reduce peak shaving demand and use more renewable energy.
This paper has proposed a collaborative optimization model of industrial high‐energy consumption park under different peak regulation capacity requirements. The coordinated optimization model of green transportation and industrial load as well as the indeterminacy of source‐load‐storage are proposed considering the charging characteristics of charging piles.
Depletion of medial smooth muscle cell (SMC) is a major pathological characteristic of abdominal aortic aneurysm (AAA), although the mechanism by which these cells are eliminated remains incompletely ...understood. We reasoned that necroptosis, a recently described form of necrosis mediated by receptor-interacting protein kinase 3 (RIP3), may contribute to AAA pathology through the induction of SMC death and the significant production of inflammatory cytokines.
To test the hypothesis that RIP3-mediated necroptosis is actively involved in aneurysm pathogenesis.
RIP3 and RIP1 levels were found to be elevated in human AAAs, most noticeably in SMCs. Elevations of RIP3 and SMC necrosis were also observed in the elastase-induced mouse model of AAAs. Deletion of one or both copies of Rip3 prevented AAA formation. By transplanting Rip3(+/-) aortae to Rip3(+/+) mice, we demonstrated that reduced Rip3 expression in arterial wall was the primary cause of aneurysm resistance. In vitro, adenoviral overexpression of RIP3 was sufficient to trigger SMC necroptosis. Protein kinase C-delta contributed to tumor necrosis factor-α-induced SMC necroptosis by regulating Rip3 expression. Furthermore, Rip3 deficiency impaired tumor necrosis factor-α-induced inflammatory gene expression in aortic SMCs, which was at least in part because of attenuation of p65 Ser536 phosphorylation. In vivo, the lack of RIP3 diminished activation of p65 in SMCs, implicating a necrosis independent function of RIP3 in aneurysms.
Enhanced RIP3 signaling in aneurysmal tissues contributes to AAA progression by causing SMC necroptosis, as well as stimulating vascular inflammation, and therefore may serve as a novel therapeutic target for AAA treatment.
Background/Aims: Induced pluripotent stem cells (iPSCs) hold great promise for regenerative medicine, disease modeling, and drug development. Thus, generation of non-integration and feeder-free iPSCs ...is highly desirable for clinical applications. Peripheral blood mononuclear cells (PBMCs) are an attractive resource for cell reprogramming because of their properties of easy accessibility and the limited invasiveness of blood collection. However, derivation of iPSCs is technically demanding due to the low reprogramming efficiency and nonadherent features of PBMCs. Methods: iPSCs were generated from PBMCs using non-integrative Sendai viruses carrying the reprogramming factors Oct4, Sox2, Klf4, and cMyc. The derived iPSCs were fully characterized at the levels of gene and protein, and then they were transplanted into immunocompromised mice for evaluation of in vivo differentiation potential. Three types of extracellular substrates (Geltrex, vitronectin, and rhLaminn-521) were tested for their influences on cell reprogramming under feeder-free conditions. We also sought to establish approaches to efficient cell recovery post-thaw and single cell passaging of iPSCs employing Rock inhibitors. Results: iPSCs were efficiently generated from PBMCs under feeder-free conditions. The derived iPSCs proved to be pluripotent and transgene-free. Furthermore, they demonstrated multi-lineage differentiation potentials when transplanted into immunocompromised mice. Among the three substrates, Geltrex and rhLaminin-521 could effectively support the initial cell reprogramming process, but vitronectin failed. However, the vitronectin, similar to Geltrex and rhLaminin-521, could effectively maintain cell growth and expansion of passaged iPSCs. In addition, RevitaCell supplement (RVC) was more potent on cell recovery post-thaw than Y-27632. And RVC and Y-27632 could significantly increase the cell survival when the cells were passaged in single cells, and they showed comparable effectiveness on cell recovery. Conclusion: We have successfully derived non-integration and feeder-free human iPSCs from peripheral blood cells, and established effective strategies for efficient cell recovery and single cell passaging. This study will pave the way to the derivation of clinical-grade human iPSCs for future clinical applications.
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