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Background: Cholangiocarcinoma (CCA) is a malignant tumor of the gastrointestinal tract with a poor prognosis. Immunotherapy plays an important role in the treatment of CCA. This study aimed to investigate the research hotspots and trends in immunotherapy for CCA. Methods: The Web of Science Core Collection was searched for literature related to CCA immunotherapy research from January 1, 2014, to December 31, 2023, and features such as country, institution, authors, references, and keywords in the included literature were quantitatively and visually analyzed using the VOS viewer and CiteSpace software. Results: A total of 252 English publications published between 2014 and 2023 were included. The publications were mainly from China and the United States, with Fudan University being the institution that published the most papers. The highest number of publications came from Frontiers in Oncology. The most prolific authors were Jia Fan, Jian Zhou from China and Pa-Thai Yenchitsomanus from Thailand, while the Journal of Clinical Oncology ranked first in the number of citations among the co-cited journals. In recent years, the focus of research has shifted from "immune checkpoint" and "chemotherapy" to "immunotherapy combined therapy." Currently, the research frontiers are "microenvironment," "immune cells," and "macrophages." Conclusion: Our study analyzes the research hotspots and trends in CCA to provide a knowledge map of immunotherapy research, which will serve as a reference and direction for future research. [ABSTRACT FROM AUTHOR]

Objective: Aneurysmal subarachnoid hemorrhage (aSAH) is an aggressive disease with higher mortality rate in the elderly population. Unfortunately, the previous models for predicting clinical prognosis are still not accurate enough. Therefore, we aimed to construct and validate a visualized nomogram model to predict online the 3-month mortality in elderly aSAH patients undergoing endovascular coiling. Method: We conducted a retrospective analysis of 209 elderly aSAH patients at People's Hospital of Hunan Province, China. A nomogram was developed based on multivariate logistic regression and forward stepwise regression analysis, then validated using the bootstrap validation method (n = 1000). In addition, the performance of the nomogram was evaluated by various indicators to prove its clinical value. Result: Morbid pupillary reflex, age, and using a breathing machine were independent predictors of 3-month mortality. The AUC of the nomogram was 0.901 (95% CI: 0.853–0.950), and the Hosmer–Lemeshow goodness-of-fit test showed good calibration of the nomogram (p = 0.4328). Besides, the bootstrap validation method internally validated the nomogram with an area under the curve of the receiver operator characteristic (AUROC) of 0.896 (95% CI: 0.846–0.945). Decision curve analysis (DCA) and clinical impact curve (CIC) indicated the nomogram's excellent clinical utility and applicability. Conclusion: An easily applied visualized nomogram model named MAC (morbid pupillary reflex-age-breathing machine) based on three accessible factors has been successfully developed. The MAC nomogram is an accurate and complementary tool to support individualized decision-making and emphasizes that patients with higher risk of mortality may require closer monitoring. Furthermore, a web-based online version of the risk calculator would greatly contribute to the spread of the model in this field. [ABSTRACT FROM AUTHOR]

Background: Non-coding RNAs play important roles in liver regeneration; however, their functions and mechanisms of action in the regeneration of fibrotic liver have not been elucidated. We aimed to clarify the expression patterns and regulatory functions of lncRNAs, circRNAs, miRNAs, and mRNAs in the proliferative phase of fibrotic liver regeneration. Methods: Based on a mouse model of liver fibrosis with 70% hepatectomy, whole-transcriptome profiling was performed using high-throughput sequencing on samples collected at 0, 12, 24, 48, and 72 h after hepatectomy. Hub genes were selected by weighted gene co-expression network analysis and subjected to enrichment analysis. Integrated analysis was performed to reveal the interactions of differentially expressed (DE) lncRNAs, circRNAs, miRNAs, and mRNAs, and to construct lncRNA–mRNA cis- and trans-regulatory networks and lncRNA/circRNA–miRNA–mRNA ceRNA regulatory networks. Real-Time quantitative PCR was used to validate part of the ceRNA network. Results: A total of 1,329 lncRNAs, 48 circRNAs, 167 miRNAs, and 6,458 mRNAs were differentially expressed, including 812 hub genes. Based on these DE RNAs, we examined several mechanisms of ncRNA regulatory networks, including lncRNA cis and trans interactions, circRNA parental genes, and ceRNA pathways. We constructed a cis-regulatory core network consisting of 64 lncRNA–mRNA pairs (53 DE lncRNAs and 58 hub genes), a trans-regulatory core network consisting of 103 lncRNA–mRNA pairs (18 DE lncRNAs and 85 hub genes), a lncRNA–miRNA–mRNA ceRNA core regulatory network (20 DE lncRNAs, 12 DE miRNAs, and 33 mRNAs), and a circRNA–miRNA–mRNA ceRNA core regulatory network (5 DE circRNAs, 5 DE miRNAs, and 39 mRNAs). Conclusions: These results reveal the expression patterns of lncRNAs, circRNAs, miRNAs, and mRNAs in the proliferative phase of fibrotic liver regeneration, as well as core regulatory networks of mRNAs and non-coding RNAs underlying liver regeneration. The findings provide insights into molecular mechanisms that may be useful in developing new therapeutic approaches to ameliorate diseases that are characterized by liver fibrosis, which would be beneficial for the prevention of liver failure and treatment of liver cancer. [ABSTRACT FROM AUTHOR]

This paper investigates the performance of spatially distributed reconfigurable intelligent surface (RIS)-aided non-orthogonal multiple access (NOMA) systems over Rician fading channels, where the spatial locations of multiple RISs are modeled by invoking the stochastic geometry. Accurate and asymptotic closed-form expressions in terms of the outage probability and ergodic rate are derived based on an optimal selection scheme. Accordingly, diversity orders are obtained to gain more insights on the considered network. It is revealed by simulations that the outage behaviour of distributed RIS-NOMA system outperforms that of RIS-aided orthogonal multiple access (OMA) and conventional multiple relays-aided NOMA counterparts, and the ergodic rate of distributed RIS-NOMA is superior to that of distributed RIS-OMA in the low signal-to-noise ratio region. Additionally, the performance enhancements through more densely deployed of RISs and/or more reflecting elements of RIS as well as the increased Rician factors are corroborated by the simulations. [ABSTRACT FROM AUTHOR]

Mobile crowd sensing is a novel large-scale sensing pattern, which applies users' smart devices to analyze social context and human activity, and then learns the intelligent information serving for various innovative services. An augmented reality (AR) system can bring more authentic experience for human life, and more and more scholars are increasingly interested in this technology. However, there are some problems in the previous methods, such as the expensive deployment, low accuracy, and high latency. These problems greatly limit the application of augmented reality systems. In this paper, we design a lightweight augmented reality system, called LAR, which can recognize the target object quickly and precisely by using a feature matching algorithm. In LAR, the target object is shot twice to get the distance between the user and the object, and we take the distance as the feature of the target object. Furthermore, the feature extraction algorithm, named s-SURF, is designed to extract image features. LAR combines the distance with image feature and then matches with these images stored in database. In addition, the flutter-free algorithm is used to denoise and get a clearer image. Finally, we design a prototype system to evaluate LAR performance. The accuracy of LAR is 86%, and the time delay achieves 141 ms. [ABSTRACT FROM AUTHOR]

Activation of the cGAS/STING innate immunity pathway is essential and effective for anti-tumor immunotherapy. However, it remains largely elusive how tumor-intrinsic cGAS signaling is suppressed to facilitate tumorigenesis by escaping immune surveillance. Here, we report that the protein arginine methyltransferase, PRMT1, methylates cGAS at the conserved Arg133 residue, which prevents cGAS dimerization and suppresses the cGAS/STING signaling in cancer cells. Notably, genetic or pharmaceutical ablation of PRMT1 leads to activation of cGAS/STING-dependent DNA sensing signaling, and robustly elevates the transcription of type I and II interferon response genes. As such, PRMT1 inhibition elevates tumor-infiltrating lymphocytes in a cGAS-dependent manner, and promotes tumoral PD-L1 expression. Thus, combination therapy of PRMT1 inhibitor with anti-PD-1 antibody augments the anti-tumor therapeutic efficacy in vivo. Our study therefore defines the PRMT1/cGAS/PD-L1 regulatory axis as a critical factor in determining immune surveillance efficacy, which serves as a promising therapeutic target for boosting tumor immunity. cGAS/STING mediated immunity is linked to the anti-tumor response, but how tumor-intrinsic cGAS signals are countered during tumorigenesis and immune evasion is poorly understood. Here the authors show PRMT1 suppresses the anti-tumor immune response via arginine methylation of cGAS. [ABSTRACT FROM AUTHOR]

In this paper, we investigate the problem of downlink precoding for the narrowband massive multi-user multiple-input multiple-output (MU-MIMO) system with low-resolution digital-to-analog converters (DACs). We introduce a low-complexity precoding scheme based on the alternating direction method of multipliers (ADMM) framework in this work. An efficient gradient descent (GD) algorithm with adaptive step-size determination mechanism (ASGD) is proposed to alleviate the computational complexity bottleneck of the inherent matrix inversion. Numerical results demonstrate that the ASGD precoder achieves an attractive trade-off between the performance and computational complexity compared with other counterparts. [ABSTRACT FROM AUTHOR]

Intracranial aneurysms (IAs) remain a major public health concern and endovascular treatment (EVT) has become a major tool for managing IAs. However, the recurrence rate of IAs after EVT is relatively high, which may lead to the risk for aneurysm re-rupture and re-bleed. Thus, we aimed to develop and assess prediction models based on machine learning (ML) algorithms to predict recurrence risk among patients with IAs after EVT in 6 months. Patient population included patients with IAs after EVT between January 2016 and August 2019 in Hunan Provincial Peopleʼs Hospital, and an adaptive synthetic (ADASYN) sampling approach was applied for the entire imbalanced dataset. We developed five ML models and assessed the models. In addition, we used SHapley Additive exPlanations (SHAP) and local interpretable model-agnostic explanation (LIME) algorithms to determine the importance of the selected features and interpret the ML models. A total of 425 IAs were enrolled into this study, and 66 (15.5%) of which recurred in 6 months. Among the five ML models, gradient boosting decision tree (GBDT) model performed best. The area under curve (AUC) of the GBDT model on the testing set was 0.842 (sensitivity: 81.2%; specificity: 70.4%). Our study firstly demonstrated that ML-based models can serve as a reliable tool for predicting recurrence risk in patients with IAs after EVT in 6 months, and the GBDT model showed the optimal prediction performance. [ABSTRACT FROM AUTHOR]

Functioning as a master kinase, 3-phosphoinositide-dependent protein kinase 1 (PDK1) plays a fundamental role in phosphorylating and activating protein kinases A, B and C (AGC) family kinases, including AKT. However, upstream regulation of PDK1 remains largely elusive. Here we report that ribosomal protein S6 kinase beta 1 (S6K1), a member of AGC kinases and downstream target of mechanistic target of rapamycin complex 1 (mTORC1), directly phosphorylates PDK1 at its pleckstrin homology (PH) domain, and impairs PDK1 interaction with and activation of AKT. Mechanistically, S6K1-mediated phosphorylation of PDK1 augments its interaction with 14-3-3 adaptor protein and homo-dimerization, subsequently dissociating PDK1 from phosphatidylinositol 3,4,5 triphosphate (PIP3) and retarding its interaction with AKT. Pathologically, tumor patient-associated PDK1 mutations, either attenuating S6K1-mediated PDK1 phosphorylation or impairing PDK1 interaction with 14-3-3, result in elevated AKT kinase activity and oncogenic functions. Taken together, our findings not only unravel a delicate feedback regulation of AKT signaling via S6K1-mediated PDK1 phosphorylation, but also highlight the potential strategy to combat mutant PDK1-driven cancers. The direct upstream regulation of PDK1 is not fully understood. Here the authors demonstrate that S6K1 directly phosphorylates PDK1 to inhibit AKT kinase activity and its ability to drive tumourigenesis. [ABSTRACT FROM AUTHOR]

In this paper, we propose a joint signal detection algorithm under the framework of the expectation propagation (EP) algorithm for uplink massive multiuser multiple-input multiple-output (MIMO) systems with generalized spatial modulation (GSM). By projecting the discrete probability distribution into a multivariate complex Gaussian function, the symbol beliefs of the tridimensional GSM constellation are calculated via the iterative propagation of the mean vectors and covariance matrices. To reduce the computational complexity, an efficient separate signal detection called two-stage EP (TS-EP) algorithm is designed. In the first stage, the active transmit antenna indices are determined via the EP. Each vector-valued variable node (VN) in the factor graph is decomposed into multiple sub-VNs, and the invalid sub-VNs of the determined silent transmit antennas are pruned from the factor graph. In the second stage, since the modulation symbols are independent conditioned on the active transmit antennas, the symbols are independently detected by adopting the EP with univariate complex Gaussian approximations, and the number of probability calculations for each symbol belief is significantly reduced in the subsequent EP update. Simulation results illustrate that the proposed EP and TS-EP signal detection schemes outperform the recently proposed counterparts. Moreover, the proposed TS-EP algorithm strikes a desirable and flexible performance-complexity tradeoff. [ABSTRACT FROM AUTHOR]

Intelligent reflecting surface (IRS) is deemed a promising technique for future wireless and mobile technologies due to its ability to reconfigure the radio propagation environment. In this paper, we analyze the physical layer security (PLS) of a downlink non-orthogonal multiple access (NOMA) network through an IRS intended for assisting the wireless transmission, taking into account the external and internal eavesdropping scenarios. Considering the hardware limitations, a 1-bit coding scheme is utilized to investigate the secrecy performance of the IRS-aided NOMA (IRS-NOMA) network. Exact and asymptotic expressions in terms of the secrecy outage probability (SOP) and the effective secrecy throughput (EST) are presented, which are in consideration of the imperfect successive interference cancellation (ipSIC) and perfect SIC (pSIC). Based on the analytical results, the secrecy diversity orders are related to the number of reflecting elements and EST ceilings are observed in the high SNR regime. Monte Carlo simulations are presented to corroborate the correctness of the analyses and illustrate that the IRS-NOMA scheme is superior in the secrecy outage performance to the IRS-aided orthogonal multiple access scheme. In addition, the SOP performance enhancement through the increased number of reflecting elements and the improvement of EST through proper target secrecy rate are also evidenced by the simulations. [ABSTRACT FROM AUTHOR]

Decentralized baseband processing (DBP) architecture, which partitions the base station antennas into multiple antenna clusters, has been recently proposed to alleviate the excessively high interconnect bandwidth, chip input/output data rates, and detection complexity for massive multi-user multiple-input multiple-output (MU-MIMO) systems. In this paper, we propose a novel decentralized Gaussian message passing (GMP) detection for the DBP architecture. Based on the message passing rule, each antenna cluster iteratively calculated the local means and variances which are fused to generate the global symbol beliefs for demodulation. The state evolution framework of the decentralized GMP algorithm is presented under the assumptions of large-system limit and Gaussian sources. Analytical results corroborated by simulations demonstrate that the nonuniform antenna cluster partition scheme exhibits a higher convergence rate than the uniform counterpart. Simulation results illustrate that the proposed decentralized GMP detection outperforms the recently proposed decentralized algorithms. [ABSTRACT FROM AUTHOR]

A full AKT activation event requires phosphorylation of AKT at Thr SP 308 sp (AKT-pThr SP 308 sp ) in the activation loop by PDK1 and Ser SP 473 sp (AKT-pSer SP 473 sp ) in the hydrophobic motif in a manner mediated by mTORC2 ([20]). Sin1-4A mutant inhibits AKT-pSer 473 in response to DNA damage.(A) MCF7- Sin1 KO cells were reconstituted with Sin1-WT or Sin1-4A. EV was a negative control. I ECT2 i -depleted cells exhibited similar reduction of AKT-pSer SP 473 sp as cells expressing Sin1-4A, and depletion of I ECT2 i in Sin1-4A-expressing cells had no additive effects in AKT-pSer SP 473 sp reduction (Fig. To investigate whether Sin1-pSQ governs mTORC2 activation in response to DNA damage, we reconstituted Sin1-WT or Sin1-4A mutant at comparable levels in I Sin1 i -knockout MCF7 cells ( I Sin1 i SP KO sp ) and I Sin1 i SP -/- sp MEFs. [Extracted from the article]

In this work, we introduce the pattern-domain pilot design paradigm based on a “superposition of orthogonal-building-blocks” with significantly larger contention space to enhance the massive machine-type communications (mMTC) random access (RA) performance in massive multiple-input multiple-output (MIMO) systems. Specifically, the pattern-domain pilot is constructed based on the superposition of $L$ cyclically-shifted Zadoff-Chu (ZC) sequences. The pattern-domain pilots exhibit zero correlation values between non-colliding patterns from the same root and low correlation values between patterns from different roots. The increased contention space, i.e., from N to $\binom{N}{L}$ , where $\binom{N}{L}$ denotes the number of all L-combinations of a set N, and low correlation values lead to a significantly lower pilot collision probability without compromising excessively on channel estimation performance for mMTC RA in massive MIMO systems. We present the framework and analysis of the RA success probability of the pattern-domain based scheme with massive MIMO systems. Numerical results demonstrate that the proposed pattern division random access (PDRA) scheme achieves an appreciable performance gain over the conventional one, while preserving the existing physical layer virtually unchanged. The extension of the “superposition of orthogonal-building-blocks” scheme to “superposition of quasi-orthogonal-building-blocks” is straightforward. [ABSTRACT FROM AUTHOR]

We introduce a joint weighted Neumann series (WNS) and Gauss–Seidel (GS) approach to implement an approximated linear minimum mean-squared error (LMMSE) detector for uplink massive multiple-input multiple-output (M-MIMO) systems. We first propose to initialize the GS iteration by a WNS method, which produces a closer-to-LMMSE initial solution than the conventional zero vector and diagonal-matrix based scheme. Then the GS algorithm is applied to implement an approximated LMMSE detection iteratively. Furthermore, based on the WNS, we devise a low-complexity approximate log-likelihood ratios (LLRs) computation method whose performance loss is negligible compared with the exact method. Numerical results illustrate that the proposed joint WNS-GS approach outperforms the conventional method and achieves near-LMMSE performance with significantly lower computational complexity. [ABSTRACT FROM AUTHOR]

Practical data detectors must achieve low error-rate at low-complexity for massive multiple-input multiple-output (MIMO) wireless systems. Since near-optimal minimum mean square error (MMSE) detection exhibits high computational complexity for such wireless systems, various iterative methods as well as their enhanced variants have been proposed. The efficiency of iterative approaches, however, is not satisfying due to slow convergence rate and reduced accuracy. This paper proposes a novel semi-iterative data detection algorithm for massive MIMO systems that simultaneously achieves a large improvement in convergence and accuracy with respect to the corresponding iterative method. We provide a general three-term recurrence expression for semi-iterative detection and incorporate it with Richardson method as a show case. To further improve the convergence rate of the proposed technique, a new trace-diagonal based low-complexity initial method is developed. A sufficient condition for convergence of the proposed method is also provided. We analyze the associated complexity of semi-iterative detector, and provide numerical results which demonstrate that the proposed detector is superior to recently introduced iterative detectors in terms of both the error-rate performance and computational complexity. [ABSTRACT FROM AUTHOR]

Copper plays pivotal roles in metabolic homoeostasis, but its potential role in human tumorigenesis is not well defined. Here, it is revealed that copper activates the phosphoinositide 3‐kinase (PI3K)‐protein kinase B (PKB, also termed AKT) oncogenic signaling pathway to facilitate tumorigenesis. Mechanistically, copper binds 3‐phosphoinositide dependent protein kinase 1 (PDK1), in turn promotes PDK1 binding and subsequently activates its downstream substrate AKT to facilitate tumorigenesis. Blocking the copper transporter 1 (CTR1)‐copper axis by either depleting CTR1 or through the use of copper chelators diminishes the AKT signaling and reduces tumorigenesis. In support of an oncogenic role for CTR1, the authors find that CTR1 is abnormally elevated in breast cancer, and is subjected by NEDD4 like E3 ubiquitin protein ligase (Nedd4l)‐mediated negative regulation through ubiquitination and subsequent degradation. Accordingly, Nedd4l displays a tumor suppressive function by suppressing the CTR1‐AKT signaling. Thus, the findings identify a novel regulatory crosstalk between the Nedd4l‐CTR1‐copper axis and the PDK1‐AKT oncogenic signaling, and highlight the therapeutic relevance of targeting the CTR1‐copper node for the treatment of hyperactive AKT‐driven cancers. [ABSTRACT FROM AUTHOR]

Impulsive noise significantly deteriorates the performance of orthogonal frequency-division multiplexing (OFDM)-based underwater acoustic (UWA) communication systems. The pulse blanking (PB) based approach can mitigate the impulsive noise. However, it causes inter-carrier interference (ICI) and signal attenuation to the receiver. In this work, we first show that the ICI introduces pronounced non-Gaussianity to the receiver chain and leads to significant performance degradation. We then propose a non-Gaussianity-aware iterative ICI cancelation scheme to mitigate the adverse impacts of PB. A companding transformation scheme is incorporated into the soft symbol computation to alleviate the non-Gaussianity of the log-likelihood ratios (LLRs) caused by the residual ICI and impulsive noise. Simulation results illustrate that the proposed non-Gaussianity-aware iterative receiver achieves significant performance gains over the conventional non-Gaussianity-agnostic one with even lower computational complexity. [ABSTRACT FROM AUTHOR]

In this letter, we propose to utilize the expectation propagation (EP) framework for soft-input soft-output (SISO) signal detection in massive spatial modulation (SM) multiple-input multiple-output (MIMO) systems. By using a multivariate complex Gaussian approximation approach, the symbol beliefs of the transmitted symbol vectors are constructed based on the propagation of the mean vectors and covariance matrixes. The log-likelihood ratios (LLRs) of the antenna index bits and the modulation index bits are computed by partitioning the symbol beliefs into different regions. Simulation results illustrate that the proposed SISO EP detector outperforms the state-of-the-art soft-decision algorithms and strikes a desirable performance-complexity tradeoff. [ABSTRACT FROM AUTHOR]

This paper investigates the secrecy outage performance for a large-scale downlink system with full-duplex (FD) non-orthogonal multiple access (NOMA) transmission aided by artificial noise (AN). In the system, legitimate users (LUs) are randomly distributed according to homogeneous Poisson point processes whereas a passive eavesdropper (Eve) is certainly located. We introduce a secure cooperative communication scheme, in which nearby NOMA users operating in FD mode act as jammers and generate AN to enhance the physical layer security (PLS) of the legitimate transmission. Closed-form expressions in terms of the secrecy outage probability (SOP) for a user pair are acquired. Following the mathematical results, secrecy diversity order analysis is further carried out for two scenarios, i.e., 1) fixed transmit signal-to-noise ratio (SNR) at the Eve, and 2) transmit SNR at the Eve being proportional to that of LUs. Closed-form expressions of asymptotic SOP for the two scenarios are also obtained. Monte Carlo simulations are performed to certify the veracity of the theoretic analysis and illustrate that the proposed scheme employing both AN and FD-NOMA is superior in the secrecy outage to the NOMA scheme without AN and the orthogonal multiple access scheme with AN. Furthermore, the SOP performance enhancement through proper secrecy rate target selection and power allocation optimization is also evidenced by the simulations. [ABSTRACT FROM AUTHOR]

Multiuser detection based on the expectation propagation (EP) algorithm for the massive multiple-input multiple-output (M-MIMO) system has received considerable attention in recent years due to its good performance-complexity tradeoff. However, its performance degrades when the system is highly overloaded. Furthermore, the computational complexity increases fast as the number of receive antennas increases. In this work, we propose an improved EP detector via channel sparsification based approach, which is shortened as S-EP. The key idea is to sparsify the channel first, such that the average degree of the variable node (VN) and function node (FN) in the associated factor graph (FG) is significantly decreased, thus rendering a reduced effective interference. Therefore, the inference accuracy can be enhanced. The associated computational complexity of the message computation can also be eliminated. Analytical and simulation results illustrate that the proposed S-EP based detection scheme achieves noticeable performance gains compared with the conventional EP based one while requiring even a lower computational complexity. [ABSTRACT FROM AUTHOR]

Background: Persistent infection with hepatitis B virus (HBV) accounts for the majority of hepatocellular carcinoma (HCC), but the molecular mechanisms underlying liver carcinogenesis are still not completely understood. Increasing evidence demonstrates that microRNAs (miRNAs) play significant functional roles in virus–host interactions. The aim of this study was to explore differentially expressed miRNA profiles and investigate the molecular mechanism of miR-0308-3p in HBV-positive HCC carcinogenesis. Methods: High-throughput sequencing was used to detect novel miRNAs in three samples of HBV-positive HCC tissue compared to matched HBV-negative HCC tissue. The Cancer Genome Atlas (TCGA) database was used to mine miRNAs related to HBV-positive HCC. Bioinformatics analyses were conducted to predict the miRNAs' possible biological and pathway regulatory functions. Quantitative polymerase chain reaction (qPCR) was then applied to evaluate the expression levels of randomly selected miRNAs. CCK-8 was used to measure cell proliferation and cell cycles were analyzed using flow cytometry. A dual luciferase reporter gene assay was used to confirm the downstream targets of miR-0308-3p. Results: In total, there were 34 overlapping miRNAs in both our miRNA-seq data and the TCGA database. We found two overlapping miRNAs in both the HBV-positive HCC samples and the TCGA database, and 205 novel pre-miRNA sequences were predicted. miR-522 and miR-523 were markedly overexpressed in HBV-positive HCC and were associated with a significantly poorer long-term prognosis (miR-522, HR 2.19, 95% CI 1.33–3.6, p = 0.0015; miR-523HR 1.5, 95% CI 1–2.44, p = 0.0047). Of note, we found that the novel miR-0308-3p was markedly downregulated in HBV-positive HCC samples and HCC cancer cell lines compared with HBV-negative HCC samples and adjacent normal hepatic tissue. Moreover, elevated expression of miR-0308-3p was found to inhibit proliferation of cancer cells by promoting G1/S cell cycle arrest but did not influence the apoptosis of cancer cells. A dual luciferase reporter activity assay identified that miR-0308-3p acted directly on the target sequence of the CDK6 and Cyclin D1 mRNA 3ʹUTR to suppress CDK6 and Cyclin D1 expression. Conclusions: MiR-0308-3p upregulation dramatically suppressed HCC cell proliferation and induced G1/S cell cycle arrest by directly targeting CDK6/Cyclin D1. These findings reveal a novel molecular mechanism for activation of G1/S arrest in HCC and may prove clinically useful for developing new therapeutic targets. [ABSTRACT FROM AUTHOR]

Background: Although polyacrylamide hydrogel (PAAG) injection for breast augmentation has been prohibited for many years, the long-term complications will be significant for a long period. Few research articles have focused on the clinicopathological analysis. Materials and Methods: We summarized clinical and pathological features of 90 cases after PAAG-injected breast augmentation, including 2 cases of breast cancer developed following PAAG injection. Results: All patients were females between the ages of 30 and 64 years (mean, 44 years). The complications included masses (75.58%), pain (45.35%), migration (22.09%), deformation (18.60%), infection (16.28%), induration (4.65%), and psychological fear (2.33%). Microscopically, the PAAG presented as purple gel pools, and the foreign body reaction was noted in all 90 patients. The proportion of fibrous component exceeded 90% in 26 cases (28.89%). Chronic and acute inflammation was noted in 70 (77.78%) and 9 (10%) patients, respectively. The mammary gland around the gel displayed atrophy in 18 cases (20.00%), adenosis in 33 cases (36.67%), ductal carcinoma in situ in 1 case (1.11%), and invasive carcinoma in 1 case (1.11%). Conclusion: The long-term complications of PAAG-injected breast augmentation are various and complex. Pathologically, these complications are associated with foreign body reaction, fibrosis, and inflammation. [ABSTRACT FROM AUTHOR]

Bone tissue engineering provides a substitute for bone transplantation to address various bone defects. However, bone regeneration involves a large number of cellular events. In addition, obtaining sufficient source material for autogenous bone or alloplastic bone substitutes remains an unsolved issue. In previous studies, it was confirmed that bone marrow stromal cells (BMSCs) and endothelial progenitor cells (EPCs) had the capacity to promote bone regeneration. Additionally, bone morphogenetic protein-2 (BMP-2) has been demonstrated to be an active inducer of osteoblast differentiation. Therefore, the aim of the present study was to produce an effective integration system, including a scaffold, reparative cells and growth factors, that may enhance bone regeneration. Firstly, bone marrow-derived BMSCs and EPCs were isolated and identified by flow cytometry. Cell proliferation ability, secreted BMP-2 levels and alkaline phosphatase (ALP) activity were highest in the cell sheets containing BMP-2-modified BMSCs and EPCs. In addition, the expression levels of osteogenesis-associated genes, including runt related transcription factor 2 (Runx2), distal-less homeobox 5 (Dlx5), ALP and integrin-binding sialoprotein (Ibsp), and osteogenesis-associated proteins, including Runx2, Dlx, ALP, Ibsp, vascular endothelial growth factor, osteonectin, osteopontin and type I collagen, gradually increased during the co-culture of ad-BMP-2-BMSCs/EPCs. The levels of these genes and proteins were increased compared with those observed in the BMSC, EPC and BMP-2-modified BMSC groups. Finally, scanning electron microscopy observation also demonstrated that the BMP2-modified BMSCs were able to combine well with EPCs to construct a cell sheet for bone formation. Collectively, these results describe an adenovirus (ad)-BMP2-BMSCs/EPCs co-culture system that may significantly accelerate bone regeneration compared with a BMSCs/EPCs co-culture system or ad-BMP2-BMSCs alone. [ABSTRACT FROM AUTHOR]

Abstract: Yes‐associated protein (YAP) is a transcriptional co‐activator and a major effector of the Hippo pathway that promotes cell proliferation and stemness, while inhibiting apoptosis. YAP plays a central role in organ size control, and its deregulation strongly promotes cancer initiation and progression. However, the mechanisms by which YAP promotes cell invasion and metastasis are not fully understood. Here, we report that YAP induces leukocyte‐specific integrin β2 (ITGB2) expression in cancer cells, thereby promoting cell invasion through the endothelium in a manner mimicking leukocytes. Through independent biochemical purification and a functional screen, we further identified PR/SET domain 4 (PRDM4) as a transcription factor interacting with the WW domains of YAP to mediate ITGB2 expression and cell invasion. Consistently, ITGB2 and PRDM4 mRNA levels are significantly increased in metastatic prostate cancer. In addition, PRDM4 contributes to YAP‐induced tumorigenesis possibly via mediating the expression of other YAP target genes. Our results demonstrate that YAP promotes cell invasion by inducing leukocyte‐specific integrin expression, and identify PRDM4 as a novel transcription factor for YAP targets. [ABSTRACT FROM AUTHOR]

The anticipated 1000-fold increase in mobile data traffic over the next decade and the explosion of new services and applications pose great challenges for the current orthogonal multiple access (OMA)-based 4G systems. A promising solution to address these challenges is to shift from the currently predominant OMA to non-orthogonal multiple access (NOMA). This article first introduces the principle of the complexity-constrained capacity-achieving NOMA design. Then a non-orthogonal pattern division multiple access (PDMA) scheme is proposed to meet the exponentially growing demand of mobile users for computing and information application services. The key feature of the PDMA scheme is a joint design of transmitter and receiver, which allows low-complexity successive interference cancellation (SIC)-based multi-user detection with substantially improved performance over conventional OMA schemes. More specifically, the patterns of multiple users are judiciously designed so that the data symbols of different users are of appropriate diversity disparity at the symbol level and power disparity at the resource element level. The appropriate disparity in diversity and power can be effectively exploited by the low-complexity SICbased detector to realize the near-perfect cancellation of multi-user interference. Moreover, the PDMA system parameters can be flexibly adjusted to provide different levels of overload, rendering it suitable to meet the diverse traffic requirements in future 5G systems. Link-level simulations illustrate that PDMA is capable of accommodating a 300 percent overload, while it still enjoys transmission reliability close to conventional OMA schemes. The results demonstrated in this article indicate that PDMA can be a promising multiple access technology with low signaling overhead, low latency, and massive connectivity support for 5G. [ABSTRACT FROM PUBLISHER]

B Correction to: Neurological Sciences (2023) b https://doi.org/10.1007/s10072-023-06777-x The Authors agreed to swap the order of JianJun Zou and XiaoMing Dai to ensure that the corresponding author list in the official publication matches the original manuscript submission. Correction to: A visualized MAC nomogram online predicts the risk of three-month mortality in Chinese elderly aneurysmal subarachnoid hemorrhage patients undergoing endovascular coiling The original article can be found online at https://doi.org/10.1007/s10072-023-06777-x. [Extracted from the article]

In this work, a low-complexity hardware-friendly discrete Fourier transform (DFT)-based channel estimator with almost no inherent 'edge effect' is designed for the long-term evolution (LTE) uplink channel. Specifically, we propose to perform the border symmetric extension (BSE) operation on the border subcarriers of the channel frequency response (CFR), such that the length of the extended CFR fulfills $$2^{\lceil {{\text {log}}_2N}\rceil }$$ , where N denotes the non-radix-2 length of the original CFR, and $$\lceil {x}\rceil$$ stands for the integer ceiling function. Based on the proposed BSE operation, the discontinuities at the CFR's border subcarriers are significantly lessened and a better power concentration of the transform-domain channel impulse response is realized. As a result, the inherent 'edge effect' caused by the virtual subcarriers in LTE systems can be substantially reduced. A further advantage of the proposed method is that the cumbersome application specific integrated circuit-based implementation of 34 different non-radix-2 length DFT/IDFT operations can be accomplished in a single structure by their fast Fourier transform and inverse fast Fourier transform counterparts. Numerical results illustrate that the proposed DFT-based channel estimator with BSE achieves significant performance gains over the conventional counterpart, despite imposing a reduced computational complexity. [ABSTRACT FROM AUTHOR]

The recent concept of beamspace multiple input multiple output (MIMO) with discrete lens array can utilize beam selection to reduce the number of radio-frequency chains (RF) required in terahertz (THz) massive MIMO systems. However, to achieve the capacity-approaching performance, beam selection requires information on a beamspace channel of large size. This is difficult to obtain since the user mobility usually leads to the fast variation of THz beamspace channels, and the conventional real-time channel estimation schemes involve unaffordable pilot overhead. To solve this problem, in this paper, we propose the a priori aided (PA) channel tracking scheme. Specifically, by considering a practical user motion model, we first excavate a temporal variation law of the physical direction between the base station and each mobile user. Then, based on this law and the special sparse structure of THz beamspace channels, we propose to utilize the obtained beamspace channels in the previous time slots to predict the prior information of the beamspace channel in the following time slot without channel estimation. Finally, aided by the obtained prior information, the time-varying beamspace channels can be tracked with low pilot overhead. Simulation results verify that to achieve the same accuracy, the proposed PA channel tracking scheme requires much lower pilot overhead and signal-to-noise ratio (SNR) than the conventional schemes. [ABSTRACT FROM AUTHOR]

We propose a statistical information-based approach to enhance the performance of the noniterative quasi-maximum-likelihood (QML) receiver (detector plus decoder) recorded at the output of the channel decoder for coded multiple-input–multiple-output (MIMO) systems. As an illustrative example, the QR decomposition with an $M$-algorithm (QRD-M)-based noniterative QML receiver is employed in this paper. We first illustrate that there is a large discrepancy between the amplitude of the raw log-likelihood ratio (LLR) generated by the complexity-constrained QRD-M detector and its reliability, particularly for LLRs with high amplitudes. The discrepancy is shown to be the main underlying cause of degraded performance in coded MIMO systems. Then, we propose a reliability-aware transformation technique, which exploits the statistical relationship between the raw LLR's amplitude and its reliability to adjust the raw LLR's amplitude to a level commensurate with its reliability. By using the proposed statistical knowledge-based technique, the performance of the receiver (detector plus decoder) recorded at the output of the channel decoder is significantly enhanced for high-order modulations. The extension of the proposed method to other QML receivers such as the list sequential (LISS) detector and list sphere detector (LSD)-based receivers is straightforward. [ABSTRACT FROM AUTHOR]

With the increase of the number of base station (BS) antennas in massive multiple-input multiple-output (MIMO) systems, linear precoding schemes are able to achieve the near-optimal performance, and thus are more attractive than nonlinear precoding techniques. However, conventional linear precoding schemes such as zero-forcing (ZF) precoding involve the matrix inversion of large size with high computational complexity, especially in massive MIMO systems. To reduce the complexity, in this letter, we propose a low-complexity linear precoding scheme based on the symmetric successive over relaxation (SSOR) method. Moreover, we propose a simple way to approximate the optimal relaxation parameter of the SSOR-based precoding by exploiting the channel property of asymptotical orthogonality in massive MIMO systems. We show that the proposed SSOR-based precoding can reduce the complexity of the classical ZF precoding by about one order of magnitude without performance loss, and it also outperforms the recently proposed linear approximate precoding schemes in typical fading channels. [ABSTRACT FROM PUBLISHER]

Traumas, infections, tumors, and some congenital malformations can lead to bone defects or even bone loss. The goal of the present study was to investigate whether inclusion of endothelial progenitor cells derived from peripheral blood (PB–EPCs) in cell-seeded partially deproteinized bone (PDPB) implants would stimulate recruitment of systemically injected bone marrow stromal cells (BMSCs) to the implant. Methods: BMSCs were injected intravenously with lentiviral expression vector expressing enhanced green fluorescent protein (eGFP) for tracing. Recruitment of eGFP-positive BMSCs was tested for the following implant configurations: 1) seeded with both BMSC and PB-EPC, 2) BMSC alone, 3) PB-EPC alone, and 4) unseeded PDPB. Protein and mRNA levels of endogenous stromal-derived factor-1 (SDF-1) and its receptor CXCR4, as well as monocyte chemotactic protein-1 (MCP-1) and its receptor CCR2, were evaluated on the 8th week. Immunohistochemical staining was performed to determine eGFP-positive areas at the defective sites. Masson’s trichrome staining was conducted to observe the distribution of collagen deposition and evaluate the extent of osteogenesis. Results: The mRNA and protein levels of SDF-1 and CXCR4 in the co-culture group were higher than those in other groups (p < 0.05) 8 weeks after the surgery. MCP-1 mRNA level in the co-culture group was also higher than that in the other groups (p < 0.05). Immunohistochemical assays revealed that the area covered by eGFP-positive cells was larger in the co-culture group than in the other groups (p < 0.05) after 4 weeks. Masson’s trichrome staining revealed better osteogenic potential of the co-culture group compared to the other groups (p < 0.05). Conclusion: These experiments demonstrate an association between PB-EPC and BMSC recruitment mediated by the SDF-1/CXCR4 axis that can enhance repair of bone defects. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented regarding the Yes-associated protein (YAP), a transcription co-activator and a potent growth promoter, that activates the Hippo pathway in a negative feedback loop.

Focusing on auto control of parking brake system of the medium and heavy duty vehicles, the key problems are studied including the system design and control strategies. The structure and working principle of the parking brake system of the medium and heavy duty vehicles are analyzed. The functions of EPB are proposed. The important information of the vehicle are analyzed which could influence the EPB system. The overall plan of the pneumatic EPB system is designed, which adopts the two-position three-way electromagnetic valve with double coil as actuator. The system could keep the vehicle parking brake status or parking release status for a long time without power supply. The function modules of the system are planned, and the control strategies of automatic parking brake and parking release are made. The experiment is performed on a medium-sized commercial vehicle which is experimentally modified. The overall plan of the pneumatic EPB system and the automatic parking function are proved through real vehicle tests. [ABSTRACT FROM AUTHOR]

In uplink massive multiple‐input multiple‐output (MIMO) systems, the conventional minimum mean square error‐interference rejection combining (MMSE‐IRC) signal detection algorithm needs to compute the inverse of the interference and noise covariance matrix, which incurs high computational complexity, especially when the number of antennas is large. A low‐complexity MMSE‐IRC signal detection algorithm based on the eigenvalue decomposition of the interference and noise covariance matrix is proposed. The proposed algorithm exploits a dimension‐reduction technique to reduce the computation‐intensive of the matrix inversion compared with the conventional algorithm. Meanwhile, the proposed algorithm is shown to be equivalent to the conventional MMSE‐IRC algorithm under the assumption of uncorrelated interference and noise. Analysis and simulation results show the effectiveness of the proposed algorithm. [ABSTRACT FROM AUTHOR]

An iterative detection and decoding (IDD) technique has recently received much attention due to its capacity approaching performance and manageable complexity for (parallel) turbo-coded systems. The existing IDD receivers process indiscriminately the a priori information of the systematic bits and the parity bits generated by the turbo decoder in the front-end detection. In this paper, we first show that the parity bits of the parallel turbo codes are inherently less protected than the systematic bits, which leads to suboptimality for the IDD receivers. Based on this observation, we then propose an unequal-error-correcting-capability-aware technique to mitigate the associated performance loss. As an illustrative example, the minimum-mean-square-error (MMSE) filtering and soft interference cancelation (MMSE-SIC)-aided iterative receiver for parallel-turbo-coded multiple-input–multiple-output (MIMO) systems is employed in this paper. Numerical results manifest that the MMSE-SIC-aided iterative receiver based on the proposed paradigm achieves noticeable performance gains over the conventional unequal-error-correcting-capability-agnostic one even with reduced computational complexity. The extension of the proposed principle to other iterative algorithms for parallel-turbo-coded data transmission is straightforward. [ABSTRACT FROM PUBLISHER]

This work investigates the impact of inherent residual transceiver impairments of multiple-input multiple-output (MIMO) systems on the performance of linear minimum mean-squared error filtering and parallel interference cancellation (LMMSE-PIC) based iterative receiver. The residual transceiver impairments are first modeled as Gaussian noise at the transmitter in this work. Then a residual-transceiver-impairments-aware technique with empirically determined transmitter noise is proposed to mitigate the performance loss associated with the residual transceiver impairments. Numerical results based on MIMO systems with typical residual transceiver impairments show that the proposed method achieves significant performance gain over the conventional one which is designed for ideal transceivers. [ABSTRACT FROM PUBLISHER]

A detection scheme built on a combination of a simplified branch metric based search and refined calculation is proposed in this work to reduce the computational complexity of the quasi-maximum-likelihood (QML) detectors, such as the QR-decomposition combined with M-algorithm (QRD-M), list sequential sphere decoder (LISS) and list sphere decoding (LSD), for multiple-input multiple-output (MIMO) multiplexing systems, while maintaining similar performance to the original methods. More specifically, the proposed method utilizes a multiplication-free accumulated branch metric to first identify the potential candidates with significantly reduced search complexity. The optimal solution is then determined by the standard squared Euclidean distance metric from the initial candidates. The key idea of the proposed method lies in the fact that the best candidate identified by the simplified branch metric coincides with that of which is based on the conventional one with a high probability for a properly designed parameter. Numerical results demonstrates that the QRD-M detector using the proposed method achieves significantly better performance than the conventional one with comparable (or even less) computational complexity. [ABSTRACT FROM PUBLISHER]

We have explored the optimal seeding density and timing for transplantation of the tissue-engineered bone with BMMSCs (bone marrow mesenchymal stem cells) and PDPB (partially deproteinized bone) in vitro. Rabbit BMMSCs of different densities were seeded into PDPB generated from fresh pig vertebrates to reconstruct tissue-engineered bone in vitro. Adhesion and proliferation of BMMSCs were analysed by MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2 H-tetrazolium bromide] assay from which growth curves of BMMSCs on the PDPB materials were generated. The data show that BMMSCs began to adhere to PDPB after 24 h of primary culture, all groups reaching peak growth on the 6th day, after which the value of A decreased gradually and reached a plateau phase. The optimal BMMSCs seeding density of 5×106/ml achieved an excellent adhesion and proliferation activity on PDPB. In summary, the best cell seeding density of constructing tissue-engineered bone with BMMSCs in vitro is 5×106/ml, the optimal timing to transplant is the 6th day. [ABSTRACT FROM AUTHOR]

This paper proposes a rotation and scaling based transformation method to simplify the (quasi-)maximum-likelihood (ML) detectors (such as QRD-M, sphere decoding (SD), etc.) for the square quadrature amplitude modulation (S-QAM) modulated multiple-input and multiple-output (MIMO) systems with no performance degradation. The key idea of the simplification is to utilize the symmetric shape of the S-QAM constellation so that after rotation and scaling, real multiplication and addition with certain constellation points in symbol replica generation simply transform into bit shifting or even vanish. As an illustrative example, the QRD-M detector is employed in this work. By using the proposed method, the number of real multiplications of the symbol replica generation required for the QRD-M detector is reduced by 50% and 25% for 4-QAM and 16-QAM, respectively. The numbers of real addition reduction is twice the amount of multiplication. The underlying principle of the proposed rotation and scaling transformation can be straightforwardly extended to amplitude and phase-shift keying (APSK) modulated MIMO systems employing the QRD-M, SD, list sequential sphere decoder (LISS), list sphere decoding (LSD), and the full ML detectors. [ABSTRACT FROM AUTHOR]