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This article proposes and demonstrates a retrodirective array (RDA) for two-way wireless communication with automatic beam tracking. The proposed RDA is enabled by specifically designed chips made using a domestic complementary metal-oxide semiconductor (CMOS) process. The highly integrated CMOS chip includes a receiving (Rx) chain, a transmitting (Tx) chain, and a unique tracking phase-locked loop (PLL) for the crucial conjugated phase recovery in the RDA. This article also proposes a method to reduce the beam pointing error (BPE) in a conventional RDA. To validate the above ideas simply yet without loss of generality, a 2.4 GHz RDA is demonstrated through two-way communication links between the Rx and Tx chains, and an on-chip quadrature coupler is designed to achieve a non-retrodirective signal suppression of 23 dBc. The experimental results demonstrate that the proposed RDA, which incorporates domestically manufactured low-cost 0.18 μm CMOS chips, is capable of automatically tracking beams covering ±40° with a reduced BPE. Each CMOS chip in the RDA has a compact size of 4.62 mm2 and a low power consumption of 0.15 W. To the best of the authors’ knowledge, this is the first research to demonstrate an RDA with a fully customized CMOS chip for wireless communication with automatic beam tracking.

Background: Nuclear cap-binding protein 2 (NCBP2), as the component of the cap-binding complex, participates in a number of biological processes, including pre-mRNA splicing, transcript export, translation regulation and other gene expression steps. However, the role of NCBP2 on the tumor cells and immune microenvironment remains unclear. To systematically analyze and validate functions of NCBP2, we performed a pan-cancer analysis using multiple approaches. Methods: The data in this study were derived from sequencing, mutation, and methylation data in the TCGA cohort, normal sample sequencing data in the GTEx project, and cell line expression profile data in the CCLE database. Results: Survival analyses including the Cox proportional-hazards model and log-rank test revealed the poor prognostic role of NCBP2 in multiple tumors. We further validated the oncogenic ability of NCBP2 in prostate cancer cell lines, organoids and tumor-bearing mice. A negative correlation was observed between NCBP2 expression and immune score by the ESTIMATE algorithm. Simultaneously, the NCBP2-induced immunosuppressive microenvironment might be related to the decline in CD8+ T cells and the increase in regulatory T cells and neutrophils, examined by flow cytometry experiments for NCBP2 overexpressed tumor-bearing mice. Conclusion: This research offered strong proof supporting NCBP2 as the prognostic marker and the therapeutic target in the future.

This study presents a solution for push-out failure for the staged bond-slip constitutive relationship between the structural steel and high strength concrete, taking into account the concrete strength grade, anchoring length, and stirrup ratio. The critical point coordinates for different stages are determined by the tests of 14 steel-reinforced high strength concrete (SRHSC) specimens. It is observed that with the increase in the concrete strength grade and anchorage length, the ultimate load of the specimens increased significantly, but the influence on the residual bond strength was not significant. The effect of the stirring ratio was mainly manifested in a slight increase in the initial bond strength. The formula for calculating SRHSC characteristic bond strength and characteristic slip value is established, and the bond-slip constitutive relation of SRHSC is proposed based on the tests. The material constitutive model considering the effect of bond-slip is implanted into the software in the case of the ABAQUS finite element platform. The material is applied to the numerical simulation analysis of the SRHSC exterior joints. The rationality and accuracy of the new material are verified by comparing the simulation results with the test results.

Abstract Mitochondria are multifaceted and dynamic organelles regulating various important cellular processes from signal transduction to determining cell fate. As dynamic properties of mitochondria, fusion and fission accompanied with mitophagy, undergo constant changes in number and morphology to sustain mitochondrial homeostasis in response to cell context changes. Thus, the dysregulation of mitochondrial dynamics and mitophagy is unsurprisingly related with various diseases, but the unclear underlying mechanism hinders their clinical application. In this review, we summarize the recent developments in the molecular mechanism of mitochondrial dynamics and mitophagy, particularly the different roles of key components in mitochondrial dynamics in different context. We also summarize the roles of mitochondrial dynamics and target treatment in diseases related to the cardiovascular system, nervous system, respiratory system, and tumor cell metabolism demanding high‐energy. In these diseases, it is common that excessive mitochondrial fission is dominant and accompanied by impaired fusion and mitophagy. But there have been many conflicting findings about them recently, which are specifically highlighted in this view. We look forward that these findings will help broaden our understanding of the roles of the mitochondrial dynamics in diseases and will be beneficial to the discovery of novel selective therapeutic targets.

Abstract Heart failure is a complex clinical syndrome caused by the progression to severe stages of various cardiac diseases, characterized by high morbidity and mortality. With the increasing aging of the population and the poor control of high-risk factors for heart failure such as hypertension and diabetes, the incidence of heart failure remains high. Therefore, there is widespread global attention regarding the various treatments for heart failure. Currently, pharmacological therapy, associated device therapy, interventional therapy, and end-stage surgical related therapy are the main clinical treatments for heart failure. Heart failure treatment is gradually evolving to be more precise, safe, and effective, as traditional therapies can no longer match clinical needs. A number of cutting-edge research studies are being conducted on the treatment of heart failure, based on the different pathogenesis and causes of heart failure, to treat patients with heart failure in a multifaceted and integrated way. This article summarizes the current clinical treatment of heart failure and the latest therapeutic advances in heart failure in current research to further promote the standardized management and treatment of heart failure and improve patient prognosis.

Abstract Vibrio species (Vibrio sp.) is a class of Gram-negative aquatic bacteria that causes vibriosis in aquaculture, which have resulted in big economic losses. Utilization of antibiotics against vibriosis has brought concerns on antibiotic resistance, and it is essential to explore potential antibiotic alternatives. In this study, seven compounds (compounds 1–7) were isolated from the Arctic endophytic fungus Penicillium sp. Z2230, among which compounds 3, 4, and 5 showed anti-Vibrio activity. The structures of the seven compounds were comprehensively elucidated, and the antibacterial mechanism of compounds 3, 4, and 5 was explored by molecular docking. The results suggested that the anti-Vibrio activity could come from inhibition of the bacterial peptide deformylase (PDF). This study discovered three Penicillium-derived compounds to be potential lead molecules for developing novel anti-Vibrio agents, and identified PDF as a promising antibacterial target. It also expanded the bioactive diversity of polar endophytic fungi by showing an example in which the secondary metabolites of a polar microbe were a good source of natural medicine. Graphical Abstract

Abstract Aims We aim to investigate the correlation between high levels of the systemic immune‐inflammation index (SII) and long‐term mortality and major cardiovascular adverse events in advanced chronic heart failure patients with renal dysfunction. Methods and results Seven hundred seventeen advanced chronic heart failure patients with renal dysfunction, who visited the First affiliated hospital of Zhengzhou University from September 2019 to December 2020, were included. All‐cause mortalities (ACM) were selected as primary endpoints and major cardiovascular adverse events (MACEs) as the secondary endpoints. Based on the receiver operating characteristic (ROC) curve and the Youden index, the optimal cut‐off values of SII for ACM and MACEs were 1228 and 1406. In the group where ACM were the primary endpoint, patients were categorized into the low‐SII group (n = 479) and the high‐SII group (n = 238). Patients in the group using MACEs as the secondary endpoint were also categorized into the low‐SII groups (n = 514) and the high‐SII groups (n = 203). Univariate and multivariate COX regression were used to screen the independent predictors for ACM and MACEs, revealing the relationship between SII levels and endpoints. According to the univariate COX analysis, SII was the risk factor (hazard ratio [HR] = 2.144, 95% confidence interval [CI]: 1.565–2.938, P

Abstract Background Mounting evidence has revealed the dynamic variations in the cellular status and phenotype of the smooth muscle cell (SMC) are vital for shaping the atherosclerotic plaque microenvironment and ultimately mapping onto heterogeneous clinical outcomes in coronary artery disease. Currently, the underlying clinical significance of SMC evolutions remains unexplored in atherosclerosis. Methods The dissociated cells from diseased segments within the right coronary artery of four cardiac transplant recipients and 1070 bulk samples with atherosclerosis from six bulk cohorts were retrieved. Following the SMC fate trajectory reconstruction, the MOVICS algorithm integrating the nearest template prediction was used to develop a stable and robust molecular classification. Subsequently, multi-dimensional potential biological implications, molecular features, and cell landscape heterogeneity among distinct clusters were decoded. Results We proposed an SMC cell fate decision signature (SCFDS)-based atherosclerosis stratification system and identified three SCFDS subtypes (C1–C3) with distinguishing features: (i) C1 (DNA-damage repair type), elevated base excision repair (BER), DNA replication, as well as oxidative phosphorylation status. (ii) C2 (immune-activated type), stronger immune activation, hyper-inflammatory state, the complex as well as varied lesion microenvironment, advanced stage, the most severe degree of coronary stenosis severity. (iii) C3 (stromal-rich type), abundant fibrous content, stronger ECM metabolism, immune-suppressed microenvironment. Conclusions This study uncovered atherosclerosis complex cellular heterogeneity and a differentiated hierarchy of cell populations underlying SMC. The novel high-resolution stratification system could improve clinical outcomes and facilitate individualized management.

The accumulation of myeloid derived suppressor cells (MDSC) has been associated with prostate cancer progression and castration resistance. Here the authors show that loss of ARID1A, a subunit of the SWI/SNF chromatin remodeling complex, results in polymorphonuclear-MDSC infiltration and cooperates with Pten loss to accelerate prostate tumorigenesis.

Acute myocardial infarction (AMI) remains a dominant origin of morbidity, mortality and disability worldwide. Increases in reactive oxygen species (ROS) are key contributor to excessive cardiac injury after AMI. Here we developed an immobilized enzyme with Superoxide Dismutase (SOD) activity cross-link with Zr-based metal-organic framework (ZrMOF) (SOD-ZrMOF) for mitigate ROS-caused injury. In vitro and in vivo evidence indicates that SOD-ZrMOF exhibits excellent biocompatibility. By efficiently scavenging ROS and suppressing oxidative stress, SOD-ZrMOF can protect the function of mitochondria, reduce cell death and alleviate inflammation. More excitingly, long-term study using an animal model of AMI demonstrated that SOD-ZrMOF can reduce the infarct area, protect cardiac function, promote angiogenesis and inhibit pathological myocardial remodeling. Therefore, SOD-ZrMOF holds great potential as an efficacious and safe nanomaterial treatment for AMI.

IFN-γ–stimulated MHC class I (MHC-I) antigen presentation underlies the core of antitumor immunity. However, sustained IFN-γ signaling also enhances the programmed death ligand 1 (PD-L1) checkpoint pathway to dampen antitumor immunity. It remains unclear how these opposing effects of IFN-γ are regulated. Here, we report that loss of the histone dimethyltransferase WHSC1 impaired the antitumor effect of IFN-γ signaling by transcriptional downregulation of the MHC-I machinery without affecting PD-L1 expression in colorectal cancer (CRC) cells. Whsc1 loss promoted tumorigenesis via a non-cell-autonomous mechanism in an Apcmin/+ mouse model, CRC organoids, and xenografts. Mechanistically, we found that the IFN-γ/STAT1 signaling axis stimulated WHSC1 expression and, in turn, that WHSC1 directly interacted with NLRC5 to promote MHC-I gene expression, but not that of PD-L1. Concordantly, silencing Whsc1 diminished MHC-I levels, impaired antitumor immunity, and blunted the effect of immune checkpoint blockade. Patient cohort analysis revealed that WHSC1 expression positively correlated with enhanced MHC-I expression, tumor-infiltrating T cells, and favorable disease outcomes. Together, our findings establish a tumor-suppressive function of WHSC1 that relays IFN-γ signaling to promote antigen presentation on CRC cells and provide a rationale for boosting WHSC1 activity in immunotherapy.

Abstract Lung cancer (LC) is the leading cause of cancer-related death worldwide due to its late diagnosis and poor outcomes. As has been found for other types of tumors, there is increasing evidence that myeloid-derived suppressor cells (MDSCs) play important roles in the promotion and progression of LC. Here, we briefly introduce the definition of MDSCs and their immunosuppressive functions. We next specifically discuss the multiple roles of MDSCs in the lung tumor microenvironment, including those in tumor growth and progression mediated by inhibiting antitumor immunity, and the associations of MDSCs with a poor prognosis and increased resistance to chemotherapy and immunotherapy. Finally, we also discuss preclinical and clinical treatment strategies targeting MDSCs, which may have the potential to enhance the efficacy of immunotherapy.

Plasma exosomes derived from healthy people have been shown to be beneficial in terms of protecting against ischemia-reperfusion injury or acute myocardial infarction (AMI). However, a pathological condition may severely affect the constitution and biological activity of exosomes. In our study, we isolated plasma exosomes from healthy volunteers and convalescent AMI patients (3–7 d after onset). Compared to exosomes from healthy controls (Nor-Exo), exosomes from convalescent AMI patients (AMI-Exo) exhibited an impaired ability to repair damaged cardiomyocytes both in vitro and in vivo. miRNA sequencing and PCR analysis indicated that miR-342-3p was significantly downregulated in AMI-Exo. Moreover, miR-342-3p alleviated H2O2-induced injury and reduced apoptosis and autophagy in H9c2 cardiomyocytes, while in vivo restoration of miR-342-3p expression enhanced the reparative function of AMI-Exo. Further mechanistic studies revealed that the SOX6 and TFEB genes were two direct and functional targets of miR-342-3p. Taken together, during the early convalescent phase after AMI, dysregulated miR-342-3p in plasma exosomes might be responsible for their impaired cardioprotective potential. miR-342-3p contributed to exosome-mediated heart repair by inhibiting cardiomyocyte apoptosis and autophagy through targeting SOX6 and TFEB, respectively. Our work provided novel insights on the role of plasma exosomes in the natural process of cardiac repair after AMI and suggestions for therapy development.

Atherosclerotic cardiovascular disease (ASCVD) is one of the leading causes of mortality worldwide. Because of the limited regenerative capacity of adult myocardium to compensate for the loss of heart tissue after ischemic infarction, scientists have been exploring the possible mechanisms involved in the pathological process of ASCVD and searching for alternative means to regenerate infarcted cardiac tissue. Although numerous studies have pursued innovative solutions for reversing the pathological process of ASCVD and improving the effectiveness of delivering therapeutics, the translation of those advances into downstream clinical applications remains unsatisfactory because of poor safety and low efficacy. Recently, nanomaterials (NMs) have emerged as a promising new strategy to strengthen both the efficacy and safety of ASCVD therapy. Thus, a comprehensive review of NMs used in ASCVD treatment will be useful. This paper presents an overview of the pathophysiological mechanisms of ASCVD and the multifunctional mechanisms of NM-based therapy, including antioxidative, anti-inflammation and antiapoptosis mechanisms. The technological improvements of NM delivery are summarized and the clinical transformations concerning the use of NMs to treat ASCVD are examined. Finally, this paper discusses the challenges and future perspectives of NMs in cardiac regeneration to provide insightful information for health professionals on the latest advancements in nanotechnologies for ASCVD treatment.

As one of few animals with the capability to execute agile yawing maneuvers, it is quite desirable to take inspiration from hummingbird flight aerodynamics. To understand the wing and body kinematics and associated aerodynamics of a hummingbird performing a free yawing maneuver, a crucial step in mimicking the biological motion in robotic systems, we paired accurate digital reconstruction techniques with high-fidelity computational fluid dynamics (CFD) simulations. Results of the body and wing kinematics reveal that to achieve the pure yaw maneuver, the hummingbird utilizes very little body pitching, rolling, vertical, or horizontal motion. Wing angle of incidence, stroke, and twist angles are found to be higher for the inner wing (IW) than the outer wing (OW). Unsteady aerodynamic calculations reveal that drag-based asymmetric force generation during the downstroke (DS) and upstroke (US) serves to control the speed of the turn, a characteristic that allows for great maneuvering precision. A dual-loop vortex formation during each half-stroke is found to contribute to asymmetric drag production. Wake analysis revealed that asymmetric wing kinematics led to leading-edge vortex strength differences of around 59% between the IW and OW. Finally, analysis of the role of wing flexibility revealed that flexibility is essential for generating the large torque necessary for completing the turn as well as producing sufficient lift for weight support.

Abstract Background The development of novel oral anticoagulants (NOACs) has changed the landscape of non-valvular atrial fibrillation (NVAF) management. In this study, the effectiveness and the safety of several NOACs were evaluated in a real-world setting among Asian patients with NVAF. Methods The literature search was conducted crossing different databases including Embase, MEDLINE, and the Cochrane Library from inception through March 1, 2019, for studies which included real-world perspectives comparing the individual NOACs with each other or with warfarin among Asians with NVAF. The primary outcomes were defined as stroke or systemic embolism (SSE) and major bleeding; ischemic stroke, all-cause death as well as intracranial bleeding were classified as the secondary outcomes. Results From sixteen real-world studies, a total of 312,827 Asian patients were included in this analysis. In comparison with warfarin, the utilization of apixaban, dabigatran, and rivaroxaban significantly lowered the risk of major bleeding (apixaban: HR 0.47, 95%CI 0.35–0.63; dabigatran: HR 0.59, 95%CI 0.47–0.73; rivaroxaban: HR 0.66, 95%CI 0.52–0.83) and lessened the all-cause death rate (apixaban: HR 0.29, 95%CI 0.16–0.52; dabigatran: HR 0.40, 95%CI 0.27–0.60; rivaroxaban: HR 0.42, 95%CI 0.28–0.65). Apixaban (HR 0.59; 95%CI 0.40–0.85) reduced the possibility of ischemic stroke when compared against dabigatran. Rivaroxaban showed a higher chance of causing an ischemic stroke (HR 1.61; 95%CI 1.08–2.41) and major bleeding (HR 1.39; 95%CI 1.02–1.90) than Apixaban. Conclusions Apixaban, dabigatran and rivaroxaban were more effective than warfarin on reducing the risks of stroke and haemorrhage; meanwhile, apixaban was likely to lower the risk of major bleeding comparing to rivaroxaban. Trial registration PROSPERO registry number: CRD42018086914.

Background: Thymosin alpha-1 (TA) has been reported to inhibit tumor growth as an immunomodulator. However, its mechanism of action in immunosuppressive cells is unclear. The purpose of this study was to investigate whether TA can reshape the immune microenvironment by inhibiting the function of myeloid-derived suppressor cells (MDSCs) in non-small cell lung carcinoma (NSCLC). Methods: The effects of TA on peripheral blood monocytic MDSCs (M-MDSCs) in patients with NSCLC and on the apoptosis and migration of M-MDSCs were studied. A mouse subcutaneous xenograft tumor model was constructed, and the effect of TA on M-MDSC migration was evaluated. Quantitative real-time PCR, Western blotting, flow cytometry and immunohistochemistry were used to examine the mechanism by which TA affects M-MDSCs. Results: TA not only promoted the apoptosis of M-MDSCs by reducing the Bcl-2/BAX ratio but also and more importantly inhibited the migration of MDSCs to the tumor microenvironment by suppressing the production of vascular endothelial growth factor (VEGF) through the downregulation of hypoxia-inducible factor (HIF)-1α in tumor cells. Conclusions: TA may have a novel antitumor effect mediated by decreasing M-MDSC accumulation in the tumor microenvironment through reduced VEGF production.

As a leading contributor to coronary artery disease (CAD) and stroke, atherosclerosis has become one of the major cardiovascular diseases (CVD) negatively impacting patients worldwide. The endothelial injury is considered to be the initial step of the development of atherosclerosis, resulting in immune cell migration and activation as well as inflammatory factor secretion, which further leads to acute and chronic inflammation. In addition, the inflammation and lipid accumulation at the lesions stimulate specific responses from different types of cells, contributing to the pathological progression of atherosclerosis. As a result, recent studies have focused on using molecular biological approaches such as gene editing and nanotechnology to mediate cellular response during atherosclerotic development for therapeutic purposes. In this review, we systematically discuss inflammatory pathogenesis during the development of atherosclerosis from a cellular level with a focus on the blood cells, including all types of immune cells, together with crucial cells within the blood vessel, such as smooth muscle cells and endothelial cells. In addition, the latest progression of molecular-cellular based therapy for atherosclerosis is also discussed. We hope this review article could be beneficial for the clinical management of atherosclerosis. [ABSTRACT FROM AUTHOR]