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Abstract Myofibroblast buildup and prostatic fibrosis play a crucial role in the development of benign prostatic hyperplasia (BPH). Treatments specifically targeting myofibroblasts could be a promising approach for treating BPH. Tadalafil, a phosphodiesterase type 5 (PDE5) inhibitor, holds the potential to intervene in this biological process. This study employs prostatic stromal fibroblasts to induce myofibroblast differentiation through TGFβ1 stimulation. As a result, tadalafil significantly inhibited prostatic stromal fibroblast proliferation and fibrosis process, compared to the control group. Furthermore, our transcriptome sequencing results revealed that tadalafil inhibited FGF9 secretion and simultaneously improved miR-3126-3p expression via TGFβ1 suppression. Overall, TGFβ1 can trigger pro-fibrotic signaling through miR-3126-3p in the prostatic stroma, and the use of tadalafil can inhibit this process.

Abstract Néel spin-orbit torque allows a charge current pulse to efficiently manipulate the Néel vector in antiferromagnets, which offers a unique opportunity for ultrahigh density information storage with high speed. However, the reciprocal process of Néel spin-orbit torque, the generation of ultrafast charge current in antiferromagnets has not been demonstrated. Here, we show the experimental observation of charge current generation in antiferromagnetic metallic Mn2Au thin films using ultrafast optical excitation. The ultrafast laser pulse excites antiferromagnetic magnons, resulting in instantaneous non-equilibrium spin polarization at the antiferromagnetic spin sublattices with broken spatial symmetry. Then the charge current is generated directly via spin-orbit fields at the two sublattices, which is termed as the reciprocal phenomenon of Néel spin-orbit torque, and the associated THz emission can be detected at room temperature. Besides the fundamental significance on the Onsager reciprocity, the observed magnonic charge current generation in antiferromagnet would advance the development of antiferromagnetic THz emitter.

Abstract Neural network force fields have significantly advanced ab initio atomistic simulations across diverse fields. However, their application in the realm of magnetic materials is still in its early stage due to challenges posed by the subtle magnetic energy landscape and the difficulty of obtaining training data. Here we introduce a data-efficient neural network architecture to represent density functional theory total energy, atomic forces, and magnetic forces as functions of atomic and magnetic structures. Our approach incorporates the principle of equivariance under the three-dimensional Euclidean group into the neural network model. Through systematic experiments on various systems, including monolayer magnets, curved nanotube magnets, and moiré-twisted bilayer magnets of CrI3, we showcase the method’s high efficiency and accuracy, as well as exceptional generalization ability. The work creates opportunities for exploring magnetic phenomena in large-scale materials systems.

Abstract Background Glioblastoma (GBM) is the most common malignant tumor of the central nervous system. It is an aggressive tumor characterized by rapid proliferation, diffuse tumor morphology, and poor prognosis. Unfortunately, current treatments, such as surgery, radiotherapy, and chemotherapy, are unable to achieve good outcomes. Therefore, there is an urgent need to explore new treatment targets. A detailed mechanistic exploration of the role of the nuclear pore transporter KPNB1 in GBM is lacking. This study demonstrated that KPNB1 regulated GBM progression through a transcription factor YBX1 to promote the expression of post-protrusion membrane protein NLGN3. This regulation was mediated by the deubiquitinating enzyme USP7. Methods A tissue microarray was used to measure the expression of KPNB1 and USP7 in glioma tissues. The effects of KPNB1 knockdown on the tumorigenic properties of glioma cells were characterized by colony formation assays, Transwell migration assay, EdU proliferation assays, CCK-8 viability assays, and apoptosis analysis using flow cytometry. Transcriptome sequencing identified NLGN3 as a downstream molecule that is regulated by KPNB1. Mass spectrometry and immunoprecipitation were performed to analyze the potential interaction between KPNB1 and YBX1. Moreover, the nuclear translocation of YBX1 was determined with nuclear-cytoplasmic fractionation and immunofluorescence staining, and chromatin immunoprecipitation assays were conducted to study DNA binding with YBX1. Ubiquitination assays were performed to determine the effects of USP7 on KPNB1 stability. The intracranial orthotopic tumor model was used to detect the efficacy in vivo. Results In this study, we found that the nuclear receptor KPNB1 was highly expressed in GBM and could mediate the nuclear translocation of macromolecules to promote GBM progression. Knockdown of KPNB1 inhibited the progression of GBM, both in vitro and in vivo. In addition, we found that KPNB1 could regulate the downstream expression of Neuroligin-3 (NLGN3) by mediating the nuclear import of transcription factor YBX1, which could bind to the NLGN3 promoter. NLGN3 was necessary and sufficient to promote glioma cell growth. Furthermore, we found that deubiquitinase USP7 played a critical role in stabilizing KPNB1 through deubiquitination. Knockdown of USP7 expression or inhibition of its activity could effectively impair GBM progression. In vivo experiments also demonstrated the promoting effects of USP7, KPNB1, and NLGN3 on GBM progression. Overall, our results suggested that KPNB1 stability was enhanced by USP7-mediated deubiquitination, and the overexpression of KPNB1 could promote GBM progression via the nuclear translocation of YBX1 and the subsequent increase in NLGN3 expression. Conclusion This study identified a novel and targetable USP7/KPNB1/YBX1/NLGN3 signaling axis in GBM cells.

Abstract Background The development of radioresistance seriously hinders the efficacy of radiotherapy in lung cancer. However, the underlying mechanisms by which radioresistance occurs are still incompletely understood. The N6-Methyladenosine (m6A) modification of RNA is involved in cancer progression, but its role in lung cancer radioresistance remains elusive. This study aimed to identify m6A regulators involved in lung cancer radiosensitivity and further explore the underlying mechanisms to identify therapeutic targets to overcome lung cancer radioresistance. Methods Bioinformatic mining was used to identify the m6A regulator IGF2BP2 involved in lung cancer radiosensitivity. Transcriptome sequencing was used to explore the downstream factors. Clonogenic survival assays, neutral comet assays, Rad51 foci formation assays, and Annexin V/propidium iodide assays were used to determine the significance of FBW7/IGF2BP2/SLC7A5 axis in lung cancer radioresistance. Chromatin immunoprecipitation (ChIP)-qPCR analyses, RNA immunoprecipitation (RIP) and methylated RNA immunoprecipitation (MeRIP)-qPCR analyses, RNA pull-down analyses, co-immunoprecipitation analyses, and ubiquitination assays were used to determine the feedback loop between IGF2BP2 and SLC7A5 and the regulatory effect of FBW7/GSK3β on IGF2BP2. Mice models and tissue microarrays were used to verify the effects in vivo. Results We identified IGF2BP2, an m6A “reader”, that is overexpressed in lung cancer and facilitates radioresistance. We showed that inhibition of IGF2BP2 impairs radioresistance in lung cancer both in vitro and in vivo. Furthermore, we found that IGF2BP2 enhances the stability and translation of SLC7A5 mRNA through m6A modification, resulting in enhanced SLC7A5-mediated transport of methionine to produce S-adenosylmethionine. This feeds back upon the IGF2BP2 promoter region by further increasing the trimethyl modification at lysine 4 of histone H3 (H3K4me3) level to upregulate IGF2BP2 expression. We demonstrated that this positive feedback loop between IGF2BP2 and SLC7A5 promotes lung cancer radioresistance through the AKT/mTOR pathway. Moreover, we found that the ubiquitin ligase FBW7 functions with GSK3β kinase to recognize and degrade IGF2BP2. Conclusions Collectively, our study revealed that the m6A “reader” IGF2BP2 promotes lung cancer radioresistance by forming a positive feedback loop with SLC7A5, suggesting that IGF2BP2 may be a potential therapeutic target to control radioresistance in lung cancer.

In this paper, we present a novel computational approach (named ACA-BM-SBM) for the calculation of 2D acoustic sensitivity by combining the Burton-Miller-type singular boundary method (BM-SBM) with the adaptive cross-approximation (ACA) algorithm. The BM-SBM circumvents the source singularities of the fundamental solutions by introducing the origin intensity factors, and it eliminates the fictitious frequency problem in external acoustic fields by introducing the Burton-Miller formula. As a semi-analysis meshless method, the BM-SBM can accurately solve the external acoustic problem governed by the Helmholtz equation. Nevertheless, the computational inefficiency introduced by the dense coefficient matrix renders this method suboptimal, particularly for large-scale simulations. As the number of nodes increases, the computation time and store memory increase dramatically. ACA is a purely algebraic method based on hierarchical matrices which can be used to partition the coefficient matrix step by step. By employing ACA, the BM-SBM can be effectively accelerated, and this results in less computation time, as well as fewer memory requirements. Numerical experiments, including Dirichlet and Neumann boundary conditions, illustrate that the proposed approach is an accurate, efficient and fast numerical method for acoustic sensitivity analysis.

Incorporating renewable energy sources into the grid poses challenges due to their volatility and uncertainty in optimizing dispatch strategies. In response, this article proposes a cloud–edge collaborative scheduling strategy for distributed multi-energy systems, operating across various time scales. The strategy integrates day-ahead dispatch, intra-day optimization, and real-time adjustments to minimize operational costs, reduce the wastage of renewable energy, and enhance overall system reliability. Furthermore, the cloud–edge collaborative framework helps mitigate scalability challenges. Crucially, the strategy considers the multi-timescale characteristics of two types of energy storage systems (ESSs) and three types of demand response (DR), aimed at optimizing resource allocation efficiently. Comparative simulation results evaluate the strategy, providing insights into the significant impacts of different ESS and DR types on system performance. By offering a comprehensive approach, this strategy aims to address operational complexities. It aims to contribute to the seamless integration of renewable energy into distributed systems, potentially enhancing sustainability and resilience in energy management.

Over recent years, thermoplastic polyurethane (TPU) has been widely used as a substrate material for flexible strain sensors due to its remarkable mechanical flexibility and the ease of combining various conductive materials by electrospinning. Many research advances have been made in the preparation of flexible strain sensors with better ductility, higher sensitivity, and wider sensing range by using TPU in combination with various conductive materials through electrospinning. However, there is a lack of reviews that provide a systematic and comprehensive summary and outlook of recent research advances in this area. In this review paper, the working principles of strain sensors and electrospinning technology are initially described. Subsequently, recent advances in strain sensors based on electrospun TPU are tracked and discussed, with a focus on the incorporation of various conductive fillers such as carbonaceous materials, MXene, metallic materials, and conductive polymers. Moreover, the wide range of applications of electrospun TPU flexible strain sensors is thoroughly discussed. Finally, the future prospects and challenges of electrospun TPU flexible strain sensors in various fields are pointed out.

This paper presents a new framework for efficient and accurate analysis of transient elastodynamic cracks by using the generalized finite difference method (GFDM). The method first discretizes the solution domain into a set of overlapping small subdomains, and then in each of the subdomains, the unknown functions and their derivatives are approximated by using the local Taylor series expansions and moving-least square approximation. The degree of the Taylor series used in the local subdomain is increased automatically in the regions near the crack-tips, in order to appropriately describe the local asymptotic behavior of near-tip displacement and stress fields. The path-independent J-integral and sub-domain technique are adopted to compute the dynamic stress intensity factors (SIFs) of the cracked bodies. Preliminary numerical experiments for dynamic SIFs with both uniform and variable loading conditions are given to show the efficient and accuracy of the present method for transient elastodynamic crack analysis.

Robots play a critical role as the physical agent of human operators in exploring the ocean. However, it remains challenging to grasp objects reliably while fully submerging under a highly pressurized aquatic environment with little visible light, mainly due to the fluidic interference on the tactile mechanics between the finger and object surfaces. This study investigates the transferability of grasping knowledge from on‐land to underwater via a vision‐based soft robotic finger that learns 6D forces and torques (FT) using a supervised variational autoencoder (SVAE). A high‐framerate camera captures the whole‐body deformations while a soft robotic finger interacts with physical objects on‐land and underwater. Results show that the trained SVAE model learns a series of latent representations of the soft mechanics transferable from land to water, presenting a superior adaptation to the changing environments against commercial FT sensors. Soft, delicate, and reactive grasping enabled by tactile intelligence enhances the gripper's underwater interaction with improved reliability and robustness at a much‐reduced cost, paving the path for learning‐based intelligent grasping to support fundamental scientific discoveries in environmental and ocean research.

Abstract The mantle plumes modify geophysical and geochemical features along and across mid‐ocean ridges. Despite abundant studies of plume‐ridge interaction, few geodynamic studies focus on the Arctic Ocean. The Jan Mayen Hotspot is located at the southern end of the Mohns Ridge and offset by the Jan Mayen Transform Fault, which creates an ideal area to study plume‐ridge‐transform fault interaction at the ultra‐slow spreading ridge. Through analyzing geophysical observations, we revealed that the M factor and crustal thickness decrease and the axial relief increases northeastward along the Mohns Ridge within a distance of ∼370 km to the Jan Mayen Hotspot. Combined with modeling results, the properties of the Jan Mayen plume were estimated, which has a diameter of 75 km, a temperature anomaly of 100°C, and a buoyancy flux of 0.22 Mg/s. Additionally, our model results indicate that the along‐ridge dispersion of plume is slightly enhanced by the transform fault.

Our previous studies have demonstrated that human papillomavirus (HPV)-16 E7 oncoprotein promoted epithelial-mesenchymal transition (EMT) in non-small cell lung cancer (NSCLC) cells. Moreover, recent studies have found that exosomes can mediate EMT of NSCLC cells and epidermal growth factor receptor (EGFR) is related to the progression of NSCLC. Here, we further investigated the role of exosomal EGFR in HPV-16 E7-induced EMT of NSCLC cells. Our results showed that the exosomes derived from the stable HPV-16 E7-overexpressing A549 and NCI-H460 NSCLC cells (E7 Exo) significantly increased migration, invasion, and proliferation abilities of NSCLC cells as compared with the exosomes derived from empty vector-infected NSCLC cells (ev Exo). Moreover, both in vitro and in vivo results demonstrated that E7 Exo dramatically enhanced EMT of NSCLC cells and promoted the growth of subcutaneous NSCLC xenografts. Additionally, HPV-16 E7 enhanced the expression of EGFR and p-EGFR in both NSCLC cells and exosomes. Furthermore, the inhibition of EGFR activation or exosome secretion suppressed E7 Exo-induced migration, invasion, and EMT of NSCLC. Moreover, 12 kinds of differentially expressed miRNAs between E7 Exo and ev Exo (fold change≥2, P ≤ .05) were screened out, of which 7 miRNAs were up-regulated while 5 miRNAs were down-regulated in A549 E7 Exo. Taken together, our findings suggest that exosomal EGFR is involved in HPV-16 E7-induced EMT of NSCLC cells, which may play a key role in the progression of HPV-related NSCLC.

Abstract Scientific planning, digital management of construction and intelligent service are needed for a smart city. This paper focusses on city management based on the smart information system and digital technologies in China. The establishment of the smart intercommunication system of landscape, water conservancy, environmental protection and other industries is basic for a smart city. This paper introduced a framework of digital technologies for the construction of a smart city, which made full use of the city information modelling based on the geographic information system, building information modelling, internet of things, and integrated digital system and service platform such as satellite remote sensing, global navigation satellite system, mobile applications, cloud computing, visualisation technology etc. The study of the case implemented show that the framework is applicable to the smart city with digital technologies that includes the data model and system, integrating the urban basic geographic data, and data of infrastructure and other public facilities related to traffic, urban construction, ‘One Map’ of land and resources etc. The governance is more effective through data acquisition, data transmission, data analysis and processing based on the data platform and system.

Objective: This study aimed to evaluate the safety, efficacy, and feasibility of the rituximab, fotemustine, pemetrexed, and dexamethasone (R-FPD) regimen followed by whole-brain radiotherapy (WBRT) for patients with primary central nervous system lymphoma (PCNSL). Methods: A prospective, single-center phase II clinical trial was conducted. Patients with PCNSL newly diagnosed at the First Affiliated Hospital of Zhengzhou University between July 2018 and July 2020 were studied. The R-FPD regimen consisted of rituximab (375 mg/m2 i.v. on D0), fotemustine (100 mg/m2 i.v. on D1), pemetrexed (600 mg/m2 i.v. on D1), and dexamethasone (40 mg i.v. on D1-5). Patients 60 years or younger who showed a complete response (CR) were treated with 23.4 Gy of WBRT after the end of chemotherapy; those older than 60 years with CR were treated with a wait-and-see approach; and those who did not show CR after the 4th cycle of chemotherapy were given salvage WBRT 30 Gy + local tumor field irradiation up to 45 Gy, regardless of age. Results: A total of 30 patients were included. After 2 cycles, the objective response rate (ORR) was 96.5% (28/29, 1 CR, 27 PR, 0 SD, and 1 PD). After 4 cycles, the ORR was 73.1% (19/26, 11 CR, 8 PR, 4 SD, and 3 PD). After WBRT, the ORR was 90.9% (10/11, 7 CR, 3 PR, and 1 SD). The grade III and IV toxicity responses were mainly leukopenia (20.0%), thrombocytopenia (23.3%), and anemia (10.0%). Conclusions: Fotemustine-based therapy in combination with rituximab chemotherapy followed by WBRT can improve outcomes, providing ORR benefits and favorable tolerability in patients newly diagnosed with PCNSL.

Background Massive or repeated intestinal resections for Crohn’s disease (CD) could lead to disabling consequences. The present study aimed to assess the effect of preoperative anti-TNF therapy on the length of resected bowel and identify risk factors for postoperative morbidity following ileocolic resection for CD. Methods Patients undergoing elective ileocolic resection for CD were included prospectively. Medical variables including demographics, Montréal classification, preoperative treatment, surgical details and 30-day postoperative morbidity were collected. Potential impact of preoperative anti-TNF treatment on length of ileocolic specimen and risk factors for postoperative morbidity were investigated. Results One hundred and eight-four patients were included in this study, and 66 (35.9%) of them received anti-TNF agents within 8 weeks prior to surgery. Primary anastomosis was performed in 145 patients (78.8%). The mean length of resected intestine was 10 cm shorter in subjects receiving preoperative anti-TNF treatment than those without preoperative anti-TNF therapy (P

Ferromagnet/spacer/ferromagnet sandwiches have been studied extensively, and used in a variety of spintronic devices. Here, Zhou et al. create an all anti-ferromagnetic sandwich of Fe2O3/Cr2O3/Fe2O3, and demonstrate strong orthogonal coupling between the top and bottom Fe2O3 layers.

BackgroundThe rapid growth of publications on the gut microbiome and colorectal cancer (CRC) makes it feasible for text mining and bibliometric analysis.MethodsPublications were retrieved from the Web of Science. Bioinformatics analysis was performed, and a machine learning-based Latent Dirichlet Allocation (LDA) model was used to identify the subfield research topics.ResultsA total of 5,696 publications related to the gut microbiome and CRC were retrieved from the Web of Science Core Collection from 2000 to 2022. China and the USA were the most productive countries. The top 25 references, institutions, and authors with the strongest citation bursts were identified. Abstracts from all 5,696 publications were extracted for a text mining analysis that identified the top 50 topics in this field with increasing interest. The colitis animal model, expression of cytokines, microbiome sequencing and 16s, microbiome composition and dysbiosis, and cell growth inhibition were increasingly noticed during the last two years. The 50 most intensively investigated topics were identified and further categorized into four clusters, including “microbiome sequencing and tumor,” “microbiome compositions, interactions, and treatment,” “microbiome molecular features and mechanisms,” and “microbiome and metabolism.”ConclusionThis bibliometric analysis explores the historical research tendencies in the gut microbiome and CRC and identifies specific topics of increasing interest. The developmental trajectory, along with the noticeable research topics characterized by this analysis, will contribute to the future direction of research in CRC and its clinical translation.

Gut microbiota represents a hidden treasure vault encompassing trillions of microorganisms that inhabit the intestinal epithelial barrier of the host. In the past decade, numerous in-vitro, animal and clinical studies have revealed the profound roles of gut microbiota in maintaining the homeostasis of various physiological functions, especially immune modulation, and remarkable differences in the configuration of microbial communities between cancers and healthy individuals. In addition, although considerable efforts have been devoted to cancer treatments, there remain many patients succumb to their disease with the incremental cancer burden worldwide. Nevertheless, compared with the stability of human genome, the plasticity of gut microbiota renders it a promising opportunity for individualized treatment. Meanwhile, burgeoning findings indicate that gut microbiota is involved in close interactions with the outcomes of diverse cancer immunotherapy protocols, including immune checkpoint blockade therapy, allogeneic hematopoietic stem cell transplantation, and chimeric antigen receptor T cell therapy. Here, we reviewed the evidence for the capacity of gut microflora to modulate cancer immunotherapies, and highlighted the opportunities of microbiota-based prognostic prediction, as well as microbiotherapy by targeting the microflora to potentiate anticancer efficacy while attenuating toxicity, which will be pivotal to the development of personalized cancer treatment strategies.

Lightweight composites consisting of 6063 aluminum alloy matrix reinforced with AlCoCrFeNi high-entropy alloy (HEA) particles were fabricated by the powder metallurgy through hot pressing and hot extrusion under vacuum. A detailed microstructural characterization was carried out along with the analysis of mechanical properties. The results revealed that the observed uniform distribution of HEA powders and a good bonding strength resulted in an effective strengthening and increased plastic strain of the reinforced composite. The tensile properties of composites were effectively improved by the addition of 10 and 30 vol % of reinforcing HEA particles.

Abstract Metal ions have been identified as important bone metabolism regulators and widely used in the field of bone tissue engineering, however their exact role during bone regeneration remains unclear. Herein, the aim of study was to comprehensively explore the interactions between osteoinductive and osteo-immunomodulatory properties of these metal ions. In particular, the osteoinductive role of zinc ions (Zn2+), as well as its interactions with local immune microenvironment during bone healing process, was investigated in this study using a sustained Zn2+ delivery system incorporating Zn2+ into β-tricalcium phosphate/poly(L-lactic acid) (TCP/PLLA) scaffolds. The presence of Zn2+ largely enhanced osteogenic differentiation of periosteum-derived progenitor cells (PDPCs), which was coincident with increased transition from M1 to M2 macrophages (M $$\varphi $$ φ s). We further confirmed that induction of M2 polarization by Zn2+ was realized via PI3K/Akt/mTOR pathway, whereas marker molecules on this pathway were strictly regulated by the addition of Zn2+. Synergically, this favorable immunomodulatory effect of Zn2+ further improved the osteogenic differentiation of PDPCs induced by Zn2+ in vitro. Consistently, the spontaneous osteogenesis and pro-healing osteoimmunomodulation of the scaffolds were thoroughly identified in vivo using a rat air pouch model and a calvarial critical-size defect model. Taken together, Zn2+-releasing bioactive ceramics could be ideal scaffolds in bone tissue engineering due to their reciprocal interactions between osteoinductive and immunomodulatory characteristics. Clarification of this synergic role of Zn2+ during osteogenesis could pave the way to develop more sophisticated metal-ion based orthopedic therapeutic strategies.

Abstract Steel fibre (SF) reinforcement has been shown to improve the ductility of high strength concrete (HSC), which is known to be brittle. Research conducted to date on steel fibre reinforced concrete and its effects have emphasised post-failure performance and cracking mechanism. The difficulty in predicting the behaviour of fibres is due to the randomly distributed nature of the material within the matrix leading to a probability distribution of results. Published literature has shown a benefit of adding steel fibres in terms of the ductility performance of structures. Clearly, there is a potential for such material as replacement of conventional steel reinforcement. This study proposes a theoretical model of evaluating the potential of using steel fibres as a replacement material to conventional steel reinforcement bars based on the case study, laboratory and theoretical methodologies. The compressive strength of the concrete at key dates, the effective fibre cross-sectional were measured, and a prediction model was created based on the measurement parameters. The use of four-point flexural testing, standard compressive testing and software image modelling provided the study with relevant data used to analyse and compare to the prediction. Greater ductility performance and toughness were observed with increased fibre volumes, confirming proposed predictions and conclusion drawn from published literature. No consistent or conclusive correlations between fibre volumes and the compressive strength of concrete were found. A relationship between fibre volumes and predicted moment capacities of steel fibre reinforced concrete beams was found based on the proposed theoretical flexural analysis method.

Abstract NK/T cell lymphoma (NKTCL) represents an aggressive lymphoid malignancy characterized by dismal prognosis. Immune-checkpoint blockade has shown promising efficacy in NKTCL. However, the molecular mechanisms underlying immune evasion in NKTCL have never been explored. Here, proteomic analysis was used to identify the differentially expressed proteins between NKTCL patients and healthy individuals. We found that S100A9, an immunosuppressive molecule, was much higher in NKTCL patients both in serum and tumor stroma. Elevated level of S100A9 was associated with advanced stage, poor overall response and early recurrence. Moreover, percentage of myeloid-derived suppressor cells (MDSCs) in peripheral blood was positively correlated with levels of S100A9. Low concentration of S100A9 promoted proliferation of NKTCL cells, while did not affect cell apoptosis and cell cycles. Furthermore, programmed death ligand 1 (PD-L1) expression on NKTCL cells was up-regulated by S100A9 through activation of ERK1/2 signaling. Inhibition of ERK1/2 signaling significantly decreased tumor growth and PD-L1 expression induced by S100A9. In conclusion, our research firstly identified S100A9 as an immune suppressor in the tumorigenesis of NKTCL via accumulation of MDSCs and upregulation of PD-L1 expression. S100A9 may serve as a potential target to increase the efficacy of immunotherapy in NKTCL.

Numerous studies explored the therapeutic effects of erythropoietin (EPO) on neurodegenerative diseases. Few studies provided comprehensive and latest knowledge of EPO treatment for ischemic stroke. In the present review, we introduced the structure, expression, function of EPO, and its receptors in the central nervous system. Furthermore, we comprehensively discussed EPO treatment in pre-clinical studies, clinical trials, and its therapeutic mechanisms including suppressing inflammation. Finally, advanced studies of the therapy of EPO derivatives in ischemic stroke were also discussed. We wish to provide valuable information on EPO and EPO derivatives’ treatment for ischemic stroke for basic researchers and clinicians to accelerate the process of their clinical applications.

Oceanic transform faults (TFs) are commonly viewed as single, narrow strike-slip seismic faults that offset two mid-ocean ridge segments. However, broad zones of complex deformation are ubiquitous at TFs. Here, we propose a new conceptual model for the progressive deformation within broad zones at oceanic TFs through detailed morphological, seismic, and stress analyses. We argue that, under across-transform extension due to a change in plate motion, plate deformation occurs first along high-angle transtensional faults (TTFs) within the transform valleys. Off-transform normal faults (ONFs) form when across-transform deviatoric extensional stresses exceed the yield strength of the adjacent oceanic lithosphere. With further extension, these normal faults can develop into off-transform rift zones (ORZs), some of which can further develop into transform plate boundaries. We illustrate that such progressive complex deformation is an inherent feature of oceanic TFs. The new conceptual model provides a unifying theory to explain the observed broad deformation at global transform systems.

In two-dimensional semiconductors, light can generate spin polarisations, however this effect is typically limited to low temperatures. By combining Lead Iodide (PbI2) with transition metal dichalcogenides (TMDCs), the authors demonstrate room temperature light induced near-unity spin polarisations.

Traditional centralized access control has some shortcomings in robustness, trustworthiness and circulation. Blockchains have the advantages of fault tolerance and trust. Smart contracts have the characteristics of automatic execution and flexible expansion. Tokens can well record credential information and transfer easily. In this paper, blockchain, smart contract and token are integrated and applied to access control to solve the shortcomings of traditional access control. First, access control, blockchain, smart contract and token are briefly described. Second, this paper proposes a solution by giving the general data structure of access control token, elaborating the equivalence, split, merge and verification algorithms of access control token, and explaining the system architecture of token-based access control. Last, this paper uses a token-based access control simulation system to verify that token-based access control has certain comparative advantages in robustness, trustworthiness, circulation, concurrency and so on.

Older adults want to remain independent with dignity for as long as possible, especially the solitary older adults. Activity recognition plays an essential role in elderly care and rehabilitation by detecting activity shifts among the elderly population. Despite over a decade of research and development in activity recognition, accurate and reliable systems for older adults in use are few. We propose an automatic data collecting and labeling system by addressing the annotation issue, and a novel coarse-to-fine activities of daily living(ADLs) recognition algorithm for older adults, by combining supervised and unsupervised machine learning methods. The automatic data collecting and labeling system targets at the annotation issue caused by the diversity of ADLs in free-living situations. Multiple sensors fusion strategy is employed to interpret and annotate the ADLs. Leveraging supervised and unsupervised machine learning methods, we can discover and recognize ambulatory and trivial ADLS for older adults. The performance of the automatic data collecting and labeling system is double-checked in a four days long test. With the reliable ground truth, we evaluate the coarse-to-fine ADLs recognition algorithm. The performance of our algorithm is promising, the recognition accuracy is larger than 91%.

Background: Gastric signet ring cell carcinoma (GSRCC) is a subset of gastric cancer with distinct histological and inconsistent prognosis outcome. Currently, the association between the adequate regional lymph node and proper nodal staging in GSRCC is rarely noticed. Materials and methods: Clinical data of GSRCC were retrieved from the Surveillance, Epidemiology, and End Results database. Beta-binomial distribution model was employed for the estimation of the probability of missing nodal disease, followed by the development of a nodal staging score (NSS). Results: A total of 561 GSRCC patients were included in this study, with 193 in lymph node-negative and 368 in lymph node-positive diagnoses. As the number of examined lymph nodes increased, the probability of missing nodal disease decreased rapidly, with T stage-specific curves. The probability of missing nodal disease in T4 was lower than that in T1. NSS calculation indicated that T1 stage patients commonly had NSS > 0.8. However, with the NSS of T2–T4 to reach 0.8, the number of examined lymph node was required to be larger than 12 in T2, 17 in T3 and 27 in T4. NSS ≥ 0.75 (quantile 75%) subgroup in T2–T4 subgroups tended to have better outcome; however, without significant prognostic value. Conclusions: NSS is served as a reliable and feasible tool in adequate nodal staging of GSRCC with statistical basis and provides further evidence for clinical decision making.

Natural killer/T cell lymphoma (NKTCL) is a rare and aggressive disease. Here, the authors identify recurrent somatic mutations of GNAQ in NKTCL, and model how this mutation contributes to NKTCL pathogenesis.

Aim: To compare the outcomes of GDPT [gemcitabine (G), cisplatin (D), prednisone (P), thalidomide (T)] versus CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) in treating newly diagnosed PTCL (peripheral T-cell lymphoma). Methods: An open-label prospective clinical trial with 153 newly diagnosed PTCL patients conducted between January 2010 and December 2018 was designed. Patients were randomly assigned to the GDPT (77 cases) and CHOP (76 cases) groups. Patients in each group were further divided into four subgroups: PTCL, not otherwise specified (PTCL-NOS); anaplastic large cell lymphoma (ALCL), angioimmunoblastic T cell lymphoma (AITL), and other types subgroup, in accordance with pathological patterns. Based on expression of RRM1, TOP2A, TUBB3 , and ERCC1 , patients were divided into groups with high and low gene expression levels. Clinical characteristics, side effects, efficacy, progression-free survival (PFS), and overall survival (OS) were compared. Results: There were no significant differences in the basic clinical features or side effects between the GDPT and CHOP groups. The overall response rate (ORR) of the GDPT group was better than that of the CHOP group (66.3% versus 50.0%, p = 0.042), as was the complete remission (CR) rate (42.9% versus 27.6%, p = 0.049). Patients in the GDPT group had a longer PFS and OS than the CHOP group. The 4-year PFS and OS rates in the GDPT group were both superior to those in the CHOP group (63.6% versus 53.0% for PFS, p = 0.035; 66.8% versus 53.6% for OS, p = 0.039). In the GDPT group, the difference in CR between the four subgroups was statistically significant ( p = 0.046). In the CHOP group, differences in both CR and ORR among the four subgroups were statistically significant ( p

Abstract Background Indoleamine 2,3-dioxygenase 1 (IDO1) catalyzes the first and rate-limiting step in converting tryptophan to kynurenine. Chimeric antigen receptor (CAR) T cells are T cells with recombinant receptors targeting tumor-associated antigens. The Food and Drug Administration has approved CAR T cells that target CD19 for treatment of advanced B cell leukemia and lymphoma. However, CAR T cell therapy in solid tumors has been hampered by multiple obstacles. Preclinical and clinical studies suggest that combinatorial immune checkpoint blockade and IDO1 inhibition provide durable therapeutic efficacy against cancer. Yet, the combination of IDO1 inhibition and CAR T has not been attempted. Methods We analyze IDO1 downregulation by miR-153 in colon cancer cells and the association of IDO1 and miR-153 expression with colorectal patient survival. We generate CAR T cells targeting the epidermal growth factor receptor variant III and measure their tumor killing effects against colon cancer cells with or without miR-153 overexpression by killing assays and in xenografts. Results IDO1 is highly expressed in colorectal tumors and is inversely associated with patient survival. miR-153 directly inhibits IDO1 expression by targeting its 3′ untranslated region in colon cancer cells; yet, miR-153 overexpression does not affect cancer cell survival, apoptosis, and colony formation. When colon cancer cells are targeted by CAR T cells, miR-153 overexpression within tumor cells significantly enhances T cell killing in vitro and suppresses xenograft tumor growth in mice. Conclusions These findings indicate that miR-153 inhibits IDO1 expression in colon cancer cells and is a tumor-suppressive miRNA that enhances CAR T cell immunotherapy. This study supports the combinatorial use of IDO1 inhibitors and CAR T cells in treating solid tumors.

ABSTRACT PURPOSE To evaluate the safety and efficacy of a new mesh in the pre-peritoneal repair of inguinal hernia. METHODS We randomly divided 120 patients undergoing pre-peritoneal repair into 2 groups between March 2012 and December 2013. The patients were randomized to receive the Swing mesh (n=60; study group) or the Modified Kugel mesh (n=60; control group). The primary end point of this study was to compare postoperative groin pain of the two groups. Complications, recurrence and analgesic use were also recorded. RESULTS There were no recurrent cases in either group throughout the study period. There was no significant difference between the groups with respect to postoperative complications. The VAS of early postoperative pain was 1.32±1.69 in study group and 1.52±1.93 in control group, with the difference being not statistically significant (p = 0.547). Concerning chronic pain, no remarkable statistically significant difference was observed between the two groups at 3-month, 6-month, 12- and 18-month follow-up period. CONCLUSION Swing mesh can be safely and effectively used in inguinal hernia repair with the same advantage compared to the Modified Kugel mesh.

The aircraft hydraulic system is very important for the actuation system and its failure has led to a number of catastrophic accidents in the past few years. The reasons for hydraulic loss can be leakage, blockage, and structural damage. Fortunately, the development of more electric aircraft (MEA) provides a new means of solving this difficult problem. This paper designs an active fault tolerant control (AFTC) method for MEA suffering from total hydraulic loss and actuation system failure. Two different kinds of scenarios are considered: leakage/blockage and vertical tail damage. With the application of the dissimilar redundant actuation system (DRAS) in MEA, a switching mechanism can be used to change the hydraulic actuation (HA) system into an electro-hydrostatic actuation (EHA) system when the whole hydraulic system fails. Taking account of the gap between HA and EHA, a degraded model is built. As for vertical tail damage, engine differential thrust control is adopted to help regain lateral-directional stability. The engine thrust dynamics are modeled and the mapping relationship between engine differential thrust and rudder deflection is formulated. Moreover, model reference control (MRC) and linear quadratic regulator (LQR) are used to design the AFTC method. Comparative simulation with the NASA generic transportation model (GTM) is carried out to prove the proposed strategy.

Aim: The aim of this study was to observe the possible change of microRNAs (miRNAs) in serum extracellular vesicles (EVs) from hepatocellular carcinoma (HCC) patients.Methods: The serum EVs were purified from 17 healthy donors, 16 chronic hepatitis B (CHB) patients and 24 HCC patients. The sequenced microRNAs in the purified EVs were analyzed to obtain highly differentially expressed genes (DEGs). Finally, the expression pattern of DEGs was validated using qRT-PCR.Results: We found that the expression of hsa-miR-21-5p and hsa-miR-144-3p were significantly higher in EVs and liver cancer tissues compared with serum and the distal liver tissues in HCC patients. The ratio of hsa-miR-144-3p/hsa-miR-21-5p was significantly decreased in the patients with CHB but significantly increased in patients with HCC developed from CHB (P < 0.05). Hsa-144-3p/hsa-miR-21-5p exhibited greater performance than alpha-fetoprotein (AUC 0.780, 95% CI 0.601–0.960, versus AUC 0.626, 95% CI 0.410–0.843) in ROC curve analysis.Conclusion: Extracellular vesicle-associated hsa-miR-21-5p and hsa-miR-144-3p are markedly elevated in serum of patients with HCC. The potential role of these microRNAs in the pathogenesis of HCC is worth of further study.

To address sustainability issues by facilitating the use of high-volume fly ash (HVFA) concrete in industry, this paper investigates the early age hydration properties of HVFA binders in concrete and the correlation between hydration properties and compressive strengths of the cement pastes. A new method of calculating the chemically bound water of HVFA binders was used and validated. Fly ash (FA) types used in this study were sourced from Indonesia and Australia for comparison. The water to binder (w/b) ratio was 0.4 and FA replacement levels were 40%, 50% and 60% by weight. Isothermal calorimetry tests were conducted to study the heat of hydration which was further converted to the adiabatic temperature rise. Thermo-gravimetric analysis (TGA) was employed to explore the chemically bound water (WB) of the binders. The results showed that Australian FA pastes had higher heat of hydration, adiabatic temperature rise, WB and compressive strength compared to Indonesian FA pastes. The new method of calculating chemically bound water can be successfully applied to HVFA binders. Linear correlation could be found between the WB and compressive strength.

We here evaluated the potential anti-colorectal cancer activity by erastin, a voltage-dependent anion channel (VDAC)-binding compound. Our in vitro studies showed that erastin exerted potent cytotoxic effects against multiple human colorectal cancer cell lines, possibly via inducing oxidative stress and caspase-9 dependent cell apoptosis. Further, mitochondrial permeability transition pore (mPTP) opening was observed in erastin-treated cancer cells, which was evidenced by VDAC-1 and cyclophilin-D (Cyp-D) association, mitochondrial depolarization, and cytochrome C release. Caspase inhibitors, the ROS scavenger MnTBAP, and mPTP blockers (sanglifehrin A, cyclosporin A and bongkrekic acid), as well as shRNA-mediated knockdown of VDAC-1, all significantly attenuated erastin-induced cytotoxicity and apoptosis in colorectal cancer cells. On the other hand, over-expression of VDAC-1 augmented erastin-induced ROS production, mPTP opening, and colorectal cancer cell apoptosis. In vivo studies showed that intraperitoneal injection of erastin at well-tolerated doses dramatically inhibited HT-29 xenograft growth in severe combined immunodeficient (SCID) mice. Together, these results demonstrate that erastin is cytotoxic and pro-apoptotic to colorectal cancer cells. Erastin may be further investigated as a novel anti-colorectal cancer agent.

It has been reported that backward surface waves of Tamm state can be supported by a multilayered metal–dielectric metamaterial with different partner materials, such as left-handed metamaterial or dissimilar metallic–dielectric metamaterial. In this paper, the transfer-matrix method is employed to reveal that transverse-magnetic (TM)-polarized backward surface waves can be realized by a multilayered metal–dielectric metamaterial in contact with a conventional homogenous dielectric medium. Owing to the strong optical nonlocality, the existence of such backward surface waves is proved to be dependent on the order of the metallic/dielectric layers. The relevant anomalous dispersion relations can also be dramatically engineered by varying the unit-cell thickness and the filling factor. Additionally, the distribution of the energy flow is presented to further unfold the physical mechanism of the backward surface waves. Finally, a numerical simulation of backward surface wave excited by a TM-polarized Gaussian beam based on a prism-coupled configuration is displayed.

The original article [1] contains a spelling error in the authorship; the authors would like to note the correct spelling of the second author, Jiajia Xi.