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Exploring materials with multiple properties who can endow a simple device with integrated functionalities has attracted enormous attention in the microelectronic field. One reason is the imperious demand for processors with continuously higher performance and totally new architecture. Combining ferroelectric with semiconducting properties is a promising solution. Here, we show that logic, in-memory computing, and optoelectrical logic and non-volatile computing functionalities can be integrated into a single transistor with ferroelectric semiconducting α-In2Se3 as the channel. Two-input AND, OR, and non-volatile NOR and NAND logic operations with current on/off ratios reaching up to five orders, good endurance (1000 operation cycles), and fast operating speed (10 μs) are realized. In addition, optoelectrical OR logic and non-volatile implication (IMP) operations, as well as ternary-input optoelectrical logic and in-memory computing functions are achieved by introducing light as an additional input signal. Our work highlights the potential of integrating complex logic functions and new-type computing into a simple device based on emerging ferroelectric semiconductors.

Purpose This study aims to develop a new method to treat the numerical singularity at the critical nodes of two skew coordinates, and optimize the leakage of micro herringbone grooved journal bearings (MHGJBs) with this method. Design/methodology/approach A side leakage numerical algorithm is proposed by using the skew meshes with a virtual node (SMVN) method to evaluate the effects of groove angle, bank/groove ratio, groove depth and groove number on load capacity, friction and side leakage of MHGJB. Findings The SMVN method is effective in treating the numerical singularity at the critical nodes of two skew coordinates. Besides, a group of optimized parameters of micro herringbone groove is obtained which can not only minimize the side leakage but also improve the load capacity and friction force. Originality/value A virtual node method was proposed, which can significantly improve the calculation accuracy in the side leakage model.

Introduction Although hyperkalemia and metabolic acidosis often co-occur in patients with chronic kidney disease (CKD), the prevalence of metabolic acidosis among patients with CKD and hyperkalemia is understudied. Therefore, we used medical record data from the Research Action for Health Network to estimate this prevalence. Methods Adult patients with CKD stage 3–5, ≥ 1 outpatient potassium value > 5.0 mEq/l, and ≥ 1 outpatient bicarbonate value available were identified. Patients with end stage kidney disease (ESKD) in the prior year were excluded. The prevalence of metabolic acidosis in each calendar year from 2014 to 2017 among patients with CKD and hyperkalemia was estimated using two definitions of hyperkalemia (potassium > 5.0 mEq/l and > 5.5 mEq/l) and metabolic acidosis (bicarbonate 5.0 mEq/l and ranged from 33 to 39% when hyperkalemia was defined by potassium > 5.5 mEq/l. Conclusion Results demonstrated that prevalence estimates of metabolic acidosis varied based on the definition of hyperkalemia and metabolic acidosis utilized.

Cardiac coronary angiography is a major technique that assists physicians during interventional heart surgery. Under X-ray irradiation, the physician injects a contrast agent through a catheter and determines the coronary arteries’ state in real time. However, to obtain a more accurate state of the coronary arteries, physicians need to increase the frequency and intensity of X-ray exposure, which will inevitably increase the potential for harm to both the patient and the surgeon. In the work reported here, we use advanced deep learning algorithms to find a method of frame interpolation for coronary angiography videos that reduces the frequency of X-ray exposure by reducing the frame rate of the coronary angiography video, thereby reducing X-ray-induced damage to physicians. We established a new coronary angiography image group dataset containing 95,039 groups of images extracted from 31 videos. Each group includes three consecutive images, which are used to train the video interpolation network model. We apply six popular frame interpolation methods to this dataset to confirm that the video frame interpolation technology can reduce the video frame rate and reduce exposure of physicians to X-rays.

It has been demonstrated that neural precursor cell expressed developmentally downregulated protein (NEDD) plays crucial roles in tumorigenesis and may serve as potential biomarkers in cancer diagnosis and prognosis. However, few studies systematically investigated the expression of NEDD family members in acute myeloid leukaemia (AML). We systemically determined the expression of NEDD family members in AML and determined their clinical significance. We identified that NEDD9 expression was the only member among NEDD family which was significantly increased in AML. NEDD9 overexpression was more frequently classified as FAB‐M4/M5 (p = 0.008 and 0.013, respectively), hardly as FAB‐M2/M3. Moreover, NEDD9 overexpression was significantly associated with complex karyotype and TP53 mutation. The significant association between NEDD9 overexpression and survival was also observed in whole‐cohort AML and non‐M3 AML patients. Notably, AML patients with NEDD9 overexpression may benefit from hematopoietic stem cell transplantation (HSCT), whereas those cases without NEDD9 overexpression did not. Finally, a total of 822 mRNAs and 31 microRNAs were found to be differentially expressed between two groups. Among the microRNAs, miR‐381 was also identified as a microRNA that could direct target NEDD9. Taken together, our findings demonstrated that NEDD9 overexpression is associated with genetic abnormalities as well as prognosis and might act as a potential biomarker guiding the choice between HSCT and chemotherapy in patients with AML after achieving complete remission.

High-strength cable-steel bridge is the “lifeline” of steel structure bridges, which requires high comprehensive mechanical properties, and cold-drawing is the most important process to produce high-strength cable-steel bridge. Therefore, through the ABAQUS platform, a bridge wire drawing model was established, and the simulation analysis on the process of stress strain law and strain path trends for high-strength bridge steel wire from Φ 12.65 mm by seven cold-drawing to Φ 6.90 mm was conducted. The simulation results show that the wire drawing the heart of the main axial deformation, surface and sub-surface of the main axial and radial deformation occurred, with the increase in the number of drawing the road, the overall deformation of the wire was also more obvious non-uniformity. In the single-pass drawing process, the change in the potential relationship of each layer of material was small, and multiple inflection points appeared in the strain path diagram; the change in the seven-pass potential relationship was more drastic, which can basically be regarded as a simple superposition of multiple single-pass pulls.

Background First-line (1L) immunotherapy (I-O) has improved outcomes in patients with advanced non-small cell lung cancer (NSCLC) in clinical trials and is now routinely used alone or combined with chemotherapy. Although efficacy and safety of I-O therapies have been established in clinical trials, little is known about their performance and long-term efficacy in the real-world setting. We aimed to characterize real-world outcomes for patients with advanced NSCLC treated with 1L I-O therapy in the United States. Methods Patients aged ≥18 years with confirmed advanced (stage III–IV) NSCLC who received either 1L I-O monotherapy or single-agent I-O combined with chemotherapy on or after January 1, 2016 were identified from the Flatiron Health database. Primary objectives were to examine overall survival (OS) and real-world progression-free survival. Index date was defined as date of 1L treatment initiation; data cut-off date was June 30, 2020. Results Among 4271 patients receiving I-O plus chemotherapy, median OS was 10.6 (95 % confidence interval [CI], 9.3–11.8) months in patients with squamous NSCLC (n=814) and 12.0 (95 % CI, 11.3–12.8) months in those with non-squamous disease (n=3457). Regardless of histology, patients with high (≥50 %) tumor programmed death ligand 1 (PD-L1) expression demonstrated longer median OS vs those with low expression. Among 3041 patients receiving I-O monotherapy, median OS was 11.3 (95 % CI, 9.8–12.8) months in patients with squamous NSCLC (n=875) and 14.1 (95 % CI, 12.4–15.8) months in those with non-squamous disease (n=2166). OS benefit appeared to be greatest in the ≥50 % tumor PD-L1 expression group of the non-squamous cohort. Conclusion Survival estimates were generally lower than those reported in pivotal clinical trials. These findings indicate that there remains room for improvement of real-world survival outcomes in patients with advanced NSCLC who receive 1L I-O–based regimens and for identification of subgroups of patients not benefitting from treatment with current I-O regimens.

Background Gastric cancer (GC) is one of the most common tumors and the major cause of cancer-related mortality in the world. The purpose of this study is to identify new biomarker and reveal its potential molecular mechanism in GC. Methods The expression of CAP2 was observed by the bioinformatics analysis and western blot assays. The effects of CAP2 on cell proliferation and growth were tested by MTT assay, EdU assay, colony formation assay, and flow cytometric assay, respectively. ChIP and dual-luciferase assays were confirmed that SOX9 binding sites were putative regulatory elements in the transcriptional activation of CAP2. Furthermore, western blot and xenograft assays were applied to examine whether SOX9 was involved in the regulation of CAP2 expression. Results We reported that CAP2 is overexpressed in GC cells and tissues and related to a poorer prognosis for GC patients. Moreover, we found that knockdown of CAP2 suppressed the proliferation, growth, and cell cycle of GC cells. Besides, the transcription factor SOX9 participated in the CAP2-mediated proliferation of GC cells in vitro and in vivo. Conclusions Our results provide novel evidence that CAP2 plays an essential role in the genesis and development of GC, thus potentially highlighting this gene as a therapeutic target.

Objective To assess the clinical outcomes of open calcaneal fractures with medial wounds treated with one‐stage management, including early modern wound care, sequential reduction, and frame structure fixation using percutaneous Kirschner wires. Methods A total of 19 patients with open calcaneal fractures admitted to our hospital from May 2016 to March 2019 were selected in this study. Twelve type‐II and seven type‐IIIA medial open injuries were identified according to the classification of Gustilo and Anderson. Fractures were stratified by Sanders classification, including nine type‐II fractures, seven type‐III fractures, and three type‐IV fractures. All patients accepted one‐stage irrigation and debridement, sequential reduction of calcaneal fractures through the open medial wound, percutaneous Kirschner wire fixation, and primary closure of wounds covered with vacuum‐assisted closure (VAC) device. The Bohler angle, the Gissane angle, and the width of the calcaneus were compared before and after surgery. The functional results were evaluated according to the Paley and Hall score system, visual analogue scale (VAS), American Orthopaedic Foot and Ankle Society (AOFAS) ankle and hindfoot score, Maryland Foot Score, and related complications. Results The follow‐up duration for all patients ranged from 14 to 28 months (mean, 22.7 months). The angle of Bohler and Giasane was increased from (−7.6° ± 15.0°) and (96.6° ± 7.6°) before surgery to (23.7° ± 6.1°) and (124.1° ± 7.1°) postoperatively (P, Open calcaneus fractures with medial wound is treated by one‐stage sequential reduction and frame structure fixation using percutaneous Kirschner wires. This technique allows direct restoration of calcaneal morphology with a minimal invasion of soft tissues at an early stage.

Background Thousands of papers on testicular germ cell tumor (TGCT) have been published over the past two decades. This study aimed to assess the key topics and future trends in TGCT research from a comprehensive perspective. Methods All literature defined as review and article type on TGCT published between 2000 and 2020 was identified and retrieved from the Web of Science Core Collection (WoSCC) database. Bibliometric analysis was conducted by the online analysis platform and VOSviewer (version 1.6.16). The key directions and future trends in the research field of TGCT were evaluated using Bibliographic Item Co-occurrence Matrix Builder (version 2.0) and gCLUTO software. Results Ultimately, a total of 4,550 papers between 2000 and 2020 were included in the field of TGCT. The leadership of the United States in global TGCT research with 1,549 publications during the last two decades was obvious. The Indiana University was the most productive institution with 360 publications, and it was also the institution most frequently involved in research cooperation. Journal of Urology published the highest number of publications on TGCT. Looijenga LHJ, Bokemeyer C, Ulbright TM, Sheinfeld J and Dieckmann KP were the top productive contributors to TGCT research. Further, five research hotspots have been identified: (I) epidemiology of TGCT; (II) TGCT-related infertility; (III) pathological classification with TGCT; (IV) management options for TGCT; and (V) Prevention of cancer metastasis in TGCT patients. Conclusions During the last two decades, the United States was a global leader, and research hotspots included epidemiology, male infertility, pathology, and therapy in the field of TGCT. Furthermore, the genetics mechanisms and cisplatin resistance will remain hotspots in future TGCT research.

Quantum cryptography is a major ingredient of the future quantum internet that promises various secure communication tasks. Quantum conference key agreement (CKA) is an important cryptographic primitive of quantum cryptography, which provides the conference key among multiple users simultaneously. However, quantum CKA is currently far from practical application due to the low conference key rate. Here, we propose a quantum CKA protocol of three users with information-theoretic security. Our protocol only requires phase-randomized weak coherent sources and threshold single-photon detectors, and is anticipated to be experimentally demonstrated over 600 km under current technology. Our scheme can be widely implemented in the approaching large-scale quantum network., Comment: 6 pages, 3 figures, accepted by IEEE Access

Jiale Duan,1,* Yanping Yang,1,* Lei Yin,1 Xue Zhang,2 Yi Tang,1 Shuxian Zhang,1 Hanjuan Gong,1 Ming Xiao,1 Ming Li,1 Qingshu Li,1 Xian Li,1 Lian Yang,1 Qi Fan,2 Yalan Wang1 1Department of Pathology, Molecular Medicine and Cancer Research Center, Chongqing Medical University, Chongqing 400016, People’s Republic of China; 2School of Pharmacy, Chongqing Medical University, Chongqing 400016, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yalan WangDepartment of Pathology, Molecular Medicine and Cancer Research Center, Chongqing Medical University, Chongqing 400016, People’s Republic of ChinaEmail wangyalan@cqmu.edu.cnIntroduction: In metastatic colorectal cancer (mCRC), the B-type Raf kinase (BRAF)V600E mutation is a molecular biomarker of poor prognosis and is of great importance to drug target. Currently, the commonly used methods for detecting BRAFV600E mutation include immunohistochemistry (IHC) and gene sequencing, but both present certain limitations. Near-infrared (NIR) spectroscopy is a spectroscopy technology that takes advantage of the electromagnetic wavelength between visible light and mid-infrared light.Methods: IHC was used to detect the expression of BRAFV600E protein with the BRAFV600E (VE1) antibody in 42 cases of paraffin-embedded (FFPE) mCRC tissue sections. The NIR-discriminant analysis model (NIRS-DA) was established using 6 cases of wild-type and 6 cases of mutant-type BRAF specimens.Results: IHC detection results revealed 13 cases of weakly positive (+), 1 case of moderately positive (++), and 28 cases of negative (−) CRC. Compared with the next-generation sequencing (NGS) results, the positive rate was 66.7%. The classification accuracy of calibration (CAC) was 100% compared with the results of NGS, demonstrating that the BRAFV600E mutant NIRS-DA model, verified by 2 cases of wild-type and 2 cases of mutant-type CRC samples was established. The NIRS-DA model was used to predict gene mutation in the CRC samples, 7 cases were positive (+), and 35 cases were negative (−), and the classification accuracy of prediction (CAP) was 83.3% (35/42).Discussion: The NIRS-DA model-predicted results were in high agreement with the detection results of NGS, and the difference in IHC is not statistically significant (P> 0.05). However, this study is a preliminary discussion on a methodology due to its small sample size.Keywords: colorectal cancer, BRAFV600E mutant, near-infrared spectroscopy, next-generation sequencing, immunohistochemistry

Overcoming the sub-5 nm gate length limit and decreasing the power dissipation are two main objects in the electronics research field. Besides advanced engineering techniques, considering new material systems may be helpful. Here, we demonstrate two-dimensional (2D) subthermionic field-effect transistors (FETs) with sub-5 nm gate lengths based on ferroelectric (FE) van der Waals heterostructures (vdWHs). The FE vdWHs are composed of graphene, MoS2, and CuInP2S6 acting as 2D contacts, channels, and ferroelectric dielectric layers, respectively. We first show that the as-fabricated long-channel device exhibits nearly hysteresis-free subthermionic switching over three orders of magnitude of drain current at room temperature. Further, we fabricate short-channel subthermionic FETs using metallic carbon nanotubes as effective gate terminals. A typical device shows subthermionic switching over five-to-six orders of magnitude of drain current with a minimum subthreshold swing of 6.1 mV/dec at room temperature. Our results indicate that 2D materials system is promising for advanced highly-integrated energy-efficient electronic devices.

Based on the quarterly data of listed companies on the ‘hudongyi’ Internet platform of the Shenzhen Stock Exchange from 2011 to 2018, this study uses the economic policy uncertainty (EPU) index to ...

The topography of gear meshing interfaces is one of the key factors affecting the dynamic characteristics of the gear transmission system. In order to obtain the contact characteristics of meshing gear pair with different surface micro-topographies, an interface feature model and a tribo-dynamics coupling model for the gear system are proposed in this paper. The effects of the gear tooth surface micro-topography on the oil film distribution, contact damping and friction are considered. The time-varying meshing stiffness and the static transmission error are included in the abovementioned models. An exemplary gear pair is analyzed using the proposed models to investigate the influence of the surface micro-topography on the dynamic characteristics of gear system under different micro-topographies and input torque conditions. Simulation results show that the effects of gear tooth micro-topography on the gear dynamic responses (including the friction and the vicious damping at the gear meshing interface and the vibration in the direction of offline of action) are highly dependent on the regularity of tooth surface. The vibration and noise can be significantly controlled by manufacturing a regular gear tooth profiles instead of random profiles.

BACKGROUND: Marital status has been considered as an independent prognostic factor for various types of cancer survival. The objectives of our study were to investigate the function of marital status on the survival of upper tract urothelial carcinoma (UTUC) patients. METHODS: The patients diagnosed with UTUC between 1988 and 2015 were captured within the Surveillance, Epidemiology, and End Results (SEER) database. Patients were classified into married, divorced/separated, widowed and single cohorts. Kaplan-Meier and Cox regression analysis was conducted to assess the effects of marital status on overall survival (OS) and cancer-specific survival (CSS). A 1:1 matched‐pair analysis was performed to optimize the final statistical results by propensity score matching (PSM). RESULTS: Among the 10,852 eligible patients, the percentage of married, divorced/separated, widowed and single patients accounted for 58.2% (6,321), 9.0% (980), 23.3% (2,526) and 9.4% (1,025) respectively. The widowed patients had the worst OS and CSS. Marital status was a predictive factor for OS and CSS of UTUC patients. The results of multivariate Cox regression showed that the worst OS [hazard ratio (HR): 1.41; 95% confidence interval (CI): 1.33–1.49, P

Ternary layered compound materials (bismuth oxyhalides and metal phosphorus trichalcogenides) stand out in electronic and optoelectronic fields due to their interesting physical properties. However, few studies focus on the preparation of high-quality two-dimensional (2D) BiOBr crystals with a typical layered structure, let alone their optoelectronic applications. Here, for the first time, high-quality 2D BiOBr crystals with ultrathin thicknesses (less than 10 nm) and large domain sizes (~100 μm) were efficiently prepared via a modified space-confined chemical vapor deposition (SCCVD) method. It is demonstrated that a moderate amount of H2O molecules in the SCCVD system greatly promote the formation of high-quality 2D BiOBr crystals because of the strong polarity of H2O molecules. In addition, a linear relationship between the thickness of BiOBr nanosheets and Raman shift of A 1g (1) mode was found. Corresponding theoretical calculations were carried out to verify the experimental data. Furthermore, the BiOBr-based photodetector was fabricated, exhibiting excellent performances with a responsivity of 12.4 A W−1 and a detectivity of 1.6×1013 Jones at 365 nm. This study paves the way for controllable preparation of high-quality 2D BiOBr crystals and implies intriguing opportunities of them in optoelectronic applications.

Background Coronary heart disease is one of the diseases with the highest mortality rate. Due to the important position of cardiovascular disease prevention and diagnosis in the medical field, the segmentation of cardiovascular images has gradually become a research hotspot. How to segment accurate blood vessels from coronary angiography videos to assist doctors in making accurate analysis has become the goal of our research. Method Based on the U-net architecture, we use a context-based convolutional network for capturing more information of the vessel in the video. The proposed method includes three modules: the sequence encoder module, the sequence decoder module, and the sequence filter module. The high-level information of the feature is extracted in the encoder module. Multi-kernel pooling layers suitable for the extraction of blood vessels are added before the decoder module. In the filter block, we add a simple temporal filter to reducing inter-frame flickers. Results The performance comparison with other method shows that our work can achieve 0.8739 in Sen, 0.9895 in Acc. From the performance of the results, the accuracy of our method is significantly improved. The performance benefit from the algorithm architecture and our enlarged dataset. Conclusion Compared with previous methods that only focus on single image analysis, our method can obtain more coronary information through image sequences. In future work, we will extend the network to 3D networks.

Tamoxifen is widely used as a highly effective drug for treating estrogen‑receptor (ER) alpha‑positive breast cancer. However, tamoxifen resistance developed during cancer treatment remains a significant challenge. Tongue cancer resistance‑related protein1 (TCRP1), which is recognized as a novel drug target, is related to chemo‑resistance in human cancers, moreover, it is often overexpressed in various cancer cells, such as in lung cancer, breast cancer, and tongue cancer. However, the effects of TCRP1 on tamoxifen‑resistant breast cancer cells and tissues are far from clear. The present study revealed that TCRP1 induced tamoxifen resistance in breast cancer cells. Western blotting, quantitative real‑time polymerase chain reaction (RT‑PCR) and immunohistochemical staining were performed to detect the expression level of TCRP1 in vivo and in vitro between primary breast cancer tissues and tamoxifen‑resistant breast cancer tissues. The data revealed that the expression of TCRP1 was upregulated in the tamoxifen‑resistant breast cancer tissues and human breast cancer cell line, MCF‑7. Further study revealed that knocking down TCRP1 inhibited the growth of MCF‑7 cells with tamoxifen‑resistance (MCF7‑R cells) and induced cell apoptosis. Moreover, TCRP1 promoted serum‑ and glucocorticoid‑inducible kinase 1 (SGK1) activation via phosphorylation of phosphoinositide‑dependent kinase 1 (PDK1) in MCF7‑R cells. In addition, it was also observed that knocking down TCRP1 inhibited tumorigenesis of MCF‑7 cells in nude mice. In conclusion, these data indicated that TCRP1 could induce tamoxifen resistance by regulating the PDK1/SGK1 signaling pathway. Thus, TCRP1 could be explored as a promising candidate for treating tamoxifen‑resistant breast cancer in the future.

Optoelectronic synaptic devices have been attracting increasing attention due to their critical role in the development of neuromorphic computing based on optoelectronic integration. Here we start with silicon nanomembrane (Si NM) to fabricate optoelectronic synaptic devices. Organolead halide perovskite (MAPbI3) is exploited to form a hybrid structure with Si NM. We demonstrate that synaptic transistors based on the hybrid structure are very sensitive to optical stimulation with low energy consumption. Synaptic functionalities such as excitatory post-synaptic current (EPSC), paired-pulse facilitation, and transition from short-term memory to long-term memory (LTM) are all successfully mimicked by using these optically stimulated synaptic transistors. The backgate-enabled tunability of the EPSC of these devices further leads to the LTM-based mimicking of visual learning and memory processes under different mood states. This work contributes to the development of Si-based optoelectronic synaptic devices for neuromorphic computing.

Transfusion of autologous blood is a timesaving, convenient, safe, and effective therapy from a clinical perspective, and often employed for the treatment of diabetic patients. Stabilization of HIF-1α has been widely reported to be a critical factor in the improvement of wound healing in diabetes. Therefore, our study reveals the roles of improved autologous blood in wound healing in diabetes, through autologous blood transfusion in a mouse model. Initially, BALB/c mice were subjected to streptozotocin for diabetic mouse model establishment. Diabetic mice were transfused with improved or standard autologous blood in perfusion culture system. Roles of improved autologous blood in mediating HIF-1α pathway were determined by measuring expression of VEGF, EGF, HIF-1α, and HSP-90. In order to assess the detailed regulatory mechanism of improved autologous blood in perspective of wound healing, cell proliferation, migration and cell cycle, fibroblasts isolated from diabetic mice were transfected with HIF-1α siRNA. Mice transfused with improved autologous blood exhibited increased levels of CD31 and α-SMA in skin tissues, and reduced TNF-α, IL-1β, and IL-6 levels, indicating that improved autologous blood promoted wound healing ability and reduced the release of inflammatory factors. Diabetic mice transfused with improved autologous blood presented activated HIF-1α pathway. The survival rate, proliferation, and migration of fibroblasts were elevated via activation of the HIF-1α pathway. Taken together, improved blood preservation solution could enhance the oxygen carrying capacity of red blood cells and wound healing in mice with diabetes, which is achieved through regulation of HIF-1α pathway.

Aim: Ozanimod and fingolimod are sphingosine 1-phosphate receptor–modulating therapies for relapsing multiple sclerosis. Patients & methods: Comparative effectiveness was assessed by matching adjusted indirect comparisons of safety and efficacy trial outcomes at first-dose cardiac monitoring, 1 year and 2 years. Results: After adjustment, baseline characteristics were similar. Ozanimod was associated with a lower risk of extended first-dose monitoring, conduction abnormalities including atrioventricular block. One-year risks of any adverse event (AE), mean lymphocyte count reductions and abnormal liver enzymes were lower with ozanimod. Two-year risks of AEs leading to discontinuation, any AEs, herpetic infections, bradycardia and abnormal liver enzymes were lower with ozanimod. Analyses of efficacy outcomes were similar. Conclusion: Ozanimod appears to have a favorable benefit-risk profile versus fingolimod.

The roles of M2 macrophages on promoting tumor progression and chemotherapy resistance have been well studied in many cancers, such as pancreatic cancer, kidney cancer and so on, but its linkage to HCC cells still remains unclear. Here we found that M2 macrophages could alter miR-149-5p to increase MMP9 expression in HCC cells and mechanism dissection revealed that miR-149-5p might directly target the 3'UTR of MMP9-mRNA to suppress its translation. The in vivo orthotopic xenografts mouse model with oemiR-149-5p also validated in vitro data. Together, these findings suggest that M2 macrophages may through altering the miR-149-5p to promote HCC progression and targeting the M2 macrophages/miR149-5P/MMP9 signaling may help in the development of the novel therapies to better suppress the HCC progression.

Background As a compound Chinese medicine, Zhenqing Recipe (ZQR) has been shown to ameliorate hyperglycemia, hyperlipidemia, fatty liver and insulin resistance in patients with diabetes and diabetic rats. In this paper, we further examined the effect of ZQR on diabetes complicated by non-alcoholic fatty liver disease (NAFLD) and the underlying molecular mechanisms. Methods Diabetic rats with NAFLD were developed by a high-fat diet (HFD) with low-dose streptozotocin (STZ) injection for 4 weeks. These rats were randomly separated into the diabetic model (DM), ZQR, metformin (Met), adenovirus expressing-salt-induced kinase 1 (Ad-SIK1) and adenovirus labeled with green fluorescent protein (Ad-GFP) groups. The effects on hepatic expression of gluconeogenic genes, glycolipid metabolism and pathological changes were subsequently detected. Results Serum glucose, triglycerides (TG), total cholesterol (TC) and hepatic TG were reduced in the ZQR group. The histopathological and immunohistochemical changes in the liver and pancreas in the ZQR group were significantly alleviated. The decrease of SIK1 expression was observed in the liver of diabetic rats induced by HFD and STZ. SIK1 overexpression in the liver relieved hyperglycemia, hyperlipidemia and fatty liver. Both the mRNA and protein levels of CREB-regulated transcription co-activator 2 (CRTC2), phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase) in the liver were drastically reduced, whereas those of SIK1 were markedly increased in the ZQR group compared to levels in the DM group. Compared with the DM group, Ser577 phosphorylation of SIK1 was obviously reduced in the liver, while T182 phosphorylation of SIK1 and S171 phosphorylation of CRTC2 were evidently increased in the Ad-SIK1, Met and ZQR groups. Conclusions ZQR ameliorates hepatic gluconeogenesis and lipid storage in diabetic rats induced by HFD and STZ by activating the SIK1/CRTC2 signaling pathway. Upregulating hepatic SIK1 by ZQR may represent an efficient strategy for treating diabetes with NAFLD.

Breast cancer is the most prevalent malignancy among women. Although endocrine therapy is effective, the development of endocrine resistance is a major clinical challenge. The tumor microenvironment (TME) promotes tumor malignancy, and tumor‐associated macrophages (TAM) within the TME play a crucial role in endocrine resistance. Herein, we aimed to elucidate the relationship between TAM and the endocrine‐resistant phenotype of breast cancer. Macrophages were cultured with conditioned medium (CM) from tamoxifen‐sensitive (MCF7‐S) or ‐resistant (MCF7‐R) MCF7 breast cancer cells. M2 polarization was detected by CD163 immunofluorescence. To determine the effect on endocrine resistance, MCF7 cells were cultured in the supernatant of different TAM, and then treated with tamoxifen. CC‐chemokine ligand 2 (CCL2) immunohistochemistry was carried out on pathological sections from 100 patients with invasive estrogen receptor‐positive breast cancer. We found that macrophages cultured in the CM of MCF7‐S and MCF7‐R cells were induced into TAM, with a more obvious M2 polarization in the latter. Tamoxifen resistance was increased by culture in TAM medium. TAM secreted CCL2, which increased endocrine resistance in breast cancer cells through activation of the PI3K/Akt/mTOR signaling pathway. High expression of CCL2 was correlated with infiltration of CD163+macrophages (r = 0.548, P, This study investigated the mechanisms underlying tumor‐associated macrophage (TAM)‐mediated endocrine resistance in breast cancer cells. We found that endocrine‐resistant breast cancer cells can induce M2 polarization of TAM, and M2‐polarized TAM in turn further promote endocrine resistance in breast cancer cells. We believe that this article will be of interest to the readership of this journal because we uncovered the underlying mechanism of TAM‐induced endocrine resistance: TAM secrete the cytokine CCL2, which activates the PI3K/Akt/mTOR signaling pathway.

Mixed-dimensional van der Waals (vdW) heterostructures based on two-dimensional (2D) materials exhibit immense potential in infrared optoelectronic applications. However, the weak vdW coupling results in limiting performance of infrared optoelectronic device. Here, we exploit a gapless heterostructure that S dangling bonds of nonlayered PbS are connected to the bonding sites of MoS

International audience; The band alignment, interface states, interface coupling, and carrier transport of semiconductor heterojunctions (SHs) need to be well understood for the design and fabrication of various important semiconductor structures and devices. Scanning tunneling microscopy (STM) with high spatial resolution and scanning tunneling spectroscopy (STS) with high energy resolution are significantly contributing to the understanding on the important properties of SHs. In this work, the recent progress on the use of STM and STS to study lateral, vertical and bulk SHs is reviewed. The spatial structures of SHs with atomically flat surface have been examined with STM. The electronic band structures (e. g., the band offset, interface state, and space charge region) of SHs are measured with STS. Combined with the spatial structures and the tunneling spectra features, the mechanism for the carrier transport in the SH may be proposed. © 2021 Wiley-VCH GmbH

BackgroundInflammation is widely considered an important hallmark of cancer and associated with poor postoperative survival. The objective of this study is to assess the significance of preoperative C-NLR, a new inflammation-based index that includes preoperative C-reactive protein (CRP) and neutrophil-to-lymphocyte ratio (NLR), on therapeutic outcomes for bladder cancer (BC) patients after radical cystectomy (RC).Materials and MethodsBC patients who underwent RC between 2010 and 2019 were retrospectively analyzed from our medical center. The predictive effect of CRP, NLR, and C-NLR on the survival of BC patients were analyzed by the receiver operating characteristic (ROC) curves. The relationship between C-NLR and postoperative survival was investigated by Cox regression. The corresponding nomograms were built based on the Cox regression results of overall survival (OS) and disease-free survival (DFS), which were further validated by ROC curves, decision curve analysis (DCA) curves, and calibration curves.ResultsOf the 199 eligible patients, 83 (41.70%) were classified as high C-NLR group and the remaining 116 (58.30%) were classified as low C-NLR group. ROC analysis showed that C-NLR had the largest area under curve (AUC) compared to CRP and NLR. Multivariate analysis revealed that T-stage and C-NLR [high C-NLR vs. low C-NLR, hazard ratio (HR) = 2.478, 95% confidence interval (CI), 1.538–3.993, p < 0.001] were independent predictors of OS, whereas T-stage, M-stage, and C-NLR (high C-NLR vs. low C-NLR, HR = 2.817, 95% CI, 1.667–4.762, p < 0.001) were independent predictors of DFS. ROC and DCA analysis demonstrated better accuracy and discrimination of 3- and 5-year OS and DFS with C-NLR-based nomogram compared to TNM stage. The calibration curve reconfirmed the accurate predicting performance of nomograms.ConclusionC-NLR is a reliable predictor of long-term prognosis of BC patients after RC and will contribute to the optimization of individual therapy for BC patients.

Discrete-modulated continuous-variable quantum key distribution with homodyne detection is widely recognized for its ease of implementation, efficiency with respect to error correction, and its compatibility with modern optical communication devices. However, recent studies report that the application of homodyne detection obtains poor tolerance to excess noise and insufficient transmission distance, hence seriously restricting the large-scale deployment of quantum secure communication networks. In this paper, we propose a homodyne detection protocol using the quadrature phase shift keying technique. By limiting information leakage, our proposed protocol enhances excess noise tolerance to a high level. Furthermore, we demonstrate that homodyne detection performs better than heterodyne detection in quaternary-modulated continuous-variable quantum key distribution under the untrusted detector noise scenario. The security is analyzed using the tight numerical method against collective attacks in the asymptotic regime. Our results imply that the current protocol is able to distribute keys in nearly intercity area and thus paves the way for constructing low-cost quantum secure communication networks., 14 pages, 10 figures. Accepted by PRX Quantum

Twin-field quantum key distribution (TFQKD), using single-photon-type interference, offers a way to exceed the rate-distance limit without quantum repeaters. However, it still suffers from the photon losses and dark counts, which impose an ultimate limit on its transmission distance. In this letter, we propose a scheme to implement TFQKD with an entangled coherent state source in the middle to increase its range, as well as comparing its performance under coherent attacks with that of TFQKD variants. Simulations show that our protocol has a theoretical distance advantage of 400 kilometers. Moreover, the scheme has great robustness against the misalignment error and finite-size effects. Our work is a promising step toward long-distance secure communication and is greatly compatible with future global quantum network., 4+4 pages, 5 figures

IntroductionThe classical pathway for the therapy of low- to intermediate-risk localized prostate cancer is radical prostatectomy or radiation therapy, which has shown a high incidence of complications, including erectile dysfunction, urinary incontinence, and bowel injury. An alternative pathway is to perform an ablation by some energy to the localized lesion, known as focal therapy. High-frequency irreversible electroporation (H-FIRE) is nonthermal energy that can be used in cancer ablation to deliver pulsed high-voltage but low-energy electric current to the cell membrane and to invoke cell death. An H-FIRE pathway has been reported to be tissue-selective, which leads to fewer side effects.Methods and AnalysisThis is a multicenter and single-arm objective performance criteria (OPC) study, in which all men with localized prostate cancer are allocated to H-FIRE ablation. This trial will assess the efficacy and safety of the H-FIRE ablation for prostate cancer. Efficacy will be assessed by prostate biopsy 6 months after treatment while safety will be assessed by adverse event reports and questionnaires. The main inclusion criteria are moderate to low-risk prostate cancer in NCCN risk classification and had no previous therapy for prostate cancer. A sample size of 110 participants is required. The primary objective is to determine whether the detection rate of clinically significant cancer by prostate biopsy is less than 20% after the H-FIRE ablation.Ethics and DisseminationThis study has obtained ethical approval by the ethics committee of all participating centers. The results of the study will be submitted for dissemination and publication in peer-reviewed journals.ConclusionsThis multicenter single-arm objective performance criteria trial will evaluate the efficacy and safety of the use of high-frequency irreversible electroporation in treating prostate cancer.Strengths and Limitations of This StudyA comprehensive evaluation of imaging and histopathology is used to determine the effect of treatment. Questionnaires were used to assess the treatment side effects. Multicenter and pragmatic designs capacitate higher generalizability. A limitation of this trial is that the prostate biopsy as an endpoint may not be as accurate as of the specimen from prostate prostatectomy. Another limitation is the 6-month follow-up time, making this trial challenging to come to firm conclusions regarding the efficacy and safety of IRE in the long term.Clinical Trial RegistrationClinicalTrials.gov, NCT03838432

Quantum digital signatures (QDSs) promise information-theoretic security against repudiation and forgery of messages. Compared with currently existing three-party QDS protocols, multiparty protocols have unique advantages in the practical case of more than two receivers when sending a mass message. However, complex security analysis, numerous quantum channels and low data utilization efficiency make it intractable to expand three-party to multiparty scenario. Here, based on six-state non-orthogonal encoding protocol, we propose an effective multiparty QDS framework to overcome these difficulties. The number of quantum channels in our protocol only linearly depends on the number of users. The post-matching method is introduced to enhance data utilization efficiency and make it linearly scale with the probability of detection events even for five-party scenario. Our work compensates for the absence of practical multiparty protocols, which paves the way for future QDS networks., Comment: 9 pages, 6 figures

Key Points Question Is a multicomponent hypertension control intervention in low-income settings in Argentina cost-effective in the long term? Findings In this economic evaluation, compared with usual care, a multicomponent hypertension control intervention was cost-effective in a lifetime horizon in Argentina from a health care system perspective. Meaning These findings suggest that a multicomponent hypertension control intervention may be transferrable to other settings in Argentina or other low- and middle-income countries., This economic evaluation examines the long-term cost-effectiveness of a multicomponent hypertension management program compared with usual care among patients with hypertension receiving care in public clinics in Argentina from a health care system perspective., Importance Hypertension is highly prevalent in low- and middle-income countries, and it is an important preventable risk factor for cardiovascular diseases (CVDs). Understanding the economic benefits of a hypertension control program is valuable to decision-makers. Objective To evaluate the long-term cost-effectiveness of a multicomponent hypertension management program compared with usual care among patients with hypertension receiving care in public clinics in Argentina from a health care system perspective. Design, Setting, and Participants This economic evaluation used a Markov model to estimate the cost-effectiveness of a hypertension management program among adult patients with uncontrolled hypertension in a low-income setting. Patient-level data (743 individuals for multicomponent intervention; 689 for usual care) from the Hypertension Control Program in Argentina trial (HCPIA) were used to estimate treatment effects and the risk of CVD. Three health states were included in each strategy: (1) low risk of CVD, (2) high risk of CVD, and (3) death. The total time horizon was the lifetime, and each cycle lasted 6 months. Main Outcomes and Measures Model inputs were based on trial data and other published sources. Cost and utilities were discounted at a rate of 5% annually. The incremental cost-effectiveness ratio (ICER) between the multicomponent intervention and usual care was calculated using the difference in costs in 2017 international dollars (INT $) divided by the difference in effectiveness in quality-adjusted life-years (QALYs). One-way sensitivity analysis and probabilistic sensitivity analysis were performed to assess the uncertainty and robustness of the results. Results In the original trial, the 743 participants in the intervention group (349 [47.0%] men) had a mean (SD) age of 56.2 (12.0) years, and the 689 participants in the control group (311 [45.1%] men) had a mean (SD) age of 56.2 (11.7) years. In the base-case analysis, the HCPIA program yielded 8.42 discounted QALYs and accrued INT $3096 discounted costs, while usual care yielded 8.29 discounted QALYs and accrued INT $2473 discounted costs. The ICER for the HCPIA program was INT $4907/QALY gained. The model results remained robust in sensitivity analyses, and the model was most sensitive to parameters of program costs. Conclusions and Relevance In this study, the HCPIA multicomponent intervention vs usual care was a cost-effective strategy to improve hypertension management and reduce the risk of associated CVD among patients with hypertension who received services at public clinics in Argentina. This intervention program is likely transferable to other settings in Argentina or other lower- and middle-income countries.

Human exposure to organic mercury (Hg) as methylmercury (MeHg) from seafood consumption is widely considered a health risk because pure methylmercury is extremely neurotoxic. In contrast, the clinical significance of Hg exposure from amalgam (AMG) dental restorations, the only other major nonoccupational source of Hg exposure, has long been debated. Here, we examined data from the two most recent National Health and Nutrition Examination Surveys (NHANES) on 14 181 subjects to assess the contributions of seafood consumption versus AMG to blood total mercury (THg), inorganic mercury (IHg), and methyl mercury (MeHg) and to urine creatinine corrected mercury (UTHg). All subjects were also classified as to their self-reported qualitative consumption of seafood (59% fish and 44% shellfish). Subjects with restorations were grouped into three groups (0) those without AMG (64.4%), (1) those with 1–5 dental AMG restorations (19.7%), (2) those with more than five AMG (16%). Seafood consumption increased total mercury in urine (UTHg) and total mercury (THg) and methyl mercury (MeHg) in blood, but unlike AMG, seafood did not increase blood inorganic mercury (IHg). Using stratified covariate (ANOVA) and multivariate (GLM) analyses revealed a strong correlation of blood (THg and IHg) and urine (UTHg) levels with the number of AMGs. In a subpopulation without fish consumption, having more than five AMG restorations raised blood THg (103%), IHg (221%), and urine UTHg (221%) over the group without AMG. The most striking difference was noted in classification by age: subjects under 6 years old with more than five AMG restorations had the highest blood IHg and urine UTHg among all age groups. Elevation of bivalent IHg on a large scale in children warrants urgent in-depth risk assessment with specific attention to genetic- and gender-associated vulnerabilities.

Lung cancer is the leading cause of cancer-associated deaths accounting for 24% of all cancer deaths. As a crucial phase of tumor progression, lung cancer metastasis is linked to over 70% of these mortalities. In recent years, exosomes have received increasing research attention in their role in the induction of carcinogenesis and metastasis in the lung. In this review, recent studies on the contribution of exosomes to lung cancer metastasis are discussed, particularly highlighting the role of lung tumor-derived exosomes in immune system evasion, epithelial-mesenchymal transition, and angiogenesis, and their involvement at both the pre-metastatic and metastatic phases. The clinical application of exosomes as therapeutic drug carriers, their role in antitumor drug resistance, and their utility as predictive biomarkers in diagnosis and prognosis are also presented. The metastatic activity, a complex multistep process of cancer cell invasion, survival in blood vessels, attachment and subsequent colonization of the host's organs, is integrated with exosomal effects. Exosomes act as functional mediating factors in cell–cell communication, influencing various steps of the metastatic cascade. To this end, lung cancer cell-derived exosomes enhance cell proliferation, angiogenesis, and metastasis, regulate drug resistance, and antitumor immune activities during lung carcinogenesis, and are currently being explored as an important component in liquid biopsy assessment for diagnosing lung cancer. These nano-sized extracellular vesicles are also being explored as delivery vehicles for therapeutic molecules owing to their unique properties of biocompatibility, circulatory stability, decreased toxicity, and tumor specificity. The current knowledge of the role of exosomes highlights an array of exosome-dependent pathways and cargoes that are ripe for exploiting therapeutic targets to treat lung cancer metastasis, and for predictive value assessment in diagnosis, prognosis, and anti-tumor drug resistance.

BackgroundManagement of comminuted radial fractures remains controversial. Currently, the emergence of on-table reconstruction technique has made fixation in comminuted radial head fractures more viable. However, the present study reported an intro-operative unstable displacement from the reconstructed radial head to the neck during plate fixation, characterized by a poor radiocapitellar contact and incongruity between the radial head and neck. A hybrid technique combining with intramedullary pining was performed in our study to restore the normal alignment and maintain the stability of fixation. Therefore, the purpose of this article aimed to prove the feasibility of unstable comminuted radial head fractures treated with the extramedullary plate and intramedullary pinning fixation using titanium elastic nails.MethodsThe clinical, functional and radiographic outcomes of the groups were compared during follow-up. The radiographic examination was conducted to evaluate the status of bone union, heterotopic ossification and post-traumatic arthritis. The functional assessment was performed to evaluate clinical effects, which included measurements of range of motion (ROM) in the elbow, Visual Analog Scale (VAS) score, Elbow Self-Assessment score (ESAS), Mayo Elbow Performance score (MEPS), and Disabilities of the Arm, Shoulder, and Hand (DASH)Outcome Measure score.ResultsThirteen patients with unstable fractures were participated with an average follow-up of (38.6 ± 4.5) months for the experimental group and (32.0 ± 6.3) months for the control group, respectively. The functional outcomes in the experimental group, including MEPS and DASH, were significantly superior to the control group. However, no significant difference was observed in the elbow ROM and VAS score between two groups. In the last follow-up, one patient with post-traumatic arthritis rated as grades 1 and two with heterotopic ossifications were observed in the experimental group. In the control group, degenerative changes were observed in three cases (grade 1 in two cases and grade 2 in one case) and heterotopic ossifications rated as grade I were found in two patients.ConclusionCollectively, intramedullary pinning with extramedullary plate fixation is feasible in unstable comminuted radial head fractures, which can be considered as a remedial surgery for on-table reconstruction technique.

While results from clinical trials are important in determining the efficacy of treatment, restrictive eligibility criteria may limit generalizability to patient populations in the real-world setting. Real-world analyses can therefore identify subgroups of patients who may respond differently to specific therapeutic regimens. This supplementary data is supportive to the research article entitled “Real-world outcomes of immunotherapy–based regimens in first-line advanced non-small cell lung cancer” [1] . Using electronic health records data from a large demographically and geographically diverse oncology database, we present real-world progression-free survival (rwPFS) outcomes for patients with advanced non-small cell lung cancer in the United States treated with either first-line immunotherapy as monotherapy or single-agent immunotherapy combined with chemotherapy. rwPFS was estimated for patients in each treatment group using Kaplan-Meier methods; analyses were conducted separately for patients with squamous and non-squamous histology and stratified by Eastern Cooperative Oncology Group performance status, tumor programmed death ligand-1 expression, and presence of brain metastases.

BRAF V600E mutations are common in papillary thyroid carcinoma (PTC) and some de-differentiated thyroid cancers. In this study, we summarize AUS/FLUS diagnosed cases from thyroid fine needle aspirations in our center from 2015 to 2017 to explore the impact of BRAF V600E detection on the cytopathological diagnosis of PTC. BRAF V600E detection could significantly reduce the AUS/FLUS diagnosis rates from 11.59 to 8.42% when all BRAF V600E-mutated AUS/FLUS cases were diagnosed as conforming to PTC (20.01 to 19.13% in 2016 and 10.92 to 7.93% in 2017, respectively). The AUS/M rates decreased from 0.67 to 0.64 in 2016 and from 0.33 to 0.23 in 2017. We further discuss a case with a single BRAF V600E cytological mutant lacking a postoperative PTC diagnosis and discuss the limitations of BRAF V600E detection using puncture elution fluid. Our findings support the notion that BRAF V600E detection can effectively reduce the diagnostic rates of AUS/FLUS and help clinicians decide both treatment strategies and patient prognosis.

Objective To evaluate the outcome of Mason type II radial head fractures treated by intramedullary pinning. Methods From May 2013 to March 2017, we respectively reviewed 25 patients affected by Mason type II radial head fractures. A total of 12 patients who met criteria for inclusion and exclusion were collected and analyzed. They were all isolated displaced partial articular radial head fractures and treated with intramedullary pinning using titanium elastic nails (TEN). The patients comprised eight men and four women with the mean age of 40 years (range, 21-58 years). The clinical evaluation included the range of motion (ROM) in the elbow, the shortened disabilities of the arm, shoulder and hand questionnaire (QuickDASH), the visual analogue scale (VAS) for pain rating, and the Mayo Elbow Performance Score (MEPS). Follow-up radiographs to monitor related complications were evaluated as well. Results All patients were followed-up with a mean of 21.8 months (range, 12-28 months). The average range of elbow flexion-extension was barely unaffected in the injured side when compared to the uninjured side (139.08° ± 3.14° vs 140.16° ± 3.01°, P = 0.398) as were pronation of the forearm (86.50° ± 2.75° vs 87.83° ± 2.12°, P = 0.197) and supination of the forearm (87.41° ± 2.53° vs 88.17° ± 1.95°, P = 0.425). The MEPS was 93.75 ± 5.28 points (range, 85-100), the QuickDASH revealed good to excellent results with 2.33 ± 4.56 points (range, 0-14), and the VAS for pain was 0.33 ± 0.78 (range, 0-2). Only two patients had a minor complication with constant affection of the superficial branch of radial nerve. Conclusion Intramedullary pinning technique in the treatment of Mason type II radial head fractures is minimally traumatic and effective and represents good to excellent results in adults.

To summarize the experience of retroperitoneal laparoscopic ureterolithotomy (RLU) in the treatment of upper ureteral calculi and long-term follow-up results and compare them with ureteroscopic lithotomy (URL) and percutaneous nephrolithotomy (PCNL).The clinical data of 585 patients with complex upper ureteral calculi who met the inclusion criteria from January 2006 to December 2017 were retrospectively analyzed. There were 206 cases treated with RLU, 201 cases treated with URL and 178 cases treated with PCNL. The operation time, hospitalization time, stone clearance rate, incidence of postoperative complications and recurrence rate were observed and compared among the three groups.Among 585 eligible patients, 206 cases were treated with RLU, 201 cases were treated with URL and 178 cases were treated with PCNL. The stone clearance rate (98.54%), postoperative complication types and rate (0.97%) in the RLU group were superior to those in the URL group and the PCNL group (P 0.05). There was no significant difference in the recurrence rate (3.88%) between the RLU group and the other two groups (P 0.05).Retroperitoneal laparoscopic ureterolithotomy has many advantages in the treatment of upper ureteral calculi, including high stone clearance rate, less complications especially in ureteral stricture. Retroperitoneal laparoscopic ureterolithotomy is also safe to treat upper ureteral calculi accompanied with severe urinary tract infection.

Impaired wound healing is a debilitating complication of diabetes. The long non-coding RNA (lncRNA) metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) has been recognized to be differentially expressed in various diseases. However, its underlying mechanism in diabetes has not been fully understood. Notably, we aim to examine the expression of MALAT1 in diabetic mice and its role in wound healing involving the hypoxia-inducible factor-1α (HIF-1α) signaling pathway with a modified autologous blood preservative solution reported. A mouse model of diabetes was established. MALAT1 was identified to promote the activation of the HIF-1α signaling pathway and to be enriched in autologous blood through modified preservation, which might facilitate the improvement of physiological function of blood cells. Through gain- or loss-of-function approaches, viability of fibroblasts cultured in high glucose, wound healing of mice, and collagen expression in wound areas were enhanced by MALAT1 and HIF-1α. Taken together, the present study demonstrated that the physiological status of mouse blood was effectively improved by modified autologous blood preservation, which exhibited upregulated MALAT1, thereby accelerating the fibroblast activation and wound healing in diabetic mice via the activation of the HIF-1α signaling pathway. The upregulation of MALAT1 activating the HIF-1α signaling pathway provides a novel insight into drug targets against diabetes., Graphical Abstract

Two-dimensional (2D) magnetic materials provide an ideal platform for the application in spintronic devices due to their unique spin states in nanometer scale. However, recent research on the exfoliated monolayer magnetic materials suffers from the instability in ambient atmosphere, which needs extraordinary protection. Hence the controllable synthesis of 2D magnetic materials with good quality and stability should be addressed. Here we report for the first time the van der Waals (vdW) epitaxial growth of one-unit-cell-thick air-stable ferrimagnet Cr2S3 semiconductor via a facile chemical vapor deposition method. Single crystal Cr2S3 with the domain size reaching to 200 μm is achieved. Most importantly, we observe the as grown Cr2S3 with a Neel temperature (TN) of up to 120 K and a maximum saturation magnetic momentum of up to 65 μemu. As the temperature decreases, the samples show a transition from soft magnet to hard magnet with the highest coercivity of 1000 Oe. The one-unit-cell-thick Cr2S3 devices sh...

With the development of computer technology and artificial intelligence (AI), service robots are widely used in our daily life. While the manufacturing cost of the robots is too expensive for most small technology companies. The biggest technical limitations are the design of the robot service and the resources sharing of the robot groups. As far as we know, there is no complete and open-source service robot cloud service platform. To solve the above problems, in this paper, a novel robot cloud platform called cloud robotics intelligent cloud platform (CRICP) is designed, which consists of gateway layer, an interface layer, service pool, and algorithm layer. Gateway layer mainly solves the problem of robot access control and service invocation requests scheduling. In addition, a standardized access method is proposed to overcome the problem that heterogeneous service robots cannot access the cloud platform. Interface layer is responsible for protocol injection, including motoring protocol, a management protocol, and other algorithms invocation protocol or service invocation interfaces protocol. Service Pool consists of different kinds of robot services which could scale based on the historical data analysis. In Algorithm layer, we can implement machine learning (ML) algorithm, deep learning (DL) algorithm, distributed algorithm, and so on. Finally, voice recognition service invocation experiment and cloud service dynamic scaling test are taken as an example to verify the availability and accuracy of our platform. Moreover, the compared results with a local framework and SOA also verifies the superiority of our platform.

Objective The objective of this study was to determine the value of dual-energy computed tomography (DECT) for the diagnosis of cervical lymph node metastasis in papillary thyroid cancer. Methods The normalized iodine concentration (NIC) and the slope of the spectral Hounsfield unit curve (λHU) in the arterial and venous phases were measured using iodine-overlay images and spectral curves. Quantitative DECT data and qualitative conventional CT data were analyzed by radiologists. Results The best qualitative parameter for lymph node metastasis detection was obvious node enhancement, and the best quantitative parameter for detection was arterial-phase NIC, which showed high sensitivity, specificity, and accuracy values at an optimal threshold of 25.8%. The best combination of qualitative and quantitative parameters consisted of obvious enhancement and arterial-phase NIC; this combination showed a sensitivity of 90.8% and a specificity of 80.5%. Conclusions The DECT quantitative parameters NIC and λHU can be an additional tool to diagnose cervical lymph node metastasis.

Although the particle swarm optimizer (PSO) has been widely used to address various complicated engineering problems, it is likely to suffer lack of diversity and ineffectiveness of balance between the global search ability and the local search ability in the search process. In this paper, we report an innovative and improved optimization method called ameliorated particle swarm optimizer (A-PSO), which is different from the original PSO algorithm and its variants in parameter update and the position generation of each particle. In A-PSO, the nonlinear dynamic acceleration coefficients, logistic map and a modified particle position update approach are introduced in PSO to improve the solution quality and accelerate the global convergence rate. Twenty well-known numerical optimization functions are adopted to evaluate the effectiveness of the proposed method and it is illustrated that, for most numerical optimization problems, the convergence performance and search accuracy of the A-PSO method are superior to the similar heuristic optimization algorithms and other well-known PSO variants. Namely, the proposed A-PSO technique has a faster convergence rate and is more stable than other PSO variants and similar population-based methods for almost all numerical optimization problems. Therefore, the A-PSO method is successfully used as a new optimization technique for solving numerical optimization problems.

Aims To investigate the clinical characteristics of health care-seeking men presenting with lower urinary tract symptoms (LUTS) in China and to reveal risk factors for symptom severity. Methods This multicenter, hospital-based, cross-sectional study recruited 1477 eligible male subjects, who were at least 45 years, seeking health care at 9 participating hospitals across the mainland China. The general medical information and subjective symptoms were recorded, followed by the measurement of prostate volume, urodynamic indices, and laboratory tests for kidney function, plus glucose/lipid metabolism. Univariate and multivariate linear regression were employed for the detection of risk factors for symptom severity. Results The proportion of mild, moderate, and severe LUTS was 14.6%, 32.6%, and 52.8%, respectively, with 62.2% reporting the triple combination of storage, voiding, and postmicturition symptoms. Median prostate volume was 44.6 ml, and 71.1% were experiencing comorbidities. Thirteen independent risk factors for LUTS severity were identified, namely, nocturnal voiding episodes and the presence of straining and weak steam; the triple combination of symptom subtypes; general and nocturia quality of life; Qmax and bladder outlet obstruction index; and numbers of comorbidities, hypertension, estimated glomerular filtration rate, and cholesterol and glycosylated hemoglobin. Conclusions The majority of health care-seeking LUTS men present with moderate-to-severe and overlapping symptoms, with a high prevalence of both lower urinary tract dysfunction and systemic comorbidities. The evidence from both urological and nonurological independent risk factors demonstrate the multifactorial nature of LUTS, for which a multidisciplinary management is essential.

Endocrine therapy is the standard treatment for estrogen receptor (ER)-positive breast cancer, but tumors eventually develop resistance. However, endocrine therapy resistance mechanisms mediated through interactions between breast cancer cells and tumor-associated macrophages (TAMs) are still unclear. Here, we characterized sodium/glucose cotransporter 1 (SGLT1) overexpression drives the highly glycolytic phenotype of tamoxifen-resistant breast cancer cells where enhanced lactic acid secretion promotes M2-like TAM polarization via the hypoxia-inducible factor-1α/signal transducer and activator of transcription-3 pathway. In turn, M2-like TAMs activate breast cancer cells through EGFR/PI3K/Akt signaling, providing feedback to upregulate SGLT1 and promote tamoxifen resistance and accelerate tumor growth in vitro and in vivo. Higher expression of SGLT1 and CD163+ TAMs was associated with endocrine-resistant ER-positive breast cancers. Our study identifies a novel vicious cycle of metabolic reprogramming, M2-like TAM polarization, and endocrine therapy resistance, which involves SGLT1, proposing SGLT1 as a therapeutic target to overcome endocrine therapy resistance in breast cancer.