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ABSTRACT Background Hepatocellular carcinoma (HCC) is a prevalent malignancy with a high mortality rate worldwide. Suppressor of cytokine signaling (SOCS) family members play important roles in the proliferation, metabolism, and immunity of HCC cells by regulating cytokines and growth factors. However, it remains uncertain whether the level of SOCS family members can affect the prognosis of HCC patients. Aims This study aimed to comprehensively assess the role and mechanisms of SOCS family members in the development of HCC and to guide clinical selection. Methods We investigated the expression levels of SOCS family genes in HCC patients and their associations with various clinicopathological characteristics. We also utilized a public database to analyze the changes in the expression, potential functions, transcription factors, and immune invasion of SOCS family members. Additionally, we examined the prognostic value of the SOC family for HCC and its correlation with the SOC family and ferroptosis‐related genes. Results This study revealed that the expression of SOCS2‐7, and CISH was downregulated in HCC. The SOCS4, SOCS5, and SOCS7 genes were associated with the clinicopathological features of HCC patients. SOCS family genes are mainly related to the PIK3R3, GHR, and TNS4 pathways. Additionally, this study revealed that STAT3, PPAR‐gamma 2, and IRF‐2 are important transcription factors that regulate SOCS family members. The expression levels of SOCS family members are closely related to immune infiltration in liver cancer. The study also indicated that SOCS2 and SOCS4 are risk‐related genes for predicting the prognosis of patients with liver cancer. Finally, this study suggested that the SOCS2 gene may be involved in the development and progression of HCC. Conclusion Our study enhances the current understanding of SOCS gene function in liver cancer and can help clinicians select appropriate drugs and predict the prognosis of HCC patients.

BackgroundCurrently, the prognosis of advanced intrahepatic cholangiocarcinoma (ICC) is poor, and the current treatment methods are not effective.ObjectiveThe aim of this study was to evaluate the anticancer efficacy of chemotherapy combined with PD-1 inhibitors and tyrosine kinase inhibitors (TKIs) in patients with ICC.MethodsWe retrospectively screened patients with advanced intrahepatic cholangiocarcinoma (ICC) who received chemotherapy combined with lenvatinib and PD-1. We evaluated overall survival (OS), progression-free survival (PFS), the objective response rate (ORR), the disease control rate (DCR), the tumor shrinkage rate, and safety.ResultsWe enrolled 95 patients with ICC and divided them into three groups with a median follow-up duration of 15.1 months. The chemotherapy group (chemo-regimen group), chemotherapy combined with immune checkpoint inhibitors (dual-regimen group), and chemotherapy combined with lenvatinib (triple-regimen group) had median OS times of 13.1 months, 20.8 months, and 39.6 months, respectively. Notably, the triple-regimen group had a significantly longer OS than did the chemo-regimen and dual-regimen groups. The chemo-regimen group, dual-regimen group, and triple-regimen group reported median PFS durations of 4.8 months, 11.9 months, and 23.4 months, respectively. Both combination groups exhibited significantly longer PFS than the chemotherapy-only group (P

Aiming at the main problems that affect the security of airborne computing platform after virtualization, such as time-space isolation, fault isolation and schedulability, this paper studies the security level evaluation of airborne computing platform under virtualization environment. Considering the characteristics of virtualized avionics system, a security calculation method based on analytic hierarchy process(AHP) and gray correlation analysis(GARD) is proposed. The safety evaluation decision tree of airborne virtualization computing platform is established, and the weight of each safety capability is calculated by AHP method, and the overall safety score of the system is given. On this basis, combined with GRAP method and referring to the safety evaluation of avionics system, the safety level with the highest adaptability between the test system and DAL safety level requirements is calculated, realizing security grade evaluation of airborne computing platform under virtualization environment.

The past few years have witnessed an increasing incidence of nodular goiter (NG), with a well-documented higher prevalence in females than males. This gender disparity has led research to focus primarily on female subjects, potentially overlooking common pathogenic mechanisms in both sexes. In this study, we investigated the shared pathogenesis of NG in males and females. Utilizing a rat model and RNA sequencing, we identified differentially expressed genes associated with the disease. We further validated these findings in normal human thyroid cells and human papillary thyroid cancer cells. A randomized experiment was conducted with equal numbers of male and female rats divided into control and NG model groups. The NG model was established using propylthiouracil and various assessments such as thyroid ultrasonography, thyroid index, thyroid function, and thyroid histology were performed. Transcriptome analysis revealed numerous upregulated and downregulated genes in both male and female model groups. Key genes like KDR, FLT1, PDGFB, and CAV1, and pathways including PI3K-Akt, MAPK, Ras, fluid shear stress and atherosclerosis, calcium signaling, and Rap1 signaling pathways were linked with the disease. Western blot and immunofluorescence analysis confirmed these findings, which were further supported by cell-based experiments. In conclusion, our findings suggest that abnormal expression of specific genes and pathways leading to irregular cell growth, blood vessel formation, and inflammation may be common factors in the pathogenesis of NG in both males and females.

This paper explores the formation mechanisms of various architectural forms in a cultural transition region. A field investigation involving 504 ancestral shrines with Guangfu and Hakka styles in Shenzhen was performed. Then, spatial distribution analysis was conducted to reveal the regional structure of aggregation, penetration and juxtaposition of the architectural forms. Case studies were adopted to explain the integration modes of the architectural forms. The results show that, juxtaposition, as a typical mode of coexistence of architectural forms in cultural transition zones, mainly occurs in regions dominated by weak cultures. Through gathering densely in a small region, a weak culture can gain the ability to compete with a strong culture, thus forming a basis for achieving an equilibrium state. The approaches to the integration of architectural forms are diverse. The transformation of the architectural plane involves changes in social organization and cultural essence. The alteration of construction details and decoration involves a compromise regarding noncritical elements adopted by the weak culture to maintain its original characteristics. Finally, their shared human and natural environmental “genes” give the buildings in the cultural transition region an underlying commonality. This study offers a significant addition to the cultural geography and architectural morphology literature.

A novel type of integral damping gear （IDG） is developed and designed to study the influence of different damping liquid viscosity of IDG on the vibration and noise reduction characteristics of the gear transmission system. The IDG damping mechanical model is established, and the effectiveness of IDG control of gear system vibration is analyzed. An experimental platform for the first-order spur gear transmission system is built to compare the vibration at the support of the ordinary spur gear system and the IDG system with different damping liquid viscosity. The results show that IDG can effectively control the vibration of the gear transmission shaft system. In the range of damping fluid viscosity used in this experiment, with the increase of the damping fluid viscosity used in IDG, the vibration of the gear shaft system decreases gradually, and the average vibration reduction amplitude of IDG under the maximum viscosity is more than 50%. At the same time, IDG can effectively reduce the noise of the gear system, and the maximum viscosity can reduce 7.6 dB（A） noise. It is further proved that IDG has excellent vibration and noise reduction characteristics, which ensures the smooth operation of the gear transmission system and provides a new idea for vibration and noise reduction of the gear system.

Abstract Due to the rise of 5G, IoT, AI, and high-performance computing applications, datacenter traffic has grown at a compound annual growth rate of nearly 30%. Furthermore, nearly three-fourths of the datacenter traffic resides within datacenters. The conventional pluggable optics increases at a much slower rate than that of datacenter traffic. The gap between application requirements and the capability of conventional pluggable optics keeps increasing, a trend that is unsustainable. Co-packaged optics (CPO) is a disruptive approach to increasing the interconnecting bandwidth density and energy efficiency by dramatically shortening the electrical link length through advanced packaging and co-optimization of electronics and photonics. CPO is widely regarded as a promising solution for future datacenter interconnections, and silicon platform is the most promising platform for large-scale integration. Leading international companies (e.g., Intel, Broadcom and IBM) have heavily investigated in CPO technology, an inter-disciplinary research field that involves photonic devices, integrated circuits design, packaging, photonic device modeling, electronic-photonic co-simulation, applications, and standardization. This review aims to provide the readers a comprehensive overview of the state-of-the-art progress of CPO in silicon platform, identify the key challenges, and point out the potential solutions, hoping to encourage collaboration between different research fields to accelerate the development of CPO technology. Graphical Abstract

By leveraging a multiscale geographically weighted regression (MGWR) model, this paper delves into the intricate factors that influence housing prices in the prototypical mountainous cityscape of Chongqing’s central urban area. The key findings are as follows: Firstly, the distribution of housing prices in the study region exhibits pronounced spatial heterogeneity, with the core area exhibiting a distinct “high-high” clustering pattern and manifesting characteristics of a multicenter group distribution. Secondly, the MGWR model effectively assigns an individual bandwidth to each feature quantity, allowing for a more nuanced portrayal of the varying influence scales exerted by diverse variables. Lastly, the study reveals that factors such as property cost, greening rate, building age, and proximity to rivers have a notable negative impact on housing prices, whereas, educational facilities exert a marked positive influence. Elevation, floor area ratio, and distance from the Central Business District (CBD) exhibit a more complex influence on housing prices.

A multi-layer stacked Dynamic Random Access Memory (DRAM) platform is introduced to address the memory wall issue. This platform features high-density vertical interconnects established between DRAM units for high-capacity memory and logic units for computation, utilizing Wafer-on-Wafer (WoW) hybrid bonding and mini Through-Silicon Via (TSV) technologies. This 3DIC architecture includes commercial DRAM, logic, and 3DIC manufacturing processes. Their design documents typically come from different foundries, presenting challenges for signal integrity design and analysis. This paper establishes a lumped circuit based on 3DIC physical structure and calculates all values of the lumped elements in the circuit model with the transmission line model. A Cross-Process Signal Integrity Analysis (CPSIA) method is introduced, which integrates three different manufacturing processes by modeling vertical stacking cells and connecting DRAM and logic netlists in one simulation environment. In combination with the dedicated buffer driving method, the CPSIA method is used to analyze 3DIC impacts. Simulation results show that the timing uncertainty introduced by 3DIC crosstalk ranges from 31 ps to 62 ps. This analysis result explains the stable slight variation in the maximum frequency observed in vertically stacked memory arrays from different DRAM layers in the physical testing results, demonstrating the effectiveness of this CPSIA method.

BackgroundRumination impedes problem solving and is one of the most important factors in the onset and maintenance of multiple psychiatric disorders. The current study aims to investigate the impact of social rejection on rumination and explore the underlying neural mechanisms involved in this process.MethodsWe utilized psychological questionnaire and resting-state brain imaging data from a sample of 560 individuals. The predictive model for rumination scores was constructed using resting-state functional connectivity data through connectome-based predictive modeling. Additionally, a mediation analysis was conducted to investigate the mediating role of the prediction network in the relationship between social rejection and rumination.ResultsA positive correlation between social rejection and rumination was found. We obtained the prediction model of rumination and found that the strongest contributions came from the intra- and internetwork connectivity within the default mode network (DMN), dorsal attention network (DAN), frontoparietal control network (FPCN), and sensorimotor networks (SMN). Analysis of node strength revealed the significance of the supramarginal gyrus (SMG) and angular gyrus (AG) as key nodes in the prediction model. In addition, mediation analysis showed that the strength of the prediction network mediated the relationship between social rejection and rumination.ConclusionThe findings highlight the crucial role of functional connections among the DMN, DAN, FPCN, and SMN in linking social rejection and rumination, particular in brain regions implicated in social cognition and emotion, namely the SMG and AG regions. These results enhance our understanding of the consequences of social rejection and provide insights for novel intervention strategies targeting rumination.

Abstract For the first time, a configurable NbOx memristor is achieved that can be configured as an artificial synapse or neuron after fabrication by controlling the forming compliance current (FCC). When the FCC ≤ 2 mA, the memristors exhibit the resistive‐switching (RS) property, enabling multiple types of synaptic plasticity, including short‐term potentiation, paired‐pulse facilitation, short‐term memory, and long‐term memory. When the FCC ≥ 3 mA, the memristors can be electroformed and exhibit the threshold switching (TS) property with excellent endurance (>1012), thus achieving various biological neuron characteristics, such as threshold‐triggering, strength‐modulation of spike frequency, and leaky integrate‐and‐fire. This enables the successful implementation of a spiking Pavlov's dog that employs the spikes as information carrier by connecting an RS NbOx memristor as artificial synapse and a TS memristor as artificial neuron in series. Furthermore, a fully NbOx memristors‐based single‐layer spiking neural network is simulated. It is first found that, due to the forgetting property of synapse, the recognition accuracy for the Modified National Institute of Standards and Technology handwritten digits is increased from 85.49% to 91.45%. This study provides a solid foundation for the development of neuromorphic machines based on the principles of the human brain.

BackgroundColorectal cancer (CRC) patients with BRAF mutation have very poor prognosis. It is urgent to search for prognostic factors of BRAF mutant CRC. RNF43 is a ENF ubiquitin ligase of Wnt signaling. Mutation of RNF43 has been observed frequently in various types of human cancers. However, few studies have evaluated the role of RNF43 in CRC. The present study aimed to explore the impact of RNF43 mutations on molecular characteristics and prognosis in BRAF mutant CRC.MethodsSamples of 261 CRC patients with BRAF mutation were retrospectively analyzed. Tumor tissue and matched peripheral blood samples were collected and subjected to targeted sequencing with a panel of 1021 cancer-related genes. The association of molecular characteristics and survival in patients were then analyzed. 358 CRC patients with BRAF mutation from the cBioPortal dataset were used for further confirmation.ResultsThis study was inspired by a CRC patient with BRAF V600E and RNF43 co-mutation, who achieved a best remission of 70% and a progression free survival (PFS) of 13 months. Genomic analysis indicated that RNF43 mutation affected the genomic characteristics of patients with BRAF mutation, including microsatellite instability (MSI), tumor mutation burden (TMB) and the proportion of common gene mutations. Survival analysis showed that RNF43 mutation was a predictive biomarker for better PFS and OS in BRAF mutant CRC.ConclusionCollectively, we identified that RNF43 mutations were correlated with favorable genomic features, resulting in a better clinical outcome for BRAF mutant CRC patients.

Abstract Objective To evaluate the safety of performing surgery on cavernous haemangiomas in the liver larger than 10 cm and establish preoperative predictors of intraoperative blood transfusion and morbidity. Methods A total of 373 patients with haemangiomas larger than 10 cm who underwent surgery in our hospital were retrospectively analysed. According to tumour diameter, the patients were divided into a giant haemangioma (GH) group (241 cases) (10 cm ≤ diameter

IntroductionNurses have a high prevalence of occupational low back pain, especially since the outbreak of the COVID-19 pandemic, which has increased the nurses' workloads. It has brought a huge burden on nurses and their professional development. Nurses' occupational low back pain prevention capacity is the logical starting point and core of interventions to prevent its occurrence. To date, there is no study investigating it with a scientific scale. Therefore, a multicenter cross-sectional study was conducted to explore the current status of nurses' capacity in occupational low back pain prevention and its influencing factors in China.MethodsUsing a two-stage, purposive and convenience mixed sampling method, 1331 nurses from 8 hospitals across 5 provinces (Hubei, Zhejiang, Shandong, Henan, and Sichuan) in the southern, western, northern, and central areas of mainland China were involved in this study. The demographic questionnaire and occupational low back pain prevention behavior questionnaire were used for data collection. The descriptive analysis, univariate analysis, and multiple stepwise linear regression were used for data analysis.ResultsThe results showed that the occupational low back pain prevention behavior questionnaire score was 89.00 (80.00, 103.00) [M (Q1, Q3)], which indicated that nurses' ability was at a moderate level. Participation in prevention training before, perceived stress at work, and working hours per week were predictors for nurses' occupational low back pain prevention capacity.DiscussionTo improve nurses' prevention ability, nursing managers should organize various training programs, strengthen regulations to reduce nurses' workload and stress, provide a healthy workplace, and offer incentives to motivate nurses.

Abstract Mismatch in the binary‐weighted capacitive digital‐to‐analog converter (DAC) greatly affects the linearity of the successive‐approximation‐register (SAR) ADC by deteriorating the total harmonic distortion (THD). In this study, a theoretical relationship between the THD and the mismatch error of DAC array in SAR ADC is derived through discrete Fourier transform (DFT) analysis of the time‐based integral error (TIE) of the ADC's output codes, which has no specific requirement on the type of the input signals. Guided by the theoretical THD expression, the trade‐off among the linearity, design complexity, power consumption and chip area can be balanced easily. The presented formula is verified by a design example of 12‐bit SAR ADC with dynamic‐element‐matching (DEM) technique, where the 3‐bit LSBs from the SAR ADC are used to generate the randomised DEM state according to the previous THD evaluation. The linearity is enhanced by 9 dB approximately with very low hardware complexity and extremely small extra power consumption of 2 μW.

With the emergence of new 5G business, architecture and technology, more and more researchers pay attention to security issues and potential security risks. Massive machine type communication is one of the three major application scenarios of 5G. It provides high performance such as large connection and low power consumption. Due to factors such as limited resources of MTC equipment, it may also weaken the security of 5G networks. At the same time, different scenarios and applications have obvious demands for network performance, service quality and security level. The flexibility of 5G networking is realized by network slicing technology. It meets the diversity and customization of 5G network services, but also brings new security threats. 5G commercial rapid development. The number of IoT devices has increased exponentially. In order to ensure that 5G networks provide more efficient and safe on-demand services, it is particularly important to study the security mechanism and strategy of network slicing for 5G mMTC application scenarios. Therefore, the characteristics and security requirements of 5G mMTC were analyzed. The main security threats of network slicing were listed. In view of the above security requirements and threats, the contribution and deficiency of existing security schemes around the aspects of specific network slice authentication, slice security isolation, security management and arrangement were summarized and expounded. And the future research in this field was prospected. A SM2-based secondary authentication and security isolation model for 5G mMTC network slicing was proposed. This model framework meeted the efficiency of large-scale authentication for 5G devices and users by introducing batch authentication and pre-authentication mechanisms. By hierarchical encryption of different communication data, the security isolation between 5G mMTC network slices was realized. The performance and security of the model were also analyzed.

Abstract Background Ovarian cancer is a common gynecological malignant disease in women. Our work aimed to study the specific functions of ZNF252P antisense RNA 1 (ZNF252P-AS1) in ovarian cancer. Methods ZNF252P-AS1, miR-324-3p, and lymphocyte antigen 6 family member K (LY6K) expression were analyzed by bioinformatics tools in ovarian cancer tissues and was quantified by qRT-PCR in ovarian cancer cells. The effect of ZNF252P-AS1 knockdown, miR-324-3p suppression, and LY6K over-expression on apoptosis, cell viability, invasion, migration, and epithelial to mesenchymal transition (EMT) was determined in vitro by using colony formation and EdU assays, flow cytometry, transwell assay, and Western blot. The interactions between ZNF252P-AS1 and miR-324-3p and between miR-324-3p and LY6K were validated by luciferase assays. The effects of restraining ZNF252P-AS1 in vivo were studied using BALB/c male nude mice. Results ZNF252P-AS1 and LY6K levels were up-regulated, while miR-324-3p was declined in ovarian cancer tissues and cells. ZNF252P-AS1 knockdown reduced ovarian cancer cell proliferation, invasion, migration, and EMT, whereas promoted its apoptosis. Besides, ZNF252P-AS1 interacted with miR-324-3p and reversely regulated its level, and miR-324-3p was directly bound to LY6K and negatively regulated its expression. Moreover, ZNF252P-AS1 knockdown reversed the effect of miR-324-3p on cancer cell apoptosis, growth, migration, invasion, and EMT. Similar results were discovered in the rescue experiments between miR-324-3p and LY6K. Additionally, mouse models in vivo experiments further validated that ZNF252P-AS1 knockdown distinctly inhibited tumor growth. Conclusion ZNF252P-AS1 mediated miR-324-3p/LY6K signaling to facilitate progression of ovarian cancer.

Objective To investigate the protective effects and primary mechanism of ginsenoside Rg1 on cardiac muscle of aging mice induced by D-galactose (D-gal). Methods C57BL/6 J mice were randomly divided into normal control, model, Rg1 intervention and negative control groups, with 10 animals in each group. D-gal (200 mg/kg) was injected intraperitoneally to the mice for 42 d to establish the model group, and the mice of the Rg1 intervention group was given 40 mg/kg Rg1 per day for 26 d intraperitoneally from the 16th day of model establishment. The mice of the normal control group were given same amount of normal saline for 42 d, and those of the negative control group were treated with normal saline after model establishment. On the 2nd day after treatment, the hearts were taken to measure the organ index. HE staining and transmission electron microscopy were performed to observe the morphology and micro-structures of the heart tissue from each group. The activities of aspartate aminotransferase (AST), lactate dehydrogenase (LDH), total superoxide dismutase (T-SOD), catalase (CAT) and contents of malondialdehyde (MDA) in the myocardial tissue homogenate were tested by enzyme-labeled colorimetry; The expression levels of Nrf2, Keap1 and HO-1 in the heart tissue were detected by Western blotting. Results Compared with the control group, the model group had significantly increased heart index (P < 0.01); larger amount of deposited collagen fibers between myocardial fibers, disordered myofibril bundles, thicker myocardial fibers, and abnormally swollen mitochondria; enhanced AST and LDH activities, declined T-SOD and CAT activities, and increased MDA content (P < 0.05); remarkably down-regulation of Nrf2 and HO-1 (P < 0.05), and no changed Keap1 level. While in the Rg1 intervention group, all the above phenomena were greatly improved after the intervention, with obviously decreased heart index (P < 0.01), not notable morphological changes with normal control mice, reversed AST, LDH, T-SOD and CAT activities and MDA contents(P < 0.05), and elevated protein levels of Nrf2 and HO-1, and decreased level of Keap1 (P < 0.01). Conclusion Rg1 effectively alleviates the damage of D-gal to the morphology and ultrastructure of mouse myocardium, and its mechanism may be related to the inhibition of oxidative stress and the up-regulation of the Nrf2 antioxidant signal pathway.

Endothelial oxidative stress and inflammation attributable to the activation of a Nox2-NADPH oxidase are key features of many cardiovascular diseases. Here, we report a novel small chemical compound (LMH001, MW = 290.079), by blocking phosphorylated p47phox interaction with p22phox, inhibited effectively angiotensin II (AngII)-induced endothelial Nox2 activation and superoxide production at a small dose (IC50 = 0.25 μM) without effect on peripheral leucocyte oxidative response to pathogens. The therapeutic potential of LMH001 was tested using a mouse model (C57BL/6J, 7-month-old) of AngII infusion (0.8 mg/kg/d, 14 days)-induced vascular oxidative stress, hypertension and aortic aneurysm. Age-matched littermates of p47phox knockout mice were used as controls of Nox2 inhibition. LMH001 (2.5 mg/kg/d, ip. once) showed no effect on control mice, but inhibited completely AngII infusion-induced excess ROS production in vital organs, hypertension, aortic walls inflammation and reduced incidences of aortic aneurysm. LMH001 effects on reducing vascular oxidative stress was due to its inhibition of Nox2 activation and was abrogated by knockout of p47phox. LMH001 has the potential to be developed as a novel drug candidate to treat oxidative stress-related cardiovascular diseases.

Abstract Lysine 2-hydroxyisobutyrylation (Khib) is a novel naturally occurring post-translational modification. The system Khib identification at proteomics level has been performed in various species and tissues to characterize the role of Khib in biological activities. However, the study of Khib in plant species is relatively less. In the present study, the first plant root tissues lysine 2-hydroxyisobutyrylome analysis was performed in wheat with antibody immunoprecipitation affinity, high resolution mass spectrometry-based proteomics and bioinformatics analysis. In total, 6328 Khib sites in 2186 proteins were repeatedly identified in three replicates. These Khib proteins showed a wide subcellular location distribution. Function and pathways characterization of these Khib proteins indicated that many cellular functions and metabolism pathways were potentially affected by this modification. Protein and amino acid metabolism related process may be regulated by Khib, especially ribosome activities and proteins biosynthesis process. Carbohydrate metabolism and energy production related processes including glycolysis/gluconeogenesis, TCA cycle and oxidative phosphorylation pathways were also affected by Khib modification. Besides, root sulfur assimilation and transformation related enzymes exhibited Khib modification. Our work illustrated the potential regulation role of Khib in wheat root physiology and biology, which could be used as a useful reference for Khib study in plant root.

An amendment to this paper has been published and can be accessed via the original article.

The spontaneous bioelectrical activity of pacemaker cells in sinoatrial node (SAN) triggers the heartbeats. Here, the authors perform single-cell RNA sequencing in the mouse SAN and identify molecular and cellular features of the SAN conserved in rabbit and cynomolgus monkey, identifying a new potential SAN marker.

In recent years, circular RNAs (circRNAs) have been shown to have critical regulatory roles in the resistance to anti-cancer drugs. However, the contributions of circRNAs to sorafenib resistance in hepatocellular carcinoma (HCC) remain largely unknown. The present study aims to explore the involvement of circFN1 in sorafenib resistance and how circFN1 is associated with the miR-1205/E2F1 pathway, which have been demonstrated to mediate this resistance in HCC cells. We investigated the expression of circRNAs in five paired sorafenib-sensitive HepG2 cells and sorafenib-resistant (SR)-HepG2 cells by microarray analysis. The quantitative real-time PCR analysis was used to investigate the expression pattern of circFN1 in HCC patient tissues and cell lines. Then, the effects of circFN1 on sorafenib resistance, cell proliferation, and apoptosis were assessed in HCC in vitro and in vivo. In this study, circFN1 was observed to be upregulated in HCC patient tissues and cell lines. Overexpression of circFN1 in HCC was significantly correlated with aggressive characteristics and served as an independent risk factor for overall survival in patients with HCC. Our in vivo and in vitro data indicated that inhibition of circFN1 enhances the sorafenib sensitivity of HCC cells. Mechanistically, we found that circFN1 could promote the expression of E2F1 by sponging miR-1205. In summary, our study demonstrated that circFN1 contributes to sorafenib resistance by regulating the miR-1205/E2F1 signaling pathway. These results indicate that circFN1 may represent a potentially valuable target for overcoming sorafenib resistance for HCC.

Microwave Digestion-Triple Quadrupole Inductively Coupled Plasma Mass Spectrometry (ICP-MS/MS) was used to determine sulfur in crop samples, and a high sensitivity sulfur detection method in crop samples was provided. The measurement mode, interference elimination effect, linear range, detection limit and accuracy of the method were tested. The results show that the MS/MS oxygen mode can effectively eliminate the mass spectrum interference of sulfur, the method has high sensitivity, the detection limit of the method reaches 1.8 µg/g, and the sample with sulfur content below 2% can be directly analyzed by the method. The method was verified by national standard material, and the measured values were within the range of nominal value. It can be used as a new detection method for sulfur element analysis in crop samples.

Abstract Flexible materials and devices that can simultaneously reflect multimodal information are highly desired for novel flexible electronics and intelligent flexible sensing systems. In this regard, flexible magnetic films have great potential for wireless multimodal flexible sensor due to the curvature and azimuth angle‐dependent ferromagnetic resonance. However, a key challenge now is to build the precise relationship among the mechanical bending, azimuth angle, and the ferromagnetic resonance of the film, which involves multi‐physics and coupled process. In this work, the physical problem is solved by combining material engineering and machine learning. Material domain engineering is applied to form localized multi‐peak ferromagnetic resonance features for increasing sensitivity. Besides, convolutional neural network algorithm is utilized to help recognize the bending and azimuth angle modulated ferromagnetic resonance in flexible film systems. It is found that the bending information for the flexible film with engineered domain structure can be mapped to the ferromagnetic profile with accuracy over 99%, while the accuracy sharply decreases to less than 50% in the control group of high‐quality film. This study provides a versatile platform for developing machine learning‐based novel sensing materials.

Platinum-based cytotoxic chemotherapy is considered the standard treatment for advanced gastric cancer (GC). However, cisplatin chemoresistance often occurs with the mechanisms being not well clarified, which results in the cancer recurrence and poor survival. Ginsenoside Rg3, isolated from the Chinese Herb Panax Ginseng, is recognized as an anti-cancer agent. Herein, we aimed to reveal whether Ginsenoside Rg3 alleviates cisplatin resistance and sensitizes GC cells to cisplatin-induced apoptosis, and draw out the underlying molecular mechanism in cisplatin-resistant GC cells. The lower expression of miR-429 was found in AGSR-CDDP cells; it was also in association with cisplatin-resistance in GC cells and expression of which was restored following Ginsenoside Rg3 treatment. We also demonstrated that miR-429 made a contribution toward chemosensitivity in GC cells partly through SOX2 regulation. SOX2 was found to contribute to developing platinum resistance and was an authentic target for miR-429 in AGSR-CDDP cells. Importantly, enforced expression of SOX2 with a pcDNA3-SOX2 construct lacking the 3′-UTR miRNA binding site diminished the cytotoxic effects of miR-429 in AGSR-CDDP cells. We demonstrated that Ginsenoside Rg3 enhanced chemosensitivity in AGSR-CDDP GC cells, at least in part, through up-regulating miR-429, thereby targeting SOX2 and modulating downstream PI3K/AKT/mTOR signaling. Ginsenoside Rg3 was also found to regulate apoptosis-related genes via miR-429 in cisplatin-resistant GC cells. Ginsenoside Rg3 treatment significantly suppressed the migration rate of AGSR-CDDP GC cells, while following transfection with anti-miR-429, the anti-migratory effects of Ginsenoside Rg3 was partially abolished. This data suggested that Ginsenoside Rg3 may impede the chemoresistance and migration of GC cells mainly mediated through miR-429. We concluded that miR-429-regulated SOX2 expression was one of the main mechanisms by which Ginsenoside Rg3 dramatically promoted its anticancer effects on cisplatin-resistant GC cells. We also underscored a supporting model in which miR-429 adjusted PI3K/AKT/mTOR signaling by regulating SOX2 in cisplatin-resistant GC cells.

Abstract Background Medical science students represent valuable labour resources for better future medicine and medical technology. However, little attention was given to the health and well-being of these early career medical science professionals. The aim of this study is to investigate the impact of lifestyle components on cardiorespiratory fitness and heart rate recovery measured after moderate exercise in this population. Methods Volunteers without documented medical condition were recruited randomly and continuously from the first-year medical science students during 2011–2014 at the University of Surrey, UK. Demographics and lifestyle components (the levels of smoking, alcohol intake, exercise, weekend outdoor activity and screen-time, daily sleep period, and self-assessment of fitness) were gathered through pre-exercise questionnaire. Cardiorespiratory fitness (VO2max) and heart rate recovery were determined using Åstrand–Rhyming submaximal cycle ergometry test. Data were analysed using SPSS version 25. Results Among 614 volunteers, 124 had completed both lifestyle questionnaire and the fitness test and were included for this study. Within 124 participants (20.6 ± 4 years), 46.8% were male and 53.2% were female, 11.3% were overweight and 8.9% were underweight, 8.9% were current smokers and 33.1% consumed alcohol beyond the UK recommendation. There were 34.7% of participants admitted to have

Topological optics is an emerging research area in which various topological and geometrical ideas are being proposed to design and manipulate the behaviors of photons. Here, the photonic spin Hall effect on the surfaces of topological Weyl semimetal (WSM) films was studied. Our results show that the spin-dependent splitting (i.e. photonic spin Hall shifts) induced by the spin-orbit interaction is little sensitive to the tilt αt of Weyl nodes and the chemical potential μ in type-I WSM film. In contrast, photonic spin Hall shifts in both the in-plane and transverse directions present versatile dependent behaviors on the αt and μ in type-II WSM film. In particular, the largest in-plane and transverse spin Hall shifts appear at the tilts between −2 and −3, which are ~40 and ~10 times of the incident wavelength, respectively. Nevertheless, the largest spin Hall shifts for type-II WSM film with positive αt are only several times of incident wavelength. Moreover, the photonic spin Hall shifts also exhibit different variation trends with decreasing the chemical potential for different signs of αt in type-II WSM films. This dependence of photonic spin Hall shifts on tilt orientation in type-II WSM films has been explained by time-reversal-symmetry-breaking Hall conductivities in WSMs.

The photonic spin Hall effect (PSHE) is a promising candidate for controlling the spin states of photons and exploiting next-generation photonic devices based on spinoptics. Herein, the influences of a perpendicular magnetic field on the PSHE appearing on the surface of monolayer black phosphorus (BP) are investigated. Results reveal that both the in-plane and transverse spin-dependent shifts are quantised and show an oscillating pattern due to the splitting of Landau levels (LLs) induced by the external magnetic field B. And the oscillation period of spin Hall shifts gradually increases with strengthening B because of the increase of LL spacings. By contrast, for a fixed magnetic field, as the LL spacings become smaller and smaller with increasing the LL index, the oscillation period of spin Hall shifts gradually decreases as the photonic energy increases. Moreover, it is possibly due to the synergistic role of intrinsic anisotropy, high crystallinity, and quantisation-incurred localised decreases in beating-like complex conductivities of the BP film, giant spin Hall shifts, hundreds of times of the incident wavelength, are obtained in both transverse and in-plane directions. These unambiguously confirm the strong impact of the external magnetic field on the PSHE and shed important insights into understanding the rich magneto-optical transport properties in anisotropic two-dimensional atomic crystals.

Urban planners have been long interested in understanding how urban structure and activities are mutually influenced. Human mobility and economic activities naturally drive the formation of road network structure and the accessibility of the latter shapes the patterns of movement flow across urban space. In this paper, we perform an exploratory study on the relationship between the street network structure and the intensity of human movement in urban areas. We focus on two cities and we utilize a dataset of geo-tagged tweets that can form a proxy to urban mobility and the corresponding street networks as obtained from OpenStreetMap. We apply three network centrality measures, including closeness, betweenness and straightness centrality, calculated at a global or local scale, as well as under mixed or individual transportation mode (e.g., driving, biking and walking) with its directional accessibility, to uncover the structural properties of urban street networks. We further design an urban area transition network and apply PageRank to capture the intensity of human mobility. Our correlation analysis indicates different centrality metrics have different levels of correlation with the intensity of human movement. The closeness centrality consistently shows the highest correlation (with a coefficient around 0.6) with human movement intensity when calculated at a global scale, while straightness centrality often shows no correlation at the global scale or weaker correlation ρ≈0.4 at the local scale. The correlation levels further depend on the type of directional accessibility and of various types of transportation modes. Hence, the directionality and transportation mode, largely ignored in the analysis of road networks, are crucial. Furthermore, the strength of the correlation varies in the two cities examined, indicating potential differences in urban spatial structure and human mobility patterns.

Hypertension is caused by polygenic inheritance and the interaction of various environmental factors. Abnormal function of the renin-angiotensin-aldosterone system (RAAS) is closely associated with changes in blood pressure. As an essential factor in the RAAS, angiotensin II (Ang II) contributes to vasoconstriction and inflammatory responses. However, the effects of overproduction of Ang II on the whole body-metabolism have been unclear. In this study, we established a hypertensive mouse model by micro-osmotic pump perfusion of Ang II, and the maximum systolic blood pressure reached 140 mmHg after 2 weeks. By ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry, the metabolites in the serum of hypertensive model and control mice were analyzed. Partial least squares discriminant analysis (PLS-DA) in both positive and negative ionization modes showed clear separation of the two groups. Perfusion of Ang II induced perturbations of multiple metabolic pathways in mice, such as steroid hormone biosynthesis and galactose metabolism. Tandem mass spectrometry revealed 40 metabolite markers with potential diagnostic value for hypertension. Our data indicate that non-targeted metabolomics can reveal biochemical pathways associated with Ang II-induced hypertension. Although researches about the clinical use of these metabolites as potential biomarkers in hypertension is still needed, the current study improves the understanding of systemic metabolic response to sustained release of Ang II in hypertensive mice, providing a new panel of biomarkers that may be used to predict blood pressure fluctuations in the early stages of hypertension.

Low-frequency electronic noise is an important parameter used for the electronic and sensing applications of transistors. Here, we performed a systematic study on the low-frequency noise mechanism for both p-channel and n-channel MoTe2 field-effect transistors (FET) at different temperatures, finding that low-frequency noise for both p-type and n-type conduction in MoTe2 devices come from the variable range hopping (VRH) transport process where carrier number fluctuations (CNF) occur. This process results in the broad distribution of the waiting time of the carriers between successive hops, causing the noise to increase as the temperature decreases. Moreover, we found the noise magnitude for p-type MoTe2 FET hardly changed after exposure to the ambient conditions, whereas for n-FET, the magnitude increased by nearly one order. These noise characteristics may provide useful guidelines for developing high-performance electronics based on the emerging transition metal dichalcogenides.

Background: Chromosomal abnormalities play an important role in the diagnosis and prognosis of patients with myelodysplastic syndromes (MDSs). The single-nucleotide polymorphism array (SNP-A) technique has gained popularity due to its improved resolution compared to that of metaphase cytogenetic (MC) analysis.Methods: A total of 376 individuals were recruited from two medical centers in China, including 350 patients and 26 healthy individuals. Among these patients, 200 were diagnosed with de novo MDS, 25 with myeloproliferative neoplasm (MPN), 63 with primary acute myeloid leukemia (AML), and 62 with idiopathic cytopenia of undetermined significance (ICUS). We evaluated the significance of abnormal chromosomes detected by SNP-A in the diagnosis and prognosis of MDS-related disorders.Results: (1) When certain chromosomal abnormalities could not be detected by conventional MC methods, these abnormalities could be detected more efficiently by the SNP-A method. With SNP-A, the detection rates of submicroscopic or cryptic aberrations in the MDS, MPN, and AML patients with normal MC findings were 32.8, 30.8, and 30%, respectively. (2) The chromosomal abnormalities detected by SNP-A had a very important value for the prognosis of patients with MDSs, especially in the low-risk group. The survival of patients with abnormal chromosomes detected by SNP-A was significantly lower than that of patients with no detected chromosomal abnormalities; this difference was observed in overall survival (OS) (P = 0.001) and progression-free survival (PFS) [24 months vs. not reach (NR); P = 0.008]. The patients with multiple chromosomal abnormalities detected by SNP-A had an inferior prognosis, and SNP-A abnormalities (≥3 per patient) were found to be an independent predictor of poor prognosis in patients with MDSs [hazard ratio (HR) = 2.40, P = 0.002]. (3) Patients with ICUS may progress to myeloid malignancies, but most patients often maintain a stable ICUS status for many years without progression. An ICUS patient found to have an MDS-related karyotype would be rediagnosed with MDS. SNP-A can efficiently detect chromosomal abnormalities, which would be important for assessing the evolution of ICUS. In our study, 17 ICUS patients with SNP-A-detected abnormalities developed typical MDSs.Conclusions: SNP-A can help evaluate the prognosis of patients with MDSs and better assess the risk of disease progression for patients with ICUS.

Abstract Background Preeclampsia (PE) is a common pregnancy‐related syndrome characterized by hypertension and proteinuria, and a major cause of maternal mortality. Therefore, there is an urgent need to identify early biomarkers of PE. The aim of the present study was to identify the functions of miR‐576‐5p in PE. Methods Effects of miR‐576‐5p and transcription factor AP‐2α (TFAP2A) on invasion of human trophoblast HTR8/SVneo cells were investigated. Real‐time quantitative polymerase chain reaction (RT‐qPCR) and western blotting were used to assess the expression of miR‐576‐5p, TFAP2A, E‐cad, and Vimentin in PE tissues and cells. Additionally, immunofluorescence was used to detect the expression of TFAP2A in PE trophoblastic tissue. Subsequently, constructed miR‐576‐5p mimics, miR‐576‐5p inhibitor, and siRNA‐TFAP2A plasmids were transfected into HTR8/SVneo cells for further experiments, including a CCK‐8 assay for cell proliferation, Transwell assay for cell invasion and the luciferase reporter gene system was employed for target verification. Results A lower expression of miR‐576‐5p and a higher expression of TFAP2A were identified in PE rats. E‐cadherin was highly expressed while Vimentin was downregulated. Further statistical analysis indicated that cell proliferation of HTR8/SVneo cells decreased in the miR‐576‐5p inhibitor group and increased in the miR‐576‐5p mimics and siRNA‐TFAP2A groups. miR‐576‐5p inhibitor suppressed cell invasion, and miR‐576‐5p mimics and siRNA‐TFAP2A improved cell invasion. The analysis of luciferase reporter demonstrated a decreased luciferase activity in miR‐576‐5p mimics group compared with control group, which indicates that TFAP2A may be a target of miR‐576‐5p. Interference of TFAP2A could downregulate E‐cadherin and upregulate Vimentin expression. Conclusion Overexpression of miR‐576‐5p and knockdown of TFAP2A may elevate cell proliferation and invasion of human trophoblast cells in vitro. Therefore, miR‐576‐5p may be used as a notable biomarker for the diagnosis, prevention, and treatment of PE. miR‐576‐5p targeting TFAP2A deserve further investigation in order to explore their potential role in PE.

The p47phox is a key regulatory subunit of Nox2-containing NADPH oxidase (Nox2) that by generating reactive oxygen species (ROS) plays an important role in Angiotensin II (AngII)-induced cardiac hypertrophy and heart failure. However, the signalling pathways of p47phox in the heart remains unclear. In this study, we used wild-type (WT) and p47phox knockout (KO) mice (C57BL/6, male, 7-month-old, n = 9) to investigate p47phox-dependent oxidant-signalling in AngII infusion (0.8 mg/kg/day, 14 days)-induced cardiac hypertrophy and cardiomyocyte apoptosis. AngII infusion resulted in remarkable high blood pressure and cardiac hypertrophy in WT mice. However, these AngII-induced pathological changes were significantly reduced in p47phox KO mice. In WT hearts, AngII infusion increased significantly the levels of superoxide production, the expressions of Nox subunits, the expression of PKCα and C-Src and the activation of ASK1 (apoptosis signal-regulating kinase 1), MKK3/6, ERK1/2, p38 MAPK and JNK signalling pathways together with an elevated expression of apoptotic markers, i.e., γH2AX and p53 in the cardiomyocytes. However, in the absence of p47phox, although PKCα expression was increased in the hearts after AngII infusion, there was no significant activation of ASK1, MKK3/6 and MAPKs signalling pathways and no increase in apoptosis biomarker expression in cardiomyocytes. In conclusion, p47phox-dependent redox-signalling through ASK1, MKK3/6 and MAPKs plays a crucial role in AngII-induced cardiac hypertrophy and cardiomyocyte apoptosis.

Abstract Background Although gemcitabine-based chemotherapy has been established as a core multimodal therapy for non-small cell lung cancer (NSCLC) treatment, its clinical efficacy remains limited by the development of acquired resistance following tumor metastasis and relapse. In this study, we investigated how gemcitabine-resistant (GR) cells contribute to the development of NSCLC tumor malignancy via exosome-mediated transfer of microRNAs. Methods We first studied the mechanism of exosome internalization via PKH-67 staining and an immunofluorescence assay, then confirmed our finding by transmission electron microscopy and western blot analysis. Candidate miRNAs were identified through microarray analysis. Thereafter, RT-PCR, MTS, Transwell and soft agar assays were performed to assess the role of exosomic miR-222-3p in vitro. A 3’ untranslated region reporter assay was applied to identify the target of miR-222-3p. A lung metastasis mouse model was constructed to evaluate tumor growth and metastasis in vivo. Finally, clinical samples were used for correlation analysis between exosomic miR-222-3p levels and patients’ response to gemcitabine. Results A549-GR–derived exosomes were internalized by receipt cells via caveolin- and lipid raft-dependent endocytosis, which allowed the transfer of miR-222-3p. Exosomic miR-222-3p enhanced the proliferation, gemcitabine resistance, migration, invasion, and anti-anoikis of parental sensitive cells by directly targeting the promoter of SOCS3. In addition, a higher level of exosomic miR-222-3p in sera usually predicted worse prognosis in NSCLC patients. Conclusion Our data demonstrate that exosomic-miR-222-3p functions as a principal regulator of gemcitabine resistance and malignant characteristics by targeting SOCS3. The exosomic miR-222-3p level in sera may be a potential prognostic biomarker for predicting gemcitabine sensitivity in NSCLC patients.

BackgroundHeart failure is a complex syndrome characterized by cardiac contractile impairment with high mortality. Defective intracellular Ca2+ homeostasis is the central cause under this scenario and tightly links to ultrastructural rearrangements of sarcolemmal transverse tubules and the sarcoplasmic reticulum (SR); however, the modulators of the SR architecture remain unknown. The SR has been thought to be a specialized endoplasmic reticulum membrane system. Receptor accessory proteins (REEPs)/DP1/Yop1p are responsible for shaping high‐curvature endoplasmic reticulum tubules. This study aimed to determine the role of REEPs in SR membrane shaping and thus cardiac function. Methods and ResultsWe identified REEP5 (receptor accessory protein 5) as more highly expressed than other REEP members in adult rat ventricular myocardium, and it was downregulated in the failing hearts. Targeted inactivation of REEP5 in rats specially deformed the cardiac SR membrane without affecting transverse tubules, and this was visualized by focused ion beam scanning electron microscopy–based 3‐dimensional reconstruction. Accordingly, simultaneous recordings of depolarization‐induced Ca2+ currents and Ca2+ transients in REEP5‐null cardiomyocytes revealed normal L‐type Ca2+ channel currents but a depressed SR Ca2+ release. Consequently, the excitation–contraction coupling gain of cardiomyocytes and consequent cardiac contractility were compromised. REEP5 deficiency did not alter the expression of major proteins involved in Ca2+ handling in the heart. ConclusionsREEP5 modulates cardiac function by shaping the SR. REEP5 defect deforms the SR architecture to depress cardiac contractility. REEP5‐dependent SR shaping might have potential as a therapeutic target for heart failure.