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Abstract Background EphrinA5 belongs to a subclass of ephrin ligands. Abnormal signal transduction of EFNA5 shows a relationship to the development of various tumors. In this study, we explored the level of EFNA5 in hepatoma cells and the influence of up regulation of EFNA5 expression level on the proliferation, invasion, and migration of HepG2 and LM3 cells. Additionally, this work focused on examining its possible mechanism of action, and future impacts on clinical practice. Methods Immunohistochemistry was utilized to explore the connection between EFNA5 and hepatoma. Real-time quantitative polymerase chain reaction was used for determining the expression levels of EFNA5 in several hepatoma cell lines and normal hepatocytes. Cells were transfected with a pCMV3-EFNA5-flag plasmid and an EFNA5 plasmid. The expression efficiency of EFNA5 was identified through qRT-PCR. For the purpose of further identifying cell proliferation, the Cell Counting Kit-8 assay was applied. To identify changes of cell migration and invasion ability, Transwell and Boyden tests were utilized. Western blot was employed to identify the expressions mof EFNA5 and possible downstream molecules. Results Data acquired from The Cancer Genome Atlas demonstrated that the level of EFNA5 in hepatoma was significantly downregulated in relative to the normal hepatocytes (P

Abstract One-dimensional metallic transition-metal chalcogenide nanowires (TMC-NWs) hold promise for interconnecting devices built on two-dimensional (2D) transition-metal dichalcogenides, but only isotropic growth has so far been demonstrated. Here we show the direct patterning of highly oriented Mo6Te6 NWs in 2D molybdenum ditelluride (MoTe2) using graphite as confined encapsulation layers under external stimuli. The atomic structural transition is studied through in-situ electrical biasing the fabricated heterostructure in a scanning transmission electron microscope. Atomic resolution high-angle annular dark-field STEM images reveal that the conversion of Mo6Te6 NWs from MoTe2 occurs only along specific directions. Combined with first-principles calculations, we attribute the oriented growth to the local Joule-heating induced by electrical bias near the interface of the graphite-MoTe2 heterostructure and the confinement effect generated by graphite. Using the same strategy, we fabricate oriented NWs confined in graphite as lateral contact electrodes in the 2H-MoTe2 FET, achieving a low Schottky barrier of 11.5 meV, and low contact resistance of 43.7 Ω µm at the metal-NW interface. Our work introduces possible approaches to fabricate oriented NWs for interconnections in flexible 2D nanoelectronics through direct metal phase patterning.

Abstract Background Postoperative pulmonary complications (PPCs) are among the most severe complications following total hip arthroplasty revision (THAR), imposing significant burdens on individuals and society. This study examined the prevalence and risk factors of PPCs following THAR using the NIS database, identifying specific pulmonary complications (SPCs) and their associated risks, including pneumonia, acute respiratory failure (ARF), and pulmonary embolism (PE). Methods The National Inpatient Sample (NIS) database was used for this cross-sectional study. The analysis included patients undergoing THAR based on NIS from 2010 to 2019. Available data include demographic data, diagnostic and procedure codes, total charges, length of stay (LOS), hospital information, insurance information, and discharges. Results From the NIS database, a total of 112,735 THAR patients in total were extracted. After THAR surgery, there was a 2.62% overall incidence of PPCs. Patients with PPCs after THAR demonstrated increased LOS, total charges, usage of Medicare, and in-hospital mortality. The following variables have been determined as potential risk factors for PPCs: advanced age, pulmonary circulation disorders, fluid and electrolyte disorders, weight loss, congestive heart failure, metastatic cancer, other neurological disorders (encephalopathy, cerebral edema, multiple sclerosis etc.), coagulopathy, paralysis, chronic pulmonary disease, renal failure, acute heart failure, deep vein thrombosis, acute myocardial infarction, peripheral vascular disease, stroke, continuous trauma ventilation, cardiac arrest, blood transfusion, dislocation of joint, and hemorrhage. Conclusions Our study revealed a 2.62% incidence of PPCs, with pneumonia, ARF, and PE accounting for 1.24%, 1.31%, and 0.41%, respectively. A multitude of risk factors for PPCs were identified, underscoring the importance of preoperative optimization to mitigate PPCs and enhance postoperative outcomes.

Abstract Quantum confinement is a restriction on the motion of electrons in a material to specific region, resulting in discrete energy levels rather than continuous energy bands. In certain materials, quantum confinement could dramatically reshape the electronic structure and properties of the surface with respect to the bulk. Here, in the recently discovered kagome superconductors CsV3Sb5, we unveil the dominant role of quantum confinement in determining their surface electronic structure. Combining angle-resolved photoemission spectroscopy (ARPES) measurement and density-functional theory simulation, we report the observations of two-dimensional quantum well states due to the confinement of bulk electron pocket and Dirac cone to the nearly isolated surface layer. The theoretical calculations on the slab model also suggest that the ARPES observed spectra are almost entirely contributed by the top two layers. Our results not only explain the disagreement of band structures between the recent experiments and calculations, but also suggest an equally important role played by quantum confinement, together with strong correlation and band topology, in shaping the electronic properties of this material.

Cancer patients undergoing chemotherapy are susceptible to various bacterial infections, necessitating prompt and precise antimicrobial treatment with antibiotics. Ciprofloxacin is a clinically utilized broad-spectrum antimicrobial agent known for its robust antiseptic activity. While ferroptosis, an oxidative form of cell death, has garnered attention as a promising avenue in cancer therapy, the potential impact of ciprofloxacin on the anticancer effects of ferroptosis remains unclear. This study seeks to investigate the potential influence of antibiotics on ferroptosis in human pancreatic ductal adenocarcinoma (PDAC) cells. Here, we report a previously unrecognized role of ciprofloxacin in inhibiting ferroptosis in human PDAC cells. Mechanistically, ciprofloxacin suppresses erastin-induced endoplasmic reticulum (ER) stress through the activating transcription factor 6 (ATF6) and ER to nucleus signaling 1 (ERN1) pathway. Excessive ER stress activation can trigger glutathione peroxidase 4 (GPX4) degradation through autophagic mechanisms. In contrast, ciprofloxacin enhances the protein stability of GPX4, a crucial regulator that suppresses ferroptosis by inhibiting lipid peroxidation. Thus, our study demonstrates the anti-ferroptotic role of ciprofloxacin, highlighting the importance of careful consideration when contemplating the combination of ciprofloxacin with specific ferroptosis inducers in PDAC patients.

Abstract Background Plasmodium berghei has been used as a preferred model for studying human malaria, but only a limited number of disease-associated genes of P. berghei have been reported to date. Identification of new disease-related genes as many as possible will provide a landscape for better understanding the pathogenesis of P. berghei. Methods Network module analysis method was developed and applied to identify disease-related genes in P. berghei genome. Sequence feature identification, gene ontology annotation, and T-cell epitope analysis were performed on these genes to illustrate their functions in the pathogenesis of P. berghei. Results 33,314 genes were classified into 4,693 clusters. 4,127 genes shared by six malaria parasites were identified and are involved in many aspects of biological processes. Most of the known essential genes belong to shared genes. A total of 63 clusters consisting of 405 P. berghei genes were enriched in rodent malaria parasites. These genes participate in various stages of parasites such as liver stage development and immune evasion. Combination of these genes might be responsible for P. berghei infecting mice. Comparing with P. chabaudi, none of the clusters were specific to P. berghei. P. berghei lacks some proteins belonging to P. chabaudi and possesses some specific T-cell epitopes binding by class-I MHC, which might together contribute to the occurrence of experimental cerebral malaria (ECM). Conclusions We successfully identified disease-associated P. berghei genes by network module analysis. These results will deepen understanding of the pathogenesis of P. berghei and provide candidate parasite genes for further ECM investigation.

We are concerned with the Riemann problem for the isentropic Euler equations of mixed type in the dark energy fluid. This system is non-strictly hyperbolic on the boundary curve of elliptic and hyperbolic regions. We obtain the unique admissible shock waves by utilizing the viscosity criterion. Assuming fixed left states are in the elliptic and hyperbolic regions, respectively, we construct the unique Riemann solution for the mixed-type models with the initial right state in some feasible regions. Finally, we present numerical simulations which are consistent with our theoretical results.

A labeled multi-Bernoulli filter is used to obtain estimates of the identities and states of targets in complex environments. However, when tracking multiple targets in dense clutters, the computational complexity of the traditional labeled multi-Bernoulli filter will increase exponentially. A labeled multi-Bernoulli tracking algorithm based on maximum likelihood recursive update is proposed, which can reduce the computational scale while maintaining tracking accuracy. Specifically, when performing posterior estimation, a maximum likelihood recursive update method is proposed to replace the complete enumeration, truncated enumeration, or sampling enumeration methods used in many traditional methods. Furthermore, combined with the Gaussian mixture technique, a maximum likelihood recursive updating labeled multi-Bernoulli tracking algorithm is constructed. Simulation results demonstrated that the proposed filter obtained a good balance between the tracking accuracy and computational efficiency.

Abstract Space groups describing the symmetry of lattice structure allow the emergence of fermionic quasiparticles with various degeneracy in the band structure. Theoretical efforts have predicted many materials hosting fermions with the highest degeneracy, i.e., eightfold fermions, yet lacking experimental realization. Here, we explore the band degeneracies in TaCo2Te2 crystals. Through systematic experimental and theoretical analyses, we establish TaCo2Te2 as a nonsymmorphic crystal with negligible spin–orbit coupling (SOC) and long-range magnetic order. These critical properties guarantee the realization of practical eightfold fermions and fourfold van Hove singularity, as directly observed by photoemission spectroscopy. TaCo2Te2 serves as a topological quantum critical platform, which can be tuned into various magnetic, topologically trivial, and nontrivial phases by adding strain, magnetic field, or SOC. The latter is demonstrated by our first-principles calculations, which show that enhancing SOC in TaCo2Te2 will promote the experimental observation of bulk hourglass fermions. Our results establish TaCo2Te2 as a platform to explore the interplay between symmetry and band topology.

Abstract Background Speckle-type POZ protein(SPOP), a substrate adaptor of Cul3 ubiquitin ligase, plays crucial roles in solid neoplasms by promoting the ubiquitination and degradation of substrates. Limited studies have shown that SPOP is overexpressed in human renal cell carcinoma (RCC) tissue. However, the exact role of SPOP in RCC remains unclear and needs to be further elucidated. The present study showed that SPOP was expressed at different levels in different RCC cell lines. The purpose of this study was to explore the roles of SPOP in the biological features of RCC cells and the expression levels of SPOP in human tissue microarray (TMA) and kidney tissues. Methods Here, SPOP was overexpressed by lentiviral vector transfection in ACHN and Caki-1 cells, and SPOP was knocked down in Caki-2 cells with similar transfection methods. The transfection efficiency was evaluated by quantitative PCR and western blotting analyses. The role of SPOP in the proliferation, migration, invasion and apoptosis of cell lines was determined by the MTT, wound-healing, transwell and flow cytometry assays. Moreover, the cells were treated with different drug concentrations in proliferation and apoptosis assays to investigate the effect of sunitinib and IFN-α2b on the proliferation and apoptosis of SPOP-overexpressing cells and SPOP-knockdown RCC cells. Finally, immunohistochemical staining of SPOP was performed in kidney tissues and TMAs, which included RCC tissues and corresponding adjacent normal tissues. Results Overexpression of SPOP inhibited cell proliferation, migration and invasion and increased cell apoptosis. Interestingly, sunitinib and IFN-α2b at several concentrations increased the proliferation inhibitory rate and total apoptosis rate of cells overexpressing SPOP. The findings of the present study showed that the SPOP protein was significantly expressed at low levels in most clear cell RCC (ccRCC) tissues and at relatively high levels in the majority of adjacent normal tissues and kidney tissues. Kaplan–Meier survival analysis showed that there was no statistically significant difference in cumulative survival based on the data of different SPOP expression levels in TMA and patients. Conclusions In contrast to previous studies, our findings demonstrated that overexpression of SPOP might suppress the progression of RCC cells, which was supported by cell experiments and immunohistochemical staining. SPOP could be a potential tumour inhibitor in RCC.

Tunability of ferroelectric domain structure is significant in ferroelectric materials. Here, the authors present in-plane ferroelectricity in 2D Bi2TeO5 in which the ferroelectric domain size and shape can be continuously tuned by the Bi/Te ratio.

Helium is the second most abundant element in the universe, and at low temperatures it becomes a quantum crystal with exotic physical properties such as second sound, superfluidity, and giant plasticity. Here authors prepare 2D solid helium at room temperature through diamond lattice confinement.

Abstract Lorentz‐violating type‐II Dirac nodal line semimetals (DNLSs), hosting curves of band degeneracy formed by two dispersion branches with the same sign of slope, represent a novel state of matter. While being studied extensively in theory, convincing experimental evidence of type‐II DNLSs remain elusive. Recently, vanadium‐based kagome materials have emerged as a fertile ground to study the interplay between lattice symmetry and band topology. This work studies the low‐energy band structure of double‐kagome‐layered CsV8Sb12 and identifies it as a scarce type‐II DNLS protected by mirror symmetry. This work observes multiple DNLs consisting of type‐II Dirac cones close to or almost at the Fermi level via angle‐resolved photoemission spectroscopy (ARPES), which provides an electronic explanation for the nonsaturating magnetoresistance effect as observed. First‐principles theory analyses show that spin‐orbit coupling only opens a small gap, resulting in effectively gapless ARPES spectra, yet generating large spin Berry curvature. These type‐II DNLs, together with the interaction between a low‐energy van Hove singularity and quasi‐one‐dimensional band as observed in the same material, suggest CsV8Sb12 as an ideal platform for exploring novel transport properties.

Abstract Background As the most common malignant tumor of primary renal tumor, renal cell carcinoma (RCC) is the highly invasive disease with high mortality. AKT is a serine/threonine kinase that play a critical role in the phosphoinositide 3-kinase (PI3K) signaling pathway, and it is an attractive target for RCC treatment. The aim of present study was to investigate the effect of AKT silence on malignant behavior of renal cell carcinoma cells. Methods AKT expression was quantified by immunohistochemistry in tumor tissues and normal tissues. The human RCC cell lines Caki-2 cell were chosen for this study. The optimal silencing siRNA was subsequently selected by RT-qPCR and western blot. The effect of AKT silence on RCC cells was investigated by CCK8 assay, transwell assay, scratch test and flow cytometry. The AKT1 expression in human renal cell carcinoma tissue was detected by immunohistochemical staining. Results The AKT in Caki-2 cells was silenced successfully. The results shown AKT silence could inhibit cell proliferation, invasion, and, migration. In addition, AKT silence could promote Caki-2 cell apoptosis with prevention of RCC cells move from G1 phase to S phase. Immunohistochemical staining revealed significant difference of expression of AKT1 in RCC tissues and normal renal tissues. Taken together, AKT family members might involve in malignant growth of RCC, and might be a potential therapeutic target. Conclusion Our data show that AKT silence inhibited cell proliferation, invasion, and, migration of Caki-2 cell, and promoted Caki-2 cell apoptosis. Moreover, AKT silence prevented RCC cells move from G1 phase to S phase. Therefore, AKT may act as an effective therapeutic target for RCC.

In response to the imbalance between power generation and demand, demand response (DR) projects are vigorously promoted. However, customers' DR behaviors are still difficult to be simulated accurately and objectively. To tackle this challenge, we propose a new DR behavioral learning method based on a generative adversary network to learn customers' DR habits. The proposed method is also extended to maximize the economic revenues of generated DR policies on the premise of obeying customers' DR habits, which is hard to be realized simultaneously by existing model-based methods and traditional learning-based methods. To further consider customers' time-varying DR patterns and trace the changes dynamically, we de-fine customers' DR participation positivity as an indicator of their DR pattern and propose a condition regulation approach improving the natural generative adversary framework to generate DR policies conforming to customers' current DR patterns. The proposed method is applied to hourly electricity price optimization to reduce the fluctuation of system aggregate loads. An online parameter updating method is also utilized to train the proposed behavioral learning model in continuous DR simulations during electricity price optimization. Finally, numerical simulations are conducted to verify the effectiveness and superiority of the proposed method.

In two dimensions magnetic order without magnetic anisotropy is forbidden, making 2D magnetic systems a rich playground for interesting physics. Here, Xian et al. fabricate monolayers of CrTe2, and demonstrate antiferromagnetic ordering, with spin reorientation at finite magnetic fields.

Abstract Demand response (DR) is an effective load management method. To attract customers to participate, DR policies need to both satisfy customers' individual DR habits and be economically profitable. However, customers’ individual DR habits are hard to be formulated with few hypotheses when other objectives are simultaneously considered. To tackle this challenge, a novel DR behavioural learning method is proposed. We learn customers’ DR habits by an inverse reinforcement learning (IRL) method to reduce the subjectivity in DR model formulation. Meanwhile, in contrast to traditional learning‐based methods, the proposed method can adapt to multiple DR objectives more than just following customers’ DR habits, like obtaining higher economic revenues. Additionally, we consider the diversity and changes of customer DR behaviour patterns and offer an enhancement for the proposed DR behavioural learning method via building a DR pattern clustering and inference module. The proposed method can work with customer‐side energy storage systems to diversify the DR policies and make the DR behaviours more flexible. Case studies show the proposed method can reduce about 10–20% behavioural learning deviations than the compared model‐based methods, while daily charges of the proposed method can be further reduced by over 4% than the compared supervised‐learning‐based methods.

Rapid tumor progression, metastasis, and diagnosis in advanced stages of disease are the main reasons for the short survival time and high mortality rate of patients with hepatocellular carcinoma (HCC). Ephrin A4 (EFNA4), the ligand of the EPH family, participates in the development of blood vessels and epithelium by regulating cell migration and rejection. In our study, based on bioinformatics analyses, we found that EFNA4 was highly expressed and led to poor prognosis in patients with HCC. We demonstrated that overexpression of EFNA4 significantly promoted HCC cell proliferation and migration in vivo or in vitro. In addition, knockdown of EFNA4 inhibited the proliferation and migration of HCC cells. Furthermore, EFNA4 was found to directly interact with EPHA2 and promote its phosphorylation at Ser897, followed by recruitment of phosphoinositide-3-kinase regulatory subunit 2 (PIK3R2) and activation of the glycogen synthase kinase-3beta (GSK3β)/β-catenin signaling pathway. Moreover, overexpression of β-catenin further promoted the expression of PIK3R2, which formed a positive feedback loop. The results revealed that abnormal expression of EFNA4 is the main switch of the PIK3R2/GSK3β/β-catenin loop that influenced the proliferation and migration of HCC cells and suggest that EFNA4 is a potential prognostic marker and a prospective therapeutic target in patients with HCC.

Background: Clear cell renal cell carcinoma (ccRCC) is the most common pathological type of renal cell carcinoma. Tetratricopeptide repeat domain 21A (TTC21A), known as a component of intraflagellar transport complex A which is essential for the function of cilia, However, the role of TTC21A remains unclear in ccRCC. For the first time, we explore the role and potential mechanism of TTC21A in ccRCC based on multiple databases.Methods: TTC21A expression across all TCGA tumor was analyzed via Tumor Immune Estimation Resource (TIMER) site. The correlation between TTC21A and clinicopathologic characteristics of ccRCC was analyzed with TCGA database. The diagnostic and prognostic value of TTC21A was evaluated by receiver operation characteristic curve, Kaplan-Meier plotter and Cox regression respectively. Moreover, functional enrichment analysis of TTC21A and the co-expression genes were performed by Gene Set Enrichment Analysis. The correlation of TTC21A and immune infiltration were evaluated by single sample Gene Set Enrichment Analysis.Results: Pan-cancer analysis indicated that TTC21A was highly expressed in ccRCC and other cancer. In addition, elevated expression of TTC21A was associated with worse overall survival in ccRCC patients. Functional enrichment analysis showed that TTC21A and the co-expressed genes enriched in glucose metabolism and energy metabolism. Moreover, TTC21A expression was associated with infiltrating levels of dendritic cell, nature killer cell and other immune marker sets.Conclusion: The results of analysis indicate that expression of TTC21A is associated with poor prognosis and immune infiltrating in ccRCC, which suggested TTC21A might be used as a potential predictor and target of treatment in ccRCC.

To broaden the scope of van der Waals 2D magnets, we report the synthesis and magnetism of covalent 2D magnetic Cr2Te3 with a thickness down to one-unit-cell. The 2D Cr2Te3 crystals exhibit robust ferromagnetism with a Curie temperature of 180 K, a large perpendicular anisotropy of 7 × 105 J m−3, and a high coercivity of ∼4.6 kG at 20 K. First principles calculations further show a transition from canted to collinear ferromagnetism, a transition from perpendicular to in-plane anisotropy, and emergent half-metallic behavior in atomically-thin Cr2Te3, suggesting its potential application for injecting carriers with high spin polarization into spintronic devices.

Software defect prediction (SDP) can help developers reasonably allocate limited resources for locating bugs and prioritizing their testing efforts. Existing methods often serialize an Abstract Syntax Tree (AST) obtained from the program source code into a token sequence, which is then inputted into the deep learning model to learn the semantic features. However, there are different ASTs with the same token sequence, and it is impossible to distinguish the tree structure of the ASTs only by a token sequence. To solve this problem, this paper proposes a framework called Semantic Feature Learning via Dual Sequences (SFLDS), which can capture the semantic and structural information in the AST for feature generation. Specifically, based on the AST, we select the representative nodes in the AST and convert the program source code into a simplified AST (S-AST). Our method introduces two sequences to represent the semantic and structural information of the S-AST, one is the result of traversing the S-AST node in pre-order, and another is composed of parent nodes. Then each token in the dual sequences is encoded as a numerical vector via mapping and word embedding. Finally, we use a bi-directional long short-term memory (BiLSTM) based neural network to automatically generate semantic features from the dual sequences for SDP. In addition, to leverage the statistical characteristics contained in the handcrafted metrics, we also propose a framework called Defect Prediction via SFLDS (DP-SFLDS) which combines the semantic features generated from SFLDS with handcrafted metrics to perform SDP. In our empirical studies, eight open-source Java projects from the PROMISE repository are chosen as our empirical subjects. Experimental results show that our proposed approach can perform better than several state-of-the-art baseline SDP methods.

Background Charcot neuroarthropathy of the ankle is an extremely challenging clinical dilemma, and its surgical management can be highly complicated. The goal of Charcot ankle treatment is to to restore a plantigrade and stable foot, and thus to avoid ulceration with subsequent infection. This report aims to introduce a method of correcting ankle deformity using a novel 3D printing technique. Patient and methods One patient with Charcot ankle deformity was operated in this study. The ankle deformity of this patient was quantified in three dimensions through computed tomography. On the basis of the computed tomography scans, a new titanium implant was designed and manufactured using 3D printing. The implant was applied in the surgery of tibio-talo-calcaneal arthrodesis to restore local anatomy of the affected ankle of the patient with Charcot neuroarthropathy. Results Evaluation of the post-operative radiography indicated union in the affected ankle. After surgery, the planar foot in this patient was restored. The patient was satisfied with the post-operative course, and joint fusion was successful as indicated by 2-year post-operative evaluation. The results of post-operative follow-up showed that the lower limb length of the patient with Charcot neuroarthropathy was salvaged, and the patient retained the plantigrade foot. Conclusion Three-dimensional printing technique combined with tibio-talo-calcaneal arthrodesis may help to correct ankle deformity in patients with Charcot neuroarthropathy.

Summary: Objective: To introduce the application of Ilizarov techniques in the treatment of syndactyly. Methods: From January 2016 to January 2019, 6 cases of pediatric syndactyly were treated by the simple Ilizarov external fixator device in our hospital. The skin and soft tissue between involved fingers were lengthened with external fixator slow traction. The speed was controlled at 1–2 ​mm per day, six times a day. When the length of the interphalangeal soft tissue is up to the requirement, Z-plasty incision and finger web flap were performed to separate the fingers. Skin grafting is generally not required. Results: All the 6 cases had been followed up over 12 months. In all cases, sufficient skin was obtained without infection or necrosis. The appearance and function of the released fingers were satisfactory. Conclusion: According to the principle of stress–strain, with the aid of simple Ilizarov external fixator, sufficient skin had been obtained to reconstruct the finger web and cover the finger side defect. With functional rehabilitation, excellent functions and satisfactory appearance of the fingers were achieved. The translational potential of this article: This paper reviews recent progress on the treatment of syndactyly, and report the clinical application a new simple Ilizarov external fixator device to treat the complete syndactyly and get good results.

Abstract Background It is well known that androgen-deprivation therapy (ADT) can inevitably drive prostate cancer (PCa) cells into a castration-resistant state. According to the “Warburg effect”, the metabolism of aggressive tumor cells increases significantly. The growth of cancer cells depends on glycolysis, which may be a potential target for cancer control. 6-Phosphofructo-2-kinase/fructose-2,6-biphosphatase 4 (PFKFB4) plays key roles in the proliferation and metastasis of PCa cells. However, there is very limited knowledge on the role of PFKFB4 in the conversion to castration resistance. The present study aimed to determine the changes in glucose consumption and PFKFB4 expression in LNCaP cells and androgen-independent LNCaP (LNCaP-AI) cells during the whole process of androgen-independent growth. Additionally, PFKFB4 expression in human PCa tissues was evaluated. Methods We established an androgen-independent LNCaP-AI cell line derived from LNCaP cells to mimic the traits of castration resistance in vitro. LNCaP-AI and LNCaP cells were cultured in the corresponding medium containing the same amount of glucose. At the end of experiments, the medium supernatant and blank medium were collected, and absorbance was measured. LNCaP-AI and LNCaP cells were harvested to detect PFKFB4 expression by Western blotting. Prostate tissue samples including PCa tissue, carcinoma-adjacent tissue and benign prostatic hyperplasia (BPH) tissue specimens were evaluated for PFKFB4 expression using immunohistochemistry. Results In 18 h supernatant samples, the glucose consumption and lactate secretion of LNCaP-AI cells were higher than those of LNCaP cells. The Western blot results indicated that PFKFB4 expression was increased in LNCaP-AI cells compared with LNCaP cells. Immunohistochemistry revealed that the expression of PFKFB4 in PCa tissue specimens was higher than that in BPH and adjacent tissue specimens. However, the differences in PCa tissue before and after ADT were not statistically significant. Conclusion PFKFB4 may be associated with enhanced glycolysis during the androgen-independent growth of PCa cells in vitro. PFKFB4 may be a marker of PCa progression. Our results provide a rationale for further clinical investigation of PCa treatment focused on controlling PFKFB4 expression.

Designing and realizing local configurations can activate the in-plane chalcogen atoms of transition metal dichalcogenide to enhance the HER activity. We combine the theoretical screening (charge transfer capability) and experimental realization to achieve highly active local configurations

Compared with traditional network security defense methods,industrial system security protection research based on process flow has become an important research direction in the field of industrial security.An improved backward cloud algorithm based on first order absolute central moment (BC-1stM) non-deterministic reverse cloud method was proposed,which was modeled by the time series and the normal state of the process flow.The security protection detection and alarm based on the process attack mode in the industrial system was realized,and Tennessee Eastman chemical process platform was adopted to validate the algorithm.The results show that the model had a high precision in the detection of attack behavior and detection of attack points,and improved the security protection capability of industrial systems.

Cross-project defect prediction (CPDP) is a promising approach to help to allocate testing efforts efficiently and guarantee software reliability in the early software lifecycle. A CPDP method usually trains a software defect classifier based on labeled data sets. Then the trained classifier can predict new projects without labeled data. Most previous CPDP techniques focused on manually designing handcrafted features. However, these handcrafted features ignore the programs' semantic information. Moreover, some other existing defect prediction approaches learned semantic features from source code to build classifiers directly. However, they did not consider the distribution divergence between source and target projects. To address these limitations, we put forward a new method called Adversarial Discriminative Convolutional Neural Network (ADCNN). It can extract the transferable semantic features from source code for CPDP tasks. Specifically, we first parse source files into token vectors and then map them to integer vectors via word embedding. Second, we combine adversarial learning with discriminative feature learning to train the ADCNN model. The key of the ADCNN model is to learn the discriminative mapping of the target project to the source feature space by deceiving a domain discriminator. A domain discriminator tries to distinguish the target project files from the source project files. Finally, we use the extracted transferable semantic features to build a classifier for CPDP tasks. We evaluate our method on ten benchmark projects in terms of F-measure, AUC, and PofB20 (an effort-aware evaluation metric). The experimental results demonstrate that our ADCNN method performs better compared with other related CPDP methods.

Introduction: Sciatic nerve injury is a common injury of the nervous system. Stem cell-based therapies, drug-based therapies and rehabilitation physiotherapy therapies are currently available, but their limited therapeutic efficacy limits their use. Here, we aimed to explore a novel lentiviral-based gene therapeutic strategy and to elaborate its mechanism.Materials and Methods: Recombinant GDF11 protein was used for the in vitro treatment of dorsal root ganglion (DRG) cells. Lentivirus was used to construct a vector system for the in vivo expression of GDF11. The nerve conduction function was detected using action-evoked potentials at different time periods, and the regulatory effect of nerves on target organs was detected by weighing the gastrocnemius muscle. Immunofluorescence of NF200 and S100 was used to show the regeneration of the sciatic nerve, and myelin and Nissl staining were performed to observe the pathological features of the tissue. Western was used to validate signaling pathways. The expression of related genes was observed by qPCR and Western blotting, and cell apoptosis was detected by flow cytometry.Result: GDF11 promotes the axonal growth of DRG cells and inhibits DGR cell apoptosis in vitro. GDF11 acts by activating the Smad pathway. GDF11 promotes the recovery of damaged sciatic nerve function in rats, the regeneration of damaged sciatic nerves in rats, and myelin regeneration of damaged sciatic nerves in rats. GDF11 also exerts a protective effect on neuronal cells in rats.Conclusion: Based on the present study, we conclude that GDF11 promotes axonal growth and inhibits DRG cell apoptosis in vitro through the Smad pathway, and lentivirus-mediated GDF11 overexpression in vivo can promote the recovery of sciatic nerves after transection by promoting axonal growth and inhibiting neuronal apoptosis in the spinal cord.

Abstract Probing large‐scale intrinsic structure of air‐sensitive 2D materials with atomic resolution is so far challenging due to their rapid oxidization and contamination. Here, by keeping the whole experiment including growth, transfer, and characterizations in an interconnected atmosphere‐control environment, the large‐scale intact lattice structure of air‐sensitive monolayer 1T’‐WTe2 is directly visualized by atom‐resolved scanning transmission electron microscopy. Benefit from the large‐scale atomic mapping, collective lattice distortions are further unveiled due to the presence of anisotropic rippling, which propagates perpendicular to only one of the preferential lattice planes in the same WTe2 monolayer. Such anisotropic lattice rippling modulates the intrinsic point defect (Te vacancy) distribution, in which they aggregate at the constrictive inner side of the undulating structure, presumably due to the ripple‐induced asymmetric strain as elaborated by density functional theory. The results pave the way for atomic characterizations and defect engineering of air‐sensitive 2D layered materials.

Two-dimensional transition metal dichalcogenides with peculiar spin–orbit coupling may lead to exotic phenomena. Here, the authors report a large in-plane upper critical field with a two-fold symmetry, suggesting a novel asymmetric spin–orbit coupling in few-layer 1T d-MoTe2.

Substitutional doping is a powerful strategy to modulate the properties and functionalities of two-dimensional (2D) materials while control of dopants during the process is still challenging. Recently, we invented a dissolution–precipitation (DP) method to grow 2D materials. Here, we further extend this method by developing a double-faced precursor supply DP growth strategy to substitutionally dope metal atoms into monolayer MoS2 lattices. In this double-faced precursor supply DP method, the Mo source and dopant source are supplied from the bottom and top surface of the glass substrate, respectively, to separate their diffusion paths. As a result, monolayer MoS2 incorporated with different concentrations of V atoms were grown by tuning the amount of V precursor, which exhibited different types of electrical transport properties. This new doping method is universal in growing several transition metal atom doped MoS2, including Re, Fe, and Cr, which will extend the applications of 2D materials.

Long noncoding RNAs (lncRNAs) have been substantially reported to have critical roles in regulating tumorigenesis in recent years. However, the expression pattern and biological function of SNHG17 in hepatocellular carcinoma (HCC) remain unclear. Bioinformatics analysis and qRT-PCR were performed to detect the expression pattern of SNHG17 in HCC tissues, adjacent nontumorous tissues, and cell lines. The effect of SNHG17 on proliferation, migration, and apoptosis of HCC was investigated by knockdown and overexpressing SNHG17 in HCC cell lines. RNA sequencing was utilized to explore the underlying mechanism. Utilizing publicly available TCGA-LIHC, GSE102079 HCC datasets, and qRT-PCR, we found SNHG17 was significantly upregulated in HCC tissues and cell lines and was notably associated with larger tumor size, poorly differentiation, presence of vascular invasion, and advanced TNM stage. Furthermore, gain- and loss-of-function studies demonstrated that SNHG17 promoted cell proliferation and migration and inhibited apoptosis of HCC. By employing RNA sequencing, we found knockdown of SNHG17 caused 1037 differentially expressed genes, highly enriched in several pathways, including metabolic, PI3K-Akt, cell adhesion, regulation of cell proliferation, and apoptotic pathway; among them, 92 were overlapped with SNHG17-related genes in the TCGA-LIHC dataset. Furthermore, ERH, TBCA, TDO2, and PDK4 were successfully validated and found significantly dysregulated in HCC tissues. Moreover, HCC patients with higher SNHG17 expression had a relatively poor overall survival and disease-free survival, and ERH and PDK4 also played a marked role in the prognosis of HCC. Broadly, our findings illustrate that SNHG17 acts as a noncoding oncogene in HCC progression, suggesting its potential value as a novel target for HCC therapy.

The onset of liver cancer is insidious. Currently, there is no effective method for the early detection of hepatocellular carcinoma (HCC). Transcriptomic profiles of 826 tissue samples from the Gene Expression Omnibus (GEO), The Cancer Genome Atlas (TCGA), Genotype tissue expression (GTEx), and International Cancer Genome Consortium (ICGC) databases were utilized to establish models for early detection and surveillance of HCC. The overlapping differentially expressed genes (DEGs) were screened by elastic net and robust rank aggregation (RRA) analyses to construct the diagnostic prediction model for early HCC (DP.eHCC). Prognostic prediction genes were screened by univariate cox regression and lasso cox regression analyses to construct the survival risk prediction model for early HCC (SP.eHCC). The relationship between the variation of transcriptome profile and the oncogenic risk-score of early HCC was analyzed by combining Weighted Correlation Network Analysis (WGCNA), Gene Set Enrichment Analysis (GSEA), and genome networks (GeNets). The results showed that the AUC of DP.eHCC model for the diagnosis of early HCC was 0.956 (95% CI: 0.941–0.972; p < 0.001) with a sensitivity of 90.91%, a specificity of 92.97%. The SP.eHCC model performed well for predicting the overall survival risk of HCC patients (HR = 10.79; 95% CI: 6.16–18.89; p < 0.001). The oncogenesis of early HCC was revealed mainly involving in pathways associated with cell proliferation and tumor microenvironment. And the transcription factors including EZH2, EGR1, and SOX17 were screened in the genome networks as the promising targets used for precise treatment in patients with HCC. Our findings provide robust models for the early diagnosis and prognosis of HCC, and are crucial for the development of novel targets applied in the precision therapy of HCC.

In semiconductor nanocrystals, efficient carrier multiplication counteracts hot carrier thermalization, increasing the overall carrier generation yield. Here, de Weerd et al. observe a quantum yield of up to 98% in CsPbI3 nanocrystals as a result of efficient carrier multiplication.

The mid-infrared technologies are essential to various applications but suffer from limited materials with suitable bandgap. Here the authors demonstrate that two-dimensional atomically thin PtSe2 with variable bandgaps in the mid-infrared via layer and defect engineering is highly promising for mid-infrared optoelectronics.

This paper focuses on how to improve the operation ability of a soft robotic hand (SRH). A trigger-based dexterous operation (TDO) strategy with multimodal sensors is proposed to perform autonomous choice operations. The multimodal sensors include optical-based fiber curvature sensor (OFCS), gas pressure sensor (GPS), capacitive pressure contact sensor (CPCS), and resistance pressure contact sensor (RPCS). The OFCS embedded in the soft finger and the GPS series connected in the gas channel are used to detect the curvature of the finger. The CPCS attached on the fingertip and the RPCS attached on the palm are employed to detect the touch force. The framework of TDO is divided into sensor detection and action operation. Hardware layer, information acquisition layer, and decision layer form the sensor detection module; action selection layer, actuator drive layer, and hardware layer constitute the action operation module. An autonomous choice decision unit is used to connect the sensor detecting module and action operation module. The experiment results reveal that the TDO algorithm is effective and feasible, and the actions of grasping plastic framework, pinching roller ball pen and screwdriver, and handshake are executed exactly.

Magnesium rechargeable batteries potentially offer high-energy density, safety, and low cost. Here the authors show a battery that reversibly intercalates magnesium monochloride cations with excellent rate and cycle performances in addition to the large capacity.

Two-dimensional superconductors will likely have applications not only in devices, but also in the study of fundamental physics. Here, Wang et al. demonstrate the CVD growth of superconducting NbSe2 on a variety of substrates, making these novel materials increasingly accessible.

Abstract Purpose: To investigate the effect of intermittent vibration at different intervals on bone fracture healing and optimize the vibration interval. Methods: Ninety sheep were randomized to receive no treatment (the control group), incision only (the sham control group), internal fixation with or without metatarsal fracture (the internal fixation group), and continuous vibration in addition to internal fixation of metatarsal fracture, or intermittent vibration at 1, 2, 3, 5, 7 and 17-day interval in addition to internal fixation of metatarsal fracture (the vibration group). Vibration was done at frequency F=35 Hz, acceleration a=0.25g, 15 min each time 2 weeks after bone fracture. Bone healing was evaluated by micro-CT scan, bone microstructure and mechanical compression of finite element simulation. Results: Intermittent vibration at 7-day interval significantly improved bone fracture healing grade. However, no significant changes on microstructure parameters and mechanical properties were observed among sheep receiving vibration at different intervals. Conclusions: Clinical healing effects should be the top concern. Quantitative analyses of bone microstructure and of finite element mechanics on the process of fracture healing need to be further investigated.

Long noncoding RNAs (lncRNAs) and microRNAs (miRNAs/miRs) are noncoding RNAs that function as regulators of tumor suppressors and oncogenes. The aim of the present study was to investigate the potential mechanism associated with the involvement of urothelial cancer associated 1 (UCA1) in melanoma. Reverse transcription-quantitative polymerase chain reaction and western blot analysis were performed in order to determine the expression levels of UCA1, miR-143, miR-216b, and hexokinase 2 (HK2) in the melanoma and control groups, as well as the influence of UCA1, miR-143, and miR-216b on the expression of HK2, and the effect of lactate and UCA1 on the phosphorylation of p38 mitogen-activated protein kinase (p38 MAPK). Bioinformatics algorithm analysis and a luciferase assay were performed in order to predict miRNA targets. In addition, an MTT assay was performed in order to determine the effect of lactate and UCA1 expression on cell proliferation. A total of 39 participants, consisting of 18 patients with melanoma and 21 healthy control subjects, were included in the present study. The present study demonstrated that the expression levels of UCA1 mRNA, and HK2 mRNA and protein were enhanced in patients with melanoma compared with healthy controls; whereas the expression levels of miR-143 and miR-216b mRNA were suppressed in patients with melanoma compared with healthy controls. Furthermore, it was revealed that UCA1 negatively modulated the expression of miR-143 and miR-216b, and that miR-143 and miR-216b directly targeted the HK2 protein by binding to the HK2 3′ untranslated region (UTR). In addition, it was demonstrated that miR-143 and miR-216 suppressed the luciferase activity exhibited by wild-type HK2 3′-UTR. Furthermore, it was revealed that transfection with UCA1 small interfering RNA, and miR-143 and miR-216b mimics markedly suppressed HK2 mRNA and protein expression levels as well as lactate levels in human umbilical vein endothelial cells; however, O 2 consumption was revealed to be enhanced post transfection. By contrast, transfection with UCA1 enhanced HK2 mRNA and protein expression levels as well as lactate production; however, O 2 consumption was revealed to be suppressed post transfection. Lactate-induced phosphorylation of p38 MAPK was revealed to occur in a concentration-dependent manner, and UCA1 enhanced the phosphorylation level of p38 MAPK via the inhibition of miR-143 and miR-216b expression. Lactate and UCA1 were demonstrated to enhance cell proliferation. In conclusion, the present study demonstrated that the lncRNA UCA1/miR-143 miR-216b/HK2/lactic acid/MAPK axis may be involved in the pathogenesis of melanoma via the modulation of endothelial cells, and thus, lncRNA UCA1 may serve as a potential therapeutic target for melanoma treatment.

Abstract TINCR is a well-known lncRNA which acts as a master regulator in somatic differentiation development. However, it is still unclear whether TINCR is also involved in caner occurrence and progression. In this study, we observed that TINCR was up-regulated in bladder cancer tissues and cells and contributed to oncogenesis and cancer progression. Silencing TINCR expression inhibited cell proliferation and promoted apoptosis in vitro, indicating that TINCR may be the potential therapeutic target for treating bladder urothelial carcinoma. Thus we used the synthetic biology approach to create theophylline controllable RNAi-based genetic switches which silenced TINCR in a dosage-dependent manner. Both RNAi-OFF and ON switches can be used to quantitatively control the expression of TINCR in bladder cancer to suppress the progression of bladder cancer. These findings suggest that lncRNA-TINCR could promote bladder cancer development and progression and artificial control of its expression through inducible RNAi may represent a new kind of therapeutic strategy for treating human bladder cancer.

Two dimensional materials are promising for electronic applications, which await the exploration of cooperative phenomena. Here, Liu et al. report switchable ferroelectric polarization in thin CuInP2S6film at room temperature, demonstrating good memory behaviour with on/off ratio of ∼100 based on two-dimensional ferroelectricity.

Compared with traditional rigid gripper with joint-linkage structure, novel soft robotic gripper gives rise to continuous concern for the advantages of no-damage grasping, convenient manufacture, easy control, and low cost. In this study, we design and built two kinds of soft robotic grippers with four fiber-reinforced soft actuators which are distributed in circular and rectangle shapes for single and twin contacts grasping. A novel hybrid valve pneumatic control scheme combining proportional and solenoid valves is proposed. Also, a mode controllable hybrid valve pressure control method is proposed to adjust internal pressure of soft robotic grippers to adapt to different grasping tasks. The experiment results verify that the performances of hybrid valve outperform those of individual proportional valve or solenoid valve in the aspects of response time and steady-state accuracy. The hybrid valve has wide range of pressure regulation, result in that the soft robotic grippers are qualified to grasp various objects with different shapes, sizes, and weights.

Abstract Ribonucleic acid interference (RNAi) based on microRNA (miRNA) may provide efficient and safe therapeutic opportunities. However, natural microRNAs can not easily be regulated and usually cause few phenotypic changes. Using the engineering principles of synthetic biology, we provided a novel and standard platform for the generation of tetracycline (Tet)-inducible vectors that express artificial microRNAs in a dosage-dependent manner. The vector generates a Pol II promoter-mediated artificial microRNA which was flanked by ribozyme sequences. In order to prove the utility of this platform, we chose β-catenin and HIF-1α as the functional targets and used the bladder cancer cell lines 5637 and T24 as the test models. We found that the Tet-inducible artificial microRNAs can effectively silence the target genes and their downstream genes and induce anti-cancer effects in the two bladder cancer cell lines. These devices can inhibit proliferation, induce apoptosis and suppress migration of the bladder cancer cell lines 5637 and T24. The Tet-inducible synthetic artificial microRNAs may represent a kind of novel therapeutic strategies for treating human bladder cancer.

We report a method in making transmission electron microscopy sample for both CVD-grown and exfoliated 2D materials without etching process, thus gentle to those 2D materials that are sensitive to water and reactive etchants. Large-scale WS2 monolayer grown on glass, NbS2 atomic layers grown on exfoliated h-BN flakes, and water-sensitive exfoliated TiS2 flakes are given as representative examples. We show that the as-transferred samples not only retain excellent structural integrity down to atomic scale but also have little oxidations, presumably due to the minimum contact with water/etchants. This method paves the way for atomic scale structural and chemical investigations in sensitive 2D materials.