JAM3 promotes cervical cancer metastasis by activating the HIF-1α/VEGFA pathway.

Cervical cancer is the fourth most common cancer and the leading cause of mortality among women worldwide. Tumor metastasis is an important cause of poor prognosis. Determining the exact mechanisms of metastasis and potential targeted therapies is urgently needed. Junctional adhesion molecule 3 (JAM3) is an important member of the TJ tight junction (TJ) family, and its biological function in cervical cancer needs to be further clarified. We found that JAM3 was highly expressed in cervical cancer patients with lymph node metastasis and that high expression of JAM3 promoted cervical cancer cell metastasis both in vitro and in vivo. In addition, overexpression of JAM3 induces epithelial-mesenchymal transition (EMT). Moreover, silencing JAM3 suppressed cervical cancer cell migration and invasion in vitro. Finally, JAM3 overexpression activated the HIF-1α/VEGFA pathway. In conclusion, our results suggested that JAM3 promotes cervical cancer cell migration and invasion by activating the HIF-1α/VEGFA pathway. JAM3 may be a promising biomarker and effective therapeutic target for cervical cancer.

A novel combination of niraparib and anlotinib in platinum-resistant ovarian cancer: Efficacy and safety results from the phase II, multi-center ANNIE study.

Background: Patients with platinum-resistant recurrent ovarian cancer (PROC) face poor prognosis and limited treatment options. Single-agent antiangiogenics and poly (ADP-ribose) polymerase (PARP) inhibitors both show some activities in platinum-resistant diseases. The ANNIE study aimed to evaluate the efficacy and safety of the novel combination of the PARP inhibitor niraparib and the antiangiogenic anlotinib in patients with PROC. Methods: ANNIE is a multicentre, single-arm, phase 2 study (ClinicalTrials.gov identifier NCT04376073) conducted at three hospitals in China. Eligible patients had histologically confirmed epithelial ovarian, fallopian tube, or primary peritoneal cancer that recurred within 6 months of last platinum-based chemotherapy. Patients with prior PARP inhibitor exposure were excluded. The enrolled patients received oral niraparib 200 mg or 300 mg (baseline body weight-directed) once daily continuously and anlotinib 10 mg (12 mg before protocol amendment) once daily on days 1-14 of each 21-day cycle until disease progression or intolerable toxicity. The primary endpoint was objective response rate (ORR). Findings: Between May 22, 2020, and April 22, 2021, 40 patients were enrolled and treated. Thirty-six patients underwent post-baseline tumour assessments. By data cut-off (January 31, 2022), median follow-up was 15.4 months (95% CI 12.6-17.7). Intention-to-treat ORR was 50.0% (95% CI 33.8-66.2), including one complete response and 19 partial responses. Median (95% CI) progression-free survival and overall survival were 9.2 months (7.4-11.9) and 15.3 months (13.9-not evaluable), respectively. Drug-related, grade ≥3 TEAEs were reported in 26 (68%) patients. There were no treatment-related deaths. Interpretation: Niraparib plus anlotinib showed promising antitumour activity in patients with PROC. This oral combination warrants further investigation as a potential novel, convenient treatment option for patients with PROC. Funding: Zai Lab (Shanghai) Co., Ltd; Jiangsu Chia Tai-Tianqing Pharmaceutical Co., Ltd; the National Natural Science Foundation of China (No. 82102783).

A New Axial Stress Measurement Method for High-Strength Short Bolts Based on Stress-Dependent Scattering Effect and Energy Attenuation Coefficient.

The accurate estimation of axial stresses is a major problem for high-strength bolted connections that needs to be overcome to improve the assembly quality and safety of aviation structures. However, the conventional acoustoelastic effect based on velocity-stress dependence is very weak for short bolts, which leads to large estimation errors. In this article, the effect of axial stress on ultrasonic scattering attenuation is investigated by calculating the change in the energy attenuation coefficient of ultrasonic echoes after applying axial preload. Based on this effect, a stress-dependent attenuation estimation model is developed to measure the bolt axial stress. In addition, the spectrum of the first and second round-trip echoes is divided into several frequency bands to calculate the energy attenuation coefficients, which are used to select the frequency band sensitive to the axial stress changes. Finally, the estimation model between axial stress and energy attenuation coefficients in the sensitive frequency band is established under 20 steps of axial preloads. The experimental results show that the energy attenuation coefficient in the sensitive band corresponds well with axial stress. The average relative error of the predicted axial stress is 6.28%, which is better than that of the conventional acoustoelastic effect method. Therefore, the proposed approach can be used as an effective method to measure the axial stress of short bolts in the assembly of high-strength connections.

A Gaussian Process State Space Model Fusion Physical Model and Residual Analysis for Fatigue Evaluation.

Residual stress is closely related to the evolution process of the component fatigue state, but it can be affected by various sources. Conventional fatigue evaluation either focuses on the physical process, which is limited by the complexity of the physical process and the environment, or on monitored data to form a data-driven model, which lacks a relation to the degenerate process and is more sensitive to the quality of the data. This paper proposes a fusion-driven fatigue evaluation model based on the Gaussian process state-space model, which considers the importance of physical processes and the residuals. Through state-space theory, the probabilistic space evaluation results of the Gaussian process and linear physical model are used as the hidden state evaluation results and hidden state change observation function, respectively, to construct a complete Gaussian process state-space framework. Then, through the solution of a particle filter, the importance of the residual is inferred and the fatigue evaluation model is established. Fatigue tests on titanium alloy components were conducted to verify the effectiveness of the fatigue evaluation model. The results indicated that the proposed models could correct evaluation results that were far away from the input data and improve the stability of the prediction.

Risk Stratification of Early-Stage Cervical Cancer with Intermediate-Risk Factors: Model Development and Validation Based on Machine Learning Algorithm.

BACKGROUND: Adjuvant therapy for patients with cervical cancer (CC) with intermediate-risk factors remains controversial. The objectives of the present study are to assess the prognoses of patients with early-stage CC with pathological intermediate-risk factors and to provide a reference for adjuvant therapy choice. MATERIALS AND METHODS: This retrospective study included 481 patients with stage IB-IIA CC. Cox proportional hazards regression analysis, machine learning (ML) algorithms, Kaplan-Meier analysis, and the area under the receiver operating characteristic curve (AUC) were used to develop and validate prediction models for disease-free survival (DFS) and overall survival (OS). RESULTS: A total of 35 (7.3%) patients experienced recurrence, and 20 (4.2%) patients died. Two prediction models were built for DFS and OS using clinical information, including age, lymphovascular space invasion, stromal invasion, tumor size, and adjuvant treatment. Patients were divided into high-risk or low-risk groups according to the risk score cutoff value. The Kaplan-Meier analysis showed significant differences in DFS (p = .001) and OS (p = .011) between the two risk groups. In the traditional Sedlis criteria groups, there were no significant differences in DFS or OS (p > .05). In the ML-based validation, the best AUCs of DFS at 2 and 5 years were 0.69/0.69, and the best AUCs of OS at 2 and 5 years were 0.88/0.63. CONCLUSION: Two prognostic assessment models were successfully established, and risk grouping stratified the prognostic risk of patients with CC with pathological intermediate-risk factors. Evaluation of long-term survival will be needed to corroborate these findings. IMPLICATIONS FOR PRACTICE: The Sedlis criteria are intermediate-risk factors used to guide postoperative adjuvant treatment in patients with cervical cancer. However, for patients meeting the Sedlis criteria, the choice of adjuvant therapy remains controversial. This study developed two prognostic models based on pathological intermediate-risk factors. According to the risk score obtained by the prediction model, patients can be further divided into groups with high or low risk of recurrence and death. The prognostic models developed in this study can be used in clinical practice to stratify prognostic risk and provide more individualized adjuvant therapy choices to patients with early-stage cervical cancer.

A Coarse-to-Fine Method for Estimating the Axis Pose Based on 3D Point Clouds in Robotic Cylindrical Shaft-in-Hole Assembly.

In this work, we propose a novel coarse-to-fine method for object pose estimation coupled with admittance control to promote robotic shaft-in-hole assembly. Considering that traditional approaches to locate the hole by force sensing are time-consuming, we employ 3D vision to estimate the axis pose of the hole. Thus, robots can locate the target hole in both position and orientation and enable the shaft to move into the hole along the axis orientation. In our method, first, the raw point cloud of a hole is processed to acquire the keypoints. Then, a coarse axis is extracted according to the geometric constraints between the surface normals and axis. Lastly, axis refinement is performed on the coarse axis to achieve higher precision. Practical experiments verified the effectiveness of the axis pose estimation. The assembly strategy composed of axis pose estimation and admittance control was effectively applied to the robotic shaft-in-hole assembly.

Life Prediction of Battery Using a Neural Gaussian Process with Early Discharge Characteristics.

The state of health (SOH) prediction of lithium-ion batteries (LIBs) is of crucial importance for the normal operation of the battery system. In this paper, a new method for cycle life and full life cycle capacity prediction is proposed, which combines the early discharge characteristics with the neural Gaussian process (NGP) model. The cycle data sets of commercial LiFePO4(LFP)/graphite cells generated under different operating conditions are analyzed, and the power characteristic P is extracted from the voltage and current curves of the early cycles. A Pearson correlation analysis shows that there is a strong correlation between P and cycle life. Our model achieves 8.8% test error for predicting cycle life using degradation data for the 20th to 110th cycles. Based on the predicted cycle life, capacity degradation curves for the whole life cycle of the cells are predicted. In addition, the NGP method, combined with power characteristics, is compared with other classical methods for predicting the remaining useful life (RUL) of LIBs. The results demonstrate that the proposed prediction method of cycle life and capacity has better battery life and capacity prediction. This work highlights the use of early discharge characteristics to predict battery performance, and shows the application prospect in accelerating the development of electrode materials and optimizing battery management systems (BMS).

Fault Diagnosis of Wind Turbine Gearbox Based on the Optimized LSTM Neural Network with Cosine Loss.

The gearbox is one of the most fragile parts of a wind turbine (WT). Fault diagnosis of the WT gearbox is of great importance to reduce operation and maintenance (O&M) costs and improve cost-effectiveness. At present, intelligent fault diagnosis methods based on long short-term memory (LSTM) networks have been widely adopted. As the traditional softmax loss of an LSTM network usually lacks the power of discrimination, this paper proposes a fault diagnosis method for wind turbine gearboxes based on optimized LSTM neural networks with cosine loss (Cos-LSTM). The loss can be converted from Euclid space to angular space by cosine loss, thus eliminating the effect of signal strength and improve the diagnosis accuracy. The energy sequence features and the wavelet energy entropy of the vibration signals are used to evaluate the Cos-LSTM networks. The effectiveness of the proposed method is verified with the fault vibration data collected on a gearbox fault diagnosis experimental platform. In addition, the Cos-LSTM method is also compared with other classic fault diagnosis techniques. The results demonstrate that the Cos-LSTM has better performance for gearbox fault diagnosis.

Variation of flow rate and angle of injected venous needle on influencing intimal hyperplasia at the venous anastomosis of the hemodialysis graft.

During hemodialysis, arteriovenous (AV) grafts tends to result in intimal hyperplasia (IH) at the venous anastomosis which leads to graft failure. It is well documented that hemodynamic factors have been implicated in IH, as well as pathogenesis of graft stenosis. In this paper, we investigate the flow rate and angle of injection of a venous needle on damaging the hemodialysis graft. Such damage is mainly caused by hemodynamics rather than the actual physical puncture of the needle. By computational fluid dynamic analysis of flow through the AV grafts, we demonstrate that slower flow rate of the needle preserve a larger region of low wall shear stress (WSS). High needle flow angle and fast flow rate tends to induce high shearing of blood against the graft wall, and therefore resulting in a concentrated region of high WSS. Despite that, the increased flow rate causes more significant change to wall shear stress gradient than the flow angle. Obviously, it is important to optimize the injection rate since a high angle can reduce the size of the injection puncture and have smaller injury for the vessel walls; but a slower injection rate may delay hemodialysis. Therefore, the ideal angle and flow rate of needle is sought in this study.

Huaier extract synergizes with tamoxifen to induce autophagy and apoptosis in ER-positive breast cancer cells.

Tamoxifen (TAM) is the most widely used endocrine therapy for estrogen receptor (ER)-positive breast cancer patients, but side effects and the gradual development of insensitivity limit its application. We investigated whether Huaier extract, a traditional Chinese medicine, in combination with TAM would improve treatment efficacy in ER-positive breast cancers. MTT, colony formation, and invasion and migration assays revealed that the combined treatment had stronger anticancer effects than either treatment alone. Huaier extract enhanced TAM-induced autophagy, apoptosis, and G0/G1 cell cycle arrest, as measured by acidic vesicular organelle (AVO) staining, TUNEL, flow cytometry, and western blot. Additionally, combined treatment inhibited tumorigenesis and metastasis by suppressing the AKT/mTOR signaling pathway. Huaier extract also enhanced the inhibitory effects of TAM on tumor growth in vivo in a xenograft mouse model. These results show that Huaier extract synergizes with TAM to induce autophagy and apoptosis in ER-positive breast cancer cells by suppressing the AKT/mTOR pathway.

JAM3 methylation status as a biomarker for diagnosis of preneoplastic and neoplastic lesions of the cervix.

DNA methylation is clinically relevant to important tumorigenic mechanisms. This study evaluated the methylation status of candidate genes in cervical neoplasia and determined their diagnostic performance in clinical practice. Cervical cancer and normal cervix tissue was used to select the top 5 discriminating loci among 27 loci in 4 genes (CCNA1, CADM1, DAPK1, JAM3), and one locus of JAM3 (region M4) was identified and confirmed with 267 and 224 cervical scrapings from 2 independent colposcopy referral studies. For patients with atypical squamous cells of unknown significance and those with low-grade squamous intraepithelial lesion, with JAM3-M4 compared to a triage marker of hrHPV testing, the specificity for cervical intraepithelial neoplasia 3 CIN3 and cancer cases (CIN3+) / no neoplasia and CIN1 (CIN1-) was significantly increased, from 21.88 to 81.82 and 15.38 to 85.18, respectively. The corresponding positive predictive value (PPV) was increased from 26.47 to 57.14 and 18.52 to 63.64, respectively. For hrHPV-positive patients, compared to a triage marker of cytology testing, JAM3-M4 showed increased specificity and PPV, from 30.67 to 87.65 and 38.82 to 82.14, respectively. We assessed whether JAM3-M4 could distinguish productive from transforming CIN2; the coincidence rate of JAM3-M4 and P16 was as high as 60.5%.

Huaier aqueous extract inhibits cervical cancer cell proliferation via JNK/p38 pathway.

Although the anticancer effects of Huaier extract have been widely investigated, including anti-proliferate, anti-angiogenic and anti-metastatic activities, the mechanisms are not well understood. This study aimed to elucidate the inhibitory effect of Huaier extract on tumor growth in cervical cancer cells and its molecular mechanisms. Cell viability and motility were measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, colony assays, migration, and invasive assays, respectively. The distribution of the cell cycle was analyzed by flow cytometry. Huaier inhibited cell viability of SiHa and C33A cells in a time- and dose-dependent manner; cell migration and invasiveness were also suppressed; Huaier was able to cause G2/M cell cycle arrest in C33A cells. The western blot results confirmed Huaier dose-dependently increased expression of phosphorylated c-Jun N-terminal kinase (JNK), p-38 and downregulated the expression of phosphorylated extracellular signal-regulated kinase (ERK) in a time- and dose-dependently manner. In vivo experiments showed that Huaier significantly suppressed the tumor volume of SiHa cell xenografts. These data suggest that Huaier may inhibit tumor proliferation in cervical cancer via the JNK/p38 signaling pathway.

Observation of giant positive magnetoresistance in a Cooper pair insulator.

Ultrathin amorphous Bi films, patterned with a nanohoneycomb array of holes, can exhibit an insulating phase with transport dominated by the incoherent motion of Cooper pairs (CP) of electrons between localized states. Here, we show that the magnetoresistance (MR) of this Cooper pair insulator (CPI) phase is positive and grows exponentially with decreasing temperature T, for T well below the pair formation temperature. It peaks at a field estimated to be sufficient to break the pairs and then decreases monotonically into a regime in which the film resistance assumes the T dependence appropriate for weakly localized single electron transport. We discuss how these results support proposals that the large MR peaks in other unpatterned, ultrathin film systems disclose a CPI phase and provide new insight into the CP localization.

Superconducting pair correlations in an amorphous insulating nanohoneycomb film.

The Cooper pairing mechanism that binds single electrons to form pairs in metals allows electrons to circumvent the exclusion principle and condense into a single superconducting or zero-resistance state. We present results from an amorphous bismuth film system patterned with a nanohoneycomb array of holes, which undergoes a thickness-tuned insulator-superconductor transition. The insulating films exhibit activated resistances and magnetoresistance oscillations dictated by the superconducting flux quantum h/2e. This 2e period is direct evidence indicating that Cooper pairing is also responsible for electrically insulating behavior.

Fabrication of anodic aluminium oxide templates on curved surfaces.

Aluminium anodization provides a simple and inexpensive way to obtain nanoporous templates with uniform and controllable pore diameters and periods over a wide range. Moreover, one of the interesting possibilities afforded by the anodization process is that the anodization can take place on arbitrary surfaces, such as curved surfaces, which has not yet been well studied or applied in nanofabrication. In this paper, we characterize the anodization of Al films on silicon substrates with a curved top surface. The structures of the resultant anodic aluminium oxide (AAO) films are examined by scanning electron microscopy. Unique features including cessation, bending, and branching of pore channels are observed in the curved area. Possible growth mechanisms are proposed, which can also contribute to the understanding of the self-organization mechanism in the formation of porous AAO membranes. The new structures may open new opportunities in optical, electronic and electrochemical applications.

Electric field tuning of plasmonic response of nanodot array in liquid crystal matrix.

In this work we demonstrate the feasibility of electric-field tuning of the plasmonic spectrum of a novel gold nanodot array in a liquid crystal matrix. As opposed to previously reported microscopically observed near-field spectral tuning of individual gold nanoparticles, this system exhibits macroscopic far-field spectral tuning. The nanodot-liquid crystal matrix also displays strong anisotropic absorption characteristics, which can be effectively described as a collective ensemble within a composite matrix in the lateral dimension and a group of noninteracting individual particles in the normal direction. The effective medium model and the Mie theory are employed to describe the experimental results.

Site-specific assembly of DNA and appended cargo on arrayed carbon nanotubes.

We describe a strategy that permits discrete regions of arrayed carbon nanotubes (CNTs) to be functionalized simultaneously and specifically with DNA oligonucleotides. The different chemical properties of two regions on single CNTs and orthogonal chemical coupling strategies have been exploited to derivatize CNTs within highly ordered arrays with multiple DNA sequences. Through duplex hybridization, we then targeted different DNA sequences with appended metal nanoparticles to distinct sites on the CNT architecture with precise spatial control. The materials generated from these studies represent the first CNTs with bipartite functionalization. The approach described provides a high level of precision in parallel and directed assembly of DNA sequences and appended cargo and is useful for the preparation of novel hybrid bionanomaterials.