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Patient-derived tumor organoids (PDTOs) shows great potential as a preclinical model. However, the current methods for establishing PDTOs primarily focus on modulating local properties, such as sub-micrometer topographies. Nevertheless, they neglect to capture the global millimeter or intermediate mesoscale architecture that have been demonstrated to influence tumor response to therapeutic treatment and tumor progression. In this study, we present a rapid technique for generating collagen bundles with an average length of 90 ± 27 μm and a mean diameter of 5 ± 1.5 μm from tumor tissue debris that underwent mechanical agitation following enzymatic digestion. The collagen bundles were subsequently utilized for the fabrication of biomimetic hydrogels, incorporating microbial transglutaminase (mTG) crosslinked gelatin. These biomimetic hydrogels, referred to as MC-gel, were specifically designed for patient-derived tumor organoids. The lung cancer organoids cultured in MC-gel exhibited larger diameters and higher cell viability compared to those cultured in gels lacking the mesoscale collagen bundle; moreover, their irregular morphology more closely resembled that observed in vivo. The MC-gel-based lung cancer organoids effectively replicated the histology and mutational landscapes observed in the original donor patient’s tumor tissue. Additionally, these lung cancer organoids showed a remarkable similarity in their gene expression and drug response across different matrices. This recently developed model holds great potential for investigating the occurrence, progression, metastasis, and management of tumors, thereby offering opportunities for personalized medicine and customized treatment options.

Biodegradable magnesium (Mg) and its alloys exhibit excellent biocompatibility and mechanical compatibility, demonstrating tremendous potential for applications in orthopedics. However, the rapid degradation rate has limited their clinical application. Polycaprolactone (PCL) is commonly employed as a polymer coating to impede the rapid degradation of Mg. Unfortunately, its long-term anti-corrosion capability and bioactivity are inadequate. To address these issues, polydopamine (PDA)-modified zeolitic imidazolate framework-8 (PZIF-8) bioactive nanoparticles are fabricated and incorporated into the PCL coating. The PZIF-8 particles, featuring catechol motifs, can enhance the compactness of the PCL coating, reduce its defects, and possess biomineralization ability, thereby effectively improving its anti-corrosive and bioactive properties. Moreover, the active substances released from the degradation of the PZIF-8 particles such as Zn2+ and PDA are beneficial for osteogenesis. The corrosion tests indicate that the corrosion current density of PCL-treated sample decreases by more than one order of magnitude and the amount of H2 released decreases from 0.23 ± 0.12 to 0.08 ± 0.08 ml cm−2 after doping with the PZIF-8. Furthermore, the improved corrosion resistance and released PDA and Zn2+ from the coating can promote osteogenic differentiation by up-regulating the expression of alkaline phosphatase activity, related osteogenic genes, and proteins. In addition, in vivo implantation experiments in rabbit femur defects further offer strong evidence that the doping of PZIF-8 nanoparticles accelerates bone reconstruction of the PCL coating. In summary, this work implies a new strategy to fabricate a PCL-based coating on Mg-based implants by introducing the PZIF-8 particles for orthopedic applications.

Although advanced deep learning techniques have significantly improved SAR ship detection, accurately detecting small ships remains challenging due to their limited size and the few appearance and geometric clues available. In order to solve this problem, we propose several small object detection strategies. The backbone network uses space-to-depth convolution to replace stride and pooling. It reduces information loss during down-sampling. The neck integrates multiple layers of features globally and injects global and local information into different levels. It avoids the inherent information loss of traditional feature pyramid networks and strengthens the information fusion ability without significantly increasing latency. The proposed intersection-of-union considers the center distance and scale of small ships specifically. It reduces the sensitivity of intersection-of-union to positional deviations of small ships, which is helpful for training toward small ships. During training, the smaller the localization loss of small ships, the greater their localization loss gains are. By this, the supervision of small ships is strengthened in the loss function, which can make the losses more biased toward small ships. A series of experiments are conducted on two commonly used datasets, SSDD and SAR-Ship-Dataset. The experimental results show that the proposed method can detect small ships successfully and thus improve the overall performance of detectors.

Background: The 2018 United Network for Organ Sharing organ allocation change aimed to distribute donor hearts to the sickest patients on the waitlist. Whether this change differentially affected outcomes in heart-only vs heart-kidney transplant recipients is unknown. Methods: This study used the Scientific Registry of Transplant Recipients to compare outcomes, including survival, of heart-only and heart-kidney transplant recipients from 2015 to 2021, from the old vs new allocation system, including use of mechanical circulatory support (MCS), prior to transplant. Results: During the study period, 16,696 patients underwent heart transplant alone (9,320 in the old and 7,376 in the new system) and 1,156 patients underwent heart-kidney transplant (529 in the old and 627 in the new system). For both heart and heart-kidney transplant populations, there was a 3- to 5-fold increase in the use of temporary MCS. Heart-only recipients had worse survival when temporary MCS was used in the old allocation system. Heart-only recipients with durable MCS had worse survival both in the old and the new allocation system. There was no difference in survival in heart-kidney recipients in the old vs new allocation system, regardless of MCS use. Conclusions: The new heart allocation system was associated with increased use of temporary MCS in both heart and heart-kidney recipients. However, this change only differentially affected survival in heart-only recipients with improved survival if on temporary MCS, but worse survival if on durable MCS. Unlike prior studies, heart-kidney recipients did not have different outcomes after the heart allocation change, which may reflect outcomes in more current times.

Bone fractures and critical-size bone defects are significant public health issues, and clinical treatment outcomes are closely related to the intrinsic properties of the utilized implant materials. Zinc (Zn)-based biodegradable metals (BMs) have emerged as promising bioactive materials because of their exceptional biocompatibility, appropriate mechanical properties, and controllable biodegradation. This review summarizes the state of the art in terms of Zn-based metals for bone repair and regeneration, focusing on bridging the gap between biological mechanism and required bioactivity. The molecular mechanism underlying the release of Zn ions from Zn-based BMs in the improvement of bone repair and regeneration is elucidated. By integrating clinical considerations and the specific bioactivity required for implant materials, this review summarizes the current research status of Zn-based internal fixation materials for promoting fracture healing, Zn-based scaffolds for regenerating critical-size bone defects, and Zn-based barrier membranes for reconstituting alveolar bone defects. Considering the significant progress made in the research on Zn-based BMs for potential clinical applications, the challenges and promising research directions are proposed and discussed.

Abstract Ubiquitin-specific protease 4 (USP4) represents a potential oncogene involved in various human cancers. Nevertheless, the biological roles and precise mechanism of USP4 in esophageal squamous cell carcinoma (ESCC) progression are not understood. Here, USP4 expression was found to be markedly upregulated in ESCC tumor tissues and cells. Loss- and gain-of-function assays suggested that USP4 silencing inhibited ESCC cell proliferation, migration, and invasion, while USP4 overexpression promoted these behaviors. Consistently, USP4 silencing repressed tumor growth and metastasis in an ESCC nude mouse model in vivo. As a target molecule of USP4, transforming growth factor-β-activated kinase 1 (TAK1) also showed high expression in ESCC. Moreover, we observed that USP4 specifically interacted with TAK1 and stabilized TAK1 protein levels via deubiquitination in ESCC cells. Importantly, USP4 promotes ESCC proliferation, migration, and invasion via the MEK/ERK signaling pathway and can be inhibited by U0126. Neutral red (NR), an inhibitor of USP4 can suppress ESCC progression in vitro and in vivo. Overall, this study revealed that USP4/TAK1 plays crucial roles in ESCC progression by modulating proliferation, migration, and invasion, and USP4 might be a potential therapeutic target in ESCC.

SAR (synthetic aperture radar) ship detection is a hot topic due to the breadth of its application. However, limited by the volume of the SAR image, the generalization ability of the detector is low, which makes it difficult to adapt to new scenes. Although many data augmentation methods—for example, clipping, pasting, and mixing—are used, the accuracy is improved little. In order to solve this problem, the adversarial training is used for data generation in this paper. Perturbation is added to the SAR image to generate new samples for training, and it can make the detector learn more abundant features and promote the robustness of the detector. By separating batch normalization between clean samples and disturbed images, the performance degradation on clean samples is avoided. By simultaneously perturbing and selecting large losses of classification and location, it can keep the detector adaptable to more confrontational samples. The optimization efficiency and results are improved through K-step average perturbation and one-step gradient descent. The experiments on different detectors show that the proposed method achieves 8%, 10%, and 17% AP (Average Precision) improvement on the SSDD, SAR-Ship-Dataset, and AIR-SARShip, compared to the traditional data augmentation methods.

Aeromagnetic surveys are widely used in geological exploration, mineral resource assessment, environmental monitoring, military reconnaissance, and other areas. It is necessary to perform magnetic compensation for interference in these fields. In recent years, large unmanned aerial vehicles (UAVs) have been more suitable for magnetic detection missions because of the greater loads they can carry. This article proposes some methods for the magnetic compensation of large multiload UAVs. Because of the interference of the large platform and instrument noise, the standard deviations (stds) of the compensation data used in this paper are larger. At the beginning of this article, using the traditional T-L model, we avoid the shortcomings of the anti-magnetic interference ability of triaxial magnetic gate magnetometers. The direction cosine information is obtained by using an inertial navigation system, the global positioning system, and a triaxial magnetic gate magnetometer. Then, we increase the amplitude of the maneuvers in the compensation process; this reduces the multicollinearity problems in the compensation matrix to a certain extent, but it also results in greater magnetic field interference. Lastly, we employ the method of Lasso regularization Newton iteration (LRNM). Compared to the traditional methods of least squares (LS) and singular value decomposition (SVD), LRNM provides improvements of 34% and 27%, respectively. In summary, this series of schemes can be used to perform effective compensation for large multi-load UAVs and improve the actual use of large UAVs, making them more accurate in the measurement of aeromagnetic survey data.

Single-point magnetic gradient tensor positioning methods are greatly affected by geomagnetic field estimation errors, and multi-point magnetic gradient tensor positioning methods are easy to get trapped in local optima. To address these issues, a two-point magnetic gradient tensor positioning method was proposed. Based on the single-point magnetic gradient tensor positioning algorithm, this method used two-point magnetic gradient tensor measurement data and superimposed the constraints of tensor geometric invariants to construct a nonlinear objective function about the target position coordinates, and it used the natural selection-based particle swarm optimization(NSPSO) algorithm to solve the target position coordinates. Simulation experiments demonstrate that the proposed method is less affected by geomagnetic field estimation errors and can search for global optima. It exhibits high localization accuracy. The simulation analysis considers the positioning performance of the proposed method for magnetic targets under different system baseline lengths and magnetometer sensitivities. The results indicate that as the system baseline length and the magnetometer sensitivity improve, the positioning error for magnetic targets decreases.

Background: Whether minimally invasive esophagectomy (MIE) is superior to open esophagectomy (OE) in the treatment of esophageal squamous cell carcinoma (ESCC) is still uncertain. Therefore, this multicenter prospective study aimed to compare MIE with OE in postoperative parameters and long-term survival. Methods: All hospitalized patients with cT1b-3N0–1M0 thoracic ESCC treated by MIE or OE were enrolled from 19 selected centers from April 1, 2015 to December 31, 2018. The propensity score matching (PSM) was performed to minimize the selection bias. The basic clinicopathological characteristics and 3-year overall survival (OS) as well as disease-free survival (DFS) of two groups were compared by R version 3.6.2. Results: MIE were performed in 1,387 patients and OE in 335 patients. 335 cases in each group were finally matched by PSM, and no significant differences in the essential demographic characteristics were observed between the MIE and OE groups after PSM. Compared with OE, MIE had significantly less intraoperative bleeding, less total drainage volume, shorter postoperative hospital stay, and harvested significantly more lymph nodes (LNs) (all P < 0.001). There were no significant differences in the major postoperative complications and death rates between MIE and OE. The 3-year OS and DFS were 77.0% and 68.1% in the MIE group versus 69.3% and 60.9% in the OE group (OS: P = 0.03; DFS: P = 0.09), and the rates were 75.1% and 66.5% in the MIE group versus 66.9% and 58.6% in the OE group for stage cII patients (OS: P = 0.04, DFS: P = 0.09), respectively. Conclusions: Compared with OE, MIE is a safe and effective treatment approach with similar mortality and morbidity. It has the advantages in harvesting more LNs, improving postoperative recovery and survival of stage cII ESCC patients.

Biodegradable metals such as magnesium (Mg) and its alloys have attracted extensive attention in biomedical research due to their excellent mechanical properties and biodegradability. However, traditional casting, extrusion, and commercial processing have limitations in manufacturing components with a complex shape/structure, and these processes may produce defects such as cavities and gas pores which can degrade the properties and usefulness of the products. Compared to conventional techniques, additive manufacturing (AM) can be used to precisely control the geometry of workpieces made of different Mg-based materials with multiple geometric scales and produce desirable medical products for orthopedics, dentistry, and other fields. However, a detailed and thorough understanding of the raw materials, manufacturing processes, properties, and applications is required to foster the production of commercial Mg-based biomedical components by AM. This review summarizes recent advances and important issues pertaining to AM of Mg-based biomedical products and discusses future development and application trends.

Abstract Background PTPRF interacting protein alpha 1 (PPFIA1) is reportedly related to the occurrence and progression of several kinds of malignancies. However, its role in esophageal squamous cell carcinoma (ESCC) is unclear. This current study investigated the prognostic significance and biological functions of PPFIA1 in ESCC. Methods Oncomine, Gene Expression Profiling Interactive Analysis (GEPIA), and Gene Expression Omnibus (GEO) were used to investigate PPFIA1 expression in esophageal cancer. The relationship between PPFIA1 expression and clinicopathological characteristics and patient survival was evaluated in GSE53625 dataset, and verified in the cDNA array based on qRT–PCR and tissue microarray (TMA) dataset based on immunohistochemistry. The impact of PPFIA1 on the migration and invasion of cancer cells were investigated by wound-healing and transwell assays, respectively. Results The expression of PPFIA1 was obviously increased in ESCC tissues versus adjacent esophageal tissues according to online database analyses (all P

Abstract Purpose Pyroptosis, a type of programmed cell death, is implicated in the tumorigenesis, development and migration of cancer, which can be regulated by long non‐coding RNAs (lncRNAs). Our research aimed to investigate the prognostic role of pyroptosis‐related lncRNAs and the relationship to the tumor immune microenvironment through bioinformatics analysis. Methods The clinical and RNA‐sequencing data of bladder cancer patients were downloaded from The Cancer Genome Atlas (TCGA). And 412 bladder cancer subjects with clinical information were divided into training and testing cohort. And 52 reported pyroptosis‐related genes were used to screen pyroptosis‐related lncRNAs. A pyroptosis‐related lncRNA signature was constructed based on Cox regression analyses. Results A 9‐pyroptosis‐related‐lncRNA signature was identified to separate patients with bladder cancer into two groups. The prognosis of bladder cancer patients in the high‐risk group was significantly inferior compared with those in the low‐risk group. Risk scores were validated to develop an independent prognostic indicator based on multivariate Cox regression analysis. Receiver operating characteristic curve (ROC) analysis examined the signature on overall survival. The area under time‐dependent ROC curve (AUC) at 1‐, 3, and 5‐years measured 0.747, 0.783, and 0.768, respectively. Analysis of the immune landscape and PD‐L1 expression showed that PD‐L1 is upregulated in the high‐risk group. The immunocyte subtypes of the two groups were different. Conclusion A novel pyroptosis‐related lncRNA signature was identified with prognostic value for bladder cancer patients. Pyroptosis‐related lncRNAs have a potential role in cancer immunology and may serve as prognostic or therapeutic targets.

The presence of complex electromagnetic noise in the ocean significantly impacts the accuracy of ship shaft-rate electric field signal detection, necessitating the development of an effective denoising method to enhance detection precision. Nevertheless, traditional denoising methods encounter issues like low frequency resolution, challenging threshold configuration, and mode mixing. This study introduces a method that integrates variational mode decomposition (VMD) with multi-window spectral subtraction (MSS). The intrinsic mode functions (IMFs) of noisy signals are extracted using VMD, and the noise components within different IMFs are identified. The spectral features of both signal and noise within different IMFs are leveraged to eliminate noise signals via MSS. Subsequently, the denoised components of IMFs are rearranged to derive the denoised ship shaft-rate electric field signals, achieving noise reduction across various frequency bands. Following validation using simulation signals and empirical data, the noise reduction efficacy of VMD-MSS surpasses that of alternative methods, demonstrating robust performance even at low signal-to-noise ratios. The marine electromagnetic noise is effectively suppressed in the empirical data, while preserving the characteristics of ship’s shaft-rate signals, thereby validating the method’s efficacy and demonstrating its practical engineering value.

Currently, magnetic gradient tensor-based localization methods face challenges such as significant errors in geomagnetic field estimation, susceptibility to local optima in optimization algorithms, and inefficient performance. In addressing these issues, this article propose a two-point localization method under the constraint of overlaying geometric invariants. This method initially establishes the relationship between the target position and the magnetic gradient tensor by substituting an intermediate variable for the magnetic moment. Exploiting the property of the eigenvector corresponding to the minimum absolute eigenvalue being perpendicular to the target position vector, this constraint is superimposed to formulate a nonlinear system of equations of the target’s position. In the process of determining the target position, the Nara method is employed for obtaining the initial values, followed by the utilization of the Levenberg–Marquardt algorithm to derive a precise solution. Experimental validation through both simulations and experiments confirms the effectiveness of the proposed method. The results demonstrate its capability to overcome the challenges faced by a single-point localization method in the presence of some errors in geomagnetic field estimation. In comparison to traditional two-point localization methods, the proposed method exhibits the highest precision. The localization outcomes under different noise conditions underscore the robust noise resistance and resilience of the proposed method.

BackgroundAlthough many CTC isolation and detection methods can provide information on cancer cell counts, downstream gene and protein analysis remain incomplete. Therefore, it is crucial to develop a technology that can provide comprehensive information on both the number and profile of CTC.MethodsIn this study, we developed a novel microfluidics-based CTC separation and enrichment platform that provided detailed information about CTC.ResultsThis platform exhibits exceptional functionality, achieving high rates of CTC recovery (87.1%) and purification (∼4 log depletion of WBCs), as well as accurate detection (95.10%), providing intact and viable CTCs for downstream analysis. This platform enables successful separation and enrichment of CTCs from a 4 mL whole-blood sample within 15 minutes. Additionally, CTC subtypes, selected protein expression levels on the CTC surface, and target mutations in selected genes can be directly analyzed for clinical utility using immunofluorescence and real-time polymerase chain reaction, and the detected PD-L1 expression in CTCs is consistent with immunohistochemical assay results.ConclusionThe microfluidic-based CTC enrichment platform and downstream molecular analysis together provide a possible alternative to tissue biopsy for precision cancer management, especially for patients whose tissue biopsies are unavailable.

The Doppler information in complement to the intensity of radar backscatter has been verified useful for ocean synthetic aperture radar (SAR) applications. An accurate estimate of the ocean surface motions requires an accurate estimate of the Doppler centroid. When we process the real SAR data, we find that different methods yield different mean values of the estimates. After a careful analysis, we find that it is caused by the underestimation of the centroids for conventional methods. The estimate bias depends on the Doppler centroid itself. To overcome this problem, we carefully study the conventional methods and the Cramér–Rao bound of the estimation. Based on the maximum-likelihood principle, a novel method is proposed. By adaptively adjusting the center and the bandwidth of the weighting function after a coarse estimation of the spectrum, the symmetry of the spectrum is maintained. The estimate bias of conventional methods is eliminated. It is a fully optimal method meeting the Cramér–Rao bound no matter whether the true Doppler centroid is high or low. Both the simulated and the real SAR data validate our novel method. In the simulation, an estimate error of tens of Hz could be avoided when the true Doppler center is hundreds of hertz. In real SAR estimation, an accuracy of 3–6 Hz can be improved. The result of the estimation is consistent with the simulation and theoretical analysis, validating the efficiency of our improved method.

Recently, deep learning has greatly promoted the development of synthetic aperture radar (SAR) ship detection. But the detectors are usually heavy and computation intensive, which hinder the usage on the edge. In order to solve this problem, a lot of lightweight networks and acceleration ideas are proposed. In this survey, we review the papers that are about real-time SAR ship detection. We first introduce the model compression and acceleration methods. They are pruning, quantization, knowledge distillation, low-rank factorization, lightweight networks, and model deployment. They are the source of innovation in real-time SAR ship detection. Then, we summarize the real-time object detection methods. They are two-stage, single-stage, anchor free, trained from scratch, model compression, and acceleration. Researchers in SAR ship detection usually learn from these ideas. We then spend a lot of content on the review of the 70 real-time SAR ship detection papers. The years, datasets, journals, deep-learning frameworks, and hardwares are introduced first. After that, 10 public datasets and the evaluation metrics are shown. Then, we survey the 70 papers according to anchor free, trained from scratch, YOLO series, constant false alarm rate+convolutional neural network, lightweight backbone, pruning, quantization, knowledge distillation, and hardware deployment. The experimental results show that the algorithms have been greatly developed in speed and accuracy. In the end, we pointed out the problems of 70 papers and the directions to be studied in the future. This article can enable researchers to quickly understand the research status in this field.

Abstract Background Esophageal squamous cell carcinoma (ESCC) has a dismal prognosis, and hypoxia plays a key role in metastasis and proliferation of ESCC. Thus, we aimed to develop a hypoxia‐based gene signature to assist in the treatment decisions and prognosis. Methods We performed consensus clustering analysis on samples from GSE53625 dataset from the Gene Expression Omnibus (GEO) database and used weighted gene co‐expression network analysis to filter out candidate modules, which were then intersected with differentially expressed genes from clustered subgroups to obtain hypoxia‐related genes (HRGs). After that, the aforementioned genes were used to construct risk score models and validated in The Cancer Genome Atlas (TCGA) database and Cox regression analysis were used to construct a nomogram. Immunohistochemical was used to detect protein expression levels of relevant genes. Moreover, the relationship between risk scores and tumor microenvironment was explored. Results A hypoxia risk model containing six genes (PNPLA1, CARD18, IL‐18, SLC37A2, ADAMTS18, and FAM83C) was constructed by screening key HRGs. Poorer prognosis in the high‐risk group than in the low‐risk group. And Cox regression analysis showed that risk score was an independent prognostic factor. The nomogram based on risk scores could well predict 1‐, 3‐, and 5‐year survival. P53, Wnt, and hypoxia signaling pathways may be some regulatory mechanisms of hypoxia associated with the tumor microenvironment. In addition, we confirmed the high expression of BGN and low expression of IL‐18 in ESCC tissues. Conclusions Our study determined the prognostic value of a 6‐hypoxia gene signature and a prognostic model, providing potential prognostic predictors and therapeutic targets for ESCC.

Abstract Background Patients with esophageal squamous cell carcinoma (ESCC) with lymph node metastasis may be misclassified as pN0 due to an insufficient number of lymph nodes examined (LNE). The purpose of this study was to confirm that patients with ESCC are indeed pN0 and to propose an adequate number for the correct nodal stage using the nodal staging score (NSS) developed by the beta‐binomial model. Methods A total of 1249 patients from the Surveillance, Epidemiology, and End Results (SEER) database between 2000 and 2017, and 1404 patients diagnosed with ESCC in our database between 2005 and 2018 were included. The NSS was developed to assess the probability of pN0 status based on both databases. The effectiveness of NSS was verified using survival analysis, including Kaplan–Meier curves and Cox models. Results Many patients were misclassified as pN0 based on our algorithm due to insufficient LNE. As the number of LNE increased, false‐negative findings dropped; accordingly, the NSS increased. In addition, NSS was an independent prognostic indicator for pN0 in patients with ESCC in the SEER database (hazard ratio [HR] 0.182, 95% confidence interval [CI] 0.046–0.730, p = 0.016) and our database (HR 0.215, 95% CI 0.055–0.842, p = 0.027). A certain number of nodes must be examined to achieve 90% of the NSS. Conclusions NSS could determine the probability of true pN0 status for patients, and it was sufficient in predicting survival and obtaining adequate numbers for lymphadenectomy.

Abstract Background Synchronous multiple primary esophageal squamous cell carcinoma (S-MPESCC) refers to more than one primary esophageal carcinoma detected in a solitary patient at the time of initial presentation. The purpose of this study was to evaluate the clinicopathological features, appropriate surgical approaches and long-term survival in patients with S-MPESCC by comparing with those with solitary esophageal squamous cell carcinoma (SESCC). Methods In total, 567 patients with esophageal squamous cell carcinoma surgically resected in Tianjin Medical University Cancer Institute and Hospital from January 2012 to December 2018 were screened for retrospective analysis (50 in the S-MPESCC group and 516 in the SESCC group). Results No significant difference was observed in terms of other characteristics except total alcohol consumption (P = 0.029). S-MPESCC had higher lymph node rate than SESCC (62.0% and 44.1%, respectively; P = 0.015) especially in upper mediastinal (32.0% and 18.6%, respectively; P = 0.023) and abdominal (38.0% and 22.8%, respectively; P = 0.017) regions. The survival was not different between the two groups, and the 5-year survival rates of S-MPESCC and SESCC were 46.2% and 50.8%, respectively (P = 0.507). But for patients with pT3-4 cancers, the survival in S-MPESCC was worse than that in SESCC (P = 0.033). In the multivariate analysis, pT stage of primary cancer was an important independent predictor of prognosis in patients with S-MPESCC (hazard ratio [HR], 3.968; 95% confidence interval [CI], 1.031 to 15.268; P = 0.045). Conclusions S-MPESCC was significantly different from SESCC in terms of clinicopathological characteristics include alcohol intake and pattern of lymphatic metastasis. Furthermore, S-MPESCC showed worse long-term survival than SESCC with increasing depth of primary cancer infiltration.

Objective: Anterior cervical corpectomy and fusion (ACCF) has been widely used in the treatment of cervical spondylotic myelopathy (CSM) but is accompanied by unavoidable motion loss and destruction of vertebra. We aim to evaluate the range of motion (ROM) of caprine cervical spine constructs implanted with cervical artificial disc and vertebra system (ADVS). The purpose of this study was to investigate the biomechanical properties of the ADVS from an in vivo caprine cervical spine non-fusion model. Methods: Twelve goats were randomly divided into ADVS or control group, with 6 animals in each group. The animals in the ADVS group were implanted with ADVS at the C4 level. The cervical spine constructs were harvested 6 months after the operation. The ROM of cervical spine specimens in the ADVS group was recorded. Biomechanical testing of the specimens in the control group were conducted to evaluate the ROM of the cervical spine specimens under intact and fixed condition (C3-C5) by an anterior plate, respectively. Results: The biomechanical outcomes showed that the ROM of the levels (C3-C5) implanted with ADVS was maintained. The ROM in the adjacent level (C2-3) did not increase significantly comparing with intact group. Conclusions: In general, ADVS could preserve the ROM of operative levels and could reconstruct the height of the vertebra. ADVS did not increase the ROM of upper adjacent level. This device provides a non-fusion method for the treatment of patients suffering from CSM. However, improvements on the design of ADVS are still needed. Translational potential statement: This study introduced a novel cervical spinal implant, which was designed to have the ability of motion preservation and vertebra construction. Our study provided a non-fusion procedure in the treatment of CSM after ACCF.

Background The tumour-node-metastasis (TNM) staging system is insufficient to precisely distinguish the long-term survival of patients who underwent pneumonectomy for primary lung cancer. Therefore, this study sought to identify determinants of disease-free (DFS) and overall survival (OS) for incorporation into web-based dynamic nomograms. Methods The clinicopathological variables, surgical methods and follow-up information of 1,261 consecutive patients who underwent pneumonectomy for primary lung cancer between January 2008 and December 2018 at Sun Yat-sen University Cancer Center were collected. Nomograms for predicting DFS and OS were built based on the significantly independent predictors identified in the training cohort (n = 1,009) and then were tested on the validation cohort (n = 252). The concordance index (C-index) and time-independent area under the receiver-operator characteristic curve (AUC) assessed the nomogram’s discrimination accuracy. Decision curve analysis (DCA) was applied to evaluate the clinical utility. Results During a median follow-up time of 40.5 months, disease recurrence and death were observed in 446 (35.4%) and 665 (52.7%) patients in the whole cohort, respectively. In the training cohort, a higher C-reactive protein to albumin ratio, intrapericardial pulmonary artery ligation, lymph node metastasis, and adjuvant therapy were significantly correlated with a higher risk for disease recurrence; similarly, the independent predictors for worse OS were intrapericardial pulmonary artery and vein ligation, higher T stage, lymph node metastasis, and no adjuvant therapy. In the validation cohort, the integrated DFS and OS nomograms showed well-fitted calibration curves and yielded good discrimination powers with C-index of 0.667 (95% confidence intervals CIs [0.610–0.724]) and 0.697 (95% CIs [0.649–0.745]), respectively. Moreover, the AUCs for 1-year, 3-year, and 5-year DFS were 0.655, 0.726, and 0.735, respectively, and those for 3-year, 5-year, and 10-year OS were 0.741, 0.765, and 0.709, respectively. DCA demonstrated that our nomograms could bring more net benefit than the TNM staging system. Conclusions Although pneumonectomy for primary lung cancer has brought encouraging long-term outcomes, the constructed prediction models could assist in precisely identifying patients at high risk and developing personalized treatment strategies to further improve survival.

Generalized broadband operation facilitates multifunction or multiband highly integrated applications, such as modern transceiver systems, where ultra-wideband bidirectional passive mixers are favored to avoid a complex up/down-conversion scheme. In this paper, a modified Ruthroff-type transmission line transformer (TLT) balun is presented to enhance the isolation of the mixer from the local oscillator (LO) to the radio frequency (RF). Compared to the conventional methods, the proposed Ruthroff-type architecture adopts a combination of shunt capacitors and parallel coupled lines to improve the return loss at the LO port, thus effectively avoiding the area consumption for the diode-to-balun impedance transformation while simultaneously providing a suitable point for IF extraction. In addition, a parallel compensation technique consisting of an inductor and resistor is applied to the RF balun to significantly improve the amplitude/phase balance performance over a wide bandwidth. Benefiting from the aforementioned operations, an isolation-enhanced 8–30 GHz passive double-balanced mixer is designed as a proof-of-principle demonstration via 0.15-micrometer GaAs p-HEMT technology. It exhibits ultra-broadband performance with 7 dB average conversion loss and 50 dB LO-to-RF isolation under 15 dBm LO power. The monolithic microwave integrated circuit area is 0.96 × 1.68 mm2 including all pads.

In a beamforming circuit for a modern broadband phased-array system, high accuracy and compactness have received sufficient attention as they are directly related to side lobe level and fabrication cost, respectively. In order to meet the low phase error required, this paper proposed an ultra-broadband 6-bit digital step switched-type attenuator (STA) with capacitive/inductive compensation networks. Compared to the conventional methods, the proposed technique employs an improved simplified T-structure with capacitive compensation networks, which simultaneously achieves low insertion loss and high-accuracy amplitude/phase control. In addition, on-chip level shifting circuit is integrated to avoid complex control schemes. The strategy of prioritizing return loss is adopted to alleviate the performance degradation caused by impedance mismatch after cascade. As a proof-of-principle demonstration, a wideband 6-bit STA with core area of only 0.5 mm × 1.8 mm was designed via 0.15-micrometer GaAs pHEMT technology. It exhibits ultra-broadband operation with a 31.5 dB amplitude tuning range and a 0.5 dB tuning step. The insertion loss of the reference state is 4–5.3 dB. The return loss is better than 15 dB for all the 64 states. The RMS amplitude and phase errors are less than 0.2 dB and 2° over the 10 to 20 GHz.

Bioactive porous structure coatings have received extensive attention because they can significantly improve the surface bioactivity of medical metal implants. However, traditional porous making technologies were restricted by the “upward growth” mode, with an obvious interface with the substrate, resulting in weak bonding and biological safety problems. This research innovatively proposed to selectively dissolve harmful Al element on the surface of Ti6Al4V alloy through an electrochemical dealloying process, forming a three-dimensional grid porous structure in situ on the surface, with the following three notable advantages: (1) The dealloying process was a “downward growth” mode, there was no obvious interface between the porous layer and the substrate, so the bond was firm; (2) The harmful element Al was effectively removed, and the biological safety was greatly improved; (3) The three-dimensional grid porous structure owned high-efficiency osteogenic activity, which solved the problem of Ti6Al4V biological inertness. The electrode potential and corrosion current density difference of metal elements were studied by electrochemical methods to analyze the corrosion and dissolution mechanism, the successful removal of the element Al, and the thickness of the porous layer were analyzed by XPS sputtering. Furthermore, the bioactivity was verified by co-cultivation with osteoblasts. Interestingly, the results of ALP expression, collagen secretion, and calcification all implied that the dealloyed porous structure could significantly promote the osteogenic differentiation of cells. Employing the electrochemical dealloying, a “subtractive” structure was formed on the surface of Ti6Al4V, which greatly improves the bioactivity and at the same time increased its osteogenic activity, which displayed extremely high research value and bright application value.

Non‐small cell lung cancer (NSCLC) is the most common subtype of lung cancer, and it is characterized by a high incidence. It is important to understand the molecular mechanisms that determine the progression and metastasis of NSCLC in order to develop more effective therapies and identify novel diagnostic indicators of NSCLC. RSPH14 has been reported to be related to multiple human diseases, including duodenal adenocarcinoma and meningiomas, but the role of RSPH14 in NSCLC remains unclear. The present study aimed to investigate the molecular function and clinical significance of RSPH14 in NSCLC. Analyses of public datasets and clinical samples demonstrated that RSPH14 expression was upregulated in NSCLC samples compared with normal samples. In addition, high RSPH14 expression was associated with a shorter overall survival time in patients with NSCLC. Notably, RSPH14 knockdown suppressed the proliferation and cell cycle progression and enhanced the apoptosis of NSCLC cells. Mechanically, tandem mass tag analysis demonstrated that RSPH14 can affect multiple processes, including the AMPK signaling pathway, calcium ion import regulation, glucose transmembrane transporter activity, and glucose transmembrane transport. Taken together, the results of the present study suggest that RSPH14 may be a promising prognostic factor and therapeutic target for NSCLC.

Abstract Background The purpose of this study was to assess the prognostic performance of the log odds of positive lymph nodes (LODDS) value compared with the pathological N stage and lymph node ratio (LNR) in patients with esophageal squamous cell carcinoma (ESCC). Method In total 1144 patients diagnosed with ESCC from the Surveillance, Epidemiology, and End Results (SEER) database and 930 patients from our validation cohort were eligible. Kaplan–Meier plotter and multivariate Cox proportional hazards models were conducted to investigate the prognostic value of the N stage, LNR stage, and LODDS stage. The homogeneity, discriminatory ability, and monotonicity of these variables were evaluated using the linear trend χ2 test, likelihood ratio χ2 test, Akaike information criterion (AIC), and consistency index (C‐index) to determine the potential superiorities. Results The prognostic LODDS cutoff values were determined to be −1.49 and −0.55 (p

Magnesium (Mg) alloys are attractive biodegradable implant materials. The degradation products on Mg alloys play a critical role in the stability of the interface between implant and surrounding tissue. In the present study, the effects of dynamic deformation on the interface layer of biomedical Mg-1Zn alloy were investigated using the constant extension rate tensile tests (CERT) coupled with electrochemical impedance spectroscopy (EIS). The deformation of the Mg-1Zn alloy had an adverse influence on the impedance of the surface degradation layer formed in simulated body fluid that only containing inorganic compounds. However, the surface degradation layer with improved corrosion resistance was obtained for the strained samples tested in protein-containing simulated body fluid. The spontaneous or enhanced adsorption of protein into the degradation product led to a flexible and stable hybrid anti-corrosive layer. A relationship between the dynamic deformation of Mg alloy and the impendence of the degradation layer was established, which demonstrates the necessity for in situ characterisation of the evolution of the surface layer under dynamic condition.

BackgroundWith its growing popularity and potential outcome, preoperative three-dimensional reconstruction of chest computed tomography (CT) has been widely used in video-assisted thoracic surgery (VATS) segmentectomy for treating non-small cell lung cancer (NSCLC). This study aimed to summarize the experience of anatomical variation analysis of left upper pulmonary blood vessels and bronchi based on the three-dimensional reconstruction of chest CT.Materials and methodsA total of 103 patients with early-stage NSCLC were chosen to undergo VATS segmentectomy based on preoperative three-dimensional reconstruction of chest CT in our institute from September 2019 to July 2022. Data such as clinical characteristics and variations in blood vessels and bronchi were reviewed in this study.ResultsThe branches of the left lingular pulmonary artery may mutate into the LS1 + 2 + 3. A1 + 2 has four subtypes. The distribution of variation is relatively balanced, and the most common variation is type I (35/103, 33.9%). Most lingular arteries originate from the oblique cleft side of the lingular bronchus (79/103,76.7%). Most V(1 + 2)c* are small developments (70/103, 68.0%). The venous return of the proper segment mainly depends on V(1 + 2)b + c. The variation in the left upper lobe bronchus is complex. The most common variant is the bifurcation type (type A to G, 92/103, 89.3%) and bifurcation type A (62/103, 60.2%). The posterior apical segment artery of the left upper lobe is not accompanied by its bronchus.ConclusionsThe variation types of blood vessels and bronchus in the upper lobe of the left lung are complex. Preoperative CT-based three-dimensional reconstruction of pulmonary arteries, veins, and bronchi is of great significance. It can help understand the variations, accurately locate lesions before the surgery, and effectively plan surgeries.

Abstract Obesity is closely related to a poor prognosis in patients with advanced colorectal cancer (CRC), but the mechanisms remain unclear. Ferroptosis is a form of nonapoptotic cell death characterized by lipid reactive oxygen species (ROS) accumulation and iron dependency and is associated with the chemoresistance of tumors. Here, it is shown that adipose‐derived exosomes reduce ferroptosis susceptibility in CRC, thus promoting chemoresistance to oxaliplatin. It is found that microsomal triglyceride transfer protein (MTTP) expression is increased in the plasma exosomes of CRC patients with a high body fat ratio, serving as an inhibitor of ferroptosis and reducing sensitivity to chemotherapy. Mechanistically, the MTTP/proline‐rich acidic protein 1 (PRAP1) complex inhibited zinc finger E‐box binding homeobox 1 expression and upregulated glutathione peroxidase 4 and xCT, leading to a decreased polyunsaturated fatty acids ratio and lipid ROS levels. Moreover, experiments are carried out in organoids, and a tumor implantation model is established in obese mice, demonstrating that the inhibition of MTTP increases the sensitivity to chemotherapy. The results reveal a novel intracellular signaling pathway mediated by adipose‐derived exosomes and suggest that treatments targeting secreted MTTP might reverse oxaliplatin resistance in CRC.

Abstract Angiogenesis is the process of capillary sprouting from pre-existing vessels and it plays a critical role in the carcinogenic process of lung adenocarcinoma (LUAD). However, the association of angiogenesis regulators with the prognosis and progression of LUAD needs to be further elucidated. In this study, we adopted differential expression analysis, Cox proportional hazards (PH) regression analysis and experimental validation to identify angiogenesis regulators correlated with a poor prognosis, immune infiltration and cancer progression in LUAD. These results showed that the diagnostic and prognostic models based on COL5A2 and EPHB2 served as independent biomarkers with superior predictive ability. The patients in the high-risk group exhibited a worse prognosis in the TCGA cohort (P

Abstract Background The efficacy of postoperative treatment of squamous cell carcinoma of the esophagus has not yet been determined. In this retrospective study, we investigated whether postoperative adjuvant chemotherapy (POCT) confers a survival benefit on patients who undergo curative esophagectomy. Methods A total of 782 patients were enrolled in our study. The patients were divided into surgery alone (S) and surgery plus postoperative chemotherapy (S + POCT) groups. Propensity score matching (PSM) was used to eliminate the differences in baseline characteristics. The primary endpoint was overall survival (OS), which was calculated by the Kaplan–Meier method and compared with the log‐rank test. A Cox proportional hazards model was used to identify factors influencing the prognosis. Results Of 782 patients, 343 (43.9%) underwent S alone, and 439 (56.1%) underwent S + POCT before PSM. The five‐year OS rates were 42.3% and 47.8% in the S and S + POCT groups (p = 0.080), respectively. After PSM (296 patients per group), the five‐year OS rates were 48.7% and 56.2% in the S and S + POCT groups (p = 0.025), respectively. For different cycles of POCT, patients with more than three cycles had a better survival than those with less than three cycles. The significant predictive factors for OS were pN stage (HR = 1.861, 95% CI: 1.310–2.645, p = 0.001), number of dissected nodes (HR = 0.621, 95% CI: 0.494–0.781, p

Studies that have attempted to validate the staging systems and the predictors of survival for patients with primary malignant melanoma of the esophagus (PMME) have been underpowered given their scarcity and small scale. We aimed to review a large number of PMME cases to know more about its clinicopathological features, TNM staging systems, and survival predictors of PMME. Case reports on PMME were extracted from PubMed/Medline through bibliography search and our center. A total of 287 PMME cases were identified. The majority of the patient population was male (72.08%). The most common location of PMME was the lower esophagus (50.62%) and middle esophagus (35.39%). Among the patients, 82.28% received surgical intervention. The median overall survival (OS) duration was 15 months (0.5–244). The American Joint Commission on Cancer staging classification (AJCC) for the mucosal melanoma of the upper aerodigestive tract with stage IVB and IVC integrated in stage IVA showed better distribution of OS than that for esophageal carcinoma. T stage, N stage, and surgery had significant impacts on OS duration in univariate analysis. However, only T stage and N stage were identified as independent factors for OS duration in the multivariate Cox models. PMME is an aggressive tumor with poor prognosis. The AJCC staging system for mucosal melanoma with stage IVB and IVC integrated in stage IVA may be a better option for staging PMME patients. T stage and N stage are independent factors for OS.

BackgroundImmunotherapy has achieved remarkable efficacy in treating oesophageal squamous cell carcinoma (ESCC). However, this treatment has limited efficacy in some patients. An increasing number of evidence suggested that immune cells within the tumour microenvironment (TME) are strongly related to immunotherapy response and patient prognosis. Thus, the landscape of immune cell infiltration (ICI) in ESCC needs to be mapped.MethodsIn the study, the ICI pattern in 206 cases of ESCC was characterised by two algorithms, namely, CIBERSORT and single-sample gene set enrichment analysis (ssGSEA). The ICI score of each specimen was calculated by principal component analysis (PCA) according to ICI signature genes A (ICISGA) and B (ICISGB). The prognostic difference was evaluated by using the Kaplan–Meier method. The related pathways of ICI score were investigated by applying gene set enrichment analysis (GSEA). The R packages of ‘regplot’, ‘timeROC’ and ‘rms’ were applied for the construction of nomogram model.ResultThree TME subtypes were identified with no prognostic implication. A total of 333 differentially expressed genes (DEGs) among immune subtypes were determined, among which ICISGA and ICISGB were identified. Finally, ICI scores were constructed, and the patients were grouped into high or low ICI score group. Compared with the low ICI score group, the high ICI score group had better prognosis. GSEA revealed that the high ICI score group referred to multiple signalling pathways, including B cell receptor, Fc gamma R-mediated phagocytosis, NOD-like receptor and TGF-β signalling pathways. In addition, the nomogram model was constructed to evaluate 1-, 3- and 5-year probability of death in an ESCC patient. The ROC and calibration curves indicated that the model has a good discrimination ability.ConclusionWe depicted a comprehensive ICI landscape in ESCC. ICI score may be used as a predictor of survival rate, which may be helpful for guiding immunotherapy in the future.

Esophageal cancer is the eighth most common malignant tumor and the sixth leading cause of cancer-related death worldwide. Esophageal squamous cell carcinoma (ESCC) is the main histological type of esophageal cancer, and accounts for 90% of all cancer cases. Despite the progress made in surgery, chemotherapy, and radiotherapy, the mortality rate from esophageal cancer remains high, and the overall 5-year survival rate is less than 20%, even in developed countries. The C-X-C motif chemokine ligand 12 (CXCL12) is a member of the CXC chemokine subgroup, which is widely expressed in a variety of tissues and cells. CXCL12 participates in the regulation of many physiological and pathological processes by binding to its specific receptor, C-X-C motif chemokine receptor type 4 (CXCR4), where it causes embryonic development, immune response, and angiogenesis. In addition, increasing evidence indicates that the CXCL12/CXCR4 axis plays an important role in the biological processes of tumor cells. Studies have shown that CXCL12 and its receptor, CXCR4, are highly expressed in ESCC. This abnormal expression contributes to tumor proliferation, lymph node and distant metastases, and worsening prognosis. At present, antagonists and imaging agents against CXCL12 or CXCR4 have been developed to interfere with the malignant process and monitor metastasis of tumors. This article summarizes the structure, function, and regulatory mechanism of CXCL12/CXCR4 and its role in the malignancy of ESCC. Current results from preclinical research targeting CXCL12/CXCR4 are also summarized to provide a reference for the clinical diagnosis and treatment of ESCC.

Abstract Background A nomogram was developed to predict lymph node metastasis (LNM) for patients with early-stage esophageal squamous cell carcinoma (ESCC). Methods We used the clinical data of ESCC patients with pathological T1 stage disease who underwent surgery from January 2011 to June 2018 to develop a nomogram model. Multivariable logistic regression was used to confirm the risk factors for variable selection. The risk of LNM was stratified based on the nomogram model. The nomogram was validated by an independent cohort which included early ESCC patients underwent esophagectomy between July 2018 and December 2019. Results Of the 223 patients, 36 (16.1%) patients had LNM. The following three variables were confirmed as LNM risk factors and were included in the nomogram model: tumor differentiation (odds ratio [OR] = 3.776, 95% confidence interval [CI] 1.515–9.360, p = 0.004), depth of tumor invasion (OR = 3.124, 95% CI 1.146–8.511, p = 0.026), and tumor size (OR = 2.420, 95% CI 1.070–5.473, p = 0.034). The C-index was 0.810 (95% CI 0.742–0.895) in the derivation cohort (223 patients) and 0.830 (95% CI 0.763–0.902) in the validation cohort (80 patients). Conclusions A validated nomogram can predict the risk of LNM via risk stratification. It could be used to assist in the decision-making process to determine which patients should undergo esophagectomy and for which patients with a low risk of LNM, curative endoscopic resection would be sufficient.

Abstract Background Surgical resection is an appropriate treatment option for synchronous bilateral pulmonary nodules with ground-glass opacities. The applicability of simultaneous uniportal video-assisted thoracic surgery is not fully understood. We evaluated the feasibility and safety of performing such surgeries at our hospital. Methods Clinical data of 35 patients who underwent simultaneous bilateral pulmonary resection with uniportal video-assisted thoracic surgery at our hospital were reviewed retrospectively. Results Simultaneous bilateral pulmonary resection with uniportal video-assisted thoracic surgery was performed for 35 patients (15 men, 20 women); 97 nodules were operated on, and the average nodule diameter was 11.4 mm (range, 1–38 mm). Computerized tomography showed that most nodules had ground-glass opacity (52/97, 53.6%); solid nodules (24/97, 24.7%) and nodules with mixed ground-glass opacity (21/97, 21.7%) were noted. Surgical resection included lobar-sublobar resection (11/35, 31.4%) and sublobar-sublobar resection (24/35, 68.6%). Wound infection and postoperative 30-day mortality were not observed. Pneumonia was the major postoperative complication, with a higher incidence in the lobar-sublobar group (6/10, 60%) than in the sublobar-sublobar group (4/25, 16%; P = 0.016). Pneumonia did not correlate with operative time (mean, 262.3 ± 108.1 vs. 261.9 ± 87.5 min, P = 0.991), duration of chest drainage (mean, 7.0 ± 4.0 vs 5.4 ± 2.1 days, P = 0.124), and postoperative hospital stay (mean, 10.2 ± 3.6 vs 10.2 ± 6.4 days, P = 0.978). The mean follow-up time was 8 (range, 3–22) months. Recurrence of primary lung cancer or mortality was not noted at the final follow-up. Conclusions Simultaneous bilateral pulmonary resection with uniportal video-assisted thoracic surgery is feasible and safe for appropriate patients. Simultaneous lobar-sublobar pulmonary resection for bilateral nodules can increase the risk of developing pneumonia.

Due to the advantages of Synthetic Aperture Radar (SAR), the study of Automatic Target Recognition (ATR) has become a hot topic. Deep learning, especially in the case of a Convolutional Neural Network (CNN), works in an end-to-end way and has powerful feature-extracting abilities. Thus, researchers in SAR ATR also seek solutions from deep learning. We review the related algorithms with regard to SAR ATR in this paper. We firstly introduce the commonly used datasets and the evaluation metrics. Then, we introduce the algorithms before deep learning. They are template-matching-, machine-learning- and model-based methods. After that, we introduce mainly the SAR ATR methods in the deep-learning era (after 2017); those methods are the core of the paper. The non-CNNs and CNNs, that is, those used in SAR ATR, are summarized at the beginning. We found that researchers tend to design specialized CNN for SAR ATR. Then, the methods to solve the problem raised by limited samples are reviewed. They are data augmentation, Generative Adversarial Networks (GAN), electromagnetic simulation, transfer learning, few-shot learning, semi-supervised learning, metric leaning and domain knowledge. After that, the imbalance problem, real-time recognition, polarimetric SAR, complex data and adversarial attack are also reviewed. The principles and problems of them are also introduced. Finally, the future directions are conducted. In this part, we point out that the dataset, CNN architecture designing, knowledge-driven, real-time recognition, explainable and adversarial attack should be considered in the future. This paper gives readers a quick overview of the current state of the field.

BackgroundThe tumor microenvironment plays an important role in the occurrence and development of tumors. However, there are gaps in understanding the molecular and cellular interactions between tumor cells and the immune tumor microenvironment (TME). The aim of this study was to identify a novel gene that played an important role in the tumor microenvironment of lung adenocarcinoma (LUAD).MethodsThe gene expression profile and clinical data for LUAD were downloaded from TCGA database. First, we used the ESTIMATE algorithm to evaluate the immune and stromal scores accordingly. Also, we analyzed differentially expressed immune-related genes (IRGs) in the high and low immune/stromal score groups. Then, we used the protein–protein interaction network (PPI network) and a univariate Cox regression analysis to identify the hub gene. After that, we analyzed the relationship between CSF2RB expression and TNM stage/prognosis. Furthermore, gene set enrichment analysis (GSEA) was used to analyze the pathway regulated by CSF2RB and the Pearson correlation analysis method was used to analyze the correlation between the CSF2RB and immune cells. Finally, we used Western blot, real-time quantitative PCR (RT-qPCR), and immunohistochemistry (IHC) to validate CSF2RB expression in cancer and para-cancerous tissues.ResultsWe identified that CSF2RB played an important role in the tumor microenvironment of LUAD. The expression of CSF2RB in tumor tissues was lower than that in normal tissues. Furthermore, the Kaplan–Meier plotter showed that a low CSF2RB expression was associated with poor survival and multivariate COX regression analysis revealed that the CSF2RB gene was an independent risk factor for prognosis, independent of whether patients received chemotherapy or radiotherapy. More importantly, a high expression of CSF2RB was related to early T, N, and clinical stages. GSEA analysis revealed that CSF2RB associated with diverse immune-related pathways, including T-cell receptor signaling pathway, Toll-like receptor signaling pathway, and B-cell receptor signaling pathway. CSF2RB expression levels were also positively related with the levels of infiltrating CD4+ T cells, macrophages, NK cells, and monocytes in LUAD. Finally, tumor tissues from LUAD patients were used for the assessment of CSF2RB expression. It was significantly lower in tumor sites than in adjacent normal tissues, which was consistent with data analysis.ConclusionCSF2RB effectively predicted the prognosis of patients with lung adenocarcinoma which could also be a potential target for cancer treatment and prevention. However, further studies are required to elucidate the function and regulatory mechanisms of CSF2RB and to develop some novel treatment strategies.

Anaplastic lymphoma kinase (ALK) alterations in non-small cell lung cancer (NSCLC) can be effectively treated with a variety of ALK-targeted drugs. After the approval of the first-generation ALK inhibitor crizotinib which achieved better results in prolonging the progression-free survival (PFS) compared with chemotherapy, a number of next-generation ALK inhibitors have been developed including ceritinib, alectinib, brigatinib, and ensartinib. Recently, a potent, third-generation ALK inhibitor, lorlatinib, has been approved by the Food and Drug Administration (FDA) for the first-line treatment of ALK-positive (ALK+) NSCLC. These drugs have manageable toxicity profiles. Responses to ALK inhibitors are however often not durable, and acquired resistance can occur as on-target or off-target alterations. Studies are underway to explore the mechanisms of resistance and optimal treatment options beyond progression. Efforts have also been undertaken to develop further generations of ALK inhibitors. This review will summarize the current situation of targeting the ALK signaling pathway.

ObjectiveDue to the low incidence of pulmonary large cell neuroendocrine carcinoma (LCNEC), the survival analysis for comparing lobectomy and sublobar resection (SLR) for stage IA LCNEC remains scarce.MethodsPatients diagnosed with pathological stage IA LCNEC between 1998 and 2016 were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. The oncological outcomes were cancer-specific survival (CSS) and overall survival (OS). Kaplan–Meier analysis and Cox multivariate analysis were used to identify the independent prognostic factors for OS and CSS. Furthermore, propensity score matching (PSM) was performed between SLR and lobectomy to adjust the confounding factors.ResultsA total of 308 patients with stage IA LCNEC met the inclusion criteria: 229 patients (74.4%) received lobectomy and 79 patients (25.6%) received SLR. Patients who underwent SLR were older (P < 0.001), had smaller tumor size (P = 0.010), and less lymph nodes dissection (P < 0.001). The 5-year CSS and OS rates were 56.5 and 42.9% for SLR, and 67.8 and 55.7% for lobectomy, respectively (P = 0.037 and 0.019, respectively). However, multivariate analysis did not identify any differences between the SLR group and lobectomy group in CSS (P = 0.135) and OS (P = 0.285); and the PSM also supported these results. In addition, the age at diagnosis and laterality of tumor were identified as significant predictors for CSS and OS, whereas the number of lymph nodes dissection was a significant predictor for CSS.ConclusionsAlthough SLR is not inferior to lobectomy in terms of oncological outcomes for patients with stage IA LCNEC, more lymph nodes can be dissected or sampled during lobectomy. Lobectomy should still be considered as a standard procedure for patients with early-stage LCNEC who are able to withstand lobectomy.

P(VDF-TrFE) is a promising material for flexible acoustic devices owing to its good piezoelectric performance and excellent stretchability. However, the high density of internal pores and large surface roughness of the conventional P(VDF-TrFE) results in a high propagation attenuation for acoustic waves, which limits its use in flexible acoustic devices. In this paper, a novel method based on two-step annealing is proposed to effectively remove the pores inside the P(VDF-TrFE) film and reduce its surface roughness. The obtained P(VDF-TrFE) film possesses excellent characteristics, including a high breakdown strength of >300 kV/mm, a high-purity β-phase content of more than 80%, and high piezoelectric coefficients (d33) of 42 pm/V. Based on the low-porosity β-phase P(VDF-TrFE) film, we fabricated flexible film bulk acoustic resonators (FBARs) which exhibit high sharp resonance peaks. The pressure sensor was made by sandwiching the FBARs with two PDMS microneedle patches. Heartbeat and respiration rate monitoring were achieved using the pressure sensor. This work demonstrates the feasibility of high-performance flexible piezoelectric acoustic resonators based on low-porosity P(VDF-TrFE) films, which could see wider applications in the wearable sensors for both physical and chemical sensing.

Solving the problem of the low temperature and low salt resistances of conventional polyacrylamide and the high cost of functional monomers, and thus, introducing it to the interlayer space provided by a layered structure for polymer modification, is a promising option. In this study, montmorillonite was used as the inorganic clay mineral, and an intercalated polyacrylamide/clay nanocomposite was synthesized via in situ intercalation polymerization. The optimal synthesis conditions were a clay content of 10.7%, preparation temperature of 11 °C, initiator concentration of 2.5 × 10−4 mol/L, and chain extender concentration of 5%. The IR results showed that the polymer was successfully introduced to the nanocomposite. The synthesized intercalated polyacrylamide/clay nanocomposite exhibited a better thickening effect, good viscoelasticity, and better salt resistance and thermal stability than polyacrylamide. In addition, the thickening capacity and thermal stability were superior to the salt-resistant polymer, with a 16.0% higher thickening viscosity and a 15.1% higher viscosity retention rate at 85 °C for 60 d. The intercalated polyacrylamide/clay nanocomposite further expanded the application of polyacrylamide in petroleum exploitation.

BackgroundAlternative splicing (AS) is a gene regulatory mechanism that drives protein diversity. Dysregulation of AS is thought to play an essential role in cancer initiation and development. This study aimed to construct a prognostic signature based on AS and explore the role in the tumor immune microenvironment (TIME) in lung adenocarcinoma.MethodsWe analyzed transcriptome profiling and clinical lung adenocarcinoma data from The Cancer Genome Atlas (TCGA) database and lists of AS-related and immune-related signatures from the SpliceSeq. Prognosis-related AS events were analyzed by univariate Cox regression analysis. Gene set enrichment analyses (GSEA) were performed for functional annotation. Prognostic signatures were identified and validated using univariate and multivariate Cox regression, LASSO regression, Kaplan–Meier survival analyses, and proportional hazards model. The context of TIME in lung adenocarcinoma was also analyzed. Gene and protein expression data of Cyclin-Dependent Kinase Inhibitor 2A (CDKN2A) were obtained from ONCOMINE and Human Protein Atlas. Splicing factor (SF) regulatory networks were visualized.ResultsA total of 19,054 survival-related AS events in lung adenocarcinoma were screened in 1,323 genes. Exon skip (ES) and mutually exclusive exons (ME) exhibited the most and fewest AS events, respectively. Based on AS subtypes, eight AS prognostic signatures were constructed. Patients with high-risk scores were associated with poor overall survival. A nomogram with good validity in prognostic prediction was generated. AUCs of risk scores at 1, 2, and 3 years were 0.775, 0.736, and 0.759, respectively. Furthermore, the prognostic signatures were significantly correlated with TIME diversity and immune checkpoint inhibitor (ICI)-related genes. Low-risk patients had a higher StromalScore, ImmuneScore, and ESTIMATEScore. AS-based risk score signature was positively associated with CD8+ T cells. CDKN2A was also found to be a prognostic factor in lung adenocarcinoma. Finally, potential functions of SFs were determined by regulatory networks.ConclusionTaken together, our findings show a clear association between AS and immune cell infiltration events and patient outcome, which could provide a basis for the identification of novel markers and therapeutic targets for lung adenocarcinoma. SF networks provide information of regulatory mechanisms.

BackgroundSMARCA4, the essential ATPase subunit of SWI/SNF chromatin remodeling complex, regulates transcription through the control of chromatin structure and is increasingly thought to play significant roles in human cancers. This study aims to explore the potential role of SMARCA4 with a view to providing insights on pathologic mechanisms implicated here.MethodsThe potential roles of SMARCA4 in different tumors were explored based on The Cancer Genome Atlas (TCGA), Genotype-tissue expression (GTEx), Tumor Immune Estimation Resource (TIMER), and Gene Set Enrichment Analysis (GSEA) datasets. The expression difference, mutation and phosphorylation status, survival, pathological stage, DNA methylation, tumor mutation burden (TMB), microsatellite instability (MSI), mismatch repair (MMR), tumor microenvironment (TME), and immune cell infiltration related to SMARCA4 were analyzed.ResultsHigh expression levels of SMARCA4 were observed in most cancer types. SMARCA4 expression in tumor samples correlates with poor overall survival in several cancers. Lung adenocarcinoma cases with altered SMARCA4 showed a poorer prognosis. Enhanced phosphorylation levels of S613, S695, S699, and S1417 were observed in several tumors, including breast cancer. SMARCA4 correlated with tumor immunity and associated with different immune cells and genes in different cancer types. TMB, MSI, MMR, and DNA methylation correlated with SMARCA4 dysregulation in cancers. SMARCA4 expression was negatively associated with CD8+ T-cell infiltration in several tumors. Furthermore, the SWI/SNF superfamily-type complex and ATPase complex may be involved in the functional mechanisms of SMARCA4, albeit these data require further confirmation.ConclusionsOur study offers a comprehensive understanding of the oncogenic roles of SMARCA4 across different tumors. SMARCA4 may correlate with tumor immunity.

Zn and its alloys have recently emerged as new options for orthopedic implants due to their desirable biodegradation rate and mechanical strength. However, whether Zn metallic implants attenuate bone tunnel enlargement (BTE) after anterior cruciate ligament (ACL) reconstruction and, if so, the underlying mechanism by which this occurs remains elusive. In present study, we explored the possibility of using pure Zn screws to attenuate BTE in rabbits, and the potential molecular mechanism was further explored in primary osteoblasts. Here, our study showed that the pure Zn screws more effectively attenuated BTE after ACL reconstruction in rabbits compared with pure Mg and Ti screws. This was attributed to the fact that the pure Zn screw-released Zn element diminished the size of the femoral tunnels, enhanced the bone mass around the screws, boosted the fixation strength, and promoted the tendon-bone integration. Several lines of cellular evidences suggested that Zn metallic implant-released Zn element induced upregulation of sodium-dependent vitamin C transporter 2 in primary osteoblasts and ultimately elevated the expressions of the osteogenic transcription factors to trigger osteogenic differentiation. This study showed that biodegradable Zn metallic materials were promising candidates for interference screw to attenuate BTE after ACL reconstruction.

As for metal matrix composites (MMCs), the selection and application of reinforcements play a vital role in their comprehensive properties. In this work, the CrCoNi medium entropy alloy (MEA) was selected as reinforcement for Al matrix composites, and the effects of the content of the CrCoNi MEA on the mechanical properties and friction resistance were systematically investigated. It was found that the CrCoNi MEA can effectively improve the mechanical properties of the Al matrix composites, especially the 5 wt.% CrCoNi/Al composite can achieve a high strength without the sacrifice of ductility, due to the strengthened interfacial bonding between the Al matrix and the CrCoNi reinforcements caused by the element interdiffusion and the high mechanical performance of the CrCoNi MEA itself. In addition, the wear resistance of the composites can be enhanced by the inclusion of the CrCoNi MEA reinforcement, because the CrCoNi MEA can substantially improve the hardness of the composites and promote the formation of the oxidative protection film during the friction process. This work paves a new route for preparing Al matrix composites with high mechanical properties and friction resistance.

Abstract Background In recent years, diagnosis of early squamous cell carcinoma of the esophagus has been increasingly emphasized. The application of endoscopic submucosal dissection (ESD) has enabled safe resection of esophageal lesions. Minimally invasive esophagectomy (MIE) is also safe and feasible for early stages of the cancer. This study aimed to compare the therapeutic effects of early esophageal carcinoma treatment, and find the best predictive factor for the selection of treatment for T1a patients. Methods We performed a retrospective study of early‐stage patients admitted to Tianjin Medical University Cancer Institute and Hospital between January 2015 and December 2018. A total of 128 patients underwent MIE, while 78 patients underwent ESD. The depth of the tumor invasion, lymph node metastasis, and complications were compared between the two groups. Results In the ESD group, 76.92% of the patients were stage T1a, while 34.38% in the MIE group were stage T1a. The lymph node metastasis rate was 16.41% in the MIE group (6.98% in T1a stage), which related to tumor differentiation, tumor length (≥37.5 mm), depth of invasion, and angiolymphatic invasion. However, the R0 resection rate was only 73.08% in the ESD group. Comprehensive analysis of all T1 patients in the two groups revealed that the positive margin was related to tumor differentiation, tumor width (≥13.5 mm), and depth of invasion (≥3.25 mm). Conclusion For early‐stage cases, lymph node metastasis and positive margins are risk factors affecting long‐term survival. Efficient predictive factors mentioned in our study would provide a proper indication for treatment strategy selection.