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The small molecule chemical compound cinobufotalin (CB) is reported to be a potential antitumour drug that increases cisplatin (DDP) sensitivity in nasopharyngeal carcinoma. In this study, we first found that CB decreased DDP resistance, migration and invasion in lung adenocarcinoma (LUAD). Mechanistic studies showed that CB induced ENKUR expression by suppressing PI3K/AKT signalling to downregulate c-Jun, a negative transcription factor of ENKUR. Furthermore, ENKUR was shown to function as a tumour suppressor by binding to β-catenin to decrease c-Jun expression, thus suppressing MYH9 transcription. Interestingly, MYH9 is a binding protein of ENKUR. The Enkurin domain of ENKUR binds to MYH9, and the Myosin_tail of MYH9 binds to ENKUR. Downregulation of MYH9 reduced the recruitment of the deubiquitinase USP7, leading to increased c-Myc ubiquitination and degradation, decreased c-Myc nuclear translocation, and inactivation of epithelial-mesenchymal transition (EMT) signalling, thus attenuating DDP resistance. Our data demonstrated that CB is a promising antitumour drug and may be a candidate chemotherapeutic drug for LUAD patients.

Platelets are reprogrammed by cancer via a process called education, which favors cancer development. The transcriptional profile of tumor-educated platelets (TEPs) is skewed and therefore practicable for cancer detection. This intercontinental, hospital-based, diagnostic study included 761 treatment-naïve inpatients with histologically confirmed adnexal masses and 167 healthy controls from nine medical centers (China, n = 3; Netherlands, n = 5; Poland, n = 1) between September 2016 and May 2019. The main outcomes were the performance of TEPs and their combination with CA125 in two Chinese (VC1 and VC2) and the European (VC3) validation cohorts collectively and independently. Exploratory outcome was the value of TEPs in public pan-cancer platelet transcriptome datasets. The AUCs for TEPs in the combined validation cohort, VC1, VC2, and VC3 were 0.918 (95% CI 0.889–0.948), 0.923 (0.855–0.990), 0.918 (0.872–0.963), and 0.887 (0.813–0.960), respectively. Combination of TEPs and CA125 demonstrated an AUC of 0.922 (0.889–0.955) in the combined validation cohort; 0.955 (0.912–0.997) in VC1; 0.939 (0.901–0.977) in VC2; 0.917 (0.824–1.000) in VC3. For subgroup analysis, TEPs exhibited an AUC of 0.858, 0.859, and 0.920 to detect early-stage, borderline, non-epithelial diseases and 0.899 to discriminate ovarian cancer from endometriosis. TEPs had robustness, compatibility, and universality for preoperative diagnosis of ovarian cancer since it withstood validations in populations of different ethnicities, heterogeneous histological subtypes, and early-stage ovarian cancer. However, these observations warrant prospective validations in a larger population before clinical utilities.

Myeloproliferative neoplasms (MPNs) are characterized by upregulation of proinflammatory cytokines and immune dysregulation, which provide a reasonable basis for immunotherapy in patients. Megakaryocytes are crucial in the pathogenesis of primary myelofibrosis (PMF), the most clinically aggressive subtype of MPN. In this study, we aimed to explore PD‐L1 (programmed death‐ligand 1) expression in megakaryocytes and its clinical implications in PMF. We analyzed PD‐L1 expression on megakaryocytes in PMF patients by immunohistochemistry and correlated the results with clinicopathological features and molecular aberrations. We employed a two‐tier grading system considering both the proportion of cells positively stained and the intensity of staining. Among the 85 PMF patients, 41 (48%) showed positive PD‐L1 expression on megakaryocytes with the immune‐reactive score ranging from 1 to 12. PD‐L1 expression correlated closely with higher white blood cell count (p = 0.045), overt myelofibrosis (p = 0.010), JAK2V617F mutation (p = 0.011), and high‐molecular risk mutations (p = 0.045), leading to less favorable overall survival in these patients (hazard ratio 0.341, 95% CI 0.135–0.863, p = 0.023). Our study provides unique insights into the interaction between immunologic and molecular phenotypes in PMF patients. Future work to explore the translational potential of PD‐L1 in the clinical setting is needed.

Mitochondria are the organelles that generate energy for the cells. Many studies have suggested that mitochondrial dysfunction or impairment may be related to cancer and other neurodegenerative disorders such as Alzheimer’s and Parkinson’s diseases. Therefore, morphologically detailed alterations in mitochondria and 3D reconstruction of mitochondria are highly demanded research problems in the performance of clinical diagnosis. Nevertheless, manual mitochondria segmentation over 3D electron microscopy volumes is not a trivial task. This study proposes a two-stage cascaded CNN architecture to achieve automated 3D mitochondria segmentation, combining the merits of top-down and bottom-up approaches. For top-down approaches, the segmentation is conducted on objects’ localization so that the delineations of objects’ contours can be more precise. However, the combinations of 2D segmentation from the top-down approaches are inadequate to perform proper 3D segmentation without the information on connectivity among frames. On the other hand, the bottom-up approach finds coherent groups of pixels and takes the information of 3D connectivity into account in segmentation to avoid the drawbacks of the 2D top-down approach. However, many small areas that share similar pixel properties with mitochondria become false positives due to insufficient information on objects’ localization. In the proposed method, the detection of mitochondria is carried out with multi-slice fusion in the first stage, forming the segmentation cues. Subsequently, the second stage is to perform 3D CNN segmentation that learns the pixel properties and the information of 3D connectivity under the supervision of cues from the detection stage. Experimental results show that the proposed structure alleviates the problems in both the top-down and bottom-up approaches, which significantly accomplishes better performance in segmentation and expedites clinical analysis.

Modern development of flexible electronics has made use of bioelectronic materials as artificial tissue in vivo. As hydrogels are more similar to nerve tissue, functional hydrogels have become a promising candidate for bioelectronics. Meanwhile, interfacing functional hydrogels and living tissues is at the forefront of bioelectronics. The peripheral nerve injury often leads to paralysis, chronic pain, neurologic disorders, and even disability, because it has affected the bioelectrical signal transmission between the brain and the rest of body. Here, a kind of light-stimuli-responsive and stretchable conducting polymer hydrogel (CPH) is developed to explore artificial nerve. The conductivity of CPH can be enhanced when illuminated by near-infrared light, which can promote the conduction of the bioelectrical signal. When CPH is mechanically elongated, it still has high durability of conductivity and, thus, can accommodate unexpected strain of nerve tissues in motion. Thereby, CPH can better serve as an implant of the serious peripheral nerve injury in vivo, especially in the case that the length of the missing nerve exceeds 10 mm.

Lithium dendrite related problems form a major barrier that limits the application of lithium metal anode for Li-ion batteries. Here a copper coated 3D soft fabric anode was developed to show superior battery performance under an optimized mechanical stress for the lithium metal anode application. A scalable two-step dip-coating method was applied to coat Cu onto various insulating cloth fabrics, making them electrically conductive. In our battery tests, the 3D soft conductive fabric contributes to a more uniform lithium deposition during the battery cycling, which works for more than 1000 h. The mechanism for suppressing lithium dendrite growth by the mechanical interaction with 3D Cu-fabric was also revealed by a combination of microscopy characterization, electrochemical test and theoretical modeling, which provides the design principle for their future applications in lithium metal anode batteries.

The magnetic skyrmion transport driven by pure voltage-induced strain gradient is proposed and studied via micromagnetic simulation. Through combining the skyrmion with multiferroic heterojunction, a voltage-induced uniaxial strain gradient is adjusted to move skyrmions. In the system, a pair of short-circuited trapezoidal top electrodes can generate the symmetric strain. Due to the symmetry of strain, the magnetic skyrmion can be driven with a linear motion in the middle of the nanostrip without deviation. We calculate the strain distribution generated by the trapezoidal top electrodes pair, and further investigate the influence of the strain intensity as well as the strain gradient on the skyrmion velocity. Our findings provide a stable and low-energy regulation method for skyrmion transport.

The rapid growth of miniaturized electronic devices has raised the demand for compact, flexible, wearable, and non-volatile memory units. However, integration into nanoelectronic devices requires a scaled-down data-storage component, but this often results in the deterioration of the ferroelectric switching performance. Herein, we demonstrate a simple and scalable fabrication of poly (vinylidene fluoride trifluoroethylene) [P(VDF-TrFE)] film with graphene oxide (GO) nanosheets. Using piezoresponse force microscopy (PFM), the storage features of this multilayer film were investigated, including establishment of two stable memory states, ferroelectric switching dynamics in the point-polarization and linear-polarization modes, and time and thermal stability of information storage. Remarkably, the GO-P(VDF-TrFE) film favored formation of low-temperature (LT) ferroelectric phase with much more ordered sequences of trans conformations relative to pristine P(VDF-TrFE) due to the presence of electrostatic interaction between GO nanosheets and C F dipoles of P(VDF-TrFE), thus affording improved ferroelectric properties. The GO-P(VDF-TrFE) film showed several excellent storage features, such as ultra-high density of more than 300 Gbits in−2, good writing & erasing repeatability, long data retention time, and elevated device operation temperature. In-depth understanding and utilization of the excellent non-volatile memory performance of this new GO-ferroelectric system will open new avenues for the next generation of nanoelectronic devices.

Wireless micro- and nanorobots are biomedical devices with a potential use in high-precision minimally invasive therapies. Here, a highly integrated multifunctional soft microrobot is developed for targeted cell therapy applications, featuring targeted cell transportation and induced cell differentiation. The micromachines are made of composites consisting of a soft piezoelectric polymer matrix in which magnetic nanoparticles are dispersed. The magnetic nanoparticles serve as the component for the device's magnetic actuation, while the piezoelectric polymer acts as both a steerable scaffold and an acoustically responsive cell electrostimulation platform. With the application of a rotating magnetic field, the microrobots swim in a corkscrew motion in different liquid environments that mimic human body fluids. When the swimmers are subjected to acoustic waves, their piezoelectric body is electrically polarized which induces cell differentiation of neuron-like PC12 cells loaded on the swimmers surface. This combinatorial technique may open up new avenues for bioelectronic therapies., Materials Horizons, 6 (7)

Background: Morpho-physiological alternations of platelets provided a rationale to harness RNA sequencing of tumor-educated platelets (TEPs) for preoperative diagnosis of cancer. Timely, accurate, and non-invasive detection of ovarian cancer in women with adnexal masses presents a significant clinical challenge. Patients and Methods: This intercontinental, hospital-based, diagnostic study included 761 treatment-naïve inpatients with histologically confirmed adnexal masses and 167 healthy controls from nine medical centers (China, n=3; Netherlands, n=5; Poland, n=1) between September 2016 and May 2019. The main outcomes were the performance of TEPs and their combination with CA125 in two Chinese (VC1 and VC2) and the European (VC3) validation cohorts collectively and independently. Exploratory outcome was the value of TEPs in public pan-cancer platelet transcriptome datasets. Results: The AUCs for TEPs in the combined validation cohort, VC1, VC2, and VC3 were 0.918 (95% CI 0.889-0.948), 0.923 (0.855-0.990), 0.918 (0.872-0.963), and 0.887 (0.813-0.960), respectively. Combination of TEPs and CA125 demonstrated an AUC of 0.922 (0.889-0.955) in the combined validation cohort; 0.955 (0.912-0.997) in VC1; 0.939 (0.901-0.977) in VC2; 0.917 (0.824-1.000) in VC3. For subgroup analysis, TEPs exhibited an AUC of 0.858, 0.859, and 0.920 to detect early-stage, borderline, non-epithelial diseases and 0.899 to discriminate ovarian cancer from endometriosis. Analysis of public datasets suggested that TEPs had potential to detect multiple malignancies (Table 1). Conclusions: TEPs had robustness, compatibility, and universality for preoperative diagnosis of ovarian cancer since it withstood validations in populations of different ethnicities, heterogeneous histological subtypes, early-stage ovarian cancer as well as other malignancies. However, these observations warrant prospective validations in a larger population before clinical utilities. Table 1. Performance for TEPs in public pan-cancer datasets. Disease n Healthy Control AUC, area under the curve (95% CI) Women NSCLC (non-small-cell lung cancer) 126 77 0.758 (0.691-0.825) Breast cancer 38 77 0.817 (0.726-0.909) Colorectal cancer 18 77 0.973 (0.945-1.000) Pancreatic cancer 16 77 0.993 (0.981-1.000) Glioblastoma 10 77 0.923 (0.831-1.000) Men NSCLC 119 82 0.746 (0.677-0.815) Colorectal cancer 25 82 0.933 (0.884-0.982) Pancreatic cancer 22 82 0.993 (0.984-1.000) Glioblastoma 19 82 0.981 (0.959-1.000) All NSCLC 245 159 0.774 (0.728-0.820) Colorectal cancer 40 159 0.978 (0.961-0.996) Breast cancer 38 159 0.821 (0.736-0.906) Pancreatic cancer 35 159 0.987 (0.974-0.999) Glioblastoma 35 159 0.931 (0.890-0.972) Hepatobiliary carcinomas 14 159 0.991 (0.978-1.000) Citation Format: Yue Gao, Chun-Jie Liu, Hua-Yi Li, Xiao-Ming Xiong, Sjors G.j.g. In ‘t Veld, Gui-Ling Li, Jia-Hao Liu, Guang-Yao Cai, Gui-Yan Xie, Shao-Qing Zeng, Yuan Wu, Jian-Hua Chi, Qiong Zhang, Xiao-Fei Jiao, Lin-Li Shi, Wan-Rong Lu, Wei-Guo Lv, Xing-Sheng Yang, Jurgen M.j. Piek, Cornelis D de Kroon, C.a.r. Lok, Anna Supernat, Sylwia Łapińska-Szumczyk, Anna Łojkowska, Anna J. Żaczek, Jacek Jassem, Bakhos A. Tannous, Nik Sol, Edward Post, Myron G. Best, Bei-Hua Kong, Xing Xie, Ding Ma, Thomas Wurdinger, An-Yuan Guo, Qing-Lei Gao. Platelet RNA signature enables early and accurate detection of ovarian cancer: An intercontinental, biomarker identification study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr LB168.

With the continuous growth of data volume in the information age, it is becoming more and more difficult for people to obtain information they care about. The traditional way of manually collecting information from such massive data is inconvenient and inefficient. In order to solve this problem, we design an web information subscription system based on intelligent crawler. In this paper, the first section introduces the design of the system, which includes the two confirmations to determine the specific monitoring area, the original xpath-based information positioning and block method, the task management based on apscheduler and so on. The second section introduces the implementation of the system, which included the process of how to operate the system. The third hows the running interface and results of the system. And finally the experiments show that the system can help users quickly obtain useful web information.

The degeneration of dopaminergic neurons is a major contributor to the pathogenesis of mid-brain disorders. Clinically, cell therapeutic solutions, by increasing the neurotransmitter dopamine levels in the patients, are hindered by low efficiency and/or side effects. Here, a strategy using electromagnetized nanoparticles to modulate neural plasticity and recover degenerative dopamine neurons in vivo is reported. Remarkably, electromagnetic fields generated by the nanoparticles under ultrasound stimulation modulate intracellular calcium signaling to influence synaptic plasticity and control neural behavior. Dopaminergic neuronal functions are reversed by upregulating the expression tyrosine hydroxylase, thus resulting in ameliorating the neural behavioral disorders in zebrafish. This wireless tool can serve as a viable and safe strategy for the regenerative therapy of the neurodegenerative disorders.

A high-optical-resolution artificial retina system that accurately communicates with the optic nerve is the main challenge in the modern biological science and bionic field. Here, we developed a bionic artificial retina possessing phototransduction "cells" with measurements even smaller than that of the neural cells. Using the technique of micrometer processing, we constructed a pyramid-shape periodic microarray of a photoreceptor. Each "sensing cell" took advantage of polythiophene derivative/fullerene derivative (PCBM) as a photoelectric converter. Because folic acid played an essential role in eye growth, we particularly modified the polythiophene derivatives with folic acid tags. Therefore, the artificial retina could enlarge the contact area and even recognize the nerve cells to improve the consequence of nerve stimulation. We implanted the artificial retina into blinded rats' eyes. Electrophysiological analysis revealed its recovery of photosensitive function 3 months after surgery. Our work provides an innovative idea for fabricating a high-resolution bionic artificial retina system. It shows great potential in artificial intelligence and biomedicine.

Herein, the crystallization behavior, thermal stability, phase composition, and magnetic properties of Co66.5Si15.5B12Fe4Ni2 amorphous alloy were determined via differential scanning calorimetry, X-ray diffraction analysis, and vibrating sample magnetometry. The heating rate was found to strongly affect the glass-transition and crystallization behavior of Co66.5Si15.5B12Fe4Ni2 solidified ribbon. Based on the crystallization behavior, the relationship between the glass-transition temperature (Tg) and the heating rate (lnβ) was derived as Tg = 6lnβ + 709 and the glass-transition activation energy, initial crystallization activation energy, first crystallization peak activation energy, and the second crystallization peak activation energy were also calculated. Based on the results, the nucleation mechanism of the crystallization of Co66.5Si15.5B12Fe4Ni2 amorphous alloy and the crystallization products of the annealing crystallization process were discussed. The phase composition after short-term annealing at a low temperature was found to be β-Co + α-Co + Ni3Fe + Ni4B + Ni2Si. Following high-temperature, long-term annealing, Ni2Si disappeared completely and a new phase, FeSi, was formed. By studying the coercivity, remanence, saturation magnetization, and magnetic anisotropy of the alloy, we obtained the best processing parameters for comprehensive soft magnetic properties. The results provide guidance on the development of new soft magnetic materials.

Marine biofouling can be better governed by using super-hydrophobic and lubricant leaching behavior. It was prepared for a long time super-hydrophobic fouling release coating with the incorporation of phenylmethylsilicone oil as lubricant. With the reasonable control of the mass ratio of mixed nano-particles (hydroxylated multi-walled carbon nanotube and nano-magnetite), prepared reinforced coating has excellent super-hydrophobicity and lubricant leaching efficiency. Comparable studies with reported FR coating and commercial silicone coating, it exhibits excellent anti-biofilm adhesion performance with up to 98 % of biofilm adhesion removal rate. More beneficial, the isolation layer composed of the leached phenylmethylsilicone oil can make a good buffer effect for the reinforced coating surface, alleviating the deformation or damage caused by the friction between sand and the reinforced coating surface, effectively. This work is establishing new investments in environment-friendly fouling release coatings.

A bioinspired photodetector with signal transmissible to neuron cells is fabricated. Photoisomerization of the dye molecules embedded in the ferroelectric polymer membrane achieves electric polarization change under visible light. The photodetector realizes high sensitivity, color recognition, transient response, and 3D visual detection with resolution of 25 000 PPI, and, impressively, directly transduces the signal to neuron cells.

Ferroelectric polymers are of interest as most promising electroactive materials. Flexible transducers from ferroelectric polymer thin film with underneath semiconducting polymer active layer for high sensitive and versatile detection of physiological signals are described. When attached directly on the wrist, the flexible transducers can distinguish the transient pulse waves non-invasively and in situ, due to their fast response (milliseconds) and high sensitivity (down to several Pascal) to instantaneous change of blood pressure. High-resolution picture of one pulse wave is available to provide two most common parameters for arterial stiffness diagnosis. The transducers are also suitable for dynamic recognizing physiological signals under both physical exercise and medicine treatment, demonstrating their enormous potential for warning the risk of cardiovascular disease, and evaluating the efficacy of heart medicines. The transducers are easy to carry around with an operating voltage of 1 V and the power consumption less than 1 μW. Thus, they are valuable for applications like electronic skin and mobile health monitoring.

Artificial intelligence refers to the ability of a machine to study and think like a human. In the human brain, these functions rely on changes and transmission of electrical polarization among neurons. Ferroelectric polymer membranes exhibit electrical polarization that is tunable under the action of external stimuli, such as mechanical stresses and electric fields, and they, thus, exhibit signal transmission characteristics similar to those of neurons. In this paper, we describe the fabrication of a flexible computing device based on ferroelectric polymers that are capable of performing Boolean logic operations and have data retention capabilities and high state discrimination down to the nanoscale, thereby enabling dense packaging and low-power logic state switching. It is also able to adhere to human skin. This demonstration of a logical computing system based on polarization will help in the further exploration and development of artificial intelligence.

Phase structures and transitions of a series of biphenyl containing side-chain liquid crystalline polyacetylenes (SCLCPAs) with different length of spacer and alkyl tail, poly((m + 2)-{[(4′-alkyloxy-4-biphenylyl)carbonyl]oxy}-1-yne) [P-m,7 (m = 4, 5, 8), P-m,5 (m = 9), P-m,5L (m = 3, 9), m is the number of methylene units in the spacer], were studied by differential scanning calorimeter, polarized light microscopy, one- and two-dimensional wide-angle X-ray diffraction. It is revealed that phase structures of the samples are strongly dependent on the lengths of spacer and alkyl tail. The samples with short spacer (m ≤ 4) render the molecular shape of sheet-like due to the strong coupling between the backbone and the biphenyl groups on side-chains. They form highly ordered smectic phase with an additional ordering on the subnanometer scale (SmXo) at low temperatures. For m > 5, P-m,7 exhibits the low-temperature phase of smectic B (SmB), while P-9,5 and P-9,5L form smectic E (SmE). As the long spacers adopt...

A multimodal cancer therapeutic nanoplatform is reported. It demonstrates a promising approach to synergistically regulating the tumor microenvironment. The combination of intracellular reactive oxygen species (ROS) generated by irradiation of photosensitizer and endoplasmic reticulum (ER) stress induced by 2-deoxy-glucose (2-DG) has a profound effect on necrotic or apoptotic cell death. Especially, targeting metabolic pathway by 2-DG is a promising strategy to promote the effect of photodynamic therapy and chemotherapy. The nanoplatform can readily release its cargoes inside cancer cells and combines the advantages of ROS-sensitive releasing chemotherapeutic drugs, upregulating apoptosis pathways under ER stress, light-induced generation of cytotoxic ROS, achieving tumor accumulation, and in vivo fluorescence imaging capability. This work highlights the importance of considering multiple intracellular stresses as design parameters for nanoscale functional materials in cell biology, immune response, as well as medical treatments of cancer, Alzheimer's disease, etc.

The aim of the present study was to identify whether the responses of oxidative stress in zebrafish liver are similar to those in mammalians upon low doses of Cd2+ exposure in short durations. Fish were exposed to 1.78 μM Cd2+ (treatment) and 0.0 μM Cd2+ (control) for 0, 1, 3, and 6 h. The reactive oxygen species (ROS) and lipid peroxidation (LPO) of hepatic tissues significantly increased after 3 and 6 h of Cd2+ exposure, respectively. Antioxidants glutathione peroxidase (gpx1a), superoxide dismutase (sod), and catalase (cat) were up regulated after 1–3 h, and metallothionein isoforms (smtB and mt2) increased after 3–6 h of Cd2+ exposure. The caspase-3 and p53 mRNA expressions significantly increased threefolds after 1 h of Cd2+ exposure. Results confirmed that oxidative stress in the hepatic tissue was induced by Cd2+ within 3 h. However, anti-oxidative functions immediately up regulated, causing cell apoptosis levels to decrease after 6 h of Cd2+ exposure.

Through utilizing individual nanodots, as smallest memory units, to convert stress into readable electronic information, we report force-induced high-density data storage in the periodic nanostructure of ferroelectric polymer fabricated by nanoimprinting lithography. The nanostructure is ideal for the stress concentration and increasing the non-uniformity of strains, thus leading to strain gradients inversely proportional to the feature size. A force as low as 400 nN is applied to generate the internal electric field in response to strain gradients and switch polarization state of each memory unit. It can achieve storage density theoretically up to TB/inch2 with the up-to-date nanofabrication technology to miniaturize the unit size.