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Platinum-based anticancer drugs, including cisplatin, carboplatin, oxaliplatin, nedaplatin, and lobaplatin, are heavily applied in chemotherapy regimens. However, the intrinsic or acquired resistance severely limit the clinical application of platinum-based treatment. The underlying mechanisms are incredibly complicated. Multiple transporters participate in the active transport of platinum-based antitumor agents, and the altered expression level, localization, or activity may severely decrease the cellular platinum accumulation. Detoxification components, which are commonly increasing in resistant tumor cells, can efficiently bind to platinum agents and prevent the formation of platinum-DNA adducts, but the adducts production is the determinant step for the cytotoxicity of platinum-based antitumor agents. Even if adequate adducts have formed, tumor cells still manage to survive through increased DNA repair processes or elevated apoptosis threshold. In addition, autophagy has a profound influence on platinum resistance. This review summarizes the critical participators of platinum resistance mechanisms mentioned above and highlights the most potential therapeutic targets or predicted markers. With a deeper understanding of the underlying resistance mechanisms, new solutions would be produced to extend the clinical application of platinum-based antitumor agents largely.

Polyps are abnormal tissue clumps growing primarily on the inner linings of the gastrointestinal tract. While such clumps are generally harmless, they can potentially evolve into pathological tumors, and thus require long-term observation and monitoring. Polyp segmentation in gastrointestinal endoscopy images is an important stage for polyp monitoring and subsequent treatment. However, this segmentation task faces multiple challenges: the low contrast of the polyp boundaries, the varied polyp appearance, and the co-occurrence of multiple polyps. So, in this paper, an implicit edge-guided cross-layer fusion network (IECFNet) is proposed for polyp segmentation. The codec pair is used to generate an initial saliency map, the implicit edge-enhanced context attention module aggregates the feature graph output from the encoding and decoding to generate the rough prediction, and the multi-scale feature reasoning module is used to generate final predictions. Polyp segmentation experiments have been conducted on five popular polyp image datasets (Kvasir, CVC-ClinicDB, ETIS, CVC-ColonDB, and CVC-300), and the experimental results show that the proposed method significantly outperforms a conventional method, especially with an accuracy margin of 7.9% on the ETIS dataset.

Engineering wearable devices that can wirelessly track intraocular pressure and offer feedback-medicine administrations are highly desirable for glaucoma treatments, yet remain challenging due to issues of limited sizes, wireless operations, and wireless cross-coupling. Here, we present an integrated wireless theranostic contact lens for in situ electrical sensing of intraocular pressure and on-demand anti-glaucoma drug delivery. The wireless theranostic contact lens utilizes a highly compact structural design, which enables high-degreed integration and frequency separation on the curved and limited surface of contact lens. The wireless intraocular pressure sensing modulus could ultra-sensitively detect intraocular pressure fluctuations, due to the unique cantilever configuration design of capacitive sensing circuit. The drug delivery modulus employs an efficient wireless power transfer circuit, to trigger delivery of anti-glaucoma drug into aqueous chamber via iontophoresis. The minimally invasive, smart, wireless and theranostic features endow the wireless theranostic contact lens as a highly promising system for glaucoma treatments. Towards intelligent treatment for glaucoma, here authors demonstrate integrated wireless theranostic contact lenses for in situ electrical sensing of intraocular pressure and on demand anti-glaucoma drug delivery.

s High- k metal oxide films are vital for the future development of microelectronics technology. In this work, ZrO 2 films were grown on silicon by atomic layer deposition (ALD) using tetrakis(dimethylamido)zirconium and ozone as precursors. The relatively constant deposition rate of 0.125 nm/cycle is obtained within the ALD temperature window of 200–250 °C. The film thickness can be precisely controlled by regulating the number of ALD cycle. The ZrO 2 films formed at 200–250 °C have an O/Zr atomic ratio of 1.85–1.9 and a low content of carbon impurity. ZrO 2 film begins to crystallize in ALD process above 210 °C, and the crystal structure is changed from cubic and orthorhombic phases to monoclinic and orthorhombic phases with increasing the deposition temperature to 350 °C. Moreover, the effect of annealing temperature on dielectric properties of ZrO 2 film was studied utilizing ZrO 2 -based MIS device. The growth of the interface layer between ZrO 2 and Si substrate leads to the decrease in the capacitance and the leakage current of dielectric layer in the MIS device after 1000 °C annealing. ZrO 2 film exhibits the relatively high dielectric constant of 32.57 at 100 kHz and the low leakage current density of 3.3 × 10 −6  A cm −2 at 1 MV/cm.

In privacy protection methods based on location services, constructing anonymous areas using location information shared by collaborative users is the main method. However, this collaborative process not only increases the risk of mobile users’ location privacy being leaked, but also reduces positioning accuracy. In response to this problem, we propose a balancing strategy, which transforms the problem of protecting mobile users’ location privacy and improving positioning accuracy into a balance issue between location privacy and positioning accuracy. The cooperation of mobile users with different collaborating users is then modeled as an objective optimization problem, and location privacy and positioning accuracy are evaluated separately to make different selection strategies. Finally, an optimization function is constructed to select the optimal selection strategies. Experimental results show that our proposed strategy can effectively achieve the balance between location privacy and positioning accuracy.

Background Maintaining the stability and maturation of blood vessels is of paramount importance for the vessels to carry out their physiological function. Smooth muscle cells (SMCs), pericytes, and mesenchymal stem cells (MSCs) are involved in the maturation process of the newly formed vessels. The aim of this study was to investigate whether transforming growth factor beta 1 (TGF-β1) treatment could enhance pericyte-like properties of dental pulp stem cells (DPSCs) and how TGF-β1-treated DPSCs for 7 days (T-DPSCs) stabilize the newly formed blood vessels. Methods We utilized TGF-β1 to treat DPSCs for 1, 3, 5, and 7 days. Western blotting and immunofluorescence were used to analyze the expression of SMC markers. Functional contraction assay was conducted to assess the contractility of T-DPSCs. The effects of T-DPSC-conditioned media (T-DPSC-CM) on human umbilical vein endothelial cell (HUVEC) proliferation and migration were examined by MTT, wound healing, and trans-well migration assay. Most importantly, in vitro 3D co-culture spheroidal sprouting assay was used to investigate the regulating role of vascular endothelial growth factor (VEGF)-angiopoietin (Ang)-Tie2 signaling on angiogenic sprouting in 3D co-cultured spheroids of HUVECs and T-DPSCs. Angiopoietin 2 (Ang2) and VEGF were used to treat the co-cultured spheroids to explore their roles in angiogenic sprouting. Inhibitors for Tie2 and VEGFR2 were used to block Ang1/Tie2 and VFGF/VEGFR2 signaling. Results Western blotting and immunofluorescence showed that the expression of SMC-specific markers (α-SMA and SM22α) were significantly increased after treatment with TGF-β1. Contractility of T-DPSCs was greater compared with that of DPSCs. T-DPSC-CM inhibited HUVEC migration. In vitro sprouting assay demonstrated that T-DPSCs enclosed HUVECs, resembling pericyte-like cells. Compared to co-culture with DPSCs, a smaller number of HUVEC sprouting was observed when co-cultured with T-DPSCs. VEGF and Ang2 co-stimulation significantly enhanced sprouting in HUVEC and T-DPSC co-culture spheroids, whereas VEGF or Ang2 alone exerted insignificant effects on HUVEC sprouting. Blocking Tie2 signaling reversed the sprouting inhibition by T-DPSCs, while blocking VEGF receptor (VEGFR) signaling boosted the sprouting inhibition by T-DPSCs. Conclusions This study revealed that TGF-β1 can induce DPSC differentiation into functional pericyte-like cells. T-DPSCs maintain vessel stability through Ang1/Tie2 and VEGF/VEGFR2 signaling.

Over 12 years of continuous monitoring of Changbaishan volcano in the border region of China and North Korea by means of volcanic seismicity, ground deformation, and volcanic gas geochemistry yields new evidence for magmatic unrest of the volcano between 2002 and 2006. In this so‐called “active period,” the frequency of volcanic earthquakes increased by about 2 orders of magnitude compared to that of the background “inactive periods.” The active period was also accompanied by ground inflation, high values of CO2, He, H2, and high ratios of N2/O2 and 3He/4He in volcanic gases released from three hot springs near the caldera rim. The monitoring evidence implies pressurization of the magma chamber, possibly caused by incremental magma recharge. The ground deformation data from both GPS and precise leveling are modeled to suggest the corresponding deformation source is at 2–60 km depth beneath the volcano's summit, where earthquake swarms were detected in 2002 and 2003. Our findings suggest that the magma chamber beneath Changbaishan volcano has awakened and resumed activity after remaining dormant since AD 1903. There is an urgent need to keep close watch on this active and very hazardous volcano in northeast China. Key Points The unrest of Changbaishan volcano during 2002‐2006 was detected The unrest process may be a long term precursor of eruptive activity in future Need to keep close watch on the volcano

The research into the molecular dynamics (MD) behaviour of coal gangue (CG)–ground granulated blast furnace slag (GGBFS) geopolymers contributes to uncovering the strength formation mechanism of geopolymer. Geopolymers were prepared by using CG and GGBFS, and Na 2 SiO 3 as alkali activator. This study systematically investigated the unconfined compressive strength (UCS) and microstructure of geopolymers via a synergistic approach combining experimental testing and MD simulation. A validated C(N)–A–S–H molecular model was established, and the polymerisation characteristics were revealed through microstructural and kinetic analyses.The results indicate that the UCS of alkali‐activated CG‐ground‐granulated blast furnace slag geopolymer increases with curing age. Furthermore, the design of appropriate mix proportions can result in geopolymers with high UCS. Prepared with a GGBFS content of 40%, an alkali activator content of 25%–26% and an alkali activator modulus of 0.8–1.0, achieved a UCS of 34.1 MPa at 28 days of curing. MD simulations were performed to obtain three kinetic parameters, including the radial distribution function (RDF) analysis, the mean square displacement (MSD) analysis and the potential energy components (PEC). Analysis based on RDF indicates that systems with appropriate bond lengths and excellent coordination environments correspond to higher macroscopic mechanical properties, whereas excessively long bond lengths and distorted coordination structures lead to a reduction in macroscopic mechanical properties. The optimal formulation (40% GGBFS, 26% alkali activator, modulus 1.0) achieves 34.1 MPa at 28 days, attributed to ideal bond lengths and low degree of coordination distortion. The trends in the MSD and UCS are primarily influenced by the synergistic effects of the Si/Al and Ca/Si ratios.Furthermore, the system exhibits optimal UCS when the Ca/Si ratio exceeds 0.27, and the Si/Al ratio exceeds 2.0. A Pearson correlation analysis between PEC and UCS revealed a strong positive correlation between the two. This indicates a potential trend of association between micro‐energy and UCS. These findings provide valuable insights into the preparation mechanisms of geopolymers.

This paper presents the recent research on the study of the strategies for the flexible operation of the thermal power plant to meet the requirement of load balance. The study aimed to investigate the feasibility of bringing the High Temperature Thermal Energy Storage (HTTES) to the thermal power plant steam-water cycle, to identify the suitable HTTES in the cold (hot) section of the reheating pipeline and to test the efficiency of the HTTES integration to increase the flexibility of peak shaving and energy efficiency via thermal power plant with HTTTES modelling and simulation. Thermoflex was adopted to perform the simulation and a 300 MW subcritical coal-fired power plant model was implemented onto the software platform. The simulation results show that it is feasible to extract steam from the steam turbine to charge the HTTES, and to discharge the stored thermal energy back to the power generation process, and to analyse the improved capability of the plant flexible operation with HTTES. Then the study was extended to analyse the effect of thermal energy temperature, the opening of the regulating valve, and the pipeline pressure loss aspects on thermal efficiency of the whole plant. The study is beneficial to achieve more economic operation of the thermal power plant with HTTES integration. It is concluded that the introduction of the HTTES can improve the consumption of wind power, and these ideas and methods for solving the energy consumption of the renewable energy and reducing the peak energy consumption are provided.

Heart failure (HF) is a growing global health concern, driven by factors such as increased mechanical load of the heart muscle tissue. This pathogenic condition is the result of remodeling processes, partially mediated by the cytokine transforming growth factor β (TGF- β1), with progressive deposition of extracellular matrix within the myocardium that ultimately increases tissue stiffness. To elucidate early cellular and molecular processes underlying cardiac remodeling, translational experimental models are required. Living myocardial slices (LMS) represent a promising ex vivo model with preserved multicellularity, and physiology. In this study, we developed a disease model with hypertrophic and fibrotic features in porcine LMS. For this, LMS were prepared from porcine left ventricular tissue and cultured under mechanical overload with or without TGF-β1 stimulation. LMS cultured under overload showed reduced contractile performance, while adding TGF- β1 resulted in higher collagen deposition in the tissue, increase in secretion levels of pro-fibrotic miR-21 into the culture supernatant and increased expression of pro-fibrotic and hypertrophic marker genes. Our findings demonstrate early fibrotic changes in pig LMS induced by both mechanical and chemical stimulations. This ex vivo model could provide valuable insights into the early changes in heart failure pathogenesis and could be utilized as a screening platform to validate treatment strategies targeting cardiac remodeling.