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Abstract Stretchable phosphorescence materials potentially enable applications in diverse advanced fields in wearable electronics. However, achieving room-temperature phosphorescence materials simultaneously featuring long-lived emission and good stretchability is challenging because it is hard to balance the rigidity and flexibility in the same polymer. Here we present a multiphase engineering for obtaining stretchable phosphorescent materials by combining stiffness and softness simultaneously in well-designed block copolymers. Due to the microphase separation, copolymers demonstrate an intrinsic stretchability of 712%, maintaining an ultralong phosphorescence lifetime of up to 981.11 ms. This multiphase engineering is generally applicable to a series of binary and ternary initiator systems with color-tunable phosphorescence in the visible range. Moreover, these copolymers enable multi-level volumetric data encryption and stretchable afterglow display. This work provides a fundamental understanding of the nanostructures and material properties for designing stretchable materials and extends the potential of phosphorescence polymers.

Ketone compounds are important neutral aroma components in heated cigarette smoke, and which play a significant role in the taste of heated cigarettes. In order to analyze the content of ketone aroma components in heated cigarette smoke, a method of gas chromatography-tandem mass spectrometry (GC-MS/MS) was established for the simultaneous quantitative determination of 28 kinds of ketone aroma substances. A tube furnace was used to heat the cigarette core material, and the ketone aroma components in the smoke were captured by the solvent absorption method. The ketone aroma capture device can realize the release and capture of flue gas under different atmospheres and multi-gradient temperatures. The method was verified through limit of detection (LOD), limit of quantification (LOQ), repeatability experiment and spike recovery experiment. The heated cigarettes with different flavors were heated and their smoke were captured by using the tube furnace heating-organic solvent absorption method. After heating and capturing, 1 mL of smoke absorption liquid was taken and filtered through a 0.22 µm organic filter, then the sample was continuously injected 6 times to the chromatographic instrument to measure the content of ketone compounds in the smoke absorption liquid, and this step was repeated for 6 days, finally the intra-day and inter-day RSDs of 28 kinds of ketone substances were calculated. With the above detected amount as the benchmark, a mixed standard solution of 28 kinds of ketone flavor substances was added to the smoke absorption liquid, in which the amount of each ketone substance added was 50%, 100% and 200%, respectively, the recovery rate for each ketone was calculated. The results showed that the LODs and LOQs of 28 kinds of ketone compounds are 0.65-2.77 μg/L and 2.18-9.24 μg/L, respectively, the recovery rate is 81.88%-119.32%, and the intra-day precision is 0.04%-3.51% (n=6), the inter-day precision is 0.11%-3.36% (n=6). The analytical method can meet the requirements of quantitative analysis and effectively distinguish dihydro-β-ionone/geranylacetone and farnesyl acetone/farnesylacetone. This method was used to detect ketone aroma substances in the smoke of 27 heated cigarettes with different flavor. The results showed that the total content of ketones is different in the smoke of different heated cigarettes with different flavor, and the content of some ketones varies greatly, which gives the heated cigarette different flavor. This method may conduct in-depth analysis of tobacco products and is of great significance to the development of new tobacco products.

Abstract B-Myb has received considerable attention for its critical tumorigenic function of supporting DNA repair. However, its modulatory effects on chemotherapy and immunotherapy have rarely been reported in colorectal cancer. Bortezomib (BTZ) is a novel compound with chemotherapeutic and immunotherapeutic effects, but it fails to work in colorectal cancer with high B-Myb expression. The present study was designed to investigate whether B-Myb deletion in colorectal cancer could potentiate the immune efficacy of BTZ against colorectal cancer and to clarify the underlying mechanism. Stable B-Myb knockdown was induced in colorectal cancer cells, which increased apoptosis of the cancer cells relative to the control group in vitro and in vivo. We found that BTZ exhibited more favourable efficacy in B-Myb–defective colorectal cancer cells and tumor-bearing mice. BTZ treatment led to differential expression of genes enriched in the p53 signaling pathway promoted more powerful downstream DNA damage, and arrested cell cycle in B-Myb–defective colorectal cancer. In contrast, recovery of B-Myb in B-Myb–defective colorectal cancer cells abated BTZ-related DNA damage, cell cycle arrest, and anticancer efficacy. Moreover, BTZ promoted DNA damage–associated enhancement of immunogenicity, as indicated by potentiated expression of HMGB1 and HSP90 in B-Myb–defective cells, thereby driving M1 polarization of macrophages. Collectively, B-Myb deletion in colorectal cancer facilitates the immunogenic death of cancer cells, thereby further promoting the immune efficacy of BTZ by amplifying DNA damage. The present work provides an effective molecular target for colorectal cancer immunotherapy with BTZ.

After ischemic stroke (IS), secondary injury is intimately linked to endoplasmic reticulum (ER) stress and body-brain crosstalk. Nonetheless, the underlying mechanism systemic immune disorder mediated ER stress in human IS remains unknown. In this study, 32 candidate ER stress-related genes (ERSRGs) were identified by overlapping MSigDB ER stress pathway genes and DEGs. Three Key ERSRGs (ATF6, DDIT3 and ERP29) were identified using LASSO, random forest, and SVM-RFE. IS patients with different ERSRGs profile were clustered into two groups using consensus clustering and the difference between 2 group was further explored by GSVA. Through immune cell infiltration deconvolution analysis, and middle cerebral artery occlusion (MCAO) mouse scRNA analysis, we found that the expression of 3 key ERSRGs were closely related with peripheral macrophage cell ER stress in IS and this was further confirmed by RT-qPCR experiment. These ERS genes might be helpful to further accurately regulate the central nervous system and systemic immune response through ER stress and have potential application value in clinical practice in IS.

Abstract Developing low‐cost and safe batteries with high energy density is promising for large‐scale energy storage applications. Currently, aqueous zinc ion batteries (AZIBs) using Zn metal as the anode have attracted tremendous research attention as the next generation of energy storage devices due to their advantages of high energy density, environmental friendliness, and natural Zn abundance. The utilization of synchrotron X‐ray analytical techniques for in situ/ex situ characterizations offers a comprehensive understanding of the atomic local structure, crystalline structure, chemical states, coordination environment, interface properties, morphologies, and other physicochemical properties of materials on a variety of temporal and length scales, providing valuable insights into the fundamental mechanisms of AZIBs. This review highlights the recent advances and accomplishments of various synchrotron X‐ray techniques, which have been employed to investigate different components of AZIBs and show great promise for battery research and development.

Abstract Magnon polarons are novel elementary excitations possessing hybrid magnonic and phononic signatures, and are responsible for many exotic spintronic and magnonic phenomena. Despite long-term sustained experimental efforts in chasing for magnon polarons, direct spectroscopic evidence of their existence is hardly observed. Here, we report the direct observation of magnon polarons using neutron spectroscopy on a multiferroic Fe2Mo3O8 possessing strong magnon-phonon coupling. Specifically, below the magnetic ordering temperature, a gap opens at the nominal intersection of the original magnon and phonon bands, leading to two separated magnon-polaron bands. Each of the bands undergoes mixing, interconverting and reversing between its magnonic and phononic components. We attribute the formation of magnon polarons to the strong magnon-phonon coupling induced by Dzyaloshinskii-Moriya interaction. Intriguingly, we find that the band-inverted magnon polarons are topologically nontrivial. These results uncover exotic elementary excitations arising from the magnon-phonon coupling, and offer a new route to topological states by considering hybridizations between different types of fundamental excitations.

The project of China initiative Accelerator Driven Subcritical (CiADS) system has been started to construct in southeast China's Guangdong province since 2019, which is expected to be checked and accepted in the year 2025. In order to make the students in University of Chinese Academy of Sciences (UCAS) better understand the main characteristic and the operation condition in the subcritical nuclear facility, the training platform for CiADS has been developed based on the Cave Automatic Virtual Environment (CAVE) in the Institute of Modern Physics Chinese Academy of Sciences (IMPCAS). The CAVE platform is a kind of non-head mounted virtual reality display system, which can provide the immersive experience and the alternative training platform to substitute the dangerous operation experiments with strong radioactivity. In this paper, the CAVE platform for the training scenarios in CiADS system has been presented with real-time simulation feature, where the required devices to generate the auditory and visual senses with the interactive mode have been detailed. Moreover, the three dimensional modeling database has been created for the different operation conditions, which can bring more freedom for the teachers to generate the appropriate training courses for the students. All the user-friendly features will offer a deep realistic impression to the students for the purpose of getting the required knowledge and experience without the large costs in the traditional experimental nuclear reactor.

In this study, a highly efficient magnetic molecularly imprinted polymer nanocomposite material was prepared using multi-walled carbon nanotubes as carriers. The characterization of the obtained nanocomposite material was conducted using Fourier transform infrared spectroscopy, a vibrating sample magnetometer, a thermogravimetric analyzer, a scanning electron microscope, and a transmission electron microscope. The adsorption properties of the nanocomposite material were evaluated through adsorption experiments, including static adsorption, dynamic adsorption, and selective recognition studies. The prepared nanocomposite material, serving as a selective adsorbent, was applied in magnetic solid-phase extraction. Subsequently, the derivatized samples were analyzed for glucose in fish serum using liquid chromatography–tandem mass spectrometry. Under optimal conditions, the detection limit was 0.30 ng/mL, the quantitation limit was 0.99 ng/mL, satisfactory spiked recovery rates were obtained, and the relative standard deviation was less than 1.1%. Using 2-deoxy-D-ribose as the template molecule and a structural analog of glucose allowed us to eliminate the potential template leakage in qualitative and quantitative analyses, effectively avoiding the issues of false positives and potential quantitative errors, compared to traditional methods. A method for detecting glucose levels in fish serum based on molecularly imprinted polymer technology has been successfully developed to determine the stress and health levels of fish.

Lead-cooled fast reactors exhibit strong inherent safety performance and good economic features, while material degradation due to corrosion and irradiation is still challenging. Oxide dispersion-strengthened steels are one of the promising candidates for fuel cladding materials. The effects of both irradiation and corrosion on ODS steel need to be further studied. In this work, MX-ODS steel was irradiated by Fe ions at 500 °C up to 46 dpa. Later, the as-received specimen and the irradiated specimen were used to conduct corrosion tests in oxygen-saturated Pb at 550 °C for 1 h. In the as-received specimen, discontinuous oxides penetrated by Pb and Pb in contact with steel matrix were observed, demonstrating unsatisfactory corrosion resistance of the material. However, in the irradiated specimen after corrosion experiment, a protective oxide layer formed and prevented Pb attack. The oxidation behavior differences between the two specimens can be attributed to the defects produced by irradiation and the structural discrepancy in oxides caused by the formation process. A possible mechanism of irradiation on the corrosion is discussed. In the as-received specimen, Fe atoms loss led to voids in the oxides, and lead penetrated the oxides through these voids. In the irradiated specimen, defects left by previous irradiation helped to form a more uniform oxide layer. The adhesive outer magnetite oxide and the Fe ions generated from where grain boundary oxidation developed retarded the presence of voids and made the oxide layer protective.

Abstract Cancer immunotherapy is revolutionizing oncology. The marriage of nanotechnology and immunotherapy offers a great opportunity to amplify antitumor immune response in a safe and effective manner. Here, electrochemically active Shewanella oneidensis MR-1 can be applied to produce FDA-approved Prussian blue nanoparticles on a large-scale. We present a mitochondria-targeting nanoplatform, MiBaMc, which consists of Prussian blue decorated bacteria membrane fragments having further modifications with chlorin e6 and triphenylphosphine. We find that MiBaMc specifically targets mitochondria and induces amplified photo-damages and immunogenic cell death of tumor cells under light irradiation. The released tumor antigens subsequently promote the maturation of dendritic cells in tumor-draining lymph nodes, eliciting T cell-mediated immune response. In two tumor-bearing mouse models using female mice, MiBaMc triggered phototherapy synergizes with anti-PDL1 blocking antibody for enhanced tumor inhibition. Collectively, the present study demonstrates biological precipitation synthetic strategy of targeted nanoparticles holds great potential for the preparation of microbial membrane-based nanoplatforms to boost antitumor immunity.

Conjugate heat transfer between liquid metal and solid is a common phenomenon in a liquid-metal-cooled fast reactor's fuel assembly and heat exchanger, dramatically affecting the reactor’s safety and economy. Therefore, comprehensively studying the sophisticated conjugate heat transfer in a liquid-metal-cooled fast reactor is profound. However, it has been evidenced that the traditional Simple Gradient Diffusion Hypothesis (SGDH), assuming a constant turbulent Prandtl number (Prt, usually 0.85 - 1.0), is inappropriate in the Computational Fluid Dynamics (CFD) simulations of liquid metal. In recent decades, numerous studies have been performed on the four-equation model, which is expected to improve the precision of liquid metal’s CFD simulations but has not been introduced into the conjugate heat transfer calculation between liquid metal and solid. Consequently, a four-equation model, consisting of the Abe k−ε turbulence model and the Manservisi kθ−εθ heat transfer model, is applied to study the conjugate heat transfer concerning liquid metal in the present work. To verify the numerical validity of the four-equation model used in the conjugate heat transfer simulations, we reproduce Johnson’s experiments of the liquid lead-bismuth-cooled turbulent pipe flow using the four-equation model and the traditional SGDH model. The simulation results obtained with different models are compared with the available experimental data, revealing that the relative errors of the local Nusselt number and mean heat transfer coefficient obtained with the four-equation model are considerably reduced compared with the SGDH model. Then, the thermal-hydraulic characteristics of liquid metal turbulent pipe flow obtained with the four-equation model are analyzed. Moreover, the impact of the turbulence model used in the four-equation model on overall simulation performance is investigated. At last, the effectiveness of the four-equation model in the CFD simulations of liquid sodium conjugate heat transfer is assessed. This paper mainly proves that it is feasible to use the four-equation model in the study of liquid metal conjugate heat transfer and provides a reference for the research of conjugate heat transfer in a liquid-metal-cooled fast reactor.

Glucose metabolic disorders (GMD) can promote insulin resistance (IR) and diabetes, and damage liver and kidney. Gynostemma pentaphyllum is commonly used in the clinical treatment of diabetes, but the research on its main active constituents and GMD has not been reported yet. This study explores the therapeutic potential of gypenosides of heat-processed Gynostemma pentaphyllum (HGyp) on high-fat diet-induced GMD in mice. HGyp was administered at different doses for 12 weeks. The investigation encompassed an array of parameters, including body weight, blood lipids, blood glucose, and liver tissue components. Metabolomic and network analyses were conducted to uncover potential targets and pathways associated with HGyp treatment. The results revealed that HGyp alleviated GMD by reducing body weight, blood glucose, and improving blood lipids levels, while increasing liver glycogen and antioxidant enzyme levels. Additionally, HGyp exhibited protective effects on liver and kidney health by reducing tissue damage. Fourteen blood components were detected by LC-MS. Metabolomic and network analyses indicated the potential engagement of the AGE-RAGE signaling pathway in the therapeutic effects of HGyp.Furthermore, Western blot and ELISA assays confirmed that HGyp upregulated GLO1 and GLUT4 while down-regulating AGEs and RAGE expression in liver tissue. In light of these findings, HGyp demonstrates promise as a potential therapeutic candidate for combating GMD, warranting further exploration in the development of therapeutic strategies or functional products.

The present study focuses on the thermal hydraulic characteristics of fuel assemblies in the China Initiative Accelerator Driven subcritical System (CiADS), which utilizes grid-type spacers to support lead bismuth eutectic (LBE) cooled fast reactors. While the structural design and mechanical analysis of CiADS triangular fuel assemblies with grid-type spacers have been preliminarily investigated, there is a pressing need to study the thermal hydraulic behavior of liquid LBE within these fuel assemblies. This analysis is crucial for assessing the safety and economy of the CiADS subcritical reactor. The sub-channel analysis code, based on the lumped parameter method, plays a vital role in rapidly evaluating the safety features of LBE-cooled fast reactor fuel assemblies. To comprehensively evaluate the thermal hydraulic performance of fuel assemblies with grid-type spacers in the CiADS LBE cooling system, the flow pressure drop model, turbulent mixing model, and convective heat transfer model for the fuel assembly structure with grid-type spacers were incorporated into the existing CiADS sub-channel analysis code. This enhanced code has been successfully employed in the thermal hydraulic analysis of fuel assemblies utilizing wire-type spacers in the CiADS system. To verify the validity and accuracy of the modified CiADS sub-channel analysis code in calculating triangular fuel assemblies with grid-type spacers, the code was first utilized to replicate a 19-rods flow heat transfer experiment with grid-type spacers cooling liquid LBE. A comparison between the simulation and experimental results confirms that the CiADS sub-channel analysis code can predict the coolant temperature and fuel rod surface temperature in fuel assemblies with grid-type spacers. Subsequently, the structure and thermal hydraulic design of the latest CiADS fuel assembly with grid-type spacers were reviewed. Finally, taking into account the aforementioned enhancements to the CiADS sub-channel analysis code, a comprehensive thermo-hydraulic calculation of the CiADS fuel assembly with grid-type spacers was conducted. The results demonstrate that the coolant outlet temperature, maximum cladding temperature, and maximum fuel pellet temperature all fall within the design parameters of CiADS. Furthermore, the impact of the number of rods in different rod bundles (91, 61, 37, and 7 rods) on thermal hydraulic performance was analyzed. The findings indicate that, while ensuring calculation accuracy and efficiency, the results obtained from the 37-rod bundle can effectively reflect the thermal hydraulic behavior of the reactor core.

The core power control is an important issue for the study of dynamic characteristics in China initiative accelerator driven subcritical system (CiADS), which has direct impact on the control strategy and safety analysis process. The CiADS is an experimental facility that is only controlled by the proton beam intensity without considering the control rods in the current engineering design stage. In order to get the optimized operation scheme with the stable and reliable features, the variation of beam intensity using the continuous and periodic control approaches has been adopted, and the change of collimator and the adjusting of duty ratio have been proposed in the power control process. Considering the neutronics and the thermal-hydraulics characteristics in CiADS, the physical model for the core power control has been established by means of the point reactor kinetics method and the lumped parameter method. Moreover, the multi-inputs single-output (MISO) logical structure for the power control process has been constructed using proportional integral derivative (PID) controller, and the meta-heuristic algorithm has been employed to obtain the global optimized parameters for the stable running mode without producing large perturbations. Finally, the verification and validation of the control method have been tested based on the reference scenarios in considering the disturbances of spallation neutron source and inlet temperature respectively, where all the numerical results reveal that the optimization method has satisfactory performance in the CiADS core power control scenarios.

Vacuum-sliding electrical contacts find extensive application in aerospace components, yet they face limitations related to inadequate lubrication performance. In this study, we analyzed the design of an emerging conductive lubricant material, NbSe2. A series of NbSe2-Ti films with varying doped Ti contents were prepared through magnetron sputtering technology. We investigated the correlation between the sputtering current and composition, microstructure, mechanical properties, and current-carrying tribological properties of the films. The results indicate that under vacuum and current-carrying conditions, the NbSe2-Ti films demonstrate significant advantages over existing electrical-contact lubrication materials. Compared with electroplated gold films, the NbSe2-Ti films reduced the coefficient of friction from 0.25 to 0.015, thereby improving the wear life by more than six times. This result demonstrates that magnetron-sputtered NbSe2 film can be used as a lubricant for space current-carrying sliding contacts.

The authors achieved the X-ray-excited organic phosphorescent scintillation from copolymers through copolymerization of bromine-substituted chromophores and acrylic acid and demonstrated their potential application in X-ray radiography.

The accelerator-driven subcritical system has a strong transmutation ability and high inherent safety, and it is internationally recognized as the most promising long-life nuclear waste disposal device. This study involves the construction of a Visual Hydraulic ExperimentaL Platform (VHELP) for the purpose of evaluating the applicability of Reynolds-averaged Navier–Stokes (RANS) models and analyzing the pressure distribution within the fuel bundle channel of China initiative accelerator-driven system (CiADS). Measurements of thirty differential pressures in edge subchannels within a 19-pin wire-wrapped fuel bundle channel were obtained under different conditions using deionized water. The pressure distribution in the fuel bundle channel at Reynolds numbers of 5000, 7500, 10,000, 12,500, and 15,000 was simulated using Fluent. The results show that RANS models obtained accurate results, and the shear stress transport k-ω model provided the most accurate prediction of the pressure distribution. The difference between the results of the Shear stress transport (SST) k-ω model and experimental data was the smallest, and the maximum difference was ±5.57%. Moreover, the error between the experimental data and numerical results of the axial differential pressure was smaller than that of the transverse differential pressure. The pressure periodicity in axial and transverse directions (one pitch) and a relatively three-dimensional pressure measurements were studied. The static pressure fluctuated and decreased periodically as the z-axis coordinate increased. These results can facilitate research on the cross-flow characteristics of liquid metal-cooled fast reactors.

Summary: The arginine dependency of cancer cells creates metabolic vulnerability. In this study, we examine the impact of arginine availability on DNA replication and genotoxicity resistance. Using DNA combing assays, we find that limiting extracellular arginine results in the arrest of cancer cells at S phase and a slowing or stalling of DNA replication. The translation of new histone H4 is arginine dependent and influences DNA replication. Increased proliferating cell nuclear antigen (PCNA) occupancy and helicase-like transcription factor (HLTF)-catalyzed PCNA K63-linked polyubiquitination protect arginine-starved cells from DNA damage. Arginine-deprived cancer cells display tolerance to genotoxicity in a PCNA K63-linked polyubiquitination-dependent manner. Our findings highlight the crucial role of extracellular arginine in nutrient-regulated DNA replication and provide potential avenues for the development of cancer treatments.

Ginsenoside Rg3, Rk1, and Rg5, rare ginsenosides from Panax ginseng, have many pharmacological effects, which have attracted extensive attention. They can be obtained through the heat treatment of Gynostemma pentaphyllum. In this study, scanning electron microscopy (SEM) and thermal gravity-differential thermal gravity (TG-DTG) were employed to investigate this process and the content change in ginsenosides was analyzed using liquid chromatography-mass spectrometry (LC-MS). SEM and TG-DTG were used to compare the changes in the ginsenosides before and after treatment. In SEM, the presence of hydrogen bond rearrangement was indicated by the observed deformation of vascular bundles and ducts. The before-and-after changes in the peak patterns and peaks values in TG-DTG indicated that the content of different kinds of compounds produced changes, which all revealed that the formation of new saponins before and after the heat treatment was due to the breakage or rearrangement of chemical bonds. Additionally, the deformation of vascular bundles and vessels indicated the presence of hydrogen bond rearrangement. The glycosidic bond at the 20 positions could be cleaved by ginsenoside Rb3 to form ginsenoside Rd, which, in turn, gave rise to ginsenoside Rg3(S) and Rg3(R). They were further dehydrated to form ginsenoside Rk1 and Rg5. This transformation process occurs in a weak acidic environment provided by G. pentaphyllum itself, without the involvement of endogenous enzymes. In addition, the LC-MS analysis results showed that the content of ginsenoside Rb3 decreased from 2.25 mg/g to 1.80 mg/g, while the contents of ginsenoside Rk1 and Rg5 increased from 0.08 and 0.01 mg/g to 3.36 and 3.35 mg/g, respectively. Ginsenoside Rg3(S) and Rg3(R) were almost not detected in G. pentaphyllum, and the contents of them increased to 0.035 and 0.23 mg/g after heat treatment. Therefore, the rare ginsenosides Rg3(S), Rg3(R), Rk1, and Rg5 can be obtained from G. pentaphyllum via heat treatment.

Abstract Background Many long non-coding RNAs (lncRNAs) have key roles in different human biologic processes and are closely linked to numerous human diseases, according to cumulative evidence. Predicting potential lncRNA-disease associations can help to detect disease biomarkers and perform disease analysis and prevention. Establishing effective computational methods for lncRNA-disease association prediction is critical. Results In this paper, we propose a novel model named MAGCNSE to predict underlying lncRNA-disease associations. We first obtain multiple feature matrices from the multi-view similarity graphs of lncRNAs and diseases utilizing graph convolutional network. Then, the weights are adaptively assigned to different feature matrices of lncRNAs and diseases using the attention mechanism. Next, the final representations of lncRNAs and diseases is acquired by further extracting features from the multi-channel feature matrices of lncRNAs and diseases using convolutional neural network. Finally, we employ a stacking ensemble classifier, consisting of multiple traditional machine learning classifiers, to make the final prediction. The results of ablation studies in both representation learning methods and classification methods demonstrate the validity of each module. Furthermore, we compare the overall performance of MAGCNSE with that of six other state-of-the-art models, the results show that it outperforms the other methods. Moreover, we verify the effectiveness of using multi-view data of lncRNAs and diseases. Case studies further reveal the outstanding ability of MAGCNSE in the identification of potential lncRNA-disease associations. Conclusions The experimental results indicate that MAGCNSE is a useful approach for predicting potential lncRNA-disease associations.

This article reviews the currently used therapeutic strategies to target DNA replication stress for cancer treatment in the clinic, highlighting their effectiveness and limitations due to toxicity and drug resistance. Cancer cells experience enhanced spontaneous DNA damage due to compromised DNA replication machinery, elevated levels of reactive oxygen species, loss of tumor suppressor genes, and/or constitutive activation of oncogenes. Consequently, these cells are addicted to DNA damage response signaling pathways and repair machinery to maintain genome stability and support survival and proliferation. Chemotherapeutic drugs exploit this genetic instability by inducing additional DNA damage to overwhelm the repair system in cancer cells. However, the clinical use of DNA-damaging agents is limited by their toxicity and drug resistance often arises. To address these issues, the article discusses a potential strategy to target the cancer-associated isoform of proliferating cell nuclear antigen (caPCNA), which plays a central role in the DNA replication and damage response network. Small molecule and peptide agents that specifically target caPCNA can selectively target cancer cells without significant toxicity to normal cells or experimental animals.

Abstract Background Electrostimulation (ES) therapy for wound healing is limited in clinical use due to barriers such as cumbersome equipment and intermittent delivery of therapy. Methods We adapted a human skin xenograft model that can be used to directly examine the nanogenerator-driven ES (NG-ES) effects on human skin in vivo—an essential translational step toward clinical application of the NG-ES technique for wound healing. Results We show that NG-ES leads to rapid wound closure with complete restoration of normal skin architecture within 7 days compared to more than 30 days in the literature. NG-ES accelerates the inflammatory phase of wound healing with more rapid resolution of neutrophils and macrophages and enhances wound bed perfusion with more robust neovascularization. Conclusion Our results support the translational evaluation and optimization of the NG-ES technology to deliver convenient, efficient wound healing therapy for use in human wounds. Graphic abstract

Anesthetics are essential for cancer surgery, but accumulated research have proven that some anesthetics promote the occurrence of certain cancers, leading to adverse effects in the lives of patients. Although anesthetic technology is mature, there is no golden drug selection standard for surgical cancer treatment. To afford the responsibility of human health, a more specific regimen for cancer resection is indeed necessary. Immunosuppression in oncologic surgery has an adverse influence on the outcomes of patients. The choice of anesthetic strategies influences perioperative immunity. Among anesthetics, propofol has shown positive effects on immunity. Apart from that, propofol’s anticancer effect has been generally reported, which makes it more significant in oncologic surgery. However, the immunoregulative function of propofol is not reorganized well. Herein, we have summarized the impact of propofol on different immunocytes, proposed its potential mechanism for the positive effect on cancer immunity, and offered a conceivable hypothesis on its regulation to postoperative inflammation. We conclude that the priority of propofol is high in oncologic surgery and propofol may be a promising immunomodulatory drug for tumor therapy.

Understanding and predicting nuclear fuel behavior is the cornerstone for fuel design and optimization, and the safe and economic operation of nuclear reactors. Due to the excellent neutronic economy and safe operational characteristics of lead/lead-bismuth-based liquid metal coolant, lead-cooled fast reactor (LFR) has received much attention and has been regarded as one of the top candidate reactors for Generation IV nuclear power plants. Mixed oxide (MOX) fuel is beneficial to improve fuel cycle utilization and consume weapons-grade plutonium, among which hollow MOX fuel has excellent heat transfer advantages, which can further improve fuel economy and safety, and has good development prospects. In this work, an annular uranium-plutonium mixed oxide (MOX) fuel operating in a liquid lead/lead-bismuth cooled fast reactor is modeled and simulated to predict its behavior under transient and steady-state operation. This model has several modules working in a fully coupled approach based on COMSOL Multiphysics, such as heat transfer, fuel burnup, oxygen redistribution, plutonium redistribution, porosity evolution, fission gas release, JOG growth, and grain size evolution. The modeling results were benchmarked with the existing codes and experimental data, and the results were in satisfactory agreement. The parameters analysis was carried out in this work. Consistent with the solid MOX fuel, the O/M ratio (or deviation from the stoichiometry of oxygen) significantly affects temperature evolution, fission gas migration and release behavior, and plutonium redistribution. Linear power also has a significant influence on fuel performance.

Boron neutron capture therapy (BNCT), a cellular-level particle radiation therapy, combines boron compounds selectively delivered to tumor tissue with neutron irradiation. Boronophenylalanine (BPA) is a boron compound widely used in malignant melanoma, malignant brain tumors, and recurrent head and neck cancer. However, neither basic nor clinical research was reported for the treatment of gastric cancer using BPA. Selective distribution of boron in tumors rather than that in blood or normal tissue prior to neutron irradiation is required for the successful treatment of BNCT. This study evaluated the pharmacokinetics and safety of 10B-labeled BPA (10B-BPA, abbreviated as BPA) and its uptakes in gastric cancer. Pharmacokinetics and safety were evaluated in Sprague–Dawley (SD) rats intravenously injected with BPA. The uptakes of boron in gastric cancer cell line MKN45 and in cell-derived xenografts (CDX) and patient-derived xenografts (PDX) animal models were measured. The results showed that the boron concentration in the blood of rats decreased fast in the first 30 min followed by a steady decrease following the observation time, having a half-life of 44.11 ± 8.90 min and an AUC-last of 815.05 ± 62.09 min×μg/ml. The distribution of boron in different tissues (heart, liver, lung, stomach, and small intestine) of rats revealed a similar pattern in blood except for that in the brain, kidney, and bladder. In MKN45 cells, boron concentration increased in a time- and concentration-dependent manner. In both CDX and PDX animal models, the boron is preferentially distributed in tumor tissue rather than in blood or normal tissues. In addition, BPA had no significant adverse effects in rats. Taken together, the results suggested that BPA revealed a fast decrease in boron concentration in rats and is more likely to distribute in tumor cells and tissue.

Compared to assuming a constant turbulent Prandtl number model, an advanced four-equation model has the potential to improve the numerical heat transfer calculation accuracy of low–Prandtl number (Pr) fluids. Generally, a four-equation model consists of a two-equation k−ε turbulence model and a two-equation kθ−εθ heat transfer model. It is essential to analyze the influence of dissimilar turbulence models on the overall calculation accuracy of the four-equation model. The present study aims to study the effect of using different turbulence models on the same kθ−εθ heat transfer model. First, based on the open-source computational fluid dynamics software OpenFOAM, an advanced two-equation kθ−εθ heat transfer model was introduced into the solver buoyant2eqnFoam, which was developed based on the self-solver buoyantSimpleFoam of OpenFOAM. In the solver buoyant2eqnFoam, various turbulence models built into OpenFOAM can be conveniently called to close the Reynolds stress and an advanced two-equation heat transfer model can be utilized to calculate the Reynolds heat flux of low-Pr fluids. Subsequently, the solver buoyant2eqnFoam was employed to study the fully developed flow heat transfer of low-Pr fluids in a bare 19-rod bundle. The numerical results were compared and analyzed with the experimental correlations and other simulation results to validate the effectiveness and feasibility of the solver buoyant2eqnFoam. Furthermore, the influence of combining different turbulence models with the same two-equation kθ−εθ heat transfer model was also presented in this study. The results show that the turbulence model has a considerable influence on the prediction of turbulent heat transfer in the high Peclet number range, suggesting that it should be prudent when picking a turbulence model in the simulations of low-Pr fluids.

Glioblastoma multiforme (GBM) is the most malignant primary tumour in the central nervous system, but the molecular mechanisms underlying its pathogenesis remain unclear. In this study, data set GSE50161 was used to construct a co‐expression network for weighted gene co‐expression network analysis. Two modules (dubbed brown and turquoise) were found to have the strongest correlation with GBM. Functional enrichment analysis indicated that the brown module was involved in the cell cycle, DNA replication, and pyrimidine metabolism. The turquoise module was primarily related to circadian rhythm entrainment, glutamatergic synapses, and axonal guidance. Hub genes were screened by survival analysis using The Cancer Genome Atlas and Human Protein Atlas databases and further tested using the GSE4290 and Gene Expression Profiling Interactive Analysis databases. The eight hub genes (NUSAP1, SHCBP1, KNL1, SULT4A1, SLC12A5, NUF2, NAPB, and GARNL3) were verified at both the transcriptional and translational levels, and these gene expression levels were significant based on the World Health Organization classification system. These hub genes may be potential biomarkers and therapeutic targets for the accurate diagnosis and management of GBM.

ObjectivesECT is a rapid and effective treatment for depression. While efficacy is often remarkable over the initial 3–4 sessions, the efficacy of later sessions is less rapid, and the side-effects, especially cognitive impairment limit its use. To preliminarily compare the efficacy and acceptability of a novel hybrid-ECT (HECT) protocol for patients with major depressive disorder (MDD) with standard ECT, we conducted this pilot trial.MethodsThirty patients were randomly assigned to ECT or HECT. Both arms received three ECT sessions (phase 1) but, in phase 2, the HECT arm received low-charge electrotherapy instead of ECT. The primary outcome was the change in 24-item Hamilton depression rating scale (HAMD-24) scores between baseline and the end of treatment. Cognitive function was assessed by repeatable battery for the assessment of neuropsychological status (RBANS), Stroop color word, and orientation recovery tests (ORT). Safety was measured by the drop-out rate and adverse events (AEs). Four visits were conducted at baseline, post-phase 1, post-phase 2, and at 1-month follow-up. Trial registration: Chinese Clinical Trial Registry (http://www.chictr.org.cn/), identifier: ChiCTR1900027701.ResultsPatients in both arms showed significant within-group improvements in HAMD-24, but the between-group differences were non-significant. Participants in the HECT arm outperformed ECT patients for most cognitive tests at the end of treatment or at follow-up. There was a significantly lower AE rate and shorter ORT in phase 2 of the HECT ar.ConclusionIn this pilot trial, HECT was associated with fewer AEs and better cognitive function including executive and memory function, but its possible similar antidepressive efficacy needs to be further investigated in future.

Stretchable triboelectric nanogenerators have attracted increasing interests in the field of Internet of Things and sensor network. Therefore, great efforts have been made to realize the stretchability of electronic devices via elaborated material configurations and ingenious device designs. In this work, a flexible and stretchable TENG is developed with a coaxial spring-like structure. The unique structure allows it to generate electrical energy for different degrees of stretching deformations. Its output demonstrates good response to the strain and frequency of the mechanical deformation. At the same time, it exhibits excellent stability and washability. The TENG can be worn on the human fingers, elbow, and knee to monitor the body activities. Furthermore, a self-powered temperature sensor system is fabricated by integrating the TENG with a temperature sensor to identify the operating ambient temperature in real time. A combination of this flexible and stretchable TENG with body motions and a temperature sensor brings a novel insight into wearable functional electronics and user-friendly health monitoring, which has an important basic research significance and practical application value in biometric systems.

In the simple gradient diffusion hypothesis, the turbulent Prandtl number (Prt) with a constant of 0.85 is difficult to accurately predict for liquid metals having low Prandtl numbers (Pr), while a four-equation model can improve this solution by introducing the turbulence time-scale into the calculation of turbulent thermal diffusivity. However, the four-equation model’s transport form and numerical stability are so complex that suitable commercial code is lacking. Therefore, an isotropic four-equation model with simple Dirichlet wall boundary conditions is built in the present work. Based on the open-source computational fluid dynamics program OpenFOAM, the fully developed velocity, temperature, Reynolds stress, and heat flux of low Pr fluids (Pr = 0.01–0.05) in the parallel plane are obtained by numerical simulation. The results show that the time-average statistics predicted using the present four-equation model are in good agreement with the direct numerical simulation data. Then, the isotropic four-equation model is used to analyze the flow and heat of liquid metal (Pr = 0.01) in a quadrilateral infinite rod bundle. The numerical results are compared with the various and available experimental relationships. The Nusselt numbers calculated using the isotropic four-equation model are betweenness the available correlations, while the turbulent Prandtl number model using a constant of 0.85 over predicts heat transfer. More detailed local heat transfer phenomena and distribution of low Pr fluids are obtained using the present isotropic four-equation model.

Abstract Background Kümmell’s disease is a special type of osteoporotic vertebral fracture that causes chronic low back pain and deformity, which seriously affects the living quality of patients. PVP is commonly used to treat osteoporotic vertebral fractures and can quickly relieve low back pain. So, the objective of this study was to analyze the clinical efficacy and experience of bipedicular percutaneous vertebroplasty combined with postural reduction for the treatment of Kümmell’s disease. Methods A retrospective analysis of patients with Kümmell’s disease who underwent bipedicular percutaneous vertebroplasty was conducted from February 2016 to May 2018. Operative time, VAS, bone cement injection volume, cement leakage rate, compression improvement of vertebral front edge and vertebral center, and correction degree of kyphosis were collected and analyzed meticulously. Results The operative time was 45.33 ± 7.64 min. The volume of bone cement injected was 5.38 ± 1.33 ml. The compression improvement of vertebral front edge was 7.31 ± 1.21%. The compression improvement of vertebral center was 10.34 ± 1.15% and the correction degree of kyphosis was − 2.73 ± 0.31゜. Bone cement leakage occurred in 6 of 39 patients (15.38%), but no clinical symptoms were observed. The VAS scores were significantly lower at 1 day after the surgery, 6 months and at the last follow-up than before the surgery (P = 0.000, respectively). The VAS score was lower at the last follow-up than at 1 day after the surgery (P = 0.001). Conclusion Bipedicular percutaneous vertebroplasty combined with postural reduction could achieve satisfactory analgesic effect in the treatment of Kümmell’s disease, and restore the height of the vertebral body and improve kyphosis to some extent.

Functional materials displaying tunable emission and long-lived luminescence are a powerful tool in information encryption, organic electronics and bioelectronics. Here the authors design a color-tunable ultralong organic room temperature phosphorescence polymer through radical multiple component cross-linked copolymerization.

Increasing the output current density is the key challenge for nanogenerators. Here, a new piezoelectric nanogenerator with a three-dimensional intercalation electrode is developed to reach 290 μA cm−2 by creating and utilizing many boundary interfaces.

The hypoxic microenvironment in solid tumors limits the efficacy of photodynamic therapy (PDT) since oxygen is necessary to produce high cytotoxic singlet oxygen species. Here, the authors develop an improved self-assembled single-atom nanozyme which allows oxygen generation to enhance PDT efficacy.

Abstract Personal electronic devices have a general development trend of miniaturization, functionality, and wearability. Their wireless, sustainable, and independent operation is critically important, which requests new power technologies that can harvest the ambient environmental energy. Here, we report a new kind of 2D woven wearable triboelectric nanogenerator (2DW-WTNG) composed of core-shell fibers via the twisting process and weaving process in the textile manufacture. The 2DW-WTNG can convert the body motion energy into electricity with an output current of 575 nA and an output voltage of 6.35 V. At an external load of 50 MΩ, it generated a maximum power density of 2.33 mW/m2. Electricity can be produced from the 2DW-WTNG driven in arbitrary in-plane directions. A tiny displacement of 0.4 mm can drive the 2DW-WTNG, which verified its capability to harvest energy from small human movement. The robust 2DW-WTNG can work continuously for 12 h without obvious performance degradation.

Arterial hypertension is considered the most prevalent risk factor for stroke. Both pathophysiologic and clinical data previously acquired suggest a strong correlation between the hemodynamic nature of arterial hypertension and an increase in the risk of ischemic insult to tissues. However, the knowledge of specific molecular interactions between hypertension and ischemic stroke (IS) is limited. In this study, we performed systematic bioinformatics analysis of stroke-prone spontaneous hypertensive brain tissue samples of rats (GSE41452), middle cerebral artery occlusion of brain tissue samples of rats (GSE97537), and peripheral blood array data of IS patients (GSE22255). We identified that Fos, an immediate-early gene (IEG) that responds to alterations in arterial blood pressure, has a strong correlation with the occurrence and prognosis of IS. To further evaluate the potential function of Fos, the oxygen–glucose deprivation model and RNA sequencing of HT22 neuronal cells were performed. Consistent with the sequencing results, real-time quantitative PCR and Western blot indicate that Fos was elevated at 3 h and returned to normal levels at 6 h after oxygen–glucose deprivation. Knock-down of Fos by lentivirus significantly increased the oxidative stress level, neuronal apoptosis, and inhibited the mitochondrial function. In conclusion, Fos acts as an important link between hypertension and IS. Furthermore, Fos can be used as a potential biomarker for target therapy in the prevention of stroke among hypertensive patients and also potential treatment targeting apoptosis and oxidative stress after its onset.

The China initiative Accelerator Driven System (CiADS) and the corresponding lead-bismuth eutectic (LBE) cooled subcritical reactor, as the research subject of one of the major national science and technology infrastructure projects, are undertaken by the Institute of Modern Physics-Chinese Academy of Sciences (IMP-CAS). And in the first phase, UO2 fuels will be loaded in the subcritical core to test the coupling technology and achieve a long-term steady operation. A brief description of CiADS subcritical reactor, fuel assembly and fuel element are presented here, and a multi-physics performance analysis and design evaluation of CiADS UO2 fuel are carried out by means of the FUTURE code. FUTURE is a fuel performance analysis code to evaluate the synergy of phenomena occurring in the fuel element and their impact on the fuel design improvement for the liquid metal fast reactor, which was developed jointly by IMP-CAS and Xi’an Jiaotong University (XJTU). In this paper, the FUTURE code was modified and updated focusing on characteristics of CiADS fuels. Relocation and densification models were added. Results of the hottest fuel element, mainly concerning the thermo-mechanical behaviors, are discussed concerning both fuel and cladding performance on the basis of indicative design limits. According to the preliminary design, the CiADS UO2 fuel exhibits good performance, and the main safety parameters are far below the indicative limits. The Fuel Cladding Mechanical Interaction (FCMI) is not very serious, and the permanent cladding strains and Cumulative Damage Fraction (CDF) are small and even negligible thanks to the low level of fuel temperature and corresponding stress. However, some critical issues may still exist, especially on LBE corrosion near the coolant inlet, where protective oxide layers are very thin from BoL to EoL. The modeling is useful for providing feedback to the conceptual design of the CiADS LBE-cooled subcritical reactor and the update of FUTURE code.

A kind of annular uranium nitride (UN) fuel suitable for lead-cooled fast reactor applications has been designed in this study. The design is directly targeting two main issues of UN fuel: severe swelling and thermal decomposition of UN fuel at high temperatures. A performance analysis program based on FORTRAN programming language has been developed for UN fuel in fast reactors. The program contains heat transfer, fuel stress-strain analysis, cladding stress-strain analysis, fission gas release and fuel-cladding mechanical interaction (FCMI) modules, etc. Extensive code verification has been performed by comparing simulation results obtained with the code and those obtained via the COMSOL Multiphysics platform. Preliminary code validation has been conducted as well by comparing code simulation results with experimental data. The results showed that this program could predict the fuel temperature, stress-strain, and displacement of UN fuel during reactor operation with a reasonable accuracy.

Large magnetic field-induced strains can be achieved in modulated martensite for Ni-Mn-In alloys; however, the metastability of the modulated martensite imposes serious constraints on the ability of these alloys to serve as promising sensor and actuator materials. The phase stability, magnetic properties, and electronic structure of the modulated martensite in the Ni2Mn1.5In0.5 alloy are systematically investigated. Results show that the 6M and 5M martensites are metastable and will eventually transform to the NM martensite with the lowest total energy in the Ni2Mn1.5In0.5 alloy. The physical properties of the incommensurate 7M modulated martensite (7M–IC) and nanotwinned 7M martensite (7M−(52¯)2) are also calculated. The austenite (A) and 7M−(52¯)2 phases are ferromagnetic (FM), whereas the 5M, 6M, and NM martensites are ferrimagnetic (FIM), and the FM coexists with the FIM state in the 7M–IC martensite. The calculated electronic structure demonstrates that the splitting of Jahn–Teller effect and the strong Ni–Mn bonding interaction lead to the enhancement of structural stability.