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Zirconium-based metallic glasses (Zr-MGs) are demonstrated to exhibit high mechanical strength, low elastic modulus and excellent biocompatibility, making them promising materials for endosseous implants. Meanwhile, tantalum (Ta) is also well known for its ideal corrosion resistance and biological effects. However, the metal has an elastic modulus as high as 186 GPa which is not comparable to the natural bone (10–30 GPa), and it also has a relative high cost. Here, to fully exploit the advantages of Ta as endosseous implants, a small amount of Ta (as low as 3 at. %) was successfully added into a Zr-MG to generate an advanced functional endosseous implant, Zr58Cu25Al14Ta3MG, with superior comprehensive properties. Upon carefully dissecting the atomic structure and surface chemistry, the results show that amorphization of Ta enables the uniform distribution in material surface, leading to a significantly improved chemical stability and extensive material-cell contact regulation. Systematical analyses on the immunological, angiogenesis and osteogenesis capability of the material are carried out utilizing the next-generation sequencing, revealing that Zr58Cu25Al14Ta3MG can regulate angiogenesis through VEGF signaling pathway and osteogenesis via BMP signaling pathway. Animal experiment further confirms a sound osseointegration of Zr58Cu25Al14Ta3MG in achieving better bone-implant-contact and inducing faster peri-implant bone formation.

In high-dimensional environment, the interaction among particles significantly affects their movements in searching the vast solution space and thus plays a vital role in assisting particle swarm optimization (PSO) to attain good performance. To this end, this article designs a random contrastive interaction (RCI) strategy for PSO, resulting in RCI-PSO, to tackle large-scale optimization problems (LSOPs) effectively and efficiently. Unlike existing interaction mechanisms for low-dimensional problems, RCI randomly chooses several different peers from the current swarm to construct a random interaction topology for each particle. Then, it lets the particle interact with the selected peers based on their current evolutionary information instead of their historical evolutionary information. Within the topology, RCI only propagates the evolutionary information of two contrastive dominators with the largest difference in fitness to direct the evolution of the particle. Therefore, particles with no more than two dominators in their topologies are not updated. Furthermore, a dynamic topology size adjustment scheme is devised to gradually enlarge the interaction topology. In this way, the swarm gradually switches from exploring the immense search space dispersedly to exploiting the found optimal regions intensively as the evolution continues. With these two strategies, RCI-PSO expectedly compromises search diversity and search convergence well at the swarm level and the particle level. Finally, extensive experiments executed on two public LSOP suites verify that RCI-PSO performs competitively with or even much better than totally 40 state-of-the-art large-scale approaches and preserves a good capability and scalability in tackling complex LSOPs.

The exploitation of new green polymerization avenues for the effective synthesis of polymers by reversible-deactivation radical polymerization plays a critical role in pursuing the development of polymeric materials. In this work, serials of deep eutectic solvents (DES) with intermolecular-hydrogen-bonding interaction were constructed as catalysts and medium for actuating reversible complexation-mediated polymerization (RCMP) for the first time, yielding methacrylate polymers with high monomer conversion and narrow dispersion molecular weight in both water and oil systems. The mechanism and elementary reaction of RCMP were explored deeply, revealing that the complexation of initiator with DES to generate radicals was a ratecontrolling step and intermolecular-hydrogen-bond was primary factor to influence polymerization rate. Moreover, the insights of density functional theory calculations revealed that negative electrostatic potential ensured nucleophilic capacity. This investigation demonstrated the considerable potential of DES for RCMP, which is anticipated for other polymerization applications as a novel medium mode.

3-Fucosyllactose (3-FL), an important fucosylated human milk oligosaccharide in breast milk, offers numerous health benefits to infants. Previously, we metabolically engineered Escherichia coliBL21(DE3) for the in vivobiosynthesis of 3-FL. In this study, we initially optimized culture conditions to double 3-FL production. Competing pathway genes involved in in vivoguanosine 5′-diphosphate-fucose biosynthesis were subsequently inactivated to redirect fluxes toward 3-FL biosynthesis. Next, three promising transporters were evaluated using plasmid-based or chromosomally integrated expression to maximize extracellular 3-FL production. Additionally, through analysis of α1,3-fucosyltransferase (FutM2) structure, we identified Q126 residues as a highly mutable residue in the active site. After site-saturation mutation, the best-performing mutant, FutM2-Q126A, was obtained. Structural analysis and molecular dynamics simulations revealed that small residue replacement positively influenced helical structure generation. Finally, the best strain BD3-A produced 6.91 and 52.1 g/L of 3-FL in a shake-flask and fed-batch cultivations, respectively, highlighting its potential for large-scale industrial applications.

Photo‐induced reversible complexation‐mediated polymerization (RCMP) is a green and economical method to prepare polymers with precise molecular weights, narrow molecular weight distributions and functionally active chain ends. Covalent organic frameworks (COFs) are a promising heterogeneous photocatalyst for mediating RCMP due to their adjustable structure, band gap, and porosity. In this work, 1,3,5‐triformylphloroglucinol (Tp) and p‐azoaniline (Azo) were selected to construct 2D β‐ketoenamine linked Tp‐Azo‐COF as a heterogeneous photocatalyst to trigger RCMP under white light irradiation. A series of polymers with controllable molecular weight and narrow molecular weight distribution were successfully prepared by using Tp‐Azo‐COF as photocatalysis. On/off light experiments confirmed the good spatiotemporal control feature, and chain expansion experiments demonstrated the high “activity” of polymer chain ends. Furthermore, the mechanistic research elucidated that electron transfer between Tp‐Azo‐COF and initiator occurred, allowing the formation of reactive radicals to mediate RCMP. Density functional theory calculations revealed that the coordination of iodine on the initiator to catalyst obviously reduced the bond dissociation energy, leading to enhance in the polymerization rate. This work provides a platform for constructing heterogeneous photocatalysts with more efficient and stable to mediate RCMP.

Dry sliding friction and wear test of Cu/CrB2composites manufactured by ex situ method was studied, and the mechanical properties were also measured to assistant analysis wear behaviour. When CrB2content is 3 vol.-%, both the mechanical and tribological properties reach the maximum values, viz., 113 HV, 304 MPa and 9.1 × 10−5mm3N−1m−1of the normal load is 10 N, higher 71.2%, 33.3%, lower 52.8% than that of pure Cu, respectively, which can be ascribed to the increase of hardness and the transfer of main wear mechanisms of Cu matrix from adhesive to abrasive wear by the addition of CrB2. Further increase CrB2content to above 5 vol.-%, wear resistance would decreases since the pulled out of CrB2particles.

ABSTRACTPancreatic ductal adenocarcinoma (PDAC) and low-grade ovarian cancer (LGSOC) are characterized by the prevalence of KRAS oncogene mutations. DIRAS3 is the first endogenous non-RAS protein that heterodimerizes with RAS, disrupts RAS clustering, blocks RAS signaling, and inhibits cancer cell growth. Here, we found that DIRAS3-mediated KRAS inhibition induces ROS-mediated apoptosis in PDAC and LGSOC cells with KRAS mutations, but not in cells with wild-type KRAS, by downregulating NFE2L2/Nrf2 transcription, reducing antioxidants, and inducing oxidative stress. DIRAS3 also induces cytoprotective macroautophagy/autophagy that may protect mutant KRAS cancer cells from oxidative stress, by inhibiting mutant KRAS, activating the STK11/LKB1-PRKAA/AMPK pathway, increasing lysosomal CDKN1B/p27 localization, and inducing autophagic gene expression. Treatment with chloroquine or the novel dimeric chloroquine analog DC661 significantly enhances DIRAS3-mediated inhibition of mutant KRAS tumor cell growth in vitro and in vivo. Taken together, our study demonstrates that DIRAS3 plays a critical role in regulating mutant KRAS-driven oncogenesis in PDAC and LGSOC.Abbreviations:AFR: autophagic flux reporter; ATG: autophagy related; CQ: chloroquine; DCFDA: 2’-7’-dichlorodihydrofluorescein diacetate; DIRAS3: DIRAS family GTPase 3; DOX: doxycycline; KRAS: KRAS proto-oncogene, LGSOC: low-grade serous ovarian cancer; MiT/TFE: microphthalmia family of transcription factors; NAC: N-acetylcysteine; PDAC: pancreatic ductal adenocarcinoma; ROS: reactive oxygen species; TFEB: transcription factor EB

Solar ultraviolet (UV) radiation may induce adverse effects on skin health, and portable UV dosimeters are often deficient for UV dose monitoring due to their insufficient precision and/or high power consumption. We demonstrate a low-voltage UV dosimeter based on organic field-effect transistor (OFET) memory. While remaining unchanged both in the dark and under visible light, the drain current of the dosimeter decreased monotonically under 365 nm UV radiation. The change of normalized drain current coincided with the cumulative UV dose, irrespective of instantaneous UV light intensity, thereby qualifying the device as a practical UV dosimeter. With low power consumption, as well as excellent sensitivity, selectivity, and flexibility, such an electronic dosimeter has great potential in monitoring human exposure to UV radiation.

Objective: In B-cell acute lymphoblastic leukemia (B-ALL), current intensive chemotherapies for adult patients fail to achieve durable responses in more than 50% of cases, underscoring the urgent need for new therapeutic regimens for this patient population. The present study aimed to determine whether HZX-02-059, a novel dual-target inhibitor targeting both phosphatidylinositol-3-phosphate 5-kinase (PIKfyve) and tubulin, is lethal to B-ALL cells and is a potential therapeutic for B-ALL patients. Methods: Cell proliferation, vacuolization, apoptosis, cell cycle, and in-vivotumor growth were evaluated. In addition, Genome-wide RNA-sequencing studies were conducted to elucidate the mechanisms of action underlying the anti-leukemia activity of HZX-02-059 in B-ALL. Results: HZX-02-059 was found to inhibit cell proliferation, induce vacuolization, promote apoptosis, block the cell cycle, and reduce in-vivotumor growth. Downregulation of the p53 pathway and suppression of the phosphoinositide 3-kinase (PI3K)/AKT pathway and the downstream transcription factors c-Myc and NF-κB were responsible for these observations. Conclusion: Overall, these findings suggest that HZX-02-059 is a promising agent for the treatment of B-ALL patients resistant to conventional therapies.

The integration of Artificial Intelligence (AI) with the Internet of Things (IoT), known as the Artificial Intelligence of Things (AIoT), enhances the devices’ processing and analysis capabilities and disrupts such sectors as healthcare, industry, and oil. However, AIoT’s complexity and scale are challenging for traditional machine learning (ML). Deep learning offers a solution but has limited testability, verifiability, and interpretability. In turn, the neuro-symbolic paradigmaddresses these challenges by combining the robustness of symbolic AI with the flexibility of DL, enabling AI systems to reason, make decisions, and generalize knowledge from large datasets better. This paper reviews state-of-the-art DL models for IoT, identifies their limitations, and explores how neuro-symbolic methods can overcome them. It also discusses key challenges and research opportunities in enhancing AIoT reliability with neuro-symbolic approaches, including hard-coded symbolic AI, multimodal sensor data, biased interpretability, trading-off interpretability, and performance, complexity in integrating neural networks and symbolic AI, and ethical and societal challenges.

Due to the low efficiency of a single metal Bi in the CO2reduction reaction (CO2RR) to formates, enhancing the conductivity and yield through surface engineered composites is an alluring approach. In this study, we reconstruct Bi nanoparticles in situgrowth in 3D nanoporous copper structures. Benefiting from the 3D nanoporous conductive network and the strong interaction between Cu and Bi, the Fermi level becomes shifted upward and the resulting Bi@np-Cu displays a surprising CO2RR performance. Bi@np-Cu demonstrates a formate faradaic efficiency of 97.7% at a potential of −0.97 V vs. reversible hydrogen electrode with a remarkable current density of 82 mA cm−2. Importantly, this catalyst also has a faradaic efficiency of more than 90% for a continuous CO2RR of 40 h. Density function theory calculations reveal that np-Cu effectively modulates the electronic states of Bi, optimizing the intermediate adsorption energy and leading to increased intrinsic activity of Bi. This study provides a novel perspective on the applications of nanoporous metals in catalysis.

The lattice square degree, denoted by the c/avalue, is a crucial factor that influences the slip mode of α-Ti alloys and thereby affects their plasticity. However, the relationship between the c/avalue and the plasticity of α-Ti alloys has not been fully clarified. In this study, the powder metallurgy method (PM) was used to prepare Ti alloys with different square degrees by introducing interstitial O and substitutional Si solutes into α-Ti crystal. Then the mechanical properties, particularly plasticity, and lattice parameters of the resulted alloys were measured. By combining first-principles calculation with experimental studying, a plastic criterion based on the square degree was established. Subsequently, the mechanism of strength and plasticity was investigated by means of the density of states and charge density difference. Finally, the composition of α-Ti alloys with both O and Si solution atoms was designed, whose c/avalues were calculated by the first-principles calculation and accorded with the proposed square degree criterion, and then the reliability of this criterion was verified by the experimental results. As a result, a high strength and plasticity α-Ti alloy with tensile strength 1106 MPa and elongation 23.2 % was successfully prepared. The findings of this research offer new insights into the alloying design of α-Ti alloys with high strength and moderate plasticity.

In recent years, spark plasma sintering (SPS) has emerged as a widespread method to produce high-quality intermetallic-based materials. This paper prepared the Nb–16Si–10Mo alloy and Nb–16Si–10Mo–10Ti alloy using SPS at 1400 °C, 1450 °C, and 1500 °C at a pressure of 30 MPa and a time of 15 min. The influence of temperature on the microstructure and mechanical properties of the two alloys at room temperature was investigated. The corresponding results showed that the relative density of the two alloys exceeded 99.4 %. Besides, adding Ti decreased the relative density and made the microstructure evolve from Nbss + Nb3Si + Nb5Si3phases to Nbss + Nb5Si3+Tissphases, and the fracture type varied from brittle fracture to the coexistence of brittle fracture and ductile fracture. As the temperature increased, the flexural strength and the fracture toughness decreased, and the maximum hardness and compressive strength existed at 1450 °C. Furthermore, the appropriate sintering temperature was 1450 °C for a connected mechanical property and microstructure. The flexural strength, fracture toughness, hardness, and compressive strength of Nb–16Si–10Mo alloy and Nb–16Si–10Mo–10Ti alloy sintered at 1450 °C were 462.6 MPa and 565.3 MPa, 6.76 MPa m1/2and 8.81 MPa m1/2, 757.6 HV and 626.5 HV, 2359 MPa and 2143 MPa, respectively.

The time-domain balanced homodyne detector (TBHD) is critical component in continuous-variable quantum key distribution (CVQKD). The shot-noise-limited attribute of a TBHD depends on the whole frequency spectrum of the detector, in contrast to a frequency-domain balanced homodyne detector that focuses only on part of the frequency spectrum. We propose a method for accurate calibration of the shot-noise-limited attribute of the TBHD by overlapping the gain lines of the TBHD and an integral photodetector which is realized by blocking one photodiode of the TBHD. The overlapping of two lines indicates that the detector is indeed shot noise limited, which is crucial to the security of CVQKD. Experimentally, we use this method to obtain a calibration error of $\pm 1$‰. Theoretical analysis showed that the CVQKD security is very sensitive to calibration errors of shot noise, and proper countermeasure was proposed to eliminate this issue. The presented methods are expected to contribute to CVQKD security and TBHD standardization.

ABSTRACTIntroductionLung cancer is one of the cancer types with the highest mortality rate, exploring a more effective treatment modality that improves therapeutic efficacy while mitigating side effects is now an urgent requirement. Designing multifunctional nanoparticles can be used to overcome the limitations of drugs and conventional drug delivery systems. Nanotechnology has been widely researched, and through different needs, suitable nanocarriers can be selected to load anti-cancer drugs to improve the therapeutic effect. It is foreseeable that with the rapid development of nanotechnology, more and more lung cancer patients will benefit from nanotechnology. This paper reviews the merits of various multifunctional nanoparticles in the treatment of lung cancer to provide novel ideas for lung cancer treatment.Areas coveredThis review focuses on summarizing various nanoparticles for targeted lung cancer therapy and their advantages and disadvantages, using nanoparticles loaded with anti-cancer drugs, delivered to lung cancer sites, enhancing drug half-life, improving anti-cancer drug efficacy and reducing side effects.Expert opinionThe delivery mode of nanoparticles with superior pharmacokinetic properties in the in vivo circulation enhances the half-life of the drug, and provides tissue-targeted selectivity and the ability to overcome biological barriers, bringing a revolution in the field of oncology.

Preparation of polymer-based packaging materials with rapid heat dissipation capacity is crucial for ensuring high-power equipment’s service life. To achieve this, boron nitride (BN) and multi-walled carbon nanotubes (MWCNTs) were used in different ratios to prepare thermally conductive epoxy composites. These composites were created through a simple mixing and curing process, resulting in a heat transmission path. Then, BN and MWCNTs were separately functionalized with dopamine and acid to enhance their dispersibility and interfacial compatibility within the epoxy resin. This was done to further explore their influence on the formation of serial heat transfer pathways. The BN/MWCNTs/epoxy composites with a filler ratio of 15:1 and a total filler loading of 30 wt % exhibited a thermal conductivity of 0.92 W/mK, which is 118% higher than pure epoxy. These composites also displayed favorable mechanical properties and thermal stability. This study provides guidance for designing high-performance epoxy composites to meet modern electronic devices’ thermal management requirements.

The underlying mechanisms of Cinnamomum kanehirae-stimulated growth and metabolism of Antrodia camphorataremain unknown. Herein, we first observed that the methanol extract of C. kanehiraetrunk (MECK) (2 g/L) showed a potent stimulatory effect on A. camphoratatriterpenoids production (115.6 mg/L). Second, MECK treatment considerably increased the category and abundance of many secondary metabolites in the mycelia. We identified 93 terpenoids (8 newly formed and 49 upregulated) in the MECK-treated mycelia, wherein 21 terpenoids were the same as those in the fruiting bodies. Third, 42 out of the 93 terpenoids were annotated in the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, mainly involving monoterpenoids and diterpenoids syntheses. Finally, 27 monoterpenes and 16 sesquiterpenes were detected in the MECK, and the two terpenoids with the highest abundance (linalool and α-pinene) were selected for verification and found to considerably increase the terpenoids production of A. camphorataand demonstrate the regulation of mRNA expression levels of nine key genes in the mevalonate pathway via RT-qPCR. This study is beneficial for elucidating the terpenoids synthesis mechanism in A. camphorata.

The Qilian Mountain permafrost area located in the northern of Qinghai-Tibet Plateau is a favorable place for natural gas hydrate formation and enrichment, due to its well-developed fractures and abundant gas sources. Understanding the formation and distribution of multi-component gas hydrates in fractures is crucial in accurately evaluating the hydrate reservoir resources in this area. The hydrate formation experiments were carried out using the core samples drilled from hydrate-bearing sediments in Qilian Mountain permafrost area and the multi-component gas with similar composition to natural gas hydrates in Qilian Mountain permafrost area. The formation and distribution characteristics of multi-component gas hydrates in core samples were observed in situby X-ray Computed Tomography (X-CT) under high pressure and low temperature conditions. Results show that hydrates are mainly formed and distributed in the fractures with good connectivity. The ratios of volume of hydrates formed in fractures to the volume of fractures are about 96.8% and 60.67% in two different core samples. This indicates that the fracture surface may act as a favorable reaction site for hydrate formation in core samples. Based on the field geological data and the experimental results, it is preliminarily estimated that the inventory of methane stored in the fractured gas hydrate in Qilian Mountain permafrost area is about 8.67×1013m3, with a resource abundance of 8.67×108m3/km2. This study demonstrates the great resource potential of fractured gas hydrate and also provides a new way to further understand the prospect of natural gas hydrate and other oil and gas resources in Qilian Mountain permafrost area.

A pair of zinc(II)-based one-dimensional (1D) homologous coordination polymers, [Zn(Hdba)2(bib)]n(1) and [Zn(Hdba)2(bmib)]n(2), where H2dba = 3-hydroxybenzoic acid, bib = 1,4-bis(1-imidazolyl)benzene, and bmib = 1,4-bis(2-methyl-1H-imidazol-1-yl)benzene were hydrothermally synthesized and characterized through infrared spectroscopy (IR), elemental and thermal analysis (EA), powder X-ray diffraction (PXRD), and single-crystal X-ray diffraction (SCXRD) analyses. The results revealed that 1and 2have the same zigzaginfinite chain framework through the partially deprotonated Hdba–monodentate linkage and with μ2-bib bridging the Zn(II) atoms in 1, and with μ2-bmib bridges for the Zn(II) atoms in 2. For both 1and 2, each zinc atom has a slightly twisted tetrahedral configuration with a N2O2donor set. These chains of 1and 2are further connected into three-dimensional (3D) supramolecular structures through O–H···O, C–H···O hydrogen bonds and π···π, C–H···π stacking interactions for 1, and O–H···O, C–H···O hydrogen bonds for 2. Topologically, the 3D hydrogen-bonded organic framework or the 2D π-stacking structure of 1can be simplified as a 4-connected dia Diamondtype with a Schläfli symbol {66}, or as a 4-connected sqltype with a Schläfli symbol {44·62} and a Shubnikov tetragonal plane net. The thermal stability and the solid-state fluorescence properties of 1and 2were investigated.

Background and aims: The end of the zero-COVID-19 policy placed a large number of older adults in China at increased risk of COVID-19 infection. SARS-CoV-2 rapid antigen testing (RAT) is a promising tool for scaling up testing and ensuring that patient management and public health measures can be implemented without delay. We aimed to understand the knowledge and willingness of RAT, and its correlates among older adults in China. Methods: A nationwide cross-sectional survey on knowledge and willingness about RAT among older adults in China was conducted between January 14 and 28, 2023, shortly after the end of the zero-COVID-19 policy. An online questionnaire was used to collect information on sociodemographic characteristics, health characteristics, sources to access RAT information, and attitudes toward COVID-19 and its RAT. Logistic regression was used to assess correlates of knowledge of RAT and willingness to take RAT among older adults. Results: A total of 1030 older adults (494 women and 536 men, mean age 68.7 ± 7.0 years) were recruited. 49.4% of the participants had a high level of RAT knowledge. After adjusting for sociodemographic characteristics, chronic diseases (0.70, 0.49–0.99), learning RAT from new media (5.46, 3.48–8.68) and traditional media (3.35, 2.13–5.34), and perceiving RAT as convenient (4.03, 2.80–5.85) were associated with levels of RAT knowledge. 53.3% of the participants were willing to take RAT. After adjusting for sociodemographic characteristics, learning RAT from new media (8.46, 5.26–14.0) and traditional media (1.63, 1.04–2.55), perceiving RAT as convenient (2.97, 2.10–4.22), and worrying about (re)infection with COVID-19 (2.12, 1.55–2.92) were associated with willingness to take RAT. Conclusion: The levels of RAT knowledge and willingness to take RAT among older adults in China may hinder the scale-up of RAT. Health education about RAT should be strengthened among older adults. Special efforts should be made to integrate traditional and new media to promote RAT among older adults, specifically, for virus susceptibility and the convenience of RAT. Given the reopening of society, our study could inform our response to future novel infectious diseases and aid in the timely scale-up of RAT.

High-dimensional optimization problems are increasingly pervasive in real-world applications nowadays and become harder and harder to optimize due to increasingly interacting variables. To tackle such problems effectively, this paper designs a random elite ensemble learning swarm optimizer (REELSO) by taking inspiration from human observational learning theory. First, this optimizer partitions particles in the current swarm into two exclusive groups: the elite group consisting of the top best particles and the non-elite group containing the rest based on their fitness values. Next, it employs particles in the elite group to build random elite neighbors for each particle in the non-elite group to form a positive learning environment for the non-elite particle to observe. Subsequently, the non-elite particle is updated by cognitively learning from the best elite among the neighbors and collectively learning from all elites in the environment. For one thing, each non-elite particle is directed by superior ones, and thus the convergence of the swarm could be guaranteed. For another, the elite learning environment is randomly formed for each non-elite particle, and hence high swarm diversity could be maintained. Finally, this paper further devises a dynamic partition strategy to divide the swarm into the two groups dynamically during the evolution, so that the swarm gradually changes from exploring the immense solution space to exploiting the found optimal areas without serious diversity loss. With the above mechanisms, the devised REELSO is expected to explore the search space and exploit the found optimal areas properly. Abundant experiments on two popularly used high-dimensional benchmark sets prove that the devised optimizer performs competitively with or even significantly outperforms several state-of-the-art approaches designed for high-dimensional optimization.

Photodetectors (PDs) based on organic materials exhibit potential advantages such as low-temperature processing, and superior mechanical properties and form factors. They have seen rapid strides toward achieving performance metrics comparable to inorganic counterparts. Here, a simplified device architecture is employed to realize stable and high-performance organic PDs (OPDs) while further easing the device fabrication process. In contrast to the sequential deposition of the hole blocking layer (HBL) and active layer (conventional ‘two-step’ processing), the proposed strategy forms a self-assembled HBL and active layer in a ‘single-step’ process. A high-performance UV-Vis-NIR OPD based on the PM6:BTP-eC9 system is demonstrated using this cost-effective processing strategy. The green solvent processed proof-of-concept device exhibits remarkable responsivity of ∼0.5 A W−1, lower noise current than conventional two-step OPD, ultrafast rise/fall times of 1.4/1.6 μs (comparable to commercial silicon diode), and a broad linear dynamic range of 140 dB. Importantly, highly stable (light and heat) devices compared to those processed by the conventional method are realized. The broad application potential of this elegant strategy is proven by demonstrating the concept in three representative systems with broadband sensing competence.

Single-phase monoclinic-phase carbon-coated Li3V2(PO4)3nanocrystallites were developed by a citric acid gel technique. Mg2+was doped to replace V3+in Li3V2(PO4)3to generate defects and enhance the charge/discharge efficiency of the Li3V2(PO4)3material. The Li-ion transfer coefficient was enhanced by adding more Li+ions to the lattice, which balanced the formation of Li3+2x(MgxV1-x)2(PO4)3. Li3+2x(MgxV1-x)2(PO4)3(x = 0, 0.05, 0.1, and 0.15) was synthesized as a single-phase monoclinic sodium super ionic conductor (NASICON) structure having a space group of P21/n, having high crystallinity and little secondary phase, suggesting that the working amount is x < 0.15. The x = 0.1 sample displayed a specific discharge capacity of 123.1 mAh g−1at 0.1C with 97.1 % coulombic efficiency and 43.3 % performance at 10C, while maintaining 99.5 % capacity retention also after 100 cycles from 3.0 to 4.3 V. The Li-ion diffusion coefficient was DCV = 2.58 × 10−10cm2s−1, indicating that the electrochemical performance can be improved by doping with an appropriate amount of Mg2+to Li3V2(PO4)3.

Deficit of oxygen and nutrients in the tumor microenvironment (TME) triggers abnormal angiogenesis that produces dysfunctional and leaky blood vessels, which fail to adequately perfuse tumor tissues. Resulting hypoxia, exacerbation of metabolic disturbances, and generation of an immunosuppressive TME undermine the efficacy of anticancer therapies. Use of carefully scheduled angiogenesis inhibitors has been suggested to overcome these problems and normalize the TME. Here, we propose an alternative agonist-based normalization approach using a derivative of the C-type natriuretic peptide (dCNP). Multiple gene expression signatures in tumor tissues were affected in mice treated with dCNP. In several mouse orthotopic and subcutaneous solid tumor models including colon and pancreatic adenocarcinomas, this well-tolerated agent stimulated formation of highly functional tumor blood vessels to reduce hypoxia. Administration of dCNP also inhibited stromagenesis and remodeling of the extracellular matrix and decreased tumor interstitial fluid pressure. In addition, treatment with dCNP reinvigorated the antitumor immune responses. Administration of dCNP decelerated growth of primary mouse tumors and suppressed their metastases. Moreover, inclusion of dCNP into the chemo-, radio-, or immune-therapeutic regimens increased their efficacy against solid tumors in immunocompetent mice. These results demonstrate the proof of principle for using vasculature normalizing agonists to improve therapies against solid tumors and characterize dCNP as the first in class among such agents.

Tumor-infiltrating regulatory T cells (TI-Tregs) elicit immunosuppressive effects in the tumor microenvironment (TME) leading to accelerated tumor growth and resistance to immunotherapies against solid tumors. Here, we demonstrate that poly-(ADP-ribose)-polymerase-11 (PARP11) is an essential regulator of immunosuppressive activities of TI-Tregs. Expression of PARP11 correlates with TI-Treg cell numbers and poor responses to immune checkpoint blockade (ICB) in human patients with cancer. Tumor-derived factors including adenosine and prostaglandin E2 induce PARP11 in TI-Tregs. Knockout of PARP11 in the cells of the TME or treatment of tumor-bearing mice with selective PARP11 inhibitor ITK7 inactivates TI-Tregs and reinvigorates anti-tumor immune responses. Accordingly, ITK7 decelerates tumor growth and significantly increases the efficacy of anti-tumor immunotherapies including ICB and adoptive transfer of chimeric antigen receptor (CAR) T cells. These results characterize PARP11 as a key driver of TI-Treg activities and a major regulator of immunosuppressive TME and argue for targeting PARP11 to augment anti-cancer immunotherapies.

The LC3/GABARAP family of proteins is involved in nearly every stage of autophagy. Inhibition of LC3/GABARAP proteins is a promising approach to blocking autophagy, which sensitizes advanced cancers to DNA-damaging chemotherapy. Here, we report the structure-based design of stapled peptides that inhibit GABARAP with nanomolar affinities. Small changes in staple structure produced stapled peptides with very different binding modes and functional differences in LC3/GABARAP paralog selectivity, ranging from highly GABARAP-specific to broad inhibition of both subfamilies. The stapled peptides exhibited considerable cytosolic penetration and resistance to biological degradation. They also reduced autophagic flux in cultured ovarian cancer cells and sensitized ovarian cancer cells to cisplatin. These small, potent stapled peptides represent promising autophagy-modulating compounds that can be developed as novel cancer therapeutics and novel mediators of targeted protein degradation.

Global warming and the response to it have become a topic of concern in today’s society and are also a research focus in the global scientific community. As the world’s third pole, the global warming amplifier, and the starting region of China’s climate change, the Qinghai-Tibet Plateau is extremely sensitive to climate change. The permafrost on the Qinghai-Tibet Plateau is rich in natural gas hydrates (NGHs) resources. Under the background of global warming, whether the NGHs will be disassociated and enter the atmosphere as the air temperature rises has become a major concern of both the public and the scientific community. Given this, this study reviewed the trend of global warming and accordingly summarized the characteristics of the temperature increase in the Qinghai-Tibet Plateau. Based on this as well as the distribution characteristics of the NGHs in the permafrost on the Qinghai-Tibet Plateau, this study investigated the changes in the response of the NGHs to global warming, aiming to clarify the impacts of global warming on the NGHs in the permafrost of the plateau. A noticeable response to global warming has been observed in the Qinghai-Tibet Plateau. Over the past decades, the increase in the mean annual air temperature of the plateau was increasingly high and more recently. Specifically, the mean annual air temperature of the plateau changed at a rate of approximately 0.308–0.420°C/10a and increased by approximately 1.54–2.10°C in the past decades. Moreover, the annual mean ground temperature of the shallow permafrost on the plateau increased by approximately 1.155–1.575°C and the permafrost area decreased by approximately 0.34×106km2from about 1.4×106km2to 1.06×106km2in the past decades. As indicated by simulated calculation results, the thickness of the NGH-bearing permafrost on the Qinghai-Tibet Plateau has decreased by 29–39 m in the past 50 years, with the equivalent of (1.69 – 2.27)×1010–(1.12–1.51)×1012m3of methane (CH4) being released due to NGHs dissociation. It is predicted that the thickness of the NGH-bearing permafrost will decrease by 23 m and 27 m, and dissociated and released NGHs will be the equivalent of (1.34–88.8)×1010m3and (1.57–104)×1010m3of CH4, respectively by 2030 and 2050. Considering the positive feedback mechanism of NGHs on global warming and the fact that CH4has a higher greenhouse effect than carbon dioxide, the NGHs in the permafrost on the Qinghai-Tibet Plateau will emit more CH4into the atmosphere, which is an important trend of NGHs under the background of global warming. Therefore, the NGHs are destructive as a time bomb and may lead to a waste of efforts that mankind has made in carbon emission reduction and carbon neutrality. Accordingly, this study suggests that human beings should make more efforts to conduct the exploration and exploitation of the NGHs in the permafrost of the Qinghai-Tibet Plateau, accelerate research on the techniques and equipment for NGHs extraction, storage, and transportation, and exploit the permafrost-associated NGHs while thawing them. The purpose is to reduce carbon emissions into the atmosphere and mitigate the atmospheric greenhouse effect, thus contributing to the global goal of peak carbon dioxide emissions and carbon neutrality.

Graphical abstract:

A robust symbol timing and carrier frequency synchronization scheme applicable to orthogonal frequency division multiplexing system is presented. The proposed method is based on correlation and energy detection in time domain. The estimator has a steep timing metric and can provide delay-spread information about the channel. It means that the proposed method can distinguish ISI (Inter-symbol interference) free region from ISI region with optimum timing position acquired. The computer simulation results show that the proposed algorithm can track time varying channel condition and has much smaller MSE (Mean Squares Error) than that of ML estimation algorithms (1). Index Terms--carrier frequency synchronization, DVB-H, ML estimation, OFDM, symbol timing synchronization

Cu matrix composites reinforced by ex-situ added CrB2ceramic particles were prepared by powder metallurgy and hot extrusion, and then the effect of CrB2content on microstructure and mechanical properties was studied. Results show that the strength of Cu matrix composites depends mainly on the dispersion degree of CrB2particles, which is closely corresponded to the content of CrB2particles. When the content is below 3vol.%, CrB2particles disperses uniformly in the Cu matrix, and the strength of Cu matrix composites increases continuously with the content of CrB2. However, when the content is above 3vol.%, the strength of Cu matrix composites decreases significantly with the increase of CrB2content, which is ascribed to the serious agglomeration phenomenon. Although both the electrical conductivity and plasticity decrease with the increase of CrB2content, they remain quite a high level. The excellent combination properties are obtained when the content of CrB2is 3vol.%, viz. The tensile strength is 304 MPa, the elongation is 22% and the electrical conductivity is 90 %IACS, better than most of the reported Cu matrix composites especially electrical conductivity prepared by in-situ method. Furthermore, dislocation strengthening caused by thermal mismatch and Orowan strengthen of CrB2is demonstrated as the main strengthening mechanism of Cu/CrB2composites, based on the theoretical and experimental investigations.

The high active catalyst, polypyrazoles, is designed and synthesized for the cycloaddition of CO2with epoxides to give a high yield of cyclic carbonates under mild conditions. Notably, the easy transition between the solid phase and liquid phase of polypyrazole can be realized by temperature adjustment, providing a novel guideline for the design of catalyst.

The synthesis of cyclic polymer is an important topic in polymer chemistry. Herein, we report a one-step method to prepare cyclic polypyrazoles. Monomers with two functional groups, diazo and alkyne, were synthesized and polymerized via1,3-diploar cycloaddition in bulk under heating without any catalyst. Polypyrazoles with molecular weights in the range of 3800-4400 g/mol and yields in the range of 78.8-98.7% were successfully synthesized. No chain end group was detected by LC-QTOF-MS and FTIR, which proves the cyclic structure of polypyrazoles. What is noteworthy is that the cyclic polypyrazoles can self-assemble into vesicles during the reprecipitation process, which was proved by the results of SEM and TEM. The reason for that is the formation of intermolecular hydrogen bond between NH and ester groups.

Synthetic towards homogeneous heparin oligosaccharides are increasing in terms of the number of products and the synthetic scale. The dual-function glycosyltransferase Pasteurella multocidaheparosan synthase 2 (PmHS2) is widely used in these synthetic approaches. However, the unwanted degradation (caused by multi-step reverse-glycosylation) action of PmHS2 limits the catalytic efficiency of the process and the purity of the products, especially when the target oligosaccharide is longer than a hexasaccharide. Here, we found that the degradation is due to the coexistence of two catalytic domains in PmHS2, which suggested that an approach employing single-function glycosyltransferases could overcome this problem. By screening members of the KfiA family, we obtained a novel single-function heparosan: α1-4-N-acetylglucosaminyltransferase from Neisseria animaloris, which had an excellent recombinant expression level in Escherichia coli. Then, multiple rounds of structure-guided site-directed mutagenesis of the enzyme, named NaKfiA, were performed, producing an NaKfiA C16L/S165K double-mutant with drastically improved enzyme activity and stability compared with wild-type NaKfiA, but retaining the excellent production level and substrate promiscuity. NaKfiA(C16L/S165K) purified from the cell lysate of 1 liter of fermented E. coliproduced 14.65 mmol α1,4-linkage. Combining NaKfiA(C16L/S165K) with the single-function glucuronyltransferase EcKfiC from E. coliK5, size-defined heparosan oligosaccharides were accessible with 96–98% yield in sequential enzymatic reactions, while unwanted oligosaccharide byproducts were minimized. Overall, our study resulted in an efficient engineered biocatalyst and established a biocatalytic approach for size-controlled synthesis of heparosan oligosaccharides relying on two single-function glycosyltransferases.

Anomalous phase separation in metallic glasses is a longstanding issue that has been controversial since it was first implied in 1969 due to the influence of microstructure artifacts and the lack of direct large-scale (over nanoscale) evidence. This study confirms an ultralarge scale anomalous glass phase separation phenomenon in a Cr-Fe-Co-Ni-Zr high-entropy metallic glass in which any pair of atomic components has a nonpositive heat of mixing using interferencefree visible-light, atomic force, scanning electron, and double spherical aberration-corrected atomic resolution analytical electron microscopes. The second glassy phase separated from the glassy matrix has an ultralarge size of tens of micrometers, which can be controlled by the cooling rate during sample preparation. A mechanism of before-monotectic-like liquid immiscibility is introduced to interpret the phenomenon, which helps understand the anomalous phase separation in metallic glasses and in other fields, such as liquid-liquid phase separation in cells.

The influence of selective laser melting (SLM) process parameters on the microstructure and mechanical properties of a typical Ni-based superalloy was researched. The optimum parameters of P= 170 W, V= 0.8 m/s were determined, under which the SLMed samples exhibited both the largest relative density of 99.57% and the best mechanical properties, including the microhardness (329.3 ± 3.8 HV), yield strength (726 ± 8.1 MPa), ultimate tensile strength (900 ± 5.9 MPa) and elongation ((31.9 ± 0.24)%). The average grain size ranges of SLMed samples are from 15.2 to 17.4 μm, with a typical mixed grain structure. Owing to the high cooling rate and remelting during SLM process, a large number of low-angle grain boundaries (LAGBs), dislocations and sub-grains were formed, and the fraction of LAGBs reached above 65%. At the same time, the content of low-Σcoincidence site lattice (CSL) boundaries was mostly less than 1%, while there was almost no γ′ phase precipitated in the matrix. The texture of SLMed samples was weak, and there was no obvious preferred growth direction. Combining with the microstructure characterization, both grain refinement strengthening and dislocation strengthening were considered as the main strengthening mechanisms. Moreover, the fracture mechanism of the optimum sample belonged to ductile fracture.

The influence of induction heating on the grain boundary character distribution (GBCD) in near-surface regions of a cold-rolled Nickel-based superalloy was researched. After induction heating, most of low-Σcoincidence site lattice (CSL) boundaries were Σ3 boundaries, which were mainly formed via the growth accident model. Moreover, the grain structures evolution during induction heating had a great influence on the evolution of GBCD. At the low strain of 0.1, both the fraction of Σ3 boundaries and grain size increased with the increasing temperatures, while the former was closely related to the better development of grain-clusters at the higher temperature. In addition, the coherent Σ3 boundaries were easier to be formed at the higher temperature during induction heating, owing to their low interface energy and mobility. At the large strain of 0.5, the fraction of Σ3 boundaries also increased with the increasing temperatures, but the grain size exhibited the opposite trend, which was closely related to the well development of static recrystallization (SRX) behaviors. Meanwhile, there was a “symbiotic relationship” between the SRX grains and Σ3 boundaries during induction heating. Through the electrochemical corrosion tests, it was proved that induction heating can contribute to the improvement of corrosion properties of superalloys via increasing the fraction of Σ3 boundaries, while the best corrosion resistance appeared in the samples treated at 800 °C with the strain of 0.5. Moreover, the evolution of both Σ9 and Σ27 boundaries was also closely related to strains and induction heating temperatures, but their fractions were less than 4%.

Photoinduced atom transfer radical polymerization (ATRP) is an economical and environment‐friendly method for synthesizing polymers with pre‐designable structures and precise molecular weight. Although significant progress for copper‐mediated photoinduced ATRP has been achieved, several drawbacks still remain, such as poor electron transfer capability and absorption bands of photocatalysts near UV region. Herein, imine‐based covalent organic framework, TAPPy‐TPA‐COF, has been synthesized as potential heterogeneous photocatalyst for photoinduced ATRP. The “living” feature of polymerizations of methyl methacrylate (MMA) can be well controlled by efficiency maintain the balance between activation and inactivation of CuIand CuII. The chain extension experiments have further demonstrated the chain‐end fidelity of polymers. Meanwhile, the catalyst recycle experiments have revealed stability of TAPPy‐TPA‐COFtoward ATRP processes. These results support the feasibility of using COFs as heterogeneous photocatalysts for copper‐mediated ATRP under visible light irradiation.

By decreasing the rate of physical vapor deposition, ZrCuAl metallic glasses with improved stability and mechanical performances can be formed, while the microscopic structural mechanisms remain unclear. Here, with scanning transmission electron microscopy and high-energy synchrotron X-ray diffraction, we found that the metallic glass deposited at a higher rate exhibits a heterogeneous structure with compositional fluctuations at a distance of a few nanometers, which gradually disappear on decreasing the deposition rate; eventually, a homogeneous structure is developed approaching ultrastability. This microscopic structural evolution suggests the existence of the following two dynamical processes during ultrastable metallic glass formation: a faster diffusion process driven by the kinetic energy of the depositing atoms, which results in nanoscale compositional fluctuations, and a slower collective relaxation process that eliminates the compositional and structural heterogeneity, equilibrates the deposited atoms, and strengthens the local atomic connectivity.

The fundamental understanding of sodium storage mechanisms in amorphous carbon is essential to develop high-performance anode materials for sodium-ion batteries. However, the intrinsic relation between the structure of amorphous carbon and Na+storage remains to be debated due to the difficulty in controlling and characterizing the local atomic configurations of amorphous carbon. Here we report quantitative measurements of Na+storage in a low-temperature dealloyed hard carbon with a tunable local structure from completely disordered micropores to gradually increased graphitic order domains. The structure-capacity-potential correlation not only verifies the disputing “adsorption–intercalation” mechanisms, i.e., Na+intercalation into local graphitic domains for the low-voltage plateaus and adsorption in fully disordered carbon for the sloping voltage profiles, but also unveils a new mechanism of Na+adsorption on defective sites of graphitic carbon in the medium-potential sloping region. The quantitative investigations provide essential insights into the reaction mechanisms of Na+with amorphous carbon for designing advanced sodium-ion battery anodes.