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The freckle formation and distribution in large-size directional solidified nickel-based superalloy blades at different withdrawal rates were investigated. The microstructure of freckles was analyzed by optical microscope (OM), and scanning electron microscope (SEM). The crystallographic orientation in the freckle regions was characterized by electron backscattered diffraction (EBSD). The solute segregation patterns on the surface of freckle regions were obtained by X-ray fluorescence (XRF). Numerical simulations for the temperature field were performed to analyze the mushy zone evolution during directional solidification. The experimental results indicated that the root region is prone to form freckles. The freckle chains were only distributed on the outward surface of the root region at low and middle withdrawal rates, and the inward side was free of freckles. When a high withdrawal rate was applied, a few freckles occurred on the inward side of the root region. The number and length of freckle chains increased as the withdrawal rate increased. The XRF results indicated that channel segregation formed on the surface of the root region. The segregation channels predicted by the macrosegregation simulation agreed well with the experimental observation. The concave or inclined solidification interface increased the propensity for freckle formation.

Here, we present a high ductility of the Be–Al alloy manufactured by investment casting. It was superior to most Be–Al based alloys reported so far, exhibiting high yield strength of 53∼58 MPa, ultimate tensile strength of 111∼117 MPa, and high tensile strain of 14.1–18.8 %. The many < c + a> dislocations in the Be phase were primarily responsible for the exceptionally high mechanical characteristics. A high Schmid factor for pyramidal slip led to slip transfer between the Be grains and Al grains, which may contribute to relieving stress concentration and delaying early fracture.The profuse activated pyramidal < c + a> dislocations could render the unusual high tensile strain. The high strength was attributed to both the good interfacial strength and the constraint of hard Be phase, which makes the soft Al phase strong like the hard Be phase. It demonstrates the strong texture microstructure design of the Be phase had a synergistic improvement in the strength-ductility balance, suggesting that this could be a useful tactic for enhancing the mechanical characteristics of Be–Al alloys.

Abstract The precise targeted delivery of therapeutic agents to deep regions of the brain is crucial for the effective treatment of various neurological diseases. However, achieving this goal is challenging due to the presence of the blood‒brain barrier (BBB) and the complex anatomy of the brain. Here, a biomimetic self‐propelled nanomotor with cascade targeting capacity is developed for the treatment of neurological inflammatory diseases. The self‐propelled nanomotors are designed with biomimetic asymmetric structures with a mesoporous SiO2 head and multiple MnO2 tentacles. Macrophage membrane biomimetic modification endows nanomotors with inflammatory targeting and BBB penetration abilities The MnO2 agents catalyze the degradation of H2O2 into O2, not only by reducing brain inflammation but also by providing the driving force for deep brain penetration. Additionally, the mesoporous SiO2 head is loaded with curcumin, which actively regulates macrophage polarization from the M1 to the M2 phenotype. All in vitro cell, organoid model, and in vivo animal experiments confirmed the effectiveness of the biomimetic self‐propelled nanomotors in precise targeting, deep brain penetration, anti‐inflammatory, and nervous system function maintenance. Therefore, this study introduces a platform of biomimetic self‐propelled nanomotors with inflammation targeting ability and active deep penetration for the treatment of neurological inflammation diseases.

Abstract Chronic diabetic wounds are at lifelong risk of developing diabetic foot ulcers owing to severe hypoxia, excessive reactive oxygen species (ROS), a complex inflammatory microenvironment, and the potential for bacterial infection. Here we develop a programmed treatment strategy employing live Haematococcus (HEA). By modulating light intensity, HEA can be programmed to perform a variety of functions, such as antibacterial activity, oxygen supply, ROS scavenging, and immune regulation, suggesting its potential for use in programmed therapy. Under high light intensity (658 nm, 0.5 W/cm2), green HEA (GHEA) with efficient photothermal conversion mediate wound surface disinfection. By decreasing the light intensity (658 nm, 0.1 W/cm2), the photosynthetic system of GHEA can continuously produce oxygen, effectively resolving the problems of hypoxia and promoting vascular regeneration. Continuous light irradiation induces astaxanthin (AST) accumulation in HEA cells, resulting in a gradual transformation from a green to red hue (RHEA). RHEA effectively scavenges excess ROS, enhances the expression of intracellular antioxidant enzymes, and directs polarization to M2 macrophages by secreting AST vesicles via exosomes. The living HEA hydrogel can sterilize and enhance cell proliferation and migration and promote neoangiogenesis, which could improve infected diabetic wound healing in female mice.

Air entrainment defect is a common type of defect in the casting process, which will seriously affect the quality of the casting. Numerical simulation technology can predict the occurrence of casting defects according to the evolution law of liquid metal in the process of fill ing and solidification. The simulation of air entrainment process is a hot and difficult issue in the field of numerical simulation. The evolution law of air entrainment and the tracking of induced bubbles in the process of metal filling are still lacking. So is the quantitative prediction of trained gas. In this paper, based on the numerical simulation software of Inte CAST, this paper proposes an algorithm for air entrainment search and tracking, which is used to develop a quantitative prediction system for air entrainment. The feasibility of the system is verified through the simulation calculation of the typical test pieces of the air entrainment and the prediction of air entrainment defects of the casting in the process of filling is obtained through the simulation calculation of the actual casting, which can provide a certain guiding role for the optimization of the process in the production practice.

Abstract The dense stroma of desmoplastic tumor limits nanotherapeutic penetration and hampers the antitumor immune response. Here, we report a denaturation-and-penetration strategy and the use of tin monosulfide nanoparticles (SnSNPs) as nano-sonosensitizers that can overcome the stromal barrier for the management of desmoplastic triple-negative breast cancer (TNBC). SnSNPs possess a narrow bandgap (1.18 eV), allowing for efficient electron (e−)-hole (h+) pair separation to generate reactive oxygen species under US activation. More importantly, SnSNPs display mild photothermal properties that can in situ denature tumor collagen and facilitate deep penetration into the tumor mass upon near-infrared irradiation. This approach significantly enhances sonodynamic therapy (SDT) by SnSNPs and boosts antitumor immunity. In mouse models of malignant TNBC and hepatocellular carcinoma (HCC), the combination of robust SDT and enhanced cytotoxic T lymphocyte infiltration achieves remarkable anti-tumor efficacy. This study presents an innovative approach to enhance SDT and antitumor immunity using the denaturation-and-penetration strategy, offering a potential combined sono-immunotherapy approach for the cancer nanomedicine field.

Abstract The exogenous excitation requirement and electron-hole recombination are the key elements limiting the application of catalytic therapies. Here a tumor microenvironment (TME)-specific self-triggered thermoelectric nanoheterojunction (Bi0.5Sb1.5Te3/CaO2 nanosheets, BST/CaO2 NSs) with self-built-in electric field facilitated charge separation is fabricated. Upon exposure to TME, the CaO2 coating undergoes rapid hydrolysis, releasing Ca2+, H2O2, and heat. The resulting temperature difference on the BST NSs initiates a thermoelectric effect, driving reactive oxygen species production. H2O2 not only serves as a substrate supplement for ROS generation but also dysregulates Ca2+ channels, preventing Ca2+ efflux. This further exacerbates calcium overload-mediated therapy. Additionally, Ca2+ promotes DC maturation and tumor antigen presentation, facilitating immunotherapy. It is worth noting that the CaO2 NP coating hydrolyzes very slowly in normal cells, releasing Ca2+ and O2 without causing any adverse effects. Tumor-specific self-triggered thermoelectric nanoheterojunction combined catalytic therapy, ion interference therapy, and immunotherapy exhibit excellent antitumor performance in female mice.

Abstract Mononuclear phagocytes (MPs) are vital components of host immune defenses against cancer. However, tumor‐infiltrating MPs often present tolerogenic and pro‐tumorigenic phenotypes via metabolic switching triggered by excessive lipid accumulation in solid tumors. Inspired by viral infection‐mediated MP modulation, here enveloped immunometabolic nanoparticles (immeNPs) are designed to co‐deliver a viral RNA analog and a fatty acid oxidation regulator for synergistic reshaping of intratumoral MPs. These immeNPs are camouflaged with cancer cell membranes for tumor homing and opsonized with anti‐CD163 antibodies for specific MP recognition and uptake. It is found that internalized immeNPs coordinate lipid metabolic reprogramming with innate immune stimulation, inducing M2‐to‐M1 macrophage repolarization and tolerogenic‐to‐immunogenic dendritic cell differentiation for cytotoxic T cell infiltration. The authors further demonstrate that the use of immeNPs confers susceptibility to anti‐PD‐1 therapy in immune checkpoint blockade‐resistant breast and ovarian tumors, and thereby provide a promising strategy to expand the potential of conventional immunotherapy.

The solutal convection is able to affect the dendrite growth and solute distribution during directional solidification. The solutal convection is raised by the solute difference-caused buoyancy. When solutal convection becomes intensive, solute plumes will occur, which may cause freckle defects in directional solidification of superalloys. The onset of solutal plumes depends on the solidification condition. In this study, the dendrite growth with solutal convection during directional solidification of nickel-based superalloy was investigated by two-dimensional phase-field simulations. The lattice Boltzmann method was used to solve the flow field driven by solute difference caused-buoyancy force. The pseudo-binary alloy approximation was adopted for simplification of the multicomponent alloy. The effects of the temperature gradient, pulling velocity, and isotherm inclination angle on dendrite growth and solutal convection were investigated. The dendrite growth dynamics and solutal convection pattern under different solidification conditions were analyzed. Dendrite growth velocity oscillation was observed. The effect of pulling velocity on dendrite growth velocity oscillation was analyzed.

The quality of Ti alloy casing is crucial for the safe and stable operation of aero engines. However, the fluctuation of key process parameters during the investment casting process of titanium alloy casings has a significant influence on the volume and number of porosity defects, and this influence cannot be effectively suppressed at present. Therefore, this paper proposes a strategy to control the influence of process parameters on shrinkage volume and number. This study constructed multiple regression prediction models and neural network prediction models of porosity volume and number for a ZTC4 casing by simulating the gravity investment casting process. The results show that the multiple regression prediction model and neural network prediction model of shrinkage cavity total volume have an accuracy of over 99%. The accuracy of the neural network prediction model is higher than that of the multiple regression model, and the neural network model realizes the accurate prediction of shrinkage defect volume and defect number through pouring temperature, pouring time, and mold shell temperature. The sensitivity degree of casing defects to key process parameters, from high to low, is as follows: pouring temperature, pouring time, and mold temperature. Further optimizing the key process parameter window reduces the influence of process parameter fluctuation on the volume and number of porosity defects in casing castings. This study provides a reference for actual production control process parameters to reduce shrinkage cavity and loose defects.

Abstract The advent of immunotherapy has marked a new era in cancer treatment, offering significant clinical benefits. Cell membrane as drug delivery materials has played a crucial role in enhancing cancer therapy because of their inherent biocompatibility and negligible immunogenicity. Different cell membranes are prepared into cell membrane nanovesicles (CMNs), but CMNs have limitations such as inefficient targeting ability, low efficacy, and unpredictable side effects. Genetic engineering has deepened the critical role of CMNs in cancer immunotherapy, enabling genetically engineered‐CMN (GCMN)‐based therapeutics. To date, CMNs that are surface modified by various functional proteins have been developed through genetic engineering. Herein, a brief overview of surface engineering strategies for CMNs and the features of various membrane sources is discussed, followed by a description of GCMN preparation methods. The application of GCMNs in cancer immunotherapy directed at different immune targets is addressed as are the challenges and prospects of GCMNs in clinical translation.

Cancer therapies based on energy conversion, such as photothermal therapy (PTT, light-to-thermal energy conversion) and photodynamic therapy (PDT, light-to-chemical energy conversion) have attracted extensive attention in preclinical research. However, the PTT-related hyperthermia damage to surrounding tissues and shallow penetration of PDT-applied light prevent further advanced clinical practices. Here, we developed a thermoelectric therapy (TET) based on thermoelectric materials constructed p-n heterojunction (SrTiO3/Cu2Se nanoplates) on the principle of light-thermal-electricity-chemical energy conversion. Upon irradiation and natural cooling-induced the temperature gradient (35–45 oC), a self-build-in electric field was constructed and thereby facilitated charges separation in bulk SrTiO3 and Cu2Se. Importantly, the contact between SrTiO3 (n type) and Cu2Se (p type) constructed another interfacial electric field, further guiding the separated charges to re-locate onto the surfaces of SrTiO3 and Cu2Se. The formation of two electric fields minimized probability of charges recombination. Of note, high-performance superoxide radicals and hydroxyl radicals’ generation from O2 and H2O under catalyzation by separated electrons and holes, led to intracellular ROS burst and cancer cells apoptosis without apparent damage to surrounding tissues. Construction of bulk and interfacial electric fields in heterojunction for improving charges separation and transfer is also expected to provide a robust strategy for diverse applications.

Hydrogen sulfide (H2S) is the most recently discovered gasotransmitter molecule that activates multiple intracellular signaling pathways and exerts concentration-dependent antitumor effect by interfering with mitochondrial respiration and inhibiting cellular ATP generation. Inspired by the fact that H2S can also serve as a promoter for intracellular Ca2+ influx, tumor-specific nanomodulators (I-CaS@PP) have been constructed by encapsulating calcium sulfide (CaS) and indocyanine green (ICG) into methoxy poly (ethylene glycol)-b-poly (lactide-co-glycolide) (PLGA-PEG). I-CaS@PP can achieve tumor-specific biodegradability with high biocompatibility and pH-responsive H2S release. The released H2S can effectively suppress the catalase (CAT) activity and synergize with released Ca2+ to facilitate abnormal Ca2+ retention in cells, thus leading to mitochondria destruction and amplification of oxidative stress. Mitochondrial dysfunction further contributes to blocking ATP synthesis and downregulating heat shock proteins (HSPs) expression, which is beneficial to overcome the heat endurance of tumor cells and strengthen ICG-induced photothermal performance. Such a H2S-boosted Ca2+-involved tumor-specific therapy exhibits highly effective tumor inhibition effect with almost complete elimination within 14-day treatment, indicating the great prospect of CaS-based nanomodulators as antitumor therapeutics.

Mechanical stability of lamellar microstructure in γ-TiAl has been studied, for the first time, from the perspective of three different γ/γ lamellar interfaces evolution at atomic scale via molecular dynamics simulations. Results indicate that small lamellar spacing promotes the formation of longitudinal twinning, thus influences the mechanical stability of TiAl lamellar structure. Pseudo-twin (PT) and rotational boundary (RB) lamellar interfaces transfer to each other while the true-twin (TT) lamellar interface migrates directly and annihilates resulting from interaction with longitudinal twinning during deformation. Therefore, compared with the TiAl lamellar structure with TT interface, structure with PT and RB interfaces exhibit higher mechanical stability.

Chemodynamic therapy relies on Fenton or Fenton-like reactions to produce hydroxyl radical in the tumor region. Here the authors design a two-dimensional interplanar heterojunction with in situ hydroxyl radical generation under ultrasound irradiation, showing anti-cancer activity in preclinical models.

Breast cancer is the leading cause of cancer-related fatalities in female worldwide. Effective therapies with low side effects for breast cancer treatment and prevention are, accordingly, urgently required. Targeting anticancer materials, breast cancer vaccines and anticancer drugs have been studied for many years to decrease side effects, prevent breast cancer and suppress tumors, respectively. There are abundant evidences to demonstrate that peptide-based therapeutic strategies, coupling of good safety and adaptive functionalities are promising for breast cancer therapy. In recent years, peptide-based vectors have been paid attention in targeting breast cancer due to their specific binding to corresponding receptors overexpressed in cell. To overcome the low internalization, cell penetrating peptides (CPPs) could be selected to increase the penetration due to the electrostatic and hydrophobic interactions between CPPs and cell membranes. Peptide-based vaccines are at the forefront of medical development and presently, 13 types of main peptide vaccines for breast cancer are being studied on phase III, phase II, phase I/II and phase I clinical trials. In addition, peptide-based vaccines including delivery vectors and adjuvants have been implemented. Many peptides have recently been used in clinical treatments for breast cancer. These peptides show different anticancer mechanisms and some novel peptides could reverse the resistance of breast cancer to susceptibility. In this review, we will focus on current studies of peptide-based targeting vectors, CPPs, peptide-based vaccines and anticancer peptides for breast cancer therapy and prevention.

A parallel three-dimensional (3D) cellular automaton (CA) model is developed for dendritic growth simulation during solidification of binary alloy. The CA model is implemented using the graphic processing unit (GPU). Compute Unified Device Architecture (CUDA) is combined with Message Passing Interface (MPI) to perform large-scale simulation on the multi-GPU architecture. A CUDA-Aware OpenMPI is used to reduce the communication cost between different GPU cards. The accuracy and the speedup ratio of the CA model are investigated. First, the simulated steady-state tip velocity under different undercooling is compared with the LGK analytical solution. Then, dendritic growth during directional solidification and equiaxed multi-dendrite growth are simulated. Dendritic growth simulation with a domain size up to 453 million grids is performed. Finally, the speedup ratio of the CA model using four GPUs is compared with that using four CPU processes via MPI, which leads to a maximal speedup ratio of 152.19. The developed CA model achieves high parallel performance compared with the MPI-based parallel model. The developed CA model is capable of predicting the columnar to equiaxed transition (CET) event during directional solidification. The results indicate that increasing cooling rate promotes the occurrence of the equiaxed dendrites in the melt ahead of the solidification front, and equiaxed dendrites are prone to nucleate in the columnar dendrite groove zone when a middle cooling rate is applied.

Hydrogels have blossomed as superstars in various fields, owing to their prospective applications in tissue engineering, soft electronics and sensors, flexible energy storage, and biomedicines. Two-dimensional (2D) nanomaterials, especially 2D mono-elemental nanosheets (Xenes) exhibit high aspect ratio morphology, good biocompatibility, metallic conductivity, and tunable electrochemical properties. These fascinating characteristics endow numerous tunable application-specific properties for the construction of Xene-based hydrogels. Hierarchical multifunctional hydrogels can be prepared according to the application requirements and can be effectively tuned by different stimulation to complete specific tasks in a spatiotemporal sequence. In this review, the synthesis mechanism, properties, and emerging applications of Xene hydrogels are summarized, followed by a discussion on expanding the performance and application range of both hydrogels and Xenes. Public summary: • Two-dimensional mono-elemental nanosheets (Xenes) endow tunable application • Synthesis mechanism, properties, and applications of Xene hydrogels are summarized • Expanding performance and applications of both hydrogels and Xenes are presented

Multifunctional materials with a number of effects are important for dealing with the complex environment in cancer therapy. Here, the authors report on surface-oxidized arsenene nanosheets coated with polydopamine and cancer cell membrane as a multi theranostic tumour targeting cancer therapy.

Abstract Background Duckweed is considered a promising feedstock for bioethanol production due to its high biomass and starch production. The starch content can be promoted by plant growth regulators after the vegetative reproduction being inhibited. Maleic hydrazide (MH) has been reported to inhibit plant growth, meantime to increase biomass and starch content in some plants. However, the molecular explanation on the mechanism of MH action is still unclear. Results To know the effect and action mode of MH on the growth and starch accumulation in Spirodela polyrrhiza 7498, the plants were treated with different concentrations of MH. Our results showed a substantial inhibition of the growth in both fronds and roots, and increase in starch contents of plants after MH treatment. And with 75 µg/mL MH treatment and on the 8th day of the experiment, starch content was the highest, about 40 mg/g fresh weight, which is about 20-fold higher than the control. The I2-KI staining and TEM results confirmed that 75 µg/mL MH-treated fronds possessed more starch and big starch granules than that of the control. No significant difference for both in the photosynthetic pigment content and the chlorophyll fluorescence parameters of PII was found. Differentially expressed transcripts were analyzed in S. polyrrhiza 7498 after 75 µg/mL MH treatment. The results showed that the expression of some genes related to auxin response reaction was down-regulated; while, expression of some genes involved in carbon fixation, C4 pathway of photosynthesis, starch biosynthesis and ABA signal transduction pathway was up-regulated. Conclusion The results provide novel insights into the underlying mechanisms of growth inhibition and starch accumulation by MH treatment, and provide a selective way for the improvement of starch production in duckweed.

Abstract Stanene (Sn)-based materials have been extensively applied in industrial production and daily life, but their potential biomedical application remains largely unexplored, which is due to the absence of the appropriate and effective methods for fabricating Sn-based biomaterials. Herein, we explored a new approach combining cryogenic exfoliation and liquid-phase exfoliation to successfully manufacture two-dimensional (2D) Sn nanosheets (SnNSs). The obtained SnNSs exhibited a typical sheet-like structure with an average size of ~ 100 nm and a thickness of ~ 5.1 nm. After PEGylation, the resulting PEGylated SnNSs (SnNSs@PEG) exhibited good stability, superior biocompatibility, and excellent photothermal performance, which could serve as robust photothermal agents for multi-modal imaging (fluorescence/photoacoustic/photothermal imaging)-guided photothermal elimination of cancer. Furthermore, we also used first-principles density functional theory calculations to investigate the photothermal mechanism of SnNSs, revealing that the free electrons in upper and lower layers of SnNSs contribute to the conversion of the photo to thermal. This work not only introduces a new approach to fabricate 2D SnNSs but also establishes the SnNSs-based nanomedicines for photonic cancer theranostics. This new type of SnNSs with great potential in the field of nanomedicines may spur a wave of developing Sn-based biological materials to benefit biomedical applications.

Dissimilar friction stir lap welded joints of AA6061-T6 and Ti6Al4V were successfully welded using suitable parameters, and the effect of tool rotational speed was studied to investigate the influence on mechanical properties, microstructure, and fracture mechanisms. It was observed that tool rotational speed has a great effect on the strength of the welded joint, as it controls the amount of heat input and plasticity at Al/Ti interface as well as the formation of intermetallic compounds (IMCs) and different brittle phases that were formed at the Al/Ti mixture. The maximum shear strength of 3.5 KN was achieved using low rotational speed of 600 rpm and maximum hardness of 384 HV, while minimum shear strength of 2.5 KN was attained at 1000 rpm with minimum hardness of 343.2 HV. Hybrid fracture surface was produced at lower rotation speed which had both brittle and ductile characteristics, while brittle fracture mechanisms were observed at high rotational speed due to the concentration of brittle IMCs layers, TiAl, and TiAl3 phases at the interface due to the excessive heat input which causes pores and cracks and thus deteriorating joint strength.

Clay-based nanomaterials are of wide interest but problems extracting the 2D functional core layers have limited potential applications. Here, the authors report on the wet exfoliation of vermiculite by alkali etching to obtain the core layers and explore the application of the materials in cancer theranostics.

Abstract Exogenous stimulation catalytic therapy has received enormous attention as it holds great promise to address global medical issues. However, the therapeutic effect of catalytic therapy is seriously restricted by the fast charge recombination and the limited utilization of exogenous stimulation by catalysts. In the past few decades, many strategies have been developed to overcome the above serious drawbacks, among which heterojunctions are the most widely used and promising strategy. This review attempts to summarize the recent progress in the rational design and fabrication of heterojunction nanomedicine, such as semiconductor–semiconductor heterojunctions (including type I, type II, type III, PN, and Z–scheme junctions) and semiconductor–metal heterojunctions (including Schottky, Ohmic, and localized surface plasmon resonance–mediated junctions). The catalytic mechanisms and properties of the above junction systems are also discussed in relation to biomedical applications, especially cancer treatment and sterilization. This review concludes with a summary of the challenges and some perspectives on future directions in this exciting and still evolving field of research.

Polyelectrolyte-doped microcapsules (PDM) was fabricated by coaxial electrospray of a mixture of glycerol and water containing 10 mg/mL cationic polyelectrolyte poly(allylamine hydrochloride) (PAH) fed as the core phase solution, and a N,N-dimethylacetylamide solution of 10 wt% polyurethane fed as the shell phase solution. Multi-enzyme system involving Candida Antarctica lipase B (CALB), glucose oxidase (GOD), and horseradish peroxidase (HRP) for cascade reaction was assembled in the PDM at three different places, namely, surface, shell, and lumen. Placing of enzyme inside aqueous lumen of the PDM was realized by in situ encapsulation through adding the enzyme in the core-phase solution for coaxial electrospray. By ion-pairing of enzyme with cationic surfactant CTAB, an organic soluble enzyme-CTAB complex was prepared, so that in situ embedding of enzyme in the shell of the PDM was realized by adding it into the shell phase solution. Surface attachment of enzymes was achieved by layer-by-layer (LbL) technology, which is based on the ion-exchange interactions between oppositely charged enzymes and PAH that was doped in PDM. The enzyme-decorated microcapsule was then studied as a micro-bioreactor, in which 1-Oxododecyla-α-glucopyranoside was converted by CALB to glucose, which was oxidised by GOD to gluconolactone in a second step. The hydrogen peroxide produced was then used by HRP to oxidize ABTS to form coloured radical cation ABTS•+ for activity analysis. The successful fabrication of the PDM and precise localization of enzymes in the PDM by different strategies were fully characterized. By varying the immobilization strategy, totally six PDM bioreactors with three enzymes precisely positional assembled in different strategies were constructed and their activities for the cascade reaction were investigated and compared. The PDM micro-bioreactor prepared by novel electrospray technologies provide a smart platform for positional assembly of multi-enzyme cascade reaction in a precise and well-controlled manner.

A balance between high stability and rapid degradation is required for effective photothermal anti-cancer agents. Here, the authors use Cu2+ to accelerate the degradation of black phosphorus nanosheets while enhancing its photothermal ability and apply this material for PET-guided, CDT-enhanced combination cancer therapy in mice.

Aluminum alloys have low weldability by conventional fusion welding processes. Friction stir welding (FSW) is a promising alternative to traditional fusion welding techniques for producing high quality aluminum joints. The quality of the welded joints is highly dependent on the process parameters used during welding. In this research, a new approach was developed to predict the process parameters and mechanical properties of AA6061-T6 aluminium alloy joints in terms of ultimate tensile strength (UTS). A new hybrid artificial neural network (ANN) approach has been proposed in which Henry Gas Solubility Optimization (HGSO) algorithm has been incorporated to improve the performance of Random Vector Functional Link (RVFL) network. The HGSO-RVFL model was constructed with four parameters; rotational speed, welding speed, tilt angle, and pin profile. The validity of the model was tested, and it was demonstrated that the HGSO-RVFL model is a powerful technique for predicting the UTS of friction stir welded (FSWD) joints. In addition, the effects of process parameters on UTS of welded joints were discussed, where a significant agreement was observed between experimental results and predicted results which indicates the high performance of the model developed to predict the appropriate welding parameters that achieve optimal UTS.

Measurements on refractive index and its distribution of microfluidics are widely applied in the field of biological detection, chemical analysis, material researches, medical diagnostics, and lab on a chip. Since the volume of the microfluidics is ultra-small, such as nanoliters or even picoliters, measuring the refractive index of microfluidics is challenging. We here presents an effective method to measure the refractive index and its two-dimensional distribution of picoliter microfluidics by the SWLI (scanning white light interference) microscopy technology. This method has the advantages of simplicity, low cost, non-contact, wide measurement range and high precision. We conduct the experiment to measure the refractive index of 2.4 picoliters liquid. The resolution is 10-4RIU (refractive index unit), and the relative error is 10-4 compared with the Abbe refractometer. We obtained the relationship between refractive index and concentration of glucose solution. In addition, we can measure the 2D (two-dimensional) distribution of RI (refractive index) of liquids. We can observe the liquid interface between deionized water and liquid paraffin clearly. Besides, we can observe the process of solute dissolution in the liquid and the change of refractive index.

Abstract Neighboring carbon and sandwiched between non‐metals and metals in the periodic table of the elements, boron is one of the most chemically and physically versatile elements, and can be manipulated to form dimensionally low planar structures (borophene) with intriguing properties. Herein, the theoretical research and experimental developments in the synthesis of borophene, as well as its excellent properties and application in many fields, are reviewed. The decade‐long effort toward understanding the size‐dependent structures of boron clusters and the theory‐directed synthesis of borophene, including bottom‐up approaches based on different foundations, as well as up‐down approaches with different exfoliation modes, and the key factors influencing the synthetic effects, are comprehensively summarized. Owing to its excellent chemical, electronic, mechanical, and thermal properties, borophene has shown great promise in supercapacitor, battery, hydrogen‐storage, and biomedical applications. Furthermore, borophene nanoplatforms used in various biomedical applications, such as bioimaging, drug delivery, and photonic therapy, are highlighted. Finally, research progress, challenges, and perspectives for the future development of borophene in large‐scale production and other prospective applications are discussed.

In this paper, the deviation from eutectic composition in boundary layer for eutectic growth is studied by phase-field method. According to a series of artificial phase diagram, the lamellar eutectic growth of these alloy is simulated during directional solidification. At steady state, average growth velocity of eutectic lamella is equal to the pulling velocity. With the increasing of the liquidus slope of β phase, the average composition in boundary layer would deviate from eutectic composition and the deviation increases. The constitutional undercooling difference between both solid phases caused by the deviation increases with the increasing of the deviation. The β phase would develop a depression under the influence of the deviation.

Abstract The development of effective and safe vehicles to deliver small interfering RNA (siRNA) and chemotherapeutics remains a major challenge in RNA interference-based combination therapy with chemotherapeutics, which has emerged as a powerful platform to treat drug-resistant cancer cells. Herein, we describe the development of novel all-in-one fluorescent silicon nanoparticles (SiNPs)-based nanomedicine platform for imaging-guided co-delivery of siRNA and doxorubicin (DOX). This approach enhanced therapeutic efficacy in multidrug-resistant breast cancer cells (i.e., MCF-7/ADR cells). Typically, the SiNP-based nanocarriers enhanced the stability of siRNA in a biological environment (i.e., medium or RNase A) and imparted the responsive release behavior of siRNA, resulting in approximately 80% down-regulation of P-glycoprotein expression. Co-delivery of P-glycoprotein siRNA and DOX led to > 35-fold decrease in the half maximal inhibitory concentration of DOX in comparison with free DOX, indicating the pronounced therapeutic efficiency of the resultant nanocomposites for drug-resistant breast cancer cells. The intracellular time-dependent release behaviors of siRNA and DOX were revealed through tracking the strong and stable fluorescence of SiNPs. These data provide valuable information for designing effective RNA interference-based co-delivery carriers.

Abstract Biotite, also called black mica (BM), is a group of sheet silicate minerals with great potential in various fields. However, synthesis of high‐quality BM nanosheets (NSs) remains a huge challenge. Here, an exfoliation approach is provided that combines calcination, n‐butyllithium exchange and intercalation, and liquid exfoliating processes for the high‐yield synthesis of ultrathin BM NSs. Due to the presence of MgO, Fe2O3, and FeO in these NSs, PEGylated BM can be engineered as an intelligent theranostic platform with the following unique features: i) Fe3+ can damage the tumor microenvironment (TME) through glutathione consumption and O2 production; ii) Generated O2 can be further catalyzed by MgO with oxygen vacancy to generate ·O2−; iii) The Fe2+‐catalyzed Fenton reaction can produce ·OH by disproportionation reactions of H2O2 in the TME; iv) Reactions in (i) and (iii) circularly regenerate Fe2+ and Fe3+ for continuous consumption of glutathione and H2O2 and constant production of ·OH and O2; v) The NSs can be triggered by a 650 nm laser to generate ·O2− from O2 as well as by an 808 nm laser to generate local hyperthermia; and vi) The fluorescent, photoacoustic, and photothermal imaging capabilities of the engineered NSs allow for multimodal imaging‐guided breast cancer treatment.

To accelerate the large-scale cellular automaton (CA) simulation for grain growth, a parallel CA model for grain growth was developed. The model was implemented based on the compute unified device architecture (CUDA) parallel computing platform. The model was verified by the grain growth of a single crystal and the columnar-to-equiaxed transition (CET) of an Al-7wt% Si specimen of uniform undercooling with a constant cooling rate. The grid independence of the model was verified. The grain growth of a plate-like casting of nickel-based superalloy during directional solidification process was simulated and the obtained results of grain density at each section with different heights were compared with the experimental data. The CET transition of directional solidified Al-7wt% Si cylindrical ingot was simulated. The grain texture and cooling curves were in good agreement with experimental results from the literature. Finally, high parallel performance of the CA model was obtained and evaluated.

Biochemical analysis in reliable, low-toxicity, and real-time manners are essentially important for exploring and unraveling biological events and related mechanisms. Silicon nanomaterial-based sensors and probes have potentiality to satisfy the above-mentioned requirements. Herein, we present an overview of the recent significant improvement in large-scale and facile synthesis of high-quality silicon nanomaterials and the research progress of biosensing and bioimaging analysis based on silicon nanomaterials. We especially illustrate the advanced applications of silicon nanomaterials in the field of ultrasensitive biomolecular detection and dynamic biological imaging analysis, with a focus on real-time and long-term detection. In the final section of this review, we discuss the major challenges and promising development in this domain.

The mesoscopic grain model is a multiscale model which takes into account both the dendrite growth mechanism and the vast numerical computation of the actual castings. Due to the pursuit of efficient computation, the mesoscopic grain calculation accuracy is lower than that of dendrite growth model. Improving the accuracy of mesoscopic grain model is a problem to be solved urgently. In this study, referring to the calculation method of solid fraction in microscopic dendrite growth model, a cellular automata model of 3D mesoscopic grain evolution for solid fraction calculated quantitatively at the scale of cell is developed. The developed model and algorithm validation for grain growth simulation is made by comparing the numerical results with the benchmark experimental data and the analytical predictions. The results show that the 3D grain envelopes simulated by the developed model and algorithm are coincident with the shape predicted by the analytical model to a certain extent. Then, the developed model is applied to the numerical simulation of solidification process of nickel-based superalloys, including equiaxed and columnar dendritic grain growth. Our results show good agreement with the related literature.

Abstract LHPP has been shown to be a new tumor suppressor, and has a tendency to be under-expressed in a variety of cancers. Oncolytic virotheray is a promising therapeutics for lung cancer in recent decade years. Here we successfully constructed a new recombinant oncolytic adenovirus GD55-LHPP and investigated the effect of GD55-LHPP on the growth of lung cancer cells in vitro and in vivo. The results showed that LHPP had lower expression in either lung cancer cells or clinical lung cancer tissues compared with normal cells or tissues, and GD55-LHPP effectively mediated LHPP expression in lung cancer cells. GD55-LHPP could effectively inhibit the proliferation of lung cancer cell lines and rarely affected normal cell growth. Mechanically, the oncolytic adenovirus GD55-LHPP was able to induce stronger apoptosis of lung cancer cells compared with GD55 through the activation of caspase signal pathway. Notably, GD55-LHPP also activated autophagy-related signal pathway. Further, GD55-LHPP efficiently inhibited tumor growth in lung cancer xenograft in mice and prolonged animal survival rate compared with the control GD55 or PBS. In conclusion, the novel construct GD55-LHPP provides a valuable strategy for lung cancer-targeted therapy and develop the role of tumor suppress gene LHPP in lung cancer gene therapy.

Abstract Suicidal behavior and non-suicidal self-injury (NSSI) are common in adolescent patients with major depressive disorder (MDD). Thus, delineating the unique characteristics of suicide attempters having adolescent MDD with NSSI is important for suicide prediction in the clinical setting. Here, we performed psychological and biochemical assessments of 130 youths having MDD with NSSI. Participants were divided into two groups according to the presence/absence of suicide attempts (SAs). Our results demonstrated that the age of suicide attempters is lower than that of non-attempters in participants having adolescent MDD with NSSI; suicide attempters had higher Barratt Impulsiveness Scale (BIS-11) impulsivity scores and lower serum CRP and cortisol levels than those having MDD with NSSI alone, suggesting levels of cortisol and CRP were inversely correlated with SAs in patients with adolescent MDD with NSSI. Furthermore, multivariate regression analysis revealed that NSSI frequency in the last month and CRP levels were suicidal ideation predictors in adolescent MDD with NSSI, which may indicate that the increased frequency of NSSI behavior is a potential risk factor for suicide. Additionally, we explored the correlation between psychological and blood biochemical indicators to distinguish suicide attempters among participants having adolescent MDD with NSSI and identified a unique correlation network that could serve as a marker for suicide attempters. Our research data further suggested a complex correlation between the psychological and behavioral indicators of impulsivity and anger. Therefore, our study findings may provide clues to identify good clinical warning signs for SA in patients with adolescent MDD with NSSI.

With a significant increase in the obesity epidemic in China, addressing adolescent obesity should be highlighted as a priority. The current qualitative study aims to explore the perspectives of key stakeholders regarding adolescent obesity, providing guidance for developing effective obesity interventions for Chinese adolescents. A total of 12 focus group discussions were convened with a range of representative stakeholders including adolescents (n = 37), parents (n = 28), and school staff (n = 21) from sample schools. Semi-structured topic guides were used for data collection. All data were transcribed verbatim and analyzed thematically. From multiple stakeholder perspectives, we finally identified 3 overarching themes ( Understanding adolescent obesity, Key healthy lifestyles, and Barriers to obesity prevention practices ) and 8 sub-themes. While participants had mixed perceptions of status and prevalence of adolescent obesity, all acknowledged the serious health consequences associated with it. As significant modifiable risk factors, unhealthy diet and physical activity were identified to be prevalent among Chinese teenagers and lead to excessive weight gain. However, a variety of individual, environmental and sociocultural factors hindered the implementation of healthy lifestyles, affecting adolescent obesity prevention and control. Given adolescent obesity is a complex, multifactorial and multilevel public issue, comprehensive lifestyle interventions are recommended that synergistically engage multiple stakeholders across key communities to fight the ongoing obesity epidemic.

Propylene glycol (PG) and vegetable glycerin (VG) are the most common solvents used in electronic cigarette liquids. No long-term inhalation toxicity assessments have been performed combining conventional and multi-omics approaches on the potential respiratory effects of the solvents in vivo. In this study, the systemic toxicity of aerosol generated from a ceramic heating coil-based e-cigarette was evaluated. First, the aerosol properties were characterized, including carbonyl emissions, the particle size distribution, and aerosol temperatures. To determine toxicological effects, rats were exposed, through their nose only, to filtered air or a propylene glycol (PG)/ glycerin (VG) (50:50, %W/W) aerosol mixture at the target concentration of 3 mg/L for six hours daily over a continuous 28-day period. Compared with the air group, female rats in the PG/VG group exhibited significantly lower body weights during both the exposure period and recovery period, and this was linked to a reduced food intake. Male rats in the PG/VG group also experienced a significant decline in body weight during the exposure period. Importantly, rats exposed to the PG/VG aerosol showed only minimal biological effects compared to those with only air exposure, with no signs of toxicity. Moreover, the transcriptomic, proteomic, and metabolomic analyses of the rat lung tissues following aerosol exposure revealed a series of candidate pathways linking aerosol inhalation to altered lung functions, especially the inflammatory response and disease. Dysregulated pathways of arachidonic acids, the neuroactive ligand-receptor interaction, and the hematopoietic cell lineage were revealed through integrated multi-omics analysis. Therefore, our integrated multi-omics approach offers novel systemic insights and early evidence of environmental-related health hazards associated with an e-cigarette aerosol using two carrier solvents in a rat model.

Providencia as an opportunistic pathogen can cause serious infection, and moreover the emergence of multi-drug-resistant Providencia strains poses a potentially life-threatening risk to public health. However, a comprehensive genomic study to reveal the population structure and dissemination of Providencia is still lacking. In this study, we conducted a genomic epidemiology analysis on the 580 global sequenced Providencia isolates, including 257 ones sequenced in this study (42 ones were fully sequenced). We established a genome sequence-based species classification scheme for Providencia, redefining the conventional 11 Providencia species into seven genocomplexes that were further divided into 18 genospecies, providing an extensively updated reference for Providencia species discrimination based on the largest Providencia genome dataset to date. We then dissected the profile of antimicrobial resistance genes and the prevalence of multi-drug-resistant Providencia strains among these genocomplexes/genospecies, disclosing the presence of diverse and abundant antimicrobial resistance genes and high resistance ratios against multiple classes of drugs in Providencia. We further dissected the genetic basis for the spread of blaNDM-1 in Providencia. blaNDM-1 genes were mainly carried by five incompatible (Inc) groups of plasmids: IncC, IncW, IncpPROV114-NR, IncpCHS4.1-3, and IncpPrY2001, and the last three were newly designated in this study. By tracking the spread of blaNDM-1-carrying plasmids, IncC, IncpPROV114-NR, IncpCHS4.1-3, and IncpPrY2001 plasmids were found to be highly involved in parallel horizontal transfer or vertical clonal expansion of blaNDM-1 among Providencia. Overall, our study provided a comprehensive genomic view of species differentiation, antimicrobial resistance prevalence, and plasmid-mediated blaNDM-1 dissemination in Providencia.

The high risk for anxiety and depression among individuals with stress has become a growing concern globally. Stress-related mental disorders are often accompanied by symptoms of metabolic dysfunction. Cordycepin is a Chinese herbal medicine commonly used for its metabolism-enhancing effects. We aimed to investigate the dose-dependent effects of cordycepin on psycho-metabolic disorders induced by stress. Our behavioral tests revealed that 12.5 mg/kg cordycepin by oral gavage significantly attenuated the anxiety- and depression-like behaviors induced by stress in mice. At 25 mg/kg, cordycepin restored the reduced weight and cell size of adipose tissues caused by stress. Besides ameliorating the metabolic dysbiosis of gut microbiota due to stress, cordycepin significantly reduced the elevated contents of 5-hydroxyindoleacetic acid in the serum and prefrontal cortex at 12.5 mg/kg and reversed the decrease in adipose induced by stress at 25 mg/kg. Correlation analyses further revealed that 12.5 mg/kg cordycepin reversed stress-induced changes in the intestinal microbiome of NK4A214_group and decreased serum Myristic acid and PC(15:0/18:1(11Z)) and cytokines, such as IFN-γ and IL-1β. 25 mg/kg cordycepin reversed stress-induced changes in the abundances of Prevoteaceae_UCG-001 and Desulfovibrio, increased serum L-alanine level, and decreased serum Inosine-5'-monophosphate level. Cordycepin thereby ameliorated the anxiety- and depression-like behaviors as well as disturbances in the adipose metabolism of mice exposed to stress. Overall, these findings offer evidence indicating that the prominent effects of cordycepin in the brain and adipose tissues are dose dependent, thus highlight the importance of evaluating the precise therapeutic effects of different cordycepin doses on psycho-metabolic diseases.

Abstract Pediatric steroid-sensitive nephrotic syndrome (pSSNS) is the most common childhood glomerular disease. Previous genome-wide association studies (GWAS) identified a risk locus in the HLA Class II region and three additional independent risk loci. But the genetic architecture of pSSNS, and its genetically driven pathobiology, is largely unknown. Here, we conduct a multi-population GWAS meta-analysis in 38,463 participants (2440 cases). We then conduct conditional analyses and population specific GWAS. We discover twelve significant associations—eight from the multi-population meta-analysis (four novel), two from the multi-population conditional analysis (one novel), and two additional novel loci from the European meta-analysis. Fine-mapping implicates specific amino acid haplotypes in HLA-DQA1 and HLA-DQB1 driving the HLA Class II risk locus. Non-HLA loci colocalize with eQTLs of monocytes and numerous T-cell subsets in independent datasets. Colocalization with kidney eQTLs is lacking but overlap with kidney cell open chromatin suggests an uncharacterized disease mechanism in kidney cells. A polygenic risk score (PRS) associates with earlier disease onset. Altogether, these discoveries expand our knowledge of pSSNS genetic architecture across populations and provide cell-specific insights into its molecular drivers. Evaluating these associations in additional cohorts will refine our understanding of population specificity, heterogeneity, and clinical and molecular associations.

The increasing global prevalence of nonalcoholic fatty liver disease (NAFLD) starves for effective therapy, but no agent has been approved yet. We sought to evaluate the therapy of cefminox sodium (CMNX) on fatty accumulation in animal and cell models and explore the underlying mechanisms. The results revealed that CMNX reduced the gain of the liver and alleviated fatty accumulation both in high-fat high-sugar diet (HFHSD) mice's livers and WRL-68 cells. In HFHSD mice's livers and FFAs exposure hepatic cells, ACC1, SREBP-1c, and CYP2E1 were enhanced expression, which were reversed by CMNX treatment. In addition, PPARγ, PPARα, PCK1, and ACSL4 expressions were increased in CMNX-treated WRL-68 cells. These findings suggest that CMNX improves fatty accumulation in HFHSD mice/hepatic cells by restraining fatty acid synthesis and facilitating fatty acid oxidation.

Since their introduction in the United States and Europe in 2007, electronic cigarettes (E-Cigs) have become increasingly popular among smokers. Nicotine, a key component in both tobacco and e-cigarettes, can exist in two forms: nicotine-freebase (FBN) and nicotine salts (NS). While nicotine salt is becoming more popular in e-cigarettes, the effect of nicotine salts on reinforcement-related behaviors remains poorly understood. This study aimed to compare the reinforcing effects of nicotine and nicotine salts in animal models of drug self-administration and explore potential mechanisms that may contribute to these differences. The results demonstrated that three nicotine salts (nicotine benzoate, nicotine lactate, and nicotine tartrate) resulted in greater reinforcement-related behaviors in rats compared to nicotine-freebase. Moreover, withdrawal-induced anxiety symptoms were lower in the three nicotine salt groups than in the nicotine-freebase group. The study suggested that differences in the pharmacokinetics of nicotine-freebase and nicotine salts in vivo may explain the observed behavioral differences. Overall, this study provides valuable insights into the reinforcing effects of nicotine as well as potential differences between nicotine-freebase and nicotine salts.

BackgroundTuberculosis (TB) remains a major global health concern, ranking as the second most lethal infectious disease following COVID-19. Smear-Negative Pulmonary Tuberculosis (SNPT) and Smear-Positive Pulmonary Tuberculosis (SPPT) are two common types of pulmonary tuberculosis characterized by distinct bacterial loads. To date, the precise molecular mechanisms underlying the differences between SNPT and SPPT patients remain unclear. In this study, we aimed to utilize proteomics analysis for identifying specific protein signatures in the plasma of SPPT and SNPT patients and further elucidate the molecular mechanisms contributing to different disease pathogenesis.MethodsPlasma samples from 27 SPPT, 37 SNPT patients and 36 controls were collected and subjected to TMT-labeled quantitative proteomic analyses and targeted GC-MS-based lipidomic analysis. Ingenuity Pathway Analysis (IPA) was then performed to uncover enriched pathways and functionals of differentially expressed proteins.ResultsProteomic analysis uncovered differential protein expression profiles among the SPPT, SNPT, and Ctrl groups, demonstrating dysfunctional immune response and metabolism in both SPPT and SNPT patients. Both groups exhibited activated innate immune responses and inhibited fatty acid metabolism, but SPPT patients displayed stronger innate immune activation and lipid metabolic inhibition compared to SNPT patients. Notably, our analysis uncovered activated antigen-presenting cells (APCs) in SNPT patients but inhibited APCs in SPPT patients, suggesting their critical role in determining different bacterial loads/phenotypes in SNPT and SPPT. Furthermore, some specific proteins were detected to be involved in the APC activation/acquired immune response, providing some promising therapeutic targets for TB.ConclusionOur study provides valuable insights into the differential molecular mechanisms underlying SNPT and SPPT, reveals the critical role of antigen-presenting cell activation in SNPT for effectively clearing the majority of Mtb in bodies, and shows the possibility of APC activation as a novel TB treatment strategy.

IntroductionNon-tuberculous mycobacteria (NTM) is a major category of environmental bacteria in nature that can be divided into rapidly growing mycobacteria (RGM) and slowly growing mycobacteria (SGM) based on their distinct growth rates. To explore differential molecular mechanisms between RGM and SGM is crucial to understand their survival state, environmental/host adaptation and pathogenicity. Comparative genomic analysis provides a powerful tool for deeply investigating differential molecular mechanisms between them. However, large-scale comparative genomic analysis between RGM and SGM is still uncovered.MethodsIn this study, we screened 335 high-quality, non-redundant NTM genome sequences covering 187 species from 3,478 online NTM genomes, and then performed a comprehensive comparative genomic analysis to identify differential genomic characteristics and featured genes/protein domains between RGM and SGM.ResultsOur findings reveal that RGM has a larger genome size, more genes, lower GC content, and more featured genes/protein domains in metabolism of some main substances (e.g. carbohydrates, amino acids, nucleotides, ions, and coenzymes), energy metabolism, signal transduction, replication, transcription, and translation processes, which are essential for its rapid growth requirements. On the other hand, SGM has a smaller genome size, fewer genes, higher GC content, and more featured genes/protein domains in lipid and secondary metabolite metabolisms and cellular defense mechanisms, which help enhance its genome stability and environmental adaptability. Additionally, orthogroup analysis revealed the important roles of bacterial division and bacteriophage associated genes in RGM and secretion system related genes for better environmental adaptation in SGM. Notably, PCoA analysis of the top 20 genes/protein domains showed precision classification between RGM and SGM, indicating the credibility of our screening/classification strategies.DiscussionOverall, our findings shed light on differential underlying molecular mechanisms in survival state, adaptation and pathogenicity between RGM and SGM, show the potential for our comparative genomic pipeline to investigate differential genes/protein domains at whole genomic level across different bacterial species on a large scale, and provide an important reference and improved understanding of NTM.

The rapid spread of carbapenemase-producing Klebsiella pneumoniae (cpKP) poses serious threats to public health; however, the underlying genetic basis for its dissemination is still unknown. We conducted a comprehensive genomic epidemiology analysis on 420 cpKP isolates collected from 70 hospitals in 24 provinces/autonomous regions/municipalities of China during 2009–2017 by short-/long-read sequencing. The results showed that most cpKP isolates were categorized into clonal group 258 (CG258), in which ST11 was the dominant clone. Phylogenetic analysis revealed three major clades including the top one of Clade 3 for CG258 cpKP isolates. Additionally, carbapenemase gene analysis indicated that blaKPC was dominant in the cpKP isolates, and most blaKPC genes were located in five major incompatibility (Inc) groups of blaKPC-harboring plasmids. Importantly, three advantageous combinations of host–blaKPC-carrying plasmid (Clade 3.1+3.2–IncFIIpHN7A8, Clade 3.1+3.2–IncFIIpHN7A8:IncR, and Clade 3.3–IncFIIpHN7A8:IncpA1763-KPC) were identified to confer cpKP isolates the advantages in both genotypes (strong correlation/coevolution) and phenotypes (resistance/growth/competition) to facilitate the nationwide spread of ST11/CG258 cpKP. Intriguingly, Bayesian skyline analysis illustrated that the three advantageous combinations might be directly associated with the strong population expansion during 2007–2008 and subsequent maintenance of the population of ST11/CG258 cpKP after 2008. We then examined drug resistance profiles of these cpKP isolates and proposed combination treatment regimens for CG258/non-CG258 cpKP infections. Thus, the findings of our systematical analysis shed light on the molecular epidemiology and genetic basis for the dissemination of ST11/CG258 cpKP in China, and much emphasis should be given to the close monitoring of advantageous cpKP–plasmid combinations.

The treatment of diabetic ulcer (DU) remains a major clinical challenge due to the complex wound-healing milieu that features chronic wounds, impaired angiogenesis, persistent pain, bacterial infection, and exacerbated inflammation. A strategy that effectively targets all these issues has proven elusive. Herein, we use a smart black phosphorus (BP)-based gel with the characteristics of rapid formation and near-infrared light (NIR) responsiveness to address these problems. The in situ sprayed BP-based gel could act as 1) a temporary, biomimetic "skin" to temporarily shield the tissue from the external environment and accelerate chronic wound healing by promoting the proliferation of endothelial cells, vascularization, and angiogenesis and 2) a drug "reservoir" to store therapeutic BP and pain-relieving lidocaine hydrochloride (Lid). Within several minutes of NIR laser irradiation, the BP-based gel generates local heat to accelerate microcirculatory blood flow, mediate the release of loaded Lid for "ondemand" pain relief, eliminate bacteria, and reduce inflammation. Therefore, our study not only introduces a concept of in situ sprayed, NIR-responsive pain relief gel targeting the challengingwound-healing milieu in diabetes but also provides a proof-of-concept application of BP-based materials in DU treatment. [ABSTRACT FROM AUTHOR]