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Inefficient drug penetration hurdled by the stroma in the tumor tissue leads to a diminished therapeutic effect for drugs and a reduced infiltration level of immune cells. Herein, we constructed a PEGylated dendritic epirubicin (Epi) prodrug (Epi-P4D) to regulate the metabolism of cancer-associated fibroblasts (CAFs), thus enhancing Epi penetration into both multicellular tumor spheroids (MTSs) and tumor tissues in mouse colon cancer (CT26), mouse breast cancer (4T1) and human breast cancer (MDA-MB-231) models. Enhanced cytotoxicity against CT26 MTSs and remarkable antitumor efficacy of Epi-P4D were ascribed to reduced fibronectin, α-SMA, and collagen secretion. Besides, thinning of the tumor tissue stroma and efficient eradication of tumor cells promoted the immunogenic cell death effect for dendritic cell (DC) maturation and subsequent immune activation, including elevating the CD4+ T cell population, reducing CD4+ and CD8+ T cell hyperactivation and exhaustion, and amplifying the natural killer (NK) cell proportion and effectively activating them. As a result, this dendritic nanomedicine thinned the stroma of tumor tissues to enhance drug penetration and facilitate immune cell infiltration for elevated antitumor efficacy.

Summary: Increasing evidence indicates that immunotherapy is hindered by a hostile tumor microenvironment (TME) featured with deprivation of critical nutrients and pooling of immunosuppressive metabolites. Tumor cells and immunosuppressive cells outcompete immune effector cells for essential nutrients. Meanwhile, a wide range of tumor cell-derived toxic metabolites exerts negative impacts on anti-tumor immune response, diminishing the efficacy of immunotherapy. Nanomedicine with excellent targetability offers a novel approach to improving cancer immunotherapy via metabolically reprogramming the immunosuppressive TME. Herein, we review recent strategies of enhancing immunotherapeutic effects through rewiring tumor metabolism via nanomedicine. Attention is drawn on immunometabolic tactics for immune cells and stromal cells in the TME via nanomedicine. Additionally, we discuss future directions of developing metabolism-regulating nanomedicine for precise and efficacious cancer immunotherapy.

Summary: The traditional parameter adjustment design makes it difficult to effectively regulate the acoustic insulation performance of periodic sandwich structures while meeting the lightweight and mechanical stiffness requirements. A dynamic three-field floating projection topology optimization (FPTO) method for periodic structures is proposed to meet the optimization requirements of low-noise and high-stiffness performance of lightweight periodic sandwich structures. The sound transmission loss is taken as the optimization objective, and the lightweight volume and mechanical stiffness performance are taken as the multiple constraints. The results show that a smooth topology configuration with superior sound insulation performance, high stiffness, and a freely customizable number of periodic cores can be obtained via the proposed method. The accuracy and effectiveness of the presented method are verified via 3D printing technology and impedance tube sound insulation experiments, providing an important reference for the optimal design of lightweight composite structures for vibration and noise reduction in transportation equipment.

Despite the great potential of anti-PD-L1 antibodies for immunotherapy, their low response rate due to an immunosuppressive tumor microenvironment has hampered their application. To address this issue, we constructed a cell membrane-coated nanosystem (mB4S) to reverse an immunosuppressive microenvironment to an immuno-supportive one for strengthening the anti-tumor effect. In this system, Epirubicin (EPI) as an immunogenic cell death (ICD) inducer was coupled to a branched glycopolymer via hydrazone bonds and diABZI as a stimulator of interferon genes (STING) agonist was encapsulated into mB4S. After internalization of mB4S, EPI was acidic-responsively released to induce ICD, which was characterized by an increased level of calreticulin (CRT) exposure and enhanced ATP secretion. Meanwhile, diABZI effectively activated the STING pathway. Treatment with mB4S in combination with an anti-PD-L1 antibody elicited potent immune responses by increasing the ratio of matured dendritic cells (DCs) and CD8+ T cells, promoting cytokines secretion, up-regulating M1-like tumor-associated macrophages (TAMs) and down-regulating immunosuppressive myeloid-derived suppressor cells (MDSCs). Therefore, this nanosystem for co-delivery of an ICD inducer and a STING agonist achieved promotion of DCs maturation and CD8+ T cells infiltration, creating an immuno-supportive microenvironment, thus potentiating the therapy effect of the anti-PD-L1 antibody in both 4T1 breast and CT26 colon tumor mice.

Abstract To address the limitations of traditional photothermal therapy (PTT)/ photodynamic therapy (PDT) and real-time cancer metastasis detection, a pH-responsive nanoplatform (NP) with dual-modality imaging capability was rationally designed. Herein, 1 H,1 H-undecafluorohexylamine (PFC), served as both an oxygen carrier and a 19F magnetic resonance imaging (MRI) probe, and photosensitizer indocyanine green (ICG) were grafted onto the pH-responsive peptide hexahistidine (H6) to form H6-PFC-ICG (HPI). Subsequently, the heat shock protein 90 inhibitor, gambogic acid (GA), was incorporated into hyaluronic acid (HA) modified HPI (HHPI), yielding the ultimate HHPI@GA NPs. Upon self-assembly, HHPI@GA NPs passively accumulated in tumor tissues, facilitating oxygen release and HA-mediated cell uptake. Once phagocytosed by lysosomes, protonation of H6 was triggered due to the low pH, resulting in the release of GA. With near-infrared laser irradiation, GA-mediated decreased HSP90 expression and PFC-mediated increased ROS generation amplified the PTT/PDT effect of HHPI@GA, leading to excellent in vitro and in vivo anticancer efficacies. Additionally, the fluorescence and 19F MRI dual-imaging capabilities of HHPI@GA NPs enabled effective real-time primary cancer and lung metastasis monitoring. This work offers a novel approach for enhanced cancer phototherapy, as well as precise cancer diagnosis.

Abstract Understanding the intricate nanoscale architecture of neuronal myelin during central nervous system development is of utmost importance. However, current visualization methods heavily rely on electron microscopy or indirect fluorescent method, lacking direct and real-time imaging capabilities. Here, we introduce a breakthrough near-infrared emissive curcumin-BODIPY derivative (MyL-1) that enables direct visualization of myelin structure in brain tissues. The remarkable compatibility of MyL-1 with stimulated emission depletion nanoscopy allows for unprecedented super-resolution imaging of myelin ultrastructure. Through this innovative approach, we comprehensively characterize the nanoscale myelinogenesis in three dimensions over the course of brain development, spanning from infancy to adulthood in mouse models. Moreover, we investigate the correlation between myelin substances and Myelin Basic Protein (MBP), shedding light on the essential role of MBP in facilitating myelinogenesis during vertebral development. This novel material, MyL-1, opens up new avenues for studying and understanding the intricate process of myelinogenesis in a direct and non-invasive manner, paving the way for further advancements in the field of nanoscale neuroimaging. Graphical Abstract

The ecological sustainability of arid and semi-arid areas is under increasing threat due to global climate change, and well-established ecological networks are essential for improving landscape connectivity and conserving biodiversity. This study takes the Tacheng-Emin Basin in China as an example. Based on the “source-resistance-corridor” research paradigm and sustainable development theory, the “contribution-organization-vitality-resilience” and circuit theory of the ecosystem are incorporated into the construction of the ecological networks. The results show that (1) the ecosystem service value of the Tacheng-Emin basin is 5.85 × 1010 Yuan, the ecosystem of the basin is of medium health level, and the ecological security hierarchy has low level and uncoordinated problems. (2) The total integrated resistance surface in the basin is of medium level, dominated by natural resistance, and characterized by evident fragmentation. (3) 25 ecological sources, 58 ecological corridors, 32 ecological stepping stones, 39 obstacle points, and 46 ecological fracture points were extracted at the threshold of 10,000 in the circuit model. (4) The reconstruction cost of the ecological network is 1,007.41 × 104 Yuan, and the reconstructed ecological network have increased 2 ecological sources, 1 stepping stone, and reduced 3 obstacle points, while the closure of the ecological networks structure has been significantly improved and the ecological networks has developed toward a stable multi-grid structure. (5) The ecological zoning protection and restoration scheme of “one ring, one belt, one sink, multiple zones, and multiple corridors” is conducive to the sustainable ecological development of the basin. The results of this study can serve as a reference for ecological management and sustainable development in arid and semi-arid regions of Central Asia.

Effective tumor treatment depends on optimizing drug penetration and accumulation in tumor tissue while minimizing systemic toxicity. Nanomedicine has emerged as a key solution that addresses the rapid clearance of free drugs, but achieving deep drug penetration into solid tumors remains elusive. This review discusses various strategies to enhance drug penetration, including manipulation of the tumor microenvironment, exploitation of both external and internal stimuli, pioneering nanocarrier surface engineering, and development of innovative tactics for active tumor penetration. One outstanding strategy is organelle-affinitive transfer, which exploits the unique properties of specific tumor cell organelles and heralds a potentially transformative approach to active transcellular transfer for deep tumor penetration. Rigorous models are essential to evaluate the efficacy of these strategies. The patient-derived xenograft (PDX) model is gaining traction as a bridge between laboratory discovery and clinical application. However, the journey from bench to bedside for nanomedicines is fraught with challenges. Future efforts should prioritize deepening our understanding of nanoparticle-tumor interactions, re-evaluating the EPR effect, and exploring novel nanoparticle transport mechanisms.

Abstract Nanozyme catalytic therapy for cancer treatments has become one of the heated topics, and the therapeutic efficacy is highly correlated with their catalytic efficiency. In this work, three copper‐doped CeO2 supports with various structures as well as crystal facets are developed to realize dual enzyme‐mimic catalytic activities, that is superoxide dismutase (SOD) to reduce superoxide radicals to H2O2 and peroxidase (POD) to transform H2O2 to ∙OH. The wire‐shaped CeO2/Cu‐W has the richest surface oxygen vacancies, and a low level of oxygen vacancy (Vo) formation energy, which allows for the elimination of intracellular reactive oxygen spieces (ROS) and continuous transformation to ∙OH with cascade reaction. Moreover, the wire‐shaped CeO2/Cu‐W displays the highest toxic ∙OH production capacity in an acidic intracellular environment, inducing breast cancer cell death and pro‐apoptotic autophagy. Therefore, wire‐shaped CeO2/Cu nanoparticles as an artificial enzyme system can have great potential in the intervention of intracellular ROS in cancer cells, achieving efficacious nanocatalytic therapy.

This paper focuses on the level of urban–rural integration development and its spatio–temporal evolution patterns in the Chengdu-Chongqing Economic Circle. It constructs an evaluation indicator system encompassing five dimensions: population, economy, society, ecology, and space. By comprehensively using statistical data and multi-source spatio–temporal data and employing methods such as the entropy method, ESDA, obstacle degree model, and various statistical techniques, the study measures and analyzes the level of urban–rural integration development at three time points: 2010, 2015, and 2020. The findings are as follows: (1) The overall level of urban–rural integration is low, predominantly at low to lower-middle levels, with a clear core-periphery spatial pattern where central urban areas such as Chengdu’s central seven districts and Chongqing’s central urban districts are high-value cores, whereas peripheral and central regional areas are less integrated. (2) From 2010 to 2020, there was a steady increase in integration levels, transitioning from a single-core to a more dynamic point-axis structure with emerging regional growth poles. However, this transition was accompanied by reduced inequality of urban–rural integration within each city, while disparities among central urban areas within its cities gradually increased. (3) The analysis of obstacles across dimensions indicates that spatial integration faces the most significant barriers, mainly due to geographical conditions and development constraints in southwestern mountainous counties. In contrast, barriers to economic and social integration, though initially lower, have gradually increased, highlighting imbalances between economic growth and social service provision. Overall, this study not only provides a systematic measurement and analytical framework for the integration and development of urban and rural areas in the Chengdu-Chongqing Economic Circle but also offers theoretical and empirical support for global research and practice on urban–rural integration. Additionally, it proposes targeted policy recommendations.

The oasis serves as the primary supply of cultivable land, along with the hub for human production and habitation in Xinjiang. Accordingly, predicting the land use of these areas based on various goals is an effective instrument for encouraging the sensible distribution of resource space. The study investigated the creation of a land use-allocation optimization model based on the various objectives of ecological protection, food security, and urban growth using the Weigan–Kuche River oasis as an example. The GMOP-PLUS model’s restriction conversion area was adjusted to include the findings of the land suitability evaluation. Additionally, it optimized and simulated the spatial arrangement and quantitative structure of land usage in the Weigan–Kuche River oasis in 2035. The results indicate the following: (1) the model’s overall accuracy is 89.36%, and its Kappa coefficient is 0.872, more than 0.8. Thus, the model can be considered for adoption in the future when predicting changes in land use in the districts and counties of the Weigan–Kuche River oasis; (2) based on the results of the land suitability evaluation, the percentage of areas that are most suited for agricultural development, urban development, and ecological protection is 39.32%, 24.21%, and 14.06%, respectively; and (3) the three scenarios satisfy the various demands for growth within the oasis, and the land use structure of the oasis varies considerably in response to the various development objectives, with the construction and cultivated land undergoing the most substantial modifications. The multi-scenario simulation of land usage in the oasis can provide essential support and a range of perspectives for future land spatial planning and socioeconomic development decision-making in the Weigan–Kuche River oasis. This is essential for both the efficient use of land resources and sustainable development.

Brain metastasis is the leading cause of death in most cancer patients; thus, anti‐brain metastasis is a crucial step in cancer treatment. The unique microenvironment and pathophysiological characteristics of brain metastases hamper the development of effective treatment methods, while the advances in nanomedicine demonstrate its immense potential for addressing this challenge. In recent years, due to breakthroughs in nanotechnology, functional and complex nanomedicine is prepared and it has been extensively explored to improve the treatment of brain metastasis. Compared to traditional treatment methods, nanomedicine can combine multiple traditional treatment methods into one single medicinal format and target unique characteristics of brain metastases to enhance the treatment efficacy. This review summarizes the main obstacles in the field of brain metastasis treatment and clinical/preclinical studies and surveys the use of a variety of nanomedicine candidates as antibrain metastasis strategies for different types of brain metastases.

Abstract Combined chemotherapy and targeted therapy holds immense potential in the management of advanced gastric cancer (GC). GC tissues exhibit an elevated expression level of protein kinase B (AKT), which contributes to disease progression and poor chemotherapeutic responsiveness. Inhibition of AKT expression through an AKT inhibitor, capivasertib (CAP), to enhance cytotoxicity of paclitaxel (PTX) toward GC cells is demonstrated in this study. A cathepsin B‐responsive polymeric nanoparticle prodrug system is employed for co‐delivery of PTX and CAP, resulting in a polymeric nano‐drug BPGP@CAP. The release of PTX and CAP is triggered in an environment with overexpressed cathepsin B upon lysosomal uptake of BPGP@CAP. A synergistic therapeutic effect of PTX and CAP on killing GC cells is confirmed by in vitro and in vivo experiments. Mechanistic investigations suggested that CAP may inhibit AKT expression, leading to suppression of the phosphoinositide 3‐kinase (PI3K)/AKT signaling pathway. Encouragingly, CAP can synergize with PTX to exert potent antitumor effects against GC after they are co‐delivered via a polymeric drug delivery system, and this delivery system helped reduce their toxic side effects, which provides an effective therapeutic strategy for treating GC.

To improve the response rate of immune checkpoint inhibitors such as anti-PD-L1 antibody in immunosuppressive cancers like triple-negative breast cancer (TNBC), induction of immunogenic cell death (ICD) at tumor sites can increase the antigenicity and adjuvanticity to activate the immune microenvironment so that tumors become sensitive to the intervention of immune checkpoint inhibitors. Herein, a self-amplified biomimetic nanosystem, mEHGZ, was constructed by encapsulation of epirubicin (EPI), glucose oxidase (Gox) and hemin in ZIF-8 nanoparticles and coating of the nanoparticles with calreticulin (CRT) over-expressed tumor cell membrane. EPI acts as an ICD inducer, Gox and hemin medicate the cascade generation of reactive oxygen species (ROS) to strengthen the ICD effect, and CRT-rich membrane as “eat me” signal promote presentation of the released antigens by dendritic cells (DCs) to invoke the tumor-immunity cycle. The biomimetic delivery system displays an amplified ICD effect via Gox oxidation, hydroxyl radical generation and glutathione (GSH) depletion. The induced potent ICD effect promotes DCs maturation and cytotoxic T lymphocytes (CTLs) infiltration, reversing an immunosuppressive tumor microenvironment to an immunoresponsive one. Treatment with the nanosystem in combination with anti-PD-L1 antibody results in distinctive inhibition of tumor growth and lung metastasis, supporting that a potent ICD effect can significantly boost the therapeutic efficacy of the anti-PD-L1 antibody. This self-amplified biomimetic nanoplatform offers a promising means of raising the response rate of immune checkpoint inhibitors.

Nanoprobes that offer both fluorescence imaging (FI) and magnetic resonance imaging (MRI) can provide supplementary information and hold synergistic advantages. However, synthesis of such dual-modality imaging probes that simultaneously exhibit tunability of functional groups, high stability, great biocompatibility and desired dual-modality imaging results remains challenging. In this study, we used an amphiphilic block polymer from (ethylene glycol) methyl ether methacrylate (OEGMA) and N-(2-hydroxypropyl) methacrylamide (HPMA) derivatives as a carrier to conjugate a MR contrast agent, Gd-DOTA, and a two-photon fluorophore with an aggregation-induced emission (AIE) effect, TPBP, to construct a MR/two-photon fluorescence dual-modality contrast agent, Gd-DOTA-TPBP. Incorporation of gadolinium in the hydrophilic chain segment of the OEGMA-based carrier resulted in a high r1 value for Gd-DOTA-TPBP, revealing a great MR imaging resolution. The contrast agent specifically accumulated in the tumor region, allowing a long enhancement duration for vascular and tumor contrast-enhanced MR imaging. Meanwhile, coupling TPBP with AIE properties to the hydrophobic chain segment of the carrier not only improved its water solubility and reduced its cytotoxicity, but also significantly enhanced its imaging performance in an aqueous phase. Gd-DOTA-TPBP was also demonstrated to act as an excellent fluorescence probe for two-photon-excited bioimaging with higher resolution and greater sensitivity than MRI. Since high-resolution, complementary MRI/FI dual-modal images were acquired at both cellular and tissue levels in tumor-bearing mice after application of Gd-DOTA-TPBP, it has great potential in the early phase of disease diagnosis.

Abstract With the continuous enhancement of human activities, the contradiction between regional development and ecological protection is prominent in the ecologically fragile arid areas. It is of great significance for regional sustainable development to understand the ecological supply and demand problems caused by transformation of land using and formulate ecological compensation scheme scientifically. This study takes Xinjiang in China as the research area. It explores the land use transition characteristics and the changes in carbon supply and demand of Xinjiang using methods such as GIS spatial analysis and modified comparative ecological radiation forcing. Finally, the ecological compensation scheme is studied based on the theory of ecological radiation. The research shows that (I) in the study chronology, most of the areas produced only one change in land use. Land use is gradually developing towards the direction of ecological protection. After 2000, grassland recovered well, and 14,298 km2 of other ecological land was transformed into grassland. (II) The change in the carbon sink of the Xinjiang ecosystem first decreased and then increased, and the ecological deficit area started to appear after 2010. The growth of grassland and cropland areas is essential to enhance the carbon sink capacity of arid zones. (III) The amount of ecological compensation in Xinjiang is 31.47 * 108 yuan, and the proportion of the amount received by ecological compensation areas is related to the distance between the supply and demand areas, the amount of carbon sequestration, and the area of the region. This study provides a reference for achieving the healthy development of sustainable land use ecosystems in arid zones.

Abstract Circular RNAs (circRNAs) are a kind of noncoding RNAs that have different biological functions. CircRNAs play very important parts in the progression of cancers. Nevertheless, the exact mechanism and function of many circRNAs in glioma are not clear. In our study, circKIF4A was identified as a remarkably upregulated circRNA expressed in glioma tissues and cell lines. We performed loss-off function and gain-of-function experiments to inquire into the biological function of circKIF4A in the progression of glioma. We discovered that knockdown of circKIF4A remarkably decreased the proliferation and invasion ability of glioma cells. Moreover, subcutaneous tumorigenesis model and intracranial injection of orthotopic glioma model were established to investigate the functions of circKIF4A in vivo. Suppression of circKIF4A remarkably enhanced the sensitivity of glioma to temozolomide treatment. The glycolysis rate was accelerated by circKIF4A overexpression, which promoted glioma growth and temozolomide resistance. The glycolysis regulating enzyme ALDOA was regulated by circKIF4A through the mechanism of interactivity with miR-335-5p in glioma cells. In a word, our data showed that the upregulation of circKIF4A facilitates glioma progression by means of binding miR-335-5p and upregulating ALDOA expression.

Bridge inspection and monitoring are usually used to evaluate the status and integrity of bridge structures to ensure their safety and reliability. Computer vision (CV)-based methods have the advantages of being low cost, simple to operate, remote, and non-contact, and have been widely used in bridge inspection and monitoring in recent years. Therefore, this paper reviews three significant aspects of CV-based methods, including surface defect detection, vibration measurement, and vehicle parameter identification. Firstly, the general procedure for CV-based surface defect detection is introduced, and its application for the detection of cracks, concrete spalling, steel corrosion, and multi-defects is reviewed, followed by the robot platforms for surface defect detection. Secondly, the basic principle of CV-based vibration measurement is introduced, followed by the application of displacement measurement, modal identification, and damage identification. Finally, the CV-based vehicle parameter identification methods are introduced and their application for the identification of temporal and spatial parameters, weight parameters, and multi-parameters are summarized. This comprehensive literature review aims to provide guidance for selecting appropriate CV-based methods for bridge inspection and monitoring.

Precisely delivering combinational therapeutic agents has become a crucial challenge for anti-tumor treatment. In this study, a novel redox-responsive polymeric prodrug (molecular weight, MW: 93.5 kDa) was produced by reversible addition–fragmentation chain transfer (RAFT) polymerization. The amphiphilic block polymer-doxorubicin (DOX) prodrug was employed to deliver a hydrophobic photosensitizer (PS), chlorin e6 (Ce6), and the as-prepared nanoscale system [NPs(Ce6)] was investigated as a chemo-photodynamic anti-cancer agent. The glutathione (GSH)-cleavable disulfide bond was inserted into the backbone of the polymer for biodegradation inside tumor cells, and DOX conjugated onto the polymer with a disulfide bond was successfully released intracellularly. NPs(Ce6) released DOX and Ce6 with their original molecular structures and degraded into segments with low MWs of 41.2 kDa in the presence of GSH. NPs(Ce6) showed a chemo-photodynamic therapeutic effect to kill 4T1 murine breast cancer cells, which was confirmed from a collapsed cell morphology, a lifted level in the intracellular reactive oxygen species, a reduced viability and induced apoptosis. Moreover, ex vivo fluorescence images indicated that NPs(Ce6) retained in the tumor, and exhibited a remarkable in vivo anticancer efficacy. The combinational therapy showed a significantly increased tumor growth inhibition (TGI, 58.53%). Therefore, the redox-responsive, amphiphilic block polymeric prodrug could have a great potential as a chemo-photodynamic anti-cancer agent.

Cancer immunotherapy is an effective antitumor approach through activating immune systems to eradicate tumors by immunotherapeutics. However, direct administration of “naked” immunotherapeutic agents (such as nucleic acids, cytokines, adjuvants or antigens without delivery vehicles) often results in: (1) an unsatisfactory efficacy due to suboptimal pharmacokinetics; (2) strong toxic and side effects due to low targeting (or off-target) efficiency. To overcome these shortcomings, a series of polysaccharide-based nanoparticles have been developed to carry immunotherapeutics to enhance antitumor immune responses with reduced toxicity and side effects. Polysaccharides are a family of natural polymers that hold unique physicochemical and biological properties, as they could interact with immune system to stimulate an enhanced immune response. Their structures offer versatility in synthesizing multifunctional nanocomposites, which could be chemically modified to achieve high stability and bioavailability for delivering therapeutics into tumor tissues. This review aims to highlight recent advances in polysaccharide-based nanomedicines for cancer immunotherapy and propose new perspectives on the use of polysaccharide-based immunotherapeutics.

Abstract Amorphization and crystalline grain boundary engineering are adopted separately in improving the catalytic kinetics for water electrolysis. Yet, the synergistic effect and advance in the cooperated form of crystalline/amorphous interfaces (CAI) have rarely been elucidated insightfully. Herein, a trimetallic FeCo(NiS2)4 catalyst with numerous CAI (FeCo(NiS2)4‐C/A) is presented, which shows highly efficient catalytic activity toward both hydrogen and oxygen evolution reactions (HER and OER). Density functional theory (DFT) studies reveal that CAI plays a significant role in accelerating water electrolysis kinetics, in which Co atoms on the CAI of FeCo(NiS2)4‐C/A catalyst exhibit the optimal binding energy of 0.002 eV for H atoms in HER while it also has the lowest reaction barrier of 1.40 eV for the key step of OER. H2O molecules are inclined to be absorbed on the interfacial Ni atoms based on DFT calculations. As a result, the heterostructural CAI‐containing catalyst shows a low overpotential of 82 and 230 mV for HER and OER, respectively. As a bifunctional catalyst, it delivers a current density of 10 mA cm−2 at a low cell voltage of 1.51 V, which enables it a noble candidate as metal‐based catalysts for water splitting. This work explores the role of CAI in accelerating the HER and OER kinetics for water electrolysis, which sheds light on the development of efficient, stable, and economical water electrolysis systems by facile interface‐engineering implantations.

The adoption of intensive farming has exacerbated disease outbreaks in aquaculture, particularly vibriosis caused by Vibrio parahaemolyticus. The use of probiotics to control V. parahaemolyticus is recognized as a good alternative to antibiotics for avoiding the development of antibiotic-resistant bacteria. In this study, two strains of B. HLJ1 and B. C1 with strong inhibitory activity on V. parahaemolyticus were isolated from aquaculture water and identified as Bacillus subtilis and Bacillus pumilus, respectively. Both B. HLJ1 and B. C1 lacked antibiotic resistance and virulence genes, suggesting that they are safe for use in aquaculture. In addition, these two strains can tolerate acid environments, produce spores, secrete extracellular enzymes, and co-aggregate as well as auto-aggregate with V. parahaemolyticus. B. HLJ1 and B. C1 produced the same anti-V. parahaemolyticus substance, which was identified as AI-77-F and belongs to amicoumacins. Both B. C1 and B. HLJ1 showed inhibitory activity against 11 different V. parahaemolyticus and could effectively control the growth of V. parahaemolyticus in simulated aquaculture wastewater when the concentration of B. C1 and B. HLJ1 reached 1 × 107 CFU/mL. This study shows that B. HLJ1 and B. C1 have great potential as aquaculture probiotics.

Abstract Background Macromoleculization of nitroxides has been an effective strategy to improve low relaxivities and poor in vivo stability, however, nitroxides-based metal-free magnetic resonance imaging (MRI) macromolecular contrast agents (mCAs) are still under-performed. These mCAs do not possess a high nitroxides content sufficient for a cumulative effect. Amphiphilic nanostructures in these mCAs are not stable enough for highly efficient protection of nitroxides and do not have adequate molecular flexibility for full contact of the paramagnetic center with the peripheral water molecules. In addition, these mCAs still raise the concerns over biocompatibility and biodegradability due to the presence of macromolecules in these mCAs. Results Herein, a water-soluble biodegradable nitroxides-based mCA (Linear pDHPMA-mPEG-Ppa-PROXYL) was prepared via covalent conjugation of a nitroxides (2,2,5,5-tetramethyl-1-pyrrolidinyl-N-oxyl, PROXYL) onto an enzyme-sensitive linear di-block poly[N-(1, 3-dihydroxypropyl) methacrylamide] (pDHPMA). A high content of PROXYL up to 0.111 mmol/g in Linear pDHPMA-mPEG-Ppa-PROXYL was achieved and a stable nano-sized self-assembled aggregate in an aqueous environment (ca. 23 nm) was formed. Its longitudinal relaxivity (r 1 = 0.93 mM− 1 s− 1) was the highest compared to reported nitroxides-based mCAs. The blood retention time of PROXYL from the prepared mCA in vivo was up to ca. 8 h and great accumulation of the mCA was realized in the tumor site due to its passive targeting ability to tumors. Thus, Linear pDHPMA-mPEG-Ppa-PROXYL could provide a clearly detectable MRI enhancement at the tumor site of mice via the T1WI SE sequence conventionally used in clinical Gd3+-based contrast agents, although it cannot be compared with DTPA-Gd in the longitudinal relaxivity and the continuous enhancement time at the tumor site of mice. Additionally, it was demonstrated to have great biosafety, hemocompatibility and biocompatibility. Conclusions Therefore, Linear pDHPMA-mPEG-Ppa-PROXYL could be a potential candidate as a substitute of metal-based MRI CAs for clinical application. Graphic Abstract

Abstract Background In order to address the potential toxicity of metal-based magnetic resonance imaging (MRI) contrast agents (CAs), a concept of non-metallic MRI CAs has emerged. Currently, paramagnetic nitroxides (such as (2,2,5,5-tetramethylpyrrolidine-1-oxyl, PROXYL), (2,2,6,6-tetramethylpiperidine-1-oxide, TEMPO), etc.) are being extensively studied because their good stability and imaging mechanism are similar to metal-based contrast agents (such as Gd3+ chelate-based clinical CAs). However, a lower relaxivity and rapid in vivo metabolism of nitroxides remain to be addressed. Previous studies have demonstrated that the construction of macromolecular nitroxides contrast agents (mORCAs) is a promising solution through macromolecularization of nitroxides (i.e., use of large molecules to carry nitroxides). Macromolecular effects not only increase the stability of nitroxides by limiting their exposure to reductive substances in the body, but also improve the overall 1H water relaxation by increasing the concentration of nitroxides and slowing the molecular rotation speed. Results Branched pDHPMA-mPEG-Ppa-PROXYL with a high molecular weight (MW = 160 kDa) and a nitroxides content (0.059 mmol/g) can form a nanoscale (~ 28 nm) self-assembled aggregate in a water environment and hydrophobic PROXYL can be protected by a hydrophilic outer layer to obtain strong reduction resistance in vivo. Compared with a small molecular CA (3-Carboxy-PROXYL (3-CP)), Branched pDHPMA-mPEG-Ppa-PROXYL displays three prominent features: (1) its longitudinal relaxivity (0.50 mM− 1 s− 1) is about three times that of 3-CP (0.17 mM− 1 s− 1); (2) the blood retention time of nitroxides is significantly increased from a few minutes of 3-CP to 6 h; (3) it provides long-term and significant enhancement in MR imaging of the tumor, liver, kidney and cardiovascular system (heart and aortaventralis), and this is the first report on nitroxides-based MRI CAs for imaging the cardiovascular system. Conclusions As a safe and efficient candidate metal-free magnetic resonance contrast agent, Branched pDHPMA-mPEG-Ppa-PROXYL is expected to be used not only in imaging the tumor, liver and kidney, but also the cardiovascular system, which expands the application scope of these CAs. Graphical abstract

Pacific white shrimp (Litopenaeus vannamei) is one of the most prevalent crustacean species, understanding the metabolomics during gonad maturation in female L. vannamei is important to understand the regulatory mechanism of reproductive process. LC-MS-based untargeted metabolomics was used to identify the metabolite profile in the hepatopancreas and ovary during ovarian maturation in L. vannamei in this study. A total of 452 and 3887 differential metabolites were identified in the hepatopancreas and ovary, respectively. The most enriched pathways of differential metabolites in hepatopancreas were metabolic pathway, linoleic acid metabolism, biosynthesis of unsaturated fatty acids and steroid biosynthesis, and the most enriched pathways identified in the ovary were metabolic pathway, arachidonic acid metabolism, biosynthesis of unsaturated fatty acids, tryptophan metabolism, neuroactive ligand-receptor interaction and steroid biosynthesis. Among these significant differential metabolites, unsaturated fatty acids, such as eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and arachidonic acid (ARA), decreased significantly in the maturing ovary. Prostaglandins E2 and F2α, the metabolites of ARA, decreased > 50% in the maturing ovary. The contents of vitamin D3 and vitamin E increased more than five-fold at maturing stages, while vitamin A decreased significantly during ovarian maturation. 3-hydroxy-L-kynurenine (3OHKyn), the metabolite of tryptophan and the precursor of ommochrome, accumulated in the maturing ovary. The content of cholesterol and sn-glycerol-3-phosphate also increased in the mature ovary. Furthermore, the expression profiles of genes involved in total cholesterol (TC) and triglyceride (TAG) synthesis were determined to reveal the molecular mechanism of these biosynthesis processes in L. vannamei. The current study revealed the metabolomics profile and found some new metabolites that were critical for ovary development in L. vannamei.

Abstract Background Nanocarriers-derived antitumor therapeutics are often associated with issues of limited tumor penetration and dissatisfactory antitumor efficacies. Some multistage delivery systems have been constructed to address these issues, but they are often accompanied with complicated manufacture processes and undesirable biocompatibility, which hinder their further application in clinical practices. Herein, a novel dual-responsive multi-pocket nanoparticle was conveniently constructed through self-assembly and cross-linking of amphiphilic methoxypolyethylene glycol-lipoic acid (mPEG-LA) conjugates to enhance tumor penetration and antitumor efficacy. Results The multi-pocket nanoparticles (MPNs) had a relatively large size of ~ 170 nm at physiological pH which results in prolonged blood circulation and enhanced accumulation at the tumor site. But once extravasated into acidic tumor interstices, the increased solubility of PEG led to breakage of the supramolecular nanostructure and dissolution of MPNs to small-sized (

Multi-modal therapeutics are emerging for simultaneous diagnosis and treatment of cancer. Polymeric carriers are often employed for loading multiple drugs due to their versatility and controlled release of these drugs in response to a tumor specific microenvironment. A theranostic nanomedicine was designed and prepared by complexing a small gadolinium chelate, conjugating a chemotherapeutic drug PTX through a cathepsin B-responsive linker and covalently bonding a fluorescent probe pheophorbide a (Ppa) with a branched glycopolymer. The branched prodrug-based nanosystem was degradable in the tumor microenvironment with overexpressed cathepsin B, and PTX was simultaneously released to exert its therapeutic effect. The theranostic nanomedicine, branched glycopolymer-PTX-DOTA-Gd, had an extended circulation time, enhanced accumulation in tumors, and excellent biocompatibility with significantly reduced gadolinium ion (Gd3+) retention after 96 h post-injection. Enhanced imaging contrast up to 24 h post-injection and excellent antitumor efficacy with a tumor inhibition rate more than 90% were achieved from glycopolymer-PTX-DOTA-Gd without obvious systematic toxicity. This branched polymeric prodrug-based nanomedicine is very promising for safe and effective diagnosis and treatment of cancer.

Large-scale integration of wind power into a power system introduces uncertainties to its operation and planning, making the power system operation scenario highly diversified and variable. In conventional power system planning, some key operation modes and most critical scenarios are typically analyzed to identify the weak and high-risk points in grid operation. While these scenarios may not follow traditional empirical patterns due to the introduction of large-scale wind power. In this paper, we propose a weighted clustering method to quickly identify a system’s extreme operation scenarios by considering the temporal variations and correlations between wind power and load to evaluate the stability and security for system planning. Specifically, based on an annual time-series data of wind power and load, a combined weighted clustering method is used to pick the typical scenarios of power grid operation, and the edge operation points far from the clustering center are extracted as the extreme scenarios. The contribution of fluctuations and capacities of different wind farms and loads to extreme scenarios are considered in the clustering process, to further improve the efficiency and rationality of the extreme-scenario extraction. A set of case studies was used to verify the performance of the method, providing an intuitive understanding of the extreme scenario variety under wind power integration.

Voltage rise caused by reverse power flows and intermittency in renewable power is the main limiting factor for integration of photovoltaic(PV) generation in low voltage networks. Inverter voltage control techniques have been developed to provide effective voltage control and support higher penetration integration of PV generation. In this paper, the common Volt-VAR control, PF(P) and Q(U) control of photovoltaic inverter methods are detailed compared. A set of simulation study-cases have been designed based on a generic LV grid model, which is considered as representative for the Bornholm network. Observations of the influence of different Volt-VAR control strategies upon different electrical parameters on hosting capacity increase potential have been performed. Results show that inverter controls can greatly contribute the integration of PV in LV networks in the perspective of avoiding overvoltage.

Most research on computer vision (CV)-based vibration measurement is limited to the determination of discrete or coarse mode shapes of the structure. The continuous edge of the structure in images has rich optical features, and thus, by identifying and tracking the movement of the structure’s edge, it is possible to determine high-resolution full-field mode shapes of the structure without a preset target. The present study proposes a CV-based method of full-field mode shape identification using the subpixel edge detection and tracking techniques. Firstly, the Canny operator is applied on each frame of the structure vibration video to extract the pixel-level edges, and the improved Zernike orthogonal moment (ZOM) subpixel edge detection technique is adopted to relocate the precise structure edges. Then, all the detected edge points are tracked to obtain the full-field dense displacement time history that is subsequently used to determine the structure frequencies and compute full-field mode shapes by combining the covariance driven stochastic subspace identification (SSI-COV) with the hierarchical cluster analysis. Finally, the proposed method is verified on the aluminum cantilever beam in the laboratory and the Humen Bridge in the field. The results show that the proposed method is able to detect more precise structure edges and identify the full-field displacement and mode shapes of structures without the need for installing artificial targets on the structure in advance, which provides valuable information for the structural condition assessment, especially for structures with small-amplitude vibrations.

Abstract Supramolecular self‐assemblies of dendritic peptides with well‐organized nanostructures have great potential as multifunctional biomaterials, yet the complex self‐assembly mechanism hampers their wide exploration. Herein, a self‐stabilized supramolecular assembly (SSA) constructed from a PEGylated dendritic peptide conjugate (PEG‐dendritic peptide‐pyropheophorbide a, PDPP), for augmenting tumor retention and therapy, is reported. The supramolecular self‐assembly process of PDPP is concentration‐dependent with multiple morphologies. By tailoring the concentration of PDPP, the supramolecular self‐assembly is driven by noncovalent interactions to form a variety of SSAs (unimolecular micelles, oligomeric aggregates, and multi‐aggregates) with different sizes from nanometer to micrometer. SSAs at 100 nm with a spherical shape possess extremely high stability to prolong blood circulation about 4.8‐fold higher than pyropheophorbide a (Ppa), and enhance tumor retention about eight‐fold higher than Ppa on day 5 after injection, which leads to greatly boosting the in vivo photodynamic therapeutic efficiency. RNA‐seq demonstrates that these effects of SSAs are related to the inhibition of MET‐PI3K‐Akt pathway. Overall, the supramolecular self‐assembly mechanism for the synthetic PEGylated dendritic peptide conjugate sheds new light on the development of supramolecular assemblies for tumor therapy.

As a pleiotropic regulator, Antibiotic resistant protein B (AbrB) was reported to play important roles in various cellular processes in Bacilli and some Clostridia strains. In Clostridium tyrobutyricum, abrB (CTK_C 00640) was identified to encode AbrB by amino acid sequence alignment and functional domain prediction. The results of abrB deletion or overexpression in C. tyrobutyricum showed that AbrB not only exhibited the reported characteristics such as the negative regulation on sporulation, positive effects on biofilm formation and stress resistance but also exhibited new functions, especially the negative regulation of carbon metabolism. AbrB knockout strain (Ct/ΔabrB) could alleviate glucose-mediated carbon catabolite repression (CCR) and enhance the utilization of xylose compared with the parental strain, resulting in a higher butyrate titer (14.79 g/L vs. 7.91 g/L) and xylose utilization rate (0.19 g/L·h vs. 0.02 g/L·h) from the glucose and xylose mixture. This study confirmed the pleiotropic regulatory function of AbrB in C. tyrobutyricum, suggesting that Ct/ΔabrB was the potential candidate for butyrate production from abundant, renewable lignocellulosic biomass mainly composed of glucose and xylose.

A new chiral molecularly imprinted polymer (MIP) sensor with dual recognition ability was developed for the highly selective separation of enantiomers with toxic side effects in drugs. The sensor contains double-stranded deoxyribonucleic acid (dsDNA) as the element that immobilizes the chiral molecular conformation: the dsDNA enables the imprinted cavities to match the three-dimensional structure and functional groups from the chiral molecule. By embedding the spatial orientation of dsDNA in MIPs, one can accurately capture and immobilize the molecular conformation, eliminating the influence of interfering analogues. Herein, L-penicillamine (L-Pen) was selected as the chiral template molecule and embedded into dsDNA to form dsDNA-L-Pen complex, which was then embedded into the MIPs by electropolymerization. After elution, the stereo-selective imprinted cavities were obtained. The ATATATATATAT-TATATATATATA base sequence showed a high affinity for the embedded L-Pen, which endowed the imprinted cavities with a larger number of sites and improved the selectivity toward Pen enantiomers. Under the optimal working conditions, the current response of the MIP/dsDNA sensor exhibited a positive linear relationship with the logarithm of the L-Pen concentration in the range of 3.0 × 10−16 to 3.0 × 10−13 mol/L, and the detection limit was 2.48 × 10−16 mol/L. After the introduction of dsDNA into the MIP, the selectivity of the sensor toward D-Pen increased by 6.4 times, and the sensor was successfully applied in the analysis of L-Pen in penicillamine tablets.

The model-free predictive control (MFPC) scheme is an effective scheme to enhance the parameter robustness of model predictive control. However, the MFPC scheme can be affected by the current gradient updating frequency. This paper proposes an improved MFPC scheme for a T-type three-level inverter. First, a novel current gradient updating method is designed to estimate all current gradients per control period, which uses the current gradient relationship between different voltage vectors and eliminates the effect of current gradients updating stagnation. Moreover, a sector judgment method based on the current gradient is proposed. Redundant small vectors are accurately judged and the computational burden is greatly reduced. Finally, simulation and experimental comparisons on a T-type three-level inverter verify the effectiveness of the proposed MFPC scheme.

Hepatic fibrosis is induced by chronic hepatic injuries before it turns into hepatic cirrhosis/carcinoma. It is characterized by the formation of collagen and other extracellular matrices around damaged hepatic tissues; consequently, the normal architecture of liver would be disrupted and its function impaired. Diagnosis of hepatic fibrosis, especially at the early stage, is crucial because most fibrotic changes are reversible during the hepatic fibrosis stage. However, early and more accurate diagnosis of hepatic fibrosis still remains a great challenge. With their promising structural adjustability and targeting ability, nanomedicines have recently been introduced to improve diagnosis of hepatic fibrosis. By targeting fibrogenic cells, receptors, and extracellular matrix components, these nanomedicines can achieve detection of hepatic tissues with high sensitivity and specificity at the early stage. The use of nanomedicines can also enable theranostics of this chronic hepatic disease. This review aims to present an overview of recent advances of nanomedicines in diagnosis and theranostics of hepatic fibrosis.

With the advantage of high strength, lightness, and good environmental resistance, glass fiber reinforced polymer (GFRP) pultruded profile is regarded as an innovative way that has been used in infrastructure over the last few decades. However, some disadvantages also limited its widespread application in practice, including relatively low elastic and shear modulus and high deformability due to buckling failure. To overcome these disadvantages, some composite structure systems are proposed, such as GFRP-concrete composite structure system. This paper presents an innovative GFRP-concrete composite bridge prototype system, which mainly includes two I-shaped GFRP girders with corrugated webs combined with a thin steel fiber reinforced self-compacting concrete (SFRCC) deck. This composite bridge system is proved to improve structure shear stability and bending stiffness. Three-dimensional finite element (FEA) models are created to simulate the flexural behavior of two-I-shaped-girder composite bridge with straight webs, and the model result is validated with experimental data. Furthermore, the revised FE model that uses corrugated webs instead of straight webs is created, and the static and dynamic behaviors are investigated, including shearing stability properties, bending vibration frequency due to bending and torsion, mid-span vertical deflection, and lateral displacement due to wind load. Further research efforts on the influence of parameters dimension variation in corrugated webs girder composite system are needed. A total of four variable parameters are selected to test, which are GFRP corrugated web width, thickness, height, and SFRCC top slab thickness, respectively. All these conclusions will provide some design recommendations and guideline of a GFRP-concrete corrugated webs composite bridge in further study.

Abstract Herein, two water‐soluble PROXYL‐based magnetic resonance imaging (MRI) macromolecular organic contrast agents (mORCAs) are designed and synthesized: linear and cross‐linked PCE‐mPEG‐Ppa‐PROXYL. They are prepared by conjugating linear and cross‐linked poly(carboxylate ester) (PCE) with poly(ethylene glycol) (mPEG2000)‐modified nitroxides (PROXYL), respectively. Both mORCAs form self‐assembled aggregates in an aqueous phase and PROXYL is protected inside a hydrophobic core to achieve great resistance to reduction in the physiological environment, and they have low toxicity. Since cross‐linked PCE‐mPEG‐Ppa‐PROXYL possess a branched architecture, its self‐assembled aggregate is more stable and compact with a greater particle size. Cross‐linked PCE‐mPEG‐Ppa‐PROXYL outperform the linear one in the following aspects: 1) its longitudinal relaxivity (r1 = 0.79 mm−1 s−1) is higher than that of the linear one (r1 = 0.64 mm−1 s−1) and both excel the best mORCA reported so far (r1 = 0.42 mm−1 s−1); 2) its blood retention time (≈48 h) is longer than that of its linear counterpart (≈10 h); 3) cross‐linked PCE‐mPEG‐Ppa‐PROXYL provided better MR imaging contrast resolution in normal organs (liver and kidney) and tumor of mice than the linear one. Overall, cross‐linked PCE‐mPEG‐Ppa‐PROXYL may have great potential to be a novel metal‐free macromolecular contrast agent for MR imaging.

Abstract A stimuli‐responsive polymeric prodrug‐based nanotheranostic system with imaging agents (cyanine5.5 and gadolinium‐chelates) and a therapeutic agent paclitaxel (PTX) is prepared via polymerization and conjugating chemistry. The branched polymeric PTX‐Gd‐based nanoparticles (BP‐PTX‐Gd NPs) demonstrate excellent biocompatibility, and high stability under physiological conditions, but they stimuli‐responsively degrade and release PTX rapidly in a tumor microenvironment. The in vitro behavior of NPs labeled with fluorescent dyes is effectively monitored, and the NPs display high cytotoxicity to 4T1 cells similar to free PTX by impairing the function of microtubules, downregulating anti‐apoptotic protein Bcl‐2, and upregulating the expression of Bax, cleaved caspase‐3, cleaved caspase‐9, cleaved‐PARP, and p53 proteins. Great improvement in magnetic resonance imaging (MRI) is demonstrated by these NPs, and MRI accurately maps the temporal change profile of the tumor volume after injection of NPs and the tumor treatment process is also closely correlated with the T1 values measured from MRI, demonstrating the capability of providing real‐time feedback to the chemotherapeutic treatment effectiveness. The imaging‐guided chemotherapy to the 4T1 tumor in the mice model achieves an excellent anti‐tumor effect. This stimuli‐responsive polymeric nano‐agent opens a new door for efficient breast cancer treatment under the guidance of fluorescence/MRI.

This paper studies the cluster synchronization of a kind of complex networks by means of impulsive pinning control scheme. These networks are subject to stochastic noise perturbations and Markovian switching, as well as internal and outer time-varying delays. Using the Lyapunov-Krasovskii functional, Itö’s formula, and some linear matrix inequalities (LMI), several novel sufficient conditions are obtained to guarantee the desired cluster synchronization. At the end of this writing, a numerical simulation is given to demonstrate the effectiveness of those theoretical results.