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The management of burn injuries presents a significant challenge in clinical settings, yet an optimal solution remains elusive. Therefore, this study aimed to develop a topical therapeutic formulation to address the complex issues hindering burn wound healing. Emphasizing the sustained presence of bioactive principles, we synthesized a bioactive gel derived from decellularized caprine small intestine submucosa (D-CIS) and encapsulated it with nano-formulations of cerium oxide and curcumin to create a burn wound dressing material with enhanced properties. The choice of encapsulated components was guided by their antimicrobial, antioxidant, and immune-modulating characteristics, along with their inherent ability to gradually release bioactive substances. The encapsulated (cerium oxide and curcumin) D-CIS bioactive gel demonstrated a range of properties, including antimicrobial, antioxidant, and anti-inflammatory effects, along with sustained release kinetics of bioactive molecules. These combined effects facilitated accelerated burn wound healing by mitigating oxidative stress, reducing inflammation, and promoting cell recruitment for epithelial and vascular regeneration. This study contributes to the development of a novel bioactive gel incorporating cerium oxide and curcumin, offering a promising approach to enhance burn wound healing.

Abstract Bacteriophages (phages) represent a unique category of viruses with a remarkable ability to selectively infect host bacteria, characterized by their assembly from proteins and nucleic acids. Leveraging their exceptional biological properties and modifiable characteristics, phages emerge as innovative, safe, and efficient delivery vectors. The potential drawbacks associated with conventional nanocarriers in the realms of drug and gene delivery include a lack of cell-specific targeting, cytotoxicity, and diminished in vivo transfection efficiency. In contrast, engineered phages, when employed as cargo delivery vectors, hold the promise to surmount these limitations and attain enhanced delivery efficacy. This review comprehensively outlines current strategies for the engineering of phages, delineates the principal types of phages utilized as nanocarriers in drug and gene delivery, and explores the application of phage-based delivery systems in disease therapy. Additionally, an incisive analysis is provided, critically examining the challenges confronted by phage-based delivery systems within the domain of nanotechnology. The primary objective of this article is to furnish a theoretical reference that contributes to the reasoned design and development of potent phage-based delivery systems. Graphical abstract

Here, we describe a new species of Crotalaria L. discovered in Mengla County, Xishuangbanna Dai Autonomous Prefecture, Yunnan, China. The new species, Crotalaria menglaensis S.A.Rather, was confirmed by identifying diagnostic morphological characteristics, performing principal component analyses of phenotypic traits, and phylogenetic analyses based on nuclear ITS and plastid matK sequences. Phylogenetic analyses recovered the two accessions of the new species to be sister to C. bracteata Roxb. ex DC. In turn, these two species formed the sister clade to the two accessions of C. incana L. The morphometric analyses revealed that all three species were distinct, while the analyses of distinctive characters enabled unambiguous distinction of the new species by its growth habit, leaflets, flower structure and pod morphology. In contrast to the two related species, the new species is currently known only from ca. 100 mature individuals. Thus, this species is considered to be critically endangered.

Chronic and infected wounds, particularly those caused by bacterial infections, present significant challenges in medical treatment. This study aimed to develop a novel nanoparticle formulation to enhance wound healing by combining antimicrobial and photothermal therapy using albumin as a carrier for Tanshinone IIA and the near-infrared photothermal agent IR780. The nanoparticles were synthesized to exploit the antimicrobial effects of Tanshinone IIA and the photothermal properties of IR780 when exposed to near-infrared laser irradiation. Characterization of the nanoparticles was performed using Transmission Electron Microscopy (TEM) and spectroscopic analysis to confirm their successful synthesis. In vitro antibacterial activity was evaluated using cultures of methicillin-resistant Staphylococcus aureus (MRSA), and in vivo efficacy was tested in a mouse model of MRSA-infected wounds. Wound healing progression was assessed over 16 days, with statistical analysis performed using two-way ANOVA followed by Tukey’s post-hoc test. The nanoparticles demonstrated significant photothermal properties, enhancing bacterial eradication and promoting the controlled release of Tanshinone IIA. In vitro studies showed superior antibacterial activity, especially under photothermal activation, leading to a substantial reduction in bacterial viability in MRSA cultures. In vivo, nanoparticle treatment combined with near-infrared laser irradiation significantly improved wound closure rates compared to controls and treatments without photothermal activation. By the 16th day post-treatment, significant improvements in wound healing were observed, highlighting the potential of the combined photothermal and pharmacological approach. These findings suggest that albumin-loaded nanoparticles containing Tanshinone IIA and IR780, activated by near-infrared light, could offer an effective therapeutic strategy for managing chronic and infected wounds, promoting both infection control and tissue repair.

Abstract Ionic conductive hydrogels (ICHs) have recently gained prominence in biosensing, indicating their potential to redefine future biomedical applications. However, the integration of these hydrogels into sensor technologies and their long‐term efficacy in practical applications pose substantial challenges, including a synergy of features, such as mechanical adaptability, conductive sensitivity, self‐adhesion, self‐regeneration, and microbial resistance. To address these challenges, this study introduces a novel hydrogel system using an imidazolium salt with a ureido backbone (UL) as the primary monomer. Fabricated via a straightforward one‐pot copolymerization process that includes betaine sulfonate methacrylate (SBMA) and acrylamide (AM), the hydrogel demonstrates multifunctional properties. The innovation of this hydrogel is attributed to its robust mechanical attributes, outstanding strain responsiveness, effective water retention, and advanced self‐regenerative and healing capabilities, which collectively lead to its superior performance in various applications. Moreover, this hydrogel exhibited broad‐spectrum antibacterial activity. Its potential for biomechanical monitoring, especially in tandem with contact and noncontact electrocardiogram (ECG) devices, represents a noteworthy advancement in precise real‐time cardiac monitoring in clinical environments. In addition, the conductive properties of the hydrogel make it an ideal substrate for electrophoretic patches aimed at treating infected wounds and consequently enhancing the healing process.

Abstract Immune checkpoint inhibitor (ICI)-derived evolution offers a versatile means of developing novel immunotherapies that targets programmed death-ligand 1 (PD-L1)/programmed death-1 (PD-1) axis. However, one major challenge is T cell exhaustion, which contributes to low response rates in "cold" tumors. Herein, we introduce a fluorinated assembly system of LFNPs/siTOX complexes consisting of fluorinated EGCG (FEGCG), fluorinated aminolauric acid (LA), and fluorinated polyethylene glycol (PEG) to efficiently deliver small interfering RNA anti-TOX (thymus high mobility group box protein, TOX) for synergistic tumor cells and exhausted T cells regulation. Using a microfluidic approach, a library of LFNPs/siTOX complexes were prepared by altering the placement of the hydrophobe (LA), the surface PEGylation density, and the siTOX ratio. Among the different formulations tested, the lead formulation, LFNPs3-3/siTOX complexes, demonstrated enhanced siRNA complexation, sensitive drug release, improved stability and delivery efficacy, and acceptable biosafety. Upon administration by the intravenous injection, this formulation was able to evoke a robust immune response by inhibiting PD-L1 expression and mitigating T cell exhaustion. Overall, this study provides valuable insights into the fluorinated assembly and concomitant optimization of the EGCG-based delivery system. Furthermore, it offers a promising strategy for cancer immunotherapy, highlighting its potential in improving response rates in ‘‘cold’’ tumors. Graphical Abstract

Phosphogypsum (PG) is an industrial by-product that is difficult to manage and poses serious environmental threats. Long-term accumulation of PG can potentially pollute land and water due to its acidity and harmful impurities. In this study, the raw PG and carbide slag (CS)-modified PG were used to replace anhydrite in calcium sulfoaluminate (CSA) cement, and the performance and micromechanisms of PG-CSA and CS-PG-CSA were investigated. The engineering performances including setting time, fluidity, compressive strength, and hydration characteristics of PG-CSA and CS-PG-CSA were investigated. Furthermore, the crystalline phases and microstructure evolutions of hydration products were confirmed by hydration heat, X-ray diffraction (XRD), thermogravimetry-differential thermal analysis (TG-DTA) and scanning electron microscopy- energy dispersive spectrometer (SEM-EDS) tests. The results showed that CS could effectively remove the acidity and impurities of PG by converting PO43- and F- into Ca3(PO4)2 and CaF2. When 20 % raw PG was mixed with CSA clinker, the strength of PG-CSA reached a maximum of 65.83 MPa, which is 41.81 % higher than that of commercial CSA cement. Compared to commercial CSA cement, PG-CSA exhibits a delayed hydration heat release peak, resulting in a longer setting time and greater fluidity. However, CS effectively increases the strength of PG-CSA, but it shortens the setting time and reduces the fluidity. The early and late hydration products of PG-CSA and CS-PG-CSA are mainly ettringite (AFt) and aluminum hydroxide (AH3), respectively. The results of the environmental assessment unequivocally demonstrate that the developed product surpasses traditional cement in all evaluated metrics, achieving a remarkable reduction in CO2 emissions of nearly 50 %. The key findings indicate that the use of CS-modified PG in CSA cement can not only improve engineering performance but also promote sustainability and economic efficiency, demonstrating significant potential for widespread application.

Summary: Imaging transcriptomics offers opportunities to uncover the genetic profiles underlying brain imaging-derived phenotypes (IDPs) but lacks explanation from gene to IDPs. Here, we present a protocol for combining imaging transcriptomics with gene set variation analysis (GSVA) to detect spatio-molecular profiles underlying IDPs in the human cerebellum. We describe the steps for data preparation, model training, model evaluation, key gene identification, and GSVA. Our protocol broadens the way to interpret the biological pathways shaping a wide range of neuroimaging-derived cerebellar properties.For complete details on the use and execution of this protocol, please refer to Wang et al.1 : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.

Tumor metastasis presents a formidable challenge in cancer treatment, necessitating effective tools for anti-cancer drug development. Conventional 2D cell culture methods, while considered the “gold standard” for invasive studies, exhibit limitations in representing cancer hallmarks and phenotypes. This study proposes an innovative approach that combines the advantages of 3D tumor spheroid culture with impedance-based biosensing technologies to establish a high-throughput 3D cell invasion assay for anti-metastasis drug screening through multicellular tumor spheroids. In addition, the xCELLigence device is employed to monitor the time-dependent kinetics of cell behavior, including attachment and invasion out of the 3D matrix. Moreover, an iron chelator (deferoxamine) is employed to monitor the inhibition of epithelial–mesenchymal transition in 3D spheroids across different tumor cell types. The above results indicate that our integrated 3D cell invasion assay with impedance-based sensing could be a promising tool for enhancing the quality of the drug development pipeline by providing a robust platform for predicting the efficacy and safety of anti-metastatic drugs before advancing into preclinical or clinical trials.

Purposes With the continuous promotion of the dual carbon goal, new energy has ushered in explosive development, and the capacity and space for new energy consumption have become a concern for all sectors of society. In the research on existing new energy consumption capacity and space, the consumption measures are relatively single and focus more on theoretical research, which is not applicable, propose specific methods and processes. Methods In this article the time series production simulation method was adopted to build a new energy consumption capacity and consumption space method and process for large-scale new energy grid connection on the Panoramic Power System Operation Simulation Analysis Platform. Findings The new energy consumption capacity of Shanxi Province during the 14th and 15th Five Year Plans was estimated. On the basis. Based on this, comprehensive consumption measures were taken to increase its new energy utilization rate to over 95%, improving the new energy consumption capacity. On the basis of a new energy utilization rate of 95%, the new energy consumption space under various scenarios was calculated for different proportion of newly added wind and solar power, different production timing, different new energy utilization rates, and different years, guiding the new energy planning of Shanxi Province and assisting in the implementation of the dual carbon target.

In the original publication [...]

Abstract Immune therapy that targets PD-L1 (programmed cell death-ligand 1) is attractive to augment immune response by breaking the programmed cell death-1 (PD-1)/PD-L1 axis. However, T cell exhaustion associated with insufficient T cells infiltration may diminish the efficacy of cancer therapy. Here, we report a novel delivery system of FEGCG/FPEI@siTOX composed of fluorinated EGCG (FEGCG) and fluorinated polyethyleneimine (FPEI) for delivery of small interfering RNA anti-TOX (thymus high mobility group box protein, TOX) to treat tumor and metastasis. In this way, the reduction in PD-L1 expression by FEGCG can promote T-cell function, while inhibition of TOX expression with siTOX can alleviate T-cell exhaustion. FPEI are designed to deliver siRNA with high efficiency and low toxicity compared to classical PEI. Integrating FEGCG, FPEI and siTOX into such a novel system resulted in excellent anti-tumor and antimetastatic effects. It is a promising delivery system and potential strategy for the treatment of “cold” tumors.

The goal of carbon emission peak and carbon neutrality requires China to vigorously develop renewable energy. However, renewable energy has obvious randomness and volatility. Therefore, it is necessary to configure energy storage systems for renewable energy stations to ensure the safe and stable operation of power systems. Given the problem of energy storage system configuration in renewable energy stations, it is necessary to consider the system load characteristics and design appropriate principles to formulate planned output curves for renewable energy stations, so that the joint output curve of renewable energy and energy storage system can match the system load curve as much as possible, which will reduce the system peak shaving pressure and promote the utilization of renewable energy. This paper first considers the impact of renewable energy stations with the different installed scales on the power system and designs the standardized supply curves differentially, and defines the supply curve deviation index to characterize the difference between the renewable energy–energy storage system joint output curve and the standardized supply curve. Then, to minimize energy storage system investment costs and supply deviation costs, an optimization model for energy storage system configuration in renewable energy stations is established, and output deviation control constraints are set to ensure that the operation of energy storage systems conforms to actual conditions. Finally, case studies analyze the energy storage system configuration results and the typical scenario operation results of a single renewable energy station and a renewable energy power generation base, which verify the rationality and effectiveness of the method proposed in this paper.

Under the background of high proportion of renewable energy, the frequency security of the power system is facing challenges, which makes it necessary to consider and respond in the optimal dispatching. In this paper, the frequency security constraint is introduced into the basic unit commitment model and the unit commitment model considering the frequency security constraint is proposed. Different from the traditional research, a dynamic modeling method for the unbalanced power of the system is presented. Based on the system frequency response model of primary frequency response, the analytic and linearized frequency safety constraint sets are constructed for the frequency nadir, quasi steady frequency and maximum rate-of-change-of-frequency. The experimental results show that the proposed model not only ensures sufficient frequency security, but also fully considers the actual operation state of the frequency response unit. Compared with the traditional model whose unbalanced power is constant, the proposed model can save operating costs.

In adapting to the double-high development trend of high-voltage direct current (HVDC) receiving-end power systems and solving optimization problems in emergency frequency control (EFC) supporting virtual power plants (VPPs) in large-scale power systems, a parameter estimation method for a VPP frequency response model based on a successive linear programming (SLP) method is proposed. First, a “centralized/decentralized” hierarchical control architecture for VPP participation in EFC is designed. Second, the frequency response characteristics of multiple flexible resources are scientifically analyzed, and the system frequency response (SFR) model and equivalent model of VPP are constructed. Subsequently, parameter estimation of the VPP frequency response model is carried out based on the SLP method, aiming to balance the accuracy and computational efficiency of the model. Finally, the effectiveness of the proposed methodology is verified by using PSD-BPA to simulate and test the three-zone HVDC recipient area grid.

The underwater laser polarization detection technology integrates the polarization characteristics of light into the detection and identification of underwater targets. Addressing the challenge of poor accuracy in identifying targets in strong underwater scattering environments, this article proposes an overall scheme for a laser polarization underwater detection device that suppresses scatter using polarized pulse signals. By overcoming key technological barriers in the design of polarization-preserving optical detection systems and utilizing the method of differential amplitude to measure polarization, a laser polarization underwater detection device was developed and underwater polarization detection experiments were conducted, achieving precise detection of underwater targets. The results indicate that the underwater detection device we designed has a root mean square error of less than 5.7% to detect the polarization of the target, demonstrating the accuracy and precision of the underwater detection device.

Purpose: It is well known that inhibition of Ca2+/calmodulin-dependent protein kinase II (CaMKII) provides cardiac protection in cases of myocardial ischemia–reperfusion injury. However, there are currently no cytoplasm-impermeable drugs that target CaMKII. The aim of this study was to develop curcumin albumin nanoparticles (HSA-CCM NPs) containing AC3-I and investigate their protective effects on hypoxia–reoxygenation (H/R)-induced injuries in adult rat cardiomyocytes and ischemia–reperfusion (I/R) injuries in isolated rat hearts. Methods: HSA-CCM NPs were synthesized using β-ME methods, while the membrane-impermeable peptide AC3-I was covalently linked via a disulfide bond to synthesize AC3-I@HSA-CCM NPs (AC3-I@NPs). Nanoparticle stability and drug release were characterized. To assess the cardiomyocyte uptake of AC3-I@NPs, AC3-I@NPs were incubated with cardiomyocytes under normoxia and hypoxia, respectively. The cardioprotective effect of AC3-I@NPs was determined by using a lactate dehydrogenase kit (LDH) and PI/Hoechst staining. The phosphorylation of phospholamban (p-PLB) was detected by Western blotting in hypoxia–reoxygenation and electric field stimulation models. To further investigate the protective role of AC3-I@NPs against myocardial ischemia–reperfusion injury, we collected coronary effluents and measured creatine kinase (CK) and LDH release in Langendorff rat hearts. Results:AC3-I@NPs were successfully prepared and characterized. Both HSA-CCM NPs and AC3-I@NPs were taken up by cardiomyocytes. AC3-I@NPs protected cardiomyocytes from injury caused by hypoxia–reoxygenation, as demonstrated by decreased cardiomyocyte death and LDH release. AC3-I@NPs reduced p-PLB levels evoked by hypoxia–reoxygenation and electrical field stimulation in adult rat cardiac myocytes. AC3-I@NPs decreased the release of LDH and CK from coronary effluents. Conclusions: AC3-I@NPs showed protective effects against myocardial injuries induced by hypoxia–reoxygenation in cardiomyocytes and ischemia–reperfusion in isolated hearts.

Collaborative efforts to reduce pollution and carbon emissions are a notable feature of the current era. Achieving the “pollution reduction” and “carbon reduction” dual-driven new development model is the inevitable requirement and significant practical measure for building a new development pattern and realizing a comprehensive green transformation of economic and social development. The synergistic effects between pollution reduction and carbon reduction (PRCR) have been demonstrated. However, the measurement and quantitative analysis of the coupling coordination degree (CCD) of PRCR have not received enough attention. Therefore, the evaluation index system was constructed based on the scientific connotation of PRCR, and the CCD of PRCR in cities along the Yellow River Basin (YRB) from 2009 to 2018 was measured quantitatively by constructing the coupling coordination model in this paper. In addition, we comprehensively investigated its spatial pattern, distribution characteristics, and evolution trend using ESDA, Kernel density estimation, and Markov chain. The primary findings can be summarized as: (1) PRCR levels and their CCD fluctuated and increased in the YRB, with “east-high and west-low” spatial differentiation characteristics, and the coupling phenomenon of “pollution reduction is hindered and carbon reduction is lagging”. (2) There is a phenomenon of “spatial club” clustering in the coordination degree of PRCR in the YRB, with most cities in the downstream areas belonging to the type of high-high clustering, while the middle and upstream areas had the opposite type. (3) The CCD of PRCR in the whole and upper reaches of the YRB have transformed from low-level divergence to high-level convergence. (4) Spatial geographic factors have a significant spillover effect on the evolution of the CCD of PRCR, and there is a phenomenon of the “Matthew effect”. This paper provides a comprehensive framework for analyzing the synergistic effects between PRCR, and the research findings can also provide insights for other regions.

Abstract Subarachnoid hemorrhage (SAH) is a devastating subtype of stroke with high mortality and disability rate. Meningeal lymphatic vessels (mLVs) are a newly discovered intracranial fluid transport system and are proven to drain extravasated erythrocytes from cerebrospinal fluid into deep cervical lymph nodes after SAH. However, many studies have reported that the structure and function of mLVs are injured in several central nervous system diseases. Whether SAH can cause mLVs injury and the underlying mechanism remain unclear. Herein, single‐cell RNA sequencing and spatial transcriptomics are applied, along with in vivo/vitro experiments, to investigate the alteration of the cellular, molecular, and spatial pattern of mLVs after SAH. First, it is demonstrated that SAH induces mLVs impairment. Then, through bioinformatic analysis of sequencing data, it is discovered that thrombospondin 1 (THBS1) and S100A6 are strongly associated with SAH outcome. Furthermore, the THBS1‐CD47 ligand‐receptor pair is found to function as a key role in meningeal lymphatic endothelial cell apoptosis via regulating STAT3/Bcl‐2 signaling. The results illustrate a landscape of injured mLVs after SAH for the first time and provide a potential therapeutic strategy for SAH based on mLVs protection by disrupting THBS1 and CD47 interaction.

The large-scale integration of renewable energy resources in the power system challenges its economic and secure operation. Particularly, the increasing penetration of renewable energy will result in insufficient system voltage regulation and reactive power support capabilities, and may cause high risks of nodal voltage and branch flow violations. Therefore, to hedge the operational risks under the worst realization of uncertainties of renewable energy sources, a two-stage robust unit commitment (UC) model is developed. Meanwhile, the convexified AC power flow model is incorporated in the robust UC model to more accurately characterize the real-time operating status of power systems. On this basis, an AC power flow-constrained robust unit commitment (ACRUC) model is formulated. A circular linearization method is then adopted to handle the quadratic constraints in the original AC power flow model, transforming them into tractable linear constraints. Furthermore, to reduce the computational complexity caused by the large-scale newly-added constraints after the linearization process, a customized redundant constraint identification (RCI) method is developed, in which two different modes (i.e., cold and warm start modes) are designed considering the difference in base case system operating condition for linearizing branch losses. Then, the redundant network security constraints could be identified by solving a series of relatively simple optimization subproblems. Numerical results on the modified NERL-118 test system indicate that the proposed model could accurately depict actual operation and scheduling conditions, and also verify that the proposed customized RCI method could effectively reduce the problem scale and improve the solution efficiency.

In order to mitigate the risk of irreversible drowning injuries, this study introduces an enhanced YOLOv5 algorithm aimed at improving the efficacy of indoor swimming pool drowning detection and facilitating the timely rescue of endangered individuals. To simulate drowning and swimming positions accurately, four swimmers were deliberately chosen and observed, with monitoring conducted by drones flying above the swimming pool. The study was approved by the ethics committee of our institution, with the registration number 2022024. The images captured by the drones underwent a meticulous evaluation, and only those deemed suitable were selected to construct the self-made dataset, comprising a total of 8572 images. Furthermore, two enhancements were implemented in the YOLOv5 algorithm. Firstly, the inclusion of the ICA module strengthened category classification and the localization of water behavioral postures, which is improved from the coordinated attention module (CA). Secondly, the PAN module was replaced with the bi-directional feature pyramid network (BiFPN). Subsequently, the improved YOLOv5 algorithm underwent training using the self-made dataset. Evaluation of the algorithm’s performance revealed a notably improved detection accuracy rate, recall rate, and an impressive mean Average Precision (mAP) score of 98.1%, 98.0%, and 98.5%, respectively. Our paper introduces the improved YOLOv5 algorithm, surpassing the original YOLOv5 algorithm in terms of recognition accuracy for instances of drowning.

Abstract Immunosuppressive tumor microenvironment is a crucial factor that impedes the success of tumor immunotherapy, and tumor-associated macrophages (TAMs) are essential for the formation of tumor immunosuppressive microenvironment. Hyaluronic acid (HA) is highly important brick for glioblastoma microenvironment, but whether it contributes to TAM polarization and glioblastoma immunosuppressive microenvironment is less well known. In our study, we observed that disrupting glioblastoma HA synthesis or blocking HA binding to its receptor CD44 on macrophages increased the proportion of M1 macrophages by upregulating SIRPα in macrophages, the underlying mechanism was elevated SIRPα enhanced STAT1 phosphorylation and suppressed STAT3 phosphorylation in macrophages. Subsequently, the induced macrophages could inhibit glioblastoma growth via a feedback effect. In addition, 4-methylumbelliferone (4MU), a cholecystitis drug, can disrupt the CD47/SIRPα axis by disturbing glioblastoma HA synthesis. Collectively, these findings indicated that HA plays a crucial role in macrophages polarization and CD47/SIRPα signaling between glioblastoma cells and macrophages, and suppressing the HA pathway may be a new immunotherapeutic approach for glioblastoma.

Substrate-controlled diversity-oriented synthesis of polycyclic frameworks via [4 + 2] and [3 + 2] annulations between ninhydrin-derived Morita–Baylis–Hillman (MBH) adducts and 3,4-dihydroisoquinolines under similar reaction conditions have been developed. The reaction provides diversity-oriented synthesis of a series of novel and structurally complex spiro multi heterocyclic skeletons in good yields (up to 87% and 90%, respectively) with excellent diastereoselectivities (up to >25:1 dr). In particular, the switchable [4 + 2] and [3 + 2] annulation reactions are controlled by tuning the hydroxyl protecting group on the ninhydrin-derived MBH adduct to deliver structural diverse spiro[indene-2,2′-[1,3]oxazino[2,3-a]isoquinoline] and spiro[indene-2,1′-pyrrolo[2,1-a]isoquinoline], respectively. Furthermore, the relative configuration and chemical structure of two kinds of cycloadducts were confirmed through X-ray diffraction analysis.

Background: The CCN family of stromal proteins is involved in the regulation of many important biological functions. However, the role of dysregulated CCN proteins in lower-grade glioma (LGG) remain less understand.Methods: The clinical significance of the CCN proteins was explored based on RNA-seq profiles from multiple cohorts. A CCNScore was constructed using LASSO regression analysis. The PanCanAtlas data and MEXPRESS database were employed to elucidate molecular underpinnings.Results: The expression of CCN4 was associated with poor prognosis in LGG. The CCNScore (CCN1 = 0.06, CCN4 = 0.86) showed implication in prognosis prediction, subtype assessment and therapy selection. The gene mutation pattern of the high-CCNScore group was similar with glioblastoma, including EGFR, PTEN, and NF1 mutation frequently. Besides, the high-CCNScore group was comprised of samples mainly classic-like and mesenchymal-like, had lower methylation levels, higher stemness, higher inflammation, higher levels of extracellular matrix remodel and dysfunction of metabolic pathways. On the other hand, the low-CCNScore group consisted mainly of IDH-mutation LGG, and was characterized by TP53, CIC, and ATRX gene mutations, hyper-methylation status, lower stemness, lower proliferation, immune quietness and low extracellular matrix stiffness.Conclusion: In summary, these results outlined the role of CCN family in LGG and provided a potential and promising therapeutic target.

Abstract Background RBC membrane derived nanoparticles (NPs) represent an emerging platform with prolonged circulation capacity for the delivery of active substances. For functionalize derived RBCs NPs, various strategies, such as biomimetic rebuilding of RBCs, chemical modification or inserting ligands, have been carried out to improve their performance. However, one potential adverse effect for these methods is the structural failure of membrane proteins, consequently affecting its original immune escape function. Results In this study, we reported a green technology of “disassembly-reassembly” to prepare biomimetic reconstituted RBCs membrane (rRBCs) by separating the endogenous proteins and lipids from nature RBC membrane. IR780 iodide was used as a pattern drug to verify the property and feasibility of rRBCs by constructing IR780@rRBC NPs with IR780@RBC NPs and free IR780 as controls. The results demonstrated the superiority of IR780@rRBC NPs in toxicity, stability, pharmacokinetics and pharmacodynamics compared with IR780@rRBC and free IR780. Conclusions The reported “disassembly-reassembly” strategy shows great potential to produce controllable and versatile rRBC membrane-inspired delivery platform, which may be used to overcome the deficiency of functionalization in cell membrane coated nanoparticles . Graphic abstract

Background: The latest research identified cuproptosis as an entirely new mechanism of cell death. However, as a key regulator in copper-induced cell death, the prognostic and immunotherapeutic value of FDX1 in pan-cancer remains unclear.Methods: Data from the UCSC Xena, GEPIA, and CPTAC were analyzed to conduct an inquiry into the overall differential expression of FDX1 across multiple cancer types. The expression of FDX1 in GBM, LUAD and HCC cell lines as well as their control cell lines was verified by RT-QPCR. The survival prognosis, clinical features, and genetic changes of FDX1 were also evaluated. Finally, the relationship between FDX1 and immunotherapy response was further explored through Gene Set Enrichment Analysis enrichment analysis, tumor microenvironment, immune cell infiltration, immune gene co-expression and drug sensitivity analysis.Results: The transcription and protein expression of FDX1 were significantly reduced in most cancer types and had prognostic value for the survival of certain cancer patients such as ACC, KIRC, HNSC, THCA and LGG. In some cancer types, FDX1 expression was also markedly correlated with the clinical characteristics, TMB, MSI, and antitumor drug susceptibility or resistance of different tumors. Gene set enrichment analysis showed that FDX1 was significantly associated with immune-related pathways. Moreover, the expression level of FDX1 was confirmed to be strongly correlated with immune cell infiltration, immune checkpoint genes, and immune regulatory genes to a certain extent.Conclusion: This study comprehensively explored the potential value of FDX1 as a prognostic and immunotherapeutic marker for pan-cancer, providing new direction and evidence for cancer therapy.

Ginsenoside Rb1 is a potential anti-inflammatory natural molecule, but its therapeutic efficacy was tremendously hampered by the low solubility and non-targeted delivery. In this study, we innovatively developed a mannose (Man)-modified albumin bovine serum albumin carrier (Man-BSA) to overcome the previously mentioned dilemmas of Rb1. The constructed Man-BSA@Rb1 NPs could improve the solubility and increase the cellular uptake of Rb1, finally leading to the enhanced anti-inflammatory effects. The robust therapeutics of Man-BSA@Rb1 NPs were measured in terms of nitrite, tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) levels, which might be achieved by potently inhibiting nuclear factor-κB (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways in lipopolysaccharide (LPS)-induced Raw264.7 cells. Moreover, the therapeutic efficacy of Man-BSA@Rb1 NPs was further confirmed in the d-Gal/LPS-induced liver injury model. The results indicated that Man-BSA may offer a promising system to improve the anti-inflammatory therapy of Rb1.

Bacteria communities associated with plants have been given increasing consideration because they are arguably beneficial to their host plants. To understand the ecological and evolutionary impact of these mutualistic associations, it is important to explore the vast unknown territory of bacterial genomic diversity and their functional contributions associated with the major branches of the tree-of-life. Arguably, this aim can be achieved by profiling bacterial communities by applying high throughput sequencing approaches, besides establishing model plant organisms to test key predictions. This study utilized the Illumina Miseq reads of bacterial 16S rRNA sequences to determine the bacterial diversity associated with the endosphere of the leaves of the highly specialized rock spleenwort Asplenium delavayi (Aspleniaceae). By documenting the bacterial communities associated with ferns collected in natural occurrence and cultivation, this study discovered the most species-rich bacterial communities associated with terrestrial ferns reported until now. Despite the substantial variations of species diversity and composition among accessions, a set of 28 bacterial OTUs was found to be shared among all accessions. Functional analyses recovered evidence to support the predictions that changes in bacterial community compositions correspond to functional differentiation. Given the ease of cultivating this species, Asplenium delavayi is introduced here as a model organism to explore the ecological and evolutionary benefits created by mutualistic associations between bacteria and ferns.

Glioma is the most common intracranial malignant tumor in adults and the 5-year survival rate of glioma patients is extremely poor, even in patients who received Stupp treatment after diagnosis and this forces us to explore more efficient clinical strategies. At this time, immunotherapy shows great potential in a variety of tumor clinical treatments, however, its clinical effect in glioma is limited because of tumor immune privilege which was induced by the glioma immunosuppressive microenvironment, so remodeling the immunosuppressive microenvironment is a practical way to eliminate glioma immunotherapy resistance. Recently, increasing studies have confirmed that ferroptosis, a new form of cell death, plays an important role in tumor progression and immune microenvironment and the crosstalk between ferroptosis and tumor immune microenvironment attracts much attention. This work summarizes the progress studies of ferroptosis in the glioma immune microenvironment.

Abstract The tumor microenvironment plays an important role in tumor progression. Hyaluronic acid (HA), an important component of the extracellular matrix in the tumor microenvironment, abnormally accumulates in a variety of tumors. However, the role of abnormal HA accumulation in glioma remains unclear. The present study indicated that HA, hyaluronic acid synthase 3 (HAS3), and a receptor of HA named CD44 were expressed at high levels in human glioma tissues and negatively correlated with the prognosis of patients with glioma. Silencing HAS3 expression or blocking CD44 inhibited glioma cell proliferation in vitro and in vivo. The underlying mechanism was attributed to the inhibition of autophagy flux and maintaining glioma cell cycle arrest in G1 phase. More importantly, 4-methylumbelliferone (4-MU), a small competitive inhibitor of Uridine diphosphate (UDP) with the ability to penetrate the blood-brain barrier (BBB), also inhibited glioma cell proliferation in vitro and in vivo. Thus, approaches that interfere with HA metabolism by altering the expression of HAS3 and CD44 and the administration of 4-MU potentially represent effective strategies for glioma treatment.

The overlying weakly cemented, and poorly performing strata in Jurassic mines of western China have mechanical properties that are generally lower than those in the Carboniferous-Permian coal mines of central and east China. During coal mining, the overlying strata easily deform and fracture. These then formed water-conducting channels, triggering a series of eco-environmental issues, including ground fracturing, collapsed surfaces, declined underground water levels, deserted lands, and even severe water/sand burst accidents. To study the fracture characteristics of weakly cemented overlying strata and the evolution law of water-conducting fractures in Jurassic coal mines in western China, this study selected Tashidian Erjingtian Mine in Korla, Xinjiang, as the research object. Based on the simulation data obtained with physical analog model testing and field monitoring results, the authors investigated the development of water-conducting fractures in the weakly cemented overlying strata during the coal seam mining process. We simultaneously determined the location of key strata in the working face based on key stratum theory. According to the present research results, key strata controlled the development height of water-conducting fractures. When the primary key stratum or sub-key stratum was not fractured, the development of water-conducting fractures was stagnant; water-conducting fractures developed abruptly when the primary key stratum or sub-key stratum was cracked. The heights of water-conducting fractures in the weakly cemented overlying strata of western China exceeded that of similar stopes of central and east China. These research results provided theoretical and technical support for safety in production at Tashidian Coal Mine. In addition, they offered a reference for green and safe production in Jurassic coal mines of western China.

Tunnel excavation inevitably causes surface deformation. In urban areas, surface deformation could lead to the deformation of surrounding buildings, which may cause damage to communities when accumulated to a certain extent. However, the current construction organization and management mainly rely on on-site deformation measurements, and there is still a lack of reliable prediction methods. Here, we proposed an effective evaluation method for frame building deformation based on the stochastic medium theory and the equivalent beam theory. This method could effectively evaluate the surface and building deformation after a horseshoe tunnel excavation by considering the non-uniform convergence. Furthermore, its accuracy and practicability were verified using the Nanyan Fourth Circuit Transmission Reconstruction located in Dalian, China. The results show that the spatial distribution and characteristic values of the maximum tensile strains were closely related to the ratio of Young’s modulus to the shear modulus (E/G), the building height (h), the tunnel depth (H), the tangent of the tunnel influence angle (tan β) and the convergence radius (ΔR). These achievements can provide a theoretical basis and analytical ideas for investigating the influence of shallow buried tunnel excavation on frame structure buildings in cities.

Transdermal drug delivery for local or systemic therapy provides a potential anticancer modality with a high patient compliance. However, the drug delivery efficiency across the skin is highly challenging due to the physiological barriers, which limit the desired therapeutic effects. In this study, we prepared liposome-in-hydrogels containing a tumor targeting photosensitizer IR780 (IR780/lipo/gels) for tumor photothermal therapy (PTT). The formulation effectively delivered IR780 to subcutaneous tumor and deep metastatic sites, while the hydrogels were applied on the skin overlying the tumor or on an area of distant normal skin. The photothermal antitumor activity of topically administered IR780/lipo/gels was evaluated following laser irradiation. We observed significant inhibition of the rate of the tumor growth without any toxicity associated with the topical administration of hydrogels. Collectively, the topical administration of IR780/lipo/gels represents a new noninvasive and safe strategy for targeted tumor PTT.

The complete chloroplast genome of a staghorn fern species (Platycerium wallichii) was sequenced. The total genome was 158,286 bp in length, containing four regions: large single-copy (LSC) region (79,087 bp), small single-copy (SSC) region (21,397 bp), and two inverted repeat regions (IRs; 28,901 bp per each). In total 129 genes were annotated including 88 coding genes, 33 tRNAs, and 8 rRNAs. The overall GC content of the genome is 40.5%. Phylogenetic analysis supported the monophyly of both the subfamily Platycerioideae and the genus Platycerium. The genome data provides crucial information to support the future conservation and horticulture research.

Abstract Background Chemotherapy is a standard cancer treatment which uses anti-cancer drugs to destroy or slow the growth of cancer cells. However, chemotherapy has limited therapeutic effects in bladder cancer. One of the reasons of this resistance to chemotherapy is that higher levels of glutathione in invasive bladder cancer cells. We have fabricated nanoparticles that respond to high concentrations of glutathione and near-infrared laser irradiation in order to increase the drug accumulation at the tumor sites and combine chemotherapy with photothermal therapy to overcome the challenges of bladder cancer treatment. Methods The DOX&IR780@PEG-PCL-SS NPs were prepared by co-precipitation method. We investigated the tumor targeting capability of NPs in vitro and in vivo. The orthotopic bladder cancer model in C57BL/6 mice was established for in vivo study and the photothermal effects and therapeutic efficacy of NPs were evaluated. Results The DOX&IR780@PEG-PCL-SS NPs were synthesized using internal cross-linking strategy to increase the stability of nanoparticles. Nanoparticles can be ingested by tumor cells in a short time. The DOX&IR780@PEG-PCL-SS NPs have dual sensitivity to high levels of glutathione in bladder cancer cells and near-infrared laser irradiation. Glutathione triggers chemical structural changes of nanoparticles and preliminarily releases drugs, Near-infrared laser irradiation can promote the complete release of the drugs from the nanoparticles and induce a photothermal effect, leading to destroying the tumor cells. Given the excellent tumor-targeting ability and negligible toxicity to normal tissue, DOX&IR780@PEG-PCL-SS NPs can greatly increase the concentration of the anti-cancer drugs in tumor cells. The mice treated with DOX&IR780@PEG-PCL-SS NPs have a significant reduction in tumor volume. The DOX&IR780@PEG-PCL-SS NPs can be tracked by in vivo imaging system and have good tumor targeting ability, to facilitate our assessment during the experiment. Conclusion A nanoparticle delivery system with dual sensitivity to glutathione and near-infrared laser irradiation was developed for delivering IR780 and DOX. Chemo-photothermal synergistic therapy of both primary bladder cancer and their metastases was achieved using this advanced delivery system.

Recent years have witnessed the increasing risk of subsea gas leaks with the development of offshore gas exploration, which poses a potential threat to human life, corporate assets, and the environment. The optical imaging-based monitoring approach has become widespread in the field of monitoring underwater gas leakage, but the shortcomings of huge labor costs and severe false alarms exist due to related operators’ operation and judgment. This study aimed to develop an advanced computer vision-based monitoring approach to achieve automatic and real-time monitoring of underwater gas leaks. A comparison analysis between the Faster Region Convolutional Neural Network (Faster R-CNN) and You Only Look Once version 4 (YOLOv4) was conducted. The results demonstrated that the Faster R-CNN model, developed with an image size of 1280 × 720 and no noise, was optimal for the automatic and real-time monitoring of underwater gas leakage. This optimal model could accurately classify small and large-shape leakage gas plumes from real-world datasets, and locate the area of these underwater gas plumes.

Abstract Background Regarding plant cell wall polysaccharides degradation, multimodular glycoside hydrolases (GHs) with two catalytic domains separated by one or multiple carbohydrate-binding domains are rare in nature. This special mode of domain organization endows the Caldicellulosiruptor bescii CelA (GH9-CBM3c-CBM3b-CBM3b-GH48) remarkably high efficiency in hydrolyzing cellulose. CbXyn10C/Cel48B from the same bacterium is also such an enzyme which has, however, evolved to target both xylan and cellulose. Intriguingly, the GH10 endoxylanase and GH48 cellobiohydrolase domains are both dual functional, raising the question if they can act synergistically in hydrolyzing cellulose and xylan, the two major components of plant cell wall. Results In this study, we discovered that CbXyn10C and CbCel48B, which stood for the N- and C-terminal catalytic domains, respectively, cooperatively released much more cellobiose and cellotriose from cellulose. In addition, they displayed intramolecular synergy but only at the early stage of xylan hydrolysis by generating higher amounts of xylooligosaccharides including xylotriose, xylotetraose, and xylobiose. When complex lignocellulose corn straw was used as the substrate, the synergy was found only for cellulose but not xylan hydrolysis. Conclusion This is the first report to reveal the synergy between a GH10 and a GH48 domain. The synergy discovered in this study is helpful for understanding how C. bescii captures energy from these recalcitrant plant cell wall polysaccharides. The insight also sheds light on designing robust and multi-functional enzymes for plant cell wall polysaccharides degradation.

The division of focal plane (DoFP) polarization imaging sensors, which can simultaneously acquire the target’s two-dimensional spatial information and polarization information, improves the detection resolution and recognition capability by capturing the difference in polarization characteristics between the target and the background. In this paper, we propose a novel polarization imaging method based on deep compressed sensing (DCS) by adding digital micromirror devices (DMD) to an optical system and simulating the polarization transmission model of the optical system to reconstruct high-resolution images under low sampling rate conditions. By building a simulated dataset, training a polarization super-resolution imaging network, and showing excellent reconstructions on real shooting scenes, compared to current algorithms, our model has a higher peak signal-to-noise ratio (PSNR), which validates the feasibility of our approach.

Phototheranostics that concurrently integrates accurate diagnosis (e.g., fluorescence and photoacoustic (PA) imaging) and in situ therapy (e.g., photodynamic therapy (PDT) and photothermal therapy (PTT)) into one platform represents an attractive approach for accelerating personalized and precision medicine. The second near-infrared window (NIR-II, 1000–1700 nm) has attracted considerable attention from both the scientific community and clinical doctors for improved penetration depth and excellent spatial resolution. NIR-II agents with a PDT property as well as other functions are recently emerging as a powerful tool for boosting the phototheranostic outcome. In this minireview, we summarize the recent advances of photodynamic NIR-II aggregation-induced emission luminogens (AIEgens) for biomedical applications. The molecular design strategies for tuning the electronic bandgaps and photophysical energy transformation processes are discussed. We also highlight the biomedical applications, such as image-guided therapy of both subcutaneous and orthotopic tumors, and multifunctional theranostics in combination with other treatment methods, including chemotherapy and immunotherapy; and the precise treatment of both tumor and bacterial infection. This review aims to provide guidance for PDT agents with long-wavelength emissions to improve the imaging precision and treatment efficacy. We hope it will provide a comprehensive understanding about the chemical structure–photophysical property–biomedical application relationship of NIR-II luminogens.

An efficient, three-component reaction of aldehydes and benzofuran-3-ones was developed. This process provides a new approach for the preparation of synthetically and biologically important spirobenzofuran-3-one derivatives with moderate-to-good yields under mild conditions. A switch of intramolecular to intermolecular domino Michael–aldol–lactonization leading to differential product formation was achieved by different NHCs catalysis.

Abstract Background Glioblastoma is a disease with high heterogeneity that has long been difficult for doctors to identify and treat. ARHI is a remarkable tumor suppressor gene in human ovarian cancer and many other cancers. We found over-expression of ARHI can also inhibit cancer cell proliferation, decrease tumorigenicity, and induce autophagic cell death in human glioma and inhibition of the late stage of autophagy can further enhance the antitumor effect of ARHI through inducing apoptosis in vitro or vivo. Methods Using MTT assay to detect cell viability. The colony formation assay was used to measure single cell clonogenicity. Autophagy associated morphological changes were tested by transmission electron microscopy. Flow cytometry and TUNEL staining were used to measure the apoptosis rate. Autophagy inhibitor chloroquine (CQ) was used to study the effects of inhibition at late stage of autophagy on ARHI-induced autophagy and apoptosis. Protein expression were detected by Western blot, immunofluorescence and immunohistochemical analyses. LN229-derived xenografts were established to observe the effect of ARHI in vivo. Results ARHI induced autophagic death in glioma cells, and blocking late-stage autophagy markedly enhanced the antiproliferative activites of ARHI. In our research, we observed the inhibition of RAS-AKT-mTOR signaling in ARHI-glioma cells and blockade of autophagy flux at late stage by CQ enhanced the cytotoxicity of ARHI, caused accumulation of autophagic vacuoles and robust apoptosis. As a result, the inhibition of RAS augmented autophagy of glioma cells. Conclusion ARHI may also be a functional tumor suppressor in glioma. And chloroquine (CQ) used as an auxiliary medicine in glioma chemotherapy can enhance the antitumor effect of ARHI, and this study provides a novel mechanistic basis and strategy for glioma therapy.

Proteins such as albumin, gelatin, casein, transferrin, and collagen are widely used as drug delivery systems. However, only albumin-based paclitaxel (PTX) formulation Abraxane® (PTX-albumin NPs prepared by nab-technology) has been successfully developed for treating metastatic breast cancer clinically due to abundant materials, simple industrial scale-up process, and well tumor-targeting ability. Hemoglobin (Hb) is another protein used for drug delivery with similar advantages. In this study, we successfully synthesized PEG-Hb nanoparticles loading with PTX based on previously well-established acid-denatured method. PEG-Hb-PTX NPs showed enhanced cellular uptake and great cellular inhibition ability in vitro. Moreover, our animal study showed that PEGylated NPs greatly accumulated in tumor tissues and exhibited excellent anticancer activity in vivo. We found that PEG-Hb-PTX NPs possess a better in vivo antitumor effect than the commercially available Taxol® formulation. We believe that PEG-Hb has great potential as an efficient drug delivery system for further clinic study.

The quality of a mine’s microseismic network layout directly affects the location accuracy of the microseismic network. Introducing the microseismic probability factor Fe, the microseismic importance factor FQ, and the effective range factor FV, an improved particle swarm algorithm with bacterial foraging algorithm is proposed to optimize the mine’s microseismic network layout and evaluation system based on the D-value optimization design theory. Through numerical simulation experiments, it is found that the system has the advantages of fast optimization speed and good network layout effect. Combined with the system application at Xiashijie Coal Mine in Tongchuan City, Shaanxi Province, the method in this paper successfully optimizes the layout of the 20-channel network, ensuring that the positioning error of key monitoring areas is controlled within 20 m, and the minimum measurable magnitude can reach −3.26. Finally, it is verified by blasting tests that the maximum spatial positioning accuracy of the site is within 12.2 m, and the positioning capability of the site network is more accurately evaluated. The relevant research can provide a reference for the layout of the microseismic monitoring network for similar projects.

Malignant cancer is a devastating disease often associated with a poor clinical prognosis. For decades, modern drug discoveries have attempted to identify potential modulators that can impede tumor growth. Cancer stem cells however are more resistant to therapeutic intervention, which often leads to treatment failure and subsequent disease recurrence. Here in this study, we have developed a specific multi-target drug delivery nanoparticle system against breast cancer stem cells (BCSCs). Therapeutic agents curcumin and salinomycin have complementary functions of limiting therapeutic resistance and eliciting cellular death, respectively. By conjugation of CD44 cell-surface glycoprotein with poly(lactic-co-glycolic acid) (PLGA) nanoparticles that are loaded with curcumin and salinomycin, we investigated the cellular uptake of BCSCs, drug release, and therapeutic efficacy against BCSCs. We determined CD44-targeting co-delivery nanoparticles are highly efficacious against BCSCs by inducing G1 cell cycle arrest and limiting epithelial–mesenchymal transition. This curcumin and salinomycin co-delivery system can be an efficient treatment approach to target malignant cancer without the repercussion of disease recurrence.

A mild and efficient strategy for the synthesis of tricyclic 1,2,4-oxadiazolines-fused tetrahydro-isoquinolines derivatives via [3 + 2] cycloaddition reaction is reported. The reactions provided the functionalized tricyclic 1,2,4-oxadiazolines in high yields (up to 96%). This protocol is simple and easy to handle. Moreover, a gram-scale experiment further highlights the synthetic utility. The chemical structure of the product was determined by X-ray single-crystal structure analysis. A possible mechanism for this transformation is proposed to explain the reaction process.

Reclaimed soil is the key substrate for land reclamation and ecological restoration in the mine areas. The change of the density of reclaimed soil of the nonmetallic mines in Xinjiang during the land reclamation process was studied in this paper. Firstly, the in situ test method of static load was used to simulate the compaction of reclaimed soil with different thickness of overlying soil by different compaction times of mines reclamation machinery, and field in situ test compaction data were obtained. Then, the numerical simulation method was used to simulate the variation process of displacement and porosity at different depths for different thickness of the reclaimed soil under different compaction conditions. The numerical simulation and the in situ test results verified each other to acquire the compaction process and results of reclaimed soil under different compaction. The results showed that the numerical simulation results were consistent with the in situ test. The reclaimed soil thickness and compaction times were crucial factors affecting the compaction effect of the soil. The difference between the three times compaction and the uncompacted soil was obvious, and the effect of single compaction was weakened with the increase of compaction times. Under the same compaction action, the thicker the soil was, the less obvious the compaction effect would be. In the process of reclamation, the compaction effect of the surface part (at the depth of 10 cm) was visible, and the amount of compression and springback was larger. The research results can provide a reference to the land reclamation of nonmetallic mines in Xinjiang, China.

The microseismic signals in the coal minefield are very complex because of its special environment with a large number of blast vibration signals, and how to effectively identify the microseismic signals is still a big problem. S transform (ST) and Manifold Learning (ML) methods are introduced to extract the characteristics of the microseismic signals, and Gaussian Mixture Model based on the improved Bee Colony optimization algorithm (IBC-GMM) is established to identify the microseismic signals accurately. Firstly, the time-frequency characteristics of microseismic signals in coal mine are extracted by ST analysis. It is found that there are obvious time-frequency differences between rock-fracturing signals and blast vibration signals. Blast vibration signals have short duration, high frequency, and complex frequency spectrum, and their dominant frequencies are mainly over 100 Hz. However, rock-fracturing signals are relatively slow, with low frequency and stable spectrum change, and their dominant frequencies are generally below 100 Hz. Then, combining with the microseismic data of Xiashinjie coal mine in Tongchuan, China, the feature dimension reduction is carried out by Manifold Learning (ML) method, and the processed feature vectors are automatically recognized by IBC-GMM. Field test results show that the method summarizes the characteristics of the microseismic wave which are difficult to emerge as the learning vector, and the features reflect the key features of microseismic signals well. The identification accuracy is as high as 94%, and its recognition effect is superior to other recognition models (such as traditional Gaussian Mixture Model based on Expectation-Maximum (EM-GMM), Backpropagation (BP) neural network, Random Forests (RF), Bayes (Bayes) methods, and Logistic Regression (LR) method). Therefore, IBC-GMM could be used to mine engineering microseismic monitoring waveform recognition to provide the reference.

N-acetylglucosamine (GlcNAc) is an amino sugar that has been widely used in the nutraceutical and pharmaceutical industries. Recently, microbial production of GlcNAc has been developed. One major challenge for efficient biosynthesis of GlcNAc is to achieve appropriate carbon flux distribution between growth and production. Here, a synergistic substrate co-utilization strategy was used to address this challenge. Specifically, glycerol was utilized to support cell growth and generate glutamine and acetyl-CoA, which are amino and acetyl donors, respectively, for GlcNAc biosynthesis, while glucose was retained for GlcNAc production. Thanks to deletion of the 6-phosphofructokinase (PfkA and PfkB) and glucose-6-phosphate dehydrogenase (ZWF) genes, the main glucose catabolism pathways of Escherichia coli were blocked. The resultant mutant showed a severe defect in glucose consumption. Then, the GlcNAc production module containing glucosamine-6-phosphate synthase (GlmS*), glucosamine-6-phosphate N-acetyltransferase (GNA1*) and GlcNAc-6-phosphate phosphatase (YqaB) expression cassettes was introduced into the mutant, to drive the carbon flux from glucose to GlcNAc. Furthermore, co-utilization of glucose and glycerol was achieved by overexpression of glycerol kinase (GlpK) gene. Using the optimized fermentation medium, the final strain produced GlcNAc with a high stoichiometric yield of 0.64 mol/mol glucose. This study offers a promising strategy to address the challenge of distributing carbon flux in GlcNAc production.

Background/Aims: Glioblastoma multiforme (GBM) is the most devastating and widespread primary central nervous system tumour in adults, with poor survival rate and high mortality rates. Existing treatments do not provide substantial benefits to patients; therefore, novel treatment strategies are required. Peiminine, a natural bioactive compound extracted from the traditional Chinese medicine Fritillaria thunbergii, has many pharmacological effects, especially anticancer activities. However, its anticancer effects on GBM and the underlying mechanism have not been demonstrated. This study was conducted to investigate the potential antitumour effects of peiminine in human GBM cells and to explore the related molecular signalling mechanisms in vitro and in vivo Methods: Cell viability and proliferation were detected with MTT and colony formation assays. Morphological changes associated with autophagy were assessed by transmission electron microscopy (TEM). The cell cycle rate was measured by flow cytometry. To detect changes in related genes and signalling pathways in vitro and in vivo, RNA-seq, Western blotting and immunohistochemical analyses were employed. Results: Peiminine significantly inhibited the proliferation and colony formation of GBM cells and resulted in changes in many tumour-related genes and transcriptional products. The potential anti-GBM role of peiminine might involve cell cycle arrest and autophagic flux blocking via changes in expression of the cyclin D1/CDK network, p62 and LC3. Changes in Changes in flow cytometry results and TEM findings were also observed. Molecular alterations included downregulation of the expression of not only phospho-Akt and phospho-GSK3β but also phospho-AMPK and phospho-ULK1. Furthermore, overexpression of AKT and inhibition of AKT reversed and augmented peiminine-induced cell cycle arrest in GBM cells, respectively. The cellular activation of AMPK reversed the changes in the levels of protein markers of autophagic flux. These results demonstrated that peiminine mediates cell cycle arrest by suppressing AktGSk3β signalling and blocks autophagic flux by depressing AMPK-ULK1 signalling in GBM cells. Finally, peiminine inhibited the growth of U251 gliomas in vivo. Conclusion: Peiminine inhibits glioblastoma in vitro and in vivo via arresting the cell cycle and blocking autophagic flux, suggesting new avenues for GBM therapy.

Due to the different geological conditions and construction methods associated with different projects, rockbursts in deep-buried tunnels often present different precursor characteristics, bringing major challenges to the early warning of rockbursts. To adapt to the complexity of engineering, it is necessary to review the latest advancements in rockburst early warning and to discuss general early warning methods. In this article, first, microseismic monitoring and localization methods applicable under tunneling construction are reviewed. Based on the latest engineering examples and research progress, the microseismic evolution characteristics of the rockburst formation process are summarized, and the formation process and mechanism of structure-type and delayed rockbursts are analyzed. The different methods for predicting the risk and level of rockbursts using microseismic indices are reviewed, and the implementation methods and application cases for predicting potential rockburst areas and rockburst probability based on a mechanical model are expounded. Finally, combined with the new practice in early warning methods, development directions for the early warning of rockbursts are put forward.