Yolk-Shell Construction of Na3 V2 (PO4 )2 F3 with Copper Substitution Microsphere as High-Rate and Long-Cycling Cathode Materials for Sodium-Ion Batteries.

Na3 V2 (PO4 )2 F3 (NVPF) is emerging as a promising cathode material for high-voltage sodium-ion batteries. Whereas, the inferior intrinsic electrical conductivity leading to poor rate performance and cycling stability. To address this issue, a strategy of synthesizing unique yolk-shell structured NVPF with copper substitution via spray drying method is proposed. Besides, the synergistic modulation of both crystalline structure and interfacial properties results in significantly enhanced intrinsic and interfacial conductivity of NVPF. The optimized yolk-shell structured cathode materials can possess a high capacity of 117.4 mAh g-1 at 0.1 C, and remains a high-capacity retention of 91.3% after 5000 cycles. A detailed investigation of kinetic properties combined with in situ XRD technology and DFT calculations, has been implemented, particularly with regard to electron conduction and sodium ion diffusion. Consequently, the yolk-shell structured composition of Na3 V1.94 Cu0.06 (PO4 )2 F3 with nitrogen-modified carbon coating layer shows the lowest polarization potential because of the effectively enhanced electronic conductivity and Na+ diffusion process in the bulk phase. The robust electrochemical performance suggests that developing the unique yolk-shell structure with the collaboration of interface and bulk crystal properties is a favorable strategy to design cathode material with a high performance for sodium-ion batteries.

Advancing Gastrointestinal Health: Curcumin's Efficacy and Nanopreparations.

Curcumin (CCM) is a polyphenol compound extracted from the turmeric rhizome. It has various biological activities, including antibacterial, anti-inflammatory, anti-cancer, and antioxidant. Due to its diverse activities, it is often used by researchers to study the therapeutic effects on various diseases. However, its poor solubility leads to poor bioavailability, and it is necessary to increase the water solubility with the help of carriers to improve the therapeutic effect. Gastrointestinal disease is a major global health problem that continues to affect human health. In this review, we have summarized the possible mechanism and therapeutic effect of CCM in various gastrointestinal diseases, and the improvement in the curative effect of CCM with nanopreparation. Finally, we concluded that there have been many clinical trials of CCM in combination with other drugs for the treatment of gastrointestinal disease, but so far, few have used CCM nanomaterials for treatment. Although in vitro and preclinical experiments have shown that nanopreparations can improve the efficacy of CCM, there are still insufficient studies on the safety of carriers.

Silver Mesoporous Silica Nanoparticles: Fabrication to Combination Therapies for Cancer and Infection.

The integration of silver nanoparticles (Ag NPs) with mesoporous silica nanoparticles (MSNs) protects the former from aggregation and promotes the controlled release of silver ions, resulting in therapeutic significance on cancer and infection. The unique size, shape, pore structure and silver distribution of silver mesoporous silica nanoparticles (Ag-MSNs) embellish them with the potential to perform combined imaging and therapeutic actions via modulating optical and drug release properties. Here, we comprehensively review the recent progress in the fabrication and application of Ag-MSNs for combination therapies for cancer and infection. We first elaborate on the fabrication of star-shaped structure, core-shell structure, and Janus structure Ag-MSNs. We then highlight Ag-MSNs as a multifunctional nanoplatform to surface-enhanced Raman scattering-based detection, non-photo-based cancer theranostics and photo-based cancer theranostics. In addition, we detail Ag-MSNs for combined antibacterial therapy via drug delivery and phototherapy. Overall, we summarize the challenges and future perspectives of Ag-MSNs that make them promising for diagnosis and therapy of cancer and infection.

Current WHO Guidelines and the Critical Role of Genetic Parameters in the Classification of Glioma: Opportunities for Immunotherapy.

OPINION STATEMENT: In the 5 years since the fourth edition of the WHO Classification of Tumors of the Central Nervous System (CNS) (revised) was released, the development of targeted sequencing and omics technology has helped researchers in the field of neuro-oncology to identify some new tumor types in clinical practice, as well as a series of genetic parameters related to tumor occurrence and development, poor prognosis, treatment response, etc. These findings not only provide basic knowledge for the classification of glioma, but also promote the progress of the treatment of gliomas. As a revolution in cancer treatment, immunotherapy has become a promising strategy since the pioneering discovery of lymphatics in the CNS. The advancement and clinical application of immunotherapy have strengthened the demand for accurate classification of glioma. In June 2021, the WHO and the International Agency for Research on Cancer (IARC) published the fifth edition of the WHO Classification of Tumors of the CNS. The fifth edition focuses on advancing the role of genetic parameters in the classification of glioma and divides glioma into more biologically and molecularly defined entities, with better natural history characteristics, and introduced new tumor types and subtypes, especially in the pediatric population. Most importantly, these updated classifications will enable clinicians to better assess the prognosis and formulate the optimal treatment of gliomas.

Molecular and clinical characterization of Galectin-9 in glioma through 1,027 samples.

In recent years, research on glioma immunotherapy have grown rapidly. However, the autoimmune-like side effects that are caused by blocking immunological checkpoints hinder their clinical application in gliomas currently. Galectin-9, a ligand for T-cell immunoglobulin mucin 3, has shed a new light on the treatment of malignant glioma. However, the potential mechanism of Galectin-9 is still under discussion. In this study, first, we methodically gathered 1,027 glioma patients with RNA-seq and 986 patients with survival data to explore the role and mechanism of Galectin-9 in gliomas. Second, we analyzed glioma samples from 50 patients in the Department of Neurosurgery, Tianjin Medical University General Hospital. Finally, we found that Galectin-9 was strongly upregulated in glioblastoma multiforme compared with normal brain tissues and lower-grade glioma. Patients with Galectin-9 overexpression had a significantly shorter overall survival. Moreover, the tissue microarray data displayed that the expression of Galectin-9 in the core of tumor is higher than that in the border and was correlated with the shorter survival in glioma patients. Galectin-9 is more highly expressed in the mesenchymal subtype of glioblastoma multiforme than in the other subtypes. Simultaneously, Galectin-9 was closely associated with the immune response and lymphocyte activation, especially T-cell activation. To further determine the underlying role of Galectin-9 in the immune response, we selected seven immune metagenes. Through cluster analysis and correlation analysis, we discovered that Galectin-9 was highly correlated with immune checkpoint molecules and M2 tumor-associated macrophages. In summary, Galectin-9 serves as a potential therapeutic target to treat glioblastoma multiforme.

The potential diagnostic power of CD138+ microparticles from the plasma analysis for multiple myeloma clinical monitoring.

Multiple myeloma (MM) is malignant tumor with abnormal proliferation of bone marrow plasma cells. The existing clinical tools used to determine treatment response and tumor relapse are limited in sensitivity. We investigated the CD138+ microparticles (MPs) of MM patients to find out whether MPs could provide a novel means to monitor the malignant cells in MM patients. Our study showed that the levels of MPs were significantly elevated in MM patients. The MP counts in peripheral blood from new diagnosed MM patients were significantly higher than patients in CR and HD. Consist with the total MPs, the number of the PC-derived MPs (CD138+) increased in BM from MM patients compared with CR and HD. The ratio of the PC-derived MPs (CD138+) in BM increased in MM patients compared with CR and HD. The correlation test revealed that the CD138+ MPs in BM and PB were all positively correlated with the plasmacyte ratio in bone marrow (BMPC) and the ß2 -MG. New diagnosed MM patients and controls were compared, and ROC curves were used to identify cutoff points with optimal sensitivity and specificity concerning the ratios and counts of CD138+ MPs in BM and PB. The AUC of the CD138+ MP counts in BM was 0.767, and in PB was 0.680. The AUC of the CD138+ MP ratios in BM was 0.714, and in PB was 0.666. According to this, the counts of CD138+ MPs in BM showed to be a powerful marker of diagnosis. We demonstrated that CD138+ MPs from the plasma provide support for a potential monitoring biomarker of MM.

Off-Stoichiometry of Sodium Iron Pyrophosphate as Cathode Materials for Sodium-Ion Batteries with Superior Cycling Stability.

As one of the important devices for large-scale electrochemical energy storage, sodium-ion batteries have received much attention due to the abundant resources of raw materials. However, whether it is a base station power source, an energy storage power station, or a start-stop power supply, long energy cycle life (more than 5000 cycles), high stability, and safety performance are application prerequisites. Regrettably, currently, few sodium-ion batteries can meet this requirement, mainly due to shortcomings in positive electrode performance. We report a sufficiently stable sodium-ion battery cathode material, Na2Fe0.95P2O7, that retains 97.5% capacity after 5000 charge/discharge cycles. The use of nonstoichiometry in the lattice enables simultaneous modification of the crystal and electronic structure, promoting Na2Fe0.95P2O7 to be extremely stable while still being able to achieve a capacity of 92 mAh g-1 and stable cycling at high temperatures up to 60 °C. Our results confirm the positive effect of nonstoichiometric ratios on the performance of Na2Fe0.95P2O7 and provide a reliable idea to promote the practical application of sodium-ion batteries.

A High-Entropy Intergrowth Layered-Oxide Cathode with Enhanced Stability for Sodium-Ion Batteries.

Layered transition metal oxides are widely considered as ideal cathode materials for SIBs. However, the existing P2 and O3 structures possess specific issues, which limit their practical applications. To address these issues, this work designed a novel intergrowth layered oxide cathode with P2 and O3 phases by implementing Cu and Ti into the structure with the formation of high-entropy cathode materials with superior performance for SIBs. The electrochemical test results show that the optimized high-entropy cathode with the P2/O3 intergrowth structure possesses a high initial discharge capacity of 157.85 mAh g-1 at 0.1 C, an excellent rate performance of 84.41 mAh g-1 at 10 C, and long-term stability with capacity retention of 83.25% after 500 cycles at 5C. Furthermore, the analysis results of ex situ XRD and in situ XRD indicate that the adverse phase transition of P2-O2 under high voltage is effectively suppressed. This work indicates that the integration of high-entropy strategy with the two-phase intergrowth structure can effectively stabilize the layered structure, suppress the slipping of transition metal layers, and improve electrochemical performance, which provides a new approach for designing high-performance and practical layered transition metal oxide cathode materials for advanced SIBs.

Hydrogen Attenuates Cognitive Impairment in Rat Models of Vascular Dementia by Inhibiting Oxidative Stress and NLRP3 Inflammasome Activation.

Vascular dementia (VaD) is the second most common form of dementia worldwide. Oxidative stress and neuroinflammation are important factors contributing to cognitive dysfunction in patients with VaD. The antioxidant and anti-inflammatory properties of hydrogen are increasingly being utilized in neurological disorders, but conventional hydrogen delivery has the disadvantage of inefficiency. Therefore, magnesium silicide nanosheets (MSNs) are used to release hydrogen in vivo in larger quantities and for longer periods of time to explore the appropriate dosage and regimen. In this study, it is observed that hydrogen improved learning and working memory in VaD rats in the Morris water maze and Y-maze, which elicits improved cognitive function. Nissl staining of neurons shows that hydrogen treatment significantly improves edema in neuronal cells. The expression and activation of reactive oxygen species (ROS), Thioredoxin-interacting protein (TXNIP), NOD-like receptor protein 3 (NLRP3), caspase-1, and IL-1ß in the hippocampus are measured via ELISA, Western blotting, real-time qPCR, and immunofluorescence. The results show that oxidative stress indicators and inflammasome-related factors are significantly decreased after 7dMSN treatment. Therefore, it is concluded that hydrogen can ameliorate neurological damage and cognitive dysfunction in VaD rats by inhibiting ROS/NLRP3/IL-1ß-related oxidative stress and inflammation.

Comprehensive analysis of m6A subtype classification for immune microenvironment of pituitary adenomas.

BACKGROUND: N6-methyladenosine (m6A) RNA methylation and tumor immune microenvironment (IME) have an essential role in tumor development. However, their relationships in pituitary adenomas (PAs) remains unclear. METHODS: PA datasets from the Gene Expression Omnibus (GEO) and European Bioinformatics Institute (EMBL-EBI) were used. We utilized hierarchical clustering algorithms based on the m6A regulator gene set to identify m6A subtypes. ESTIMATE and CIBERSORT algorithms were applied to explore the compositions of stromal and immune cells. A nomogram model was constructed for the prediction of m6A subtypes in PAs. Immunohistochemistry and multiplex immunofluorescence staining were used to analyze the expression level of m6A regulator YTHDF2 in relation to M2 macrophages and immune checkpoints in PAs. RESULTS: We concluded the IME landscape of m6A subtype classification and characterized two emerging m6A subtypes. Different IME between these two m6A subtypes were identified. Simultaneously, a polygenic nomogram model was constructed for predicting m6A subtype classification, with excellent predictive performance (training set, AUC = 0.984; validation set, AUC = 0.986). YTHDF2 was highly expressed in PAs and accompanied by upregulated M2 macrophages and expression of PD-L1. CONCLUSIONS: We proposed two novel m6A subtypes in PAs for the first time and constructed a reliable and clinically accessible nomogram model for them. Meanwhile, YTHDF2 was first identified as a promising biomarker for immunotherapy and potential molecular target in PAs.

A decellularized lung extracellular matrix/chondroitin sulfate/gelatin/chitosan-based 3D culture system shapes breast cancer lung metastasis.

Distal metastasis of breast cancer is a primary cause of death, and the lung is a common metastatic target of breast cancer. However, the role of the lung niche in promoting breast cancer progression is not well understood. Engineered three-dimensional (3D) in vitro models capable of bridging this knowledge gap can be specifically designed to mimic crucial characteristics of the lung niche in a more physiologically relevant context than conventional two-dimensional systems. In this study, two 3D culture systems were developed to mimic the late stage of breast cancer progression at a lung metastatic site. These 3D models were created based on a novel decellularized lung extracellular matrix/chondroitin sulfate/gelatin/chitosan composite material and on a porcine decellularized lung matrix (PDLM), with the former tailored with comparable properties (stiffness, pore size, biochemical composition, and microstructure) to that of the in vivo lung matrix. The different microstructure and stiffness of the two types of scaffolds yielded diverse presentations of MCF-7 cells in terms of cell distribution, cell morphology, and migration. Cells showed better extensions with apparent pseudopods and more homogeneous and reduced migration activity on the composite scaffold compared to those on the PDLM scaffold. Furthermore, alveolar-like structures with superior porous connectivity in the composite scaffold remarkably promoted aggressive cell proliferation and viability. In conclusion, a novel lung matrix-mimetic 3D in vitro breast cancer lung metastasis model was developed to clarify the underlying correlativity between lung ECM and breast cancer cells after lung colonization. A better understanding of the effects of biochemical and biophysical environments of the lung matrix on cell behaviors can help elucidate the potential mechanisms of breast cancer progression and further improve target discovery of therapeutic strategies.

Pycnoporus sanguineus Polysaccharides as Reducing Agents: Self-Assembled Composite Nanoparticles for Integrative Diabetic Wound Therapy.

Purpose: Diabetic foot ulcers (DFU) are severe complications of diabetes, posing significant health and societal challenges. Elevated levels of reactive oxygen species (ROS) at the ulcer site hinder wound healing in most patients, while individuals with diabetes are also more susceptible to bacterial infections. This study aims to synthesize a comprehensive therapeutic material using polysaccharides from Pycnoporus sanguineus to promote DFU wound healing, reduce ROS levels, and minimize bacterial infections. Methods: Polysaccharides from P.sanguineus were employed as reducing and stabilizing agents to fabricate polysaccharide-based composite particles (PCPs) utilizing silver ions as templates. PCPs were characterized via UV-Vis, TEM, FTIR, XRD, and DLS. The antioxidant, antimicrobial, and cytotoxic properties of PCPs were assessed through in vitro and cellular experiments. The effects and mechanisms of PCPs on wound healing were evaluated using a diabetic ulcer mouse model. Results: PCPs exhibited spherical particles with an average size of 57.29±22.41 nm and effectively combined polysaccharides' antioxidant capacity with silver nanoparticles' antimicrobial function, showcasing synergistic therapeutic effects. In vitro and cellular experiments demonstrated that PCPs reduced cellular ROS levels by 54% at a concentration of 31.25 µg/mL and displayed potent antibacterial activity at 8 µg/mL. In vivo experiments revealed that PCPs enhanced the activities of superoxide dismutase (SOD) and catalase (CAT), promoting wound healing in DFUs and lowering the risk of bacterial infections. Conclusion: The synthesized PCPs offer a novel strategy for the comprehensive treatment of DFU. By integrating antioxidant and antimicrobial functions, PCPs effectively promote wound healing and alleviate patient suffering. The present study demonstrates a new strategy for the integrated treatment of diabetic wounds and expands the way for developing and applying the polysaccharide properties of P. sanguineus.

Gas therapy strategies for depression and schizophrenia: A review.

Depression and schizophrenia are 2 serious mental disorders. Their effective treatment is an urgent medical and social problem at present. Drug treatment is the basic measure to improve mental disorders, especially serious mental disorders. However, the side effects of traditional antipsychotic drugs cannot be avoided. Surprisingly, in recent years, it has been found that nitric oxide (NO), carbon monoxide (CO), hydrogen sulfide (H2S) and hydrogen (H2) can regulate corresponding signal pathways to treat mental diseases in animal models. More importantly, as gas signal molecules, they will not bring toxicity and side effects after metabolism. Therefore, in this review, we analyzed the effects of gas on depression and schizophrenia through endogenous gas generation and external gas delivery strategies in some animal models. Endogenous gas generation strategy: summarized the therapeutic mechanism of gas signaling molecules on depression and schizophrenia, and listed the main ways to inhibit or stimulate gas generation. External gas delivery strategy: The common external stimuli-responsive gasotransmitter prodrugs and some study of these prodrugs in the treatment of depression and schizophrenia are summarized. We also analyzed the prospects of nano-gas carrier in the treatment of depression and schizophrenia. Through this review, we hope to provide guidance for treating depression and schizophrenia by regulating relevant gas signal pathways, and provide reference for developing safe and effective drugs for treating mental disorders by summarizing exogenous gas drugs.

Controlled Cascade-Release and High Selective Sterilization by Core-Shell Nanogels for Microenvironment Regulation of Aerobic Vaginitis.

Aerobic vaginitis (AV) is a gynecological disease associated with vaginal flora imbalance. The nonselective bactericidal nature of antibiotics and low customization rate of probiotic supplementation in existing treatments lead to AV recurrence. Here, a drug delivery strategy is proposed that works with the changing dynamics of the bacterial flora. In particular, a core-shell nanogel (CSNG) is designed to encapsulate prebiotic inulin and antimicrobial peptide Cath 30. The proposed strategy allows for the sequential release of both drugs using gelatinase produced by AV pathogenic bacteria, initially selectively killing pathogenic bacteria and subsequently promoting the proliferation of beneficial bacteria in the vagina. In a simulated infection environment in vitro, the outer layer of CSNGs, Cath 30 is rapidly degraded and potently killed the pathogenic bacterium Staphylococcus aureus at 2-6 h. CSNGs enhances proliferation of the beneficial bacterium Lactobacillus crispatus by more than 50% at 24 h. In a rat AV model, the drug delivery strategy precisely regulated the bacterial microenvironment while controlling the inflammatory response of the vaginal microenvironment. This new treatment approach, configured on demand and precisely controlled, offers a new strategy for the treatment of vaginal diseases.

Hypocapnia Stimuli-Responsive Engineered Exosomes Delivering miR-218 Facilitate Sciatic Nerve Regeneration.

Therapeutic strategies of microRNAs (miRNAs) and exosomes have been systematically explored as an enhancing application by paracrine and modulating cellular activity after internalization of recipient cells in vitro, and progressively developed to meet the requirements of peripheral nerve regeneration in vivo. However, how to obtain exosomes with superior properties and effectively deliver miRNAs becomes a key challenge. Hypocapnia environment might play unexpected outcomes in strengthening exosome function when culturing adipose-derived stem cells (ASCs). Previously, we discovered the intensive regulation of miR-218 on the differentiation of ASCs. In the present study, we analyzed the functional differences of secreted exosomes in response to hypocapnia stimulation, and explored the application in combination with miR-218 to facilitate sciatic nerve regeneration. Our results indicated that the delivery system of engineered exosomes derived from ASCs remarkably loads upregulated miR-218 and promotes cellular activity in the recipient cells (PC12 cells), and hypocapnia stimuli-responsive exosomes exhibit strengthening properties. Furthermore, in a sciatic nerve injury model, exosomes delivering miR-218 combined with engineered scaffold facilitated the regeneration of injured sciatic nerves. In the hypocapnia-stimulated exosome group, more encouraging promotion was revealed on the regeneration of motor and nerve fibers. Hypoc-miR-218-ASC exosomes are suggested as a promising cell-free strategy for peripheral nerve repair.

An Improved Multitask Learning Model with Matching Network and Its Application in Traditional Chinese Medicine Syndrome Recommendation.

Multitask learning (MTL) is an open and challenging problem in various real-world applications, such as recommendation systems, natural language processing, and computer vision. The typical way of conducting multitask learning is establishing some global parameter sharing mechanism among all tasks or assigning each task an individual set of parameters with cross-connections between tasks. However, for most existing approaches, the raw features are abstracted step by step, semantic information is mined from input space, and matching relation features are not introduced into the model. To solve the above problems, we propose a novel MMOE-match network to model the matches between medical cases and syndrome elements and introduce the recommendation algorithm into traditional Chinese medicine (TCM) study. Accurate medical record recommendation is significant for intelligent medical treatment. Ranking algorithms can be introduced in multi-TCM scenarios, such as syndrome element recommendation, symptom recommendation, and drug prescription recommendation. The recommendation system includes two main stages: recalling and ranking. The core of recalling and ranking is a two-tower matching network and multitask learning. MMOE-match combines the advantages of recalling and ranking model to design a new network. Furtherly, we try to take the matching network output as the input of multitask learning and compare the matching features designed by the manual. The data show that our model can bring significant positive benefits.

N6-methyladenosine-related microRNAs risk model trumps the isocitrate dehydrogenase mutation status as a predictive biomarker for the prognosis and immunotherapy in lower grade gliomas.

Aim: Lower grade gliomas [LGGs; World Health Organization (WHO) grades 2 and 3], owing to the heterogeneity of their clinical behavior, present a therapeutic challenge to neurosurgeons. The aim of this study was to explore the N6-methyladenosine (m6A) modification landscape in the LGGs and to develop an m6A-related microRNA (miRNA) risk model to provide new perspectives for the treatment and prognostic assessment of LGGs. Methods: Messenger RNA (mRNA) and miRNA expression data of LGGs were extracted from The Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Atlas (CGGA) databases. An m6A-related miRNA risk model was constructed via least absolute shrinkage and selection operator (LASSO), univariate, and multivariate Cox regression analysis. Next, Kaplan-Meier analysis, principal-component analysis (PCA), functional enrichment analysis, immune infiltrate analysis, dynamic nomogram, and drug sensitivity prediction were used to evaluate this risk model. Results: Firstly, six m6A-related miRNAs with independent prognostic value were selected based on clinical information and used to construct a risk model. Subsequently, compared with low-risk group, LGGs in the high-risk group had a higher m6A writer and reader scores, but a lower eraser score. Moreover, LGGs in the high-risk group had a significantly worse clinical prognosis than those in the low-risk group. Simultaneously, this risk model outperformed other clinicopathological variables in the prognosis prediction of LGGs. Immune infiltrate analysis revealed that the proportion of M2 macrophages, regulatory T (Treg) cells, and the expression levels of exhausted immune response markers were significantly higher in the high-risk group than in the low-risk group. Finally, this study constructed an easy-to-use and free dynamic nomogram to help clinicians use this risk model to aid in diagnosis and prognosis assessment. Conclusions: This study developed a m6A-related risk model and uncovered two different m6A modification landscapes in LGGs. Moreover, this risk model may provide guidance and help in clinical prognosis assessment and immunotherapy response prediction for LGGs.

BACH1 as a potential target for immunotherapy in glioblastomas.

Glioblastoma (GBM, WHO grade 4) is a highly heterogeneous and aggressive primary malignant brain tumor. BTB domain and CNC homology 1 (BACH1) is a transcription factor, and it plays an essential role in regulating tumor metastasis, tumor metabolism, and tumor stem cell self-renewal. However, its role in glioma is still unclear. In this research, we confirmed that BACH1 as an independent prognostic indicator was enriched in GBMs. BACH1 was strongly correlated with immune responses in GBMs, especially the M0 and M2 tumor-associated macrophage (TAM) mediated immune responses. GBMs with high expression of BACH1 express high levels of immune checkpoints (ICs), glioma cell-derived TAM chemokines, and M2 TAM markers. Interestingly, single cell RNA-seq analysis showed that the expression level of BACH1 in TAMs was higher than that in the other cell types in GBM. Transcriptome analysis of U87-MG cells showed that compared with the BACH1-vector U87-MG group, glioma cell-derived TAM chemokines (including monocyte chemotactic protein-1 (MCP-1), granulocyte-macrophage colony-stimulating factor (GM-CSF), and EGF) and ICs (including CD276, TIM-3, LAG3, TIGIT and LGALS9) were enriched in the BACH1-overexpressing U87-MG group. In addition, we constructed a polygenic risk scoring model and compound nomogram model based on BACH1, which might provide a reliable prognosis assessment tool for clinicians and aid in treatment decision-making in the clinic. In conclusion, this research identified that BACH1 might be a potential molecular signature for survival and immunotherapy response. GBMs with high expression of BACH1 have a stronger immunosuppressive tumor microenvironment (TME). Overexpression of BACH1 can upregulate the expression of glioma cell-derived TAM chemokines and ICs in vitro. Moreover, the risk model and nomogram model based on BACH1 can provide a reliable prognosis assessment tool. Therefore, BACH1 is a promising therapeutic target for GBMs.

A nanoconcrete welding strategy for constructing high-performance wound dressing.

Engineering biomaterials to meet specific biomedical applications raises high requirements of mechanical performances, and simultaneous strengthening and toughening of polymer are frequently necessary but very challenging in many cases. In this work, we propose a new concept of nanoconcrete welding polymer chains, where mesoporous CaCO3 (mCaCO3) nanoconcretes which are composed of amorphous and nanocrystalline phases are developed to powerfully weld polymer chains through siphoning-induced occlusion, hydration-driven crystallization and dehydration-driven compression of nanoconcretes. The mCaCO3 nanoconcrete welding technology is verified to be able to remarkably augment strength, toughness and anti-fatigue performances of a model polymer poly(3-hydroxybutyrate-co-3-hydroxyvalerate)-based porous membrane. Mechanistically, we have revealed polymer-occluded nanocrystal structure and welding-derived microstress which is much stronger than interfacial Van der Waals force, thus efficiently preventing the generation of microcracks and repairing initial microcracks by microcracks-induced hydration, crystallization and polymer welding of mCaCO3 nanoconcretes. Constructed porous membrane is used as wound dressing, exhibiting a special nanoplates-constructed surface topography as well as a porous structure with plentiful oriented, aligned and opened pore channels, improved hydrophilicity, water vapor permeability, anti-bacterial and cell adherence, in support of wound healing and skin structural/functional repairing. The proposed nanoconcrete-welding-polymer strategy breaks a new pathway for improving the mechanical performances of polymers.

Roles of the m6A Modification of RNA in the Glioblastoma Microenvironment as Revealed by Single-Cell Analyses.

Purpose: Glioblastoma multiforme (GBM) is a common and aggressive form of brain tumor. The N6-methyladenosine (m6A) mRNA modification plays multiple roles in many biological processes and disease states. However, the relationship between m6A modifications and the tumor microenvironment in GBM remains unclear, especially at the single-cell level. Experimental Design: Single-cell and bulk RNA-sequencing data were acquired from the GEO and TCGA databases, respectively. We used bioinformatics and statistical tools to analyze associations between m6A regulators and multiple factors. Results: HNRNPA2B1 and HNRNPC were extensively expressed in the GBM microenvironment. m6A regulators promoted the stemness state in GBM cancer cells. Immune-related BP terms were enriched in modules of m6A-related genes. Cell communication analysis identified genes in the GALECTIN signaling network in GBM samples, and expression of these genes (LGALS9, CD44, CD45, and HAVCR2) correlated with that of m6A regulators. Validation experiments revealed that MDK in MK signaling network promoted migration and immunosuppressive polarization of macrophage. Expression of m6A regulators correlated with ICPs in GBM cancer cells, M2 macrophages and T/NK cells. Bulk RNA-seq analysis identified two expression patterns (low m6A/high ICP and high m6A/low ICP) with different predicted immune infiltration and responses to ICP inhibitors. A predictive nomogram model to distinguish these 2 clusters was constructed and validated with excellent performance. Conclusion: At the single-cell level, m6A modification facilitates the stemness state in GBM cancer cells and promotes an immunosuppressive microenvironment through ICPs and the GALECTIN signaling pathway network. And we also identified two m6A-ICP expression patterns. These findings could lead to novel treatment strategies for GBM patients.