Spatioselective Occlusion of Copolymer Nanoparticles within Calcite Crystals Generates Organic-Inorganic Hybrid Materials with Controlled Internal Structures.

Efficient occlusion of particulate additives into a single crystal has garnered an ever-increasing attention in materials science because it offers a counter-intuitive yet powerful platform to make crystalline nanocomposite materials with emerging properties. However, precisely controlling the spatial distribution of the guest additives within a host crystal remains highly challenging. We herein demonstrate a unique, straightforward method to engineer the spatial distribution of copolymer nanoparticles within calcite (CaCO3) single crystals by judiciously adjusting initial [Ca2+] concentration used for the calcite precipitation. More specifically, polymerization-induced self-assembly is employed to synthesize well-defined and highly anionic poly(3-sulfopropyl methacrylate potassium)41-block-poly(benzyl methacrylate)500 [PSPMA41-PBzMA500] diblock copolymer nanoparticles, which are subsequently used as model additives during the growth of calcite crystals. Impressively, such guest nanoparticles are preferentially occluded into specific regions of calcite depending on the initial [Ca2+] concentration. These unprecedented phenomena are most probably caused by dynamic change in electrostatic interaction between Ca2+ ions and PSPMA41 chains based on systematic investigations. This study not only showcases a significant advancement in controlling the spatial distribution of guest nanoparticles within host crystals, enabling the internal structure of composite crystals to be rationally tailored via a spatioselective occlusion strategy, but also provides new insights into biomineralization.

In Situ Polymerized Zwitterionic Copolymer Ionic Gel Electrolytes with High Performance for Lithium-Ion Batteries.

Gel electrolytes are a promising research direction due to their high safety. However, its poor room temperature conductivity along with complex preparation process hinder its practical application. In this article, a type of zwitterionic gel electrolyte is prepared by in situ polymerization. The introduction of charged but nonmigrating zwitterionic copolymer in the polymer chain is beneficial to the dissociation of the lithium salt, improving the ion transport of the electrolyte on this account. At room temperature, the conductivity of lithium ion reaches 9.1 × 10-4 S cm-1, which contributes to achieve excellent electrochemical performance at high rates. The assembled Li|LiFePO4 cell also shows a capacity retention rate of 90.5% after 150 cycles at 0.5 C at room temperature as well as remarkable cycle stability at 1 C. These offer a novel tactic for the efficient and safe commercial application of lithium-ion batteries.

Weak Solvation Chemistry in Fluorinated Nonflammable Electrolytes Achieves Stable Cycling in High-Voltage Lithium Metal Batteries.

High-voltage (>4.35 V) lithium nickel-cobalt-manganese batteries are star candidates due to their higher energy density for next-generation power batteries. This poses higher demands for electrolyte design, including compatibility with lithium metals, stability on high-voltage cathodes, speedy interfacial ion transport kinetics, and appropriate concentration. However, electrolytes at the current level of research struggle to balance these demands. Here, we took advantage of the reduced affinity with Li+ and enhanced oxidative stability of three fluorinated linear carbonates to design a series of weakly solvating electrolytes (WSEs) at a low salt concentration of 1 M, which contain abundant ionic cluster structures, leading to the optimization of interfacial chemistry. As a result, WSEs can support the stable cycling of 4.6 V high-voltage Li||NCM811 cells for 300 cycles with a capacity retention of nearly 80%. Moreover, benefiting from the lower desolvation energy of Li+, WSEs achieve superior cycling stability and low polarization under -20 °C. Our work extends the application of WSEs for high-voltage LMBs, providing a promising solution in electrolytes for high-specific-energy lithium batteries.

Hypoxia-inducible factor prolyl hydroxylase inhibitor alleviates heatstroke-induced acute kidney injury by activating BNIP3-mediated mitophagy.

Hypoxia-induced inflammation and apoptosis are important pathophysiological features of heat stroke-induced acute kidney injury (HS-AKI). Hypoxia-inducible factor (HIF) is a key protein that regulates cell adaptation to hypoxia. HIF-prolyl hydroxylase inhibitor (HIF-PHI) stabilizes HIF to increase cell adaptation to hypoxia. Herein, we reported that HIF-PHI pretreatment significantly improved renal function, enhanced thermotolerance, and increased the survival rate of mice in the context of HS. Moreover, HIF-PHI could alleviate HS-induced mitochondrial damage, inflammation, and apoptosis in renal tubular epithelial cells (RTECs) by enhancing mitophagy in vitro and in vivo. By contrast, mitophagy inhibitors Mdivi-1, 3-MA, and Baf-A1 reversed the renoprotective effects of HIF-PHI. Mechanistically, HIF-PHI protects RTECs from inflammation and apoptosis by enhancing Bcl-2 adenovirus E18 19-kDa-interacting protein 3 (BNIP3)-mediated mitophagy, while genetic ablation of BNIP3 attenuated HIF-PHI-induced mitophagy and abolished HIF-PHI-mediated renal protection. Thus, our results indicated that HIF-PHI protects renal function by upregulating BNIP3-mediated mitophagy to improve HS-induced inflammation and apoptosis of RTECs, suggesting HIF-PHI as a promising therapeutic agent to treat HS-AKI.

Imipenem reduces the efficacy of vancomycin against Elizabethkingia species.

BACKGROUND: Elizabethkingia spp. are emerging as nosocomial pathogens causing various infections. These pathogens express resistance to a broad range of antibiotics, thus requiring antimicrobial combinations for coverage. However, possible antagonistic interactions between antibiotics have not been thoroughly explored. This study aimed to evaluate the effectiveness of antimicrobial combinations against Elizabethkingia infections, focusing on their impact on pathogenicity, including biofilm production and cell adhesion. METHODS: Double-disc diffusion, time-kill, and chequerboard assays were used for evaluating the combination effects of antibiotics against Elizabethkingia spp. We further examined the antagonistic effects of antibiotic combinations on biofilm formation and adherence to A549 human respiratory epithelial cells. Further validation of the antibiotic interactions and their implications was performed using ex vivo hamster precision-cut lung sections (PCLSs) to mimic in vivo conditions. RESULTS: Antagonistic effects were observed between cefoxitin, imipenem and amoxicillin/clavulanic acid in combination with vancomycin. The antagonism of imipenem toward vancomycin was specific to its effects on the genus Elizabethkingia. Imipenem further hampered the bactericidal effect of vancomycin and impaired its inhibition of biofilm formation and the adhesion of Elizabethkingia meningoseptica ATCC 13253 to human cells. In the ex vivo PCLS model, vancomycin exhibited dose-dependent bactericidal effects; however, the addition of imipenem also reduced the effect of vancomycin. CONCLUSIONS: Imipenem reduced the bactericidal efficacy of vancomycin against Elizabethkingia spp. and compromised its capacity to inhibit biofilm formation, thereby enhancing bacterial adhesion. Clinicians should be aware of the potential issues with the use of these antibiotic combinations when treating Elizabethkingia infections.

STAR-RL: Spatial-temporal Hierarchical Reinforcement Learning for Interpretable Pathology Image Super-Resolution.

Pathology image are essential for accurately interpreting lesion cells in cytopathology screening, but acquiring high-resolution digital slides requires specialized equipment and long scanning times. Though super-resolution (SR) techniques can alleviate this problem, existing deep learning models recover pathology image in a black-box manner, which can lead to untruthful biological details and misdiagnosis. Additionally, current methods allocate the same computational resources to recover each pixel of pathology image, leading to the sub-optimal recovery issue due to the large variation of pathology image. In this paper, we propose the first hierarchical reinforcement learning framework named Spatial-Temporal hierARchical Reinforcement Learning (STAR-RL), mainly for addressing the aforementioned issues in pathology image super-resolution problem. We reformulate the SR problem as a Markov decision process of interpretable operations and adopt the hierarchical recovery mechanism in patch level, to avoid sub-optimal recovery. Specifically, the higher-level spatial manager is proposed to pick out the most corrupted patch for the lower-level patch worker. Moreover, the higher-level temporal manager is advanced to evaluate the selected patch and determine whether the optimization should be stopped earlier, thereby avoiding the over-processed problem. Under the guidance of spatial-temporal managers, the lower-level patch worker processes the selected patch with pixel-wise interpretable actions at each time step. Experimental results on medical images degraded by different kernels show the effectiveness of STAR-RL. Furthermore, STAR-RL validates the promotion in tumor diagnosis with a large margin and shows generalizability under various degradation. The source code is to be released.

Editorial Perspective: Extending IPDMA methodology to drive treatment personalisation in child mental health.

To improve outcomes for youth who do not respond optimally to existing treatments, we need to identify robust predictors, moderators, and mediators that are ideal targets for personalisation in mental health care. We propose a solution to leverage the Individual Patient Data Meta-analysis (IPDMA) approach to allow broader access to individual-level data while maintaining methodological rigour. Such a resource has the potential to answer questions that are unable to be addressed by single studies, reduce researcher burden, and enable the application of newer statistical techniques, all to provide data-driven strategies for clinical decision-making. Using childhood anxiety as the worked example, the editorial perspective outlines the rationale for leveraging IPDMA methodology to build a data repository, the Platform for Anxiety Disorder Data in Youth. We also include recommendations to address the methods and challenges inherent in this endeavour.

Coloration in Equine: Overview of Candidate Genes Associated with Coat Color Phenotypes.

Variation in coat color among equids has attracted significant interest in genetics and breeding research. The range of colors is primarily determined by the type, concentration, and distribution of melanin pigments, with the balance between eumelanin and pheomelanin influenced by numerous genetic factors. Advances in genomic and sequencing technologies have enabled the identification of several candidate genes that influence coat color, thereby clarifying the genetic basis of these diverse phenotypes. In this review, we concisely categorize coat coloration in horses and donkeys, focusing on the biosynthesis and types of melanin involved in pigmentation. Moreover, we highlight the regulatory roles of some key candidate genes, such as MC1R, TYR, MITF, ASIP, and KIT, in coat color variation. Moreover, the review explores how coat color relates to selective breeding and specific equine diseases, offering valuable insights for developing breeding strategies that enhance both the esthetic and health aspects of equine species.

Cigarette smoking-related OLC1 overexpression associated with poor prognosis in bladder urothelial carcinoma.

AIMS: To explore the clinical significance of OLC1 and cigarette smoking in bladder urothelial carcinoma (UBC). MATERIALS AND METHODS: OLC1 mRNA expression was detected in 106 UBC samples by mRNA array or reverse real-time PCR. OLC1 protein expression in 114 UBC samples was detected by immunohistochemical staining. Wild-type C57BL/6J mice were injected with cigarette smoke condensate (n = 12) or exposed to cigarette smoke (n = 6) to investigate the correlations between cigarette smoking and OLC1 expression using mRNA array. KEY FINDINGS: The mRNA and protein expression of OLC1 were higher in tumor samples (p < 0.01) and significantly correlated with tumor stage (p < 0.05). OLC1 protein expression and smoking history were correlated with disease-free survival (p < 0.05). OLC1 expression was significantly elevated in smoking patients with higher smoking intensity on both mRNA and protein levels (p < 0.05). Cigarette smoke exposure experiments revealed that OLC1 mRNA overexpressed in bladder uroepithelium of mice. SIGNIFICANCE: OLC1 could serve as a potential prognosis biomarker of UBC, especially for smoking patients.

VISTA deficiency exerts anti-tumor effects in breast cancer through regulating macrophage polarization.

Growing evidence had showed that tumor-associated macrophages (TAMs) have a tumor-promoting M2 phenotype which could drive pathological phenomena. In breast cancer, TAMs are abundantly present and may play an important role in the development of breast cancer. V-domain immunoglobulin suppressor of T cell activation (VISTA) is a novel inhibitory checkpoint and immunotherapy target for tumor through regulating immune response. However, its effects on macrophages have not been investigated, which was also the focus of this study. Here, the scRNA-seq data further revealed that VISTA was highly expressed in multiple macrophage subclusters. In vitro experiments showed that the absence of VISTA enhanced the M1 polarization of macrophages, inhibited the M2 polarization of macrophages and the proliferation and phagocytosis of 4 T1 cells induced by M2-CM. VISTA regulated the activation of STAT1 and STAT6 signaling pathways in the process of macrophage polarization. In vivo experiments demonstrated that VISTA deficient mice exhibited reduced tumor growth, possibly due to the increase of M1 macrophages and the decrease of M2 macrophages. In summary, our study is the first to reveal the effect of VISTA on macrophages in breast cancer, which showed that VISTA affects tumor growth by critically regulating the macrophage polarization through the STAT pathway.

Mask-aware transformer with structure invariant loss for CT translation.

Multi-phase enhanced computed tomography (MPECT) translation from plain CT can help doctors to detect the liver lesion and prevent patients from the allergy during MPECT examination. Existing CT translation methods directly learn an end-to-end mapping from plain CT to MPECT, ignoring the crucial clinical domain knowledge. As clinicians subtract the plain CT from MPECT images as subtraction image to highlight the contrast-enhanced regions and further to facilitate liver disease diagnosis in the clinical diagnosis, we aim to exploit this domain knowledge for automatic CT translation. To this end, we propose a Mask-Aware Transformer (MAFormer) with structure invariant loss for CT translation, which presents the first effort to exploit this domain knowledge for CT translation. Specifically, the proposed MAFormer introduces a mask estimator to predict the subtraction image from the plain CT image. To integrate the subtraction image into the network, the MAFormer devises a Mask-Aware Transformer based Normalization (MATNorm) as normalization layer to highlight the contrast-enhanced regions and capture the long-range dependencies among these regions. Moreover, aiming to preserve the biological structure of CT slices, a structure invariant loss is designed to extract the structural information and minimize the structural similarity between the plain and synthetic CT images to ensure the structure invariant. Extensive experiments have proven the effectiveness of the proposed method and its superiority to the state-of-the-art CT translation methods. Source code is to be released.

Metabolomics of Vitis davidii Foëx. grapes from southern China: Flavonoids and volatiles reveal the flavor profiles of five spine grape varieties.

The spine grapes (Vitis davidii Foëx.) are wild grape species that grow in southern China, and can be used for table grapes, juicing and winemaking. To systematically investigate the flavor profiles of spine grapes, flavonoids and volatile compounds were detected in five spine grape varieties (Seputao, Ziqiu, Miputao, Tianputao and Baiputao) using HPLC-QqQ-MS/MS and GC-MS. The content of flavonoids highly depended on the variety, such as the total concentrations of anthocyanins (91.43-328.85 mg/kg FW) and flavonols (33.90 to 83.16 mg/kg FW). The volatile compounds with higher odor active value were selected to describe the aroma of spine grapes. Hexanal, (E)-2-hexenal and (E, Z)-2,6-nonadienal contributed to the higher herbaceous flavor to Baiputao and Ziqiu. ß-Damascenone and (E)-2-nonenal gave Baiputao a flavor with more floral, fruity and earthy. Their characteristic flavor compounds were subsequently revealed using multivariate statistical analysis. The results helped producers to further develop and utilize the spine grapes.

Electroacupuncture treatment improves postoperative ileus by inhibiting the Th1 cell-mediated inflammatory response through the vagus nerve.

BACKGROUND: Electroacupuncture (EA) has been reported to improve intestinal motility in mice with postoperative ileus (POI). Previous studies, however, have yielded heterogeneous results regarding the effect of EA on POI. METHODS: Herein, a POI mouse model was constructed by intestinal manipulation. To evaluate the effect of EA treatment on colonic transit, the levels of inflammatory markers (macrophage inflammatory protein (MIP)-1α, interleukin (IL)-1ß, IL-6, monocyte chemotactic protein (MCP)-1 and intercellular adhesion molecule (ICAM)-1) were detected by enzyme-linked immunosorbent assay (ELISA); immune cell infiltration was detected by immunohistochemical staining of myeloperoxidase (MPO), ectodysplasin (ED)-1 and ED-2, and the percentage of CD4+ interferon (IFN)-γ+ Th1 cells and IFN-γ secretion levels were determined. Activated Th1 cells and pentoxifylline, a cell differentiation inhibitor, were used to assess the role of Th1 cells in EA treatment of POI. Neostigmine administration and unilateral vagotomy were performed to confirm whether the effects of EA treatment on Th1 cells were mediated by the vagus nerve (VN). RESULTS: The results revealed that EA treatment at ST36 improved POI, as indicated by a decreased level of inflammatory-related markers and immune cell infiltration and shortened colonic transit time. The activated Th1 cells abolished the effects of EA treatment on POI. The effects of EA treatment on POI were enhanced by stimulation of the VN along with a decreased level of Th1 cells, but these effects were abolished by vagotomy along with an increased percentage of Th1 cells; this result indicates that the VN mediates the role of Th1 cells in the effects of EA treatment of POI. CONCLUSION: Our findings showed that the effects of EA treatment of POI were mainly mediated by Th1 cells through the stimulation of the VN and inhibition of the inflammatory response.

Recent progress in Porphyra haitanensis polysaccharides: Extraction, purification, structural insights, and their impact on gastrointestinal health and oxidative stress management.

Porphyra haitanensis, a red seaweed species, represents a bountiful and sustainable marine resource. P. haitanensis polysaccharide (PHP), has garnered considerable attention for its numerous health benefits. However, the comprehensive utilization of PHP on an industrial scale has been limited by the lack of comprehensive information. In this review, we endeavor to discuss and summarize recent advancements in PHP extraction, purification, and characterization. We emphasize the multifaceted mechanisms through which PHP promotes gastrointestinal health. Furthermore, we present a summary of compelling evidence supporting PHP's protective role against oxidative stress. This includes its demonstrated potent antioxidant properties, its ability to neutralize free radicals, and its capacity to enhance the activity of antioxidant enzymes. The information presented here also lays the theoretical groundwork for future research into the structural and functional aspects of PHP, as well as its potential applications in functional foods.

Bioactive Compounds Protect Mammalian Reproductive Cells from Xenobiotics and Heat Stress-Induced Oxidative Distress via Nrf2 Signaling Activation: A Narrative Review.

Oxidative stress occurs when there is an imbalance between the production of reactive oxygen species (ROS) and the body's antioxidant defenses. It poses a significant threat to the physiological function of reproductive cells. Factors such as xenobiotics and heat can worsen this stress, leading to cellular damage and apoptosis, ultimately decreasing reproductive efficiency. The nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway plays a crucial role in defending against oxidative stress and protecting reproductive cells via enhancing antioxidant responses. Dysregulation of Nrf2 signaling has been associated with infertility and suboptimal reproductive performance in mammals. Recent advancements in therapeutic interventions have underscored the critical role of Nrf2 in mitigating oxidative damage and restoring the functional integrity of reproductive cells. In this narrative review, we delineate the harmful effects of heat and xenobiotic-induced oxidative stress on reproductive cells and explain how Nrf2 signaling provides protection against these challenges. Recent studies have shown that activating the Nrf2 signaling pathway using various bioactive compounds can ameliorate heat stress and xenobiotic-induced oxidative distress and apoptosis in mammalian reproductive cells. By comprehensively analyzing the existing literature, we propose Nrf2 as a key therapeutic target for mitigating oxidative damage and apoptosis in reproductive cells caused by exposure to xenobiotic exposure and heat stress. Additionally, based on the synthesis of these findings, we discuss the potential of therapies focused on the Nrf2 signaling pathway to improve mammalian reproductive efficiency.

Atorvastatin combined with imipenem alleviates lung injury in sepsis by inhibiting neutrophil extracellular trap formation via the ERK/NOX2 signaling pathway.

Sepsis is a systemic inflammatory response syndrome caused by the invasion of pathogenic microorganisms. Despite major advances in diagnosis and technology, morbidity and mortality remain high. The level of neutrophil extracellular traps (NETs) is closely associated with the progression and prognosis of sepsis, suggesting the regulation of NET formation as a new strategy in sepsis treatment. Owing to its pleiotropic effects, atorvastatin, a clinical lipid-lowering drug, affects various aspects of sepsis-related inflammation and immune responses. To align closely with clinical practice, we combined it with imipenem for the treatment of sepsis. In this study, we used a cecum ligation and puncture-induced lung injury mouse model and employed techniques including western blot, immunofluorescence, and enzyme-linked immunosorbent assay to measure the levels of NETs and other sepsis-related lung injury indicators. Our findings indicate that atorvastatin effectively inhibited the formation of NETs. When combined with imipenem, it significantly alleviated lung injury, reduced systemic inflammation, and improved the 7-day survival rate of septic mice. Additionally, we explored the inhibitory mechanism of atorvastatin on NET formation in vitro, revealing its potential action through the ERK/NOX2 pathway. Therefore, atorvastatin is a potential immunomodulatory agent that may offer new treatment strategies for patients with sepsis in clinical settings.

Infection may play an important role in the pathogenesis of alveolar osteonecrosis following facial herpes zoster: a case report and literature review.

BACKGROUND: Herpes zoster (HZ) is one of the most common skin diseases caused by viruses. Facial HZ develops when the varicella-zoster virus affects the trigeminal nerve, and alveolar osteonecrosis is a rare complication. However, the exact pathogenesis of postherpetic alveolar osteonecrosis remains unclear. CASE DESCRIPTION: We encountered a patient who presented to the dermatology clinic with facial HZ and tooth exfoliation in the upper right jaw, and panoramic radiography revealed decreased bone density and poor alveolar socket healing in his right maxilla. Biopsy of the alveolar process revealed fragments of nonvital lamellar bone, which were devoid of osteoblasts and osteocytes and were surrounded by numerous neutrophils and bacterial aggregates. Thus, the diagnosis of alveolar osteonecrosis following facial HZ was confirmed. He then underwent resection of the osteonecrotic tissue. The pathological findings of postoperative tissue were similar to those of previous biopsies. Varicella-zoster virus and multiple types of bacteria were detected through next-generation sequencing, and the species of bacteria were consistent with the results of bacterial culture. Antibiotics and valaciclovir were administered during the perioperative period. The patient showed good recovery at the 9-month follow-up. CONCLUSIONS: The coexistence of bacterial and viral infection may play an important role in the pathogenesis of alveolar osteonecrosis following HZ. To our knowledge, we are the first to directly explore microbial pathogens in a case of postherpetic alveolar osteonecrosis through next-generation sequencing and bacterial culture. We recommend that oral examinations be carefully conducted for patients who are diagnosed with facial HZ, even if their facial rashes have faded away. We suggest that a prolonged and full-dose antiviral therapy course may be beneficial for the treatment of facial HZ with intraoral lesions. The implementation of dental preventive measures should be considered for patients with facial HZ. The application of antibiotics and excision of necrotic bone may reduce the abundance of bacteria in lesions and improve wound healing.

Protective Role of MerTK in Diabetic Peripheral Neuropathy via Inhibition of the NF-κB Signaling Pathway.

INTRODUCTION: Diabetic peripheral neuropathy (DPN) impacts patient quality of life. In such patients, increased expression of mer tyrosine kinase (MerTK) has been demonstrated; however, its mechanism of action remains unclear. In this study, type 2 diabetes mellitus (T2DM) and DPN models were established in Sprague Dawley rats via low-dose streptozotocin and a high-fat diet and the mode of action of MerTK was examined. METHODS: MerTK-specific inhibitors were administered by gavage once daily for 2 weeks. Sciatic nerve conduction velocity and nerve structure were measured. The levels of MerTK, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1ß), and relevant biochemical indexes were detected. RESULTS: The study revealed upregulation of MerTK expression in T2DM and more so in DPN groups. Inhibiting MerTK led to reduced nerve conduction velocity and further deterioration of sciatic nerve structure, as evidenced by structural morphology. Concurrently, serum levels of total cholesterol, glycated hemoglobin, and triglyceride significantly increased. Moreover, levels of NF-κB increased in both serum and nerve tissue, alongside a significant rise in TNF-α and IL-1ß expressions. MerTK could bind to the inhibitor of kappa B kinase beta (Ikbkb) in Schwann cells, establishing Ikbkb as a precursor to NF-κB activation. DISCUSSION: Inhibition of MerTK exacerbates neuropathy, indicating its protective role in DPN by suppressing the NF-κB pathway, highlighting a potential new target for its diagnosis and treatment.

Co-expression of immune checkpoints in glioblastoma revealed by single-nucleus RNA sequencing and spatial transcriptomics.

Glioblastoma (GBM) is one of the most malignant tumors of the central nervous system. The pattern of immune checkpoint expression in GBM remains largely unknown. We performed snRNA-Seq and spatial transcriptomic (ST) analyses on untreated GBM samples. 8 major cell types were found in both tumor and adjacent normal tissues, with variations in infiltration grade. Neoplastic cells_6 was identified in malignant cells with high expression of invasion and proliferator-related genes, and analyzed its interactions with microglia, MDM cells and T cells. Significant alterations in ligand-receptor interactions were observed, particularly between Neoplastic cells_6 and microglia, and found prominent expression of VISTA/VSIG3, suggesting a potential mechanism for evading immune system attacks. High expression of TIM-3, VISTA, PSGL-1 and VSIG-3 with similar expression patterns in GBM, may have potential as therapeutic targets. The prognostic value of VISTA expression was cross-validated in 180 glioma patients, and it was observed that patients with high VISTA expression had a poorer prognosis. In addition, multimodal cross analysis integrated SnRNA-seq and ST, revealing complex intracellular communication and mapping the GBM tumor microenvironment. This study reveals novel molecular characteristics of GBM, co-expression of immune checkpoints, and potential therapeutic targets, contributing to improving the understanding and treatment of GBM.

Remodeling Microenvironment for Implant-Associated Osteomyelitis by Dual Metal Peroxide.

Implant-associated osteomyelitis (IAOM) is characterized by bone infection and destruction; current therapy of antibiotic treatment and surgical debridement often results in drug resistance and bone defect. It is challenging to develop an antibiotic-free bactericidal and osteogenic-enhanced strategy for IAOM. Herein, an IAOM-tailored antibacterial and osteoinductive composite of copper (Cu)-strontium (Sr) peroxide nanoparticles (CSp NPs), encapsulated in polyethylene glycol diacrylate (PEGDA) (CSp@PEGDA), is designed. The dual functional CSp NPs display hydrogen peroxide (H2O2) self-supplying and Fenton catalytic Cu2+ ions' release, generating plenty of hydroxyl radical (•OH) in a pH-responsive manner for bacterial killing, while the released Sr2+ promotes the in vitro osteogenicity regarding cell proliferation, alkaline phosphatase activity, extracellular matrix calcification, and osteo-associated genes expression. The integration of Cu2+ and Sr2+ in CSp NPs together with the coated PEGDA hydrogel ensures the stable and sustainable ion release during short- and long-term periods. Benefitted from the injectablity and photo-crosslink ability, CSp@PEGDA is able to thoroughly fill the infectious site and gelate in situ for bacterial elimination and bone regeneration, which is verified through in vivo evaluation using a clinical-simulating IAOM mouse model. These favorable abilities of CSp@PEGDA precisely meet the multiple therapeutic needs and pave a promising way for implant-associated osteomyelitis treatment.