The vasculogenic mimicry related signature predicts the prognosis and immunotherapy response in renal clear cell carcinoma.

BACKGROUND: Clear cell carcinoma of the kidney is a common urological malignancy characterized by poor patient prognosis and treatment outcomes. Modulation of vasculogenic mimicry in tumor cells alters the tumor microenvironment and the influx of tumor-infiltrating lymphocytes, and the combination of its inducers and immune checkpoint inhibitors plays a synergistic role in enhancing antitumor effects. METHODS: We downloaded the data from renal clear cell carcinoma samples and vasculogenic mimicry-related genes to establish a new vasculogenic mimicry-related index (VMRI) using a machine learning approach. Based on VMRI, patients with renal clear cell carcinoma were divided into high VMRI and low VMRI groups, and patients' prognosis, clinical features, tumor immune microenvironment, chemotherapeutic response, and immunotherapeutic response were systematically analyzed. Finally, the function of CDH5 was explored in renal clear cell carcinoma cells. RESULTS: VMRI can be used for prognostic and immunotherapy efficacy prediction in a variety of cancers, which consists of four vasculogenic mimicry-related genes (CDH5, MMP9, MAPK1, and MMP13), is a reliable predictor of survival and grade in patients with clear cell carcinoma of the kidney and has been validated in multiple external datasets. We found that the high VMRI group presented higher levels of immune cell infiltration, which was validated by pathological sections. We performed molecular docking prediction of vasculogenic mimicry core target proteins and identified natural small molecule drugs with the highest affinity for the target protein. Knockdown of CDH5 inhibited the proliferation and migration of renal clear cell carcinoma. CONCLUSIONS: The VMRI identified in this study allows for accurate prognosis assessment of patients with renal clear cell carcinoma and identification of patient populations that will benefit from immunotherapy, providing valuable insights for future precision treatment of patients with renal clear cell carcinoma.

The Clinical Intervention Effects of Evidence-based Nursing Measures in General Anesthesia Patients in the Postoperative Recovery Period.

Objective: This work investigated the clinical intervention effect of evidence-based nursing (EBN) measures for patients in the recovery stage after general anesthesia (GA), aiming to provide a nursing reference for patients in the recovery stage after surgery. Methods: The enrolled participants were 102 patients who underwent surgical treatment in our hospital from December 2021 to December 2022. According to the principle of randomized control, they were enrolled into an observation group (51 cases, Obs group) and a control group (51, cases, Ctrl group), and the general nursing methods and EBN measures were respectively implemented. The incidence of restlessness, complication rate, and nursing satisfaction were compared among patients. The recovery period and visual analog scale (VAS) were evaluated. Results: The eye-opening time, palm-holding time, and extubation time in the Obs group were shorter than those in the Ctrl group (P < .05). The incidence of agitation during convalescence under GA in the Obs group was significantly lower than in the Ctrl group, with a statistically significant difference among both groups (P < .05). Compared to the Ctrl group, the VAS score of patients in the Obs group receiving the EBN was lower at 6 h, 12 h, and 24 h after the surgery (P < .05). The patients in the Obs group presented a substantially lower complication rate and remarkably higher nursing satisfaction (P < .05). Conclusion: The application of EBN measures in patients after GA could effectively shorten the recovery time, lower the incidence of agitation and complication rate during the recovery, and improve nursing satisfaction.

Effect of Fiber Loading on Mechanical and Flame-Retardant Properties of Poplar-Fiber-Reinforced Gypsum Composites.

Gypsum-based composites were prepared via a slurry casting process using construction gypsum as the binding material and poplar fibers as reinforcing material. The effects of different fiber content and curing time on the mechanical properties, water resistance, and flame retardancy of these composites were investigated, and the influence mechanism was characterized by infrared spectroscopy, scanning electron microscopy, and X-ray diffractometry. The results showed that the best composite mechanical strength was achieved with 10% poplar fiber- content, and the absolute dry flexural and compressive strengths reached 3.59 and 8.06 MPa, respectively. Compared with pure gypsum, the flexural strength and compressive strength increased by 10% and 19%, respectively. The inclusion of fibers somewhat prevented the migration of free water within the composites and enhanced their water resistance. At 10% fiber content, the composite's 24 h water absorption rate was 34.3%, 8% lower than that of pure gypsum, with a softening coefficient of 0.55. However, fiber content increases the porosity of gypsum-based composites. When heated, this increased porosity accelerates' heat conduction within the matrix, raising the peak and total exothermic rates, thereby weakening the composites' inherently flame-retardant properties. Poplar-fiber-reinforced gypsum-based composites offered superior performance in commercial applications, compared to pure gypsum board, providing a sustainable and green alternative for ceilings, partitions, and other applications, while broadening the prospects for gypsum-based composites in the engineering field.

Vina-GPU 2.0: Further Accelerating AutoDock Vina and Its Derivatives with Graphics Processing Units.

Modern drug discovery typically faces large virtual screens from huge compound databases where multiple docking tools are involved for meeting various real scenes or improving the precision of virtual screens. Among these tools, AutoDock Vina and its numerous derivatives are the most popular and have become the standard pipeline for molecular docking in modern drug discovery. Our recent Vina-GPU method realized 14-fold acceleration against AutoDock Vina on a piece of NVIDIA RTX 3090 GPU in one virtual screening case. Further speedup of AutoDock Vina and its derivatives with graphics processing units (GPUs) is beneficial to systematically push their popularization in large-scale virtual screens due to their high benefit-cost ratio and easy operation for users. Thus, we proposed the Vina-GPU 2.0 method to further accelerate AutoDock Vina and the most common derivatives with new docking algorithms (QuickVina 2 and QuickVina-W) with GPUs. Caused by the discrepancy in their docking algorithms, our Vina-GPU 2.0 adopts different GPU acceleration strategies. In virtual screening for two hot protein kinase targets, RIPK1 and RIPK3, from the DrugBank database, our Vina-GPU 2.0 reaches an average of 65.6-fold, 1.4-fold, and 3.6-fold docking acceleration against the original AutoDock Vina, QuickVina 2, and QuickVina-W while ensuring their comparable docking accuracy. In addition, we develop a friendly and installation-free graphical user interface tool for their convenient usage. The codes and tools of Vina-GPU 2.0 are freely available at https://github.com/DeltaGroupNJUPT/Vina-GPU-2.0, coupled with explicit instructions and examples.

Single-molecule optical mapping of the distribution of DNA phosphorothioate epigenetics.

DNA phosphorothioate (PT) modifications, with the nonbridging phosphate oxygen replaced by sulfur, governed by DndABCDE or SspABCD, are widely distributed in prokaryotes and have a highly unusual feature of occupying only a small portion of available consensus sequences in a genome. Despite the presence of plentiful non-PT-protected consensuses, DNA PT modification is still employed as a recognition tag by the restriction cognate, for example, DndFGH or SspE, to discriminate and destroy PT-lacking foreign DNA. This raises a fundamental question about how PT modifications are distributed along DNA molecules to keep the restriction components in check. Here, we present two single-molecule strategies that take advantage of the nucleophilicity of PT in combination with fluorescent markers for optical mapping of both single- and double-stranded PT modifications across individual DNA molecules. Surprisingly, PT profiles vary markedly from molecule to molecule, with different PT locations and spacing distances between PT pairs, even in the presence of DndFGH or SspE. The results revealed unprecedented PT modification features previously obscured by ensemble averaging, providing novel insights into the riddles regarding unusual target selection by PT modification and restriction components.

Liposomes for Tumor Targeted Therapy: A Review.

Liposomes, the most widely studied nano-drug carriers in drug delivery, are sphere-shaped vesicles consisting of one or more phospholipid bilayers. Compared with traditional drug delivery systems, liposomes exhibit prominent properties that include targeted delivery, high biocompatibility, biodegradability, easy functionalization, low toxicity, improvements in the sustained release of the drug it carries and improved therapeutic indices. In the wake of the rapid development of nanotechnology, the studies of liposome composition have become increasingly extensive. The molecular diversity of liposome composition, which includes long-circulating PEGylated liposomes, ligand-functionalized liposomes, stimuli-responsive liposomes, and advanced cell membrane-coated biomimetic nanocarriers, endows their drug delivery with unique physiological functions. This review describes the composition, types and preparation methods of liposomes, and discusses their targeting strategies in cancer therapy.

Microfluidics-Assisted Fluorescence Mapping of DNA Phosphorothioation.

As the key player of a new restriction modification system, DNA phosphorothioate (PT) modification, which swaps oxygen for sulfur on the DNA backbone, protects the bacterial host from foreign DNA invasion. The identification of PT sites helps us understand its physiological defense mechanisms, but accurately quantifying this dynamic modification remains a challenge. Herein, we report a simple quantitative analysis method for optical mapping of PT sites in the single bacterial genome. DNA molecules are fully stretched and immobilized in a microfluidic chip by capillary flow and electrostatic interactions, improving the labeling efficiency by maximizing exposure of PT sites on DNA while avoiding DNA loss and damage. After screening 116 candidates, we identified a bifunctional chemical compound, iodoacetyl-polyethylene glycol-biotin, that can noninvasively and selectively biotinylate PT sites, enabling further labeling with streptavidin fluorescent nanoprobes. With this method, PT sites in PT+ DNA can be easily detected by fluorescence, while almost no detectable ones were found in PT- DNA, achieving real-time visualization of PT sites on a single DNA molecule. Collectively, this facile genome-wide PT site detection method directly characterizes the distribution and frequency of DNA modification, facilitating a better understanding of its modification mechanism that can be potentially extended to label DNAs in different species.

Intestinal fibrosis classification in patients with Crohn's disease using CT enterography-based deep learning: comparisons with radiomics and radiologists.

OBJECTIVES: Accurate evaluation of bowel fibrosis in patients with Crohn's disease (CD) remains challenging. Computed tomography enterography (CTE)-based radiomics enables the assessment of bowel fibrosis; however, it has some deficiencies. We aimed to develop and validate a CTE-based deep learning model (DLM) for characterizing bowel fibrosis more efficiently. METHODS: We enrolled 312 bowel segments of 235 CD patients (median age, 33 years old) from three hospitals in this retrospective study. A training cohort and test cohort 1 were recruited from center 1, while test cohort 2 from centers 2 and 3. All patients performed CTE within 3 months before surgery. The histological fibrosis was semi-quantitatively assessed. A DLM was constructed in the training cohort based on a 3D deep convolutional neural network with 10-fold cross-validation, and external independent validation was conducted on the test cohorts. The radiomics model (RM) was developed with 4 selected radiomics features extracted from CTE images by using logistic regression. The evaluation of CTE images was performed by two radiologists. DeLong's test and a non-inferiority test were used to compare the models' performance. RESULTS: DLM distinguished none-mild from moderate-severe bowel fibrosis with an area under the receiver operator characteristic curve (AUC) of 0.828 in the training cohort and 0.811, 0.808, and 0.839 in the total test cohort, test cohorts 1 and 2, respectively. In the total test cohort, DLM achieved better performance than two radiologists (*1 AUC = 0.579, *2 AUC = 0.646; both p < 0.05) and was not inferior to RM (AUC = 0.813, p < 0.05). The total processing time for DLM was much shorter than that of RM (p < 0.001). CONCLUSION: DLM is better than radiologists in diagnosing intestinal fibrosis on CTE in patients with CD and not inferior to RM; furthermore, it is more time-saving compared to RM. KEY POINTS: • Question Could computed tomography enterography (CTE)-based deep learning model (DLM) accurately distinguish intestinal fibrosis severity in patients with Crohn's disease (CD)? • Findings In this cross-sectional study that included 235 patients with CD, DLM achieved better performance than that of two radiologists' interpretation and was not inferior to RM with significant differences and much shorter processing time. • Meaning This DLM may accurately distinguish the degree of intestinal fibrosis in patients with CD and guide gastroenterologists to formulate individualized treatment strategies for those with bowel strictures.

Noninvasive prenatal diagnosis targeting fetal nucleated red blood cells.

Noninvasive prenatal diagnosis (NIPD) aims to detect fetal-related genetic disorders before birth by detecting markers in the peripheral blood of pregnant women, holding the potential in reducing the risk of fetal birth defects. Fetal-nucleated red blood cells (fNRBCs) can be used as biomarkers for NIPD, given their remarkable nature of carrying the entire genetic information of the fetus. Here, we review recent advances in NIPD technologies based on the isolation and analysis of fNRBCs. Conventional cell separation methods rely primarily on physical properties and surface antigens of fNRBCs, such as density gradient centrifugation, fluorescence-activated cell sorting, and magnetic-activated cell sorting. Due to the limitations of sensitivity and purity in Conventional methods, separation techniques based on micro-/nanomaterials have been developed as novel methods for isolating and enriching fNRBCs. We also discuss emerging methods based on microfluidic chips and nanostructured substrates for static and dynamic isolation of fNRBCs. Additionally, we introduce the identification techniques of fNRBCs and address the potential clinical diagnostic values of fNRBCs. Finally, we highlight the challenges and the future directions of fNRBCs as treatment guidelines in NIPD.

Mycobacterium tuberculosis Rv1515c antigen enhances survival of M. smegmatis within macrophages by disrupting the host defence.

Mycobacterium tuberculosis (Mtb) infection is the major cause of tuberculosis. Mtb regions of difference (RD) genes are vital for survival of the pathogen within hosts and for the attenuation of the bacillus Calmette-Guérin vaccine. However, the function of most RD proteins largely remains unexplored. In the present study, we focused on Rv1515c, an RD6 member from M. tuberculosis, and characterised it as a cell surface-associated protein that functions in disrupting the cytokine profile and promoting endoplasmic reticulum stress-mediated apoptosis. Rv1515c expression in M. smegmatis, a nonpathogenic species, resulted in enhanced resistance of the bacterium to various in vitro stressors (such as low pH, sodium dodecyl sulfate, oxidative pressure, and nitrogen intermediate) and its cellular survival within macrophages. Our study is the first to identify the role of Rv1515c in the physiology and pathogenesis of mycobacterium.

Highly sensitive and rapid isolation of fetal nucleated red blood cells with microbead-based selective sedimentation for non-invasive prenatal diagnostics.

Non-invasive prenatal diagnostics (NIPD) has been an emerging field for prenatal diagnosis research. Carrying the whole genome coding of the fetus, fetal nucleated red blood cells (FNRBCs) have been pursued as a surrogate biomarker traveling around in maternal blood. Here, by combining a unique microbead-based centrifugal separation and enzymatic release, we demonstrated a novel method for FNRBC isolation from the blood samples. First, the gelatin-coated silica microbeads were modified with FNRBC-specific antibody (anti-CD147) to capture the target cells in the blood samples. Then, the density difference between microbead-bound FNRBCs and normal blood cells enables the purification of FNRBCs via an improved high-density percoll-based separation. The non-invasive release of FNRBCs can then be achieved by enzymatically degrading the gelatin film on the surface of the microbeads, allowing a gentle release of the captured target cells with as high as 84% efficiency and ∼80% purity. We further applied it to isolate fetal cells from maternal peripheral blood. The released cells were analyzed by real-time polymerase chain reaction to verify their fetal origin and fluorescent in situ hybridization to detect fetal chromosome disorders. This straightforward and reliable alternative platform for FNRBC detection may have the potential for realizing facile NIPD.

First succinyl-proteome profiling of extensively drug-resistant Mycobacterium tuberculosis revealed involvement of succinylation in cellular physiology.

Protein lysine succinylation, an emerging protein post-translational modification widespread among eukaryotic and prokaryotic cells, represents an important regulator of cellular processes. However, the extent and function of lysine succinylation in Mycobacterium tuberculosis, especially extensively drug-resistant strain, remain elusive. Combining protein/peptide prefractionation, immunoaffinity enrichment, and LC-MS/MS analysis, a total of 686 succinylated proteins and 1739 succinylation sites of M. tuberculosis were identified, representing the first global profiling of M. tuberculosis lysine succinylation. The identified succinylated proteins are involved in a variety of cellular functions such as metabolic processes, transcription, translation, and stress responses and exhibit different subcellular localization via GO, protein interaction network, and other bioinformatic analysis. Notably, proteins involved in protein biosynthesis and carbon metabolism are preferred targets of lysine succinylation. Moreover, two prevalent sequence patterns: EK(suc) and K*****K(suc), can be found around the succinylation sites. There are 109 lysine-succinylated homologues in E. coli, suggesting highly conserved succinylated proteins. Succinylation was found to occur at the active sites predicted by Prosite signature including Rv0946c, indicating that lysine succinylation may affect their activities. There is extensive overlapping between acetylation sites and succinylation sites in M. tuberculosis. Many M. tuberculosis metabolic enzymes and antibiotic resistance proteins were succinylated. This study provides a basis for further characterization of the pathophysiological role of lysine succinylation in M. tuberculosis.

Red Blood Cell Membrane as a Biomimetic Nanocoating for Prolonged Circulation Time and Reduced Accelerated Blood Clearance.

For decades, poly(ethylene glycol) (PEG) has been widely incorporated into nanoparticles for evading immune clearance and improving the systematic circulation time. However, recent studies have reported a phenomenon known as "accelerated blood clearance (ABC)" where a second dose of PEGylated nanomaterials is rapidly cleared when given several days after the first dose. Herein, we demonstrate that natural red blood cell (RBC) membrane is a superior alternative to PEG. Biomimetic RBC membrane-coated Fe(3)O(4) nanoparticles (Fe(3)O(4) @RBC NPs) rely on CD47, which is a "don't eat me" marker on the RBC surface, to escape immune clearance through interactions with the signal regulatory protein-alpha (SIRP-α) receptor. Fe(3)O(4) @RBC NPs exhibit extended circulation time and show little change between the first and second doses, with no ABC suffered. In addition, the administration of Fe(3)O(4) @RBC NPs does not elicit immune responses on neither the cellular level (myeloid-derived suppressor cells (MDSCs)) nor the humoral level (immunoglobulin M and G (IgM and IgG)). Finally, the in vivo toxicity of these cell membrane-camouflaged nanoparticles is systematically investigated by blood biochemistry, hematology testing, and histology analysis. These findings are significant advancements toward solving the long-existing clinical challenges of developing biomaterials that are able to resist both immune response and rapid clearance.

Phylogenomics of Mycobacterium Nitrate Reductase Operon.

NarGHJI operon encodes a nitrate reductase that can reduce nitrate to nitrite. This process enhances bacterial survival by nitrate respiration under anaerobic conditions. NarGHJI operon exists in many bacteria, especially saprophytic bacteria living in soil which play a key role in the nitrogen cycle. Most actinomycetes, including Mycobacterium tuberculosis, possess NarGHJI operons. M. tuberculosis is a facultative intracellular pathogen that expands in macrophages and has the ability to persist in a non-replicative form in granuloma lifelong. Nitrogen and nitrogen compounds play crucial roles in the struggle between M. tuberculosis and host. M. tuberculosis can use nitrate as a final electron acceptor under anaerobic conditions to enhance its survival. In this article, we reviewed the mechanisms regulating nitrate reductase expression and affecting its activity. Potential genes involved in regulating the nitrate reductase expression in M. tuberculosis were identified. The conserved NarG might be an alternative mycobacterium taxonomic marker.

Study on the release of fenofibrate nanosuspension in vitro and its correlation with in situ intestinal and in vivo absorption kinetics in rats.

As an oral delivery carrier for poorly water soluble drugs, the nanosuspension was prepared by melt emulsification method combined with high-pressure homogenization. The objective of this study was to clarify the absorption mechanism in rats of fenofibrate nanosuspension using the model of in situ gut perfusion. The release rate of drug from nanosuspension was fast which about 70% of the drug would be released within 5 minutes. The absorption of fenofibrate nanosuspension in the gastrointestinal (GI) tract was studied by the in situ closed loop method in rats. It was found that the absorption process in intestine was first-process with passive diffusion mechanism, and the whole intestine was the major segment for the drug absorption. Additionally, GI absorption in situ studies indicated that the fenofibrate nanosuspension had great success in regard to enhancement of intestinal absorption compared to the fenofibrate suspension of coarse powder. The pharmacokinetic characteristics were studied in rats after oral administration of fenofibrate nanosuspension or suspension at the dosage of 27 mg/kg. The plasma concentration-time curve was fitted to the one-compartment model. The correlation between in vitro dissolution (P), in situ intestinal absorption (F) and in vivo absorption (Fa) in rats was investigated with the results as follows: Fa = 6.2061P-456.38(r = 0.9559), F = 3.6911P-2.2169(r = 0.970), F = 0.5095P + 44.189(r = 0.9609). The highest level A could be obtained from the in vitro--in vivo correlation (IVIVC) between dissolution percentage and intestinal absorption of the fenofibrate nanosuspension in rats. Consequently, the in situ intestinal perfusion model could be used to predict the in vivo pharmacokinetic characteristics in rats.

Efficacy and Safety of Snap Needles in the Treatment of Postoperative Hemorrhoidal Pain: A Systematic Review and Meta-Analysis.

Purpose: The aim of this study is to evaluate the efficacy and safety of Snap Needles (SN) in the management of Postoperative Hemorrhoidal Pain (POHP). Patients and Methods: A systematic search was conducted in various databases, including EMBASE, Web of Science, PubMed, WanFang database, China National Knowledge Infrastructure (CNKI), China Biomedical Literature Database (CBM), and China Science and Technology Journal Database (VIP), spanning from their inception to August 2023, to identify relevant randomized controlled trials (RCTs) on SN for POHP. The primary outcome measure was the Visual Analog Scale (VAS), while secondary outcomes encompassed the Total Effective Rate (TER), Wound Healing Time (WHT), Pain Relief Time (PRT), Pain Disappearance Time (PDT), and Adverse Events (AEs). The Cochrane Risk of Bias Tool was employed to assess the quality of individual studies. A meta-analysis was conducted using RevMan 5.4.1 software. Results: The meta-analysis included 11 RCTs involving 1188 POHP patients, with an overall assessment of study quality ranging from very low to moderate. The findings revealed that the SN group exhibited significant improvements in treatment outcomes when compared to the control group (CG). These improvements were reflected in reduced VAS scores (mean difference [MD] = -1.10, 95% confidence interval [CI]: -1.31, -0.89, P < 0.05), shorter WHT (MD = -2.55, 95% CI: -3.02, -2.09, P < 0.05), quicker PRT (MD = -7.99, 95% CI: -8.48, -7.49, P < 0.05), fewer AEs (risk ratio [RR] = 0.38, 95% CI: 0.22, 0.67, P < 0.05), improved TER (RR = 1.18, 95% CI: 1.09, 1.27, P < 0.05), and faster PDT (MD = 19.24, 95% CI: 14.17, 24.31, P < 0.05). Conclusion: The use of SN appears to yield favorable outcomes in the treatment of POHP, and is potentially an alternative therapy to western drug therapy.

Sprayable chitosan nanogel with nitric oxide to accelerate diabetic wound healing through bacteria inhibition, biofilm eradication and macrophage polarization.

Bacterial infection and chronic inflammation are two major risks in diabetic wound healing, which increase patient mortality. In this study, a multifunctional sprayable nanogel (Ag-G@CS) based on chitosan has been developed to synergistically inhibit bacterial infection, eradicate biofilm, and relieve inflammation of diabetic wounds. The nanogel is successfully crafted by encapsulating with a nitric oxide (NO) donor and performing in-situ reduction of silver nanoparticles (Ag). The released NO enhances the antibacterial efficacy of Ag, nearly achieving complete eradication of biofilms in vitro. Upon application on both normal or diabetic chronic wounds, the combination effects of released NO and Ag offer a notable antibacterial effect. Furthermore, after bacteria inhibition and biofilm eradication, the NO released by the nanogel orchestrates a transformation of M1 macrophages into M2 macrophages, significantly reducing tumor necrosis factor α (TNF-α) release and relieving inflammation. Remarkably, the released NO also promotes M2a to M2c macrophages, thereby facilitating tissue remodeling in chronic wounds. More importantly, it upregulates the expression of vascular endothelial growth factor (VEGF), further accelerating the wound healing process. Collectively, the formed sprayable nanogel exhibits excellent inhibition of bacterial infections and biofilms, and promotes chronic wound healing via inflammation resolution, which has excellent potential for clinical use in the future.

Genetically Engineered Cytomembrane Nanovaccines for Cancer Immunotherapy.

Cancer nanovaccines have attracted widespread attention by inducing potent cytotoxic T cell responses to improve immune checkpoint blockade (ICB) therapy, while the lack of co-stimulatory molecules limits their clinical applications. Here, a genetically engineered cancer cytomembrane nanovaccine is reported that simultaneously overexpresses co-stimulatory molecule CD40L and immune checkpoint inhibitor PD1 to elicit robust antitumor immunity for cancer immunotherapy. The CD40L and tumor antigens inherited from cancer cytomembranes effectively stimulate dendritic cell (DC)-mediated immune activation of cytotoxic T cells, while the PD1 on cancer cytomembranes significantly blocks PD1/PD-L1 signaling pathway, synergistically stimulating antitumor immune responses. Benefiting from the targeting ability of cancer cytomembranes, this nanovaccines formula shows an enhanced lymph node trafficking and retention. Compared with original cancer cytomembranes, this genetically engineered nanovaccine induces twofold DC maturation and shows satisfactory precaution efficacy in a breast tumor mouse model. This genetically engineered cytomembrane nanovaccine offers a simple, safe, and robust strategy by incorporating cytomembrane components and co-stimulatory molecules for enhanced cancer immunotherapy.

A Light-Responsive Injectable Hydrogel with Remodeling Tumor Microenvironment for Light-Activated Chemodynamic Therapy.

Chemodynamic therapy (CDT) based on Fenton-like reaction is often limited by the tumor microenvironment (TME), which has insufficient hydrogen peroxide, and single CDT treatment is often less efficacious. To overcome these limitations, a hydrogel-based system is designed to enhance the redox stress (EOH) by loading the composite nanomaterial Cu-Hemin-Au, into the agarose hydrogels. The hydrogels can reach the tumor site upon intratumoral injection, and then coagulate and stay for extended period. Once irradiated with near-infrared light, the Cu-Hemin-Au act as a photothermal agent to convert the light energy into heat, and the EOH gradually heated up and softened, releasing the Cu-Hemin-Au residing in it to achieve photothermal therapy (PTT). Benefiting from the glucose oxidase (GOx)-like activity of the Au nanoparticles, glucose in the tumor cells is largely consumed, and hydrogen peroxide (H2 O2 ) is generated in situ, and then Cu-Hemin-Au react with sufficient H2 O2 to generate a large amount of reactive oxygen species, which promote the complete inhibition of tumor growth in mice during the treatment cycle. The hydrogel system for the synergistic enhancement of oxidative stress achieves good PTT/CDT synergy, providing a novel inspiration for the next generation of hydrogels for application in antitumor therapy.