Macrophages-Based Biohybrid Microrobots for Breast Cancer Photothermal Immunotherapy by Inducing Pyroptosis.

Pyroptosis-based immunotherapy can escape drug resistance as well as inhibit metastasis. It is urgently required to develop a delivery platform to induce targeted tumor-specific pyroptosis for cancer immunotherapy. Herein, macrophages-based biohybrid microrobots (IDN@MC) are constructed with IR-macrophage and decitabine-loaded Metal-organic frameworks (DZNPs). The integration of fluorescence photosensitizers and pH-sensitive DZNPs endow the microrobots properties such as photothermal conversion, fluorescent navigation, targeted drug delivery, and controlled drug release. In light of the inherent tumor targeting, tumor accumulation of IDN@MC is facilitated. Due to the sustained release of decitabine from packaged DZNPs, the host macrophages are differentiated into M1 phenotypes to exert the tumor phagocytosis at the tumor site, directly transporting the therapeutic agents into cancer cells. With laser control, the rapid and durable caspase 3-cleaved gasdermin E (GSDME)-related tumor pyroptosis is achieved with combined photothermal-chemotherapy, releasing inflammatory factors such as lactate dehydrogenase and interleukin-18. Subsequently, the robust and adaptive immune response is primed with dendritic cell maturation to initiate T-cell clone expansion and modulation of the immune suppressive microenvironment, thus enhancing the tumor immunotherapy to inhibit tumor proliferation and metastasis. This macrophages-based biohybrid microrobot is an efficient strategy for breast cancer treatment to trigger photo-induced pyroptosis and augment the immune response.

Fluidic MXene Electrode Functionalized with Iron Single Atoms for Selective Electrocatalytic Nitrate Transformation to Ammonia.

The growth of renewable energy industries and the ongoing need for fertilizer in agriculture have created a need for sustainable production of ammonia (NH3) using low-cost, environment-friendly techniques. The electrocatalytic nitrate (NO3-) reduction reaction (NO3RR) has the potential to improve both the management of environmental nitrogen and the recycling of synthetic nutrients. However, NO3RR is frequently hindered by the incomplete NO3- conversion, sluggish reaction kinetics, and suppression of the hydrogen evolution reaction (HER). Inspired by specific local electronic structures that are adjustable for single-atom catalysts, this work presents a nanohybrid electrocatalytic filter with iron single atoms (FeSA) immobilized on MXene. The fabricated FeSA/MXene filter exhibited maximum NH3 Faradaic efficiency and selectivity (82.9 and 99.2%, respectively) that were higher than those for filters made of Fe nanoparticles anchored on MXene (FeNP/MXene) (69.2 and 81.3%, respectively) and MXene alone (32.8 and 52.4%, respectively), measured at an initial pH of 7 and an applied potential of -1.4 V vs Ag/AgCl. Density functional theory calculations revealed that, compared to the FeNP/MXene filter, the FeSA/MXene filter prevented the competition from the HER and reduced the activation energy of the potential-limiting step (*NO to *NHO) that made the NH3 synthesis thermodynamically favorable . This work highlights an alternative strategy for achieving a synergistic NO3- removal and nutrient recovery with durable catalytic activity and stability.

A Mini-Review on the Thermal Fatigue Properties of Copper Materials Applied at the Front-End of Synchrotron Radiation Facilities.

Oxygen-free high-conductivity copper (OFHC), chromium-zirconium copper (CuCrZr), and Glidcop® AL-15 are widely used in the high heat load absorber elements at the front end of synchrotron radiation facilities. It is necessary to choose the most suitable material according to the actual engineering conditions (such as the specific heat load, material performance, and costs). In the long-term service period, the absorber elements have to bear hundreds or kilowatts of high heat load and its "load-unload" cyclic loading mode. Therefore, the thermal fatigue and thermal creep properties of the materials are critical and have been extensively studied. In this paper, based on the published pieces of the literature, the thermal fatigue theory, experimental principles, methods, test standards, test types of equipment, and key indicators of the thermal fatigue performance of typical copper metal materials used in the front end of synchrotrons radiation Facilities are reviewed, as well as the relevant studies carried out by the well-known synchrotron radiation institutions. In particular, the fatigue failure criteria for these materials and some effective methods for improving the thermal fatigue resistance performance of the high-heat load components are also presented.

Vacuum joints of CuCrZr alloy for high-heat-load photon absorber.

A photon absorber, as a critical component of a synchrotron front-end, is mainly used to handle high-heat-load synchrotron radiation. It is mostly made of dispersion strengthened copper or CuCrZr which can retain high performance at elevated temperatures. Joining processes for vacuum, including tungsten inert gas welding (TIG) and electron beam welding (EBW), are novel ways to make a long photon absorber from two short ones and reduce power density. The mechanical properties of TIG joints and EBW joints of CuCrZr to the same material are obtained by tensile tests at 20°C, 100°C, 200°C, 300°C and 400°C. Testing results indicate that the tensile strength and yield strength of both vacuum joints decline as temperature increases. Compared with TIG joints, EBW joints have higher strength, better ductility and a more stable performance. An engineering conservative acceptance criteria of the vacuum joints is created by the polynomial fitting method. A novel welded photon absorber with a total length of 600 mm has been successfully designed and manufactured. Finite-element analysis by ANSYS shows that the maximum temperature, equivalent stress and strain are only 31.5%, 36.2% and 1.3%, respectively, of the corresponding thresholds. The welded photon absorbers with EBW joints will be applicable in the highest-heat-load front-end in the Shanghai Synchrotron Radiation Facility Phase-II beamline project.

Mo Vacancy-Mediated Activation of Peroxymonosulfate for Ultrafast Micropollutant Removal Using an Electrified MXene Filter Functionalized with Fe Single Atoms.

Developing advanced heterogeneous catalysts with atomically dispersed active sites is an efficient strategy to boost the kinetics of peroxymonosulfate (PMS) activation for micropollutant removal. Here, we report a binary Mo2TiC2Tx MXene-based electroactive filter system with abundant surface Mo vacancies for effective activation of PMS. The Mo vacancies assumed two essential roles: (i) as anchoring sites for Fe single atoms (Fe-SA) and (ii) as cocatalytic sites for the Fenton-like reaction. Fe-SA formed strong metal-oxygen bonds with the Mo2TiC2Tx support, stabilizing at the sites previously occupied by Mo. The resulting Fe-SA/Mo2TiC2Tx nanohybrid filter achieved 100% degradation of sulfamethoxazole (SMX) in the single-pass mode (hydraulic retention time <2 s) when assisted by an electric field (2.0 V). The rate constant (k = 2.89 min-1) for SMX removal was 24 and 67 times greater than that of Fe nanoparticles immobilized on Mo2TiC2Tx and the pristine Mo2TiC2Tx filter, respectively. Operation in the flow-through configuration outperformed the conventional batch reactor model (k = 0.17 min-1) due to convection-enhanced mass transport. The results obtained from experimental investigations and theoretical calculations suggested that atomically dispersed Fe-SA, anchored on Mo vacancies, was responsible for the adsorption and activation of PMS to produce sulfate radicals (SO4•-) in the presence of an electric field. This study provides a proof-of-concept demonstration of an electroactive Fe-SA/Mo2TiC2Tx filter for broader application in the treatment of water contaminated by emerging micropollutants.

Pharmacological Signatures of the Exenatide Nanoparticles Complex Against Myocardial Ischemia Reperfusion Injury.

BACKGROUND/AIMS: Myocardial ischemia/reperfusion (I/R) injury (MI/RI) is a critical cause of death in patients with heart disease. However, the pharmaco-therapeutical outcome for MI/RI remains unsatisfactory. Innovative approaches for enhancing drug sensitivity and recovering myocardial function in MI/RI treatment are urgently needed. The purpose of this study was to evaluate the protective effects of exenatide-loaded poly(L-lysine)-poly(ethylene glycol)-poly(L-lysine) (PLL-PEG-PLL) nanoparticles (NPs) against MI/RI. METHODS: The size of PLL-PEG-PLL NPs and the loading and release rates of exenatide were determined. The in vitro NP cytotoxicity was evaluated using newborn rat cardiomyocytes. Rats pretreated with free exenatide or exenatide/PLL-PEG-PLL polyplexes were subjected to 0.5-h ischemia and 2-h reperfusion in the left anterior descending coronary artery. The histopathologic lesions were assessed using hematoxylin-eosin staining. The general physiological indices, including blood pressure (BP), heart rate (HR), the left ventricular ejection fraction (LVEF) and end-diastolic pressure (LEVDP), and the left ventricular pressure maximal rate of rising (dp/dtmax), were monitored using a non-invasive blood pressure analyzer and color Doppler echocardiography. The antioxidative activity in the myocardial tissue was measured. The myocardial enzymatic activity was further estimated by determining the serum levels of creatine kinase (CK), lactate dehydrogenase (LDH), cardiac troponin T (cTnT), and glucagon-like peptide-1 (GLP-1), as well as the expression of GLP-1R in the myocardial tissue. RESULTS: Exenatide preconditioning attenuated the oxidative stress injury and promoted the myocardial function in I/R-induced myocardial injury, while the application of block copolymer PLL-PEG-PLL as a potential exenatide nanocarrier with sustained release significantly enhanced the bioavailability of exenatide. CONCLUSION: The block copolymer PLL-PEG-PLL may function as a potent exenatide nanocarrier for augmenting pharmacotherapy against MI/RI with unprecedented clinical benefits. Further study is needed to better clarify the underlying mechanisms.

Energy Migration Upconversion in Ce(III)-Doped Heterogeneous Core-Shell-Shell Nanoparticles.

One major challenge in upconversion research is to develop new materials and structures to expand the emission spectrum. Herein, a heterogeneous core-shell-shell nanostructure of NaYbF4 :Gd/Tm@NaGdF4 @CaF2 :Ce is developed to realize efficient photon upconversion in Ce3+ ions through a Gd-mediated energy migration process. The design takes advantage of CaF2 host that reduces the 4f-5d excitation frequency of Ce3+ to match the emission line of Gd3+ . Meanwhile, CaF2 is isostructural with NaGdF4 and can form a continuous crystalline lattice with the core layer. As a result, effective Yb3+ → Tm3+ → Gd3+ → Ce3+ energy transfer can be established in a single nanoparticle. This effect enables efficient ultraviolet emission of Ce3+ following near infrared excitation into the core layer. The Ce3+ upconversion emission achieved in the core-shell-shell nanoparticles features broad bandwidth and long lifetime, which offers exciting opportunities of realizing tunable lasing emissions in the ultraviolet spectral region.

Associations of CYP4A11 gene-gene and gene-smoking interactions with essential hypertension in the male eastern Chinese Han population.

OBJECTIVES: The aim of this study was to investigate the impact of CYP4A11 single-nucleotide polymorphisms (SNP), additional gene-gene and gene-environment interactions on essential hypertension (EH) risk. METHODS: A total of 1648 participants (788 males, 860 females), with a mean age of 56.1 ± 14.1 years old, were selected, including 820 EH patients and 828 normotension subjects. Logistic regression was performed to investigate association of SNPs within CYP4A11 gene with high DBP, high SBP and EH risk, and generalized multifactor dimensionality reduction (GMDR) was used to analyze the gene-gene interaction and gene-smoking interaction. RESULTS: Logistic regression analysis showed that EH risk was significantly higher in carriers of C allele of the rs1126742 polymorphism than those with TT genotype (TC+CC versus TT, adjusted OR (95%CI) = 1.56 (1.24-1.91). In addition, we also found that EH risk was also significantly higher in carriers of G allele of the rs3890011polymorphism than those with CC genotype (CG+ GG versus CC, adjusted OR (95%CI) = 1.31 (1.15-2.03). GMDR analysis indicated a potential gene-gene interaction between rs1126742 and rs3890011 and a gene-environment interaction between rs1126742 and smoking. We found that subjects with TC or CC of rs1126742 and CG or GG of rs3890011genotype have the highest EH risk, OR (95%CI) was 2.52 (1.28-3.57). Smokers with TC or CC of rs1126742 genotype have the highest EH risk, OR (95%CI) was 2.20 (1.28-3.40). CONCLUSIONS: Gene-gene interaction between rs1126742 and rs3890011 and gene-environment interaction between rs1126742 and smoking were associated with increased EH risk.

Downregulation of T-bet/GATA-3 ratio induced by IL-11 treatment is responsible for Th1/Th2 balance restoration in human immune thrombocytopenic purpura (ITP).

Abnormal cellular immunity induced by deranged Th1/Th2 profile has been revealed to play a critical role in the pathogenesis of immune thrombocytopenic purpura (ITP). Correction of the shifted Th1/Th2 balance represents a potential therapeutic approach to treat ITP. Here, we investigated the effects of IL-11 on the restoration of Th1/Th2 balance in the peripheral blood mononuclear cells (PBMCs) isolated from adult ITP patients. As shown here, we observed a higher ratio of T-bet/GATA-3 gene expression by quantitative real-time PCR in the PBMCs from ITP patients, consistent with the presence of an abnormally high Th1/Th2 ratio. Remarkably, upon IL-11 treatment, a reversal of T-bet/GATA-3 ratio in ITP was achieved and was shown to be responsible for the restoration of Th1/Th2 balance, with IL-11 at 100 ng/ml demonstrating the highest efficiency. T-bet and GATA-3 are the two transcriptional factors that have been indicated to be the master regulators for Th1 and Th2 lineage commitment, respectively. In the presence of 100 ng/ml IL-11, GATA-3 transcript abundance rose up to ~85-fold of that measured in untreated cells, whereas T-bet transcripts were lowered merely to ~41%, suggesting that GATA-3 was the major contributor for the reversal of T-bet/GATA-3 ratio. Thus, our findings may very well encourage the development of novel medicines that specifically target and correct the T-bet/GATA-3 imbalance identified in ITP.

Research on vibration stability of a mirror bender system for synchrotron radiation.

This paper accurately predicts and quantifies the vibration response characteristics of a mirror bender system with the finite element simulation and experiment. The results show that the fundamental frequency of the roll angle vibration is 24.66 Hz, and the fundamental frequency of the pitch angle vibration is 116.21 Hz. The overall error is within 11.15% in comparision with the first six natural frequencies obtained from experiments and simulations. The vertical support rod, being one of the weakest links in the overall structural stiffness, is a crucial factor limiting the increase in the natural frequency of the mirror system. Before and after the injection of cooling water, the pitch angle vibration was 123.63 and 199.04 nrad, respectively. An increase in the cooling water flow rate from 1 to 1.5 l/min has almost no effect on pitch angle vibrations. This study provides references and guidance for improving the stability of the mirror system.

Genome Sequencing Analysis of a Rare Case of Blood Infection Caused by Flavonifractor plautii.

BACKGROUND Flavonifractor plautii belongs to the clostridium family, which can lead to local infections as well as the bloodstream infections. Flavonifractor plautii caused infection is rarely few in the clinic. To understand better Flavonifractor plautii, we investigated the drug sensitivity and perform genome sequencing of Flavonifractor plautii isolated from blood samples in China and explored the drug resistance and pathogenic mechanism of the bacteria. CASE REPORT The Epsilometer test method was used to detect the sensitivity of flavonoid bacteria to antimicrobial agents. PacBio sequencing technology was employed to sequence the whole genome of Flavonifractor plautii, and gene prediction and functional annotation were also analyzed. Flavonifractor plautii displayed sensitivity to most drugs but resistance to fluoroquinolones and tetracycline, potentially mediated by tet (W/N/W). The total genome size of Flavonifractor plautii was 4,573,303 bp, and the GC content was 59.78%. Genome prediction identified 4,506 open reading frames, including 9 ribosomal RNAs and 66 transfer RNAs. It was detected that the main virulence factor-coding genes of the bacteria were the capsule, polar flagella and FbpABC, which may be associated with bacterial movement, adhesion, and biofilm formation. CONCLUSIONS The results of whole-genome sequencing could provide relevant information about the drug resistance mechanism and pathogenic mechanism of bacteria and offer a basis for clinical diagnosis and treatment.

Integrated transcriptomic and proteomic analyses uncover the early response mechanisms of Catharanthus roseus under ultraviolet-B radiation.

Catharanthus roseus produces a large array of terpenoid indole alkaloids (TIAs) that are important natural source for many drugs. Ultraviolet B (UVB) radiation have been proved to have regulatory effect towards biosynthesis of TIAs, which were meaningful for boost of TIA production. To decipher more comprehensive molecular characteristics in C. roseus under UVB radiation, integrated analysis of the nuclear proteome together with the transcriptome data under UVB radiation were performed. Expression of genes related to transmembrane transporters gradually increased during the prolonged exposure to UVB radiation. Some of known TIA transporters were affected by UVB. Abundance of proteins associated with spliceosome and nucleocytoplasmic transport increased. Homologs belonging to ORCA and CrWRKY transcription factors family increased at both transcriptomic and proteomic levels. At the same time, the numbers of differential alternative splicing events between UVB-radiated and white-light-treated plants continuously increased. These results suggest that the nucleus participated in early response of C. roseus under UVB radiation, where alternative splicing events occurred and might regulate multiple pathways. Furthermore, integrative omics analysis indicates that expression of enzymes at the terminal stages of seco-iridoid pathway decreased with the prolonged radiation exposure, potentially inhibiting further rise of TIA synthesis under extended UVB exposure.

Signal amplified colorimetric nucleic acid detection based on autocatalytic hairpin assembly.

Herein, a nucleic acid assay based on autocatalytic hairpin assembly (ACHA) was proposed. In this system, two split G-quadruplex sequences were integrated into H1 and H2, respectively. And a DNA strand with the same sequence to target DNA was integrated into the assistant hairpin H3. In the presence of target DNA, the hairpin structure of H1 was opened and catalytic hairpin assembly (CHA) was activated, and then a series of DNA assembly steps based on the toehold-mediated DNA strand displacement were triggered and the product H1-H2 with sticky ends on both sides was formed. On the one side of H1-H2, the split two G-quadruplex sequences were close enough to form the intact G-quadruplex for the signal readout. At the same time, two sticky ends on the other side of H1-H2 hybridized with H3 and a new sticky end with the sequence same to the target DNA was exposed, which can immediately trigger the autocatalytic hairpin assembly reaction, and then the reaction rate of CHA was effectively accelerated and the colorimetric signal was significantly amplified. This ACHA signal amplified strategy has been successfully applied for the rapid and colorimetric nucleic acid detection.

A Twindrive Precise Delivery System of Platelet-Neutrophil Hybrid Membrane Regulates Macrophage Combined with CD47 Blocking for Postoperative Immunotherapy.

During wound healing after cancer surgery, platelets, neutrophils, and macrophages accumulate at the wound site and induce important pathophysiological features. Utilizing these pathophysiological features, the development of targeted delivery systems for postoperative tumor immunotherapy is an important strategy. Herein, a twindrive precise delivery system of hybrid membrane combined with CD47 blocking is developed for targeted delivery and targeted regulation to induce postoperative immunotherapy. The precise delivery system consists of IR820-modified platelet-neutrophil hybrid membranes loaded with R848 nanoparticles. Based on the pathological characteristics of platelet aggregation and neutrophil tendency caused by the wound inflammatory microenvironment after tumor surgery, the twindrive delivery system could achieve targeted delivery and targeted regulation of immune drugs to tumor sites. After precise delivery guided by fluorescence imaging, R848 is targeted to reprogram M2 macrophages into M1 macrophages, stimulate dendritic cell maturation as an adjuvant, and then activate T cell immunity. R848 polarization and CD47 blockade together enhanced the phagocytosis function of macrophages, which combined with T cell-mediated cellular immune response to finally effectively inhibit postsurgical tumor recurrence, metastasis, and prolonged survival time. It develops a targeted delivery and regulatory system for cell-specific responses to the pathophysiological features of wound healing for postoperative immunotherapy.

An improved algorithm for thermal compensation of synchrotron radiation optical mirrors based on Hessian matrix.

The heaters-based thermal-compensated adaptive adjustment of a reflection mirror at Shanghai high repetition rate X-ray Free-Electron Laser and extreme light facility (SHINE) is presented here based on finite element analysis. The correction performance of different control algorithms [singular value decomposition and gradient descent (GD)] is analyzed and compared. This study has demonstrated that a significant control algorithm can further improve the surface shape accuracy of the mirror. After optimizing the mirror control algorithm, the calculated slope errors and height errors of the mirror are reduced to nearly less than 50 nrad rms and 0.5 nm rms, respectively. The optimization result indicates that the GD control algorithm based on the Hessian matrix exhibits superior performance and practicality compared to the control algorithm before optimization.

Anti-bacterial mechanism of baicalin-tobramycin combination on carbapenem-resistant Pseudomonas aeruginosa.

BACKGROUND: Pseudomonas aeruginosa (P. aeruginosa) is an important cause of nosocomial infections, and contributes to high morbidity and mortality, especially in intensive care units. P. aeruginosa is considered a 'critical' category bacterial pathogen by the World Health Organization to encourage an urgent need for research and development of new antibiotics against its infections. AIM: To investigate the effectiveness of baicalin combined with tobramycin therapy as a potential treatment method for carbapenem-resistant P. aeruginosa (CRPA) infections. METHODS: Polymerase chain reaction (PCR) and RT-PCR were used to detect the expression levels of drug-resistant genes (including VIM, IMP and OprD2) and biofilm-related genes (including algD, pslA and lasR) in CRPA that confer resistance to tobramycin, baicalin and tobramycin combined with baicalin (0, 1/8, 1/4, 1/2 and 1MIC). RESULTS: There was a correlation between biofilm formation and the expression of biofilm-related genes. In addition, VIM, IMP, OprD2, algD, pslA and lasR that confer biofilm production under different concentrations in CRPA were significantly correlated. The synergistic effect of baicalin combined with tobramycin was a significant down-regulation of VIM, IMP, algD, pslA and lasR. CONCLUSION: Baicalin combined with tobramycin therapy can be an effective treatment method for patients with CRPA infection.

Identification of CD147-positive extracellular vesicles as novel non-invasive biomarkers for the diagnosis and prognosis of colorectal cancer.

BACKGROUND: The mortality rate of colorectal cancer (CRC) can be decreased with effective screening and early diagnosis. Exosomes are released from cancer cells into the bloodstream, and circulating exosomes may serve as novel biomarkers. This study aimed to identify a sensitive and rapid method of exosome collection and measurement using specific antibodies. METHODS: ExoCounter, a high-sensitive exosome-counting system, allows the identification of exosomes without enrichment or purification, based on the identification of the transmembrane protein-CD147-on serum exosomes that are associated with CRC. RESULTS: Receiver operating characteristic curves between healthy donors and CRC patients were described and assessed by CD147-specific exosomes (exo-CD147), CEA, and CA19-9. And area under curves for exo-CD147, CEA, and CA19-9 were 0.827 (95%CI: 0.764-0.891), 0.630 (95%CI: 0.536-0.724), and 0.659 (95%CI: 0.559-0.759), respectively. Drawing a clinical decision curve of exo-CD147 for the diagnosis of CRC metastases showed that when the threshold probability of exo-CD147 was between 20% and 92%, the net clinical utilization rate was higher than for all patients with or without metastases. A nomogram was constructed using multivariate COX regression analysis to select significant variables such as the high CD147 group (>34 × 105 particles). Calibration curves for 1-, 3-, and 5-year survival rates of CRC patients showed that the actual 1-, 3-, and 5-year survival rates were in excellent agreement with the survival rates predicted by the nomogram. CONCLUSIONS: The increased CD147 expression in exosomes could serve as a diagnostic and prognostic biomarker for CRC.

A General Strategy to Synthesize Fluidic Single Atom Electrodes for Selective Reactive Oxygen Species Production.

Fine-tuning the geometric and electronic structure of catalytic metal centers via N-coordination engineering offers an effective design for the electrocatalytic transformation of O2 to singlet oxygen (1O2). Herein, we develop a general coordination modulation strategy to synthesize fluidic single-atom electrodes for selective electrocatalytic activation of O2 to 1O2. Using a single Cr atom system as an example, >98% 1O2 selectivity can be achieved from electrocatalytic O2 activation due to the subtle engineering of Cr-N4 sites. Both theoretical simulations and experimental results determined that "end-on" adsorption of O2 onto the Cr-N4 sites lowers the overall activation energy barrier of O2 and promotes the breakage of Cr-OOH bonds to form •OOH intermediates. In addition, the flow-through configuration (k = 0.097 min-1) endowed convection-enhanced mass transport and improved charge transfer imparted by spatial confinement within the lamellar electrode structure compared to that of batch reactor (k = 0.019 min-1). In a practical demonstration, the Cr-N4/MXene electrocatalytic system exhibits a high selectivity toward electron-rich micropollutants (e.g., sulfamethoxazole, bisphenol A, and sulfadimidine). The flow-through design of the fluidic electrode achieves a synergy with the molecular microenvironment that enables selective electrocatalytic 1O2 generation, which could be used in numerous ways, including the treatment of environmental pollution.

Neutrophil Camouflaged Stealth Nanovehicle for Photothermal-Induced Tumor Immunotherapy by Triggering Pyroptosis.

The regulation of tumor immunosuppressive microenvironments via precise drug delivery is a promising strategy for preventing tumor recurrence and metastasis. Inspired by the stealth strategy, a stealthy nanovehicle based on neutrophil camouflage is developed to achieve precise delivery and tumor immunotherapy by triggering pyroptosis. The nanovehicle comprises anti-CD11b- and IR820-conjugated bovine serum albumin nanoparticles loaded with decitabine. Camouflaged by neutrophils, the nanovehicles achieve efficient tumor delivery by neutrophil hitchhiking owing to the biotropism of neutrophils for tumors. The fluorescent signal molecule, IR820, on the nanovehicle acts as a navigation monitor to track the precise delivery of the nanovehicle. The released decitabine upregulates gasdermin E, and laser irradiation activates caspase-3, thereby resulting in pyroptosis, which improves the system's adaptive immune response. In a triple-negative breast cancer animal model, it regulates the immunosuppressive microenvironment for effective tumor immunotherapy and induces a long-lasting and strong immune memory to prevent lung metastasis.

Exosomal miR-200c and miR-141 as cerebrospinal fluid biopsy biomarkers for the response to chemotherapy in primary central nervous system lymphoma.

BACKGROUND: To improve early diagnosis and chemotherapy efficacy monitoring in primary central nervous system lymphoma (PCNSL), cerebrospinal fluid (CSF) exosomal microRNA (miRNA) studies were performed. METHOD: Small RNA sequencing was performed to identify candidate exosomal miRNAs as CSF biopsy biomarkers from two patients with de novo PCNSL and two patients in remission after chemotherapy. miR-200c and miR-141 expression in CSF exosomes was further validated using relative quantitative real-time polymerase chain reaction in patients with PCNSL (n = 20), patients with other neurological diseases (n = 10), and normal subjects (n = 10). Receiver operating characteristic (ROC) curve analyses of miR-200c and miR-141 in the diagnosis and prediction of chemotherapy efficacy in PCNSL were performed in patients treated with methotrexate. Additionally, bioinformatics tools were utilized to predict the potential targets of miR-200c and miR-141. RESULTS: Exosomal miR-200c and miR-141 levels in CSF from patients with PCNSL were significantly lower than those in control subjects. Importantly, miR-200c and miR-141 were upregulated in patients with PCNSL after chemotherapy (P = 0.002). There was a significant correlation between the levels of miR-141 and IL-10 in CSF (P = 0.04). The combination of miR-200c and miR-141 yielded an area under the ROC curve of 0.761 for distinguishing PCNSL with sensitivity and specificity of 60.0% and 96.7%, respectively. The potential target genes of miR-200c and miR-141 in PCNSL included ATP1B3, DYNC1H1, MATR3, NUCKS1, ZNF638, NUDT4, RCN2, GNPDA1, ZBTB38, and DOLK. CONCLUSION: Collectively, miR-200c and miR-141 are likely to be upregulated in CSF exosomes after chemotherapy in patients with PCNSL, highlighting their potential as reliable liquid biopsy biomarkers for PCNSL diagnosis and chemotherapy efficacy monitoring.