Characteristics and immune functions of the endogenous CRISPR-Cas systems in myxobacteria.

The clustered regularly interspaced short palindromic repeats and their associated proteins (CRISPR-Cas) system widely occurs in prokaryotic organisms to recognize and destruct genetic invaders. Systematic collation and characterization of endogenous CRISPR-Cas systems are conducive to our understanding and potential utilization of this natural genetic machinery. In this study, we screened 39 complete and 692 incomplete genomes of myxobacteria using a combined strategy to dispose of the abridged genome information and revealed at least 19 CRISPR-Cas subtypes, which were distributed with a taxonomic difference and often lost stochastically in intraspecies strains. The cas genes in each subtype were evolutionarily clustered but deeply separated, while most of the CRISPRs were divided into four types based on the motif characteristics of repeat sequences. The spacers recorded in myxobacterial CRISPRs were in high G+C content, matching lots of phages, tiny amounts of plasmids, and, surprisingly, massive organismic genomes. We experimentally demonstrated the immune and self-target immune activities of three endogenous systems in Myxococcus xanthus DK1622 against artificial genetic invaders and revealed the microhomology-mediated end-joining mechanism for the immunity-induced DNA repair but not homology-directed repair. The panoramic view and immune activities imply potential omnipotent immune functions and applications of the endogenous CRISPR-Cas machinery. IMPORTANCE: Serving as an adaptive immune system, clustered regularly interspaced short palindromic repeats and their associated proteins (CRISPR-Cas) empower prokaryotes to fend off the intrusion of external genetic materials. Myxobacteria are a collective of swarming Gram-stain-negative predatory bacteria distinguished by intricate multicellular social behavior. An in-depth analysis of their intrinsic CRISPR-Cas systems is beneficial for our understanding of the survival strategies employed by host cells within their environmental niches. Moreover, the experimental findings presented in this study not only suggest the robust immune functions of CRISPR-Cas in myxobacteria but also their potential applications.

Interplay between mesenchymal stem cells and macrophages: Promoting bone tissue repair.

The repair of bone tissue damage is a complex process that is well-orchestrated in time and space, a focus and difficulty in orthopedic treatment. In recent years, the success of mesenchymal stem cells (MSCs)-mediated bone repair in clinical trials of large-area bone defects and bone necrosis has made it a candidate in bone tissue repair engineering and regenerative medicine. MSCs are closely related to macrophages. On one hand, MSCs regulate the immune regulatory function by influencing macrophages proliferation, infiltration, and phenotype polarization, while also affecting the osteoclasts differentiation of macrophages. On the other hand, macrophages activate MSCs and mediate the multilineage differentiation of MSCs by regulating the immune microenvironment. The cross-talk between MSCs and macrophages plays a crucial role in regulating the immune system and in promoting tissue regeneration. Making full use of the relationship between MSCs and macrophages will enhance the efficacy of MSCs therapy in bone tissue repair, and will also provide a reference for further application of MSCs in other diseases.

Life regression based patch slimming for vision transformers.

Vision transformers have achieved remarkable success in computer vision tasks by using multi-head self-attention modules to capture long-range dependencies within images. However, the high inference computation cost poses a new challenge. Several methods have been proposed to address this problem, mainly by slimming patches. In the inference stage, these methods classify patches into two classes, one to keep and the other to discard in multiple layers. This approach results in additional computation at every layer where patches are discarded, which hinders inference acceleration. In this study, we tackle the patch slimming problem from a different perspective by proposing a life regression module that determines the lifespan of each image patch in one go. During inference, the patch is discarded once the current layer index exceeds its life. Our proposed method avoids additional computation and parameters in multiple layers to enhance inference speed while maintaining competitive performance. Additionally, our approach1 requires fewer training epochs than other patch slimming methods.

High TPX2 expression results in poor prognosis, and Sp1 mediates the coupling of the CX3CR1/CXCL10 chemokine pathway to the PI3K/Akt pathway through targeted inhibition of TPX2 in endometrial cancer.

INTRODUCTION: Approximately 30% of individuals with advanced EC have unsatisfactory prognosis. Evidence suggests that TPX2 is frequently upregulated in malignancies and related to cancer progression. Its role and pathological mechanism in EC need further research. METHODS: GSEA and TPX2 expression, GO, KEGG, and prognostic analyses were performed with TCGA data by bioinformatic approaches. Relationships between TPX2 expression and clinicopathological parameters were investigated immunohistochemically and statistically. shRNA and overexpression plasmids were constructed and transfected into AN3CA and Ishikawa cells to evaluate phenotypic changes and injected into nude mouse axillae. Coimmunoprecipitation and chromatin immunoprecipitation were used to identify interacting proteins and promoter-binding sequences. Changes in TPX2 expression were identified by Western blotting and RT-qPCR. RESULTS: TPX2 expression was significantly higher in EC tissues than in normal tissues in TCGA and in-house specimens (all p < 0.001). In survival analysis, high TPX2 expression was associated with poor prognosis (p = 0.003). TPX2 overexpression stimulated cancer cell proliferation, promoted the G0-G1-to-G2/M transition, enhanced invasion and migration, and accelerated tumor growth in nude mice. TPX2 regulated the CX3CR1/CXCL10 chemokine pathway and activated the PI3K/Akt signaling pathway. Sp1 negatively regulated TPX2 expression, affecting the malignant progression of endometrial cancer cells by coupling the CX3CR1/CXCL10 chemokine pathway to the PI3K/Akt signaling pathway. CONCLUSION: TPX2 could be a prognostic biomarker for EC and play an important role in the CX3CR1/CXCL10 chemokine pathway and PI3K/Akt pathway via Sp1.

An Injectable Composite Hydrogel of Verteporfin-Bonded Carboxymethyl Chitosan and Oxidized Sodium Alginate Facilitates Scarless Full-Thickness Skin Regeneration.

Full-thickness skin defect has always been a major challenge in clinics due to fibrous hyperplasia in the repair process. Hydrogel composite dressings loaded with anti-fibrotic drugs have been considered as a promising strategy for scarless skin regeneration. In this work, a hydrogel composite (VP-CMCS-OSA) of carboxymethyl chitosan (CMCS) and oxidized sodium alginate (OSA), with loading anti-fibrotic drug verteporfin (VP), is developed based on two-step chemical reactions. Verteporfin is bonded with carboxymethyl chitosan through EDC/NHS treatment to form VP-CMCS, and then VP-CMCS is crosslinked with oxidized sodium alginate by Schiff base reaction to form VP-CMCS-OSA hydrogel. The characterization by SEM, FTIR, and UV-Vis shows the microstructure and chemical bonding of VP-CMCS-OSA. VP-CMCS-OSA hydrogel demonstrates the properties of high tissue adhesion, strong self-healing, and tensile ability. In the full-thickness skin defect model, the VP-CMCS-OSA composite hydrogels hasten wound healing due to the synergistic effects of hydrogels and verteporfin administration. The histological examination reveals the regular collagen arrangement and more skin appendages after VP-CMCS-OSA composite hydrogel treatment, indicating the full-thickness skin regeneration without potential scar formation. The outcomes suggest that the verteporfin-loaded composite hydrogel could be a potential method for scarless skin regeneration.

A Nanozyme-Based Electrode for High-Performance Neural Recording.

Implanted neural electrodes have been widely used to treat brain diseases that require high sensitivity and biocompatibility at the tissue-electrode interface. However, currently used clinical electrodes cannot meet both these requirements simultaneously, which hinders the effective recording of electronic signals. Herein, nanozyme-based neural electrodes incorporating bioinspired atomically precise clusters are developed as a general strategy with a heterogeneous design for multiscale and ultrasensitive neural recording via quantum transport and biocatalytic processes. Owing to the dual high-speed electronic and ionic currents at the electrode-tissue interface, the impedance of nanozyme electrodes is 26 times lower than that of state-of-the-art metal electrodes, and the acquisition sensitivity for the local field potential is ≈10 times higher than that of clinical PtIr electrodes, enabling a signal-to-noise ratio (SNR) of up to 14.7 dB for single-neuron recordings in rats. The electrodes provide more than 100-fold higher antioxidant and multi-enzyme-like activities, which effectively decrease 67% of the neuronal injury area by inhibiting glial proliferation and allowing sensitive and stable neural recording. Moreover, nanozyme electrodes can considerably improve the SNR of seizures in acute epileptic rats and are expected to achieve precise localization of seizure foci in clinical settings.

[Pollution Level and Risk Assessment of OPEs in Typical River Basins of China].

Organophosphate esters(OPEs), as a substitute for brominated flame retardants, are widely used in production and life, and their environmental pollution and toxic effects have attracted widespread attention. In this study, the concentrations and distribution characteristics of OPEs in seven major drainage basins of China were sorted out. The average daily dose of OPEs in Chinese adults, adolescents, and children was calculated to assess the health risks, and the reliability of the results was evaluated using Monte Carlo simulation. The toxic effect concentrations of 12 OPEs on aquatic organisms were investigated, and the species sensitivity distribution(SSD) curve was constructed to assess the ecological risk. The results showed that the 5th percentile concentration of ΣOPEs in the seven drainage basins was 52.61 ng·L-1 under the low exposure scenario. The median concentration of ΣOPEs in the seven basins was 499.74 ng·L-1, with trichloroethyl phosphate(TCEP), triethyl phosphate(TEP), and triethyl phosphate(1,3-dichloro-2-propyl) esters(TDCP) as the main contaminants. Under the high exposure scenario, the 95th percentile concentration of ΣOPEs in the seven basins was 1904.4 ng·L-1, 3.8 times that of the intermediate exposure scenario, and the Yangtze River Basin had the highest ΣOPEs concentration under the high exposure scenario. The health risk assessment showed that the non-carcinogenic risk of OPEs exposure through drinking water was within acceptable limits for different populations. Trimethyl phosphate(TMP), triisobutyl phosphate(TiBP), and TCEP were the main contributors to cancer risk. The results of ecological risk assessment showed that TCEP had medium ecological risk at the high exposure level, tributyl phosphate(TnBP) had medium ecological risk under the intermediate exposure scenario, and there was higher ecological risk under the high exposure scenario. Triphenyl phosphate(TPhP) had a risk quotient greater than 1 under the low, intermediate, and high exposure scenarios, and there was a high ecological risk, which requires special attention.

Modifying the amino acids in conformational motion pathway of the α-amylase of Geobacillus stearothermophilus improved its activity and stability.

Amino acids along the conformational motion pathway of the enzyme molecule correlated to its flexibility and rigidity. To enhance the enzyme activity and thermal stability, the motion pathway of Geobacillus stearothermophilus α-amylase has been identified and molecularly modified by using the neural relational inference model and deep learning tool. The significant differences in substrate specificity, enzymatic kinetics, optimal temperature, and thermal stability were observed among the mutants with modified amino acids along the pathway. Mutants especially the P44E demonstrated enhanced hydrolytic activity and catalytic efficiency (kcat/KM) than the wild-type enzyme to 95.0% and 93.8% respectively, with the optimum temperature increased to 90°C. This mutation from proline to glutamic acid has increased the number and the radius of the bottleneck of the channels, which might facilitate transporting large starch substrates into the enzyme. The mutation could also optimize the hydrogen bonding network of the catalytic center, and diminish the spatial hindering to the substrate entry and exit from the catalytic center.

Interval-locked dual-frequency φ-OFDR with an enhanced strain dynamic range and a long-term stability.

We report on an interval-locked dual-frequency phase-sensitive optical frequency-domain reflectometry relying on a common-reference optical phase-locked loop. With a shared unbalanced interferometry, this design allows for synchronizing the frequency drift of two lasers, leading to a steadily stabilized dual frequency with an arbitrary interval. Equivalently to a longer synthetic wavelength, their phase difference is utilized to demodulate the ambient changes of interest with an enhanced dynamic range and long-term stability. With a stabilized interval of 1 THz, it allows for an enhancement in a strain measurement range of up to 193-fold in theory. Demonstration in terms of distributed strain sensing covering a distance of 500 m with a 10 cm spatial resolution has been verified, showing a significant extension in the achievable strain dynamic range with a preserved sensitivity over 1 h.

Selective Organ-Targeting Hafnium Oxide Nanoparticles with Multienzyme-Mimetic Activities Attenuate Radiation-Induced Tissue Damage.

Radioprotective agents hold clinical promises to counteract off-target adverse effects of radiation and benefit radiotherapeutic outcomes, yet the inability to control drug transport in human organs poses a leading limitation. Based upon a validated rank-based multigene signature model, radiosensitivity indices are evaluated of diverse normal organs as a genomic predictor of radiation susceptibility. Selective ORgan-Targeting (SORT) hafnium oxide nanoparticles (HfO2 NPs) are rationally designed via modulated synthesis by α-lactalbumin, homing to top vulnerable organs. HfO2 NPs like Hensify are commonly radioenhancers, but SORT HfO2 NPs exhibit surprising radioprotective effects dictated by unfolded ligands and Hf(0)/Hf(IV) redox couples. Still, the X-ray attenuation patterns allow radiological confirmation in target organs by dual-beam spectral computed tomography. SORT HfO2 NPs present potent antioxidant activities, catalytically scavenge reactive oxygen species, and mimic multienzyme catalytic activities. Consequently, SORT NPs rescue radiation-induced DNA damage in mouse and rabbit models and provide survival benefits upon lethal exposures. In addition to inhibiting radiation-induced mitochondrial apoptosis, SORT NPs impede DNA damage and inflammation by attenuating activated FoxO, Hippo, TNF, and MAPK interactive cascades. A universal methodology is proposed to reverse radioenhancers into radioprotectors. SORT radioprotective agents with image guidance are envisioned as compelling in personalized shielding from radiation deposition.

The interplay of self-acceptance, social comparison and attributional style in adolescent mental health: cross-sectional study.

BACKGROUND: Adolescence is a pivotal stage vulnerable to mental health problems such as anxiety and depression. Although self-acceptance and social comparison are known to affect adolescent mental health, their interactive and moderating roles are not fully understood. AIMS: To explore the role of self-acceptance, social comparison and attributional style in predicting these mental health outcomes among adolescents in clinical settings. METHOD: A cross-sectional study was conducted on a sample of 242 adolescents. Participants completed measures assessing self-acceptance, social comparison, attributional style and mental health outcomes (depression and anxiety). Mediation models and multi-group analysis were used to examine the relationships among these variables. RESULTS: Our findings demonstrated a significant relationship between self-acceptance, social comparison, depression and anxiety (rs = 0.32-0.88). Specifically, lower self-acceptance and higher social comparison were associated with higher levels of depression and anxiety. Additionally, individuals with external attributional tendencies reported higher depression (Cohen's d = 0.61) and anxiety (d = 0.58) compared with those with internal tendencies. Mediation modelling showed that social comparison is a mediator between self-acceptance and depression (effect size -0.04, 95% CI -0.08 to -0.01) and anxiety (effect size -0.06, 95% CI -0.10 to -0.02). Crucially, multi-group analysis showed that the impact of social comparison on mental health outcomes varied significantly based on attributional style. CONCLUSIONS: These findings underscore the importance of considering self-acceptance, social comparison and attributional style in understanding and addressing mental health challenges during adolescence. This could inform the development of targeted interventions to promote mental health and well-being among adolescents. However, further research is needed to confirm these findings in diverse populations and to explore the underlying mechanisms in greater detail.

Network analysis of emotion regulation and reactivity in adolescents: identifying central components and implications for anxiety and depression interventions.

Difficulties in emotion regulation (DER) and emotion reactivity (ER) are important causes and consequences of psychiatric disorders such as depression and anxiety, and previous research suggests that there are many interactions between them. Understanding the structure of their relationship, and which components may play a key role, will help provide insight into emotion disorders in adolescents and provide guidance for clinical interventions. In this study, we collected data from 483 adolescents and used network analysis methods to explore the relationship between DER and ER, specifically looking for core nodes. The results showed that "limited access to emotion regulation strategies" was the most central node in the network. Furthermore, by adding nodes for depression and anxiety to this network, we found that anxiety had the strongest relationship with ER, while depression had a stronger relationship with DER. Thus, our findings suggest that for anxiety disorders, the strong association with ER highlights a potentially promising area for intervention development, whereas for depression, the association with DER points to the possibility of clarifying emotions and exploring coping strategies, acknowledging the complex interplay between depressive and anxious symptoms.

Exploring the Effectiveness of Natural Food Flavors in Protecting Carbon Steel against CO2-Induced Corrosion.

Two food flavors, furfuryl mercaptan (2-FFT) and difurfuryl disulfide (DFDS), were investigated as green corrosion inhibitors for the N80 steel in a CO2-saturated solution containing 3.5% NaCl. Experimental methods, quantum chemical calculations, and molecular dynamics simulation were employed to evaluate the effectiveness of 2-FFT and DFDS. The results of the study indicate that both 2-FFT and DFDS act as mixed corrosion inhibitors, with a dominant inhibition effect on the cathodic reaction. 2-FFT is physiochemically adsorbed on the steel surface in a tiled form through the furan ring and the - SH groups as adsorption sites. On the other hand, DFDS is chemisorbed on the steel surface through the - S-S- groups in a parallel manner. DFDS exhibits a higher tendency for electron transfer and stronger adsorption to steel compared to 2-FFT. Overall, this study highlights the potential of natural food flavors as effective and environmentally friendly corrosion inhibitors for carbon steel in CO2-saturated environments. The findings of this research can contribute to the development of sustainable and nontoxic corrosion inhibitors for the oil and gas industry.

Clinicopathological characteristics and its association with digestive system tumors of 1111 patients with Schistosomiasis japonica.

Schistosomiasis japonicum can cause different degrees of organ damage and complex human immune pathological reactions, which often invade the intestine and liver. The purpose of this study was to explore the pathological types and pathological changes of Schistosomiasis and their correlation with some digestive system tumors. Hematoxylin eosin staining was performed on the diseased tissues of 1111 Schistosomiasis cases. We counted the deposition sites of Schistosoma eggs, analyzed the pathological characteristics, and compared the clinicopathological characteristics of Schistosomiasis associated digestive system tumors and non-Schistosomiasis digestive system tumors. We found that Schistosoma japonicum can cause multi organ and multi system damage, with 469 cases of inflammation, 47 cases of adenoma, and 519 cases of adenocarcinoma. Other types include cysts, stromal tumors, malignant lymphomas, and neuroendocrine tumors. Schistosomiasis associated tumors, including gastric cancer, liver cancer, colon cancer and rectal cancer, were compared with non-Schistosomiasis tumors. There were significant differences in age, gender and tumor differentiation between the two groups. Our study shows Schistosomiasis is a systemic disease, causing multiple organ and system damage in the human body. Its clinicopathological types are diverse, and there may be a pathological change process of "Inflammation-adenoma-carcinoma". Schistosomiasis associated digestive system tumors differ from non-Schistosomiasis tumors in some clinicopathological features.

Guideline on treating community-acquired pneumonia with Chinese patent medicines.

Community-acquired pneumonia (CAP) is one of the most common infectious diseases, and its morbidity and mortality increase with age. Resistance and mutations development make the use of anti-infective therapy challenging. Chinese patent medicines (CPMs) are often used to treat CAP in China and well tolerable. However, currently there are no evidence-based guideline for the treatment of CAP with CPMs, and the misuse of CPMs is common. Therefore, we established a guideline panel to develop this guideline. We identified six clinical questions through two rounds of survey, and we then systematically searched relevant evidence and performed meta-analyses, evidence summaries and GRADE decision tables to draft recommendations, which were then voted on by a consensus panel using the Delphi method. Finally, we developed ten recommendations based on evidence synthesis and expert consensus. For the treatment of severe CAP in adults, we recommend Tanreqing injection, Reduning injection, Xuebijing injection, Shenfu injection, and Shenmai injection respectively. For the treatment of non-severe CAP in adults, we recommend Tanreqing injection, Reduning injection, Lianhua Qingwen capsule/granule, Qingfei Xiaoyan Pill and Shufeng Jiedu capsule respectively. CPMs have great potential to help in the fight against CAP worldwide, but more high-quality studies are still needed to strengthen the evidence.

A near-infrared fluorescence-enhancing plasmonic biosensing microarray identifies soluble PD-L1 and ICAM-1 as predictive checkpoint biomarkers for cancer immunotherapy.

Sensitive and accurate biomarker-driven assay guidance has been widely adopted to identify responsive patients for immune checkpoint blockade (ICB) therapy to impede disease progression and extend survival. However, most current assays are invasive, requiring surgical pathology specimens and only informing monochronic information. Here, we report a multiplexed enhanced fluorescence microarray immunoassay (eFMIA) based on a nanostructured gold nanoisland substrate (AuNIS), which macroscopically amplifies near-infrared fluorescence (NIRF) of a structurally symmetric IRDye78 fluorophore by over two orders of magnitude of 202.6-fold. Aided by non-contact piezo-driven micro-dispensing (PDMD), eFMIA simultaneously and semi-quantitatively detected intracellular and secreted programmed death-ligand 1 (PD-L1) and intercellular adhesion molecule-1 (ICAM-1) in human nasopharyngeal carcinoma (NPC) cells. The assay performance was superior to fluorescence immunoassays (FIA) and enzyme-linked immunosorbent assays (ELISA), with lower detection limits. Using eFMIA, we found significantly differential levels of soluble PD-L1 (sPD-L1) and sICAM-1 in the sera of 28 cancer patients, with different clinical outcomes following anti-PD-1 ICB therapy. With a well-characterized mechanism, the high-performance plasmonic multiplexed assay with the composite biomarkers may be a valuable tool to assist clinicians with decision-making and patient stratification to afford predictive ICB therapy responses.

Perioperative intravenous lidocaine for postoperative pain in patients undergoing breast surgery: a meta-analysis with trial sequential analysis of randomized controlled trials.

Background: The effectiveness of intravenous lidocaine infusion in managing acute and chronic pain following breast surgery has been a topic of debate. This meta-analysis aims to assess the impact of perioperative intravenous lidocaine on the relief of postoperative pain among patients undergoing breast surgery. Methods: A systematic search of databases was conducted to identify randomized controlled trials (RCTs) that compared the effects of intravenous lidocaine infusion with placebo or routine care in patients undergoing breast surgery. The primary outcome of interest was the occurrence of chronic post-surgical pain (CPSP) at the longest follow-up. Meta-analyses, incorporating trial sequential analysis, were performed using a random-effects model to assess the overall effect. Results: A total of twelve trials, involving 879 patients, were included in the analysis. Perioperative intravenous lidocaine demonstrated a significant reduction in the incidence of CPSP at the longest follow-up (risk ratio [RR] 0.62, 95% confidence interval [CI] 0.48-0.81; P = 0.0005; I2 = 6%). Trial sequential analysis (TSA) indicated that the cumulative z curve crossed the trial sequential monitoring boundary for benefit, providing sufficient and conclusive evidence. Furthermore, intravenous lidocaine was associated with decreased opioid consumption and a shorter length of hospital stay. Conclusion: Perioperative intravenous lidocaine is effective in relieving acute and CPSP in patients undergoing breast surgery. Systematic review registration: https://inplasy.com/, identifier INPLASY2022100033.

The Motion Paradigm of Pre-Dock Zearalenone Hydrolase Predictions with Molecular Dynamics and the Docking Phase with Umbrella Sampling.

Zearalenone (ZEN) is one of the most prevalent estrogenic mycotoxins, is produced mainly by the Fusarium family of fungi, and poses a risk to the health of animals. Zearalenone hydrolase (ZHD) is an important enzyme capable of degrading ZEN into a non-toxic compound. Although previous research has investigated the catalytic mechanism of ZHD, information on its dynamic interaction with ZEN remains unknown. This study aimed to develop a pipeline for identifying the allosteric pathway of ZHD. Using an identity analysis, we identified hub genes whose sequences can generalize a set of sequences in a protein family. We then utilized a neural relational inference (NRI) model to identify the allosteric pathway of the protein throughout the entire molecular dynamics simulation. The production run lasted 1 microsecond, and we analyzed residues 139-222 for the allosteric pathway using the NRI model. We found that the cap domain of the protein opened up during catalysis, resembling a hemostatic tape. We used umbrella sampling to simulate the dynamic docking phase of the ligand-protein complex and found that the protein took on a square sandwich shape. Our energy analysis, using both molecular mechanics/Poisson-Boltzmann (Generalized-Born) surface area (MMPBSA) and Potential Mean Force (PMF) analysis, showed discrepancies, with scores of -8.45 kcal/mol and -1.95 kcal/mol, respectively. MMPBSA, however, obtained a similar score to that of a previous report.

Nanochannel Electro-Injection as a Versatile Platform for Efficient RNA/DNA Programming on Dendritic Cells.

The utilization of dendritic cell (DC) vaccines is a promising approach in cancer immunotherapy, and the modification of DCs for the expression of tumor-associated antigens is critical for successful cancer immunotherapy. A safe and efficient method for delivering DNA/RNA into DCs without inducing maturation is beneficial to achieve successful DC transformation for cell vaccine applications, yet remains challenging. This work presents a nanochannel electro-injection (NEI) system for the safe and efficient delivery of a variety of nucleic acid molecules into DCs. The device is based on track-etched nanochannel membrane as key components, where the nano-sized channels localize the electric field on the cell membrane, enabling lower voltage (<30 V) for cell electroporation. The pulse conditions of NEI are examined so that the transfection efficiency (>70%) and biosafety (viability >85%) on delivering fluorescent dyes, plasmid DNA, messenger RNA, and circular RNA (circRNA) into DC2.4 are optimized. Primary mouse bone marrow DC can also be transfected with circRNA with 68.3% efficiency, but without remarkably affecting cellular viability or inducing DC maturation. These results suggest that NEI can be a safe and efficient transfection platform for in vitro transformation of DCs and possesses a promising potential for developing DC vaccines against cancer.

Intelligent Pd1.7Bi@CeO2 Nanosystem with Dual-Enzyme-Mimetic Activities for Cancer Hypoxia Relief and Synergistic Photothermal/Photodynamic/Chemodynamic Therapy.

Reactive oxygen species-mediated therapeutic strategies, including chemodynamic therapy (CDT) and photodynamic therapy (PDT), have exhibited translational promise for effective cancer management. However, monotherapy often ends up with the incomplete elimination of the entire tumor due to inherent limitations. Herein, we report a core-shell-structured Pd1.7Bi@CeO2-ICG (PBCI) nanoplatform constructed by a facile and effective strategy for synergistic CDT, PDT, and photothermal therapy. In the system, both Pd1.7Bi and CeO2 constituents exhibit peroxidase- and catalase-like characteristics, which not only generate cytotoxic hydroxyl radicals (•OH) for CDT but also produce O2 in situ and relieve tumor hypoxia for enhanced PDT. Furthermore, upon 808 nm laser irradiation, Pd1.7Bi@CeO2 and indocyanine green (ICG) coordinately prompt favorable photothermia, resulting in thermodynamically amplified catalytic activities. Meanwhile, PBCI is a contrast agent for near-infrared fluorescence imaging to determine the optimal laser therapeutic window in vivo. Consequently, effective tumor elimination was realized through the above-combined functions. The as-synthesized unitary PBCI theranostic nanoplatform represents a potential one-size-fits-all approach in multimodal synergistic therapy of hypoxic tumors.