Nanoplastics Shape Adaptive Anticancer Immunity in the Colon in Mice.

The impact of nanoplastics (NPs) on human health is still not well understood, and more research is needed to better understand the risks associated with these particles. In this study, we found that oral administration of polyethylene (PE) NPs in a mice model significantly disrupted the intestinal microenvironment, which shapes adaptive immune response and favors the established in situ colorectal tumor growth. Using single-cell RNA sequencing technology, we show that NPs triggered colon IL-1ß-producing macrophages by inducing lysosome damage, leading to colonic Treg and Th17 differentiation associated with T cell exhaustion, which creates a colon environment that favors the tumor initiation and progress. A similar effect is also observed in polystyrene NPs. Our result provides insight into the potential link between NPs ingestion and colon tumorigenesis, and the urgency of addressing plastic pollution worldwide.

Survival rate prediction of nasopharyngeal carcinoma patients based on MRI and gene expression using a deep neural network.

To achieve a better treatment regimen and follow-up assessment design for intensity-modulated radiotherapy (IMRT)-treated nasopharyngeal carcinoma (NPC) patients, an accurate progression-free survival (PFS) time prediction algorithm is needed. We propose developing a PFS prediction model of NPC patients after IMRT treatment using a deep learning method and comparing that with the traditional texture analysis method. One hundred and fifty-one NPC patients were included in this retrospective study. T1-weighted, proton density and dynamic contrast-enhanced magnetic resonance (MR) images were acquired. The expression level of five genes (HIF-1α, EGFR, PTEN, Ki-67, and VEGF) and infection of Epstein-Barr (EB) virus were tested. A residual network was trained to predict PFS from MR images. The output as well as patient characteristics were combined using a linear regression model to provide a final PFS prediction. The prediction accuracy was compared with that of the traditional texture analysis method. A regression model combining the deep learning output with HIF-1α expression and Epstein-Barr infection provides the best PFS prediction accuracy (Spearman correlation R2  = 0.53; Harrell's C-index = 0.82; receiver operative curve [ROC] analysis area under the curve [AUC] = 0.88; log-rank test hazard ratio [HR] = 8.45), higher than a regression model combining texture analysis with HIF-1α expression (Spearman correlation R2  = 0.14; Harrell's C-index =0.68; ROC analysis AUC = 0.76; log-rank test HR = 2.85). The deep learning method does not require a manually drawn tumor region of interest. MR image processing using deep learning combined with patient characteristics can provide accurate PFS prediction for nasopharyngeal carcinoma patients and does not rely on specific kernels or tumor regions of interest, which is needed for the texture analysis method.

Efficacy of Near-Infrared Fluorescence Video-Assisted Thoracoscopic Surgery for Small Pulmonary Nodule Resection with Indocyanine Green Inhalation: A Randomized Clinical Trial.

BACKGROUND: Small pulmonary nodules (<3 cm) can sometimes be unrecognizable and nonpalpable in video-assisted thoracoscopic surgery (VATS). Near-infrared fluorescence (NIF) VATS after indocyanine green (ICG) inhalation may effectively guide surgeons to locate the nodules. OBJECTIVE: This study aimed to investigate the safety, feasibility, and efficacy of ICG inhalation-based NIF imaging for guiding small pulmonary nodule resections. METHODS: Between February and May 2021, the first-stage, non-randomized trial enrolled 21 patients with different nodule depth, ICG inhalation doses, post-inhalation surgery times, and nodule types at a tertiary referral hospital. Between May 2021 and May 2022, the second-stage randomized trial enrolled 56 patients, who were randomly assigned to the fluorescence VATS (FLVATS) or the white-light VATS (WLVATS) group. The ratio of effective guidance and the time consumption for nodule localization were compared. RESULTS: The first-stage trial proved this new method is safe and feasible, and established a standardized protocol with optimized nodule depth (≤1 cm), ICG dose (0.20-0.25 mg/kg), and surgery window (50-90 min after ICG inhalation). In the second-stage trial, the FLVATS achieved 87.1% helpful nodule localization guidance, which was significantly higher than the WLVATS (59.1%, p < 0.05). The mean nodule locating time (standard deviation) was 1.8 [0.9] and 3.3 [2.3] min, respectively. Surgeons adopting FLVATS were significantly faster (p < 0.01), especially when locating small ground-glass opacities (1.3 [0.6] min vs. 7.0 [3.5] min, p < 0.05). Five of 31 nodules (16.1%) were only detectable by FLVATS, whereas both white light and palpation failed. CONCLUSIONS: This new method is safe and feasible for small pulmonary nodule resection. It significantly improves nodule localization rates with less time consumption, and hence is highly worthy for clinical promotion. Clinical Trial Registration Chinese Clinical Trial Registry Identifier: ChiCTR2100047326.

Multifunctional Nanotheranostics for Dual-Modal Imaging-Guided Precision Therapy of Nasopharyngeal Carcinoma.

Currently, the low survival rate and poor prognosis of patients with nasopharyngeal carcinoma are ascribed to the lack of early and accurate diagnosis and resistance to radiotherapy. In parallel, the integration of imaging-guided diagnosis and precise treatment has gained much attention in the field of theranostic nanotechnology. However, constructing dual-modal imaging-guided nanotheranostics with desired imaging performance as well as great biocompatibility remains challenging. Therefore, we developed a simple but multifunctional nanotheranostic GdCPP for the early and accurate diagnosis and efficient treatment of nasopharyngeal carcinoma (NPC), which combined fluorescence imaging and magnetic resonance imaging (MRI) onto a single nanoplatform for imaging-guided subsequent photodynamic therapy (PDT). GdCPP had an appropriate particle size (81.93 ± 0.69 nm) and was highly stable, resulting in sufficient tumor accumulation, which along with massive reactive oxygen species (ROS) generation upon irradiation further significantly killed tumor cells. Moreover, GdCPP owned much stronger r1 relaxivity (9.396 mM-1 s-1) compared to clinically used Gd-DTPA (5.034 mM-1 s-1) and exhibited better T1WI MRI performance. Under dual-modal imaging-guided PDT, GdCPP achieved efficient therapeutic outcomes without causing any noticeable tissue damage. The results of in vitro and in vivo studies indicated that GdCPP may be a suitable candidate for dual-modal imaging-guided precision tumor therapy.

Modelling an evaluation of the efficacy and safety of gemcitabine combined with platinum in the treatment of non-small cell lung cancer.

WHAT IS KNOWN AND OBJECTIVES: Gemcitabine combined with platinum is currently the recommended first-line chemotherapy for advanced non-small cell lung cancer (NSCLC). This study aimed to quantitatively compare the efficacy and safety of gemcitabine-platinum combinations in the treatment of advanced NSCLC under different dosing regimens based on extensive literature data. METHODS: The PubMed and Cochrane Library databases were systematically searched for clinical trials in patients with NSCLC treated with a gemcitabine-platinum regimen. A parametric survival function was used to analyse the time course of overall survival (OS). The objective response rate (ORR) and the incidence of grade 3/4 adverse events were summarized using the random-effects model of a single-arm meta-analysis. RESULTS: The study included 63 arms from 47 publications, with a total sample size of 4344 patients for analysis. The model revealed that East Asians has a better survival benefit than non-East Asians, with a median OS of 16.4 (95% CI: 14.3-19.0) and 9.9 (95% CI: 8.1-12.4) months, respectively. Moreover, the OS of patients that underwent a 6-cycle treatment was significantly longer than those that had a 4-cycle treatment in non-East Asians, with a median OS of 10.2 (95% CI: 9.5-11.1) and 8.4 (95% CI: 7.7-9.3) months, respectively. However, the incidence of neutropenia, nausea and vomiting also increased after 6 cycles of treatment. When the dose of gemcitabine increased from 1000 mg/m2 to 1250 mg/m2 , the median OS was extended by approximately 1 month, but the incidence of grade 3/4 adverse reactions did not increase. WHAT IS NEW AND CONCLUSION: Race is an important factor affecting OS in the treatment of advanced NSCLC, which should be considered when conducting international multicentre clinical trials. Additionally, this study found that the OS increased with an increase in gemcitabine exposure, so it is necessary to construct an exposure-response model to obtain the best benefit-risk ratio for patients.

Evaluating smoking control policies in the e-cigarette era: a modelling study.

BACKGROUND: In jurisdictions in which electronic cigarettes are currently prohibited, policy makers must weigh the potentially lower risk compared with conventional cigarettes against the risk of initiation of e-cigarettes among non-smokers. METHODS: We simulated a synthetic population over a 50-year time horizon with an open cohort model using data from Singapore, a country where e-cigarettes are currently prohibited, and data from the USA, the UK and Japan. Using the smoking prevalence and the quality-adjusted life year gained calculated, we compared tobacco control policies without e-cigarettes-namely, raising the minimum legal age (MLA), introducing a smoke-free generation (SFG) and tax rises on tobacco consumption-with policies legalising e-cigarettes, either taking a laissez-faire approach or under some form of restriction. We also evaluated combinations of these policies. RESULTS: Regardless of the country informing the transition probabilities to and from e-cigarette use in Singapore, a laissez-faire e-cigarette policy could reduce the smoking prevalence in the short term, but it is not as effective as other policies in the long term. The most effective single policies evaluated were SFG and aggressive tax rises; the most effective combination of policies considered was MLA plus moderate tax rises and e-cigarettes on prescription. CONCLUSION: Policy makers in jurisdictions in which e-cigarettes are not yet established may be advised not to prioritise e-cigarettes in their tobacco end-game strategy, unless their use can be restricted to current smokers seeking to quit.

Hepatocellular carcinoma with inferior vena cava and right atrial tumor thrombus: A case report.

This is a case report of a 45-year-old patient admitted with the symptom of bilateral leg swelling. Ultrasonography revealed a hyperechoic mass in the right lobe of the liver, which invaded the right hepatic vein (RHV) and extended into the inferior vena cava (IVC) and right atrium (RA). Based on the high alpha-fetoprotein (AFP) level and the ultrasonography findings, the patient was diagnosed as having hepatocellular carcinoma (HCC) with a RHV, IVC, and RA tumor thrombus and secondary Budd-Chiari syndrome (BCS). HCC with a tumor thrombus extending into the IVC and RA has rarely been observed, and as a cause of secondary BCS, this type of HCC has been even more rarely reported.

Probiotic strategies to prevent necrotizing enterocolitis in preterm infants: a meta-analysis.

PURPOSE: We aimed to compare probiotics with placebo for necrotizing enterocolitis in preterm infants and to evaluate the safety and effect and strict effect of specific probiotic genera. METHODS: Data recorded until January 2019 were searched, and relevant academic articles from PubMed, MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials were selected by two independent reviewers. Two reviewers independently included randomized controlled trials that compared probiotics and placebo in preterm infants. The outcomes included more than one of the following outcomes: incidence of necrotizing enterocolitis, necrotizing enterocolitis-related mortality, incidence of sepsis, and all-cause mortality. Two reviewers independently extracted data and assessed the risk of bias and quality of evidence. RESULTS: We identified 34 eligible studies of 9161 participants. This meta-analysis showed an overall advantage of probiotics to prevent the incidence of necrotizing enterocolitis (3.54%) and gut-associated sepsis (15.59%), and decrease mortality (5.23%) in preterm infants. A probiotic mixture showed a huge advantage and vitality in preventing necrotizing enterocolitis (2.48%) and gut-associated sepsis (18.39%), and in reducing mortality (5.57%) in preterm infants. CONCLUSION: The probiotic mixture showed advantages over the single strains to decrease the incidences of necrotizing enterocolitis and gut-associated sepsis, and mortality in preterm infants.

A review of cardiovascular toxicity of TiO2, ZnO and Ag nanoparticles (NPs).

To ensure the safe use of nanoparticles (NPs) in modern society, it is necessary and urgent to assess the potential toxicity of NPs. Cardiovascular system is required for the systemic distribution of NPs entering circulation. Therefore, the adverse cardiovascular effects of NPs have gained extensive research interests. Metal based NPs, such as TiO2, ZnO and Ag NPs, are among the most popular NPs found in commercially available products. They may also have potential applications in biomedicine, which could increase their contact with cardiovascular systems. This review aimed at providing an overview about the adverse cardiovascular effects of TiO2, ZnO and Ag NPs. We discussed about the bio-distribution of NPs following different exposure routes. We also discussed about the cardiovascular toxicity of TiO2, ZnO and Ag NPs as assessed by in vivo and in vitro models. The possible mechanisms and contribution of physicochemical properties of metal based NPs were also discussed.

Comprehensive Review of the Determination and Reduction of the Minimum Miscibility Pressure during CO2 Flooding.

With the increasing oil demand, more attention has been paid to enhancing oil recovery in old oil fields. CO2 flooding is popular due to its high oil displacement efficiency and ability to reduce greenhouse gas emissions. Laboratory experiments and on-site application cases have shown that the minimum miscibility pressure has a greater impact on CO2 flooding than other factors. If the reservoir pressure is below the minimum miscible pressure, then there is CO2 immiscible flooding. Both theoretical analysis and experimental results show that the recovery rate of CO2 miscible flooding is 2-5 times higher than that of immiscible flooding. If the reservoir pressure is increased by water flooding before CO2 injection, it is easily limited by the physical property parameters. Therefore, accurately determining and effectively reducing the minimum mixing pressure has become the focus of research. Currently, there are two types of methods for determining the minimum miscible pressure: experimental and theoretical methods. The experimental method is generally considered more accurate, including the slim tube test, rising bubble apparatus, and vanishing interfacial tension, etc. However, it is worth noting that the minimum miscibility pressure is dynamically changing, and there will be high economic costs if measured repeatedly through experimental methods during reservoir development. Therefore, it is recognized that the minimum mixing pressure can be determined at any time using theoretical calculation of initial data, which will reduce economic and time costs to a high degree. In this paper, the theoretical calculation method is divided into empirical correlation, state equation, and artificial intelligence algorithm. The techniques for reducing the minimum miscibility pressure can be classified into two categories: miscible solvents and surfactant methods. The miscible solvent method can be further divided into monocomponent and polycomponent methods. This paper compares the advantages and disadvantages of the existing techniques for measuring and reducing MMP and selects the best method.

Insights into the role of mesenchymal stem cells in cutaneous medical aesthetics: from basics to clinics.

With the development of the economy and the increasing prevalence of skin problems, cutaneous medical aesthetics are gaining more and more attention. Skin disorders like poor wound healing, aging, and pigmentation have an impact not only on appearance but also on patients with physical and psychological issues, and even impose a significant financial burden on families and society. However, due to the complexities of its occurrence, present treatment options cannot produce optimal outcomes, indicating a dire need for new and effective treatments. Mesenchymal stem cells (MSCs) and their secretomics treatment is a new regenerative medicine therapy that promotes and regulates endogenous stem cell populations and/or replenishes cell pools to achieve tissue homeostasis and regeneration. It has demonstrated remarkable advantages in several skin-related in vivo and in vitro investigations, aiding in the improvement of skin conditions and the promotion of skin aesthetics. As a result, this review gives a complete description of recent scientific breakthroughs in MSCs for skin aesthetics and the limitations of their clinical applications, aiming to provide new ideas for future research and clinical transformation.

Polymorphisms of CYP7A1 and HADHB Genes and Their Effects on Milk Production Traits in Chinese Holstein Cows.

Our preliminary research proposed the cytochrome P450 family 7 subfamily A member 1 (CYP7A1) and hydroxyacyl-coenzyme A dehydrogenase trifunctional multienzyme complex beta subunit (HADHB) genes as candidates for association with milk-production traits in dairy cattle because of their differential expression across different lactation stages in the liver tissues of Chinese Holstein cows and their potential roles in lipid metabolism. Hence, we identified single-nucleotide polymorphisms (SNPs) of the CYP7A1 and HADHB genes and validated their genetic effects on milk-production traits in a Chinese Holstein population with the goal of providing valuable genetic markers for genomic selection (GS) in dairy cattle, This study identified five SNPs, 14:g.24676921A>G, 14:g.24676224G>A, 14:g.24675708G>T, 14:g.24665961C>T, and 14:g.24664026A>G, in the CYP7A1 gene and three SNPs, 11:g.73256269T>C, 11:g.73256227A>C, and 11:g.73242290C>T, in HADHB. The single-SNP association analysis revealed significant associations (p value ≤ 0.0461) between the eight SNPs of CYP7A1 and HADHB genes and 305-day milk, fat and protein yields. Additionally, using Haploview 4.2, we found that the five SNPs of CYP7A1 formed two haplotype blocks and that the two SNPs of HADHB formed one haplotype block; notably, all three haplotype blocks were also significantly associated with milk, fat and protein yields (p value ≤ 0.0315). Further prediction of transcription factor binding sites (TFBSs) based on Jaspar software (version 2023) showed that the 14:g.24676921A>G, 14:g.24675708G>T, 11:g.73256269T>C, and 11:g.73256227A>C SNPs could alter the 5' terminal TFBS of the CYP7A1 and HADHB genes. The 14:g.24665961C>T SNP caused changes in the structural stability of the mRNA for the CYP7A1 gene. These alterations have the potential to influence gene expression and, consequently, the phenotype associated with milk-production traits. In summary, we have confirmed the genetic effects of CYP7A1 and HADHB genes on milk-production traits in dairy cattle and identified potential functional mutations that we suggest could be used for GS of dairy cattle and in-depth mechanistic studies of animals.

Association between lactate dehydrogenase and the risk of diabetic kidney disease in patients with type 2 diabetes.

Objective: This study aims to investigate the association between lactate dehydrogenase (LDH) and the risk of diabetic kidney disease (DKD) in patients with type 2 diabetes (T2D). Methods: The study enrolled patients with diagnosis of T2D between 2009 and 2018 from the National Nutrition and Health Examination Survey (NHANES) database. Demographic information, laboratory test, and diagnostic data were collected. Restricted cubic spline (RCS) plots were used to assess the dose-effect relationship between LDH levels and the risk of DKD in patients with T2D. Based on LDH levels, individuals were divided into higher and lower groups using dichotomy, and multivariate logistic regression analysis was conducted to explore the relationship between different LDH levels and the risk of DKD in T2D patients. Stratified analysis was performed to assess the consistency of the result. Results: A total of 4888 patients were included in the study, with 2976 (60.9%) patients without DKD and 1912 (39.1%) patients with DKD. RCS plots showed that the risk of DKD increased with increasing LDH levels. Multifactorial logistic regression analysis revealed that T2D patients with higher LDH levels had a 45% increased risk of DKD compared to those with lower LDH levels (OR=1.45; 95% CI: 1.11-1.89). Furthermore, each standard deviation increase in LDH level was associated with a 24% increase in DKD incidence among T2D patients (OR=1.24; 95% CI: 1.07-1.44). Stratified analysis consistently supported these findings. Conclusions: LDH can serve as a valuable biomarker for screening DKD in patients with T2D.

Intraoperative Fluorescence Visualization in Thoracoscopic Surgery.

We report a clinical case of using indocyanine green inhalation to achieve intraoperative near-infrared fluorescence visualization of pulmonary ground-glass opacity in thoracoscopic wedge resection. The patient underwent thoracoscopic wedge resection under the real-time navigation of a near-infrared fluorescence imaging system with the indocyanine green inhalation performed 85 minutes before the surgery. The nebulized inhalation of indocyanine green (dose of 0.25 mg/kg) successfully guided surgeons to localize the small ground-glass opacity due to a filling defect of the fluorescence. The thoracoscopic near-infrared fluorescence navigation system delineated the tumor margin with high contrast and helped to minimize the damage to lung function.

Blood Clot Scaffold Loaded with Liposome Vaccine and siRNAs Targeting PD-L1 and TIM-3 for Effective DC Activation and Cancer Immunotherapy.

Tumor vaccines have been showing a relatively weak response rate in cancer patients, while deficiencies in delivery efficiency to dendritic cells (DCs), as well as DC-intrinsic immunosuppressive signals, contribute to a great extent. In this work, we report an implantable blood clot loaded with liposomes-protamine-hyaluronic acid nanoparticles (LPH NPs) containing vaccine (LPH-vaccine) and LPH NPs containing siRNA (LPH-siRNA) for synergistic DC recruitment and activation. The subcutaneously implanted blood clot scaffold can recruit abundant immune cells, particularly DCs, to form a DC-rich environment in vivo. Within the scaffold, LPH-vaccine effectively delivers antigens and adjuvants to the recruited DCs and induces the maturation of DCs. More importantly, LPH-siRNA that targets programmed death-ligand 1 (PD-L1) and T cell immunoglobulin and mucin-containing molecule 3 (TIM-3) can reduce immunosuppressive signals in mature DCs and prevent the DCs from expressing a regulatory program in the scaffold. The activated DCs correlate with an improved magnitude and efficacy of T cell priming, resulting in the production of tumor antigen-specific T cells in multiple mouse models. Our strategy can also be used for patient-tailored therapy by change of tumor neoantigens, suggesting a promising strategy for cancer therapy in the clinic.

Oral feeding of nanoplastics affects brain function of mice by inducing macrophage IL-1 signal in the intestine.

Nanoplastics (NPs) as contaminants in food and water have drawn increasing public attention. However, little is known about how NPs shape the gut immune landscape after injection. In this study, we fabricate NPs (∼500 nm) and microplastics (MPs) (∼2 µm) and evaluate their in vivo effects by feeding them to mice. The results suggest that NPs show a better ability to induce gut macrophage activation than MPs. In addition, NPs trigger gut interleukin-1 (IL-1)-producing macrophage reprogramming via inducing lysosomal damage. More importantly, IL-1 signaling from the intestine can affect brain immunity, leading to microglial activation and Th17 differentiation, all of which correlates with a decline in cognitive and short-term memory in NP-fed mice. Thus, this study provides insight into the mechanism of action of the gut-brain axis, delineates the way NPs reduce brain function, and highlights the importance of fixing the plastic pollution problem worldwide.

Therapeutic mechanism of Liangxue-Guyuan-Yishen decoction on intestinal stem cells and tight junction proteins in gastrointestinal acute radiation syndrome rats.

On the basis of the previous research, the Traditional Chinese Medicine theory was used to improve the drug composition for gastrointestinal acute radiation syndrome (GI-ARS). The purpose of this study was to study the therapeutic mechanism of Liangxue-Guyuan-Yishen decoction (LGYD) on GI-ARS and to provide a new scheme for the treatment of radiation injury. Here, we investigated the effects of LGYD on intestinal stem cells (ISCs) in a GI-ARS rat model. Rat health and survival and the protective efficacy of LGYD on the intestines were analyzed. The active principles in LGYD were detected using liquid chromatography-mass spectrometry (LC-MS). ISC proliferation, intestinal epithelial tight junction (TJ) protein expression and regulatory pathways were explored using immunohistochemistry, western blotting (WB) and reverse transcription quantitative polymerase chain reaction (RT-qPCR), respectively. Involvement of the WNT and MEK/ERK pathways in intestinal recovery was screened using network pharmacology analysis and validated by WB and RT-qPCR. LGYD administration significantly improved health and survival in GI-ARS rats. Pathological analysis showed that LGYD ameliorated radiation-induced intestinal injury and significantly promoted LGR5+ stem cell regeneration in the intestinal crypts, upregulated TJ protein, and accelerated crypt reconstruction in the irradiated rats. LC-MS revealed ≥13 constituents that might contribute to LGYD's protective effects. Collectively, LGYD can promote crypt cell proliferation and ISCs after radiation damage, the above effect may be related to WNT and MEK/ERK pathway.

Genome-Wide Identification and Characterization of the NAC Gene Family and Its Involvement in Cold Response in Dendrobium officinale.

The NAC (NAM, ATAF1/2 and CUC2) gene family is one of the largest plant-specific transcription factor families, functioning as crucial regulators in diverse biological processes such as plant growth and development as well as biotic and abiotic stress responses. Although it has been widely characterized in many plants, the significance of the NAC family in Dendrobium officinale remained elusive up to now. In this study, a genome-wide search method was conducted to identify NAC genes in Dendrobium officinale (DoNACs) and a total of 110 putative DoNACs were obtained. Phylogenetic analysis classified them into 15 subfamilies according to the nomenclature in Arabidopsis and rice. The members in the subfamilies shared more similar gene structures and conversed protein domain compositions. Furthermore, the expression profiles of these DoNACs were investigated in diverse tissues and under cold stress by RNA-seq data. Then, a total of five up-regulated and five down-regulated, cold-responsive DoNACs were validated through QRT-PCR analysis, demonstrating they were involved in regulating cold stress response. Additionally, the subcellular localization of two down-regulated candidates (DoNAC39 and DoNAC58) was demonstrated to be localized in the nuclei. This study reported the genomic organization, protein domain compositions and expression patterns of the NAC family in Dendrobium officinale, which provided targets for further functional studies of DoNACs and also contributed to the dissection of the role of NAC in regulating cold tolerance in Dendrobium officinale.

Engineering of dendritic cell bispecific extracellular vesicles for tumor-targeting immunotherapy.

Advances in the development of therapeutic extracellular vesicles (EVs) for cancer immunotherapy have allowed them to emerge as an alternative to cell therapy. In this proof-of-concept work, we develop bispecific EVs (BsEVs) by genetically engineering EV-producing dendritic cells (DCs) with aCD19 scFv and PD1 for targeting tumor antigens and blocking immune checkpoint proteins simultaneously. We find that these bispecific EVs (EVs-PD1-aCD19) have an impressive ability to accumulate in huCD19-expressing solid tumors following intravenous injection. In addition, EVs-PD1-aCD19 can remarkably reverse the immune landscape of the solid tumor by blocking PD-L1. Furthermore, EVs-PD1-aCD19 can also target tumor-derived EVs in circulation, which prevents the formation of a premetastatic niche in other tissues. Our technology is a demonstration of bispecific EV-based cancer immunotherapy, which may inspire treatments against various types of tumors with different surface antigens and even a patient-tailored therapy.

Neurological disorders after severe pneumonia are associated with translocation of endogenous bacteria from the lung to the brain.

Neurological disorders are a common feature in patients who recover from severe acute pneumonia. However, the underlying mechanisms remain poorly understood. Here, we show that the neurological syndromes after severe acute pneumonia are partly attributed to the translocation of endogenous bacteria from the lung to the brain during pneumonia. Using principal components analysis, similarities were found between the brain's flora species and those of the lungs, indicating that the bacteria detected in the brain may originate from the lungs. We also observed impairment of both the lung-blood and brain-blood barriers, allowing endogenous lung bacteria to invade the brain during pneumonia. An elevated microglia and astrocyte activation signature via bacterial infection-related pathways was observed, indicating a bacterial-induced disruption of brain homeostasis. Collectively, we identify endogenous lung bacteria that play a role in altering brain homeostasis, which provides insight into the mechanism of neurological syndromes after severe pneumonia.