Reprogramming Tumor-Associated Macrophages with a Se-Based Core-Satellite Nanoassembly to Enhance Cancer Immunotherapy.

Tumor-associated macrophages (TAMs), as the most prevalent immune cells in the tumor microenvironment, play a pivotal role in promoting tumor development through various signaling pathways. Herein, we have engineered a Se@ZIF-8 core-satellite nanoassembly to reprogram TAMs, thereby enhancing immunotherapy outcomes. When the nanoassembly reaches the tumor tissue, selenium nanoparticles and Zn2+ are released in response to the acidic tumor microenvironment, resulting in a collaborative effort to promote the production of reactive oxygen species (ROS). The generated ROS, in turn, activate the nuclear factor κB (NF-κB) signaling pathway, driving the repolarization of TAMs from M2-type to M1-type, effectively eliminating cancer cells. Moreover, the nanoassembly can induce the immunogenic death of cancer cells through excess ROS to expose calreticulin and boost macrophage phagocytosis. The Se@ZIF-8 core-satellite nanoassembly provides a potential paradigm for cancer immunotherapy by reversing the immunosuppressive microenvironment.

Organelle-based immunotherapy strategies for fighting against cancer.

Destruction of subcellular organelles can cause dysfunction and even death of cells to elicit immune responses. In this review, the characteristics and functions of important organelles are mainly summarized. Then, the intelligent immunotherapeutic strategies and suggestions based on influencing the organelles are further highlighted. This review will provide ideas for developing novel and effective immunotherapy strategies and advance the development of cancer immunotherapy.

A GalNAc-modified CaCO3 nano-immunomodulator for targeted and responsive immunotherapy against orthotopic liver cancer.

A nano-immunomodulator modified with N-acetylgalactosamine (GalNAc) on calcium carbonate (CaCO3) was prepared for targeted and responsive immunotherapy. And the immunologic adjuvant (CpG ODNs) and doxorubicin (DOX) were released to synergistically improve immune response for treating orthotopic liver cancer.

MicroProteinDB: A database to provide knowledge on sequences, structures and function of ncRNA-derived microproteins.

Omics-based technologies have revolutionized our comprehension of microproteins encoded by ncRNAs, revealing their abundant presence and pivotal roles within complex functional landscapes. Here, we developed MicroProteinDB (http://bio-bigdata.hrbmu.edu.cn/MicroProteinDB), which offers and visualizes the extensive knowledge to aid retrieval and analysis of computationally predicted and experimentally validated microproteins originating from various ncRNA types. Employing prediction algorithms grounded in diverse deep learning approaches, MicroProteinDB comprehensively documents the fundamental physicochemical properties, secondary and tertiary structures, interactions with functional proteins, family domains, and inter-species conservation of microproteins. With five major analytical modules, it will serve as a valuable knowledge for investigating ncRNA-derived microproteins.

Simultaneous extraction of five heavy metal ions from root vegetables via dual-frequency ultrasound-assisted enzymatic digestion.

The dual-frequency ultrasound-assisted enzymatic digestion (DUED) technique was developed for synchronous green extraction of five heavy metal ions in root vegetables. The combination of α-amylase, cellulase, and papain showed significant advantageous in extracting heavy metal ions. Under optimized dual-frequency ultrasonic conditions, the extraction rates of Cr, As, Cd, Pb, and Hg in carrots reached 99.04%, 105.88%, 104.65%, 104.10%, and 103.13% respectively. And the extraction process is highly efficient, completing in just 15 min. Compared to conventional microwave-assisted acid hydrolysis method, this technique eliminates the need for high-temperature concentrated acid, enhancing its environmental sustainability while maintaining mild reaction conditions, making it ideal for biosensors application. Additionally, simultaneous extraction and detection of four heavy metals in lotus roots were successfully achieved by using DUED and a fluorescent paper-based microfluidic chip. The obtained results are consistent with those obtained using conventional methods.

Treatment of intracranial aneurysms with pipeline embolization device: a single-center experience.

Background: Endovascular therapy is the primary treatment modality for intracranial aneurysms (IA). The objective of this study was to assess the effectiveness and safety of a pipeline embolization device (PED) for the treatment of IA. Methods: This retrospective study was conducted at a single center. Data were collected for all patients who underwent PED treatment at the Fourth Affiliated Hospital of Xinjiang Medical University between December 2018 and January 2022. Clinical characteristics, aneurysm-related characteristics, treatment details, and clinical and imaging outcomes were collected and analyzed. Results: A total of 60 consecutive patients with 60 IAs were treated with a PED. The mean age of the participants was 61.8 years, with 53% being female. The average size of the aneurysms was 14.7 mm, with 54 located in the anterior circulation and six in the posterior circulation. The median last follow-up time was 13.0 months (range, 11-24 months). All patients underwent final digital subtraction angiography (DSA) for angiographic follow-up, and 50 aneurysms (83.3%) were completely occluded. The overall complication rate was 3.3%, and there were no reported mortalities. Among the 12 cases of ruptured aneurysms, all of which underwent adjunctive coil embolization, the complete occlusion rate was 91.7% with a complication rate of 16.6% [ischemic complication and modified Rankin scale (mRS) deteriorated]. In the 6 cases of posterior circulation aneurysms (2 in the basilar artery), 5 cases achieved complete occlusion and 1 case achieved near-complete occlusion, with no reported complications or mortality. Conclusions: The use of PEDs appears to be an effective treatment option for IA, demonstrating high occlusion rates and low complication rates. While the application of PEDs for the treatment of ruptured aneurysms did not increase the risk of secondary aneurysm rupture, caution is still warranted due to a higher complication rate. In the treatment of aneurysms of the vertebrobasilar artery using PEDs, this study achieved favorable efficacy outcomes without complications nor patient mortality. However, further studies are needed to validate these findings.

Sensitive fluorescence ELISA for the detection of zearalenone based on self-assembly DNA nanocomposites and copper nanoclusters.

Zearalenone (ZEN), produced by Fusarium species, is a potential risk to human health. Traditional enzyme-linked immunosorbent assay (ELISA) is restricted due to low sensitivity for the detection of ZEN. Herein, enzyme nanocomposites (ALP-SA-Bio-ssDNA, ASBD) were prepared with the self-assembly strategy based on streptavidin-labeled alkaline phosphatase (SA-ALP) and dual-biotinylated ssDNA (B2-ssDNA). The enzyme nanocomposites improved the loading amount of ALP and catalyzed more ascorbic acid 2-phosphate to generate ascorbic acid (AA). Subsequently, Cu2+ could be reduced to copper nanoclusters (CuNCs) having strong fluorescence signal by AA with poly T. Benefiting from the high enzyme load of nanocomposites and the strong signal of CuNCs, the fluorescence ELISA was successfully established for the detection of ZEN. The proposed method exhibited lower limit of detection (0.26 ng mL-1) than traditional ELISA (1.55 ng mL-1). The recovery rates ranged from 92.00% to 108.38% (coefficient of variation < 9.50%) for the detection of zearalenone in corn and wheat samples. In addition, the proposed method exhibited no cross reaction with four other mycotoxins. This proposed method could be used in trace detection for food safety.

Endovascular re-canalization for symptomatic non-acute intracranial large artery occlusion: a single-center retrospective study.

Background: Managing patients with symptomatic non-acute intracranial large artery occlusion (SNA-ILAO) poses a significant challenge due to the high morbidity and risk of recurrent critical ischemic events, even with standard medical therapy. This unique subgroup of patients requires specialized attention. The aim of this study is to evaluate the feasibility and safety of endovascular interventional recanalization for SNA-ILAO. Methods: We retrospectively collected data of patients with SNA-ILAO who underwent endovascular interventional therapy at the Fourth Affiliated Hospital of Xinjiang Medical University from 2018 to 2021. The collected data included clinical demography, imaging data, treatment details, and prognosis. Follow-up imaging assessments were conducted for the patients, and descriptive statistics were performed. Results: A total of 24 patients were enrolled, with a majority being male (58.3%) and a mean age of 62.0±9.3 years. The pre-treatment median modified Rankin scale (mRS) and the National Institutes of Health Stroke Scale (NIHSS) scores at baseline were 3 and 1, respectively. The most common occlusion location was the middle cerebral artery (MCA), including M1 (70.8%), M2 (20.8%), and M3 (4.7%). Successful recanalization was achieved in all 24 patients, with 21 cases (87.5%) achieving thrombolysis in cerebral infarction (TICI) 3 reperfusion and the remaining 3 cases (12.5%) achieving TICI 2b reperfusion. Asymptomatic intracranial hemorrhage (ICH) occurred in 2 patients (8.3%). During the first 30-day clinical follow-up, none of these patients experienced any recurrent cerebral ischemic events. During the 29.5-month follow-up period for vessel imaging, only 12.5% (3/24) of patients who had follow-up imaging experienced re-stenosis. Conclusions: Endovascular recanalization is a potentially safe and effective procedure for patients with SNA-ILAO. However, it is important to note that there is still a non-negligible rate of complications associated with this treatment. Therefore, exercising caution and implementing strict controls when administering this procedure is crucial.

Epichloë Endophyte Enhanced Insect Resistance of Host Grass Leymus Chinensis by Affecting Volatile Organic Compound Emissions.

In plant-herbivore interactions, plant volatile organic compounds (VOCs) play an important role in anti-herbivore defense. Grasses and Epichloë endophytes often form defensive mutualistic symbioses. Most Epichloë species produce alkaloids to protect hosts from herbivores, but there is no strong evidence that endophytes can affect the insect resistance of their hosts by altering VOC emissions. In this study, a native dominant grass, sheepgrass (Leymus chinensis), and its herbivore, oriental migratory locust (Locusta migratoria), were used as experimental materials. We studied the effect of endophyte-associated VOC emissions on the insect resistance of L. chinensis. The results showed that endophyte infection enhanced insect resistance of the host, and locusts preferred the odor of endophyte-free (EF) leaves to that of endophyte-infected (EI) leaves. We determined the VOC profile of L. chinensis using gas chromatography-mass spectrometry (GC-MS), and found that endophyte infection decreased the pentadecane (an alkane) emission from uneaten plants, and increased the nonanal (an aldehyde) emission from eaten plants. The olfactory response experiment showed that locusts were attracted by high concentration of pentadecane, while repelled by high concentration of nonanal, indicating that Epichloë endophytes may increase locust resistance of L. chinensis by decreasing pentadecane while increasing nonanal emission. Our results suggest that endophytes can induce VOC-mediated defense in hosts in addition to producing alkaloids, contributing to a better understanding the endophyte-plant-herbivore interactions.

Systematic analysis of DNA methylation-mediated TF dysregulation on lncRNAs reveals critical roles in tumor immunity.

Emerging evidence suggests that DNA methylation affects transcriptional regulation and expression perturbations of long non-coding RNAs (lncRNAs) in cancer. However, a comprehensive investigation into the transcriptional control of DNA methylation-mediated dysregulation of transcription factors (TFs) on lncRNAs has been lacking. Here, we integrated the transcriptome, methylome, and regulatome across 21 human cancers and systematically identified the transcriptional regulation of DNA methylation-mediated TF dysregulations (DMTDs) on lncRNAs. Our findings reveal that TF regulation of lncRNAs is significantly impacted by DNA methylation. Comparative analysis of DMTDs on mRNAs revealed a conserved pattern of TFs involvement. Pan-cancer Methylation TFs (MethTFs) and Methylation LncRNAs (MethLncRNAs) were identified, and were found to be closely associated with cancer hallmarks and clinical features. In-depth analysis of co-expressed mRNAs with pan-cancer MethLncRNAs unveiled frequent disruptions in cancer immunity, particularly in the context of inflammatory response. Furthermore, we identified five immune-related network modules that contribute to immune cell infiltration in cancer. Immune-related subtypes were subsequently classified, characterized by high levels of immune cell infiltration, expression of immunomodulatory genes, and relevant immune cytolytic activity score, major histocompatibility complex score, response to chemotherapy, and prognosis. Our findings provide valuable insights into cancer immunity from the epigenetic and transcriptional regulation perspective.

A multiple lateral flow immunoassay based on AuNP for the detection of 5 chemical contaminants in milk.

Melamine (MEL), enrofloxacin (ENR), sulfamethazine (SMZ), tetracycline (TC), and aflatoxin M1 (AFM1) are the main chemical contaminants in milk. It is necessary to detect these miscellaneous chemical contaminants in milk synchronously to ensure the safety of the milk. In this study, a multiple lateral flow immunoassay (LFIA) was developed for the detection of MEL, ENR, SMZ, TC, and AFM1 in milk. Under optimal experimental conditions, the cutoff values were 25 ng/mL for MEL, 1 ng/mL for ENR, 2.5 ng/mL for SMZ, 2.5 ng/mL for TC, and 0.25 ng/mL for AFM1 in milk samples. The limits of detection of LFIA were 0.173 ng/mL for MEL, 0.078 ng/mL for ENR, 0.059 ng/mL for SMZ, 0.082 ng/mL for TC, and 0.0064 ng/mL for AFM1. The recovery rates of LFIA in milk were 83.2-104.4% for MEL, 76.5-127.3% for ENR, 96.8-113.5% for SMZ, 107.1-166.6% for TC, and 93.5-130.3% for AFM1. The coefficients of variation were all less than 15%. As a whole, the developed multiple lateral flow immunoassay showed potential as a highly reliable and excellent tool for the rapid and sensitive screening of MEL, ENR, SMZ, TC, and AFM1 in milk.

A CaCO3-based synergistic immunotherapy strategy for treating primary and distal tumors.

Low response rate limits the widespread application of cancer immunotherapy. To improve the response rate of immunotherapy, a CaCO3-based composite nanomaterial was developed to induce immunogenic cell death for enhancing immunotherapy against 4T1 primary and distal tumors.

Dual-AND Logic Gate-Based Strip Assay for Amplified Detection of Four miRNAs and Diagnosis of Lung Cancer.

The detection of circulating tumor microRNAs (miRNAs) holds great promise for the noninvasive and early-stage diagnosis of cancer. However, the low abundance of lung cancer-related miRNAs and the false-positive results of single miRNA detection limited the development of strip-based point-of-care testing methods in clinic. We developed a duplex-specific nuclease (DSN)-mediated and dual-AND logic gate-based triple-line lateral flow strip detection system for the rapid and simultaneous detection of four miRNAs of lung cancer in a single strip test. This system combines DSN-mediated signal amplification with AND logic gate-based simple signal output. Meanwhile, the limit of detection of this platform was calculated to be 26.51 fM. Furthermore, this assay was used to detect lung cancer-related miRNAs from serum in a homogeneous and separation-free format, which could discriminate lung cancer patients from healthy individuals with an accuracy of 100%. Our approach provides a simple and easy-to-handle method for the diagnosis of lung cancer in clinic.

Imaging strategies for receptor tyrosine kinase dimers in living cells.

Receptor tyrosine kinases (RTKs) are the essential regulators of cell signal transduction pathways and play important roles in biological processes. RTK dimerization is generally considered the first step in receptor activation and cell communication. And the abnormal expression of RTK dimers is closely related to the occurrence and development of many diseases. Therefore, the visualization of RTK dimerization is of great significance for monitoring physiological processes. The genetic and nongenetic imaging strategies have attracted widespread attention due to their high efficiency and high sensitivity. In this review, the RTKs and their dimers as well as the advances in strategies for imaging RTK dimers are introduced. Furthermore, we analyze the limitations of existing imaging strategies and put forward suggestions for the future development of imaging probes. We expect that this review will inspire more in-depth investigation of RTK dimers, which will also broaden the application of strategies of RTK dimers in biomedical areas.

IEAtlas: an atlas of HLA-presented immune epitopes derived from non-coding regions.

Cancer-related epitopes can engage the immune system against tumor cells, thus exploring epitopes derived from non-coding regions is emerging as a fascinating field in cancer immunotherapies. Here, we described a database, IEAtlas (http://bio-bigdata.hrbmu.edu.cn/IEAtlas), which aims to provide and visualize the comprehensive atlas of human leukocyte antigen (HLA)-presented immunogenic epitopes derived from non-coding regions. IEAtlas reanalyzed publicly available mass spectrometry-based HLA immunopeptidome datasets against our integrated benchmarked non-canonical open reading frame information. The current IEAtlas identified 245 870 non-canonical epitopes binding to HLA-I/II allotypes across 15 cancer types and 30 non-cancerous tissues, greatly expanding the cancer immunopeptidome. IEAtlas further evaluates the immunogenicity via several commonly used immunogenic features, including HLA binding affinity, stability and T-cell receptor recognition. In addition, IEAtlas provides the biochemical properties of epitopes as well as the clinical relevance of corresponding genes across major cancer types and normal tissues. Several flexible tools were also developed to aid retrieval and to analyze the epitopes derived from non-coding regions. Overall, IEAtlas will serve as a valuable resource for investigating the immunogenic capacity of non-canonical epitopes and the potential as therapeutic cancer vaccines.

Dual-target electrochemical DNA sensor for detection of Pb2+ and Hg2+ simultaneously by exonuclease I-assisted recycling signal amplification.

With the development of exonuclease, the exonuclease has been used to construct a variety of aptasensor and to realize the signal amplification. Among them, based on silver nanoparticles (Ag NPs) and exonuclease I (Exo I)-assisted cycle signal amplification strategy, we designed a novel high-sensitivity dual-target electrochemical biosensor to detect Pb2+ or Hg2+ in water. In the presence of Hg2+, the Hg2+ was fixed to the aptamer chain by thymine-Hg2+-thymine (T-Hg2+-T), resulting in the decrease of signal. When Pb2+ was present, DNA single strand S2 dissociated and was bound to Pb2+, which automatically triggered Exo I to selectively cut the single chain from the recognition site to achieve the cyclic amplification of the electrochemical signal. The interaction between aptamer and Exo I was investigated by gel electrophoresis. Under the optimum conditions in the scan range -0.20 to 0.60 V, the biosensor had high sensitivity with a linear range of 100 pg/L to 10.0 mg/L, Pb2+ or Hg2+, and the detection limits were 17.0 pg/L (R2 = 0.993) and 12.0 pg/L (R2 = 0.993), respectively. The relative standard deviation (RSD) of the sensor was 0.5-2.6%, and the recovery of spiked standard solutions was between 98.3 and 110%. The cycle amplification strategy supported by this enzyme has promising applications in detection of the two metal ions in various fields.

COF-DNA Bicolor Nanoprobes for Imaging Tumor-Associated mRNAs in Living Cells.

Developing probes for the simultaneous detection of multiple tumor-associated mRNAs is beneficial for the precise diagnosis and early therapy of cancer. In this work, we prepared two COF-DNA bicolor probes at room temperature and freezing conditions and evaluated their performances in simultaneous imaging of intracellular tumor-associated mRNAs. By loading dye-labeled survivin- and TK1-mRNA recognition sequences on porphyrin COF NPs, nucleic acid-specific "off-on" nanoprobes were obtained. The nanoprobe prepared by the freezing method exhibits higher ssDNA loading density and better fluorescence quenching efficiency. Moreover, its signal-to-noise ratio is significantly higher than that prepared at room temperature, and the target recognition effect was unaffected. Significantly, the freezing-method-prepared nanoprobe has higher signal intensities in target-overexpressed cells compared to the room-temperature-prepared probe, while their signals in cells with low target expression are similar. Thus, the freezing-method-prepared nanoprobe is a promising tool for improved cancer diagnostic imaging. This work can offer new insights into the exploration of high-performance COF-based nanoprobes for multiple biomarker detection.

Electrochemiluminescence biosensor for determination of lead(II) ions using signal amplification by Au@SiO2 and tripropylamine-endonuclease assisted cycling process.

MXene@Au as the base and Au@SiO2 as signal amplification factor were used for constructing an ultrasensitive "on-off" electrochemiluminescence (ECL) biosensor for the detection of Pb2+ in water. The use of MXene@Au composite provided a good interface environment for the loading of tris(2,2-bipyridyl)ruthenium(II) (Ru(bpy)32+) on the electrode. Based on resonance energy transfer, the Au (core) SiO2 (shell) (Au@SiO2) nanoparticles stimulate electron transport and promote tripropylamine (TPrA) oxidation. The luminescence effect of Au@SiO2 was five times that of AuNPs and SiO2 nanomaterials alone, and the ECL intensity was greatly improved. In addition, Pb2+ activated the aptamer to exert its endonuclease activity, which realized the signal cycle amplification in the process of Pb2+ detection. When Pb2+ was added, the ECL signal weakened, and the Pb2+ concentration was detected according to the decreased ECL intensity. Under optimized experimental conditions, this aptamer sensor for Pb2+ has a wide detection range (0.1 to 1 × 106 ng L-1) and a low detection limit (0.059 ng L-1). The relative standard deviation (RSD) of the sensor is 0.39-0.99%, and the recovery of spiked standard is between 90.00 and 125.70%. The sensor shows good selectivity and high sensitivity in actual water sample analysis. This signal amplification strategy possibly provides a new method for the detection of other heavy metal ions and small molecules.

Dual-Target Electrochemical Sensor Based on 3D MoS2-rGO and Aptamer Functionalized Probes for Simultaneous Detection of Mycotoxins.

A dual-target aptamer functionalized probes (DTAFP) was applied for the detection of aflatoxin B1 (AFB1) and zearalenone (ZEN) simultaneously, which has not been reported. Meanwhile, two functional materials for signal amplification of the DTAFP were synthesized: 1) a three-dimensional molybdenum disulfide-reduced graphene oxide (MoS2-rGO) as a favorable loading interface; 2) a double-probes gold nanoparticles (AuNPs) modified by Thionin (Thi) and 6-(Ferrocenyl) hexanethiol (FC6S) as distinguishable and non-interfering signals. Mycotoxins on the electrode surface release into solution under the function of the DTAFP, leading a reduction of the differential peak impulse in signal response. Under the optimum conditions, the aptasensor exhibited a detection range of 1.0 pg mL-1-100 ng mL-1 for AFB1 and ZEN, with no observable cross reactivity. In addition, the aptasensor performed excellent stability, reproducibility, specificity, and favorable recovery in the detection of edible oil. This work demonstrated a novel method for the construction of a simple, rapid, and sensitive aptasensor in the detection of multiple mycotoxins simultaneously.