In Situ Sprayed Exosome-Cross-Linked Gel as Artificial Lymph Nodes for Postoperative Glioblastoma Immunotherapy.

One key challenge in postoperative glioblastoma immunotherapy is to guarantee a potent and durable T-cell response, which is restricted by the immunosuppressive microenvironment within the lymph nodes (LNs). Here, we develop an in situ sprayed exosome-cross-linked gel that acts as an artificial LN structure to directly activate the tumor-infiltrating T cells for prevention of glioma recurrence. Briefly, this gel is generated by a bio-orthogonal reaction between azide-modified chimeric exosomes and alkyne-modified alginate polymers. Particularly, these chimeric exosomes are generated from dendritic cell (DC)-tumor hybrid cells, allowing for direct and robust T-cell activation. The gel structure with chimeric exosomes as cross-linking points avoids the quick clearance by the immune system and thus prolongs the durability of antitumor T-cell immunity. Importantly, this exosome-containing immunotherapeutic gel provides chances for ameliorating functions of antigen-presenting cells (APCs) through accommodating different intracellular-acting adjuvants, such as stimulator of interferon genes (STING) agonists. This further enhances the antitumor T-cell response, resulting in the almost complete elimination of residual lesions after surgery. Our findings provide a promising strategy for postsurgical glioma immunotherapy that warrants further exploration in the clinical arena.

Risk factors for suspected pulmonary embolism in children: Complication of Mycoplasma pneumoniae pneumonia.

PURPOSE: Pulmonary embolism (PE) is not a rare complication of Mycoplasma pneumoniae pneumonia (MPP) in children. We sought to determine the incidence of PE in children with MPP who underwent clinically indicated CT pulmonary angiography (CTPA) and to evaluate the risk factors for PE. METHODS: All 106 children with MPP who were clinically suspected of having PE and who underwent CTPA were retrospectively enrolled from June 2018 to December 2021. The clinical features, laboratory data, and radiological parameters were recorded (e.g., lung consolidation involved and the Qanadli score). A Cox proportional hazards model and area under the receiver operating characteristic (ROC) curve were used to evaluate the risk factors and prognostic discriminatory capacity for PE. RESULTS: PE was detected in 26 of 106 (24.5 %) children (mean age, 6.2 years ± 3.3 years; 53 boys). Sixteen of the 26 (61.5 %) children with PE were boys. The mean age of the children with PE was 8.1 ± 2.9 years, and the mean Qanadli score was 15.3 ± 10.2. Children with PE had higher D-dimer levels (9.3 ± 7.1 mg/Lvs. 3.6 ± 3.8 mg/L) and a greater frequency of lung lobe consolidation (25 (96.2 %) vs. 64 (80.0 %)) (all P < 0.05). For children with MPP, age (hazard ratio (HR) = 1.96 (95 % CI1.04, 3.71; P = 0.037), D-dimer level (HR = 1.52, 95 % CI: 1.03, 2.24; P = 0.029), and bilateral lung consolidation (HR = 2.41, 95 % CI: 1.03, 5.58; P = 0.043) were found to be independent predictors of PE. CONCLUSION: Clinical and CT radiological predictors could be used to predict PE in children with MPP. The use of risk factor assessment as a tool has the potential to guide more appropriate use of CTPA in children.

Flexible Janus Black Silicon Photothermal Conversion Membranes for Highly Efficient Solar-Driven Interfacial Water Purification.

Photothermal conversion materials are critical in the development of solar-driven interfacial evaporation techniques; however, achieving a high energy conversion efficiency remains challenging owing to the high cost and instability of light-absorbing materials, in addition to the difficulties of simultaneously improving light absorption while suppressing heat loss. A black silicon (Si) powder with a porous structure was prepared by chemical etching of a low-cost commercial micron-sized Al-Si alloy, and a flexible Janus black Si photothermal conversion membrane was constructed. The partially broken spherical particles and porous structure obtained after etching enhanced the refraction of light from the Si powder, imparting the prepared membrane with an average light absorption rate of 95.95% over the solar spectrum. Evaporation from the membrane increased the intermediate water content and reduced the equivalent evaporation enthalpy. The thermal conduction loss was inhibited through a one-dimensional water transport structure, and the membrane achieved a water evaporation rate of 2.17 kg m-2 h-1 and a photothermal efficiency of 94.95% under 1 sun illumination. Benefiting from the broadband absorption and high photothermal efficiency of black Si powder, surface modification of hydrophobic polydimethylsiloxane, and directional salt-out structure design, the evaporation rate of the Janus black Si membrane-based system in a 10% NaCl solution was maintained >2.10 kg m-2 h-1 after 7 days of continuous evaporation cycles. The removal rate of metal ions from simulated seawater and from practical wastewater containing complex heavy metals reached >99.9%, indicating the promising potential of black Si membrane for application in solar-driven interfacial water purification.

Unveiling the structural properties and induced resistance activity in rice of Chitin/Chitosan-Glucan Complex of Rhizoctonia solani AG1 IA inner cell wall.

Phytopathogen cell wall polysaccharides have important physiological functions. In this study, we isolated and characterized the alkali-insoluble residue on the inner layers of the Rhizoctonia solani AG1 IA cell wall (RsCW-AIR). Through chemical composition and structural analysis, RsCW-AIR was mainly identified as a complex of chitin/chitosan and glucan (ChCsGC), with glucose and glucosamine were present in a molar ratio of 2.7:1.0. The predominant glycosidic bond linkage of glucan in ChCsGC was ß-1,3-linked Glcp, both the α and ß-polymorphic forms of chitin were presented in it by IR, XRD, and solid-state NMR, and the ChCsGC exhibited a degree of deacetylation measuring 67.08 %. RsCW-AIR pretreatment effectively reduced the incidence of rice sheath blight, and its induced resistance activity in rice was evaluated, such as inducing a reactive oxygen species (ROS) burst, leading to the accumulation of salicylic acid (SA) and the up-regulation of SA-related gene expression. The recognition of RsCW-AIR in rice is partially dependent on CERK1.

Efficient Electrochemical Microsensor for the Simultaneous Measurement of Hydrogen Peroxide and Ascorbic Acid in Living Brains.

Hydrogen peroxide (H2O2) and ascorbic acid (AA), acting as two significant indicative species, correlate with the oxidative stress status in living brains, which have historically been considered to be involved mainly in neurodegenerative disorders such as Alzheimer's disease, Huntington's disease, and Parkinson's disease (PD). The development of efficient biosensors for the simultaneous measurement of their levels in living brains is vital to understand their roles played in the brain and their interactive relationship in the progress of these diseases. Herein, a robust ratiometric electrochemical microsensor was rationally designed to realize the determination of H2O2 and AA simultaneously. Therefore, a specific probe was designed and synthesized with both recognition units responsible for reacting with H2O2 to produce a detectable signal on the microsensor and linkage units helping the probe modify onto the carbon substrate. A topping ingredient, single-walled carbon nanotubes (SWCNTs) was added on the surface of the electrode, with the purpose of not only facilitating the oxidation of AA but also absorbing methylene blue (MB), prompting to read out the inner reference signal. This proposed electrochemical microsensor exhibited a robust ability to real-time track H2O2 and AA in linear ranges of 0.5-900 and 10-1000 µM with high selectivity and accuracy, respectively. Eventually, the efficient electrochemical microsensor was successfully applied to the simultaneous measurement of H2O2 and AA in the rat brain, followed by microinjection, and in the PD mouse brain.

Discrimination and prediction of Qingzhuan tea storage year using quantitative chemical profile combined with multivariate analysis: Advantages of MRMHR based targeted quantification metabolomics.

The duration of storage significantly influences the quality and market value of Qingzhuan tea (QZT). Herein, a high-resolution multiple reaction monitoring (MRMHR) quantitative method for markers of QZT storage year was developed. Quantitative data alongside multivariate analysis were employed to discriminate and predict the storage year of QZT. Furthermore, the content of the main biochemical ingredients, catechins and alkaloids, and free amino acids (FAA) were assessed for this purpose. The results show that targeted marker-based models exhibited superior discrimination and prediction performance among four datasets. The R2Xcum, R2Ycum and Q2cum of orthogonal projection to latent structure-discriminant analysis discrimination model were close to 1. The correlation coefficient (R2) and the root mean square error of prediction of the QZT storage year prediction model were 0.9906 and 0.63, respectively. This study provides valuable insights into tea storage quality and highlights the potential application of targeted markers in food quality evaluation.

Advancements in Brain Research: The In Vivo/In Vitro Electrochemical Detection of Neurochemicals.

Neurochemicals, crucial for nervous system function, influence vital bodily processes and their fluctuations are linked to neurodegenerative diseases and mental health conditions. Monitoring these compounds is pivotal, yet the intricate nature of the central nervous system poses challenges. Researchers have devised methods, notably electrochemical sensing with micro-nanoscale electrodes, offering high-resolution monitoring despite low concentrations and rapid changes. Implantable sensors enable precise detection in brain tissues with minimal damage, while microdialysis-coupled platforms allow in vivo sampling and subsequent in vitro analysis, addressing the selectivity issues seen in other methods. While lacking temporal resolution, techniques like HPLC and CE complement electrochemical sensing's selectivity, particularly for structurally similar neurochemicals. This review covers essential neurochemicals and explores miniaturized electrochemical sensors for brain analysis, emphasizing microdialysis integration. It discusses the pros and cons of these techniques, forecasting electrochemical sensing's future in neuroscience research. Overall, this comprehensive review outlines the evolution, strengths, and potential applications of electrochemical sensing in the study of neurochemicals, offering insights into future advancements in the field.

Amperometry and Electron Microscopy show Stress Granules Induce Homotypic Fusion of Catecholamine Vesicles.

An overreactive stress granule (SG) pathway and long-lived, stable SGs formation are thought to participate in the progress of neurodegenerative diseases (NDs). To understand if and how SGs contribute to disorders of neurotransmitter release in NDs, we examined the interaction between extracellular isolated SGs and vesicles. Amperometry shows that the vesicular content increases and dynamics of vesicle opening slow down after vesicles are treated with SGs, suggesting larger vesicles are formed. Data from transmission electron microscopy (TEM) clearly shows that a portion of large dense-core vesicles (LDCVs) with double/multiple cores appear, thus confirming that SGs induce homotypic fusion between LDCVs. This might be a protective step to help cells to survive following high oxidative stress. A hypothetical mechanism is proposed whereby enriched mRNA or protein in the shell of SGs is likely to bind intrinsically disordered protein (IDP) regions of vesicle associated membrane protein (VAMP) driving a disrupted membrane between two closely buddled vesicles to fuse with each other to form double-core vesicles. Our results show that SGs induce homotypic fusion of LDCVs, providing better understanding of how SGs intervene in pathological processes and opening a new direction to investigations of SGs involved neurodegenerative disease.

CTA-Based Radiomics and Area Change Rate Predict Infrarenal Abdominal Aortic Aneurysms Patients Events: A Multicenter Study.

RATIONALE AND OBJECTIVES: Clinical assessment of abdominal aortic aneurysm (AAA) intervention and rupture risk relies primarily on maximum diameter, but studies have shown that sole dependence on diameter has limitations. CTA-based radiomics, aneurysm and lumen area change rates (AACR, LACR) are measured to predict potential AAA events. MATERIALS AND METHODS: Between January 2017 and November 2022, 260 AAA patients from four centers who underwent two preoperative CTA examinations were included in this retrospective study. The endpoint event is defined as AAA rupture or repair. Patients were categorized into event and no-event groups based on the occurrence of endpoint event during follow-up. AACR and LACR were assessed using baseline and follow-up CTA, with radiomics features extracted from the baseline images. C-statistics and the Kaplan-Meier analysis were used to evaluate the predictive performance. RESULTS: A total of 193 eligible infrarenal AAA patients were included, 176 (91.2%) were man and 17 (8.8%) were woman. The median follow-up was 33.4 (14.2, 57.4) months. Seven models were constructed, comprising the aneurysm-based Radscore model, lumen-based Radscore model, intraluminal thrombus (ILT)-based Radscore model, AACR model, LACR model, clinical model (including high-density lipoprotein, D-dimer, and baseline aneurysm diameter), and a merged model. On the external validation set, the C-index of seven models were 0.713 (0.574-0.853), 0.642 (0.499-0.786), 0.727 (0.600-0.854), 0.619 (0.484-0.753), 0.680 (0.530-0.830), 0.690 (0.557-0.824) and 0.760 (0.651-0.869), in that order. In the Kaplan-Meier analysis, the merged model was best-divided patients into high/low-risk groups with Log-rank p < 0.0001. The AARC and LARC between non-event and event groups have significant differences (AACR: 1.4 cm2/y vs. 2.3 cm2/y, p < 0.0001; LACR: 0.3 cm2/y vs. 1.1 cm2/y, p < 0.0001). CONCLUSION: CTA-based radiomics, AACR and LACR have good predictive value for outcome event in infrarenal AAA patients.

RNA-binding protein RPS7 promotes hepatocellular carcinoma progression via LOXL2-dependent activation of ITGB1/FAK/SRC signaling.

BACKGROUND: Metastasis is one of the leading cause contributes to treatment failure and poor prognosis of hepatocellular carcinoma (HCC) patients. The underlying mechanism of HCC metastasis remains to be determined. Although several RNA binding proteins (RBPs) have been found to participate in tumorigenesis and progression of liver cancer, the role of RBPs in HCC patients with extrahepatic metastases is poorly understood. METHODS: By performing RNA-seq of primary HCC tissues (including HCC with extrahepatic metastasis and those did not develop metastasis), we identified a set of HCC metastasis-associated RBPs candidates. Among which, ribosomal protein S7 (RPS7) was found to be remarkably increased in HCC tissues and be strongly related to HCC poor survival. Overexpression or CRISPR-Cas9-mediated knockout were applied to investigate the role of RPS7 on the metastasis-associated phenotypes of HCC cells. RNA sequencing, RIP, RNA-pull down, dual luciferase reporter assay, nascent RNA capture assay, and RNA decay and so on, were applied to reveal the underlying mechanism of RPS7 induced HCC metastasis. RESULTS: Gain- and loss- of function analyses revealed that RPS7 promoted HCC cells adhesion, migration and invasion capabilities, as well as lung metastasis. Mechanistically, we uncovered that lysyl oxidase-like 2 (LOXL2) was a critical downstream target of RPS7. RPS7 could stabilize LOXL2 mRNA by binding to AUUUA motifs in the 3155-3375 region of the 3'UTR of LOXL2 mRNA, thus increased LOXL2 expression via elevating LOXL2 mRNA abundance. Further research revealed that LOXL2 could accelerate focal adhesion formation through maintaining the protein stability of ITGB1 and activating ITGB1-mediated FAK/SRC signaling pathway, and thereby contribute to the pro-metastasis effect of RPS7. CONCLUSIONS: Taken together, our data reveal a novel function of RPS7 in HCC metastasis, also reveal the critical roles of the RPS7/LOXL2/ITGB1 axis in HCC metastasis and shed new light on the exploration of molecular drugs against HCC.

UHPLC-QTOF-MS-based untargeted metabolomic authentication of Chinese red wines according to their grape varieties.

Wine is a very popular alcoholic drink owing to its health benefits of antioxidant effects. However, profits-driven frauds of wine especially false declarations of variety frequently occurred in markets. In this work, an UHPLC-QTOF-MS-based untargeted metabolomics method was developed for metabolite profiling of 119 bottles of Chinese red wines from four varieties (Cabernet Sauvignon, Merlot, Cabernet Gernischt, and Pinot Noir). The metabolites of red wines from different varieties were assessed using orthogonal partial least-squares discriminant analysis (OPLS-DA) and analyzed using KEGG metabolic pathway analysis. Results showed that the differential compounds among different varieties of red wines are mainly flavonoids, phenols, indoles and amino acids. The KEGG metabolic pathway analysis showed that indoles metabolism and flavonoids metabolism are closely related to wine varieties. Based on the differential compounds, OPLS-DA models could identify external validation wine samples with a total correct rate of 90.9 % in positive ionization mode and 100 % in negative ionization mode. This study indicated that the developed untargeted metabolomics method based on UHPLC-QTOF-MS is a potential tool to identify the varieties of Chinese red wines.

Characterization of heteropolysaccharides from Rhizoctonia solani AG1 IA cell wall and comparison of their effect on inducing plant defense.

Rhizoctonia solani (R. solani) is an important pathogenic fungus that causes symptoms of sheath blight, and the polysaccharide-rich cell wall plays a major role in plant-pathogen interactions. However, the composition and structure of its cell wall polysaccharides are insufficiently understood, and its specific function in plant-pathogen interactions is unknown, which makes effective control of sheath blight difficult at present. Herein, five cell wall polysaccharides (WF-1, WF-2, CAF-1, HAF-1 and HAF 2-1) were sequentially extracted by boiling water, cold and hot alkali from R. solani AG1 IA. They were heteropolysaccharides containing mainly glucose, mannose and galactose and less fucose, with molecular weights above 1100 kDa. These five polysaccharides mainly composed of →4)-Glcp-(1→, →6)-Glcp-(1→, →4,6)-Glcp-(1→, →3,4)-Glcp-(1→, and Manp-(1→. Several polysaccharides, except WF-1, showed different induced resistance degrees on rice plant, with HAF 2-1 having the most significant effect. Further analysis using NMR confirmed that the backbone of HAF 2-1 mainly consisted of →4)-α-D-Glcp-(1→ and →6)-α-D-Glcp-(1→ with branches of →4,6)-D-Glcp-(1→. HAF 2-1 enhance the resistance of rice against R. solani through salicylic acid (SA)-mediated immune signaling pathway. This work improves our knowledge of the cell wall polysaccharides in plant pathogens and facilitates the study of pathogenic mechanisms and effective disease control.

Third-order calibration applied to process surfactant-modulated excitation-emission matrix four-way fluorescence data for the direct determination of four polycyclic aromatic hydrocarbons in oilfield produced water.

Fluorescence spectroscopy is a powerful tool to determine polycyclic aromatic hydrocarbons (PAHs) owing to the strong endogenous fluorescence of these compounds. However, the presence of unknown interferences and overlapped spectra hinders the accurate determination of PAHs in oilfield produced water. Moreover, surfactants frequently coexist in oilfield produced water and will seriously affect the fluorescence signals of PAHs. Herein, a new methodology applying third-order calibration to process four-way (4D) fluorescence data was proposed to solve these problems and achieve accurate determination of pyrene, fluorene, phenanthrene, and fluoranthene as an example in oilfield produced water. The methodology is based on excitation-emission matrix fluorescence modulated by different concentrations of sodium dodecyl benzene sulfonate (SDBS) in the analyzed samples. The 4D fluorescence data were processed by third-order calibration methods including four-way parallel factor analysis (4-PARAFAC) and alternating weighted residue constraint quadrilinear decomposition (AWRCQLD), and the results were compared with those of second-order calibration methods. It was proved that third-order calibration was capable of accurately identifying and quantifying PAHs together with SDBS in oilfield produced water, which has better quantitative results and figures of merit compared to second-order calibration. This study provided a new approach to generating 4D fluorescence data and opened up an avenue for the accurate determination of PAHs in complex oilfield produced water with surfactants.

Chimeric Exosomes Functionalized with STING Activation for Personalized Glioblastoma Immunotherapy.

A critical challenge of existing cancer vaccines is to orchestrate the demands of antigen-enriched furnishment and optimal antigen-presentation functionality within antigen-presenting cells (APCs). Here, a complementary immunotherapeutic strategy is developed using dendritic cell (DC)-tumor hybrid cell-derived chimeric exosomes loaded with stimulator of interferon genes (STING) agonists (DT-Exo-STING) for maximized tumor-specific T-cell immunity. These chimeric carriers are furnished with broad-spectrum antigen complexes to elicit a robust T-cell-mediated inflammatory program through direct self-presentation and indirect DC-to-T immunostimulatory pathway. This chimeric exosome-assisted delivery strategy possesses the merits versus off-the-shelf cyclic dinucleotide (CDN) delivery techniques in both the brilliant tissue-homing capacity, even across the intractable blood-brain barrier (BBB), and the desired cytosolic entry for enhanced STING-activating signaling. The improved antigen-presentation performance with this nanovaccine-driven STING activation further enhances tumor-specific T-cell immunoresponse. Thus, DT-Exo-STING reverses immunosuppressive glioblastoma microenvironments to pro-inflammatory, tumoricidal states, leading to an almost obliteration of intracranial primary lesions. Significantly, an upscaling option that harnesses autologous tumor tissues for personalized DT-Exo-STING vaccines increases sensitivity to immune checkpoint blockade (ICB) therapy and exerts systemic immune memory against post-operative glioma recrudesce. These findings represent an emerging method for glioblastoma immunotherapy, warranting further exploratory development in the clinical realm.

Hippocampal circAnk3 Deficiency Causes Anxiety-like Behaviors and Social Deficits by Regulating the miR-7080-3p/IQGAP1 Pathway in Mice.

BACKGROUND: Circular RNAs are highly enriched in the synapses of the mammalian brain and play important roles in neurological function by acting as molecular sponges of microRNAs. circAnk3 is derived from the 11th intron of the ankyrin-3 gene, Ank3, a strong genetic risk factor for neuropsychiatric disorders; however, the function of circAnk3 remains elusive. In this study, we investigated the function of circAnk3 and its downstream regulatory network for target genes in the hippocampus of mice. METHODS: The DNA sequence from which circAnk3 is generated was modified using CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats/Cas9) technology, and neurobehavioral tests (anxiety and depression-like behaviors, social behaviors) were performed in circAnk3+/- mice. A series of molecular and biochemical assays were used to investigate the function of circAnk3 as a microRNA sponge and its downstream regulatory network for target genes. RESULTS: circAnk3+/- mice exhibited both anxiety-like behaviors and social deficits. circAnk3 was predominantly located in the cytoplasm of neuronal cells and functioned as a miR-7080-3p sponge to regulate the expression of Iqgap1. Inhibition of miR-7080-3p or restoration of Iqgap1 in the hippocampus ameliorated the behavioral deficits of circAnk3+/- mice. Furthermore, circAnk3 deficiency decreased the expression of the NMDA receptor subunit GluN2a and impaired the structural plasticity of dendritic synapses in the hippocampus. CONCLUSIONS: Our results reveal an important role of the circAnk3/miR-7080-3p/IQGAP1 axis in maintaining the structural plasticity of hippocampal synapses. circAnk3 might offer new insights into the involvement of circular RNAs in neuropsychiatric disorders.

Transesophageal echocardiography combined with ProAQT/PulsioFlex hemodynamic monitoring in anesthetic management of a patient with septic shock associated with septic cardiomyopathy: A case report.

Patients with septic shock complicated by septic cardiomyopathy (SCM) can be extremely ill and at high risk for mortality. If early assessment of cardiac function is neglected during treatment, sepsis may be further exacerbated. We report a 77-year-old male patient with severe septic shock who underwent intraoperative transesophageal echocardiography (TEE) because of progressive circulatory instability, SCM was diagnosed. Further perioperative treatment to support the circulation was successfully adjusted based on TEE and pulse index continuous cardiac output (CO) by ProAQT/PulsioFlex hemodynamic monitoring. We should consider a diagnosis of SCM in the perioperative period and perform ultrasonography routinely. The use of TEE with ProAQT/PulsioFlex offers a new option for anesthetic management.

Small but strong: the emerging role of small nucleolar RNA in cardiovascular diseases.

Cardiovascular diseases (CVDs) are the leading cause of mortality and disability worldwide. Numerous studies have demonstrated that non-coding RNAs (ncRNAs) play a primary role in CVD development. Therefore, studies on the mechanisms of ncRNAs are essential for further efforts to prevent and treat CVDs. Small nucleolar RNAs (snoRNAs) are a novel species of non-conventional ncRNAs that guide post-transcriptional modifications and the subsequent maturation of small nuclear RNA and ribosomal RNA. Evidently, snoRNAs are extensively expressed in human tissues and may regulate different illnesses. Particularly, as the next-generation sequencing techniques have progressed, snoRNAs have been shown to be differentially expressed in CVDs, suggesting that they may play a role in the occurrence and progression of cardiac illnesses. However, the molecular processes and signaling pathways underlying the function of snoRNAs remain unidentified. Therefore, it is of great value to comprehensively investigate the association between snoRNAs and CVDs. The aim of this review was to collate existing literature on the biogenesis, characteristics, and potential regulatory mechanisms of snoRNAs. In particular, we present a scientific update on these snoRNAs and their relevance to CVDs in an effort to cast new light on the functions of snoRNAs in the clinical diagnosis of CVDs.