Clinical value of circulating tumour cells in evaluating the efficacy of continuous hepatic arterial infusion among colorectal cancer patients.

Few studies have been conducted to evaluate the efficacy of HAIC using circulating tumour cells (CTCs). In this study, a total of 100 patients who received HAIC treatment and CTC detection were selected. The results showed that after HAIC treatment, the levels of CTC, carbohydrate antigen 19-9 (CA19-9) and carcinoembryonic antigen (CEA) decreased. Postoperative progression-free survival (PFS) rates between patients with positive and negative preoperative CTC results, and for CA19-9, CEA were significantly different. The positive rate of CTCs was 61% before chemotherapy and 23% after chemotherapy, and the correlation coefficient between the two was 0.385. Those whose CTC values increased after chemotherapy had shorter PFS rates. CTCs are an independent predictor of recurrence. Patients with CTC-positive results are more susceptible to recurrence. The CTC count in peripheral blood has a close bearing on the postoperative chemotherapy efficacy of patients with CRC and affects patients' PFS.

ATF3/EGR1 regulates myocardial ischemia/reperfusion injury induced autophagy and inflammation in cardiomyocytes.

Myocardial ischemia/reperfusion injury (MIRI) is an irreversible adverse event during the management of coronary heart disease that lacks effective controls. The underlying mechanism of MIRI still requires further investigation. Recent studies have suggested that overexpression of ATF3 protects against MIRI by regulating inflammatory responses, ferroptosis, and autophagy. The downstream target of ATF3, EGR1, also showed cardioprotective properties against MIRI by promoting autophagy. Therefore, further investigating the effect of ATF3/EGR1 pathway on MIRI-induced inflammation and autophagy is needed. Cardiomyocyte MIRI model was established by challenging H9C2 cells with hypoxia/reoxygenation (H/R). The ATF3 overexpression-H/R cell model by transfecting ATF3 plasmid into the H9C2 cell line. The transcription levels of ATF3 and EGR1 were determined using RT-qPCR, the levels of TNF-α and IL-6 were determined using ELISA kits, the protein expression of LC3 I, LC3 II, and P62 was determined via WB, and microstructure of H9C2 cell was observed by transmission electron microscopy (TEM). Overexpression of ATF3 significantly downregulated Egr1 levels, indicating that EGR1 might be the target of ATF3. By upregulating ATF3 levels, the extracellular levels of the inflammatory cytokines TNF-α and IL-6 significantly decreased, and the protein expression of the autophagy markers LC3 I, LC3 II, and P62 significantly increased. TEM results revealed that the cell line in the H/R-ATF3 group exhibited a higher abundance of autophagosome enclosures of mitochondria. The results indicated that ATF3/EGR1 may alleviate inflammation and improve autophagy in an H/R-induced MIRI model of cardiomyocytes.

Optical and electronic properties of BCN films deposited by magnetron sputtering.

Boron carbonitride (BCN) films containing hybridized bonds involving B, C, and N over wide compositional ranges enable an abundant variety of new materials, properties, and applications; however, their electronic performance is still limited by the presence of structural and electronic defects, yielding sluggish mobility and electrical conductivity. This work reports on mechanically stable BCN films and their corresponding optical and electronic properties. The ternary BCN films consisting of hybridized B-C-N bonds have been achieved by varying N2 flow by the radio frequency magnetron sputtering method. The BCN films show a bandgap value ranging from 3.32 to 3.82 eV. Hall effect measurements reveal an n-type conductivity with an improved hall mobility of 226 cm2/V s at room temperature for the optimal film. The n-BCN/p-Si heterojunctions exhibit a nonlinear rectifying characteristic, where the tunneling behavior dominates the injection regimes due to the density of defects, i.e., structural disorder and impurities. Our work demonstrates the tunable electrical properties of BCN/Si p-n diodes and, thus, is beneficial for the potential application in the fields of optics, optoelectronics, and electrics.

A simple mitochondria-immobilized fluorescent probe for the detection of hydrogen peroxide.

Hydrogen peroxide (H2O2), as one of reactive oxygen species (ROS) widely present in the human body, is involved in a variety of physiological activities. Many human diseases are associated with abnormal levels of H2O2 in the body. Mitochondria are the main organelles producing H2O2 in the human body, and monitoring the level of H2O2 in mitochondria can help to deepen the understanding of the detailed functions of H2O2 in physiological activities. However, due to the highly dynamic nature of the cells, real-time quantitative monitoring of H2O2 levels in mitochondria remains an ongoing challenge. Herein, a novel highly immobilized mitochondria-targeting fluorescent probe (QHCl) for detection of H2O2 was reasonably constructed based on quinolinium dye containing benzyl chloride moiety. Spectral experimental results demonstrated QHCl possessed outstanding selectivity toward H2O2 (λex/em = 380/513 nm). In addition, QHCl can quantitatively detect H2O2 in the concentration range of 0-20 µM with excellent sensitivity (LOD = 0.58 µM) under the PBS buffer solution (10 mM, pH = 7.4). Finally, bioimaging experiments demonstrated that the probe QHCl was able to be used for accurately detecting both endogenous and exogenous H2O2 in the mitochondria of living cells and zebrafish by its unique mitochondrial immobilization.

Exploration of a new approach for detection of nitrite with hydroxyl radical fluorescence probe in aqueous solutions.

Nitrite (NO2-) has been widely recognized by the international community as an important substance affecting water quality safety and human health, and the detection of NO2- has always been a hot topic for researchers. Fluorescent probe method is an emerging and ideal way for detecting NO2-. Due to the high dependence of the reported reactive NO2- fluorescent probes on strong acidic systems, using the idea of photochemistry, a fluorescence analysis method for detecting NO2- was proposed in this work to change the necessity of strong acidic solutions in probe detection process. A 365 nm UV-LED lamp was used to irradiate NO2- in aqueous solution to convert it into hydroxyl radicals (HO·), and capture the photodegradation product of NO2- using coumarin-3-carboxylic acid as probe 3-CCA that can react with HO· to generate only one type of strong fluorescent substance. This probe has excellent photostability, selectivity, and anti-interference ability, and can realize the quantitative detection of NO2- (0-15 µM) in pure aqueous solution with pH of 7.4. In addition, its application in actual water samples is also satisfactory, with a recovery rate of (85.91 %-109.15 %). Importantly, we hope that this photolysis strategy can open up the novel thinking to develop suitable fluorescent probes for the analysis and detection of some hardly detected analytes.

Sirt5-mediated lysine desuccinylation regulates oxidative stress adaptation in Magnaporthe oryzae during host intracellular infection.

Plant pathogenic fungi elaborate numerous detoxification strategies to suppress host reactive oxygen species (ROS), but their coordination is not well-understood. Here, we show that Sirt5-mediated protein desuccinylation in Magnaporthe oryzae is central to host ROS detoxification. SIRT5 encodes a desuccinylase important for virulence via adaptation to host oxidative stress. Quantitative proteomics analysis identified a large number of succinylated proteins targeted by Sirt5, most of which were mitochondrial proteins involved in oxidative phosphorylation, TCA cycle, and fatty acid oxidation. Deletion of SIRT5 resulted in hypersuccinylation of detoxification-related enzymes, and significant reduction in NADPH : NADP+ and GSH : GSSG ratios, disrupting redox balance and impeding invasive growth. Sirt5 desuccinylated thioredoxin Trx2 and glutathione peroxidase Hyr1 to activate their enzyme activity, likely by affecting proper folding. Altogether, this work demonstrates the importance of Sirt5-mediated desuccinylation in controlling fungal process required for detoxifying host ROS during M. oryzae infection.

ABCG2 is an itaconate exporter that limits antibacterial innate immunity by alleviating TFEB-dependent lysosomal biogenesis.

Itaconate is a metabolite that synthesized from cis-aconitate in mitochondria and transported into the cytosol to exert multiple regulatory effects in macrophages. However, the mechanism by which itaconate exits from macrophages remains unknown. Using a genetic screen, we reveal that itaconate is exported from cytosol to extracellular space by ATP-binding cassette transporter G2 (ABCG2) in an ATPase-dependent manner in human and mouse macrophages. Elevation of transcription factor TFEB-dependent lysosomal biogenesis and antibacterial innate immunity are observed in inflammatory macrophages with deficiency of ABCG2-mediated itaconate export. Furthermore, deficiency of ABCG2-mediated itaconate export in macrophages promotes antibacterial innate immune defense in a mouse model of S. typhimurium infection. Thus, our findings identify ABCG2-mediated itaconate export as a key regulatory mechanism that limits TFEB-dependent lysosomal biogenesis and antibacterial innate immunity in inflammatory macrophages, implying the potential therapeutic utility of blocking itaconate export in treating human bacterial infections.

Fluorescence and magnetic resonance imaging of ONL-93 cells in a rat model of ischemic.

OBJECTIVES: The current methods for detecting myelin changes in ischemic stroke are indirect and cannot accurately reflect their status. This study aimed to develop a novel fluorescent-magnetic resonance dual-modal molecular imaging probe for direct imaging of myelin. METHODS: Compounds 7a and 7b were synthesized by linking the MeDAS group and Gadolinium (III) 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetate. Compound 7a was selected for characterization and further study. Cell uptake, cytotoxicity, and magnetic resonance imaging scans were performed on cells. In vitro experiments on frozen brain sections from 7-day-old, 8-week-old, and ischemic stroke rats were compared with commercially available Luxol Fast Blue staining. After HPLC and MR scanning, brain tissue was soaked in 7a and scanned using T1WI and T1maps sequences. RESULTS: Spectrophotometer results showed that compounds 7a and 7b had fluorescent properties. MR scans indicated that the compounds had contrast agent properties. Cells could uptake 7a and exhibited high signals in imaging scans. Compound 7a brain tissue staining showed more fluorescence in myelin-rich regions and identified injury sites in ischemic stroke rats. MR scanning of brain sections provided clear myelin contrast. CONCLUSION: A novel fluorescent-magnetic resonance dual-modal molecular imaging probe for direct imaging of myelin was successfully developed and tested in rats with ischemic stroke. These findings provide new insights for the clinical diagnosis of demyelinating diseases.

The mechanisms of tumor necrosis factor α in regulating Krüpple-like factor 4 expression in SK-BR-3 breast cancer cells.

OBJECTIVE: To explore the expression and functional role of Krüpple-like factor 4 (KLF4) protein stimulated by tumor necrosis factor α (TNF-α) in SK-BR-3 breast cancer cells. METHODS: SK-BR-3 cells were stimulated with various concentrations of TNF-α at 0, 1, 5, 10, and 20 ng/mL. Expression levels of KLF4 protein were detected by Western blotting. In the detection of apoptosis, flow cytometry, and DAPI staining were used for detecting the level of apoptosis. RESULTS: KLF4 expression was markedly elevated following stimulation of SK-BR-3 with TNF-α. At the same time, the expression of KLF4 protein increased gradually with the increase of TNF-α stimulation concentration. TNF-α stimulation of SK-BR-3 cells increased apoptosis as measured by apoptosis levels. By overexpressing KLF4 protein in SK-BR-3 cells, it similarly increased apoptosis and promoted cell death of SK-BR-3 cells. CONCLUSION: TNF-α promotes KLF4 expression, while TNF-α promotes apoptosis in SK-BR-3 cells, a process that may be due to elevated KLF4 protein expression.

A long-wavelength mitochondria-targeted CO fluorescent probe for living cells and zebrafish imaging.

Carbon monoxide (CO) not only causes damage to life and health as an environmental pollutant, but also undertakes many physiological functions in organisms. In particular, developing means that can be used for the determination of CO in organelles will provide insight into the vital role it plays. Studies have shown that mitochondrial respiration is closely related to CO concentrations, so it is critical to develop tools for CO detection in mitochondria. Here, we use a rhodamine derivative that can target mitochondria as fluorophores to construct a mitochondrial-labeled CO fluorescence probe (Rh-CO) with high sensitivity (detection limit: 9.4 nM), excellent water-solubility, and long emission (λem = 630 nm). Prominently, the probe has outstanding mitochondria-targeting capabilities. Moreover, we used transient glucose deprivation (TGD) and heme to stimulate endogenous CO production in living cells and zebrafish, respectively, and the probe exhibited excellent imaging capabilities. All in all, we expect this probe to contribute to a deeper understanding of the role played by CO in mitochondria.

Alleviation of experimental autoimmune encephalomyelitis by transferring low RelB expression tolerogenic dendritic cells.

AIMS: Experimental autoimmune encephalomyelitis (EAE) is a widely used mouse model of multiple sclerosis. Rather than inducing immune response, tolerogenic dendritic cells (tDCs) have the ability to induce immune tolerance. In previous studies, we induced tDCs by 1,25-(OH)2D3 and 1,25-(OH)2D3 DCs significantly alleviated EAE symptoms. As downstream targets of 1,25-(OH)2D3, inhibition of RelB and MyD88 expression in DCs might induce tDCs and has therapeutic effect of MS. METHODS: Knockdown the expression of RelB and MyD88 with shRNA lentivirus to induce tDCs, adoptive transfer these tDCs to EAE mice, and investigate their therapeutic effects. RESULTS: Reduction of RelB expression induced tDCs. After transferring into EAE mice, tDCs with low RelB expression significantly alleviate their symptoms as well as reduce the immune cell infiltration and demyelination in spinal cord. CONCLUSION: RelB plays a key role in the antigen presenting function of DCs, and tDCs with low RelB expression is a potential treatment for EAE and MS.

Finite element analysis of sagittal screw expander appliance in the treatment of anterior maxillary hypoplasia.

The skeletal anterior crossbite is a common malocclusion in clinic. However, there have been no reports on the maxillary sagittal expansion to correct the premaxillary hypoplasia, which greatly influences the facial morphology and masticatory function, using finite element analysis. In the present study, a three-dimensional finite element model of craniomaxillofacial complex with maxillary sagittal hypoplasia is constructed and the treatment for premaxillary hypoplasia by the sagittal screw expander appliance is simulated. The hypoplasia of the left premaxilla is more serious than that of the right and thus the size of the left part of premaxillary expander baseplate is designed to be larger than that of the right part and the loading is applied at 10° leftward to the sagittal plane and 30° forward and downward to the maxillary occlusal plane. The displacements or equivalent stress distributions of the maxilla, teeth and their periodontal ligaments, are analyzed under the loads of 5.0 N, 10.0 N, 15.0 N, and 20.0 N. Consequently, as the load increases, the displacements or equivalent stresses of the maxilla, teeth and their periodontal ligaments all increase. Almost the whole premaxilla markedly move forward, downward, and leftward while other areas in the craniomaxillofacial complex remain almost static or have little displacement. The equivalent stress concentration zone of the maxilla mainly occurs around and in front of the incisive foramina. The displacements of left premaxilla are generally greater than those of the right under the loading forces. The maximum equivalent stress on the teeth and their periodontal ligaments are 2.34E-02 MPa and 2.98E-03 MPa, respectively. Taken together, the sagittal screw expander appliance can effectively open the premaxillary suture to promote the growth of the premaxilla. An asymmetrical design of sagittal screw expander appliance achieves the asymmetric expansion of the premaxilla to correct the uneven hypoplasia and obtains the more symmetrical aesthetic presentation. This study might provide a solid basis and theoretical guidance for the clinical application of sagittal screw expander appliance in the efficient, accurate, and personalized treatment of premaxillary hypoplasia.

Recent advances in small-molecule fluorescent probes with the function of targeting cancer receptors.

Cancer is "the sword of Damocles" that threatens human life and health. Therefore, the diagnosis and treatment of cancer have been receiving much attention. Many overexpressed receptors on the surface of cancer cells provide us with an effective way to specifically identify the cancer cells, and receptor targeting strategies are becoming one of the hot ideas to enhance the ability of fluorescent probes to target tumors. Fluorescent probes connected to ligands are targeted at cancer cell surfaces through receptor-mediated endocytosis. Receptor-targeting probes can image and track cancer cells, determine tumor boundaries, monitor deep lesions, and play a role in clinical medicine, such as fluorescent imaging-guided surgery. In this review, based on the perspective of small molecule fluorescent probes, we reviewed the design ideas, photophysical properties, and applications of receptor-targeting probes for detecting biomarkers in imaging and tracing cancer cells and prospected the future developmental direction of such probes. We hope that this review will provide more ideas for the design and development of active targeting probes for receptors and lead to more applications in the medical field.

Recent progress in epidemiology, clinical features, and therapy of multiple sclerosis in China.

Multiple sclerosis (MS) is a demyelinating disease of the central nervous system characterized by inflammation, demyelination, and neurodegeneration. It mainly affects young adults, imposing a heavy burden on families and society. The epidemiology, clinical features, and management of MS are distinct among different countries. Although MS is a rare disease in China, there are 1.4 billion people in China, so the total number of MS patients is not small. Because of the lack of specific diagnostic biomarkers for MS, there is a high misdiagnosis rate in China, as in other regions. Due to different genetic backgrounds, the clinical manifestations of MS in Chinese are different from those in the West. Herein, this review aims to summarize the disease comprehensively, including clinical profile and the status of disease-modifying therapies in China based on published population-based observation and cohort studies, and also to compare with data from other countries and regions, thus providing help to develop diagnostic guideline and the novel therapeutic drugs. Meanwhile, we also discuss the problems and challenges we face, specifically for the diagnosis and treatment of MS in the middle- and low-income countries.

Anti-PRL-3 Monoclonal Antibody inhibits the Growth and Metastasis of colorectal adenocarcinoma.

Background: Colon cancer is the one of leading causes of cancer-related death. Chemotherapy, radiotherapy and immunotherapy will be the mainstream in inoperable advanced cancer in clinics. Precision treatment is still lack in colon cancer. Materials and Methods: We developed a series of mAbs targeting PRL-3 through different types of immunogens. The binding domains of mAbs were identified through the ELISA and Western blotting experiments. The antitumor activity of mAbs was verified by cell proliferation, migration and invasion experiments. Xenograft subcutaneous and metastatic models and patient derived Xenograft (PDX) model were established. Results: mAb 12G12 targeting 77-120AA exhibited inhibition in migration and invasion experiments. 12G12 inhibited the migration of multiple types of cancer cells, including colon cancer, gastric cancer, esophagus cancer, liver cancer, lung cancer and pancreatic cancer cells. 12G12 decreased the tumor growth and metastasis in Xenograft subcutaneous and metastatic tumor model, respectively. The antitumor activity of mAb 12G12 was also confirmed in PDX model of gastric cancer. PRL-3 interacted with Golgi protein TMED10. Knockdown of TMED10 expression attenuated the cell migration triggered by purified GST-PRL-3 protein. Conclusion: Our results confirmed the antitumor activity of mAb 12G12 in colorectal adenocarcinoma and provided a new potential targeted therapy of colon cancer.

Multifunctional Theranostic Probe Based on the Pim-1 Kinase Inhibitor with the Function of Tracking pH Fluctuations during Treatment.

Currently, kinase inhibitors have been applied in the diagnosis or treatment of cancer with their unique advantages. It is of great significance to develop some comprehensive theranostic reagents based on kinase inhibitors to improve the performance of reagents for biomedical applications. Besides, tracking changes in the intracellular environment (e.g., pH) during cancer development and drug delivery is also critical for cancer research and treatment. Therefore, it is an urgent desire to design some novel multifunctional reagents based on kinase inhibitor strategies that can trace changes in the microenvironment of cancer cells. In this paper, a multifunctional theranostic reagent based on Pim-1 kinase inhibitor 5-bromobenzofuran-2-carboxylic acid is proposed. The theranostic probe binds to tumor-specific Pim-1 kinase, releases strong fluorescence, and produces cytotoxicity, thus achieving cell screening and killing effects. Furthermore, the probe can specifically target lysosomes and sensitively respond to pH. It can be used to track the pH changes in the intracellular environment under conditions of autophagy and external stimulation, as a visual tool to monitor pH fluctuations during cancer treatment. In conclusion, this simple but multifunctional theranostic reagent proposed in this work is expected to provide a promising method for cancer diagnosis and therapy.

A reversible and ratiometric fluorescent probe based on rhodol derivative with an ESIPT unit for monitoring copper ion content and in situ evaluation of related drugs in cells.

The amount of copper ions in the environment has an immediate effect on ecology and food safety, Menkes syndrome and Wilson's disease cause accumulation and deficiency of copper ions in the body, respectively, and neurodegenerative diseases are also closely related to copper ion levels. However, the current copper ion detection technology has a high cost, complex operation, and other disadvantages. In this study, a ratiometric fluorescent probe (RB-DH) was rationally constructed to detect copper ions by coupling benzothiazole to rhodol derivatives. It can be used to determine copper ion concentrations in water samples, agricultural products, cells, and zebrafish. Importantly, due to the reversible response of RB-DH to copper ions, the fluctuation of intracellular copper ion content during the release of copper ion-related drugs (Copper gluconate and D-penicillamine) was successfully monitored with RB-DH for the first time. This study demonstrates RB-DH's potential application in the evaluation of related drug release effects and serves as a guide for the establishment of portable detection techniques for other important substances.

Effect of Preliminary Treatment by Pulsed Electric Fields and Blanching on the Quality of Fried Sweet Potato Chips.

The effects of pulsed electric fields (PEF) and blanching pretreatments on frying kinetics, oil content, color, texture, acrylamide (AA) content, and microstructure have been investigated in this paper. The total PEF pretreatment duration was tPEF = 0.2 s with an intensity of E = 1 kV/cm; blanching was studied at 85 °C for 5 min. The results demonstrated that pretreatment significantly reduced the moisture ratio and oil content by 25% and 40.33%, respectively. The total color change ΔE value of the pretreated samples was lower than that of the untreated samples. In addition, pretreatment increased the hardness of the sample after frying, and the AA content in the fried samples pretreated with PEF + blanching was reduced by approximately 46.10% (638 µg/kg). Finally, fried sweet potato chips obtained by the combined pretreatment exhibited a smoother and flatter cross-sectional microstructure.

The rational utilization of organelle microenvironment for imaging of lysosomal SO2 with high fidelity.

Nowadays, more and more studies have linked the abnormal expression of active molecules in organelles with the occurrence of diseases, so there is an urgent need to develop tools for detecting active molecules in specific organelles. However, the recognition receptors of most organelle-targeting probes currently developed always remain active, which easily causes them to react with the analyte in the cytoplasm, thus misjudging the role of the analyte in the physiological and pathological processes. Therefore, it is of great significance to develop a new strategy for the design of probes capable of high-fidelity imaging of the analyte in specific organelles. Herein, we propose a new strategy that the activation of recognition receptors that can be triggered by the microenvironment of targeting organelles. Based on this strategy, we develop a novel lysosome-targeting fluorescent probe (Lyso-SO2) for imaging of sulfur dioxide (SO2) with high-fidelity in lysosomes. The inert probe is activated by the acidic environment in the lysosome and then responds quickly (<2 s) and sensitively (LOD = 0.34 µM) to SO2. This paradigm by taking full advantage of the features of the organelle microenvironment provides a promising methodology for developing organelle-targeting probes for high-fidelity imaging.

Descending thoracic aortic dissection after covered stent for adult aortic coarctation: Technical or physiopathologic?

Covered stent graft implantation is currently the most commonly used modality for the management of adult aortic coarctation. Although the risk of descending thoracic aortic dissection after covered stent graft implantation is low, sometimes it may cause serious medical consequences or even death. We report one adult aortic coarctation patient with early postoperative descending thoracic aortic dissection after covered stent graft implantation. The patient underwent second operation of thoracic endovascular aortic reconstruction and was discharged 6 days after the operation. This case is not rare, but we hope that the complete diagnosis and treatment process of this case and discussion pertaining to surgical treatment method and its complications could serve as a reference for clinicians in dealing with such situations.