A case report of the treatment of carotid artery stenosis by staged angioplasty based on intraoperative TCD monitoring.

Objective: Cerebral hyperperfusion syndrome (CHS) is the most severe complication of carotid artery stenting (CAS) or endarterectomy (CEA). Staging treatment can effectively reduce the risk of CHS without increasing the risk of ischemic stroke. The first stage of balloon dilatation is critical for staged treatment. However, the successful criterion of the first stage balloon dilatation is still inconsistent. Method: In the current study presents a case of a 61-year-old male with bilateral internal carotid subtotal occlusion, transcranial doppler (TCD) was used to measure middle cerebral artery (MCA) flow rate on the narrow side of surgery and the results are promising. Result: Intraoperative TCD monitoring is expected to be an evaluation criterion for staged angioplasty for carotid artery stenosis. Conclusion: The approach of blood flow velocity in the brain based on intraoperative measurement of TCD during the treatment of this patient is a new idea for staging treatment in the future.

A dynamic nomogram for predict individual risk of malignant brain edema after endovascular thrombectomy in acute ischemic stroke.

The aim of this study was to develop a dynamic nomogram combining clinical and imaging data to predict malignant brain edema (MBE) after endovascular thrombectomy (EVT) in patients with large vessel occlusion stroke (LVOS). We analyzed the data of LVOS patients receiving EVT at our center from October 2018 to February 2023, and divided a 7:3 ratio into the training cohort and internal validation cohort, and we also prospectively collected patients from another stroke center for external validation. MBE was defined as a midline shift or pineal gland shift > 5 mm, as determined by computed tomography (CT) scans obtained within 7 days after EVT. A nomogram was constructed using logistic regression analysis, and its receiver operating characteristic curve (ROC) and calibration were assessed in three cohorts. A total of 432 patients were enrolled in this study, with 247 in the training cohort, 100 in the internal validation cohort, and 85 in the external validation cohort. MBE occurred in 24% (59) in the training cohort, 16% (16) in the internal validation cohort and 14% (12) in the external validation cohort. After adjusting for various confounding factors, we constructed a nomogram including the clot burden score (CBS), baseline neutrophil count, core infarct volume on CTP before EVT, collateral index, and the number of retrieval attempts. The AUCs of the training cohorts were 0.891 (95% CI 0.840-0.942), the Hosmer-Lemeshow test showed good calibration of the nomogram (P = 0.879). And our nomogram performed well in both internal and external validation data. Our nomogram demonstrates promising potential in identifying patients at elevated risk of MBE following EVT for LVOS.

Roles of Matrix Metalloproteinases 2 and 9 in Uterine Leiomyosarcoma.

BACKGROUND/AIM: Uterine leiomyosarcoma (uLMS) is a rare, highly malignant, and invasive cancer, with early metastasis. Mismatch repair (MMR) proteins and matrix metalloproteinases (MMPs) are associated with the occurrence, proliferation, and invasion of most malignant cancers; however, their abnormal expression in uLMS remains poorly clarified. PATIENTS AND METHODS: Immunohistochemistry was performed to assess MMR protein and MMP2/9 expression as well as Ki67 marker proliferation in benign and malignant uterine smooth muscle tumors. Data from 28 cases of uterine leiomyoma and 31 cases of uLMS were analyzed. RESULTS: Tumor tissues from patients with uLMS had higher expression levels of MMP2 (p<0.001), MMP9 (p<0.05), and Ki67 (p<0.001) than those from patients with uterine leiomyoma; MMR protein expression showed the opposite trend (p<0.05). uLMS proliferation and metastasis correlated positively with MMP2 (p=0.012 and 0.015, respectively) but negatively with MMP9 (p=0.021 and 0.04, respectively). MMR protein expression did not correlate with uLMS proliferation or metastasis (p>0.05). CONCLUSION: Expression levels of MMP2 and MMP9 were upregulated in malignant uLMS tumors when compared with those in benign uterine leiomyoma tumors. Increased MMP2 expression might promote uLMS invasion and migration. MMP9 overexpression might be related to uLMS occurrence; however, it protects against uLMS invasion and metastasis. MMP2 and MMP9 may be potential predictors of uLMS cell proliferation, metastasis, and prognosis. These findings could be helpful in developing new strategies for diagnosing and treating uLMS.

Disulfidptosis and ferroptosis related genes predict prognosis and personalize treatment for hepatocellular carcinoma.

Background: Understanding the interplay between disulfidptosis, ferroptosis, and hepatocellular carcinoma (HCC) could provide valuable insights into the pathogenesis of HCC and potentially identify novel therapeutic targets for the treatment of this deadly disease. This study aimed to identify a prognostic signature for HCC by examining the differential expression of genes related to disulfidptosis and ferroptosis (DRG-FRG), and to assess its clinical applicability. Methods: By integrating 23 disulfidptosis and 259 ferroptosis related genes with HCC messenger RNA (mRNA) expression data from The Cancer Genome Atlas (TCGA), differentially expressed DRG-FRG genes were identified. From these, 11 DRG-FRG genes were selected to construct a risk signature model using least absolute shrinkage and selection operator regression analyses. The prognostic performance of this model was evaluated by Kaplan-Meier survival analysis and time-dependent receiver operating characteristic (ROC) analysis. Subsequently, a nomogram was built by combining the signature with clinical variables. To further delve into the underlying mechanisms, we performed bioinformatics analysis using a variety of databases. Results: A prognostic signature based on 11 DRG-FRG genes effectively categorized HCC patients into high- and low-risk groups, showing a significant survival difference. Even after considering clinical variables, this signature remained an independent prognostic factor. Furthermore, the signature played a role in various critical biological processes and pathways that drive HCC progression. Potential therapeutic benefits could be derived from small molecule drugs targeting NQO1 and SLC7A11. Interestingly, the high-risk group exhibited resistance to several chemotherapeutic drugs, yet showed sensitivity to others when contrasted with the low-risk group. Lastly, the DRG-FRG genes signature had a strong correlation with the tumor immune microenvironment, marked by an elevated expression of immune checkpoint molecules in the high-risk group. Conclusions: The signature based on 11 DRG-FRG genes stands out as a promising prognostic biomarker for HCC. Beyond its predictive value, it sheds light on the intricate crosstalk between DRG-FRG genes and HCC. Importantly, these findings could pave the way for enhanced prognostic prediction, informed treatment decisions, and the advancement of immunotherapy for HCC patients.

Real-world effectiveness of cytology and HPV-based screening strategy in cervical cancer screening: A cross-sectional population-based study in Chengdu, China.

Cervical cancer poses a significant health challenge in developing countries, emphasizing the need for appropriate screening strategies to accelerate the elimination of this disease. This study summarized the results of a large-scale community-based cervical cancer screening program conducted in Chengdu, China, to understand the prevalence of HPV infection and cervical lesions in the population, and to compare the real-world effectiveness of two different screening methods implemented in the program. From January 2021 to December 2022, a total of 363,376 women aged 35-64 years in Chengdu received free screenings. Among these participants, 70.1% received cytology screening and 29.9% received HPV testing combined with 16/18 genotyping and cytology triage. Ultimately, 824 cases of high-grade lesions and cervical cancer were detected, with a total detection rate of cervical cancer and precancerous lesions of 226.8 per 100,000. The follow-up rate of patients with high-grade lesions and above was 98.9%, and the treatment rate was 86.6%. The overall high-risk HPV infection rate was 11.7%, with the HPV 16/18 infection rate of 1.4%. The rate of abnormal cytology results was 2.8%. The attendance rates for colposcopy and histopathology were 71.6% and 86.1%, respectively. By calculating the age-standardized rates to eliminate the different age composition between the two group, the HPV-based screening strategy had a higher rate of primary screening abnormalities (3.4% vs. 2.8%, P<0.001), higher attendance rates of colposcopy (76.5% vs. 68.9%, P<0.001) and histopathological diagnosis (94.1% vs. 78.0%, P<0.001), higher percentage of abnormal colposcopy results (76.0% vs. 44.0%, P<0.001), and higher detection rate of cervical precancerous lesions and cancer (393.1 per 100,000 vs. 156.4 per 100,000, P<0.001) compared to cytology screening. Our study indicates that the combination of HPV testing with 16/18 genotyping and cytology triage has demonstrated superior performance in cervical cancer screening compared to cytology alone in large-scale population.

Label-free fluorescence detection of human 8-oxoguanine DNA glycosylase activity amplified by target-induced rolling circle amplification.

BACKGROUND: Human 8-oxoG DNA glycosylase 1 (hOGG1) is one of the important members of DNA glycosylase for Base excision repair (BER), the abnormal activity of which can lead to the failure of BER and the appearance of various diseases, such as breast cancer, bladder cancer, Parkinson's disease and lung cancer. Therefore, it is important to detect the activity of hOGG1. However, traditional detection methods suffer from time consuming, complicated operation, high false positive results and low sensitivity. Thus, it remains a challenge to develop simple and sensitive hOGG1 analysis strategies to facilitate early diagnosis and treatment of the relative disease. RESULTS: A target-induced rolling circle amplification (TIRCA) strategy for label-free fluorescence detection of hOGG1 activity was proposed with high sensitivity and specificity. The TIRCA strategy was constructed by a hairpin probe (HP) containing 8-oxoG site and a primer probe (PP). In the presence of hOGG1, the HP transformed into dumbbell DNA probe (DDP) after the 8-oxoG site of which was removed. Then the DDP formed closed circular dumbbell probe (CCDP) by ligase. CCDP could be used as amplification template of RCA to trigger RCA. The RCA products containing repeated G4 sequences could combine with ThT to produce enhanced fluorescence, achieving label-free fluorescence sensing of hOGG1. Given the high amplification efficiency of RCA and the high fluorescence quantum yield of the G4/ThT, the proposed TIRCA achieved highly sensitive measurement of hOGG1 activity with a detection limit of 0.00143 U/mL. The TIRCA strategy also exhibited excellent specificity for hOGG1 analysis over other interference enzymes. SIGNIFICANCE: This novel TIRCA strategy demonstrates high sensitivity and high specificity for the detection of hOGG1, which has also been successfully used for the screening of inhibitors and the analysis of hOGG1 in real samples. We believe that this TIRCA strategy provides new insight into the use of the isothermal nucleic acid amplification as a useful tool for hOGG1 detection and will play an important role in disease early diagnosis and treatment.

A binary system based DNA tetrahedron and fluorogenic RNA aptamers for highly specific and label-free mRNA imaging in living cells.

Developing simple, rapid and specific mRNA imaging strategy plays an important role in the early diagnosis of cancer and the new drugs development. Herein, we have established a novel binary system based DNA tetrahedron and fluorogenic RNA aptamers for highly specific and label-free mRNA imaging in living cells. This developed system consisted of tetrahedron probe A (TPA) and tetrahedron probe B (TPB). TK1 mRNA was chosen as the study model. After TPA and TPB enter into the live cells, the TK1 mRNA induces TPA and TPB to approach and activate the fluorescent aptamer, resulting in enhanced fluorescent signal in the presence of small molecules of DFHBI-1T. By this design, the high specificity label-free detection of nucleic acids was achieved with a detection limit of 1.34 nM. Confocal fluorescence imaging experiments had proved that this strategy could effectively distinguish the TK1 mRNA expression level between normal cell and cancer cell. The developed method is expected to provide a new tool for early diagnosis of diseases and new drug development.

Endogenous Enzyme-Powered DNA Nanomotor Operating in Living Cells for microRNA Imaging.

Accurate and specific imaging of low-abundance microRNA (miRNA) in living cells is extremely important for disease diagnosis and monitoring of disease progression. DNA nanomotors have shown great potential for imaging molecules of interest in living cells. However, inappropriate driving forces and complex design and operation procedures have hindered their further application. Here, we proposed an endogenous enzyme-powered DNA nanomotor (EEPDN), which employs an endogenous APE1 enzyme as fuel to execute repetitive cycles of motion for miRNA imaging in living cells. The whole motor system is constructed based on gold nanoparticles without other auxiliary additives. Due to the high efficiency of APE1, this EEPDN system has achieved highly sensitive miRNA imaging in living cells within 1.5 h. This strategy was also successfully used to differentiate the expression of specific miRNA between tumor cells and normal cells, demonstrating a high tumor cell selectivity. This strategy can promote the development of novel nanomotors and is expected to be a perfect intracellular molecular imaging tool for biological and medical applications.

The effects of high plasma levels of Aß1-42 on mononuclear macrophage in mouse models of Alzheimer's disease.

More and more evidences are proving that microglia play a crucial role in the pathogenesis of Alzheimer's disease (AD) and the plasma Aß1-42 levels significantly increased 15 years before the onset of dominantly inherited AD. However, the effects of high plasma levels of Aß1-42 on mononuclear macrophage, the peripheral counterparts of microglia, remain unclear. In the present study, we used APP/PS1 transgenic (Tg) mice and a parabiotic model of wild type (Wt) mice and Tg mice (Parabiotic Wt-Tg, Pa (Wt-Tg)) to investigate the effects of high plasma levels of Aß1-42 on peripheral mononuclear macrophage. Our results showed that in the early stage of Tg mice (7 months) and Pa (Wt-Tg) mice (4 months), the proportions of pro-inflammatory macrophages in peritoneal cavity, myeloid derived suppressor cells (MDSCs) in spleen, granulocyte-monocyte progenitors (GMPs) in bone marrow, and the plasma levels of interleukin-6 (IL-6) were significantly decreased. While the proportions of pro-inflammatory macrophages, MDSCs, GMPs, and the plasma levels of IL-6 and tumor necrosis factor (TNF)-α, as well as the numbers of bone marrow-derived macrophages (BMDMs) in mice brain were increased in the late stage of Tg mice (11 months) and Pa (Wt-Tg) mice (8 months). In addition, the proportions of monocytes in spleen and the proliferation of bone marrow cells (BMCs) were enhanced consistently, and the phagocytic function of macrophages kept stably after high plasma levels of Aß1-42 sustaining stimulation. These results demonstrated that high plasma levels of Aß1-42 play a biphasic regulating role at different stages of the disease, namely inhibiting effects on peripheral pro-inflammatory macrophages in the early stage of AD model, while promoting effects in the late stage of AD model. The mechanism behind this may be associated with their effects on MDSCs in spleen and myeloid progenitor cells in bone marrow. Therefore, intervening the effects of plasma Aß1-42 on pro-inflammatory macrophages might offer a new therapeutic approach to AD.

Targeting of Head and Neck Cancer by Radioiodinated CLR1404 in Murine Xenograft Tumor Models with Partial Volume Corrected Theranostic Dosimetry.

Background: Delivery of radiotherapeutic dose to recurrent head and neck cancer (HNC) is primarily limited by locoregional toxicity in conventional radiotherapy. As such, HNC patients stand to benefit from the conformal targeting of primary and remnant disease achievable with radiopharmaceutical therapies. In this study, the authors investigated the tumor targeting capacity of 131I-CLR1404 (iopofosine I-131) in various HNC xenograft mouse models and the impact of partial volume correction (PVC) on theranostic dosimetry based on 124I-CLR1404 (CLR 124) positron emission tomography (PET)/computed tomography (CT) imaging. Methods: Mice bearing flank tumor xenograft models of HNC (six murine cell line and six human patient derived) were intravenously administered 6.5-9.1 MBq of CLR 124 and imaged five times over the course of 6 d using microPET/CT. In vivo tumor uptake of CLR 124 was assessed and PVC for 124I was applied using a novel preclinical phantom. Using subject-specific theranostic dosimetry estimations for iopofosine I-131 based on CLR 124 imaging, a discrete radiation dose escalation study (2, 4, 6, and 8 Gy) was performed to evaluate tumor growth response to iopofosine I-131 relative to a single fraction of external beam radiation therapy (6 Gy). Results: PET imaging demonstrated consistent tumor selective uptake and retention of CLR 124 across all HNC xenograft models. Peak uptake of 4.4% ± 0.8% and 4.2% ± 0.4% was observed in squamous cell carcinoma-22B and UW-13, respectively. PVC application increased uptake measures by 47%-188% and reduced absolute differences between in vivo and ex vivo uptake measurements from 3.3% to 1.0 percent injected activity per gram. Tumor dosimetry averaged over all HNC models was 0.85 ± 0.27 Gy/MBq (1.58 ± 0.46 Gy/MBq with PVC). Therapeutic iopofosine I-131 studies demonstrated a variable, but linear relationship between iopofosine I-131 radiation dose and tumor growth delay (p < 0.05). Conclusions: Iopofosine I-131 demonstrated tumoricidal capacity in preclinical HNC tumor models and the theranostic pairing with CLR 124 presents a promising new treatment approach for personalizing administration of iopofosine I-131.

The effectiveness of pay-it-forward in addressing HPV vaccine delay and increasing uptake among 15-18-year-old adolescent girls compared to user-paid vaccination: a study protocol for a two-arm randomized controlled trial in China.

BACKGROUND: Human papillomavirus (HPV) vaccination could prevent cervical and other HPV-associated cancers attributable to vaccine-associated HPV types. However, HPV vaccination coverage among women aged 9-18 years old is low in China. Common barriers include poor financial affordability, minimal public engagement, and low confidence in domestically produced HPV vaccines. Pay-it-forward offers an individual a free or subsidized service then an opportunity to voluntarily donate and/or create a postcard message to support future people. This study aims to assess the effectiveness of pay-it-forward as compared to standard-of-care self-paid vaccination to improve HPV vaccine uptake among adolescent girls aged 15-18 years, who are left out in the current pilot free HPV vaccination task force in some parts of China. METHODS: This is a two-arm randomized controlled trial in Chengdu, China. Eligible adolescent girls (via caregivers) will be randomly selected and recruited through four community health centers (one in the most developed urban areas, one in higher middle-income and one in lower middle-income suburban areas, and one in the least developed rural areas) using the resident registration list. A total of 320 participants will be randomized into two study arms (user-paid versus pay-it-forward vaccination) in a 1:1 ratio. The intervention assignment will be blinded to recruiters and participants using envelop concealment until the research assistants open the envelop to determine which treatment to deliver to each individual. The primary outcome of the study will be HPV vaccine uptake by administrative data. Secondary outcomes include costs, vaccine hesitancy, and the completion rates of the 3-dose HPV vaccination series. DISCUSSION: This study will investigate an innovative pay-it-forward strategy's effectiveness and economic costs to improve HPV vaccination among 15-18-year-old adolescent girls. Study findings will have implications for increasing HPV vaccine uptake in places where HPV vaccines are provided for a fee. TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR), ChiCTR2200055542. Registered on 11 January 2022.

Overexpression of the FERONIA receptor kinase MdMRLK2 confers apple drought tolerance by regulating energy metabolism and free amino acids production.

Drought is a major abiotic stress limiting the growth and production of apple trees worldwide. The receptor-like kinase FERONIA is involved in plant growth, development and stress responses; however, the function of FERONIA in apple under drought stress remains unclear. Here, the FERONIA receptor kinase gene MdMRLK2 from apple (Malus domestica) was shown to encode a plasma membrane-localized transmembrane protein and was significantly induced by abscisic acid and drought treatments. 35S::MdMRLK2 apple plants showed less photosystem damage and higher photosynthetic rates compared with wild-type (WT) plants, after withholding water for 7 days. 35S::MdMRLK2 apple plants also had enhanced energy levels, activated caspase activity and more free amino acids, than the WT, under drought conditions. By performing yeast two-hybrid screening, glyceraldehyde-3-phosphate dehydrogenase and MdCYS4, a member of cystatin, were identified as MdMRLK2 interaction partners. Moreover, under drought conditions, the 35S::MdMRLK2 apple plants were characterized by higher abscisic acid (ABA) content. Overall, these findings demonstrated that MdMRLK2 regulates apple drought tolerance, probably via regulating levels of energetic matters, free amino acids and ABA.

Knockout of a papain-like cysteine protease gene OCP enhances blast resistance in rice.

Papain-like cysteine proteases (PLCPs) play an important role in the immune response of plants. In Arabidopsis, several homologous genes are known to be involved in defending against pathogens. However, the effects of PLCPs on diseases that afflict rice are largely unknown. In this study, we show that a PLCP, an oryzain alpha chain precursor (OCP), the ortholog of the Arabidopsis protease RD21 (responsive to dehydration 21), participates in regulating resistance to blast disease with a shorter lesion length characterizing the knockout lines (ocp-ko), generated via CRISPR/Cas9 technology. OCP was expressed in all rice tissues and mainly located in the cytoplasm. We prove that OCP, featuring cysteine protease activity, interacts with OsRACK1A (receptor for activated C kinase 1) and OsSNAP32 (synaptosome-associated protein of 32 kD) physically in vitro and in vivo, and they co-locate in the rice cytoplasm but cannot form a ternary complex. Many genes related to plant immunity were enriched in the ocp-ko1 line whose expression levels changed significantly. The expression of jasmonic acid (JA) and ethylene (ET) biosynthesis and regulatory genes were up-regulated, while that of auxin efflux transporters was down-regulated in ocp-ko1. Therefore, OCP negatively regulates blast resistance in rice by interacting with OsRACK1A or OsSNAP32 and influencing the expression profiles of many resistance-related genes. Moreover, OCP might be the cornerstone of blast resistance by suppressing the activation of JA and ET signaling pathways as well as promoting auxin signaling pathways. Our research provides a comprehensive resource of PLCPs for rice plants in defense against pathogens that is also of potential breeding value.

Light-Controlled Recruitable Hybridization Chain Reaction on Exosome Vehicles for Highly Sensitive MicroRNA Imaging in Living Cells.

Sensitive imaging of intracellular microRNA (miRNA) in living cells is of great significance. Isothermal hybridization chain reaction (HCR)-based methods, although have been widely used to monitor intracellular low-abundance miRNA, are still subjected to the challenges of limited signal amplification efficiency and compromised imaging resolution. In this work, we design a light-controlled recruitable HCR (LCR-HCR) strategy that enables us to well overcome these limitations. Exosomes as delivery and recruitment vehicles are modified with three cholesterol-modified hairpins (H1, H2, and H3), in which H1 is for anchoring target miRNA and H2 and H3 with photocleavable linkers (PC-linkers) are designed for spatiotemporal HCR. By controllably releasing probes with high local concentrations to efficiently trigger HCR and further recruiting the generated double-stranded DNA (dsDNA) polymers instead of dispersion in the cytoplasm, the LCR-HCR method can significantly improve the imaging contrast by confining all of the reactants on exosome vehicles. For a proof-of-concept demonstration, the miR-21 was analyzed by LCR-HCR with a limit of detection (LOD) down to 3.3 pM (corresponding to 165 amol per 50 µL) in vitro and four times higher response than traditional HCR in vivo. In general, the LCR-HCR method provides a powerful tool for sensitive miRNA imaging in living cells and cancer diagnosis.

The apple FERONIA receptor-like kinase MdMRLK2 negatively regulates Valsa canker resistance by suppressing defence responses and hypersensitive reaction.

Valsa canker, caused by the fungus Valsa mali, is one of the most destructive diseases of apple trees in China and other East Asian countries. The plant receptor-like kinase FERONIA is involved in plant cell growth, development, and immunity. However, little is known about the function of FERONIA in apple defence against V. mali. In this study, we found that MdMRLK2 was highly induced by V. mali in twigs of V. mali-susceptible Malus mellana but not in those of the resistant species Malus yunnaensis. 35S:MdMRLK2 apple plants showed compromised resistance relative to wild-type (WT) plants. Further analyses indicated that 35S:MdMRLK2 apple plants had enhanced abscisic acid (ABA) levels and reduced salicylic acid (SA) levels relative to the WT on V. mali infection. MdMRLK2 overexpression also suppressed polyphenol accumulation and inhibited the activities of phenylalanine ammonia-lyase (PAL), ß-1,3-glucanase (GLU), and chitinase (CHT) during V. mali infection. Moreover, MdMRLK2 interacted with MdHIR1, a hypersensitive-induced response protein, and suppressed the MdHIR1-mediated hypersensitive reaction (HR), probably by impairing MdHIR1 self-interaction. Collectively, these findings demonstrate that overexpression of MdMRLK2 compromises Valsa canker resistance, probably by (a) altering ABA and SA levels, (b) suppressing polyphenol accumulation, (c) inhibiting PAL, GLU, and CHT activities, and (d) blocking MdHIR1-mediated HR by disrupting MdHIR1 self-interaction.

Cancer cell identification by facile imaging of intracellular reductive substances with fluorescent nanosensor.

Ascorbic acid (AA) and glutathione (GSH), the most abundant intracellular reductive substances, have been widely used as biomarkers for cancer cells identification. The current methods relying on imaging of AA or GSH alone to identify cancer cells may cause systematic errors, since a mutual conversion relationship exists between AA and GSH. In this work, we propose a fluorescent nanosensor for the simultaneous imaging of intracellular reductive substances including AA and GSH. Biocompatible fluorescent silicon nanoparticles (SiNPs) with rich surface amine and carboxyl groups were synthesized. The fluorescence of the SiNP was initially quenched by chelation of Fe3+ ions, forming SiNP/Fe3+ complex as the fluorescent nanosensor. Upon the redox reaction with reductive substances, the nanosensor showed sensitively fluorescent recovery. Moreover, benefited from the efficient cellular uptake of the SiNP/Fe3+ and the overexpressed intracellular reductive substances in cancer cells, the fluorescent nanosensor was used to accurately identify the human breast carcinoma (MCF-7) cells from normal mammary epithelial (MCF-10A) cells by imaging of intracellular AA and GSH simultaneously. This strategy would be promising in imaging-guided precision cancer diagnosis.

Nuclear factor kappa B inhibitor suppresses experimental autoimmune neuritis in mice via declining macrophages polarization to M1 type.

Guillain-Barré syndrome (GBS) is an acute inflammatory and immune-mediated demyelinating disease of the peripheral nervous system (PNS). Macrophages play a central role in its animal model, experimental autoimmune neuritis (EAN), which has been well accepted. Additionally, nuclear factor (NF)-κB inhibitors have been used to treat cancers and have shown beneficial effects. Here, we investigated the therapeutic effect of M2 macrophage and the NF-κB pathway's correlation with macrophage activation in EAN in C57BL/6 mice. We demonstrate that M2 macrophage transfusion could alleviate the clinical symptoms of EAN by reducing the proportion of M1 macrophage in the peak period, inhibiting the phosphorylation of NF-κB p65. The NF-κB inhibitor (BAY-11-7082) could alleviate the clinical symptoms of EAN and shorten the duration of symptoms by reducing the proportion of M1 macrophages and the expression of proinflammatory cytokines. Consequently, BAY-11-7082 exhibits strong potential as a therapeutic strategy for ameliorating EAN by influencing the balance of M1/M2 macrophages and inflammatory cytokines.

Fluorescence on-off-on with small and charge-tunable nanoparticles enables highly sensitive intracellular microRNA imaging in living cells.

Nanomaterial-based on-off-on fluorescence sensing strategies are significant particularly in intracellular nucleic acids imaging assay. There still remains challenge to rationally balance fluorescence quenching efficiency and recovery dynamics. We assume that the performance of on-off-on fluorescence sensing strategy can be fundamentally improved on small zero-dimensional (0D) nanomaterial with precisely modulated surface charge. For a proof-of-concept demonstration, silicon nanoparticle (SiNP) with ~4 nm was synthesized and used as the quencher model, of which the surface charge density was modulated by modification of triphenylphosphonium (TPP). The influence of particle size, surface charge and charge density of the nanomaterials on sensing performance was systematically investigated. The strategy showed a low limit of detection (LOD) as 26 pM for target model miR-494, which is one of the lowest in nanomaterial-based on-off-on sensing platforms. And the LOD is even comparable to amplification-based methods in a greatly shortened assay time (2.5 h). The miR-494 expresses in cancerous and normal living cells of human cervical carcinoma (HeLa), human lung carcinoma (A549), human breast cancer (MCF-7), and normal human mammary epithelial (MCF-10A) cells were imaged and localized with significantly improved sensitivity and specificity. These excellent performances insure it a promising candidate as convenient and non-enzymatic sensing platform for miRNA-associated disease detection and early diagnosis.

Dietary Inflammatory Index and Epithelial Ovarian Cancer in Southern Chinese Women: A Case-Control Study.

The association between inflammatory properties of diet and ovarian cancer risk has been investigated in some Western populations. However, little evidence is available from Asian women whose ovarian cancer incidence rates are low and dietary and lifestyle patterns are very different from their Western counterparts. We aimed to examine whether more pro-inflammatory diets, as indicated by higher dietary inflammatory index (DII®) scores, are associated with increased odds of epithelial ovarian cancer in southern China. A case-control study was conducted during 2006-2008 in Guangzhou, Guangdong Province. Energy-adjusted DII (E-DII) scores were calculated based on dietary intake assessed by a validated food frequency questionnaire administered to 500 incident epithelial ovarian cancer patients and 500 hospital-based controls. Logistic regression models were used to assess the relationship between E-DII scores and odds of ovarian cancer. Positive associations were observed between higher E-DII scores and ovarian cancer odds, using both continuous DII scores (odds ratio (OR) 1.87; 95% confidence interval (CI) 1.65, 2.13) and by DII tertiles (ORtertile3vs1 7.04, 95% CI: 4.70, 10.54, p for trend < 0.001). Likewise, a more pro-inflammatory diet was associated with a higher chance of serous and mucinous ovarian tumors. Our results suggest that a pro-inflammatory diet was associated with increased odds of developing epithelial ovarian cancer in southern Chinese women. The findings add to epidemiological evidence for the role of dietary inflammatory potential in ovarian cancer development.

EBNA2-deleted Epstein-Barr virus (EBV) isolate, P3HR1, causes Hodgkin-like lymphomas and diffuse large B cell lymphomas with type II and Wp-restricted latency types in humanized mice.

EBV transforms B cells in vitro and causes human B-cell lymphomas including classical Hodgkin lymphoma (CHL), Burkitt lymphoma (BL) and diffuse large B-cell lymphoma (DLBCL). The EBV latency protein, EBNA2, transcriptionally activates the promoters of all latent viral protein-coding genes expressed in type III EBV latency and is essential for EBV's ability to transform B cells in vitro. However, EBNA2 is not expressed in EBV-infected CHLs and BLs in humans. EBV-positive CHLs have type II latency and are largely driven by the EBV LMP1/LMP2A proteins, while EBV-positive BLs, which usually have type I latency are largely driven by c-Myc translocations, and only express the EBNA1 protein and viral non-coding RNAs. Approximately 15% of human BLs contain naturally occurring EBNA2-deleted viruses that support a form of viral latency known as Wp-restricted (expressing the EBNA-LP, EBNA3A/3B/3C, EBNA1 and BHRF1 proteins), but whether Wp-restricted latency and/or EBNA2-deleted EBV can induce lymphomas in humanized mice, or in the absence of c-Myc translocations, is unknown. Here we show that a naturally occurring EBNA2-deleted EBV strain (P3HR1) isolated from a human BL induces EBV-positive B-cell lymphomas in a subset of infected cord blood-humanized (CBH) mice. Furthermore, we find that P3HR1-infected lymphoma cells support two different viral latency types and phenotypes that are mutually exclusive: 1) Large (often multinucleated), CD30-positive, CD45-negative cells reminiscent of the Reed-Sternberg (RS) cells in CHL that express high levels of LMP1 but not EBNA-LP (consistent with type II viral latency); and 2) smaller monomorphic CD30-negative DLBCL-like cells that express EBNA-LP and EBNA3A but not LMP1 (consistent with Wp-restricted latency). These results reveal that EBNA2 is not absolutely required for EBV to form tumors in CBH mice and suggest that P3HR1 virus can be used to model EBV positive lymphomas with both Wp-restricted and type II latency in vivo.