RNA modifications in pulmonary diseases.

Threatening public health, pulmonary disease (PD) encompasses diverse lung injuries like chronic obstructive PD, pulmonary fibrosis, asthma, pulmonary infections due to pathogen invasion, and fatal lung cancer. The crucial involvement of RNA epigenetic modifications in PD pathogenesis is underscored by robust evidence. These modifications not only shape cell fates but also finely modulate the expression of genes linked to disease progression, suggesting their utility as biomarkers and targets for therapeutic strategies. The critical RNA modifications implicated in PDs are summarized in this review, including N6-methylation of adenosine, N1-methylation of adenosine, 5-methylcytosine, pseudouridine (5-ribosyl uracil), 7-methylguanosine, and adenosine to inosine editing, along with relevant regulatory mechanisms. By shedding light on the pathology of PDs, these summaries could spur the identification of new biomarkers and therapeutic strategies, ultimately paving the way for early PD diagnosis and treatment innovation.

Type III interferon exerts thymic stromal lymphopoietin in mediating adaptive antiviral immune response.

Previously, it was believed that type III interferon (IFN-III) has functions similar to those of type I interferon (IFN-I). However, recently, emerging findings have increasingly indicated the non-redundant role of IFN-III in innate antiviral immune responses. Still, the regulatory activity of IFN-III in adaptive immune response has not been clearly reported yet due to the low expression of IFN-III receptors on most immune cells. In the present study, we reviewed the adjuvant, antiviral, antitumor, and disease-moderating activities of IFN-III in adaptive immunity; moreover, we further elucidated the mechanisms of IFN-III in mediating the adaptive antiviral immune response in a thymic stromal lymphopoietin (TSLP)-dependent manner, a pleiotropic cytokine involved in mucosal adaptive immunity. Research has shown that IFN-III can enhance the antiviral immunogenic response in mouse species by activating germinal center B (GC B) cell responses after stimulating TSLP production by microfold (M) cells, while in human species, TSLP exerts OX40L for regulating GC B cell immune responses, which may also depend on IFN-III. In conclusion, our review highlights the unique role of the IFN-III/TSLP axis in mediating host adaptive immunity, which is mechanically different from IFN-I. Therefore, the IFN-III/TSLP axis may provide novel insights for clinical immunotherapy.

Translation and validation of the Chinese version of the orthorexia nervosa assessment questionnaires among college students.

PURPOSE: The main objective of the study was to translate, validate, and compare the Chinese ORTO scales (ORTO-15 and ORTO-R). The secondary objective was to assess factors that may be related with risk of orthorexia nervosa (ON). METHODS: Two cross-sectional surveys were conducted on March-to-June 2021 for ORTO-15 and April 2022 for ORTO-R. ORTO questionnaires were translated into Chinese using the forward-backward-forward method. Exploratory factor analysis (EFA), discriminant validity and confirmatory factor analysis (CFA) were used to examine the construct validity of the questionnaires. The internal consistency was assessed using the Cronbach alpha coefficient and the test-retest reliability. Multivariate linear regression analysis was used to explore potential factors related with ON scores. RESULTS: Totally, 1289 and 1084 eligible participants were included for assessment of ORTO-15 and ORTO-R, with the mean age of 20.9 ± 2.0 years and 21.0 ± 2.3 years. The internal consistency of Chinese ORTO-15 scale and ORTO-R scale were both satisfactory (α = 0.79, ICC = 0.79; α = 0.77, ICC = 0.82). However, all ORTO-15 models showed a poor fit using CFA whereas the ORTO-R was characterized by acceptable goodness-of-fit. Multivariate linear regression indicated that physical activities and mental disorders were positively associated with ON risk assessed by both ORTO-R and ORTO-15. CONCLUSION: The Chinese ORTO-R scale was a more reliable tool to screen for ON tendencies than the Chinese version of ORTO-15. Mental disorders and physical activities might be associated with the increased ON risk. LEVEL OF EVIDENCE: Level V (descriptive cross-sectional study).

Global, Regional, and National Burden of Cancer in Children Younger Than 5 Years, 1990-2019: Analysis of the Global Burden of Disease Study 2019.

Objectives: To quantify the burden and variation trends of cancers in children under 5 years at the global, regional, and national levels from 1990 to 2019. Methods: Epidemiological data for children under 5 years who were diagnosed with any one childhood cancer were obtained from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) from 1990 to 2019. The outcomes were the absolute numbers and rates of incidence, prevalence, mortality, and disability-adjusted life-years (DALYs) for different types of cancer. Results: In 2019, 8,774,979.1 incident cases (95% uncertainty interval [UI]: 6,243,599.2 to11,737,568.5) and 8,956,583.8 (6,446,323.9 to 12,364,520.8) prevalent cases of cancer in children under 5 years were identified worldwide; these cancers resulted in 44,451.6 (36,198.7 to 53,905.9) deaths and 3,918,014.8 (3,196,454.9 to 4,751,304.2) DALYs. From 1990 to 2019, although the numbers of incident and prevalent cases only decreased by -4.6% (-7.0 to -2.2) and -8.3% (-12.6 to -3.4), respectively, the numbers of deaths and DALYs clearly declined by -47.8% (-60.7 to -26.4) and -47.7% (-60.7 to -26.2), respectively. In 2019, the middle sociodemographic index (SDI) regions had the highest incidence and prevalence, whereas the low SDI regions had the most mortality and DALYs. Although all of the SDI regions displayed a steady drop in deaths and DALYs between 1990 and 2019, the low-middle and low SDI regions showed increasing trends of incidence and prevalence. Leukemia remained the most common cancer globally in 2019. From 1990 to 2019, the burdens of leukemia, liver cancer, and Hodgkin's lymphoma declined, whereas the incidence and prevalence of other cancers grew, particularly testicular cancer. Conclusions: The global childhood cancer burden in young children has been steadily decreasing over the past three decades. However, the burdens and other characteristics have varied across different regions and types of cancers. This highlights the need to reorient current treatment strategies and establish effective prevention methods to reduce the global burden of childhood cancer.

The global burden and associated factors of ovarian cancer in 1990-2019: findings from the Global Burden of Disease Study 2019.

BACKGROUND: Ovarian cancer (OC) is a major cause of cancer-related deaths among women. The aim of this study was to estimate and report data on the current burden of ovarian cancer worldwide over the past 30 years. METHOD: Based on the data provided by GBD 2019, we collected and interpreted the disease data of ovarian cancer by incidence, mortality, disability-adjusted life-years (DALYs), and used corresponding age-standardized rates as indicators. Also, we categorized the data by attributed risk factors and captured deaths due to high fasting plasma glucose, occupational exposure to asbestos and high body-mass index, respectively. All outcomes in the study were reported using mean values and corresponding 95% uncertainty intervals (95% UI). RESULTS: Globally, there were 294422 (260649 to 329727) incident cases in 2019, and the number of deaths and DALYs were 198412 (175357 to 217665) and 5.36 million (4.69 to 5.95). The overall burden was on the rise, with a percentage change of 107.8% (76.1 to 135.7%) for new cases, 103.8% (75.7 to 126.4%) for deaths and 96.1% (65.0 to 120.5%) for DALYs. Whereas the age-standardized rates kept stable during 1990-2019. The burden of ovarian cancer increased with age. and showed a totally different trends among SDI regions. Although high SDI region had the declining rates, the burden of ovarian cancer remained stable in high-middle and low SDI regions, and the middle and low-middle SDI areas showed increasing trends. High fasting plasma glucose was estimated to be the most important attributable risk factor for ovarian cancer deaths globally, with a percentage change of deaths of 7.9% (1.6 to 18.3%), followed by occupational exposure to asbestos and high body mass index. CONCLUSIONS: Although the age-standardized rates of ovarian cancer didn't significantly change at the global level, the burden still increased, especially in areas on the lower end of the SDI range. Also, the disease burden due to different attributable risk factors showed heterogeneous, and it became more severe with age.

Aggregation-induced emission luminogens for image-guided surgery in non-human primates.

During the past two decades, aggregation-induced emission luminogens (AIEgens) have been intensively exploited for biological and biomedical applications. Although a series of investigations have been performed in non-primate animal models, there is few pilot studies in non-human primate animal models, strongly hindering the clinical translation of AIE luminogens (AIEgens). Herein, we present a systemic and multifaceted demonstration of an optical imaging-guided surgical operation via AIEgens from small animals (e.g., mice and rabbits) to rhesus macaque, the typical non-human primate animal model. Specifically, the folic conjugated-AIE luminogen (folic-AIEgen) generates strong and stable fluorescence for the detection and surgical excision of sentinel lymph nodes (SLNs). Moreover, with the superior tumor/normal tissue ratio and rapid tumor accumulation, folic-AIEgen successfully images and guides the precise resection of invisible cancerous metastases. Taken together, the presented strategies of folic-AIEgen based fluorescence intraoperative imaging and visualization-guided surgery show potential for clinical applications.

Calcium phosphate engineered photosynthetic microalgae to combat hypoxic-tumor by in-situ modulating hypoxia and cascade radio-phototherapy.

Rationale: Hypoxia is one of the crucial restrictions in cancer radiotherapy (RT), which leads to the hypoxia-associated radioresistance of tumor cells and may result in the sharp decline in therapeutic efficacy. Methods: Herein, living photosynthetic microalgae (Chlorella vulgaris, C. vulgaris), were used as oxygenators, for in situ oxygen generation to relieve tumor hypoxia. We engineered the surface of C. vulgaris (CV) cells with calcium phosphate (CaP) shell by biomineralization, to form a biomimetic system (CV@CaP) for efficient tumor delivery and in-situ active photosynthetic oxygenation reaction in tumor. Results: After intravenous injection into tumor-bearing mice, CV@CaP could remarkably alleviate tumor hypoxia by continuous oxygen generation, thereby achieving enhanced radiotherapeutic effect. Furthermore, a cascade phototherapy could be fulfilled by the chlorophyll released from photosynthetic microalgae combined thermal effects under 650 nm laser irradiation. The feasibility of CV@CaP-mediated combinational treatment was finally validated in an orthotropic breast cancer mouse model, revealing its prominent anti-tumor and anti-metastasis efficacy in hypoxic-tumor management. More importantly, the engineered photosynthetic microalgae exhibited excellent fluorescence and photoacoustic imaging properties, allowing the self-monitoring of tumor therapy and tumor microenvironment. Conclusions: Our studies of this photosynthetic microsystem open up a new dimension for solving the radioresistance issue of hypoxic tumors.

A comparative genomics analysis of lung adenocarcinoma for Chinese population by using panel of recurrent mutations.

Previous studies have demonstrated that Chinese lung adenocarcinoma (LUAD) patients have unique genetic characteristics, however, the specific genomic features relating to the development and treatment of LUAD in the Chinese population are not fully understood. Here, we applied the ultra-deep targeted sequencing to 66 Chinese LUAD samples, accompanied by comparative analysis with 162 Caucasian LUAD in The Cancer Genome Atlas. We focused on the 68 recurrently mutated genes and results revealed that the panel-based tumor mutational burden (pTMB) is significantly higher in the Chinese LUAD ( P=0.0017). Additionally, the percentage of smoking-associated C>A transversion is significantly lower in Chinese LUAD (15.5% vs. 39.7%, P=5.69×10 -27), while C>T transition is more frequent in Chinese LUAD (35.8% vs. 25.7%, P=2.67×10 -5), which indicated the ethnic difference in mutation types. Notably, novel driver genes ( GNAS and JAK1) that are peculiar to Chinese LUAD were identified, and a more convergent distribution of mutations was observed in the Chinese cohort ( P=0.012) compared with scattered mutations in Caucasian LUAD. Our results present a distinct genomic profile of Chinese LUAD compared to Caucasians LUAD and elucidate the ethnic difference in mutation distribution besides the type and rate.

Biomineralized Biohybrid Algae for Tumor Hypoxia Modulation and Cascade Radio-Photodynamic Therapy.

Biomineralization of biomaterials has shown extraordinary potential in cancer treatment, but the exploration of their in vivo applications is still insufficient. Here, we report a biohybrid microalgae system using a biomineralization approach to improve their biocompatibility, while keeping their living activities for radiation and photodynamic synergistic therapy in breast cancer. The biohybrid algae (Algae@SiO2) synthesized by a one-step biomimetic silicification method could significantly enhance their cytotoxicity and tolerance, improving the living activity in the tumor area. The innate chlorophyll and unique optical property make Algae@SiO2 possess dual imaging ability, namely, photoacoustic imaging and fluorescence imaging. Algae@SiO2 accumulated in tumor sites could generate oxygen in situ by external light-mediated photosynthesis, relieve tumor hypoxia, and then enhance the efficiency of radiation therapy. As a natural photosensitizer, the released chlorophyll from Algae@SiO2 could provide reactive oxygen species to kill the cancer cells for the cascaded photodynamic therapy. The significant suppression of tumor growth in the mice bearing 4T1 tumor successfully demonstrates the promising anti-tumor effect of the Algae@SiO2-mediated synergistic therapy. Our results show that biohybrid algae, integrated with PAI/FI dual imaging, radiosensitization, and cascaded photothermal therapy, is a promising multifunctional efficient biosystem for cancer treatment.

H2 S-Scavenged and Activated Iron Oxide-Hydroxide Nanospindles for MRI-Guided Photothermal Therapy and Ferroptosis in Colon Cancer.

Overproduced hydrogen sulfide (H2 S) is of vital importance for the progress of colon cancer and promotes cancer cellular proliferation. Devising pharmacological nanomaterials for tumor-specific H2 S activation will be significant for precise colon cancer treatment. Herein, a biocompatible fusiform iron oxide-hydroxide nanospindles (FeOOH NSs) nanosystem for magnetic resonance imaging (MRI), ferroptosis, and H2 S based cascade reaction-enhanced combinational colon cancer treatment is developed. The FeOOH NSs can effectively scavenge endogenous H2 S via the reduction reaction to prohibit the growth of CT26 colon cancer. The cascade produced FeS driven by overexpressed H2 S exhibits near-infrared-triggered photothermal therapy capability and Fe2+ -mediated ferroptosis functionality. Meanwhile, the as-prepared FeOOH NSs can light up tumor tissues as a potent MRI contrast agent. Additionally, FeOOH NSs present desirable biosafety in a murine model for up to three months and avoid any long-term toxicity. Furthermore, it is found that these H2 S-responsible nanotheranostics do not cause any cure effects on other cancer types, such as 4T1 breast cancer. Overall, the findings illustrate that the biocompatible FeOOH NSs can be successfully employed as a theranostic for specifically treating colon cancer, which may promote the clinical translation and development of H2 S-responsive nanoplatforms.

Mild temperature photothermal assisted anti-bacterial and anti-inflammatory nanosystem for synergistic treatment of post-cataract surgery endophthalmitis.

Rationale: Endophthalmitis, which is one of the severest complications of cataract surgeries, can seriously threaten vision and even lead to irreversible blindness owing to its complicated microenvironment, including both local bacterial infection and severe inflammation. It is urgent to develop a comprehensive treatment for both anti-bacterial and anti-inflammatory effects. Methods: Herein, we developed AuAgCu2O-bromfenac sodium nanoparticles (AuAgCu2O-BS NPs), which was designed to combine anti-bacterial and anti-inflammatory effects for integrated therapy of endophthalmitis after cataract surgery. The AuAgCu2O-BS NPs could eradicate methicillin-resistant Staphylococcus aureus (MRSA) bacterial strain relied on their photodynamic effects and the release of metal ions (Ag+ and Cu+) by the hollow AuAgCu2O nanostructures mediated mild photothermal effects. The anti-inflammatory drug, bromfenac sodium, released from the nanoparticles were able to significantly reduce the local inflammation of the endophthalmitis and promote tissue rehabilitation. In vivo bacterial elimination and anti-inflammation were confirmed by a postcataract endophthalmitis rabbit model. Results: Excellent antibacterial ability of AuAgCu2O-BS NPs was verified both in vitro and in vivo. Ophthalmological clinical observation and pathologic histology analysis showed prominent treatment of inflammatory reaction. Importantly, the mild temperature photothermal effect not only promoted the release of metal ions and bromfenac sodium but also avoided the thermal damage of the surrounding tissues, which was more suitable for the practical application of ophthalmology due to the complex structure of the eyeball. Moreover, superior biocompatibility was approved by the preliminary toxicity investigations, including low cytotoxicity, negligible damage to major organs, and stable intraocular pressure. Conclusions: Our studies of nanosystem provide a promising synergic therapeutic strategy for postcataract endophthalmitis treatment with favorable prognosis and promise in clinical translations.

Engineered algae: A novel oxygen-generating system for effective treatment of hypoxic cancer.

Microalgae, a naturally present unicellular microorganism, can undergo light photosynthesis and have been used in biofuels, nutrition, etc. Here, we report that engineered live microalgae can be delivered to hypoxic tumor regions to increase local oxygen levels and resensitize resistant cancer cells to both radio- and phototherapies. We demonstrate that the hypoxic environment in tumors is markedly improved by in situ-generated oxygen through microalgae-mediated photosynthesis, resulting in notably radiotherapeutic efficacy. Furthermore, the chlorophyll from microalgae produces reactive oxygen species during laser irradiation, further augmenting the photosensitizing effect and enhancing tumor cell apoptosis. Thus, the sequential combination of oxygen-generating algae system with radio- and phototherapies has the potential to create an innovative treatment strategy to improve the outcome of cancer management. Together, our findings demonstrate a novel approach that leverages the products of photosynthesis for treatment of tumors and provide proof-of-concept evidence for future development of algae-enhanced radio- and photodynamic therapy.

Light-Activatable Synergistic Therapy of Drug-Resistant Bacteria-Infected Cutaneous Chronic Wounds and Nonhealing Keratitis by Cupriferous Hollow Nanoshells.

Due to the inability to spontaneously heal and vulnerability to bacterial infection, diabetic patients are frustrated by unexpected epithelium injuries in daily life. Notably, a drug-resistant bacterial infection may result in a long-term impact to the natural function of damaged organs. It is imperative to develop strategies that promote injury recovery and eradicate drug-resistant infection simultaneously. Here, we present a composite structured cupriferous hollow nanoshell (AuAgCu2O NS) that consists of a hollow gold-silver (AuAg) core and Cu2O shell as a photothermal therapeutic agent for a cutaneous chronic wound and nonhealing keratitis with drug-resistant bacterial infection. The controllable photothermal therapeutic effect and released silver ion from the hollow AuAg core possess a synergistic effect to eradicate multi-drug-resistant bacteria, including extended-spectrum ß-lactamase Escherichia coli (ESBL E. coli) and methicillin-resistant Staphylococcus aureus (MRSA). Meanwhile, the released copper ion from the Cu2O shell could expedite endothelial cell angiogenesis and fibroblast cell migration, thus boosting wound-healing effects. In both infection-complicated disease models, the ophthalmic clinical score, wound closure rates, and histopathology analysis demonstrate that the AuAgCu2O NSs could facilitate the re-epithelialization at the wound area and eliminate the complicated bacterial infection from diabetic mice. A primary signal path involved in the promoted healing effect was further illustrated by comprehensive assays of immunohistochemical evaluation, Western blot, and quantitative polymerase chain reaction. Taken together, our AuAgCu2O NSs are shown to be potent candidates for clinical utilization in the treatment of diabetic epithelium injuries.

Gram-scale synthesis of highly biocompatible and intravenous injectable hafnium oxide nanocrystal with enhanced radiotherapy efficacy for cancer theranostic.

Based on the ionizing radiation applied to the malignant tumor tissue, radiation therapy (RT) is the frequently-used non-surgical approach for cancer treatment. Hafnium Oxide (HfO2) based nanoagent has been used in clinical trials for radiosensitized tumor therapy. However, the current reported clinically used HfO2 nanoparticles are relay on intratumoral injectable, and the unmodified HfO2 nanoparticles tend to be aggregated in serum and cannot be injected by intravenous route, which significantly limited the types of treatable cancer. To overcome the limitation, in this work, we developed a large-scalable, intravenously injectable, and clearable HfO2 nanoassemblies (NAs) to enhance the radiotherapeutic effects. The HfO2 NAs exhibited meaningfully promoted free-radical generation upon X-ray radiation for cancer cell killing due to the improved the sensitiveness of the breast cancer cells. The PEGylated HfO2 NAs demonstrated efficient tumor-homing ability via intravenous injection and manifested by HfO2 NAs enhanced CT imaging in a 4T1 breast tumor model. Utilizing the radiation sensitization function of HfO2 NAs, excellent tumor killing efficacy was achieved via both intratumoral and intravenously injection administration. Importantly, our HfO2 NAs could be degraded and excreted efficiently in a reasonable period in living body and avoid long-term toxicity. Taken together, our work provides a new technique by an injectable CT imaging-guided radio-sensitivitiable nanosystem for the further potential clinic translation.

Laser-triggered aggregated cubic α-Fe2O3@Au nanocomposites for magnetic resonance imaging and photothermal/enhanced radiation synergistic therapy.

Theranostic nanoparticles (NPs) have recently generated substantial interest in translational cancer research due to their capabilities for multimodal diagnostic imaging and anti-cancer therapy. We herein developed cubic alpha-iron(III) oxide (α-Fe2O3) nanoparticles coated with ultrasmall gold nanoseeds, abbreviated as α-Fe2O3@Au, for the synergistic treatment of radiotherapy and photothermal therapy in breast cancer. The resultant NPs, with an average diameter of 49 nm, exhibited satisfactory biosafety profiles and provided tumor contrast in T2-weighted magnetic resonance (MR) imaging. The coating of ultrasmall Au nanoseeds exhibited strong absorption of near-infrared (NIR) laser that enabled to an efficacious photothermal therapy. It also sensitized radiotherapy, X-ray in this study, by generating large quantities of tumoricidal reactive oxygen species (ROS). Moreover, with the aid of NIR laser irradiation, the α-Fe2O3 substrate showed partial ablation and the Au NPs on its surface aggregated into a larger size (~13 nm), which has been proven to be the optimized size for radiotherapy. When tested in 4T1 murine breast cancer model, the α-Fe2O3@Au NPs significantly suppressed tumor growth (P < 0.01) when irradiated with a low-power laser (1.5 W/cm2 for 3 min) and an intermediate X-ray dose (6 Gy). Our results demonstrate that α-Fe2O3@Au, integrated with MRI, photothermal therapy, and radiosensitization, is a promising multifunctional theranostic nanomedicine for clinical applications.

Investigation of Controlled Release Molecular Mechanism of Oil Phase in Spilanthol Emulsion: Development and In Vitro, In Vivo Characterization.

The aim of the present study was to develop a spilanthol emulsion and investigate the effect of oil and drug physicochemical properties on drug release and skin retention at molecular level. Formulation factors including oil, emulsifier, and humectant were investigated by in vitro skin retention/permeation study and the optimized formulation was evaluated in vitro and in vivo. In addition, the controlled release effect of oil was characterized using drug emulsion distribution study, drug release study, FT-IR, and molecular modeling. The optimized emulsion (squalane as oil phase) obtained the maximum skin retention (118.71 ± 10.30 µg/g), which significantly restored skin hydroxyproline content (23.99 ± 2.21 µg/g), compared with the positive group (14.75 ± 1.84 µg/g) and the negative group (15.55 ± 2.03 µg/g). It was caused by high drug release of squalene and good drug-skin miscibility. FT-IR and molecular modeling showed that spilanthol (SPI) interacted with squalene through Van der Waals force, which was weaker than a hydrogen bond formed with other oils, thus exhibited good drug release properties. And the released drug was stored in the skin due to good drug-skin miscibility, which was proved by miscibility calculation and molecular modeling. In conclusion, an effective emulsion was developed and the controlled release effect of oil phase was proved through drug-excipient interaction.

Designing pH-triggered drug release iron oxide nanocomposites for MRI-guided photothermal-chemoembolization therapy of liver orthotopic cancer.

Hepatic carcinoma (HCC) is a kind of aggressive malignancy with high levels of morbidity and mortality. Transcatheter intra-arterial (IA) injection has been recommended as an impactful local delivery method for HCC owing to the limited delivery efficiency of ordinary intravenous injection when used for clinical application. Herein, we developed a doxorubicin (DOX)-loaded and pH-responsive magnetic drug-loaded nanosystem containing single-crystal hematite (α-Fe2O3) nanocubes and pH-sensitive synthetic polydopamine (PDA) mixed with lipiodol for magnetic resonance imaging (MRI)-guided photothermal-chemoembolization treatment in an orthotopic liver cancer model. The synthesized nanosystem showed highly sensitive T2 weighted MRI contrast images owing to the stronger magnetic performance of cubical structured α-Fe2O3 NPs, and unambiguous pH-triggered drug release properties in the acidic tumor environment because of introducing the pH-sensitive PDA. Moreover, the PDA shell could provide a highly efficient photothermal cancer-killing effect under near-infrared (NIR) laser irradiation owing to its high photothermal conversion efficiency. In an orthotopic HCC rat model, the nanosystem was successfully delivered to the tumour site by IA injection. Notably, the IA administered nanosystem with NIR laser irradiation under MRI guidance showed remarkable tumor growth inhibition. These results indicate that the nanosystem platform has the potential to be used as a therapeutic agent for liver-directed IA treatment of HCC.

An Oomycete CRN Effector Reprograms Expression of Plant HSP Genes by Targeting their Promoters.

Oomycete pathogens produce a large number of CRN effectors to manipulate plant immune responses and promote infection. However, their functional mechanisms are largely unknown. Here, we identified a Phytophthora sojae CRN effector PsCRN108 which contains a putative DNA-binding helix-hairpin-helix (HhH) motif and acts in the plant cell nucleus. Silencing of the PsCRN108 gene reduced P. sojae virulence to soybean, while expression of the gene in Nicotiana benthamiana and Arabidopsis thaliana enhanced plant susceptibility to P. capsici. Moreover, PsCRN108 could inhibit expression of HSP genes in A. thaliana, N. benthamiana and soybean. Both the HhH motif and nuclear localization signal of this effector were required for its contribution to virulence and its suppression of HSP gene expression. Furthermore, we found that PsCRN108 targeted HSP promoters in an HSE- and HhH motif-dependent manner. PsCRN108 could inhibit the association of the HSE with the plant heat shock transcription factor AtHsfA1a, which initializes HSP gene expression in response to stress. Therefore, our data support a role for PsCRN108 as a nucleomodulin in down-regulating the expression of plant defense-related genes by directly targeting specific plant promoters.

Identification of IMPDH2 as a tumor-associated antigen in colorectal cancer using immunoproteomics analysis.

BACKGROUND AND AIMS: Sera from cancer patients contain tumor-specific autoantibodies directly against antigenic proteins. The identification of tumor autoantigens may have utility in cancer diagnosis, prognosis, and therapy. In this study, we used immunoproteomics analysis to identify tumor proteins that elicit humoral response in colorectal cancer (CRC). MATERIALS AND METHODS: The CRC cell line HCT116 was used as a source of proteins for two-dimensional polyacrylamide gel electrophoresis and subsequent Western blot analysis in which individual serum from patients with CRC was analyzed for autoantibodies. Proteins that specifically react with sera from cancer patients were identified by matrix-assisted laser desorption ionization time-of-flight mass spectrometric analysis. In addition, the selected protein expression in tumor tissues collected from 40 patients with CRC were assessed by immunohistochemistry. RESULTS: An autoantibody against inosine monophosphate dehydrogenase II (IMPDH2) identified by mass spectrometry was detected in eight out of 25 patients with CRC. However, none of the 15 healthy controls demonstrated autoantibody to IMPDH2.The expression of IMPDH2 in tumor tissue was significantly higher in patients with CRC than that in healthy subjects. CONCLUSIONS: The result confirmed that the immunoproteomics analysis holds considerable promise for the discovery of tumor-associated antigens. IMPDH2 may be a protein biomarker and novel therapeutic target in CRC.

[Inhibition of activator protein 4 gene expression by RNA interference in human colon carcinoma cell line SW480].

OBJECTIVE: To construct an expression plasmid of siRNA against activator protein 4(AP-4) gene and to investigate its biological behavioral effect on human colon carcinoma cell line SW480. METHODS: The specific siRNA target exon 7 of AP-4 gene was constructed and transfected into SW480 cells by liposome. Expression levels of AP-4 mRNA and protein from SW480 after transfection were examined by RT-PCR and Western blot respectively. Cell proliferation was detected by cell counting and MTT assay. Flow cytometry(FCM) and Western blot were used to detect cell apoptosis and cell cycle. The invasiveness of SW480 cells in vitro was measured quantitatively by the matrigel invasion assay. RESULTS: After AP-4 siRNA transfection into SW480 cells for 96 hours, the cell AP-4 mRNA reduced by 57.8% and the AP-4 protein concentration in culture supernatant decreased by 75.2%. The cell growth was significantly inhibited by 61%-78%. The apoptosis rate of SW480 cells was significantly higher in AP-4 siRNA group than that in negative control group[(21.7 +/- 2.51)% vs. (2.31 +/- 0.14)%, P<0.01]. Cells in G0-G1 phase increased by 22.43% and in G2-M phase decreased by 14.52% (P<0.05). AP-4 siRNA significantly inhibited AP-4-induced invasion of SW480 cells to matrigel (P<0.05). CONCLUSIONS: Silencing AP-4 gene by the siRNA technology can actively suppress the expression of AP-4 gene, and then inhibit the growth and proliferation of SW480 cell, and induce apoptosis of SW480 cell. The successful application of AP-4 siRNA extends the list of available therapeutic modalities in the treatment of human colon cancer.