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Members of the MT-A70 family are key catalytic proteins involved in m 6 A methylation modifications in plants. They play diverse roles at the posttranscriptional level by regulating RNA secondary structure, selective splicing, stability, and translational efficiency, which collectively affect plant growth, development, and stress responses. In this study, we explored the function of the gene SlMTC, a Class C member of the MT-A70 family, in tomatoes by using CRISPR/Cas9 technology. Compared with the wild-type (WT), the CR-slmtc mutants exhibited decreased seed size and slower growth rates during the seedling stage, along with weaker salt tolerance and significant downregulation of stress-related genes, such as PR1, PR5, and P5CS. The qRT-PCR results revealed that the expression levels of genes involved in auxin biosynthesis (FZY1, FZY3, and FZY4) and polar transport (PIN1, PIN4, and PIN8) were lower in CR-slmtc plants than in the WT plants. In addition, yeast two-hybrid assays showed that SlMTC could interact with SlMTA, a Class A member of the MT-A70 family, providing insights into the potential mode of action of SlMTC in tomatoes. Overall, our findings indicate the critical role of SlMTC in plant growth and development as well as in response to salt stress., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interest, (Copyright © 2024 Elsevier B.V. All rights reserved.)

Synergistic therapy has shown greater advantages compared with monotherapy. However, the complex multiple-administration plan and potential side effects limit its clinical application. A transformable specific-responsive peptide (TSRP) is utilized to one-step achieve synergistic therapy integrating anti-tumor, anti-angiogenesis and immune response. The TSRP is composed of: i) Recognition unit could specifically target and inhibit the biological function of FGFR-1; ii) Transformable unit could self-assembly and trigger nanofibers formation; iii) Reactive unit could specifically cleaved by MMP-2/9 in tumor micro-environment; iv) Immune unit, stimulate the release of immune cells when LTX-315 (Immune-associated oncolytic peptide) exposed. Once its binding to FGFR-1, the TSRP could cleaved by MMP-2/9 to form the nanofibers on the cell membrane, with a retention time of up to 12 h. Through suppressing the phosphorylation levels of ERK 1/2 and PI3K/AKT signaling pathways downstream of FGFR-1, the TSRP significant inhibit the growth of tumor cells and the formation of angioginesis. Furthermore, LTX-315 is exposed after TSRP cleavage, resulting in Calreticulin activation and CD8 + T cells infiltration. All above processes together contribute to the increasing survival rate of tumor-bearing mice by nearly 4-folds. This work presented a unique design for the biological application of one-step synergistic therapy of bladder cancer., (© 2024 Wiley‐VCH GmbH.)

Selective semi-hydrogenation of alkynes is a significant reaction for preparing functionalized alkenes. Electrochemical semi-hydrogenation presents a sustainable alternative to the traditional thermal process. In this research, affordable copper acetylacetonate is employed as a catalyst precursor for the electrocatalytic hydrogenation of alkynes, using MeOH as the hydrogen source in an undivided cell. Good to excellent yields for both aromatic and aliphatic internal/terminal alkynes are obtained under constant current conditions. Notably, up to 99% Z selectivity is achieved for various internal alkynes. Mechanistic investigations revealed the formation of copper nanoparticles (NPs) at the cathode during electrolysis, acting as the catalyst for the selective semireduction of alkynes. The copper NPs deposited cathode demonstrated reusable for further hydrogenation., (© 2024 Wiley‐VCH GmbH.)

Purpose: The incomplete resection of non-muscle invasive bladder cancer (NMIBC) augments the risk of disease recurrence. Imaging-guided surgery by molecular probes represents a pivotal strategy for mitigating postoperative recurrence. Traditional optical molecular probes, primarily composed of antibodies/peptides targeting tumour cells and fluorescent groups, are challenged by the high heterogeneity of NMIBC cells, leading to inadequate probe sensitivity. We have developed a collagen-adhesive probe (CA-P) to target the collagen within the tumour microenvironment, aiming to address the issue of insufficient imaging sensitivity., Methods: The distribution characteristics of collagen in animal bladder cancer models and human bladder cancer tissues were explored. The synthesis and properties of CA-P were validated. In animal models, the imaging performance of CA-P was tested and compared with our previously reported near-infrared probe PLSWT7-DMI. The clinical translational potential of CA-P was assessed using human ex vivo bladder tissues., Results: The distribution of collagen on the surface of tumour cells is distinct from its expression in normal urothelium. In vitro studies have demonstrated the ability of the CA-P to undergo a "sol-gel" transition upon interaction with collagen. In animal models and human ex vivo bladder specimens, CA-P exhibits superior imaging performance compared to PLSWT7-DMI. The sensitivity of this probe is 94.1%, with a specificity of 81%., Conclusion: CA-P demonstrates the capability to overcome tumour cell heterogeneity and enhance imaging sensitivity, exhibiting favorable imaging outcomes in preclinical models. These findings provide a theoretical basis for the application of CA-P in intraoperative navigation for NMIBC., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Engineered macrophages are a promising tool for drug delivery and immunotherapy in cancer treatment. However, simultaneous targeted enrichment and controllable immunological activation of these macrophages at the tumor site remains challenging. As a solution, macrophages loaded with an advanced nanoparticle encapsulating CpG-conjugated magnetic nanoclusters (MNC) with indocyanine green (ICG) and nigericin (NIG) (MNC-ICG-NIG@SiO 2 (MINS)), utilizing Se─Se bond-modified SiO 2 , are designed and applied in bladder cancer, which is typically managed surgically, followed by Bacillus Calmette-Guerin (BCG) adjuvant instillation therapy. Upon intravenous administration, BCG-mediated tumor-localized inflammation leads to targeted accumulation of MINS@MΦ. MINS@MΦ accumulates within the tumor tissue and is immunologically activated through laser irradiation, leading to ICG-mediated generation of reactive oxygen species, Se─Se bond cleavage, and subsequent NIG release to induce self-pyroptosis. Consequently, MINS@MΦ releases Fe 2+ ions and CpG, thus promoting the M1 polarization of tumor-associated macrophages and secretion of appropriate antitumor cytokines. However, without intervention, MINS@MΦ undergoes apoptosis in the bloodstream after 48 h without eliciting any immune response. Therefore, this innovative approach optimizes and enhances the efficacy of BCG immunotherapy by precisely modulating the cytokines for effective bladder cancer treatment without inducing a systemic inflammatory response., (© 2023 Wiley‐VCH GmbH.)

α-PD-L1 therapy has shown encouraging results at harnessing the immune system to combat cancer. However, the treatment effect is relatively low due to the dense extracellular matrix (ECM) and tumor immunosuppressive microenvironment (TIME). Therefore, an ultrasound (US)-responsive nanosensitizer (URNS) is engineered to deliver losartan (LST) and polyethylenimine (PEI) to remolde the TME, driving "cold"-"hot" tumor transformation and enhancing the sensitivity of α-PD-L1 therapy. In the tumor site, noninvasive US can make MTNP generate ROS, which cleave ROS-sensitive bonds to dissociate MTNP tK @LST-PEI, shedding PEI and releasing LST from mesoporous spheres. The results demonstrated that URNS combined with α-PD-L1 therapy effectively inhibited tumor growth with an inhibition rate as high as 90%, which was 1.7-fold higher than that of the α-PD-L1 treatment in vivo . In summary, the URNS improves the sensitivity of α-PD-L1 therapy by remodeling the TME, which provides promising insights for optimizing cancer immunotherapy.

Reducing the imaging time while maintaining reconstruction accuracy remains challenging for single-pixel imaging. One cost-effective approach is nonuniform sparse sampling. The existing methods lack intuitive and intrinsic analysis in sparsity. The lack impedes our comprehension of the form's adjustable range and may potentially limit our ability to identify an optimal distribution form within a confined adjustable range, consequently impacting the method's overall performance. In this Letter, we report a sparse sampling method with a wide adjustable range and define a sparsity metric to guide the selection of sampling forms. Through a comprehensive analysis and discussion, we select a sampling form that yields satisfying accuracy. These works will make up for the existing methods' lack of sparsity analysis and help adjust methods to accommodate different situations and needs.

Key Message: Overexpression of SlPRE3 is detrimental to the photosynthesis and alters plant morphology and root development. SlPRE3 interacts with SlAIF1/SlAIF2/SlPAR1/SlIBH1 to regulate cell expansion. Basic helix-loop-helix (bHLH) transcription factors play crucial roles as regulators in plant growth and development. In this study, we isolated and characterized SlPRE3, an atypical bHLH transcription factor gene. SlPRE3 exhibited predominant expression in the root and moderate expression in the senescent leaves. Comparative analysis with the wild type revealed significant differences in plant morphology in the 35S:SlPRE3 lines. These differences included increased internode length, rolling leaves with reduced chlorophyll accumulation, and elongated yet fewer adventitious roots. Additionally, 35S:SlPRE3 lines displayed elevated levels of GA 3 (gibberellin A3) and reduced starch accumulation. Furthermore, utilizing the Y2H (Yeast two-hybrid) and the BiFC (Bimolecular Fluorescent Complimentary) techniques, we identified physical interactions between SlPRE3 and SlAIF1 (ATBS1-interacting factor 1)/SlAIF2 (ATBS1-interacting factor 2)/SlPAR1 (PHYTOCHROME RAPIDLY REGULATED 1)/SlIBH1 (ILI1-binding bHLH 1). RNA-seq analysis of root tissues revealed significant alterations in transcript levels of genes involved in gibberellin metabolism and signal transduction, cell expansion, and root development. In summary, our study sheds light on the crucial regulatory role of SlPRE3 in determining plant morphology and root development., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Trihelix proteins are plant-specific transcription factors that are classified as GT factors due to their binding specificity for GT elements, and they play crucial roles in development and stress responses. However, their involvement in fruit ripening and transcriptional regulatory mechanisms remains largely unclear. In this study, we cloned SlGT31, encoding a trihelix protein in tomato (Solanum lycopersicum), and determined that its relative expression was significantly induced by the application of exogenous ethylene whereas it was repressed by the ethylene-inhibitor 1-methylcyclopropene. Suppression of SlGT31 expression resulted in delayed fruit ripening, decreased accumulation of total carotenoids, and reduced ethylene content, together with inhibition of expression of genes related to ethylene and fruit ripening. Conversely, SlGT31-overexpression lines showed opposite results. Yeast one-hybrid and dual-luciferase assays indicated that SlGT31 can bind to the promoters of two key ethylene-biosynthesis genes, ACO1 and ACS4. Taken together, our results indicate that SlGT31 might act as a positive modulator during fruit ripening., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Renal cancer stem cells (RCSCs) derived from clear cell renal cell carcinoma (ccRCC) tissues with higher microvessel density (MVD) have strong stemness and endothelial progenitor cells-like (EPCs-like) characteristics. A high level of lncRNA PVT1 expression is essential for simultaneously retaining strong RCSC stemness and EPCs-like characteristics. PVT1 binds with TAZ protein and prevents its phosphorylation, which promotes RCSC stemness. Moreover, RCSCs support endothelial differentiation and angiogenesis, which are mediated via the PVT1/miR-15b/KDR axis. This report provides insight into the determinants of RCSC impact on stemness and highlights the critical role of RCSC in angiogenesis. The presented findings suggest that targeting RCSC through PVT1 expression may be a new treatment strategy for ccRCC., (© 2023 The Authors. The FASEB Journal published by Wiley Periodicals LLC on behalf of Federation of American Societies for Experimental Biology.)

The single-pixel imaging technique uses multiple patterns to modulate the entire scene and then reconstructs a two-dimensional (2-D) image from the single-pixel measurements. Inspired by the statistical redundancy of natural images that distinct regions of an image contain similar information, we report a highly compressed single-pixel imaging technique with a decreased sampling ratio. This technique superimposes an occluded mask onto modulation patterns, realizing that only the unmasked region of the scene is modulated and acquired. In this way, we can effectively decrease 75% modulation patterns experimentally. To reconstruct the entire image, we designed a highly sparse input and extrapolation network consisting of two modules: the first module reconstructs the unmasked region from one-dimensional (1-D) measurements, and the second module recovers the entire scene image by extrapolation from the neighboring unmasked region. Simulation and experimental results validate that sampling 25% of the region is enough to reconstruct the whole scene. Our technique exhibits significant improvements in peak signal-to-noise ratio (PSNR) of 1.5 dB and structural similarity index measure (SSIM) of 0.2 when compared with conventional methods at the same sampling ratios. The proposed technique can be widely applied in various resource-limited platforms and occluded scene imaging.

Nanoscale drug carriers play a crucial role in reducing side effects of chemotherapy drugs. However, the mononuclear phagocyte system (MPS) and the drug protonation after nanoparticles (NPs) burst release still limit the drug delivery efficiency. In this work, a self-disguised Nanospy is designed to overcome this problem. The Nanospy is composed of: i) poly (lactic-co-glycolic acid)-polyethylene glycol (PLGA-PEG) loading doxorubicin is the core structure of the Nanospy. ii) CD47 mimic peptides (CD47p) is linked to NPs which conveyed the "don't eat me" signal. iii) 4-(2-aminoethyl) benzenesulfonamide (AEBS) as the inhibitor of Carbonic anhydrase IX (CAIX) linked to NPs. Briefly, when the Nanospy circulates in the bloodstream, CD47p binds to the regulatory protein α (SIRPα) on the surface of macrophages, which causes the Nanospy escapes from phagocytosis. Subsequently, the Nanospy enriches in tumor and the AEBS reverses the acidic microenvironment of tumor. Due to above characteristics, the Nanospy reduces liver macrophage phagocytosis by 25% and increases tumor in situ DOX concentration by 56% compared to PLGA@DOX treatment. In addition, the Nanospy effectively inhibits tumor growth with a 63% volume reduction. This work presents a unique design to evade the capture of MPS and overcomes the influence of acidic tumor microenvironment (TME) on weakly alkaline drugs., (© 2023 Wiley-VCH GmbH.)

Key Message: 1. Purple flowering stalk (Brassica campestris L. ssp. chinensis L. var. purpurea Bailey) is a crop with the high-level anthocyanin. 2. Increased abundance of LBGs promoted the synthesis of anthocyanin. 3. TTG2 (WRKY) interacted with TTG1 (WD40), probably regulating anthocyanin accumulation by shaping a MBWW complex. Brassica crops are a class of nutrient-rich vegetables. Here, two Brassica Crops-Flowering Stalk cultivars, purple flowering stalk (Brassica campestris L. var. purpurea Bailey) and pakchoi (Brassica campestris ssp. chinensis var. communis) were investigated. HPLC-ESI-MS/MS analysis demonstrated that Cy 3-p-coumaroylsophoroside-5-malonylglucoside and Cy 3-diferuloylsophoroside-5-malonylglucoside were identified as the major anthocyanin in peel of purple flowering stalk. The transcript level of structural genes including C4H, CHS, F3H, DFR, ANS and UFGT, and regulatory genes such as TT8, TTG1, Bra004162, Bra001917 and TTG2 in peel of purple flowering stalk were significantly higher than that in peel of pakchoi. In addition, the TTG2(WRKY) interacted only with TTG1(WD40) and the interaction between TT8 (bHLH) and TTG1/Bra004162(MYB)/Bra001917(MYB) were identified. Else, the WD40-WRKY complex (TTG1-TTG2) could activate the transcript of TT12. Our study laid a foundation for the research on the anthocyanin accumulation in Brassica crops., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)

The sweet potato is very sensitive to low temperature. Our previous study revealed that IbMPK3 -overexpressing transgenic sweet potato (M3) plants showed stronger low-temperature stress tolerance than wild-type plants (WT). However, the mechanism of M3 plants in response to low-temperature stress is unclear. To further analyze how IbMPK3 mediates low-temperature stress in sweet potato, WT and M3 plants were exposed to low-temperature stress for 2 h and 12 h for RNA-seq analysis, whereas normal conditions were used as a control (CK). In total, 3436 and 8718 differentially expressed genes (DEGs) were identified in WT at 2 h (vs. CK) and 12 h (vs. CK) under low-temperature stress, respectively, whereas 1450 and 9291 DEGs were detected in M3 plants, respectively. Many common and unique DEGs were analyzed in WT and M3 plants. DEGs related to low temperature were involved in Ca 2+ signaling, MAPK cascades, the reactive oxygen species (ROS) signaling pathway, hormone transduction pathway, encoding transcription factor families ( bHLH , NAC , and WRKY ), and downstream stress-related genes. Additionally, more upregulated genes were associated with the MAPK pathway in M3 plants during short-term low-temperature stress (CK vs. 2 h), and more upregulated genes were involved in secondary metabolic synthesis in M3 plants than in the WT during the long-time low-temperature stress treatment (CK vs. 12 h), such as fatty acid biosynthesis and elongation, glutathione metabolism, flavonoid biosynthesis, carotenoid biosynthesis, and zeatin biosynthesis. Moreover, the interaction proteins of IbMPK3 related to photosynthesis, or encoding CaM, NAC, and ribosomal proteins, were identified using yeast two-hybrid (Y2H). This study may provide a valuable resource for elucidating the sweet potato low-temperature stress resistance mechanism, as well as data to support molecular-assisted breeding with the IbMPK3 gene.

Background: Bladder cancer is the fifth most common malignancy in humans. Cystoscopy under white light imaging is the gold standard for bladder cancer diagnosis, but some tumors are difficult to visualize and can be overlooked, resulting in high recurrence rates. We previously developed a phage display-derived peptide-based near-infrared imaging probe, PLSWT7-DMI, which binds specifically to bladder cancer cells and is nontoxic to animals. Here, we report a clinical research of this probe for near-infrared fluorescence endoscopic detection of bladder cancer., Results: The purity, efficacy, safety, and nontoxicity of PLSWT7-DMI were confirmed prior to its clinical application. Twenty-two patients diagnosed with suspected non-muscle invasive bladder cancer were enrolled in the present study. Following intravesical administration of the probe, the entire mucosa was imaged under white and near-infrared imaging using an in-house developed endoscope that could switch between these two modes. The illuminated lesions under near-infrared light were biopsied and sent for histopathological examination. We observed a 5.1-fold increase in the fluorescence intensity in the tumor samples compared to normal tissue, and the probe demonstrated a sensitivity and specificity of 91.2% and 90%, respectively. Common diagnostic challenges, such as small satellite tumors, carcinoma in situ, and benign suspicious mucosa, were visualized and could be distinguished from cancer. Furthermore, no adverse effects were observed in humans. These first-in-human results indicate that PLSWT7-DMI-based near-infrared fluorescence endoscopy is a safe and effective approach for the improved detection of bladder cancer, and may enable thorough resection to prevent recurrence., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

A higher-order robust correlation Kalman filtering approach is presented to achieve attitude estimation for satellites with unknown modeling errors. A robust correlation Kalman filter (RCKF) is preliminarily derived by using the sequence orthogonal principle. To improve its performance further, a higher-order sigma version of the RCKF is designed by incorporating a novel sigma point generation algorithm. This modified filter can capture the third and the fourth central moment's information of the system posteriori probability density function. It is proved that the proposed filter achieves better estimation accuracy and robustness. The effectiveness of the developed filter is demonstrated by simulation results with it applied to the satellite attitude estimation problem., Competing Interests: Declaration of Competing Interest No author associated with this paper has disclosed any potential or pertinent conflicts which may be perceived to have impending conflict with this work. For full disclosure statements refer to https://doi.org/10.1016/j.isatra.2019.12.009., (Copyright © 2020 ISA. Published by Elsevier Ltd. All rights reserved.)

Pigmentation of various components leads to different colors in tulip flowers. To understand the molecular basis of the petal coloration in tulip, integrative analyses of the pigment components and transcriptome profiles were conducted on four tulip cultivars with different petal colors. A total of four major anthocyanins and 46 carotenoids were identified. The anthocyanin cyanidin 3-O-galactoside showed markedly higher abundances in the B cultivar than in the other varieties, and among the 46 kinds of carotenoids, (E/Z)-phytoene, violaxanthin myristate and violaxanthin palmitate were the major components. The RNA-seq and qRT-PCR results indicated that the pigment accumulation was linked to the expression of genes involved in the anthocyanin and carotenoid biosynthesis pathways. Yeast two-hybrid (Y2H) assays showed the interaction between different regulator factors in tulip MYB-bHLH-WD40 (MBW) complexes. Co-expression analyses of genes were performed, which include anthocyanin and carotenoid biosynthesis genes and transcription factors involved in MYB, bHLH, WRKY, AUX-IAA and MADS-box. The co-expression network and related analysis provide a basis for the discovery of color regulatory factors. Taken together, our study sheds light on the anthocyanin and carotenoid synthesis pathways and candidate regulatory transcription factors underlying flower coloration and shows the potential of flower breeding or pigments engineering in tulips., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Bladder cancer (BCa) is the most costly solid tumor owing to its high recurrence. Relapsed cancer is known to acquire chemoresistant features after standard intravesical chemotherapy. This cancer state is vulnerable to ferroptosis, which occurs when lipid peroxides generated by iron metabolism accumulate to lethal levels. Increasing the labile iron pool (LIP) by iron oxide nanoparticles (IONPs) promises to inhibit chemoresistant BCa (CRBCa), but systemically administered IONPs do not sufficiently accumulate at the tumor site. Therefore, their efficacy is weakened. Here, we present a three-tier delivery strategy through a mucoadhesive hydrogel platform conveying hyaluronic acid-coated IONPs (IONP-HA). When instilled, the hydrogel platform first adhered to the interface of the tumor surface, sustainably releasing IONP-HA. Subsequently, the tumor stiffness and interstitial fluid pressure were reduced by photothermal therapy, promoting IONP-HA diffusion into the deep cancer tissue. As CRBCa expressed high levels of CD44, the last delivery tier was achieved through antibody-mediated endocytosis to increase the LIP, ultimately inducing ferroptosis. This three-tiered strategy delivered the IONPs stepwise from anatomical to cellular levels and increased the iron content by up to 50-fold from that of systematic administration, which presents a potential regimen for CRBCa.

Bladder cancer displays multiple biological features aided in drug resistance; therefore, single therapy fails to induce complete tumor regression. To address this issue, various kinds of cell death of cancer cells as well as restoring tumor immune microenvironment need to be taken into consideration. Here, we introduce a gel system termed AuNRs&IONs@Gel, which target-delivers a combination of photothermal, ferroptotic, and immune therapy through intravesical instillation. AuNRs&IONs@Gel consists of a gel delivery platform, embedded gold nanorods (AuNRs), and iron oxide nanoparticles (IONs). The targeted delivery gel platform provides dextran aldehyde-selective adhesion with cancer collagen. In this condition, photothermal therapy can be performed by gold nanorods (AuNRs) under imaging-guided near-infrared radiation. Local high concentrations of IONs can be absorbed by cancer cell to induce ferroptosis. Moreover, tumor-associated macrophages which often display an immune-suppressive M2-like phenotype will be repolarized by IONs into the antitumor M1-like phenotype, exerting a direct antitumor effect and professional antigen presentation of dead cancer cells. This process triggers a potent immune response of innate and adapt immunities to protect tumor rechallenge in long terms. Our triple-therapy strategy employs FDA-approved nanoparticles to inhibit bladder cancer which may possess great potential for clinical translation.

With the rapid development of nanotechnology, nanomaterial drug delivery systems have provided an alternative for designing controllable drug delivery systems due to their spatiotemporally controllable properties. As a new type of porous material, metal-organic frameworks (MOFs) have been widely used in biomedical applications, especially drug delivery systems, owing to their tunable pore size, high surface area and pore volume, and easy surface modification. Here, we demonstrate an MOF as a theranostic nanoplatform to combine drug therapy and phototherapy after labeling targeting peptide iRGD. The micropore Fe-MOF was used as MRI agents for locating tumors and as nanocarriers to upload chemotherapeutic drugs. Moreover, MOF showed excellent targeting performance under different administration including intravenous injection for breast cancer and local instillation for bladder cancer. Notably, when irradiated with an 808 nm laser, the agent demonstrates the high efficacy of photothermal therapy and heat release efficiency of the drug around the tumor site. This combination therapy provides an alternative drug administration method and can be adapted to a series of cancer cell types and molecular targets associated with disease progression.

Continuously updated diagnostic methods and advanced imaging methods have led to an increase in the early detection rate of small liver cancer; however, even with current diagnosis methods, it is still challenging to accurately judge a nodule with a diameter less than 2 cm whether it is hepatocellular carcinoma or liver cirrhosis. To solve this issue, a new technology is needed to distinguish above two kinds of liver nodules. There is an emerging imaging method that improves tissue resolution and sensitivity to detect micronodules with diameters less than 2 cm. To detect micronodules, photoacoustic imaging was used to provide noninvasive images at depths of several centimeters with a resolution of approximately 100 μm. To improve specificity, we developed a probe that specifically targets hepatocellular carcinoma by recognizing the biomarker GPC3 on the hepatocellular carcinoma cell membrane. The probe not only has a strong photoacoustic signal but also has a magnetic resonance signal. Furthermore, the material owns photothermal effect that absorbs longer wavelength light and releases heat that effectively and accurately kills tumor cells, thus improving patient's survival and postoperative quality of life. Herein, we present a new technology that uses photoacoustic imaging to image and target microhepatocellular carcinoma biological processes derived from liver cirrhosis with high spatial resolution.

Background: Clear cell renal cell carcinoma (CCRCC) is characterized by a highly metastatic potential. The stromal communication between stem cells and cancer cells critically influences metastatic dissemination of cancer cells., Methods: The effect of exosomes isolated from cancer stem cells (CSCs) of CCRCC patients on the progress of epithelial-mesenchymal transition (EMT) and lung metastasis of CCRCC cells were examined., Results: CSCs exosomes promoted proliferation of CCRCC cells and accelerated the progress of EMT. Bioactive miR-19b-3p transmitted to cancer cells by CSC exosomes induced EMT via repressing the expression of PTEN. CSCs exosomes derived from CCRCC patients with lung metastasis produced the strongest promoting effect on EMT. Notably, CD103 + CSC exosomes were enriched in tumor cells and in lung as well, highlighting the organotropism conferred by CD103. In addition, CD103 + exosomes were increased in blood samples from CCRCC patients with lung metastasis., Conclusions: CSC exosomes transported miR-19b-3p into CCRCC cells and initiated EMT promoting metastasis. CD103 + acted to guide CSC exosomes to target cancer cells and organs, conferring the higher metastatic capacity of CCRCC to lungs, suggesting CD103 + exosomes as a potential metastatic diagnostic biomarker. ᅟ.

Bladder cancer is a common human malignancy. Conventional ultrasound and white-light cystoscopy are often used for bladder cancer diagnosis and resection, but insufficient specificity results in a high bladder cancer recurrence rate. New strategies for the diagnosis and resection of bladder cancer are needed. In this study, we developed a highly specific peptide-based probe for bladder cancer photoacoustic imaging (PAI) diagnosis and near-infrared (NIR)-imaging-guided resection after instillation. A bladder cancer-specific peptide (PLSWT7) was selected by in vivo phage-display technology and labeled with IRDye800CW to synthesize a bladder cancer-specific dual-modality imaging (DMI) probe (PLSWT7-DMI). The feasibility of PLSWT7-DMI-based dual-modality PAI-NIR imaging was assessed in vitro , in mouse models, and ex vivo human bladders. An air-pouch bladder cancer (APBC) model suitable for probe instillation was established to evaluate the probe-based bladder cancer PAI diagnosis and NIR-imaging-guided resection. Human bladders were used to assess whether the PLSWT7-DMI-based DMI strategy is a translatable approach for bladder cancer detection and resection. The probe exhibited excellent selectivity and specificity both in vitro and in vivo Postinstillation of the probe, tumors <3 mm were detectable by PAI, and NIR-imaging-guided tumor resection decreased the bladder cancer recurrence rate by 90% and increased the survival in the mouse model. Additionally, ex vivo NIR imaging of human bladders indicated that PLSWT7-DMI-based imaging would potentially allow precise resection of bladder cancer in clinical settings. This PLSWT7-DMI-based DMI strategy was a translatable approach for bladder cancer diagnosis and resection and could potentially lower the bladder cancer recurrence rate. Mol Cancer Ther; 17(10); 2100-11. ©2018 AACR ., (©2018 American Association for Cancer Research.)

Single instillation (SI) reduces recurrence of non-muscle-invasive bladder cancer by chemoresecting floating tumor cells and residual tumor lesions (RTLs) after transurethral resection of the bladder, but with limited efficacy. Current studies improved this by prolonging retention time and increasing penetration to bladder wall, ignoring that the two separate factors should be treated in different ways. Here, we introduced a smart gel system-based SI to prevent re-implantation of tumor cells (RTCs) and ablate RTLs in a "divide-and-rule" approach. The gel system was synthesized by PEG-PAMAM and dextran aldehyde and composed of gold nanorods and gemcitabine for photothermal therapy and chemotherapy, respectively. It was developed to provide dextran aldehyde-selective adhesion with tissue amines. Since tumor surface expressed high levels of collagen, the exposed amines could act as adhesion points for the gel system. Thus, the gel presented more affinity to tumor tissues. When being instilled, it could form a protective layer on the inner face of the entire bladder wall immediately, preventing RTCs in early time. And it persisted long at the tumor site, ablating RTLs. Our data proved the gel system improved intravesical treatment efficacy in a "divide-and-rule" approach and might be a promising treatment strategy for SI., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background/aims: Emerging novel optical imaging techniques with cancer-specific molecular imaging agents offer a powerful and promising platform for cancer detection and resection. White-light cystoscopy and random bladder biopsies remain the most appropriate but nonetheless suboptimal diagnostic technique for bladder cancer, which is associated with high morbidity and recurrence. However, white-light cystoscopy has intrinsic shortcomings. Although current optical imaging technologies hold great potential for improved diagnostic accuracy, there are few imaging agents for specific molecular targeting. Carbonic anhydrase IX (CAIX) plays a pivotal role in tumorigenesis and tumor progression with potential value as an imaging target. Here, we investigated the feasibility of CAIX as a target and validated the diagnostic performance and significance of CAIX as an imaging agent., Methods: We first analyzed the data from The Cancer Genome Atlas (TCGA). Pairs of samples comprising bladder cancer and adjacent normal tissue were collected. All tissue samples were used for real-time PCR and immunohistochemistry to compare CAIX expression in normal and cancer tissue. Using blue-light cystoscopy, we observed the optical distribution of fluorescently labeled CAIX antibody in freshly excised human bladders and obtained random bladder biopsies to assess sensitivity and specificity., Results: The TCGA data revealed that CAIX expression was significantly higher in bladder cancer specimens than in normal tissue. The outcome was similar in quantitative real-time PCR analysis. In immunohistochemical analysis, bladder cancer specimens classified in four pathological subtypes presented a variety of positive staining intensities, whereas no benign specimens showed CAIX staining. Using blue-light cystoscopy, we distinguished bladder cancers that were mainly papillary, some variants of urothelial carcinoma, and less carcinoma in situ, from benign tissue, despite the presence of suspicious-appearing mucosa. The sensitivity and specificity for CAIX-targeted imaging were 88.00% and 93.75%, respectively., Conclusions: CAIX-targeted molecular imaging could be a feasible and adaptive alternative approach for the accurate diagnosis and complete resection of bladder cancer., (© 2018 The Author(s). Published by S. Karger AG, Basel.)

Objective: To compare efficacy and safety of laparoscopicnephrectomy (LN) versus open nephrectomy (ON) in the management of autosomal dominant polycystic kidney disease (ADPKD), we conducted a systematic review and meta-analysis., Methods: A systematic search of the electronic databases PubMed, Scopus, and the Cochrane Library was performed up to October 2014. This systematic review was performed based on observational comparative studies that assessed the two techniques. The weighted mean difference (WMD) and risk ratio (RR), with their corresponding 95% confidence interval (CI), were calculated to compare continuous and dichotomous variables, respectively., Results: Seven studies were identified, including 195 cases (118 LN/77 ON). Although LN was associated with longer operative time (WMD 30.236, 95%CI 14.541 -45.932, P<0.001) and the specimen might not have been resected as heavy as the ON group (WMD -986.516, 95%CI -1883.24--89.795, P = 0.031), patients in this group might benefit from a shorter length of hospital stay (WMD -3.576, 95%CI 4.976--2.176, P <0.001), less estimated blood loss (WMD -180.245, 95%CI -317.939--42.556, P = 0.010), and lower need of transfusion (RR 0.345, 95%CI 0.183-0.650, P = 0.001). The LN group also had less overall complications (RR 0.545, 95%CI 0.329-0.903, P = 0.018). The need of narcotic analgesics between the two groups might have no significant difference (WMD -54.66, 95%CI -129.76-20.44, P = 0.154)., Conclusion: LN for giant symptomatic ADPKD was feasible, safe and efficacious. Morbidity was significantly reduced compared with the open approach. For an experienced laparoscopist, LN might be a better alternative.

Optical tracking and measurement for flying targets is unlike the close range photography under a controllable observation environment, which brings extreme conditions like diverse target changes as a result of high maneuver ability and long cruising range. This paper first designed and realized a distributed image interpretation and measurement processing system to achieve resource centralized management, multisite simultaneous interpretation and adaptive estimation algorithm selection; then proposed a real-time interpretation method which contains automatic foreground detection, online target tracking, multiple features location, and human guidance. An experiment is carried out at performance and efficiency evaluation of the method by semisynthetic video. The system can be used in the field of aerospace tests like target analysis including dynamic parameter, transient states, and optical physics characteristics, with security control.