Endogenous AND Logic DNA Nanomachine for Highly Specific Cancer Cell Imaging.

Intracellular cancer-related biomarker imaging strategy has been used for specific identification of cancer cells, which was of great importance to accurate cancer clinical diagnosis and prognosis studies. Localized DNA circuits with improved sensitivity showed great potential for intracellular biomarkers imaging. However, the ability of localized DNA circuits to specifically image cancer cells is limited by off-site signal leakage associated with a single-biomarker sensing strategy. Herein, we integrated the endogenous enzyme-powered strategy with logic-responsive and localized signal amplifying capability to construct a self-assembled endogenously AND logic DNA nanomachine (EDN) for highly specific cancer cell imaging. When the EDN encountered a cancer cell, the overexpressed DNA repairing enzyme apurinic/apyrimidinic endonuclease 1 (APE1) and miR-21 could synergistically activate a DNA circuit via cascaded localized toehold-mediated strand displacement (TMSD) reactions, resulting in amplified fluorescence resonance energy transfer (FRET) signal. In this strategy, both endogenous APE1 and miR-21, served as two "keys" to activate the AND logic operation in cancer cells to reduce off-tumor signal leakage. Such a multiplied molecular recognition/activation nanomachine as a powerful toolbox realized specific capture and reliable imaging of biomolecules in living cancer cells.

Optimizing efficiency and resilience of no-take marine protected areas for fish conservation under climate change along the coastlines of China Seas.

Climate change is one of the major threats to coastal fish biodiversity, and optimization of no-take marine protected areas (MPAs) is imminent. We predicted fish redistribution under climate change in coastal China Seas with joint species distribution modeling and prioritized areas for conservation with Zonation, for which we used core area zonation (CAZ) and additive benefit function (ABF). Based on our results, we devised an expansion plan of no-take MPAs. Under climate change, fish were redistributed northward along the coast. These redistributions were segmented by the Yangtze River estuary and its adjacent waters, indicating a possible biogeographical barrier. Under CAZ and ABF, significantly more fish habitat was conserved than under random prioritization (p < 0.001, Cohen's d = -0.36 and -0.62, respectively). The ABF better represented areas with higher species richness, whereas CAZ better represented core habitats for species with narrow distributions. Without accounting for species redistribution, the expanded MPAs were mainly distributed in the northwest of the South China Sea, the East China Sea, the north of the Yellow Sea, and the west of the Bohai Sea. When accounting for species redistribution, the proposed MPAs were mainly distributed in the north of the Bohai Sea and southwest of the Yellow Sea, corresponding to the northern species redistributions. These MPAs conserved less habitat for fishes at present but protected more and better quality habitat for fishes in 2050 and 2100 than those MPAs that did not account for species redistribution, indicating improved fish conservation under climate change. Incorporating species redistribution and trade-offs between areas with high species richness and areas that contain habitats for rare species are suggested to address coastal fish conservation under climate change. This work provides valuable information for fish conservation and is a precursor to systematic conservation planning along the coastlines of China Seas.

Mejora de la eficiencia y la resiliencia de las áreas marinas protegidas con veda para la conservación de peces bajo el cambio climático en la costa de los mares de China Resumen El cambio climático es una de las principales amenazas para la biodiversidad de peces costeros, y la mejora de las área marinas protegidas (AMP) con vedas es inevitable. Pronosticamos la redistribución de los peces por el cambio climático en la costa de los mares de China con un modelo de distribución de especies y las áreas priorizadas para la conservación con Zonation, para el cual usamos zonación de las áreas núcleo (ZAN) y la función del beneficio aditivo. (FBA). Con base en nuestros resultados, diseñamos un plan de expansión de AMP con veda. Con el cambio climático, los peces se redistribuyeron hacia el norte a lo largo de la costa. Esta redistribución fue segmentada por el estuario del río Yangtze y las aguas vecinas, indicador de una posible barrera biogeográfica. Con la ZAN y la FBA, se conservó una cantidad significativa de peces en comparación con una priorización aleatoria (p < 0.001, d de Cohen = ­0.36 y ­0.62, respectivamente). La FBA representó de mejor manera las áreas con una riqueza de especies elevada, mientras que la ZAN representó de mejor manera los hábitats nucleares de las especies con una distribución reducida. Sin contar la redistribución de las especies, las AMP expandidas se localizaron principalmente en el noroeste del Mar del Sur de China, del Mar del Este de China, al norte del Mar Amarillo y al oeste del Mar Bohai. Cuando consideramos la redistribución de las especies, las AMP propuestas se localizaron principalmente al norte del Mar de Bohai y al suroeste del Mar Amarillo, lo que corresponde a la redistribución hacia el norte de las especies. Estas AMP conservaron un menor hábitat de los peces en el presente pero protegieron un mejor hábitat y de mayor calidad para los peces en 2050 y 2100 que las AMP que no consideraron la redistribución de especies, lo que indica una mejora en la conservación de peces bajo el cambio climático. Se sugiere que la incorporación de la redistribución de especies y las compensaciones entre las áreas con una riqueza de especies elevada y las áreas que albergan hábitats para especies raras abordarán la conservación de peces costeros bajo el cambio climático. Esta investigación proporciona información valiosa para la conservación de peces y es un precursor de la planeación sistemática de la conservación a lo largo de la costa de los mares de China.

Tissue damage, antioxidant capacity, transcriptional and metabolic regulation of red drum Sciaenops ocellatus in response to nanoplastics exposure and subsequent recovery.

Nanoplastics are recognized as emerging contaminants that can cause severe toxicity to marine fishes. However, limited researches were focusing on the toxic effects of nanoplastics on marine fish, especially the post-exposure resilience. In this study, red drum (Sciaenops ocellatus) were exposed to 5 mg/L polystyrene nanoplastics (100 nm, PS-NPs) for a 7-day exposure experiment, and a 14-day recovery experiment that followed. The aim was to evaluate the dynamic alterations in hepatic and branchial tissue damage, hepatic antioxidant capacity, as well as hepatic transcriptional and metabolic regulation in the red drum during exposure and post-exposure to PS-NPs. Histopathological observation found that PS-NPs primarily triggered hepatic lipid droplets and branchial epithelial liftings, a phenomenon persistently discernible up to the 14 days of recovery. Although antioxidant capacity partially recovered during recovery periods, PS-NPs resulted in a sustained reduction in hepatic antioxidant activity, causing oxidative damage throughout the entire exposure and recovery phases, as evidenced by decreased total superoxide dismutase activities and increased malondialdehyde content. At the transcriptional and metabolic level, PS-NPs primarily induced lipid metabolism disorders, DNA damage, biofilm disruption, and mitochondrial dysfunction. In the gene-metabolite correlation interaction network, numerous CcO (cytochrome c oxidase) family genes and lipid metabolites were identified as key regulatory genes and metabolites in detoxification processes. Among them, the red drum possesses one additional CcO6B in comparison to human and zebrafish, which potentially contributes to its enhanced capacity for maintaining a stable and positive regulatory function in detoxification. This study revealed that nanoplastics cause severe biotoxicity to red drum, which may be detrimental to the survival of wild populations and affect the economics of farmed populations.

Periodic Distributions and Ultrafast Dynamics of Hot Electrons in Plasmonic Resonators.

Understanding and managing hot electrons in metals are of fundamental and practical interest in plasmonic studies and applications. A major challenge for the development of hot electron devices requires the efficient and controllable generation of long-lived hot electrons so that they can be harnessed effectively before relaxation. Here, we report the ultrafast spatiotemporal evolution of hot electrons in plasmonic resonators. Using femtosecond-resolution interferometric imaging, we show the unique periodic distributions of hot electrons due to standing plasmonic waves. In particular, this distribution can be flexibly tuned by the size, shape, and dimension of the resonator. We also demonstrate that the hot electron lifetimes are substantially prolonged at hot spots. This appealing effect is interpreted as a result of the locally concentrated energy density at the antinodes in standing hot electron waves. These results could be useful to control the distributions and lifetimes of hot electrons in plasmonic devices for targeted optoelectronic applications.

Whether including exotic species alters conservation prioritization: a case study in the Min River in southeastern China.

Conservation practices from the perspective of functional diversity (FD) and conservation prioritization need to account for the impacts of exotic species in freshwater ecosystems. This work first simulated the influence of exotic species on the values of FD in a schemed mechanistic model, and then a practical case study of conservation prioritization was performed in the Min River, the largest river in southeastern China, to discuss whether including exotic species alters prioritization. The mechanistic model revealed that exotic species significantly altered the expected FD if the number of exotic species occupied 2% of the community. Joint species distribution modelling indicated that the highest FD occurred in the west, northwest and north upstreams of the Min River. Values of FD in 64.69% of the basin decreased after the exotic species were removed from calculation. Conservation prioritization with the Zonation software proved that if first the habitats of exotic species were removed during prioritization, 62.75% of the highest prioritized areas were shifted, average species representation of the endemic species was improved and mean conservation efficiency was increased by 7.53%. Existence of exotic species will significantly alter the metrics of biodiversity and the solution for conservation prioritization, and negatively weighting exotic species in the scope of conservation prioritization is suggested to better protect endemic species. This work advocates a thorough estimate of the impacts of exotic species on FD and conservation prioritization, providing complementary evidence for conservation biology and valuable implications for local freshwater fish conservation.

Prioritizing the multifaceted community and species uniqueness for the conservation of lacustrine fishes in the largest subtropical floodplain, China.

Hydrological variations affect habitat characteristics and fish distribution in floodplain lakes. Assessing the contributions of the local community (i.e., LCBD, community uniqueness) and species to overall ß diversity (i.e., SCBD, species uniqueness) of fish assemblages is valuable for habitat and species conservation planning, particularly from functional and phylogenetic perspectives. We examined the changes in multifaceted LCBD and SCBD of fish across different hydrological periods in the Poyang Lake, China, and analyzed their responsive mechanisms using regression models, based on which the conservation priorities of habitats and species were evaluated. The findings revealed that taxonomic, functional, and phylogenetic LCBD and SCBD were lowest during the wet season compared to the normal and dry seasons, emphasizing the regulatory effects of hydrological regimes on fish assemblages. Taxonomic and functional LCBD were significantly impacted by the mean abundance of migratory fish, highlighting the importance of specific species combinations on community uniqueness. Taxonomic and functional SCBD exhibited positive correlations primarily with mean abundance, suggesting the potential uniqueness of certain common species. Additionally, we identified the river-lake junction (Hukou station) and natural reserve (Xingzi and Nanjishan stations) with high overall community uniqueness as critical habitats. We also emphasized the necessity for increased conservation efforts for species having high overall species uniqueness during different hydrological periods, including Coilia brachygnathus, Ctenopharyngodon idella, Coilia nasus, Saurogobio dabryi, Hypophthalmichthys molitrix, Megalobrama amblycephala, and Parabramis pekinensis. This research underscores the significance of integrating multiple ecological perspectives to manage biodiversity changes and maintain ecological conservation values effectively.

Plasmonic Cavity-Catalysis by Standing Hot Carrier Waves.

Manipulating active sites of catalysts is crucial but challenging in catalysis science and engineering. Beyond the design of the composition and structure of catalysts, the confined electromagnetic field in optical cavities has recently become a promising method for catalyzing chemical reactions via strong light-matter interactions. Another form of confined electromagnetic field, the charge density wave in plasmonic cavities, however, still needs to be explored for catalysis. Here, we present an unprecedented catalytic mode based on plasmonic cavities, called plasmonic cavity-catalysis. We achieve direct control of catalytic sites in plasmonic cavities through standing hot carrier waves. Periodic catalytic hotspots are formed because of localized energy and carrier distribution and can be well tuned by cavity geometry, charge density, and excitation angle. We also found that the catalytic activity of the cavity mode increases several orders of magnitude compared with conventional plasmonic catalysis. We ultimately demonstrate that the locally concentrated long-lived hot carriers in the standing wave mode underlie the formation of the catalytic hotspots. Plasmonic cavity-catalysis provides a new approach to manipulate the catalytic sites and rates and may expand the frontier of heterogeneous catalysis.

DNA-Programed Plasmon Rulers Decrypt Single-Receptor Dimerization on Cell Membrane.

Decrypting the dynamics of receptor dimerization on cell membranes bears great importance in identifying the mechanisms regulating diverse cellular activities. In this regard, long-term monitoring of single-molecule behavior during receptor dimerization allows deepening insight into the dimerization process and tracking of the behavior of individual receptors, yet this remains to be realized. Herein, real-time observation of the receptor tyrosine kinases family (RTKs) at single-molecule level based on plasmon rulers was achieved for the first time, which enabled precise regulation and dynamic monitoring of the dimerization process by DNA programming with excellent photostability. Additionally, those nanoprobes demonstrated substantial application in the regulation of RTKs protein dimerization/phosphorylation and activation of downstream signaling pathways. The proposed nanoprobes hold considerable potential for elucidating the molecular mechanisms of single-receptor dimerization as well as the conformational transitions upon dimerization, providing a new paradigm for the precise manipulation and monitoring of specific single-receptor crosslink events in biological systems.

A Cascade Nanoreactor of Metal-Protein-Polyphenol Capsule for Oxygen-Mediated Synergistic Tumor Starvation and Chemodynamic Therapy.

Starvation therapy kills tumor cells via consuming glucose to cut off their energy supply. However, since glucose oxidase (GOx)-mediated glycolysis is oxygen-dependent, the cascade reaction based on GOx faces the challenge of a hypoxic tumor microenvironment. By decomposition of glycolysis production of H2 O2 into O2 , starvation therapy can be enhanced, but chemodynamic therapy is limited. Here, a close-loop strategy for on demand H2 O2 and O2 delivery, release, and recycling is proposed. The nanoreactor (metal-protein-polyphenol capsule) is designed by incorporating two native proteins, GOx and hemoglobin (Hb), in polyphenol networks with zeolitic imidazolate framework as sacrificial templates. Glycolysis occurs in the presence of GOx with O2 consumption and the produced H2 O2 reacts with Hb to produce highly cytotoxic hydroxyl radicals (•OH) and methemoglobin (MHb) (Fenton reaction). Benefiting from the different oxygen carrying capacities of Hb and MHb, oxygen on Hb is rapidly released to supplement its consumption during glycolysis. Glycolysis and Fenton reactions are mutually reinforced by oxygen supply, consuming more glucose and producing more hydroxyl radicals and ultimately enhancing both starvation therapy and chemodynamic therapy. This cascade nanoreactor exhibits high efficiency for tumor suppression and provides an effective strategy for oxygen-mediated synergistic starvation therapy and chemodynamic therapy.

Deep learning-based clinical decision support system for gastric neoplasms in real-time endoscopy: development and validation study.

BACKGROUND : Deep learning models have previously been established to predict the histopathology and invasion depth of gastric lesions using endoscopic images. This study aimed to establish and validate a deep learning-based clinical decision support system (CDSS) for the automated detection and classification (diagnosis and invasion depth prediction) of gastric neoplasms in real-time endoscopy. METHODS : The same 5017 endoscopic images that were employed to establish previous models were used for the training data. The primary outcomes were: (i) the lesion detection rate for the detection model, and (ii) the lesion classification accuracy for the classification model. For performance validation of the lesion detection model, 2524 real-time procedures were tested in a randomized pilot study. Consecutive patients were allocated either to CDSS-assisted or conventional screening endoscopy. The lesion detection rate was compared between the groups. For performance validation of the lesion classification model, a prospective multicenter external test was conducted using 3976 novel images from five institutions. RESULTS : The lesion detection rate was 95.6 % (internal test). On performance validation, CDSS-assisted endoscopy showed a higher lesion detection rate than conventional screening endoscopy, although statistically not significant (2.0 % vs. 1.3 %; P = 0.21) (randomized study). The lesion classification rate was 89.7 % in the four-class classification (advanced gastric cancer, early gastric cancer, dysplasia, and non-neoplastic) and 89.2 % in the invasion depth prediction (mucosa confined or submucosa invaded; internal test). On performance validation, the CDSS reached 81.5 % accuracy in the four-class classification and 86.4 % accuracy in the binary classification (prospective multicenter external test). CONCLUSIONS : The CDSS demonstrated its potential for real-life clinical application and high performance in terms of lesion detection and classification of detected lesions in the stomach.

AgMAsS3 (M = Cd, Hg): Double d10 Cation-Containing Thioarsenites(III) Exhibiting High Photocurrent Response and Moderate Second Harmonic Generation.

Thioarsenites(III) are an advanced functional material platform owing to the stereochemically active lone pair cations. In this paper, two novel quaternary thioarsenites(III), AgMAsS3 (M = Cd, Hg), are successfully obtained by introducing double d10 cations. In the compounds, d10 cations show a variety of different coordination modes ([AgS4] and [HgS4] in AgHgAsS3 vs [AgS5] and [CdS6] in AgCdAsS3). As a result, AgHgAsS3 and AgCdAsS3 crystallize in the noncentrosymmetric Cc space group and centrosymmetric C2/c space group, respectively. The band gaps of AgHgAsS3 and AgCdAsS3 are determined experimentally as 1.90 and 2.20 eV, respectively. Meanwhile, title compounds exhibit strong photocurrent responses. Specifically, AgHgAsS3 has a large birefringence of 0.18 at 2100 nm and a moderate second harmonic generation of (0.5 × AgGaS2). Moreover, the origin of linear and nonlinear optical responses is investigated based on first-principles calculations. This study enriches the family of MI-MII-As-Q (M = Ag, Cu; MII = Zn, Cd, Hg; Q = chalcogen) chalcogenides and helps to understand and design other multifunctional optical materials.

CRISPR-mediated MECOM depletion retards tumor growth by reducing cancer stem cell properties in lung squamous cell carcinoma.

Targeted therapy for lung squamous cell carcinoma (LUSC) remains a challenge due to the lack of robust targets. Here, we identified MECOM as a candidate of therapeutic target for LUSC by screening 38 genes that were commonly amplified in three pairs of primary tumors and patient-derived xenografts (PDXs) using a clustered regularly interspaced short palindromic repeats (CRISPR)-mediated approach. High MECOM expression levels were associated with poor prognosis. Forced expression of MECOM in LUSC cell lines promoted cancer stem cell (CSC) properties, and its knockout inhibited CSC phenotypes. Furthermore, systemic delivery of CRISPR-mediated MECOM depletion cassette using adenovirus with an adaptor, which is composed of a single-chain fragment variable (scFv) against epithelial cell adhesion molecules (EpCAM) fused to the ectodomain of coxsackievirus and adenovirus receptor, and a protector, which consists of the scFv connected to the hexon symmetry of the adenovirus, could specifically target subcutaneous and orthotopic LUSC and retard tumor growth. This study could provide a novel therapeutic strategy for LUSC with high efficacy and specificity.

Photothermally Triggered Copper Payload Release for Cuproptosis-Promoted Cancer Synergistic Therapy.

Cuproptosis is a new form of programmed cell death and exhibits enormous potential in cancer treatment. However, reducing the undesirable Cu ion release in normal tissue and maximizing the copper-induced therapeutic effect in cancer sites are two main challenges. In this study, we constructed a photothermally triggered nanoplatform (Au@MSN-Cu/PEG/DSF) to realize on-demand delivery for synergistic therapy. The released disulfiram (DSF) chelated with Cu2+ in situ to generate highly cytotoxic bis(diethyldithiocarbamate)copper (CuET), causing cell apoptosis, and the formed Cu+ species promoted toxic mitochondrial protein aggregation, leading to cell cuproptosis. Synergistic with photothermal therapy, Au@MSN-Cu/PEG/DSF could effectively kill tumor cells and inhibit tumor growth (inhibition rate up to 80.1 %). These results provide a promising perspective for potential cancer treatment based on cuproptosis, and may also inspire the design of advanced nano-therapeutic platforms.

Tracking Ion Transport in Nanochannels via Transient Single-Particle Imaging.

The transport behavior of ions in the nanopores has an important impact on the performance of the electrochemical devices. Although the classical Transmission-Line (TL) model has long been used to describe ion transport in pores, the boundary conditions for the applicability of the TL model remain controversial. Here, we investigated the transport kinetics of different ions, within nanochannels of different lengths, by using transient single-particle imaging with temporal resolution up to microseconds. We found that the ion transport kinetics within short nanochannels may deviate significantly from the TL model. The reason is that the ion transport under nanoconfinement is composed of multi basic stages, and the kinetics differ much under different stage domination. With the shortening of nanochannels, the electrical double layer (EDL) formation would become the "rate-determining step" and dominate the apparent ion kinetics. Our results imply that using the TL model directly and treating the in-pore mobility as an unchanged parameter to estimate the ion transport kinetics in short nanopores/nanochannels may lead to orders of magnitude bias. These findings may advance the understanding of the nanoconfined ion transport and promote the related applications.

Decrypting Material Performance by Wide-field Femtosecond Interferometric Imaging of Energy Carrier Evolution.

Energy carrier evolution is crucial for material performance. Ultrafast microscopy has been widely applied to visualize the spatiotemporal evolution of energy carriers. However, direct imaging of a small amount of energy carriers on the nanoscale remains difficult due to extremely weak transient signals. Here, we present a method for ultrasensitive and high-throughput imaging of energy carrier evolution in space and time. This method combines femtosecond pump-probe techniques with interferometric scattering microscopy (iSCAT), named Femto-iSCAT. The interferometric principle and unique spatially modulated contrast enhancement enable the exploration of new science. We address three important and challenging problems: transport of different energy carriers at various interfaces, heterogeneous hot-electron distribution and relaxation in single plasmonic resonators, and distinct structure-dependent edge-state dynamics of carriers and excitons in optoelectronic semiconductors. Femto-iSCAT holds great potential as a universal tool for ultrasensitive imaging of energy carrier evolution in space and time.

SrAgAsS4: A Noncentrosymmetric Sulfide with Good Infrared Nonlinear Optical Performance Induced by Aliovalent Substitution from Centrosymmetric SrGa2S4.

A new noncentrosymmetric (NCS) quaternary sulfide, SrAgAsS4, was obtained via the strategy of aliovalent substitution based on centrosymmetric (CS) SrGa2S4. The new compound features two-dimensional [AgAsS4]2- layers, which are composed of alternately connected [AsS4] tetrahedra and [AgS4] tetrahedra. Importantly, SrAgAsS4 exhibits a strong phase-matched second-harmonic generation response (1.35 × AgGaS2 at 2100 nm) and has a suitable birefringence (0.15@2100 nm) and moderate band gap (2.31 eV). The first-principles calculations revealed the significant contribution of [AsS4] and [AgS4] tetrahedra to its optical properties. This work will promote the application of the aliovalent substitution strategy in the design of NCS-structure-based functional materials.

Evaluation of acute kidney injury by urinary tissue inhibitor metalloproteinases-2 and insulin-like growth factor-binding protein 7 after pediatric cardiac surgery.

BACKGROUND: With adult patients, the measurement of [TIMP-2]*[IGFBP7] can predict the risk of moderate to severe AKI within 12 h of testing. In pediatrics, however, the performance of [TIMP-2]*[IGFBP7] as a predictor of AKI was less studied and yet to be widely utilized in clinical practice. This study was conducted to validate the utility of [TIMP-2]*[IGFBP7] as an earlier biomarker for AKI prediction in Chinese infants and small children. METHODS: We measured urinary [TIMP-2]*[IGFBP7] using NEPHROCHECK® at eight perioperative time points in 230 patients undergoing complex cardiac surgery and evaluated the performance of [TIMP-2]*[IGFBP7] for predicting severe AKI within 72 h of surgery. RESULTS: A total of 50 (22%) of 230 developed AKI stages 2-3 within 72 h after CPB initiation. In the AKI stage 2-3 patients, two patterns of serum creatinine (SCr) elevations were observed. The patients with only a transient increase in SCr within 24 h (< 24 h, early AKI 2-3) did not experience a worse outcome than patients in AKI stage 0-1. AKI stage 2-3 patients with SCr elevation after 24 h (24-72 h, late AKI 2-3), as well as AKI dialysis patients (together designated severe AKI), did experience worse outcomes. Compared to AKI stages 0-1, significant elevations of [TIMP-2]*[IGFBP7] values were observed in severe AKI patients at hours T2, T4, T12, and T24 following CPB initiation. The AUC for predicting severe AKI with [TIMP-2]*[IGFBP7] at T2 (AUC = 0.76) and maximum T2/T24 (AUC = 0.80) are higher than other time points. The addition of the NEPHROCHECK® test to the postoperative parameters improved the risk assessment of severe AKI. CONCLUSIONS: Multiple AKI phenotypes (early versus late AKI) were identified after pediatric complex cardiac surgery according to SCr-based AKI definition. Urinary [TIMP-2]*[IGFBP7] predicts late severe AKI (but not early AKI) as early as 2 h following CPB initiation. A higher resolution version of the Graphical abstract is available as Supplementary information.

Transurethral enucleation of the prostate combined with laparoscopic bladder diverticulectomy.

OBJECTIVE: We present a one-session procedure for treating bladder diverticula combined with benign prostatic hyperplasia (BPH). MATERIAL AND METHODS: Between January 2015 and April 2019, transurethral plasmakinetic enucleation of the prostate (TUEP) followed by laparoscopic bladder diverticulectomy (LD) were performed in 12 patients at our institution, in four of them combined with bladder stone(s) and in one patient combined with diverticular tumor. Clinical data were retrospectively collected. RESULTS: The mean size of the prostate was 137.3 ± 96.3 (65.5-403.3) ml. The mean maximal diameter of the diverticulum was 8.0 ± 2.7 (3.2-12.0) cm. The mean total operation time was 214.2 ± 69.0 (120-300) min, and the mean enucleation time was 23.2 ± 6.4 (12-35) min. The mean intraoperative blood loss was 52.1 ± 14.9 (30-80) ml. The average pre- and post-operative maximum flow rate was 5.1 ± 1.4 (2.4-8.5) ml/s and 12.8 ± 2.3 (9.6-17.1) ml/s. Except for urinary infection in one patient, no other severe peri- or postoperative complications were observed. CONCLUSIONS: TUEP accompanied by LD in one session provides an effective and minimally invasive surgical treatment for bladder diverticula combined with BPH, with or without bladder stones, and permits reasonable operation time and rapid discharge.

Transient Plasmonic Imaging of Ion Migration on Single Nanoparticles and Insight for Double Layer Dynamics.

Single-nanoparticle electrochemistry offers electrochemical behaviors of individual entities beyond the ensemble system. An electric double layer (EDL) exists on any charged particle-liquid interface because of counter-ion accumulation, while direct measuring of the interfacial ion migration remains a challenge. Herein, a plasmonic-based transient microscopic method, with a temporal resolution of 1-2 µs, was demonstrated to directly track the ion migration dynamics on single charged nanoparticles. We found that the dynamics of EDL formation might deviate significantly from the prediction made by using the classical resistance-capacitance (RC) model under nanoscale and transient conditions. Under ultrafast charging, due to the limit migration rate of ions in the solution, the actual time scale of the EDL formation could be up to 5 times slower than the predicted value from the RC model. We then proposed a new theoretical model to describe the transient dynamics of EDL formation. These results may expand our current knowledge about nano-electrochemistry and transient electrochemistry.

Quadruple-editing of the MAPK and PI3K pathways effectively blocks the progression of KRAS-mutated colorectal cancer cells.

Mutated KRAS promotes the activation of the MAPK pathway and the progression of colorectal cancer (CRC) cells. Aberrant activation of the PI3K pathway strongly attenuates the efficacy of MAPK suppression in KRAS-mutated CRC. The development of a novel strategy targeting a dual pathway is therefore highly essential for the therapy of KRAS-mutated CRC. In this study, a quadruple-depleting system for the KRAS, MEK1, PIK3CA, and MTOR genes based on CRISPR/SaCas9 was developed. Adenovirus serotype 5 (ADV5) was integrated with two engineered proteins, an adaptor and a protector, to form ADV-protein complex (APC) for systemic delivery of the CRISPR system. Quadruple-editing could significantly inhibit the MAPK and PI3K pathways in CRC cells with oncogenic mutations of KRAS and PIK3CA or with KRAS mutation and compensated PI3K activation. Compared with MEK and PI3K/MTOR inhibitors, quadruple-editing induced more significant survival inhibition on primary CRC cells with oncogenic mutations of KRAS and PIK3CA. The adaptor specifically targeting EpCAM and the hexon-shielding protector could dramatically enhance ADV5 infection efficiency to CRC cells and significantly reduce off-targeting tropisms to many organs except the colon. Moreover, quadruple-editing intravenously delivered by APC significantly blocked the dual pathway and tumor growth of KRAS-mutated CRC cells, without influencing normal tissues in cell- and patient-derived xenograft models. Therefore, APC-delivered quadruple-editing of the MAPK and PI3K pathways shows a promising therapeutic potential for KRAS-mutated CRC.