High-Entropy Lanthanide-Organic Framework as an Efficient Heterogeneous Catalyst for Cycloaddition of CO2 with Epoxides and Knoevenagel Condensation.

Multimetallic synergistic effects have the potential to improve CO2 cycloesterification and Knoevenagel reaction processes, outperforming monometallic MOFs. The results demonstrate superior performance in these processes. To investigate this, we created and characterized a selection of single-component Ln(III)-MOFs (Ln=Eu, Tb, Gd, Dy, Ho) and high-entropy lanthanide-organic framework (HE-LnMOF) using solvent-thermal conditions. The experiments revealed that HE-LnMOF exhibited heightened catalytic efficiency in CO2 cycloesterification and Knoevenagel reactions compared to single-component Ln(III) MOFs. Moreover, the HE-LnMOF displayed significant stability, maintaining their structural integrity after five cycles while sustaining elevated conversion and selectivity rates. The feasible mechanisms of catalytic reactions were also discussed. HE-LnMOF possess multiple unsaturated metal centers, acting as Lewis acid sites, with oxygen atoms connecting the metal, and hydroxyl groups on the ligand serving as base sites. This study introduces a novel method for synthesizing HE-LnMOF and presents a fresh application of HE-LnMOF for converting CO2.

Comparative study of the multiple wavelength lasing of nitrogen ions: the role of vibrational level-dependent photoionization.

We report on an optical amplification and energy threshold of the two most prominent emission lines, 391.4 and 427.8 nm, of the cavity-less lasing of nitrogen ions pumped by femtosecond laser pulses. It was found that the two transitions both show optical amplification under a low gas pressure condition, while the 391.4 nm emission is barely amplified under high gas pressure. Moreover, the 427.8 nm emission presents a significant lower pump laser energy threshold and a larger gain factor than the 391.4 nm emission. Numerical simulations based on a three-state coupling model suggest that the smaller ionization Franck-Condon factor from the ground state of N2 to the vibrational level ν = 1 in X 2 Σ g+ state of N2 + favors the formation of population inversion corresponding to the 427.8 nm emission. Meanwhile, the competition between the strong field ionization and excitation induced by the pumping laser requires higher laser intensity to acquire the population inversion for the 391.4 nm radiation, leading to a corresponding larger energy threshold.

Enhanced Electrocatalytic Oxygen Evolution by In Situ Growth of Tetrametallic Metal-Organic Framework Electrocatalyst FeCoNiMn-MOF on Nickel Foam.

Developing highly efficient, cost-effective, non-noble-metal-based electrocatalysts with superior performance and stability for oxygen evolution reactions is of immense challenge as well as great importance for the upcoming sustainable and green energy conversion technologies. The multivariate metal-organic frameworks with hierarchical porous structures and unsaturated coordination modes are considered to be promising emerging energy materials. In this work, a series of multimetallic MOFs were directly grown on nickel foam (NF) through the solvothermal method. Notably, the optimized tetrametallic FeCoNiMn-MOF/NF shows a low overpotential of 239 mV to achieve a current density of 50 mA cm-2 with a Tafel slope of 62.05 mV dec-1 for OER in 1 M KOH. It also exhibits excellent stability and durability over 100 h in chronoamperometric studies. The enhanced performance is closely tied to the high activity of iron and nickel ions and the decomposed and reconstructed Ni/Fe-OOH intermediates of the FeCoNiMn-MOF/NF during the OER process, which are revealed by XPS analysis and in situ Raman spectroscopy. This present work demonstrates the feasibility and advantage of utilizing highly efficient and durable multimetallic MOFs for electrocatalytic oxygen evolution.

Case study on long-term deformation monitoring and numerical simulation of layered rock slopes on both sides of Wudongde dam reservoir area.

Layered rock slope exists widely. Because of its special slope structure, it is prone to bending deformation and toppling failure, which is a serious threat to engineering construction and safety operation. At present, the research of layered rock slope still has great innovation potential. During the construction of Wudongde Hydropower Station on Jinsha River, safety and stability problems such as slope geological structure development, face rock unloading and relaxation, and even slip and large deformation were encountered. Through field exploration, it is found that the rock and soil stratification of the slope on both sides of Wudongde Hydropower Station is highly obvious. At present, there is a lack of research on-site long-term displacement monitoring of layered rock high-steep slope, especially for layered slope in complex hydrogeology and construction environment. In order to strengthen the research on the deformation and stability of layered rock slope, this paper analyzes the measured displacement data of Wudongde hydropower station slope, and establishes three-dimensional geological finite element model with the help of numerical simulation software. The stability of the slope is calculated by combining the finite difference method and the strength reduction method. Finally, the evolution mechanism of the deformation of the layered rock slope is explained according to the geological structure characteristics. The main conclusions of this paper are as follows: the layered slope in the dam reservoir area is prone to deformation under the combined action of long-term construction disturbance and fissure water seepage, and the construction disturbance has a strong influence on the artificial excavation area below 1070 m, and the maximum rock mass deformation and surface displacement in the artificial excavation area of the slope reach 92.2 mm and 312.5 mm, respectively. However, the influence of construction disturbance on the natural mountain above 1070 m is limited, the valley deformation of the natural mountain on the left bank of the reservoir area is higher than that on the right bank, and the cumulative deformation is still less than 20 mm. The influence of seepage on the displacement of the area with higher elevation at the top of the slope is more obvious, and the influence of excavation and other disturbances on the displacement of the artificial excavation area with lower elevation is more obvious. The deformation of the river valley in the water cushion pond behind the dam increases slowly, and the change trend of the field deformation data is mostly consistent with that of the numerical calculation. The horizontal shrinkage of the mountains on both sides shows a contraction trend on the whole, and the maximum horizontal shrinkage calculated by numerical simulation is close to 20 mm, which is located at the elevation of 990 m.

A copper-platinum nanoplatform for synergistic photothermal and chemodynamic tumor therapy via ROS outburst and GSH exhaustion.

A multifunctional nanoplatform is obtained by modifying copper hexacyanoferrate (Cu-HCF) nanozyme with hyaluronic acid (HA) and further loading platinum (Pt) nanoparticles. This Cu-HCF-HA@Pt platform shows peroxidase-like and glutathione oxidase-like dual-enzyme catalytic activities and photothermal properties, enabling synergistic chemodynamic and photothermal tumor therapy. HA binds to the CD44 receptor, which is highly expressed on the exterior surface of tumor cells, endowing the nanoplatform with tumor specificity. Cu-HCF-HA@Pt catalyzes the decomposition of H2O2 to produce abundant hydroxyl radicals within tumor cells, increasing intracellular oxidative stress levels and inducing tumor cell apoptosis. Meanwhile, Cu-HCF-HA@Pt catalyzes the conversion of intracellular reduced glutathione (GSH) to oxidized glutathione, resulting in GSH exhaustion. The conversion of CuII to CuI in Cu-HCF via a Fenton-like reaction can improve the peroxidase-like property of Cu-HCF-HA@Pt. After the probe is targeted to the tumor site, irradiation by an 808 nm near-infrared laser causes local heating and brings about photothermal tumor apoptosis when reaching 45 °C. The prepared Cu-HCF-HA@Pt combines nanozyme-catalyzed therapy with photothermal therapy to induce apoptosis in tumor cells.

Molybdenum Disulfide-Integrated Iron Organic Framework Hybrid Nanozyme-Based Aptasensor for Colorimetric Detection of Exosomes.

Tumor-derived exosomes are considered as a potential marker in liquid biopsy for malignant tumor screening. The development of a sensitive, specific, rapid, and cost-effective detection strategy for tumor-derived exosomes is still a challenge. Herein, a visualized and easy detection method for exosomes was established based on a molybdenum disulfide nanoflower decorated iron organic framework (MoS2-MIL-101(Fe)) hybrid nanozyme-based CD63 aptamer sensor. The CD63 aptamer, which can specifically recognize and capture tumor-derived exosomes, enhanced the peroxidase activity of the hybrid nanozyme and helped to catalyze the 3,3',5,5'-tetramethylbenzidine (TMB)-H2O2 system to generate a stronger colorimetric signal, with its surface modification on the hybrid nanozyme. With the existence of exosomes, CD63 aptamer recognized and adsorbed them on the surface of the nanozyme, which rescued the enhanced peroxidase activity of the aptamer-modified nanozyme, resulting in a deep-to-moderate color change in the TMB-H2O2 system where the change is visible and can be monitored with ultraviolet-visible spectroscopy. In the context of optimal circumstances, the linear range of this exosome detection method is measured to be 1.6 × 104 to 1.6 × 106 particles/µL with a limit of detection as 3.37 × 103 particles/µL. Generally, a simple and accessible approach to exosome detection is constructed, and a nanozyme-based colorimetric aptamer sensor is proposed, which sheds light on novel oncological biomarker measurements in the field of biosensors.

Measuring small displacements of an optical point source with digital holography.

The image of an optical point source is blurred due to light diffraction so that estimating small displacements of the point source with direct imaging demands elaborate processing on the observation data of a camera. Using quantum parameter estimation, we show that for the imaging systems with a real point spread function, any measurement basis constituted by a complete set of real-valued spatial-mode functions is optimal for estimating the displacement. For small displacements, we can concentrate the information about the value of displacement to the measurement of a few spatial modes, which can be selected in terms of the Fisher information distribution. We use digital holography with a phase-only spatial light modulator to implement two simple estimation strategies that are mainly based on the projection measurement of two spatial modes and the readout of a single pixel of a camera.

Surface astigmatism correction using segmented freeform surfaces for a progressive addition lens.

The undesired distribution of irregular surface astigmatism (SA) on the freeform surface has been the major concern of progressive addition lens (PAL) design. Herein, we proposed a segmented freeform surface (SFS) construction method, which relies on the lines of curvature to rule the surface segmentation and then eliminates the difference between principal curvatures to correct the SA. Based on ray tracing and numerical simulation results, the SFS-PAL design has superior performance in image quality within a dynamic field of view over the conventional freeform PAL. To verify the feasibility and the real performance of the new design, we used the diamond turning method with a fast tool servo to realize the rapid prototyping, and then used injection molding for the mass production of the high-quality SFS-PALs.

PDA-coated CPT@MIL-53(Fe)-based theranostic nanoplatform for pH-responsive and MRI-guided chemotherapy.

Theranostic nanoplatforms for multimodal diagnosis and treatment of tumors are a current research hotspot in the field of nanomedicine. MOF-based theranostic nanoplatforms integrating drug delivery with magnetic resonance imaging (MRI) have attracted broad attention in cancer diagnosis and therapy. However, due to the poor chemical and colloidal stability of MOFs, as well as their poor biocompatibility, MOF-based theranostic nanoplatforms still face critical challenges in cancer treatment applications. Here, we devised a theranostic nanoplatform based on a bioinspired polydopamine (PDA)-functionalized metal-organic framework MIL-53(Fe) loaded with camptothecin (CPT) for MRI-guided pH-sensitive chemotherapy. On the nanoplatform, MIL-53(Fe) with good biodegradability has large pore volume and showed a high loading content of antitumor drug CPT (43.07%). To overcome the disadvantages of poor aqueous solubility of MIL-53(Fe) and easy photodecomposition of CPT, the CPT-loaded MIL-53(Fe) was coated with a layer of PDA, resulting in theranostic nanoparticles (PDA@CPT@MIL-53(Fe)). The theranostic nanoparticles exhibited excellent stability and pH-sensitive drug release. In vitro toxicity studies showed that the nanoparticles could be efficiently taken up by breast cancer MCF-7 cells and exhibited high cytotoxicity. In vivo antitumor assay showed the great antitumor effect of the theranostic nanoparticles by using a zebrafish xenograft model. Furthermore, the incorporation of Fe affords the PDA@CPT@MIL-53(Fe) with potential MRI; in vitro MRI showed the nanoparticles exhibit an excellent MRI performance with an r2 value up to 50 mM-1 s-1. These results suggest that CPT-loaded MIL-53(Fe) coated with PDA is a promising theranostic platform for MRI imaging and cancer therapy.

Photoelectrochemical determination of diclofenac using oriented single-crystalline TiO2 nanoarray modified with molecularly imprinted polypyrrole.

A novel molecular imprint photoelectrochemical (PEC) sensor has been prepared based on oriented single-crystalline TiO2 nanoarray (TNA) material for sensitive detection of diclofenac (DCF). The TNA obtained by the one-step hydrothermal method was characterized by XRD, SEM, and TEM. Polypyrrole film was formed on the TNA by electrochemical method, and DCF was imprinted on the polymer film as the template molecule. After the removal of DCF, there appeared lots of specific recognition sites that matched template molecules. The experimental results demonstrated that the constructed PEC sensor has good sensitivity and selectivity for the detection of DCF, which can be attributed to the high photoelectric conversion efficiency of TNA and the high selectivity of molecular imprinting technology. The fabricated PEC sensor showed a wide detection range (0.05-1000 µM) and a low limit of detection (0.0034 µM) for DCF, as well as good repeatability and stability. The proposed PEC sensor provided an effective strategy in the monitoring of environmental pollutants.

An insight into the drag effect of water, land, and energy on economic growth across space and time: the application of improved Solow growth model.

Economies that depend on natural resources can experience a resource drag effect when economic growth is limited by constraints on the availability of those resources. Therefore, this study uses panel data and the improved Solow growth model to explore the resource drag effect on China's regional economic growth from 1987 to 2017 and makes innovative contributions to address these four gaps in the previous literature: the resources gap, the consistent measurement gap, the regional gap, and the temporal gap. The empirical results indicate that the resource drag effect reduced China's overall annual economic growth by 0.58% during the study period, with reductions of 1.07%, 0.29%, 0.79%, and 0.46% in the Eastern, Western, Central, and Northeastern regions, respectively. In the meantime, the resources drag effect changed in individual regions and across regions. The results on energy drag are most notable. Policies such as "West-to-East Electricity Transmission" and "West-to-East Gas Transmission" promoted economic growth of the Eastern and Western Region, facilitating continued growth in both regions and attracted the return of labor to the Western region. The results indicate that the policies such as west-to-east energy transfer for helping to even out the economic growth conditions in different regions. Labor force mobility has also been important to alleviate resource dependence of agricultural production in Central regain, while other regions have managed to continually grow through improvements in inefficiency. Also, growth in some regions/provinces continues to depend upon increases in water, land, and energy availability and export. This will become increasingly problematic as the social prices of these inputs rise to account for environmental damage. Therefore, the government should adjust the industrial structure of each region to optimize use of resource endowments, alleviate dependence on natural resources, and achieve sustainable economic development.

Multifunctional Magnesium Organic Framework-Based Microneedle Patch for Accelerating Diabetic Wound Healing.

Diabetic wound healing is one of the major challenges in the biomedical fields. The conventional single drug treatments have unsatisfactory efficacy, and the drug delivery effectiveness is restricted by the penetration depth. Herein, we develop a magnesium organic framework-based microneedle patch (denoted as MN-MOF-GO-Ag) that can realize transdermal delivery and combination therapy for diabetic wound healing. Multifunctional magnesium organic frameworks (Mg-MOFs) are mixed with poly(γ-glutamic acid) (γ-PGA) hydrogel and loaded into the tips of MN-MOF-GO-Ag, which slowly releases Mg2+ and gallic acid in the deep layer of the dermis. The released Mg2+ induces cell migration and endothelial tubulogenesis, while gallic acid, a reactive oxygen species-scavenger, promotes antioxidation. Besides, the backing layer of MN-MOF-GO-Ag is made of γ-PGA hydrogel and graphene oxide-silver nanocomposites (GO-Ag) which further enables excellent antibacterial effects for accelerating wound healing. The therapeutic effects of MN-MOF-GO-Ag on wound healing are demonstrated with the full-thickness cutaneous wounds of a diabetic mouse model. The significant improvement of wound healing is achieved for mice treated with MN-MOF-GO-Ag.

Renal Ewing's sarcoma/primitive neuroectodermal tumor (PNET): a case series of 7 patients and literature review.

BACKGROUND: Primitive neuroectodermal tumor (PNET) is a rare kind of sarcoma that is primarily found in the kidney and has a very poor prognosis. Here, we review and summarize the clinical data of patients with renal PNET in our center and follow up the patients for survival status. Although the current literature suggests that chemotherapy may benefit the survival of these patients, the information from our center suggests that this may not be the case. METHODS: We retrospectively analyzed the clinical data of patients with renal PNET diagnosed pathologically at Peking University First Hospital from January 1, 2007, to January 1, 2018. All of the patients were followed up for survival status. RESULTS: Seven patients with renal PNET were found. The ratio of males to females was 6:1. The median age was 29 years (21-72 years) at the time of diagnosis. The preoperative imaging examination showed a large renal mass protruding outwards from the renal contour, with internal necrosis and hemorrhage. Six/7 patients were diagnosed with distant metastasis or retroperitoneal lymph node metastasis. The main clinical manifestations of patients were pain (5/7) and fever (3/7). In immunohistochemistry, all patients' samples were CD99 positive. All patients died in our follow-up, with an average overall survival (OS) of 12.09 months (1.90-26.77 months). CONCLUSIONS: As a rare renal tumor, renal PNET has a propensity to occur in young males. Most patients have distant metastasis when they are diagnosed, and the prognosis is very poor. Effective treatments are urgently needed.

Liquid exfoliated biocompatible WS2@BSA nanosheets with enhanced theranostic capacity.

Ultrathin transition metal dichalcogenides (TMDs) seem to have a promising future in the field of theranostic agents due to their excellent near-infrared light absorption capacity and large specific surface area. Plenty of previous studies focused on the therapeutic effects of the materials, but were less concerned with the detailed studies of biocompatibility for clinical transformation. In this work, ultrathin WS2 nanosheets coated with bovine serum protein (BSA) (WS2@BSA NSs) were selected as experimental subjects with favorable biocompatibility to explore their potential as a theranostic agent. Firstly, ultrathin WS2 nanosheets were prepared by ultrasound-assisted exfoliation using n-methyl pyrrolidone (NMP) as the liquid phase, followed by coating with bovine serum protein. The physical and chemical properties of WS2@BSA NSs were investigated. Secondly, the biocompatibility experiments that are most relevant to clinical transformation were divided into cell level experiments and in vivo experiments with zebrafish as the model organism. Finally, to explore further applications for the diagnosis and treatment of tumors, the in vitro photothermal effect and the X-ray computed tomography (CT) imaging capability of WS2@BSA NSs were investigated. The obtained results were promising in terms of biocompatibility and theranostics, which suggested the potential of WS2@BSA NSs for use as a multifunctional theranostic agent in clinics.

A frequency band constrained filtered-x least mean square algorithm for feedback active control systems.

The generalized leaky filtered-x least mean square (GLFxLMS) algorithm can reduce the noise amplification caused by the waterbed effect in feedback active control systems effectively; however, it suffers from a high computation complexity. Hence, a frequency band constrained filtered-x least mean square algorithm is proposed to reduce the computation complexity of the GLFxLMS algorithm by replacing the penalty term containing a symmetric Toeplitz matrix in the cost function with the mean square of a penalty signal. The simulation results based on the measured transfer functions of an active headrest system show that the proposed algorithm has the same performance as the GLFxLMS algorithm, but with much lower computation complexity.

Lanthanide-Doped Upconversion-Linked Immunosorbent Assay for the Sensitive Detection of Carbohydrate Antigen 19-9.

Lanthanide-doped upconversion nanoparticles (UCNPs) have attracted considerable attention in detection of biological analytes and bioimaging owing to their superior optical properties, including high photochemical stability, sharp emission bandwidth, large anti-Stokes shifts, and low toxicity. In this work, we fabricated UCNP-linked immunosorbent assay (ULISA) for the sensitive detection of carbohydrate antigen 19-9 (CA19-9). The design is based on amino-functionalized SiO2-coated Gd-doped NaYF4:Yb3+,Er3+ upconversion nanoparticles (UCNPs@SiO2-NH2) as a direct background-free luminescent reporter; a secondary anti-IgG antibody (Ab2) was conjugated to the surface of UCNPs@SiO2-NH2 (UCNP-Ab2), and UCNP-Ab2 was used for specific targeting of CA19-9. The UCNPs were well characterized by TEM, SEM, XRD, FT-IR, and UV-vis. The detection process was similar to enzyme-linked immunosorbent assay (ELISA). UCNPs were used as signal transducer to replace the color compounds for an enzyme-mediated signal amplification step. An anti-CA19-9 primary antibody (Ab1) was fixed for capturing the CA19-9, and the fluorescence signal was obtained from the specific immunoreaction between UCNP-Ab2 and CA19-9. Under optimum conditions, this ULISA shows sensitive detection of CA19-9 with a dynamic range of 5-2,000 U/ml. The ULISA system shows higher detection sensitivity and wider detection range compared with the traditional ELISA for CA19-9 detection. This strategy using UCNPs as signal transducer may pave a new avenue for the exploration of rare doped UCNPs in ELISA assay for clinical applications in the future.

Sonochemical assisted synthesis of dual functional BSA nanoparticle for the removal of excessive bilirubin and strong anti-tumor effects.

In this study, we prepared a dual functional albumin-based nanoparticle (gal-BSA-NPs) by sonochemical method which allowed an efficient encapsulation for Bilirubin (BR) through its adsorption capacity and hydrophobic interaction. Our study provided a possibility that the blank gal-BSA-NPs can replace BSA with better ability for the adsorption of excessive BR. Additionally, we unearthed the potential anti-tumor activity of BR on HepG2 cells and developed GSH-responsive BR-loaded gal-BSA-NPs for the treatment of liver cancer. The results showed BR-loaded gal-BSA-NPs effectively enhanced cellular uptake and exerted strong inhibition on tumor cell proliferation and migration. In vivo anti-tumor study revealed BR-loaded gal-BSA-NPs showed strong anti-tumor effects. Our study not only revealed the anti-tumor potency of BR, but also brought conventional BSA with novel application in liver cancer treatment.

A FRET-based fluorescent probe for hydrogen peroxide based on the use of carbon quantum dots conjugated to gold nanoclusters.

In the Fenton reaction, ferrous ion acts as a catalyst and reacts with hydrogen peroxide (H2O2) to produce hydroxy radicals (·OH) and hydroperoxy radicals (·OOH). Both have much stronger oxidization ability than H2O2. A fluorescent probe for H2O2 is described here that was obtained by covalent conjugation of carbon quantum dots to gold nanoclusters (AuNCs). The conjugate, under 360 nm photoexcitation, displays dual (blue and red) emission, with peaks located at 450 and 640 nm. When introducing ·OH radicals via the Fenton reaction, the fluorescence intensities of both the CQDs and the AuNCs are decreased. The ratio of the fluorescence at the two peaks is related to the concentration of H2O2 in the 1.25 nM to 10 µM concentration range, and the detection limit is 0.16 nM. The probe was applied to the determination of H2O2 in milk and toothpaste and to cell imaging. Graphical abstract Schematic diagram of the FRET-based fluorescent probe and enhanced performance of hydrogen peroxide detection via Fenton reaction. The fluorescence intensity of CQD-AuNCs nanoaster was decreased as introducing H2O2 to the probe, and can be applied to the determination of milk and toothpaste and cells imaging.

Circulating Tumor Cells with Stem-Like Phenotypes for Diagnosis, Prognosis, and Therapeutic Response Evaluation in Hepatocellular Carcinoma.

Background: In the present study, we assessed the clinical value of circulating tumor cells (CTC) with stem-like phenotypes for diagnosis, prognosis, and surveillance in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) by an optimized qPCR-based detection platform.Methods: Differing subsets of CTCs were investigated, and a multimarker diagnostic CTC panel was constructed in a multicenter patient study with independent validation (total n = 1,006), including healthy individuals and patients with chronic hepatitis B infection (CHB), liver cirrhosis (LC), benign hepatic lesion (BHL), and HBV-related HCC, with area under the receiver operating characteristic curve (AUC-ROC) reflecting diagnostic accuracy. The role of the CTC panel in treatment response surveillance and its prognostic significance were further investigated.Results: The AUC of the CTC panel was 0.88 in the training set [sensitivity = 72.5%, specificity = 95.0%, positive predictive value (PPV) = 92.4, negative predictive value (NPV) = 77.8] and 0.93 in the validation set (sensitivity = 82.1%, specificity = 94.2%, PPV = 89.9, NPV = 89.3). This panel performed equally well in detecting early-stage and α-fetoprotein-negative HCC, as well as differentiating HCC from CHB, LC, and BHL. The CTC load was decreased significantly after tumor resection, and patients with persistently high CTC load showed a propensity of tumor recurrence after surgery. The prognostic significance of the CTC panel in predicting tumor recurrence was further confirmed [training: HR = 2.692; 95% confidence interval (CI), 1.617-4.483; P < 0.001; and validation: HR = 3.127; 95% CI, 1.360-7.190; P = 0.007].Conclusions: Our CTC panel showed high sensitivity and specificity in HCC diagnosis and could be a real-time parameter for risk prediction and treatment monitoring, enabling early decision-making to tailor effective antitumor strategies. Clin Cancer Res; 24(9); 2203-13. ©2018 AACR.

Inhibition of Rho kinase protects against colitis in mice by attenuating intestinal epithelial barrier dysfunction via MLC and the NF-κB pathway.

The aim of the present study was to investigate the role of Rho kinase (also known as ROCK) inhibitor in 2,4,6-trinitrobenzene sulfonic acid induced mouse colitis; and to elucidate the underlying mechanism of ROCK1/ROCK2 inhibition in enhancing intestinal epithelial barrier (IEB) function. A specific inhibitor of ROCK, Y-27632, was used to examine the role of ROCK in mouse colitis models. ROCK1 and ROCK2 were silenced respectively using RNA interference in Caco-2 cells. The expression of tight junction proteins and the downstream molecules of ROCK were assessed. Y-27632 alleviated colonic inflammation and decreased intestinal permeability. ROCK-myosin light chain (MLC) and ROCK-NF-κB pathway were activated in colitis and inhibited by Y-27632. In vitro, ROCK1 RNAi primarily downregulated the phosphorylation of myosin phosphatase-targeting subunit-1 (MYPT-1) and MLC, while ROCK2 RNAi inhibited phosphorylation of nuclear factor-κB (NF-κB). In conclusion, the results suggested that the ROCK inhibitor alleviated colitis and IEB dysfunction. Inhibition of phospho-MYPT-1 and MLC by ROCK1 knockout or inhibition of NF-κB phosphorylation by ROCK2 knockout may be the underlying mechanisms.