Clay Nanosheet-Based Nanocomposite Supramolecular Hydrogel Enabling Rapid, Reversible Phase Transition Only with Visible Light.

High mechanical properties and rapid sol/gel phase transition are mutually exclusive in the hydrogels reported to date, most likely because the 3D crosslinked networks of mechanically robust hydrogels comprise bundled thick fibers that are not rapidly dissociable or formable.  Herein, we report a visible light-responsive hydrogel that showed a rapid, reversible sol/gel phase transition despite its relatively high mechanical properties (storage modulus ~1000 Pa).  To construct its 3D crosslinked network, we used a design strategy analogous to that employed for our highly water-rich yet mechanically robust nanocomposite supramolecular hydrogel ("aqua material").  In this case, multiple poly(ethylene glycol) chains carrying ortho-tetramethoxyazobenzene termini (AzoPEG) were noncovalently crosslinked by clay nanosheets (CNSs) with surface-immobilized ß-cyclodextrin units using their seven guanidinium ion (Gu+) pendants (GuCD) via a multivalent salt-bridge.  When exposed to visible light at 625 and 450 nm, the azobenzene termini isomerized from trans-to-cis and cis-to-trans, respectively, and were detached from and attached to the surface-immobilized GuCD units.  The advantage of this CNS-based nanocomposite supramolecular system is its simple 3D network structure, which forms and breaks rapidly without slow chain entangling and disentangling processes.

Photo-Enhanced Chemo-Transistor Platform for Ultrasensitive Assay of Small Molecules.

Compared with traditional assay techniques, field-effect transistors (FETs) have advantages such as fast response, high sensitivity, being label-free, and point-of-care detection, while lacking generality to detect a wide range of small molecules since most of them are electrically neutral with a weak doping effect. Here, we demonstrate a photo-enhanced chemo-transistor platform based on a synergistic photo-chemical gating effect in order to overcome the aforementioned limitation. Under light irradiation, accumulated photoelectrons generated from covalent organic frameworks offer a photo-gating modulation, amplifying the response to small molecule adsorption including methylglyoxal, p-nitroaniline, nitrobenzene, aniline, and glyoxal when measuring the photocurrent. We perform testing in buffer, artificial urine, sweat, saliva, and diabetic mouse serum. The limit of detection is down to 10-19 M methylglyoxal, about 5 orders of magnitude lower than existing assay technologies. This work develops a photo-enhanced FET platform to detect small molecules or other neutral species with enhanced sensitivity for applications in fields such as biochemical research, health monitoring, and disease diagnosis.

A Nomogram to Predict the Risk for MACCE within 1 Year after Discharge of Patients with NVAF and HFpEF: A Multicenter Retrospective Study.

Background: To develop and validate a nomogram prediction model for assessing the risk of major adverse cardiovascular and cerebrovascular events (MACCE) in patients with nonvalvular atrial fibrillation (NVAF) and heart failure with preserved ejection fraction (HFpEF) within one year of discharge. Methods: We enrolled 828 patients with NVAF and HFpEF from May 2017 to March 2022 in Zhongda Hospital as the training cohort, and 564 patients with NVAF and HFpEF in Taizhou People's Hospital between August 2018 and March 2022 as the validation cohort. A total of 35 clinical features, including baseline characteristics, past medical records, and detection index, were used to create a prediction model for MACCE risk. The optimized model was verified in the validation cohort. Calibration plots, the Hosmer-Lemeshow test, and decision curve analyses (DCA) were utilized to assess the accuracy and clinical efficacy of the nomogram. Results: MACCE occurred in 23.1% of all patients within one year of discharge. The nomogram identified several independent risk factors for MACCE, including atrial fibrillation duration ≥ 6 years, poor medication compliance, serum creatinine level, hyperthyroidism, serum N-terminal pro-brain natriuretic peptide level, and circumferential end-diastolic stress. The DCA demonstrated the excellent efficacy of the prediction model for the MACCE end-point, with a wide range of high-risk threshold probabilities in both cohorts. The Hosmer-Lemeshow test confirmed that momogram predictions fit for both the training (p = 0.573) and validation (p = 0.628) cohorts. Conclusions: This nomogram prediction model may offer a quantitative tool for estimating the risk of MACCE in patients with NVAF and HFpEF within one year of discharge.

Early Addition of Evolocumab to Statin Treatment in Patients with Acute Coronary Syndrome and Multivessel Disease Undergoing Percutaneous Coronary Intervention.

Background: Evolocumab has been demonstrated to significantly reduce ischemic cardiovascular events in patients with stable coronary heart disease. However, it is currently unclear whether this benefit extends to patients with acute coronary syndrome (ACS) and multivessel disease (MVD) undergoing percutaneous coronary intervention (PCI). The objective of this study was to assess the safety, efficacy and feasibility of the early addition of evolocumab to statin treatment for ACS patients with MVD undergoing PCI. Methods: The authors conducted a multicenter, retrospective cohort study involving 1199 ACS patients with MVD undergoing PCI and with elevated low-density lipoprotein cholesterol (LDL-C) levels. Patients were divided into an evolocumab group or a standard-of-care group based on evolocumab use or not. The 18-month primary efficacy endpoint was a composite of ischemic stroke, death from cardiac causes, recurrent myocardial infarction (MI), unplanned coronary revascularization or unstable angina requiring hospitalization. The principal secondary efficacy endpoint was a composite of ischemic stroke, death from cardiac causes or recurrent MI. Results: After propensity score matching, the addition of evolocumab to statin treatment lowered LDL-C levels by 42.62% compared with statin therapy alone at 18 months, from a mean baseline level of 3.37-0.75 mmol/L (p < 0.001). Relative to standard therapy, evolocumab added to statins was associated with significant reductions in the primary efficacy endpoint (8.3% vs. 13.3%; adjusted hazard ratio [HR], 0.60; 95% confidence interval [CI], 0.39 to 0.91; p = 0.017) and the principal secondary efficacy endpoint (6.1% vs. 10.2%; adjusted HR, 0.61; 95% CI, 0.37 to 0.99; p = 0.048) after multivariable Cox regression adjustment. The treatment effect of evolocumab was consistent across all prespecified subgroups. There were no significant between-group differences in terms of adverse events. Conclusions: In ACS patients with MVD taken for PCI, early initiation of evolocumab along with statin treatment was associated with a significant reduction in LDL-C levels and a reduced risk of recurrent cardiovascular events. Clinical Trial Registration: Chinese Clinical Trials Registry, identifier ChiCTR2000035165. Date: 2 August 2020. URL: https://www.chictr.org.cn/.

The Improved DC Breakdown Strength Induced by Enhanced Interaction between SiO2 Nanoparticles and LLDPE Matrix.

Direct current (DC) power transmission systems have received great attention because it can easily integrate many types of renewable energies and have low energy loss in long-distance and large-capacity power transmission for electricity global sharing. Nanoparticles (NPs) have a positive effect on the insulation properties of polymers, but weak interaction between NPs and polymer matrix greatly decreases the effort of NPs on the enhancement of insulation properties, and thereby limits its engineering application. In this work, grafting strategy was used to link the modified NPs and polymer matrix to improve their interactions. Silica NPs (SiO2-NPs) were modified by 3-(methacrylyloxy) propyl-trimethoxysilane (MPS) to introduce highly active groups on the SiO2-NPs surface, followed by the pre-irradiated linear low-density polyethylene (LLDPE) being easily grafted onto the MPS modified SiO2-NPs (MPS-SiO2-NPs) in the melt blending process to obtain LLDPE-g-MPS-SiO2-NPs nanocomposites. Fourier-transform infrared (FT-IR) spectrum and X-ray photoelectron spectroscopy (XPS) confirm the successful incorporation of MPS into SiO2-NPs. Transmission electron microscopy (TEM) verifies that the modified SiO2-NPs exhibits more uniform distribution. The rheology result shows that the interaction between MPS-SiO2-NPs and LLDPE significantly improves. More importantly, the LLDPE-g-MPS-SiO2-NPs nanocomposites displays superior DC breakdown strength to that fabricated by conventional modification methods. When the addition of MPS-SiO2-NPs is 0.1 wt%, the highest DC breakdown strength values of 525 kV/mm and 372 kV/mm are obtained at 30 °C and 70 °C, respectively, and high DC breakdown strength can be well maintained in a wide loading range of NPs.

TBX6 compound inheritance leads to congenital vertebral malformations in humans and mice.

Congenital vertebral malformations (CVMs) are associated with human TBX6 compound inheritance that combines a rare null allele and a common hypomorphic allele at the TBX6 locus. Our previous in vitro evidence suggested that this compound inheritance resulted in a TBX6 gene dosage of less than haploinsufficiency (i.e. <50%) as a potential mechanism of TBX6-associated CVMs. To further investigate this pathogenetic model, we ascertained and collected 108 Chinese CVM cases and found that 10 (9.3%) of them carried TBX6 null mutations in combination with common hypomorphic variants at the second TBX6 allele. For in vivo functional verification and genetic analysis of TBX6 compound inheritance, we generated both null and hypomorphic mutations in mouse Tbx6 using the CRISPR-Cas9 method. These Tbx6 mutants are not identical to the patient variants at the DNA sequence level, but instead functionally mimic disease-associated TBX6 variants. Intriguingly, as anticipated by the compound inheritance model, a high penetrance of CVM phenotype was only observed in the mice with combined null and hypomorphic alleles of Tbx6. These findings are consistent with our experimental observations in humans and supported the dosage effect of TBX6 in CVM etiology. In conclusion, our findings in the newly collected human CVM subjects and Tbx6 mouse models consistently support the contention that TBX6 compound inheritance causes CVMs, potentially via a gene dosage-dependent mechanism. Furthermore, mouse Tbx6 mutants mimicking human CVM-associated variants will be useful models for further mechanistic investigations of CVM pathogenesis in the cases associated with TBX6.

Enhanced Catalytic Oxidation of Chlorobenzene over MnO2 Grafted In Situ by Rare Earth Oxide: Surface Doping Induces Lattice Oxygen Activation.

A series of highly active MnO2@REOx (RE = Gd, Sm, Ce, and La) catalysts were successfully synthesized via in situ growth on the surface of MnO2, wherein the rare earth oxides were planted on the defect sites left by hydrogen peroxide etching of the surface of MnO2. Their physicochemical performance was investigated by scanning electron microscopy with energy-dispersive spectroscopy (SEM-EDS), X-ray diffraction (XRD), N2 adsorption-desorption, X-ray photoelectron spectroscopy (XPS), temperature-programmed reduction with hydrogen (H2-TPR), and temperature-programmed desorption of oxygen (O2-TPD). The catalytic properties are compared through the catalytic oxidation of chlorobenzene. Among all catalysts, MnO2@GdOx showed better mobility of surface lattice oxygen and higher molar ratios of Mn4+/Mn3+ (1.10) and Oads/Olatt (0.45), which promoted the superior low-temperature catalytic activity for chlorobenzene oxidation. The long-term chlorobenzene oxidation test (18 h) at different temperatures and the experiments with a mixture of VOCs showed that the as-prepared catalyst not only possessed a high stability but also was suitable for the efficient and simultaneous removal of multicomponent VOCs (toluene, benzene, acetone, and chlorobenzene). This work also provided an idea for the further development of high-efficiency catalysts for the purification of VOCs from complex atmosphere environment.

Proliferation of Cells with Severe Nuclear Deformation on a Micropillar Array.

Cellular responses on a topographic surface are fundamental topics about interfaces and biology. Herein, a poly(lactide- co-glycolide) (PLGA) micropillar array was prepared and found to trigger significant self-deformation of cell nuclei. The time-dependent cell viability and thus cell proliferation was investigated. Despite significant nuclear deformation, all of the examined cell types (Hela, HepG2, MC3T3-E1, and NIH3T3) could survive and proliferate on the micropillar array yet exhibited different proliferation abilities. Compared to the corresponding groups on the smooth surface, the cell proliferation abilities on the micropillar array were decreased for Hela and MC3T3-E1 cells and did not change significantly for HepG2 and NIH3T3 cells. We also found that whether the proliferation ability changed was related to whether the nuclear sizes decreased in the micropillar array, and thus the size deformation of cell nuclei should, besides shape deformation, be taken into consideration in studies of cells on topological surfaces.

Cell Type and Nuclear Size Dependence of the Nuclear Deformation of Cells on a Micropillar Array.

While various cellular responses to materials have been published, little concerns the deformation of cell nuclei. Herein we fabricated a polymeric micropillar array of appropriate dimensions to trigger the significant self-deformation of cell nuclei and examined six cell types, which could be classified into cancerous cells (Hela and HepG2) versus healthy cells (HCvEpC, MC3T3-E1, NIH3T3, and hMSC) or epithelial-like cells (Hela, HepG2, and HCvEpC) versus fibroblast-like cells (MC3T3-E1, NIH3T3, and hMSC). While all of the cell types exhibited severe nuclear deformation on the poly(lactide- co-glycolide) (PLGA) micropillar array, the difference between the epithelial-like and fibroblast-like cells was much more significant than that between the cancerous and healthy cells. We also examined the statistics of nuclear shape indexes of cells with an inevitable dispersity of nuclear sizes. It was found that larger nuclei favored more significant deformation on the micropillar array for each cell type. In the same region of nuclear size, the parts of the epithelial-like cells exhibited more significant nuclear deformation than those of the fibroblast-like cells. Hence, this article reports the nuclear size dependence of the self-deformation of cell nuclei on micropillar arrays for the first time and meanwhile strengthens the cell-type dependence.

Highly Active Mn3-xFexO4 Spinel with Defects for Toluene Mineralization: Insights into Regulation of the Oxygen Vacancy and Active Metals.

A series of highly defected Mn3-xFexO4 spinels with different amounts of oxygen vacancies and active metals were successfully synthesized by regulating the insertion of Fe ions into the crystal structure of Mn3O4 via self-polymerizable monomer adjustment of the molten Mn-Fe salt dispersion. The characterization of X-ray diffraction, Raman, scanning electron microscopy, X-ray photoelectron spectroscopy, and N2 adsorption-desorption showed that the doping of Fe increased the lattice defects, oxygen vacancy concentration, specific surface area, mesoporosity, and catalytic properties compared to Cu ions doping. Temperature-programmed reduction with hydrogen and oxygen pulse chemisorption tests determined that the doping level of Fe ions had an important influence on the oxygen vacancy content and the dispersion of active metals on the catalysts' surfaces. For the best Mn-dispersed and most active Mn2.4Fe0.6O4 catalyst, a long-term toluene oxidation measurement running for 120 h of uninterrupted reaction, at the low temperature of 240 °C, high humidity (relative humidity = 100%), and high weight hourly space velocity of 60000 mL·g-1·h-1, was also carried out, which indicated that the catalyst possessed high stability and endurability. Moreover, the continuous oxidation route and internal principle for toluene oxidation were also revealed by the in situ diffuse-reflectance infrared Fourier transform spectroscopy and gas chromatography-mass spectrometry techniques and deep dynamics study.

Catalytic Oxidation of VOCs over SmMnO3 Perovskites: Catalyst Synthesis, Change Mechanism of Active Species, and Degradation Path of Toluene.

Highly active samarium manganese perovskite oxides were successfully prepared by employing self-molten-polymerization, coprecipitation, sol-gel, and impregnation methods. The physicochemical properties of perovskite oxides were investigated by XRD, N2 adsorption-desorption, XPS, and H2-TPR. Their catalytic performances were compared via the catalytic oxidation of toluene. The perovskite prepared by self-molten-polymerization possessed the highest catalytic capacity, which can be ascribed to its higher oxygen adspecies concentration (Olatt/Oads = 0.53), higher surface Mn4+/Mn3+ ratio (Mn4+/Mn3+ = 0.95), and best low-temperature reducibility (H2 consumption = 0.27; below 350 °C). The most active catalyst also exhibited good cycling and long-term stability for toluene oxidation. After a multistep cycle reaction and a long-term reaction of 42 h, the toluene conversion maintained above 99.9% at 270 °C. Mechanistic study hinted that lattice oxygen was involved in toluene oxidation. The oxidation reaction was dependent on the synergism of lattice oxygen, adsorbed oxygen, and oxygen vacancies. The degradation pathway of toluene, researched by diffuse reflectance infrared Fourier transform spectroscopy and online mass spectrometry technologies, demonstrated that a series of organic byproducts existed at a relatively low temperature. This work provides an efficient and practical method for selecting highly active catalysts and for exploring the catalytic mechanism for the removal of atmospheric environmental pollution.

Selective Dual-Channel Imaging on Cyanostyryl-Modified Azulene Systems with Unimolecularly Tunable Visible-Near Infrared Luminescence.

Although organic light-emitting molecules have received a growing attention and applicability in modern bioimaging science, the design and control of complex photoluminescent properties in unimolecularly selective imaging remains a challenging topic. Considering that tunable multipathway imaging can be advantagedly connected with treatment processes in therapy, the integration of an azulene and a cyanostyryl moiety into one skeleton is carried out for the generation of in situ stimuli-responsive luminescent materials, with the aim to achieve tunable and effective emissions in distinct channels through smart molecular design on a single-molecular platform. This strategy takes advantage of 1) the Z/E isomerization of the cyanostyryl unit that can vary the push-pull effect of the substitution on azulene, accompanied by altering absorption and emission of individual excited states, and 2) an optimized excited-state regulation for opening a near infrared emissive channel and making up for a controllable dual-pathway luminescent system together with the utilization of visible emission. As exemplified by a demonstration of manipulating the luminescence at the cell level, the materials exhibit a superior application potential for unimolecularly selective imaging, labeling and probing events.

Prevalence of kidney stones in China: an ultrasonography based cross-sectional study.

OBJECTIVES: To investigate the prevalence and associated factors of kidney stones among adults in China. SUBJECTS AND METHODS: A nationwide cross-sectional survey was conducted among individuals aged ≥18 years across China, from May 2013 to July 2014. Participants underwent urinary tract ultrasonographic examinations, completed pre-designed and standardised questionnaires, and provided blood and urine samples for analysis. Kidney stones were defined as particles of ≥4 mm. Prevalence was defined as the proportion of participants with kidney stones and binary logistic regression was used to estimate the associated factors. RESULTS: A total of 12 570 individuals (45.2% men) with a mean (sd, range) age of 48.8 (15.3, 18-96) years were selected and invited to participate in the study. In all, 9310 (40.7% men) participants completed the investigation, with a response rate of 74.1%. The prevalence of kidney stones was 6.4% [95% confidence interval (CI) 5.9, 6.9], and the age- and sex-adjusted prevalence was 5.8% (95% CI 5.3, 6.3; 6.5% in men and 5.1% in women). Binary logistic regression analysis showed that male gender, rural residency, age, family history of urinary stones, concurrent diabetes mellitus and hyperuricaemia, increased consumption of meat, and excessive sweating were all statistically significantly associated with a greater risk of kidney stones. By contrast, consumption of more tea, legumes, and fermented vinegar was statistically significantly associated with a lesser risk of kidney stone formation. CONCLUSION: Kidney stones are common among Chinese adults, with about one in 17 adults affected currently. Some Chinese dietary habits may lower the risk of kidney stone formation.

Novel expression and characterization of a light driven proton pump archaerhodopsin 4 in a Halobacterium salinarum strain.

Archaerhodopsin 4 (AR4), a new member of the microbial rhodopsin family, is isolated from Halobacterium species xz515 in a Tibetan salt lake. AR4 functions as a proton pump similar to bacteriorhodopsin (BR) but with an opposite temporal order of proton uptake and release at neutral pH. However, further studies to elucidate the mechanism of the proton pump and photocycle of AR4 have been inhibited due to the difficulty of establishing a suitable system in which to express recombinant AR4 mutants. In this paper, we report a reliable method for expressing recombinant AR4 in Halobacterium salinarum L33 with a high yield of up to 20mg/l. Experimental results show that the recombinant AR4 retains the light-driven proton pump characteristics and photo-cycling kinetics, similar to that in the native membrane. The functional role of bacterioruberin in AR4 and the trimeric packing of AR4 in its native and recombinant forms are investigated through light-induced kinetic measurements, two-dimensional solid-state NMR experiments, dynamic light scattering (DLS) and Fourier transform infrared spectroscopy (FTIR). Such approaches provide new insights into structure-function relationships of AR4, and form a basis for other archaeal rhodopsins.

Fabrication of RGD micro/nanopattern and corresponding study of stem cell differentiation.

Micropatterns of gold (Au) nanoarrays on inorganic and polymeric substrates were fabricated by combining block copolymer micelle nanolithography to obtain gold nanoarrays on glass, photolithography plus hydrofluoric acid (HF) etching to generate microislands, and transfer lithography to shift the gold micro/nanopatterns from glass to a bioinert poly(ethylene glycol) (PEG) hydrogel surface. Further the modification of the gold nanodots via cell-adhesive arginine-glycine-aspartate (RGD) ligands was carried out to achieve peptide micro/nanopatterns. Whereas the micro/nanopatterns of noble metals could be useful in various applications, the peptide micro/nanopatterns especially enable persistent cell localization on adhesive micropatterns of RGD nanoarrays on the background of potently nonfouling PEG hydrogels, and thus offer a powerful tool to investigate cell-material interactions on both molecular and cellular levels. As a demonstration, we cultured human mesenchymal stem cells (hMSCs) on micro/nanopatterns with RGD nanoarrays of nanospacings 46 and 95 nm, and with micropans of side lengths 35 and 65 µm (four groups in total). The osteogenic and adipogenic differentiation of hMSCs was conducted, and the potential effect of RGD nanospacing and the effect of cell spreading size on cell differentiation were decoupled for the first time. The results reveal that RGD nanospacing, independent of cell spreading size, acts as a strong regulator of cell tension and stem cell differentiation, which cannot be concluded unambiguously based on either merely micropatterns or nanopatterns.

Effects of Nanoscale Spatial Arrangement of Arginine-Glycine-Aspartate Peptides on Dedifferentiation of Chondrocytes.

Cell dedifferentiation is of much importance in many cases such as the classic problem of dedifferentiation of chondrocytes during in vitro culture in cartilage tissue engineering. While cell differentiation has been much investigated, studies of cell dedifferentiation are limited, and the nanocues of cell dedifferentiation have little been reported. Herein, we prepared nanopatterns and micro/nanopatterns of cell-adhesive arginine-glycine-aspartate (RGD) peptides on nonfouling poly(ethylene glycol) (PEG) hydrogels to examine the effects of RGD nanospacing on adhesion and dedifferentiation of chondrocytes. The relatively larger RGD nanospacing above 70 nm was found to enhance the maintainence of the chondrocyte phenotype in two-dimensional culture, albeit not beneficial for adhesion of chondrocytes. A unique micro/nanopattern was employed to decouple cell spreading, cell shape, and cell-cell contact from RGD nanospacing. Under given spreading size and shape of single cells, the large RGD nanospacing was still in favor of preserving the normal phenotype of chondrocytes. Hence, the nanoscale spatial arrangement of cell-adhesive ligands affords a new independent regulator of cell dedifferentiation, which should be taken into consideration in biomaterial design for regenerative medicine.

Matrix Stiffness and Nanoscale Spatial Organization of Cell-Adhesive Ligands Direct Stem Cell Fate.

One of the breakthroughs in biomaterials and regenerative medicine in the latest decade is the finding that matrix stiffness affords a crucial physical cue of stem cell differentiation. This statement was recently challenged by another understanding that protein tethering on material surfaces instead of matrix stiffness was the essential cue to regulate stem cells. Herein, we employed nonfouling poly(ethylene glycol) (PEG) hydrogels as the matrix to prevent nonspecific protein adsorption, and meanwhile covalently bound cell-adhesive arginine-glycine-aspartate (RGD) peptides onto the hydrogel surfaces in the form of well-defined nanoarrays to control specific cell adhesion. This approach enables the decoupling of the effects of matrix stiffness and surface chemistry. Mesenchymal stem cells (MSCs) were cultured on four substrates (two compressive moduli of the PEG hydrogels multiplied by two RGD nanospacings) and incubated in the mixed osteogenic and adipogenic medium. The results illustrate unambiguously that matrix stiffness is a potent regulator of stem cell differentiation. Moreover, we reveal that RGD nanospacing affects spreading area and differentiation of rat MSCs, regardless of the hydrogel stiffness. Therefore, both matrix stiffness and nanoscale spatial organization of cell-adhesive ligands direct stem cell fate.

Thermogelling polymer-platinum(IV) conjugates for long-term delivery of cisplatin.

In this study, we suggest a novel strategy of constituting an in situ-formed hydrogel composed of polymer-platinum(IV) conjugate to realize a long-term delivery of cisplatin. A unique conjugate was designed and synthesized by covalent linking of Pt(IV) complex to the hydrophobic end of two methoxyl poly(ethylene glycol)-b-poly(d,l-lactide) (mPEG-PLA) copolymer chains, resulting in the formation of Bi(mPEG-PLA)-Pt(IV). The conjugate could self-assemble into micelles in water, and its concentrated solution exhibited a thermoreversible sol-gel transition and formed a semisolid thermogel at body temperature. The incorporation of the cisplatin analogue Pt(IV) prodrug into the conjugate had a significant influence on its thermogelling properties and the conjugate thermogelation was attributed to the micellar aggregation. In vitro release experiments of Pt(IV)-conjugated thermogel showed that the platinum release lasted as long as two months. Furthermore, we demonstrated that the Pt(IV) prodrug was released mainly in the form of micelles and micellar aggregates from the gel depot. Compared with free cisplatin, the formation of conjugate micelles led to the enhanced in vitro cytotoxicity against cancer cells due to the effective accumulation into cells via endocytosis.

Epithelial-Mesenchymal Transition of Cancer Cells on Micropillar Arrays.

Epithelial-mesenchymal transition (EMT) is critical for tumor invasion and many other cell-relevant processes. While much progress has been made about EMT, no report concerns the EMT of cells on topological biomaterial interfaces with significant nuclear deformation. Herein, we prepared a poly(lactide-co-glycolide) micropillar array with an appropriate dimension to enable significant deformation of cell nuclei and examined EMT of a human lung cancer epithelial cell (A549). We show that A549 cells undergo serious nuclear deformation on the micropillar array. The cells express more E-cadherin and less vimentin on the micropillar array than on the smooth surface. After transforming growth factor-ß1 (TGF-ß1) treatment, the expression of E-cadherin as an indicator of the epithelial phenotype is decreased and the expression of vimentin as an indicator of the mesenchymal phenotype is increased for the cells both on smooth surfaces and on micropillar arrays, indicating that EMT occurs even when the cell nuclei are deformed and the culture on the micropillar array more enhances the expression of vimentin. Expression of myosin phosphatase targeting subunit 1 is reduced in the cells on the micropillar array, possibly affecting the turnover of myosin light chain phosphorylation and actin assembly; this makes cells on the micropillar array prefer the epithelial-like phenotype and more sensitive to TGF-ß1. Overall, the micropillar array exhibits a promoting effect on the EMT.

K-clip™, a Novel Transcatheter Treatment in Patients with Severely Tricuspid Regurgitation.

Patients who suffer from severe tricuspid regurgitation (TR) and who are at high surgical risk have no standard care therapy. Therefore, minimally invasive and safer methods are sought. K-clip™, the first ultrasound-positioned interventional tricuspid annuloplasty instrument intended for percutaneous transcatheter repair. We report a patient with severe functional TR and high surgical risk who underwent K-clip™ tricuspid annuloplasty under echocardiography and fluoroscopy guidance.