Serum GGT/ALT ratio predicts vascular invasion in HBV-related HCC.

BACKGROUND: The gamma-glutamyl transferase (GGT) to alanine aminotransferase (ALT) ratio has been reported as an effective predictor of the severity of hepatitis and HCC. The purpose of this study was to determine the role of the GGT/ALT ratio in the prediction of vascular invasion and survival outcomes in patients with hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). METHODS: The risk factors for vascular invasion were determined by univariate/multivariate logistic analysis. The cut-off value of GGT/ALT in predicting vascular invasion was calculated using the receiver operating characteristic (ROC) curve. The prognostic value of GGT/ALT was examined by Cox analysis and Kaplan-Meier curves. Sensitivity analysis, such as subgroup analysis and propensity score matching (PSM), was performed to reduce potential confounding bias. RESULTS: A high GGT/ALT ratio was identified as an independent risk factor for vascular invasion (P = 0.03). The correlation analysis suggested that higher GGT/ALT was associated with more severe tumour burdens, including vascular invasion (P < 0.001), tumour volume > 5 cm (P < 0.001), poor pathological differentiation (P = 0.042), more severe BCLC (P < 0.001) and ALBI grade (P = 0.007). In the survival analysis, a high GGT/ALT ratio was associated with poor overall survival (OS) (HR: 1.38; 95% CI 1.03, 1.87; P < 0.0001) and disease-free survival (DFS) (HR: 1.32; 95% CI 1.03, 1.87; P < 0.0001). In the subgroup analysis, similar results were consistently observed across most subgroups. In PSM analysis, GGT/ALT remained independently associated with vascular invasion (OR, 186; 95% CI 1.23, 3.33). CONCLUSION: The GGT/ALT ratio was a potential effective factor in the prediction of vascular invasion and prognosis in patients with HBV-related HCC.

A near-infrared fluorescent probe for highly specific and ultrasensitive detection of hypochlorite ions in living cells.

Hypochlorite (ClO-) is an important reactive oxygen species (ROS) in organisms. In this work, a fluorescent probe DBTM based on triphenylamine was synthesized successfully and characterized by spectral methods. The designed probe can rapidly respond to ClO- in just 1 min, followed by the apparent color change from red to yellow. The colorimetric and ratiometric absorbance change of DBTM was attributed to the strong oxidation of ClO-, which broke the connected double bonds and destroyed the conjugate system. The probe DBTM showed an excellent selectivity towards ClO- in comparison with other ROS probes. Besides, the DBTM probe exhibited a highly sensitive response to ClO-, with the detection limits calculated to be 3.3 nM. The probe can be applied in the form of cotton swabs and test strips that could detect ClO- easily, suggesting its potential use as imaging agents for realistic ClO- detection. In particular, DBTM exhibited very low background fluorescence in living cells and was able to detect the minor variation of endogenous hypochlorite in L929 cells. Based on these advantages, the probe DBTM could be a good candidate for detecting ClO- in biological systems.

Topological quantum computation based on chiral Majorana fermions.

The chiral Majorana fermion is a massless self-conjugate fermion which can arise as the edge state of certain 2D topological matters. It has been theoretically predicted and experimentally observed in a hybrid device of a quantum anomalous Hall insulator and a conventional superconductor. Its closely related cousin, the Majorana zero mode in the bulk of the corresponding topological matter, is known to be applicable in topological quantum computations. Here we show that the propagation of chiral Majorana fermions leads to the same unitary transformation as that in the braiding of Majorana zero modes and propose a platform to perform quantum computation with chiral Majorana fermions. A Corbino ring junction of the hybrid device can use quantum coherent chiral Majorana fermions to implement the Hadamard gate and the phase gate, and the junction conductance yields a natural readout for the qubit state.

Furin-mediated intracellular self-assembly of olsalazine nanoparticles for enhanced magnetic resonance imaging and tumour therapy.

Among the strategies used for enhancement of tumour retention of imaging agents or anticancer drugs is the rational design of probes that undergo a tumour-specific enzymatic reaction preventing them from being pumped out of the cell. Here, the anticancer agent olsalazine (Olsa) was conjugated to the cell-penetrating peptide RVRR. Taking advantage of a biologically compatible condensation reaction, single Olsa-RVRR molecules were self-assembled into large intracellular nanoparticles by the tumour-associated enzyme furin. Both Olsa-RVRR and Olsa nanoparticles were readily detected with chemical exchange saturation transfer magnetic resonance imaging by virtue of exchangeable Olsa hydroxyl protons. In vivo studies using HCT116 and LoVo murine xenografts showed that the OlsaCEST signal and anti-tumour therapeutic effect were 6.5- and 5.2-fold increased, respectively, compared to Olsa without RVRR, with an excellent 'theranostic correlation' (R2 = 0.97) between the imaging signal and therapeutic response (normalized tumour size). This furin-targeted, magnetic resonance imaging-detectable platform has potential for imaging tumour aggressiveness, drug accumulation and therapeutic response.

Quantum Error Correction in Scrambling Dynamics and Measurement-Induced Phase Transition.

We analyze the dynamics of entanglement entropy in a generic quantum many-body open system from the perspective of quantum information and error corrections. We introduce a random unitary circuit model with intermittent projective measurements, in which the degree of information scrambling by the unitary and the rate of projective measurements are independently controlled. This model displays two stable phases, characterized by the volume-law and area-law scaling entanglement entropy in steady states. The transition between the two phases is understood from the point of view of quantum error correction: the chaotic unitary evolution protects quantum information from projective measurements that act as errors. A phase transition occurs when the rate of errors exceeds a threshold that depends on the degree of information scrambling. We confirm these results using numerical simulations and obtain the phase diagram of our model. Our work shows that information scrambling plays a crucial role in understanding the dynamics of entanglement in an open quantum system and relates the entanglement phase transition to changes in quantum channel capacity.

A novel strategy for rhodamine B-based fluorescent probes with a selective glutathione response for bioimaging in living cells.

The aim of this study was to overcome the reported shortcomings of the glutathione (GSH) detection of rhodamine-based fluorescent probes, such as poor selectivity to thiol groups and reversible unstable covalent binding with the thiol groups. Here, we have developed a simple and specific fluorescent probe based on rhodamine B, which can be used to selectively detect GSH in solution and perform bioimaging in living cells. This design strategy uses a specific reaction between allenamide and the GSH thiol group, which proceeds rapidly in a phosphate buffer/tetrahydrofuran (PBS/THF) mixture with specific selectivity, and forms a stable and irreversible conjugate. The combined simplicity and specificity of the recognition process enables it to serve as a fluorescent probe for detecting GSH level changes in living cells. Such a new recognizing strategy thus may open a new window for its further application in detecting GSH levels both in vitro and in vivo.

Two highly sensitive fluorescent probes based on cinnamaldehyde with large Stokes shift for sensing of HSO3- in pure water and living cells.

Two simple and novel fluorescent probes (CDC1 and CDC2) have been designed and prepared here for sensing HSO3- with large Stokes shifts (about 250 nm). The synthesized probes can react with HSO3- just in 2 min, followed by the obvious color change from blue to colorless. The colorimetric and ratiometric absorbance response of the probes to HSO3- is due to the addition of HSO3- to the electron-deficient C=C double bond group, which prevents significant intramolecular charge transfer (ICT). Besides, CDC1 and CDC2 can detect HSO3- in pure water and detection limits of CDC1 and CDC2 reached 4.59 nM and 8.19 nM, respectively. Considering the delicate difference in the two prepared probes' molecular structures, CDC1 containing the carboxyl group has a more significant fluorescence intensity change response to HSO3- in pure water than CDC2 (with sulfinyl group). Beyond better response characteristics, CDC1 also has lower cytotoxicity and better biocompatibility compared with CDC2, which could be chosen to detect HSO3- in living cells. With these superior properties, probe CDC1 could have a potential application in the fields of environmental and biological detection.

Incorporation of dumbbell-shaped and Y-shaped cross-linkers in adjustable pullulan/polydopamine hydrogels for selective adsorption of cationic dyes.

Hydrogel adsorbents have attracted considerable attention due to their sludge minimization, good water permeability and renewable performance. Here, a promising strategy for the one-step preparation of pullulan/polydopamine hybird hydrogels (PPGels) was presented. Dumbbell-shaped cross-linker neopentyl glycol diglycidyl ether (NGDE, 2 arms) and Y-shaped cross-linker trimethylolpropane triglycidyl ether (TTE, 3 arms) were selected to study the relationship between cross-linker structure and hydrogel performances. The NGDE possessing less molecular repulsive force and higher reactivity demonstrated more effective cross-linking with the pullulan, which leaded to a decrease in pore size of the hydrogel. Meanwhile, the introduction of polydopamine significantly enhanced the adsorption ability and gave the resulting hybrid gel the specific selectivity toward cationic dyes (96 mg/g for crystal violet, 25.8 mg/g for methylene blue and barely not adsorption for azophloxine). Our data suggested that the electrostatic interaction played a vital role in the dye adsorption process, and the adsorption data could be explained by pseudo-second-order model and Langmuir isotherm model. Furthermore, the obtained PPGel could be easily separated after adsorption. This study describes the relationship between cross-linker structure and properties of pullulan/polydopamine hybrid gels, which provides a new strategy to create polysaccharide-based adsorbents for wastewater remediation.

Nitrogen-doped carbon dots as a fluorescent probe for the highly sensitive detection of Ag+ and cell imaging.

An easy hydrothermal synthesis strategy was applied to synthesize green-yellow emitting nitrogen-doped carbon dots (N-CDs) using 1,2-diaminobenzene as the carbon source, and dicyandiamide as the dopant. The nitrogen-doped CDs resulted in improvement in the electronic characteristics and surface chemical activities. N-CDs exhibited bright fluorescence emission and could response to Ag+ selectively and sensitively. Other ions produced nearly no interference. A N-CDs based fluorescent probe was then applied to sensitively determine Ag+ with a detection limit of 5 × 10-8  mol/L. The method was applied to the determination of Ag+ dissolved in water. Finally, negligibly cytotoxic, excellently biocompatibile, and highly fluorescent carbon dots were applied for HepG2 cell imaging and the quenched fluorescence by adding Ag+ , which indicated its potential applications.

Salecan-Based pH-Sensitive Hydrogels for Insulin Delivery.

Stimuli-responsive polymeric hydrogels are promising and appealing delivery vehicles for protein/peptide drugs and have made protein/peptide delivery with both dosage- and spatiotemporal-controlled manners possible. Here a series of new Salecan-based pH-sensitive hydrogels were fabricated for controlled insulin delivery via the graft copolymerization reaction between Salecan and 2-acrylamido-2-methyl-1-propanesulfonic acid. In this study, on one hand, Salecan played a key role in modifying the structure and the pore size of the developing hydrogel. On the other hand, Salecan tuned the water content and the water release rate of the obtained hydrogel, leading to a controllable release rate of the insulin. More importantly, in vitro release experiments validated that the release of insulin from this intelligent system could be also tailored by the environmental pH of the release medium. For SGA2, the amount of encapsulated insulin released at gastric conditions (pH 1.2) was relatively low (about 26.1 wt % in 24 h), while that released at intestinal conditions (pH 7.4) increased significantly (over 50 wt % in 6 h). Furthermore, toxicity assays demonstrated that the designed hydrogel carriers were biocompatible. These characteristics make the Salecan-based hydrogel a promising candidate for protein/peptide drug delivery device.

Topological Superconductivity on the Surface of Fe-Based Superconductors.

As one of the simplest systems for realizing Majorana fermions, the topological superconductor plays an important role in both condensed matter physics and quantum computations. Based on ab initio calculations and the analysis of an effective 8-band model with superconducting pairing, we demonstrate that the three-dimensional extended s-wave Fe-based superconductors such as Fe_{1+y}Se_{0.5}Te_{0.5} have a metallic topologically nontrivial band structure, and exhibit a normal-topological-normal superconductivity phase transition on the (001) surface by tuning the bulk carrier doping level. In the topological superconductivity (TSC) phase, a Majorana zero mode is trapped at the end of a magnetic vortex line. We further show that the surface TSC phase only exists up to a certain bulk pairing gap, and there is a normal-topological phase transition driven by the temperature, which has not been discussed before. These results pave an effective way to realize the TSC and Majorana fermions in a large class of superconductors.

Quantum anomalous Hall effect in magnetic insulator heterostructure.

On the basis of ab initio calculations, we predict that a monolayer of Cr-doped (Bi,Sb)2Te3 and GdI2 heterostructure is a quantum anomalous Hall insulator with a nontrivial band gap up to 38 meV. The principle behind our prediction is that the band inversion between two topologically trivial ferromagnetic insulators can result in a nonzero Chern number, which offers a better way to realize the quantum anomalous Hall state without random magnetic doping. In addition, a simple effective model is presented to describe the basic mechanism of spin polarized band inversion in this system. Moreover, we predict that 3D quantum anomalous Hall insulator could be realized in (Bi2/3Cr1/3)2Te3 /GdI2 superlattice.

Generalized Kitaev models and extrinsic non-Abelian twist defects.

We present a wide class of partially integrable lattice models with two-spin interactions which generalize the Kitaev honeycomb model. These models have a conserved quantity associated with each plaquette, conserved large loop operators on the torus, and topological degeneracy. We introduce a "slave-genon" approach which generalizes the Majorana fermion approach in the Kitaev model. The Hilbert space of our spin model can be embedded in an enlarged Hilbert space of non-Abelian twist defects, referred to as genons. In the enlarged Hilbert space, the spin model is exactly reformulated as a model of non-Abelian genons coupled to a discrete gauge field. We discuss in detail a particular Z_{3} generalization, and we show that in a certain limit the model is analytically tractable and produces a non-Abelian topological phase with chiral parafermion edge states.

Position-Momentum Duality and Fractional Quantum Hall Effect in Chern Insulators.

We develop a first quantization description of fractional Chern insulators that is the dual of the conventional fractional quantum Hall (FQH) problem, with the roles of position and momentum interchanged. In this picture, FQH states are described by anisotropic FQH liquids forming in momentum-space Landau levels in a fluctuating magnetic field. The fundamental quantum geometry of the problem emerges from the interplay of single-body and interaction metrics, both of which act as momentum-space duals of the geometrical picture of the anisotropic FQH effect. We then present a novel broad class of ideal Chern insulator lattice models that act as duals of the isotropic FQH effect. The interacting problem is well-captured by Haldane pseudopotentials and affords a detailed microscopic understanding of the interplay of interactions and nontrivial quantum geometry.

One-dimensional helical transport in topological insulator nanowire interferometers.

The discovery of three-dimensional (3D) topological insulators opens a gateway to generate unusual phases and particles made of the helical surface electrons, proposing new applications using unusual spin nature. Demonstration of the helical electron transport is a crucial step to both physics and device applications of topological insulators. Topological insulator nanowires, of which spin-textured surface electrons form 1D band manipulated by enclosed magnetic flux, offer a unique nanoscale platform to realize quantum transport of spin-momentum locking nature. Here, we report an observation of a topologically protected 1D mode of surface electrons in topological insulator nanowires existing at only two values of half magnetic quantum flux (±h/2e) due to a spin Berry's phase (π). The helical 1D mode is robust against disorder but fragile against a perpendicular magnetic field breaking-time-reversal symmetry. This result demonstrates a device with robust and easily accessible 1D helical electronic states from 3D topological insulators, a unique nanoscale electronic system to study topological phenomena.

A cuttlefish ink nanoparticle-reinforced biopolymer hydrogel with robust adhesive and immunomodulatory features for treating oral ulcers in diabetes.

Oral ulcers can be managed using a variety of biomaterials that deliver drugs or cytokines. However, many patients experience minimal benefits from certain medical treatments because of poor compliance, short retention times in the oral cavity, and inadequate drug efficacy. Herein, we present a novel hydrogel patch (SCE2) composed of a biopolymer matrix (featuring ultraviolet-triggered adhesion properties) loaded with cuttlefish ink nanoparticles (possessing pro-healing functions). Applying a straightforward local method initiates the formation of a hydrogel barrier that adheres to mucosal injuries under the influence of ultraviolet light. SCE2 then demonstrates exceptional capabilities for near-infrared photothermal sterilization and neutralization of reactive oxygen species. These properties contribute to the elimination of bacteria and the management of the oxidation process, thus accelerating the healing phase's progression from inflammation to proliferation. In studies involving diabetic rats with oral ulcers, the SCE2 adhesive patch significantly quickens recovery by altering the inflamed state of the injured area, facilitating rapid re-epithelialization, and fostering angiogenesis. In conclusion, this light-sensitive hydrogel patch offers a promising path to expedited wound healing, potentially transforming treatment strategies for clinical oral ulcers.

Decreased expression of microRNA-625 is associated with tumor metastasis and poor prognosis in patients with colorectal cancer.

BACKGROUND: MicroRNAs (miRNAs) play an essential role in colorectal cancer (CRC) development and progression. Aberrant miR-625 expression has been reported in several cancers. However, the clinical significance of miR-625 in human CRC has not been addressed. METHODS: miR-625 expression was determined in 96 pairs of primary CRC and their corresponding adjacent nontumor tissues by quantitative reverse transcriptase-polymerase chain reaction. Associations of miR-625 expression with demographic and clinicopathologic features were determined. Additionally, the effects of ectopic expression of miR-625 on cell migration and invasion were investigated in vitro and in vivo. RESULTS: miR-625 was significantly downregulated in CRC tissues and cell lines. In addition, the decreased expression of miR-625 was positively associated with advanced lymph node metastasis (P = 0.038), liver metastasis (P = 0.031), poor overall survival (P = 0.002), and an unfavorable prognosis for CRC patients, as determined through a multivariate analysis (P = 0.034). Moreover, functional assays demonstrated that ectopic miR-625 expression inhibits the invasion and migration of HCT116 CRC cells both in vitro and in vivo. CONCLUSIONS: Our results suggest that miR-625 may serve as an efficient clinical biomarker and a therapeutic tool for the inhibition of metastasis in CRC.

Effects of magnetic doping on weak antilocalization in narrow Bi2Se3 nanoribbons.

We report low-temperature, magnetotransport measurements of ferrocene-doped Bi(2)Se(3) nanoribbons grown by vapor-liquid-solid method. The Kondo effect, a saturating resistance upturn at low temperatures, is observed in these ribbons to indicate presence of localized impurity spins. Magnetoconductances of the ferrocene-doped ribbons display both weak localization and weak antilocalization, which is in contrast with those of undoped ribbons that show only weak antilocalization. We show that the observed magnetoconductances are governed by a one-dimensional localization theory that includes spin orbit coupling and magnetic impurity scattering, yielding various scattering and dephasing lengths for Bi(2)Se(3). The power law decay of the dephasing length on temperature also reflects one-dimensional localization regime in these narrow Bi(2)Se(3) nanoribbons. The emergence of weak localization in ferrocene-doped Bi(2)Se(3) nanoribbons presents ferrocene as an effective magnetic dopant source.

Metformin modified chitosan as a multi-functional adjuvant to enhance cisplatin-based tumor chemotherapy efficacy.

Recently, it was newly revealed that the DNA damage induced by cis­platinum (Cis-Pt) mediated chemotherapy was significantly impaired by the highly expressed programmed death ligand-1 (PD-L1) in tumor cells. Besides, the efficacy of Cis-Pt was also limited due to its severe side effects, especially enhanced drug efflux induced by multidrug resistance protein 1 (MDR-1) and increased tumor metastasis. Up to now, few drugs or carbohydrates could simultaneously solve these defects of Cis-Pt mediated chemotherapy. Here, we newly found that metformin-modified chitosan (Ch-Met) possessed ideal selective mitochondria accumulation capacity, leading to the further disrupted mitochondrial function, which then effectively inhibited the upregulated PD-L1 expression to inhibit DNA damage repair in tumor cells, as well as impaired drug efflux and lowered tumor metastasis. Therefore, it was demonstrated that Ch-Met could sensitize the chemotherapy efficacy of Cis-Pt.

Mild Photothermal Therapy Prevents Posterior Capsule Opacification through Cytoskeletal Remodeling.

Cataract is the first leading cause of blindness in the world and posterior capsule opacification (PCO) is the most common long-term complication after surgery. The primary pathogenic processes contributing to PCO are the proliferation and migration of residual lens epithelial cells (LECs). This study aimed to explore the mild photothermal effect on LECs. Interestingly, this work finds that the mild photothermal effect significantly inhibited the proliferation and migration of LECs. The live cell fluorescence imaging reveals that the remodeling of the actin cytoskeleton and cell morphology attributed to the inhibition effect. Further mechanistic studies at molecular level suggest that the mild photothermal effect can regulate the phosphorylation of ERM, YAP, and Cofilin and thereby affect the proliferation and migration of LECs. In order to explore the potential clinical application of mild photothermal therapy for PCO prevention, PDA/PVA gel rings with photothermal effect is prepared by the repeated freeze-thaw method and conducted experiments in vivo, which achieved favorable PCO prevention effect. Overall, this study shows that the mild photothermal effect can regulate the proliferation and migration of LECs through cytoskeletal remodeling and the results of experiments in vivo demonstrate that mild photothermal effect is a promising approach for PCO prevention.