In situ injectable hydrogel encapsulating Mn/NO-based immune nano-activator for prevention of postoperative tumor recurrence

Postoperative tumor recurrence remains a predominant cause of treatment failure. In this study, we developed an in situ injectable hydrogel, termed MPB-NO@DOX + ATRA gel, which was locally formed within the tumor resection cavity. The MPB-NO@DOX + ATRA gel was fabricated by mixing a thrombin solution, a fibrinogen solution containing all-trans retinoic acid (ATRA), and a Mn/NO-based immune nano-activator termed MPB-NO@DOX. ATRA promoted the differentiation of cancer stem cells, inhibited cancer cell migration, and affected the polarization of tumor-associated macrophages. The outer MnO2 shell disintegrated due to its reaction with glutathione and hydrogen peroxide in the cytoplasm to release Mn2+ and produce O2, resulting in the release of doxorubicin (DOX). The released DOX entered the nucleus and destroyed DNA, and the fragmented DNA cooperated with Mn2+ to activate the cGAS-STING pathway and stimulate an anti-tumor immune response. In addition, when MPB-NO@DOX was exposed to 808 nm laser irradiation, the Fe-NO bond was broken to release NO, which downregulated the expression of PD-L1 on the surface of tumor cells and reversed the immunosuppressive tumor microenvironment. In conclusion, the MPB-NO@DOX + ATRA gel exhibited excellent anti-tumor efficacy. The results of this study demonstrated the great potential of in situ injectable hydrogels in preventing postoperative tumor recurrence.

Optical manipulation of the topological phase in ZrTe_(5) revealed by time-and angle-resolved photoemission

High-resolution time-and angle-resolved photoemission measurements were conducted on the topological insulator ZrTe_(5).With strong femtosecond photoexcitation,a possible ultrafast phase transition from a weak to a strong topological insulating phase was experimentally realized by recovering the energy gap inversion in a time scale that was shorter than 0.15 ps.This photoinduced transient strong topological phase can last longer than 2 ps at the highest excitation fluence studied,and it cannot be attributed to the photoinduced heating of electrons or modification of the conduction band filling.Additionally,the measured unoccupied electronic states are consistent with the first-principles calculation based on experimental crystal lattice constants,which favor a strong topological insulating phase.These findings provide new insights into the longstanding controversy about the strong and weak topological properties in ZrTe_(5),and they suggest that many-body effects including electron–electron interactions must be taken into account to understand the equilibrium weak topological insulating phase in ZrTe_(5).

Determination of the surface states from the ultrafast electronic states in a thermoelectric material

We reveal the electronic structure in Yb Cd_(2)Sb_(2),a thermoelectric material,by angle-resolved photoemission spectroscopy(ARPES)and time-resolved ARPES(tr ARPES).Specifically,three bulk bands at the vicinity of the Fermi level are evidenced near the Brillouin zone center,consistent with the density functional theory(DFT)calculation.It is interesting that the spin-unpolarized bulk bands respond unexpectedly to right-and left-handed circularly polarized probe.In addition,a hole band of surface states,which is not sensitive to the polarization of the probe beam and is not expected from the DFT calculation,is identified.We find that the non-equilibrium quasiparticle recovery rate is much smaller in the surface states than that of the bulk states.Our results demonstrate that the surface states can be distinguished from the bulk ones from a view of time scale in the nonequilibrium physics.

Topological Dirac surface states in ternary compounds GeBi_(2)Te_(4),SnBi_(2)Te_(4) and Sn_(0.571)Bi_(2.286)Se_(4)

Using high-resolution angle-resolved and time-resolved photoemission spectroscopy,we have studied the low-energy band structures in occupied and unoccupied states of three ternary compounds GeBi_(2)Te_(4),SnBi_(2)Te_(4) and Sn_(0.571)Bi_(2.286)Se_(4) near the Fermi level.In previously confirmed topological insulator GeBi_(2)Te_(4) compounds,we confirmed the existence of the Dirac surface state and found that the bulk energy gap is much larger than that in the first-principles calculations.In SnBi_(2)Te_(4) compounds,the Dirac surface state was observed,consistent with the first-principles calculations,indicating that it is a topological insulator.The experimental detected bulk gap is a little bit larger than that in calculations.In Sn_(0.571)Bi_(2.286)Se_(4) compounds,our measurements suggest that this nonstoichiometric compound is a topological insulator although the stoichiometric SnBi_(2)Se_(4) compound was proposed to be topological trivial.

Unusual Band Splitting and Superconducting Gap Evolution with Sulfur Substitution in FeSe

High-resolution angle-resolved photoemission measurements were taken on FeSe;S;(x=0,0.04,and 0.08)superconductors.With an ultrahigh energy resolution of 0.4 meV,unusual two hole bands near the Brillouin-zone center,which was possibly a result of additional symmetry breaking,were identified in all the sulfur-substituted samples.In addition,in both of the hole bands highly anisotropic superconducting gaps with resolution limited nodes were evidenced.We find that the larger superconducting gap on the outer hole band is reduced linearly to the nematic transition temperature while the gap on the inner hole is nearly S-substitution independent.Our observations strongly suggest that the superconducting gap increases with enhanced nematicity although the superconducting transition temperature is not only governed by the pairing strength,demonstrating strong constraints on theories in the FeSe family.

Biosynthetic pathway of prescription cucurbitacin IIa and high-level production of key triterpenoid intermediates in engineered yeast and tobacco

Cucurbitacin IIa is a triterpenoid isolated exclusively from Hemsleya plants and a non-steroidal anti-inflammatory drug that functions as the main ingredient of prescription Hemslecin capsules and tablets in China.Synthetic biology provides new strategies for production of such valuable cucurbitacins at a large scale;however,the biosynthetic pathway of cucurbitacin IIa has been unknown,and the heterologous production of cucurbitacins in galactose medium has been expensive and low yielding.In this study,we characterized the functions of genes encoding two squalene epoxidases(HcSE1-2),six oxidosqualene cyclases(HcOSC1-6),two CYP450s(HcCYP87D20 and HcCYP81Q59),and an acyltransferase(HcAT1)in cucurbitacin IIa biosynthesis by heterologous expression in Saccharomyces cerevisiae and Nicotiana benthamiana.We achieved high-level production of the key cucurbitacin precursor 11-carbonyl-20b-hydroxy-Cuol from glucose in yeast via modular engineering of the mevalonate pathway and optimization of P450 expression levels.The resulting yields of 46.41 mg/l 11-carbonyl-20b-hydroxy-Cuol and 126.47 mg/l total cucurbitacin triterpenoids in shake flasks are the highest yields yet reported from engineered microbes.Subsequently,production of 11-carbonyl-20b-hydroxy-Cuol by transient gene expression in tobacco resulted in yields of 1.28 mg/g dry weight in leaves.This work reveals the key genes involved in biosynthesis of prescription cucurbitacin IIa and demonstrates that engineered yeast cultivated with glucose can produce high yields of key triterpenoid intermediates.We describe a low-cost and highly efficient platform for rapid screening of candidate genes and high-yield production of pharmacological triterpenoids.

Abnormal Metabolic Connectivity in Rats at the Acute Stage of Ischemic Stroke

Stroke at the acute stage is a major cause of disability in adults, and is associated with dysfunction of brain networks. However, the mechanisms underlying changes in brain connectivity in stroke are far from fully elucidated. In the present study, we investigated brain metabolism and metabolic connectivity in a rat ischemic stroke model of middle cerebral artery occlusion （MCAO） at the acute stage using 18F-fluorodeoxyglucose positron emission tomography. Voxel-wise analysis showed decreased metabolism mainly in the ipsilesional hemi- sphere, and increased metabolism mainly in the contrale- sional cerebellum. We used further metabolic connectivity analysis to explore the brain metabolic network in MCAO. Compared to sham controls, rats with MCAO showed most significantly reduced nodal and local efficiency in the ipsilesional striatum. In addition, the MCAO group showed decreased metabolic central connection of the ipsilesional striatum with the ipsilesional cerebellum, ipsilesional hippocampus, and bilateral hypothalamus. Taken together, the present study demonstrated abnormal metabolic con- nectivity in rats at the acute stage of ischemic stroke, which might provide insight into clinical research.

Facile preparation of nano-g-C_(3)N_(4)/UiO-66-NH_(2) composite as sorbent for high-efficient extraction and preconcentration of food colorants prior to HPLC analysis

In this work,the nano-g-C_(3)N_(4)/Ui O-66-NH_(2)composite was prepared by one-step solvothermal method.The as-prepared composite was characterized by scanning electron microscopy,Brunner-Emmet-Teller measurement,energy dispersive spectrometer,X-ray diffraction,and Fourier transform infrared spectroscopy.By using nano-g-C_(3)N_(4)/Ui O-66-NH_(2)composite as sorbent,a dispersive solid-phase extraction coupled with high-performance liquid chromatography was developed to sensitive analysis of food colorants including tartrazine,amaranth,carmine,sunset yellow,allura red and bright blue.The experiment parameters including the amount of sorbent,adsorption time,the p H of adsorption solution,desorption time,desorption solvent,the p H of desorption solution as well as the proportion between desorption solvent and buffer solvent were investigated.Under the optimized conditions,the limits of detection(S/N=3) and limits of quantitation (S/N=10) were determined in the ranges of 0.08-0.8 and 0.2-2.0 ng/m L,respectively.With the developed sample pretreatment method,carmine and brilliant blue were determined from blueberry juice by HPLC-DAD.The contents were calculated as 1.53μg/m L and0.17μg/mL,respectively.

An Automatic Method for Generating an Unbiased Intensity Normalizing Factor in Positron Emission Tomography Image Analysis After Stroke

Positron emission tomography （PET） imaging of functional metabolism has been widely used to investigate functional recovery and to evaluate therapeutic efficacy after stroke. The voxel intensity of a PET image is the most important indicator of cellular activity, but is affected by other factors such as the basal metabolic ratio of each subject. In order to locate dysfunctional regions accurately, intensity normalization by a scale factor is a prerequisite in the data analysis, for which the global mean value is most widely used. However, this is unsuitable for stroke studies. Alternatively, a specified scale factor calculated from a reference region is also used, comprising neither hyper- nor hypo-metabolic voxels. But there is no such recognized reference region for stroke studies. Therefore, we proposed a totally data-driven automatic method for unbiased scale factor generation. This factor was generated iteratively until the residual deviation of two adjacent scale factors was reduced by 〈 5%. Moreover, both simulated and real stroke data were used for evaluation, and these suggested that our proposed unbiased scale factor has better sensi- tivity and accuracy for stroke studies.

Combined nanosuspensions from two natural active ingredients for cancer therapy with reduced side effects

Tumor drug resistance and systemic side effects of chemotherapeutic drugs are the main reasons for the failure of cancer treatment.In recent years,it was found that some natural active ingredients can reverse MDR and regulate body immunity to enhance the efficacy and reduce toxicity of chemotherapeutic drugs.In this paper,a new nanosuspensions,HCPT and QUR hybrid nanosuspensions(HQ-NPs),was prepared by the microprecipitation-high pressure homogenization method to reverse tumor drug resistance,reduce toxicity,and increase therapeutic efficacy.The in vitro investigation results showed that HQ-NPs had a unique shape(particle size was about 216.3±5.9 nm),changed crystalline,and different dissolution rates compared with HCPT-NPs and QUR-NPs,which is attributed to the strong intermolecular forces between HCPT and QUR as indicated by the results of the molecule dock.It was verified that the HQ-NPs could double the retention of HCPT in cells and enhance the cytotoxicity to A549/PTX cells in vitro tests compared with HCPT-NPs.We also found that HQ-NPs can significantly enhance the accumulation of HCPT in tumor sites,improve the antitumor activity of HCPT,and protect the immune organs and other normal tissues(P<0.01),compared with HCPT-NPs.Therefore,hybrid nanosuspensions can offer promising potential as the drug delivery system for HCPT and QUR to increase the therapeutic efficacy and reduce the toxicity of HCPT.

Factors affecting the voxel-based analysis of diffusion tensor imaging

Diffusion tensor imaging(DTI)provides a unique method to reveal the integrity of white matter microstructure noninvasively.Voxel-based analysis(VBA),which is a highly reproducible and user-independent technique,has been used to analyze DTI data in a number of studies.Fractional anisotropy(FA),which is derived from DTI,is the most frequently used parameter.The parameter setting during the DTI data preprocessing might affect the FA analysis results.However,there is no reliable evidence on how the parameters affect the results of FA analysis.This study sought to quantitatively investigate the factors that might affect the voxel-based analysis of FA;these include the interpolation during spatial normalization,smoothing kernel and statistical threshold.Because it is difficult to obtain the true information of the lesion in the patients,we simulated lesions on the healthy FA maps.The DTI data were obtained from 20 healthy subjects.The FA maps were calculated using DTIStudio.We randomly divided these FA maps into two groups.One was used as a model patient group,and the other was used as a normal control group.Simulated lesions were added to the model patient group by decreasing the FA intensities in a specified region by 5%–50%.The model patient group and the normal control group were compared by two-sample t test statistic analysis voxelby-voxel to detect the simulated lesions.We evaluated these factors by comparing the difference between the detected lesion through VBA and the simulated lesion.The result showed that the space normalization of FA image should use the trilinear interpolation,and the smoothing kernel should be 2–3 times the voxel size of spatially normalized FA image.For lesions with small intensity change,FWE correction must be cautiously used.This study provided an important reference to the analysis of FA with VBA method.