Dip2a regulates stress susceptibility in the basolateral amygdala

Dysregulation of neurotransmitter metabolism in the central nervous system contributes to mood disorders such as depression, anxiety, and post–traumatic stress disorder. Monoamines and amino acids are important types of neurotransmitters. Our previous results have shown that disco-interacting protein 2 homolog A(Dip2a) knockout mice exhibit brain development disorders and abnormal amino acid metabolism in serum. This suggests that DIP2A is involved in the metabolism of amino acid–associated neurotransmitters. Therefore, we performed targeted neurotransmitter metabolomics analysis and found that Dip2a deficiency caused abnormal metabolism of tryptophan and thyroxine in the basolateral amygdala and medial prefrontal cortex. In addition, acute restraint stress induced a decrease in 5-hydroxytryptamine in the basolateral amygdala. Additionally, Dip2a was abundantly expressed in excitatory neurons of the basolateral amygdala, and deletion of Dip2a in these neurons resulted in hopelessness-like behavior in the tail suspension test. Altogether, these findings demonstrate that DIP2A in the basolateral amygdala may be involved in the regulation of stress susceptibility. This provides critical evidence implicating a role of DIP2A in affective disorders.

Apatinib reduces liver cancer cell multidrug resistance by modulating NF-κB signaling pathway

Objectives:This investigation aimed to elucidate the inhibitory impact of apatinib on the multidrug resistance of liver cancer both in vivo and in vitro.Methods:To establish a Hep3B/5-Fu resistant cell line,5-Fu concentrations were gradually increased in the culture media.Hep3B/5-Fu cells drug resistance and its alleviation by apatinib were confirmed via flow cytometry and Cell Counting Kit 8(CCK8)test.Further,Nuclear factor kappa B(NF-κB)siRNA was transfected into Hep3B/5-Fu cells to assess alterations in the expression of multidrug resistance(MDR)-related genes and proteins.Nude mice were injected with Hep3B/5-Fu cells to establish subcutaneous xenograft tumors and then categorized into 8 treatment groups.The treatments included oxaliplatin,5-Fu,and apatinib.In the tumor tissues,the expression of MDRrelated genes was elucidated via qRT-PCR,immunohistochemistry,and Western blot analyses.Results:The apatinibtreated mice indicated slower tumor growth with smaller size compared to the control group.Both the in vivo and in vitro investigations revealed that the apatinib-treated groups had reduced expression of MDR genes GST-pi,LRP,MDR1,and p-p65.Conclusions:Apatinib effectively suppresses MDR in human hepatic cancer cells by modulating the expression of genes related to MDR,potentially by suppressing the NF-κB signaling pathway.

Engineering Cu_(2)O/Cu/N-C interface to induce directional migration of charge for driving photocatalytic homo-coupling of terminal alkynes

The efficient utilization of visible light catalysts for organic reactions necessitates not only the effective separation of photogenerated electrons and holes to participate in the reaction,but also their ability to form key intermediates with reactant molecules.The present study successfully synthesized a crusiform-like mesoporous structure of nitrogen-doped carbon-coated Cu_(2)O/Cu(Cu_(2)O/Cu/N-C)with a Cu_(2)O/dual electron acceptor interface using etched HKUST-1 as the precursor.A series of theoretical and experimental studies have demonstrated that the Cu_(2)O/Cu/N-C interface in the photocatalytic homo-coupling of terminal alkynes not only effectively enhances the separation of photogenerated electron−hole pairs,but also facilitates the formation of the key intermediate[Cu_(2)O/Cu/N-C]-phenylacetylide and promotes the rearrangement of its internal charges.As a result,the homo-coupling reaction can be effectively facilitated.The primary reason for the functional role of Cu_(2)O/Cu/N-C interface lies in the downward bending of energy band from Cu_(2)O to N-doped C layers,induced by the different work functions of Cu_(2)O,Cu and N-doped C layers.Consequently,Cu_(2)O/Cu/N-C photocatalysts demonstrate exceptional photocatalytic activity in the homo-coupling reaction of terminal alkynes under blue-light irradiation and air atmosphere.The present study presents a novel research methodology for the development of highly efficient visible light catalysts to facilitate organic reactions in future applications.

A photosensitizer-loaded zinc oxide-polydopamine core-shell nanotherapeutic agent for photodynamic and photothermal synergistic therapy of cancer cells

In clinical cancer research,it is quite promising to develop multimodal synergistic therapeutic strategies.Photodynamic and photothermal synergistic therapy is a very desirable multimodal therapy strategy.Herein,we report a facile and simple method to construct a nanotherapeutic agent for photodynamic and photothermal therapy.This nanotherapeutic agent(ZnO@Ce6-PDA)is composed of a ZnO nanoparticle core,an interlayer of photosensitizer chlorin e6(Ce6)and an outer layer of polydopamine(PDA).Due to the existence of Ce6,the ZnO@Ce6-PDA can efficiently generate singlet oxygen(1O2)under 660 nm laser irradiation.Moreover,the ZnO@Ce6-PDA can serve as a photothermal agent,because of the excellent photothermal conversion efficiency of the PDA coating layer in the presence of 780 nm laser.Experiment results demonstrated that the designed nanotherapeutic agent had outstanding phototoxicity upon the combination of laser irradiation at 660 and 780 nm.Thus,our work proves that the ZnO@Ce6-PDA is a promising photodynamic/photothermal dual-modal nanotherapeutic agent for enhanced cancer therapy.

NIR-triggered drug delivery system based on phospholipid coated ordered mesoporous carbon for synergistic chemo-photothermal therapy of cancer cells

Chemo-photothermal treatment is one of the most efficient strategies for cancer therapy.However,traditional drug carriers without near-infrared absorption capacity need to be loaded with materials behaving photothermal properties,as it results in complicated synthesis process,inefficient photothermal effects and hindered NIR-mediated drug release.Herein we report a facile synthesis of a polyethylene glycol(PEG)linked liposome(PEG-liposomes)coated doxorubicin(DOX)-loaded ordered mesoporous carbon(OMC)nanocomponents(PEG-LIP@OMC/DOX)by simply sonicating DOX and OMC in PEG-liposomes suspensions.The as-obtained PEG-LIP@OMC/DOX exhibits a nanoscale size(600±15 nm),a negative surface potential(-36.70 mV),high drug loading(131.590 mg/g OMC),and excellent photothermal properties.The PEG-LIP@OMC/DOX can deliver loaded DOX to human MCF-7 breast cancer cells(MCF-7)and the cell toxicity viability shows that DOX unloaded PEG-LIP@OMC has no cytotoxicity,confirming the PEG-LIP@OMC itself has excellent biocompatibility.The NIR-triggered release studies demonstrate that this NIR-responsive drug delivery system enables on-demand drug release.Furthermore,cell viability results using human MCF-7 cells demonstrated that the combination of NIR-based hyperthermal therapy and triggered chemothe rapy can provide higher therapeutic efficacy than re spective monothe rapies.With these excellent features,we believe that this phospholipid coating based multifunctional delivery system strategy should promote the application of OMC in nanomedical applications.

Near-infrared photothermal release of hydrogen sulfide from nanocomposite hydrogels for anti-inflammation applications

A novel near-infrared light photothemal-activated H2S-donating nanocomposite hydrogel was developed,through combination of a thermo-labile H2S donor and photothermal nanoparticles in agarose hydrogel.The polyethylenimine dithiocarbamate polymer,a thermo-labile compound,was synthesized as a novel H2S donor.The combination of a thermo-labile hydrogen sulfide donor and photothermal nanoparticles enabled the generation of H2S in agarose hydrogel upon irradiation with near-infrared light.The ability to modulate the photoirradiation for controlled generation and spatiotemporally release of H2S are its specific advantages.This photothermal spatiotemporally controlled H2S-releasing strategy was successfully applied to anti-inflammation treatment in a rat model,demonstrating its utility as a novel H2S-based therapeutic approach.

Dithienylethene metallodendrimers with high photochromic efficiency

It has been challenging to achieve multi-photochromic systems without affecting the individual photoswitching properties of the constituent units. Herein, we present the design and synthesis of a new family of platinum-acetylide dendrimers containing up to twenty-one photochromic dithienylethene(DTE)units that exhibit both high photochromic efficiency and individual switching properties. Upon irradiation with ultraviolet(UV) and visible(vis) light, the resultant metallodendrimers display high conversion yield and good fatigue resistance. More interestingly, cyclization-cycloreversion kinetics revealed that the photochromic property of each DTE unit in these metallodendrimers is unaffected by its neighbor and the full ring-closure of up to twenty-one DTE units in one single dendrimer has been achieved.

A Well-Conditioned, Nonconforming Nitsche’s Extended Finite Element Method for Elliptic Interface Problems

In this paper,we introduce a nonconforming Nitsche’s extended finite element method(NXFEM)for elliptic interface problems on unfitted triangulation elements.The solution on each side of the interface is separately expanded in the standard nonconforming piecewise linear polynomials with the edge averages as degrees of freedom.The jump conditions on the interface and the discontinuities on the cut edges(the segment of edges cut by the interface)are weakly enforced by the Nitsche’s approach.In the method,the harmonic weighted fluxes are used and the extra stabilization terms on the interface edges and cut edges are added to guarantee the stability and the well conditioning.We prove that the convergence order of the errors in energy and L 2 norms are optimal.Moreover,the errors are independent of the position of the interface relative to the mesh and the ratio of the discontinuous coefficients.Furthermore,we prove that the condition number of the system matrix is independent of the interface position.Numerical examples are given to confirm the theoretical results.

Interaction between Cu^(2+) and different types of surface-modified nanoscale zero-valent iron during their transport in porous media

This study investigated the interaction between Cu^2＋and nano zero-valent iron（NZVI）coated with three types of stabilizers（i.e., polyacrylic acid [PAA], Tween-20 and starch） by examining the Cu^2＋ uptake, colloidal stability and mobility of surface-modified NZVI（SM-NZVI） in the presence of Cu^2＋. The uptake of Cu^2＋ by SM-NZVI and the colloidal stability of the Cu-bearing SM-NZVI were examined in batch tests. The results showed that NZVI coated with different modifiers exhibited different affinities for Cu^2＋, which resulted in varying colloidal stability of different SM-NZVI in the presence of Cu^2＋. The presence of Cu^2＋ exerted a slight influence on the aggregation and settling of NZVI modified with PAA or Tween-20. However, the presence of Cu^2＋caused significant aggregation and sedimentation of starch-modified NZVI, which is due to Cu^2＋complexation with the starch molecules coated on the surface of the particles. Column experiments were conducted to investigate the co-transport of Cu^2＋ in association with SM-NZVI in water-saturated quartz sand. It was presumed that a physical straining mechanism accounted for the retention of Cu-bearing SM-NZVI in the porous media. Moreover, the enhanced aggregation of SM-NZVI in the presence of Cu^2＋ may be contributing to this straining effect.

Simultaneous and multiplex detection of exosomal microRNAs based on the asymmetric Au@Au@Ag probes with enhanced Raman signal

Simultaneous and quantitative detection of multiple exosomal micro RNAs(miRNAs)was successfully performed by a surface-enhanced Raman scattering(SERS)assay consisting of Raman probes and capture probes.In this design,the asymmetric core-shell structured Au@Au@Ag nanoparticles were first synthesized by layer-by-layer self-assembly method and modified with different Raman molecules and recognition sequences(poly A-DNA)to prepare the surface-enhanced Raman probes.Then,the streptavidinmodified magnetic beads were used to immobilize the biotinylated DNA capture sequences(biotin-DNA)to obtain capture probes.In the presence of target exosomal miRNAs,the Raman probes and capture probes could bind to the target exosomal miRNAs in the partial hybridization manner.Thus,the developed SERS sensor could indicate the target miRNAs levels in the buffer solution.Using breast cancerrelated miRNAs as model targets,the limits of detection of this sensor were determined to be 1.076 fmol/L for synthetic miR-21,0.068 fmol/L for synthetic miR-126,and 4.57 fmol/L for synthetic miR-1246,respectively.Such SERS sensors were further employed to detect the miR-21 in 20%human serum and the extraction solution of exosomes,respectively.Therefore,simultaneous and multiplex detection of cancerrelated exosomal miRNAs by this assay could provide new opportunities for further biomedical applications.

Rapidly and mildly transferring anatase phase of graphene-activated TiO2 to rutile with elevated Schottky barrier:Facilitating interfacial hot electron injection for Vis-NIR driven photocatalysis

Visible and even infrared(IR)light-initiated hot electrons of graphene(Gr)catalysts are a promising driven power for green,safe,and sustainable H2O2 synthesis and organic synthesis without the limitation of bandgap-dominated narrow light absorption to visible light confronted by conventional photocatalyst.However,the life time of photogenerated hot electrons is too short to be efficiently used for various photocatalytic reactions.Here,we proposed a straightforward method to prolong the lifetime of photogenerated hot electrons from graphene by tuning the Schottky barrier at Gr/rutile interface to facilitate the hot electron injection.The rational design of Gr-coated TiO2 heterojunctions with interface synergy-induced decrease in the formation energy of the rutile phase makes the phase transfer of TiO2 support proceed smoothly and rapidly via ball milling.The optimized Gr/rutile dyad could provide a H2O2 yield of 1.05 mM·g-1·h-1 under visible light irradiation(λ≥400 nm),which is 30 times of the state-of-the-art noble-metal-free titanium oxide-based photocatalyst,and even achieves a H2O2 yield of 0.39 mM·g-1·h-1 on photoexcitation by near-infrared-region light(~800 nm).

Phase-separated bienzyme compartmentalization as artificial intracellular membraneless organelles for cell repair

Implanting artificial organelles in living cells is capable of correcting cellular dysfunctionalities for cell repair and biomedical applications. In this work, phase-separated bienzyme-loaded coacervate microdroplets are established as a model of artificial membraneless organelles in endothelial dysfunctional cells for the cascade enzymatic production of nitric oxide(NO) with a purpose of correcting cellular NO deficiency. We prepared the coacervate microdroplets via liquid-liquid phase separation of oppositely charged polyelectrolytes, in which glucose oxidase/horseradish peroxidase-mediated cascade reaction was compartmented. After the coacervate microdroplets were implanted in NO-deficient dysfunctional cells, the compartments maintained a phase-separated liquid droplet structure, which facilitated a significant enhancement of NO production in the dysfunctional cells. The recovery of NO production was further exploited to inhibit clot formation in blood plasma located in the cell suspension. This demonstrated a proof-of-concept design of artificial organelles in dysfunctional cells for cell repair and anticoagulation-related medical applications. Our results demonstrate an approach for the construction of coacervate droplets through phase separation for the generation of artificial membraneless organelles, which can be designed to provide an array of functionalities in living organisms that have the potential to be used in the field of cell engineering and medical therapy.

A novel fluorescent label based on biological fluores-cent nanoparticles and its application in cell recognition

Uniform-sized fluorescent nanoparticles have been prepared by employing silica as the shell and a highly luminescent dye complex of ruthenium ion and bipyridyl, tris(2,2 ’-bipyridyl) dichlororuthenium( II) hexahydrate as the core of the nanoparticles. A novel fluorescent label method is proposed, which is based on the biological fluorescent nanoparticles on the foundation of nanotechnology, biotechnology and fluorescent label technology. In comparison with the conventional fluorophores as fluorescent labels such as fluorescein isothiocyanate (FITC) label, this new label shows more superiority in photochemical stability, detection sensitivity and application scope for the biomedicine research. SmIgG+ B lymphocytes isolated from the circulating blood of human beings can be easily recognized by using this new fluorescent label.

A pH-responsive activatable aptamer probe for targeted cancer imaging based on i-motif-driven conformation alteration

We present here a pH-responsive activatable aptamer probe for targeted cancer imaging based on i-motif-driven conformation alteration. This pH-responsive activatable aptamer probe is composed of two single-stranded DNA. One was used for target recognition, containing a central, target specific aptamer sequence at the 3＇-end and an extension sequence at the 5＇-end with 5-carboxytetramethylrhodamine （TAMRA） label （denoted as strand A）. The other （strand ｜）, being competent to work on the formation of i-motif structure, contained four stretches of the cytosine （C） rich domain and was labeled with a Black Hole Quencher 2 （BHQ2） at the 3＇-end. At neutral or slightly alkaline pH, strand ｜ was hybridized to the extension sequence of strand A to form a double-stranded DNA probe, termed i-motif-based activatable aptamer probe （I-AAP）. Because of proximity- induced energy transfer, the I-AAP was in a ＂signal off＇ state. The slightly acidic pH enforced the strand I to form an intramo- lecular i-motif and then initiated the dehybridization of I-AAP, leading to fluorescence readout in the target recognition. As a demonstration, AS1411 aptamer was used for MCF-7 cells imaging. It was displayed that the I-AAP could be carried out for target cancer cells imaging after being activated in slightly acidic environment. The applicability of I-AAP for tumor tissues imaging has been also investigated by using the isolated MCF-7 tumor tissues. These results implied the I-AAP strategy is promising as a novel approach for cancer imaging.