Generation of induced pluripotent stem cell line (XWHNi003-A) from a female with APOE gene mutation.

Apolipoprotein E (APOE)is the gene with greatest genetic risk for Alzheimer's disease (AD). We successfully established a human induced pluripotent stem cell(iPSC) line from a woman mutated by APOE gene. The cell line was isolated from this woman's peripheral blood mononuclear cells using a non-integrated Sendai virus, which retained the original genotype, showed a normal karyotype, highly expressed pluripotent markers and could differentiate into three germ layers.

Generation of human induced pluripotent stem cell line (XWHNi004-A) from a male with APOE gene mutation.

Genetic polymorphism of apolipoprotein E (APOE) confers differential susceptibility to Alzheimer's disease (AD), and APOE ɛ4 variants is the most powerful risk factor for this disease. Here, we report the generation of a human induced pluripotent stem cell (iPSC) line carrying the APOE ɛ4/ɛ4 genotype from peripheral blood mononuclear cells (PBMCs) isolated from a male with a family history of AD utilizing non-integrative Sendai virus vector. The iPSC maintains their original genotype, highly express endogenous pluripotency markers, displays a normal karyotype, and retains the ability to differentiate into cells representative of the three germ layers.

Reciprocal associations between commitment, forgiveness, and different aspects of marital well-being among Chinese newlywed couples.

This study examined the reciprocal prospective associations between commitment, forgiveness, and different aspects of marital well-being (marital satisfaction and marital instability) among Chinese newlywed couples and the gender differences in these associations. The Vulnerability-Stress-Adaptation (VSA) model posits reciprocal associations between adaptive processes and relationship satisfaction. However, the directionality of the associations between adaptive processes and marital satisfaction may differ from the associations between adaptive processes and marital instability in Chinese societies due to the emphasis on relationship maintenance. Based on three annual waves of data from 268 Chinese newlywed couples (Mage = 29.59, SD = 3.25 for husbands; Mage = 28.08, SD = 2.51 for wives), a cross-lagged approach was used to examine the reciprocal associations between commitment, forgiveness, and marital satisfaction/instability. We found: (a) reciprocal associations between commitment/forgiveness and marital satisfaction (wives only); (b) reciprocal associations between forgiveness and marital instability (husbands only); and (c) wives' commitment at Wave 2 mediated the association between wives' commitment at Wave 1 and wives' marital satisfaction at Wave 3. Extending the VSA model, findings suggest different reciprocal associations between commitment, forgiveness, and different aspects of marital well-being among Chinese newlywed couples. Results highlight the important role of culture and gender in marital relationships and clinical practice.

Dual-Frequency Polarized Reconfigurable Terahertz Antenna Based on Graphene Metasurface and TOPAS.

A hybrid dual-frequency polarized reconfigurable terahertz antenna is designed and studied. Graphene and TOPAS are employed as the polarization conversion metasurface and dielectric substrate, respectively, enabling tunable polarization conversion and circular polarization. TOPAS is a good substrate material for broadband THz components due to its low absorption. By adjusting the chemical potential of graphene between 0 eV and 0.5 eV, the polarization state in the band of 1 THz (0.76-1.02 THz) and 2.5 THz (2.43-2.6 THz) can be reconstructed. Thanks to the multilayer graphene structure and low absorption TOPAS, the graphene metasurface exhibits a broad bandwidth of 0.26 and 0.17 THz, respectively, in the band of 1 THz and 2.5 THz. The working state of the circularly polarized antenna and linearly polarized antenna can be switched in the bands around 1 THz (0.7-0.75 THz, 0.96-1.04 THz) and 2.5 THz (2.42-2.52 THz), respectively, without changing the physical geometry. Moreover, the graphene antenna, metasurface, and hybrid structure are tested, respectively, to verify that the components do not interfere with each other in performance. The hybrid antenna shows great potential in tunable terahertz devices and related applications.

An injectable thermosensitive hydrogel self-supported by nanoparticles of PEGylated amino-modified PCL for enhanced local tumor chemotherapy.

We synthesized amino-modified poly(ε-caprolactone) PCN-b-PEG-b-PCN (PECN) triblock copolymers and studied the contribution of the introduced amino groups to the drug delivery efficiency of PECN nanoparticles (NPs) and their injectable thermosensitive hydrogels. PECN15 with an optimal amino group content was obtained. Firstly, the hydrophobic drug paclitaxel (PTX) was loaded into PECN15 up to 5.91% and formed PTX/PECN NPs 90 nm in size and with a slightly positive charge (7.3 mV). Furthermore, the injectable PTX/PECN NPs aqueous solution (25 wt%) at ambient temperature could undergo fast gelation at 37 °C and sustainedly release PTX/PECN NPs in 10 days. More importantly, compared with our previously reported PECT NPs, the PECN NPs without an increase in toxicity could improve the cell uptake and enhance intracellular drug release by responding to the acidic environment of the endosome. Thus, the PTX/PECN NPs presented a lower IC50 of 3.14 µg mL-1 than that of the PTX/PECT NPs (7.67 µg mL-1) and free PTX (4.65 µg mL-1). Moreover, through peritumoral injection, the PTX/PECNGel showed 94.27% inhibition rate of tumor growth on day 19, higher than PTX/PECTGel (72.28%) and Taxol® (47.03%). Therefore, the PECN NPs hydrogel provided a more effective injectable platform to enhance local cancer chemotherapy, and also provided the possibility of further functionalization by the reactive amino groups.

Cascade of reactive oxygen species generation by polyprodrug for combinational photodynamic therapy.

The redox status of cancer cells is well regulated by the balance between the reactive oxygen species (ROS) generation and elimination. Thus, the overall elevation of ROS level above the cellular tolerability threshold would lead to apoptotic or necrotic cell death. Herein, cinnamaldehyde (CA), a kind of oxidative stress amplified agent, was combined with photosensitizer pheophorbide A (PA) to promote the generation of ROS though synergistically endogenous and exogenous pathways. Firstly, acid-responsive polygalactose-co-polycinnamaldehyde polyprodrug (termed as PGCA) was synthesized, which could self-assemble into stable nanoparticles for the delivery of PA (termed as PGCA@PA NPs). The abundant expression of galactose receptor on tumor cells facilitated the positive targeting and cellular uptake efficiency of PGCA@PA NPs, after which PA could be synchronously released in company with the intracellular disassembly of PGCA NPs, due to the detaching of CA moieties under acidic microenvironment in endo/lysosomal compartment. Significantly increased ROS level was induced by the combined action of CA and PA with light irradiation, resulting in dramatically enhanced apoptosis of cancer cells. Importantly, intravenous injection of PGCA@PA NPs potently inhibited the tumor growth in hepatocellular carcinoma with negligible adverse effects. Moreover, combined with anti-programmed cell death protein 1 (anti-PD-1) therapy, PGCA@PA NPs treatment elicited anti-melanoma T-cell immune response and significantly promoted T cells infiltration in tumors. Hence, this novel polyprodrug nano delivery system was able to target and modulate the unique redox regulatory mechanisms of cancer cells through endogenous and exogenous pathways, providing a feasible approach to achieve synergetic therapeutic activity and selectivity.

"Off/on" fluorescence imaging-guided cancer diagnosis and multi-modal therapy.

An efficient theranostic nanoplatform responding to tumour microenvironments with characters of simple and flexible combinations owns great potential in cancer diagnosis and therapy. Herein, a series of triblock copolymers, mPEG-b-PDPA-b-P(nBMA-r-cystamine) (EPB), were synthesized and among them, the structure of EPB-3 was optimized for both fluorescence imaging-guided cancer diagnosis and multi-modal therapy with good biocompatibility. (1) The self-assembled nanoparticles of EPB-3-ICG1 obtained by conjugating one ICG on EPB-3 via S-S bonds effectively performed reduction-sensitive OFF/ON fluorescence signal transition, thus inducing tumour cell-specific amplified fluorescence imaging in vitro and in vivo. (2) By entrapping Au nanorods into the co-assembled NPs of EPB-3 and EPB-3-ICG1, EPB-3-ICG1@Au NPs could synchronously induce strong tumour fluorescence imaging and high local photothermal effect, indicating the potential of imagine-guided photothermal therapy. (3) EPB-3 NPs could efficiently co-load paclitaxel (PTX) and ICG to form stable EPB-3@PTX@ICG NPs, which provided long periods of intracellular pH-sensitive sustainable drug release and highly enhanced apoptosis of 4T1 cells in vitro by the chemo-photothermal effect. Excitingly, a single intravenous injection of EPB-3@PTX@ICG NPs followed by a one-time local near-infrared light (NIR, 808 nm) irradiation treatment for 10 min could lead to significant inhibition of tumour growth, avoiding tumor metastasis and extending the survival of mice. All the above-mentioned results suggest that EPB-3 provides a nanoplatform with the characters of simple structure, convenience of use and flexible combination, holding potential for multi-modal diagnosis and therapy.

Analogues of xanthones--Chalcones and bis-chalcones as α-glucosidase inhibitors and anti-diabetes candidates.

Two series of compounds (chalcones and bis-chalcones) were designed, synthesized, and evaluated as α-glucosidase inhibitors (AGIs) with 1-deoxynojirimycin as positive control in vitro. Most of the compounds with two or four hydroxyl groups showed better inhibitory activities than 1-deoxynojirimycin towards α-glucosidase with noncompetitive mechanism. Moreover, most of the hydroxy bis-chalcones exhibit good α-glucosidase inhibitory activities in enzyme test. Inspiringly, bis-chalcones 2g (at 1 µM concentration) has stronger effect than 1-deoxynojirimycin on reducing the glucose level in HepG-2 cells (human liver cancer cell line).

Delivery of Liposomes with Different Sizes to Mice Brain after Sonication by Focused Ultrasound in the Presence of Microbubbles.

Imaging or therapeutic agents larger than the blood-brain barrier's (BBB) exclusion threshold of 400 Da could be delivered locally, non-invasively and reversibly by focused ultrasound (FUS) with circulating microbubbles. The size of agents is an important factor to the delivery outcome using this method. Liposomes are important drug carriers with controllable sizes in a range of nanometers. However, discrepancies among deliveries of intact liposomes with different sizes, especially those larger than 50 nm, across the BBB opened by FUS with microbubbles remain unexplored. In the present study, rhodamine-labeled long-circulating pegylated liposomes with diameters of 55 nm, 120 nm and 200 nm were delivered to mice brains after BBB disruption by pulsed FUS with microbubbles. Four groups of peak rarefactional pressure and microbubble dosages were used: 0.53 MPa with 0.1 µL/g (group 1), 0.53 MPa with 0.5 µL/g (group 2), 0.64 MPa with 0.1 µL/g (group 3) and 0.64 MPa with 0.5 µL/g (group 4). The delivery outcome was observed using fluorescence imaging of brain sections. It was found that the delivery of 55-nm liposomes showed higher success rates than 120-nm or 200-nm liposomes from groups 1-3. The result indicated that it may be more difficult to deliver larger liposomes (>120 nm) passively than 55-nm liposomes after BBB opening by FUS with microbubbles. The relative fluorescence area of 55-nm liposomes to the total area of the sonicated region was statistically larger than that of the 120-nm or 200-nm liposomes. Increasing peak rarefactional pressure amplitude or microbubble dose could induce more accumulation of liposomes in the brain using FUS with microbubbles. Moreover, the distribution pattern of delivered liposomes was heterogeneous and characterized by separated fluorescence spots with cloud-like periphery surrounding a bright center, indicating confined diffusion in the extracellular matrix after extravasation from the microvasculature. These findings are expected to provide useful information for developing FUS with microbubbles as an effective trans-BBB liposomal drug delivery strategy.

Fluorescence imaging of Evans blue extravasation into mouse brain induced by low frequency ultrasound with microbubble.

Blood-Brain Barrier (BBB) can be opened locally, noninvasively and reversibly by low frequency focused ultra-sound (FUS) in the presence of microbubbles. In this study, Evans blue (EB) dye extravasation across BBB was enhanced by 1 MHz FUS at acoustic pressure of 0.35 MPa in the presence of microbubbles at clinically comparable dosage. The spatial distribution of EB extravasation was visualized using fluorescence imaging method. The center region of BBB disruption area showed more enhanced fluorescence signal than the surrounding region in general. However, EB dye deposition was heterogeneous in the center region. The findings in this study indicated potential use of fluorescence imaging to evaluate large molecules delivery across BBB.